BACKGROUND: Conflicting results exist between the potential protective effects of metformin and the prognosis of urologic cancers. This meta-analysis summarized the effects of metformin exposure on the recurrence, progression, cancer-specific survival (CSS), and overall survival (OS) of the three main urologic cancers (kidney cancer, bladder cancer, and prostate cancer). METHODS: We systematically searched PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases (January 2010 to December 2019), which identified studies regarding metformin users and nonusers with urologic cancers and extracted patient data. A random effect model or fixed effect model was used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among the 1883 confirmed studies, 27 eligible studies were identified, including 123,212 participants. In prostate cancer, patients using metformin have significant benefits for recurrence (HR = 0.74; 95% CI: 0.61-0.90; P = 0.007; I 2 = 56%), CSS (HR = 0.74; 95% CI: 0.61-0.91; P = 0.002; I 2 = 79%), and OS (HR = 0.76; 95% CI: 0.65-0.90; P < 0.001; I 2 = 86%). Moreover, further subgroup analysis showed that the beneficial effects of metformin may be more significant for patients receiving radical radiotherapy. For kidney cancer, metformin was beneficial for progression (HR = 0.80; 95% CI: 0.65-0.98; P = 0.14; I 2 = 46%). Analysis revealed that the effect of metformin on the overall survival of kidney cancer patients may be related to nationality (American: HR = 0.76; 95% CI: 0.59-0.98; P = 0.88; I 2 = 0%). For bladder cancer, no obvious benefits of metformin use were identified. However, subgroup analysis indicated that metformin may improve the recurrence of bladder cancer, but this improvement was only found in patients with a median follow-up time of more than 4 years (HR = 0.43; 95% CI: 0.28-0.67; P = 0.61; I 2 = 0%).

This study is aimed at exploring the possible mechanism of action of the Suanzaoren decoction (SZRD) in the treatment of Parkinson's disease with sleep disorder (PDSD) based on network pharmacology and molecular docking. Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the bioactive components and targets of SZRD, and their targets were standardized using the UniProt platform. The disease targets of "Parkinson's disease (PD)" and "Sleep disorder (SD)" were collected by OMIM, GeneCards, and DisGeNET databases. Thereafter, the protein-protein interaction (PPI) network was constructed using the STRING platform and visualized by Cytoscape (3.7.2) software. Then, the DAVID platform was used to analyze the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Cytoscape (3.7.2) software was also used to construct the network of the "herb-component-target-pathway." The core active ingredients and core action targets of the drug were verified by molecular docking using AutoDock software. A total of 135 Chinese herbal components and 41 corresponding targets were predicted for the treatment of PDSD using SZRD. Fifteen important signaling pathways were screened, such as the cancer pathway, TNF signaling pathway, PI3K-AKT signaling pathway, HIF-1 signaling pathway, and Toll-like receptor signaling pathway. The results of molecular docking showed that the main active compounds could bind to the representative targets and exhibit good affinity. This study revealed that SZRD has the characteristics and advantages of "multicomponent, multitarget, and multipathway" in the treatment of PDSD; among these, the combination of the main active components of quercetin and kaempferol with the key targets of AKT1, IL6, MAPK1, TP53, and VEGFA may be one of the important mechanisms. This study provides a theoretical basis for further study of the material basis and molecular mechanism of SZRD in the treatment of PDSD.

In this study, the seroprevalence of the intestinal worms Taenia solium and Trichinella spiralis in humans and pigs was assessed. A cross-sectional serological study design was performed. Blood samples were collected from 322 humans and 245 pigs used in the study. These were tested for markers of antibodies for Taenia solium and Trichinella spp. Demographic data such as sex, age, education, pig farming practices, and water source used were also obtained. An overall seroprevalence of 3.1% was recorded for Taenia solium in humans. There was also a statistical association between pig management system employed by pig farmers and seropositivity to Taenia solium (p = 0.005). Factors such as mode of waste disposal (p = 0.003) and water source used statistically correlated with Taenia solium seroprevalence among humans. For the pig samples, a Taenia solium seroprevalence of 24.9% was recorded. All the pig samples which tested positive for Taenia solium were reared on the free-ranged system. This study also recorded a seroprevalence of 0.31% for Trichinella spp. for humans and a seroprevalence of 4.5% for Trichinella spp. for pigs. Again, all the samples that showed serological evidence of Trichinella spp. among pigs came from those pigs which were raised on the free-ranged system. Proper pig management practice is a very important tool for controlling these intestinal parasites in both humans and animals. This study recommends public health education among the general public and good pig farming practices.

INTRODUCTION: This study presents an empirical method to model the curve of electron beam percent depth dose (PDD) by using the primary-tail function in electron beam radiation therapy. The modeling parameters N and n can be used to predict the minimal side length when the field size is reduced below that required for lateral scatter equilibrium (LSE) in electron radiation therapy. METHODS AND MATERIALS: The electrons' PDD curves were modeled by the primary-tail function in this study. The primary function included the exponential function and the main parameters of N and μ, while the tail function was composed of a sigmoid function with the main parameter of n. The PDD of five electron energies was modeled by the primary and tail function by adjusting the parameters of N, μ, and n. The R 50 and R p can be derived from the modeled straight line of 80% to 20% region of PDD. The same electron energy with different cone sizes was also modeled by the primary-tail function. The stopping power of different electron energies in different depths can also be derived from the parameters N, μ, and n. RESULTS: The main parameters N and n increase but μ decreases in the primary-tail function for characterizing the electron beam PDD when the electron energy increased. The relationship of parameter n, N, and ln(-μ) with electron energy are n = 31.667E 0 - 88, N = 0.9975E 0 - 2.8535, and ln(-μ) = -0.1355E 0 - 6.0986, respectively. Percent depth dose was derived from the percent reading curve by multiplying the stopping power relevant to the depth in water at a certain electron energy. The stopping power of different electron energies can be derived from n and N with the following equation: stopping power = (-0.042ln(N E 0 ) + 1.072)e (-nE0 · 5 · 10-5 + 0.0381)·x , where x is the depth in water. The lateral scatter equivalence (LSE) of the clinical electron beam can be described by the parameters E 0, n, and N in the equation of Seq = (n E 0 - N E 0 )0.288/(E 0/n E 0 )0.0195. The LSE was compared with the root mean square scatter angular distribution method and shows the agreement of depth dose distributions within ±2%. CONCLUSIONS: The PDD of the electron beam at different energies and cone sizes can be modeled with an empirical model to deal with what is the minimal field size without changing the percent depth dose when approximate LSE is given in centimeters of water.

Diabetes mellitus- (DM-) associated hyperglycemia promotes apoptosis of disc nucleus pulposus (NP) cells, which is a contributor to intervertebral disc degeneration (IDD). Melatonin is able to protect against cell apoptosis. However, its effects on apoptosis of NP cell in a high-glucose culture remain unclear. The purpose of the present study was to investigate the effects and molecular mechanism of melatonin on NP cell apoptosis in a high-glucose culture. NP cells were cultured in the baseline medium supplemented with a high-glucose concentration (0.2 M) for 3 days. The control cells were only cultured in the baseline medium. Additionally, the pharmaceutical inhibitor LY294002 was added along with the culture medium to investigate the possible role of the PI3K/Akt pathway. Apoptosis, autophagy, and activity of the PI3K/Akt pathway of NP cells among these groups were evaluated. Compared with the control NP cells, high glucose significantly increased cell apoptosis ratio and caspase-3/caspase-9 activity and decreased mRNA expression of Bcl-2, whereas it increased mRNA or protein expression of Bax, caspase-3, cleaved caspase-3, cleaved PARP, and autophagy-related molecules (Atg3, Atg5, Beclin-1, and LC3-II) and decreased protein expression of p-Akt compared with the control cells. Additionally, melatonin partly inhibited the effects of high glucose on those parameters of cell apoptosis, autophagy, and activation of PI3K/Akt. In conclusion, melatonin attenuates apoptosis of NP cells through inhibiting the excessive autophagy via the PI3K/Akt pathway in a high-glucose culture. This study provides new theoretical basis of the protective effects of melatonin against disc degeneration in a DM patient.

Screening and preliminary identification of high DNMT1 expression-related lncRNA, which is involved in various interrelated signaling pathways, has led to the development of a theoretical basis for various types of disease mechanisms. Differential expression profiles of lncRNA and mRNA were identified in a microarray. Ten lncRNAs with high levels of variation were identified by qRT-PCR. KEGG and GO analyses were used to identify differentially expressed mRNAs. Six signaling pathways were selected based on the KEGG results of the lncRNA-mRNA expression network analysis. From the microarrays in the experimental and control groups, we found a total of 6987 differentially expressed lncRNAs, and 7421 differentially expressed mRNAs were obtained (P < 0.05; fold change > 2.0x). GO analysis and KEGG pathway analysis showed high expression of DNMT1 in esophageal epithelial cells. Nine pathways were involved in mRNA upregulation, including natural killer cell-mediated cytotoxicity and many other prominent biochemical pathways. Forty-six pathways were associated with downregulated mRNAs and ribosomes involving multiple biological pathways. Coexpression network analysis showed that 8 mRNAs and 16 lncRNAs were linked to the p53 signaling pathway. In Helicobacter pylori infections, interactions occurred between 22 lncRNAs and 11 mRNAs in the ErbB signaling pathway and between 19 lncRNAs and 8 mRNAs in epithelial cell signal transduction. Interactions were present between 19 lncRNAs and 5 mRNAs in the sphingolipid signaling pathway, along with interactions between 21 lncRNAs and 12 mRNAs in the PI3K-Akt signaling pathway. Cytotoxicity interactions occurred between 22 lncRNAs and 9 mRNAs in natural killer cells.

Stephania abyssinica is a medicinal plant used in Cameroon alternative medicine to treat arterial hypertension (AHT). Previous in vitro studies demonstrated the endothelium nitric oxide-independent vasorelaxant property of the aqueous extract from Stephania abyssinica (AESA). But its effect on AHT is unknown. The present study was undertaken to explore other vasorelaxant mechanisms and to determine the antihypertensive effects of AESA in male Wistar rats. Phytochemical analysis of AESA was carried out using the liquid chromatography-mass spectrometry (LC-MS) method. The vasorelaxant effects of AESA (1-1000 μg/mL) were studied on rat isolated thoracic aorta rings, in the absence or presence of indomethacin (10 μM) or methylene blue (10 μM). The inhibitory effect of AESA on phenylephrine (PE, 10 μM) or KCl- (60 mM) induced contraction as well as the intracellular calcium release was also evaluated. The in vivo antihypertensive activity of AESA (43, 86, or 172 mg/kg/day) or captopril (20 mg/kg/day) administered orally was assessed in L-NAME- (40 mg/kg/day) treated rats. Blood pressure and heart rate (HR) were measured at the end of each week while serum or urinary nitric oxide (NO), creatinine, and glomerular filtration rate (GFR) were determined at the end of the 6 weeks of treatment, as well as histological analysis of the heart and the kidney. The LC-MS profiling of AESA identified 9 compounds including 7 alkaloids. AESA produced a concentration-dependent relaxation on contraction induced either by PE and KCl, which was significantly reduced in endothelium-denuded vessels, as well as in vessels pretreated with indomethacin and methylene blue. Moreover, AESA inhibited the intracellular Ca2+ release-induced contraction. In vivo, AESA reduced the AHT, heart rate (HR), and ventricular hypertrophy and increased serum NO, urine creatinine, and GFR. AESA also ameliorated heart and kidney lesions as compared to the L-NAME group. These findings supported the use of AESA as a potential antihypertensive drug.

Currently, it still remains a difficult problem to treat apical insufficiency of young permanent teeth resulted from pulp necrosis or periapical periodontitis. Previous studies have demonstrated that the treatment of revascularization using stem cells from apical papilla (SCAPs) results in increased root length and thickness of traumatized immature teeth and necrotic pulp. In this study, we investigated the role of 1,25-dihydroxyvitamin D3 in regulating the adhesion, spreading, proliferation, and osteogenic differentiation of SCAP, laying the foundation for subsequent clinical drug development. The immature tooth samples were collected in clinical treatment. SCAPs with stable passage ability were isolated and cultured. The multidifferentiation potential was determined by directed induction culture, while the stem cell characteristics were identified by flow cytometry. There were three groups: group A-SCAPs general culture group; group B-SCAPs osteogenesis induction culture group; and group C-SCAPs osteogenesis induction culture+1,25-dihydroxyvitamin D3 group, and the groups were compared statistically. The proliferation of SCAPs in each groups was detected through CCK-8 assay. RT-qPCR was used to detect the transcription levels of Runx2, ALP, Col I, and OCN of SCAPs in each groups. Results exhibited that the isolated SCAPs had multidifferentiation potential and stem cell characteristics. After 24 h culturing, cells in group C spread better than those in groups A and B. The proliferation activity of SCAPs factored by CCK-8 ranked as group C > group B > group A, while the transcription levels of Runx2, ALP, Col I, and OCN leveled as group C > group B > group A. These results suggested that 1,25-dihydroxyvitamin D3 can significantly promote the adhesion, spreading, and proliferation of SACPs and improve the osteogenic differentiation of SCAPs by means of regulating upward the transcription level of osteogenic differentiation marker.

As an important ligand in T lymphocyte costimulatory pathways, B7-H5 is involved deeply in the immune response in various diseases. However, its clinical usefulness as an early indicator in acute pancreatitis (AP) remains unclear. In this study, the levels of sB7-H5 and cytokines in plasma samples of 75 AP patients, 20 abdominal pain patients without AP, and 20 healthy volunteers were determined. Then, the correlation of sB7-H5 and clinical features, cytokines, the Ranson score, APACHE II score, Marshall score, and BISAP score was analysed, and the value of sB7-H5 for diagnostic, severity, and prognosis of AP was evaluated. We found that the levels of sB7-H5 were specifically upregulated in AP patients. Receiver operating characteristic (ROC) analysis revealed that sB7-H5 can identify AP patients from healthy or abdominal pain patients with 78.9% or 86.4% sensitivity and 93.3% or 90.0% specificity. Further analysis showed that the levels of sB7-H5 were significantly correlated with WBC (p = 0.004), GLU (p = 0.008), LDH (p < 0.001), Ca2+ (p = 0.006), AST (p = 0.009), PLT (p = 0.041), IL-6 (p < 0.001), IL-10 (p < 0.001), and TNF-α (p < 0.001). And levels of sB7-H5 were gradually increased among patients with mildly acute pancreatitis (MAP), moderately severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP). It can distinguish the severity of AP with good sensitivity and specificity. Moreover, when dividing the patients into two groups according to the median level of sB7-H5, the local complication and length of stay of low levels of the sB7-H5 group were significantly less than those in high levels of the sB7-H5 group. And the levels of sB7-H5 in AP patients were significantly correlated with the Ranson score (p < 0.001), APACHE II score (p < 0.001), Marshall score (p < 0.001), and BISAP score (p < 0.001). The AUCs of assessing local complications of sB7-H5 at day 1 and day 3 were 0.704 (p = 0.0024) and 0.727 (p = 0.0373). These results showed the potential value of sB7-H5 as a diagnostic, severity, and prognosis marker of AP.

OBJECTIVE: This study was performed to investigate the association between urinary Alzheimer-associated neuronal thread protein (AD7c-NTP) with cerebral microbleeds (CMBs) based on the apolipoprotein E (APOE) genotypes. METHODS: A total of 471 patients with acute cerebral infarction screened by magnetic sensitive imaging were enrolled in this study. Among them, twenty-seven cases of mixed CMBs were excluded. A total of 444 patients were divided into two groups according to the presence or absence of CMBs: CMBs group (n = 92) and noncerebral microbleeds group (nCMBs) (n = 352). Urine AD7c-NTP levels were measured using a human enzyme immunoassay kit. RESULTS: In patients with lobar CMBs, there was an interaction between urine AD7c-NTP levels and APOE genotypes (p = 0.01). In patients with APOE ε3/ε3 allele, the odds ratio of lobar CMBs per standard deviation of urinary AD7c-NTP levels was 0.92 (95% CI: 0.70-1.19). In patients with APOE ε2+ or ε4+ allele, the multivariate-corrected odds ratio of lobar CMBs per standard deviation of urinary AD7c-NTP levels was 2.95 (95% CI: 1.38-6.27). CONCLUSION: A higher level of urinary AD7c-NTP is involved in lobar CMBs, not deep CMBs.

Health big data has already been the most important big data for its serious privacy disclosure concerns and huge potential value of secondary use. Measurements must be taken to balance and compromise both the two serious challenges. One holistic solution or strategy is regarded as the preferred direction, by which the risk of reidentification from records should be kept as low as possible and data be shared with the principle of minimum necessary. In this article, we present a comprehensive review about privacy protection of health data from four aspects: health data, related regulations, three strategies for data sharing, and three types of methods with progressive levels. Finally, we summarize this review and identify future research directions.

OBJECTIVE: The aim of this study was to assess the effectiveness of a 3-week rehabilitation programme focusing only on the cervical region, pain intensity, range of motion in the cervical spine, head posture, and temporomandibular joint (TMJ) functioning in subjects with idiopathic neck pain who did not report TMJ pain. DESIGN: A parallel group trial with follow-up. METHODS: The study included 60 participants divided into 2 groups: experimental: n = 25, 27-57 years old, experiencing idiopathic neck pain and who underwent a 3-week rehabilitation programme, and the control, n = 35, 27-47 years, who were cervical pain-free. At baseline and after 3 weeks of treatment in the experimental group and with a 3-week time interval in the control group, pain intensity, head posture in the sagittal plane, range of motion in the cervical spine, and TMJ functioning were evaluated. RESULTS: After 3 weeks of rehabilitation, there was a significant decrease in pain intensity, improved range of motion of the cervical spine and head posture, and improved clinical condition of TMJ in participants with idiopathic neck pain who did not report TMJ pain. CONCLUSION: The study suggested that idiopathic neck pain is associated with limited range of motion in the cervical spine, incorrect head posture, and TMJ dysfunction. Our data suggests that therapy focusing only on the cervical region may improve the clinical condition of the TMJ in subjects with idiopathic neck pain who do not report TMJ pain. These observations could be helpful in physiotherapeutic treatment of neck and craniofacial area dysfunctions. This trial is registered with ISRCTN Registry ISRCTN14511735.

BACKGROUND: Type 2 deiodinase (Dio2) is a selenoenzyme that is mainly expressed in the endoplasmic reticulum of the central nervous system, brown adipose tissue, and placenta and is responsible for outer ring deiodination of thyroxine (T4) to form biologically active triiodothyronine (T3). The Thr92Ala polymorphism of Dio2 has been found to be a potential risk factor for various diseases beyond the hypothalamus-pituitary-thyroid (HPT) axis. METHODS: We searched the relevant studies in the PubMed, Embase, and Cochrane Library databases and Google Scholar. A systematic review and meta-analysis of studies on the Thr92Ala polymorphism and metabolic parameters beyond the HPT axis (e.g., BMI, fasting glycemic traits, plasma lipid levels, and hypertension risk) were performed. RESULTS: Six eligible studies that analyzed the relationship between the Thr92Ala polymorphism and metabolic parameters beyond the thyroid were identified. All selected studies excluded patients with thyroid dysfunction, and diabetic patients were also excluded when fasting glucose and fasting insulin levels were meta-analyzed. The Thr92Ala polymorphism was found to be a significant risk factor for higher BMI (Std. mean difference 0.31 (0.01, 0.60), p = 0.04) and higher fasting glucose levels (Std. mean difference 1.18 (0.05, 2.31), p = 0.04). However, fasting insulin levels, plasma lipid levels, and hypertension risk showed a nonsignificant association with the Thr92Ala polymorphism. CONCLUSION: Compared with euthyroid noncarriers (Thr/Thr), euthyroid Ala92-Dio2 carriers showed increased BMI levels, and Ala92-Dio2 carriers also had higher fasting plasma glucose levels than matched euthyroid nondiabetic noncarriers.

BACKGROUND: Although the long-term success rate of dental implants is currently close to 95%, it is necessary to provide more evidence on the factors related to the failure of osseointegration and survival. PURPOSE: To establish the risk factors associated with the failure of osseointegration and survival of dental implants with an internal connection and machined collar and to establish a predictive statistical model. MATERIALS AND METHODS: An analytical, retrospective, and observational clinical study of a sample of 297 implants with a follow-up of up to 76 months. Independent variables related to the implant, patient, and surgical and rehabilitative procedures were identified. The dependent variables were failure of osseointegration and failure of implant survival after prosthetic loading. A survival analysis was carried out by applying the Kaplan-Meier model (significance for p < 0.05). The log-rank test and the Cox regression analysis were applied to the factors that presented differences. Finally, the regression logit function was used to determine whether it is possible to predict the risk of implant failure according to the analyzed variables with the data obtained in this study. RESULTS: The percentages of osseointegration and survival were 97.6 and 97.2%, respectively. For osseointegration, there were significant differences according to gender (p = 0.048), and the risk of nonosseointegration was 85% lower in women. Regarding survival, the Cox analysis converged on only two factors, which were smoking and treatment with anticoagulant drugs. The risk of loss was multiplied by 18.3 for patients smoking more than 10 cigarettes per day and by 28.2 for patients treated with anticoagulants. CONCLUSIONS: The indicated risk factors should be considered, but the analysis of the results is not sufficient to create a predictive model.

