PURPOSE: Capsular formation around breast implants can produce various complications, including erythema, tenderness, discomfort, and breast deformation. Moreover, the capsule is thought to be correlated with breast implant-associated anaplastic large cell lymphoma. The proposed technique of capsule reduction can prevent some of these complications. Thus, the authors suggest a no-touch technique in two-stage, implant-based breast reconstruction. Patients and Methods. This single-center retrospective study evaluated the medical records and digitalized pathological slides of patients who underwent two-stage, implant-based breast reconstruction between February 2018 and May 2019. The selected patients were divided into group A and group B. Group A underwent a no-touch technique that included the following two steps: (1) using a sizer as the frame to create the submuscular and acellular dermal matrix (ADM) pocket for expander insertion and (2) inserting the expander through the funnel. After the second stage of implant insertion, the capsule was harvested for biopsy of the ADM, chest wall, and muscle. RESULTS: This study included 33 breasts (31 patients): 18 in group A and 15 in group B. The capsular thicknesses of the ADM, the chest wall, and the muscle of group A were significantly thinner than those in group B. Pearson's correlation coefficient indicated negative correlations between capsular thickness and age; underlying disease; lesion side; interval of two-stage implant insertion; size of the expander; and radiotherapy, chemotherapy, or hormone therapy. CONCLUSION: To reduce the incidence of capsular formation following breast reconstruction using prostheses, a no-touch technique that uses a funnel and sizer to avoid implant contact is both efficient and beneficial.

Helicobacter pylori (H. pylori) infection is the most common cause of gastric cancer (GC). This microorganism is genetically diverse; GC is caused by several genetic deregulations in addition to environmental factors and bacterial virulence factors. lncRNAs (long noncoding RNAs) are significant biological macromolecules in GC, have specific functions in diseases, and could be therapeutic targets. Altered lncRNAs can lead to the abnormal expression of adjacent protein-coding genes, which may be important in cancer development. Their mechanisms have not been well understood, so we are going to investigate the risk of GC in a population with both high lncRNA and H. pylori infection.

OBJECTIVE: To investigate the role and mechanism of aspirin in myocardial injury induced by myocardial ischemia-reperfusion in rats through STAT3 signaling pathway. METHODS: Sixty rats were randomly divided into three groups: the sham operation group, MI/R group, and MI/R+aspirin group (aspirin group). The rats in the sham operation group did not ligate the LAD coronary artery, while the aspirin group ligated the LAD coronary artery, which caused the suture to be loosened after 30 minutes ischemia, and 60 mg/kg aspirin was injected into the tail vein 10 minutes before reperfusion. After three hours of reperfusion, the ultrasound system was used to collect hemodynamic parameters, including ejection fraction (EF%), shortening fraction (FS%), and left ventricular end-systolic pressure (LVESP%) and left ventricular end-diastolic pressure (LVEDP%). Finally, the rats were euthanized; then, blood samples were taken for biochemical examination, myocardial tissue was collected, and the left ventricle was used for subsequent experiments. The gene expression levels of Bax and Bcl-2 were detected by PCR. The protein expression levels of Bcl-2, Bax, p-JAK2, total JAK2, p-STAT3, and total STAT3 were detected by Western blot. RESULTS: Compared with the sham operation group and the aspirin group, the area of myocardial infarction in the MI/R was significantly increased (p < 0.05). In terms of hemodynamic parameters, LVEDP was significantly elevated in the MI/R group. The results of PCR showed that compared with the MI/R group, the mRNA expression of Bax in the aspirin group was significantly decreased, while that of Bcl-2 was significantly increased (p < 0.05). Western blot analysis showed that compared with the MI/R group, aspirin pretreatment significantly increased the expression levels of p-STAT3 and p-JAK2 (p < 0.05). CONCLUSION: The mechanism of aspirin preconditioning to protect the heart from MI/R injury appears to be related to JAK2/STAT3 and related to the activation of the signaling pathway.

Total concentrations of As, Cd, Cr, Cu, Pb, and Zn in sediment samples obtained from Wami Estuary in Tanzania were used to generate contaminant probability density distributions and species sensitivity distributions using the AQUARISK model. Results of tier 1 assessment showed that As, Cd, Cr, Pb, and Zn were not of concern as their measured values and the 99th percentile of the fitted distributions were lower than the SQG low-trigger values. However, Cu was identified as of concern in this estuary. According to the Bur III distributional analysis of the exotoxicological data, the estimated percentage of species likely to be affected is 3.4, 79.4, 79.8, 99.9, 98.4, and 98.0 for As, Cd, Cr, Cu, Pb, and Zn, respectively. Lowering of the current median concentrations of metals (Cd, Cr, Cu, Pb, and Zn) is recommended as they exceeded modeled median target sediment concentration to achieve 95% or higher for species protection. With the ongoing increase in anthropogenic activities in the Wami River catchment, the environmental regulatory bodies may use the findings of the present study and augmented with AQUARISK to set discharge standards for various contaminants in order to minimize impacts to the receiving ecosystems.

Temporomandibular joint osteoarthritis (TMJOA) is characterized by chronic inflammatory degradation of mandibular condylar cartilage (MCC). Studies have found a positive correlation between inflammation and cyclooxygenase- (COX-) 2 in OA pathology. NF-κB is a crucial transcription factor of inflammatory and immune responses in the cause of TMJOA pathology. Resveratrol (RES) plays a critical role in antioxidation and anti-inflammation. But, studies on the effects of RES on TMJOA are very limited. So, the purpose of this study is to investigate the antioxidant and protective effects of RES against MCC degradation through downregulating COX-2/NF-κB expression. In vitro studies, the MCC cells were divided into three groups: the NC group, OA group, and RES group. The optimum dose of RES (10 μM) was determined. The TMJOA model of mice was created by injection of collagenase. And mice were injected with RES (100 μg/10 μl) 3 times one week for 4 weeks in the RES group. The expressions of COX-2, P65, MMP1, MMP13, COL2, and ACAN were measured by RT-PCR. Morphological changes of MCC were studied with HE staining. The results showed that inflammation could induce MCC degradation in vitro and vivo, while RES could reverse the degradation. Meanwhile, RES could downregulate COX-2/NF-κB/MMP expression and increase cartilage markers in vitro and vivo studies. The results indicated that RES treatment had antioxidant effects against chondrocyte apoptosis by downregulating the COX-2/NF-κB pathway in created TMJOA.

BACKGROUND: Various studies reported that the prognosis of patients with cervical cancer (CC) was significantly associated with immunity, whereas limited studies have explored whether immune-associated genes could be classifiers for recurrence-free survival (RFS) of stage I CC. Thus, an improved immune-related gene signature for stage I CC patients' prognosis is urgently required. MATERIALS AND METHODS: We retrospectively analyzed the gene expression profiles of stage I CC patients in the GSE44001 set from the Gene Expression Omnibus (GEO) database. The stage I CC patients were randomly divided into the training group and the internal validation group. The training patients were adopted to develop a prognostic immune gene-based signature; meanwhile, the internal validation patients were used to validate the power of the selected immune gene-related signature using univariate Cox proportional hazard analysis, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis. The accuracy and reliability of the immune gene-related signature were evaluated based on Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) curves. RESULTS: High power of the 8-immune gene signature was found on the basis of ROC analysis (AUC at 1, 3, and 5 years were exhibited in the internal validation group (0.702, 0.715, and 0.728, respectively), external validation group (0.702, 0.825, and 0.842, respectively), and entire GEO dataset (0.840, 0.894, and 0.852, respectively)). Besides, C-index, ROC, calibration plots, and decision curve analysis (DCA) also acted well in our nomogram, suggestive of a high ability of the nomogram to elevate the prognostic prediction of stage I CC patients. CONCLUSIONS: In this study, we successfully constructed an integrated 8-immune gene-based signature which could accurately identify patients with low prognostic risk from those with high prognostic risk. In addition, we developed an immune-related nomogram which can elevate the prognostic prediction of stage I CC patients.

PURPOSE: The purpose of this study is to investigate the treatment efficacy of total knee arthroplasty (TKA) on locomotive syndrome (LS) focusing on total clinical decision limit (CDL) stage 3 leading to revealing the motor function indicators that can predict LS improvement in knee osteoarthritis patients who had received TKA. METHODS: This prospective cohort study was conducted in 47 patients evaluated as total CDL stage 3 before TKA who received primary TKA on the operated side and were diagnosed with Kellgren-Lawrence grade 2, 3, or 4 knee osteoarthritis on the nonoperated side. LS was evaluated using stand-up test, two-step test, and 25-Question Geriatric Locomotive Function Scale. In addition, the motor function indicators which could predict the LS improvement were examined. All assessments were conducted before TKA and three months after TKA. RESULTS: Of the 47 subjects who were evaluated to be in total CDL stage 3 before TKA, 13 patients (27.7%) were determined to show improvements in total CDL. From the result of the decision tree analysis, when the CDL of the two-step test before TKA was 1 or less, the improvement rate was 83.3%. Even if the CDL of the two-step test before TKA was higher than 1 and if the 3 m-Timed Up and Go test (3m-TUG) before TKA was 9.6 or less, the improvement rate was 50%. CONCLUSIONS: As of three months after surgery, TKA can improve LS in about 30% of knee osteoarthritis patients. A two-step test before TKA and 3m-TUG before TKA can be used as motor function indicators to predict LS improvement. This study provides useful information for setting the goal for rehabilitation prior to surgery.

Pancreatic enzyme replacement therapy (PERT) and fat predigestion are key in ensuring the optimal growth of patients with cystic fibrosis. Our study attempted to highlight differences between fat predigestion and conventional PERT on body composition of young pigs with exocrine pancreatic insufficiency (EPI). EPI and healthy pigs were fed with high-fat diet for six weeks. During the last two weeks of the study, all pigs received additional nocturnal alimentation with Peptamen AF (PAF) and were divided into three groups: H-healthy pigs receiving PAF; P-EPI pigs receiving PAF+PERT; and L-EPI pigs receiving PAF predigested with an immobilized microbial lipase. Additional nocturnal alimentation increased the body weight gain of EPI pigs with better efficacy in P pigs. Humerus length and area in pigs in groups L and P were lower than that observed in pigs in group H (p value 0.005-0.088). However, bone mineral density and strength were significantly higher in P and L as compared to that of H pigs (p value 0.0026-0.0739). The gut structure was improved in P pigs. The levels of neurospecific proteins measured in the brain were mainly affected in P and less in L pigs as compared to H pigs. The beneficial effects of the nocturnal feeding with the semielemental diet in the prevention of EPI pigs' growth/development retardation are differently modified by PERT or fat predigestion in terms of growth, bone properties, neurospecific protein distribution, and gut structure.

OBJECTIVE: Leucine-rich α2 glycoprotein 1 (LRG1) is a novel cytokine, which is believed to be involved in the inflammatory process of a series of diseases. However, the relationship between LRG1 and spinal cord injury (SCI) has not been reported. The purpose of our study is to determine the predictive value of LRG1 for the prognosis of pediatric SCI (PSCI). METHODS: This study recruited 64 patients with confirmed PSCI and 40 healthy controls at Foshan Traditional Chinese Medicine Hospital from January 2016 to December 2020. The clinical information of all participants at the time of admission was recorded. Peripheral blood was collected, and commercial reagents were used to detect the level of serum LRG1. At the same time, the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) was used to assess the severity of PSCI. RESULTS: All participants were divided into PSCI group (n = 64) and NC group (n = 40). There was no significant difference in clinical information (age, gender, heart rate, systolic blood pressure, diastolic blood pressure, sampling time from injury, white blood cells, and C-reactive protein) between the two groups (p > 0.05). According to the interquartile range of serum LRG1, we compared the motor and sensory scores of ISNCSCI and found that serum LRG1 levels were negatively correlated with the prognosis of PSCI patients (p < 0.001). The results of receiver operating curve (ROC) showed that the sensitivity, specificity, and AUC (Area Under the Curve) of serum LRG1 level in predicting the prognosis of PSCI were 68.4%, 69.1%, and 0.705, respectively. The cut-off value of serum LRG1 level predicting the prognosis of PSCI is 21.1 μg/ml. CONCLUSIONS: Serum LRG1 level is significantly increased in PSCI patients, and the elevated LRG1 level is negatively correlated with the prognosis of PSCI patients. Serum LRG1 may be a potentially useful biomarker for predicting PSCI.

DNA released from cells into the peripheral blood is known as cell-free DNA (cfDNA), representing a promising noninvasive source of biomarkers that could be utilized to manage Diffuse Large B-Cell Lymphoma (DLBCL), among other diseases. The procedure for purification and handling of cfDNA is not yet standardized, and various preanalytical variables may affect the yield and analysis of cfDNA, including the purification kits, blood collection tubes, and centrifugation regime. Therefore, we aimed to investigate the impact of these preanalytical variables on the yield of cfDNA by comparing three different purification kits DNeasy Blood & Tissue Kit (Qiagen), QIAamp Circulating Nucleic Acid Kit (Qiagen), and Quick-cfDNA Serum & Plasma Kit (Zymo Research). Two blood collection tubes (BCTs), EDTA-K2 and Cell-Free DNA (Streck), stored at four different time points before plasma was separated and cfDNA purified, were compared, and for EDTA tubes, two centrifugation regimes at 2000 × g and 3000 × g were tested. Additionally, we have tested the utility of long-term archival blood samples from DLBCL patients to detect circulating tumor DNA (ctDNA). We observed a higher cfDNA yield using the QIAamp Circulating Nucleic Acid Kit (Qiagen) purification kit, as well as a higher cfDNA yield when blood samples were collected in EDTA BCTs, with a centrifuge regime at 2000 × g. Moreover, ctDNA detection was feasible from archival plasma samples with a median storage time of nine years.

OBJECTIVE: To describe handgrip strength (HGS) and identify associated factors in community-dwelling older adults in rural Vietnam. METHODS: A cross-sectional study was conducted in community-dwelling older adults 80 years and over in five rural communities in Hanoi, Vietnam. Age-gender-BMI stratified HGS values were reported as means and standard deviations. Demographic characteristics, malnutrition, risk of fall, basic activities of daily living (ADL), and instrumental activities of daily living (IADL) were investigated. Multivariate linear regression explored the association between HGS and these factors. RESULTS: In 308 participants, mean age was 85.4 ± 4.2 years. Mean HGS was 21.6 ± 6.1 kg for males and 15.3 ± 4.3 kg for females. HGS in our sample was generally lower than that in other European countries and Asian threshold. Low HGS was correlated with older age (β = -0.196, p < 0.001), female (β = -0.443, p < 0.001), low education (β = -0.130, p < 0.05), risk of falls (β = -0.114, p < 0.05), and lower IADL (β = 0.153, p = 0.001). CONCLUSIONS: The age-gender-BMI stratified HGS values of 80 years and over community-dwellers in rural Vietnam were described. HGS decreased with advanced age, female, low education, high risk of falls, and impaired IADLs. The results could provide useful reference data for further investigations and measures in clinical practice.

Erratum in Biomed Res Int. 2022 Oct 14;2022:9796317.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Chronic hyperglycemia and high blood pressure are the main risk factors for the development of DN. In general, screening for microalbuminuria should be performed annually, starting 5 years after diagnosis in type 1 diabetes and at diagnosis and annually thereafter in type 2 diabetes. Standard therapy is blood glucose and blood pressure control using the renin-angiotensin system blockade, targeting A1c < 7%, and <130/80 mmHg. Regression of albuminuria remains an important therapeutic goal. However, there are problems in diagnosis and treatment of nonproteinuric DN (NP-DN), which does not follow the classic pattern of DN. In fact, the prevalence of DN continues to increase, and additional therapy is needed to prevent or ameliorate the condition. In addition to conventional therapies, vitamin D receptor activators, incretin-related drugs, and therapies that target inflammation may also be promising for the prevention of DN progression. This review focuses on the role of inflammation and oxidative stress in the pathogenesis of DN, approaches to diagnosis in classic and NP-DN, and current and emerging therapeutic interventions.

Sarcandra glabra has significant metabolically active bioingredients of pharmaceutical importance. The deficiency of molecular markers for S. glabra is a hindrance in molecular breeding for genetic improvement. In this study, 57.756 million pair-end reads were generated by transcriptome sequencing in S. glabra (Thunb.) Nakai and its subspecies S. glabra ssp. brachystachys. A total of 141,954 unigenes with 646.63 bp average length were assembled. A total of 25,620 simple sequence repeats, 726,476 single nucleotide polymorphisms, and 42,939 insertions and deletions were identified, and the associated unigenes and differentially expressed genes were characterized. This work enhanced the molecular marker resources and will facilitate molecular breeding and gene mining in S. glabra spp.

The purpose of the study was to investigate the relationship between postoperative bone marrow lesions (BMLs) and pain severity in patients undergoing open wedge high tibial osteotomy (OWHTO). We reviewed the patients undergoing OWHTO between April 2018 and April 2020. The demographic and clinical data of patients were collected. Clinically, VAS and Knee injury and Osteoarthritis Outcome Score (KOOS) were used to assess pain level and functional outcomes of patients. The MRI Osteoarthritis Knee Score (MOAKS) was used to assess the total BMLs size in medial tibiofemoral (MTF), lateral tibiofemoral (LTF), and patellofemoral (PF) joints. 98 patients were enrolled in the study, including 57 male and 41 female patients. The VAS scores improved significantly from 6.1 ± 0.8 to 1.5 ± 0.9 (p < 0.001), and all subscales of KOOS improved significantly after surgery (p < 0.001). There were no significant differences between the pre- and postoperative total BML size of PF and LTF joints (p > 0.05). We observed significant improvements in the total BML size of MTF joint (p < 0.001). The VAS scores and KOOS pain scores improved better in patients without postoperative MTF joint BMLs (p < 0.001). Postoperative MTF joint BMLs were correlated with postoperative VAS (p < 0.001) and KOOS pain (p < 0.001). Our study demonstrates that MTF joint BMLs improved significantly after OWTHO. We confirmed that the presence of postoperative MTF joint BMLs are strongly associated with pain severity. The greater the improvement in postoperative MTF joint BMLs, the less pain. Our findings provide valuable understandings of OWHTO in the treatment of knee osteoarthritis (KOA) and potential future directions for KOA treatment approaches.

BACKGROUND: The role of miRNAs in renal cell carcinoma (RCC) is not certain. We wanted to study the biological functions and potential mechanisms of miR-101-3p in RCC. METHODS: miR-101-3p was inhibited in A498 and OSRC-2 (two RCC cell lines). We studied its effect on cell invasion and proliferation. Target EZH2 of miR-101-3p was designated by different methods, including luciferase functional analysis and Western blotting. The expression level of the target gene in treated cells was quantitatively analyzed by quantitative real-time polymerase chain reaction. In addition, induction of miR-101-3p to prevent tumor formation of A498 cells in mice was further studied. RESULTS: The overexpression of miR-101-3p significantly inhibited the proliferation, migration, and invasion in two RCC cells. Western blotting and luciferase functional analysis indicated that miR-101-3p regulated the expression of EZH2 in two cell lines. Mice inoculated with A498 and OSRC-2 cells transfected with miR-101-3p mimics showed significantly smaller xenografts and weaker EZH2 expression levels than the control group. CONCLUSIONS: miR-101-3p inhibited RCC cell proliferation, migration, and invasion by targeting EZH2.

BACKGROUND: Increasing evidence has suggested that microRNA- (miR-) 103a-3p is crucial for cancer progression. However, the specific mechanism of miR-103a-3p in non-small-cell lung cancer (NSCLC) remains unclear until now. So, it is particularly urgent to clarify the mechanism between them. METHODS: qRT-PCR and western blot were used to measure the expression of miR-103a-3p, PTEN, Akt, and p-Akt. Cell biology experiment was applied to detect the biological function of miR-103a-3p in NSCLC cell lines. Moreover, bioinformatics analysis, luciferase reporter assay, and functional complementation analysis were carried out to investigate the target gene. RESULTS: miR-103a-3p was highly expressed in primary NSCLC samples and cell lines. miR-103a-3p mimics promoted the proliferation and invasion of NSCLC cells; miR-103a-3p inhibitor had the opposite effect. A double luciferase reporter gene experiment revealed that miR-103a-3p directly targets the PTEN mRNA 3'UTR region. siPTEN inhibited the proliferation and invasion of NSCLC cells. Further mechanistic studies showed that both overexpression of miR-103a-3p and PTEN knockdown reduced the expression of the p-Akt protein. Overexpression of PTEN partially reversed the cancer-promoting effect of miR-103a-3p. CONCLUSION: miR-103a-3p promotes the progression of NSCLC via Akt signaling by targeting PTEN, highlighting the role of miR-103a-3p/PTEN/Akt signaling and suggesting miR-103a-3p as a novel therapeutic target for NSCLC.

It is generally believed that excessive production of reactive oxygen species (ROS) during cardiovascular diseases impairs endothelial function. In this study, we aimed to investigate whether miR-214-3p is involved in the endothelial dysfunction induced by oxidized low-density lipoprotein (ox-LDL). In cultured vascular endothelial cells (VECs), the effects of miR-214-3p on endothelial injury induced by 100 mg/L ox-LDL were evaluated by knockdown of miR-214-3p. Western blotting was used to determine the expression of glutathione peroxidase 4 (GPX4) and endothelial nitric oxide synthase (eNOS) in VECs under different conditions. A luciferase reporter assay was used to identify GPX4 as the target of miR-214-3p. Our data showed that 100 mg/L ox-LDL significantly decreased the expression of GPX4 and eNOS, which was associated with increases in ROS levels and impairments of VEC viability and migration. Knockdown of miR-214-3p could partially reduce the increase in ROS, restore the decreased expression of GPX4 and eNOS, and thus rescue the impaired endothelial function caused by ox-LDL. Our data demonstrated that ox-LDL could induce upregulation of miR-214-3p and result in suppression of GPX4 in VECs. Downregulation of miR-214-3p could protect VECs from ROS-induced endothelial dysfunction by reversing its inhibitory effect on GPX4 expression.

Postpartum hemorrhage is a life-threatening situation, in which hysterectomy can be performed to prevent maternal death. However, it is associated with high rates of maternal morbidity and mortality and permanent infertility. The incidence of pregnancy-related hysterectomy varies across countries, but its main indications are the following: uterine atony and placenta spectrum (PAS) disorders. PAS disorder prevalence is rising during the last years, mainly due to the increased number of cesarean sections. As a result, obstetricians should be aware of the difficulties of this emergent condition and improve its accurate antenatal diagnosis rates, as well as its modern management strategies. Of course, special skills are required during a pregnancy-related hysterectomy, so these patients should be referred to centers of excellence in antenatal care, where a multidisciplinary team approach is followed. This study is a narrative review of the literature of the last 5 years (PubMed, Cochrane) regarding postpartum hemorrhage to offer obstetricians up-to-date knowledge on this pregnancy-related life-threatening issue. However, there is a lack of available high-quality data, because most published papers are retrospective case series or observational cohorts.

Since hysterectomy could be performed with low risk, it has been part of the standard of surgical prolapse therapy for decades. This has not been scrutinized for a long time. In this review, we describe the development of this issue in recent years. The current literature suggests that hysterectomy requires its own indication. The article describes the various options for a uterine-preserving surgical technique and the available data.

COVID-19, a severe respiratory disease caused by a new type of coronavirus SARS-CoV-2, has been spreading all over the world. Patients infected with SARS-CoV-2 may have no pathogenic symptoms, i.e., presymptomatic patients and asymptomatic patients. Both patients could further spread the virus to other susceptible people, thereby making the control of COVID-19 difficult. The two major challenges for COVID-19 diagnosis at present are as follows: (1) patients could share similar symptoms with other respiratory infections, and (2) patients may not have any symptoms but could still spread the virus. Therefore, new biomarkers at different omics levels are required for the large-scale screening and diagnosis of COVID-19. Although some initial analyses could identify a group of candidate gene biomarkers for COVID-19, the previous work still could not identify biomarkers capable for clinical use in COVID-19, which requires disease-specific diagnosis compared with other multiple infectious diseases. As an extension of the previous study, optimized machine learning models were applied in the present study to identify some specific qualitative host biomarkers associated with COVID-19 infection on the basis of a publicly released transcriptomic dataset, which included healthy controls and patients with bacterial infection, influenza, COVID-19, and other kinds of coronavirus. This dataset was first analysed by Boruta, Max-Relevance and Min-Redundancy feature selection methods one by one, resulting in a feature list. This list was fed into the incremental feature selection method, incorporating one of the classification algorithms to extract essential biomarkers and build efficient classifiers and classification rules. The capacity of these findings to distinguish COVID-19 with other similar respiratory infectious diseases at the transcriptomic level was also validated, which may improve the efficacy and accuracy of COVID-19 diagnosis.

BACKGROUND: The proportion of aging in China is increasing, which needs more healthcare recourses. To analyze the risk factors of the direct medical economic burden of aging in China and provide the strategies to control the cost of treatment, the information was collected based on Guangdong Province's regular health expenditure accounting data collection plan. METHODS: The multiple linear regression models were used to explore the risk factors of inpatient expenses of the elderly in Guangdong province. RESULTS: The results revealed that hospital day, age, male patients, and patients who suffer from malignant tumors are key factors to increase the direct medical economic burden of aging. Moreover, the medical insurance for urban employees can reduce the medical economic burden, comparing with the medical insurance for urban residents. CONCLUSIONS: The basic medical insurance system and the serious illness insurance system should be improved. While striving to speed up the development of regional economy, the government should pay attention to the construction of basic medical institutions in economically backward areas, increase the allocation of health human resources, and facilitate the masses to seek medical treatment nearby.

Lead poisoning in children is a major public health concern worldwide, especially in developing countries. We conducted a cross-sectional study on 403 children aged from 3 to 14 years living nearly zinc-lead mining areas in two provinces in Vietnam (Bac Kan and Thai Nguyen) from 06/2016 to 10/2016 to identify risk factors for lead contamination. Results. The proportion of children with blood lead levels (BLLs) ≥ 10 μg/dL was 80.51% in Bac Kan and 50% in Thai Nguyen; the mean blood lead level for children was 14.41 ± 9.42 μg/dL. In linear regression analyses, the body mass index was negatively associated with elevated BLLs with r = -0.404, p < 0.05 (95% CI: -0.801, -0.006). In multivariable regression analysis, several risk factors were associated with lead contamination including male sex (aOR = 2.44, 95% CI: 1.13-5.24, p = 0.02), play areas in Bac Kan (aOR = 2.3 (1.02-5.17), p = 0.04), proximity of children's home of less than 2 kilometers from the mine (aOR = 2.90 (1.54-5.44), p = 0.001), and inattentive symptoms in Thai Nguyen (aOR = 7.85, 95% CI 3.49-17.69, p = 0.001). Environmental factors, including lead concentrations in the soil and ambient air samples in both locations, are many times higher than Vietnamese standards.

OBJECTIVE: The introduction of CAD/CAM and the development of zirconia-based restorations have allowed clinicians to use less expensive materials and faster manufacturing procedures. The purpose of the study was to analyze the differences, in terms of mechanical and biological complication, in multiunit zirconia fixed dental prosthesis (FPDs) on posterior implants produced using a digital workflow. Method and Materials. This study was a retrospective investigation, and patients treated with screw-retained monolithic or partial veneer FPDs on dental implants were selected. Periapical radiographs were taken at baseline and at the 3-year follow-up. Complications were recorded and classified as technical and biological ones. RESULTS: The study population included 25 patients. The occlusal and interproximal corrections were not clinically significant. In the study sample, the survival rate and success rate of the FPDs after 3 years were 100% and 96%, respectively. One implant failed immediately after placement. CONCLUSION: Monolithic zirconia FPDs and partial veneer FPDs showed a 100% survival rate, presenting an interesting alternative to metal ceramic restorations. The partial veneer FPDs had a higher technical complication rate than the monolithic FPDs; however, no statistically significant difference was found.

