BACKGROUND: The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. METHODS: We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t-test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients' clinical characteristics was assessed by univariate analysis. RESULTS: In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients' prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients' gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. CONCLUSION: The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

BACKGROUND: Hemoglobin/red cell distribution width (HR) and platelet/lymphocyte (PLR) ratios are considered effective prognostic markers in various cancers. We have proposed a new prognostic parameter: HR+PLR. The aim of this study is to explore the prognostic value of the HR+PLR scoring system in patients with gastric cancer liver metastasis. METHODS: This study retrospectively analyzed the clinical data of 306 patients with gastric cancer liver metastases admitted to our hospital from 2007 to 2014. According to the size of HR value and PLR value, we will divide the patients into three groups, namely, HR+PLR: (1) 0 points: HR > 1.02 and PLR < 128; (2) 1 point: HR > 1.02 and PLR > 128 and HR < 1.02 and PLR < 128; and (3) 2 points: HR < 1.02 and PLR > 128. RESULTS: The HR+PLR score was statistically different from age (P = 0.049), T stage (P < 0.001), N stage (P = 0.017), number of liver metastases (P = 0.018), gastrectomy (P < 0.001), hepatectomy (P = 0.001), peritoneal metastasis (P = 0.012), prognostic nutritional index (PNI) (P = 0.028), and neutrophil/lymphocyte ratio (NLR) (P = 0.045). The HR+PLR scoring system has a higher area under the ROC curve (AUC value) than PNI, PLR, HR, and PLR (AUC = 0.798, P < 0.001). In multivariate analysis, gastrectomy (P = 0.001), hepatectomy (P < 0.001), chemotherapy (P = 0.014), and HR+PLR score (P < 0.001) were considered independent prognostic factors. CONCLUSION: For patients with gastric cancer liver metastasis, the HR+PLR score is a simple, reliable, and economic prognostic marker.

BACKGROUND: The majority of lung cancers are adenocarcinomas, with the proportion being 40%. The patients are mostly diagnosed in the middle and late stages with metastasis and easy recurrence, which poses great challenge to the treatment and prognosis. Platinum-based chemotherapy is a primary treatment for adenocarcinoma, which frequently causes drug resistance. As a result, it is important to uncover the mechanisms of the chemoresponse of adenocarcinoma to platinum-based chemotherapy. METHODS: The genes from the dataset GSE7880 were gathered into gene modules with the assistance of weighted gene coexpression network analysis (WGCNA), the gene trait significance absolute value (|GS|), and gene module memberships (MM). The genes from hub gene modules were calculated with a protein-protein interaction (PPI) network analysis in order to obtain a screening map of hub genes. The hub genes with both a high |GS| and MM and a high degree were selected. Furthermore, genes in the hub gene modules also went through a Gene Ontology (GO) functional enrichment analysis. RESULTS: 11 hub genes in four hub gene modules (LY86, ACTR2, CDK2, CKAP4, KPNB1, RBBP4, SMAD4, MYL6, RPS27, TSPAN2, and VAMP2) were chosen as the significant hub genes. Through the GO function enrichment analysis, it was indicated that four modules were abundant in immune system functions (floralwhite), amino acid biosynthetic process (lightpink4), cell chemotaxis (navajowhite2), and targeting protein (paleturquoise). Four hub genes with the highest |GS| were verified by prognostic analysis.

BACKGROUND: The superiority of focused shockwave therapy (F-SWT) versus radial shockwave therapy (R-SWT) for treating noncalcific rotator cuff tendinopathies remains controversial. This study is aimed at comparing the effectiveness of F-SWT versus R-SWT for the management of noncalcific rotator cuff tendinopathies. METHODS: A total of 46 patients affected by noncalcific rotator cuff tendinopathies were randomly divided into 2 groups of 23 individuals. Patients in group A received 4 sessions of F-SWT, while patients in group B were treated by 4 sessions of R-SWT. In each session, mean energy flux density (EFD) for F-SW 3000 shots was 0.09 ± 0.018 mJ/mm2 with 5.1 ± 0.5 Hz, while average pressure for R-SW 3000 shots was 4.0 ± 0.35 bar with 3.2 ± 0.0 Hz. Pain level and shoulder function were assessed with the numerical rating scale (NRS) and Constant-Murley Scale (CMS). The primary endpoint was the change in the mean NRS pain score from baseline to 24 weeks after the intervention. Secondary endpoints were changes in the mean NRS pain scores at all other follow-up points, changes in the mean CMS scores, and radiographic findings. RESULTS: There were no significant differences between the two groups regarding NRS pain score and CMS score within 24 weeks after intervention (all p > 0.05). However, F-SWT resulted in significantly lower NRS compared with R-SWT at 24 weeks and 48 weeks after treatment (2.7 ± 1.0 vs. 4.5 ± 1.2 and 1.4 ± 1.0 vs. 3.0 ± 0.8, respectively, all p < 0.001). Similar results were found in CMS changes and radiographic findings. CONCLUSIONS: Both F-SWT and R-SWT are effective in patients with noncalcific rotator cuff tendinopathy. F-SWT proved to be significantly superior to R-SWT at long-term follow-up (more than 24 weeks). This trial is registered with ChiCTR1900022932.

BACKGROUND: There is increasing evidence that dietary intake of sugars may be a risk factor for prostate cancer (PCa) and elevate the concentration of serum prostate-specific antigen (PSA). However, there is limited evidence of the correlation between total dietary intake of sugars and serum PSA concentrations for adult American males. Herein, we evaluated the association between total dietary intake of sugars and serum PSA concentrations in men without a malignant tumor diagnosis in the United States (US) National Health and Nutrition Examination Survey (NHANES) database. Material and Methods. In this secondary data analysis, a total of 6,403 men aged ≥40 years and without malignant tumor history were included from 2003 to 2010. The independent variable of this study was the total dietary intake of sugars, and the dependent variable was serum PSA concentrations. Covariates included dietary, comorbidity, physical examination, and demographic data. RESULTS: The average age of participants included in this study was 58.1 years (±13.6). After adjusting for the dietary, comorbidity, physical examination, and demographic data, we observed that a dietary intake increase of one gram of total dietary intake of sugars was associated with an increase of serum PSA concentrations by 0.003 ng/mL (after log2 transformed, 95% CI: 0.001 to 0.005) with a P value for trend less than 0.05. Sensitivity analysis using the generalized additive model (GAM) supported the linear association between total dietary intake of sugars and serum PSA concentrations. CONCLUSION: The total dietary intake of sugars is independently and positively associated with serum PSA concentrations in adult American males who are without a personal history of malignant tumors.

Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly and has become a growing global health problem causing great concern. However, the pathogenesis of AD is unclear and no specific therapeutics are available to provide the sustained remission of the disease. In this study, we used comprehensive bioinformatics to determine 158 potential genes, whose expression levels changed between the entorhinal and temporal lobe cortex samples from cognitively normal individuals and patients with AD. Then, we clustered these genes in the protein-protein interaction analysis and identified six significant genes that had more biological functions. Besides, we conducted a drug-gene interaction analysis of module genes in the drug-gene interaction database and obtained 26 existing drugs that might be applied for the prevention and treatment of AD. In addition, a predictive model was built based on the selected genes using different machine learning algorithms to identify individuals with AD. These findings may provide new insights into AD therapy.

PURPOSE: The epithelial-mesenchymal transition (EMT) is a key hallmark of cancer which promotes malignant progression, especially during the process of cancer invasion. A better understanding of EMT will help elucidate the molecular mechanism underlying colorectal cancer (CRC) metastasis and may provide new insights into the identification of potential biomarkers and therapeutic targets. METHODS: A series of bioinformatic approaches were combined and identify GLI3 as a potential key regulator in EMT. In vitro experiments were performed to knockdown GLI3 expression in two CRC cell lines and to reveal the oncogenic role of GLI3 in CRC. qRT-PCR and western blot were performed to show the influence of GLI3 in EMT and downstream pathways. The Kaplan-Meier analysis and log-rank test were used to evaluate the prognostic value of GLI3 in CRC patients. RESULTS: GLI3 was identified as a key regulator in coexpression and protein-protein interaction (PPI) networks involved in EMT. Bioinformatic analyses indicated that GLI3 had a high correlation with EMT markers in CRC. In vitro experiments showed that GLI3 knockdown attenuated the migratory and invasive capacities of CRC cells via influencing EMT property, especially by regulating phosphorylation of ERK signaling pathway. In addition, higher expression of GLI3 predicts worse prognosis in CRC patients. CONCLUSIONS: In summary, we presented the first evidence that GLI3 could promote the migratory and invasive capacities of CRC cells by regulating the EMT process. Our study might provide some useful clues to a better understanding of GLI3 in EMT during CRC progression.

BACKGROUND: The present study focused on the potential clinical significance of miR-3934 in the occurrence and development of asthma. METHODS: 80 asthma and 80 healthy controls were recruited in this study. The peripheral blood mononuclear cells (PBMCs) and serum samples of the asthma patients as well as the healthy controls were isolated, and the expression levels of miR-3934 in PBMCs were examined by RT-qPCR methods. Furthermore, the relationship between the level of miR-3934 in PBMCs and the disease severity has been analyzed, and the potential diagnostic value of miR-3934 was evaluated by the receiver operating characteristics (ROC) curve. Finally, the expression level of IL-6, IL-8, and IL-33 have been detected using the ELISA kits, and Pearson's correlation analysis was performed to investigate the relationship between the level of miR-3934 in PBMCs and the serum expression of those inflammatory cytokines in asthma patients. RESULTS: miR-3934 was dramatically decreased in PBMCs of the asthma patients, and miR-3934 was markedly reduced in PBMCs of patients with severe asthma vs. mild asthma. Furthermore, ROC analysis showed that levels of miR-3934 in PBMCs can distinguish asthma patient, especially the severe asthma patients from the controls. Finally, the levels of miR-3934 in PBMCs were negatively correlated with the serum levels of IL-6, IL-8, and IL-33 in asthma patients, respectively. CONCLUSIONS: miR-3934 was downregulated in PBMCs of asthmatic patients and may function as a potential diagnosis biomarker.

Aging is an independent risk factor for the development of age-related progressive kidney injury. As a part of the aging process, kidney aging has been indicated to be associated with oxidative stress-induced damage. Ameliorating oxidative damage is therefore considered a promising strategy for delaying kidney aging. Alginate oligosaccharide (AOS) has been reported to have a wide range of biological and pharmacological activities. However, no studies have focused on the role of AOS in delaying the kidney aging process. In this study, we aimed to evaluate the potential effects of AOS on kidney aging and its possible mechanisms. Subcutaneous injection of D-galactose (D-gal) (200 mg·kg-1·d-1) in C57BL/6J mice for 8 weeks was used to establish the aging model. AOS (200 mg·kg-1·d-1) was administered via oral gavage for the last four weeks. As a result, AOS inhibited the D-gal-induced upregulation of aging markers and significantly improved the kidney index and kidney function of D-gal-induced mice. In addition, AOS ameliorated the degree of tissue damage and fibrosis in the aging kidney. To further explore the potential mechanisms by which AOS attenuates the kidney aging process, the associated oxidative stress-induced damage was analyzed in depth. The data showed that AOS upregulated the expression of Klotho and decreased malondialdehyde levels by increasing the expression of antioxidant enzymes. Furthermore, our results suggested that AOS activated the nuclear factor erythrogen-2 associated factor 2 (Nrf2) pathway by promoting Nrf2 nuclear translocation in aging mice and upregulated the downstream expression of heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). In conclusion, the present study demonstrated that AOS is a promising agent for attenuating kidney aging, and the underlying molecular mechanisms are related to the activation of the Nrf2 signaling pathway.

Phosgene exposure can cause acute lung injury (ALI), for which there is no currently available effective treatment. Mesenchymal stem cells (MSCs) which have been proven to have therapeutic potential and be helpful in the treatment of various diseases, but the mechanisms underlying the function of MSCs against phosgene-induced ALI are still poorly explored. In this study, we compared the expression profiles of mRNAs, lncRNAs, and circRNAs in the lung tissues from rats of three groups-air control (group A), phosgene-exposed (group B), and phosgene + MSCs (group C). The results showed that 389 mRNAs, 198 lncRNAs, and 56 circRNAs were differently expressed between groups A and B; 130 mRNAs, 107 lncRNAs, and 35 circRNAs between groups A and C; and 41 mRNAs, 88 lncRNAs, and 18 circRNAs between groups B and C. GO and KEGG analyses indicated that the differentially expressed RNAs were mainly involved in signal transduction, immune system processes, and cancers. In addition, we used a database to predict target microRNAs (miRNAs) interacting with circRNAs and the R network software package to construct a circRNA-targeted miRNA gene network map. Our study showed new insights into changes in the RNA expression in ALI, contributing to explore the mechanisms underlying the therapeutic potential of MSCs in phosgene-induced ALI.

Primary graft dysfunction (PGD) and ischemia-reperfusion injury (IRI) occur in up to 30% of patients undergoing lung transplantation and may impact on the clinical outcome. Several strategies for the prevention and treatment of PGD have been proposed, but with limited use in clinical practice. In this study, we investigate the potential application of sevoflurane (SEV) preconditioning to mitigate IRI after lung transplantation. The study included two groups of swines (preconditioned and not preconditioned with SEV) undergoing left lung transplantation after 24-hour of cold ischemia. Recipients' data was collected for 6 hours after reperfusion. Outcome analysis included assessment of ventilatory, hemodynamic, and hemogasanalytic parameters, evaluation of cellularity and cytokines in BAL samples, and histological analysis of tissue samples. Hemogasanalytic, hemodynamic, and respiratory parameters were significantly favorable, and the histological score showed less inflammatory and fibrotic injury in animals receiving SEV treatment. BAL cellular and cytokine profiling showed an anti-inflammatory pattern in animals receiving SEV compared to controls. In a swine model of lung transplantation after prolonged cold ischemia, SEV showed to mitigate the adverse effects of ischemia/reperfusion and to improve animal survival. Given the low cost and easy applicability, the administration of SEV in lung donors may be more extensively explored in clinical practice.

DESIGN: A systematic document retrieval of studies published in the past 10 years reporting periprocedural stroke/mortality/MI after carotid endarterectomy (CEA) related to the time between CEA and qualifying neurological symptoms. The application database has "PubMed, EMbase and Cochrane databases." RevMan5.3 software provided by the Cochrane collaboration was used for meta-analysis. RESULTS: A systematic literature search was conducted in databases. A total of 10 articles were included in this study. They were divided into early CEA and delayed CEA with operation within 48 h, 1 w, or 2 w after onset of neurological symptoms. Incidence of the postoperative stroke in patients undergoing delayed CEA (≥48 h) was significantly higher than patients with delayed CEA (<48 h) (OR = 2.14, 95% CI: 1.43-3.21, P = 0.0002). The postoperative mortality of patients after delayed CEA (≥48 h) was significantly higher than patients after early CEA (<48 h) (OR = 1.35, 95% CI: 1.06-1.71, P = 0.02). The risk of postoperative mortality of patients treated with delayed CEA (≥7 d) was significantly higher than patients after the early CEA group (<7 d) (OR = 1.69, 95% CI: 1.21-2.32, P = 0.001). CONCLUSION: Early CEA is safe and effective for a part of patients with symptomatic carotid stenosis, but a comprehensive preoperative evaluation of patients with carotid stenosis must be performed.

OBJECTIVES: This study is aimed at investigating the root and root canal morphology by cone beam computed tomography (CBCT) and palatal furcation groove of the buccal root by microcomputed tomography (micro-CT) of maxillary first premolars in a Chinese subpopulation. METHODS: This study assessed CBCT images of 440 patients aged 14-80 years. Based on Vertucci's classification, the number of roots and the canal configuration were determined. Forty-eight maxillary first premolars with furcation grooves were analyzed by micro-CT in patients aged 18-25 years. RESULTS: Based on the CBCT assay, 70.22% and 29.32% of maxillary first premolars were 1 root and 2 roots, respectively. The configuration indicated statistical difference (P < 0.05) between male and female patients. The most common canal type was type IV and was found in 44.32% of cases, followed by type I in 27.84%, and then type II in 20.57%. Root bifurcations had 40.13% prevalence which was distributed more in the middle third than in the cervical and the apical third. For the micro-CT study, 95.83% of the furcation groove configuration was found in the bifurcated maxillary first premolars. The length varied from 1.02 to 7.63 mm. The mean depth of this groove was 0.57 mm in the root coronal, 0.47 mm in the root middle, and 0.22 mm in the root apical level. Palatal dentin width was smaller than 1 mm. CONCLUSION: The anatomy of the root and root canal system and the irregular wall width of maxillary first premolars with furcation grooves may help dentists to understand the anatomical morphology and improve the outcomes of endodontic treatment.

Prostate cancer is a life-threatening and highly heterogeneous malignancy. In the past decade, circulating tumor cells (CTCs) have been suggested to play a critical role in the occurrence and progression of prostate cancer. In particular, as the "seed" of the cancer metastasis cascade, CTCs determine numerous biological behaviors, such as tumor invasion into adjacent tissues and migration to distant organs. Many studies have shown that CTCs are necessary in the processes of tumor progression, including tumorigenesis, invasion, metastasis, and colonization. Furthermore, CTCs express various biomarkers relevant to prostate cancer and thus can be applied clinically in noninvasive tests. Moreover, CTCs can serve as potential prognostic targets in prostate cancer due to their roles in regulating many processes associated with cancer metastasis. In this review, we discuss the isolation and detection of CTCs as predictive markers of prostate cancer, and we discuss their clinical application in the diagnosis and prognosis of prostate cancer and in monitoring the response to treatment and the prediction of metastasis.

Alendronate (Aln) has been the first-line drug for osteogenesis imperfecta (OI), while the comparable efficacy of Aln and strontium ranelate (SrR) remains unclear. This study is aimed at comparing the effects of SrR and Aln treatment in a mouse model of OI. Three-week-old oim/oim and wt/wt female mice were treated with SrR (1800 mg/kg/day), Aln (0.21 mg/kg/week), or vehicle (Veh) for 11 weeks. After the treatment, the average number of fractures sustained per mouse was significantly reduced in both SrR- and Aln-treated oim/oim mice. The effect was comparable between these two agents. Both SrR and Aln significantly increased trabecular bone mineral density, bone histomorphometric parameters (bone volume, trabecular number, and cortical thickness and area), and biomechanical parameters (maximum load and stiffness) as compared with the Veh group. Both treatments reduced bone resorption parameters, with Aln demonstrating a stronger inhibitory effect than SrR. In contrast to its inhibitory effect on bone resorption, SrR maintained bone formation. Aln, however, also suppressed bone formation coupled with an inhibitory effect on bone resorption. The results of this study indicate that SrR has comparable effects with Aln on reducing fractures and improving bone mass and strength. In clinical practice, SrR may be considered an option for patients with OI when other medications are not suitable or have evident contraindications.

Musculoskeletal disorders may affect labor efficiency, cause disability, impair one's work ability, and lower one's quality of life. This consequently leads to a larger expenditure of medical resources. We aimed to design easy-to-open assistive devices for pneumatic tube systems to improve ergonomics and reduce musculoskeletal complaints of workers. We followed a design control process, including designs of motors, gears, sensors, and V-shaped connecting rods. Efficacy was evaluated by examining risks based on job strain index, user satisfaction, and musculoskeletal complaints of operators before and after the system's implementation on a Nordic musculoskeletal questionnaire. We designed three assistive devices: two semiautomatic and one automatic. Each semiautomatic device costs about 300 US dollars and required space of 10 × 18 × 38 cm3. The automatic device costs about 3000 US dollars and required space of 28 × 38 × 50 cm3. The job strain index score decreased from 36 (very high risk) to 3 (low risk) with the semiautomatic devices and to 0 with the automatic device. Musculoskeletal complaints in the neck and upper limbs were reduced, with a significantly higher satisfaction rate for female operators. Our novel design of an automatic cap opening device for a pneumatic tube system was effective in improving ergonomics and reducing musculoskeletal complaints.

Biocontrol by inoculation with beneficial microbes is a proven strategy for reducing the negative effect of soil-borne pathogens. We evaluated the effects of microbial inoculants BIO-1 and BIO-2 in reducing soil-borne wheat diseases and in influencing wheat rhizosphere microbial community composition in a plot test. The experimental design consisted of three treatments: (1) Fusarium graminearum F0609 (CK), (2) F. graminearum + BIO-1 (T1), and (3) F. graminearum F0609 + BIO-2 (T2). The results of the wheat disease investigation showed that the relative efficacies of BIO-1 and BIO-2 were up to 82.5% and 83.9%, respectively. Illumina MiSeq sequencing revealed that bacterial abundance and diversity were significantly higher (P < 0.05) in the treatment groups (T1 and T2) than in the control, with significantly decreased fungal diversity in the T2 group. Principal coordinates and hierarchical clustering analyses revealed that the bacterial and fungal communities were distinctly separated between the treatment and control groups. Bacterial community composition analysis demonstrated that beneficial microbes, such as Sphingomonas, Bacillus, Nocardioides, Rhizobium, Streptomyces, Pseudomonas, and Microbacterium, were more abundant in the treatment groups than in the control group. Fungal community composition analysis revealed that the relative abundance of the phytopathogenic fungi Fusarium and Gibberella decreased and that the well-known beneficial fungi Chaetomium, Penicillium, and Humicola were more abundant in the treatment groups than in the control group. Overall, these results confirm that beneficial microbes accumulate more easily in the wheat rhizosphere following application of BIO-1 and BIO-2 and that the relative abundance of phytopathogenic fungi decreased compared with that in the control group.

Acute kidney injury (AKI) is a disease that seriously endangers human health. At present, AKI lacks effective treatment methods, so it is particularly important to find effective treatment measures and targets. Bioinformatics analysis has become an important method to identify significant processes of disease occurrence and development. In this study, we analyzed the public expression profile with bioinformatics analysis to identify differentially expressed genes (DEGs) in two types of common AKI models (ischemia-reperfusion injury and cisplatin). DEGs were predicted in four commonly used microRNA databases, and it was found that miR-466 and miR-709 may play important roles in AKI. Then, we found key nodes through protein-protein interaction (PPI) network analysis and subnetwork analysis. Finally, by detecting the expression levels in the renal tissues of the two established AKI models, we found that Myc, Mcm5, E2f1, Oip5, Mdm2, E2f8, miR-466, and miR-709 may be important genes and miRNAs in the process of AKI damage repair. The findings of our study reveal some candidate genes, miRNAs, and pathways potentially involved in the molecular mechanisms of AKI. These data improve the current understanding of AKI and provide new insight for AKI research and treatment.

PURPOSE: The purpose of this study was to determine the incidence, risk factors, and impact of delirium on outcomes in ICU patients. In addition, the scoring systems were measured consecutively to characterize how these scores changed with time in patients with and without delirium. Material and Methods. A prospective cohort study enrolling 400 consecutive patients admitted to the ICU between 2018 and 2019 due to trauma or surgery. Patients were followed up for the development of delirium over ICU days using the Confusion Assessment Method (CAM) for the ICU and Intensive Care Delirium Screening Checklist (ICDSC). Cox model logistic regression analysis was used to explore delirium risk factors. RESULTS: Delirium occurred in 108 (27%) patients during their ICU stay, and the median onset of delirium was 4 (IQR 3-4) days after admission. According to multivariate cox regression, the expected hazard for delirium was 1.523 times higher in patients who used mechanical ventilator as compared to those who did not (HR: 1.523, 95% CI: 1.197-2.388, P < 0.001). CONCLUSION: Our findings suggest that an important opportunity for improving the care of critically ill patients may be the determination of modifiable risk factors for delirium in the ICU. In addition, the scoring systems (APACHE IV, SOFA, and RASS) are useful for the prediction of delirium in critically ill patients.

The relationship between depression, antidepressant medications (ADMs), and the risk of subsequent type 2 diabetes mellitus (T2DM) development remains controversial. Thus, we investigated this aspect by a population-based retrospective cohort study using the Longitudinal Health Insurance Database 2000 available in Taiwan. This large, observational study included 46,201 patients with depression and a 1 : 1 age- and sex-matched nondepression cohort enrolled between January 1, 2000, and December 31, 2013, and the newly diagnosed T2DM incidence rates were determined. We estimated the effects of depression on T2DM and the cumulative incidence curves by Cox proportional regression hazard models and Kaplan-Meier methods, respectively. We found that 47.97% of the patients with depression did not receive ADM. Among patients with depression who received ADM, 29.71%, 6.29%, 0.05%, 9.65%, and 6.32% received selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), heterocyclic antidepressants, and other medications, respectively. Patients without ADM treatment had a 39% higher risk of developing T2DM. However, those who received ADM treatment had a significantly lower risk of T2DM development in every treatment category. Depressive disorder treated with ADMs, especially with long-term use, was associated with an 11-48% decrease in the risk of T2DM in all ADM groups; however, heterocyclic antidepressant treatment for shorter periods (<80 days) was not significantly associated with a decreased risk of T2DM. The incidence of T2DM in Taiwan was found to be associated with an a priori history of depression and was inversely correlated with ADM treatment.

METHODS: Colitis was induced in mice using 2,4,6-trinitrobenzene-sulfonic acid (TNBS), and mice were subsequently treated with either a PD-1 inhibitor or 5-amino-salicylic acid (ASA) as a positive control. Body weight, disease activity index (DAI), colon length, and tissue damage were evaluated, and the enteric microbiota was profiled using high-throughput 16S rRNA sequencing of fecal samples from the experimental mice. RESULTS: TNBS caused mice to experience IBD-like symptoms, which were attenuated by the PD-1 inhibitor, as indicated by a decrease in DAI scores (p = 0.0002). Furthermore, in this mouse model of IBD, PD-1 inhibition improved the alpha diversity as well as restored the beta diversity of the enteric microbiome. It also significantly enriched the abundance of short-chain fatty acid- (SCFA-) producing bacteria of the Firmicutes (p < 0.05) and Bacteroidetes (p < 0.05) phyla but depopulated Proteobacteria (p < 0.05). CONCLUSION: PD-1 inhibition can partly mitigate TNBS-induced colitis and restore the enteric microbiota by enriching the abundance of SCFA-producing bacteria.

PURPOSE: To investigate whether the radiomics analysis of MR imaging in the hepatobiliary phase (HBP) can be used to predict microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). METHOD: A total of 130 patients with HCC, including 80 MVI-positive patients and 50 MVI-negative patients, who underwent MR imaging with Gd-EOB-DTPA were enrolled. Least absolute shrinkage and selection operator (LASSO) regression was applied to select radiomics parameters derived from MR images obtained in the HBP 5 min, 10 min, and 15 min images. The selected features at each phase were adopted into support vector machine (SVM) classifiers to establish models. Multiple comparisons of the AUCs at each phase were performed by the Delong test. The decision curve analysis (DCA) was used to analyze the classification of MVI-positive and MVI-negative patients. RESULTS: The most predictive features between MVI-positive and MVI-negative patients included 9, 8, and 14 radiomics parameters on HBP 5 min, 10 min, and 15 min images, respectively. A model incorporating the selected features produced an AUC of 0.685, 0.718, and 0.795 on HBP 5 min, 10 min, and 15 min images, respectively. The predictive model for HBP 5 min, 10 min and 15 min showed no significant difference by the Delong test. DCA indicated that the predictive model for HBP 15 min outperformed the models for HBP 5 min and 10 min. CONCLUSIONS: Radiomics parameters in the HBP can be used to predict MVI, with the HBP 15 min model having the best differential diagnosis ability.

OBJECTIVE: The publications of application and development of shock wave therapy showed consistent growth. The aim of this study was to investigate the global status and trends in the shock wave therapy field. METHODS: Publications about shock wave therapy from 1990 to 2019 were collected from the Web of Science database. The data were studied and indexed by using bibliometric methodology. For a visualized study, VOSviewer software was used to conduct bibliographic coupling analysis, coauthorship analysis, cocitation analysis, and co-occurrence analysis and to analyze the publication trends in shock wave therapy. RESULTS: A total of 3,274 articles were included. The number of publications was increasing per year globally. The USA made the largest contributions to the global research with the most citations (the highest h-index). The Journal of Urology had the highest publication number. The University of California System was the most contributive institution. Studies could be divided into seven clusters: urology, hepatology, cardiology, orthopedics, mechanism research of shock wave therapy, andrology, and principle of shock wave therapy. Orthopedics, andrology, and mechanism research of shock wave therapy could be the next hot topics in this field. CONCLUSIONS: Base on the trends, shock wave therapy is the theme of a globally active research field which keeps developing and extends from bench to bedside.

Gastric cancer (GC) is the second leading cause of cancer mortality and the fourth most commonly diagnosed malignant disease, with approximately 951,000 new cases diagnosed and approximately 723,000 cases of mortality each year. The highest mortality rate of GC is in East Asia, and the lowest is in North America. A large number of studies have demonstrated that GC patients are characterized by higher morbidity, metastasis rates, and mortality and lower early diagnosis rates, radical resection rates, and 5-year survival rates. All cases of GC can be divided into two important stages, namely, early- and advanced-stage GC, and the stage mainly determines the treatment strategy for and the therapeutic effect in GC patients. Patients with early-stage GC undergo radical surgery followed by chemotherapy, and the 5-year survival rate can be as high as 90%. However, patients with advanced-stage GC cannot undergo radical surgery because they are at risk for metastasis; therefore, they can choose only radiotherapy or chemotherapy and have a poor prognosis. Based on the lack of specific clinical manifestations and detection methods, most GC patients (>70%) are diagnosed in the advanced stage; therefore, continued efforts toward developing treatments have been focused on advanced-stage GC patients and include molecular targeted therapy, immunotherapy, and small molecular therapy. Nevertheless, in recent years, accumulating evidence has indicated that small molecules, especially long noncoding RNAs (lncRNAs), are involved in the occurrence, development, and progression of GC, and their abundantly dysregulated expression has been identified in GC tissues and cell lines. Therefore, lncRNAs are considered easily detectable molecules and ideal biomarkers or target-specific agents for the future diagnosis or treatment of GC. In this review, we primarily discuss the status of GC, the role of lncRNAs in GC, and the emerging systemic treatments for GC.

Otitis media (OM) is a common inflammatory disease of the middle ear cavity and mainly occurs in children. As a critical regulator of inflammation response, the nuclear factor kappa B (NF-κB) pathway has been found to play an essential role in the pathogenesis of various human diseases. The aim of this study was to explore the potential mechanism under the inflammatory response of human middle ear epithelial cells (HMEECs). We established in vitro models of OM by treating HMEECs with lipopolysaccharide (LPS) or interleukin 17A (IL-17A). Enzyme-linked immunosorbent assay and western blot analysis were used to measure the inflammatory response of HMEECs under LPS or IL-17A stimulation. The results revealed that the concentrations of proinflammatory cytokines (p < 0.001) and protein levels of mucin (MUC) (for MUC5AC, p = 0.002, p = 0.004; for MUC8, p = 0.004, p < 0.001) were significantly elevated by LPS or IL-17A stimulation in HMEECs. Moreover, we found that LPS or IL-17A treatment promoted the phosphorylation of IκBα (for p-IκBα, p = 0.018, p = 0.002; for IκBα, p = 0.238, p = 0.057) and the translocation of p65 from cytoplasm to nucleus in HMEECs (for nucleus p65, p = 0.01; for cytoplasm p65, p < 0.001). In addition, RT-qPCR analysis revealed that long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was verified to be upregulated in LPS- or IL-17A-stimulated HMEECs (p < 0.001). Western blot analysis and immunofluorescence staining assay revealed that that MALAT1 knockdown significantly suppressed the activation of the NF-κB pathway by reducing phosphorylated IκBα levels and inhibiting the nuclear translocation of p65 (p < 0.001) in LPS- or IL-17A-stimulated HMEECs (for p-IκBα, p < 0.001; for IκBα, p = 0.242, p = 0.647). Silence of MALAT1 decreased the proinflammatory cytokine production and MUC protein levels (p < 0.001). Furthermore, rescue assays revealed that the increase of proinflammatory cytokine production (for TNF-α, p = 0.002, p = 0.015; for IL-1β, p < 0.001, p = 0.006; for IL-6, p = 0.002, p < 0.001) and MUC protein levels (for MUC5AC, p = 0.001, p < 0.001; for MUC8, p < 0.001, p = 0.001) induced by MALAT1 overexpression was neutralized by 4-N-[2-(4-phenoxyphenyl) ethyl] quinazoline-4, 6-diamine (QNZ) treatment in LPS- or IL-17A-stimulated HMEECs. In conclusion, MALAT1 promotes inflammatory response in LPS- or IL-17A- stimulated HMEECs via the NF-κB signaling pathway, which may provide a potential novel insight for the treatment of OM.