PURPOSE: This study is aimed at synthesizing the available evidence regarding effectiveness of various modalities (combinations of LRS tasks) and comparison between each two modalities in terms of gingival display reduction, success rate, stability of the results, patient's satisfaction, and postoperative morbidity. MATERIALS AND METHODS: The electronic databases including PubMed, Scopus, Web of Science Cochrane Library, Google Scholar databases, ClinicalTrials.gov, and WHO International Clinical Trial Registry Platform were searched up to 27th June 2020 regarding lip repositioning surgery. The modalities were defined as the combinations of the following tasks: frenectomy (yes/no), flap thickness (full/partial), and myotomy (yes/no). Meta-analyses were performed on gingival display change from baseline to months 3, 6, and 12 in each modalities using Stata (v.16). RESULTS: 38 studies (including three clinical trials, two quasiexperimental studies, seven case series, and 26 case reports) met the criteria for final inclusion. The mean gingival display reduced from baseline to 6 months (WMD = -2.90, 95% CI: -4.85 to -0.95) in the patients undergoing the "frenectomy + full-thickness flap + myotomy" modality. This parameter decreased from baseline to 6 and 12 months, respectively (WMD = -2.68, 95% CI: -3.49 to -1.86; WMD = -2.52, 95% CI: -4.40 to -0.64), in patients undergoing the "frenectomy + partial-thickness flap + without myotomy" modality. In patients who undergone the "without frenectomy + partial-thickness flap + without myotomy" modality, gingival display reduced from baseline to 6 months (WMD = -3.22, 95% CI: -5.61 to -0.84). Almost 83% of patients with modality 1 had satisfaction. CONCLUSIONS: Gingival display within the 6 months after LRS could be reduced with all modalities. Descriptively, the greatest reduction was observed in patients with the modality not including the frenulum.

Pulmonary hypertension (PH) is occult, with no distinctive clinical manifestations and a poor prognosis. Pulmonary vascular remodelling is an important pathological feature in which pulmonary artery smooth muscle cells (PASMCs) phenotypic switching plays a crucial role. MicroRNAs (miRNAs) are a class of evolutionarily highly conserved single-stranded small noncoding RNAs. An increasing number of studies have shown that miRNAs play an important role in the occurrence and development of PH by regulating PASMCs phenotypic switching, which is expected to be a potential target for the prevention and treatment of PH. miRNAs such as miR-221, miR-15b, miR-96, miR-24, miR-23a, miR-9, miR-214, and miR-20a can promote PASMCs phenotypic switching, while such as miR-21, miR-132, miR-449, miR-206, miR-124, miR-30c, miR-140, and the miR-17~92 cluster can inhibit it. The article reviews the research progress on growth factor-related miRNAs and hypoxia-related miRNAs that mediate PASMCs phenotypic switching in PH.

Cancer remains to be the leading cause of death globally. Surgery is a mainstay treatment for solid tumors. Thus, it is critical to optimize perioperative care. Anesthesia is a requisite component for surgical tumor resection, and general anesthesia is given in the vast majority of tumor resection cases. Because anesthetics are growingly recognized as immunomodulators, it is critical to optimize anesthetic regimens for cancer surgery if the selection can affect outcomes. Here, we reviewed the role of volatile and intravenous anesthesia used for cancer surgery in cancer recurrence.

BACKGROUND: KRAS was reported to affect some metabolic genes and promote metabolic reprogramming in solid tumors. However, there was no comprehensive analysis to explore KRAS-associated metabolic signature or risk model for pancreatic cancer (PC). METHODS: In the current study, multiple bioinformatics analyses were used to identify differentially expressed metabolic genes based on KRAS mutation status in PC. Then, we developed and validated a prognostic risk model based on the selected KRAS-associated metabolic genes. Besides, we explored the association between the risk model and the metabolic characteristics as well as gemcitabine-associated chemoresistance in PC. RESULTS: 6 KRAS-associated metabolic genes (i.e., CYP2S1, GPX3, FTCD, ENPP2, UGT1A10, and XDH) were selected and enrolled to establish a prognostic risk model. The prognostic model had a high C-index of 0.733 for overall survival (OS) in TCGA pancreatic cancer database. The area under the curve (AUC) values of 1- and 3-year survival were both greater than 0.70. Then, the risk model was validated in two GEO datasets and also presented a satisfactory discrimination and calibration performance. Further, we found that the expression of some KRAS-driven glycolysis-associated genes (PKM, GLUT1, HK2, and LDHA) and gemcitabine-associated chemoresistance genes (i.e., CDA and RMM2) was significantly upregulated in high-risk PC patients evaluated by the risk model. CONCLUSIONS: We constructed a risk model based on 6 KRAS-associated metabolic genes, which predicted patients' survival with high accuracy and reflected tumor metabolic characteristics and gemcitabine-associated chemoresistance in PC.

BACKGROUND: Migraine has a great impact on public health. Current acute therapies do not satisfy all migraineurs. The novel serotonin 5-HT1F receptor agonist appears more promising for aborting migraine attacks. OBJECTIVE: To evaluate the clinical efficacy and safety of lasmiditan in treating acute migraine attacks. METHODS: The literature search was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials (RCTs) which assessed the effect and safety of lasmiditan on migraine. The risk of bias was assessed using the Cochrane Collaboration's risk of bias tool. Results were extracted and pooled as risk ratios (RRs) with a fixed or random-effects model. RESULTS: Based on the four included RCTs, pooled estimates showed that lasmiditan with the 50 mg, 100 mg, and 200 mg doses was superior to placebo at 2 h after the first dose in terms of pain freedom, absence of migraine-associated symptoms, headache relief, no/mild disability, and global impression of change (very much/much better) (RRs ranged from 1.13 to 1.96), except for nausea-free and vomiting-free. Both lasmiditan 100 mg and 200 mg resulted in significantly fewer patients using rescue medication (100 mg: RR = 0.75, 95% CI (0.61, 0.92), P = 0.007; 200 mg: RR = 0.81, 95% CI (0.66, 0.99), P = 0.04) at 2-24 h postdose, compared with placebo. Safety data showed that the proportion of patients reporting at least one treatment-emergent adverse event (TEAE) and the incidence of most common TEAEs such as dizziness, paresthesia, fatigue, somnolence, and nausea was higher in the lasmiditan groups (50 mg, 100 mg, and 200 mg), compared with placebo. There was no significant difference between lasmiditan and placebo in terms of cardiovascular-related TEAEs (RR = 2.75, 95% CI (0.81, 9.37), P = 0.11). Compared with lasmiditan 100 mg, lasmiditan 200 mg was more effective in pain freedom at 2 h after the first dose (RR = 0.83, 95% CI (0.74, 0.94), P = 0.004) but associated with a higher risk of reporting at least one TEAE (RR = 0.88, 95% CI (0.81, 0.96), P = 0.006). CONCLUSIONS: Lasmiditan with the 50 mg, 100 mg, and 200 mg doses are effective and safe in acute migraine treatment. Lasmiditan 200 mg is more effective than lasmiditan 100 mg in pain freedom, while lasmiditan 100 mg is better tolerated in the short-term follow-up. Further larger sample-size RCTs are required to verify the applicability and tolerability in the long term.

Maintaining body balance is a complex function based on the information deriving from the vestibular, visual, and proprioceptive systems. The aim of the study was to evaluate quiet single stance stability in young adults with lumbar derangement syndrome (LDS) and in the control group of the healthy subjects. The second aim of this study was to determine whether pain intensity, degree of disability, and the level of physical activity can influence postural control in patients with LDS. It is important to underline that selecting a homogeneous group of LBP patients using, for example, mechanical diagnosis and therapy method and Quebec Task Force Classification, can result in an increased sensitivity of the study. The study included 126 subjects: 70 patients with LDS (37 women, 33 men) and the control group 56 healthy volunteers (36 women, 20 men). In case of multiple group comparisons for variables with normal distribution, ANOVA post hoc test was used or, as the nonparametric equivalent, Kruskal-Wallis test. In all these calculations, the statistical significance level was set to p < 0.05. The stability index eyes open for the study group was 88.34 and for the control group 89.86. There was no significant difference in the level of postural control between the study and control groups (p > 0.05). The level of stability index eyes closed (SI EC) for the study group was 71.44 and for the control group 77.1. SI EC results showed significant differences in proprioceptive control during single leg stance between the study and control groups (p < 0.05). The level of pain intensity, the degree of disability, and physical activity level did not influence postural control in the study group with LDS. In summary, patients with LDS showed significantly worse proprioceptive control.

OBJECTIVE: Ovarian cancer is the deadliest gynaecological cancer globally. In our study, we aimed to analyze specific cell subpopulations and marker genes among ovarian cancer cells by single-cell RNA sequencing (RNA-seq). METHODS: Single-cell RNA-seq data of 66 high-grade serous ovarian cancer cells were employed from the Gene Expression Omnibus (GEO). Using the Seurat package, we performed quality control to remove cells with low quality. After normalization, we detected highly variable genes across the single cells. Then, principal component analysis (PCA) and cell clustering were performed. The marker genes in different cell clusters were detected. A total of 568 ovarian cancer samples and 8 normal ovarian samples were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed genes were identified according to ∣log2fold change (FC) | >1 and adjusted p value <0.05. To explore potential biological processes and pathways, functional enrichment analyses were performed. Furthermore, survival analyses of differentially expressed marker genes were performed. RESULTS: After normalization, 6000 highly variable genes were identified across the single cells. The cells were divided into 3 cell populations, including G1, G2M, and S cell cycles. A total of 1,124 differentially expressed genes were identified in ovarian cancer samples. These differentially expressed genes were enriched in several pathways associated with cancer, such as metabolic pathways, pathways in cancer, and PI3K-Akt signaling pathway. Furthermore, marker genes, STAT1, ANP32E, GPRC5A, and EGFL6, were highly expressed in ovarian cancer, while PMP22, FBXO21, and CYB5R3 were lowly expressed in ovarian cancer. These marker genes were positively associated with prognosis of ovarian cancer. CONCLUSION: Our findings revealed specific cell subpopulations and marker genes in ovarian cancer using single-cell RNA-seq, which provided a novel insight into the heterogeneity of ovarian cancer.

Increasing statutory retirement ages around the world are forcing employees to prolong their working lives. We study the different ways in which mid- and late-career workers respond to such changes. We distinguish between negative emotions about working longer, cognitive engagement with prolonged employment, and proactive behavior to facilitate longer working lives. We analyze data from 1,351 employees aged 40-66 from the Netherlands. We estimate a structural equation model to identify in which ways experiences of age discrimination, accessibility of accommodative HR facilities, and social norms in the workers' social networks are related to the three different types of responses. Results show that when employees do not experience age discrimination, when their employer offers easily accessible accommodative HR facilities, and the social norms support prolonged employment, employees have fewer negative emotional reactions and are more likely to behaviorally respond to facilitate longer working lives. When these contexts are misaligned, the reverse is generally found. We also find socioeconomic differences in the ways employees respond to the prospect of prolonged employment. This study shows the importance of supportive contexts at different levels-societally, in organizations, and in individuals' own lives-for policy changes such as increasing statutory retirement ages to be effective. Different responses between different socioeconomic groups may lead to growing long-term inequality.

Metastasis is the leading cause of cancer-related deaths. Understanding the pathogenesis of metastasis at the molecular levels is of great significance for cancer research. However, the molecular diagnosis or treatment of cancer metastasis is limited. Accumulating and growing evidence shows that epigenetic changes are present in all human cancers, and epigenetic regulation is an indispensable factor to promote tumor metastasis. With the deepening of research and the advancement of technology, the function and mechanism of epigenetic regulation, including DNA methylation, histone/RNA modification, and precursor messenger RNA alternative splicing and noncoding RNAs, has become more increasingly clear. At present, the application of epigenetic therapies in tumor treatment is becoming a feasible therapeutic route. In this review, we looked for the key molecules in epigenetic regulation and discuss their relative regulating mechanisms in cancer metastasis. Furthermore, we highlight promising therapeutic strategies, including monitoring serum DNA for diagnostic purposes and early phase clinical trial therapies that target DNA and histone methylation. This may also be beneficial in finding new targets for further prognosis and diagnosis of cancer metastasis.

BACKGROUND: Rituximab has been frequently used as a second-line treatment for patients with immune thrombocytopenia (ITP). The optimal dose and course of rituximab are uncertain. METHODS: A comprehensive search for randomized controlled trials reporting the use of low-dose (100 mg) or standard-dose (375 mg/m2) rituximab in ITP treatment was conducted. Meta-analyses were performed on CRR (complete response rate), ORR (overall response rate), PRR (partial response rate), SRR (sustained response rate), infection rate, SB (significant bleeding) rate, and SAE (serious adverse event) rate. RESULTS: A total of 12 studies were included, comprising 869 patients. Compared to the control group, rituximab treatment resulted in an obvious increase in CRR (P < 0.00001), ORR (P < 0.0001), and SRR at month 6 and 12 (P = 0.0007, P = 0.0003), without increasing the infection rate (P = 0.12) and SAE rate (P = 0.11). No significant differences in CRR (RR 1.61 vs. 1.42, P = 0.45), ORR (RR 1.26 vs. 1.49, P = 0.28), PRR (RR 1.25 vs. 1.00, P = 0.11), SRR at month 12 (RR 2.00 vs. RR 1.64, P = 0.54), infection rate (RR 0.85 vs. 1.46, P = 0.36), and SB rate (RR 0.14 vs. 1.19, P = 0.17) were found in subgroups of low dose and standard dose. CONCLUSION: Rituximab was effective and safe for adult patients with ITP. A low-dose rituximab regimen might be an effective alternative to the standard-dose regimen in ITP, as it showed similar CRR, ORR, and SRR at month 12 and was relatively safer with a lower cost.

Entamoeba histolytica (Eh) is a pathogenic eukaryote that often resides silently in humans under asymptomatic stages. Upon indeterminate stimulus, it develops into fulminant amoebiasis that causes severe hepatic abscesses with 50% mortality. This neglected tropical pathogen relies massively on membrane modulation to flourish and cause disease; these modulations range from the phagocytic mode for food acquisition to a complex trogocytosis mechanism for tissue invasion. Rab GTPases form the largest branch of the Ras-like small GTPases, with a diverse set of roles across the eukaryotic kingdom. Rab GTPases are vital for the orchestration of membrane transport and the secretory pathway responsible for transporting the pathogenic effectors, such as cysteine proteases (EhCPs) which help in tissue invasion. Rab GTPases thus play a crucial role in executing the cytolytic effect of E. histolytica. First, they interact with Gal/Nac lectins required for adhering to the host cells, and then, they assist in the secretion of EhCPs. Additionally, amoebic Rab GTPases are vital for encystation because substantial vesicular trafficking is required to create dormant amoebic cysts. These cysts are the infective agent and help to spread the disease. The absence of a "bonafide" vesicular transport machinery in Eh and the existence of a diverse repertoire of amoebic Rab GTPases (EhRab) hint at their contribution in supporting this atypical machinery. Here, we provide insights into a pseudoRab GTPase, EhRabX10, by performing physicochemical analysis, predictive 3D structure modeling, protein-protein interaction studies, and in silico molecular docking. Our group is the first one to classify EhRabX10 as a pseudoRab GTPase with four nonconserved G-motifs. It possesses the basic fold of the P-loop containing nucleotide hydrolases. Through this in silico study, we provide an introduction to the characterization of the atypical EhRabX10 and set the stage for future explorations into the mechanisms of nucleotide recognition, binding, and hydrolysis employed by the pseudoEhRab GTPase family.

Carbapenem-resistant Enterobacteriaceae (CRE) has been a public health risk in several countries, and recent reports indicate the emergence of CRE in food animals. This study was conducted to investigate the occurrence, resistance patterns, and phylogenetic diversity of carbapenem-resistant E. coli (CREC) from chicken. Routine bacteriology, PCR detection of E. coli species, multiplex PCR to detect carbapenemase-encoding genes, and phylogeny of CRE E. coli were conducted. The results show that 24.36% (19/78) were identified as CREC based on the phenotypic identifications of which 17 were positive for the tested carbapenemases genes. The majority, 57.99% (11/19), of the isolates harbored multiple carbapenemase genes. Four isolates harbored all bla NDM, bla OXA, and bla IMP, and five and two different isolates harbored bla NDM and bla OXA and bla OXA and bla IMP, respectively. The meropenem, imipenem, and ertapenem MIC values for the isolates ranged from 2 μg/mL to ≥256 μg/mL. Phylogenetic grouping showed that the CREC isolates belonged to five different groups: groups A, B1, C, D, and unknown. The detection of CREC in this study shows that it has become an emerging problem in farm animals, particularly, in poultry farms. This also implies the potential public health risks posed by CRE from chicken to the consumers.

BACKGROUND: Apelin is an adipokine with an intermediatory role in obesity and insulin resistance, which can be modified by dietary intake. AIMS: In this study, we aimed to determine the association of the plasma fatty acid composition with apelin plasma concentration and gene expression in visceral (VAT) and subcutaneous (SAT) adipose tissues. METHODS: In this cross-sectional study, we recruited 179 patients aged 19-75 years who were candidates for elective surgery. Through the surgery, SAT and VAT were collected to measure apelin gene expression. Anthropometric measurements, fasting blood samples, and dietary intakes were collected before surgery. Free fatty acids (FFAs) in fasting whole plasma were measured using gas chromatography with flame ionization detection. Linear regression models were used to estimate standardized β (STZ β) showing the association of individual and total FFAs with apelin gene expression after adjustment for potential confounding variables. RESULTS: In multivariable analysis, we observed a significant positive association of total plasma free fatty acids (FFAs) (STZ β = 0.241, P = 0.006), saturated fatty acid (SFA) (STZ β = 0.336, P < 0.001), and monounsaturated fatty acid (MUFA) (STZ β = 0.313, P < 0.001) concentrations with apelin gene expression from VAT after controlling for age, sex, body mass index, homeostatic model assessment for insulin resistance (HOMA-IR), physical activity, and energy intake. In the SFA family, there was a direct association with plasma concentration of myristic acid (STZ β = 0.372, P < 0.001), pentadecanoic acid (STZ β = 0.252, P = 0.002), and heptadecanoic acid (STZ β = 0.407, P < 0.001) with apelin mRNA expression in VAT. There was no significant association between FFAs and apelin plasma concentration and SAT mRNA levels. CONCLUSIONS: In conclusion, circulating plasma FFAs, SFA, and MUFA had a positive association with apelin gene expression in VAT. It seems that plasma fatty acid composition may regulate apelin gene expression in VAT.

Antimicrobial resistance (AMR) in poultry production chain is one of the major food safety concerns due to indiscriminate usage of antibiotics and the presence of pathogens such as Salmonella which causes infections in various stages of production. In the present study, 182 samples were collected from commercial broiler supply chain, viz., three hatcheries (n = 29), three commercial broiler farms (CBF; n = 99), and three retail meat shops (RMS; n = 54), and used for isolation and identification of Salmonella using three different selective agar media and a selective enrichment medium followed by PCR confirmation targeting the hilA gene. The overall prevalence of Salmonella was 47/182 (25.82%), and a significantly higher (P < 0.05) prevalence was observed in retail meat shops (46.29%), CBF (19.19%), and hatcheries (10.34%). Comparison of three agar media for isolation of Salmonella revealed that all the media were equally selective. However, PCR amplification of hilA gene fragment was significantly higher (P < 0.01) in selective enrichment culture tetrathionate brilliant green bile broth (TTB) as compared to all solid (agar-based) media. Susceptibility pattern against most frequently used antibiotics revealed that 100% of the isolates were resistant to at least one antibiotic. High resistance was observed for doxycycline (94.34%), followed by cefpodoxime (84.91%), ciprofloxacin (72.64%), gentamicin (65.09%), enrofloxacin (61.32%), colistin sulphate (40.42%), amikacin (34.91%), ampicillin (33.96%), neomycin (33.02), cefotaxime (30.19%), ceftazidime (29.25%), trimethoprim-sulfamethoxazole (23.58%), amoxicillin+clavulanic acid (21.70%), and chloramphenicol (12.26%); 16.98% of the isolates were ex-tended spectrum β-lactamase (ESBL) producers, and 76.41% were multidrug resistant (MDR). MDR Salmonella were significantly higher (P < 0.01) in RMS (91.66%) followed by CBF (82.75%), whereas no MDR isolates were present in the isolates from hatcheries. The results indicated a higher prevalence of Salmonella and AMR for commonly used antibiotics in the complete broiler supply chain, especially RMS and CBF. Also, this study idicated that TTB enrichment followed by PCR and colony PCR was found to be rapid, specific and time-saving method.

OBJECTIVE: The purpose of this study is to identify novel biomarkers for the prognosis of Ewing's sarcoma based on bioinformatics analysis. METHODS: The GSE63157 and GSE17679 datasets contain patient and healthy control microarray data that were downloaded from the Gene Expression Omnibus (GEO) database and analyzed through R language software to obtain differentially expressed genes (DEGs). Firstly, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment, protein-protein interaction (PPI) networks, and Cytoscape Molecular Complex Detection (MCODE) plug-in were then used to compute the highest scores of the module. After survival analysis, the hub genes were lastly obtained from the two module genes. RESULTS: A total of 1181 DEGs were identified from the two GSEs. Through MCODE and survival analysis, we obtain 53 DEGs from the module and 29 overall survival- (OS-) related genes. ZBTB16 was the only downregulated gene after Venn diagrams. Survival analysis indicates that there was a significant correlation between the high expression of ZBTB16 and the OS of Ewing's sarcoma (ES), and the low expression group had an unfavorable OS when compared to the high expression group. CONCLUSIONS: High expression of ZBTB16 may serve as a predictor biomarker of poor prognosis in ES patients.