Myocardial infarction is the main cause of death in patients with coronary heart disease. At present, the main method to treat cardiovascular disease is perfusion therapy. Myocardial ischemia-reperfusion will inevitably lead to reperfusion injury, which is also a major problem in the treatment of cardiovascular diseases. It has been reported that mir-451 in microRNA family participates in the protection of myocardial ischemia-reperfusion by regulating AMPK. The aim of this study was to investigate the effect of mir-451 on myocardial ischemia-reperfusion in rats by regulating AMPK signaling pathway. Sixty adult male rats were selected to establish myocardial ischemia-reperfusion animal model by ligating and loosening coronary artery. The expression level of mir-451 was regulated by injection of mir-451 virus vector and antibody, and the effect of increased or decreased mir-451 expression level on the activity of AMPK signaling pathway was detected. The myocardial infarct area and apoptosis rate of myocardial tissue were detected after 75 min ischemia-reperfusion. The results showed that when the expression level of mir-451 decreased by 15.7%, the activity index of AMPK signaling pathway was increased by 18.3%, the infarct area was reduced by 22.4%, and the apoptosis rate of myocardial cells was decreased by 25.2%. At the same time, the pathological structure of myocardial tissue was improved. Therefore, mir-451 is an inhibitor gene of AMPK signaling pathway. Reducing the expression of mir-451 can enhance the activity of AMPK signal pathway, and the increase of AMPK signal pathway activity is beneficial to reduce myocardial ischemia-reperfusion injury.

The anterolateral ligament (ALL) has been suggested as an important secondary knee restrain on the dynamic laxity in anterior cruciate ligament- (ACL-) deficient knees. Nevertheless, its kinematical contribution to the pivot-shift (PS) phenomenon has not been clearly and objectively defined, and noninvasive sensor technology could give a crucial contribution in this direction. The aim of the present study was to quantify in vitro the PS phenomenon in order to investigate the differences between an ACL-deficient knee and an ACL+ALL-deficient knee. Ten fresh-frozen paired human cadaveric knees (n = 20) were included in this controlled laboratory study. Intact, ACL-deficient, and ACL+ALL-deficient knees were subjected to a manual PS test quantified by a noninvasive triaxial accelerometer (KiRA, OrthoKey). Kinematic data (i.e., posterior acceleration of the tibial lateral compartment) were recorded and compared among the three statuses. Pairwise Student's t-test was used to compare the single groups (p < 0.05). Intact knees, ACL-deficient knees, and ACL+ALL-deficient knees showed an acceleration of 5.3 ± 2.1 m/s2, 6.3 ± 2.3 m/s2, and 7.8 ± 2.1 m/s2, respectively. Combined sectioning of ACL and ALL resulted in a statistically significant acceleration increase compared to both the intact state (p < 0.01) and the ACL-deficient state (p < 0.01). The acceleration increase determined by isolated ACL resection compared to the intact state was not statistically significant (p > 0.05). The ALL sectioning increased the rotatory laxity during the PS after ACL sectioning as measured through a user-friendly, noninvasive triaxial accelerometer.

Osteosarcoma (OS) is a type of bone malignancy with a high rate of treatment failure. To date, few evident biomarkers for the prognostic significance of OS have been established. Oncomine was used to integrate RNA and DNA-seq data from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and the published literature. The correlation of the gene Trophinin (TRO) and different types of cancers was generated using the Cancer Cell Line Encyclopedia (CCLE) online tool. Prognostic values of featured Melanoma Antigen Gene (MAGE) members were further assessed by establishing the overall survival using the Kaplan-Meier plotter. Moreover, the online tool, Database for Annotation, Visualization and Integrated Discovery version (DAVID), was used to understand the biological meaning list of the genes. MAGEB10, MAGED2, TRO, MAGEH1, MAGEB18, MAGEB6, MAGEB4, MAGEB1, MAGED4B, MAGED1, MAGEB2, and MAGEB3 were significantly overexpressed in sarcoma. TRO was further demonstrated to be distinctively upregulated in osteosarcoma cell lines and associated with shorter overall survival. TRO may play an important role in the development of OS and may be a promising potential biomarker and prognostic factor.

OBJECTIVE: We aim to investigate the correlation between FCGR2A mRNA level and prognosis of head and neck squamous cancer (HNSC) in public databases. In addition, we investigated the correlation between FCGR2A expression and clinicopathological characteristics and tumor-infiltrating immune cells in HNSC patients. METHODS: FCGR2A mRNA expression in multiple cancers was analyzed based on Gene Expression Profiling Interactive Analysis. A protein-protein interaction network was obtained based on the STRING database. The 10 proteins most closely related to FCGR2A (i.e., CD3G, PLCG2, LAT, LYN, SYK, FCGR3A, PIK3R1, HCK, ITGAM, and ITGB2) were screened, followed by establishing the protein-protein interaction network. The correlation between FCGR2A expression and immunocytes was investigated, together with the effects of FCGR2A on the metastasis, recurrence, and survival of HNSC. RESULTS: FCGR2A expression in several carcinoma tissues was significantly higher than that of adjacent tissues. Significant differences were noticed in the HNSC samples and the adjacent tissue samples except the seven samples of grade 4. There were statistical differences between the FCGR2A expression in tissues of grade 1, grade 2, and grade 3 (P < 0.05). In the tissues of grade 4, the expression of FCGR2A was the lowest. The FCGR2A protein was a type of II-a receptor in γFc of the low-affinity immunoglobulin, which could bind with the Fc region of the immunoglobulin γ. There was a correlation between the FCGR2A gene and the distal HNSC metastasis. FCGR2A gene expression was correlated with the survival and prognosis. The GSE65858 dataset was selected for the validation. The FCGR2A expression was significantly correlated with total survival (P = 0.0107) and progression-free survival (P = 0.0362). CONCLUSIONS: Our findings shed light on the importance of FCGR2A in HNSC and illustrated a potential relationship between FCGR2A and tumor-immune interactions.

Ulcerative colitis (UC) is a common disease with great variability in severity, with a high recurrence rate and heavy disease burden. In recent years, the different biological functions of competing endogenous RNA (ceRNA) networks of long noncoding RNAs (lncRNAs) and microRNAs (miRs) have aroused wide concerns, the ceRNA network of ulcerative colitis (UC) may have potential research value, and these expressed noncoding RNAs may be involved in the molecular basis of inflammation recurrence and progression. This study analyzed 490 colon samples associated with UC from 4 gene expression microarrays from the GEO database and identified gene modules by weighted correlation network analysis (WGCNA). CIBERSORT detected tissue-infiltrating leukocyte profiling by deconvolution of microarray data. LncBase and multiMIR were used to identify lncRNA-miRNA-mRNA interaction. We constructed a ceRNA network which includes 4 lncRNAs (SH3BP5-AS1, MIR4435-2HG, ENTPD1-AS1, and AC007750.1), 5 miRNAs (miR-141-3p, miR-191-5p, miR-192-5p, miR-194-5p, and miR196-5p), and 52 mRNAs. Those genes are involved in interleukin family signals, neutrophil degranulation, adaptive immunity, and cell adhesion pathways. lncRNA MIR4435-2HG is a variable in the decision tree for moderate-to-severe UC diagnostic prediction. Our work identifies potential regulated inflammation-related lncRNA-miRNA-mRNA regulatory axes. The regulatory axes are dysregulated during the deterioration of UC, suggesting that it is a risk factor for UC progression.

BACKGROUND: Oridonin is a powerful anticancer compound found in Rabdosia rubescens. However, its potential impact on bladder cancer remains uninvestigated. In this work, we aimed to detect the anticancer effect of oridonin on bladder cancer and explore the molecular mechanisms involved. METHODS: The anticancer activity of oridonin was assessed in vitro with a CCK8 assay, an annexin V-FITC apoptosis analysis, and colony formation and Transwell migration assays which were performed with the human bladder cancer cell line T24. Levels of apoptosis-related proteins, melastatin transient receptor potential channel 7 (TRPM7), and signaling molecules were examined in oridonin-treated T24 cells by western blotting or RT-PCR. Oridonin anticancer efficacy was further validated in vivo with a T24 xenograft mouse model. RESULTS: Oridonin repressed the proliferative, colony-forming, and migratory capacities of T24 cells, triggered extensive apoptosis in vitro, and retarded tumor growth in vivo. Moreover, oridonin treatment significantly increased expression levels of p53 and cleaved caspase-3 and reduced expression of TRPM7, p-AKT, and p-ERK. CONCLUSION: Oridonin exhibited outstanding antiproliferative and antimigratory effects on bladder cancer, and these effects were at least partially associated with targeting of TRPM7 through inactivation of the ERK and AKT signaling pathways. These findings provide insight for the clinical application of oridonin in bladder cancer prevention.

The purpose of this study was to propose a machine learning model and assess its ability to classify TMJ pathologies on magnetic resonance (MR) images. This retrospective cohort study included 214 TMJs from 107 patients with TMJ signs and symptoms. A radiomics platform was used to extract (Huiying Medical Technology Co., Ltd., China) imaging features of TMJ pathologies, condylar bone changes, and disc displacements. Thereafter, different machine learning (ML) algorithms and logistic regression were implemented on radiomic features for feature selection, classification, and prediction. The following radiomic features included first-order statistics, shape, texture, gray-level cooccurrence matrix (GLCM), gray-level run length matrix (GLRLM), and gray-level size zone matrix (GLSZM). Six classifiers, including logistic regression (LR), random forest (RF), decision tree (DT), k-nearest neighbors (KNN), XGBoost, and support vector machine (SVM) were used for model building which could predict the TMJ pathologies. The performance of models was evaluated by sensitivity, specificity, and ROC curve. KNN and RF classifiers were found to be the most optimal machine learning model for the prediction of TMJ pathologies. The AUC, sensitivity, and specificity for the training set were 0.89 and 1, while those for the testing set were 0.77 and 0.74, respectively, for condylar changes and disc displacement, respectively. For TMJ condylar bone changes Large-Area High-Gray-Level Emphasis, Gray-Level Nonuniformity, Long-Run Emphasis Long-Run High-Gray-Level Emphasis, Flatness, and Volume features, while for TMJ disc displacements Average Intensity, Sum Average, Spherical Disproportion, and Entropy features, were selected. This study has proposed a machine learning model by KNN and RF analysis on TMJ MR images, which can be used to classify condylar changes and TMJ disc displacements.

BACKGROUND: Platelet concentrates like leucocyte- and platelet-rich fibrin (L-PRF) have been widely evaluated in different oral surgical procedures to promote the healing process. However, liquid L-PRF products such as liquid fibrinogen have been poorly explored, especially in the biomimetic functionalization of dental implants. The aim of this in vitro study is to evaluate the interaction between 5 different dental implant surfaces and liquid fibrinogen. METHODS: Five commercially available dental implants with different surfaces (Osseospeed™, TiUnite™, SLActive®, Ossean®, and Plenum®) were immersed for 60 minutes in liquid fibrinogen obtained from healthy donors. After this period, the implants were removed and fixed for scanning electron microscopy (SEM). RESULTS: All dental implants were covered by a fibrin mesh. However, noticeable noncontact areas were observed for the Osseospeed™, TiUnite™, and SLActive® surfaces. On the other hand, Ossean® and Plenum® surfaces showed a dense and uniform layer of fibrin covering almost the entire implant surface. The Osseospeed™, TiUnite™, and SLActive® surfaces presented with lower blood cell numbers inside the fibrin mesh compared with the others. Moreover, at higher magnification, thicker fibrin fibers were observed in contact with Ossean® and Plenum® surfaces. The Plenum ®surface showed the thickest fibers which also inserted and interconnect to the microroughness. CONCLUSION: The initial contact between an implant surface and the fibrin network differs significantly among different implant brands. Further studies are necessary to explore the clinical impact of these observations in the osseointegration process of dental implants.

Peptide TT830-843 from the tetanus toxin is a universal T-cell epitope. It helps in vaccination and induces T-cell activation. However, the fine molecular interaction between this antigen and the major histocompatibility complex (MHC) remains unknown. Molecular analysis of its interaction with murine MHC (H-2) was proposed to explore its immune response efficiency. Molecular dynamics simulations are important mechanisms for understanding the basis of protein-ligand interactions, and metadynamics is a useful technique for enhancing sampling in molecular dynamics. SPR (surface plasmon resonance) assays were used to validate whether the metadynamics results are in accordance with the experimental results. The peptide TT830-843 unbinding process was simulated, and the free energy surface reconstruction revealed a detailed conformational landscape. The simulation described the exiting path as a stepwise mechanism between progressive detachment states. We pointed out how the terminus regions act as anchors for binding and how the detachment mechanism includes the opening of α-helices to permit the peptide's central region dissociation. The results indicated the peptide/H-2 receptor encounter occurs within a distance lesser than 27.5 Å, and the encounter can evolve to form a stable complex. SPR assays confirmed the complex peptide/H-2 as a thermodynamically stable system, exhibiting enough free energy to interact with TCR on the antigen-presenting cell surface. Therefore, combining in silico and in vitro assays provided significant evidence to support the peptide/H-2 complex formation.

Alzheimer's disease is a neurodegenerative disorder that is caused by the accumulation of beta-amyloid plaques in the brain. Currently, there is no definitive cure available to treat Alzheimer's disease. The available medication in the market has the ability to only slow down its progression. However, nanotechnology has shown its superiority that can be applied for medical usage and it has a great potential in the therapy of Alzheimer's disease, specifically in the disease diagnosis and providing an alternative approach to treat Alzheimer's disease. This is done by increasing the efficiency of drug delivery by penetrating and overcoming the blood-brain barrier. Having said that, there are limitations that need to be further investigated and researched in order to minimize the adverse effects and potential toxicity and to improve drug bioavailability. The recent advances in the treatment of Alzheimer's disease using nanotechnology include the regeneration of stem cells, nanomedicine, and neuroprotection. In this review, we will discuss the advancement of nanotechnology which helps in the diagnosis and treatment of neurodegenerative disorders such as Alzheimer's disease as well as its challenges.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible, high-mortality lung disease, but its pathogenesis is still unclear. Our purpose was to explore potential genes and molecular mechanisms underlying IPF. METHODS: IPF-related data were obtained from the GSE99621 dataset. Differentially expressed genes (DEGs) were identified between IPF and controls. Their biological functions were analyzed. The relationships between DEGs and microRNAs (miRNAs) were predicted. DEGs and pathways were validated in a microarray dataset. A protein-protein interaction (PPI) network was constructed based on these common DEGs. Western blot was used to validate hub genes in IPF cell models by western blot. RESULTS: DEGs were identified for IPF than controls in the RNA-seq dataset. Functional enrichment analysis showed that these DEGs were mainly enriched in immune and inflammatory response, chemokine-mediated signaling pathway, cell adhesion, and other biological processes. In the miRNA-target network based on RNA-seq dataset, we found several miRNA targets among all DEGs, like RAB11FIP1, TGFBR3, and SPP1. We identified 304 upregulated genes and 282 downregulated genes in IPF compared to controls both in the microarray and RNA-seq datasets. These common DEGs were mainly involved in cell adhesion, extracellular matrix organization, oxidation-reduction process, and lung vasculature development. In the PPI network, 3 upregulated and 4 downregulated genes could be considered hub genes, which were confirmed in the IPF cell models. CONCLUSION: Our study identified several IPF-related DEGs that could become potential biomarkers for IPF. Large-scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

BACKGROUND: There are various natural excipients which have been used as suspending agents in pharmaceutical suspensions due to the presence of mucilage in their specialized cells and their capacity to form a colloidal gel in an aqueous medium. OBJECTIVE: The purpose of this study was to evaluate the suspending capacity of Aloe elegans mucilage in suspension formulations. MATERIALS AND METHODS: Aloe elegans mucilage (AEM) was evaluated as a suspending agent in comparison with xanthan gum (XG) in paracetamol suspensions at 1, 2, 3, 4, and 5% (w/v) concentrations. The resulting suspensions were evaluated for their sedimentation volume, apparent viscosity, flow rate, rate of redispersibility, pH, assay, and dissolution profile. RESULTS: The volume of sedimentation, apparent viscosity, and redispersibility rate of the formulations were significantly increased (p < 0.05), with the concentration of the suspending agents. Meanwhile, the apparent viscosity for all formulations has significantly decreased (p < 0.05) with an increase in shear rates. Volume of sedimentation, apparent viscosity, and redispersibility degree of the formulations prepared with AEM were significantly (p < 0.05) lower than XG-containing formulations at the same concentration. Nevertheless, the sedimentation volume of all formulations with AEM was significantly (p < 0.05) higher than the suspension without any suspending agent. With regard to drug content and pH values, all formulations showed an acceptable result with the standards. All formulations showed a release of greater than 85% of drug content within 45 min. CONCLUSION: Aloe elegans mucilage could have a potential to be utilized as an alternative suspending agent in pharmaceutical suspensions.

BACKGROUND: Glioma is the most common malignant tumor of the brain in adult patients. The standardized treatment protocol is based on surgical therapy, supplemented with radiotherapy and chemotherapy. However, the prognosis is still unsatisfied. Chemoresistance is one of the most important reason for the poor prognosis of glioma patients. It has confirmed that glioma stem cell (GSC) is one of the reasons for chemoresistance. METHODS: In this study, three datasets (GSE23806, COSMIC, and TCGA) were used to perform the analysis to search for the key genes related to GSC, temozolomide (TMZ) resistance, and prognosis. The key gene for further research was selected by reviewing the previous studies. The selected gene investigated the relation between expression levels and clinical characteristics in both TCGA and CGGA dataset. The bioinformatics analysis was performed by Gene Ontology (GO) analysis. The survival analysis was performed by Kaplan-Meier survival analysis. RESULTS: AE binding protein 1 (AEBP1) was selected for further analysis. AEBP1 was overexpressed in GSCs and TMZ resistance cells. In both TCGA and CGGA dataset, the results showed that the expression level of AEBP1 was increased in glioblastoma (GBM) samples, IDH wild-type samples, and MGMT promoter unmethylated samples. Meanwhile, AEBP1 expression was positively related to several GSC markers. GO analysis showed that AEBP1 was related to immune response, cell adhesion, apoptotic process, inflammatory response, positive regulation of cell proliferation, angiogenesis, response to drug, and response to hypoxia. The survival analysis showed that the overexpressed level of AEBP1 was correlated with short survival time in both glioma and GBM patients. CONCLUSION: In summary, AEBP1 was related with GSC-induced TMZ resistance. Our study showed that AEBP1 might be an oncogene and a new effective therapeutic target for the treatment of glioma.

OBJECTIVE: This study is aimed at describing a score to assess infection control structures in Oral Health Teams (OHT) in Primary Health Care (PHC) in Brazil. METHODS: Secondary data from a national external evaluation of PHC conducted in 2017 and 2018 were analyzed. The construction of the score used 14 variables, divided into the following: structural characteristics of the PHC, infection control equipment under conditions of use, and biosafety supplies in sufficient quantity. The questions were mostly dichotomous (yes/no). Descriptive analyses were carried out to characterize the OHT and factor analyses to reduce the number of observed variables to a specific number of factors. RESULTS: Among 20,301 health units with OHT, 4,510 (22.2%) units did not have washable floors, ceilings, and walls; 8,406 (41.4%) did not have a sealer; 16,780 (82.7%) did not have taps with noncontact activation, and 4,663 (23.0%) units did not have rubber gloves. Regarding personal protective equipment (PPE), 1,618 (8.0%) units did not have a sufficient quantity of basic PPE. Three factors were defined to explain the 14 evaluated variables. The South region had the best score of infection control, while the North had the worst. CONCLUSIONS: Regional inequalities in the failures in infection control structures identified in PHC with OHT were related to the physical structure, equipment, and supplies used for infection control and the absence of PPE for OHT.

Ageing well has been associated with the responsibility to age actively, successfully, or healthily in public and research discourses. This connection of individual responsibility with ageing has been criticised in Social Gerontology for neglecting the access to social, economic, and health resources. This paper investigates (individual) responsibility, informal support, and public initiatives in discourses on older immigrants in Germany. The research framework employs a sociology of knowledge approach to discourse, which guided the discourse analysis of German policy reports, guidelines and handbooks on ageing and migration from 2000 to 2019 (43 documents in total). The results reveal that besides public initiatives concerning long-term care, health promotion, and social services, informal solutions through social networks are frequently emphasised in the data. The focus, thereby, is on long-term care, which is presented as a responsibility of the extended family. Thus, resources are situated in the family, social networks, and ethnic group, which should be opened and connected with public services; however, the focus is shifting from older immigrants towards local municipalities. This study provides a discourse perspective on the construction of resources and challenges for older immigrants concerning health, care, and social services and offers an assessment of the cultural and integrating/excluding qualities in active ageing discourses.

PURPOSE: To explore the effects of ulinastatin on the proliferation and apoptosis of breast cancer cells and the relevant mechanism of action. METHODS: Breast cancer cells (MCF-7) were cultured and randomly divided into three groups, namely, control group, ulinastatin group, and ulinastatin+extracellular-regulated protein kinase (ERK) inhibitor group. Then, the Cell Counting Kit-8 (CCK-8) assay was carried out to detect the effect of ulinastatin on the viability of breast cancer cells. The effects of ulinastatin on the proliferation and apoptosis of breast cancer cells were determined via EdU staining and Hoechst 33258 staining assays, respectively. The messenger ribonucleic acid (mRNA) and protein expression levels of ERK and forkhead box O3 (FOXO3) in breast cancer cells were measured through reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. RESULTS: In comparison with the control group, the ulinastatin group displayed decreased viability of breast cancer cells, a decreased positive rate of 5-ethynyl-2'-deoxyuridine (EdU) staining, an increased positive rate of Hoechst 33258 staining, and reduced mRNA and protein levels of ERK and FOXO3 in breast cancer cells. Compared with those in the ulinastatin group, the viability of breast cancer cells was lowered, the positive rate of EdU staining was reduced, the positive rate of Hoechst 33258 staining was raised, and the mRNA and protein levels of ERK and FOXO3 in breast cancer cells clearly declined in the ulinastatin+ERK inhibitor group. CONCLUSION: Ulinastatin inhibits the proliferation and promotes the apoptosis of breast cancer cells. The possible mechanism of action is associated with the suppression of the ERK signaling pathway.

BACKGROUND: Chemotherapeutic drugs cause severe toxicities if administered unprotected, without proper targeting, and controlled release. In this study, we developed topotecan- (TPT-) loaded solid lipid nanoparticles (SLNs) for their chemotherapeutic effect against colorectal cancer. The TPT-SLNs were further incorporated into a thermoresponsive hydrogel system (TRHS) (TPT-SLNs-TRHS) to ensure control release and reduce toxicity of the drug. Microemulsion technique and cold method were, respectively, used to develop TPT-SLNs and TPT-SLNs-TRHS. Particle size, polydispersive index (PDI), and incorporation efficiency (IE) of the TPT-SLNs were determined. Similarly, gelation time, gel strength, and bioadhesive force studies of the TPT-SLNs-TRHS were performed. Additionally, in vitro release and pharmacokinetic and antitumour evaluations of the formulation were done. RESULTS: TPT-SLNs have uniformly distributed particles with mean size in nanorange (174 nm) and IE of ~90%. TPT-SLNs-TRHS demonstrated suitable gelation properties upon administration into the rat's rectum. Moreover, drug release was exhibited in a control manner over an extended period of time for the incorporated TPT. Pharmacokinetic studies showed enhanced bioavailability of the TPT with improved plasma concentration and AUC. Further, it showed significantly enhanced antitumour effect in tumour-bearing mice as compared to the test formulations. CONCLUSION: It can be concluded that SLNs incorporated in TRHS could be a potential source of the antitumour drug delivery with better control of the drug release and no toxicity.

BACKGROUND: Colorectal cancer (CRC) is among the top three gastrointestinal malignancy in morbidity and mortality. The abnormal activation of Wnt/β-catenin pathway is considered to be a key factor in the occurrence and development of CRC. Novel inhibitor discovery against key factor in WNT pathway is important for CRC treatment and prevention. METHODS: Cell proliferation was detected after hydroxyphenyl butanone treatment in human colorectal cancer HCT116, LOVO, and normal colonic epithelial NCM460 cells. Colony formation, cell invasion ability, and cell cycle were detected with and without GSK-3β knockdown. RESULTS: Hydroxyphenyl butanone induces cycle arresting on G1-S phase of colorectal cancer cell line through GSK3β in Wnt/β-catenin pathway and inhibits malignant biological manifestations of cell proliferation, colony formation, and invasion. The inhibition in the high concentration group is stronger than that in the low concentration group, and the antitumor effect is different for different tumor cells. Under the same concentration of natural hydroxyphenyl butanone, the inhibition on normal colonic epithelial cells is significantly lower than that on tumor cells. The natural hydroxyphenyl butanone with medium and low concentration could promote the proliferation of normal colonic epithelial cells. CONCLUSION: This study illustrated natural hydroxyphenyl butanone as new inhibitor of GSK3β and revealed the mechanisms underlying the inhibitory effects in colorectal cancer.

PURPOSE: The purpose of the present study was to review the literature regarding the blood loss and postoperative pain in the isolated sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO). MATERIALS AND METHODS: Investigating the intraoperative blood loss and postoperative pain, articles were selected from 1970 to 2021 in the English published databases (PubMed, Web of Science, and Cochrane Library). Article retrieval and selection were performed by two authors, and they independently evaluated them based on the eligibility criteria. The articles meeting the search criteria had especially at least 30 patients. RESULTS: In the review of intraoperative blood loss, a total of 139 articles were retrieved and restricted to 6 articles (SSRO: 4; IVRO: 2). In the review of postoperative pain, a total of 174 articles were retrieved and restricted to 4 articles (SSRO: 3; IVRO: 1). The mean blood loss of SSRO and IVRO was ranged from 55 to 167 mL and 82 to 104 mL, respectively. The mean visual analog scale (VAS) scores of the first postoperative day were 2 to 5.3 in SSRO and 2.93 to 3.13 in IVRO. The mean VAS scores of the second postoperative day were 1 to 3 in SSRO and 1.1 to 1.8 in IVRO. CONCLUSION: Compared to traditional SSRO, IVRO had a significantly lower amount of blood loss. However, the blood transfusion is not necessary in a single-jaw operation (SSRO or IVRO). Postoperative pain was similar between SSRO and IVRO.