The present investigation is aimed at systematically analyzing the recent literature about the innovative scaffold involved in the reconstructive surgeries by applying growth factors and tissue engineering. An extensive review of the contemporary literature was conducted according to the PRISMA guidelines by accessing the PubMed, Embase, and Scopus Elsevier databases. Authors performed the English language manuscript research published from 2003 to 2020. A total of 13 relevant studies were included in the present review. The present systematic review included only papers with significant results about correlation between scaffold, molecular features of growth factor, and reconstructive surgeries in oral maxillofacial district. The initial research with filters recorded about 1023 published papers. Beyond reading and considering of suitability, only 42 and then 36 full-text papers were recorded for the revision. All the researches recorded the possibility of using growth factors on rebuilding atrophic jaws. Different growth factors like morphogenetic factors, cytokines, and inflammatory ones and their application over different scaffold materials were recorded. Further investigations should be required in order to state scientific evidence about a clear advantage of applying tissue engineering for therapeutic purpose.

Inflammation is an important biological process for eliciting immune responses against physiological and pathological stimuli. Inflammation must be efficiently regulated to ensure homeostasis in the body. Nuclear factor-kappa B (NF-κB) signaling is crucial for inflammatory and immune responses. Aberrant activation of NF-κB signaling leads to development of numerous human diseases. In this study, we investigated the function of chromosome 7 open reading frame 41 (C7ORF41) in NF-κB signaling during inflammation. C7ORF41 was upregulated in cells stimulated with tumor necrosis factor-alpha or lipopolysaccharide. Moreover, overexpression of C7ORF41 inhibited the activation of NF-κB and decreased the expression of its downstream target genes. Notably, small hairpin RNA-mediated depletion of C7ORF41 increased the levels of downstream genes and enabled the activation of NF-κB. In conclusion, C7ORF41 negatively regulated inflammation via NF-κB signaling and p65 phosphorylation in vitro. These findings may help to diagnose and prognosticate inflammatory conditions and may help develop new strategies for the management of inflammation-related diseases.

OBJECTIVE: SPHK1 and HAS2 have been reported to play important roles in tumorigenesis and development. However, their expression and prognostic value in pancreatic cancer (PC) remain unclear. This study is aimed at investigating the expression of SPHK1 and HAS2 on the prognosis of pancreatic cancer. MATERIALS AND METHODS: The expression of SPHK1 and HAS2 in pancreatic cancer tissues was analyzed through TCGA and GTEx databases and validated by qRT-PCR and Western blot in pancreatic cancer cell lines. χ 2 test was used to explore the correlation of the SPHK1 and HAS2 expressions with clinical characteristics. Kaplan-Meier survival analysis and ROC curve were used to evaluate the prognostic and diagnostic roles of SPHK1 and HAS2 in pancreatic cancer. Additionally, Spearman correlation analysis was applied to assess the correlation between the SPHK1 and HAS2 in pancreatic cancer. GO analysis and KEGG analysis were applied to explore the possible signaling pathway that SPHK1 and HAS2 coregulated genes mediated. RESULTS: The expression of SPHK1 and HAS2 was markedly upregulated in pancreatic cancer tissue and cell lines, respectively. Furthermore, there was a significant positive correlation between SPHK1 and HAS2 expressions. ROC curves showed that SPHK1 combine with HAS2 has good diagnostic value in pancreatic cancer patients with 85% sensitivity and 99.4% specificity. Kaplan-Meier analysis showed that increased expression of SPHK1 and HAS2 was significantly associated with short overall survival (OS) of pancreatic cancer patients. GO and KEGG results revealed that SPHK1 and HAS2 mainly involved cell proliferation and invasion mediated by extracellular matrix- (ECM-) receptor interaction, focal adhesion, and PI3K-AKT signaling pathways. CONCLUSIONS: Overexpression of SPHK1 and HAS2 could be important markers for the prognosis of pancreatic cancer.

Diabetes-related macrovascular and microvascular complications lead to poor prognosis. Insulin receptor substrate p53 (IRSp53) is known to act as a substrate for the insulin receptor tyrosine kinase, but its role in endothelial dysfunction remains unclear. Human umbilical vein endothelial cells (HUVECs) treated with D-glucose at different concentrations and a streptozocin-induced rat diabetes mellitus (DM) model were used to investigate the effects of hyperglycemia on the expression levels of IRSp53 and galectin-3 (gal-3) and the inflammatory state and mobility of HUVECs. Thereafter, IRSp53-overexpressing HUVECs and IRSp53-knockdown HUVECs were established using IRSp53-overexpressing lentivirus or IRSp53-siRNA to explore the role of IRSp53 in the HUVEC inflammatory state and HUVEC mobility. D-glucose at high concentration (HG) and hyperglycemia were found to induce downregulation of IRSp53 and upregulation of gal-3 in vitro and in vivo. Treatment with HG resulted in activation of NF-κB in HUVECs and impaired HUVEC mobility. Insulin restored HG-induced changes in the expression levels of IRSp53 and gal-3 in HUVECs and protected the cells from NF-κB activation and impaired mobility. Overexpression of IRSp53 inhibited the activation of NF-κB in HUVECs and strengthened HUVEC migration. Knockdown of IRSp53 facilitated the activation of NF-κB in HUVECs and decreased HUVEC migration. However, neither overexpression nor knockdown of IRSp53 altered the effects of insulin on HG-induced detrimental changes in HUVECs. HG and hyperglycemia resulted in downregulation of IRSp53 in vitro and in vivo. IRSp53 is concluded to inhibit the activation of NF-κB in HUVECs and to strengthen HUVEC migration.

Lung injury was the common and serious complication of sepsis, a systemic inflammatory response syndrome caused by severe infections. Chinese medicine had unique advantages in attenuating inflammatory response, such as Zuojinfang (ZJF). ZJF was a classical compound herb formula composed of Coptidis Rhizoma and Euodiae Fructus in a ratio of 6 : 1. In this paper, 15 ingredients in ZJF were identified and 8 of them absorbed into rat's serum were quantified by HPLC-MS/MS. Subsequently, sepsis-induced lung injury model was replicated in rats by cecal ligation and puncture. 60 SD rats were randomly divided into 6 groups (n = 10): control group (CON), sham group (Sham), model group (MOD), ZJF low-dose group (ZJF-L), ZJF high-dose group (ZJF-H), and prednisolone group (PNSL). Within the next 24 h, the levels of inflammatory factors, correlation between active ingredients and inflammatory cytokines, the pathological changes of lung tissue, and protein expression of the JAK1/STAT3 signaling pathways were analyzed one by one. Finally, the concentration order of components absorbed in rat serum was berberine > palmatine > jatrorrhizine > coptisine > evodin > chlorogenic acid > evodiamine. Compared with the MOD group, the TNF-α, IL-6, and IFN-γ in the ZJF-H group were significantly reduced (p < 0.05). Moreover, the TNF-α decreased significantly accompanied by the increase of berberine, chlorogenic acid, jatrorrhizine, palmatine, evodin, and evodiamine in serum (negative correlation, p < 0.05). Compared with the MOD, the area of lung injury, the expressions of JAK1, p-JAK1, STAT3, and p-STAT3 were significantly decreased under the treatment of ZJF (p < 0.05). Therefore, downregulating the JAK1/STAT3 signaling pathways was a potential avenue of ZJF in reversing lung injury induced by sepsis.

Parkinson's disease (PD) is an incurable progressive disorder resulting from neurodegeneration, and apoptosis is considered a dominant mechanism underlying the process of neurodegeneration. MicroRNAs (miRNAs), which are small and noncoding RNAs involved in many a biological process like apoptosis and regulation of gene expressions, have been found in postmortem brain samples of patients with PD, as well as in vitro and in vivo models of PD. To explore the impact of miR-15b-5p and Akt3 on apoptosis in the progression of PD, the method of quantitative reverse transcription polymerase chain reaction (qRT-PCR) was employed, and the analysis result showed upregulated expression of miR-15b-5p and downregulated expression of Akt3 in the serum of PD patients, MPP+-induced SH-SY5Y cells, and the brain tissues of MPTP-induced mice. Meanwhile, the dual-luciferase reporter assay was used to demonstrate the regulator-target interaction between miR-15b-5p and Akt3; flow cytometry and spectrophotometry revealed that transfection of miR-15b-5p mimic and si-Akt3 increased the rate of apoptosis and caspase-3 activity, whereas transfecting the miR-15b-5p inhibitor and Akt3-overexpression plasmid repressed the rate of apoptosis and caspase-3 activity in the MPP+-induced SH-SY5Y cell model and the MPTP-induced mouse model. Additionally, analysis of western blotting (WB) assays in vivo and in vitro revealed that proapoptosis proteins (Bax, caspase-3, GSK-3β, and β-catenin) showed markedly upregulated expression in the miR-15b-5p inhibitor and si-Akt3-overexpression groups, while the expression of an antiapoptosis gene (i.e., Bcl2) was downregulated. These analysis results indicate that downregulation of miR-15b-5p by targeting the Akt3-mediated GSK-3β/β-catenin signaling pathway would repress cell apoptosis in PD in vivo and in vitro. It is expected that the research findings would help find new therapeutic targets for treatment of PD.

Minimal change disease (MCD) is the most common cause of idiopathic nephrotic syndrome in children, and it is well known for its multifactorial causes which are the manifestation of the disease. Proteinuria is an early consequence of podocyte injury and a typical sign of kidney disease. Steroid-sensitive patients react well with glucocorticoids, but there is a high chance of multiple relapses. CD80, also known as B7-1, is generally expressed on antigen-presenting cells (APCs) in steroid-sensitive MCD patients. Various glomerular disease models associated with proteinuria demonstrated that the detection of CD80 with the increase of urinary CD80 was strongly associated closely with frequent-relapse MCD patients. The role of CD80 in MCD became controversial because one contradicts finding. This review covers the treatment alternatives for MCD with the insight of CD80 as a potential therapeutic target. The promising effectiveness of CD20 (rituximab) antibody and CD80 inhibitor (abatacept) encourages further investigation of CD80 as a therapeutic target in frequent-relapse MCD patients. Therapeutic-based antibody towards CD80 (galiximab) had never been investigated in MCD or any kidney-related disease; hence, the role of CD80 is still undetermined. A new therapeutic approach towards MCD is essential to provide broader effective treatment options besides the general immunosuppressive agents with gruesome adverse effects.

OBJECTIVE: To explore the optimal b value setting for diffusion tensor imaging of rats' spinal cord at ultrahigh field strength (7 T). METHODS: Spinal cord diffusion tensor imaging data were collected from 14 rats (5 healthy, 9 spinal cord injured) with a series of b values (200, 300, 400, 500, 600, 700, 800, 900, and 1000 s/mm2) under the condition that other scanning parameters were consistent. The image quality (including image signal-to-noise ratio and image distortion degree) and data quality (i.e., the stability and consistency of the DTI-derived parameters, referred to as data stability and data consistency) were quantitatively evaluated. The min-max normalization method was used to process the calculation results of the four indicators. Finally, the image and data quality under each b value were synthesized to determine the optimal b value. RESULTS: b = 200 s/mm2 and b = 900 s/mm2 ranked in the top two of the comprehensive evaluation, with the best image quality at b = 200 s/mm2 and the best data quality at b = 900 s/mm2. CONCLUSION: Considering the shortcomings of the ability of low b values to reflect the microstructure, b = 900 s/mm2 can be used as the optimal b value for 7 T spinal cord diffusion tensor scanning.

Natural killer T (NKT) cells are a key component of innate immunity. Importantly, a growing body of evidence indicates that NKT cells play an integral role in various acute and chronic liver injuries. NKT cells participate in the progression of an injury through the secretion of cytokines, which promote neutrophil infiltration and enhance Fas ligand (FasL) and granzyme-mediated NKT cytotoxic activity. Therefore, examining the role of NKT cells in hepatic disease is critical for a comprehensive understanding of disease pathogenesis and may provide insight into novel approaches for treatment. For more than a century, mouse models that imitate the physiopathological conditions of human disease have served as a critical tool in biological and medical basic research, including studies of liver disease. Here, we review the role of NKT cells in various mouse models of hepatitis.

Hepatocellular carcinoma (HCC) ranks fifth among common cancers and is the second most common cause of cancer-related mortality worldwide. This study is aimed at identifying an immune-related long noncoding RNA (lncRNA) signature as a potential biomarker with prognostic value to improve early diagnosis and provide potential therapeutic targets for HCC patients. The subjects of this study were HCC samples with complete transcriptome data and clinical information downloaded from The Cancer Genome Atlas (TCGA) database. We then extracted the immune-related mRNA and lncRNA expression profiles. Based on the expression profiles of immune-related lncRNAs, we identified a nine-lncRNA signature that was related to the progression of HCC. The risk score was calculated based on the expression level of the nine lncRNAs of each sample, which divided patients into high-risk and low-risk groups. We found that the increased risk score was associated with a poor prognosis of HCC patients. To assess the accuracy of the survival model, we calculated a receiver operating characteristic (ROC) for validation. The curve showed that the area under the curve (AUC) for the risk score was 0.792. Besides, both principal component analysis (PCA) and gene set enrichment analysis (GSEA) were further used for functional annotation. We found that the distribution patterns were different between the low-risk and high-risk groups in PCA, and the underlying mechanism by which the nine lncRNAs promoted the progression of HCC involved an abnormal immune status. Finally, we analyzed the infiltration of twenty-nine kinds of immune cells and the activation of immune function in HCC using the ssGSEA algorithm. The results showed that aDCs, iDCs, macrophages, Tfh, Th1, Treg, and NK cells were correlated with the progress of HCC patients. And the immune functions including APC costimulation, CCR, check point, HLA, MHC class I, and Type II IFN responses were also significantly different between the high-risk and low-risk groups. In conclusion, our study identified a nine-lncRNA signature with potential prognostic value for patients with HCC, which could be used as a new biomarker for the diagnosis and immunotherapy of HCC.

Both the management and caregiving intervention of people living with HIV (PLWH), especially during acute HIV-1 infection, represent a public health issue and a form of social support. This current study analyzed the demographic and clinical factors associated with antiretroviral therapy (ART) adherence of PLWH from positive HIV diagnosis to ART initiation in a tertiary Chinese hospital in Beijing. A total of 200 participants diagnosed with acute HIV-1 infection were enrolled in this study. We collected demographic and clinical data by the use of a self-reported questionnaire. Bivariate and multivariate logistic regressions were used to determine associations between potential variables and outcomes. We found that medication adherence was impacted by years of ART and number of reminders (all P < 0.05). In addition, medication adherence was associated with viral load at 48 weeks (P = 0.035). Future studies are needed to investigate effective interventions that could facilitate ART adherence.

The purpose of this clinical research was to evaluate peri-implant marginal changes around immediate implants placed either with the application of SCTG or XCM or without soft tissue grafting. A total of 48 patients requiring a single implant-supported restoration in the anterior jaw were selected for inclusion. Three surgical procedures were performed, as follows: type 1 implant with subepithelial connective tissue graft (SCTG), type 1 implant with xenogenic collagen matrix (XCM), and type 1 implant without soft tissue augmentation (NG) (control group). The marginal change of peri-implant soft tissue, facial soft tissue thickness (FSTT), peri-implant health status, esthetics, and patient satisfaction were assessed at one year after surgery. All of the placed implants showed a survival rate of 100%. No significant differences in FSTT were recorded between the SCTG group and the XCM group after treatment (P > 0.05), while the NG group presented a significant difference (P < 0.05). Patients in the NG group lost significantly more in the buccal marginal level than did patients in the SCTG group and those in the XCM group (P < 0.05). The favourable success rate recorded in all groups confirmed immediate tooth replacement as a choice of treatment for a missing anterior single tooth. The NG group presented significant changes of FSTT and buccal marginal level, while XCM constituted a viable alternative to SCTG.

Neonatal respiratory distress syndrome (NRDS) is a common disease that occurs in premature infants. However, the mechanisms underlying the disease remain unclear. microRNAs (miRNAs) have been indicated to play a crucial role in the development of NRDS. In this study, we aimed to explore the regulatory mechanisms of miR-296-5p in NRDS. The expression levels of miR-296-5p in preterm infants with NRDS were determined using quantitative reverse-transcription polymerase chain reaction (RT-qPCR). A549 cells were transfected with lentiviral vectors encoding miR-296-5p, and the transfection efficiency was determined using RT-qPCR. Flow cytometry and CCK8 assay were performed to measure apoptosis and proliferation of A549 cells, respectively. The protein levels of pulmonary surfactant SP-A (SFTPA1), SP-B, Wnt7b, and β-catenin were measured using western blotting. We demonstrated an upregulation of miR-296-5p in NRDS. The miR-296-5p was successfully overexpressed in A549 cells via lentivirus transfection, and the upregulation of miR-296-5p inhibited cell proliferation and secretion of SP-A and SP-B and also induced downregulation of the Wnt7b/β-catenin in vitro. Therefore, miR-296-5p inhibits cell proliferation and secretion of pulmonary surfactants in A549 cells via downregulation of Wnt7b/β-catenin signaling.

BACKGROUND: As the second most common gynecologic cancer worldwide, cervical cancer has led to morbidity and mortality in thousands of women. Our study is aimed at comparing the long-term trends of mortality rates for cervical cancer in three high-income countries-Canada, Korea, and Italy-and analyzing the detached effects of chronological age, time period, and birth cohort by age-period-cohort (APC) analysis. METHODS: Joinpoint regression was used in this study, and the age-period-cohort model combined with the intrinsic estimator method was also applied to estimate the detached effect of each age, time period, and birth cohort on cervical cancer mortality. RESULTS: For the overall trends of ASMRs for cervical cancer, the rates for Canada and Italy generally decreased during the whole observation periods while the rate for Korea exhibited a significant increase from 1986 to 2003. The APC analysis suggested that the cancer mortality risks consistently increased with age in the age groups including women aged 20 to 50 years in all areas. The period effect exhibited a general upward trend for both Korea and Italy, while a decreased trend was observed for Canada during the whole observation period. The mortality risk generally decreased with birth cohort, except there was a slight increase for younger generations in the three countries. CONCLUSIONS: Our study shows that the overall decrease in the cohort effect may have contributed to the reduced mortality rate for Italy and Canada, and the increased period effects and cohort effect in younger generations may have led to the increase in cancer mortality rate for Korea.

The study is aimed at investigating the role and mechanism of LpqH of Mycobacterium tuberculosis in the activation of NLRP3 inflammasome in mouse Ana-1 macrophages. ExPASy-ProtParam, PHYRE2, ABCpred, and SYFPEITHI were used to predict and analyze the physicochemical properties, protein structure, and B cell/T cell-associated epitopes of LpqH protein. The recombinant LpqH protein was purified, and its immunoreactivity was analyzed with western blot. The LPS-treated mouse Ana-1 macrophages were incubated with purified LpqH protein directly. The expression of NLRP3, ASC, and caspase-1 protein was detected by western blot. The secretion of IL-1β was detected by ELISA, and LDH was detected by a kit. Cell death was detected by flow cytometry. LpqH consisted of 159 amino acids and was a hydrophobic protein with stable properties. Its secondary structure contained 47% random coils, 53% β-sheets, and 3% α-helix. The tertiary structure showed a relatively loose spatial conformation. Additionally, it had 8 B cell epitopes (score > 0.8) and 10 CTL cell epitopes (score ≥ 20). The recombinant LpqH, which had strong immunoreactivity, significantly increased the levels of NLRP3, ASC, and caspase-1 p20 (P < 0.01) and promoted the secretion of IL-1β by the cells (P < 0.01). In addition, high concentration of KCl significantly inhibited the effect of LpqH on mouse Ana-1 macrophages and reduced the expression of NLRP3, ASC, and caspase-1 p20 (P < 0.01). However, there was no significant change in LDH (P > 0.05). Meanwhile, LpqH protein did not cause additional cell death (P > 0.05). LpqH protein has good immunogenicity and can activate the NLRP3 inflammasome through the potassium efflux pathway without causing cell death.

BACKGROUND: We investigated the potential safety of remimazolam and propofol in malignant hyperthermia- (HM-) susceptible patients using ryanodine receptor 1- (RYR1-) expressing human embryonic kidney- (HEK-) 293 cells. METHODS: We compared the enhanced responsiveness of HEK-293 cells expressing wild-type RYR1 with that of mutant RYR1 to caffeine following perfusion with remimazolam or propofol. Furthermore, we investigated whether RYR1 enhanced the responsiveness of cells to remimazolam or propofol and compared the median effective concentration (EC50; i.e., the concentration required to reach half-maximal activation) using an unpaired two-tailed t-test while a P < 0.05 was considered significant. RESULTS: Remimazolam and propofol did not promote the caffeine-induced increase in intracellular Ca2+ levels in HEK-293 cells expressing mutant RYR1 even with exposure to approximately 100-fold the clinically used concentration. In wild-type RYR1, EC50 values of remimazolam following refusion vs. nonperfusion were 2.86 mM vs. 2.75 mM (P = 0.76) while for propofol perfusion vs. nonperfusion, they were 2.76 mM vs. 2.75 mM, respectively (P = 0.83). In mutant RYR1, EC50 values of remimazolam refusion vs. nonperfusion were 1.58 mM vs. 1.71 mM, respectively (P = 0.63) while for propofol perfusion vs. nonperfusion, they were 1.65 mM vs. 1.71 mM, respectively (P = 0.73). Remimazolam and propofol increased intracellular Ca2+ levels in a concentration-dependent manner, but the effect was not enhanced by RYR1. EC50 values of remimazolam with non-RYR1 vs. wild-type RYR1 were 1.00 mM vs. 0.92 mM, respectively (P = 0.91) while those of propofol were 1.09 mM vs. 1.05 mM, respectively (P = 0.84). CONCLUSIONS: The increase in intracellular Ca2+ concentration caused by remimazolam or propofol was not considered an RYR1-mediated reaction. We conclude that remimazolam and propofol can be safely used as an anesthetic in MH-susceptible patients with RYR1-mutation without causing MH and may be safely substituted for an MH-triggering anesthetic when RYR1-mediated MH occurs.

PURPOSE: The study is aimed at investigating the association between different reduction classifications (anatomic reduction, positive buttress position reduction, and negative buttress position reduction) and two end points (complications and reoperations). METHODS: The study retrospectively analyzed 110 patients undergoing internal fixation with three parallel cannulated screws from January 2012 to January 2019 in Huashan Hospital. Based on the principles of the "Gotfried reduction," all enrolled patients were divided into three groups: anatomic reduction, positive buttress position reduction, and negative buttress position reduction intraoperatively or immediately after surgery. Clinical characteristics including age, sex, side, Garden classification, Pauwels classification, fracture level, reduction classification, Garden alignment index angles, cortical thickness index (CTI), tip-caput distance (TCD), angle of the inferior screw, and the two ending points (complications and reoperations) were included in the statistical analysis. The Mann-Whitney U-test, the chi-square test, Fisher's exact test, and multiple logistic regression analysis were used in the study. RESULTS: Of the 110 patients included in our study, the mean ± standard deviation (SD) of age was 51.4 ± 10.4 years; 41 patients showed anatomic reduction, 35 patients showed positive buttress position reduction, and 34 patients showed negative buttress position reduction. For the outcomes, 24 patients (anatomic reduction: 6 [14.6%]; positive buttress position reduction: 5 [14.3%]; negative buttress position reduction: 13 [38.2%]) had complications, while 18 patients (anatomic reduction: 5 [12.2%]; positive buttress position reduction: 3 [8.6%]; negative buttress position reduction: 10 [29.4%]) underwent reoperations after surgery. In the multivariate logistic regression analysis of complications, negative buttress position reduction (negative buttress position reduction vs. anatomic reduction, OR = 4.309, 95%CI = 1.137 to 16.322, and p = 0.032) was found to be correlated with higher risk of complications. The same variable (negative buttress position reduction vs. anatomic reduction, OR = 5.744, 95%CI = 1.177 to 28.042, and p = 0.031) was also identified as risk factor in the multivariate logistic regression analysis of reoperations. However, no significant difference between positive reduction and anatomical reduction was investigated in the analysis of risk factors for complications, not reoperations. CONCLUSION: Positive buttress position reduction of femoral neck fractures in young patients showed a similar incidence of complications and reoperations compared with those of anatomic reduction. For irreversible femoral neck fractures, if positive buttress position reduction has been achieved intraoperatively, it is not necessary to pursue anatomical reduction; however, negative reduction needs to be avoided.

BACKGROUND: Hepatocellular carcinoma (HCC) lacks effective treatments and has a poor prognosis. Therefore it is needed to develop more effective drug targets. Kinesin family member 11 (KIF11) has been reported to affect the progression of several cancers, and its high expression associates with the prognosis of patients. However, the relevant mechanisms of KIF11 in HCC progression have not been studied. METHOD: Through the cancer genome atlas (TCGA) database and immunohistochemical (IHC) staining of patients' specimens, we determined that KIF11 was highly expressed in HCC tissues and associated with prognosis. We established a KIF11 stably depleted hepatoma cell line, through cell-cloning experiments and cell counting kit-8 (CCK-8) assays to detect the effects on proliferation in vitro. The role of KIF11 in promoting cell proliferation was verified in mice. RESULT: The expression of KIF11 was negatively correlated with the overall survival (OS) and disease-free survival (DFS) and positively correlated with tumor size of HCC patients. KIF11 depletion inhibits cell proliferation and tumor growth in vitro and in vivo. Conclusion. KIF11 can be used as a positive correlation marker for HCC prognosis and served as a potential therapeutic target.

This study is to investigate the relationship of programmed cell death 1 (PD-1; also known as PDCD1) and programmed death-1-ligand 1 (PD-L1; also known as CD274) single nucleotide polymorphisms (SNPs) with polycystic ovary syndrome (PCOS). This study enrolled 330 PCOS patients and 350 matched controls. ELISA was used to detect the PD-1 and PD-L1 levels in serum. SnaPshot genotyping was performed to analyze the PD-1 and PD-L1 genotyping. Linkage disequilibrium and haplotype of TagSNP loci of PD-1 and PD-L1 genes were also detected. The relationship of genotypes and alleles with PCOS was analyzed. The levels of PD-1 and PD-L1 in the serum of PCOS patients were significantly lower than those in the control group (P < 0.01). The haplotype TT of PD-1 gene at rs10204525 and rs7421861 loci was significantly lower in the PCOS group than in the control group (P < 0.001, OR = 0.67, and 95%CI = 0.54-0.84). PD-L1 gene SNP loci rs2282055, rs2890658, rs10125854, and rs702275 had linkage disequilibrium. The haplotypes TAAA, GAAC, GAGC, GCAA, and TCGA of PD-L1 gene SNP loci were significantly higher in PCOS patients than in the control group, whereas haplotypes GAAA, TAAC, TCAA, GCGA, GCAC, and TCGC of PD-L1 gene SNP loci were significantly lower in PCOS patients than in the control group. PD-1 and PD-L1 SNPs may be related to the pathogenesis of PCOS. PD-1 gene SNP loci rs10204525 and rs7421861 and PD-L1 gene SNP loci rs2282055, rs2890658, rs10125854, and rs702275 may be new candidate polymorphic loci for PCOS.

PURPOSE: Ample evidence has proved that lncRNAs are pivotal regulators in acute kidney injury (AKI). Here, we focus on the role and mechanism of lncRNA SNHG14 in ischemia/reperfusion- (I/R-) caused AKI. METHODS: I/R and hypoxia/reoxygenation (H/R) were applied to induce rats and HK-2 cells to establish AKI models in vivo and in vitro. Relative expression of SNHG14, miR-124-3p, and MMP2 was determined by qRT-PCR. HE staining was used to evaluate pathological changes in renal tissues, and acute tubular necrosis (ATN) score was calculated. Renal function was evaluated by measuring serum creatinine content and blood urea nitrogen content. Levels of IL-1β, IL-6, and TNF-α were measured by ELISA. Cell viability was examined by MTT assay. Oxidative stress was assessed by measuring SOD, MDA, and ROS levels. The target of SNHG14 or miR-124-3p was verified by DLR assay. Protein expression of MMP2 was examined by western blot. RESULTS: SNHG14 was boosted in renal tissues of I/R-stimulated rats and H/R-induced HK-2 cells, while miR-124-3p was diminished in H/R-stimulated HK-2 cells. Si-SNHG14 or miR-124-3p mimics repressed inflammation and oxidative stress and enhanced cell viability in H/R-stimulated HK-2 cells. Sh-SNHG14 mitigated I/R-induced AKI in rats. MiR-124-3p was targeted by SNHG14, and MMP2 was targeted by miR-124-3p. Inhibition of miR-124-3p or upregulation of MMP2 reversed inhibitory effects of SNHG14 silence on inflammation and oxidative stress as well as the promoting effect of SNHG14 silence on cell viability in H/R-induced HK-2 cells. CONCLUSION: Knockdown of SNHG14 alleviated I/R-induced AKI by miR-124-3p-mediated downregulation of MMP2.

OBJECTIVE: Mesothelioma (MESO) is a rare tumor derived from mesothelium cells. The aim of this study was to explore key candidate genes and potential molecular mechanisms for mesothelioma through bioinformatics analysis. METHODS: The MESO expression profiles came from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. The differences in the infiltration levels of immune cells between MESO and normal tissues were assessed using CIBERSORT. Differentially expressed genes (DEGs) were identified by comprehensive analysis of multiple datasets. A protein-protein interaction (PPI) network was constructed, and a hub gene COL1A1 was selected for MESO. The expression and mutation of COL1A1 in MESO were analyzed in the cBioPortal database. The correlation between COL1A1 expression and immune cell infiltration was evaluated using the TIMER database. Gene Set Enrichment Analysis (GSEA) of COL1A1 was then performed. Finally, Kaplan-Meier survival analysis was presented to predict the survival times between high and low COL1A1 expression groups for MESO patients. RESULTS: There were distinct differences in the infiltration levels of immune cells between MESO and normal tissues. A total of 118 DEGs were identified by comprehensively analyzing three expression profile datasets. COL1A1, a hub gene, was identified to be highly expressed in MESO compared to normal tissues. COL1A1 genetic mutation occurred in 9% of MESO samples, and amplification was the most common type of mutation. COL1A1 expression was significantly correlated to the infiltration levels of CD4+ T cells, macrophages, and neutrophils. GSEA results indicated that COL1A1 could be involved in key biological processes and pathways like extracellular matrix and PI3K-Akt pathway. Patients with high COL1A1 expression usually experienced shorten overall survival time than those with its low expression. CONCLUSION: Our findings revealed that COL1A1 could become a potential prognostic biomarker for MESO, which was significantly related to immune cell infiltration.

To achieve a dose distribution conformal to the target volume while sparing normal tissues, intensity modulation with steep dose gradient is used for treatment planning. To successfully deliver such treatment, high spatial and dosimetric accuracy are crucial and need to be verified. With high 2D dosimetry resolution and a self-development property, the Ashland Inc. product EBT3 Gafchromic film is a widely used quality assurance tool designed especially for this. However, the film should be recalibrated each quarter due to the "aging effect," and calibration uncertainties always exist between individual films even in the same lot. Recently, artificial neural networks (ANN) are applied to many fields. If a physicist can collect the calibration data, it could be accumulated to be a substantial ANN data input used for film calibration. We therefore use the Keras functional Application Program Interface to build a hierarchical neural network (HNN), with the inputs of net optical densities, pixel values, and inverse transmittances to reveal the delivered dose and train the neural network with deep learning. For comparison, the film dose calculated using red-channel net optical density with power function fitting was performed and taken as a conventional method. The results show that the percentage error of the film dose using the HNN method is less than 4% for the aging effect verification test and less than 4.5% for the intralot variation test; in contrast, the conventional method could yield errors higher than 10% and 7%, respectively. This HNN method to calibrate the EBT film could be further improved by adding training data or adjusting the HNN structure. The model could help physicists spend less calibration time and reduce film usage.

MATERIALS AND METHODS: Mice were divided into four groups: normal, untreated, low- (2 mg), and high-dose (8 mg) beluga lentil treatment groups. Beluga lentil was orally administered for 2 weeks, followed by bilateral renal ischemia for 20 min and reperfusion for 30 min. Blood samples and kidney tissues were collected and analyzed to investigate renal function, histopathology, epithelial and endothelial cell damage, apoptosis, oxidative stress, and inflammatory responses. RESULTS: The pretreated groups maintained renal function, with significantly lower blood urea nitrogen (BUN) and creatinine levels, compared with the other groups. The histopathological analysis showed reduced proximal tubule injury and decreased injury-related molecule (kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)) secretion in the pretreated groups compared with the other groups. Terminal deoxynucleotidyl transferase dUTP nick-end labeling- (TUNEL-) positive cells and the secretion of apoptosis-related molecules (Fas and caspase 3) were significantly reduced in the pretreated groups compared with the other groups. The pretreated groups showed positive microvessel-associated gene (cluster of differentiation (CD31)) expression and negative adhesion molecule (intracellular adhesion molecule 1 (ICAM-1)) expression. An antioxidant effect was observed in the pretreatment groups, with reduced malonaldehyde (MDA) expression and increased antioxidant enzyme (superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GPx)) secretion. In the pretreated groups, F4/80+ macrophages and CD4+ T cell infiltration were inhibited and proinflammatory cytokine (interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α) levels decreased; however, the levels of anti-inflammatory cytokines (transforming growth factor- (TGF-) β, IL-10, and IL-22) increased. CONCLUSIONS: Beluga lentil pretreatment demonstrated protective effects against I/R-induced renal damage, via antiapoptotic, anti-inflammatory, and antioxidant activities.