Over the years, most of the research concerning manganese exposure was restricted to the toxicity of neuronal cells. Manganese is an essential trace element that in high doses exerts neurotoxic effects. However, in the last two decades, efforts have shifted toward a more comprehensive approach that takes into account the involvement of glial cells in the development of neurotoxicity as a brain insult. Glial cells provide structural, trophic, and metabolic support to neurons. Nevertheless, these cells play an active role in adult neurogenesis, regulation of synaptogenesis, and synaptic plasticity. Disturbances in glial cell function can lead to neurological disorders, including neurodegenerative diseases. This review highlights the pivotal role that glial cells have in manganese-induced neurotoxicity as well as the most sounding mechanisms involved in the development of this phenomenon.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by uncontrollable epithelial cell growth, cyst formation, and kidney malfunction. In the present study, we investigated the antiproliferative effects of the treatment with the combination of paclitaxel (PAC) and all-trans retinoic acid (ATRA) on ADPKD epithelial cells. Our results show that the combined treatment with 1 nM PAC and 10 nM ATRA significantly suppressed ADPKD cell proliferation (20%), while the treatment with ATRA or PAC alone had no such effect. Treatment with PAC and ATRA induced cell cycle arrest at the G2/M phase and apoptosis by upregulating p53 and caspase-8 expression and increased the intracellular calcium (Ca2+) level possibly by enhancing Ca2+ uptake via plasma membrane channels. In addition, this treatment suppressed extracellular signal-regulated kinase signaling possibly through mitogen-activated protein kinase phosphatase-1 activation. Thus, the combination of PAC and ATRA can be explored as a potential treatment regimen for ADPKD.

OBJECTIVE: To study the protective effect of trimetazidine on myocardial cells in rats with myocardial infarction and explore its effect on ERK signaling pathway. METHODS: 40 SD rats were randomly divided into the sham operation group, model group, low-dose group, and high-dose group (intra-abdominal injection of trimetazidine 5 mg/kg and 10 mg/kg, respectively), construction of rat myocardial infarction model by coronary artery left anterior descending artery ligation. 7 days after surgery, the survival rate and cardiac function of each group of rats were recorded. The myocardial infarct size was detected by TTC staining. The apoptosis level of rat cardiomyocytes was detected by TUNEL staining. The content of ROS in rat cardiomyocytes was detected by DCFH-DA. Western-blot was used to detection of Caspase-3, Bcl-2/Bax, and ERK signaling pathway-related proteins in myocardial tissue. RESULTS: Compared with the model group, the survival rate of the rats in the low-dose group and the high-dose group was significantly increased (P < 0.01), the cardiac function was significantly improved (P < 0.01), the myocardial infarct size was significantly decreased (P < 0.01), the level of apoptosis was significantly decreased (P < 0.01), the content of ROS in cardiomyocytes was significantly decreased (P < 0.01), the protein expression of Caspase-3 and NF-κB in cardiomyocytes was significantly decreased (P < 0.01), and the expression of Bcl-2/Bax and p-ERK were significantly increased (P < 0.01). CONCLUSION: Trimetazidine can activate ERK signaling pathway in cardiomyocytes of rats with myocardial infarction, increase the expression of p-ERK, decrease the content of ROS in cardiomyocytes, decrease the expression of apoptotic proteins, reduce myocardial infarct size, improve cardiac function, and increase myocardial function.

Dogs are the main reservoir of Leishmania infantum in endemic regions. Canine leishmaniasis, caused by L. infantum, can progress to a chronic disease resulting in death. Vaccines have been developed with a certain degree of success. The pathogenesis of this disease is not completely understood, especially in previously vaccinated dogs. We herein described clinical data, parasite load, serum levels of cytokines, and the reservoir potential in vdogs vaccinated with the fucose-mannose ligand (FML)/QuilA saponin vaccine (Leishmune™) naturally infected (Vi) and compared to vaccinated not infected dogs (Vn). Thirty-four dogs from private owners were divided into two groups: vaccinated/infected and vaccinated/uninfected. Clinical evaluation, hematological and biochemical parameters, and serum levels of cytokines were measured by conventional methods. The parasite burden in the bone marrow was measured by quantitative real-time PCR, and the transmissibility of parasites to sand flies was assessed by xenodiagnosis. Clinical, biochemical, and hematological parameters of vaccinated infected dogs were mostly normal. Vi dogs developed mild disease with low clinical scores. Serum levels of IL-10 were higher in Vi dogs, and a strong correlation was observed in IL-4 levels and the A/G ratio in Vi dogs. These results suggest a role of TH2 response in Vi dogs, although more data is needed to better understand the disease in vaccinated dogs.

BACKGROUND: B.1.617.1, a variant of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing respiratory illness is responsible for the second wave of COVID-19 and associated with a high incidence of infectivity and mortality. To mitigate the B.1.617.1 variant of SARS-CoV-2, deciphering the protein structure and immunological responses by employing bioinformatics tools for data mining and analysis is pivotal. OBJECTIVES: Here, an in silico approach was employed for deciphering the structure and immune function of the subunit of spike (S) protein of SARS-CoV-2 B.1.617.1 variant. METHODS: The partial amino acid sequence of SARS-CoV-2 B.1.617.1 variant S protein was analyzed, and its putative secondary and tertiary structure was predicted. Immunogenic analyses including B- and T-cell epitopes, interferon-gamma (IFN-γ) response, chemokine, and protective antigens for SARS-CoV 2 S proteins were predicted using appropriate tools. RESULTS: B.1.617.1 variant S protein sequence was found to be highly stable and amphipathic. ABCpred and CTLpred analyses led to the identification of two potential antigenic B cell and T cell epitopes with starting amino acid positions at 60 and 82 (for B cell epitopes) and 54 and 98 (for T cell epitopes) having prediction scores > 0.8. Further, RAMPAGE tool was used for determining the allowed and disallowed regions of the three-dimensional predicted structure of SARS-CoV-2 B.1.617.1 variant S protein. CONCLUSION: Together, the in silico analysis revealed the predicted structure of partial S protein, immunogenic properties, and possible regions for S protein of SARS-CoV-2 and provides a valuable prelude for engineering the targeted vaccine or drug against B.1.617.1 variant of SARS-CoV-2.

Over 10% of patients diagnosed with cervical intraepithelial neoplasia (CIN) have no lesions detected in their cervical conization specimens. The purpose of this study was to determine the factors related to the absence of such lesions. We particularly sought to investigate whether the expression of B7-H4 in precancerous lesions and cancer of the uterine cervix plays a role in the presence or absence of residual lesions in conization specimens and whether this protein is associated with T cells (i.e., Foxp3+ regulatory T cells, CD4+, and CD8+) and interferon-γ production. Of the 807 patients with CIN treated by conization, 104 (12.9%) had no lesions in their conization specimens. Seventy-five of these patients were deemed the study group and were matched with 75 patients who did have CIN detected in their conization specimens (the control group). Immunohistochemistry and immunofluorescence staining were used to detect B7-H4, Foxp3, CD4, CD8, and interferon-γ in the 75 pairs of specimens obtained via biopsy; 20 samples were found to have chronic cervicitis, and another 20 had squamous cell carcinoma of the cervix. Menopause, the absence of human papillomavirus, low-grade histological findings, and a diagnosis of CIN1 and CIN2 on biopsy correlated with a low probability of lesions on conization specimens. B7-H4 expression was detected in 11.1% of CIN2, 46.6% of CIN3, and 70% of cervical cancer samples, but not in tissues representing chronic cervicitis or CIN1. B7-H4 expression was associated with the presence of lesions on conization specimens, increased regulatory T cells, decreased CD8+ T cells, and lower interferon-γ production. These data suggest that close follow-up and thorough reevaluation should be considered for patients diagnosed with CIN2 who are negative for B7-H4 expression on biopsy before proceeding with cervical conization.

This paper incorporates the adaptive neurofuzzy inference system (ANFIS) technique to model the yield of bio-oil. The estimation of this parameter was performed according to pyrolysis conditions and biomass compositions of feedstock. For this purpose, this paper innovates two optimization methods including a genetic algorithm (GA) and particle swarm optimization (PSO). Primary data were gathered from previous studies and included 244 data of biodiesel oils. The findings showed a coefficient determination (R 2) of 0.937 and RMSE of 2.1053 for the GA-ANFIS model, and a coefficient determination (R 2) of 0.968 and RMSE of 1.4443 for PSO-ANFIS. This study indicates the capability of the PSO-ANFIS algorithm in the estimation of the bio-oil yield. According to the performed analysis, this model shows a higher ability than the previously presented models in predicting the target values and can be a suitable alternative to time-consuming and difficult experimental tests.

COVID-19-associated neuropsychiatric complications are soaring. There is an urgent need to understand the link between COVID-19 and neuropsychiatric disorders. To that end, this article addresses the premise that SARS-CoV-2 infection results in gut dysbiosis and an altered microbiota-gut-brain (MGB) axis that in turn contributes to the neuropsychiatric ramifications of COVID-19. Altered MGB axis activity has been implicated independently as a risk of neuropsychiatric disorders. A review of the changes in gut microbiota composition in individual psychiatric and neurological disorders and gut microbiota in COVID-19 patients revealed a shared "microbial signature" characterized by a lower microbial diversity and richness and a decrease in health-promoting anti-inflammatory commensal bacteria accompanied by an increase in opportunistic proinflammatory pathogens. Notably, there was a decrease in short-chain fatty acid (SCFA) producing bacteria. SCFAs are key bioactive microbial metabolites with anti-inflammatory functions and have been recognized as a critical signaling pathway in the MGB axis. SCFA deficiency is associated with brain inflammation, considered a cardinal feature of neuropsychiatric disorders. The link between SARS-CoV-2 infection, gut dysbiosis, and altered MGB axis is further supported by COVID-19-associated gastrointestinal symptoms, a high number of SARS-CoV-2 receptors, angiotensin-cleaving enzyme-2 (ACE-2) in the gut, and viral presence in the fecal matter. The binding of SARS-CoV-2 to the receptor results in ACE-2 deficiency that leads to decreased transport of vital dietary components, gut dysbiosis, proinflammatory gut status, increased permeability of the gut-blood barrier (GBB), and systemic inflammation. More clinical research is needed to substantiate further the linkages described above and evaluate the potential significance of gut microbiota as a diagnostic tool. Meanwhile, it is prudent to propose changes in dietary recommendations in favor of a high fiber diet or supplementation with SCFAs or probiotics to prevent or alleviate the neuropsychiatric ramifications of COVID-19.

This paper proposes a deep learning-based method for mitosis detection in breast histopathology images. A main problem in mitosis detection is that most of the datasets only have weak labels, i.e., only the coordinates indicating the center of the mitosis region. This makes most of the existing powerful object detection methods hardly be used in mitosis detection. Aiming at solving this problem, this paper firstly applies a CNN-based algorithm to pixelwisely segment the mitosis regions, based on which bounding boxes of mitosis are generated as strong labels. Based on the generated bounding boxes, an object detection network is trained to accomplish mitosis detection. Experimental results show that the proposed method is effective in detecting mitosis, and the accuracies outperform state-of-the-art literatures.

OBJECTIVES: To report the long-term results of scleral buckling using 25-gauge chandelier illumination. METHODS: The medical records of all patients presenting to Shanghai Tenth People's Hospital with simple rhegmatogenous retinal detachment (RRD) from June 2013 to Oct 2015 were retrospectively reviewed in this consecutive case series. All patients underwent preoperative and postoperative best corrected visual acuity (BCVA), B-ultrasound, fundus photography, and optical coherence tomography examination. Ultrasound biomicroscopy (UBM) was obtained postoperatively. RESULTS: Ten patients (10 eyes) were included in the final analysis. Of 10 patients, the average age was 49.3 ± 18.9 years old, the average duration of RRD was 30.9 ± 53.3 days, and the mean follow-up period was 6.2 ± 0.9 years. There were nine eyes with myopia and four eyes with macular detachment. The primary anatomical success rate was 90%. Five eyes underwent 360-degree band with element surgery, and five eyes underwent element surgery alone. The average length of encircling band and element was 68.2 ± 1.3 mm and 10.5 ± 2.5 mm, respectively. There were no intraoperative or postoperative complications that occurred. The final BCVA was greater than or equal to 20/40 in nine eyes, of which four eyes achieved 20/20. UBM examination of the 25-gauge chandelier insertion site revealed no tissue proliferation. CONCLUSIONS: For simple rhegmatogenous retinal detachment treatment, 25-gauge chandelier illumination-assisted scleral buckling is a kind of effective and safe method.

Respiratory inflammation is caused by an air-mediated disease induced by polluted air, smoke, bacteria, and viruses. The COVID-19 pandemic is also a kind of respiratory disease, induced by a virus causing a serious effect on the lungs, bronchioles, and pharynges that results in oxygen deficiency. Extensive research has been conducted to find out the potent natural products that help to prevent, treat, and manage respiratory diseases. Traditionally, wider floras were reported to be used, such as Morus alba, Artemisia indica, Azadirachta indica, Calotropis gigantea, but only some of the potent compounds from some of the plants have been scientifically validated. Plant-derived natural products such as colchicine, zingerone, forsythiaside A, mangiferin, glycyrrhizin, curcumin, and many other compounds are found to have a promising effect on treating and managing respiratory inflammation. In this review, current clinically approved drugs along with the efficacy and side effects have been studied. The study also focuses on the traditional uses of medicinal plants on reducing respiratory complications and their bioactive phytoconstituents. The pharmacological evidence of lowering respiratory complications by plant-derived natural products has been critically studied with detailed mechanism and action. However, the scientific validation of such compounds requires clinical study and evidence on animal and human models to replace modern commercial medicine.

This study is aimed at examining the feasibility and effectiveness of aerobic and resistance training (WeActive) and mindful exercise (WeMindful) interventions in improving physical activity (PA), psychological well-being (PWB), and subjective vitality among college students. Participants in this study were 77 college students who were randomly assigned to either the WeActive group (n = 43) or the WeMindful group (n = 28). The WeActive group attended two 30-minute aerobic and resistance training sessions per week, and the WeMindful group attended two 30-minute yoga and mindful exercise sessions per week for eight weeks. All participants completed the International Physical Activity Questionnaire, the World Health Organization-Five Well-Being Index, and the Subjective Vitality Scale before and after the intervention, as well as the Assessing Feasibility and Acceptability Questionnaire at the end of the intervention. The primary study outcome measures were PA, PWB, and subjective vitality. A repeated-measures ANCOVA indicated a significant main effect of time for total PA (F = 7.89, p = 0.006, η 2 = 0.049), vigorous PA (F = 5.36, p = 0.024, η 2 = 0.022), and walking (F = 7.34, p = 0.009, η 2 = 0.042) in both intervention groups. There was a significant interaction effect of time and group for PWB (F = 11.26, p = 0.001, η 2 = 0.022), where the WeActive group experienced a decrease in PWB scores while participants in the WeMindful group experienced an increase in PWB scores over time. There was a main effect of group for subjective vitality (F = 8.91, p = 0.007, η 2 = 0.088), indicating that the WeMindful group experienced a greater increase in subjective vitality than the WeActive group. Further, the participants in both groups indicated that the synchronized and asynchronized Zoom-based WeActive and WeMindful interventions were acceptable, appropriate, and feasible for participants. This study demonstrated that mindful exercise is effective in increasing PA, PWB, and subjective vitality while aerobic and resistance training may only be effective in increasing PA.

BACKGROUND: Hepatocellular carcinoma (HCC) is high-mortality primary liver cancer and the most common malignant tumor in the world. This study is based on a hepatocellular carcinoma-related dysfunction module designed to explore the dysregulation of genes in liver cancer tissue. METHODS: By downloading the relevant data on the GEO database, we performed a differential analysis of healthy liver tissue and liver cancer tissues as well as healthy liver tissue and hepatocellular carcinoma tissue and then obtained two sets of differential genes and combined them. We performed a cointerpretation analysis of these differential genes and constructed related functional disorder modules. A hypergeometric test was performed to calculate the potential regulatory effects of multiple factors on the module, and a series of ncRNA and TF regulators were identified. We obtained a total of 4479 differentially expressed genes in hepatocellular carcinoma, and these genes were clustered into ten hepatocellular carcinoma-related functional interpretation disorder modules. RESULTS: Enrichment analysis revealed that these modular genes are mainly involved in signal transduction including cell cycle, TGF-beta signal transduction, and p53 signal transduction. Depending on the predictive analysis of multidimensional regulators, 323 ncRNAs and 52 TF-mediated hepatocellular carcinoma-related dysregulation modules were found to regulate disease progression. CONCLUSIONS: Based on a series of investigations, it was found that miR-30b-5p may participate in the peroxisome signal transduction by downregulating ABCD3-mediated module 1, thereby promoting the development and progression of hepatocellular carcinoma. Our research results not only provide a theoretical basis for biologists to study hepatocellular carcinoma further but also offer new methods and new ideas for the personalized care and treatment of hepatocellular carcinoma.

INTRODUCTION: Although retrospective analysis has shown immediate placement of implants (IIP) in the maxillary esthetic zone showing promising outcomes compared to delayed placement of implants following socket preservation (DIP), a direct comparison in a prospective, well-designed randomized fashion with adequate power analysis between the two implant placement protocols is still lacking. This study is aimed at radiographically evaluating the effect of IIP after extraction as compared to implant placed in preserved sockets 4 months following extraction (DIP) in terms of changes in buccal plate thickness(CBT) after 6 months of healing and evaluation of pink esthetic score (PES) for assessment of soft tissue changes and patient-related outcome measures (PROMs) using visual analogue scale (VAS). MATERIALS AND METHODS: 25 implants were placed immediately following extraction in the IIP group, and 25 implants were placed four months following socket preservation with demineralized bovine bone mineral (DBBM) and advanced platelet-rich fibrin (A-PRF) in the DIP group, control group, in the maxillary esthetic region. CBCT was taken preoperatively and 6 months postoperatively to assess the dimensional changes in the buccal bone plates(CBT). PES and PROMs for pain threshold and patient satisfaction using VAS were evaluated at the time of implant placement and 6 months postoperatively. RESULTS: Significant differences in mean reduction in buccal plate thickness (CBT) were found in the test group (IIP) 0.2 ± 0.02 compared to the control group (DIP) which showed a mean reduction in CBT of 0.4 ± 0.1 (p < 0.001) at the end of 6 months. Although there was no statistically significant difference in PES between the groups, there was a significant difference between the groups when individual values of PES were compared at p < 0.001. CONCLUSION: The IIP group showed lesser reduction in CBT and a better PES which is an important clinical information which could be translated clinically in situations where implant placement is planned in the maxillary esthetic region. This trial is registered with CTRI/2019/06/019723.

MicroRNAs are a large group of small noncoding RNAs that work in multiple cellular pathways. miR-204, as one of the key axes in the development, maintenance, and pathogenesis of the retina, plays several roles by modulating its target genes. This study was aimed at evaluating the target genes of miR-204 involved in the development and progression of common retinopathies such as glaucoma, retinoblastoma, and age-related macular degeneration. In this study, three datasets related to retinopathies (GSE50195, GSE27276, and GSE97508) were selected from Gene Expression Omnibus. miR-204 target genes were isolated from TargeScan. The shares between retinopathy and miR-204 target genes were then categorized. Using Enrichr and STRING, we highlighted the signaling pathways and the relationships between the proteins. SHC1 events in ERBB2, adherent junction's interactions, NGF signaling via TRKA from the plasma membrane, IRF3-mediated activation of type 1 IFN, pathways in upregulated genes and G0 and early G1, RORA-activated gene expression, PERK-regulated gene expression, adherent junction's interactions, and CREB phosphorylation pathways in downregulated genes were identified in glaucoma, retinoblastoma, and age-related macular degeneration. WEE1, SMC2, HMGB1, RRM2, and POLA1 proteins were also observed to be involved in the progression and invasion of retinoblastoma; SLC24A2 and DTX4 in age-related macular degeneration; and EPHB6, EFNB3, and SHC1 in glaucoma. Continuous bioinformatics analysis has shown that miR-204 has a significant presence and expression in retinal tissue, and approximately 293 genes are controlled and regulated by miR-204 in this tissue; also, target genes of miR-204 have the potential to develop various retinopathies; thus, a study of related target genes can provide appropriate treatment strategies in the future.