Patients with multimorbidity are commonly seen in primary care. An increasing number of multimorbidity patterns are being reported in the Western literature with a few from Asia. The main objective of this systematic review was to describe patterns of associative multimorbidity, defined as associations beyond chance or patterns of diseases, in the Asian population. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE (Ovid)), Excerpta Medica Database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science (Clarivate Analytics), and Scopus (Elsevier) databases from their inception to April 22, 2019 using medical subject headings, keywords in titles, abstracts, and text. We used the Modified Newcastle-Ottawa Scale for risk-of-bias assessment. Eight articles from China, India, Indonesia, and Japan met the inclusion criteria. Patterns of associative multimorbidity were reported as dyadic/triadic disease combinations or disease clusters. The most common multimorbidity pattern, "cardiovascular and metabolic diseases," was identified in six of eight articles. The other four multimorbidity patterns are comprised of "mental health problems," "degenerative diseases," pulmonary diseases," and "cancer diseases." The eight articles showed methodological heterogeneity in terms of the list of chronic diseases, ascertainment of multimorbidity, statistical methods, and study populations. This systematic review identified five common patterns of associative multimorbidity in Asia. "Cardiovascular and metabolic diseases" and "mental diseases" were two patterns that were similarly reported in the Western world. Alignment of the definition of multimorbidity and the statistical methodology are needed to identify the unique patterns of multimorbidity in Asia so that clinical practice guidelines on multimorbidity can be developed for the Asian population.

AIMS: Although several studies have indicated that valproate (VPA) and oxcarbazepine (OXC) cause reproductive endocrine disorders and sexual dysfunction, there remains some controversy regarding these issues in males with epilepsy. This study is aimed at evaluating the effects of VPA and OXC on sexual function, sperm quality, and sex hormones in young males with epilepsy. METHODS: Males with newly diagnosed epilepsy treated with VPA and OXC were recruited, and sexual function questionnaires (International Index of Erectile Function-5 (IIEF-5)), sperm quality, and sex hormone levels were assessed before treatment and at 6 months after treatment with VPA or OXC monotherapy. RESULTS: Forty-four young males with epilepsy (23 treated with VPA, 21 treated with OXC) and 30 age-matched healthy individuals were recruited for our study. The sexual function, sperm quality, marriage rate, and fertility rate of these young males with epilepsy were lower than those of healthy controls. Sperm quality were significantly reduced in young male patients after 6 months of VPA administration. The level of follicle stimulating hormone (FSH) was increased in patients after OXC treatment. Meanwhile, sexual function and sperm quality were not affected. CONCLUSION: Sexual function and sperm quality were reduced in young males with epilepsy. VPA may exert a negative effect on sperm quality, whereas OXC has no harmful effect on sexual function and sperm quality in young males with epilepsy.

The aim of this study was to evaluate the biocompatibility and osteogenic potential of a Zeolite Socony Mobil-5 (ZSM-5) coating on a Ti-24 Nb-4 Zr-7.9 Sn (Ti-2448) surface. ZSM-5-modified Ti-2448 (ZSM-5/Ti-2448) and Ti-2448 (control) groups were employed. The physical and chemical properties of the two types of samples were evaluated by scanning electron microscopy, Fourier-transform infrared spectroscopy, nitrogen adsorption/desorption, and contact angle methods. The surface of the ZSM-5/Ti-2448 was rougher than that of the original Ti-2448, while the contact angle of the ZSM-5/Ti-2448 was smaller than that of Ti-2448. In addition, the ZSM-5/Ti-2448 largely increased the specific surface area and introduced silanol groups. A bone-like apatite layer could be formed on the surface of ZSM-5/Ti-2448 after 14 days of incubation in a simulated body fluid. ZSM-5/Ti-2448 was not cytotoxic. The number and alkaline phosphatase (ALP) activity of osteoblasts on ZSM-5/Ti-2448 were significantly higher than those on Ti-2448 surfaces, obtained in vitro using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide and ALP activity assays. Few inflammatory cells were observed around ZSM-5/Ti-2448 after insertion into the femurs of Japanese white rabbits after 4, 12, and 26 weeks through hematoxylin-eosin staining. The average gray scale of transforming growth factor-β1 (TGF-β1) on ZSM-5/Ti-2448 peaked earlier than that on Ti-2448, according to immunohistochemical staining. These results indicate that ZSM-5/Ti-2448 has a good biocompatibility and improved early osteogenic potential compared to a noncoated Ti-2448.

Kidney transplantation is the promising treatment of choice for chronic kidney disease and end-stage kidney disease and can effectively improve the quality of life and survival rates of patients. However, the allograft rejection following kidney transplantation has a negative impact on transplant success. Therefore, the present study is aimed at screening novel biomarkers for the diagnosis and treatment of allograft rejection following kidney transplantation for improving long-term transplant outcome. In the study, a total of 8 modules and 3065 genes were identified by WGCNA based on the GSE46474 and GSE15296 dataset from the Gene Expression Omnibus (GEO) database. Moreover, the results of Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that these genes were mainly involved in the immune-related biological processes and pathways. Thus, 317 immune-related genes were selected for further analysis. Finally, 5 genes (including CD200R1, VAV2, FASLG, SH2D1B, and RAP2B) were identified as the candidate biomarkers based on the ROC and difference analysis. Furthermore, we also found that in the 5 biomarkers an interaction might exist among each other in the protein and transcription level. Taken together, our study identified CD200R1, VAV2, FASLG, SH2D1B, and RAP2B as the candidate diagnostic biomarkers, which might contribute to the prevention and treatment of allograft rejection following kidney transplantation.

A fluoride-releasing adhesive system is expected to promote mineralization of demineralized dentin/enamel around a composite restoration, thereby contributing to the longevity of the restoration. Scanning electron microscopic (SEM) and transmission electron microscopic (TEM) observations revealed the formation of an "acid-base resistant zone" (ABRZ) beneath the hybrid layer when dentin was treated with a self-etch adhesive system. A thicker ABRZ was formed from the upper slope to the end of the outer lesion, indicating greater resistance against an acid-base challenge, when a fluoride-releasing self-etch adhesive system was used. The slope formation of a fluoride-releasing adhesive is believed to be due to fluoride-release from the adhesive. Quantitative assessment of the acid resistance was performed at the interface using the region of interest (ROI) mode of a digital image analysis software package. The area of the ABRZ is influenced by the concentration of fluoride release from the adhesive resin. The threshold of fluoride concentration in the adhesive may exist to influence the morphology of the ABRZ. X-ray absorption fine structure (XAFS) analysis of the dentin treated with different concentrations of NaF-mouth rinses suggested that different fluoride concentrations result in the formation of different chemical compounds, such as fluorapatite and CaF2-like structures, on the dentin surface. This may explain the differences in μTBS values and morphological appearance of the ABRZ. NaF is effective in enhancing the enamel/dentin bond durability and also helps create a high quality of ARBZ to improve the clinical success of restorations.

Early life stress is an important determinant for developing depression later in life. It is reported that maternal separation (MS) could trigger stress sensitivity in adulthood when exposed to stress again. However, it could also result in resilience to stress-induced depression. The conclusions are contradictory. To address this issue, C57BL/6N newborn pups were exposed to either daily short MS (MS for 15 min per day; MS15) or prolonged MS (MS for 180 min per day; MS180) from the first day postpartum (PD1) to PD21. Adult mice were then subjected to chronic unpredictable mild stress (CUMS) exposure from PD64 to PD105. The behavior tests such as the forced swimming test (FST), tail suspension test (TST), and open-field test were performed once a week during this time. Besides, the hippocampal neurosteroids, serum stress hormones, and hippocampal monoamine neurotransmitters were measured at PD106. We found that mice in the MS180 group displayed the reduced struggling time and the increased latency to immobility in both FST and TST. However, there was no significant difference in the MS15 group. The levels of hippocampal neurosteroids (progesterone and allopregnanolone) were decreased, and the serum levels of corticosterone, corticotropin-releasing hormone, and adrenocorticotropic hormone were overexpressed in the MS180 group. Besides, the expressions of monoamine neurotransmitters such as 5-hydroxytryptamine and 5-hydroxy indole acetic acid significantly decreased in the MS180 group, but not in the MS15 group. All findings revealed that prolonged MS, rather than short MS, could increase the susceptibility to depression-like behavior when reexposed to stress in adulthood. However, future studies are warranted to identify the underlying neuromolecular mechanism of the MS experience on the susceptibility to adult stress reexposure.

Pulsed electromagnetic field (PEMF) therapy is a type of physical stimulation that affects biological systems by producing interfering or coherent fields. Given that cell types are significantly distinct, which represents an important factor in stimulation, and that PEMFs can have different effects in terms of frequency and intensity, time of exposure, and waveform. This study is aimed at investigating if distinct positive and negative responses would correspond to specific characteristics of cells, frequency and flux density, time of exposure, and waveform. Necessary data were abstracted from the experimental observations of cell-based in vitro models. The observations were obtained from 92 publications between the years 1999 and 2019, which are available on PubMed and Web of Science databases. From each of the included studies, type of cells, pulse frequency of exposure, exposure flux density, and assayed cell responses were extracted. According to the obtained data, most of the experiments were carried out on human cells, and out of 2421 human cell experiments, cell changes were observed only in 51.05% of the data. In addition, the results pointed out the potential effects of PEMFs on some human cell types such as MG-63 human osteosarcoma cells (p value < 0.001) and bone marrow mesenchymal stem cells. However, human osteogenic sarcoma SaOS-2 (p < 0.001) and human adipose-derived mesenchymal stem cells (AD-MSCs) showed less sensitivity to PEMFs. Nevertheless, the evidence suggests that frequencies higher than 100 Hz, flux densities between 1 and 10 mT, and chronic exposure more than 10 days would be more effective in establishing a cellular response. This study successfully reported useful information about the role of cell type and signal characteristic parameters, which were of high importance for targeted therapies using PEMFs. Our findings would provide a deeper understanding about the effect of PEMFs in vitro, which could be useful as a reference for many in vivo experiments or preclinical trials.

METHODS: Thirty-three consecutive patients with 34 TVIAs were prospectively recruited and treated with endovascular techniques. The volume of TVIAs and the required length of coils were calculated by the AngioSuite software before embolization. The treatment efficacy of TVIAs was assessed using the Raymond scale (Rs) and the modified Rankin scale (mRs). RESULTS: Of the 34 aneurysms with an average volume of 7.16 mm3, 13 aneurysms were treated with sole coil embolization, 19 by stent-assisted embolization, and 2 by balloon-assisted embolization. The average coil length was 5.32 cm, and the average packing density was 41.21%. The immediate DSA showed that total occlusion (Rs = 1) was achieved in 15 aneurysms, subtotal (Rs = 2) in 9, and partial (Rs = 3) in 11. Total occlusion was achieved in 30 aneurysms and subtotal in the other 4 aneurysms at 6-month follow-up. Baseline volume and diameter of aneurysms were significantly correlated with the coil length (r = 0.801, P < 0.001; r = 0.711, P < 0.001). CONCLUSIONS: Coil embolization of TVIAs was easy to achieve high packing density. According to the data from AngioSuite, relative few coils can increase the safety in procedure and stenting may reduce risk of aneurysmal recurrence.

Platelet-rich plasma (PRP) has emerged as a significant regenerative therapy used alone or combined mainly with stem cells, autologous fat grafts, hyaluronic acid, and biomaterials in a variety of medical fields, especially in hair regrowth, wound healing, and sports and rehabilitation medicine. However, the results obtained with this biologic therapy are heterogeneous and conflicting. The observed disparities in the effectiveness of PRP therapies may be due to a lack of standardization in blood processing and preparation. This article is aimed at reviewing the main biological parameters that need to be documented for a thorough reporting of quantitative and qualitative characteristics of the PRP injected, to allow a comparison between the quality of samples and the clinically obtained results and advance the efforts towards treatment standardization.

The clinical research faces numerous challenges, from patient enrollment to data privacy concerns and regulatory requirements to spiraling costs. Blockchain technology has the potential to overcome these challenges, thus making clinical trials transparent and enhancing public trust in a fair and open process with all stakeholders because of its distinct features such as data immutability and transparency. This paper proposes a permissioned blockchain platform to ensure clinical data transparency and provides secure clinical trial-related solutions. We explore the core functionalities of blockchain applied to clinical trials and illustrate its general principle concretely. These clinical trial operations are automated using the smart contract, which ensures traceability, prevents a posteriori reconstruction, and securely automates the clinical trial. A web-based user interface is also implemented to visualize the data from the blockchain and ease the interaction with the blockchain network. A proof of concept is implemented on Hyperledger Fabric in the case study of clinical management for multiple clinical trials to demonstrate the designed approach's feasibility. Lastly, the experiment results demonstrate the efficiency and usability of the proposed platform.

Khat (Catha edulis Forsk) is a plant consumed by many people in Eastern Africa, including Ethiopia, and Southern Arabia to be stimulated. There are several human and animal studies on khat that provide information about its toxic effects. However, the potential toxic effects of khat on embryos and fetuses have not been elucidated. The aim of the present study was to investigate the embryotoxic and fetotoxic effects of khat exposure during the earliest period of gestation in rats. Pregnant Wistar albino rats were treated with khat extract at 250, 500, and 750 mg/kg doses from day 6 through day 12 of gestation. The treatment was delivered by gavage. Embryos and fetuses were recovered on gestational day 12 or day 20, respectively, and were quantitatively and qualitatively assessed for developmental anomalies. Placentae from the treatment and control groups were investigated for histopathological effects. Results of the present study showed that khat exposure during pregnancy had dose-dependent toxic effects in rat embryos and fetuses. Prenatal growth retardation such as reduced fetal weight and crown-rump length was observed in near-term fetuses, especially, in animals treated with the highest dose of khat (p < 0.05). Growth retardation and developmental anomalies were also observed in day 12 embryos of khat-treated rats. Maternal weight gain of the khat-treated group was also significantly lower than the control group. Cytolysis, decidual hypoplasia, and atrophy were observed in the placenta of the khat-treated rats. Findings of the present study revealed, for the first time, that exposure of pregnant rat to crude extract of khat causes embryotoxic and fetotoxic effects.

Stroke is one of the leading causes of death and the primary cause of acquired disability worldwide. Many stroke survivors have difficulty using their upper limbs, which have important functional roles in the performance of daily life activities. Consequently, the independence and quality of life of most stroke patients are reduced. Robot-assisted therapy is an effective intervention for improving the upper limb function of individuals with stroke. Human-robot collaborative interaction force control technology is critical for improving the flexibility and followability of the robot's motion, thereby improving rehabilitation training outcomes. However, there are few reports on the effect of robot-assisted rehabilitative training on upper limb function. We applied this technology using a robot to assist patients with task-oriented training. Posttreatment changes in Fugl-Meyer and modified Barthel index (MBI) scores were assessed to determine whether this technology could improve the upper limb function of stroke patients. One healthy adult and five stroke patients, respectively, participated in functional and clinical experiments. The MBI and Fugl-Meyer scores of the five patients in the clinical experiments showed significant improvements after the intervention. The experimental results indicate that human-robot collaborative interaction force control technology is valuable for improving robots' properties and patients' recovery. This trial was registered in the Chinese clinical trial registry (ChiCTR2000038676).

The present study is aimed at profiling circulating exosome-derived microRNAs (miRNAs/miRs) from patients with dermatomyositis (DM), in particular those complicated with interstitial lung disease (ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive. Fifteen participants were enrolled, including five patients with DM complicated with ILDs prior to treatment with circulating anti-MDA5 antibody-positive status [DM-ILD-MDA5 Ab(+)], five DM patients without ILDs who were negative for 16 detectable myositis-specific antibodies [DM-nonILD-MSA16(-)], and five age- and gender-matched healthy donor controls (HCs). The characteristics of the exosomes extracted by Ribo™ Exosome Isolation Reagent were identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. Differentially expressed miRNAs, determined by next-generation deep sequencing, were identified through the criteria of ∣log2 fold change | ≥1 and P < 0.01. A total of 38 miRNAs were significantly upregulated in exosomes from patients with DM-ILD-MDA5 Ab(+) compared to those from HC, while 21 miRNAs were significantly downregulated. Compared to exosomes derived from patients with DM-nonILD-MSA16(-), 51 miRNAs were significantly upregulated and 33 miRNAs were significantly downregulated from patients with DM-ILD-MDA5 Ab(+). A total of 73 exosomal miRNAs were significantly differentially expressed between DM-nonILD-MSA16(-) and HC. In particular, two miRNAs, Homo sapiens- (hsa-) miR-4488 and hsa-miR-1228-5p, were common differentially expressed miRNAs among three comparisons. GO and KEGG analyses suggested that several pathways may contribute the pathogenesis of DM-ILD-MDA5 Ab(+) and DM-nonILD-MSA16(-), while PPI network analysis of hsa-miR-4488 and hsa-miR-1228-5p indicated that their predicted target genes, DExD-box helicase 39B and MDM2, may be involved in the mechanisms of DM-ILD-MDA5 Ab(+).

BACKGROUND: Although the prognosis of low-grade glioma is better than that of glioblastoma, there are still some groups with poor prognosis. The integrated stress response contributes to the malignant progress of tumors. As there had limited research focused on the integrated stress status in LGG, it is urgent to profile and reclassify LGG based on the integrated stress response. METHODS: Information of glioma patients was obtained from the Chinese Glioma Genome Atlas, The Cancer Genome Atlas, and the GSE16011 cohorts. Statistical analyses were conducted using GraphPad Prism 8 and R language. RESULTS: We summarized and quantified four types of integrated stress responses. Relationships between these four types of stress states and the clinical characteristics were analyzed in low-grade glioma. We then reclassified the patients based on these four scores and found that cluster 2 had the worst prognosis, while cluster 1 had the best prognosis. We also established an accurate integrated stress response risk signature for predicting cluster 2. We found that immune response and suppressive immune cell components were more enriched in the high-risk group. We also profiled the genomic differences between the low- and high-risk groups, including the nonmissense mutation of driver genes and the copy number variations. CONCLUSION: Low-grade glioma patients were divided into three clusters based on the integrated stress status, with cluster 2 exhibiting malignant transformation trends. The signature adequately reflected the traits of cluster 2, while a high risk score indicated a worse prognosis and an enriched inhibitory immune microenvironment.

To observe the effects of luteolin on galactosamine (D-Gal)/lipopolysaccharide (LPS) induced liver injury in mice. Male C57BL/6 mice were randomly divided into 4 groups: normal control group, D-GaI/LPS group, D-GaI/LPS + luteolin (Lu, 20 mg/kg), and D-GaI/LPS + luteolin (Lu, 40 mg/kg). Mice in the normal control group and D-GaI/LPS group were given distilled water while other groups were given drugs in 7 days by gavage. 4 hours after the continuous administration, Gal (700 mg/kg) and LPS (10 mg/kg) were injected intraperitoneally. Mice in the normal control group were given the same volume of vegetable oil solution. 24 h after the establishment of the mice model, blood and liver samples were collected. Hematoxylin (HE) staining was used to observe the changes of hepatic histopathology. Alanine aminotransferase (ALT) and glutamic oxalacetic transaminase (AST) in serum, interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor (TNF-α) were measured by related kits. Western blotting was used to demonstrate the expression levels of related inflammation proteins. Lu significantly reduced levels of proinflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in serum and liver. Lu restored the pathological changes after galactosamine (D-Gal)/lipopolysaccharide (LPS) treatment. In addition, Lu regulated proteins levels of the NLRP3/NF-κB pathway in liver. Lu exhibited therapeutical effects on D-GaI/LPS induced liver injury in mice which might be related to the regulation of the NLRP3/NF-κB pathway.

Type 2 diabetes (T2D) is thought to be a complication of metabolic syndrome caused by disorders of energy utilization and storage and characterized by insulin resistance or deficiency of insulin secretion. Though the mechanism linking obesity to the development of T2D is complex and unintelligible, it is known that abnormal lipid metabolism and adipose tissue accumulation possibly play important roles in this process. Recently, nicotinamide N-methyltransferase (NNMT) has been emerging as a new mechanism-of-action target in treating obesity and associated T2D. Evidence has shown that NNMT is associated with obesity and T2D. NNMT inhibition or NNMT knockdown significantly increases energy expenditure, reduces body weight and white adipose mass, improves insulin sensitivity, and normalizes glucose tolerance and fasting blood glucose levels. Additionally, trials of oligonucleotide therapeutics and experiments with some small-molecule NNMT inhibitors in vitro and in preclinical animal models have validated NNMT as a promising therapeutic target to prevent or treat obesity and associated T2D. However, the exact mechanisms underlying these phenomena are not yet fully understood and clinical trials targeting NNMT have not been reported until now. Therefore, more researches are necessary to reveal the acting mechanism of NNMT in obesity and T2D and to develop therapeutics targeting NNMT.

It is very difficult to diagnose and distinguish tuberculous meningitis, and the current laboratory methods are unsubstantial in developing countries. The study is aimed at creating a scoring system on the basis of basic laboratory and clinical achievements that could be used as diagnostic aid for tuberculous meningitis for Chinese patients. A retrospective study of cases was conducted for comparison between clinical characteristics and laboratory features of 241 patients on admission who conformed to inclusion criteria of tuberculous meningitis (n = 141) or bacterial meningitis (n = 100). Logistic regression was employed to establish a diagnostic formula to distinguish between tuberculous meningitis and bacterial meningitis. The receiver operating characteristic curve analysis was applied to determine the best diagnostic critical point of the diagnostic formula. It was found that five variables (disease course, white blood cell count, serum sodium, total white cell count of cerebrospinal fluid, and neutrophil proportion in cerebrospinal fluid) were independently associated with tuberculous meningitis. The 87% sensitivity and 94% specificity were included in the diagnostic scoring system derived from these variables. Especially in the case of limited microbial resources, doctors can use this diagnostic scoring system to distinguish tuberculous meningitis from bacterial meningitis.

Picroside II is an important ingredient agent in Traditional Chinese medicine and hoped to reduce hepatocellular injury caused by severe acute pancreatitis (SAP). An SAP-induced hepatocellular injury model was established in rats by using pentobarbital sodium. 27 rats were divided into 3 groups: the sham group (SG), model group (MG), and Picroside groups (PG). SAP-induced hepatocellular injury was assessed using hematoxylin and eosin staining. We measured hepatocellular enzymes (amylase (AMY), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)), oxidative stress factors (superoxidase dismutase (SOD) and malondialdehyde (MDA)), and inflammatory factors (tumor necrosis factor α (TNF-α), interleukin- (IL-) 6, and IL-10), apoptotic factors (BAX and cleaved caspase 3), and inflammatory signaling (Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3), p-JAK2, and p-STAT3) in hepatocellular tissues. The SAP-induced hepatocellular injury model was successfully established. Picroside II treatment repaired hepatocellular injury by reducing the activities of AMY, ALT, and AST; reducing the levels of MDA, TNF-α, IL-1, IL-6, p-JAK2, p-STAT3, BAX, and cleaved caspase 3; and increasing the levels of SOD and IL-10. Picroside II exerted protective function for the SAP-induced hepatocellular injury model. Picroside II improved SAP-induced hepatocellular injury and antioxidant and anti-inflammatory properties by affecting JAK2/STAT3 phosphorylation signaling.

Endovascular repair including percutaneous transluminal angioplasty (PTA) and stent implantation has become the standard approach for the treatment of peripheral arterial disease; however, restenosis is still the main limited complication for the long-term success of the endovascular repair. Endothelial denudation and regeneration, inflammatory response, and neointimal hyperplasia are major pathological processes occurring during in-stent restenosis (ISR). MicroRNAs exhibit great potential in regulating several vascular biological events in different cell types and have been identified as novel therapeutic targets as well as biomarkers for ISR prevention. This review summarized recent experimental and clinical studies on the role of miRNAs in ISR modification, with the aim of unraveling the underlying mechanism and potential therapeutic strategy of ISR.

BACKGROUND: Lipid levels become decreased in cirrhotic patients and are correlated with disease severity. In the present study, we investigated the impact of serum high-density lipoprotein cholesterol (HDL-C) on prognosis in patients with HBV-associated decompensated cirrhosis (HBV-DeCi). METHODS: The medical records of 153 HBV-DeCi patients were analyzed. Patients were separated into survivors and nonsurvivors according to their 30-day survival. Univariate and multivariate analyses were performed to identify predictors of poor outcomes, and the performance of these predictors was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: The 30-day mortality in the cohort was 18.9%. HDL-C levels differed markedly between survivors and nonsurvivors. On multivariate analysis, Model for End-stage Liver Disease (MELD) score and HDL-C level were identified as independent risk factors for mortality in HBV-DeCi patients. In the ROC analyses, the prognostic accuracy for mortality was similar between HDL-C (area under ROC curve: 0.785) and MELD score (area under ROC curve: 0.853). CONCLUSIONS: Low HDL-C level had a significant correlation with mortality in HBV-DeCi patients and can be used as a simple marker for risk assessment and selection of therapeutic options.

BACKGROUND: Dental caries is the localized destruction of dental hard tissues (enamel and dentine). Decayed, Missing, and Filled Teeth (DMFT) index is the most commonly used dental caries index. Thickness of the outermost part of the tooth called the enamel is determined by the rate of deposition of enamel proteins. Relative enamel thickness (RET) gives a measure of enamel thickness with respect to dentine. Dental caries is influenced by a genetically determined factor called dermatoglyphics (DG). As the genes responsible for RET and DG lie on the same chromosome and develop during the same time of intrauterine life, it is biologically plausible to correlate RET and DG. AIMS: This study consists of two primary aims: (1) to assess RET using cone beam computed tomography images and correlate it with caries and (2) to correlate RET with DG. MATERIALS AND METHODS: 148 dental subjects were assessed for DMFT caries score and were categorized as Group 1 with DMFT = 0 and Group 2 with DMFT ≥ 1. Following this, their DG pattern was recorded digitally. The CBCT images of these subjects were assessed for RET, and the data were analyzed statistically. RESULTS: Mean RET in our sample population is 18.45 (SD 3.79) while mean DMFT is 5.34 (SD 5.13). Mean RET in Group 1 subjects was 19.82 (SD 4.05) while that in the Group 2 was 17.68 (SD 3.43). RET and DMFT showed a statistically significant negative correlation (p = 0.007). The "Single Loop" DG characteristic showed a statistically significant difference between males and females (p = 0.031). The "Simple Arch" type of DG was positively correlated with RET. CONCLUSION: This is the first in vivo study to assess RET using CBCT images and correlate with DMFT and DG. RET is inversely related to DMFT while directly proportional to the "Simple arch" DG pattern. Males and females differed in their "Single Loop" DG characteristic.

[This retracts the article DOI: 10.1155/2019/2523032.].

PURPOSE: Due to the anatomic structure of the pelvis, free-hand placement of screws in the acetabular fracture management can be difficult. Infra-acetabular screw fixation increases acetabular stability by distal fixation of the cup. Aim of this cadaveric study is to investigate if a plate-referenced drill guide can provide save placement of an infra-acetabular screw over a precontoured suprapectineal quadrilateral buttress plate (SQBP). METHODS: We constructed a drill guide for an infra-acetabular screw based on the surface of an anatomically precontoured SQBP. A total of 12 adult cadaveric acetabular specimens were used for drill guide-assisted placement of the infra-acetabular screw. The drill guide contains a radiopaque spiral to allow longitudinal fine adjustment of the SQBP along the pelvic brim to assure correct position of the plate-drill-guide construct in relation to the Koehler's teardrop. After screw placement, we conducted a computed tomography (CT) scan of all specimens to assess the actual position of the screw in relation of the infra-acetabular corridor and the acetabular joint surface. RESULTS: The position of the screw was within the infra-acetabular corridor in all cases. We did not see any intra-articular or intrapelvic screw penetration. The mean distance of the centerline of the screw to the medial border of the infra-acetabular corridor was 3.35 mm. The secure distance to the virtual surface of the femoral head to was 7.3 mm. CONCLUSIONS: A plate-referenced drill guide can provide safe placement of an infra-acetabular screw for treatment of acetabular fractures. Radiographic fine adjustment is necessary to access the optimal entry point.