An endophytic bacterium Bacillus velezensis BY6 was isolated from the wood stems of healthy Populus davidiana × P. alba var. pyramidalis (PdPap). The BY6 strain can inhibit pathogenic fungus Alternaria alternate in PdPap and promote growth of PdPap seedlings. In the present study, we used the Pacific Biosciences long-read sequencing platform, a single-molecule real-time (SMRT) technology for strain BY6, to perform complete genome sequencing. The genome size was 3,898,273 bp, the number of genes was 4,045, and the average GC content was 47.33%. A complete genome of strain BY6 contained 110 secondary metabolite gene clusters. Nine of the secondary metabolite gene clusters exhibited antifungal activity and promoted growth functions primarily involved in the synthesis of surfactin, bacteriocins, accumulated iron ions, and related antibiotics. Gene clusters provide genetic resources for biotechnology and genetic engineering, and enhance understanding of the relationship between microorganisms and plants.

Several studies have demonstrated that chronic hepatitis delta virus (HDV) infection is associated with a worsening of hepatitis B virus (HBV) infection and increased risk of hepatocellular carcinoma (HCC). However, there is limited data on the role of HDV in the oncogenesis of HCC. This study is aimed at assessing the potential mechanisms of HDV-associated hepatocarcinogenesis, especially to screen and identify key genes and pathways possibly involved in the pathogenesis of HCC. We selected three microarray datasets: GSE55092 contains 39 cancer specimens and 81 paracancer specimens from 11 HBV-associated HCC patients, GSE98383 contains 11 cancer specimens and 24 paracancer specimens from 5 HDV-associated HCC patients, and 371 HCC patients with the RNA-sequencing data combined with their clinical data from the Cancer Genome Atlas (TCGA). Afterwards, 948 differentially expressed genes (DEGs) closely related to HDV-associated HCC were obtained using the R package and filtering with a Venn diagram. We then performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the biological processes (BP), cellular component (CC), molecular function (MF), and KEGG signaling pathways most enriched for DEGs. Additionally, we performed Weighted Gene Coexpression Network Analysis (WGCNA) and protein-to-protein interaction (PPI) network construction with 948 DEGs, from which one module was identified by WGCNA and three modules were identified by the PPI network. Subsequently, we validated the expression of 52 hub genes from the PPI network with an independent set of HCC dataset stored in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, seven potential key genes were identified by intersecting with key modules from WGCNA, including 3 reported genes, namely, CDCA5, CENPH, and MCM7, and 4 novel genes, namely, CDC6, CDC45, CDCA8, and MCM4, which are associated with nucleoplasm, cell cycle, DNA replication, and mitotic cell cycle. The CDCA8 and stage of HCC were the independent factors associated with overall survival of HDV-associated HCC. All the related findings of these genes can help gain a better understanding of the role of HDV in the underlying mechanism of HCC carcinogenesis.

This study is aimed at examining the sociodemographic factors associated with the utilization of labor epidural analgesia at a large obstetric and gynecology hospital in Vietnam. This was a cross-sectional study of women who underwent vaginal delivery in September 2018 at the Hanoi Obstetrics and Gynecology Hospital. The utilization of epidural analgesia during labor was determined. Univariate and multivariate regression models were applied to evaluate the association between patient demographic and socioeconomic factors and request for labor epidural analgesia. A total of 417 women had vaginal deliveries during the study period. 207 women utilized epidural analgesia for pain relief during labor, and 210 did not. Parturients older than 35 years of age (OR 2.84, 95% CI 1.11-8.17), multiparous women (OR 2.8 95% CI 1.85-4.25), women living from an urban area, women with higher income (OR 6.47, 95% CI 2.59-19.23), and women with higher level of education were more likely to utilize labor epidurals. Factors related to a parturient request for epidural analgesia during labor at our tertiary obstetric hospital included age greater than 35 years, multiparity, and high income and education levels. Educational outreach to women about the benefits of epidural analgesia can target women who do not share these demographic characteristics.

[This retracts the article DOI: 10.1155/2014/345678.].

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan-Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.

Newcastle disease (ND) is a highly fatal, infectious, viral disease, and despite immunization with live and inactivated vaccines, the disease is still endemic, causing heavy morbidity and mortality leading to huge economic losses to the poultry industry in Pakistan. Therefore, the present study was aimed for the first time in the country at using novel virosomal technology to develop the ND vaccine using an indigenous highly virulent strain of the virus. ND virosome was prepared using Triton X-100, and SM2 Bio-Beads were used to remove the detergent and reconstitute the viral membrane into virosome. Confirmation was done by transmission electron microscopy and protein analysis by SDS-PAGE. In vitro cell adhesion property was observed by incorporating green fluorescent protein (GFP), producing plasmid into virosome and in vitro cell culture assay. Sterility, safety, and stability of the vaccine were tested before in vivo evaluation of immunogenicity and challenge protection study in commercial broiler. The virosome vaccine was administered (30 μg/bird) at days 7 and 14 through the intranasal route in comparison with commercially available live and inactivated ND vaccines. Results revealed significantly high (p < 0.05) and clinically protective hemagglutination inhibition (HI) antibody titers at 7, 14, 21, and 28 days postimmunization with the virosome vaccine in comparison to the negative control. The GMTs were comparable to live and inactivated vaccines with nonsignificant (p > 0.05) differences throughout the experiment. Antibody levels increased in all vaccinated groups gradually from the 7th day and were maximum at 28th-day postvaccination. In the virosome-administered group, GMT was 83.18 and 77.62 at 21st and 28th-days postvaccination, respectively. Challenge revealed 100%, 90%, and 80% protection in virosome, live, and inactivated vaccinated groups, respectively. Under given experimental conditions, we can conclude that ND virosome vaccine prepared from the indigenous virus was found to be safe and immunogenic.

Bone morphogenetic proteins (BMPs), a member of the transforming growth factor β (TGF-β) superfamily, are abundant in human ocular tissues and play an important role in lens development. Targeted deletion of BMP-4 in mice results in failure of lens placode formation. Following lens maturation, the formation of senile cataracts is demonstrably associated with free radical-related oxidative stress. Previous studies reported that BMPs play an antiapoptotic role in cells under oxidative stress, and the BMP-4 signal is important in inflammation regulation and homeostasis. BMP-4 evidently suppressed the apoptosis of human lens epithelial cells (HLECS) under oxidative stress induced by H2O2. This protective antiapoptotic effect is partly due to a decrease in caspase-3 activity and reactive oxygen species (ROS) level. Furthermore, the expression of activating transcription factor- (ATF-) 6 and Krüppel-like factor- (KLF-) 6 increased under oxidative stress and decreased after BMP-4 treatment.

Studies have reported that B- and T-lymphocyte attenuator (BTLA) polymorphisms may be associated with the risk to different cancers. However, the correlation between those variations and non-small-cell lung cancer (NSCLC) is still unclear. A total of 1,003 NSCLC patients and 901 noncancer controls were recruited in the study, to confirm the association of variations in BTLA gene with the risk of NSCLC. The SNPscan™ genotyping assay was used to obtain the genotypes of the four BTLA polymorphisms (BTLA rs1982809 G>A, rs16859629 T>C, rs2171513 G>A, and rs3112270 A>G). It was found that BTLA rs1982809 polymorphism reduced the risk of NSCLC (GA vs. GG: adjusted odds ratio (OR) = 0.81, 95%confidence interval (CI) = 0.66-0.99, and P = 0.043). However, the BTLA rs16859629, rs2171513, and rs3112270 polymorphisms showed no significant association between NSCLC patients and controls in overall comparison. In subgroup analyses, we found that BTLA rs1982809 polymorphism reduced the risk of NSCLC (nonsquamous cell carcinoma: GA vs. GG: adjusted OR = 0.79, 95%CI = 0.64-0.97, and P = 0.026; AA/GA vs. GG: adjusted OR = 0.81, 95%CI = 0.66-0.99, and P = 0.037; ≥59 years: GA vs. GG: P = 0.036; never alcohol consumption: GA vs. GG: P = 0.013; GA/AA vs. GG: P = 0.016; body mass index (BMI) ≥ 24 kg/m2: GA vs. GG: P = 0.030; GA/AA vs. GG: P = 0.041). The BTLA rs16859629 polymorphism increased the risk of the development of squamous cell carcinoma (CC vs. TT: adjusted OR = 9.85, 95%CI = 1.37-71.03, and P = 0.023; CC vs. TT/TC: adjusted OR = 9.55, 95%CI = 1.32-68.66, and P = 0.025). Taken together, the findings of the present suggest that BTLA rs1982809 and rs16859629 polymorphisms may influence the susceptibility to NSCLC in the Chinese population.

BACKGROUND: Diabetic cardiomyopathy is one of the cardiac complications in diabetes patients, eventually resulting in heart failure and increasing morbidity and mortality. Oxidative stress is a critical pathological feature in diabetic hearts, contributing to the development of DCM. Forskolin (FSK) was shown to reduce oxidative stress. This study was aimed at investigating the effects of FSK on diabetic hearts and the relevant molecular mechanisms. METHODS: Streptozotocin- (STZ-) induced diabetes in mice was treated with FSK through intraperitoneal injection. Cardiac functions were evaluated by echocardiography. Hematoxylin-eosin and Masson trichrome staining was employed to determine heart morphological changes and cardiac fibrosis, respectively. Cardiac fibrosis-related markers were detected by western blot. Superoxide dismutase activity, reduced/oxidized glutathione ratio, and malondialdehyde concentration in left ventricles were determined using respective commercial kits. RESULTS: Abnormal cardiac diastolic dysfunction and cardiac fibrosis were observed in diabetic hearts. FSK treatment significantly improved the cardiac diastolic function and attenuated the abnormal morphological change in diabetic hearts. Moreover, FSK treatment in diabetic mice decreased the expression of fibronectin, collagen I, TGF-β, and α-SMA and reduced myocardial fibrosis. Furthermore, we observed that FSK significantly blocked oxidative stress in diabetic hearts. CONCLUSIONS: Our study demonstrates that FSK protects against the development of DCM in STZ-induced diabetes in mice. Our study suggests that FSK might be a potential target for drug development in treating DCM.

The aim of this study is to evaluate the biological safety of tantalum (Ta) particles and to further explore the effects of Ta particles on human monocyte toxicity and inflammatory cytokine expression. Human monocyte leukemia (THP-1) cells were cultured with Ta and hydroxyapatite (HA) particles. Cell counting kit-8 method was used to evaluate the cytotoxicity of Ta and HA particles. The apoptosis effects were evaluated by flow cytometry, and the protein expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated by ELISA. The protein levels of inflammation-related signaling pathways including nuclear factor-kappa B (NF-κB) and extracellular regulated kinase (ERK) were detected by western blotting. The cytotoxicity test showed that the toxicity level of Ta in vitro was grade l, which is within the clinically acceptable range. Compared with the HA control, Ta had no significant effect on THP-1 cell apoptosis, IL-6, and TNF-α release. The phosphorylated levels of NF-κB and ERK at 3 h in the Ta group were lower than those in the HA and control groups (P < 0.001 both). These results reveal Ta particles behave good biosafety properties and provide some new insights for the future clinical use of Ta.

BACKGROUND: Wilms tumor is the most common renal malignancy of children. Identifying factors that could predict the prognosis of patients with Wilms tumor is clinically meaningful. Many studies found tumors with elevated cholesterol synthesis that are featured with dismal prognosis. Even in some clinical trials, people with excessive dietary cholesterol intake and high plasma low-density lipoprotein levels are observed to have increased risk for cancer. However, the role of cholesterol biosynthesis in Wilms tumor has not yet been well clarified. METHODS: RNA sequencing transcriptome data and all corresponding clinicopathological information used in our study were downloaded from the TARGET database. High-throughput sequencing (Fragments Per Kilobase of transcript per Million fragments mapped) data sets of 130 tumor samples and 6 normal samples were obtained for further analysis. RESULTS: Wilms tumor samples with higher activity of cholesterol synthesis are characterized with worse overall survival (P < 0.05). In addition, Wilms tumor samples with mitigated activity of cholesterol synthesis are featured with better dendritic cell (DC) function and cytolytic activity (P < 0.05). Furthermore, we constructed a prognosis model based on differential expressed cholesterol synthesis-related genes (DECSG), which could predict the OS of patients with Wilms tumor accurately. KEGG and GO analysis of differential expressed genes between tumor samples with high and low cholesterol synthesis indicated that DECSGs are highly enriched in "mitosis nuclear division," "nuclear division," "chromosome segregation," "cell cycle," "Spliceosome," and "RNA transport." CONCLUSIONS: In conclusion, our study reported increased cholesterol synthesis in Wilms tumor predicts a worse prognosis and mitigated cytolytic activity, DC function, and MHC I signature in the tumor microenvironment. We also constructed a prognosis model for predicting the OS of patients with good accuracy, which is promising in clinical translation. Future studies should focus on the detailed mechanism that caused increasing cholesterol which promotes tumor progression and undermines patients' survival.

PURPOSE: The purpose of this study was to develop and initially validate a nomogram model in order to predict the 3-year and 5-year survival rates of neuroendocrine tumor patients. METHODS: Accordingly, 348 neuroendocrine tumor patients were enrolled as study objects, of which 244 (70%) patients were included in the training set to establish the nomogram model, while 104 (30%) patients were included in the validation set to verify the robustness of the model. First, the variables related to the survival rate were determined by univariable analysis. In addition, variables that were sufficiently significant were selected for constructing the nomogram model. Furthermore, the concordance index (C-index), receiver operating characteristic (ROC), and calibration curve analysis were used to evaluate the performance of the proposed nomogram model. The survival analysis was then used to evaluate the return to survival probability as well as the indicators of constructing the nomogram model. RESULTS: According to the multivariable analysis, lymphatic metastasis, international normalized ratio (INR), prothrombin time (PT), tumor differentiation, and the number of tumor metastases were found to be independent predictors of survival rate. Moreover, the C-index results demonstrated that the model was robust in both the training set (0.891) and validation set (0.804). In addition, the ROC results further verified the robustness of the model either in the training set (AUC = 0.823) or training set (AUC = 0.768). Furthermore, the calibration curve results showed that the model can be used to predict the 3-year and 5-year survival probability of neuroendocrine tumor patients. Meaningfully, five variables were found: lymphatic metastasis (p = 0.0095), international standardized ratio (p = 0.024), prothrombin time (p = 0.0036), tumor differentiation (p = 0.0026), and the number of tumor metastases (p = 0.00096), which were all significantly related to the 3-year and 5-year survival probability of neuroendocrine tumor patients. CONCLUSION: In summary, a nomogram model was constructed in this study based on five variables (lymphatic metastasis, international normalized ratio (INR), prothrombin time (PT), tumor differentiation, and number of tumor metastases), which was shown to predict the survival probability of patients with neuroendocrine tumors. Additionally, the proposed nomogram exhibited good ability in predicting survival probability, which may be easily adopted for clinical use.

Tissue engineering scaffolds with nanofibrous structures provide positive support for cell proliferation and differentiation in biomedical fields. These scaffolds are widely used for defective tissue repair and drug delivery. However, the degradation performance and mechanical properties of scaffolds are often unsatisfactory. Here, we successfully prepared a novel poly(3-hydroxybutyrate-4-hydroxybutyrate)/polypyrrole (P34HB-PPy) core-shell nanofiber structure scaffold with electrospinning and in situ surface polymerization technology. The obtained composite scaffold showed good mechanical properties, hydrophilicity, and thermal stability based on the universal material testing machine, contact angle measuring system, thermogravimetric analyzer, and other methods. The results of the in vitro bone marrow-derived mesenchymal stem cells (BMSCs) culture showed that the P34HB-PPy composite scaffold effectively mimicked the extracellular matrix (ECM) and exhibited good cell retention and proliferative capacity. More importantly, P34HB is a controllable degradable polyester material, and its degradation product 3-hydroxybutyric acid (3-HB) is an energy metabolite that can promote cell growth and proliferation. These results strongly support the application potential of P34HB-PPy composite scaffolds in biomedical fields, such as tissue engineering and soft tissue repair.

We investigated the therapeutic effect of a postoperative hospital-based systemic rehabilitation protocol on ankle function in chronic ankle instability (CAI) patients. Thirty-five patients who underwent a modified Broström procedure for CAI were recruited in this prospective randomized controlled trial. Fifty-minute sessions of hospital-based rehabilitation were performed three times weekly for 12 weeks in the intervention group. Education-based rehabilitation was conducted at home in the control group. The outcomes were evaluated at baseline (T0), 12 weeks (T1), and 16 weeks (T2). The primary outcome was the foot and ankle outcome score (FAOS). Ankle motor strength and spatiotemporal gait metrics were assessed as secondary outcomes. There were significant time and group interaction effects on the pain, symptoms, activities of daily living, sports activities, and quality of life (QOL) domains of the FAOS (P < 0.05, all). The patients in the intervention group showed larger improvements in all domains of the FAOS than did the control group at both T1 and T2 (P < 0.05, all). The time and group interaction effects on invertor and evertor strength were also significant (P = 0.047 and P = 0.044). Invertor and evertor strength improved significantly more in the intervention group than in the control group at T1 and T2 (P < 0.05, all). The preferred walking velocity, cadence, step length on the affected side, and double stance phase duration tended to improve over time. Postoperative hospital-based rehabilitation helped improve CAI pain, symptoms, independence in activities of daily living, sports activity levels, and QOL more effectively than did conventional rehabilitation at home.

Erratum for Biomed Res Int. 2018 Jul 17;2018:3143412.

BACKGROUND: Early and accurate evaluation of severity and prognosis in acute pancreatitis (AP), especially at the time of admission is very significant. This study was aimed to develop an artificial neural networks (ANN) model for early prediction of in-hospital mortality in AP. METHODS: Patients with AP were identified from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. Clinical and laboratory data were utilized to perform a predictive model by back propagation ANN approach. RESULTS: A total of 337 patients with AP were analyzed in the study, and the in-hospital mortality rate was 11.2%. A total of 12 variables that differed between patients in survivor group and nonsurvivor group were applied to construct ANN model. Three independent variables were identified as risk factors associated with in-hospital mortality by multivariate logistic regression analysis. The predictive performance based on the area under the receiver operating characteristic curve (AUC) was 0.769 for ANN model, 0.607 for logistic regression, 0.652 for Ranson score, and 0.401 for SOFA score. CONCLUSION: An ANN predictive model for in-hospital mortality in patients with AP in MIMIC-III database was first performed. The patients with high risk of fatal outcome can be screened out easily in the early stage of AP by our model.

OBJECTIVE: To investigate the correlation between clinical manifestation and neutrophil-lymphocyte ratio, C-reactive protein (CRP), and interleukin-6 (IL-6) in the patients with severe and extremely severe oral and maxillofacial space infection (OMSI). METHODS: In this retrospective study, we included 18 patients with severe and extremely severe OMSI from November 2012 to October 2018. Pearson or Spearman correlation coefficients were calculated to measure the association between the number of complications and locations and the number and percentage of lymphocyte, leukocyte, neutrophil, eosinophil, basophil, monocyte, CRP, and IL-6. A multivariable regression model was used to predict the number of complications and locations from these measures. RESULTS: IL-6 was positively correlated with neutrophil-lymphocyte ratio (r s = 0.773, P = 0.005), percentage of neutrophil (r s = 0.927, P = 0.001), and the number of neutrophil (r s = 0.627, P = 0.039). It was negatively correlated with percentage of monocyte (r s = -0.773, P = 0.005). CRP was positively correlated with neutrophil-lymphocyte ratio (r s = 0.556, P = 0.020) and percentage of neutrophil (r s = 0.515, P = 0.035). It was negatively correlated with the number of lymphocyte (r s = -0.517, P = 0.017), percentage of lymphocyte (r s = -0.578, P = 0.015), number of eosinophil (r s = -0.560, P = 0.020), percentage of eosinophil (r s = -0.504, P = 0.039), number of basophil (r s = -0.504, P = 0.039), and percentage of basophil (r s = -0.548, P = 0.023). The number of the involved organs was positively correlated with neutrophil-lymphocyte ratio (r s = 0.511, P = 0.030). The number of complications was positively correlated with the percentage of neutrophils (r = 0.738, P = 0.001), the neutrophil-lymphocyte ratio (r = 0.576, P = 0.012), IL-6 (r s = 0.907, P = 0.001), and CRP (r s = 0.599, P = 0.011). Multivariable regression analysis showed that the neutrophil-lymphocyte ratio (β = 0.080) was a significant predictor of the number of the involved organs and the neutrophil-lymphocyte ratio (β = 0.099). In addition, IL-6 (β = 0.002) was a significant predictor of the number of complications. CONCLUSIONS: The neutrophil-lymphocyte ratio and IL-6 contributed to the assessment of general condition in severe and profound OMSI patients. These parameters can be used as predictors to evaluate the severity of OMSI.

OBJECTIVE: Gummetal is a novel multifunctional alloy which possesses distinctive properties with the potential to refine and amend the efficacy of orthodontic treatment. The objective of this critical literature review was to investigate scientific evidence concerning the mechanical and clinical features of this recently manufactured beta-titanium orthodontic wire. MATERIALS AND METHODS: Electronic databases: PubMed, PMC, Google Scholar, Ovid, and Cochrane Library were searched. Studies investigating the properties of Gummetal orthodontic wire including in vitro and clinical studies were selected, validity was assessed, and data was extracted. The risk of bias was assessed by the Cochrane risk of bias Tool 2.0 in a randomized clinical trial. Results and Discussion. Among 322 papers, 13 papers were selected and divided into two groups: prospective double-blinded randomized clinical trial and in vitro studies. CONCLUSIONS: The results of this review should be interpreted with caution because of the heterogeneity of the studies. Only single clinical trial paper was found in the literature. The studies reported different characteristics obtained by various methods; thus, it was difficult to objectively compare the results. Low bending strength, low fatigue limit, and high resilience have been confirmed. Gummetal provides lower force than Nitinol and TMA but higher than Supercable wire. Plastic deformation of Gummetal questions its superelasticity. Friction of Gummetal wire is comparable to SS and CoCr wires. Because of its nontoxic chemical composition, Gummetal might be useful in the initial phase of orthodontic treatment for patients suffering from nickel allergy. Further studies are necessary to assess the usefulness of Gummetal in the clinical practice.

PURPOSE: A meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with antiangiogenic inhibitors (A + T) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC). METHODS: PubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade ≥ 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs). RESULTS: Data were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone (HR = 0.60; P < 0.01) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A + T and TKI alone groups (HR = 0.933; P = 0.551) regardless of EGFR mutation type. The ORR for A + T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups (RR = 0.774; P = 0.008). There was no difference in the positive rates of acquired T790M mutation between the two groups (RR = 0.967; P = 0.846). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A + T group (RR = 0.881; P = 0.002). CONCLUSION: Addition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.

Sudachitin, which is a polymethoxylated flavonoid found in the peel of Citrus sudachi, has some biological activities. However, the effect of sudachitin on periodontal resident cells is still uncertain. The aim of this study was to examine if sudachitin could decrease the expression of inflammatory mediators such as cytokines, chemokines, or matrix metalloproteinase (MMP) in interleukin- (IL-) 1β-stimulated human periodontal ligament cells (HPDLC). Sudachitin inhibited IL-1β-induced IL-6, IL-8, CXC chemokine ligand (CXCL)10, CC chemokine ligand (CCL)2, MMP-1, and MMP-3 production in HPDLC. On the other hand, tissue inhibitor of metalloproteinase- (TIMP-) 1 expression was increased by sudachitin treatment. Moreover, we found that the nuclear factor- (NF-) κB and protein kinase B (Akt) pathways in the IL-1β-stimulated HPDLC were inhibited by sudachitin treatment. These findings indicate that sudachitin is able to reduce inflammatory mediator production in IL-1β-stimulated HPDLC by inhibiting NF-κB and Akt pathways.

Rheumatoid arthritis (RA) is a widespread inflammatory disease whose clinical manifestations are joint swelling, pain, and disability, affecting approximately 1% of individuals worldwide. Conventional anti-RA drugs currently used in clinic have severe side effects. The present study is aimed at investigating the antiarthritic effects of total saponins from Nigella glandulifera seeds (TSNGS) in rats with adjuvant-induced rheumatoid arthritis (AIA). Arthritis score, paw swelling, and body weight were monitored throughout the period of TSNGS treatment. The histopathological features and levels of cytokines, including IFN-γ, TNF-α, IL-1β, IL-4, IL-6, IL-10, and IL-17A, and OPG/RANKL signaling, were measured to determine the amelioration by TSNGS and its potential mechanisms on the inflammatory response and bone erosion. The differentiation of regulatory T cells (Tregs) in serum was assessed by flow cytometry. The results demonstrate that TSNGS at 10 mg/kg, 50 mg/kg, and 250 mg/kg inhibited AIA-induced clinical score, paw swelling, and histological changes. TSNGS reduced the immune-inflammatory reaction by restoring the secretion and expression of inflammatory cytokines and elevating the proportion of CD4+ CD25+ Tregs, accompanied by an increase in transcription factor Foxp3 levels. TSNGS also displayed bone protection by upregulation of the OPG/RANKL pathway. Collectively, TSNGS inhibited arthritis in AIA rats and so represents a potential novel treatment for RA.

We intended to reformulate an existing platelet-derived wound healing formula to target each phase of the healing wound with the appropriate phase-specific molecules. A decreased perfusion of the skin, often associated with conditions such as thalassemia, sickle cell disease, diabetes mellitus, and chronic vascular disease, is the most common etiology of cutaneous ulcers and chronic wounds. We had previously shown that a PDWHF topically applied to a chronic nonhealing ulcer of a β-thalassemia homozygote stimulated and accelerated closure of the wound. The PDWHF was prepared from a pooled platelet concentrate of a matching blood group, consisting of a combination of platelet α-granule-derived factors. Processing of the apheresis-pooled platelets yielded various amounts of proteins (3.36 g/mL ± 0.25 (SD) (N = 10)) by the better lysis buffer method. Immunoglobulin G was found to be the most abundant α-granule-secreted protein. Equally broad quantities of the IgG (10.76 ± 12.66% (SD) (N = 10)) and IgG/albumin ratios (0.6 ± 0.4 (SD) (N = 10)) were quantified. We have developed a method using a reformulated lysis buffer followed by size exclusion chromatography and affinity chromatography to extract, identify, quantify, and purify IgG from activated platelets. IgG purification was confirmed by Western blot and flow cytometry. It was thought unlikely that the platelet IgG could be accounted for by adsorption of plasma protein, though the variable quantities could account for diversity in wound healing rates. The IgG could protect the wound even from subclinical infections and functionally advance healing. It may be useful in the management of skin ulcers in the early phase of wound healing.

BACKGROUND: Increasing evidence has indicated that the nuclear receptor subfamily 3 group C member 2 (NR3C2) may be associated with tumorigenesis and patient prognosis for certain types of tumors. However, the clinical significance of NR3C2 is unclear in invasive breast carcinoma (BRCA). METHODS: We used bioinformatics to broadly investigate and obtain a deeper understanding of the prognostic significance between NR3C2 and BRCA. RNA-sequencing data and clinical information of patients with BRCA from the Cancer Genome Atlas database were collected for subsequent analysis. The diagnostic efficacy of NR3C2 was evaluated by calculating the receiver operating characteristic curve. The prognostic value of NR3C2 was evaluated by Kaplan-Meier analysis and Cox regression analysis for patients with BRCA. Moreover, the OSbrca database was used to validate NR3C2 as a prognostic biomarker for BRCA. Gene set enrichment analysis (GSEA) and tumor immune infiltration analysis were conducted to explore the molecular mechanism of NR3C2 in BRCA. RESULTS: The expression level of NR3C2 in BRCA tissues decreased compared to that in normal breast tissues (P < 0.001). NR3C2 presented good diagnostic efficacy (AUC = 0.908). Moreover, the expression of NR3C2 was verified using the Oncomine database. High expression of NR3C2 was statistically associated with prolonged overall survival (HR = 0.65, 95% CI: 0.47-0.91, and P = 0.012), progression-free interval (HR = 0.68, 95% CI: 0.49-0.95, and P = 0.024), and disease-specific survival (HR = 0.57, 95% CI: 0.36-0.89, and P = 0.015) for patients with BRCA. Besides, the prognostic value of NR3C2 was verified by the OSbrca database. GSEA results suggested that enriched pathways included neuroactive ligand-receptor interaction, focal adhesion, and ECM-receptor interaction. NR3C2 expression was moderately correlated with mast cells and some T cell subsets in BRCA. CONCLUSION: NR3C2 is a potential prognostic biomarker that could help clinicians develop more appropriate treatment plans for individual patients with BRCA.

Orthokeratology (OK) is widely used to slow the progression of myopia. Low-level laser therapy (LLLT) provides sufficient low energy to change the cellular function. This research is aimed at verifying the hypothesis that LLLT treatment could control myopia progression and comparing the abilities of OK lenses and LLLT to control the refractive error of myopia. Eighty-one children (81 eyes) who wore OK lenses, 74 children (74 eyes) who underwent LLLT treatment, and 74 children (74 eyes) who wore single-vision distance spectacles for 6 months were included. Changes in axial length (AL) were 0.23 ± 0.06 mm for children wearing spectacles, 0.06 ± 0.15 mm for children wearing OK lens, and -0.06 ± 0.15 mm for children treated with LLLT for 6 months. Changes in subfoveal choroidal thickness (SFChT) observed at the 6-month examination were -16.84 ± 7.85 μm, 14.98 ± 22.50 μm, and 35.30 ± 31.75 μm for the control group, OK group, and LLLT group, respectively. Increases in AL at 1 month and 6 months were significantly associated with age at LLLT treatment. Changes in AL were significantly correlated with the baseline spherical equivalent refraction (SER) and baseline AL in the OK and LLLT groups. Increases in SFChT at 1 month and 6 months were positively associated with age at enrolment for children wearing OK lens. At 6 months, axial elongation had decelerated in OK lens-wearers and LLLT-treated children. Slightly better myopia control was observed with LLLT treatment than with overnight OK lens-wearing. Evaluations of age, SER, and AL can enhance screening for high-risk myopia, improve the myopia prognosis, and help determine suitable control methods yielding the most benefits.

BACKGROUND/AIM: Irreversible electroporation (IRE) showed promising results for small-size tumors and very early cancers. However, further development is needed to evolve this procedure into a more efficient ablation technique for long-term control of tumor growth. In this work, we show that it is possible to increase the antitumor efficiency of IRE by simmultaneously injecting c-di-GMP, a STING agonist, intratumorally. MATERIALS AND METHODS: Intratumoral administration of c-di-GMP simultaneously to IRE was evaluated in murine models of melanona (B16.OVA) and hepatocellular carcinoma (PM299L). RESULTS: The combined therapy increased the number of tumor-infiltrating IFN-γ/TNF-α-producing CD4 and CD8 T cells and delayed tumor growth, as compared to the effect observed in groups treated with c-di-GMP or IRE alone. CONCLUSION: These results can lead to the development of a new therapeutic strategy for the treatment of cancer patients refractory to other therapies.

Nagashima-type palmoplantar keratosis (NPPK) is the most prevalent palmoplantar keratoderma (PPK) in East Asia. Homozygous or compound heterozygous loss-of-function mutations in serpin peptidase inhibitor, clade B (ovalbumin), and member 70 (SERPINB7), which encodes members of the serine protease inhibitor superfamily, have been identified as the cause of NPPK. Clinical manifestations of NPPK include well-demarcated erythema, mild to moderate hyperkeratosis on the whole palm, and sole with transgrediens, extending to the dorsal surfaces of the hands and feet, inner wrists, ankles, and the Achilles tendon areas. In this study, we perform a review of relevant clinical cases aimed at elucidating the clinical characteristics, genetic characterization, differential diagnoses, and clinical management of NPPK. A better understanding of the clinical characteristics and pathogenic gene characterization of NPPK will enhance the diagnosis of NPPK, identify related diseases, and inform on the precise therapy and prognosis. Moreover, it will promote the awareness of NPPK in non-Asian regions.