OBJECTIVES: Human adenoviruses (HAdV) are classified as 7 HAdV species, and some serotypes in species B like HAdV 3, HAdV 7, HAdV 21, and HAdV 55 caused severe symptoms, even fatalities. Patients may be misdiagnosed and inadequately treated without reliable and practical methods for HAdV serotyping. Developing rapid, sensitive, and specific diagnostic methods for HAdV is critical. METHODS: Detection methods were established based on a recombinase polymerase amplification (RPA) assay and lateral flow (LF) test. Specific target sequence was screened, targeting which, primers and probes were designed, synthesized, and screened for establishing assay with high amplification efficiency. Primer or probe concentrations and amplification time were optimized. Detection limit, sensitivity, and specificity were evaluated. Results and Conclusions. Simple, sensitive, and specific RPA-LF methods for detection of four serotypes of HAdV together or separately were established, which had detection limits of 10 to 280 copies/reaction comparable to real-time PCR without recognizing other pathogens. The sensitivity and specificity were >92% and >98%, respectively, evaluated by limited clinical samples. The detection can be completed in 25 min without requirement of any instrument except a constant temperature equipment, showing superior detection performance and promising for a wide use in the field and resource-limited area.

BACKGROUND: In 2014, the Ministry of Health of Morocco implemented a reform of medicine pricing that leads to lower prices. This reform has brought about a new method of pricing medicines and a reduction in the prices of more than 1,400 of the 5,000 medicines on the market. The objective of this study was to survey patients' perceptions of the impact of the reform on medicine prices and affordability of health care, including medicine. METHODS: Between September 2017 and September 2018, 360 patients that visited a community pharmacy in four selected areas of different socioeconomic levels were interviewed based on a questionnaire. Findings were studied through univariate and multivariate analyses. RESULTS: Three hundred patients (83%) were included given their completed questionnaire. The majority (89%) of respondents considered medicine prices as a potential barrier to access to health care. Lower medicine prices following the reform were not perceived to have actually impacted respondents' spending on health care. In some cases, care was delayed, in particular by lower-income respondents and people without insurance and health coverage. CONCLUSION: The majority of patients participating in the study did not perceive the decrease in medicine prices as sufficient. In addition, the study findings pointed to the relevance of further determinants of access to medicines, such as health insurance coverage. Patients think that the generalized third-party payment mode, which does not oblige patients to spend out of their pockets to have their treatment but rather their health insurance funds that will pay for them, provides optimal access to medicines.

Over recent years, feature selection (FS) has gained more attention in intelligent diagnosis. This study is aimed at evaluating FS methods in a unified framework for mammographic breast cancer diagnosis. After FS methods generated rank lists according to feature importance, the framework added features incrementally as the input of random forest which performed as the classifier for breast lesion classification. In this study, 10 FS methods were evaluated and the digital database for screening mammography (1104 benign and 980 malignant lesions) was analyzed. The classification performance was quantified with the area under the curve (AUC), and accuracy, sensitivity, and specificity were also considered. Experimental results suggested that both infinite latent FS method (AUC, 0.866 ± 0.028) and RELIEFF (AUC, 0.855 ± 0.020) achieved good prediction (AUC ≥ 0.85) when 6 features were used, followed by correlation-based FS method (AUC, 0.867 ± 0.023) using 7 features and WILCOXON (AUC, 0.887 ± 0.019) using 8 features. The reliability of the diagnosis models was also verified, indicating that correlation-based FS method was generally superior over other methods. Identification of discriminative features among high-throughput ones remains an unavoidable challenge in intelligent diagnosis, and extra efforts should be made toward accurate and efficient feature selection.

The wound healing process is essential to reform the damaged tissue and prevent its invasion by pathogens. The present study aims at evaluating the antibacterial and therapeutic properties of the Capsicum annuum L. (Solanaceae) extract against infected wound in a rat model with its mechanisms of antibacterial action. The fruit extract was prepared by maceration in methanol. The broth microdilution method was used to investigate the antibacterial activity of the methanol extract of C. annuum fruits. The therapeutic effect of the extract gel was performed on an excision wound infected with Staphylococcus aureus using a rat model. The total phenol, flavonoid, and tannin contents as well as the antibacterial mechanisms of action of the extract were determined using spectrophotometric methods. The C. annuum fruit extract showed antibacterial properties which can be linked to its total phenolic, flavonoid, and tannin contents. The antibacterial activity is due to the inhibition of the biofilm formation, ATPases/H+ proton pump, and dehydrogenase activity as well as the alteration of the bacterial cell membrane through the leakage of nucleic acids, reducing sugars and proteins. The extract gel showed a significant (p < 0.05) increase in the percentage of wound closure and eradicated S. aureus at the infection site. The extract gel was nonirritating to the skin and slightly irritating to the eyes and should be used with caution. Overall, the findings of the present study support the traditional use of the studied plant in the treatment of wounds and infectious diseases associated with the tested bacteria.

Dermal papilla cells (DPCs) are a source of nutrients and growth factors, which support the proliferation and growth of keratinocytes as well as promoting the induction of new hair follicles and maintenance of hair growth. The protection from reactive oxygen species (ROS) and the promotion of angiogenesis are considered two of the basal mechanisms to preserve the growth of the hair follicle. In this study, a noncrosslinked hyaluronic acid (HA) filler (HYDRO DELUXE BIO, Matex Lab S.p.A.) containing several amino acids was tested with in vitro assays on human follicle dermal papilla cells (HFDPCs). The experiments were carried out to investigate the possible protection against oxidative stress and the ability to increase the vascular endothelial growth factor (VEGF) release. The results demonstrated the restoration of cell viability against UVB-induced cytotoxicity and an increase in the VEGF secretion. These data demonstrate the capability of the product to modulate human dermal papilla cells, suggesting a future use in mesotherapy, a minimally invasive local intradermal therapy (LIT), after further clinical investigations.

OBJECTIVES: The aim of this study was to provide the first study to systematically analyze the efficacy and safety of PCSK9-mAbs in the treatment of familial hypercholesterolemia (FH). METHODS: A computer was used to search the electronic Cochrane Library, PubMed/MEDLINE, and Embase databases for clinical trials using the following search terms: "AMG 145", "evolocumab", "SAR236553/REGN727", "alirocumab", "RG7652", "LY3015014", "RN316/bococizumab", "PCSK9", and "familial hypercholesterolemia" up to November 2020. Study quality was assessed with the Cochrane Collaboration's tool, and publication bias was evaluated by a contour-enhanced funnel plot and the Harbord modification of the Egger test. After obtaining the data, a meta-analysis was performed using R software, version 4.0.3. RESULTS: A meta-analysis was performed on 7 clinical trials (926 total patients). The results showed that PCSK9-mAbs reduced the LDL-C level by the greatest margin, WMD -49.14%, 95% CI: -55.81 to -42.47%, on FH versus control groups. PCSK9-mAbs also significantly reduced lipoprotein (a) (Lp (a)), total cholesterol (TC), triglycerides (TG), apolipoprotein-B (Apo-B), and non-high-density lipoprotein cholesterol (non-HDL-C) levels and increased HDL-C and apolipoprotein-A1 (Apo-A1) levels of beneficial lipoproteins. Moreover, no significant difference was found between PCSK9-mAbs treatment and placebo in common adverse events, serious events, and laboratory adverse events. CONCLUSION: PCSK9-mAbs significantly decreased LDL-C and other lipid levels with satisfactory safety and tolerability in FH treatment.

BACKGROUND: Successful reconstruction of the feet and ankles remains challenging due to limited quantities of soft tissue and laxity. The free lateral arm flap (LAF) is an alternative to conventional flaps and has been widely used due to advancements in its flap characteristics. This study is aimed at utilizing the advantages of this flap to validate its increased applications for foot and ankle defects. METHODS: Twenty patients with various LAF types between May 2011 and May 2020 were enrolled. Clinical data was retrospectively collected, and defect sites were classified according to the subunit principle. We utilized various LAF types, such as LAFs with sensate, extended, osteomyocutaneous, or myocutaneous flaps, as necessary. A two-point discrimination test was performed, and results were statistically compared between flaps. RESULTS: Among the diverse etiologies of skin defects, chronic inflammation was the most common cause of defects. Various LAF types, including LAFs with fasciocutaneous, extended fasciocutaneous, musculocutaneous, and osteomyocutaneous flaps, were used. The versatility of free LAF helped successfully cover various defects in all cases. Results of the two-point discrimination test were statistically significant between groups. CONCLUSIONS: Free LAF is a unique soft tissue free flap that is more versatile than other flaps, allowing flaps to be continuously modified and applied to various foot and ankle defects under different clinical conditions.

PINK1, also known as PARK6, is a PTEN-induced putative kinase 1 that is encoded by nuclear genes. PINK1 is ubiquitously expressed and regulates mitochondrial function and mitophagy in a range of cell types. The dysregulation of PINK1 is associated with the pathogenesis and development of mitochondrial-associated disorders. Many natural products could regulate PINK1 to relieve PINK1-associated diseases. Here, we review the structure and function of PINK1, its relationship to human diseases, and the regulation of natural products to PINK1. We further highlight that the discovery of natural PINK1 regulators represents an attractive strategy for the treatment of PINK1-related diseases, including liver and heart diseases, cancer, and Parkinson's disease. Moreover, investigating PINK1 regulation of natural products can enhance the in-depth comprehension of the mechanism of action of natural products.

The lung organ of human anatomy captured by a medical device reveals inhalation and exhalation information for treatment and monitoring. Given a large number of slices covering an area of the lung, we have a set of three-dimensional lung data. And then, by combining additionally with breath-hold measurements, we have a dataset of multigroup CT images (called 4DCT image set) that could show the lung motion and deformation over time. Up to now, it has still been a challenging problem to model a respiratory signal representing patients' breathing motion as well as simulating inhalation and exhalation process from 4DCT lung images because of its complexity. In this paper, we propose a promising hybrid approach incorporating the local binary pattern (LBP) histogram with entropy comparison to register the lung images. The segmentation process of the left and right lung is completely overcome by the minimum variance quantization and within class variance techniques which help the registration stage. The experiments are conducted on the 4DCT deformable image registration (DIR) public database giving us the overall evaluation on each stage: segmentation, registration, and modeling, to validate the effectiveness of the approach.

The oral conditions of an individual are the result of different factors, including the subject's genotype, oral hygiene habits, the type of diet, and lifestyle, such as smoking. Nutrition in the first years of life can affect dental health for a long time. To prevent mouth diseases, it is also important to eliminate unfavorable eating behaviour and to amplify protective ones. Eating habits, especially in pediatric age, are an easily modifiable and controllable factor, and diet, in addition to influencing the health of the oral cavity, plays a fundamental role in systemic health. Indeed, a sugar-rich diet can lead to conditions, such as diabetes, being overweight, and obesity. The present research was an epidemiological study, with the aim of highlighting some of the associations between nutrition and oral health. In particular, we studied those lesions of hard and soft tissues that are diagnosed most frequently by dentists: caries, enamel hypoplasia, periodontal disease, and aphotoxic lesions and their associations with nutritional deficiencies and excesses including proteins, vitamin A, vitamin D, B vitamins, and iron and calcium minerals. To perform this study, we recruited 70 patients from the pediatric and orthodontic clinics, aged between 3 and 15 years (y), with mean age of 10.4 y.o. The study was conducted by providing a questionnaire to pediatric patients' (supported from their parents or guardians) on individual eating habits, followed by an accurate oral cavity specialistic examination. The nutritional data were processed by using Grana Padano Observatory (OGP) software, freely provided online by the OPG. The statistical tests performed were the chi-square (χ 2) for independence, and Cramér's V test was used to evaluate the associations between eating habits and oral pathologies. The results showed that certain nutritional vitamin deficiencies and nutritional excesses were associated with definite oral pathologies.

PURPOSE: Autophagy is a lysosomal degradation pathway that is essential for maintaining the homeostasis of the intracellular environment. Mounting evidence indicates that autophagy plays an essential role in the occurrence and development of hepatocellular cancer (HCC). This research is aimed at exploring the prognostic value of autophagy-related genes (ARGs) in HCC patients. METHODS: The Wilcoxon test was used to identify differentially expressed ARGs in The Cancer Genome Atlas (TCGA) HCC cohort. Then, the TCGA cohort was randomly divided into training and testing groups. Cox and LASSO regression models were used to screen for autophagy-related genes that affect overall survival (OS) in the TCGA training group. Based on the coefficient of risk genes, we constructed an autophagy-related gene signature for predicting the prognosis of HCC patients. Finally, we validated the prognostic significance of autophagy-related gene signature using the TCGA testing group and three external datasets. RESULTS: ATG10, BIRC5, GAPDH, and TMEM74 are risk genes for OS. According to the optimal cutoff value of risk score in each HCC dataset, HCC patients can divide into high- and low-risk groups. ARG risk score can significantly distinguish HCC patients with different survival outcomes. Meanwhile, the ARG risk score is independently correlated with OS in multiple HCC cohorts. CONCLUSIONS: The autophagy-related risk score can effectively screen high-risk HCC patients and provide guidance for clinical prevention and treatment of HCC.

Spinal cord ischemia/reperfusion (SCI/R) injury is a devastating complication usually occurring after thoracoabdominal aortic surgery. However, it remains unsatisfactory for its intervention by using pharmacological strategies. Oxidative stress is a main pharmacological process involved in SCI/R, which will elicit downstream programmed cell death such as the novel defined necroptosis. Astragalin is a bioactive natural flavonoid with a wide spectrum of pharmacological activities. Herein, we firstly evaluated the effect of astragalin to oxidative stress as well as the possible downstream necroptosis after SCI/R in mice. Our results demonstrated that astragalin improves the ethological score and histopathological deterioration of SCI/R mice. Astragalin mitigates oxidative stress and ameliorates inflammation after SCI/R. Astragalin blocks necroptosis induced by SCI/R. That is, the amelioration of astragalin to the motoneuron injury and histopathological changes. Indicators of oxidative stress, inflammation, and necroptosis after SCI/R were significantly blocked. Summarily, we firstly illustrated the protection of astragalin against SCI/R through its blockage to the necroptosis at downstream of oxidative stress.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. Liuwei Dihuang (LWDH) pills have a good effect on PD, but its mechanism remains unclear. Network pharmacology is the result of integrating basic theories and research methods of medicine, biology, computer science, bioinformatics, and other disciplines, which can systematically and comprehensively reflect the mechanism of drug intervention in disease networks. METHODS: The main components and targets of herbs in LWDH pills were obtained through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Its active components were screened based on absorption, distribution, metabolism, and excretion (ADME); the PD-related targets were obtained from the Genecards, OMIM, TTD, and DRUGBANK databases. We used R to take the intersection of LWDH- and PD-related targets and Cytoscape software to construct the drug-component-target network. Moreover, STRING and Cytoscape software was used to analyze protein-protein interactions (PPI), construct a PPI network, and explore potential protein functional modules in the network. The Metascape platform was used to perform KEGG pathway and GO function enrichment analyses. Finally, molecular docking was performed to verify whether the compound and target have good binding activity. RESULTS: After screening and deduplication, 210 effective active ingredients, 204 drug targets, 4333 disease targets, and 162 drug-disease targets were obtained. We consequently constructed a drug-component-targets network and a PPI-drug-disease-targets network. The results showed that the hub components of LWDH pills were quercetin, stigmasterol, kaempferol, and beta-sitosterol; the hub targets were AKT1, VEGFA, and IL6. GO and KEGG enrichment analyses showed that these targets are involved in neuronal death, G protein-coupled amine receptor activity, reactive oxygen species metabolic processes, membrane rafts, MAPK signaling pathways, cellular senescence, and other biological processes. Molecular docking showed that the hub components were in good agreement with the hub targets. CONCLUSION: LWDH pills have implications for the treatment of PD since they contain several active components, target multiple ligands, and activate various pathways. The hub components possibly include quercetin, stigmasterol, kaempferol, and beta-sitosterol and act through pairing with hub targets, such as AKT1, VEGFA, and IL6, to regulate neuronal death, G protein-coupled amine receptor activity, reactive oxygen species metabolic process, membrane raft, MAPK signaling pathway, and cellular senescence for the treatment of PD.

BACKGROUND: Policy changes are often necessary to contain the detrimental impact of epidemics such as those brought about by coronavirus disease (COVID-19). In the earlier phases of the emergence of COVID-19, China was the first to impose strict restrictions on movement (lockdown) on January 23rd, 2020. A strategy whose effectiveness in curtailing COVID-19 was yet to be determined. We, therefore, sought to study the impact of the lockdown in reducing the incidence of COVID-19. METHODS: Daily cases of COVID-19 that occurred in China which were registered between January 12th and March 30th, 2020, were extracted from the Johns Hopkins CSSE team COVID-19 ArcGIS® dashboards. Daily cases reported were used as data points in the series. Two interrupted series models were run: one with an interruption point of 23 January 2020 (model 1) and the other with a 14-day deferred interruption point of 6th February (model 2). For both models, the magnitude of change (before and after) and linear trend analyses were measured, and β-coefficients reported with 95% confidence interval (CI) for the precision. RESULTS: Seventy-eight data points were used in the analysis. There was an 11% versus a 163% increase in daily cases in models 1 and 2, respectively, in the preintervention periods (p ≤ 0.001). Comparing the period immediately following the intervention points to the counterfactual, there was a daily increase of 2,746% (p < 0.001) versus a decline of 207% (p = 0.802) in model 2. However, in both scenarios, there was a statistically significant drop in the daily cases predicted for this data and beyond when comparing the preintervention periods and postintervention periods (p < 0.001). CONCLUSION: There was a significant decrease the COVID-19 daily cases reported in China following the institution of a lockdown, and therefore, lockdown may be used to curtail the burden of COVID-19.

BACKGROUND: Yinchen Wuling powder is often used to treat clinical hyperlipidemia, although its mechanism of action remains unclear. In this study, we aimed to investigate the active ingredients found in Yinchen Wuling powder and find its mechanism of action when treating hyperlipidemia, using a combination of network pharmacology, molecular docking, and molecular dynamics simulation approaches. METHODS: The TCMSP database was used to obtain the principle active ingredients found in Yinchen Wuling powder and the NCBI and DisGeNet databases were used to obtain the main target genes involved in hyperlipidemia, and the intersectional targets were obtained by EXCEL. We also used Cytoscape 3.7.2 software to construct a "Traditional Chinese Medicine-Active Ingredient-Target" network and use STRING platform to conduct "protein-protein interactional" (PPI) analyses on the intersection targets. Bioconductor software and RX 64 4.0.0 software were then used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the targets. Molecular docking of core protein-ligand interactions was modeled using AutoDock Vina software. A simulation of molecular dynamics was conducted for the optimal core protein-ligand obtained by molecular docking using Amber18 software. RESULTS: A total of 63 active ingredients were found in Yinchen Wuling powder, corresponding to 175 targets, 508 hyperlipidemia targets, and 55 intersection targets in total. Cytoscape 3.7.2 showed that the key active ingredients were quercetin, isorhamnetin, taxifolin, demethoxycapillarisin, and artepillin A. The PPI network showed that the key proteins involved were AKT1, IL6, VEGFA, and PTGS2. GO enrichment analysis found that genes were enriched primarily in response to oxygen levels and nutrient levels of the vesicular lumen and were associated with membrane rafts. These were mainly enriched in AGE-RAGE (advanced glycation end products-receptor for advanced glycation end products) signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis, as well as other pathways. The molecular docking results indicated key binding activity between PTGS2-quercetin, PTGS2-isorhamnetin, and PTGS2-taxifolin. Results from molecular dynamics simulations showed that PTGS2-quercetin, PTGS2-isorhamnetin, and PTGS2-taxifolin bound more stably, and their binding free energies were PTGS2-quercetin -29.5 kcal/mol, PTGS2-isorhamnetin -32 kcal/mol, and PTGS2-taxifolin -32.9 kcal/mol. CONCLUSION: This study is based on network pharmacology and reveals the potential molecular mechanisms involved in the treatment of hyperlipidemia by Yinchen Wuling powder.

[This retracts the article DOI: 10.1155/2015/798489.].

Although hypoxia has been shown to promote keratinocyte migration and reepithelialization, the underlying molecular mechanisms remain largely unknown. ADAM17, a member of the metalloproteinase superfamily, has been implicated in a variety of cellular behaviors such as proliferation, adhesion, and migration. ADAM17 is known to promote cancer cell migration under hypoxia, and whether or how ADAM17 plays a role in hypoxia-induced keratinocyte migration has not been identified. Here, we found that ADAM17 expression and activity were significantly promoted in keratinocytes under hypoxic condition, inhibition of ADAM17 by TAPI-2, or silencing of ADAM17 using small interfering RNA which suppressed the hypoxia-induced migration of keratinocytes significantly, indicating a pivotal role for ADAM17 in keratinocyte migration. Further, we showed that p38/MAPK was activated by hypoxia. SB203580, an inhibitor of p38/MAPK, significantly attenuated the upregulation of ADAM17 as well as the migration of keratinocytes induced by hypoxia. Activation of p38/MAPK by MKK6 (Glu) overexpression, however, had adverse effects. Taken together, our study demonstrated that hypoxia-induced keratinocyte migration requires the p38/MAPK-ADAM17 signal axis, which sheds new light on the regulatory mechanisms of keratinocyte migration. Our study might also help in developing therapeutic strategies to facilitate wound healing in vivo, where cells are migrated in a hypoxic microenvironment.

The emerging science of nanotechnology sparked a research attention in its potential benefits in comparison to the conventional materials used. Oral products prepared via nanoparticles (NPs) have garnered great interest worldwide. They are used commonly to incorporate nutrients and provide antimicrobial activity. Formulation into NPs can offer opportunities for targeted drug delivery, improve drug stability in the harsh environment of the gastrointestinal (GI) tract, increase drug solubility and bioavailability, and provide sustained release in the GI tract. However, some issues like the management of toxicity and safe handling of NPs are still debated and should be well concerned before their application in oral preparations. This article will help the reader to understand safety issues of NPs in oral drug delivery and provides some recommendations to the use of NPs in the drug industry.