This paper presents a new high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method with a rapid analysis of 6 min to determine the concentration of galgravin in rat plasma so as to study its pharmacokinetic features and bioavailability in vivo. Schisandrin was selected as the internal standard (IS). After extracting the analyte from plasma samples with ethyl acetate, methanol-H2O (0.1% formic acid) (85 : 15, v/v) was used as mobile phase to achieve chromatographic separation on a C18 reversed phase column. The MS detection was performed in positive ion mode using electrospray ionization (ESI) source. This method showed good linearity over the range of 1~500 ng/mL (R 2 > 0.999), and the lower limit of quantitation (LLOQ) was 1.0 ng/mL. The intraday precision and interday precision were both within 8.5%, whereas the accuracies were in the range of -2.6%-6.0%. The average recoveries of galgravin in rat plasma were between 92.3% and 99.3%. Moreover, galgravin was stable throughout storage and processing with all RSDs below 12.1%. After the successful application of this optimized method, the oral bioavailability of galgravin was determined to be 8.5%. This study will be helpful to the future research and development of galgravin.

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder that is associated with learning, memory, and cognitive deficits. Neuroinflammation and synapse loss are involved in the pathology of AD. Diverse measures have been applied to treat AD, but currently, there is no effective treatment. Celastrol (CEL) is a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F that has been shown to enhance cell viability and inhibit amyloid-β production induced by lipopolysaccharides in vitro. In the present study, the protective effect of CEL on Aβ 25-35-induced rat model of AD was assessed. Our results showed that CEL administration at a dose of 2 mg/kg/day improved spatial memory in the Morris water maze. Further biochemical analysis showed that CEL treatment of intrahippocampal Aβ 25-35-microinjected rats attenuated hippocampal NF-κB activity; inhibited proinflammatory markers, namely, IL-1β, IL-6, and TNF-α; and upregulated anti-inflammatory factors, such as IL-4 and IL-10. Furthermore, CEL upregulated hippocampal neurexin-1β, neuroligin-1, CA1, and PSD95 expression levels, which may improve synaptic function. Simultaneously, CEL also increased glucose metabolism in Aβ 25-35-microinjected rats. In conclusion, CEL could exert protective effects against learning and memory decline induced by intrahippocampal Aβ 25-35 through anti-inflammation, promote synaptic development, and maintain hippocampal energy metabolism.

BACKGROUND: Osteosarcoma is a malignant bone tumor composed of mesenchymal cells producing osteoid and immature bone. This study is aimed at developing novel potential prognostic biomarkers and constructing a miRNA-mRNA network for progression in osteosarcoma. METHOD: GSE70367 and GSE70414 were obtained in the Gene Expression Omnibus (GEO) database. GEO software and the GEO2R calculation method were used to analyze two gene profiles. The coexpression of differentially expressed miRNAs (DEMs) and genes (DEGs) was identified and searched for in the FunRich database for pathway and ontology analysis. Cytoscape was utilized to construct the mRNA-miRNA network. Survival analysis of identified miRNAs and mRNAs was performed by utilizing the Kaplan-Meier Plotter. Besides, expression levels of DEMs and target mRNAs were verified by performing quantitative real-time PCR (qRT-PCR) and Western blot (WB). RESULTS: Six differentially expressed microRNAs (DEMs) were identified, and 8 target genes were selected after screening. By using the KM Plotter software, miRNA-124 and ARHGEF3 were obviously associated with the overall survival of patients with osteosarcoma. Furthermore, ARHGEF3 was found downregulated in osteosarcoma cells by performing qRT-PCR and WB experiments. Results also showed that downregulated ARHGEF3 may associate with invasion, metastasis, and proliferation. CONCLUSIONS: By using microarray and bioinformatics analysis, DEMs were selected, and a complete miRNA-mRNA network was constructed. ARHGEF3 may act as a therapeutic and prognostic target of osteosarcoma.

OBJECTIVES: The causes of ovarian cancer (OC) have been confirmed to be closely related to genetic factors. Identifying sequence variants of hereditary ovarian cancer (HOC) susceptibility genes can increase clinical surveillance, facilitate early detection, and provide personalized treatment for patients. This study is aimed at investigating the variation frequency of HOC susceptibility genes in the Chinese population and providing information for the etiology and genetics of OC. METHODS: 118 epithelial OC patients were recruited in this clinical study. Variants of 18-gene panel were detected in blood samples by next-generation sequencing (NGS) technology. RESULTS: Overall, 36.44% (43/118) of patients carried at least one pathogenic variant. Among these, BRCA1 pathogenic variants were detected in 31 (26.27%) patients, and 5 (4.24%) patients carried pathogenic variants of BRCA2. Moreover, 27.12% (32/118) of patients carried variants of unknown significance (VUSs). Importantly, we detected eight variants that were not reported previously. CONCLUSIONS: Our study enlarged the spectrum of HOC-associated gene sequence variants in the Chinese population and also proved the necessity of multigene testing in epithelial OC patients. The identification of patients with HOC will allow family members to undergo cascade testing where identification of unaffected carriers can facilitate early detection, risk reduction, or prevention of OC and ultimately improve long-term outcomes.

Early identification and diagnosis of mild cognitive impairment (MCI) in patients with parkinsonism (PDS) are critical. The aim of this study was to identify biomarkers of MCI in PDS using conventional electroencephalogram (EEG) power spectral analysis and detrended fluctuation analysis (DFA). In this retrospective study, patients with PDS who underwent an overnight polysomnography (PSG) study in our hospital from 2019 to 2020 were enrolled. Patients with PDS assessed by clinical examination and questionnaires were divided into two groups: the PDS with normal cognitive function (PDS-NC) group and the PDS with MCI (PDS-MCI) group. Sleep EEG signals were extracted and purified from the PSG and subjected to a conventional power spectral analysis, as well as detrended fluctuation analysis (DFA) during wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Forty patients with PDS were enrolled, including 25 with PDS-NC and 15 with PDS-MCI. Results revealed that compared with PDS-NC patients, patients with PDS-MCI had a reduced fast ratio ((alpha + beta)/(delta + theta)) and increased DFA during NREM sleep. DFA during NREM was diagnostic of PDS-MCI, with an area under the receiver operating characteristic curve of 0.753 (95% CI: 0.592-0.914) (p < 0.05). Mild cognitive dysfunction was positively correlated with NREM-DFA (r = 0.426, p = 0.007) and negatively correlated with an NREM-fast ratio (r = -0.524, p = 0.001). This suggested that altered EEG activity during NREM sleep is associated with MCI in patients with PDS. NREM sleep EEG characteristics of the power spectral analysis and DFA correlate to MCI. Slowing of EEG activity during NREM sleep may reflect contribution to the decline in NREM physiological function and is therefore a marker in patients with PDS-MCI.

BACKGROUND: It has been reported that there may be a potential link between hernia and dementia. However, the exact mechanisms of their association have not been established. This study is aimed at constructing miRNA-mRNA networks to elucidate on the potential link between dementia and hernia. METHODS: Gene expression profiles for dementia, herniation, and skeletal muscle were downloaded from the GEO database after which differentially expressed mRNAs and miRNAs were obtained. In addition, fascia tissue samples were obtained during surgery. A total of 41 patients were recruited in this study, and expression levels of candidate genes were examined using quantitative RT-PCR. Luciferase reporter gene assays were used to identify potential miRNA-mRNA regulatory pathways. RESULTS: Differentially expressed mRNAs and miRNAs were screened. A potential miRNA-mRNA network revealing the crosstalk mechanism between herniation and dementia was identified. Single cell analysis revealed that PI16 was highly enriched in adipose tissues, skeletal muscles, and in the skin. GSEA enrichment analysis showed that PI16 is involved in adipose metabolism, muscle functions, and energy metabolism. In clinical samples, PI16 was found to be upregulated in hernia, while miR-4451 was found to be downregulated. The luciferase reporter gene assay revealed that downregulation of circulating miR-4451 may be responsible for the upregulated PI16 expression in hernia sacs. CONCLUSIONS: We constructed an miRNA-mRNA network that shows the potential association between dementia and hernia. We also found that miR-4451 regulates the PI16 expression, which may be a key target and biomarker for hernia pathogenesis and dementia crosstalk.

BACKGROUND: Workplace violence is a common issue worldwide that strikes all professions, and healthcare is one of the most susceptible ones. Verbal and nonverbal miscommunications between healthcare workers and patients are major inducers for violent attacks. AIM: To study the potential impact of verbal and nonverbal miscommunications between the patients and healthcare workers upon workplace violence from the patients' perspectives. METHODS: A descriptive cross-sectional study was performed from November to December 2020. Patients and previously hospitalized patients were asked to complete a self-reported questionnaire that involved items of verbal and nonverbal miscommunication. With the use of a suitable available sample composed of 550 participants, 505 had completed the questionnaire and were included in the study. The data were analyzed by using SPSS version 22 software. RESULTS: 7.2% of the study population reported participating in nonverbal violence and 19.6% participated in verbal violence against healthcare workers. The nonverbal and verbal violence was characteristically displayed by the patients who are male, younger than 30 years old, and bachelor's degree holders. The results of the study demonstrated that the verbal and nonverbal miscommunications between the patients and healthcare workers were the major factors in provoking violent responses from patients. Factors, such as age, gender, and level of education, were significant indicators of the type of patients who were more likely to respond with violence. CONCLUSION: Workplace violence, either verbal or nonverbal, in the health sector is a public health concern in Palestine. The verbal and nonverbal communication skills of healthcare workers should be developed well enough to overcome the effect of miscommunication provoking violent acts from patients and their relatives as well.

Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown the ability to inhibit in vitro viral replications of coronaviridae viruses such as SARS-CoV and SARS-CoV-2. However, clinical trial outcomes have been disparate, suggesting that CQ and HCQ antiviral mechanisms are not fully understood. Based on three-dimensional structural similarities between HCQ and the known ACE2 specific inhibitor MLN-4760, we compared their modulation on ACE2 activity. Here we describe, for the first time, in a cell-free in vitro system that HCQ directly and dose-dependently inhibits the activity of recombinant human ACE2, with a potency similar to the MLN-4760. Further analysis suggests that HCQ binds to a noncompetitive site other than the one occupied by MLN-4760. We also determined that the viral spike glycoprotein segment that comprises the RBD segment has no effect on ACE2 activity but unexpectedly was able to partially reverse the inhibition induced by HCQ but not that by MLN-4760. In summary, here we demonstrate the direct inhibitory action of HCQ over the activity of the enzyme ACE2. Then, by determining the activity of ACE2, we reveal that the interaction with the spike protein of SARS-CoV-2 leads to structural changes that at least partially displace the interaction of the said enzyme with HCQ. These results may help to explain why the effectiveness of HCQ in clinical trials has been so variable. Additionally, this knowledge could be used for to develop techniques for the detection of SARS-CoV-2.

BACKGROUND: Abrus precatorius is used in folk medicine across Afro-Asian regions of the world. Earlier, glucose lowering and pancreato-protective effects of Abrus precatorius leaf extract (APLE) was confirmed experimentally in STZ/nicotinamide-induced diabetic rats; however, the underlying mechanism of antidiabetic effect and pancreato-protection remained unknown. OBJECTIVE: This study elucidated antidiabetic mechanisms and pancreato-protective effects of APLE in diabetic rats. MATERIALS AND METHODS: APLE was prepared by ethanol/Soxhlet extraction method. Total phenols and flavonoids were quantified calorimetrically after initial phytochemical screening. Diabetes mellitus (DM) was established in adult Sprague-Dawley rats (weighing 120-180 g) of both sexes by daily sequential injection of nicotinamide (48 mg/kg; ip) and Alloxan (120 mg/kg; ip) over a period of 7 days. Except control rats which had fasting blood glucose (FBG) of 4.60 mmol/L, rats having stable FBG (16-21 mmol/L) 7 days post-nicotinamide/Alloxan injection were considered diabetic and were randomly reassigned to one of the following groups (model, APLE (100, 200, and 400 mg/kg, respectively; po) and metformin (300 mg/kg; po)) and treated daily for 18 days. Bodyweight and FBG were measured every 72 hours for 18 days. On day 18, rats were sacrificed under deep anesthesia; organs (kidney, liver, pancreas, and spleen) were isolated and weighed. Blood was collected for estimation of serum insulin, glucagon, and GLP-1 using a rat-specific ELISA kit. The pancreas was processed, sectioned, and H&E-stained for histological examination. Effect of APLE on enzymatic activity of alpha (α)-amylase and α-glucosidase was assessed. Antioxidant and free radical scavenging properties of APLE were assessed using standard methods. RESULTS: APLE dose-dependently decreased the initial FBG by 68.67%, 31.07%, and 4.39% compared to model (4.34%) and metformin (43.63%). APLE (100 mg/kg) treatment restored weight loss relative to model. APLE increased serum insulin and GLP-1 but decreased serum glucagon relative to model. APLE increased both the number and median crosssectional area (×106 μm2) of pancreatic islets compared to that of model. APLE produced concentration-dependent inhibition of α-amylase and α-glucosidase relative to acarbose. APLE concentration dependently scavenged DPPH and nitric oxide (NO) radicals and demonstrated increased ferric reducing antioxidant capacity (FRAC) relative to standards. CONCLUSION: Antidiabetic effect of APLE is mediated through modulation of insulin and GLP-1 inversely with glucagon, noncompetitive inhibition of α-amylase and α-glucosidase, free radical scavenging, and recovery of damaged/necro-apoptosized pancreatic β-cells.

OBJECTIVE: To evaluate the long-term efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for the treatment of low-risk papillary thyroid microcarcinoma (PTMC). METHODS: From June 2012 to May 2015, 105 patients with solitary, pathologically confirmed PTMC lesions were treated with ultrasound-guided PLA. Nodule location, nodule volume, thyroid function, and clinical symptoms were evaluated before ablation. Contrast-enhanced ultrasound (CEUS) was performed 1 h after treatment to evaluate whether the ablation was complete. Ultrasound examination was performed at 1, 3, 6, and 12 months after ablation and every 6 months thereafter to determine the size of the ablation area and search for recurrence in the thyroid parenchyma and lymph node metastasis. Thyroid function was examined before and 1 month after ablation. Fine needle aspiration biopsy was performed for any suspicious metastatic lymph nodes and recurrent lesions in the thyroid. RESULTS: All 105 lesions were completely inactivated after one ablation, making the success rate for single ablation 100%. The average ablation time was 2.78 ± 1.05 min, and the average ablation energy was 505 ± 185 J. All patients could tolerate and complete the ablation. No serious complications occurred during the treatment; only minor side effects such as pain and local discomfort were reported. The volume reduction rates were -781.14 ± 653.29% at 1 h posttreatment and -268.65 ± 179.57%, -98.39 ± 76.58%, 36.78 ± 30.32%, 75.55 ± 21.81%, 96.79 ± 10.57%, and 100% at 1, 3, 6, 12, 18, and 24 months after ablation, respectively. This rate remained 100% at the later follow-up times. Overall, 28 (26.67%), 74 (70.48%), 96 (91.43%), and 103 (100%) were completely absorbed by 6, 12, 18, and 24 months after PLA. One patient developed another lesion 12 months after ablation, and two patients had central cervical lymph node metastasis 24 months after ablation. CONCLUSION: PLA is a safe and effective alternative clinical treatment for low-risk PTMC.

OBJECTIVE: To analyze the molecular regulation network of circular RNA (circRNA) in colon cancer (CC) by bioinformatics method. METHODS: hsa_circ_0007843 and hsa_circ_0007331 proved to be associated with CC in previous studies were chosen as the research object. ConSite database was used to predict the transcription factors associated with circRNA, and the CC-associated transcription factors were screened out after intersection. The CircInteractome database was used to predict the RNA-binding proteins (RBPs) interacting with circRNAs and screen out the CC-associated RBPs after an intersection. Furthermore, the CircInteractome database was used to predict the miRNAs interrelated with circRNAs, and the HMDD v3.2 database was used to search for miRNAs associated with CC. The target mRNAs of miRNA were predicted by the miRWalk v3.0 database. CC-associated target genes were screened out from the GeneCards database, and the upregulated genes were enriched and analyzed by the FunRich 3.1.3 software. Finally, the molecular regulatory network diagram of circRNA in CC was plotted. RESULTS: The ConSite database predicted a total of 14 common transcription factors of hsa_circ_0007843 and hsa_circ_0007331, among which Snail, SOX17, HNF3, C-FOS, and RORα-1 were related to CC. The CircInteractome database predicted that the RBPs interacting with these two circRNAs were AGO2 and EIF4A3, and both of them were related to CC. A total of 17 miRNAs interacting with hsa_circ_0007843 and hsa_circ_0007331 were predicted by CircInteractome database. miR-145-5p, miR-21, miR-330-5p, miR-326, and miR-766 were associated with CC according to the HMDDv3.2 database. miR-145-5p and miR-330-5p, lowly expressed in CC, were analyzed in the follow-up study. A total of 676 common target genes of these two miRNAs were predicted by the miRWalk3.0 database. And 57 target genes were involved in the occurrence and development of CC from the GeneCards database, with 23 genes downregulated and 34 genes upregulated. Additionally, GO analysis showed that the 34 upregulated genes were mainly enriched in biological processes such as signal transduction and cell communication. KEGG pathway analysis showed that the upregulated genes were closely related to integrin, ErbB receptor, and ALK1 signal pathways. Finally, a complete regulatory network of hsa_circ_0007843 and hsa_circ_0007331 in CC was proposed, whereby each one of the participants was either directly or indirectly associated and whose deregulation may result in CC progression. CONCLUSION: Predicting the molecular regulatory network of circRNAs by bioinformatics provides a new theoretical basis for further occurrence and development pathogenesis of CC and good guidance for future experimental research.

BACKGROUND: The critical role of vascular health on brain function has received much attention in recent years. At the single-cell level, studies on the developmental processes of cerebral vascular growth are still relatively few. Techniques for constructing gene regulatory networks (GRNs) based on single-cell transcriptome expression data have made significant progress in recent years. Herein, we constructed a single-cell transcriptional regulatory network of mouse cerebrovascular cells. METHODS: The single-cell RNA-seq dataset of mouse brain vessels was downloaded from GEO (GSE98816). This cell clustering was annotated separately using singleR and CellMarker. We then used a modified version of the SCENIC method to construct GRNs. Next, we used a mouse version of SEEK to assess whether genes in the regulon were coexpressed. Finally, regulatory module analysis was performed to complete the cell type relationship quantification. RESULTS: Single-cell RNA-seq data were used to analyze the heterogeneity of mouse cerebrovascular cells, whereby four cell types including endothelial cells, fibroblasts, microglia, and oligodendrocytes were defined. These subpopulations of cells and marker genes together characterize the molecular profile of mouse cerebrovascular cells. Through these signatures, key transcriptional regulators that maintain cell identity were identified. Our findings identified genes like Lmo2, which play an important role in endothelial cells. The same cell type, for instance, fibroblasts, was found to have different regulatory networks, which may influence the functional characteristics of local tissues. CONCLUSIONS: In this study, a transcriptional regulatory network based on single-cell analysis was constructed. Additionally, the study identified and profiled mouse cerebrovascular cells using single-cell transcriptome data as well as defined TFs that affect the regulatory network of the mouse brain vasculature.

PURPOSE: The aim of this study was to determine changes in the tongue area and pharyngeal airway space (PAS) after intraoral vertical ramus osteotomy (IVRO). MATERIALS AND METHODS: Serial lateral cephalograms of 40 patients with mandibular prognathism who underwent IVRO were evaluated before (T1), immediately after (T2), and more than 1 year after (T3) surgery. Paired t-tests and Pearson's correlation analysis were used to evaluate the postoperative changes in the mandible, nasopharyngeal airway (NOP), retropalatal pharyngeal airway (RPP), retroglossal pharyngeal airway (RGP), hypopharyngeal airway (HOP), PAS, and tongue area (TA). The null hypothesis states that there are no significant correlations among the extent of mandibular setback and the changes in the TA and PAS after IVRO. RESULTS: Immediately after the operation (T12), the mandible was set back by 12.6 mm. The NOP, HOP, and PAS were significantly reduced by 35.7 mm2, 116 mm2, and 185 mm2, respectively. The TA was increased by 69.6 mm2. The changes in PAS and TA revealed no significant difference between female and male patients at T12, T23, and T13. Moreover, no significant correlations were found among the extent of mandibular setback, TA changes, and PAS changes after IVRO. Thus, the null hypothesis was accepted. CONCLUSIONS: At the final follow-up (T13), no significant change was found in the PAS (including NOP, RPP, RGP, and HOP) and TA. The changes in PAS and TA revealed no significant difference between female and male patients at T12, T23, and T13.

Dracaena cinnabari (D. cinnabari) is an endemic plant located in Socotra Island, Yemen. Deep red resin attained from different plant species including D. cinnabari is commonly known as dragon's blood. In folk medicine, it is prescribed for the treatment of traumatic dermal, dental, and eye injuries as well as blood stasis, pain, and gastrointestinal diseases in humans. Numerous studies have investigated that this resinous medicine has antidiarrheal, antiulcer, antimicrobial, antiviral, antitumor, anti-inflammatory, analgesic, wound healing, and antioxidant activity. Several phytochemicals have been isolated from D. cinnabari, including the biflavonoid cinnabarone, triflavonoids, metacyclophanes, chalcones, chalcanes, dihydrochalcones, sterols, and terpenoids. The present review highlights the structures and bioactivities of main phytochemicals isolated from D. cinnabari regarding the botany and pharmacological effects of the resin derived from this plant.

METHODS: Immunohistochemical staining, sequencing, and genetic analysis of liver cancer tissues were performed. The antitumor efficacy of single-agent or combination treatment was measured by cell counting kit-8 assay and colony formation assays. Their antiproliferative and apoptosis activity is evaluated by cell cycle analyses and wound healing assays. The DNA-related proteins were also measured by Western blotting and immunohistochemical staining. The HepG2 xenograft model was used to detect the effects of lenvatinib-alisertib on the antitumor activity. RESULTS: AURKA was found to be upregulated in HCC tissues (77.3%, 17/22). Combined alisertib and lenvatinib treatment significantly enhanced the inhibition of proliferation and migration in HepG2 and Hep3B cell lines compared to single-agent treatments (all Ps < 0.01). Alisertib alone or in combination with lenvatinib demonstrated a significant increase in the percentage of super-G2 cells (lenvatinib 1 μM vs. lenvatinib 1 μM + alisertib 0.1 μM 8.84 ± 0.84 vs. 34.0 ± 1.54, P < 0.001). Discontinuous spindles and missegregated chromosomes in HCC cells treated with alisertib in combination with lenvatinib were observed. We further revealed that combined treatment inhibited the expression of DNA damage pathway proteins compared to those of single-agent treatments. In nude mice, combined administration of alisertib combined with lenvatinib significantly enhanced the suppression of tumor growth and induced apoptosis (all Ps < 0.01). CONCLUSIONS: Our findings provide evidence for the possible use of alisertib in combination with lenvatinib in the treatment of HCC for better therapeutic outcomes.

Ziziphora (Cacotti in Persian) belongs to the Lamiaceae family (mint group) and is vastly found in Iran and Asia. This traditional medicinal plant is normally used as analgesic and for treatment of particular gastrointestinal diseases. Since colorectal cancer is one of the most common causes of death in the world and the second leading cause of cancer death among adults, there is a pressing need to inhibit this malignancy by using methods with minimal side effects. One of these methods is the use of natural resources such as medical plants. This study is aimed at investigating the expression of apoptosis-related genes in the adjacent culture of colorectal cancer epithelial cells (HT-29) with Ziziphora essential oil (ZEO). The essential oil was extracted from Ziziphora leaves, and its compounds were determined and then added to the HT-29 culture medium at different concentrations. After 24 hours, the HT-29 cells were harvested from the medium and cytotoxicity was analyzed by MTT assay. After MTT assay and determination of the percentage of apoptosis by flow cytometry, RNA extraction was performed and the expression levels of Bax, Bcl-2, caspase 3 (C3), and caspase 9 (C9) were analyzed using newly designed primers by reverse transcription (RT) qPCR method and GeniX6 software. Also, specific antibodies were used for western blot analyses of those molecules. GC analysis revealed 42 different compounds in the ZEO, including pulegone (26.65%), menthone (5.74%), thymol (5.51%), and menthol (1.02%). MTT assay showed that the concentration of 200 μg/ml of ZEO had the highest HT-29 cell death during 24 hours. After incubation with the concentration of 50 μg/ml of ZEO for 24 and 48 hours, caspase 3 and 9 gene expressions in the treated group increased compared to those in the control group (P < 0.001), while the Bcl-2 expression decreased. The results showed that having anticancer compounds, ZEO can increase C3 and C9 and decrease Bcl-2 expressions, causing apoptosis in HT-29 cells in vitro. This can lead to the use of ZEO as a factor for colorectal cancer treatment.

The entire H5N1 highly pathogenic avian influenza viral genomes were identified in the frozen autopsy specimens: the trachea, lung, colon, and intestinal feces from a patient who died of the disease in 2006. Phylogenetic analysis of the viral genomes showed that these viruses belonged to clade 1 and were the reassortants generated from the reassortment of the viruses within the same clade. The sequencing data from the autopsy specimens revealed at least 8 quasispecies of the H5N1 viruses across all 4 specimen types. These sequences were compared to those derived from the virus isolates grown in Madin Darby canine kidney (MDCK) cells. The virus isolates from the trachea, lung, and fecal specimens showed 27 nucleotide substitutions, leading to the changes of 18 amino acid residues. However, there was no change in the amino acid residues that determined the viral virulence. The changes were more commonly observed in the lung, particularly in the HA and NA genes. Our study suggested that the adaptation changes for the viral fitness to survive in a new host species (MDCK cells) might involve many genes, for example, the amino acid substitution 177G or 177W adjacent to the receptor-binding residues in the HA1 globular head and the substitution M315I in PB2. However, a mutation changes near the receptor binding domain may play an important role in determining the cell tropism and is needed to be further explored.

Previous studies on the relationship between the circulating level of interleukin-17 (IL-17) and disease activity in systemic lupus erythematosus (SLE) were contradictory. This study is aimed at quantitatively assessing the correlation between the circulating IL-17 level and disease activity in SLE patients. A systematic search for related literature was conducted via PubMed, Web of Science, EMBASE, and Cochrane Library (up to January 26, 2021). The relationship between circulating IL-17 levels and SLE activity was evaluated using Fisher's z value, which was then converted to r. The standardized mean difference (SMD) and its 95% confidence interval (CI) were used to describe the difference between the circulating IL-17 level in patients with active and inactive SLE. STATA 16.0 was used to perform statistical analysis. Random-effects model was performed to synthesize data. Twenty-six studies involving 1,560 SLE patients were included in this review. The pooled r value was 0.38 (95% CI: 0.25-0.50; I 2 = 83.8%, P < 0.001) between the SLE activity and circulating level of IL-17. Patients with active SLE had higher level of circulating IL-17 than that of inactive (pooled SMD = 0.95, 95% CI: 0.38-1.53; I 2 = 90.5%, P < 0.001). The subgroup analysis suggested that the region and detection method of circulating IL-17 might not be a source of heterogeneity. No significant publication bias was found. In summary, circulating IL-17 level has a low positive relationship with SLE activity. It is necessary to carefully consider the use of circulating IL-17 as a biomarker of the disease activity in SLE patients. The relationship between the circulating level of IL-17 and SLE activity should be further confirmed in randomized controlled studies.