This study is aimed at investigating the effects of bone morphogenetic protein-7 (BMP-7) on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into neuron-like cells in vitro. The rat BMSCs were isolated and identified, which were divided into the control, empty, recombinant rhBMP-7 transfection, and Lv-BMP-7 transfection groups. BMSCs were induced under different conditions. CCK-8 assay was performed to detect cell proliferation. ALP was used to detect cell activity. Cellular morphology after induction was observed. Immunofluorescence was conducted to detect the expression and location of nerve cell markers. Quantitative real-time PCR and Western blot analysis were performed to detect the mRNA and protein expression levels, respectively. The rhBMP-7 and Lv-BMP-7 promoted the proliferation of BMSCs, accompanied with increased ALP activities. Morphological observations revealed that rhBMP-7 and Lv-BMP-7 induced BMSCs to differentiate into neuron-like cells. Immunofluorescence revealed that the rhBMP-7 and Lv-BMP-7 groups showed positive expression of MAP-2 and Nfh in BMSCs. MAP-2 was mainly distributed in the cell body and cellular protrusion, while Nfh was mainly distributed in the cytoplasm and cell protrusion. Positive mRNA and protein expressions of MAP-2 and Nfh were observed in the cells of the rhBMP-7 and Lv-BMP-7 groups, and the expression levels were significantly higher than the control and empty groups. Both exogenous BMP-7 (rhBMP-7) and endogenous BMP-7 (Lv-BMP-7) can induce BMSCs to differentiate into neuron-like cells highly expressing the neuronal markers MAP-2 and Nfh.

Both parathyroid hormone (PTH) and mechanical signals are able to regulate bone growth and regeneration. They also can work synergistically to regulate osteoblast proliferation, but little is known about the mechanisms how PTH and mechanical signals interact with each other during this process. In this study, we investigated responses of MC3T3-E1 osteoblasts to PTH and oscillatory fluid flow. We found that osteoblasts are more sensitive to mechanical signals in the presence of PTH according to ERK1/2 phosphorylation, ATP release, CREB phosphorylation, and cell proliferation. PTH may also reduce the osteoblast refractory period after desensitization due to mechanical signals. We further found that the synergistic responses of osteoblasts to fluid flow or ATP with PTH had similar patterns, suggesting that synergy between fluid flow and PTH may be through the ATP pathway. After we inhibited ATP effects using apyrase in osteoblasts, their synergistic responses to mechanical stimulation and PTH were also inhibited. Additionally, knocking down P2Y2 purinergic receptors can significantly attenuate osteoblast synergistic responses to mechanical stimulation and PTH in terms of ERK1/2 phosphorylation, CREB phosphorylation, and cell proliferation. Thus, our results suggest that PTH enhances mechanosensitivity of osteoblasts via a mechanism involving ATP and P2Y2 purinergic receptors.

OBJECTIVE: Infantile hemangiomas (IHs) are the most common benign tumors in infancy. The purpose of this study was to study the effects of propranolol on the function of human umbilical vein endothelial cells (HUVECs), in order to preliminarily elucidate the mechanism of propranolol in the treatment of IHs. METHODS: HUVECs were treated with different concentrations of propranolol (30 μM, 60 μM, 90 μM, and 120 μM) with or without VEGF. Their proliferation, migration, invasion, adhesion, and tube formation ability were tested by using CCK-8, wound healing assay, transwell, cell adhesion assay, and tube formation assay. The expressions of HUVECs angiogenesis signaling molecules pERK/ERK, pAKT/AKT, p-mTOR/mTOR, and pFAK/FAK were detected by Western blot. RESULTS: Compared with the control group, propranolol could significantly inhibit the proliferation, migration, invasion, adhesion, and tube formation of HUVECs. Further studies showed that it could not only inhibit the migration, invasion, and tube formation ability of HUVECs after VEGF induction but also inhibit the phosphorylated protein expressions of angiogenesis-related signaling molecules like AKT, mTOR, ERK, and FAK in HUVECs, with a concentration-dependent inhibitory effect. CONCLUSION: Propranolol can inhibit the proliferation, migration, invasion, adhesion, and tube formation of hemangioma endothelial cells; block VEGF-mediated angiogenesis signaling pathway; suppress the expressions of downstream angiogenesis-related signaling molecules; and ultimately achieve the effect of treatment of IHs.

OBJECTIVE: Chronological age alone does not adequately reflect the difference in health status of a patient with hypertension. Frailty is closely associated with biological age, and its assessment is clinically useful in addressing the heterogeneity of health status. The purpose of our study is to comprehensively examine the predictive value of frailty for negative health outcomes in hypertensive patients through a systematic review and meta-analysis. METHODS: Multiple English and Chinese databases were searched from inception to 04.11.2020. All cross-sectional and longitudinal studies that examined the association between frailty and relevant clinical outcomes among hypertensive patients were included. The NOS was used to assess the risk of bias of studies included in the analysis. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were pooled for outcomes associated with frailty. RESULTS: Six longitudinal studies and one cross-sectional study involving 17403 patients with hypertension were included in the meta-analysis. The risk of bias of all included studies was rated as low or moderate. The pooled HR of frailty related to mortality was 2.45 (95% CI: 2.08-2.88). The pooled HR of prefrailty and frailty-related injurious falls was 1.07 (95% CI: 0.83-1.37) and 1.89 (95% CI: 1.56-2.27), respectively. The pooled HR of prefrailty and frailty-related hospitalization was 1.54 (95% CI: 1.38-1.71) and 1.94 (95% CI: 1.17-3.24), respectively. CONCLUSIONS: This systematic review suggests that frailty was a strong predictor of mortality, hospitalization, and injurious falls among patients with hypertension. Our findings indicate that assessment of frailty in patients with hypertension to guide their management may be necessary in clinical setting. However, our finding was based on very limited amount studies; thus, future studies are required to further validate the role of frailty in prediction of negative health outcomes in hypertensive patients as well as pay more attention to the following knowledge gaps: (1) the association between frailty and hypertension-related outcomes, (2) the significance of the association between different frailty models and relevant clinical outcomes, and (3) the predictive value of prefrailty for the negative health outcomes in people with hypertension.

High-density lipoprotein- (HDL-) cholesterol measurements are generally used in the diagnosis of cardiovascular diseases. However, HDL is a complicated heterogeneous lipoprotein, and furthermore, it can be converted into dysfunctional forms during pathological conditions including inflammation. Therefore, qualitative analysis of pathophysiologically diversified HDL forms is important. A recent study demonstrated that serum amyloid A (SAA) can remodel HDL and induce atherosclerosis not only over long periods of time, such as during chronic inflammation, but also over shorter periods. However, few studies have investigated rapid HDL remodeling. In this study, we analyzed HDL samples from patients undergoing orthopedic surgery inducing acute inflammation. We enrolled 13 otherwise healthy patients who underwent orthopedic surgery. Plasma samples were obtained on preoperative day and postoperative days (POD) 1-7. SAA, apolipoprotein A-I (apoA-I), and apolipoprotein A-II (apoA-II) levels in the isolated HDL were determined. HDL particle size, surface charge, and SAA and apoA-I distributions were also analyzed. In every patient, plasma SAA levels peaked on POD3. Consistently, the HDL apoA-I : apoA-II ratio markedly decreased at this timepoint. Native-polyacrylamide gel electrophoresis and high-performance liquid chromatography revealed the loss of small HDL particles during acute inflammation. Furthermore, HDL had a decreased negative surface charge on POD3 compared to the other timepoints. All changes observed were SAA-dependent. SAA-dependent rapid changes in HDL size and surface charge were observed after orthopedic surgery. These changes might affect the atheroprotective functions of HDL, and its analysis can be available for the qualitative HDL assessment.

Sri Lanka reports a large focus of Leishmania donovani-induced cutaneous leishmaniasis (CL) with CL as the main clinical entity. Two independent, long existed, and clinicoepidemiologically different transmission foci in the northern region (NR) and southern region (SR) were recently reported. Current project is an extension to this previous study. Clinical diversity within a profile of classical cutaneous leishmaniasis (CCL) in a focus of L. donovani-induced CL is described for the first time. Patients with laboratory confirmed CCL (n = 550) from NF and SF were evaluated. Lesions in both foci were found to have all classical developmental stages (small and large nodules, ulcerating nodules, and ulcers) and other identified changes (multiplication, ulceration, and enlargement). Main difference was in the proportions of lesions progressing in to each different stages, proportions of lesion undergoing the main changes, and in timing of these changes during the course of a lesion. Northern focus reported a smaller proportion of lesions showing enlargement and ulceration, and a longer period of time was also required for these changes when compared to same in southern focus. In northern focus, most lesions remained small and nonulcerating and showed a higher tendency to multiply while most lesions reported in southern focus enlarged and ulcerated rapidly and remained single. Current study also evidenced a wider spectrum in the rate and pattern of progression of a skin lesion and high individual variation which could mask these region-based differences. Parasitic, vector-related, or a host etiology is suggested. Slow progressing nonulcerating infections in North may be the result of a well-adopted parasite strain that coevolved with its host for a long period while inducing only a minimal host response. This could be one among many reasons for previously observed silent expansion in northern focus while southern focus remained more confined and stable over time. Small nonprogressive, nondisturbing lesions can play a major role as silent parasite reservoirs in a community. In addition, the laboratory detection rate declined significantly when lesions multiplied and enlarged indicating the need for early laboratory confirmation. Usefulness of identified features in clinical screening and management needs to be considered.

We analysed whether the hydroethanolic extracts from leaves of Haplopappus baylahuen Remy (bailahuen) and Aloysia citriodora Palau (cedron) inhibit the growth and ability of Salmonella Enteritidis to form biofilms and to adhere to human intestinal epithelial cells. Herein, we first determined the total phenolic content and antioxidant and antibacterial activities of the extracts. Then, Salmonella Enteritidis was treated with the extracts to analyse biofilm formation by scanning electronic microscopy and the violet crystal test. We also measured the efflux pump activity of Salmonella Enteritidis since biofilm formation is associated with this phenomenon. Furthermore, the human intestinal cell line Caco-2 was infected with Salmonella Enteritidis pretreated with the extracts, and 30 min later, the number of bacteria that adhered to the cell surface was quantified. Finally, we determined by qPCR the expression of genes associated with biofilm formation, namely, the diguanilate cyclase AdrA protein gene (adrA) and the BapA protein gene (bapA), and genes associated with adhesion, namely, the transcriptional regulator HilA (hilA). The phenolic content and antioxidant and bactericide activities were higher in bailahuen than in the cedron extract. Biofilm formation was inhibited by the extracts in a dose-dependent manner, while the activity of efflux pumps was decreased only with the cedron extract. Adhesion to Caco-2 cells was also inhibited without differences between doses and extracts. The extracts decreased the expression of adrA; with the cedron extract being the most efficient. The expression of hilA is affected only with the cedron extract. We concluded that hydroethanolic extracts of bailahuen and cedron differentially inhibit the growth of Salmonella Enteritidis and affect its the ability to form biofilms and to adhere to human intestinal epithelial cells. These results highlight the presence of molecules in bailahuen and cedron with a high potential for the control of the Salmonella Enteritidis pathogenesis.

The current study is aimed at developing and validating a nomogram of the risk of failure of internal fixation devices in Chinese patients undergoing spinal internal fixation. We collected data from a total of 1139 patients admitted for spinal internal fixation surgery at the First Affiliated Hospital of Guangxi Medical University from May 2012 to February 2019. Of these, 1050 patients were included in the spinal internal fixation group and 89 patients in the spinal internal fixation device failure group. Patients were divided into training and validation tests. The risk assessment of the failure of the spinal internal fixation device used 14 characteristics. In the training test, the feature selection of the failure model of the spinal internal fixation device was optimized using the least absolute shrinkage and selection operator (LASSO) regression model. Based on the characteristics selected in the LASSO regression model, multivariate logistic regression analysis was used for constructing the model. Identification, calibration, and clinical usefulness of predictive models were assessed using C-index, calibration curve, and decision curve analysis. A validation test was used to validate the constructed model. In the training test, the risk prediction nomogram included gender, age, presence or absence of scoliosis, and unilateral or bilateral fixation. The model demonstrated moderate predictive power with a C-index of 0.722 (95% confidence interval: 0.644-0.800) and the area under the curve (AUC) of 0.722. Decision curve analysis depicted that the failure risk nomogram was clinically useful when the probability threshold for internal fixation device failure was 3%. The C-index of the validation test was 0.761. This novel nomogram of failure risk for spinal instrumentation includes gender, age, presence or absence of scoliosis, and unilateral or bilateral fixation. It can be used for evaluating the risk of instrumentation failure in patients undergoing spinal instrumentation surgery.

PURPOSE: The study evaluated the neuroprotective effect and pharmacokinetic profile of turmeric extract and their metabolites in the blood and brain in an aluminum-induced neurotoxic animal model. METHODS: Swiss albino mice received turmeric extract (TE), TE-essential oil combination (TE+EO) at doses of 25 and 50 mg/kg/day orally, vehicle (control), and a positive control group. Neurotoxicity was induced by injecting aluminum chloride (40 mg/kg/day, i.p.), and the effect of the intervention was studied for 45 days. The pharmacokinetic and behavioral biochemical markers of brain function and brain histopathological changes were evaluated. RESULTS: The AUC 0-t showed a 30.1 and 54.2 times higher free curcumin concentration in plasma with 25 mg/kg and 50 mg/kg of TE+EO vs. TE, respectively. The concentration of free curcumin in the brain was 11.01 and 13.71-fold higher for 25 mg/kg and 50 mg/kg of TE+EO vs. TE, respectively. Aluminum impairs spatial learning and memory, which was significantly reversed with TE+EO by 28.6% (25 mg/kg) and 39.4% (50 mg/kg). In the elevated plus maze test, 44.8% (25 mg/kg) and 67.1% (50 mg/kg) improvements were observed. A significant reduction in aluminum-induced lipid peroxidation was observed. Also, the levels of glutathione, acetylcholinesterase, and catalase were improved with TE+EO. Damage to the hippocampal pyramidal cells was averted with TE+EO. CONCLUSION: The neuroprotective and antioxidant response confirms the benefits of TE+EO against aluminum-induced neurotoxicity. The presence of free curcumin and its metabolites in the brain and plasma establishes its improved bioavailability and tissue distribution. Therefore, the benefits of TE+EO could be harnessed in neurodegenerative diseases.

Acellular allograft (ACA) improves the repair and reconstruction of long peripheral nerve defects. ω-3 Polyunsaturated fatty acids (PUFAs) carry a neuroprotective potential, and their effects on ACA bridging were elucidated. Thirty rats with long gap sciatic nerve defects (15 mm long) were randomly divided into three groups (n = 10): ACA, ACA + PUFAs, and autograft (AU). Limb condition, wet weight of tibialis anterior muscle (TAM), nerve electrophysiology, S-100, horseradish peroxidase (HRP), and percentage of splenic CD4+ and CD8 + T-lymphocytes were evaluated for 12 weeks after the operation. Rats in the AU and ACA + PUFA groups showed superior condition in affected limbs compared to the ACA group. At 12 wk after surgery, the wet weight of TAM in the ACA + PUFA group was higher than that in the ACA group (0.4519 ± 0.1185 vs. 0.3049 ± 0.1272; P < 0.01) but lower than that in the AU group (0.4519 ± 0.1185, 0.5628 ± 0.0092; P < 0.05). In all the three groups, sole irritation elicited withdrawal reflex, and S-100 staining was detected in plantar skin. Moreover, horseradish peroxidase staining was overt in both the ventral horn and dorsal root ganglion of the spinal cord. Nerve conduction velocity (m/s), amplitude of action potential (mV), or somatosensory evoked potentials in ACA + PUFAs (28.81 ± 1.04, 2.20 ± 0.27, 6.98 ± 0.29) were significantly different from that in the AU (35.71 ± 1.28, 1.81 ± 0.19, 8.15 ± 0.52; P < 0.05) and ACA (20.03 ± 1.94, 2.95 ± 0.36, 5.22 ± 0.53; P < 0.01) groups. The percentages of splenic CD4+ and CD8+ cells were similar among the three groups. Omega-3 PUFAs improve the bridging effect of ACA on long gap peripheral nerve defects by promoting neuroprotection without arousing an immune response.

Super enhancers (SEs) are large clusters of transcriptional activity enhancers, which drive and control the expression of cell identity genes, as well as differentiation of specific cell types. SEs have great application potential in pathogenic mechanism studies in developmental biology, cancer, and other diseases. However, the potential function and regulatory mechanism of SEs in the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) are unknown. Therefore, this study investigated the potential function of SEs in the osteogenic differentiation of hBMSCs and their target genes. Osteogenesis was induced in three hBMSCs groups for 14 days. Further, ChIP-seq was performed on cells before and after osteogenic differentiation. Two target genes were then selected from cells before and after osteogenic differentiation for RT-qPCR. Finally, the selected SE target genes were analyzed by bioinformatics. In total, 1,680 SEs were identified in hBMSCs. After 14 days of osteogenic induction, only 342 SEs were detected in cells, among which 1,380 unique SEs were detected in hBMSCs, 42 unique SEs were found in cells induced by osteoblast differentiation after 14 days, and 300 SEs were common in both groups. Further, 1,680 genes were found to be regulated by SEs in hBMSCs, including 1,094 genes with protein-coding function and 586 noncoding genes. Additionally, 342 genes were regulated by SEs in cells after 14 days of osteogenic differentiation induction, of which 223 and 119 had protein-coding and noncoding functions, respectively. KEGG analysis of SE target genes before and after osteogenic differentiation showed the TGF-β, PI3K-Akt, and ECM receptor signaling pathways as highly enriched and closely related to osteogenic differentiation. Further, RT-qPCR results of four selected target genes confirmed the sequencing results. Taken together, osteogenic differentiation of hBMSCs involves changes in multiple SEs, which may regulate the osteogenic differentiation of hBMSCs by regulating the expression of target genes.

OBJECTIVE: To investigate the association between poststroke depression (PSD) and psychological crisis in patients who have experienced a stroke within 6 months. METHODS: This was a retrospective cross-sectional study that enrolled patients within 6 months after stroke onset. The investigators reviewed medical charts to obtain patients' baseline characteristics, and a psychologist evaluated each patient for depression using the Taiwanese Depression Questionnaire (TDQ) and for psychological crisis using the Triage Assessment System (TAS). A generalized linear model (GLM) was used to analyze the association between the results of the TDQ and TAS. RESULTS: Ninety-seven patients with stroke were included. Age (p = 0.003), time since onset of stroke (p = 0.041), diabetes mellitus (p = 0.004), hypertension (p = 0.016), heart disease (p = 0.005), and TDQ score were significantly different between the hemorrhagic stroke group and the ischemic stroke group. The TDQ score was significantly lower in the hemorrhagic stroke group (p = 0.012). The TDQ score was associated with the TAS total score and each domain score, and the presence of heart disease was associated with poorer TAS score in the behavioral domain (p = 0.016). CONCLUSION: PSD is likely an important component of psychological crisis in stroke patients. For clinicians, a comprehensive psychologic evaluation is necessary to optimize treatment.

Hypoxia and the pH level of the tumor microenvironment have a great impact on the treatment of tumors. Here, the tumor growth is controlled by regulating the oxygen concentration and the acidity of the tumor microenvironment by introducing a two-dimensional multiscale cellular automata model of avascular tumor growth. The spatiotemporal evolution of tumor growth and metabolic variations is modeled based on biological assumptions, physical structure, states of cells, and transition rules. Each cell is allocated to one of the following states: proliferating cancer, nonproliferating cancer, necrotic, and normal cells. According to the response of the microenvironmental conditions, each cell consumes/produces metabolic factors and updates its state based on some stochastic rules. The input parameters are compatible with cancer biology using experimental data. The effect of neighborhoods during mitosis and simulating spatial heterogeneity is studied by considering multicellular layer structure of tumor. A simple Darwinist mutation is considered by introducing a critical parameter (Nmm) that affects division probability of the proliferative tumor cells based on the microenvironmental conditions and cancer hallmarks. The results show that Nmm regulation has a significant influence on the dynamics of tumor growth, the growth fraction, necrotic fraction, and the concentration levels of the metabolic factors. The model not only is able to simulate the in vivo tumor growth quantitatively and qualitatively but also can simulate the concentration of metabolic factors, oxygen, and acidity graphically. The results show the spatial heterogeneity effects on the proliferation of cancer cells and the rest of the system. By increasing Nmm, tumor shrinkage and significant increasing in the oxygen concentration and the pH value of the tumor microenvironment are observed. The results demonstrate the model's ability, providing an essential tool for simulating different tumor evolution scenarios of a patient and reliable prediction of spatiotemporal progression of tumors for utilizing in personalized therapy.

OBJECTIVES: Glioblastoma (GBM) is a malignant brain tumor which is the most common and aggressive type of central nervous system cancer, with high morbidity and mortality. Despite lots of systematic studies on the molecular mechanism of glioblastoma, the pathogenesis is still unclear, and effective therapies are relatively rare with surgical resection as the frequently therapeutic intervention. Identification of fundamental molecules and gene networks associated with initiation is critical in glioblastoma drug discovery. In this study, an approach for the prediction of potential drug was developed based on perturbation-induced gene expression signatures. METHODS: We first collected RNA-seq data of 12 pairs of glioblastoma samples and adjacent normal samples from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by DESeq2, and coexpression networks were analyzed with weighted gene correlation network analysis (WGCNA). Furthermore, key driver genes were detected based on the differentially expressed genes and potential chemotherapeutic drugs and targeted drugs were found by correlating the gene expression profiles with drug perturbation database. Finally, RNA-seq data of glioblastoma from The Cancer Genome Atlas (TCGA) dataset was collected as an independent validation dataset to verify our findings. RESULTS: We identified 1771 significantly DEGs with 446 upregulated genes and 1325 downregulated genes. A total of 24 key drivers were found in the upregulated gene set, and 81 key drivers were found in the downregulated gene set. We screened the Crowd Extracted Expression of Differential Signatures (CREEDS) database to identify drug perturbations that could reverse the key factors of glioblastoma, and a total of 354 drugs were obtained with p value < 10-10. Finally, 7 drugs that could turn down the expression of upregulated factors and 3 drugs that could reverse the expression of downregulated key factors were selected as potential glioblastoma drugs. In addition, similar results were obtained through the analysis of TCGA as independent dataset. CONCLUSIONS: In this study, we provided a framework of workflow for potential therapeutic drug discovery and predicted 10 potential drugs for glioblastoma therapy.

BACKGROUND: To explore the role of natural killer (NK) cells in the process of hepatitis B virus (HBV) clearance and whether their phenotype is related to antiviral treatment outcome in chronic hepatitis B (CHB) patients. METHOD: We performed a single-center prospective cohort study to analyze changes of NK cells at weeks 12 and 24 from baseline in CHB patients who received PEGylated-interferon- (PEG-IFN-) α-2a versus entecavir. The frequencies of NK, CD56bright, CD56dim, IFNAR2+, NKp46+, NKp46bright, and NKp46dim NK cells and mean fluorescence intensity (MFI) of receptors NKp46 and IFNAR2 on the surface of NK cells were measured. Subgroup analyses were performed by comparing treatment responders versus nonresponders with aforementioned parameters in each group. RESULTS: In PEG-IFN-α-treated patients, posttreatment CD56bright NK cell frequency increased, but CD56dim NK cell frequency decreased. Additionally, receptor NKp46 and IFNAR2 expression enhanced. In entecavir-treated patients, although NK cell frequency increased, CD56bright and CD56dim NK cell frequencies and IFNAR2 expression did not differ between baseline and posttreatment. In subgroup analyses, posttreatment CD56bright NK cell frequency and IFNAR2 expression significantly increased in PEG-IFN-α responders from baseline, while changes were absent in PEG-IFN-α nonresponders and entecavir treatment responders. Among patients with HBV viremia after entecavir therapy, NK cell frequency significantly increased, whereas NKp46bright and IFNAR2+ NK frequency and IFNAR2 MFI significantly decreased at 12 and 24 weeks from baseline. CONCLUSIONS: In CHB patients, PEG-IFN-α treatment significantly enhanced NK cell frequency and function when compared to entacavir. Positive treatment responses to either interferon or entecavir were associated with NK cell function improvement. This trial is registered with clinical trial registration no. NCT03208998.

The positive effect of low-intensity pulsed ultrasound (LIPUS) on bone fracture healing has been proved. However, during the period of LIPUS therapy, it is undetermined whether LIPUS promotes the formation of heterotopic ossification (HO), which usually occurs in muscle tissues after trauma such as bone fracture and spinal cord injury. Here, we used 6-week LIPUS therapy in a 42-year-old Chinese male patient with a fracture nonunion in combination with ultrasonography for monitoring fracture healing and HO formation. After the LIPUS therapy, the mineralized bone formation in the area of defect of the distal tibia was presented in an ultrasound image, which was consistent with the outcome of plain radiography showing callus formation and the blurred fracture line in the area exposed to LIPUS. In addition, ultrasound images revealed no evidence of HO development within soft tissues during the period of LIPUS therapy. This study suggests that ultrasonography is a potential tool to guarantee the performance of LIPUS therapy with monitoring HO formation. Easy to use, the integration of the handheld ultrasound scanner and the ultrasonic therapeutic apparatus is entirely dedicated to help orthopedists make high-quality care and diagnosis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a rare but highly aggressive tumor that is predominantly encountered in Southeast Asia and China in particular. Aside from radiotherapy, no effective therapy that specifically treats NPC is available, including targeted drugs. Finding more sensitive biomarkers is important for new drug discovery and for evaluating patient prognosis. METHODS: mRNA expression datasets from the Gene Expression Omnibus database (GSE53819, GSE64634, and GSE40290) were selected. After all samples in each dataset were subjected to quality control using principal component analyses, the qualified samples were used for additional analyses. The genes that were significantly expressed in each dataset were intersected to identify the most significant of these. Gene functional enrichment analyses were performed on these genes, using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. The protein-protein interaction network of selected genes was analyzed using the Search Tool for the Retrieval of Interacting Genes database. Significantly, differentially expressed genes were further verified with two RNA-seq datasets (GSE68799 and GSE12452), as well as in clinical samples. RESULTS: In all, 34 (8 upregulated genes and 26 downregulated) genes were identified as significantly differentially expressed. The immune response and the regulation of cell proliferation were the most enriched biological GO terms. Using reverse transcription quantitative real-time PCR (RT-qPCR), the genes MMP1, AQP9, and TNFAIP6 were detected to be upregulated, and FAM3D, CR2, and LTF were downregulated in NPC tissue samples. CONCLUSION: This study provides information on the genes that may be involved in the development of NPC and suggests possible druggable targets and biomarkers for diagnosing and evaluating the prognosis of NPC.

Patient education is important in the treatment of temporomandibular disorder (TMD), but little is known about its effect on oral behaviors. We aimed to determine the dominant oral behaviours in patients with TMD and assess the impact of education on such behaviours. Between July 2018 and April 2019, 54 patients diagnosed with TMD according to DC/TMD were recruited. They received physical therapy and were provided education on TMD and offered a list of recommendations for improving their oral behaviours. The patient education process usually lasted for 10-20 min. Of these patients, 48 were reexamined at the outpatient clinic, 3-9 months posttreatment. We recorded the Oral Behaviour Checklist (OBC) score, maximum painless mouth opening (mm), visual analogue scale (VAS) score for pain, and Jaw Functional Limitation Scale (JFLS) score pre- and posttreatment. Wilcoxon signed rank test and paired sample t-test were used for statistical analysis. Results showed that the most dominant oral behaviours included "putting pressure on the jaw" (59.3%); "chewing food on one side" (46.3%); "pressing, touching, or holding teeth together at times other than eating" (33.3%); and "eating between meals" (33.3%). Posttreatment, the patients reported a decrease in "chewing gum" (P = 0.002), "leaning with the hand on the jaw" (P = 0.013), "chewing food on one side" (P ≤ 0.001), and "eating between meals" (P = 0.007), but this change was not significant in subgroups with a follow-up interval of 9 months. We also observed a significant improvement in the maximum painless mouth opening (P ≤ 0.001), JFLS score (P ≤ 0.001), and VAS score (P ≤ 0.001) for pain, posttreatment. In conclusion, patient education can facilitate management of oral behaviours and should be targeted towards specific oral behaviours.

BACKGROUND: Elderly patients receiving nasal feeding have weaker physiological function, and placement of a nasogastric tube weakens the natural barrier of the cardia-esophageal sphincter; therefore, the risk of gastroesophageal reflux (GER) is higher. Many studies have shown that pepsin is extremely sensitive in predicting GERD, so this study intends to investigate the level of pepsin in saliva of elderly patients with nasal feeding and analyze its influencing factors. METHODS: This was a cross-sectional study. Patients admitted to the Chinese PLA General Hospital from April 2018 to October 2018 who received nasal feeding were included. One ml of saliva was collected from each patient in while sitting during fasting in the morning and 1 hour after lunch for 3 consecutive days. Pepsin was quantified by enzyme-linked immunosorbent assay (ELISA). The patients were predivided into two groups (≥7.75μg/ml or <7.75μg/ml) based on the median pepsin. Baseline and clinical factors were compared. RESULTS: The mean age of the patients was 91.09 ± 4.91 years. There were statistical differences in diabetes and feeding methods between the two groups. There was a positive correlation between the morning and postprandial pepsin levels (r = 0.442, P < 0.001), and has no statistical difference (P = 0.175). Multivariate analysis showed that the risk factors for higher pepsin levels were diabetes (odds ratio (OR): 2.67; 95% CI: 1.225-5.819, P = 0.013) and nasal feeding methods (OR: 2.475; 95% CI: 1.183-5.180, P=0.016). CONCLUSIONS: For patients undergoing nasal feeding who are older than 80 years, the fasting and 1-hour postprandial pepsin concentration were consistent. Diabetes and feeding methods are risk factors for high pepsin levels. For the elderly over 80 years old, age has no influence on pepsin concentration.

BACKGROUND: Monolithic restorations made of translucent yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) have become popular over the past few decades. However, whether aging affects the color and translucency of monolithic translucent Y-TZP is unclear. OBJECTIVE: The aim of this systematic review and meta-analysis of in vitro studies was to evaluate the effects of aging on the color and translucency of monolithic translucent Y-TZP ceramics. MATERIALS AND METHODS: This systematic review/meta-analysis was reported according to the PRISMA statement and registered in the OSF registries (https://osf.io/5qjmu). Four databases including Medline via the PubMed, Embase, and Web of Science databases and the Cochrane Library were searched using no publication year and language limits. The last search was executed on November 20, 2020. In vitro studies comparing the translucency and/or color of monolithic translucent Y-TZP ceramics before and after simulated aging were selected. Meta-analyses were performed using Review Manager software (version 5.3, Cochrane Collaboration, Oxford, UK) with random-effects models at a significance level of 0.05. A risk-of-bias assessment was also performed for the included studies. RESULTS: Of the 188 potentially relevant studies, 13 were included in the systematic review. The hydrothermal aging duration ranged from 1 to 100 h at relatively similar temperatures (~134°C). In the general meta-analyses, the aged Y-TZP ceramics exhibited similar translucency parameter (TP), L∗, and b∗ values compared with the nonaged controls (P = .73, P = .49, and P = .62, respectively). Moreover, there was a significant difference between the aged and nonaged Y-TZP ceramics in the a∗ value (P = .03; MD = -0.26; 95% CI = -0.51 to - 0.02), favoring the nonaged Y-TZP ceramics. The subgroup analyses showed that the duration of aging contributed to changes in the translucency and color of the Y-TZP ceramics. CONCLUSIONS: The optical properties of monolithic translucent Y-TZP ceramics were stable after hydrothermal aging at 134°C and 0.2 MPa for ≤20 h. Moreover, clinically unacceptable changes in the translucency and color of monolithic translucent Y-TZP ceramics were found after hydrothermal aging for >20 h.

BACKGROUND: The regeneration of dental pulp, especially in cases of pulp death of immature teeth, is the goal of the regenerative endodontic procedures (REPs) that are based on tissue engineering principles, consisting of stem cells, growth factors, and scaffolds. Photobiomodulation therapy (PBMT) showed to improve dental pulp regeneration through cell homing approaches in preclinical studies and has been proposed as the fourth element of tissue engineering. However, when a blood clot was used as a scaffold in one of these previous studies, only 30% of success was achieved. The authors pointed out the instability of the blood clot as the regeneration shortcoming. Then, to circumvent this problem, a new scaffold was developed to be applied with the blood clot. The hypothesis of the present study was that an experimental injectable chitosan hydrogel would facilitate the three-dimensional spatial organization of endogenous stem cells in dental pulp regeneration with no interference on the positive influence of PBMT. METHODS: For the in vitro analysis, stem cells from the apical papilla (SCAPs) were characterized by flow cytometry and applied in the chitosan scaffold for evaluating adhesion, migration, and proliferation. For the in vivo analysis, the chitosan scaffold was applied in a rodent orthotopic dental pulp regeneration model under the influence of PBMT (660 nm; power output of 20 mW, beam area of 0.028 cm2, and energy density of 5 J/cm2). RESULTS: The scaffold tested in this study allowed significantly higher viability, proliferation, and migration of SCAPs in vitro when PBMT was applied, especially with the energy density of 5 J/cm2. These results were in consonance to those of the in vivo data, where pulp-like tissue formation was observed inside the root canal. CONCLUSION: Chitosan hydrogel when applied with a blood clot and PBMT could in the future improve previous results of dental pulp regeneration through cell homing approaches.