OBJECTIVE: To explore the mechanisms of follicular fluids (FFs) on granulose cell (GC) apoptosis in endometriosis-associated infertility. MATERIALS AND METHODS: 60 infertile women were enrolled. The FFs from 30 endometriosis-associated infertility (EI) patients were collected and processed by ELISA hormone assay and proteomic profiling. The ovary GCs collected from 30 tubal-associated infertility (TI) patients were cultured in follicular fluids of endometriosis-associated infertility patients (EI-FFs), and the apoptosis mechanisms were explored by flow cytometry assay, real-time PCR, Western blotting, and protein-protein interaction (PPI) network analysis. RESULTS: Our results showed that the expression of 22 specific proteins was significantly different in the FFs from EI and TI patients, and the level of testosterone and anti-Müllerian hormone was not obviously different between the two groups. EI-FFs could accelerate the apoptosis process of granulose cells of tubal-associated infertility patients (TI-GCs) by regulating the expression of 5 apoptosis-related proteins including BCL2, BAX, CASP3, CASP9, and TP53. The correlation of these 22 specific proteins and 5 apoptosis-related proteins was analyzed by PPI, and 5 protein biomarkers (INS, CXCL10, ICAM1, WIF1, and TNFRSF13C) and 5 signaling pathways (cytokine-cytokine receptor interaction, apoptosis, regulation of actin cytoskeleton, MAPK, and p53 signaling pathway) were predicted. CONCLUSION: This research clarified the effect and explored the mechanisms of EI-FFs on the apoptosis of TI-GCs and indicated the protein biomarkers and signaling pathways for further study.

This study will concentrate on recent research on EEG signals for Alzheimer's diagnosis, identifying and comparing key steps of EEG-based Alzheimer's disease (AD) detection, such as EEG signal acquisition, preprocessing function extraction, and classification methods. Furthermore, highlighting general approaches, variations, and agreement in the use of EEG identified shortcomings and guidelines for multiple experimental stages ranging from demographic characteristics to outcomes monitoring for future research. Two main targets have been defined based on the article's purpose: (1) discriminative (or detection), i.e., look for differences in EEG-based features across groups, such as MCI, moderate Alzheimer's disease, extreme Alzheimer's disease, other forms of dementia, and stable normal elderly controls; and (2) progression determination, i.e., look for correlations between EEG-based features and clinical markers linked to MCI-to-AD conversion and Alzheimer's disease intensity progression. Limitations mentioned in the reviewed papers were also gathered and explored in this study, with the goal of gaining a better understanding of the problems that need to be addressed in order to advance the use of EEG in Alzheimer's disease science.

Stroke is an acute cerebrovascular disease, including ischemic and hemorrhagic stroke. Stroke is the second leading cause of death after ischemic heart disease, which accounts for 9% of the global death toll. To explore the molecular mechanisms of the effects of the dysregulated factors, in the GEO database, we obtained transcriptome data from 24 h/72 h of mice with ischemic stroke and 24 h/72 h of normal mice. We then performed differential gene analysis, coexpression analysis, enrichment analysis, and regulator prediction bioinformatics analysis to identify the potential genes. We made a comparison between the ischemic stroke 72 h and the ischemic stroke for 24 h, and 5103 differential genes were obtained (p < 0.05). Four functional barrier modules were obtained by weighted gene coexpression network analysis. The critical genes of each module were ASTL, Zfp472, Fmr1 gene, and Nap1l1. The results of the enrichment analysis showed ncRNA metabolism, microRNAs in cancer, and biosynthesis of amino acids. These three functions and pathways have the most considerable count value. The regulators of the regulatory dysfunction module were predicted by pivotal analysis of TF and noncoding RNA, and critical regulators including NFKB1 (NF-κB1), NFKBIA, CTNNB1, and SP1 were obtained. Finally, the pivotal target gene found that CTNNB1, NFKB1, NFKBia, and Sp1 are involved in 18, 32, 2, and 60 target genes, respectively. Therefore, we believe that NFKB1 and Sp1 have a potential role in the progression of ischemic stroke. The NFKB signaling pathway promotes inflammatory cytokines and regulates the progression of ischemic stroke.

BACKGROUND: Cerebral ischemia and its reperfusion injury facilitate serious neurodegenerative diseases such as dementia due to cell death; however, there is currently no treatment for it. Reactive oxygen species is one of the many factors that induce and worsen the development of such diseases, and it can be targeted by hydrogen treatment. This study examined the effect of molecular hydrogen in cerebral ischemia-reperfusion injury, which is emerging as a novel therapeutic agent for various diseases. METHODS: Ischemia-reperfusion injury was generated through bilateral common carotid artery occlusion in C57BL/6 mice. The test group received hydrogen-rich water orally during the test period. To confirm model establishment and the effect of hydrogen treatment, behavioural tests, biochemical assays, immunofluorescence microscopy, and cytokine assays were conducted. RESULTS: Open field and novel object recognition tests revealed that the hydrogen-treated group had improved cognitive function and anxiety levels compared to the nontreated group, while hematoxylin and eosin stain showed abundant pyknotic cells in a model mouse brain, and this was attenuated in the hydrogen-treated mouse brain. Total antioxidant capacity and thiobarbituric acid reactive substance assays revealed that hydrogen treatment induced antioxidative effects in the mouse brain. Immunofluorescence microscopy revealed attenuated apoptosis in the striatum, cerebral cortex, and hippocampus of hydrogen-treated mice. Western blotting showed that hydrogen treatment reduced Bax and TNFα levels. Finally, cytokine assays showed that IL-2 and IL-10 levels significantly differed between the hydrogen-treated and nontreated groups. CONCLUSION: Hydrogen treatment could potentially be a future therapeutic strategy for ischemia and its derived neurodegenerative diseases by improving cognitive abilities and inducing antioxidative and antiapoptotic effects. Hydrogen treatment also decreased Bax and TNFα levels and induced an anti-inflammatory response via regulation of IL-2 and IL-10. These results will serve as a milestone for future studies intended to reveal the mechanism of action of molecular hydrogen in neurodegenerative diseases.

Volunteering can play an important role in active aging. The resource theory of volunteering posits that volunteerism depends on human, social, and cultural capital. Benefits of volunteering have been documented at the micro-, meso-, and macrolevels, positively affecting individual older people as well as their local communities and society at large. Taking a process-oriented theoretical approach, this study focused on the mesolevel factor of the environment with the purpose of determining the relationship between perceived neighborhood safety and volunteerism over the course of a decade and the extent to which this relationship differs by gender and race. Longitudinal data from the Health and Retirement Study in the United States of America between 2008 and 2018 were used (N = 72,319 adults 60 years and older). Generalized estimating equations (GEE) with robust standard errors were employed while controlling for a number of covariates. A third of the sample volunteered in the past year (33%). The probability of volunteering among older adults who rated their perceived neighborhood safety as excellent was greater compared with those who rated their perceived neighborhood safety as fair/poor after controlling for all other model covariates (ME: 0.03, 95% CI: 0.02, 0.05). Among males rating their perceived neighborhood safety as excellent, the probability of volunteering was higher (ME: 0.04, 95% CI: 0.02, 0.07). Among females, the probability of volunteering was higher among those who perceived their neighborhood safety to be excellent (ME: 0.03, 95% CI: 0.01, 0.05) or very good (ME: 0.02, 95% CI: 0.00, 0.04). White respondents who rated their neighborhood safety as excellent (ME: 0.05, 95% CI: 0.03, 0.07) or very good (ME: 0.04, 95% CI: 0.02, 0.06) had a higher probability of volunteerism. Results were not significant among Black respondents and those who described their race as "other." This study's process-oriented theoretical approach indicates that initiatives aimed at improving neighborhood safety and older adults' perceptions of neighborhood safety could increase social capital and lead older adults to engage in more volunteering, providing benefits at micro-, meso-, and macrolevels-to older individuals, their local communities, and society at large.

The dysregulation of glucose metabolism that includes the modification of biomolecules with the help of glycation reaction results in the formation of advanced glycation end products (AGEs). The formation of AGEs may activate receptors for advanced glycation end products which induce intracellular signaling, ultimately enhancing oxidative stress, a well-known contributor to type 2 diabetes mellitus. In addition, AGEs are possible therapeutic targets for the treatment of type 2 diabetes mellitus and its complications. This review article highlights the antioxidant, anti-inflammatory, and antidiabetic properties of the Nymphaea species, and the screening of such aquatic plants for antiglycation activity may provide a safer alternative to the adverse effects related to glucotoxicity. Since oxidation and glycation are relatively similar to each other, therefore, there is a possibility that the Nymphaea species may also have antiglycating properties because of its powerful antioxidant properties. Herbal products and their derivatives are the preeminent resources showing prominent medicinal properties for most of the chronic diseases including type 2 diabetes mellitus. Among these, the Nymphaea species has also shown elevated activity in scavenging free radicals. This species has a load of phytochemical constituents which shows various therapeutic and nutritional value including anti-inflammatory and antioxidant profiles. To the best of our knowledge, this is the first article highlighting the possibility of an antiglycation value of the Nymphaea species by inhibiting AGEs in mediation of type 2 diabetes mellitus. We hope that in the next few years, the clinical and therapeutic potential may be explored and highlight a better perspective on the Nymphaea species in the inhibition of AGEs and its associated diseases such as type 2 diabetes mellitus.

MATERIALS AND METHODS: In this cross-sectional case control study, the serum level of LH, FSH, and prolactin of 40 women with lichen planus who have been referred to Shiraz Dental Faculty, Oral and Maxillofacial Disease Department during 2018-2019 has been evaluated in comparison to 40 healthy controls. Data were analyzed by SPSS version 18. Two-way ANOVA and Mann-Whitney test were used for data analysis. RESULTS: The mean serum level of FSH and LH was significantly higher in OLP patients while this difference was not reported for prolactin. Only FSH mean serum level was significantly higher in nonmenopausal OLP patients. The distribution of prolactin and FSH hormones' serum level was in normal range. CONCLUSIONS: The high serum level of FSH and LH can affect OLP pathogenesis by estrogen and progesterone modulation.

The main dose-limiting side effect of cisplatin is nephrotoxicity. The utilization of cisplatin is an issue of balancing tumour toxicity versus platinum-induced nephrotoxicity. In this study, we focused on intraorgan distribution of common essential trace elements zinc, copper, and iron in healthy mouse kidneys and distribution of platinum after cisplatin treatment. Renal distribution in 12 nontreated Nu-Nu mice (males) was assessed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Furthermore, 9 Nu-Nu mice were treated with cisplatin. The order of elements concentration in kidneys was as follows: Fe > Zn > Cu. All three metals showed the higher concentrations at the cortex and medulla (28.60, 3.35, and 93.83 μg/g for Zn, Cu, and Fe, respectively) and lower concentration at the pelvis and the urinary tract (20.20, 1.93, and 62.48 μg/g for Zn, Cu, and Fe, respectively). No statistically significant difference between cortex and medulla was observed for these elements. After platinum treatment, the concentration of platinum in kidneys was enhanced more than 60-times, p < 0.001. Platinum significantly showed the highest accumulation in cortex (2.11 μg/g) with a gradient distribution. Platinum was less accumulated in medulla and pelvis than in cortex, and the lowest accumulation occurred in the urinary tract (1.13 μg/g). Image processing has been successfully utilized to colocalize metal distribution using LA-ICP-MS and histological samples images.

OBJECTIVE: Epithelial-mesenchymal transition (EMT) exerts a key function in cancer initiation and progression. Herein, we aimed to develop an EMT-based prognostic signature in gastric cancer. METHODS: The gene expression profiles of gastric cancer were obtained from TCGA dataset as a training set and GSE66229 and GSE84437 datasets as validation sets. By LASSO regression and Cox regression analyses, key prognostic EMT-related genes were screened for developing a risk score (RS) model. Potential small molecular compounds were predicted by the CMap database based on the RS model. GSEA was employed to explore signaling pathways associated with the RS. ESTIMATE and seven algorithms (TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCPCOUNTER, XCELL, and EPIC) were applied to assess the RS and immune microenvironment. RESULTS: This study developed an EMT-related gene signature comprised of SERPINE1, PCOLCE2, MATN3, and DKK1. High-RS patients displayed poorer survival outcomes than those with low RS. ROC curves demonstrated the robustness of the model in predicting the prognosis. After external validation, the RS model was an independent risk factor for gastric cancer. Several compounds were predicted for gastric cancer treatment based on the RS model. ECM receptor interaction, focal adhesion, pathway in cancer, TGF-beta, and WNT pathways were distinctly activated in high-RS samples. Also, high RS was significantly associated with increased stromal and immune scores and increased infiltration of CD4+ T cell, CD8+ T cell, cancer-associated fibroblast, and macrophage in gastric cancer tissues. CONCLUSION: Our findings suggested that the EMT-related gene model may robustly predict gastric cancer prognosis, which could improve the efficacy of personalized therapy.

Hepatocellular carcinoma (HCC) is an aggressive cancer type with poor prognosis; thus, there is especially necessary and urgent to screen potential prognostic biomarkers for early diagnosis and novel therapeutic targets. In this study, we downloaded target data sets from the GEO database, and obtained codifferentially expressed genes using the limma R package and identified key genes through the protein-protein interaction network and molecular modules, and performed GO and KEGG pathway analyses for key genes via the clusterProfiler package and further determined their correlations with clinicopathological features using the Oncomine database. Survival analysis was completed in the GEPIA and the Kaplan-Meier plotter database. Finally, correlations between key genes, cell types infiltrated in the tumor microenvironment (TME), and hypoxic signatures were explored based on the TIMER database. From the results, 11 key genes related to the cell cycle were determined, and high levels of these key genes' expression were focused on advanced and higher grade status HCC patients, as well as in samples of TP53 mutation and vascular invasion. Besides, the 11 key genes were significantly associated with poor prognosis of HCC and also were positively related to the infiltration level of MDSCs in the TME and the HIF1A and VEGFA of hypoxic signatures, but a negative correlation was found with endothelial cells (ECs) and hematopoietic stem cells. The result determined that 11 key genes (RRM2, NDC80, ECT2, CCNB1, ASPM, CDK1, PRC1, KIF20A, DTL, TOP2A, and PBK) could play a vital role in the pathogenesis of HCC, drive the communication between tumor cells and the TME, and act as probably promising diagnostic, therapeutic, and prognostic biomarkers in HCC patients.

BACKGROUND: Cisplatin is a powerful chemotherapeutic drug mainly used in the treatment of solid tumors. Aggregation of the drug in renal proximal tubule cells causes nephrotoxicity and renal failure. Investigations showed nephrotoxicity as Cisplatin's dose-limiting side effect. One of the Cisplatin toxicity mechanisms is generation of reactive oxygen species, which leads to oxidative stress and renal damage. The purpose of this study was evaluation of the modulating effects of Gallic acid on Cisplatin-induced variations including Caspase-3 and Clusterin expression and histopathological and biochemical parameters in adult male Wistar rats. METHOD: Rats were kept under standard condition of temperature, light, and humidity. The animals were divided into 4 groups: GpI: control group (received distilled water for 10 days); GpII: Gallic acid (alone) (50 mg/kg bw, once a day for 10 days); GpIII: Cisplatin (alone), single dose (6 mg/kg bw, I.P. on 5th day of study); GpIV: Gallic acid (50 mg/kg bw, once a day for 10 days) and also injected with single dose of Cisplatin (6 mg/kg bw, I.P., on 5th day of study). After 10 days, all rats were anaesthetized and plasma collected to estimate urea, creatinine, and uric acid. The right kidneys were removed for the study of gene expression and biochemical parameters. The left kidneys were used for histopathological studies. RESULTS: The Cisplatin-induced nephrotoxicity was evident from the elevated levels of creatinine, urea, uric acid, and renal tissue MDA and also decreased levels of SOD, CAT, GPX, and GSH in renal tissue. Administration of Gallic acid significantly modulated nephrotoxicity markers, gene expression variations, and histopathological damage. CONCLUSION: Outcomes of the present investigation suggest that Gallic acid provides protection against CP-induced nephrotoxicity, but for application in people, further studies are needed.

People who receive the ChAdOx1 nCoV-19 vaccine, particularly perimenopausal women who are on birth control or postmenopausal women who take estrogen supplements, may experience thrombosis and thrombocytopenia. Estrogen and the ChAdOx1 nCoV-19 vaccine both have the potential to cause thrombus in different ways. Some postmenopausal women who are also taking estrogens may develop thrombosis and thrombocytopenia after receiving the ChAdOx1 nCoV-19 vaccine. Therefore, women are encouraged to stop taking drugs containing estrogen before receiving this vaccine. Furthermore, consuming fish oil can help reduce the risk of developing blood clots among women who are in the luteal phase and, thus, have high estrogen levels. In addition, ChAdOx1 nCoV-19's side effects in young women could be mitigated by administering it during the follicular phase.

Ovarian cancer is one of the leading causes of gynecological malignancy-related deaths. The underlying molecular development mechanism has however not been elucidated. In this study, we used bioinformatics to reveal critical molecular and biological processes associated with ovarian cancer. The microarray datasets of miRNA and mRNA expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. Besides, we performed target prediction of the identified differentially expressed miRNAs. The overlapped differentially expressed genes (DEGs) were obtained combined with miRNA targets predicted and the DEGs identified from the mRNA dataset. The Cytoscape software was used to design a regulatory network of miRNA-gene. Moreover, the overlapped DEGs in the network were subjected to enrichment analysis to explore the associated biological processes. The molecular protein-protein interaction (PPI) network was used to identify the key genes among the DEGs of prognostic value for ovarian cancer, and the genes were evaluated via Kaplan-Meier curve analysis. A total of 186 overlapped DEGs were identified. Through miRNA-gene network analysis, we found that miR-195-5p, miR-424-5p, and miR-497-5p highly exhibited targeted association with overlapped DEGs. The three miRNAs are critical in the regulatory network and act as tumor suppressors. The overlapped DEGs were mainly associated with protein metabolism, histogenesis, and development of the reproductive system and ocular tissues. The PPI network identified 10 vital genes that promote tumor progression. Survival analysis found that CEP55 and CCNE1 may be associated with the prognosis of ovarian cancer. These findings provide insights to understand the pathogenesis of ovarian cancer and suggest new candidate biomarkers for early screening of ovarian cancer.

INTRODUCTION: Dengue, a vector-borne viral illness, shows worldwide widening spatial distribution beyond its point of origination, namely, the tropical belt. The persistent hyperendemicity in Malaysia has resulted in the formation of the dengue early warning system. However, weather variables are yet to be fully utilized for prevention and control activities, particularly in east-coast peninsular Malaysia where limited studies have been conducted. We aim to provide a time-based estimate of possible dengue incidence increase following weather-related changes, thereby highlighting potential dengue outbreaks. METHOD: All serologically confirmed dengue patients in Kelantan, a northeastern state in Malaysia, registered in the eDengue system with an onset of disease from January 2016 to December 2018, were included in the study with the exclusion of duplicate entry. Using a generalized additive model, climate data collected from the Kota Bharu weather station (latitude 6°10'N, longitude 102°18'E) was analysed with dengue data. RESULT: A cyclical pattern of dengue cases was observed with annual peaks coinciding with the intermonsoon period. Our analysis reveals that maximum temperature, mean temperature, rainfall, and wind speed have a significant nonlinear effect on dengue cases in Kelantan. Our model can explain approximately 8.2% of dengue incidence variabilities. CONCLUSION: Weather variables affect nearly 10% of the dengue incidences in Northeast Malaysia, thereby making it a relevant variable to be included in a dengue early warning system. Interventions such as vector control activities targeting the intermonsoon period are recommended.

The high frequency of traumatic brain injury imposes severe economic stress on health and insurance services. The objective of this study was to analyze the association between the serum S100B protein, the Gosling pulsatility index (PI), and the level of oxygen saturation at the tip of the internal jugular vein (SjVO2%) in patients diagnosed with severe TBI. The severity of TBI was assessed by a GCS score ≤ 8 stratified by Glasgow outcome scale (GOS) measured on the day of discharge from the hospital. Two groups were included: GOS < 4 (unfavorable group (UG)) and GOS ≥ 4 (favorable group (UG)). S100B levels were higher in the UG than in the FG. PI levels in the UG were also substantially higher than in the FG. There were similar levels of SjVO2 in the two groups. This study confirmed that serum S100B levels were higher in patients with unfavorable outcomes than in those with favorable outcomes. Moreover, a clear demarcation in PI between unfavorable and FGs was observed. This report shows that mortality and morbidity rates in patients with traumatic brain injury can be assessed within the first 4 days of hospitalization using the S100B protein, PI values, and SjVO2.