OBJECTIVE: To compare the clinical and radiographic results of the supercapsular percutaneously assisted total hip (SuperPATH) approach and the conventional approach in hip arthroplasty. DESIGN: Based on a prepublished protocol (PROSPERO: CRD42020177717), we searched PubMed, Embase, and Cochrane for relevant literatures up to January 30, 2021. The methodological qualities were assessed using the guidelines provided by the Cochrane Collaboration for Systematic Reviews. Randomized- or fixed-effect models were used to calculate the weighted mean difference (WMD) or odds ratio (OR), respectively, for continuous and dichotomous variables. RESULTS: 6 articles were included in the study, and 526 patients were selected, which included 233 cases in the SuperPATH groups and 279 cases in the conventional groups, and 4 cases performed two surgeries in succession. The SuperPATH group demonstrated shorter incision length (WMD = -7.87, 95% CI (-10.05, -5.69), P < 0.00001), decreased blood transfusion rate (OR = 0.48, 95% CI (0.25, 0.89), P = 0.02), decreased visual analogue scale (VAS) (WMD = -0.40, 95% CI (-0.72, -0.08), P = 0.02), and higher Harris hip score (HHS) (WMD = 1.98, 95% CI (0.18, 3.77), P = 0.03) than the conventional group. However, there was no difference in VAS (P = 0.14) and HHS (P = 0.86) between the two groups 3 months later, nor in the acetabular abduction angle (P = 0.32) in either group. CONCLUSIONS: SuperPATH, as a minimally invasive approach with its reduced tissue damage, quick postoperative recovery, and early rehabilitation, demonstrates the short-term advantages of hip arthroplasty. As the evidences in favor of the SuperPATH technique were limited in a small number of studies and short duration of follow-up, more research is required to further analyze its long-term effect.

Long noncoding RNAs (lncRNAs) play nonnegligible roles in the metastasis of non-small-cell lung cancer (NSCLC). This study is aimed at investigating the biological role of lncRNA OXCT1-AS1 in NSCLC metastasis and the underlying regulatory mechanisms. The expression profiles of lncRNA OXCT1-AS1 in different NSCLC cell lines were examined. Then, the biological function of lncRNA OXCT1-AS1 in NSCLC metastasis was explored by loss-of-function assays in vitro and in vivo. Further, the protective effect of lncRNA OXCT1-AS1 on lymphoid enhancer factor 1 (LEF1) was examined using RNA pull-down and RNA immunoprecipitation assays. Additionally, the role of LEF1 in NSCLC metastasis was investigated. Results indicated that lncRNA OXCT1-AS1 expression was significantly increased in NSCLC cell lines. Functional analysis revealed that knockdown of lncRNA OXCT1-AS1 impaired invasion and migration in vitro. Additionally, the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis was also confirmed in vivo. Mechanistically, through direct interaction, lncRNA OXCT1-AS1 maintained LEF1 stability by blocking NARF-mediated ubiquitination. Furthermore, LEF1 knockdown impaired invasion and migration of NSCLC in vitro and in vivo. Collectively, these data highlight the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis by stabilizing LEF1 and suggest that lncRNA OXCT1-AS1 represents a novel therapeutic target in NSCLC.

Semaphorin 4D (SEMA4D), a protein originally demonstrated to regulate the immune system and axonal growth cone collapse in the developing central nervous system, is overexpressed in various human malignancies, including colorectal cancer (CRC). This investigation was undertaken to examine the effects of SEMA4D silencing on the biological properties of the CRC cell line. SW48 cells were transfected with a siRNA-targeting SEMA4D. The mRNA expression of underlying pro- and antiapoptotic proteins including Bax, Bcl-2, P53, and caspase-3, cancer stem cell (CSC) markers, epithelial-mesenchymal transition (EMT) markers, MMP-2, and MMP-9 was examined using qRT-PCR. Further, the protein expression of E-cadherin and β-catenin was confirmed by Western blot. SW48 cell migration and MMP activity were detected using scratch and zymography analysis, respectively. Finally, the apoptosis rate was assessed via the flowcytometry test. SEMA4D knock-down was associated with a considerable suppression of in vitro cell viability, EMT-related genes, CSC markers, β-catenin signaling pathway, sphere-forming, cell migration, and MMP-2 activity as well as induction of apoptosis. This study identifies the inhibitory effects of SEMA4D gene silencing on tumor progression. Thereby, this might conclude a possible alternative to cancer therapy by targeting several prominent pathways involved in cancer through SEMA4D suppression.

Peritoneal dialysis (PD) is a frequently used and growing therapy for end-stage renal diseases (ESRD). Survival analysis of PD patients is an ongoing research topic in the field of nephrology. Several biochemical parameters (e.g., serum albumin, creatinine, and blood urea nitrogen) are measured repeatedly in the follow-up period; however, baseline or averaged values are primarily associated with mortality. Although this strategy is not incorrect, it leads to information loss, resulting in erroneous conclusions and biased estimates. This retrospective study used the trajectory of common renal function indexes in PD patients and mainly investigated the association between serum albumin change and mortality. Furthermore, we considered patient-specific variability in serum albumin change and obtained personalized dynamic risk predictions for selected patients at different follow-up thresholds to investigate the effect of serum albumin trajectories on patient-specific mortality. We included 417 patients from the Erciyes University Nephrology Department whose data were retrospectively collected using medical records. A joint modeling approach for longitudinal and survival data was used to investigate the relationship between serum albumin trajectory and mortality of PD patients. Results showed that averaged serum albumin levels were not associated with mortality. However, serum albumin change was significantly and inversely associated with mortality (HR: 2.43, 95% CI: 1.48 to 4.16). Risk of death was positively associated with peritonitis rate, hemodialysis history, and the total number of comorbid and renal diseases with hazard ratios 1.74, 3.21, and 1.41. There was also significant variability between patients. The personalized risk predictions showed that overall survival estimates were not representative for all patients. Using the patient-specific trajectories provided better survival predictions within the follow-up period as more data become available in serum albumin levels. In conclusion, using the trajectory of risk predictors via an appropriate statistical method provided better predictive accuracy and prevented biased findings. We also showed that personalized risk predictions were much informative than overall estimations in the presence of significant patient variability. Furthermore, personalized estimations may play an essential role in monitoring and managing patients during the follow-up period.

Vitex agnus-castus is a medicinal plant of the Verbenaceae family, widely used in traditional medicine. This study is aimed at investigating the functional variability of phenolic compounds in different parts (leaves, stems, flowers, roots, and seeds) of Vitex agnus-castus methanolic extracts and at assessing their in vitro antidiabetic, antioxidant, and antibacterial activities. The results of HPLC-DAD-QTOF-MS indicated the presence of 25 phenolic compounds with a remarkable variability between plant parts; high levels were registered in chlorogenic, vanillic, 3,4-dihydroxybenzoic, and 3-hydroxybenzoic acids; hesperidin; and luteolin. V. agnus castus fruits and stems presented higher antioxidant activities. The extracts inhibited the growth of five pathogenic bacteria with MIC values documented between 7.81 and 31.25 mg/mL. In vitro antihyperglycemic effect revealed higher effect in flowers (2921.84 μg/mL) and seeds (2992.75 μg/mL) against α-glucosidase and of leaves (2156.80 μg/mL) and roots (2357.30 μg/mL) against α-amylase. The findings of this showed that V. agnus castus is a promising source for antidiabetic bioactive compounds. However, further investigations regarding the evaluation of in vivo antidiabetic effects of these compounds are needed.

Extracellular vesicles (EVs), like exosomes, are nanosized membrane-enveloped vesicles containing different bioactive cargo, such as proteins, lipids, mRNA, miRNA, and other small regulatory RNAs. Cell-derived EVs, including EVs originating from stem cells, may capture components from damaged cells or cells impacted by therapeutic treatments. Interestingly, EVs derived from stem cells can be preconditioned to produce and secrete EVs with different therapeutic properties, particularly with respect to heat-shock proteins and other molecular cargo contents. This behavior is consistent with stem cells that also respond differently to various microenvironments. Heat-shock proteins play roles in cellular protection and mediate cellular resistance to radiotherapy, chemotherapy, and heat shock. This review highlights the possible roles EVs play in mediating cellular plasticity and survival when exposed to different physical and chemical stressors, with a special focus on the respiratory distress due to the air pollution.

Meso-Xanthin (Meso-Xanthin F199™) is a highly active antiaging injection drug of the latest generation. The main acting compound is fucoxanthin, supplemented with several growth factors, vitamins, and hyaluronic acid. Previous examination of fucoxanthin on melanocytes showed its ability to inhibit skin pigmentation through different signaling pathways focused on suppression of melanogenic-stimulating receptors. In turn, the anticancer property of fucoxanthin is realized through MAPK and PI3K pathways. We aimed to evaluate the effect of fucoxanthin and supplemented growth factors on melanocyte growth and transformation at a proteomic level. The effect of fucoxanthin on melanocytes cultivated in three-dimensional (3D) condition was examined using high-throughput proteomic and system biology approaches to disclose key molecular events of the targeted action. Our results demonstrated significant inhibition of cell differentiation and ubiquitination processes. We found that the negative regulation of PSME1 and PTGIS largely determines the inhibition of NF-κB and MAPK2. Besides, fucoxanthin selectively inhibits cell differentiation via negative regulation of Raf signaling and the upstream activation of IL-1 signaling. It is assumed that inhibition of Raf influences the Notch-4 signaling and switches off the MAPK/MAPK2 cascade. Blockage of MAPK/MAPK2 is feasible due to suppression of Ras and NF-κB by the addressed action of IKKB, IKK2, and TRAF6. Suggestively, Meso-Xanthin F199™ can manage processes of proliferative activity and inhibition of apoptosis due to composition of fucoxanthin and growth-stimulating factors, which may increase the risk of skin cancer development under certain condition.

Early breast cancer detection is one of the most important issues that need to be addressed worldwide as it can help increase the survival rate of patients. Mammograms have been used to detect breast cancer in the early stages; if detected in the early stages, it can drastically reduce treatment costs. The detection of tumours in the breast depends on segmentation techniques. Segmentation plays a significant role in image analysis and includes detection, feature extraction, classification, and treatment. Segmentation helps physicians quantify the volume of tissue in the breast for treatment planning. In this work, we have grouped segmentation methods into three groups: classical segmentation that includes region-, threshold-, and edge-based segmentation; machine learning segmentation; and supervised and unsupervised and deep learning segmentation. The findings of our study revealed that region-based segmentation is frequently used for classical methods, and the most frequently used techniques are region growing. Further, a median filter is a robust tool for removing noise. Moreover, the MIAS database is frequently used in classical segmentation methods. Meanwhile, in machine learning segmentation, unsupervised machine learning methods are more frequently used, and U-Net is frequently used for mammogram image segmentation because it does not require many annotated images compared with other deep learning models. Furthermore, reviewed papers revealed that it is possible to train a deep learning model without performing any preprocessing or postprocessing and also showed that the U-Net model is frequently used for mammogram segmentation. The U-Net model is frequently used because it does not require many annotated images and also because of the presence of high-performance GPU computing, which makes it easy to train networks with more layers. Additionally, we identified mammograms and utilised widely used databases, wherein 3 and 28 are public and private databases, respectively.

INTRODUCTION: In recent years, the tumour immunosuppressive mechanism has attracted attention as a cause of tumour chemoresistance. Although chemoresistance and immunosuppression of tumours have been reported to be associated with a hypoxic environment, effective treatments to improve hypoxia in tumours have not yet been established. We have previously applied carbon dioxide (CO2) to squamous cell carcinoma and have shown that improvement in local oxygenation has an antitumour effect. However, the effects of local CO2 administration on tumour immunosuppression, chemoresistance, and combination with chemotherapy are unknown. In this study, we investigated the effects of local CO2 administration on squamous cell carcinoma and the effects of combined use with chemotherapy, focusing on the effects on tumour immunosuppressive factors. METHODS: Human oral squamous cell carcinoma (HSC-3) was transplanted subcutaneously into the back of a nude mouse, and CO2 and cisplatin were administered. After administration twice a week for a total of 4 times, tumours were collected and the expression of tumour immunosuppressive factors (PD-L1, PD-L2, and galectin-9) was evaluated using real-time polymerase chain reaction and immunostaining. RESULTS: Compared with the control group, a significant decrease in the mRNA expression of PD-L1 was observed in both, CO2-treated and combination groups. Similarly, the expression of PD-L2 and galectin-9 decreased in the CO2-treated and combination groups. Furthermore, immunostaining also showed a significant decrease in the protein expression of tumour immunosuppressive factors in the CO2-treated and combination groups. CONCLUSION: It was confirmed that the tumour immunosuppressive factors decreased due to local CO2 administration to the mouse model. CO2 administration has the potential to improve the hypoxic environment in tumours, and combined use with chemotherapy may also improve tumour immunosuppression.

Nucleus pulposus (NP) is the core substance to maintain the homeostasis of intervertebral disc and stability of biomechanics. The insufficient supply of nutrition (especially glucose) is an important factor that leads to the degeneration of NP cells. circRNAs play an important role in the process of intervertebral disc degeneration (IDD) by regulating the functions of NP cells. However, glucose deprivation-related circRNAs and their functions in IDD have not been reported. In this study, the differentially expressed circRNAs in NP cells after 0, 6, 12, and 24 h of glucose deprivation culture were detected by a microarray assay. Besides, time series clustering analysis by STEM software obtained the differentially up- and downregulated circRNAs during glucose deficiency. Then, the main functions and pathways of up- and downregulated circRNAs were predicted by the functional enrichment analysis. By constructing the circRNA-miRNA regulatory network, the potential mechanisms of the most differentially expressed circRNAs were predicted. In addition, according to in vitro validation, circ_0075062 was upregulated in degenerating NP tissues and glucose deprivation-induced NP cell degeneration. Based on Sanger sequencing and RNase tolerance assay, circ_0075062 was the circular transcript. Interfering with circ_0075062 expression could potentially alleviate the imbalance of extracellular matrix (ECM) synthesis and degradation in the NP cells induced by glucose deprivation. Together, these findings help us gain a comprehensive understanding of the underlying mechanisms of IDD, and circ_0075062 may be a promising therapeutic target of IDD.

OBJECTIVE: To evaluate the voids in root canal treatment of deciduous molar canals using three obturating materials and two obturation systems using micro-CT. Study Design. Thirty freshly extracted deciduous molars were used in this study. The specimens were instrumented using a ProTaper Universal rotary instrument and randomly assigned into six groups (n = 5). Mesiobuccal root canals were obturated using Ca(OH)2 and iodoform-Ca(OH)2 and ZOE cement. The materials were applied straight from the syringe up to the 2 mm coronal level of the apex. Subsequently, the Lentulo spiral and ultrasonic activation with endoactivator were used for obturation. All samples were scanned by micro-CT with 9.1 μm isotropic voxel resolution. The voids in cross-sectional images and 3D volumes of voids were measured. Differences among materials were statically evaluated (p < 0.05). RESULTS: All study groups showed voids. Ca(OH)2 and iodoform-Ca(OH)2 with ultrasonic activation produced fewer voids whereas the ZOE groups showed higher voids with statistical significance (p < 0.05). CONCLUSIONS: Ca(OH)2 and iodoform-Ca(OH)2 with ultrasonic activation decrease void formation. Further studies should be done with other obturation techniques and materials for deciduous tooth root canal management.

PDGFRα signaling is critically important in ocular development. Previous data on PDGFRα lacks an expression map with high spatial and temporal resolution and lineage information. In this study, we aim to present a detailed PDGFRα expression and lineage map from early embryogenesis to adulthood. PDGFRα-CreER; mT/mG reporter mice were analyzed. mEGFP-positive cells contributed to multiple ocular lineages in a spatiotemporally regulated manner. A dynamic PDGFRα expression was identified in corneal stromal cells, lens epithelial cells, lens fiber cells, and retinal astrocytes during the entire period of eye development, while PDGFRα expression in retinal astrocytes from E17.5 onwards and in Müller glial cells was identified within two weeks after birth. By revealing detailed characterization of gene expression and function, we present a comprehensive map of PDGFRα-expressing cells in the eye for a better understanding of PDGFRα signaling's role during eye development.

Small supernumerary marker chromosomes (sSMCs) are a group of rare chromosomal anomalies, which pose challenges in the clinical practice of prenatal diagnosis and genetic counseling. This study enrolled an extended family with an underage male patient displaying infantile seizures, intellectual disability, and retarded speech and psychomotor function. A series of multiplatform genetic detections was conducted to explore the diagnostic variation. Whole exome sequencing (WES) and chromosomal microarray analysis (CMA) indicated a mosaic sSMC derived from the pericentromeric region of chromosome 8 in the patient, which was confirmed using cytogenetic methods. The proband and his mother, who carried this mosaic variant, exhibited strong phenotypic variability. We also ruled out the pathogenicity of a KDM5C variant by extended validation. Our results emphasized the capacity of WES to detect mosaic SMCs and the importance of mosaic ratios in the appearance and severity of symptomatic phenotypes.

In the current study, our goal was to obtain a robust model to predict the speed of sound in biodiesel. For this purpose, an extensive databank has been extracted from previously published papers. Then, a Support Vector Machine (SVM) has been optimized by Grey Wolf Optimization (GWO) method to analyze these data and determine the correlation between speed of sound in biodiesel and its related properties including pressure, temperature, molecular weight, and normal melting point. The results were very satisfactory because the values of statistical parameters R 2 and RMSE were obtained 1 and 1.4024, respectively. Here, this is the first time that the sensitivity analysis is used to estimate this target value. This analysis shows that the pressure widely affects the output values with relevancy factor 87.92. Also, our proposed method is highly accurate than other machine learning methods used in papers employed for this objective.

INTRODUCTION: To date, identifying emergent large vessel occlusion (ELVO) patients in the prehospital stage is important but still challenging. In this present study, we aimed to design a modified prehospital acute stroke severity (mPASS) scale to identify ELVO patients and compared the scale to the PASS scale which has been published. METHODS: We retrospectively evaluated a consecutive cohort of acute ischemic stroke (AIS) in our stroke unit who visited the emergercy department. These patients underwent CT angiography (CTA), MR angiography (MRA), or digital subtraction angiography (DSA) at admission. The mPASS scale was calculated based on the National Institutes of Health Stroke Scale (NIHSS) items retrospectively, including the level of consciousness commands, gaze, arm weakness, and aphasia/dysarthria. Receiver operating characteristic (ROC) analysis was used to obtain the area under the curve (AUC) of the mPASS scale, NIHSS, and PASS scale. U-statistics was used to compare the AUC of the mPASS scale to the NIHSS and PASS scale. RESULTS: A total of 382 AIS patients were enrolled. The AUC and specificity of the mPASS scale (0.92, 84.4) were all higher than those of the PASS scale. Cortical symptoms such as gaze palsy and consciousness disorder were more specific indicators for ELVO than motor deficits. CONCLUSIONS: The mPASS scale had a better discrimination for identifying ELVO than the PASS scale in our retrospective cohort. It might predict ELVO in an effective and simple way for paramedics in the prehospital triage stage or emergency stage. Moreover, cortical symptoms might have relatively high specificities to predict ELVO on their own.

BACKGROUND: Gastric cancer (GC) is the most common type of cancer. It is highly malignant and is characterized by rapid and uncontrolled growth. The antitumour activity of Baicalin was studied in multiple cancers. However, its mechanism of action has not been fully elucidated. We provided a systematic understanding of the mechanism of action of baicalin against GC using a transcriptome analysis of RNA-seq. METHODS: Human GC cells (SGC-7901) were exposed to 200 μg/ml baicalin for 24 h. RNA-seq with a transcriptome, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the antitumour effects of baicalin on SGC-7901 cells in vitro. A protein-protein interaction (PPI) network of differentially expressed genes (DEGs) was constructed. A competitive endogenous RNA (ceRNA) network was constructed and further analysed after validation using qRT-PCR. RESULTS: A total of 68 lncRNAs, 20 miRNAs, and 1648 mRNAs were differentially expressed in baicalin-treated SGC-7901 GC cells. Three lncRNAs, 6 miRNAs, and 7 mRNAs were included in the ceRNA regulatory network. GO analysis revealed that the main DEGs were involved in the biological processes of the cell cycle and cell death. KEGG pathway analysis further suggested that the p53 signalling pathway was involved in the baicalin-induced antitumour effect on SGC-7901 cells. Further confirmation using qPCR indicated that baicalin induced an antitumour effect on SGC-7901 cells, which is consistent with the results of the sequencing data. CONCLUSIONS: In summary, the mechanism of baicalin against GC involves multiple targets and signalling pathways. These results provide new insight into the antitumour mechanism of baicalin and help the development of new strategies to cure GC.

BACKGROUND: Treponema pallidum subspecies pallidum (T. pallidum) infection induces significant immune responses, resulting in tissue damage. Gene expression plays an essential role in regulating the progression of syphilis infection. However, little is known about the regulatory role of microRNAs (miRNAs) in the immune response to T. pallidum infection. Here, we analyze the differential expression of miRNAs in peripheral blood mononuclear cells (PBMCs) between untreated secondary syphilis patients and healthy controls and study the correlation between miRNA expression and clinical features with bioinformatics. METHODS: The expression profile of miRNAs was measured by microarray analysis in PBMCs of untreated secondary syphilis patients and healthy controls. Weighted Gene Coexpression Network Analysis (WGCNA) was used to construct the expression of miRNAs and the clinical data of secondary syphilis patients. Gene ontology (GO) and KEGG enrichment analyses were performed on target genes of miR-142-3p. RESULTS: 244 miRNAs exhibited at least 1.0-fold differential expression between secondary syphilis patients and healthy controls. The miRNAs were divided into three modules by WGCNA. The blue module was positively correlated with TPHA, TRUST, duration of disease, and erythema. And in the blue module, the expression of miR-142-3p was significantly higher in secondary syphilis patients than in healthy controls (p = 0.02), which is also close to the clinical features of secondary syphilis. GO and KEGG pathway analyses showed that these target genes of miR-142-3p are correlated with endocytosis and positive regulation of the apoptotic process. CONCLUSION: The elevated miR-142-3p expression in PBMCs may play an important role in the immune response to T. pallidum infection and may be a potential biomarker for secondary syphilis.

LIHC (liver hepatocellular carcinoma) mostly occurs in patients with chronic liver disease. It is primarily induced by a vicious cycle of liver injury, inflammation, and regeneration that usually last for decades. The G protein nucleolar 2 (GNL2), as a protein-encoding gene, is also known as NGP1, Nog2, Nug2, Ngp-1, and HUMAUANTIG. Few reports are shown towards the specific biological function of GNL2. Meanwhile, it is still unclear whether it is related to the pathogenesis of carcinoma up to date. Here, our study attempts to validate the role and function of GNL2 in LIHC via multiple databases and functional assays. After analysis of gene expression profile from The Cancer Genome Atlas (TCGA) database, GNL2 was largely heightened in LIHC, and its overexpression displayed a close relationship with different stages and poor prognosis of carcinoma. After enrichment analysis, the data revealed that the genes coexpressed with GNL2 probably participated in ribosome biosynthesis which was essential for unrestricted growth of carcinoma. Cell functional assays presented that GNL2 knockdown by siRNA in LIHC cells MHCC97-H and SMCC-7721 greatly reduced cell proliferation, migration, and invasion ability. All in all, these findings capitulated that GNL2 could be a promising treatment target and prognosis biomarker for LIHC.

OBJECTIVES: This study investigated associations between frailty and functional disability in elder suburban Vietnamese. METHOD: Cross-sectional analysis was carried out on 251 participants aged 80 and over in Soc Son district. We used the Instrumental Activities of Daily Living (IADL) scale including 8 items, and functional disability was defined as ≥3 IADL impairment. We defined frail as ≥3 out of 5 frailty components including weight loss > 5%, weak grip, exhaustion, low walking speed, and low physical activity. RESULTS: Of 251 participants with a mean age of 84.6, 11.2% was classified as frail and 64.5% had ≥3 IADLs. Among the frailty components, low walking speed and low physical activity were significantly associated with increased odds of having ≥3 IADLs: ORs (95% CI) were 4.2 (2.3-7.9) and 3.7 (1.7-8.2). CONCLUSION: Frailty is associated with the higher likelihood of having functional disability. Further longitudinal studies are needed to examine the causal this relationship.

BACKGROUND: Baicalin is an extract from the traditional Chinese herb Scutellaria baicalensis and has the potential to treat osteosarcoma (OS). However, the transcriptome-level mechanism of baicalin-mediated antitumor effects in OS has not yet been investigated. The aim of this study was to analyze the competitive endogenous RNA (ceRNA) regulatory network involved in baicalin-induced apoptosis of OS cells. METHODS: In this study, CCK-8 and flow cytometry assays were used to detect the antitumor effects of baicalin on human OS MG63 cells. Furthermore, transcriptome sequencing was employed to establish the long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA profiles. RESULTS: Baicalin inhibited MG63 cell proliferation and induced apoptosis. Totals of 58 lncRNAs, 31 miRNAs, and 2136 mRNAs in the baicalin-treated MG63 cells were identified as differentially expressed RNAs compared to those in control cells. Of these, 2 lncRNAs, 3 miRNAs, and 18 mRNAs were included in the ceRNA regulatory network. The differentially expressed RNAs were confirmed by quantitative real-time PCR (qRT-PCR). CONCLUSIONS: By identifying the ceRNA network, our results provide new information about the possible molecular basis of baicalin, which has potential applications in OS treatment.

OBJECTIVES: This study presents a discussion on the fundamentals of polymerase chain reaction (PCR) and its use as a diagnostic tool in periodontology. MATERIALS AND METHODS: A computer-aided as well as hand-made search in PubMed and Scopus indexed journals (relevant to the topic) was done by keywords of molecular technique in periodontology, PCR, applications of PCR, and PCR in periodontics. Only the papers in the English language and outlining PCR and its association with periodontology were collected and utilized to provide a succinct review. There was no limitation for publication time. RESULTS: The results of our search showed that PCR has turned into a standard in diagnosis in the field of periodontology. A variety of researches has demonstrated that its sensitive, and specific characteristics make it a quick and effective technique of recognition, identification, and quantification of microorganisms. Identification of various immunoinflammatory markers at the mRNA expression level as well as ascertaining gene-related polymorphisms can also be performed. CONCLUSIONS: The mechanisms of periodontal disease can further become clarified using PCR. Clinical Relevance. PCR as a diagnostic method can play a main part in the validation of the clinical diagnosis of periodontal disease indicating the reason, pathogenesis, clinical steps, progress, and prognosis of the disease.