The aim of this study was to identify the recurrence rate and risk factors for the recurrence of ovarian endometriosis (OE) after laparoscopic cystectomy. This was a retrospective cross-sectional study. Subjects were OE cases who underwent laparoscopic ovarian cystectomy at Bhumibol Adulyadej Hospital (BAH). The period of this study was from January 2008 to December 2017. Ovarian histopathology and at least one-year follow-up after surgery were the prerequisite requirements. A total of 106 OE cases were included in the study. Subjects were classified into recurrence and nonrecurrence groups. It comprised of 24 and 82 cases, respectively. The mean age of the participant was 32.4 years old. The demographic characters of both groups were comparable. The recurrence rate after laparoscopic OE surgery in the present study was 22.6% (24/106). The average largest diameter of OE in the present study was 54.5 mm. Postoperative medical treatment (OR 3.15, 95% CI 1.14-8.74, p = 0.02) and postoperative pregnancy (OR 2.86, 95% CI 1.03-7.93, p = 0.04) were associated factors for recurrence decrement. The recurrence rate of OE after laparoscopic cystectomy was 22.6%. Postoperative medical treatment and postoperative pregnancy were a significant factor that lowered OE recurrence.

As a newly discovered mechanosensitive ion channel protein, the piezo1 protein participates in the transmission of mechanical signals on the cell membrane and plays a vital role in mammalian biomechanics. Piezo1 has attracted widespread attention since it was discovered in 2010. In recent years, studies on piezo1 have gradually increased and deepened. In addition to the discovery that piezo1 is expressed in the respiratory, cardiovascular, gastrointestinal, and urinary systems, it is also stably expressed in cells such as mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, chondrocytes, and nucleus pulposus cells that constitute vertebral bodies and intervertebral discs. They can all receive external mechanical stimulation through the piezo1 protein channel to affect cell proliferation, differentiation, migration, and apoptosis to promote the occurrence and development of lumbar degenerative diseases. Through reviewing the relevant literature of piezo1 in the abovementioned cells, this paper discusses the effect of piezo1 protein expression under mechanical stress stimuli on spinal degenerative disease, providing the molecular basis for the pathological mechanism of spinal degenerative disease and also a new basis, ideas, and methods for the prevention and treatment of this degenerative disease.

BACKGROUND: Ischemia-reperfusion injury and inflammation after tourniquet deflation in total knee arthroplasty are known to be associated with endothelial glycocalyx (EG) injury. This study is aimed at comparing EG injury between desflurane- and propofol-based anesthesia in patients undergoing total knee arthroplasty. MATERIALS AND METHODS: Patients were allocated to the desflurane group or propofol group. The opioid remifentanil was administered intraoperatively in both groups. Blood samples were obtained from the arterial line preoperatively, immediately before and 5 min after tourniquet deflation, and at 1, 6, and 24 h, postoperatively. Serum syndecan-1, cytokines (interleukin-1β, 6, 10, and tumour necrosis factor-α), and other laboratory values were investigated. RESULTS: Eighty patients were included in the final analysis. The change in syndecan-1 did not significantly differ between the desflurane and propofol groups (peak median level of syndecan-1; 754.5 pg/ml vs. 780.3 pg/ml, respectively, P = 0.512). Laboratory values (serum cytokines, creatinine phosphokinase, lactate dehydrogenase, and lactate levels) were also similar between the two groups. Pulmonary oxygenation was briefly improved after tourniquet deflation in the desflurane group but was similar between the two groups begging at 1 h, postoperatively. CONCLUSIONS: The effect of desflurane was not superior to that of propofol in protecting the EG from ischemia-reperfusion injury during total knee arthroplasty. This trial is registered with Trial Registry Number NCT02756715 (http://clinicaltrials.gov).

OBJECTIVES: Mycophenolate mofetil (MMF) is the standard treatment for lupus nephritis. In Japan, it was approved for lupus nephritis in 2015. We investigated its real-world safety and effectiveness in Japanese patients with systemic lupus erythematosus (SLE). METHODS: We analyzed the continuation rate, adverse events, and reasons for discontinuation of MMF in Japanese patients with SLE in a retrospective single-center study. We included 119 patients who received MMF from 31 July 2015 to 31 May 2019. To compare demographic and clinical characteristics between groups, the Mann-Whitney U-test was used for nonnormally distributed variables. Categorical variables were compared using Fisher's exact test. Kaplan-Meier curves were plotted for the discontinuation rate of MMF. RESULTS: Patients consisted of 18 males and 101 females. Thirty-five patients discontinued MMF. The cumulative discontinuation rate was 42.4%. Twenty-nine patients discontinued MMF due to adverse events, and six patients discontinued MMF due to remission of SLE or desire for childbearing. At the time of the last observation, the lupus low disease activity state achievement rate was significantly lower in patients who experienced adverse events than those who did not (64% vs. 35%, P = 0.009). We examined the concentration of mycophenolate acid (trough level) in stored frozen serum in 11 patients. Two patients had irreversible complications due to viral meningitis; their trough mycophenolate acid concentrations were 8.3 and 6.3 μg/mL, respectively. CONCLUSIONS: Although MMF may be effective in Japanese patients with SLE, physicians should pay attention to infections in patients with high mycophenolate acid concentrations.

OBJECTIVE: Sepsis is a leading cause of acute lung injury (ALI). This study attempted to investigate the effects of limb bud and heart (LBH) on the development of sepsis-induced ALI and its underlying mechanism of action. METHODS: The sepsis-induced ALI mouse model was established by cecal ligation and puncture (CLP). The lung injury score and lung wet/dry weight (W/D) ratio were used to evaluate the lung injury. In vitro, ALI was simulated by lipopolysaccharide (LPS) treatment in A549 cells. The mRNA expression of LBH, NLRP3, ASC, and proinflammatory cytokines was measured by qRT-PCR. The viability of LPS-induced A549 cells was analyzed by MTT assay. Furthermore, western blot was performed to detect the protein expression of LBH, NLRP3, and ASC. LPS-induced A549 cells were treated with MCC950 (NLRP3 inflammasome inhibitor) to confirm the effect of LBH on NLRP3 inflammasome. RESULTS: The mRNA and protein expression of LBH was decreased in sepsis-induced ALI. LBH overexpression reduced the lung injury score, lung W/D ratio, expression of proinflammatory cytokines, and NLRP3 inflammasome activation in sepsis-induced ALI mouse model. Additionally, LBH upregulation increased the viability, while it decreased the proinflammatory cytokine expression and NLRP3 inflammasome activation of LPS-induced A549 cells. Moreover, MCC950 reversed the promoting effects of LBH silencing on proinflammatory cytokine expression and NLRP3 inflammasome activation in LPS-induced A549 cells. CONCLUSIONS: LBH alleviated lung injury in sepsis-induced ALI mouse model by inhibiting inflammation and NLRP3 inflammasome, and restrained the inflammation by inhibiting NLRP3 inflammasome in LPS-induced A549 cells, providing a novel therapeutic target for ALI.

OBJECTIVE: The objective of the study was to compare polygraphic parameters and selected laboratory parameters in patients with obstructive sleep apnoea (OSA) who develop various types of left ventricular (LV) geometry. Material and Methods. The research covered 122 patients with obstructive sleep apnoea and coexisting effectively treated systemic hypertension (95 men, 27 women, average age: 54 ± 10.63). Overnight polygraphy, echocardiography, carotid artery ultrasonography, and laboratory measurements were performed. The patients were classified into four groups, depending on LV geometry. Group 1 comprised patients with normal LV geometry, group 2 included those with LV concentric remodelling. Group 3 and group 4 were patients with LV hypertrophy, concentric or eccentric, respectively. RESULTS: The most frequent type of LV geometry in the examined population was eccentric hypertrophy (36%). The highest average values of BMI and T-Ch were observed in the group of patients with concentric remodelling (group 2). The most severe respiratory disorders were found in the group of patients developing LV concentric hypertrophy (group 3); however, these differences were not statistically significant in comparison to other groups. Patients with LV eccentric hypertrophy had significantly decreased LV ejection fraction (p = 0.0008). CONCLUSIONS: LV eccentric hypertrophy is the most frequent type of LV geometry in OSA patients. Patients with severe sleep-disordered breathing are more likely to develop concentric hypertrophy, while concentric remodelling occurs more frequently among OSA patients with other coexisting conditions, such as obesity or lipid-related disorders.

The gut microbiota is very important in the initiation, progression, and dissemination of cancer, and the regulation of microbiota has been employed as a novel strategy to enhance the effect of immunotherapy. Adiponectin (APN), an adipocyte-derived hormone, plays a vital role in regulating the immune response of innate immune cells. The deficiency of APN inhibits rhabdomyosarcoma growth. However, whether this function is associated with regulating gut microbiota remains unknown. To investigate, we performed 16S ribosomal RNA (rRNA) gene sequencing on the fecal microbiome of APN gene knockout mice to determine whether APN deletion affects the gut microbiota. We found APN deficiency alters gut microbial functions involved in metabolism, genetic information processing, and cellular processes. In addition, a decreased abundance of Bacteroides and an increased abundance of Prevotella and Helicobacter were observed in rhabdomyosarcoma-bearing APN knockout mice; these bacteria were associated with the inhibition of rhabdomyosarcoma growth. These findings suggest that gut microbiota may be a potential target of APN deficiency against rhabdomyosarcoma.

PURPOSE: Statins are a class of drugs widely used in clinical practice for their lipid-lowering and pleiotropic effects. In recent years, a correlation between statins and platelet function has been unveiled in the literature that might introduce new therapeutic indications for this class of drugs. This review is aimed at summarizing the mechanisms underlying statin-platelet interaction in the cardiologic scenario and building the basis for future in-depth studies. METHODS: We conducted a literature search through PubMed, Embase, EBSCO, Cochrane Database of Systematic Reviews, and Web of Science from their inception to June 2020. RESULTS: Many pathways could explain the interaction between statins and platelets, but the specific effect depends on the specific compound. Some could be mediated by enzymes that allow the entry of drugs into the cell (OATP2B1) and others by enzymes that mediate their activation (PLA2, MAPK, TAX2, PPARs, AKT, and COX-1), recruitment and adhesion (LOX-1, CD36, and CD40L), or apoptosis (BCL2). Statins also appear to have a synergistic effect with aspirin and low molecular weight heparins. Surprisingly, they seem to have an antagonistic effect with clopidogrel. CONCLUSION: There are many pathways potentially responsible for the interactions between statins and platelets. Their effect appears to be closely related, and each single effect can be barely measured. Also, the same compound might have complex downstream signaling with potentially opposite effects, i.e., beneficial or deleterious. The multiple clinical implications that can be derived as a result of this interaction, however, represent an excellent reason to develop future in-depth studies.

BACKGROUND: The composite attachment loss during orthodontic clear aligner therapy is an adverse event that commonly happens in our daily practice. However, there is a lack of related statistical analysis and studies analyzing the related risk factors. Therefore, the aim of this study is to assess the incidence of attachment loss during orthodontic clear aligner therapy and to identify rick factors that may predict such event. MATERIALS AND METHODS: The demographics and clinical variables of 94 patients undergoing clear aligner therapy (27 males and 67 females; average age: 27.60 ± 0.86 years) were recorded. Both patient-related and tooth-related attachment loss was recorded. The chi-squared test and logistic regressive analysis were applied to identify the potential risk factors. SPSS for Mac (version 23.0, IBM, USA) was used for statistical analyses. P < 0.05 was considered statistically significant. RESULTS: Our study suggested that the risk factors for attachment loss include frequent aligner removal (≥ 5 times a day) (losing rate = 60.0%, P = 0.005), aligner wear time less than 18 hours a day (losing rate = 50.8%, P = 0.014), eating without aligners inserted (losing rate = 47.9%, P = 0.034), utilizing aligner tray seaters (losing rate = 48.2%, P = 0.006), and unilateral mastication (losing rate = 52.1%, P = 0.002). The multivariable logistic regression analysis indicates that aligner wear time less than 18 hours a day (P = 0.020, B = 0.925), using aligner tray seaters (P = 0.007, B = 1.168), and unilateral mastication (P = 0.034, B = -0.458) were considered independent factors that can predict the composite attachment loss in orthodontic clear aligner therapy. CONCLUSION: Wearing aligner less than 18 hours a day, using aligner tray seaters, and unilateral mastication may contribute to increased incidence of composite attachment loss during orthodontic clear aligner therapy.

INTRODUCTION: Human ABO blood type antigens exhibit alternative phenotypes and genetically derived glycoconjugate structures that are located on the red cell surface which play an active role in the cells' physiology and pathology. Associations between the blood type and disease have been studied since the early 1900s when researchers determined that antibodies and antigens are inherited. However, due to lack of antigens of some blood groups, there have been some contentious issues with the association between the ABO blood group and vulnerability to certain infectious and noninfectious diseases. OBJECTIVE: To review different literatures that show the association between ABO blood groups and different diseases. METHOD: Original, adequate, and recent articles on the same field were researched, and the researcher conducted a comprehensive review on this topic. Thus, taking out critical discussions, not only a descriptive summary of the topic but also contradictory ideas were fully retrieved and presented in a clear impression. In addition, some relevant scientific papers published in previous years were included. The article search was performed by matching the terms blood types/groups with a group of terms related to different diseases. The articles were screened and selected based on the title and abstract presented. RESULTS: The susceptibility to various diseases, such as cancer, cardiovascular diseases, infections and hematologic disorders, cognitive disorders, circulatory diseases, metabolic diseases, and malaria, has been linked with ABO blood groups. Moreover, blood group AB individuals were found to be susceptible to an increased risk of cognitive impairment which was independent of geographic region, age, race, and gender. Disorders such as hypertension, obesity, dyslipidemia, cardiovascular disease (CVD), and diabetes were also more prevalent in individuals with cognitive impairment. Early etiological studies indicated that blood type O has a connection with increased incidence of cholera, plague, tuberculosis infections, and mumps, whereas blood type A is linked with increased incidence of smallpox and Pseudomonas aeruginosa infection; blood type B is also associated with increased incidence of gonorrhea, tuberculosis, and Streptococcus pneumoniae, E. coli, and salmonella infections; and blood type AB is associated with increased incidence of smallpox and E. coli and salmonella infections. Diabetes mellitus, hypercholesterolemia, arterial hypertension, and family history for ischemic heart disease are the most common risk factors for cardiovascular diseases and can be genetically transmitted to offspring. Higher incidence of cancers in the stomach, ovaries, salivary glands, cervix, uterus, and colon/rectum was common in blood type A people than in O type people. The link between the ABO blood type and thromboembolic diseases and bleeding risk are intervened by the glycosyltransferase activity and plasma levels and biologic activity of vWF (Von Willebrand factor), a carrier protein for coagulation factor VIII which is low in O type. CONCLUSION: Several studies related to the ABO phenotype show that genetically determined human ABO blood groups were correspondingly linked with an increased risk of various infectious and noninfectious diseases. However, further investigations are needed particularly on the molecular level of ABO blood groups and their association with various diseases.

Osteosarcoma (OS) is a familiar malignant bone tumor that occurs mainly in adolescents. Immature colon carcinoma transcript-1 (ICT1) is an important member of the large mitoribosomal subunit in mitochondrial ribosomes, which has been shown to be closely related to tumorigenesis. Its expression and function in OS, however, remained unclear. Here, we showed that ICT1 was significantly upregulated in OS and promoted the growth of OS cells. Mechanistically, ICT1 acted as an oncogene in OS and promoted proliferation and inhibited apoptosis of OS cells through the STAT3/BCL-2 axis. These results reveal a novel insight into the role of the ICT1/STAT3/BCL-2 axis in OS and therefore may represent a novel molecular target for novel treatments.

PURPOSE: Preoperative prediction of isocitrate dehydrogenase 1 (IDH1) mutation in lower-grade gliomas (LGGs) is crucial for clinical decision-making. This study aimed to examine the predictive value of a machine learning approach using qualitative and quantitative MRI features to identify the IDH1 mutation in LGGs. MATERIALS AND METHODS: A total of 102 LGG patients were allocated to training (n = 67) and validation (n = 35) cohorts and were subject to Visually Accessible Rembrandt Images (VASARI) feature extraction (23 features) from conventional multimodal MRI and radiomics feature extraction (56 features) from apparent diffusion coefficient maps. Feature selection was conducted using the maximum Relevance Minimum Redundancy method and 0.632+ bootstrap method. A machine learning model to predict IDH1 mutation was then established using a random forest classifier. The predictive performance was evaluated using receiver operating characteristic (ROC) curves. RESULTS: After feature selection, the top 5 VASARI features were enhancement quality, deep white matter invasion, tumor location, proportion of necrosis, and T1/FLAIR ratio, and the top 10 radiomics features included 3 histogram features, 3 gray-level run-length matrix features, and 3 gray-level size zone matrix features and one shape feature. Using the optimal VASARI or radiomics feature sets for IDH1 prediction, the trained model achieved an area under the ROC curve (AUC) of 0.779 ± 0.001 or 0.849 ± 0.008 on the validation cohort, respectively. The fusion model that integrated outputs of both optimal VASARI and radiomics models improved the AUC to 0.879. CONCLUSION: The proposed machine learning approach using VASARI and radiomics features can predict IDH1 mutation in LGGs.

OBJECTIVE: To compare the difference of inflammatory cytokines and lymphocyte subsets between deceased patients and survivors with COVID-19. METHODS: This retrospective study included 254 confirmed patients from 10 January to 11 March, 2020, at Tongji Hospital of Wuhan, China. Laboratory and immunologic features were collected and analyzed, and the main outcomes focused on inflammatory cytokines and lymphocyte subsets. RESULTS: A trend of markedly higher levels of inflammatory cytokines as well as lower lymphocyte subset levels in deceased patients was observed compared with survivors. ROC curve analyses indicated that inflammatory cytokines and the decrease levels of T cell, Th (helper T cells) cell, Ts (suppressor T cells) cell, B cell, and NK cell along with Th/Ts ratio increase could be used to predict the death of COVID-19. Multivariate analyses showed that higher levels of IL-6, IL-8, and IL-10 remained significantly correlated with shorter survival time and that the amount of Ts cells was negatively associated with the possibility of death in COVID-19 patients. In conclusion, SARS-CoV-2 would cause lymphopenia and result in decreased lymphocyte subset cells, particularly in Ts cell counts, which further induces hyperinflammatory response and cytokine storm. IL-6, IL-8, IL-10, and Ts cell might be independent predictors for the poor outcome of COVID-19.

Myocardial strain is a well-validated parameter for evaluating myocardial contraction. Cardiovascular magnetic resonance myocardial feature tracking (CMR-FT) is a novel method for the quantitative measurements of myocardial strain from routine cine acquisitions. In this study, we investigated the influence of temporal resolution on tracking accuracy of CMR-FT and the intraobserver, interobserver, and interstudy reproducibilities for biventricular strain analysis in mice from self-gated CMR at 11.7 T. 12 constitutive nexilin knockout (Nexn-KO) mice, heterozygous (Het, N = 6) and wild-type (WT, N = 6), were measured with a well-established self-gating sequence twice within two weeks. CMR-FT measures of biventricular global and segmental strain parameters were derived. Interstudy, intraobserver, and interobserver reproducibilities were investigated. For the assessment of the impact of the temporal resolution for the outcome in CMR-FT, highly oversampled semi-4 chamber and midventricular short-axis data were acquired and reconstructed with 10 to 80 phases per cardiac cycle. A generally reduced biventricular myocardial strain was observed in Nexn-KO Het mice. Excellent intraobserver and interobserver reproducibility was achieved in all global strains (ICC range from 0.76 to 0.99), where global right ventricle circumferential strain (RCSSAX) showed an only good interobserver reproducibility (ICC 0.65, 0.11-0.89). For interstudy reproducibility, left ventricle longitudinal strain (LLSLAX) was the most reproducible measure of strain (ICC 0.90, 0.71-0.97). The left ventricle radial strain (LRSSAX) (ICC 0.50, 0.10-0.83) showed fair reproducibility and RCSSAX (ICC 0.36, 0.14-0.74) showed only poor reproducibility. In general, compared with global strains, the segmental strains showed relatively lower reproducibility. A minimal temporal resolution of 20 phases per cardiac cycle appeared sufficient for CMR-FT strain analysis. The analysis of myocardial strain from high-resolution self-gated cine images by CMR-FT provides a highly reproducible method for assessing myocardial contraction in small rodent animals. Especially, global LV longitudinal and circumferential strain revealed excellent reproducibility of intra- and interobserver and interstudy measurements.

OBJECTIVE: To investigate the role of implant surface debridement alone and in conjunction with systemic antibiotics on the clinical and microbiological variables of periimplantitis. MATERIALS AND METHODS: Data of forty-six patients with at least one dental implant having bleeding-on-probing (BoP), probing pocket depth (PPD) of more than 5 mm, and radiographic bone loss of more than 3 mm were retrieved from clinical records. Data was recorded for dental implant with the deepest PPD, BoP, and bone loss from each patient. "Group-A" received implant surface debridement alone, while "group-B" additionally received systemic antibiotics. Clinical and microbiological data of patients were compared before and after the treatment. RESULTS: At the implant level, a significant reduction of PPD, mucosal recession (MR), and BoP was achieved for all patients. Group B achieved significant improvement in MR and BoP compared to group A at implant level. PPD, MR, and plaque scores showed improvement at implant site level. At 3 months recall visit, 44% of group A and 52% of group B implants required surgical treatment. The presence and proportions of studied bacteria of both groups did not differ significantly at the recall visit when compared to the initial visit. However, P. intermedia and P. micros showed a significant reduction in group A at the recall visit. CONCLUSIONS: Implant surface debridement improved the clinical parameters of periimplantitis. In addition, adjunctive use of systemic antibiotics increased mucosal recession and improved bleeding on probing in periimplantitis.

Previous studies have shown that mesenchymal stem cells (MSCs) derived from various tissue sources can be differentiated into smooth muscle-like cells (SMLCs) in vitro. In this paper, dental pulp-derived mesenchymal stem cells (DPSCs) were evaluated for their differentiation ability towards smooth muscle-like cells (SMLCs) under the effect of widely used cytokines (TGF-β1 and PDGF-BB) with special focus on different culturing environments. For this purpose, both the commercially used culturing plates (Norm-c) and 0.1% gelatin-precoated (Gel-c) plates were used. Isolated cells displayed plastic adherence, pluripotency and cell surface marker profiling, and adipogenic and osteogenic differentiation potential with lineage specific marker expression. Differentiated cells induced under different culturing plates showed successful differentiation into SMLCs by positively expressing smooth muscle cell (SMC) specific markers both at the mRNA and protein levels. Gelatin coating could substantially enhance DPSC differentiation potential than Norm-c-induced cells. However, the absence of mature marker MHY-11 by immunostaining results from all treatment groups further indicated the development of immature and synthetic SMLCs. Finally, it was concluded that DPSC differentiation ability into SMLCs can be enhanced under cytokine treatment as well as by altering the cellular niche by precoating the culturing plates with suitable substrates. However, to get fully functional, contractile, and mature SMLCs, still many different cytokine cocktail combinations and more suitable coating substrates will be needed.

Innate immunity forms a protective line of defense in the early stages of pulmonary infection. The primary cellular players of the innate immunity against respiratory infections are alveolar macrophages (AMs), dendritic cells (DCs), neutrophils, natural killer (NK) cells, and innate lymphoid cells (ILCs). They recognize conserved structures of microorganisms through membrane-bound and intracellular receptors to initiate appropriate responses. In this review, we focus on the prominent roles of innate immune cells and summarize transmembrane and cytosolic pattern recognition receptor (PRR) signaling recognition mechanisms during pulmonary microbial infections. Understanding the mechanisms of PRR signal recognition during pulmonary pathogen infections will help us to understand pulmonary immunopathology and lay a foundation for the development of effective therapies to treat and/or prevent pulmonary infections.

The mobile colistin resistance (mcr) gene threatens the efficacy of colistin (COL), a last-line antibiotic used in treating deadly infections. For more than six decades, COL is used in livestock around the globe, including Africa. The use of critically important antimicrobial agents, like COL, is largely unregulated in Africa, and many other factors militate against effective antimicrobial stewardship in the continent. Currently, ten mcr genes (mcr-1 to mcr-10) have been described. In Africa, mcr-1, mcr-2, mcr-3, mcr-5, mcr-8, and mcr-9 have been detected in isolates from humans, animals, foods of animal origin, and the environment. These genes are harboured by Escherichia coli, Klebsiella, Salmonella, Citrobacter, Enterobacter, Pseudomonas, Aeromonas, Alcaligenes, and Acinetobacter baumannii isolates. Different conjugative and nonconjugative plasmids form the backbone for mcr in these isolates; however, mcr-1 and mcr-3 have also been integrated into the chromosome of some African strains. Insertion sequences (ISs) (especially ISApl1), either located upstream or downstream of mcr, class 1 integrons, and transposons, are drivers of mcr in Africa. Genes coding multi/extensive drug resistance and virulence are colocated with mcr on plasmids in African strains. Transmission of mcr to/among African strains is nonclonal. Contact with mcr-habouring reservoirs, the consumption of contaminated foods of animal/plant origin or fluid, animal-/plant-based food trade and travel serve as exportation, importation, and transmission routes of mcr gene-containing bacteria in Africa. Herein, the current status of plasmid-mediated COL resistance in humans, food-producing animals, foods of animal origin, and environment in Africa is discussed.

Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and Coronavirus Disease 2019 (COVID-19) infections are the three epidemiological diseases caused by the Coronaviridae family. Perceiving the immune responses in these infections and the escape of viruses could help us design drugs and vaccines for confronting these infections. This review investigates the innate and adaptive immune responses reported in the infections of the three coronaviruses SARS, MERS, and COVID-19. Moreover, the present study can trigger researchers to design and develop new vaccines and drugs based on immune system responses. In conclusion, due to the need for an effective and efficient immune stimulation against coronavirus, a combination of several strategies seems necessary for developing the vaccine.

INTRODUCTION: Glioblastoma (GBM) is one of the most frequent primary intracranial malignancies, with limited treatment options and poor overall survival rates. Alternated glucose metabolism is a key metabolic feature of tumour cells, including GBM cells. However, due to high cellular heterogeneity, accurately predicting the prognosis of GBM patients using a single biomarker is difficult. Therefore, identifying a novel glucose metabolism-related biomarker signature is important and may contribute to accurate prognosis prediction for GBM patients. METHODS: In this research, we performed gene set enrichment analysis and profiled four glucose metabolism-related gene sets containing 327 genes related to biological processes. Univariate and multivariate Cox regression analyses were specifically completed to identify genes to build a specific risk signature, and we identified ten mRNAs (B4GALT7, CHST12, G6PC2, GALE, IL13RA1, LDHB, SPAG4, STC1, TGFBI, and TPBG) within the Cox proportional hazards regression model for GBM. RESULTS: Depending on this glucose metabolism-related gene signature, we divided patients into high-risk (with poor outcomes) and low-risk (with satisfactory outcomes) subgroups. The results of the multivariate Cox regression analysis demonstrated that the prognostic potential of this ten-gene signature is independent of clinical variables. Furthermore, we used two other GBM databases (Chinese Glioma Genome Atlas (CGGA) and REMBRANDT) to validate this model. In the functional analysis results, the risk signature was associated with almost every step of cancer progression, such as adhesion, proliferation, angiogenesis, drug resistance, and even an immune-suppressed microenvironment. Moreover, we found that IL31RA expression was significantly different between the high-risk and low-risk subgroups. CONCLUSION: The 10 glucose metabolism-related gene risk signatures could serve as an independent prognostic factor for GBM patients and might be valuable for the clinical management of GBM patients. The differential gene IL31RA may be a potential treatment target in GBM.

Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China. However, patient survival time after surgery remains unsatisfactory, especially in those who are pN+. This retrospective study determined the value of postoperative adjuvant therapy for patients with pN+ ESCC. From Jan 2008 to Sep 2011, 453 pN+ ESCC patients who underwent R0 resection and survived for at least 1 month were retrospectively enrolled. All patients received surgery. Some patients received surgery alone (SA, n = 131), and others received postoperative chemotherapy (POCT, n = 222), radiotherapy (PORT, n = 57), or sequential chemoradiotherapy (POCRT, n = 43). The follow-up ended on 1 Dec 2019. The 5-year overall survival (OS), disease-free survival (DFS), and locoregional recurrence (LR) were significantly worse in the SA group (15.2%, 13.1%, and 71.6%, all p < 0.05) than in the POCT group (28.0%, 20.8%, and 66.5%), the PORT group (27.4%, 24.4%, and 46.9%), and the POCRT group (42.8%, 35.5%, and 43.0%). Furthermore, compared with the SA group, the median OS and DFS were significantly longer in the POCT, PORT, and POCRT groups (all p < 0.05). PORT and POCRT (but not POCT) also significantly reduced the LR (p < 0.01). Multivariate Cox analysis showed that each type of postoperative therapy was independently associated with improvements in OS, DFS, and LR. Postoperative adjuvant therapy-either POCT, PORT, or POCRT-significantly improved OS and DFS in patients with pN+ ESCC after R0 surgery. PORT and PORCT significantly reduced LR in these patients.

Osteoporosis (OP) is a metabolic disease characterized by decreased bone mass and increased risk of fragility fractures, which significantly reduces the quality of life. Stem cell-based therapies, especially using bone marrow mesenchymal stem cells (BMSCs), are a promising strategy for treating OP. Nevertheless, the survival and differentiation rates of the transplanted BMSCs are low, which limits their therapeutic efficiency. Icariin (ICA) is a traditional Chinese medicine formulation that is prescribed for tonifying the kidneys. It also promotes the proliferation and osteogenic differentiation of BMSCs, although the specific mechanism remains unclear. Based on our previous research, we hypothesized that ICA promotes bone formation via the sclerostin/Wnt/β-catenin signaling pathway. We isolated rat BMSCs and transfected them with sclerostin gene (SOST) overexpressing or knockdown constructs and assessed osteogenic induction in the presence or absence of ICA. Sclerostin significantly inhibited BMSC proliferation and osteogenic differentiation, whereas the presence of ICA not only increased the number of viable BMSCs but also enhanced ALP activity and formation of calcium nodules during osteogenic induction. In addition, the osteogenic genes including Runx2, β-catenin, and c-myc as well as antioxidant factors (Prdx1, Cata, and Nqo1) were downregulated by sclerostin and restored by ICA treatment. Mechanistically, ICA exerted these effects by activating the Wnt/β-catenin pathway. In conclusion, ICA can promote the proliferation and osteogenic differentiation of BMSCs in situ and therefore may enhance the therapeutic efficiency of BMSC transplantation in OP.

OBJECTIVE: The Barthel index (BI) is the most commonly used measure of poststroke disability. The purpose of this article is to explore the different complications and severity of the sequelae of elderly stroke patients with different BI in the emergency department, so as to provide a theoretical basis for strengthening the treatment of elderly patients with stroke sequelae. METHODS: A retrospective study was adopted, and 1896 patients were divided into two groups according to the BI: 823 patients in the bedridden group (BI ≤ 40 points) and 1073 patients in the nonbedridden group (BI > 40 points). The type and number of complications and APACHE II score were compared between the two groups. RESULTS: Compared with the two groups, pneumonia, renal insufficiency, respiratory failure, and decubitus ulcer in the bedridden group had a higher incidence, but the incidence of upper gastrointestinal bleeding and fractures in the nonbedridden group was significantly higher (P < 0.05). The APACHE II score of the patients in the bedridden group was higher than that of the nonbedridden group, and they were critical (P < 0.001). And the number of complications was higher than that in the nonbedridden group. Moreover, the BI was negatively correlated with the APACHE-II score and the number of complications, and the APACHE II score was positively correlated with the number of complications (P < 0.001). CONCLUSION: Different complications and severity of illness occur in elderly patients with sequelae of stroke after different BI in the emergency department.