BACKGROUND: The association between sleep disturbance and the menstruation in the young women population has been scarcely studied. The aim of this study is to assess the association between sleep status and phase of the menstrual cycle in healthy, young, ovulating women. METHODS: This cross-sectional study used the data collected from healthy young, ovulating Chinese females from September to December 2018. The association was analyzed by using linear regression and binary logistic analyses. RESULTS: 2260 women aged 17 to 30 were included in the analysis. The average sleep duration of the respondents was 7.24 hours (SD = 0.92). 61.7% of them admitted that they were accompanied by at least one of sleep symptoms including difficulty initiating sleep, difficulty maintaining sleep, dreaminess, early morning awakening, and somnolence. Sleep quality was significantly associated with dysmenorrhea (OR [95%CI] = 1.74 [1.40-2.17], P < 0.001) and self-awareness menstrual regularity (OR [95%CI] = 1.29 [1.06-1.56], P = 0.011). CONCLUSION: This study found that poor sleep quality is significantly associated with dysmenorrhea and self-awareness menstrual irregularity among healthy, young, ovulating, Chinese females.

The study aimed to investigate the effect of erdosteine on middle ear effusion in rats through mediating the Toll-like receptor 4 (TLR4) signaling pathway. Rats were injected with endotoxin to prepare the model of acute secretory otitis media (SOM). Then, they were divided into an acute SOM model group (model group, n = 15) and erdosteine treatment group (18 mg/kg, gavage, treatment group, n = 15). Besides, a normal group (n = 15) was set up. Two weeks later, routine biochemical indicators such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected. The inflammatory effusion due to otitis media was scored. The content of myeloperoxidase (MPO), matrix metalloproteinase (MMP), and tumor necrosis factor-beta (TNF-β) in middle ear lavage fluid was detected via enzyme-linked immunosorbent assay (ELISA). Additionally, histomorphological changes were observed with the help of hematoxylin-eosin (HE) staining, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assays were carried out to measure the expression levels of TLR4 pathway genes and proteins as well as the messenger ribonucleic acid (mRNA) expression levels of key factors for otitis media (mucin 2 (MUC2) and MUC5A). In the model group, the levels of AST, ALP, and glutamic-pyruvic transaminase (GPT) were significantly increased (p < 0.05). Besides, the content of MPO, MMP, and TNF-β was overtly raised in the model group (p < 0.05), while it was notably lowered in the treatment group (p < 0.05). In the treatment group, the cilia were slightly swollen, and inflammatory cells were fewer. The mRNA levels of MUC2, MUC5A, and pathway genes TLR4 and c-Jun N-terminal kinase (JNK) were elevated in the model group. In addition, the protein assay results revealed that the protein levels of TLR4 and JNK were evidently increased in the model group. Erdosteine can treat the middle ear effusion in rats by repressing the activation of the TLR4 signaling pathway.

BACKGROUND: The extracorporeal shock wave therapy (ESWT) has been fully utilized in orthopedics, but there are few studies in the treatment of lower limb spasm and pain caused by lumbar degenerative disorders (LDD). This study assesses the influence of ESWT in patients with LDD. METHODS: From October 2017 to June 2019, 126 patients with LDD were enrolled. All patients received shock wave therapy, once every two days for four weeks in total. Each treatment consisted of 2,000 shocks with a frequency of 8-10 shocks per second. To analyze the therapeutic progress, the following tests were performed (before and after therapy; 1- and 3-month follow-up) to assess pain and functional efficiency: (1) Visual Analog Scale (VAS), (2) the frequency and duration of muscle cramps, and (3) Fugl-Meyer (LL). RESULTS: Mean BMI of the participants was 26.1 ± 3.0 kg/m2. There was no statistically significant difference in terms of age or BMI between the groups (p > 0.05). Although all scoring parameters improved in both groups, the improvement in the ESWT group was more pronounced in pain (p < 0.001 and p < 0.001, respectively). A review of the LMA scores of our patients demonstrated moderate functional limitations before treatment and increased functional status after treatment in all patients, while overall functional status was fully improved in patients of the ESWT group (p < 0.001). CONCLUSION: The ESWT is particularly effective effect for patients with LDD. The use of ESWT has a significant long-term influence on the reduction of pain, leg cramps, and the improvement of the general functional state in relation to the conventional motor improvement program.

OBJECTIVE: The present study was aimed at assessing the impact of teledentistry, its application, and trends in uplifting dental practice and clinical care around the world. Material and Methods. The present observational study comprised of an electronic survey distributed among dental professionals around the globe. The validated survey form consisted of a total 26 questions with 5-point Likert scale response. The questionnaire used was divided into four domains: usefulness of teledentistry for patients, its usefulness in dental practice, its capacity to improve the existing practice, and the concerns attached to its use. The statistical analysis was performed using SPSS-25. ANOVA test was used to assess the effect of independent variables on dependent variables. A p value of ≤0.05 was taken as statistically significant. RESULTS: A total of 506 dental professionals participated in the study with the response rate of 89.39%. More than half of the participants (50-75%) endorsed that teledentistry is a useful tool for improving clinical practice as well as patient care. Two-thirds of the participants (69.96%) considered that teledentistry would reduce cost for the dental practices. On the other hand, about 50-70% of dental professionals expressed their concerns regarding the security of the data and consent of patients. The most preferred communication tool for teledentistry was reported to be videoconference followed by phone. The majority of participants recommended the use of teledentistry in the specialty of oral medicine, operative dentistry, and periodontics. There was a significant difference between the age, experience of dentists, and their qualifications with domains of teledentistry. CONCLUSIONS: The overall impact of dental professionals towards teledentistry was positive with adequate willingness to incorporate this modality in their clinical practice. However, the perceived concerns pertaining to teledentistry are significant impediments towards its integration within the oral health system. An in-depth study of its business model and cost-benefit needs of time, especially in the context of developing countries, in order to avail the optimum benefits of teledentistry.

Ovarian cancer is a kind of cancer from the female genital tract; the molecular mechanism still needs to be explored. lncRNA plays a vital role in tumorigenesis and development. Our aim was to identify oncogenic lncRNAs in ovarian cancer and explore the potential molecular mechanism. SNHG15 was initially identified by using GEO datasets (GSE135886 and GSE119054) and validated by tumor tissues and the cell line, identifying that SNHG15 was upregulated in ovarian cancer. Besides, high SNHG15 indicated poor prognosis in ovarian cancer. Furthermore, knockdown SNHG15 suppresses ovarian cancer proliferation and promotes apoptosis. Mechanistically, SNHG15 promotes proliferation through upregulated CDK6 via sponging miR-370-3p. Taken together, our findings emphasize the important role of SNHG15 in ovarian cancer, suggesting that SNHG15 may be a promising target for ovarian cancer.

PURPOSE: To investigate the impact of hematoma expansion (HE) on short-term functional outcome of patients with thalamic and basal ganglia intracerebral hemorrhage. METHODS: Data of 420 patients with deep intracerebral hemorrhage (ICH) that received a baseline CT scan within 6 hours from symptom onset and a follow-up CT scan within 72 hours were retrospectively analyzed. The poor functional outcome was defined as modified Rankin score (mRS) > 3 at 30 days. Receiver operating characteristic (ROC) curves for relative and absolute growth of HE were generated and compared. Multivariable logistic regression models were used to analyze the impact of HE on the functional outcome in basal ganglia and thalamic hemorrhages. The predictive values for different thresholds of HE were calculated, and correlation coefficient matrices were used to explore the correlation between the covariables. RESULTS: Basal ganglia ICH showed a higher possibility of absolute hematoma growth than thalamic ICH. The area under the curve (AUC) for absolute and relative growth of thalamic hemorrhage was lower than that of basal ganglia hemorrhage (AUC 0.71 and 0.67, respectively) in discriminating short-term poor outcome with an AUC of 0.59 and 0.60, respectively. Each threshold of HE independently predicted poor outcome in basal ganglia ICH (P < 0.001), with HE > 3 ml and > 6 ml showing higher positive predictive values and accuracy compared to HE > 33%. In contrast, thalamic ICH had a smaller baseline volume (BV, 9.55 ± 6.85 ml) and was more likely to initially involve the posterior limb of internal capsule (PLIC) (85/153, 57.82%), and the risk of HE was lower without PLIC involvement (4.76%, P = 0.009). Therefore, in multivariate analysis, the effect of thalamic HE on poor prognosis was largely replaced by BV and the involvement of PLIC, and the adjusted odds ratios (ORs) of HE was not significant (P > 0.05). CONCLUSION: Though HE is a high-risk factor for short-term poor functional outcome, it is not an independent risk factor in thalamic ICH, and absolute growth is more predictive of poor outcome than relative growth for basal ganglia ICH.

BACKGROUND: Pitted keratolysis (PK) is a superficial bacterial infection diagnosed mainly by clinical manifestations. Current data on its dermoscopic and histopathological findings, and the correlation of those findings, are limited. OBJECTIVES: To evaluate the clinical manifestations, dermoscopic, and histopathological findings of PK and to determine the correlations. METHODS: Forty naval cadets with PK and five cadets with normal feet were enrolled this cohort study and provided informed consent. Dermoscopy was independently applied and evaluated by 2 dermatologists. Shave biopsies were performed on 37 patients with PK. RESULTS: Pits were the most common dermoscopic finding (88.1%). The dermoscope had more sensitivity for the detection of PK than the naked eye examinations. Apart from the pits and the presence of bacteria, the most common histopathological finding for PK was color alteration of keratin. The presence of bacteria correlated with interrupted dermatoglyphic lines and the color alteration of keratin. Moreover, the presence of bacteria at the base of pits was related to worse treatment outcomes. CONCLUSIONS: Dermoscopy is a useful tool for PK diagnosis. Color alteration of keratin is another histopathological finding for PK. The presence of bacteria is associated with worse treatment outcomes.

OBJECTIVE: To explore the mechanism of catechol-O-methyltransferase (COMT) in tooth movement pain. METHODS: The experimental groups were randomly allocated into the healthy control, sham operation, model, model+shCOMT experimental, model+shCOMT control, and model+COMT antagonist groups. A tooth movement pain model was established. The pain stimulation and behavior test were performed. The duration of grooming behavior was determined. The appropriate experimental force and duration for application were selected. COMT shRNA vector was constructed and packaged as adenovirus. The shCOMT adenovirus was injected into the left infraorbital foramen. Seven days later, the trigeminal ganglia of all treatment groups were obtained. The COMT and IL-17 expressions were detected by western blot. The appropriate COMT antagonist concentration was selected. The pathological results of each group were detected by HE staining. The tooth movement distance was determined. The COMT gene expression was detected by FISH. The COMT and IL-17 expressions in the right trigeminal ganglion tissue of each group were detected by western blot. RESULTS: The 60 g force and 14-day duration required the lowest stimulus intensity, the duration of grooming behavior was the longest, and the effect on COMT and IL-17 was the most significant. In the model group, formation of digestive cavity was seen in the trigeminal ganglion tissue, with infiltration of inflammatory cells, upregulation of the COMT and IL-17 expressions, and significant increase in the tooth movement distance. Compared with the model group, the shCOMT experimental group and the COMT antagonist group significantly improved the trigeminal ganglion tissue injury, significantly decreased the tooth movement distance, and significantly inhibited the COMT and IL-17 expressions. CONCLUSION: The efficiency of tooth movement can be influenced by interfering the COMT-related gene expression. This proves that the COMT system can regulate the orthodontic tooth movement pain.

OBJECTIVE: Our study is aimed at investigating the efficacy and safety of Qiwei Tongbi oral liquid in patients with stable long-standing rheumatoid arthritis (RA). METHOD: 140 patients with stable long-standing RA were recruited into the Qiwei Tongbi oral liquid group or the control group. At study recruitment and after 12 weeks of treatment, their C-reactive protein (CRP) levels, interleukin-6 (IL-6) levels, erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire (HAQ), visual analogue scale (VAS), and Disease Activity Score (DAS) 28 were compared in two groups. RESULTS: Patients in the Qiwei Tongbi oral liquid group had a lower level of CRP, IL-6, VAS scale, and HAQ score compared to patients in the control group (CRP: 3.51 ± 1.57 vs.5.47 ± 1.72 mg/L, P < 0.001; IL-6: 1.62 ± 0.8 vs. 2.19 ± 0.88 pg/mL, P < 0.001; VAS scale: 1.59 ± 0.69 vs. 2.66 ± 1.02, P < 0.001; and HAQ score: 1.19 ± 0.46 vs. 1.41 ± 0.50, P = 0.005). The ESR and DAS28 did not reach statistical difference. No damage to liver and kidney functions was observed in both groups. CONCLUSION: Qiwei Tongbi oral liquid has the tendency to decrease the inflammation levels and pain score and improve patients' outcomes in patients with stable long-standing RA.

Obesity is a chronic metabolic and noncommunicable disease that affects 50% of world population. Reactive oxygen species and oxidative stress are interconnected with the obesity and several metabolic disorders, gaining the attention of scientific community to combat this problem naturally. Among various fruits, mango as a yellow fruit is rich in polyphenols, carotenoids, terpenes, and flavonoids that act as antioxidants to protect against free radicals produced in the body. The present study was performed to explore in vivo antioxidant potential of mango peels against dyslipidemia and oxidative stress in overweight subjects. The female volunteers (n = 31) between 25 and 45 years of age having a body mass index (BMI) of 25.0-29.9 (overweight) were included in this study, while participants with complications as diabetes, hypertension, cardiovascular, and liver diseases were excluded. The treatment group consumed 1 g mango peel powder for 84 days. The subjects were analyzed for biochemical analysis, antioxidant status, and anthropometric measurements at baseline and end of the study period. Further, at the end of study, the safety evaluation tests were also performed. The results showed that upon consumption of mango peel powder, low-density lipoproteins (LDL), cholesterol, triglyceride, urea, and creatinine levels were decreased and high-density lipoprotein (HDL) level was increased (P ≤ 0.05), while thiobarbituric acid reactive substances (TBARS) showed increased antioxidant status (P ≤ 0.05) which suggests that mango peels have a strong management potential against oxidative stress and dyslipidemia in obese subjects.

Erratum for Biomed Res Int. 2021 Jun 28;2021:5512340.

This study is aimed at evaluating the effects of FiberSite and glass fiber postsystems on the fracture resistance of endodontically restored teeth, when combined with various root canal sealers. Forty human mandibular premolar teeth, each having a single root with anatomically comparable dimension and length, were selected. The teeth in each experimental group (n = 10) were instrumented, obturated, and restored with the following procedures: in group 1, AH Plus root canal sealer and a glass fiber post with a composite core; in group 2, AH Plus root canal sealer and a FiberSite postsystem; in group 3, Sure-Seal Root canal sealer and a glass fiber post with a composite core; and in group 4, Sure-Seal Root canal sealer and a FiberSite postsystem. The specimens were placed on a universal test machine. The fracture resistance of all specimens was tested using generic test equipment, and the value of the force in newton (N) during fracture was measured for each root. A statistical analysis was conducted through the Kruskal-Wallis test as well as the post hoc test. The tests showed a significant difference between groups 2 and 3, with group 3 producing load values that were significantly higher than group 2. In contrast, no significant differences were found to exist between the other groups. Regardless of postsystems, groups 3 and 4 showed higher mean fracture values (but no statistically significant differences) than groups 1 and 2.

BACKGROUND: Hatikana is a traditional medicinal plant used to treat inflammation, urolithiasis, goiter, cancer, wounds and sores, gastrointestinal, tumor, tetanus, arthritis, hepatic damage, neurodegeneration, and other ailments. The goal of this study is to investigate the antidiabetic properties of Hatikana extract (HKEx) and to construct the effects of its natural constituents on the genes and biochemical indices that are connected with them. METHODS: HKEx was evaluated using GC-MS and undertaken for a three-week intervention in fructose-fed STZ-induced Wistar albino rats at the doses of HKEx50, HKEx100, and HKEx200 mg/kg bw. Following intervention, blood serum was examined for biochemical markers, and liver tissue was investigated for the mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD1) by RTPCR analysis. Most abundant compounds (oleanolic acid, 7α, 28-olean diol, and stigmasterol) from GC-MS were chosen for the network pharmacological assay to verify function-specific gene-compound interactions using STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba. RESULTS: In vivo results showed a significant (P < 0.05) decrease of blood sugar, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase of liver glycogen, glucose load, and serum insulin. Out of three antioxidative genes, catalase (CAT) and superoxide dismutase (SOD1) were found to be few fold increased. Oleanolic acid and stigmasterol were noticed to strongly interact with 27 target proteins. Oleanolic acid interacted with the proteins AKR1B10, CASP3, CASP8, CYP1A2, CYP1A2, HMGB1, NAMPT, NFE2L2, NQO1, PPARA, PTGIR, TOP1, TOP2A, UGT2B10, and UGT2B11 and stigmasterol with ABCA1, ABCG5, ABCG8, CTSE, HMGCR, IL10, CXCL8, NR1H2, NR1H3, SLCO1B1, SREBF2, and TNF. Protein-protein interaction (PPI) analysis revealed the involvement of 25 target proteins out of twenty seven. Cytoscape plugin cytoHubba identified TNF, CXCL8, CASP3, PPARA, SREBF2, and IL10 as top hub genes. Pathway analysis identified 31 KEGG metabolic, signaling, and immunogenic pathways associated with diabetes. Notable degree of PPI enrichment showed that SOD1 and CAT are responsible for controlling signaling networks and enriched pathways. CONCLUSION: The findings show that antioxidative genes have regulatory potential, allowing the HKEx to be employed as a possible antidiabetic source pending further validation.

The treatment of infectious diseases with antimicrobial agents continues to present problems in modern-day medicine with many studies showing significant increase in the incidence of bacterial resistance to several antibiotics. The screening of antimicrobial activity of plant extracts and natural products has shown that medicinal plants are made up of a potential source of new anti-infective agents. The aim of this study was to evaluate the antimicrobial and antioxidant activities of extracts and compounds from the whole plant Trifolium baccarinii Chiov. and to determine their modes of antibacterial action. The plant extracts were prepared by maceration in organic solvents. The antimicrobial activities were evaluated using the broth microdilution method. The antioxidant activity was evaluated using the 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) assays. The mechanisms of antibacterial action were determined by lysis, salt tolerance assays, and antioxidant enzyme activities. The cytotoxic effect on the erythrocytes was determined by a spectrophotometric method. Biochanin A, formononetin, luteolin, luteolin-4'-O-β-D-glucopyranoside, 4,7,2'-trihydroxy-4'-methoxyisoflavanol, sissotrin, 1-methyl-β-D-glucopyranoside, ononin, D-mannitol, and 3-O-β-D-glucuronopyranosylsoyasapogenol B were isolated from Trifolium baccarinii. The MeOH, EtOAc, and n-BuOH extracts as well as biochanin A, formononetin, luteolin, luteolin-4'-O-β-D-glucopyranoside, 4,7,2'-trihydroxy-4'-methoxyisoflavanol, and sissotrin from Trifolium baccarinii displayed the highest antimicrobial and antioxidant activities. The MeOH extract and 4,7,2'-trihydroxy-4'-methoxyisoflavanol exhibited antibacterial activity through the bacteriolytic effect and reduction of the antioxidant defenses in the bacterial cells. The present study portrays Trifolium baccarinii as a potential natural source of antibacterial, antifungal, and antioxidant agents.

OBJECTIVE: We aimed to define the safety and toxicity of both isolated and embedded cinnamaldehyde using a pharmaceutical formulation for the treatment of oral fungal infections in an in vivo study. MATERIALS AND METHODS: Acute toxicity was assessed in studies with Galleria mellonella larvae and Danio rerio embryos (zebrafish), and genotoxicity was assessed in a mouse model. The pharmaceutical formulation (orabase ointment) containing cinnamaldehyde was evaluated for verification of both in vitro antifungal activity and toxicity in keratinized oral rat mucosa. RESULTS: In Galleria mellonella larvae, cinnamaldehyde was not toxic up to the highest dose tested (20 mg/kg) and presented no genotoxicity up to the dose of 4 mg/kg in the model using mice. However, it was found to be toxic in zebrafish embryos up to a concentration of 0.035 μg/mL; LC50 0.311; EC50 0.097 (egg hatching delay); and 0.105 (Pericardial edema). In the orabase antifungal susceptibility test, cinnamaldehyde exhibited activity in concentrations greater than 200 μg/mL. As for safety in the animal model with rats, the orabase ointment proved to be safe for use on keratinized mucosa up to the maximum concentration tested (700 μg/mL). CONCLUSIONS: At the concentrations tested, cinnamaldehyde was not toxic in vertebrate and invertebrate animal models and did not exhibit genotoxic activity. In addition, when used in the form of an ointment in orabase, having already recognized antifungal activity, it was shown to be safe up to the highest concentration tested.

Bone-anchored hearing systems (BAHS) transmit sound via osseointegrated implants behind the ear. They are used to treat patients with conductive or mixed hearing loss, but speech understanding may be limited especially in users with substantial additional cochlear hearing losses. In recent years, BAHS with higher maximum power output (MPO) and more advanced digital processing including loudness compression have become available. These features may be useful to increase speech understanding in users with mixed hearing loss. We have tested the effect of 4 combinations of two different MPO levels (highest level available and level reduced by 12 dB) and two different compression thresholds (CT) levels (50 dB and 65 dB sound pressure level) in 12 adult BAHS users on speech understanding in quiet and in noise. We have found that speech understanding in quiet was not influenced significantly by any of the changes in these two fitting parameters. In contrast, in users with average bone-conduction (BC) threshold of 25 dB or more, speech understanding in noise was improved by +0.8 dB to +1.1 dB (p < 0.03) when using the higher MPO level. In this user group, there may be an additional, but very small benefit of +0.1 dB to +0.4 dB when using the lower rather than the higher CT value, but the difference was not statistically significant (p > 0.27). In users with better average BC thresholds than 25 dB, none of the improvement was statistically significant. Higher MPOs and possibly, to a lesser degree, lower CTs seem to be able to improve speech understanding in noise in users with higher BC thresholds, but even their combined effect seems to be limited.