The study is aimed at investigating the changes in expressions of heat shock protein 27 (HSP27), HSP70, and soluble glycoprotein (SGP) in heart failure (HF) rats complicated with pulmonary edema and exploring their potential correlations with cardiopulmonary functions. The rat model of HF was established, and the rats were divided into HF model group (model group, n = 15) and normal group (n = 15). After successful modeling, MRI and ECG were applied to detect the cardiac function indexes of the rats. The myocardial function indexes were determined, the injury of myocardial tissues was observed via hematoxylin and eosin (HE) staining, and the content of myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), and tumor necrosis factor-alpha (TNF-α) in the blood was measured. The partial pressure of oxygen (PaO2) and oxygenation index (OI) were observed, and the airway resistance and lung compliance were examined. Moreover, quantitative polymerase chain reaction (qPCR) and Western blotting assay were performed to detect the gene and protein expression levels of HSP27, HSP70, and SGP130. The levels of serum creatine kinase (CK), creatine (Cr), and blood urea nitrogen (BUN) were increased markedly in model group (p < 0.05). Model group had notably decreased fractional shortening (FS) and ejection fraction (EF) compared with normal group (p < 0.05), while the opposite results of left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were detected. In model group, the content of serum MPO, MMP-9, and TNF-α was raised remarkably (p < 0.05), OI and PaO2 were reduced notably (p < 0.05), the airway resistance was increased (p < 0.05), and the lung compliance was decreased (p < 0.05). Obviously elevated gene and protein expression levels of HSP27, HSP70, and SGP130 were detected in model group (p < 0.05). The expressions of HSP27, HSP70, and SGP130 are increased in HF rats complicated with pulmonary edema, seriously affecting the cardiopulmonary functions of the rats.

Lung cancer is one of the most serious leading cancers with high incidence globally. Identifying molecular markers is key for disease diagnosis and treatment. Coal dust might be important triggering factors in disease development. Here, we first performed RNA-seq-based screening in coal dust treated and nontreated RAW264.7 cell lines. PHLDB2 was found to be the top differentially expressed gene. By retrieving TCGA lung cancer dataset, we observed that PHLDB2 showed upregulations in males and smoker patients. Patients with lower PHLDB2 expression survived longer than those with higher expressions. Furthermore, PHLDB2 was negatively correlated with EMT makers, and a total of 2.74% mutation rate were observed in 1,059 patients. This finding highlights the critical role of PHLDB2 in lung cancer development. PHLDB2 might be a molecular maker for disease diagnosis or treatment.

OBJECTIVES: Gallstones can cause malnutrition in patients and further lead to cognitive impairment. This study is aimed at constructing a validated clinical prediction model for evaluating the risk of developing cognitive impairment from gallstones. METHODS: The study was a single-centre crosssectional study. Four models or methods (SVM-RFE, random forest model, Lasso model, and logistics analysis) were analyzed and compared regarding their predictive performance. The model with the best classification performance and predictive power was selected. The AUC index, C-index, and calibration curves were applied to the chosen model to further evaluate its classification and prediction performance. Finally, the nomogram was plotted, and the clinical usability, efficacy, and safety of the nomogram were assessed using decision curve analysis (DCA). RESULTS: This study included a total of 294 patients with gallstones, of which 110 had cognitive impairment. Factors such as gender, age, education, place of birth, history of alcohol consumption, abdominal circumference, sarcopenia, diabetes, anaemia, depression, and Pittsburgh Sleep Quality Index (PSQI) were incorporated into the model for nomogram construction. The calibration curve showed that the nomogram had good classification performance. Furthermore, the C-index of the model was 0.778 (95% CI, 0.674-0.882) in the test group. The DCA curves indicated that the constructed model had strong clinical applicability, efficacy, and safety. CONCLUSIONS: This study constructed a cognitive impairment risk prediction model for patients with gallstones with good classification and predictive power. The constructed predictive model allows us to screen patients with gallstones and at high risk of cognitive impairment. These efforts might also help to further increase patient compliance, assist healthcare professionals to better manage patients with gallstones, and ultimately improve their overall health status and quality of life. Future clinical studies should further evaluate the accuracy and clinical usability of this model.

BACKGROUND: Age-related hearing impairment (ARHI) is considered an unpreventable disorder. We aimed to detect specific genetic variants that are potentially related to ARHI via genome-wide association study (GWAS). METHODS: A sample of 131 dizygotic twins was genotyped for single-nucleotide polymorphism- (SNP-) based GWAS. Gene-based test was performed using VEGAS2. Pathway enrichment analysis was conducted by PASCAL. RESULTS: The twins are with a median age of 49 years, of which 128 were females and 134 were males. rs6633657 was the only SNP that reached the genome-wide significance level for better ear hearing level (BEHL) at 2.0 kHz (P = 1.19 × 10-8). Totally, 9, 10, 42, 7, 17, and 5 SNPs were suggestive evidence level for (P < 1 × 10-5) BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and pure tone average (PTA), respectively. Several promising genetic regions in chromosomes (near the C20orf196, AQPEP, UBQLN3, OR51B5, OR51I2, OR52D1, GLTP, GIT2, and PARK2) nominally associated with ARHI were identified. Gene-based analysis revealed 165, 173, 77, 178, 170, and 145 genes nominally associated with BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and PTA, respectively (P < 0.05). For BEHLs at 0.5, 1.0, and 2.0 kHz, the main enriched pathways were phosphatidylinositol signaling system, regulation of ornithine decarboxylase, eukaryotic translation initiation factor (EIF) pathway, amine compound solute carrier (SLC) transporters, synthesis of phosphoinositides (PIPS) at the plasma membrane, and phosphatidylinositols (PI) metabolism. CONCLUSIONS: The genetic variations reported herein are significantly involved in functional genes and regulatory domains that mediate ARHI pathogenesis. These findings provide clues for the further unraveling of the molecular physiology of hearing functions and identifying novel diagnostic biomarkers and therapeutic targets of ARHI.

OBJECTIVES: Depression is highly prevalent in non-Hodgkin's lymphoma (NHL) patients undergoing chemotherapy. The social stress associated with malignancy induces neurovascular pathology promoting clinical levels of depressive symptomatology. The purpose of this study was to establish an effective depressive symptomatology risk prediction model to those patients. METHODS: This study included 238 NHL patients receiving chemotherapy, 80 of whom developed depressive symptomatology. Different types of variables (sociodemographic, medical, and psychosocial) were entered in the models. Three prediction models (support vector machine-recursive feature elimination model, random forest model, and nomogram prediction model based on logistic regression analysis) were compared in order to select the one with the best predictive power. The selected model was then evaluated using calibration plots, ROC curves, and C-index. The clinical utility of the nomogram was assessed by the decision curve analysis (DCA). RESULTS: The nomogram prediction has the most efficient predictive ability when 10 predictors are included (AUC = 0.938). A nomogram prediction model was constructed based on the logistic regression analysis with the best predictive accuracy. Sex, age, medical insurance, marital status, education level, per capita monthly household income, pathological stage, SSRS, PSQI, and QLQ-C30 were included in the nomogram. The C-index was 0.944, the AUC value was 0.972, and the calibration curve also showed the good predictive ability of the nomogram. The DCA curve suggested that the nomogram had a strong clinical utility. CONCLUSIONS: We constructed a depressive symptomatology risk prediction model for NHL chemotherapy patients with good predictive power and clinical utility.

OBJECTIVES: The objective of the study was to understand and analyze the prescription patterns of dentists across various demographic locations for managing oral infections and pain with antibiotics and explore the evidence-based practices by clinicians as well as the need for further education. Materials and methods. This cross-sectional study was carried out using an online questionnaire framed to explore the knowledge, attitude, and practices among dentists with varying levels of experience and qualifications, regarding antimicrobial prescription. The questions were validated from previous published studies that explored the knowledge, attitude, and practice (KAP) with respect to antimicrobial prescription. In total, N = 300 of dentists from four different countries responded to the online questionnaire out of which 53% were specialists while 47% were general dentists. After data collection, descriptive analysis was carried out along with a one-sided hypothesis test to depict the power of the sample. RESULTS: It was seen from the results of the study that the first-choice antibiotics for 67.8% of dentists were found to be the β-lactam group while sulfonamides and tetracyclines at 20% were the second most prescribed group. Another important finding was that 45.6% of dentists ignored hypersensitivity testing before prescription of antibiotics even though 83.3% of the total dentists interviewed were aware of the increase in antibiotic resistance. CONCLUSION: In conclusion, the dentists are partially aware of the guidelines but need further training and education on antimicrobial prescription that enables evidence-based decision-making for better practices and outcomes.

OBJECTIVE: We want to explore the changing law of circulating histones in the acute stage of urosepsis and to find more sensitive and specific biomarkers for diagnosing urosepsis as early as possible. METHODS: Twenty healthy male New Zealand rabbits were randomly divided into 4 groups (N = 5): the control group, sham group, model group of LPS 600 μg/kg, and model group of LPS 1000 μg/kg. Heart rate (HR), respiration rate (RR), rectal temperature (T), and mean arterial pressure (MAP) were examined at 1, 3, 6, 12, and 24 hours after operation. Besides, peripheral blood cell counts (RBC, WBC, PLT, and Hb) and C reaction protein (CRP) were tested at 1, 3, and 6 hours after operation, while the levels of histone H3, MMP-9, TIMP-1, and procalcitonin (PCT) in the serum were tested at 1, 3, and 6 hours after operation by ELISA. The heart, left lung, liver, and left kidney were harvested for HE stain and observed to research the pathological change of these tissues. RESULTS: (1) The general status of rabbits: rabbits in the control and sham groups came out in 2 h after operation and regain to drink and eat in 12-24 h after operation. State of the rabbits in the control group was better than that in the sham group. Rabbits in the model groups were languid after operation and stopped to drink and eat. (2) Vital signs of rabbits: there was no statistic difference in HR (P = 0.238) and RR (P = 0.813) among all groups. MAP of the model groups decreased at 3 h postoperative, but transient (P < 0.001). The T of the LPS 1000 group decreased at 6 h postoperative (P = 0.003). (3) The change of biomarkers: H3 level of the LPS groups in the serum increased at 1 h postoperative (P < 0.01); MMP-9 of the LPS 1000 group increased at 1 h postoperative (P < 0.01); WBC of the model groups decreased at 3 h postoperative (P < 0.05); PLT of the LPS 1000 group is significantly increased at 1 h postoperative (P < 0.05); no statistic difference was found in CRP, PCT, and TIMP-1 among all groups. (4) Pathological sections: no abnormal performance was found in the control and sham groups. Glomerulus of the model groups was out of shape and necrosis with obvious renal tubule expansion. Pulmonary pathology showed alveolar septum diffuse increased and inflammatory infiltrate. Change of the LPS 1000 group was more serious than that of the LPS 600 group. CONCLUSIONS: Ligating the ureter after an injection of 1000 μg/kg LPS into the ureter of the rabbit can establish the animal model of urosepsis. Histone H3 increase immediately at 1 h postoperative and are promised to be biomarkers of urosepsis, which are more effective than WBC, CRP, and PCT.

Protocatechualdehyde (PCA), an important component of Salvia miltiorrhiza, has many activities, such as anti-inflammatory and antisepsis activities. However, the role of PCA in osteoclasts is not clear. We used RAW264.7 cells (a mouse leukemic monocyte/macrophage cell line) and bone marrow macrophages (BMMs) to probe the role of PCA in osteoclasts and the underlying mechanism. The effects of PCA on cell activity were evaluated with CCK-8 assays. TRAP staining detected mature osteoclasts. Corning Osteo Assay Surface plates were used to examine absorption. The levels of RNA and protein were analyzed, respectively, using RT-PCR and Western blotting. PCA (5 μg/ml) was not toxic to the two cell types but reduced the formation of osteoclasts and bone absorption. Furthermore, PCA restrained the expression of mRNAs encoding proteins associated with osteoclasts and reduced the phosphorylation of proteins in important signaling pathways. The results indicate that PCA inhibits osteoclast differentiation by suppressing NF-κB and MAPK activity.

Staphylococcus aureus is a contagious pathogen that can cause various diseases in both humans and animals. Antimicrobial-resistant S. aureus is becoming an extremely important global health problem. A cross-sectional study was conducted from December 2019 to May 2020 to assess the occurrence of S. aureus and its antimicrobial susceptibility profiles in milk and traditionally processed dairy products in selected subcities of Addis Ababa. A total of 255 dairy product samples (175 raw milk and 80 traditionally processed dairy products) were collected from farms and retail markets. Samples were cultured for S. aureus according to standard microbiology techniques, and the Kirby-Bauer disk diffusion method was used to assess antimicrobial susceptibility of isolates to a panel of 12 antimicrobials. Susceptibility to methicillin was determined based on the sensitivity of isolates to cefoxitin, and resistant isolates were investigated for the presence of mecA and mecC genes using PCR. Staphylococcus aureus was isolated from 43 (24.6%) of milk, 7 (17.5%) of yogurt, and 2 (5%) of cottage cheese. A significantly higher rate of contamination with S. aureus was recorded among milk samples compared to yogurt and cottage cheese (p = 0.019). Out of 52 S. aureus isolates investigated for susceptibility to 12 antimicrobials, 49 (94.2%) of the isolates were resistant to ampicillin and 42 (80.8%) to amoxicillin+clavulanic acid. Twenty (38.5%) of the isolates were methicillin-resistant S. aureus (MRSA) based on susceptibility to cefoxitin. However, only one of these isolates (5%) was positive for mecA gene, and none of them were positive for the mecC gene. There was no significant difference (p > 0.05) in the rate of occurrence of MRSA among isolates from different sources. In conclusion, this study demonstrated a significant level of contamination of milk and dairy products with S. aureus and most isolates were multidrug resistant. The occurrence of MRSA in raw milk and dairy products signifies a serious public health threat as the practice of consuming raw dairy products in the study area is widespread. The lack of agreement between phenotypic and genotypic detection of MRSA suggests the need for further study to identify the genetic basis for the observed resistance phenotype.

BACKGROUND: Postoperative pain, dysfunction, and significant bone loss may occur after vertebral fractures, which will lead to the occurrence of refractures and shorten the survival time, so postoperative rehabilitation is very important. Pulsed electromagnetic field therapy is noninvasive, pain-relieving, and beneficial to reduce bone loss and is an important treatment for patients to recover after surgery. Therefore, this study analyzed the effect of postmenopausal women's vertebral fracture rehabilitation after pulsed electromagnetic field treatment. METHOD: This study uses a randomized controlled study, respectively, in the pulsed electromagnetic field treatment group (40 cases) and the control group (42 cases), respectively. We studied the results of health-related quality of life scores (HRQOL), back pain, body function, hip bone density, bone microstructure of tibia, and radius after 1 month and 3 months after surgery. RESULTS: Compared with the control group, the pulsed electromagnetic field treatment group (PEMF) can improve significantly the psychological score, 6-minute walk test, and Chair Sit-and-Reach one month after the operation. And at 3 months after surgery, the pulsed electromagnetic field treatment group can improve significantly in health-related quality of life scores (HRQOL), back pain, and body function. Regarding the effect of changes in bone mass, compared with the control group, pulsed electromagnetic field treatment had no significant effect on changes in hip bone density. As a result of changes in bone microstructure, pulsed electromagnetic field treatment can significantly improve the bone microstructure of the radius and tibia three months after vertebral fractures. CONCLUSION: Pulsed electromagnetic field therapy has positive significance for improving pain, body functional changes, and bone loss after vertebral fracture surgery.

Interest in the design and manufacture of RNA and DNA aptamers as apta-biosensors for the early diagnosis of blood infections and other inflammatory conditions has increased considerably in recent years. The practical utility of these aptamers depends on the detailed knowledge about the putative interactions with their target proteins. Therefore, understanding the aptamer-protein interactions at the atomic scale can offer significant insights into the optimal apta-biosensor design. In this study, we consider one RNA and one DNA aptamer that were previously used as apta-biosensors for detecting the infection biomarker protein TNF-α, as an example of a novel computational workflow for selecting the aptamer candidate with the highest binding strength to a target. We combine information from the binding free energy calculations, molecular docking, and molecular dynamics simulations to investigate the interactions of both aptamers with TNF-α. The results reveal that the RNA aptamer has a more stable structure relative to the DNA aptamer. Interaction of aptamers with TNF-α does not have any negative effect on its structure. The results of molecular docking and molecular dynamics simulations suggest that the RNA aptamer has a stronger interaction with the protein. Also, these findings illustrate that basic residues of TNF-α establish more atomic contacts with the aptamers compared to acidic or pH-neutral ones. Furthermore, binding energy calculations show that the interaction of the RNA aptamer with TNF-α is thermodynamically more favorable. In total, the findings of this study indicate that the RNA aptamer is a more suitable candidate for using as an apta-biosensor of TNF-α and, therefore, of greater potential use for the diagnosis of blood infections. Also, this study provides more information about aptamer-protein interactions and increases our understanding of this phenomenon.

The fabrication of sensitive protein microarrays such as PCR used in DNA microarray is challenging due to lack of signal amplification. The development of microarrays is utilized to improve the sensitivity and limitations of detection towards primal cancer detection. The sensitivity is enhanced by the use of ZnO-nanorods and is investigated as a substrate which enhance the florescent signal to diagnose the hepatocellular carcinoma (HCC) at early stages. The substrate for deposition of ZnO-nanorods is prepared by the conventional chemical bath deposition method. The resultant highly dense ZnO-nanorods enhance the fluorescent signal 7.2 times as compared to the substrate without ZnO-nanorods. The microarray showed sensitivity of 1504.7 ng ml-1 and limit of detection of 0.1 pg ml-1 in wide dynamic range of 0.05 pg-10 μg ml-1 for alpha fetoprotein (AFP) detection in 10% human serum. This immunoassay was successfully applied for human serum samples to detect tumor marker with good recoveries. The ZnO-nanorod substrate is a simple protein microarray which showed a great promise for developing a low-cost, sensitive, and high-throughput protein assay platform for several applications in both fundamental research and clinical diagnosis.

PURPOSE: There may be a strong association among stress urinary incontinence (SUI), low back pain (LBP), and core muscle endurance (CME) in married women. This study is aimed at evaluating the prevalence and clinical association between SUI, CME, and LBP among married women in Saudi Arabia. METHODS: The study was based on a case-control research design, conducted among 143 women with LBP (mean age, 32 ± 7.4 years) and 160 healthy women (mean age, 31.7 ± 6.7 years). SUI, CME, and functional disability were assessed using the international consultation on the Incontinence Questionnaire-Short Form (ICIQ-SF), prone plank test (PP), and Oswestry Disability Index for LBP-United Arab Emirates edition (ODI-UAE). RESULTS: The prevalence of SUI was found to be 60% in the LBP group while 20% in the control group. CME revealed a stronger negative correlation with SUI in the LBP group (r s = -0.75) than in the control group (r s = -0.63). CONCLUSIONS: The prevalence of SUI was observed higher in women with LBP than healthy women. CME exhibited a stronger association with SUI than LBP among women with LBP compared to healthy women in Saudi Arabia. Therefore, the role of CME in SUI development or vice versa among married women with LBP may be subjected to further research.

Doxorubicin is a cornerstone chemotherapeutic drug widely used to treat various cancers; its dose-dependent cardiomyopathy, however, is one of the leading causes of treatment-associated mortality in cancer survivors. Patients' threshold doses leading to doxorubicin-induced cardiomyopathy (DIC) and heart failure are highly variable, mostly due to genetic variations in individuals' genomes. However, genetic susceptibility to DIC remains largely unidentified. Here, we combined a genetic approach in the zebrafish (Danio rerio) animal model with a genome-wide association study (GWAS) in humans to identify genetic susceptibility to DIC and heart failure. We firstly reported the cardiac and skeletal muscle-specific expression and sarcomeric localization of the microtubule-associated protein 7 domain-containing protein 1b (Map7d1b) in zebrafish, followed by expression validation in mice. We then revealed that disruption of the map7d1b gene function exaggerated DIC effects in adult zebrafish. Mechanistically, the exacerbated DIC are likely conveyed by impaired autophagic degradation and elevated protein aggregation. Lastly, we identified 2 MAP7D1 gene variants associated with cardiac functional decline and heart failure in cancer patients who received doxorubicin therapy. Together, this study identifies MAP7D1 as a clinically relevant susceptibility gene to DIC and heart failure, providing useful information to stratify cancer patients with a high risk of incurring severe cardiomyopathy and heart failure after receiving chemotherapy.

Postmenopausal women express great failure in their ovarian hormone production, especially estrogen. This deficiency may promote hypercholesterolemia and accelerate the redox imbalance. The present study was designed to evaluate the protective effect of Avena sativa against estrogen deficiency-induced liver and uterus oxidative injury in experimental ovariectomized mice. Female mice were randomly divided into five groups: group one (negative control) received normal diet and distilled water (C), group two (positive control) received daily enriched diet with oat grains and was kept on tap distilled water at a dose of 200 mg kg-1 d-1 (A), group three (ovariectomized mice) was nontreated fed with normal diet (O), group four includes ovariectomized mice treated daily with estradiol given by intraperitoneal injection at a dose of 100 μg kg-1 d-1 (OE), and the fifth group also includes ovariectomized mice which received enriched diet with oat grain parts with the same dose given to group two. The treatment period lasted two consecutive months. Both oat and hormonal treatments of ovariectomized groups resulted in a significant reduction in triglycerides and total cholesterol and increased high-density lipoprotein (HDL) levels in the plasma after 21 and 60 days of treatment. Besides, the coadministration of A. sativa has decreased the activities of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) and increased transaminase activities after 21 and 60 days of treatment. On the other hand, this cereal has restored the enzymatic (SOD, CAT, and GPx) and nonenzymatic antioxidant activities (GSH) as well as the elevated thiobarbituric acid reactive substances (AOPP and PCO) to near-normal values. The beneficial effects of this cereal were confirmed by a histological study of the liver and uterus of all previous cited groups. Our finding emphasized the antioxidant and antilipidemic effect of oat grain part, suggesting the use of this cereal in the prevention of liver and uterus diseases that occurred in postmenopausal women.

Emerging drug-resistant bacteria creates an urgent need to search for antibiotics drugs with novel mechanisms of action. Endophytes have established a reputation as a source of structurally novel secondary metabolites with a wide range of biological activities. In the present study, we explore the antibacterial potential of endophytic fungi isolated from different tissues of Terminalia mantaly, Terminalia catappa, and Cananga odorata. The crude ethyl acetate extracts of 56 different endophytic fungi were screened against seven bacterial strains using the broth microdilution method. The antibacterial modes of action of the most active extracts (04) were evaluated using E. coli ATCC 25922 and H. influenzae ATCC 49247 strains. Both the DPPH and FRAP assays were used to investigate their antioxidant activity, and their cytotoxicity against the Vero cell line was evaluated using the MTT assay. Out of the 56 crude extracts tested, about 13% were considered very active, 66% partially active, and 21% nonactive against all tested bacterial strains with MIC values ranging from 0.32 μg/mL to 25 μg/mL. The four more potent extracts (MIC <5 μg/mL) (from Aspergillus sp. N454, Aspergillus sp. N13, Curvularia sp. N101, and Aspergillus sp. N18) significantly lysed the bacteria cells, increased outer membrane permeability, reduced salt tolerance, and inhibited bacterial catalase activity. They exhibited a DPPH free radical scavenging activity with IC50 ranging from 150.71 to 936.08 μg/mL. Three of the four potent extracts were noncytotoxic against the Vero cells line (CC50 > 100 μg/mL). Results from this investigation demonstrated that endophytes from Cameroonian medicinal plants might content potent antibacterial metabolites. The bioguided fractionation of these potent extracts is ongoing to isolate and characterise potential active ingredients.

BACKGROUND: Soil-transmitted helminths (STHs) and Schistosoma mansoni are the main causes of morbidity among schoolchildren in the tropics. A school-based deworming program was launched to control and eliminate the infection in endemic countries including Ethiopia. Although periodic deworming is conducted in endemic areas, the prevalence of the infection is high in the country. In addition, periodic evaluation of the efficacy of the anthelminthic drug is limited. OBJECTIVE: This study is aimed at checking the efficacy of mebendazole and praziquantel with the respective STHs and Schistosoma mansoni parasites. METHODS: A longitudinal study was conducted from February to March 2018 among 422 schoolchildren. Stool samples were collected at baseline and at 2 and 4 weeks posttreatment and were processed using the Kato-Katz technique. Schoolchildren positive for STHs were treated with mebendazole and those positive for Schistosoma mansoni with praziquantel. After two weeks, a second round of stool was collected and examined, and then, single-dose redosing was given to each positive child. Lastly, the third stool sample was collected two weeks after the initiation of the redosing and checked for STHs and S. mansoni parasites. A close follow-up of students who were treated was done. All the data were entered and analyzed using SPSS version 20 for analysis. Descriptive statistics was used to compute the cure rate and egg reduction rate of mebendazole and praziquantel. RESULTS: Among 422 participants, the prevalence of STHs, hookworm, Ascaris lumbricoides, and S. mansoni was 44.7%, 35.1%, 21.1%, and 13.9%, respectively. The cure rate of mebendazole against A. lumbricoides increased from 60% in the single dose to 100% in redosing after two weeks. The cure rate of mebendazole against hookworm also increased from 32.4% in the single dose to 91.0% in the redosing. The cure rate of praziquantel against S. mansoni-infected children was 91.5% in the first round and 100% in the redosing phase. There was a 98.6-100% egg reduction rate in the redosing regimen of both drugs. CONCLUSION: The cure and egg reduction rates of single-dose mebendazole in the treatment of hookworm and A. lumbricoides are lower at week two than at redosing, while cure and egg reduction rates of single-dose praziquantel are satisfactory to treat S. mansoni. Therefore, single-dose praziquantel to S. mansoni and redosing of single-dose mebendazole to A. lumbricoides and hookworm infections can be used for treatment purposes.

NR-INF-02 is a standardized extract containing turmerosaccharides from Curcuma longa that has anti-inflammatory, analgesic, and chondroprotective potential. In view of its potential uses, NR-INF-02 was evaluated for its safety in Wistar rats at an oral dose of 250, 500, and 1000 mg/kg in a 90-day repeated dose subchronic toxicity study. NR-INF-02 administered at 250, 500, and 1000 mg/kg for 90 days did not show any mortality or clinical signs of toxicity. Body weight gain, food consumption, ocular and neurological examination, and hematological, blood biochemical, hormone, and urine analysis revealed no evidence of toxicity of NR-INF-02 treatment in rats. Absolute and relative organ weights were comparable to control rats. The study did not reveal any major treatment related gross pathological and histopathological alterations in the tissues or organs examined. Thus, based on study observations, the no-observed adverse effect level (NOAEL) was found to be 1000 mg/kg body weight in albino Wistar rats.

Human Runt-associated transcription factor 3 (RUNX3) plays an important role in the development and progression of endometrial cancer (EC). However, the clinical and pathological significance of RUNX3 in EC needs to be further studied. In order to clarify the clinical and pathological significance of RUNX3, a systematic review and meta-analysis was conducted in EC patients. Keywords RUNX3, endometrial cancer, and uterine cancer were searched in Cochrane Library, Web of Knowledge, PubMed, CBM, MEDLINE, and Chinese CNKI database for data up to Dec 31, 2018. References, abstracts, and meeting proceedings were manually searched in supplementary. Outcomes were various clinical and pathological features. The two reviewers performed the literature searching, data extracting, and method assessing independently. Meta-analysis was performed by RevMan5.3.0. A total of 563 EC patients were enrolled from eight studies. Meta-analysis results showed that the expression of RUNX3 has significant differences in these comparisons: lymph node (LN) metastasis vs. non-LN metastasis (P = 0.26), EC tissues vs. normal tissues (P < 0.00001), clinical stages I/II vs. II/IV (P < 0.00001), muscular infiltration < 1/2 vs. muscular infiltration ≥ 1/2 (P < 0.00001), and G1 vs. G2/G3 (P < 0.00001). The decreasing expression of RUNX3 is associated with poor TNM stage and muscular infiltration. It is indicated that RUNX3 was involved in the suppression effect of EC. However, further multicenter randomized controlled trials are needed considering the small sample size of the included trials.