Laminoplasty is widely used to decompress the spinal cord in patients with multilevel cervical lesions. Straight cervical alignment may not be a good candidate for laminoplasty because of postoperation progression of kyphosis and loss of cervical spine range of motion (ROM). However, clinical outcomes of laminoplasty did not show a strong and consistent effect based on cervical sagittal alignment. Moreover, the kyphosis progression and ROM change after operation for the patients with preoperative strange cervical alignment are still unclear. This study is to evaluate the change of cervical alignment and ROM in patients with straight cervical alignment after modified Kurokawa cervical laminoplasty. Thirty patients with multiple-level cervical spondylosis (CSM) and straight cervical alignment were included. All patients underwent laminoplasty with the reconstruction of the spinous process-ligament-muscular complex (SPLMC). The modified JOA score was analyzed for clinical assessment. The change of cervical alignment, ROM, T1 slope, and intervertebral disc space Cobb angle were analyzed for radiological assessment. The average JOA score at preoperative and 2 years follow-up were 7.8 ± 1.4 and 13.6 ± 2.1, respectively. The recovery ratio was 63%. At the 2 years follow-up, there were 18 patients who acquired lordotic cervical alignment. 10 patients remained as straight cervical curve, and 2 patients' cervical alignment developed mild kyphosis. 28 out of 30 patients showed improvement of cervical alignment. The cervical alignment was improved from 1.29 ± 10.04° preoperative to 9.58 ± 8.65° postoperative. However, the ROM decreased from 36.8 ± 18.92 preoperative to 25.08 ± 12.10° postoperative. A positive correlation was found between the C2/4 angle change and cervical alignment change, T1 slope and cervical alignment, cervical alignment, and neutral position flexion reserved ROM. A negative correlation was found between the C1/2 angle change and cervical alignment change. Laminoplasty with a reconstruction of SPLMC followed by appropriate postoperative muscle exercises may be an encouraging way to maintain or improve physiological alignment and prevent postoperation kyphosis deformity at 2 years follow-up.

BACKGROUND: More than a third of women could develop ovarian cysts during their lifetime. Jingshu granules are used for the treatment of gynecological disease of primary dysmenorrhea. However, the molecular mechanisms of Jingshu granules in ovarian cysts are still unreported. We aimed to find the active ingredients, molecular targets, and potential signaling pathways of Jingshu granules in ovarian cysts by using the systemic pharmacological analysis. METHODS: Firstly, the effect of Jingshu granules on female hormones and reproductive organs of young female rats was evaluated. Secondly, candidate pharmaceutical ingredients of Jingshu granules were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform. Potential protein targets for the active ingredients in Jingshu granules were then identified according to the oral bioavailability and drug-likeness indices. Thirdly, ovarian cyst-related gene targets were screened based on different databases. Finally, enrichment analysis was used to analyze the potential biological function of intersection targets between Jingshu granules and ovarian cysts. RESULTS: In young female rats, Jingshu granules reduced the secretion of estradiol, progesterone, and prolactin and could affect the development of the uterus. This suggested that Jingshu granules played roles in hormone secretion and reproduction. From the TCMSP, a total of 1021 pharmaceutical ingredients of Jingshu granules were retrieved. After further screening, a total of 166 active ingredients and 159 protein targets of Jingshu granules were identified. In addition, 4488 gene targets of ovarian cysts were screened out. After taking the intersection, a total of 110 intersection targets were identified between potential protein targets of Jingshu granules and gene targets of ovarian cysts. In the functional analysis of 110 intersection targets, 8 signaling pathways including progesterone-mediated oocyte maturation (MAPK8 and CDK1 involved), GnRH signaling pathway (JUN involved), T cell receptor signaling pathway and Toll-like receptor signaling pathway (MAPK1 involved), NOD-like receptor signaling pathway (TNF, IL6, and IL1B involved), p53 signaling pathway (CDK2 and CDK4 involved), VEGF signaling pathway (MAPK14 involved), and PPAR signaling pathway (PPARG involved) were obtained. CONCLUSION: Our study revealed that Jingshu granules could function in patients with ovarian cysts through a number of molecular targets and signaling pathways. Our study may provide a new field into the mechanisms of Jingshu granules in ovarian cysts, from the molecular to the signaling pathway level.

BACKGROUND: Studies indicated that the need for family planning appears to be greater for human immuno-deficiency virus- (HIV-) positive women than the general population to reduce the risk of pediatrics HIV infection and related consequences of unintended pregnancy. We aimed to assess the level of unmet need for family planning and its predictors among HIV-positive women in Ethiopia. METHODS: Online databases such as PubMed, SCOPUS, EMBASE, HINARI, Google Scholar, and digital libraries of universities were used to search for studies to be included in this systematic review and meta-analysis. Quality assessment of included studies was conducted using the Newcastle-Ottawa Quality Assessment Scale (NOS). Data were extracted using the format prepared on Excel workbook and analyzed by the Stata 11 software. Cochran (Q test) and I 2 test statistics were used to assess the heterogeneity of studies. Similarly, the funnel plot and Egger's regression asymmetry test were used to assess publication bias. RESULT: This systematic review and meta-analysis was conducted using nine primary studies with a total of 6,154 participants. The pooled prevalence of unmet need for family planning among HIV-positive women was found to be 25.72% (95% CI: 21.63%, 29.81%). Participants age 15-24 years ((OR = 3.12; 95% CI: 1.59, 6.11) I 2 = 27.5%; p = 0.252), being illiterate ((OR = 2.69; 95% CI: 1.69, 4.26) I 2 = 0.0%; p = 0.899), failure to discuss FP with partner ((OR = 3.38; 95% CI: 2.20, 5.18) I 2 = 0.0%; p = 0.861), and no access to family planning information ((OR = 4.70; 95% CI: 2.83, 7.81) I 2 = 0.0%; p = 0.993) were found to be a significant predictors of unmet need for family planning among HIV-positive women. CONCLUSION: The level of unmet need for family planning among HIV-positive women was found to be high in Ethiopia. Being young age, illiteracy, failed to discuss family planning issues with a partner, and no access to family planning information were found to be the significant predictors of unmet need for family planning among HIV-positive women in Ethiopia. Improving information access and encouraging partners' involvement in family planning counseling and services could reduce the level of unmet need for family planning.

Owing to the remarkable heterogeneity of gastric cancer (GC), population-level differentially expressed genes (DEGs) identified using case-control comparison cannot indicate the dysregulated frequency of each DEG in GC. In this work, first, the individual-level DEGs were identified for 1,090 GC tissues without paired normal tissues using the RankComp method. Second, we directly compared the gene expression in a cancer tissue to that in paired normal tissue to identify individual-level DEGs among 448 paired cancer-normal gastric tissues. We found 25 DEGs to be dysregulated in more than 90% of 1,090 GC tissues and also in more than 90% of 448 GC tissues with paired normal tissues. The 25 genes were defined as universal DEGs for GC. Then, we measured 24 paired cancer-normal gastric tissues by RNA-seq to validate them further. Among the universal DEGs, 4 upregulated genes (BGN, E2F3, PLAU, and SPP1) and 1 downregulated gene (UBL3) were found to be cancer genes already documented in the COSMIC or F-Census databases. By analyzing protein-protein interaction networks, we found 12 universally upregulated genes, and we found that their 284 direct neighbor genes were significantly enriched with cancer genes and key biological pathways related to cancer, such as the MAPK signaling pathway, cell cycle, and focal adhesion. The 13 universally downregulated genes and 16 direct neighbor genes were also significantly enriched with cancer genes and pathways related to gastric acid secretion. These universal DEGs may be of special importance to GC diagnosis and treatment targets, and they may make it easier to study the molecular mechanisms underlying GC.

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease. Accumulating evidence has demonstrated that nonalcoholic fatty liver disease (NAFLD) shares common typical features with T2DM, and they affect each other extensively. Thus, NAFLD has emerged as a novel target for T2DM prevention and care. Although Corni Fructus (CF) and its extracts have a therapeutic effect on T2DM, its effects and mechanisms on T2DM with NAFLD are far from elucidated. In this study, a mouse model of T2DM with NAFLD complication was established in ICR mice by feeding a high-fat, high-sugar (HFHS) diet and intraperitoneally injecting with a low dose of streptozotocin (STZ). Then, the effects of iridoid glycosides (IG) extracted from CF on this mouse model were investigated. We found that 4-week IG administration remarkably alleviated hyperglycemia and insulin resistance and significantly reduced inflammation, oxidative stress, and fat accumulation in the liver of T2DM with NAFLD mice. Further studies showed that IG inhibited the NF-κB but enhanced the PI3K-AKT signaling pathway. In summary, these results indicated that the IG from CF has potential therapeutic effects on T2DM with NAFLD.

Colorectal imaging improves on diagnosis of colorectal diseases by providing colorectal images. Manual diagnosis of colorectal disease is labor-intensive and time-consuming. In this paper, we present a method for automatic colorectal disease classification and segmentation. Because of label unbalanced and difficult colorectal data, the classification based on self-paced transfer VGG network (STVGG) is proposed. ImageNet pretraining network parameters are transferred to VGG network with training colorectal data to acquire good initial network performance. And self-paced learning is used to optimize the network so that the classification performance of label unbalanced and difficult samples is improved. In order to assist the colonoscopist to accurately determine whether the polyp needs surgical resection, feature of trained STVGG model is shared to Unet segmentation network as the encoder part and to avoid repeat learning of polyp segmentation model. The experimental results on 3061 colorectal images illustrated that the proposed method obtained higher classification accuracy (96%) and segmentation performance compared with a few other methods. The polyp can be segmented accurately from around tissues by the proposed method. The segmentation results underpin the potential of deep learning methods for assisting colonoscopist in identifying polyps and enabling timely resection of these polyps at an early stage.

BACKGROUNDS: Intra-aortic balloon counterpulsation is increasingly used in acute myocardial infarction complicated by cardiogenic shock. The aim of this study was to explore the preference, effect, and prognosis of intra-aortic balloon counterpulsation in acute myocardial infarction complicated by cardiogenic shock patients. METHODS: Data of acute myocardial infarction complicated by cardiogenic shock patients at the Fourth Medical Center of PLA General Hospital were collected retrospectively. A propensity score was calculated with a logistic regression which contained clinically meaningful variables and variables selected by Lasso and then used to match the control group. The cumulative incidence curve and Gray's test were employed to analyse the effect and prognosis of intra-aortic balloon counterpulsation on mortality. RESULTS: A total of 1962 acute myocardial infarction cases admitted between May 2015 and November 2018 were identified, and 223 cases with acute myocardial infarction complicated by cardiogenic shock were included as the study cohort, which contained 34 cases that received IABP and 189 cases that did not receive IABP. Patients with higher alanine aminotransferase (OR = 1.93, 95% CI 1.29-2.98), higher triglyceride (OR = 3.71, 95% CI 1.87-7.95), and higher blood glucose (OR = 1.08, 95% CI 0.99-1.18) had a higher probability of receiving intra-aortic balloon counterpulsation. In the propensity score matching analysis, 34 cases received intra-aortic balloon counterpulsation and 102 matched controls were included in the comparison. By comparing the cumulative incidence of in-hospital mortality, there was no statistically significant difference between the intra-aortic balloon counterpulsation group and matched control group (P = 0.454). CONCLUSION: The use of intra-aortic balloon counterpulsation may not improve the prognosis of the acute myocardial infarction complicated by cardiogenic shock patients.

Diabetic retinopathy is one of the main causes of blindness in human eyes, and lesion segmentation is an important basic work for the diagnosis of diabetic retinopathy. Due to the small lesion areas scattered in fundus images, it is laborious to segment the lesion of diabetic retinopathy effectively with the existing U-Net model. In this paper, we proposed a new lesion segmentation model named FFU-Net (Feature Fusion U-Net) that enhances U-Net from the following points. Firstly, the pooling layer in the network is replaced with a convolutional layer to reduce spatial loss of the fundus image. Then, we integrate multiscale feature fusion (MSFF) block into the encoders which helps the network to learn multiscale features efficiently and enrich the information carried with skip connection and lower-resolution decoder by fusing contextual channel attention (CCA) models. Finally, in order to solve the problems of data imbalance and misclassification, we present a Balanced Focal Loss function. In the experiments on benchmark dataset IDRID, we make an ablation study to verify the effectiveness of each component and compare FFU-Net against several state-of-the-art models. In comparison with baseline U-Net, FFU-Net improves the segmentation performance by 11.97%, 10.68%, and 5.79% on metrics SEN, IOU, and DICE, respectively. The quantitative and qualitative results demonstrate the superiority of our FFU-Net in the task of lesion segmentation of diabetic retinopathy.

OBJECTIVE: The use of transvaginal mesh is controversial, and over time, multiple surgical methods for the treatment of posterior vaginal prolapse (PVP) have been proposed including different surgical approaches and techniques. To date, no clear conclusion has been reached about the use of mesh for reinforcing transvaginal posterior repair. The aim of this study was to evaluate the feasibility, safety, and effectiveness of a novel, ultralightweight mesh for the treatment of PVP. METHODS: We performed a single-center, prospective observational study on consecutive patients referred for primary or recurrent, symptomatic stage II PVP (according to the international Pelvic Organ Prolapse Quantification System) from April 2017 to September 2018. In all patients, transvaginal posterior repair was augmented with a single-incision, isoelastic polypropylene mesh. Data about the postoperative outcomes were collected until December 2019. RESULTS: A total number of 15 patients were included. The median follow-up after surgery was 18 months (IQR = 14). Surgery was completed in all cases without complications. Regarding the anatomical outcomes (as measured according to POP-q classification), a significant improvement was observed in terms of Bp, D, and C (p < 0.05). The functional outcomes were significantly ameliorated after surgery, with a reduction of bulge symptom, stypsis, incomplete evacuation, and excessive staining (p < 0.05). The quality of life was significantly improved in the majority of patients (p < 0.05). Median patients' satisfaction rate was 100% (IQR = 22.5%). Neither early nor late postoperative complications occurred. CONCLUSIONS: Single-incision, ultralightweight polypropylene meshes were safe and highly effective in the treatment of PVP. As our study has some limitations, further large, controlled studies are needed.

BACKGROUND: Intrauterine balloon tamponade (IUBT) and compression sutures have been widely used in recent years in the management of postpartum hemorrhage (PPH). However, there is scant literature directly comparing the clinical scenarios that led to the discriminant selection of these management modalities and the direct clinical outcomes. The purpose of this study is to compare the patient characteristics and clinical risk factors that led to the use of IUBT and compression sutures in the management of major PPH as well as the immediate outcome in a retrospective cohort. METHODS: Patients who had IUBT or compression sutures applied due to major PPH (>1000 ml) from 2014 to 2018 in a single obstetric unit were recruited. The patient characteristics and clinical outcome of the two groups were compared. RESULTS: A total of 67 patients had IUBT and 29 patients had compression sutures applied as the first uterine sparing technique. Apart from more vaginal deliveries (25.4% vs. 3.5%) in the IUBT group compared to compression sutures, there were no significant differences between the two groups in terms of patient characteristics. The IUBT group had a slightly higher blood loss at the start of the uterine sparing procedure (239 ml, p = 0.049) and received more transfusions, despite no differences in the total blood loss, hemogloblin level, incidence of coagulopathy, and intensive care unit admission between the two groups. There was no significant difference in the overall success rate between IUBT and compression sutures to control PPH without additional surgical intervention or hysterectomy (73.1% vs. 55.1%, p = 0.15) or the success rate for PPH due to uterine atony (32.8% vs. 20.7%), though IUBT apparently performed better than compression sutures in cases of placenta praevia (77.3% vs. 16.7%, p = 0.01). Blood loss > 1.5 l at the start of the procedure, presence of placenta accreta, and presence of coagulopathy were found to be significant poor prognostic factors for both procedures to control PPH. CONCLUSIONS: There were no dominating patient characteristics that favoured the selection of either IUBT or compression sutures in the management of severe PPH except for the mode of delivery. Both procedures had equally high overall success rates to control PPH, but IUBT performed better in placenta praevia cases as compared to compression sutures.

DHEA-Box Helicase 37 (DHX37) is a putative RNA helicase. It is involved in various RNA secondary structure alteration processes, including translation, nuclear splicing, and ribosome assembly. It is reported to be associated with the neurodevelopmental disorder with brain anomalies, and a recent study suggests that DHX37 is a functional regulator of CD8 T cells. Dysregulation of the CD8 T cell function is closely related to defective antitumor immune responses. In the present study, we investigated the expression, mutation, and prognostic role of DHX37 in human cancers, mainly by mining publicly available datasets. Our results suggested that DHX37 was significantly upregulated in 17 kinds of tumors. Mutations including deletions, insertions, and substitutions of DHX37 were widely detected. Besides, the expression of DHX37 was negatively correlated with immune-related genes PD-L1, RGS16, and TOX, and it was positively associated with TIM3, LAG3, and NCOR2. Through biofunctional analysis, we observed that DHX37 was significantly enriched in cancer-related pathways such as cell cycle, DNA replication, mismatch repair, RNA degradation, and RNA polymerase. In conclusion, the study explored the significance of DHX37 in human cancers. DHX37 may serve as a potential target for cancer immunotherapy.

Erratum for Biomed Res Int. 2019 Jun 3;2019:1851740.

Hemangioma, the most common benign vascular tumor, not only affects the appearance and psychology but also has a life-threatening potential. It is considered that clonal vascular endothelial cell proliferation and excessive angiogenesis are responsible for hemangioma pathogenesis, in which abnormal cytokines/pathways are closely implicated, primarily including high expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) as well as their downstream pathways, especially phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt). These further stimulate the migration and proliferation of vascular endothelial cells and promote the formation of new vessels, ultimately leading to the occurrence and development of hemangioma. Proanthocyanidins are naturally active substance from plants and fruits. They possess multiple functions like antiproliferation, antiangiogenesis, and antitumor. It has been demonstrated that proanthocyanidins effectively work in various diseases via inhibiting the expression of various factors, e.g., HIF-1α, VEGF, PI3K, and Akt. Considering the pathogenesis of hemangioma and the effect of proanthocyanidins, we hold a hypothesis that proanthocyanidins would be applied in hemangioma via downregulating cytokine/pathway expression, suppressing vascular cell proliferation and arrest abnormal angiogenesis. Taken together, proanthocyanidins may be a potential novel way for the treatment of hemangioma.

BACKGROUND: As the most aggressive type of skin cancer, cutaneous melanoma (CM) is experiencing a rapidly rising mortality in recent years. Exploring potential prognostic biomarkers or mechanisms of disease progression therefore has a great significance for CM. The purpose of this study was to identify genetic markers and prognostic performance of N6-methyladenosine (m6A) regulators in CM. METHOD: Gene expression profiles, copy number variation (CNV), and single nucleotide polymorphism (SNP) data of patients were obtained from The Cancer Genome Atlas (TCGA) database. RESULTS: Genomic variation and association analysis of gene expressions revealed a high degree of genomic variation in the presence of m6A-regulated genes. m6A patients with high-frequency genomic variants in the regulatory gene tended to develop a worse prognosis (p < 0.01). Unsupervised cluster analysis of the expression profiles of m6A-regulated genes identified three clinically distinct molecular subtypes, including degradation-enhanced subgroup and immune-enhanced subgroup, with significant prognostic differences (p = 0.046). A novel prognostic signature, which was established according to m6A-related characteristic genes identified through genome-wide expression spectrum, could effectively identify samples with poor prognosis and enhanced immune infiltration, and the effectiveness was also verified in the dataset of the chip. CONCLUSION: We identified genetic changes in the m6A regulatory gene in CM and related survival outcomes. The findings of this study provide new insights into the epigenetic understanding of m6A in CM.

Antibody-drug conjugate therapy has attracted considerable attention in recent years. Since the selection of appropriate targets is a critical aspect of antibody-drug conjugate research and development, a big data research for discovery of candidate targets per tumor type is outstanding and of high interest. Thus, the purpose of this study was to identify and prioritize candidate antibody-drug conjugate targets with translational potential across common types of cancer by mining the Human Protein Atlas, as a unique big data resource. To perform a multifaceted screening process, XML and TSV files including immunohistochemistry expression data for 45 normal tissues and 20 tumor types were downloaded from the Human Protein Atlas website. For genes without high protein expression across critical normal tissues, a quasi H-score (range, 0-300) was computed per tumor type. All genes with a quasi H - score ≥ 150 were extracted. Of these, genes with cell surface localization were selected and included in a multilevel validation process. Among 19670 genes that encode proteins, 5520 membrane protein-coding genes were included in this study. During a multistep data mining procedure, 332 potential targets were identified based on the level of the protein expression across critical normal tissues and 20 tumor types. After validation, 23 cell surface proteins were identified and prioritized as candidate antibody-drug conjugate targets of which two have interestingly been approved by the FDA for use in solid tumors, one has been approved for lymphoma, and four have currently been entered in clinical trials. In conclusion, we identified and prioritized several candidate targets with translational potential, which may yield new clinically effective and safe antibody-drug conjugates. This large-scale antibody-based proteomic study allows us to go beyond the RNA-seq studies, facilitates bench-to-clinic research of targeted anticancer therapeutics, and offers valuable insights into the development of new antibody-drug conjugates.

Lonicera japonica Thunb is a traditional Chinese herbal medicine for treating intestinal inflammation. The extraction method of Lonicera japonica Thunb polysaccharide (LJP) has been developed previously by our research group. In this study, a Fourier transform infrared spectrometer (FT-IR) was used to perform a qualitative analysis of LJP and a precolumn derivatization high-performance liquid chromatography (HPLC) ((Palo Alto, CA, USA) method was used to explore the monosaccharide composition of LJP. Then, we studied the effect of LJP on the intestinal flora and immune functions of dextran sulfate sodium- (DSS-) induced colitis ulcerative mouse models. The results showed that LJP was consisted of 6 types of monosaccharides and had the characteristic absorption of typical polysaccharides. LJP can increase significantly the weight, organ index, serum cytokines (interleukin, tumor necrosis factor, and interferon-γ), secretory immunoglobulin A (SIgA) concentration, and natural killer (NK) cell and cytotoxic lymphocyte (CTL) activities in DSS-treated mice. The results of intestinal flora showed that a high dose (150 mg kg-1) of LJP had the best effects on improving the intestinal probiotics (Bifidobacterium and Lactobacilli) and antagonizing the pathogenic bacteria (Escherichia coli and Enterococcus). In addition, the measurement results of the spleen lymphocyte apoptosis confirmed from another perspective that LJP had protective effects of immune cells for DSS-treated mice.

METHOD: The FSI model, based on MRI data of an atherosclerosis patient, was used to simulate the deformations of the plaque and lumen during the process of two kinds of typical cSMT (the high-speed, low-amplitude spinal manipulation and the cervical rotatory manipulation). The biomechanical parameters were recorded, such as the highest wall shear stress (WSS), the maximum plaque wall stress (PWS), the wall tensile stress (Von mises stress, VWTS), and the strain. RESULT: The max_WSS was 33.77 kPa in the most extensive deformation. The highest WSS region on the plaque surface was also the highest PWS region. The max_PWS in a 12% stretch was 55.11 kPa, which was lower than the rupture threshold. The max_VWTS of the cap in 12% stretch which approached the fracture stress level was 116.75 kPa. Moreover, the vessel's max_VWTS values in 10% and 12% stretch were 554.21 and 855.19 kPa. They were higher than the fracture threshold, which might cause media fracture. Meanwhile, the 7% stretched strain was 0.29, closed to the smallest experimental green strains at rupture. CONCLUSION: The carotid arteries' higher stretch generated the higher stress level of the plaque. Cervical rotatory manipulation might cause plaque at a high risk of rupture in deformation after 12% stretch and more. Lower deformation of the plaque and artery caused by the high-speed, low-amplitude spinal manipulation might be safer.

BACKGROUND: Studies have shown complications of normal saline infusion because of its high-chloride content. Therefore, in the present study, we aimed to explore whether the use of low- versus high-chloride solutions benefited the unselected and specifically perioperative patients and was associated with different outcomes. METHODS: Studies on the use of low- versus high-chloride content intravenous solutions for perioperative patients, published up to July 15, 2019, were systematically reviewed, and primary and secondary outcomes were quantitatively summarized. RESULTS: A total of 14 eligible randomized controlled trials with 943 perioperative patients were included. Five studies reported all-cause mortality, and eight studies provided detailed data on renal replacement therapy (RRT). The pooled result suggested no statistically significant difference in the effect of low- versus high-chloride solutions on all-cause mortality (risk ratio (RR) = 1.39; 95%confidence interval (CI) = 0.23-8.26) and RRT (RR = 1.05; 95%CI = 0.63-1.76). The pooled results on acute kidney injury (AKI) and the use of allogenic blood transfusion (P > 0.05) were similar. CONCLUSION: Among specific perioperative patients, the use of low- versus high-chloride content intravenous solutions did not reduce the all-cause mortality, risk of severe AKI, or rate of RRT use. Further large randomized clinical trials are needed to confirm or refute this finding.

The present study was conducted to investigate the effects of early transplantation of the faecal microbiota from Tibetan pigs on the gut development of dextran sulphate sodium- (DSS-) challenged piglets. In total, 24 3-day-old DLY piglets were divided into four groups (n = 6 per group); a 2 × 2 factorial arrangement was used, which included faecal microbiota transplantation (FMT) (from Tibetan pigs) and DSS challenge. The whole trial lasted for 55 days. DSS infusion increased the intestinal density, serum diamine oxidase (DAO) activity, and colonic Escherichia coli count (P < 0.05), and decreased the Lactobacillus spp. count and mRNA abundances of epidermal growth factor (EGF), glucagon-like peptide-2 (GLP-2), insulin-like growth factor 1 (IGF-1), occludin, mucin 2 (MUC2), regeneration protein IIIγ (RegIIIγ), and interleukin-10 (IL-10) in the colon (P < 0.05). FMT increased the Lactobacillus spp. count and mRNA abundances of GLP-2, RegIIIγ, and IL-10 in the colon (P < 0.05), and decreased the intestinal density, serum DAO activity, and colonic E. coli number (P < 0.05). In addition, in DSS-challenged piglets, FMT decreased the disease activity index (P < 0.05) and attenuated the effect of DSS challenge on the intestinal density, serum DAO activity, and colonic E. coli number (P < 0.05). These data indicated that the faecal microbiota from Tibetan pigs could attenuate the negative effect of DSS challenge on the gut development of piglets.

PURPOSE: A recurrent neural network (RNN) and its variants such as gated recurrent unit-based RNN (GRU-RNN) were found to be very suitable for dose-volume histogram (DVH) prediction in our previously published work. Using the dosimetric information generated by nonmodulated beams of different orientations, the GRU-RNN model was capable of accurate DVH prediction for nasopharyngeal carcinoma (NPC) treatment planning. On the basis of our previous work, we proposed an improved approach and aimed to further improve the DVH prediction accuracy as well as study the feasibility of applying the proposed method to relatively small-size patient data. METHODS: Eighty NPC volumetric modulated arc therapy (VMAT) plans with local IRB's approval in recent two years were retrospectively and randomly selected in this study. All these original plans were created using the Eclipse treatment planning system (V13.5, Varian Medical Systems, USA) with ≥95% of PGTVnx receiving the prescribed doses of 70 Gy, ≥95% of PGTVnd receiving 66 Gy, and ≥95% of PTV receiving 60 Gy. Among them, fifty plans were used to train the DVH prediction model, and the remaining were used for testing. On the basis of our previously published work, we simplified the 3-layer GRU-RNN model to a single-layer model and further trained every organ at risk (OAR) separately with an OAR-specific equivalent uniform dose- (EUD-) based loss function. RESULTS: The results of linear least squares regression obtained by the new proposed method showed the excellent agreements between the predictions and the original plans with the correlation coefficient r = 0.976 and 0.968 for EUD results and maximum dose results, respectively, and the coefficient r of our previously published method was 0.957 and 0.946, respectively. The Wilcoxon signed-rank test results between the proposed and the previous work showed that the proposed method could significantly improve the EUD prediction accuracy for the brainstem, spinal cord, and temporal lobes with a p value < 0.01. CONCLUSIONS: The accuracy of DVH prediction achieved in different OARs showed the great improvements compared to the previous works, and more importantly, the effectiveness and robustness showed by the simplified GRU-RNN trained from relatively small-size DVH samples, fully demonstrated the feasibility of applying the proposed method to small-size patient data. Excellent agreements in both EUD results and maximum dose results between the predictions and original plans indicated the application prospect in a physically and biologically related (or a mixture of both) model for treatment planning.

The biological synthesis of nanoparticles, due to their environmental and biomedical properties, has been of particular interest to scientists and physicians. Here, iron nanoparticles (FeNPs) were synthesized using Satureja hortensis essential oil. Then, the chemical, functional, and morphological properties of these nanoparticles were characterized by typical experiments such as Uv-Vis, FTIR, XRD, FE-SEM, PSA, zeta potential, EDX, and EDX mapping. The results indicated Fe nanoparticles' formation with a cubic morphological structure and a particle size in the range of 9.3-27 nm. The antimicrobial effects of these nanoparticles were further evaluated using disc diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungal concentration (MFC) against two gram-positive bacterial strains (Staphylococcus aureus and Corynebacterium glutamicum), two gram-negative bacterial strains (Pseudomonas aeruginosa and Escherichia coli), and one fungus species Candida albicans. The results showed that green-synthesized Fe nanoparticles possessed higher antimicrobial properties than Satureja hortensis essential oil against selected pathogenic microorganisms, especially Gram-negative bacteria. Finally, the anticancer effect of these Fe nanoparticles was investigated on human cancer cells, K-562, and MCF-7, by the MTT assay. The results showed the anticancer effect of these nanoparticles against selected cell lines.

INTRODUCTION: Periodontal disease (PD) is a chronic inflammation of the soft tissues that support the structure of the tooth, and miRNAs are highly dynamic molecules that participate in the regulation of gene expression interfering with multiple genetic targets. The dysregulation of the expression of miRNAs has been associated with different types of pathologies; therefore, they are excellent molecules to be studied as biomarkers. Material and Methods. A search was made in the electronic databases of PubMed, Scopus, and Science Direct. The following key words were used: "microRNAs," "miRNAs," "periodontal disease," "periodontitis," and "biomarker"; employee independent search strategies with the Boolean operators "OR" and "AND"; a further search of the references of the selected studies was performed to detect potential studies that met the selection criteria. The data recollected from each article were author, country, year of publication, sample size, type of sample used to identify miRNAs, methodology used to identify miRNAs, type of periodontal disease, and miRNAs identified. RESULTS: Of the 13 selected studies, 6 used gingival tissue as a sample for the identification of miRNAs, 3 used gingival fluid, 2 used saliva, 1 used serum, and another used periodontal tissue. Chronic periodontitis was the most studied periodontal disease in 9 of the 13 selected articles; 7 used microarrays as the main technique for the identification of miRNAs. qRT-PCR was the assay choice to validate the identified miRNAs. CONCLUSION: The main type of periodontal disease on which most studies are focused is chronic periodontitis, with the main miRNAs being hsa-miR-146a, hsa-miR-146b, hsa-miR-155, and hsa-miR-200. This systematic review is one of the first to carry out an analysis of the current role of miRNAs in PD as biomarkers.

OBJECTIVE: Free triiodothyronine (FT3) is an independent risk factor for nonalcoholic fatty liver disease (NAFLD) in patients with euthyroid. However, whether FT3 has an independent effect on NAFLD in a population of type 2 diabetes remains unknown. The purpose of this study was to identify the potential role of FT3 in NAFLD with T2DM. DESIGN: A cross-sectional study. Patient. A total of 859 T2DM patients who met the inclusion criteria were included. There were 506 T2DM patients without NAFLD and 353 T2DM patients with NAFLD. METHODS: The independent samples t-test or Wilcoxon rank sum test were used for continuous variables of different distribution types, while the chi-square test was used for categorical variables. Pearson correlation analysis and linear regression were used to analyze the correlation between FT3 and clinical measurements and biochemical indicators. Multivariate logistic regression analysis was used to determine independent predictors. RESULTS: Patients with NAFLD had higher BMI, SBP, and DBP, longer duration of T2DM, and higher islet function index, blood glucose index, liver function index, renal function index, blood lipid index, and FT3. We also found that FT3 was affected by other five indicators, including ALT, CR, GGT, TC, and LDL-C only in the NAFLD group but not in the non-NAFLD group. FT3 was significantly associated with NAFLD in T2DM patients, and the prevalence of NAFLD increased gradually from the lowest FT3 tertile to the highest FT3 tertile (P for trend < 0.001). CONCLUSION: FT3 is independently associated with NAFLD in hospitalized T2DM patients after rigorous adjustment for various metabolic parameters.

Regulated necrosis (necroptosis) is crucially involved in cardiac ischaemia-reperfusion injury (MIRI). The aim of our study is to investigate whether shock wave therapy (SWT) is capable of exerting protective effects by inhibiting necroptosis during myocardial ischaemia-reperfusion (I/R) injury and the possible role of autophagy in this process. We established a hypoxia/reoxygenation (H/R) model in vitro using HL-1 cells to simulate MIRI. MTS assays and LDH cytotoxicity assay were performed to measure cell viability and cell damage. Annexin V/PI staining was used to determine apoptosis and necrosis. Western blotting was performed to assess the changes in cell signaling pathways associated with autophagy, necroptosis, and apoptosis. Reactive oxygen species (ROS) production was detected using DHE staining. Autophagosome generation and degradation (autophagic flux) were analysed using GFP and RFP tandemly tagged LC3 (tfLC3). HL-1 cells were then transfected with p62/SQSTM1 siRNA in order to analyse its role in cardioprotection. Our results revealed that SWT increased cell viability in the H/R model and decreased receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and RIPK3 expression. ROS production was also inhibited by SWT. Moreover, SWT decreased Beclin1 expression and the ratio of LC3-II/LC3-I following H/R. Simultaneously, in the tfLC3 assay, the SWT provoked a decrease in the cumulative autophagosome abundance. siRNA-mediated knockdown of p62 attenuated H/R-induced necroptosis, and SWT did not exert additive effects. Taken together, SWT ameliorated H/R injury by inhibiting necroptosis. SWT also relieved the blockade of autophagic flux in response to H/R injury. The restoration of autophagic flux by SWT might contribute to its cardioprotective effect on necroptosis following H/R injury.