Emerging evidence suggests video-assisted health education being an effective way in promoting rehabilitation. The present study was aimed at evaluating the effectiveness of video-assisted health education in promoting rehabilitation training in postoperative OA patients and at comparing it with oral education. This study was a noncontemporaneous control study involving 179 patients who underwent TKA. For the intervention group, a bedside interactive system that recorded a series of educational videos showing a rehabilitation training program was established. For the control group, oral education having the same content as that in the videos for the intervention group was provided. After education, clinical outcomes such as occurrence of complications, circulating biomarkers of inflammation, and rehabilitation progress of the patients were obtained. Furthermore, job stress and burnout in nurses who participated in the present study were assessed. Results showed that C-reactive protein levels of patients were significantly lower in the intervention group than in the control group (84.54 ± 36.09 vs. 99.45 ± 31.73 mg/L, P = 0.004). Faster achievement of postoperative knee flexion to 90 degrees (21.31 ± 5.83 vs. 35.72 ± 9.93 h, P < 0.001) and first ambulation (19.91 ± 4.57 vs. 50.15 ± 7.00 h, P < 0.001), reduced number of postoperative complications such as postoperative orthostatic intolerance (7 vs. 19, P = 0.008) and constipation (10 vs. 23, P = 0.009), and reduced length of hospital stay (7.51 ± 1.79 vs. 8.21 ± 2.15 days, P = 0.019) in the intervention group in comparison to the control group were noted. Emotional exhaustion and burnout of nurses were reduced significantly in the intervention group than in the control group (21.00 ± 8.04 vs. 36.50 ± 11.22, P = 0.002; 55.90 ± 11.57 vs. 85.50 ± 6.80, P < 0.001, respectively). Reduced personal accomplishments in nurses were improved significantly in the intervention group when compared with the control group (41.90 ± 4.91 vs. 32.80 ± 7.07, P = 0.004). We concluded that video-assisted health education may promote TKA patient recovery and reduce burnout and stress in nurses when compared with oral education. Video-assisted health education could be helpful in situation where manpower of nurse is in shortage.

PURPOSE: An experimental and mathematical study for determining the effective point of measurement (P eff) for a Farmer-type cylindrical chamber in a carbon ion passive scatter beam is presented. METHODS: The ionization depth curves measured by the Bragg peak chamber were plotted according to the position of the inner surface of the entrance window, while the Farmer chamber was plotted at the tip of the cylindrical geometric center. The ionization depth curves measured by a cylindrical chamber in the 3D water phantom were then compared with a high-precision parallel-plate PTW Bragg peak chamber for inspecting the upstream shift correction of the cylindrical chamber in the carbon ion beam. A component of the vertical and horizontal integration method and the barrier model, cosφ = 1 - [2αR L /(1 + α - R L )], for analyzing the shift of effective point of measurement in different carbon ion energies and various field sizes, were studied. RESULTS: The shift between the maximum peak of the Bragg peak chamber and the Farmer chamber in a field size of 10 cm × 10 cm with an energy of 330 MeV/u of carbon ion is 2.3 mm. This upstream shift corresponds to (0.744 ± 0.07)r, where r is the Farmer chamber inner radius of 3.05 mm. Carbon ion energy from 120 MeV/u to 400 MeV/u with different field sizes show different shifts of effective point of measurement in a range of (0.649 ± 0.02)r to (0.843 ± 0.06)r of 3 cm × 3 cm at an energy of 400 MeV/u and 10 cm × 10 cm at an energy of 120 MeV/u, respectively. The vertical and horizontal scatter analysis by the barrier model can precisely describe the shift of the effective point of measurement at different carbon ion energies with various field sizes. CONCLUSIONS: We conclude that the Farmer chamber can be used for a patient-specific dose verification check in carbon ion beam treatment if P eff is well calibrated.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare vascular disease with a poor prognosis, and the mechanism of its development remains unclear. Further molecular pathology studies may contribute to a comprehensive understanding of IPAH and provide new insights into diagnostic markers and potential therapeutic targets. Iron deficiency has been reported in 43-63% of patients with IPAH and is associated with reduced exercise capacity and higher mortality, suggesting that dysregulated iron metabolism may play an unrecognized role in influencing the development of IPAH. In this study, we explored the regulatory mechanisms of iron metabolism in IPAH by bioinformatic analysis. The molecular function of iron metabolism-related genes (IMRGs) is mainly enriched in active transmembrane transporter activity, and they mainly affect the biological process of response to oxidative stress. Ferroptosis and fluid shear stress and atherosclerosis pathways may be the critical pathways regulating iron metabolism in IPAH. We further identified 7 key genes (BCL2, GCLM, MSMO1, SLC7A11, SRXN1, TSPAN5, and TXNRD1) and 5 of the key genes (BCL2, MSMO1, SLC7A11, TSPAN5, and TXNRD1) as target genes may be regulated by 6 dysregulated miRNAs (miR-483-5p, miR-27a-3p, miR-27b-3p, miR-26b-5p, miR-199a-5p, and miR-23b-3p) in IPAH. In addition, we predicted potential IPAH drugs-celastrol and cinnamaldehyde-that target iron metabolism based on our results. These results provide insights for further definition of the role of dysregulated iron metabolism in IPAH and contribute to a deeper understanding of the molecular mechanisms and potential therapeutic targets of IPAH.

OBJECTIVES: This study is aimed at exploring the relationships between miRNAs and mRNAs and to characterize their biological functions in temporal lobe epilepsy (TLE). METHODS: Novel clinical significant miRNAs and target genes and their potential underlying mechanisms have been discovered and explored by mining miRNAs and mRNA expression data of TLE patients using various bioinformatics methods. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the bioinformatic analysis results. RESULTS: A total of 6 dysregulated miRNAs and 442 differentially expressed genes (DEGs) related to TLE were obtained from GEO database (GSE114701 and GSE127871 datasets). A protein-protein interaction (PPI) network containing the 442 DEGs was established. mRNA response elements from the 6 dysregulated miRNAs were predicted using the miRDB and TargetScan bioinformatic tools. By merging the identified targets of the dysregulated miRNAs and the 247 downregulated DEGs, a miRNA-mRNA network was constructed revealing the interaction of miR-484 with eight mRNAs (ABLIM2, CEP170B, CTD-3193O13.9, EFNA5, GAP43, PRKCB, FXYD7, and NCAN). A weighted correlation network analysis (WGCNA) based on the eight genes was established and demonstrated that these mRNAs, except FXYD7 and NCAN, were hub genes in the network. Gene Oncology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that the six hub genes were mainly involved in cellular-related biological functions and the neurotransmitter synapse pathway. The differences in expression levels of the miR-484 and the three hub genes (CTD-3193O13.9, EFNA5, and PRKCB) observed experimentally in TLE patients compared to those of healthy controls were consistent with the WGCNA prediction. CONCLUSION: Our study suggests that understanding the miRNA-mRNA interactions will provide insights into the epilepsy pathogenesis. In addition, our results indicate that miR-484 may be a promising novel biomarker for TLE.

Macrophages are important immune cells that participate in the regulation of inflammation in implant dentistry, and their activation/polarization state is considered to be the basis for their functions. The classic dichotomy activation model is commonly accepted, however, due to the discovery of macrophage heterogeneity and more functional and iconic exploration at different technologies; some studies have discovered the shortcomings of the dichotomy model and have put forward the concept of alternative activation models through the application of advanced technologies such as cytometry by time-of-flight (CyTOF), single-cell RNA-seq (scRNA-seq), and hyperspectral image (HSI). These alternative models have great potential to help macrophages divide phenotypes and functional genes.

BACKGROUND: Incisional negative wound pressure therapy (iNPWT) is a relatively novel dressing technique with the aim of reducing postoperative wound infections and dehiscence in high-risk wounds after all kinds of surgical procedures. There is a lack of theoretical knowledge about the way those dressing would ameliorate wound healing. One aspect is the reduction of superficial tension, but significant remaining seroma might still cause deep wound infections. The aim of this study was the evaluation of technical modifications of the standard iNPWT dressing to increase seroma evacuation. METHODS: iNPWT dressings were applied on the porcine abdominal wall, and an incremental pressure ramp from 50 to 200 mmHg was performed. The resulting wound pressures were measured using (i) balloon manometry and (ii) esophageal manometry catheter. Seroma evacuation was analyzed with a seroma model. All measurements were performed with (i) standard iNPWT dressing, (ii) wound gauze diverted through the incision, and (iii) placement of suction drain tube into iNPWT. RESULTS: Due to the modifications of the iNPWT dressing, the vacuum applied by the iNPWT dressing could be transferred into the wound and was not only restricted to superficial layers. More importantly, placement of wound gauzes or suction drain tubes led to complete extraction of wound seroma. The placement of the suction drain tube showed the best combination of increased intrawound pressure as well as seroma evacuation. CONCLUSION: Addition of a suction drain tube to the iNPWT dressing leads to an improved function of the iNPWT dressing in our ex vivo model.

Immune checkpoint inhibitor (ICI) therapy may benefit patients with advanced esophageal squamous cell carcinoma (ESCC); however, novel biomarkers are needed to help predict the response of patients to treatment. Differentially expressed immune-related genes within The Cancer Genome Atlas ESCC dataset were selected using the weighted gene coexpression network and lasso Cox regression analyses. Based on these data, an immune-related gene prognostic index (IRGPI) was constructed. The molecular characteristics of the different IRGPI subgroups were assessed using mutation information and gene set enrichment analysis. Differences in immune cell infiltration and the response to ICI therapy and other drugs were also analyzed. Additionally, tumor and adjacent control tissues were collected from six patients with ESCC and the expression of these genes was verified using real-time quantitative polymerase chain reaction. IRGPI was designed based on CLDN1, HCAR3, FNBP1L, and BRCA2, the expression of which was confirmed in ESCC samples. The prognosis of patients in the high-IRGPI group was poor, as verified using publicly available expression data. KMT2D mutations were more common in the high-IRGPI group. Enrichment analysis revealed an active immune response, and immune infiltration assessment showed that the high-IRGPI group had an increased infiltration degree of CD8 T cells, which contributed to the improved response to ICI treatment. Collectively, these data demonstrate that IRGPI is a robust biomarker for predicting the prognosis and response to therapy of patients with ESCC.

BACKGROUND: Acute lung injury (ALI) is a fatal syndrome frequently induced by lipopolysaccharide (LPS) released from the bacterial cell wall. LPS could also trigger autophagy of lung bronchial epithelial cell to relieve the inflammation, while the overwhelming LPS would impair the balance of autophagy consequently inducing serious lung injury. METHODS: We observed the autophagy variation of 16HBE, human bronchial epithelial cell, under exposure to different concentrations of LPS through western blot, immunofluorescence staining, and electron microscopy. Eight strands of 16HBE were divided into two groups upon 1000 ng/ml LPS stimulation or not, which were sent to be sequenced at whole transcriptome. Subsequently, we analyzed the sequencing data in functional enrichment, pathway analysis, and candidate gene selection and constructed a hsa-miR-663b-related competing endogenous RNA (ceRNA) network. RESULTS: We set a series of concentrations of LPS to stimulate 16HBE and observed the variation of autophagy in related protein expression and autophagosome count. We found that the effective concentration of LPS was 1000 ng/ml at 12 hours of exposure and sequenced the 1000 ng/ml LPS-stimulated 16HBE. As a result, a total of 750 differentially expressed genes (DEGs), 449 differentially expressed lncRNAs (DElncRNAs), 76 differentially expressed circRNAs (DEcircRNAs), and 127 differentially expressed miRNAs (DEmiRNAs) were identified. We constructed the protein-protein interaction (PPI) network to visualize the interaction between DEGs and located 36 genes to comprehend the core discrepancy between LPS-stimulated 16HBE and the negative control group. In combined analysis of differentially expressed RNAs (DERNAs), we analyzed all the targeted relationships of ceRNA in DERNAs and figured hsa-miR-663b as a central mediator in the ceRNA network to play when LPS induced the variation of autophagy in 16HBE. CONCLUSION: Our research indicated that the hsa-miR-663b-related ceRNA network may contribute to the key regulatory mechanism in LPS-induced changes of autophagy and ALI.

Gramicidin is a thoroughly studied cation ionophore widely used to experimentally manipulate the plasma membrane potential (PMP). In addition, it has been established that the drug, due to its hydrophobic nature, is capable of affecting the organization of membrane lipids. We have previously shown that modifications in the plasma membrane potential of epithelial cells in culture determine reorganizations of the cytoskeleton. To elucidate the molecular mechanisms involved, we explored the effects of PMP depolarization on some putative signaling intermediates. In the course of these studies, we came across some results that could not be interpreted in terms of the properties of gramicidin as an ionic channel. The purpose of the present work is to communicate these results and, in general, to draw attention to the fact that gramicidin effects can be misleadingly attributed to its ionic or electrical properties. In addition, this work also contributes with some novel findings of the modifications provoked on the signaling intermediates by PMP depolarization and hyperpolarization.

BACKGROUND: People with multiple sclerosis (MS) suffer from symptoms related to neural control, such as reduced central activation, lower muscle activity, and accentuated spasticity. A forced 9-week home confinement related to COVID-19 in Spain may have worsened these symptoms. However, no study has demonstrated the impact of home confinement on neuromuscular mechanisms in the MS population. This study was aimed at analyzing the effects of a 9-week home confinement on central activation, muscle activity, contractile function, and spasticity in MS patients. METHODS: Eighteen participants were enrolled in the study. Left and right knee extensor maximum voluntary isometric contraction (MVIC), maximal neural drive via peak surface electromyography (EMG) of the vastus lateralis, central activation ratio (CAR), and muscle contractile function via electrical stimulation of the knee extensor muscles, as well as spasticity using the pendulum test, were measured immediately before and after home confinement. RESULTS: Seventeen participants completed the study. CAR significantly decreased after lockdown (ES = 1.271, p < 0.001). Regarding spasticity, there was a trend to decrease in the number of oscillations (ES = 0.511, p = 0.059) and a significant decrease in the duration of oscillations (ES = 0.568, p = 0.038). Furthermore, in the left leg, there was a significant decrease in the first swing excursion (ES = 0.612, p = 0.027) and in the relaxation index (ES = 0.992, p = 0.001). Muscle contractile properties, MVIC, and EMG variables were not modified after confinement. CONCLUSIONS: The results suggest that a home confinement period of 9 weeks may lead to an increase in lower limb spasticity and a greater deficit in voluntary activation of the knee extensors.

PURPOSE: The purpose of this study was to evaluate the effect of veneering and aging on the translucency of newly introduced extra and high translucent zirconia with different thickness. MATERIALS AND METHODS: One hundred forty disk-shaped specimens were fabricated from two translucent zirconia blocks (VITA YZ XT and VITA YZ HT), and they are milled with CAD/CAM system. Then, specimens were divided into nonveneered (XT, HT) and veneered groups (XTV, HTV). Nonveneered groups were prepared with four different thicknesses (0.5-1-1.5-2 mm). Veneered groups were divided into three subgroups (n = 10) for veneering with base dentin ceramic with thicknesses of 0.5 + 0.5, 0.5 + 1, and 0.5 + 1.5 mm. A spectrophotometer was used to calculate the translucency parameter (TP) and contrast ratio (CR) of all specimens before and after aging. Statistical analysis was performed using 3-way ANOVA and Tukey HSD tests (p < 0.05). RESULTS: TP values were significantly affected by thickness of specimens (p < 0.001). VITA YZ XT was significantly found more translucent than VITA YZ HT. The highest translucency was observed in the XT-0.5 mm group. There is no significant difference between translucency of the veneered and nonveneered groups in the same thickness for XT. On the contrary, veneering significantly affected translucency of HT. TP values significantly decreased after aging for all groups. After aging, translucency value difference before and after aging was the highest in the XT-0.5 mm group whereas the HTV-2 mm group showed the lowest difference after aging. TP decreased significantly as thickness of specimen increases regardless of the material type. Extra translucent and nonveneered zirconia groups are more prone to hydrothermal aging. CONCLUSIONS: The translucency parameter of zirconia ceramics was significantly influenced by both material type and veneering. Also, extra translucent and nonveneered zirconia groups are more susceptible to hydrothermal aging.

INTRODUCTION: We present a mathematical method to adjust the leaf end position for dose calculation correction in the carbon ion radiation therapy treatment planning system. METHODS AND MATERIALS: A straggling range algorism of 400 MeV/n carbon ion beam in nine different multileaf collimator (MLC) materials was conducted to calculate the dose 50% point to derive the offset corrections in the carbon ion treatment planning system (ciPlan). The visualized light field edge position in the treatment planning system is denoted as X tang.p, and MLC position (X mlc.p) is defined as the source to leaf end midpoint projection on axis for monitor unit calculation. The virtual source position of energy at 400 MeV/n and straggling range in MLC at different field sizes were used to calculate the dose 50% position on axis. On-axis MLC offset (correction) could then be obtained from the position corresponding to 50% of the central axis dose minus the X mlc.p. RESULTS: The exact MLC position in the carbon ion treatment planning system can be used as an offset to do the correction. The offset correction of pure tungsten is the smallest among the others due to its shortest straggling range of carbon ion beam in MLC. The positions of 50% dose of all MLC materials are always located in between X tang.p and X mlc.p under the largest field of 12 cm by 12 cm. CONCLUSIONS: MLC offset should be adjusted carefully at different field sizes in the treatment planning systems especially of its small penumbra characteristic in the carbon ion beam. It is necessary to find out the dose 50% position for adjusting MLC leaf edge on-axis location in the treatment planning system to reduce dose calculation error.

In IVF centers, risk assessment applies to complex processes potentially accounting for adverse events and reactions that undergo well-established legislative oversight, and nonconformances (NCs), that lack of established tracking systems. NCs account for an integral part of the quality management system, so that their documentation is important. The study evaluated the performance of a customized tool for incident reporting (IR) to track and characterize NCs in a public IVF center. IVF operators used the IVF-customized IR tool to record NCs at the moment of detection or subsequently, and in a time-saving manner during daily practice. From February 2015 to February 2020, 635 NCs were reported leading to the implementation of 10 operative instructions and 3 procedures with corrective strategies. NCs referred to the IVF laboratory were the most numerically meaningful (454/635, 71.5%). The majority (352/454, 77.5%) accounted for NCs related to procedures of sample management; considering the analytical phase as all the procedures involving sample treatment, the intra-analytical phase (176/352, 50%) has always been more subject to NCs compared to pre- (102/352, 29%) and postanalytical (74/352, 21%) phases. Our experience showed that the IVF-customized IR tool is suitable for application in IVF with regard to NC reports and documentation, as it identifies the most vulnerable steps of treatments. It manages NCs over the time, but it requires a contextual understanding of its application in order to avoid NC underestimates that could negatively influence the safety and quality aspects of IVF treatments.

BACKGROUND: Sepsis is prevalent among intensive care units and is a frequent cause of death. Several studies have identified individual risk factors or potential predictors of sepsis-associated mortality, without defining an integrated predictive model. The present work was aimed at defining a nomogram for reliably predicting mortality. METHODS: We carried out a retrospective, single-center study based on 231 patients with sepsis who were admitted to our intensive care unit between May 2018 and October 2020. Patients were randomly split into training and validation cohorts. In the training cohort, multivariate logistic regression and a stepwise algorithm were performed to identify risk factors, which were then integrated into a predictive nomogram. Nomogram performance was assessed against the training and validation cohorts based on the area under receiver operating characteristic curves (AUC), calibration plots, and decision curve analysis. RESULTS: Among the 161 patients in the training cohort and 70 patients in the validation cohort, 90-day mortality was 31.6%. Older age and higher values for the international normalized ratio, lactate level, and thrombomodulin level were associated with greater risk of 90-day mortality. The nomogram showed an AUC of 0.810 (95% CI 0.739 to 0.881) in the training cohort and 0.813 (95% CI 0.708 to 0.917) in the validation cohort. The nomogram also performed well based on the calibration curve and decision curve analysis. CONCLUSION: This nomogram may help identify sepsis patients at elevated risk of 90-day mortality, which may help clinicians allocate resources appropriately to improve patient outcomes.

The effect of neutrophil gelatinase-associated lipocalin (NGAL) on fetal hemoglobin (HbF) levels in diabetic patients is rarely investigated. This study is aimed at investigating the possible association between NGAL and HbF levels in type 2 diabetes mellitus (T2DM). A total of 160 patients with T2DM and 61 healthy individuals were evaluated. NGAL, HbF, tumor necrosis factor-α (TNF-α), interleukin-5 (IL-5), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and urine albumin levels were measured. HbF levels were significantly higher in patients with elevated NGAL than in those without elevated NGAL (1.44% versus 0.94%, P = 0.001). High HbF was 2.3 times more prevalent in patients with elevated NGAL than in those without elevated NGAL. In addition, NGAL, TNF-α, and IL-5 levels were significantly higher in patients with high HbF than in those with low HbF; however, there was no significant difference in HbA1c and FPG levels between the two groups. HbF was positively correlated with NGAL (r = 0.275, P < 0.001), TNF-α (r = 0.256, P < 0.001), and IL-5 (r = 0.212, P < 0.001), but not with HbA1c and FPG. An elevated NGAL level led to a 1.27-fold increase in the prevalence of high HbF (odds ratio: 1.27, 95% CI: 1.03-2.51, and P < 0.001). The diagnostic efficacy of NGAL to identify an elevated HbF level was superior to that of HbA1c (area under the curve: 0.697, 95% CI: 0.609-0.786 versus 0.584, 95% CI: 0.488-0.681, and P = 0.022). In conclusion, enhanced NGAL production may be closely linked to elevated HbF in conjunction with proinflammatory cytokines in patients with T2DM.