BACKGROUND: In the intensive care units, patients need special consideration and monitor frequently with appropriate physical assessment skills. Nurses working in the intensive care units play a fundamental role in detecting patients at risk of deterioration through ongoing assessment and action in response to changing health status. Most of the nursing activities were poorly assessed in low-income countries including Ethiopia. Therefore, this study was aimed to assess the nurses' practice and barriers to physical assessment among critically ill patients in Northwest Ethiopia. METHODS: An institution-based multicenter cross-sectional study was conducted at Amhara regional state referral hospitals from March to September 2019. A total of 299 nurses working in the intensive care units were recruited through the convenience sampling method. A 30-item physical assessment practice and 36-item barriers to nurses' use of the physical assessment scale inventory were used. The linear regression analysis model was fitted, and the adjusted unstandardized beta (β) coefficient with a 95% confidence interval was used. A p value < 0.05 was considered statistically significant. RESULTS: The mean score of the nurses' practice towards physical assessment among critically ill patients was 101.26 ± 24.99. Greater perceived reliance on others and technology (β = -0.78, 95% CI (-1.07, -0.48)), ward culture (β = -0.48, 95% CI (-0.85, -0.11)), specialty area (β = -1.46, 95% CI (-2.01, -0.90)), lack of nursing role model (β = -0.54, 95% CI (-1.06, -0.02)), being unmarried (β = -6.10, 95% CI (1.75, 10.46)), taken training (β = 11.53, 95% CI (6.34, 16.72)), and knowledge score (β = 2.81, 95% CI (2.00, 3.63)) were the factors significantly associated with the nurses' practice score towards physical assessment. Reliance on others and technology towards physical assessment practice was the most important barrier followed by ward culture and specialty area. CONCLUSION: Nurses working in the intensive care units had a good practice towards physical assessment among critically ill patients. Hence, to increase the practice towards physical assessment in intensive care settings, especially for married nurses, experienced critical care nurses, and specialist professionals, practice support training, modifying ward environment, and educational support care are recommended.

BACKGROUND: Preoperative fasting is important to reduce the risk of pulmonary aspiration during anesthesia. The influence of prolonged fasting time on glucose levels during anesthesia in children remains uncertain. Therefore, this study is aimed at assessing preoperative fasting time and its association with hypoglycemia during anesthesia in pediatric patients undergoing elective procedures at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. The research hypothesis of the study is as follows: there is a prolonged preoperative fasting time, and it influences the glucose levels during anesthesia among pediatric patients undergoing elective procedures at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia. METHODS: Institutional based cross-sectional study was conducted among 258 pediatric patients who had undergone elective procedures in a tertiary care center. A systematic sampling method was used to select study participants. The data were collected through face-to-face interviews and medical record reviews. Binary logistic regression was used to identify associated factors of hypoglycemia during anesthesia among pediatric patients undergoing elective procedures. All explanatory variables with a p value of ≤0.25 from the bivariable logistic regression model were fitted into the multivariable logistic regression model to control the possible effect of confounders, and finally, the variables which had an independent association with hypoglycemia were identified based on adjusted odds ratio with 95% confidence interval, and a p value less than 0.05 was significant. RESULTS: The mean (standard deviation) fasting hours from breast milk, solid foods, and clear fluids were 7.75 (2.89), 13.25 (3.14), and 12.31 (3.22), respectively. The majority (89.9%, 57.9%, and 100%) of participants had fasted from solid, breast milk, and clear fluids for more than 8, 6, and 4 hours, respectively. More than one-fourth (26.2%) of participants were hypoglycemic immediately after induction. Residence, order of nothing per mouth, source of patient, and duration of fasting from solid foods had a significant association with hypoglycemia during anesthesia in children. CONCLUSION: Children undergoing elective procedures were exposed to unnecessarily long fasting times which were associated with hypoglycemia during anesthesia.

Endometrial carcinoma (EC) is the fifth widely occurring malignant neoplasm among women all over the world. However, there is still lacking efficacy indicators for EC's prognosis. Here, we analyzed two databases including an RNA-sequencing-based TCGA dataset and a microarray-based GSE106191. After normalizing the raw data, we identified 114 common genes with upregulation and 308 common genes with downregulation in both the TCGA and GSE106191 databases. Bioinformatics analysis showed that the differently expressed genes in EC were related to the IL17 signaling pathway, PI3K-Akt signaling pathway, and cGMP-PKG signaling pathway. Furthermore, we performed the least absolute shrinkage and selection operator (LASSO) Cox regression analysis and generated a signature featuring 17 prognosis-related genes (MAL2, ANKRD22, METTL7B, IL32, ERFE, OAS1, TRPC1, SRPX, RAPGEF4, PSD3, SIMC1, TRPC6, WFS1, PGR, PAMR1, KCNK6, and FAM189A2) and found that it could predict OS in EC patients. The further analysis showed that OAS1, MAL2, ANKRD22, METTL7B, and IL32 were significantly upregulated in EC samples after comparison with normal samples. However, TRPC1, SRPX, RAPGEF4, PSD3, SIMC1, TRPC6, WFS1, PGR, PAMR1, KCNK6, and FAM189A2 were significantly downregulated in EC samples in comparison with normal samples. And correlation analysis showed that our results showed that the expressions of 17 prognosis-related hub genes were significantly correlated based on Pearson correlation. We here offer a newly genetic biomarker for the prediction of EC patients' prognosis.

Erratum in Biomed Res Int. 2021 Nov 24;2021:9758328.

Nonunion after diaphyseal fracture of the femur or the tibia is a common but difficult complication for treatment. Currently, the main treatment modalities include nail dynamization, exchange nailing, and bone transport, but revision with compression plating in these nonunions was rarely reported. To evaluate the outcomes of compression plating in the treatment of femur and tibia shaft nonunions, we retrospectively reviewed 54 patients with diaphyseal nonunion of the tibia or the femur treated with locking compression plate (LCP) by compression technique. There were 46 aseptic and 8 septic nonunions in the case series. Patient's history, fracture characteristics, previous interventions, and types of nonunion were recorded. The possible reason which might lead to nonunion was also analyzed for each case. Patients with aseptic nonunions were revised by hardware removal and compression plating with or without bone grafting. For septic nonunions, a two-stage surgery strategy was used. Compression plating with iliac crest bone grafting (ICBG) or free vascularized fibular grafting (FVFG) was used as the final treatment for septic nonunions. The compression technique and bone grafting method were individualized in each case according to the patient's history and architecture of the nonunion. Each patient finished at least a two-year follow-up, and all cases achieved healing uneventfully. Our study showed that compression plating with LCP was an effective method to treat diaphyseal nonunions of the tibia and the femur. It is compatible with different bone grafting methods for both infected and noninfected nonunions and is a good alternative to the current treatment methods for these nonunions.

BACKGROUND: Survival of patients with portal vein tumor thrombosis (PVTT) is extremely poor; transarterial chemoembolization (TACE) is a treatment for patients with HCC and PVTT. Some studies showed that hepatic arterial infusion chemotherapy (HAIC) might improve the survival of HCC with PVTT. There were few researches of combining TACE with HAIC for patients with HCC and PVTT. AIM: This study was aimed at comparing overall survival (OS) and progression-free survival (PFS) following treatment with conventional transarterial chemoembolization plus hepatic arterial infusion chemotherapy (cTACE-HAIC) or conventional transarterial chemoembolization (cTACE) alone in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT). METHODS: From January 2011 to December 2016, 155 patients with HCC and PVTT who received cTACE-HAIC (cTACE-HAIC group) (n = 86) or cTACE alone (cTACE group) (n = 69) were retrospectively evaluated. Propensity score matching (PSM) reduced the confounding bias and yielded 60 matched patient pairs. The tumors' responses were evaluated using the modified response evaluation criteria in solid tumors (mRECIST). OS and PFS of groups were compared using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models. RESULTS: The median follow-up duration was 93 months (range: 1-93 months). The cTACE-HAIC group's OS (9.0 months) and PFS (6.0 months) were significantly longer than the cTACE group's OS (5.0 months) and PFS (2.0 months) (p = 0.018 and p = 0.045, respectively) in the matched cohort. Multivariate analyses showed that cTACE-HAIC was independently associated with OS (hazard ratio (HR) 0.602, p = 0.010) and PFS (HR 0.66, p = 0.038). The matched groups did not differ regarding grade 3 or 4 adverse events. CONCLUSION: cTACE-HAIC was superior to cTACE alone regarding OS and PFS in patients with HCC and PVTT. Treatment-associated toxicities were generally well tolerated.

The Physical Activity Questionnaire for Adolescents (PAQ-A) has been used in a variety of forms and in a range of countries. This study involves a detailed examination of the PAQ-A to determine its applicability and effectiveness in an Ethiopian setting. We administered the scale to 110 Ethiopian adolescents on two occasions, 5 weeks apart. Data were inspected for features typical of the participants and analyzed to identify interitem correlations, the scale's factor structure, and a range of descriptive statistics concerning composite scores. Most of the scale's items were satisfactorily interrelated according to lenient criteria, and most items loaded on a single factor in exploratory factor analyses. However, a number of the scale's properties were deficient according to stringent or conventionally accepted psychometric criteria. Close inspection of participants' responses highlighted problems in the way the scale is worded, interpreted by participants, and scored. Although the scale does not capture PA as an homogeneous construct, we argue that this is not a problem and neither is its poor test-retest reliability. We make recommendations concerning presentation and scoring of the PAQ-A that are likely to enhance its validity beyond Ethiopia, and we provide a modified version of the scale.

BACKGROUND: Diet and lifestyle can destroy tooth structure due to the dissolution of enamel by acidic beverages. The present study evaluated the effect of CO2 laser irradiation and CPP-ACFP (casein phosphopeptide and amorphous calcium phosphate with fluoride) paste on the remineralization of enamel eroded by carbonated soft drinks. METHODS: In the present in vitro study, 46 human sound premolar teeth were sectioned mesiodistally to achieve 84 samples. Fourteen samples were assigned to the positive control group (G1), and the remaining samples were immersed in 500 mL of cola drink for 2 minutes, followed by rinsing with distilled water for 10 seconds. This procedure was carried out three times to create erosive lesions. Then, the 60 eroded samples were randomly assigned to five groups of G2 to G6 in terms of the treatment as follows: negative control (G2), CO2 laser irradiation (G3), CPP-ACFP paste (G4), CO2 laser irradiation followed by CPP-ACFP paste application (G5), and CPP-ACFP paste application followed by CO2 laser irradiation (G6). The mean surface microhardness of the enamel surface was evaluated and determined at three points for each sample. Data were analyzed with one-way ANOVA and Tukey HSD tests (α = 0.05). RESULTS: The highest and the lowest hardness values were recorded in the G1 (314 ± 12 kg/mm2) and G2 (213.7 ± 12 kg/mm2) groups, respectively. ANOVA revealed significant differences between the study groups (P < 0.001). Two-by-two comparisons showed significant differences between the G2 group and the other groups, indicating the efficacy of all the treatment modalities in tooth remineralization and rehardening procedures (P < 0.05). Only in group G6, the enamel microhardness was not significantly different from the G1 positive control group (P > 0.05). CONCLUSION: Considering the parameters used in the present study, CO2 laser irradiation or CPP-ACFP paste application alone increased eroded enamel's surface hardness; however, their sequential application was more effective in rehardening the eroded enamel's surface to near-normal levels.

Mesenchymal stem cells (MSCs) are valuable candidates in tissue engineering and stem cell-based therapy. Traditionally, MSCs derived from various tissues have been successfully expanded in vitro using adherent culture plates commonly called as monolayer two-dimensional (2D) cultures. Recently, many studies demonstrated that stemness and multilineage differentiation potential could be enhanced to greater extent when MSCs are cultured as suspended aggregates by means of three-dimensional (3D) culturing techniques. However, there are limited reports on changed mitochondrial metabolism on 3D spheroid formation of MSCs. Therefore, the present study was aimed at investigating the stemness, differentiation potential, and mitochondrial metabolism capacity of 3D dental pulp-derived MSC (DPSC) spheroids in comparison to monolayer cultured DPSCs. We isolated dental pulp-derived MSCs (DPSCs) and successfully developed a 3D culture system which facilitated the formation of MSC spheroids. The cell aggregation was observed after 2 hours, and spheroids were formed after 24 hours and remained in shape for 72 hours. After spheroid formation, the levels of pluripotent markers increased along with enhancement in adipogenic and osteogenic potential compared to 2D cultured control cells. However, decreased proliferative capacity, cell cycle arrest, and elevated apoptosis rate were observed with the time course of the 3D culture except for the initial 24-hour aggregation. Furthermore, oxygen consumption rates of living cells decreased with the time course of the aggregation except for the initial 24 hours. Overall, our study indicated that the short-term 3D culture of MSCs could be a suitable alternative to culture the cells.

Damage and regeneration naturally occur in the peripheral nervous system. The neurotropic B vitamins thiamine (B1), pyridoxine (B6), and cobalamin (B12) are key players, which maintain the neuronal viability in different ways. Firstly, they constantly protect nerves against damaging environmental influences. While vitamin B1 acts as a site-directed antioxidant, vitamin B6 balances nerve metabolism, and vitamin B12 maintains myelin sheaths. However, nerve injury occurs at times, because of an imbalance between protective factors and accumulating stress and noxae. This will result in the so-called Wallerian degeneration process. The presence of vitamins B1, B6, and B12 paves the way out to the following important regeneration by supporting the development of new cell structures. Furthermore, vitamin B1 facilitates the usage of carbohydrates for energy production, whereas vitamin B12 promotes nerve cell survival and remyelination. Absence of these vitamins will favor permanent nerve degeneration and pain, eventually leading to peripheral neuropathy.

OBJECTIVE: To investigate the association between parental bonding styles and anxiety, depression, suicidal ideation, and self-efficacy beliefs in undergraduate medical students. METHODS: A cross-sectional, self-administered survey involving 315 Brazilian medical students was conducted online. The Parental Bonding Instrument (PBI), the Generalized Anxiety Disorder-7 (GAD-7) scale, the 9-item Patient Health Questionnaire (PHQ-9), the Suicidal Behaviors Questionnaire-Revised (SBQ-R), and the general self-efficacy (GSE) scale were used. The internal consistency of the instruments used in the study was analyzed using Cronbach's alpha. Multiple logistic regression models were applied, and the odds ratios (OR) and respective 95% confidence intervals (CI) were calculated to determine the association between parental bonding styles and anxiety, depression, suicidal ideation, and general self-efficacy beliefs. RESULTS: In the analysis adjusted for sociodemographic variables, maternal affectionless control was associated with a greater risk of anxiety (OR = 2.48; 95% CI: 1.15-5.33), depression (OR = 7.54; 95% CI: 3.20-17.78), suicidal ideation (OR = 3.62; 95% CI: 1.58-8.27), and low self-efficacy (OR = 3.81; 95% CI: 1.76-8.25), while maternal neglectful parenting was associated with depression (OR = 3.24; 95% CI: 1.17-8.96) and paternal affectionate constraint with suicidal ideation (OR = 3.09; 95% CI: 1.36-7.02). CONCLUSIONS: These findings showed dysfunctional parenting styles to be associated with mental illnesses and low self-efficacy in Brazilian undergraduate medical students. This should be taken into consideration when treating medical students with mental disorders.

BACKGROUND: Anaesthesia can alter neuronal excitability and vascular reactivity and ultimately lead to neurovascular coupling. Precise control of the skeletal muscle relaxant doses is the key in reducing anaesthetic damage. METHODS: A total of 102 patients with the normal functioning preoperative facial nerve who required parotid tumour resection were included in this study. Facial nerve monitoring was conducted intraoperatively. The surgeon stimulated the facial nerve at different myorelaxation intervals at TOF% (T4/T1) and T1% (T1/T0) and recorded the responses and the amplitude of electromyogram (EMG). Body movements (BM) or patient-ventilator asynchrony (PVA) was recorded intraoperatively. RESULTS: In parotid tumour resection, T1% should be maintained at a range of 30 to 60% while TOF% should be maintained at a range of 20 to 30%. Analysis of the decision tree model for facial nerve monitoring suggests a partial muscle relaxation level of 30% < T1% ≤ 50% and TOF ≤ 60%. A nomogram prediction model, while incorporating factors such as sex, age, BMI, TOF%, and T1%, was constructed to predict the risk of BM/PVA during surgery, showing good predictive performance. CONCLUSIONS: This study revealed an adequate level of neuromuscular blockade in intraoperative parotid tumour resection while conducting facial nerve monitoring. A visual nomogram prediction model was constructed to guide anaesthetists in improving the anaesthetic plan.

OBJECTIVE: Discectomy remains the classic procedure for treating lumbar intervertebral disc (IVD) herniation, but the occurrence of defects after discectomy is thought to be an important cause generating recurrent and accelerated IVD degeneration. Previous studies attempted suture of the annulus fissure, but the validity of this technique on restraining the degenerative process is controversial. On the other hand, cell therapies have been shown in multiple clinical and basic studies. Our purpose was to investigate the effectiveness of selective retention of autologous Bone Marrow Stromal Cells (BMSCs) with gelatin sponge in combination with annulus fibrosus suture (AFS) for the repair of IVD defects following mobile microendoscopic discectomy (MMED). METHODS: This prospective, two-armed, and controlled clinical study was conducted from December 2016 to December 2018. Written informed consent was obtained from each patient. Forty-five patients with typical symptoms, positive signs of radiculopathy, and obvious lumbar disc herniation observed by MRI were enrolled. Patients were divided into 3 groups with different treating methods: MMED (n = 15), MMED+AFS (n = 15), and MMED+AFS+BMSCs (n = 15). A postoperative 2-year follow-up was performed to evaluate the patient-reported outcomes of VAS, ODI, and SF-36. The improvement rate of VAS and ODI was calculated as [(latest-preoperative)/preoperative] to evaluate the therapeutic effect of the three groups. Assessment parameters included Pfirrmann grade, intervertebral disc height (IDH), and disc protrusion size (DPS), as measured by MRI to evaluate the morphological changes. RESULTS: All patients enrolled had a postoperative follow-up at 3, 6, 12, and 24 months. VAS and ODI scores were significantly improved compared to the preoperative status in all three groups with a mean DPS reduction rate over 50%. At the final follow-up, the improvement rate of the VAS score in the MMED+AFS+BMSCs group was significantly higher than the MMED+AFS and MMED groups (80.1% ± 7.6% vs. 71.3% ± 7.0% vs. 70.1% ± 7.8%), while ODI improvement showed a significant change (65.6% ± 8.8% vs. 59.9% ± 5.5% vs. 57.8% ± 8.1%). All participants showed significant improvement in SF-36 PCS and MCS; the differences between each group were not significant. The mean IDH loss rate of the MMED+AFS+BMSCs group was also significantly lower than other groups (-17.2% ± 1.3% vs. -27.6% ± 0.7% vs. -29.3% ± 2.2%). The Pfirrmann grade was aggravated in the MMED and MMED+AFS groups while maintained at the preoperative grade in the MMED+AFS+BMSCs group. No adverse events of cell transplantation or recurrence were found in all patients during the postoperative follow-up period. CONCLUSIONS: It is feasible and effective to repair lumbar IVD defects using SCR-enriched BMSCs with gelatin sponges, which warrants further study and development as a cell-based therapy for IVD repair.

Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system, and its early asymptomatic characteristic increases the difficulty of diagnosis and treatment. This study is aimed at obtaining some novel biomarkers with diagnostic and prognostic meaning and may find out potential therapeutic targets for HCC. We screen differentially expressed genes (DEGs) from the HCC gene expression profile GSE14520 using GEO2R. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted by using the clusterProfiler software while a protein-protein interaction (PPI) network was performed based on the STRING database. Then, prognosis analysis of hub genes was conducted using The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to further verify the expression of hub genes and explore the correlation between gene expression and clinicopathological parameters. A total of 1053 DEGs were captured, containing 497 upregulated genes and 556 downregulated genes. GO and KEGG analysis indicated that the downregulated DEGs were mainly enriched in the fatty acid catabolic process while upregulated DEGs were primarily enriched in the cell cycle. Simultaneously, ten hub genes (CYP3A4, UGT1A6, AOX1, UGT1A4, UGT2B15, CDK1, CCNB1, MAD2L1, CCNB2, and CDC20) were identified by the PPI network. Five prognosis-related hub genes (CYP3A4, CDK1, CCNB1, MAD2L1, and CDC20) were uncovered by the survival analysis based on TCGA database. The ten hub genes were further validated by qRT-PCR using samples obtained from our hospital. The prognosis-related hub genes such as CYP3A4, CDK1, CCNB1, MAD2L1, and CDC20 could be considered potential diagnosis biomarkers and prognosis targets for HCC. We also use Oncomine for further verification, and we found CCNB1, CCNB2, CDK1, and CYP3A4 which were highly expressed in HCC. Meanwhile, CCNB1, CCNB2, and CDK1 are highly expressed in almost all cancer types, which may play an important role in cancer. Still, further functional study should be conducted to explore the underlying mechanism and biological effect in the near future.

Erratum in Biomed Res Int. 2022 May 20;2022:9760864.

The aim of the study is to examine the mechanism of Aralia armata (Wall.) Seem (AAS) in improving intimal hyperplasia after vascular injury in rats. Rats with femoral artery injury were randomly divided into three groups: the model group, AAS low-dose group (40 mg/kg), and AAS high-dose group (80 mg/kg). The sham operation group was used as a control group. HE staining was used to observe the changes in femoral artery vessels. Immunohistochemistry was adopted to detect α-SMA, PCNA, GSK-3β, and β-catenin proteins in femoral artery tissue. The CCK-8 test and wound healing assay were employed to analyze the effect of AAS on proliferation and migration of vascular smooth muscle cells (VSMCs) cultured in vitro. Western blotting (WB) and polymerase chain reaction (PCR) assays were used to evaluate the molecular mechanism. AAS reduced the stenosis of blood vessels and the protein expressions of α-SMA, PCNA, GSK-3β, and β-catenin compared to the model group. In addition, AAS (0-15 μg/mL) effectively inhibited the proliferation and migration of VSMCs. Moreover, the results of WB and PCR showed that AAS could inhibit the activation of β-catenin induced by 15% FBS and significantly decrease the expression levels of Wnt3α, Dvl-1, GSK-3β, β-catenin, and cyclin D1 in the upstream and downstream of the pathway. AAS could effectively inhibit the proliferation and migration of neointima after vascular injury in rats by regulating the Wnt/β-catenin signaling pathway.

BACKGROUND: Obesity is a main contributing factor for the development of glucose intolerance and type 2 diabetes mellitus (T2D). Roux-en-Y gastric bypass (RYGB) is believed to be one of the most effective treatments to reduce body weight and improve glucose metabolism. In this study, we sought to explore the underlying mechanisms of weight reduction and insulin resistance improvement after RYGB. METHODS: This was a prospective observational study using consecutive samples of 14 obese subjects undergoing bariatric surgery. Main assessments were serum indexes (blood metabolites, glucose-lipid regulating hormones, trimethylamine-N-oxide (TMAO), and lipopolysaccharide-binding protein (LBP), fecal short-chain fatty acids (SCFAs), and gut microbiota. Correlation analysis of the factors changed by RYGB was used to indicate the potential mechanism by which surgery improves insulin resistance. RESULTS: The subjects showed significant improvement on indices of obesity and insulin resistance and a correlated change of gut microbiota components at 1 month, 3 months, and 6 months post-RYGB operation. In particular, the abundance of a counterobese strain, Akkemansia muciniphila, had gradually increased with the postoperative time. Moreover, these changes were negatively correlated to serum levels of LBP and positively correlated to serum TMAO and fecal SCFAs. CONCLUSIONS: Our findings uncovered links between intestinal microbiota alterations, circulating endotoxemia, and insulin resistance. This suggests that the underlying mechanism of protection of the intestine by RYGB in obesity may be through changing the gut microbiota.

BACKGROUND: Malaria and malnutrition are major public health problems in developing countries. This studywas mainly focused on the prevalence, patterns, and predictors of these conditions and their associations. METHODS: A cross-sectional community study was conducted from February to March 2018 among 281 participants living in two districts in Douala. A questionnaire was used to collect sociodemographic information and parasitological and anthropometric data of participants. Nutritional status was determined using age, weight, and height. Body mass index for age (BMIAZ), height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) Z scores were computed based on the World Health Organization growth reference curves. Malaria infection was diagnosed using light-emitting diode fluorescence microscopy. RESULTS: The overall prevalence of malaria was 18.9%, mostly asymptomatic cases. Malaria infection was associated with study site (p = 0.04), age (p = 0.01), WAZ (p = 0.0049), HAZ (p = 0.03), and BMI (p = 0.02). The overall prevalence of malnutrition was 43.1%, and stunting was the main form of malnutrition recorded in children under five years of age (23.6%). The risk of being stunted in this group was about quintupled in malaria-infected participants (ARR = 4.70; p = 0.02). In those aged 5-19 years, the prevalence of underweight was significantly higher in malaria-positive individuals as compared to their negative counterparts (p = 0.02). The overall prevalence of malaria and malnutrition cooccurrence was 8.5% and varied with age (p < 0.0001) and study site (p = 0.04). Conclusion and Recommendation. Malaria was associated with malnutrition among the study participants. Early detection and treatment of these ailments would reduce morbidity and mortality.

The present study is aimed at investigating the variation of phenolics (bound and free), minerals, and antioxidant potentials of the wild edible fruits (fresh and dry) native from Far North Region of Cameroon. The results showed significant (p < 0.01) differences among fruits and species for all parameters. Bound phenolic content (mgGAE/100 g) of dry fruits (DF) ranged from 95.58 to 407.72; however, the contents were varied from 28.97 to 306.04 in fresh fruits (FF). Free phenolic content varied from 46.43 to 344.73 in DF and fold from 119.54 to 315.79 for those FF. Flavonoids (4.27-256.87 mg QE/100 g), tannins (3.24-63.42 mg CE/100 g), and anthocyanin content (8.65-168.10 mg C3GE/100 g) in fruits varied also significantly in respect with DF and FF. The mineral content analysis indicates that the wild fruits are rich in valuable macro- and trace elements. For antioxidant activities, except high 2.2-diphenyl-1-picyhydrazyl (DPPH) scavenging activity obtained with free phenolics, the bound phenolics of FF and DF had significantly high ferric reducing antioxidant power (FRAP) and 2,2-azino-bis(3-ethylbenzylthiozoline-6-sulphonic acid) (ABTS) scavenging activity. Furthermore, free and bound phenolic content was highly and positively correlated with ABTS, DPPH, and FRAP activities confirmed by the principal component analysis (F1×F2: 60.17%). The present study revealed that the wild edible fruits of twenty-three species investigated are important sources of bioactive compounds, natural antioxidants, and nutraceutical potential to prevent/to treat chronic diseases which could be benefits for the consumers.