PURPOSE: To evaluate the clinical efficacy of prodom in the administration of urokinase in the vagina in couples with impaired semen liquefaction. MATERIALS AND METHODS: Overall, 261 patients with impaired semen liquefaction were randomly divided into prodom-assisted urokinase treatment (PAUT) group (n = 91), syringe-assisted urokinase treatment (SAUT) group (n = 86), and traditional treatment (TT) group (n = 84) in the first stage. If the first stage of treatment failed, other treatment methods were initiated instead and the patients were grouped according to the newer treatment method in the second stage. The pregnancy rate, time-to-conception, and treatment costs were evaluated in each group. RESULTS: In the first stage, the pregnancy rate in the PAUT, SAUT, and TT groups was 69.23%, 29.07%, and 22.62%, respectively; the time-to-conception was 2.66 ± 1.44, 3.69 ± 2.61, and 3.86 ± 3.00 months, respectively; the treatment costs were 658.18 ± 398.40, 666.67 ± 507.50, and 680.56 ± 480.94 $, respectively. The pregnancy rate and time-to-conception were different in the PAUT group compared with those in SAUT and TT groups (all P < 0.05). However, the difference in treatment costs was not significant (P = 0.717). In the second stage, 154 nonpregnant patients were divided into nine treatment groups, and the effects of changing TT to PAUT on the pregnancy rate, time-to-conception, and treatment costs were observed to be different from those of other treatments (all P < 0.05). CONCLUSION: Prodom-assisted urokinase can effectively treat male infertility secondary to impaired semen liquefaction.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). So far, there is no biomarker-based prediction tool available for EPS. Matrix metalloproteinase-2 (MMP-2) is a protein involved in the breakdown of the extracellular matrix, and the effluent MMP-2 can be a potential biomarker of EPS. This study is aimed at developing a nomogram for EPS based on effluent MMP-2 levels. Patients and Methods. We enrolled 18 EPS patients and 90 gender-matched PD patients without EPS in this cross-sectional case-controlled study. The effluent MMP-2 levels and possible risk factors for EPS were analyzed using multivariable logistic regression, and a nomogram was developed. The nomogram was validated using 200 bootstrap resamples to reduce overfit bias. RESULTS: The effluent MMP-2 levels in EPS patients were significantly higher than those in normal PD patients (p < 0.001, Manny-Whitney U test). Effluent MMP-2 levels and PD duration were independently associated with EPS risks (p < 0.001 and p = 0.001) in multivariate logistic regression. A nomogram based on MMP-2 levels and PD duration was proposed. The AUC of MMP-2 was 0.824, and the AUC of the nomogram was 0.907 (p = 0.05). CONCLUSION: A nomogram based on effluent MMP-2 levels and PD duration may predict EPS with high accuracy.

Combretum zeyheri and Combretum platypetalum have been shown to have anticancer, antibacterial, antituberculosis, and antifungal effects in both in vivo and in vitro studies. This study sought to evaluate the antiproliferative effects of compounds isolated from C. zeyheri and C. platypetalum on Jurkat T and HL-60 cancer cell lines in combination with doxorubicin and/or chlorambucil. At their GI50 concentrations, the isolated compounds were combined with the corresponding GI50 of chlorambucil and doxorubicin. The cytotoxic effects of the combined compounds were determined on BALB/c mouse peritoneal cells. All the 4 isolated compounds had significant cytotoxic effects on Jurkat T cells. Compounds CP 404 (1), CP 409 (2), CZ 453 (3), and CZ 455 (4) had GI50s on Jurkat T cells of 3.98, 19.33, 6.82, and 20.28 μg/ml, respectively. CP 404 (1), CP 409 (2), CZ 453 (3), and CZ 455 (4) showed GI50s of 14.18, 28.69, 29.87, and 16.46 μg/ml on HL-60 cancer cell lines, respectively. The most potent combination against Jurkat T cells was found to be CP 404 (1) and chlorambucil. This combination showed no cytotoxic effects when tested on BALB/c mouse peritoneal cells. It was concluded that the compounds extracted from C. zeyheri and C. platypetalum inhibit the growth of Jurkat T cells in vitro. The combination of the compounds with anticancer drugs enhanced their anticancer effects. The combination of CP 404 (1) and chlorambucil was found not to be toxic to normal mammalian cells. Therefore, CP 404 (1), 3-O-β-L-rrhamnopyranosyl-5,7,3'4',5'-pentahydroxyflavone, has the potential to be a source of lead compounds that can be developed for anticancer therapy. Further structure-activity relationship studies on this compound are warranted.

Tumor segmentation in brain MRI images is a noted process that can make the tumor easier to diagnose and lead to effective radiotherapy planning. Providing and building intelligent medical systems can be considered as an aid for physicians. In many cases, the presented methods' reliability is at a high level, and such systems are used directly. In recent decades, several methods of segmentation of various images, such as MRI, CT, and PET, have been proposed for brain tumors. Advanced brain tumor segmentation has been a challenging issue in the scientific community. The reason for this is the existence of various tumor dimensions with disproportionate boundaries in medical imaging. This research provides an optimized MRI segmentation method to diagnose tumors. It first offers a preprocessing approach to reduce noise with a new method called Quantum Matched-Filter Technique (QMFT). Then, the deep spiking neural network (DSNN) is implemented for segmentation using the conditional random field structure. However, a new algorithm called the Quantum Artificial Immune System (QAIS) is used in its SoftMax layer due to its slowness and nonsegmentation and the identification of suitable features for selection and extraction. The proposed approach, called QAIS-DSNN, has a high ability to segment and distinguish brain tumors from MRI images. The simulation results using the BraTS2018 dataset show that the accuracy of the proposed approach is 98.21%, average error-squared rate is 0.006, signal-to-noise ratio is 97.79 dB, and lesion structure criteria including the tumor nucleus are 80.15%. The improved tumor is 74.50%, and the entire tumor is 91.92%, which shows a functional advantage over similar previous methods. Also, the execution time of this method is 2.58 seconds.

Acetyl-L-carnitine (ALC) is an effective substrate for mitochondrial energy metabolism and is known to prevent neurodegeneration and attenuate heavy metal-induced injury. In this study, we investigated the function of ALC in the recovery of mouse spermatogonia cells (GC-1 cells) after heat stress (HS). The cells were randomly divided into three groups: control group, HS group (incubated at 42°C for 90 min), and HS + ALC group (treatment of 150 μM ALC after incubated at 42°C for 90 min). After heat stress, all of the cells were recovered at 37°C for 6 h. In this study, the content of intracellular lactate dehydrogenase (LDH) in the cell supernatant and the malondialdehyde (MDA) levels, catalase (CAT) levels, and total antioxidant capacity (T-AOC) were significantly increased in the HS group compared to the CON group. In addition, the mitochondrial membrane potential (MMP) was markedly decreased, while the apoptosis rate and the expression of apoptosis-related genes (Bcl-2, Bax, and caspase3) were significantly increased in the HS group compared to the CON group. Furthermore, the number of autophagosomes and the expression of autophagy-related genes (Atg5, Beclin1, and LC3II) and protein levels of p62 were increased, but the expression of LAMP1 was decreased in the HS group compared to the CON group. However, treatment with ALC remarkably improved cell survival and decreased cell oxidative stress. It was unexpected that levels of autophagy were markedly increased in the HS + ALC group compared to the HS group. Taken together, our present study evidenced that ALC could alleviate oxidative stress and improve the level of autophagy to accelerate the recovery of GC-1 cells after heat stress.

The aim of this study was to comprehensively review our experience with odontogenic infections in the head and neck region requiring treatment at a national referral center. We retrospectively reviewed 85 patients treated at the Chair and Clinic of Maxillofacial Surgery of the University Hospital in Wrocław between January 2018 and June 2019. We excluded patients with nonondontogenic infections or other than purulent clinical forms of dentivitis in the head and neck region. Several demographic, clinicopathological, and treatment variables were assessed. The majority of patients were men who were referred for inpatient treatment by a dentist or family doctor, presented to the Hospital Emergency Ward (SOR) by themselves, or transported to the SOR by paramedics SOR from their home or another hospital. All patients were treated in accordance with the current guidelines for head and neck region odontogenic infections. An incision was made and the abscess was drained. The odontogenic cause was removed followed by the collection of tissue for microbiological examination. The course of infection was monitored by means of laboratory parameters such as leukocyte counts and c-reactive protein levels. Odontogenic infections in the head and neck region are a persistent and common problem. Rapid, accurate diagnosis and treatment minimizes the risk of life-threatening complications, shortens the hospitalization period, and lowers treatment costs.

In addition to serving as the building blocks for protein synthesis, amino acids can be used as an energy source, through catabolism. The transamination, oxidative deamination, and decarboxylation processes that occur during amino acid catabolism are catalyzed by specific enzymes, including aspartate aminotransferase (AST), glutamate dehydrogenase (GDH), glutamic acid decarboxylase (GAD), and ornithine decarboxylase (ODC); however, the overall molecular mechanisms through which amino acid catabolism occurs remain largely unknown. To examine the role of mechanistic target of rapamycin complex 1 (mTORC1) on amino acid catabolism, mTORC1 was inactivated by rapamycin or shRNA targeting Raptor, versus activated by overexpressing Rheb or amino acids in human hepatocytes. The expression of amino acid catabolic genes and related transcription factor was investigated by RT/real-time PCR and western blot analysis. A few types of amino acid metabolite were examined by ELISA and HPLC analysis. The data showed that inactivated mTORC1 resulted in inhibition of NF-κB and the expression of AST, GDH, GAD, and ODC, whereas activated mTORC1 enhanced NF-κB activation and the expression levels of the catabolism-associated genes. Further, inhibition of NF-κB reduced the expression levels of AST, GDH, GAD, and ODC. mTORC1 upregulated NF-κB activation and the expression of AST and ODC in response to glutamate and ornithine treatments, whereas rapamycin inhibited the utilization of glutamate and ornithine in hepatocytes. Taken together, these results indicated that the mTORC1/NF-κB axis modulates the rate of amino acid catabolism by regulating the expression of key catabolic enzymes in hepatocytes.

Macrocybe gigantea (M. gigantea) is a macrofungus genus that contains a big number of fairly fleshy gilled mushrooms with white spores. This macrofungus produces diverse bioactive compounds, antioxidants, and water-soluble polysaccharides. However, the genomic resources of this species remain unknown. Here, we assembled the genome of M. gigantea (41.23 Mb) into 336 scaffolds with a N50 size of 374,455 bp and compared it with the genomes of eleven other macrofungi. Comparative genomics study confirmed that M. gigantea belonged to the Macrocybe genus, a stand-alone genus different from the Tricholoma genus. In addition, we found that glycosyl hydrolase family 28 (GH28) in M. gigantea shared conserved motifs that were significantly different from their counterparts in Tricholoma. The genomic resource uncovered by this study will enhance our understanding of fungi biology, especially the differences in their growth rates and energy metabolism.

BACKGROUND: To investigate the effects of phenylethanoid glycosides (PhGs) extracted from Herba Cistanches on the behavioral and cognition capacity of the APP/PSI transgenic mice with Alzheimer's disease (AD). METHODS: AD mice were randomly divided into the control group, model group, donepezil group, PhG groups, and verbascose group, respectively. Three weeks later, the animals were subject to behavioral and cognition evaluation by the nesting test, Morris water maze test, and step-down test. RESULTS: The cognition capacity in these groups showed a significant increase compared with that in the model group. The step-down test indicated that the errors induced by the memory decrease in the PhG groups and verbascose group showed a significant decrease compared with those in the model group (P < 0.05). CONCLUSIONS: PhGs attenuated the cognitive dysfunction features of the APP/PSI transgenic gene. Besides, PhGs were the active components for the anti-AD activity of H. Cistanches.

OBJECTIVE: Tranexamic acid (TXA) is increasingly used in orthopedic surgery to reduce blood loss; however, there are concerns about the risk of venous thromboembolic (VTE) complications. The aim of this study was to evaluate TXA safety in patients undergoing lower limb orthopedic surgical procedures. DESIGN: A meta-analysis was performed on the PubMed, Web of Science, and Cochrane Library databases in January 2020 using the following string (Tranexamic acid) AND ((knee) OR (hip) OR (ankle) OR (lower limb)) to identify RCTs about TXA use in patients undergoing every kind of lower limb surgical orthopedic procedures, with IV, IA, or oral administration, and compared with a control arm to quantify the VTE complication rates. RESULTS: A total of 140 articles documenting 9,067 patients receiving TXA were identified. Specifically, 82 studies focused on TKA, 41 on THA, and 17 on other surgeries, including anterior cruciate ligament reconstruction, intertrochanteric fractures, and meniscectomies. The intravenous TXA administration protocol was studied in 111 articles, the intra-articular in 45, and the oral one in 7 articles. No differences in terms of thromboembolic complications were detected between the TXA and control groups neither in the overall population (2.4% and 2.8%, respectively) nor in any subgroup based on the surgical procedure and TXA administration route. CONCLUSIONS: There is an increasing interest in TXA use, which has been recently broadened from the most common joint replacement procedures to the other types of surgeries. Overall, TXA did not increase the risk of VTE complications, regardless of the administration route, thus supporting the safety of using TXA for lower limb orthopedic surgical procedures.

Gastroesophageal reflux disease (GERD) is induced by the reflux of stomach contents or gastric acid, pepsin into the esophagus for prolonged periods of time due to defection of the lower esophageal sphincter. Reflux esophagitis is a disease found in less than 50% of GERD patients. This study is aimed at evaluating the protective effect of Curcumae longae Rhizoma 30% EtOH extract (CLR) in acute reflux esophagitis (ARE) rats. CLR measured antioxidant activity through in vitro experiments. Based on the results, we performed experiments in vivo. Before 90 min ARE induction, CLR was administered orally by concentration. ARE was derived by linking the metastatic junction between pylorus and forestomach and corpus in Sprague-Dawley rats. And rats were sacrificed 5 h after surgery. We analyzed the expression of antioxidant and inflammatory-related markers by western blot and observed the production of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reactive oxygen species (ROS), peroxynitrite (ONOO-), and thiobarbituric acid reactive substance (TBARS). The administration of CLR reduced esophagus tissue damage in rats with acute reflux esophagitis and decreased the elevated ALT, AST, ROS, ONOO-, and TBARS. In addition, CLR effectively increased antioxidant-related factors and reduced inflammatory protein. Overall, these results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE. Overall, CLR treatment informed that markedly ameliorated inactivation of NF-κB led to the inhibition of the expressions of proinflammatory proteins. These results suggest that CLR would be used as a therapeutic material in protection and treatment for ARE.

BACKGROUND: The objective of this systematic review was to evaluate current studies available reporting the antibiotic spacer combined with Ilizarov methods in the treatment of infected nonunion of tibia and to perform meta-analysis of bone results and infection recurrence to assess the efficacy of an antibiotic spacer combined with Ilizarov methods. METHODS: The MEDLINE, Embase, Cochrane Library, CNKI, and CBM (Chinese Biological Medicine) databases were searched for articles published between January 2000 and July 2020. Assessment of study quality was performed using a modified version of the Newcastle-Ottawa scale. Effect size and 95% confidence intervals were calculated for the main outcome. Heterogeneity was assessed. Fixed-effect modeling and Stata version 15.1 were used to analyze the data. Sensitivity analyses were conducted with the evidence of heterogeneity. RESULTS: 11 studies involving 210 patients with infected nonunion of tibia were finally included in our meta-analysis. Bone results and infection recurrence were analyzed based on the single-arm meta-analysis. The average of external fixation index (EFI) was 46.88 days/cm in all studies included. The excellent rate in bone results and the rate of infection recurrence was 65% (95% CI: [0.22, 0.97], I 2 = 0.0%, P = 0.932) and 6.99% (95% CI: [0.052, 0.325], I 2 = 0.0%, P = 1.000) in patients with infected nonunion of tibia treated with an antibiotic spacer combined with Ilizarov methods. CONCLUSIONS: Our meta-analysis revealed that the patients with infected nonunion of tibia treated with an antibiotic spacer combined with Ilizarov methods had a high rate of excellent bone results and a low rate of infection recurrence. Therefore, combining the antibiotic spacer with Ilizarov methods may be an applicable choice for repairing and reconstructing infected nonunion of tibia.

Intracranial aneurysm (IA) is a complex disease caused by genetic and environmental factors. Evidence indicates that inflammation plays an important role in IA occurrence. We aimed to explore the associations between inflammatory cytokine gene polymorphisms and IA in a Chinese population. This study enrolled 768 participants of Han ethnicity, including 384 patients with IA and 384 healthy individuals. Sixteen single nucleotide polymorphisms (SNPs) of IL1, IL6, IL12, and TNF-α genes were genotyped using the Sequenom MassARRAY platform. Univariate and multivariate logistic regression analyses were used to analyze the associations. We found IL12B rs3181216 was significantly associated with IA in the recessive and additive models (OR = 0.46, 95% CI = 0.23-0.89, P = 0.022; OR = 0.74, 95% CI = 0.56-0.98, P = 0.034, respectively). TNF-α rs1799964 was associated with IA in dominant and additive models (OR = 0.67, 95% CI = 0.46-0.98, P = 0.041; OR = 0.71, 95% CI = 0.51-0.98, P = 0.034, respectively). IL1A rs17561 was associated with single IA susceptibility (dominant model: OR = 0.52, 95% CI = 0.31-0.85, P = 0.040). The IL12B rs3181216 polymorphism was associated with single IA susceptibility in the recessive model (OR = 0.41, 95% CI = 0.18-0.93, P = 0.033). The IL12B rs2195940 polymorphism was associated with multiple IAs susceptibility (dominant model: OR = 0.28, 95% CI = 0.09-0.89, P = 0.031; additive model: OR = 0.28, 95% CI = 0.09-0.90, P = 0.032). TNF-α rs1799964 was associated with multiple IAs susceptibility in the dominant model (OR = 0.54, 95% CI = 0.30-0.97, P = 0.040). No associations were found between other polymorphisms and IA susceptibility. Therefore, IL1A, IL12B, and TNF-α gene polymorphisms are associated with IA susceptibility in a Chinese population.

BACKGROUND: Glycemic control is the level of glucose in diabetes patient. Evidence regarding glycemic control is scarce in resource-limited settings, and this study was conducted to generate information regarding the prevalence and predictors of glycemic control among diabetes mellitus patients attending their care from the referral hospitals of the Amhara region, Ethiopia. METHODS: A cross-sectional study design was implemented. A simple random sampling technique was used. Data were collected from March 2018 to January 2020. The data were collected using interviews, chart review, and blood samples. Hemoglobin A1c was measured using high-performance liquid chromatography. Data were entered into Epi-info software and analyzed by SPSS software. Descriptive statistics were used to estimate the prevalence of glycemic control; linear regression was used to identify the predictors of HbA1c. RESULTS: A total of 2554 diabetes patients were included giving for the response rate of 95.83%. The mean age of the study participants was 54.08 years [SD (standard deviation) ± 8.38 years]. The mean HbA1c of the study participants was 7.31% [SD ± 0.94%]. Glycemic control was poor in 55.32% [95% CI: 53.4%-57.25%] of diabetes patients. The glycemic control of diabetes patients was determined by BMI (β 0.1; [95% CI: 0.09-0.1]), type 2 diabetes (β -0.14; [95% CI: -0.11-0.16]), age (β 0.22; [95% CI: 0.02-0.024]), duration of the disease (β 0.04; [95% CI: 0.037-0.042]), the presence of hypertension (β 0.12; [95% CI:0.09-0.16]), regular physical exercise (β -0.06; [95% CI: -0.03-0.09]), medication adherence (β -0.16; [95% CI: -0.14-0.18]), and male (β 0.34; [95% CI: 0.31-.037]). CONCLUSION: The glycemic control of diabetes patients was poor, and it needs the attention of decision-makers.

BACKGROUND: Chemotherapy is the primary treatment modality used for patients with acute lymphoblastic leukemia (ALL), but inevitably causes microbiota-related oral complications. This study is aimed at investigating the effects of chemotherapy on oral health status, caries risk, and oral microbiome in pediatric patients with ALL. METHODS: Thirty-nine children with ALL receiving chemotherapy were enrolled, and a gender-, age-, dentition stage, and socioeconomic class matched healthy counterpart were recruited. Demographic information and overall health condition were obtained through the questionnaire and medical records. Oral examination was performed to assess caries and salivary status, plaque index, and other oral manifestations. Cariogram was used to assess the overall caries risk. Supragingival samples of thirteen ALL subjects and their counterparts were randomly selected to perform a 16S ribosomal RNA gene 454 pyrosequencing. Raw sequence data were screened, trimmed, and filtered using Seqcln and MOTHUR. RESULTS: The prevalence of dental caries, gingivitis, oral mucositis, xerostomia, and candidiasis in ALL groups was higher than that of the control group (p < 0.05). Children with ALL demonstrated higher caries risk compared to healthy controls (HC) based upon Cariogram (p < 0.05). The oral microbial structure of ALL patients receiving chemotherapy is different from that of healthy controls. Oral microbiota of ALL groups showed less alpha diversity and significant differences in the composition of the oral microbiome compared to healthy controls. CONCLUSIONS: ALL patients receiving chemotherapy demonstrated compromised oral health, high caries risk, alteration of caries-related factors, and dysbiosis of oral microbiota. These findings may be of clinical importance in developing better strategies for personalized preventive management of oral diseases for pediatric children with ALL.

Air pollution has become a serious public health problem globally. Recent studies support the harmful effect of air pollution on human health, in addition to scientific evidence that recognizes it as a human carcinogen. The buccal micronucleus cytome (BMC) assay is employed extensively to measure cytotoxic and genotoxic damage in a population exposed to environmental contamination. The objective of this study was to evaluate the cytotoxic and genotoxic effects in healthy young adults exposed to different levels of air pollution and to identify areas with air pollution rates above the regulatory limits. This study was performed through the BMC assay in oral mucosa samples from 80 healthy young adults from the Guadalajara metropolitan zone. Three highly contaminated areas were taken into account: Tlaquepaque, Miravalle, and Las Pintas. Las Aguilas, a less contaminated area, was used as a reference. The frequencies of nuclear abnormalities in the areas with the highest and lowest levels of air pollution were compared with the Mann-Whitney U test. In addition, an analysis of the concentration of environmental pollutants, particulate matter ≤ 10 μm (PM10), ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO), were carried out in the mentioned areas, in order to identify the events above the regulatory limits in a year period. The results showed that young adults exposed to a higher concentration of pollutants showed higher frequencies of nuclear abnormalities. The individuals from the areas of Tlaquepaque, Miravalle, and Las Pintas showed cytotoxic damage since statistically significant differences were found in the abnormalities of pyknotic nuclei (PNs), condensed chromatin (CC), karyorrhexis (KX), and karyolysis (KL). The individuals who showed the most cytotoxic damage were from the Las Pintas area with higher frequencies in nuclear abnormalities (PNs, CC, KX, and KL) (p < 0.0001). Genotoxic damage was found in individuals from two zones, Miravalle and Las Pintas, with statistically significant differences in the abnormality of nuclear buds (NBUDs) (p < 0.0001). Our results suggest that exposure to high levels of air pollution in healthy young adults has an effect on cellular and nuclear integrity and thus in human health, since areas with higher air pollution showed an increase in cytotoxicity, specifically in early and late markers of cell death (CC, KX, PN, and KL) and genotoxic damage (BUDs).

INTRODUCTION: The current study is aimed at exploring the effect of Shentong Zhuyu Decoction on the proliferation, migration, invasion, and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and its underlying molecular mechanism. MATERIALS AND METHODS: The type II collagen-induced arthritis (CIA) model was established. Subsequently, the RA-FLS were isolated from the CIA rat model and identified by immunohistochemistry. The viability, apoptosis, cell cycle, migration, and invasion of RA-FLS were detected by the cell counting kit 8 (CCK-8) assay, flow cytometry, wound-healing assay, and transwell invasion assay, respectively. The levels of MAPK p38, PPARγ, CTGF, Bcl-2, Bax, caspase-3, IL-1β, MMP-3, CDK4, and cyclin D1 were determined by qRT-PCR and western blotting, respectively. RESULTS: After treatment with Shentong Zhuyu Decoction medicated serum, the OD570 value, migrative and invasive abilities, and the secretion of IL-1β, MMP-3 were remarkably decreased in RA-FLS, while the apoptosis rate was increased. Further, results showed that Shentong Zhuyu Decoction inhibited the transition from the G1 phase to S phase. Additionally, Shentong Zhuyu Decoction significantly inhibited the expression of Bcl-2, CDK4, cyclin D1, MAPK p-p38, and CTGF, whereas elevated the levels of Bax, caspase-3, and PPARγ. Importantly, the effects of Shentong Zhuyu Decoction were consistent with the trends of MAPK P38 inhibitor (SB203580) and PPARγ agonist (GW1929). CONCLUSIONS: Shentong Zhuyu Decoction inhibited viability, inflammatory response, migration, invasion, and transition from the G1 phase to S phase and promoted apoptosis of RA-FLS via the MAPK p38/PPARγ/CTGF pathway.

OBJECTIVE: To explore the value of combined detection of peripheral blood P-selectin (CD62p) and D-dimer (D-dimer) in the judgment of acute cerebral infarction severity and short-term prognosis. METHODS: 268 patients with acute cerebral infarction from February 2015 to February 2019 were selected as the observation group. According to the National Institute of Health stroke scale, there were 90 cases (SCI group), 88 cases (MOCI group), and 90cases (MICI group) in the severe, moderate, and mild cerebral infarction groups, respectively. In the same period, 80 cases of healthy people served as the Normal group. Use flow cytometry to detect CD62p in peripheral blood and magnetic bead method to detect D-dimer level within 24 hours of onset. Logistic regression was used to analyze whether the two are factors affecting the short-term prognosis of acute cerebral infarction, and the ROC curve was drawn to evaluate the value of the combined detection of the two in the short-term prognosis of patients with acute cerebral infarction. RESULTS: Peripheral blood D-dimer and CD62p levels (2.95 ± 0.76 ng/l, 34.03 ± 5.29 ng/l) in the SCI group were higher than those in the MOCI group (2.30 ± 0.51 ng/l, 27.58 ± 5.56 ng/l) and the MICI group (1.87 ± 0.40 ng/l, 19.60 ± 3.98 ng/l); the difference between the groups was statistically significant (P < 0.05). Logistic regression analysis showed that D-dimer and CD62p were independent risk factors affecting the poor prognosis of patients with acute cerebral infarction (OR values were 3.752 and 1.213, and 95% CI were 1.612-7.934 and 1.093-1.342, respectively, both P < 0.05). The AUC of D-dimer combined with CD62p for predicting poor prognosis of acute cerebral infarction is 0.859, which is better than D-dimer and CD62p alone. CONCLUSION: Peripheral blood D-dimer combined with CD62p detection is helpful for the risk stratification and short-term prognosis assessment of patients with acute cerebral infarction. Clinical detection is of great significance for the prevention and monitoring of disease development.

INTRODUCTION: Baicalein has been shown to have antitumor activities in several cancer types. However, its acting mechanisms remain to be further investigated. This work is aimed at exploring the functional long noncoding RNA (lncRNA)/microRNA (miRNA)/messenger RNA (mRNA) triplets in response to baicalein in hepatocellular carcinoma (HCC) cell to understand the mechanisms of baicalein in HCC. METHODS: Differentially expressed lncRNAs (DELs) and miRNAs (DEMs) in HCC cell treated with baicalein were first screened using GSE95504 and GSE85511, respectively. miRNA targets for DELs were predicted and intersected with DEMs, after which the miRNA expression was validated using ENCORI and its prognostic value was assessed using Kaplan-Meier plotter. Potential miRNA targets were predicted by 3 prediction tools, after which expression level was validated at UALCAN and Human Protein Atlas. Kaplan-Meier plotter was used to evaluate the effects of these genes on overall survival and recurrence-free survival of HCC patients. Enrichment analyses for these genes were performed at DAVID. RESULTS: Here, we identified 14 overlapping DELs and 26 overlapping DEMs in the baicalein treatment group than those in the DMSO treatment group. Subsequently, by analyzing expression and clinical significance of miRNAs, hsa-miR-4443 was found as a highly potential miRNA target. Then, targets of hsa-miR-4443 were predicted and analyzed, and we found AKT1 was the most potential target for hsa-miR-4443. Hence, the lncRNAs-hsa-miR-4443-AKT1 axis that can respond to baicalein was established. CONCLUSION: Collectively, we elucidated a role of lncRNAs-hsa-miR-4443-AKT1 pathway in response to baicalein treatment in HCC, which could help us understand the roles of baicalein in inhibiting cancer progression and may provide novel insights into the mechanisms behind HCC progression.

Lung adenocarcinoma (LUAD), which accounts for 60% of non-small-cell lung cancers, is poorly diagnosed and has a low average 5-year survival rate (approximately 20%). It remains the leading cause of cancer-related deaths worldwide. Studies on long noncoding RNAs (lncRNAs) in LUAD-related competing endogenous RNA (ceRNA) networks are limited. We aimed to identify novel prognostic biomarkers for LUAD using bioinformatic tools and data analysis. We systemically integrated differentially expressed genes and clinically significant modules using weighted correlation network analysis. We performed a functional analysis of the collected candidate genes and explored three LUAD-related genes (VWF, PECAM1, and COL1A1) associated with the overall survival rates of patients with LUAD. Based on Cox proportional hazards analysis of candidate mRNAs and lncRNAs together with differentially expressed microRNAs, we constructed ceRNA networks, obtained 12 lncRNAs in the ceRNA networks, and revealed seven novel lncRNAs AC021016.2, AC079630.1, AC116407.1, AC125807.2, AF131215.5, LINC01936, and RHOXF1-AS1. These lncRNAs were found to be associated with overall survival rates and are suitable for the prediction of prognosis by Kaplan-Meier survival and receiver operating characteristic curve analyses. In particular, three lncRNAs-AF131215.5, AC125807.2, and LINC01936-showed an independent prognostic value of overall survival for patients with LUAD. We evaluated the diagnostic capabilities of seven lncRNAs for patients with LUAD using principal component analysis and the Gene Set Variation Analysis index. lncRNAs and crucial genes could be effectively used for distinguishing LUAD tumors from normal tissues in the Gene Expression Omnibus profile. In particular, AC021016.2 showed a significant prognostic value in the validation dataset. Our findings reveal the significance of exploring lncRNAs in cancer-related ceRNAs using bioinformatic strategies.

BACKGROUND: Coronary artery disease (CAD) is one of the most common causes of sudden death with high morbidity in recent years. This paper is aimed at exploring the early peripheral blood biomarkers of sudden death and providing a new perspective for clinical diagnosis and forensic pathology identification by integrated bioinformatics analysis. METHODS: Two microarray expression profiling datasets (GSE113079 and GSE31568) were downloaded from the Gene Expression Omnibus (GEO) database, and we identified differentially expressed lncRNAs, miRNAs, and mRNAs in CAD. Gene Ontology (GO) and KEGG pathway analyses of DEmRNAs were executed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified. Finally, we constructed a competitive endogenous RNA (ceRNA) regulation network among lncRNAs, miRNAs, and mRNAs. Also, the 5 miRNAs of the ceRNA network were verified by RT-PCR. RESULTS: In total, 86 DElncRNAs, 148 DEmiRNAs, and 294 DEmRNAs were dysregulated in CAD. We received 12 GO terms and 5 pathways of DEmRNAs. 31 nodes and 78 edges were revealed in the PPI network. The top 10 genes calculated by degree method were identified as hub genes. Moreover, there were a total of 26 DElncRNAs, 5 DEmiRNAs, and 13 DEmRNAs in the ceRNA regulation network. We validated the 5 miRNAs of the ceRNA network by RT-PCR, which were consistent with the results of the microarray. CONCLUSIONS: In this paper, a CAD-specific ceRNA network was successfully constructed, contributing to the understanding of the relationship among lncRNAs, miRNAs, and mRNAs. We identified potential peripheral blood biomarkers in CAD and provided novel insights into the development and progress of CAD.

Poultries including chickens, ducks, geese, and pigeons are widely used in the biological and medical research in many aspects. The genetic quality of experimental poultries directly affects the results of the research. In this study, following electrophoresis analysis and short tandem repeat (STR) scanning, we screened out the microsatellite loci for determining the genetic characteristics of Chinese experimental chickens, ducks, geese, and pigeons. The panels of loci selected in our research provide a good choice for genetic monitoring of the population genetic diversity of Chinese native experimental chickens, ducks, geese, and ducks.

Quaternary ammonium methacrylates (QAMs) are useful antimicrobial compounds against oral bacteria. Here, we investigated the effects of two QAMs, dimethylaminododecyl methacrylate (DMADDM) and dimethylaminohexadecyl methacrylate (DMAHDM), on biofilm formation, survival and development of tolerance by biofilm, and survival and development of tolerance against QAMs after prolonged starvation. Enterococcus faecalis (E. faecalis), Streptococcus gordonii (S. gordonii), Lactobacillus acidophilus (L. acidophilus), and Actinomyces naeslundii (A. naeslundii) were used. Minimum inhibitory concentration (MIC) of QAMs against multispecies biofilm was determined. Biofilm formed under sub-MIC was observed by crystal violet staining and confocal laser scanning microscopy (CLSM). Metabolic activity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactic acid production measurement. Development of tolerance was determined by MIC values before and after exposure to QAMs or after prolonged starvation. It was found that E. faecalis and S. gordonii could survive and form biofilm under sub-MIC of QAMs. Lactic acid production from biofilms formed under sub-MIC was significantly higher than control specimens (p < 0.05). The exposure to sub-MIC of QAMs promoted biofilm formation, and prolonged starvation or prolonged contact with sub-MIC helped bacteria develop tolerance against killing by QAMs.

The recently published 2019 guidelines on chronic coronary syndromes (CCS) focus on the need for noninvasive imaging modalities to accurately establish the diagnosis of coronary artery disease (CAD) and assess the risk of clinical scenario occurrence. Appropriate patient management should rely on controlling symptoms, improving prognosis, and guiding each therapeutic strategy as well as monitoring disease progress. Among the noninvasive imaging modalities, cardiovascular magnetic resonance (CMR) has gained broad acceptance in past years due to its unique features in providing a complete assessment of CAD through data on cardiac anatomy and function and myocardial viability, with high spatial and temporal resolution and without ionizing radiation. In detail, evaluation of the presence and extent of myocardial ischemia through stress CMR (S-CMR) has shown a high rule-in power in detecting functionally significant coronary artery stenosis in patients suspected of CCS. Moreover, S-CMR technique may add significant prognostic value, as demonstrated by different studies which have progressively evidenced the valuable power of this multiparametric imaging modality in predicting adverse cardiac events. The latest scientific progress supports a greater expansion of S-CMR with improvement of quantitative myocardial perfusion analysis, myocardial strain, and native mapping within the same examination. Although further study is warranted, these techniques, which are currently mostly restricted to the research field, are likely to become increasingly prevalent in the clinical setting with the scope of increasing accuracy in the selection of patients to be sent to invasive revascularization. This review investigates the diagnostic and prognostic role of S-CMR in the context of CAD, by analysing a strong, long-standing, scientific evidence together with an appraisal of new advanced techniques which may potentially enrich CAD management in the next future.

BACKGROUND: The efficacy of a thrombin-based hemostatic agent (Floseal®) on reducing postoperative blood loss after total knee arthroplasty (TKA) was still unclear. The aim of our study was to conduct a prospective randomized controlled study to compare the blood conservation effects of Floseal® and topical TXA in patients with preexisting thromboembolic risk undergoing primary minimally invasive TKA. METHODS: Our power analysis of this study was based upon the following description, to obtain a statistical power of 0.90 and an alpha error of 0.05, 30 patients were required in each group. Therefore, we enrolled a total of 103 patients with at least one of the risk factors for thromboembolism who underwent unilateral primary minimally invasive TKA, and the participants were randomly divided into the topical TXA group (n = 34), receiving intra-articular injection of 3 g of TXA in 100 mL saline after TKA, the topical Floseal® group (n = 34), receiving 10 mL of Floseal® intra-articularily during surgery, and the placebo group (n = 35), receiving an intra-articular saline injection only. The total blood loss (TBL) and hemoglobin (Hb) drop were compared among the 3 groups. RESULTS: The TXA group had a lower TBL of 645 mL (227 to 1090) in comparison with 1145 mL (535 to 1942) in the Floseal® group and 1103 mL (424 to 1711) in the placebo (p < 0.001, respectively). The TBL was similar between the Floseal® group and the placebo group (p = 0.819). No patients in any group had symptoms of venous thromboemblism. CONCLUSION: Our prospective randomized controlled study showed that intra-articular application of TXA was superior to hemostatic matrix (Floseal®) in terms of blood conservation in patients with preexisting thromboembolic risk undergoing minimally invasive TKA. This trial is registered with Clinicaltrials.gov (NCT02865174) on 08/09/2016.

In clinical endodontics, preoperative estimation of root canal curvature is crucial regarding the prevention of iatrogenic errors. Reproduction of the two-dimensional radiographic images causes certain proximal view curvatures not seen. Therefore, the present study is aimed at investigating the degree of root canal curvature identified in different radiographic views. A total of 60 human permanent single-rooted teeth with varying degrees of curvature were selected. The root canal curvature for each tooth was measured on cone-beam computed tomography (CBCT) images (clinical view), standard digital periapical view (0° angle), digital periapical horizontal parallax view (30° angle), and digital periapical proximal view (0° angle), by using the Schneider method. No statistically significant difference was found in the degree of curvatures estimated on CBCT images and standard digital periapical view (0° angle) in the same tooth. The results revealed a significant difference between the proximal view and the other three groups (p < 0.05). There was no significant difference in this respect between the horizontal parallax view (30° angle), clinical view (CBCT images), and standard digital periapical view (p > 0.05). Proximal view curvatures cannot be predicted or estimated only from examining a clinical view radiograph. A horizontal parallax view (30° angle) is highly recommended as specific guidelines on how to estimate root canal curvature in case difficulty assessment protocols.

BACKGROUND: Insomnia is an economic burden and public health problem. This study is aimed at exploring potential biological pathways and protein networks for insomnia characterized by wakefulness after sleep. METHOD: Proteomics analysis was performed in the insomnia group with wakefulness and the control group. The differentially expressed proteins (DEPs) were enriched; then, hub proteins were identified by protein-protein interaction (PPI) network and verified by parallel reaction monitoring (PRM). RESULTS: Compared with the control group, the sleep time and efficiency of insomnia patients were decreased, and awakening time and numbers after sleep onset were significantly increased (P < 0.001). The results of proteomic sequencing found 68 DEPs in serum under 1.2-fold changed standard. These DEPs were significantly enriched in humoral immune response, complement and coagulation cascades, and cholesterol metabolism. Through the PPI network, we identified 10 proteins with the highest connectivity as hub proteins. Among them, the differential expression of 9 proteins was verified by PRM. CONCLUSION: We identified the hub proteins and molecular mechanisms of insomnia patients characterized by wakefulness after sleep. It provided potential molecular targets for the clinical diagnosis and treatment of these patients and indicated that the immune and metabolic systems may be closely related to insomnia characterized by wakefulness after sleep.

BACKGROUND: Majority of prostate cancer (PCa) deaths are attributed to localized high-grade aggressive tumours which progress rapidly to metastatic disease. A critical unmet need in clinical management of PCa is discovery and characterization of the molecular drivers of aggressive tumours. The development and progression of aggressive PCa involve genetic and epigenetic alterations occurring in the germline, somatic (tumour), and epigenomes. To date, interactions between genes containing germline, somatic, and epigenetic mutations in aggressive PCa have not been characterized. The objective of this investigation was to elucidate the genomic-epigenomic interaction landscape in aggressive PCa to identify potential drivers aggressive PCa and the pathways they control. We hypothesized that aggressive PCa originates from a complex interplay between genomic (both germline and somatic mutations) and epigenomic alterations. We further hypothesized that these complex arrays of interacting genomic and epigenomic factors affect gene expression, molecular networks, and signaling pathways which in turn drive aggressive PCa. METHODS: We addressed these hypotheses by performing integrative data analysis combining information on germline mutations from genome-wide association studies with somatic and epigenetic mutations from The Cancer Genome Atlas using gene expression as the intermediate phenotype. RESULTS: The investigation revealed signatures of genes containing germline, somatic, and epigenetic mutations associated with aggressive PCa. Aberrant DNA methylation had effect on gene expression. In addition, the investigation revealed molecular networks and signalling pathways enriched for germline, somatic, and epigenetic mutations including the STAT3, PTEN, PCa, ATM, AR, and P53 signalling pathways implicated in aggressive PCa. CONCLUSIONS: The study demonstrated that integrative analysis combining diverse omics data is a powerful approach for the discovery of potential clinically actionable biomarkers, therapeutic targets, and elucidation of oncogenic interactions between genomic and epigenomic alterations in aggressive PCa.

Septic acute kidney injury (AKI) is the most common AKI syndrome in the intensive care unit (ICU), and it accounts for approximately half of AKI cases. Tofacitinib (TOFA) is a pan-Janus kinase (JAK) inhibitor that exhibits potent anti-inflammatory activity in rheumatoid arthritis. However, no study has examined the functional role of TOFA in septic AKI. In the present study, we investigated the protective effects of TOFA on septic AKI and the underlying mechanisms. A lipopolysaccharide- (LPS-) induced AKI model was established in C57BL/6 mice via an intraperitoneal injection of LPS (10 mg/kg). One hour after LPS challenge, the mice were orally administered TOFA (5, 10, or 15 mg/kg) every 6 h until sacrifice at 24 h. We found that TOFA significantly ameliorated LPS-induced renal histopathological changes and dysfunction. TOFA also suppressed the expression levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IFN-γ) and the parameters of oxidative stress (MDA, GSH, SOD, and CAT) in kidney tissues. These results may be associated with the inhibitory effect of TOFA on the JAK-STAT1/STAT3 pathway, which was significantly activated by LPS challenge. TOFA treatment also inhibited LPS-induced activation of the TLR4/NF-κB pathway. In conclusion, we revealed that TOFA had a protective effect on LPS-induced AKI, and it may be a promising therapeutic agent for septic AKI.

Exosomes are vesicles with a diameter of 30-150 nm produced by living cells and secreted into the extracellular matrix. Exosomes mediate cellular communication by carrying active molecules, such as nucleic acids, proteins, and liposomes. Although exosomes are found in various body fluids, little is known about bile-derived exosomes. This review is the first to summarize the methods of bile storage and isolation of biliary exosomes, highlighting the roles of bile-derived exosomes, especially exosomal noncoding RNAs, in physiological and disease states and discussing their potential clinical applications.

BACKGROUND: As the skin is the largest organ of the human body, it is aging inevitably and produces cosmetic and psychological problems, and even disease. Therefore, the molecular mechanisms related to the prevention of skin aging need to be further explored. METHODS: Aging models were constructed by D-galactose. Mice were administrated with polygoni multiflori radix preparat (PMRP), PMRP and 3-methyladenine, or PMRP and rapamycin intragastrically. The apparent and viscera index of aged rats was measured. Then, the physicochemical property, antioxidant ability, histological structure, mitochondrial membrane potential, ATP and ROS levels, and mitophagy of aged skins were determined. Finally, the expression of PINK1, Parkin, P62, and LC3II/I; apoptosis-related proteins; and the percentage of apoptotic cells were measured. RESULTS: PMRP relieved skin aging with reducing of thymus index, improvement of pathological damage and histological structure, increase of the expression area of fibrous tissue, the ratio of type I to type III collagen, and antioxidant ability of aged skins. Importantly, PMRP also improved mitochondrial dysfunction with an increase in the content of mitochondrial membrane potential and ATP and a decrease of ROS levels. Moreover, mitophagy was enhanced with the treatment of PMRP when observed using electron microscopy, and the expression of PINK1, Parkin, and LC3I/II was increased with PMRP treatment but P62 expression was decreased. Meanwhile, PMRP alleviated apoptosis with a decrease of apoptotic cell and the expression of Cleaved-cas3, Bax, Cyt-c, AIF, and Smac as well as an increase of Bcl-2 expression. CONCLUSION: The results demonstrated that the polygoni multiflori radix preparata may delay skin aging by inducing mitophagy.

BACKGROUND: Neck pain (NP) is a common work-related disorder, with high prevalence in the profession of teaching. The daily duties of a school teacher involve head-down postures while reading and writing, which expose them to the risk of developing NP. Deep cervical flexor (DCF) muscles have been reported to have lower endurance in patients with cervical impairment, which has additionally been associated with disability. There is limited evidence regarding the efficacy of training of DCF muscles in occupational NP. The objective of this study was to investigate the effects of DCF muscle training on pain, muscle endurance, and functional disability using pressure biofeedback in school teachers with NP. METHODS: Sixty-five teachers (age, 25-45 years) with more than 5 years of teaching experience participated in this study. They were randomly divided into two groups: the experimental (E) and control (C) groups. In the E group, the subjects underwent DCF muscle training using pressure biofeedback in addition to conventional exercises for neck pain, while those in the C group underwent conventional exercises only. Pain, muscle endurance, and disability were measured at day 0 (before the treatment) and days 14 and 42 after the treatment. Endurance of DCF muscles was measured by the craniocervical flexion test using pressure biofeedback, pain intensity was measured using the numeric pain rating scale, and functional disability was assessed using the neck disability index questionnaire. This study was performed in accordance with CONSORT guidelines. RESULTS: On day 0, there were no significant differences in the age, pain, muscle endurance, and disability levels between the groups. After initiating the intervention, although there were improvements in both groups, there was a statistically significant improvement in muscle endurance, pain, and disability in subjects who received additional training with pressure biofeedback. CONCLUSIONS: Besides increasing muscle endurance, specific training of DCF muscles in addition to conventional exercises can improve neck pain and functional disability. These results should be further correlated clinically. A dedicated time for exercises at school could help prevent the development of NP in teachers. This trial is registered with ClinicalTrials.gov NCT03537300 May 24, 2018 (retrospectively registered).

3D printing technology is widely used in the field of implantable medical device in recent decades because of its advantages in high precision, complex structure, and high material utilization. Based on the characteristics of 3D printing technology, this paper reviews the manufacturing process, materials, and some typical products of 3D printing implantable medical devices and analyzes and summarizes the development trend of 3D printed implantable medical devices.

Autolysis is an internal phenomenon following the death of an organism that leads to the degradation of tissues. In order to explore the initial stages of autolysis and attempt to establish reference standards for tissue changes after death, we studied the rapidly autolyzing tissue of the crayfish hepatopancreas. Samples from the hepatopancreas of crayfish were examined 0, 5, 10, 30, 60, and 120 minutes after death. Histological and ultrapathological examinations and evaluations and apoptotic cell counts were conducted to determine the initiation time and degree of autolysis. The results showed that autolysis in the hepatopancreas of crayfish began within 5 minutes. Initially, autolysis manifested in the swelling of hepatic tubular cells and the widening of mesenchyme. Cells undergoing autolysis showed severe organelle necrolysis. Based on these observations, tissue samples should be collected and preserved within five minutes to avoid interfering with histopathological diagnoses.

BACKGROUND: L-carnitine mediates the utilization of fatty acids and glucose in the myocardium. The potential of L-carnitine in managing dilated cardiomyopathy (DCM) in patients has been extensively reported, with additional benefits. OBJECTIVE: This meta-analysis purposed to explore the clinical efficacy of L-carnitine therapy on DCM patients. METHODS: We searched publications up to May 2020 from several databases including PubMed, Embase, Cochrane Library, Chinese Biomedical (CBM) database, Chinese Science and Technology Periodicals database (VIP), Chinese National Knowledge Infrastructure (CNKI) database, and Wanfang database. Subsequently, publications that met the inclusion criteria were systematically evaluated by two independent reviewers. RESULTS: A total of 23 RCTs conducted in China with 1455 DCM patients were included in this study. In the meta-analysis, L-carnitine therapy was associated with a considerable improvement in the overall efficacy (RR = 1.28, 95% CI (1.21-1.36), P < 0.0001), left ventricular ejection fraction (LVEF) (MD = 6.16%, 95% CI (4.50, 7.83), P < 0.0001), and cardiac output (CO) (MD = 0.88 L/min, 95% CI (0.51, 1.25), P < 0.0001) as compared to the control group. Moreover, L-carnitine therapy significantly decreased left ventricular end-diastolic dimension (LVEDD) (MD = -2.53, 95% CI (-3.95, -1.12), P = 0.0005), brain natriuretic peptide (BNP) (SMD = -1.71 ng/L, 95% CI (-3.02, -0.40), P = 0.01), and the transforming growth factor-beta (TGF-β1) (MD = -56.78 ng/L, 95% CI (-66.02, -47.53), P < 0.0001). CONCLUSIONS: L-carnitine potentially enhanced the therapeutic efficiency in DCM patients. Following weaknesses in the evidence due to low methodological quality and high clinical heterogeneity in the included studies, well-designed trials are recommended.

BACKGROUND: Thyroid cancer is the most common endocrine malignancy, with a recent global increase of 20% in age-related incidence. Ultrasonography and ultrasonography-guided fine-needle aspiration biopsy (FNAB) are the most widely used diagnostic tests for thyroid nodules; however, it is estimated that up to 25% of thyroid biopsies are cytologically inconclusive. Molecular markers can help guide patient-oriented and targeted treatment of thyroid nodules and thyroid cancer. METHODS: Datasets related to papillary thyroid cancer (PTC) or thyroid carcinoma (GSE129562, GSE3678, GSE54958, GSE138042, and GSE124653) were downloaded from the GEO database and analysed using the Limma package of R software. For functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology were applied to differentially expressed genes (DEGs) using the Metascape website. A protein-protein interaction (PPI) network was built from the STRING database. Gene expression, protein expression, immunohistochemistry, and potential functional gene survival were analysed using the GEPIA website, the Human Protein Atlas website, and the UALCAN website. Potential target miRNAs were predicted using the miRDB and Starbase datasets. RESULTS: We found 219 upregulated and 310 downregulated DEGs, with a cut-off of p < 0.01 and ∣log FC | >1.5. The DEGs in papillary thyroid cancer were mainly enriched in extracellular structural organisation. At the intersection of the PPI network and Metascape MCODEs, the hub genes in common were identified as FN1, APOE, CLU, and SDC2. In the targeted regulation network of miRNA-mRNA, the hsa-miR-424-5p was found to synchronously modulate two hub genes. Survival analysis showed that patients with high expression of CLU and APOE had better prognosis. CONCLUSIONS: CLU and APOE are involved in the molecular mechanism of papillary thyroid cancer. The hsa-miR-424-5p might have the potential to reverse the processes of papillary thyroid cancer by modulating the hub genes. These are potential targets for the treatment of patients with papillary thyroid cancer.

In the present work, a novel water-soluble polysaccharide (LWSP) was purified from Katan seeds. Polysaccharide was structurally characterized by NMR spectroscopic analysis, thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR) analysis, X-ray diffraction (XRD), and UV absorption. TLC and HPLC showed that LWSP was a polysaccharide consisted mainly of glucose, mannose, xylose, and arabinose. The FTIR spectrum and UV absorption proved polysaccharide characteristic of LWSP. According to XRD, LWSP presented a semicrystalline behavior. The molecular weight was estimated as 64.56 kDa. Results obtained through 13C and 1H nuclear magnetic resonance (NMR) indicated that LWSP is consisted of four monosaccharide residues with α and β anomers. Physicochemical and antioxidant properties of LWSP were also investigated. Results revealed that LWSP exhibited interesting 1,1-diphenyl-2-picrylhydrazyl (DPPH) (IC50 = 4.48 mg/ml) and chelating activity (IC50 = 4.79 mg/ml), and it displayed moderate reductive capacities. Overall, the findings suggested that LWSP is a promising source of natural additives in various industries fields.

BACKGROUND: Since the dawn of human history, foodborne diseases have been a problem for all societies, and it is an increasing public health issue worldwide. The objective of this study is to examine knowledge, practice, and attitude in food safety among college students in the city Gondar, northwest Ethiopia. METHODS: A cross-sectional study was conducted among 430 randomly selected college students in Gondar City, northwest Ethiopia, from October 8 to November 30, 2019. The data was gathered through a self-administered questionnaire. The collected data were checked for completeness, coded manually, and entered into Epi Info version 7, then exported to SPSS version 26 for more data checking, cleaning, and analysis. One-way ANOVA was done for examining sociodemographic variable association with KAP, and Pearson correlation analysis was conducted to measure the association among food safety knowledge, attitude, and practice scores. The p value < 0.05 was considered statistically significant for both tests. RESULTS: The number of females was higher among the study participants (65.5%). The mean age of participates was 21.1 ± 9.14 (SD) years. The higher percentage (45.7%) of the participants were students in the second year. The overall scores of the food safety knowledge, attitude, and practices of the respondents were 35.7% (good), 38.0% (good), and 29.1% (positive), respectively. Participants with differences in gender, year of study, and food safety training had a substantial variation in overall food safety knowledge (p value < 0.05). The findings have clearly shown that knowledge of food safety does not directly affect the attitude towards food safety (p value > 0.05). On the other hand, overall food safety practice differed in terms of sex, year of schooling, and knowledge of food safety (p value < 0.05) among participants. Training and knowledge score had significant correlation among respondents (p value < 0.05). CONCLUSION: This study revealed that the overall knowledge, practices, and attitude towards food safety among college students were very low. There was a significant association between knowledge and practice while food safety practices were independent with an attitude among the students. Such results indicated that there could be problems with foodborne diseases. Therefore, the findings of this study proposed that strength should be done to improve the existing food safety knowledge, practice, and attitude in college students in addition to their normal education.

Bronchopulmonary dysplasia (BPD) is the most common complication of extremely preterm birth. This study was aimed at detecting cytokine and fractional exhaled nitric oxide (FeNO) levels to evaluate their mechanisms and predicted significance for BPD. Preterm infants born at gestational age ≤ 32 weeks were recruited, and clinical data were collected. We detected ten cytokines, including IFN-γ, IL-10, IL-12p70, IL-13, IL-1β, IL-2, IL-4, IL-6, IL-8, and TNF-α on Days 1-3, Days 7-14, and Days 21-28 after birth by using the Meso Scale Discovery (MSD) technology. The FeNO levels of infants were measured when they met the discharge criteria. A total of 46 preterm infants were enrolled, consisting of 14 infants in BPD group and 32 infants in the control group. The gestational age (27.5 ± 1.3 vs. 29.9 ± 1.3 weeks) and birth weight (1021 ± 261 g vs. 1489 ± 357 g) were lower in the BPD group. The following were high-risk factors for BPD, as determined by multivariate logistic regression analysis: gestational age < 30 weeks, birth weight < 1000 g, PDA, longer mechanical ventilation, and higher FeNO. The cytokines of IL-6 and IL-8 on Days 7-14 and IL-4, IL-6, IL-8, and TNF-α on Days 21-28 were also high-risk factors for BPD. IL-6 contributed to BPD disease severity. Conclusion. The preterm infants with PDA and prolonged mechanical ventilation tended to develop BPD. The IL-6 and IL-8 were significantly increased on Days 7-14 and were high-risk factors for BPD. Moreover, the IL-6 level was associated with BPD disease severity. We speculated that NO was related to BPD via Th2 cell-mediated inflammatory responses such as IL-4 and IL-6. Cytokines might predict the occurrence of BPD.

BACKGROUND: The objective of this study was to explore the role of preoperative fibrinogen-to-prealbumin ratio (FPR) in evaluating the prognosis of patients with stage I-III colorectal cancer (CRC). METHODS: This retrospective study enrolled 584 stage I-III CRC patients undergoing surgical resection. Logistic regression analysis was used to explore the correlation between FPR and postoperative complications. The Kaplan-Meier curve and Cox proportional hazards model were used to identify the prognostic factors. The nomograms were constructed based on the prognostic factors. The concordance index and calibration curve were used to determine the accuracy of the nomograms. Time-dependent receiver operating characteristic was used to compare the predictive prognostic efficacy of nomograms and TNM stage. RESULTS: FPR was determined to be an independent factor affecting postoperative complications. Patients with a low-FPR had a significantly better prognosis than those with a high-FPR (disease-free survival, p = 0.028; overall survival, p = 0.027), especially patients with stage I CRC (disease-free survival, p = 0.015; overall survival, p = 0.017). The Cox proportional hazards model identified FPR as an independent poor prognostic factor of disease-free survival (hazard ratio (HR) = 1.459, 95% confidence interval (CI) = 1.074-1.954, p = 0.011) and overall survival (HR = 1.405, 95% CI = 1.034-1.909, p = 0.030). The prognostic nomograms had good accuracy and were superior to the traditional TNM stage. CONCLUSIONS: FPR is a potential indicator for predicting short- and long-term prognosis of stage I-III CRC patients undergoing surgical resection.

Waardenburg syndrome (WS) is a group of rare genetic disorders characterized by hearing loss, changes in coloring of hair, skin, and eyes, and alterations in the shape of the face. Tietz syndrome is another rare disorder which presented similar phenotypes to WS. Patients with Tietz/Waardenburg syndrome often present with pale blue eyes, albino skin, and distinctive hair coloring, such as a patch of white hair or hair that prematurely turns gray. At present, more than six candidate genes are responsible for four types of Waardenburg syndrome and Tietz syndrome. This study is aimed at identifying the pathogenic gene variants in a three-generation Han Chinese family with hearing loss, blue-gray iris, albino skin, and white hair. In order to discover the molecular genetic lesion underlying the disease phenotype, whole exome sequencing in the proband, with Tietz/Waardenburg syndrome phenotypes, of a Han Chinese family from HeBei, China, was conducted. A novel heterozygous c.650G>C/p.Arg217Thr variant in melanocyte inducing transcription factor (MITF) was identified. Sanger sequencing further validated that this mutation existed in three affected individuals and absent in healthy family members. Bioinformatics analysis predicted that this mutation was deleterious. Our study further identified the genetic lesion of the family. Simultaneously, our study may also contribute to genetic counseling, embryonic screening of in vitro fertilized embryos, and prenatal genetic diagnosis of patients with Tietz/Waardenburg syndrome, especially for the proband, unmarried and unpregnant women, to reduce familial transmission in this Han Chinese family.

AIM: Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) has been acknowledged as a tumor-suppressive gene in several cancers; however, there are few reports on the clinical significance of CPEB3 in melanoma. The aim of this study was to investigate the role of CPEB3 in predicting the prognosis of melanoma patients. METHODS: The association of CPEB3 expression and clinical pathologic features was performed using The Cancer Genome Atlas (TCGA) data set. The role of CPEB3 expression in prognosis was also analyzed. In addition, CPEB3 expression-related pathways were enriched by gene set enrichment analysis (GSEA). Association analysis of CPEB3 gene expression and immune infiltration was performed by ssGSEA. RESULTS: The mRNA was significantly less in melanoma than in normal tissues (p < 0.001). The decrease in CPEB3 expression in melanoma was significantly correlated with T staging (p < 0.001), clinical staging (p = 0.029), melanoma Clark level (p = 0.014), and melanoma ulceration (p = 0.003), while it was marginally significant in N staging (p = 0.089). Melanoma with low CPEB3 expression was associated with worse OS (overall survival), progression-free survival (PFS), and disease-specific survival (DSS) than in that with high expression. In the univariate analysis, expression of CPEB3, melanoma ulceration, Clark level of melanoma, age, clinical stage, T stage, and N stage were correlated with OS (p < 0.05). Further analysis by multivariate Cox regression showed that N stage (p = 0.029), melanoma ulceration (p = 0.004), and CPEB3 expression (p < 0.001) were independent prognostic factors of OS in melanoma. Moreover, GSEA showed that several pathways were enriched in CPEB3, such as PD1 signaling, CTLA4 pathway, CTCF pathway, CHEMOKIN signaling, VEGF signaling, and JAK-STAT pathway. CPEB3 was significantly correlated with the infiltration level of B cells (p < 0.001), T cells (p < 0.001), T helper cells (p < 0.001), and central memory T (Tcm) cells (p < 0.001). CONCLUSION: CPEB3 may be a potential prognostic marker in melanoma with poor survival. Moreover, PD1 signaling, CTLA4 pathway, CTCF pathway, CHEMOKIN signaling, VEGF signaling, and JAK-STAT pathway may be the key pathway regulated by CPEB3. Moreover, the expression of CPEB3 in melanoma is related to the level of immune infiltration.

Liquid biopsy is conducted through minimally invasive or noninvasive procedures, and the resulting material can be subjected to genomic, proteomic, and lipidomic analyses for early diagnosis of cancers and other diseases. Extracellular vesicles (EVs), one kind of promising tool for liquid biopsy, are nanosized bilayer particles that are secreted by all kinds of cells and that carry cargoes such as lipids, proteins, and nucleic acids, protecting them from enzymatic degradation in the extracellular environment. In this review, we provide a comprehensive introduction to the properties and applications of EVs, including their biogenesis, contents, sample collection, isolation, and applications in diagnostics based on liquid biopsy.

BACKGROUND: Since the first diagnosed case of infection with the novel coronavirus (SARS-CoV-2), there has been a rapid spread of the disease with an increasing number of cases confirmed every day, as well as a rising death toll. An association has been reported between acute kidney injury (AKI) and mortality in patients infected with SARS-CoV-2. Therefore, our study was conducted to explore possible risk factors of AKI as well as whether AKI was a risk factor for worse outcome, especially mortality among patients with coronavirus disease (COVID-19). METHODS: We included all hospital admissions with confirmed or clinically diagnosed COVID-19 from January 29 to February 25, 2020. We collected demographic and epidemiological information, past medical history, symptoms, laboratory tests, treatments, and outcome data from electronic medical records. A total of 492 patients with diagnosed or clinically diagnosed COVID-19 were included in this study. RESULTS: The prevalence rate of AKI was 7.32%. Among the factors associated with AKI, males versus females (aOR 2.73), chronic kidney disease (aOR 42.2), hypertension (aOR 2.82), increased leucocytes (aOR 6.08), and diuretic use (aOR 7.89) were identified as independent risk factors for AKI among patients infected by SARS-CoV-2. There was a significant difference in hospital fees and death in patients with and without AKI (p < 0.05). The mortality rate in patients with AKI was 63.9%. CONCLUSIONS: AKI was widespread among patients with COVID-19. The risk factors of AKI in COVID-19 patients included sex, chronic kidney disease, hypertension, infection, and diuretic use. AKI may be associated with a worse outcome, especially mortality in COVID-19 patients.

Allanblackia floribunda has been used to treat an upset stomach in African traditional medicine, but its efficacy and safety have not been scientifically studied. The present research is aimed at assessing the antiulcer property of the seed extract of the plant to validate its traditional claim. Rats were pretreated with three doses of aqueous extract of A. floribunda (AFE) at 30, 100, and 300 mg/kg or omeprazole 10 mg/kg for 1 hr before the acute gastric ulcer was induced by oral administration of 5 mL/kg of 98% ethanol. The animals were sacrificed under anesthesia, and the stomach and blood were collected. The gross histology of the stomach, percentage protection conferred by the treatment, gastric pH, and serum TNF-α and INF-γ were assessed as well as the expression of Ki67 antigens. The antioxidant properties as well as the acute toxicity profile of the plant extract were also assessed. The results show that A. floribunda conferred significant protection on the rats against gastric ulceration with % protection of 46.15, 57.69, and 65.38 for AFE 30, 100, and 300 mg/kg, respectively, as well as 69.23% for omeprazole 10 mg/kg. The plant extract caused marked reductions in gastric pH, TNF-α, and INF-γ with statistical significance (p < 0.001) for AFE 300 mg/kg and omeprazole 10 mg/kg. Also, the plant showed good antioxidant activity comparable to gallic acid. Furthermore, the plant extract modulated the expression of Ki67 antigens. All animals survived the 14-day delayed toxicity test with no significant differences in physical, hematological, and biochemical parameters between rats orally administered with supratherapeutic doses of AFE (5000 mg/kg) or normal saline. The study established that the gastroprotective effect of the seed extract of A. floribunda is attributable to its antisecretory, antioxidant, and anti-inflammatory properties. Additionally, the plant was found to promote ulcer healing via the modulation of the expression Ki67 and was safe at supratherapeutic doses.

Recently, three-dimensional (3D) printing has become increasingly popular in the medical sector for the production of anatomical biomodels, surgical guides, and prosthetics. With the availability of low-cost desktop 3D printers and affordable materials, the in-house or point-of-care manufacturing of biomodels and Class II medical devices has gained considerable attention in personalized medicine. Another projected development in medical 3D printing for personalized treatment is the in-house production of patient-specific implants (PSIs) for partial and total bone replacements made of medical-grade material such as polyetheretherketone (PEEK). We present the first in-hospital 3D printed scaphoid prosthesis using medical-grade PEEK with fused filament fabrication (FFF) 3D printing technology.