OBJECTIVE: Motivation determines the possibility of an individual's intention to accept health-related behaviors. Despite the important role of the motivational system in conducting healthy and safe nutrition behavior, this issue has not been adequately addressed. The purpose of this qualitative study was to explain the healthy and safe nutrition motivation system among Iranian adolescent girls. METHOD: In this qualitative study, conventional content analysis was used and participants were selected using the purposive sampling method. Semistructured in-depth interviews were conducted with 42 adolescent girls in Shiraz, Iran. The interviews continued until data saturation was obtained. Qualitative data were analyzed using the Graneheim and Lundman qualitative content analysis by MAX-Q-DA (version 10) software. RESULTS: The data analysis resulted in three main categories for the participants' motivational factors for healthy and safe nutrition: (1) maintaining health and social functions, (2) maintaining the family's mental and economic health, and (3) achieving goals and success in life. The first category included two subcategories: "desire to have an appropriate look and appearance" and "fear of diseases and their complications." The second category included two subcategories of "maintaining the family's mental health" and "maintaining the family's economic health." The third category consisted of two subcategories: "desire to form a family and be successful in life" and "achieving the future career goals." CONCLUSION: The motivation to maintain health and social functions, to maintain the family's mental and economic health, and to achieve goals and be successful in life has a powerful impact on the decisions and behaviors of adolescent girls to have safe and healthy nutrition. Therefore, recognizing the motivational system, as a key and determinative factor in developing the adolescents' intention to adopt health-related behaviors, is an effective step to design and develop successful interventions in promoting nutritional behaviors.

OBJECTIVE: To investigate whether lumbosacral transitional vertebrae (LSTV) affects the clinical outcomes of percutaneous endoscopic lumbar discectomy (PELD) in adolescent patients with lumbar disc herniation (LDH). METHODS: This was a retrospective study with two groups. Group A was made up of 22 adolescent LDH patients with LSTV (18 males and 4 females). Group B was made up of 44 adolescent LDH patients without LSTV (36 males and 4 females), who were matched to group A for age, sex, and body mass index. All patients underwent PELD at the L4/5 or L5/S1 single level and were followed up at 18 months after surgery. We identified LSTV on radiographs and computed tomography and assessed the imaging characteristics of all patients. Outcomes were evaluated through a numerical rating scale (NRS), the Oswestry Disability Index (ODI), the modified MacNab grading system, and the incidence of additional lumbar surgery. RESULTS: At 18 months after PELD, both groups had significant improvements in the mean NRS scores of low back pain (LBP) or leg pain and the ODI scores. In terms of the MacNab criteria, 90.9% in group A and 93.2% in group B showed excellent or good outcomes. The mean NRS scores of LBP or leg pain, ODI score, and MacNab grade after surgery were not significantly different between the 2 groups. Two patients (one patient had a recurrence; one patient had a new lumbar disc herniation) in group A and 3 patients (one patient had a recurrence; two patients had new lumbar disc herniations) in group B underwent additional lumbar surgery. CONCLUSIONS: Our study suggests that in terms of pain relief, life function improvement, and the incidence of additional lumbar surgery, LSTV has no effect on the short-term clinical outcomes of PELD in adolescents. A new lumbar disc herniation is an important reason for additional surgery in adolescents, regardless of the LSTV status.

Erratum for Biomed Res Int. 2017;2017:4176170.

BACKGROUND: Few studies have assessed the association between hypertension and risk of detailed causes of death. We investigated the association between hypertension and all-cause mortality and 67 causes of death in a large cohort. METHODS: Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for self-reported hypertension vs. no hypertension and mortality. Adults aged ≥18 years (n = 213798) were recruited in 1997-2004 and followed through December 31, 2006. RESULTS: During 5.81 years of follow-up, 11254 deaths occurred. Self-reported hypertension vs. no hypertension was associated with increased risk of all-cause mortality (HR = 1.25, 95% CI: 1.19-1.31) and mortality from septicemia (HR =1.66, 1.06-2.59), other infectious parasitic diseases (HR = 2.67, 1.09-6.51), diabetes mellitus (HR = 1.97, 1.45-2.67), circulatory disease (HR = 1.49, 1.37-1.61), hypertensive heart disease (HR = 3.23, 2.00-5.20), ischemic heart disease (HR = 1.35, 1.23-1.49), acute myocardial infarction (HR = 1.50, 1.27-1.77), other chronic ischemic heart diseases (HR = 1.35, 1.17-1.56), all other forms of heart disease (HR = 1.51, 1.21-1.89), primary hypertension and renal disease (HR = 3.11, 1.82-5.30), cerebrovascular disease (HR = 1.64, 1.37-1.97), other circulatory system diseases (HR = 1.71, 1.09-2.69), other chronic lower respiratory diseases (HR = 1.39, 1.12-1.73), other chronic liver disease (HR = 1.89, 1.06-3.37), renal failure (HR = 1.91, 1.33-2.74), motor vehicle accidents (HR = 1.60, 1.07-2.37), and all other diseases (HR =1.30, 1.10-1.54), but with lower risk of uterine cancer (HR = 0.37, 95% CI: 0.15-0.90) and Alzheimer's disease (HR = 0.65, 95% CI: 0.47-0.92). CONCLUSION: Hypertension was associated with increased risk of all-cause mortality and 17 out of 67 causes of death, with most of these being circulatory disease outcomes, however, some of the remaining associations are unlikely to be causal. Further studies are needed to clarify associations with less common causes of death and potential causality across outcomes.

Age is a key factor in intervertebral disc (IVD) degeneration; however, the changes that occur in IVDs with age are not fully understood. Tissue-resident macrophages are critical for tissue homeostasis and are regulated by transforming growth factor- (TGF-) β. We examined changes in the proportion of resident macrophages in young versus aged mice and the role of TGF-β in regulating resident macrophages in IVDs. IVDs were harvested from 4-month (young) and 18-month-old (aged) C57BL/6J mice. The proportion of macrophages in IVDs was determined using flow cytometry (n = 5 for each time point) and the expression of Cd11b, Cd206, and Tgfb genes, which encode CD11b, CD206, and TGF-β protein, respectively, using real-time PCR. To study the role of TGF-β in the polarization of resident macrophages, resident macrophages isolated from IVDs from young and aged mice were treated with recombinant TGF-β with and without a TGF-β inhibitor (SB431542). Additionally, SB431542 was intraperitoneally injected into young and aged mice, and Cd206 expression was examined using real-time PCR (n = 10 for each time point). The proportion of CD11b+ and CD11b+ CD206+ cells was significantly reduced in aged versus young mice, as was Cd11b, Cd206, and Tgfb expression. TGF-β/IL10 stimulation significantly increased the expression of Cd206, an M2 macrophage marker, in disc macrophages from both young and aged mice. Meanwhile, administration of a TGF-β inhibitor significantly reduced Cd206 expression compared to vehicle control in both groups. Conclusion. Resident macrophages decrease with age in IVDs, which may be associated with the concomitant decrease in TGF-β. Our findings provide new insight into the mechanisms of age-related IVD pathology.

In this study, 16S rRNA high-throughput sequencing technology was used to analyze the composition and diversity of bacterial and fungal communities in mushroom residue samples at different composting stages. During the composting process, the maximum temperature in the center of the pile can reach 52.4°C, and the temperature above 50°C has been maintained for about 8 days. The results showed that Actinobacteria, Firmicutes, Proteobacteria, Bacteroidetes, and Chloroflexi were the main microorganisms in the composting process, accounting for 98.9%-99.7% of the total bacteria. Furthermore, in order to obtain the protein expressed in each stage of composting, the nonstandard quantitative method (label free) was used to analyze it quantitatively by mass spectrometry, anda total of 22815 proteins were identified. It indicated that the number of identified proteins related to cellulose decomposition and the number of differentially expressed proteins were significantly enriched, and the functional proteins related to cellulose decomposition had significant stage correspondence.

Higher heating value (HHV) is one of the properties of biomass fuels which is essential in investigating their special characteristics and potentialities. In this paper, various techniques based on Gaussian process regression (GPR) were utilized to assess this value for biomass fuels, including several kernel functions, i.e., exponential, Matern, rational quadratic, and squared exponential. An extensive databank was collected from literature. The findings were compared, and the results indicated that Exponential-based model was more accurate, with the coefficient of regression (R 2) of 0.961 and the mean relative error (% MRE) of 3.11 for total data. Compared to former models presented by previous researchers, the model proposed in this study showed a higher ability to predict output values. With various analyses, it can be concluded that the proposed method has a high rate of efficiency in assessing the HHV of various biomass.

Linezolid can cause serious haematological toxicity, such as thrombocytopenia and aneamia. Heme, composed of iron and porphyrin, is an important component of hemoglobin. In order to investigate the relationship between the concentration of linezolid and heme in the plasma of infected patients, a UPLC-MS/MS method that can determine the concentrations of linezolid and heme simultaneously was developed and validated. A total of 96 healthy subjects and 81 infected patients, who received blood routine blood tests, were included and determined by the UPLC-MS/MS method. The results showed that the concentration of linezolid was 5.08 ± 3.46 μg/mL in infected patients who were treated with linezolid. The heme in healthy subjects was 7.05 ± 8.68 μg/mL, and it was significantly decreased to 0.88 ± 0.79 μg/mL in infected patients (P < 0.01). Spearman correlation analysis showed that linezolid had a high negative correlation with platelet (PLT) (R = -0.309). Heme had a high positive correlation with hemoglobin (Hb) (R = 0.249) in healthy subjects and infected patients. The ROC analysis showed that heme had diagnostic value to distinguish low Hb (110 g/L). In conclusion, there was a positive correlation between heme and Hb, and this correlation was also observed in infected patients. A high concentration of linezolid was inclined to decrease PLT. Monitoring of heme and linezolid helps in the early diagnose of low Hb and PLT.

Lectins are widely distributed in the natural world and are usually involved in antitumor activities. Auricularia auricula (A. auricula) is a medicinal and edible homologous fungus. A. auricula contains many active ingredients, such as polysaccharides, melanin, flavonoids, adenosine, sterols, alkaloids, and terpenes. In this study, we expected to isolate and purify lectin from A. auricula, determine the glycoside bond type and sugar-specific protein of A. auricula lectin (AAL), and finally, determine its antitumor activities. We used ammonium sulfate fractionation, ion exchange chromatography, and affinity chromatography to separate and purify lectin from A. auricula. The result was a 25 kDa AAL with a relative molecular mass of 18913.22. Protein identification results suggested that this lectin contained four peptide chains by comparing with the UniProt database. The FT-IR and β-elimination reaction demonstrated that the connection between the oligosaccharide and polypeptide of AAL was an N-glucoside bond. Analyses of its physical and chemical properties showed that AAL was a temperature-sensitive and acidic/alkaline-dependent glycoprotein. Additionally, the anticancer experiment manifested that AAL inhibited the proliferation of A549, and the IC50 value was 28.19 ± 1.92 μg/mL. RNA sequencing dataset analyses detected that AAL may regulate the expression of JUN, TLR4, and MYD88 to suppress tumor proliferation. Through the pulmonary flora analysis, the bacterial structure of each phylum in the lectin treatment group was more reasonable, and the colonization ability of the normal microflora was improved, indicating that lectin treatment could significantly improve the bacterial diversity characteristics.

The manual delineation of the lesion is mainly used as a conventional segmentation method, but it is subjective and has poor stability and repeatability. The purpose of this study is to validate the effect of a radiomics model based on MRI derived from two delineation methods in the preoperative T staging of patients with rectal cancer (RC). A total of 454 consecutive patients with pathologically confirmed RC who underwent preoperative MRI between January 2018 and December 2019 were retrospectively analyzed. RC patients were grouped according to whether the muscularis propria was penetrated. Two radiologists segmented lesions, respectively, by minimum delineation (Method 1) and maximum delineation (Method 2), after which radiomics features were extracted. Inter- and intraclass correlation coefficient (ICC) of all features was evaluated. After feature reduction, the support vector machine (SVM) was trained to build a prediction model. The diagnostic performances of models were determined by receiver operating characteristic (ROC) curves. Then, the areas under the curve (AUCs) were compared by the DeLong test. Decision curve analysis (DCA) was performed to evaluate clinical benefit. Finally, 317 patients were assessed, including 152 cases in the training set and 165 cases in the validation set. Moreover, 1288/1409 (91.4%) features of Method 1 and 1273/1409 (90.3%) features of Method 2 had good robustness (P < 0.05). The AUCs of Model 1 and Model 2 were 0.808 and 0.903 in the validation set, respectively (P = 0.035). DCA showed that the maximum delineation yielded more net benefit. MRI-based radiomics models derived from two segmentation methods demonstrated good performance in the preoperative T staging of RC. The minimum delineation had better stability in feature selection, while the maximum delineation method was more clinically beneficial.

The purpose of this study was to develop an efficient vitrification system for cryopreservation of dog skin tissues as a source of stable autologous stem cells. In this study, we performed vitrification using four different cryoprotectants, namely, ethylene glycol (EG), dimethyl-sulfoxide (Me2SO), EG plus Me2SO, and EG plus Me2SO plus sucrose, and analyzed the behaviors of cells established from warmed tissues. Tissues vitrified with 15% EG, 15% Me2SO, and 0.5 M sucrose had a normal histological appearance and the highest cell viability after cell isolation, and thus, this cocktail of cryoprotectants was used in subsequent experiments. We evaluated proliferation and apoptosis of cells derived from fresh and vitrified tissues. These cells had a normal spindle-like morphology after homogenization through subculture. Dog dermal skin stem cells (dDSSCs) derived from fresh and vitrified tissues had similar proliferation capacities, and similar percentages of these cells were positive for mesenchymal stem cell markers at passage 3. The percentage of apoptotic cell did not differ between dDSSCs derived from fresh and vitrified tissues. Real-time PCR analysis revealed that dDSSCs at passage 3 derived from fresh and vitrified tissues had similar expression levels of pluripotency (OCT4, SOX2, and NANOG), proapoptotic (BAX), and antiapoptotic (BCL2 and BIRC5) genes. Both types of dDSSCs successfully differentiated into the mesenchymal lineage (adipocytes and osteocytes) under specific conditions, and their differentiation potentials did not significantly differ. Furthermore, the mitochondrial membrane potential of dDSSCs derived from vitrified tissues was comparable with that of dDSSCs derived from fresh tissues. We conclude that vitrification of dog skin tissues using cocktail solution in combination of 15% EG, 15% Me2SO, and 0.5 M sucrose allows efficient banking of these tissues for regenerative stem cell therapy and conservation of genetic resources.

This study primarily focused on the effect of the long noncoding RNA (lncRNA) PVT1/miR186/KLF5 axis on the occurrence and progression of cholangiocarcinoma (CCA). miR186 was found both in the lncRNA PVT1 targeting miRNAs and KLF5 targeting miRNAs using bioinformatic analysis. The expression of lncRNA PVT1 and KLF5 in the TFK-1, QBC939, and HuCCT1 cell lines and normal biliary epithelial HIBEpiC cells was detected by RT-qPCR. The significance of lncRNA PVT1 and KLF5 on cell proliferation was analyzed using the MTT assay and clone formation assay in lncRNA PVT1 and KLF5 silencing HuCCT1 cell lines and lncRNA PVT1and KLF5 overexpressing TFK-1 and QBC939 cell lines, respectively. The potential role of lncRNA PVT1 and KLF5 in cell migration was detected using the transwell invasion assay in CCA cell lines and tumor formation assay. Additionally, lncRNA PVT1 and KLF5 were proved to be highly expressed in CCA tissues and cell lines. Silencing and overexpressing of lncRNA PVT1 or KLF5 markedly inhibited or increased the cell proliferation and cell invasion in CCA cell lines, respectively. Silencing and overexpressing of lncRNA PVT1 significantly inhibited and increased the expression of KLF5 in CCA cell lines, respectively. Silencing of lncRNA PVT1 increased the expression of miR186, and silencing of miR186 increased the expression of KLF5 in CCA cell lines. Cotransfection of lncRNA PVT1 and miR186 increased the expression of KLF5 compared with controls. Overall, these results demonstrated that the lncRNA PVT1/miR186/KLF5 axis might exert a key role in the occurrence and progression of CCA, and this axis might provide a new target for treating CCA.

Multiple sclerosis (MS) is an inflammatory disease damaging the myelin sheath in the central and peripheral nervous system in the brain and spinal cord. Optic Neuritis (ON) is one of the most prevalent ocular demonstrations of MS. The current diagnosis protocol for MS is MRI, but newer modalities like Optical Coherence Tomography (OCT) are already of interest in early detection and progression analysis. OCT reveals the symptoms of MS in the Central Nervous System (CNS) through cross-sectional images from neural retinal layers. Previous works on OCT were mostly focused on the thickness of retinal layers; however, texture features seem also to have information in this regard. In this research, we introduce a new pipeline that constructs layer-stacked (LS) images containing data from each specific layer. A variety of texture features are then extracted from LS images to differentiate between healthy controls and ON/None-ON MS cases. Furthermore, the definition of texture extraction methods is tailored for this application. After performing a vast survey on available texture analysis methods, a treasury of powerful features is collected in this paper. As a primary work, this paper shows the ability of such features in the diagnosis of HC and MS (ON and None-ON) cases. Our findings show that the texture features are powerful to diagnose MS cases. Furthermore, adding information of conventional thickness values to texture features improves considerably the discrimination between most of the target groups including HC vs. MS, HC vs. MS-None-ON, and HC vs. MS-ON.

BACKGROUND: The essential roles of the tumor microenvironment (TME) have been recognized during the initiation and progression of primary lung adenocarcinoma (LUAD). The aim of the present study was to delineate the immune landscape in both primary cancer and matched lymph node metastasis from a cohort of locally advanced stage LUAD patients with distinct outcomes. METHODS: Formalin-fixed, paraffin-embedded samples were collected from 36 locally advanced LUAD patients. Transcriptome data of the tumor immune microenvironment were resolved using an immune oncology panel RNA sequencing platform. Bioinformatics approaches were used to determine the differentially expressed genes (DEGs), dysregulated pathways, and immune cell fraction between patients with early recurrence (ER) and late recurrence (LR). RESULTS: Here, we showed that in primary cancer tissues, 23 DEGs were obtained between patients with ER and LR. Functional analysis revealed that the LR in LUAD patients may be associated with enriched gene sets belonging to the antigen presentation and MHC protein complex, innate immune response, and IFN-γ signaling pathways. Next, the transcriptome data were adopted to quantify immune cell fractions, indicating that high infiltration of mast cells and neutrophils was correlated with ER. Interestingly, similar findings were observed in metastatic lymph nodes from patients suffering from ER or LR. By analyzing the shared immune features of primary cancers and lymphatic metastases, we unraveled the prognostic value and joint utility of two DEGs, CORO1A and S100A8. CONCLUSIONS: In LUAD, the enrichment in antigen presentation, MHC protein complex, and IFN-γ signaling, and low infiltration of neutrophils in primary or metastatic nodules may be indications for a favorable prognosis. Integrated with bioinformatics approaches, transcriptome data of immune-related genes from formalin-fixed, paraffin-embedded (FFPE) samples can effectively profile the landscape of the tumor immune microenvironment and help predict clinical outcomes.

Lactobacillus rhamnoides, a human intestinal colonizer, can act through various pathways to induce microglia/macrophages to produce cytokines and to polarize microglia/macrophages to different phenotypes to reduce the inflammatory response. In this article, we evaluated the treatment potential of the Lactobacillus rhamnoides GG conditioned medium (LGG-CM) in rat model with SCI (acute spinal cord injury), including functional, neurophysiological, and histological outcomes and the underlying neuroprotective mechanisms. In our experiment, LGG-CM (30 mg/kg) was injected directly into the injury site in rats immediately after SCI. Measured by the BBB scale (Basso, Beattie, and Bresnahan locomotor rating scale) and inclined plane test, rats in the LGG-CM-treated group showed better locomotor scores. Moreover, compared to the vehicle treatment group, LGG-CM increased the mRNA level of the M2 marker (CD206), and decreased that of the M1 marker (iNOS). Western blot assays showed that LGG-CM-treated SCI rats had a higher grayscale ratio of p65 and a lower ratio of p-IκBα/IκBα. Our study shows that local injection of LGG-CM after acute SCI can inhibit inflammatory responses and improve motor function recovery. These effects may be related with the inhibition to the NF-κB (The nuclear factor-kappa B) signal pathway which leads to M2 microglia/macrophage polarization.

This article is aimed at analyzing the structure and function of the spike (S) proteins of porcine enteric coronaviruses, including transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), porcine deltacoronavirus (PDCoV), and swine acute diarrhea syndrome coronavirus (SADS-CoV) by applying bioinformatics methods. The physical and chemical properties, hydrophilicity and hydrophobicity, transmembrane region, signal peptide, phosphorylation and glycosylation sites, epitope, functional domains, and motifs of S proteins of porcine enteric coronaviruses were predicted and analyzed through online software. The results showed that S proteins of TGEV, PEDV, SADS-CoV, and PDCoV all contained transmembrane regions and signal peptide. TGEV S protein contained 139 phosphorylation sites, 24 glycosylation sites, and 53 epitopes. PEDV S protein had 143 phosphorylation sites, 22 glycosylation sites, and 51 epitopes. SADS-CoV S protein had 109 phosphorylation sites, 20 glycosylation sites, and 43 epitopes. PDCoV S protein had 124 phosphorylation sites, 18 glycosylation sites, and 52 epitopes. Moreover, TGEV, PEDV, and PDCoV S proteins all contained two functional domains and two motifs, spike_rec_binding and corona_S2. The corona_S2 consisted of S2 subunit heptad repeat 1 (HR1) and S2 subunit heptad repeat 2 (HR2) region profiles. Additionally, SADS-CoV S protein was predicted to contain only one functional domain, the corona_S2. This analysis of the biological functions of porcine enteric coronavirus spike proteins can provide a theoretical basis for the design of antiviral drugs.

The aim of this study was to explore the correlation between ultrasound-guided fine-needle aspiration cytology(US-FNAC) combined with BRAF V600E mutation analysis and central neck lymph node metastasis in cN0 papillary thyroid cancer, so as to provide reliable molecular evidence to use it for preoperative evaluation, operation procedure design, and postoperative follow-up planning in clinic. Specimens were obtained from 250 patients with cN0 thyroid cancer (TI-RADS≥4a, highly suspected of PTC by US-FNAC) after bilateral thyroidectomy and central neck lymph node dissection with accessible postoperative pathologic results of PTC and central neck lymph nodes and used for cytological diagnosis by H&E stain and BRAF V600E mutation detection. Single-factor analysis showed that differences between the central neck lymph node metastasis and nonmetastasis groups were statistically significant in gender, BRAF V600E mutation, and extracapsular extension. Logistic multivariate regression analysis showed significant differences in gender, BRAF V600E mutation, and extracapsular extension. Positive BRAF V600E mutations by US-FNAC, extracapsular extension, and male gender are risk factors of central neck lymph node metastasis in cN0 PTC metastatic PTC to central neck lymph node. Patients with those factors should undergo prophylactic central neck lymph node dissection.

Chloroflexus aurantiacus is a thermophilic bacterium that produces a multitude of proteins within its genome. Bioinformatics strategies can facilitate comprehending this organism through functional and structural interpretation assessments. This study is aimed at allocating the structure and function through an in silico approach required for bacterial protein biosynthesis. This in silico viewpoint provides copious properties, including the physicochemical properties, subcellular location, three-dimensional structure, protein-protein interactions, and functional elucidation of the protein (WP_012256288.1). The STRING program is utilized for the explication of protein-protein interactions. The in silico investigation documented the protein's hydrophilic nature with predominantly alpha (α) helices in its secondary structure. The tertiary-structure model of the protein has been shown to exhibit reasonably high consistency based on various quality assessment methods. The functional interpretation suggested that the protein can act as a translation initiation factor, a protein required for translation and protein biosynthesis. Protein-protein interactions also demonstrated high credence that the protein interconnected with 30S ribosomal subunit involved in protein synthesis. This study bioinformatically examined that the protein (WP_012256288.1) is affiliated in protein biosynthesis as a translation initiation factor IF-3 of C. aurantiacus.

INTRODUCTION: In most disasters, teeth are the only means of positive identification of an otherwise unrecognizable body, as there has been tremendous increase in the use of dental restorations that have different resistance to prolonged high temperature which is an important aid in identifying burned victims. Application of SEM/EDS in forensics was found useful in areas where there is a need for good imaging with high magnification combined with elemental analysis. The objective of this study was to analyze incineration effects on teeth and restorative materials using SEM/EDS. Materials and Method. 128 extracted teeth were collected, 96 were restored with silver amalgam, composite, and GIC of 32 each, and crown preparation was done in 32 teeth for which metal ceramic crowns were prepared. These teeth were subjected to 4 different temperatures (500°C, 700°C, 900°C, and 1100°C) for 20 minutes, and they were analyzed macroscopically and by using SEM for the changes subsequent to their exposure to such high temperatures. RESULTS: All the restorations which were very difficult to identify by naked eye were identified with the help of SEM/EDS. CONCLUSION: Elemental analysis of the specific restorative material proves to be an essential tool for the forensic odontologist.

OBJECTIVE: To investigate the role of PI3K/AKT signaling pathway in nucleus pulposus (NP) cells. METHODS: Nucleus pulposus (NP) cells were isolated from SD rat, and thereafter, passage three (P3) NP cells were divided into the following experimental groups: control, PI3K/AKT agonist IGF-1 (25 ng/ml, 50 ng/ml, and 100 ng/ml), and PI3K/AKT inhibitor LY294002 (5 μM, 10 μM, and 20 μM). Flow cytometry and BrdU cell proliferation assays were performed to assess apoptosis and the proliferation rate of NP cells. Western blot analysis was performed to examine the protein expression level of Col II, Col X, Aggrecan, and MMP13. RESULTS: PI3K/AKT inhibitor LY294002 increased the rate of apoptosis in NP cells when compared to the control and decreased the proliferation rate when compared to control. Moreover, LY294002 decreased the protein expression level of Col-II and Aggrecan in NP cells. At the same time, LY294002 increased the protein expression level of MMP13 and Col-X in NP cells. Through activating PI3K/AKT, IGF-1 increased the proliferation rate when compared to control and decreased the rate of apoptosis when compared to control. Additionally, IGF-1 decreased the protein expression level of MMP13 and Col-X and increased Col-II and Aggrecan in NP cells. CONCLUSION: The inhibition of PI3K/AKT signaling pathway accelerated the apoptosis of NP cells and facilitated the extracellular matrix degradation. However, the activation of PI3K/AKT pathway partly prevented the NP cell from apoptosis and promoted their proliferation. Meanwhile, its activation also delayed the loss of extracellular matrix.

OBJECTIVE: A crosssectional study was conducted between September 2015 and August 2016 in the district of Afar Regional State, Northeastern Ethiopia, to characterize the most prevalent bacterial pathogens and identify the associated risk factors of camel subclinical mastitis. California mastitis test (CMT) was used as a screening test, and standard bacteriological methods were carried out for isolation and identification of the pathogens. RESULTS: Among the total 96 lactating camels examined, 25 were found positive with the overall prevalence of 26%, with 25% and 1% subclinical and clinical mastitis cases, respectively. Totally, 384 quarters of udder were examined; of these, 10 of them were blind while the rest 374 were nonblind teats. The quarter level prevalence of subclinical mastitis was 8.9%. The analysis showed that statistically significant difference (P < 0.05) of tick infestation and subclinical mastitis. Additionally, among the bacteriologically tested 34 CMT positive milk samples, all of them showed growth on nutrient and blood agar plate. Out of these culture isolates, the major bacterial pathogens identified were Staphylococcus aureus (8.7%), Staphylococcus hyicus (6.52%), Staphylococcus intermedius (6.52), Coagulase-negative staphylococci (19.57%), Bacillus (19.57%), Escherichia coli (6.52%), and Pasteurella multocida (6.52%) species. Therefore, appropriate control measures and awareness creation to the community should be practiced.