The development and optimization of controlled release lipospheres (LS) from safe biocompatible behenic acid (BA) was performed for not only enhancing patient's compliance against highly prevailed chronic diabetes but also to vanquish the insufficiencies of traditional methods of drug delivery. The Box-Bhenken design (BBD) was utilized to statistically investigate the impact of formulation variables on percentage yield (Y 1), entrapment efficiency (Y 2), and SG-release (Y 3) from saxagliptin- (SG-) loaded LS, and the chosen optimized LS were subjected to a comparative in vivo pharmacokinetic analysis against commercially available SG brand. The compatibility analysis performed by DSC and FTIR established a complete lack of interaction of formulation components with SG, while p-XRD suggested a mild transformation of crystalline drug to its amorphous form during encapsulation process. The spherical, free flowing smooth surface LS having zeta potential of -32 mV and size range of 11-20 μm were conveniently formulated. The obtained data for Y 1 (30-80%), Y 2 (30-70%), and Y 3 (40-90%) showed a best fit with quadratic model. The pharmacokinetics analysis of LS showed a significantly decreased C max of SG (75.63 ± 3.85) with a sufficiently elevated T max (10.53 h) as compared to commercial brand of SG (99.66 ± 2.97 ng/mL and 3.55 ± 2.18 h). The achievement of greater bioavailability of SG was most probably attributed to higher level of half-life, mean residence time (MRT), and AUC0-24 for SG released from LS. Conclusively, the novel approach of SG-loaded LS had successfully sustained the plasma SG level for a prolonged time without increasing C max which would ultimately bring an effective management of chronic diabetes.

Disease diagnosis faces challenges such as misdiagnosis, lack of diagnosis, and slow diagnosis. There are several machine learning techniques that have been applied to address these challenges, where a set of symptoms is applied to a classification model that predicts the presence or absence of a disease. To improve on the performance of these techniques, this paper presents a technique which involves feature selection using principal component analysis (PCA), a hybrid kernel-based support vector machine (HKSVM) classification model and hyperparameter optimization using genetic algorithm (GA). The HKSVM in this paper introduces a new way of combining three kernels: Radial basis function (RBF), linear, and polynomial. Combining local (RBF) and global (linear and polynomial) kernels has the effect of improved model performance. This is because the local kernels are better able to distinguish points closer to each other while the global kernels are more suited to distinguish points that are far away from each other. The PCA-GA-HKSVM is used on 7 different medical datasets, with two datasets being multiclass datasets and 5 datasets being binary. Performance evaluation metrics used were accuracy, precision, and recall. It was observed that the PCA-GA-HKSVM offered better performance than the single kernel support vector machines (SVMs).

BACKGROUND: Postoperative cognitive dysfunction (POCD) refers to disorders affecting orientation, attention, perception, consciousness, and judgment that develop after geriatric orthopedic surgery. Cerebral blood oxygen saturation detection is a way to diagnose cerebral oxygen supply during operation. At present, more and more applications are used for early diagnosis of postoperative cognitive function. Therefore, the present study is to analyze the relationship between postoperative cognitive dysfunction and cerebral blood oxygen saturation in elderly orthopedic patients. METHODS: This study enrolled 90 elderly patients undergoing orthopedic surgery in our hospital. According to the postoperative cognitive dysfunction, they were divided into POCD group (N = 45) and no-POCD (N = 45) group. The cognitive and psychological function and cerebral blood oxygen saturation were analyzed before and 3 months after the operation. Finally, the indicators of cognitive psychological function and the indicators of cerebral blood oxygen saturation are correlated and analyzed. RESULTS: Compared with the normal group, patients with cognitive dysfunction at 3 months after surgery time below preoperative rScO2, time below a 10% decrease from preoperative rScO2, CDL preoperative, minimum rScO2 value, and maximum rScO2 value have significant changes. The results of the correlation analysis found that there is also a significant correlation between the postoperative cognitive and psychological function of the patient and the cerebral blood oxygen saturation at 3 weeks after the operation. CONCLUSION: In elderly orthopedic patients, there is a significant relationship between cerebral blood oxygen saturation detection and cognitive function 3 months after surgery.

OBJECTIVE: This study is aimed at teasing out the correlation of plasma D-dimer (D-D) levels to age, metastasis, TNM stage (tumor-node-metastasis classification), and treatment in non-small-cell lung cancer (NSCLC) patients of different ages, to facilitate early diagnosis of hypercoagulable state, choose appropriate treatment, and use appropriate anticoagulants. Hence, thrombosis and complications caused by excessive anticoagulants can be prevented; thrombus or disseminated intravascular coagulation (DIC) and other complications in elderly patients with NSCLC can be reduced or avoided. By monitoring the level of plasma D-D in patients with NSCLC, recurrence and metastasis can be predicted in the early stage and the TNM stage can be evaluated. METHODS: A total of 670 patients with NSCLC were selected in Shanxi Bethune Hospital from March 2014 to October 2020 as the experimental group, and 950 healthy people were selected from the physical examination center of the same hospital as the control group. The data of patients with NSCLC diagnosed for the first time without any treatment were collected and grouped based on metastasis, TNM stage, treatment, and pathological type, and the correlation with plasma D-D level was analyzed. Plasma D-D levels were measured by immunoturbidimetry on an ACL TOP 700 Automatic Coagulation Analyzer. The patients were further divided into two groups according to different treatment methods, and the differences in plasma D-D levels between patients receiving chemotherapy and those receiving targeted therapy in different treatment cycles were analyzed. The correlation between D-D levels and age in healthy controls was analyzed. The difference in D-D levels between NSCLC patients and healthy controls of the same age was analyzed. RESULTS: All data of both the experimental group and the control group were normally distributed. The average age of the experimental group was 61.31 ± 6.23 (range: 36-92) years. The average age of the control group was 61.14 ± 11.12 (range: 35-85) years. There was no significant difference in gender between the experimental group and the control group (p > 0.05). The plasma D-D level of NSCLC patients was significantly higher than that of the healthy controls (p < 0.05). No significant difference in plasma D-D level was found between NSCLC patients of different genders, and the finding was similar between healthy controls of different genders (p > 0.05). Significant difference in the D-D level was found between the groups of 30-59 years and 60-69 years (p < 0.05), between groups of 60-69 years and 70-79 years (p < 0.05), and between 70-79 years and ≥80 years (p < 0.05). The plasma D-D level of patients ≤ 79 years old increased with age, but it decreased in those over 80 years old. According to Pearson correlation analysis, there was a positive correlation between the D-D level and the age of NSCLC patients under 79 years old (p < 0.05). The differences in D-D levels between the four age groups were statistically significant (p < 0.05), showing an upward trend of the D-D level in healthy controls with the increase of age. There were statistically significant differences in D-D levels between NSCLC patients and healthy controls of the matching age group (p < 0.05), suggesting that NSCLC patients had significantly higher D-D levels than healthy people of the same age group. The differences in D-D levels between NSCLC patients without metastasis, NSCLC patients with metastasis, and healthy people were statistically significant (p < 0.05). The patients with metastasis had the highest D-D level, and healthy people had the lowest D-D level. The difference in plasma D-D levels between patients of different TNM stages was statistically significant (p < 0.05). Patients with an advanced TNM stage tended to have higher D-D levels. The TNM stage and D-D level of NSCLC patients changed significantly before and after treatment. An earlier stage was related to a more obvious change in D-D levels after treatment with a statistically significant difference (p < 0.05). A more advanced stage was associated with a smaller change in the D-D level after treatment, with no statistically significant difference (p > 0.05). The plasma D-D levels before and after four cycles of chemotherapy or targeted therapy were higher than those of the healthy control group, and the differences were statistically significant (p < 0.05). The D-D level of patients after chemotherapy was significantly lower than that before chemotherapy (p < 0.05), but there was no significant difference before and after targeted therapy (p > 0.05). The D-D level after the first cycle of chemotherapy was higher than that before chemotherapy. The level of D-D after the third and fourth cycles was significantly lower than that before chemotherapy (p < 0.05). No significant difference was found between the D-D level before treatment and that after four cycles of chemotherapy (p > 0.05). CONCLUSION: It is suggested that coagulation test indexes should be included to evaluate the treatment regimen for NSCLC patients. Most patients with NSCLC are in a hypercoagulable state, which is related to age, tumor invasion and metastasis, recurrence, and treatment. Regular monitoring of plasma D-D levels can facilitate early diagnosis of a hypercoagulable state and timely and appropriate use of anticoagulants, to avoid or reduce complications such as venous thromboembolism in NSCLC patients and to prevent the risk of bleeding caused by excessive anticoagulants. Clinicians can choose the treatment with less harm and maximum benefit for NSCLC patients based on the plasma D-D level. When in a hypercoagulable state, the body's blood viscosity increases, making it more conducive to the growth and infiltration of tumor cells. Our study shows that the recurrence and metastasis of NSCLC are related to coagulation indexes, which provides a theoretical basis for the early diagnosis and treatment of recurrent and metastatic NSCLC.

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults with poor prognosis. Especially for AML-M5 type, due to the strong cell migration ability, the possibility of extramedullary invasion is large and widespread, which leads to poor therapeutic effect. Previous studies have found that protein arginine methyltransferase 5 (PRMT5) could promote the proliferation and differentiation of leukemic cells in AML, but its regulation on the invasive ability of AML cells remains unclear. This study was designed to explore the role of PRMT5 in regulating the invasion of AML cells and to investigate the mechanisms. Patient samples were collected for detection of PRMT5 expression level. AML cells were used for exploring the function of PRMT5. The results of clinical samples showed that the expression of PRMT5 was significantly increased in newly diagnosed and recurrent AML patients, and the expression of leukocyte immunoglobulin-like receptor B4 (LILRB4) was positively correlated with the level of PRMT5. In the cell experiment in vitro, we found that when PRMT5 was knocked down, the invasion, migration, and adhesion capacities of MV-4-11 cells and THP-1 cells were decreased, and the mRNA and protein levels of LILRB4 were also decreased. Moreover, we screened related signaling pathways and found that PRMT5 affected the expression of downstream LILRB4 by activating mTOR pathway, which in turn enhanced the invasive ability of AML cells. Taken together, PRMT5 plays an important role in the invasion of AML, which acts via regulating the expression of LILRB4. PRMT5 could act as a potential therapeutic candidate for AML.

BACKGROUND: Control and prevention activities have brought substantial decline of malaria incidence in the last two decades in Ethiopia. However, lack of local data on the disease transmission and community knowledge, attitude, and practice about malaria are thought to reverse the trend of malaria in certain areas. Therefore, assessment of the prevalence and community awareness towards malaria plays pivotal role for the success of malaria control and prevention. OBJECTIVE: To assess malaria prevalence and knowledge, attitude, and practice about malaria among febrile patients in Bahir Dar Zuria district, Northwest Ethiopia. METHODS: A facility based crosssectional study was conducted from January to March 2020 among 149 febrile patients attending selected health centers in Bahir Dar Zuria district. Data about knowledge, attitude, and practice about malaria were collected using semistructured questionnaire. Blood sample from each participant was tested for Plasmodium species through malaria rapid diagnostic tests and blood film microscopy. Data were analyzed using statistical software for social sciences version 20. RESULTS: Among 149 participants, 22 (14.8%) were positive for Plasmodium infection at least by one diagnostic methods. Prevalence of P. falciparum and P. vivax was 3.4% and 10.1%, respectively, while that of mixed infection was 1.3%. From the total study participants, 29.5% have good knowledge, 77.2% have positive attitude, and 34.9% have good practice towards malaria. Statistically significant associations were observed on knowledge with age group (X 2 = 10.377, P = 0.035), educational level (X 2 = 15.075, P = 0.001), family size (X 2 = 7.601, P = 0.022), attitude level and practice level. Participants with family size < 5 were 6.841 (95% CI: 2.570-18.206, P ≤ 0.001) times more likely to have negative attitude as compared to those with family size ≥ 5. CONCLUSIONS: Prevalence of malaria in the study area was relatively high. Study participants had encouraging attitude; however, their knowledge and practice towards malaria were poor. Therefore, the existing malaria control activities should be supplemented with continuous health educations, aware the community, and ensure participation in the control and prevention activities.

BACKGROUND: The relationship between uncoupling protein (UCP) 1-3 polymorphisms and susceptibility to type 2 diabetes mellitus (T2DM) has been extensively studied, while conclusions remain contradictory. Thus, we performed this meta-analysis to elucidate whether the UCP1-3826A/G, UCP2-866G/A, Ala55Val, and UCP3-55C/T polymorphisms are associated with T2DM. METHODS: Eligible studies were searched from PubMed, Cochrane Library, and Web of Science database before 12 July 2020. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Heterogeneity analysis, subgroup analysis, sensitivity analysis, and publication bias were also performed. RESULTS: A total of 38 case-control studies were included in this meta-analysis. The overall results revealed significant association between T2DM and the UCP2 Ala55Val polymorphism (recessive model: OR = 1.25, 95% CI 1.12-1.40, P < 0.01; homozygous model: OR = 1.33, 95% CI 1.03-1.72, P = 0.029, respectively). In subgroup analysis stratified by ethnicity, T2DM risk was increased with the UCP2 Ala55Val polymorphism (allele model: OR = 1.17, 95% CI 1.02-1.34, P = 0.023; recessive model: OR = 1.28, 95% CI 1.13-1.45, P < 0.01; homozygous model: OR = 1.39, 95% CI 1.05-1.86, P = 0.023, respectively), while decreased with the UCP2-866G/A polymorphism in Asians (dominant model: OR = 0.86, 95% CI 0.74-1.00, P = 0.045). CONCLUSIONS: Our results demonstrate that the UCP2-866G/A polymorphism is protective against T2DM, while the UCP2 Ala55Val polymorphism is susceptible to T2DM in Asians.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders. Amphetamine addiction may cause serious of psychotic and physical damage to humans. There is some evidence that shows that amphetamine may increase the risk of PD. Thus, this study is aimed at comparing the PD serum biomarkers between amphetamine addicts and PD patients and utilizing them as diagnostic biomarkers for the early detection of PD incidence among amphetamine addicts. In the current study, nineteen amphetamine addicts, aged <40, were recruited from the Al Amal Psychiatric hospital, Jazan, Saudi Arabia. Nineteen PD patients and 19 healthy controls, who have never taken amphetamine, were also recruited. Blood samples were withdrawn from all groups. A biomarker multiplex assay from MILLIPLEX was used to assess the levels of serum amyloid-P (SAP), complement C4, C-reactive protein (CRP), and CRP/albumin ratio in serum samples (Vitros 350® slide was used to assess the albumin). All data were statistically analyzed using one-way ANOVA. The results showed that SAP and CRP levels were significantly higher in amphetamine addicts compared to healthy controls (p = 0.0001 and p = 0.0001, respectively). The results of amphetamine addicts were comparable to PD levels. However, there are no significant differences between all studied groups concerning complement C4 level. Moreover, albumin levels were significantly decreased and CRP/Albumin ratio levels were significantly increased in amphetamine addicts (p = 0.01 and p = 0.041, respectively) in contrast with controls. These findings indicate that the increased level of these inflammatory biomarkers (SAP and CRP) in the amphetamine addicts may give a potential possibility of their serum level to be used as screening markers to detect PD development in the amphetamine addict. It may be useful to evaluate the changes in easily accessible and cost-effective parameters such as the serum CRP/albumin ratio.

Shanlan upland rice, a kind of unique rice germplasm in Hainan Island, was used to evaluate genetic diversity and association between SSR markers and agronomic traits. A total of 239 alleles were detected in 57 Hainan upland rice varieties using 35 SSR markers, and the number of alleles per locus was 2-19. The observed heterozygosity was 0.0655-0.3115. The Shannon diversity index was 0.1352-0.4827. The genetic similarity coefficient was 0.6736-0.9707, and 46 varieties were clustered into one group, indicating that the genetic base of the Shanlan upland rice germplasm was narrow. A total of 25 SSR markers significantly related to plant height, effective panicle number per plant, panicle length, total grain number, filled grain number, seed rating rate, and 1000-grain weight were obtained (P < 0.01), with the percentage of the total variations explained ranging from 0.12% to 42.62%. RM208 explained 42.62% of the total variations in plant height of Shanlan upland rice. RM493 was significantly associated with 6 agronomic traits. We can speculate that RM208 may flank QTLs responsible for plant height and RM493 may flank QTLs playing a fundamental role in the intertwined regulatory network of agronomic traits of Shanlan upland rice.

Plukenetia volubilis Linneo (P. volubilis), or Sacha inca, is an oleaginous plant from the Euphorbiaceae family. The presence of terpenoids, saponins, tannins, glycosides, phytosterols, and phenolic compounds in the ethanol extracts of P. volubilis L leaves has been reported, showing a range of bioactivities including antimicrobial, anti-inflammatory, antioxidant, and analgesia. However, the safety of this plant has not yet been reported explicitly. This study thus is aimed at evaluating the toxicity of the ethanol extract of P. volubilis leaves (EtPV) by acute and subchronic toxicity tests in Swiss albino mice following standard procedures set by The Organization for Economic Cooperation and Development (OECD) with slight modifications. In the acute toxicity test, the treatment groups were administered orally with the EtPV at doses of 1000, 3000, 5000, and 7000 mg/kg body weight in small fractions during 16 hours, and the mice were then observed in 14 consecutive days. In the subchronic toxicity study, the EtPV was given at doses of 100, 300, 500, and 700 mg/kg body weight for 90 days. Changes in behavior, mortality rate, and body and the weights of vital organs, hematology, clinical biochemistry, urine analysis, and histologic morphology were evaluated. The acute toxicity study showed that the EtPV causes no sign of toxicity or mortality. The hematological, biochemical and urine analyses, changes in the weight of the body and vital organs (heart, liver and kidney), and histopathological analyses of organs indicated no evidence of toxicity at any doses. It was also revealed that oral administration of EtPV is safe at the oral doses set by acute and subchronic toxicity tests, and the oral lethal dose for the EtPV is higher than 7000 mg/kg. This study is the first to confirm the safety of P. volubilis leaf ethanol extract, and as a result, encouraging further investigation to examine EtPV potential for traditional medicine.

BACKGROUND: Small-cell lung cancer (SCLC) is a major cause of carcinoma-related deaths worldwide. The aim of this study was to identify the key biomarkers and pathways in SCLC using biological analysis. METHODS: Key genes involved in the development of SCLC were identified by downloading three datasets from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using the GEO2R online analyzer; for the functional annotation and pathway enrichment analysis of genes, Funrich software was used. Construction of protein-to-protein interaction (PPI) networks was accomplished using the Search Tool for the Retrieval of Interacting Genes (STRING), and network visualization and module identification were performed using Cytoscape. RESULTS: A total of 268 DEGs were ultimately obtained. The enriched functions and pathways of the upregulated DEGs included cell cycle, mitotic, and DNA replication, and the downregulated DEGs were enriched in epithelial-to-mesenchymal transition, serotonin degradation, and noradrenaline. Analysis of significant modules demonstrated that the upregulated genes are primarily concentrated in functions related to cell cycle and DNA replication. Kaplan-Meier analysis of hub genes revealed that they may promote the carcinogenesis and progression of SCLC. The result of ONCOMINE demonstrated that these 10 hub genes were significantly overexpressed in SCLC compared with normal samples. CONCLUSION: Identification of the molecular functions and signaling pathways of participating DEGs can deepen the current understanding of the molecular mechanisms of SCLC. The knowledge gained from this work may contribute to the development of treatment options and improve the prognosis of SCLC in the future.

The objective of this study was to explore the therapeutic effects of berberine on necrotic enteritis (NE) in broilers caused by Clostridium perfringens. A total of 240 1-day-old Arbor Acres chicks were divided into four groups, as negative controls (NC), positive controls (PC), berberine- (BER-) treated, or lincomycin- (LMY-) treated groups. Broilers were challenged with C. perfringens at 15-21 days of age, followed by BER or LMY supplied in drinking water for 7 days. Experimental results showed that C. perfringens infection significantly decreased growth performance and increased intestinal necrosis index and the number of C. perfringens present to 6.45 Log10CFU/g (P < 0.001). Proinflammatory cytokines in the ileum were significantly increased, but the expression of ileal tight junction proteins occludin and claudin-1 was significantly reduced. Both BER and LMY ameliorated some of these observations. Compared with the PC group, the number of C. perfringens in the cecum was significantly decreased following treatment (P < 0.001), and growth performance and small intestine morphology were similar to those of the NC group (P > 0.05). IL-1β, IL-6, and TNF-α levels as well as occludin and claudin-1 expression were also significantly improved (P < 0.05). BER has the potential to replace antibiotics for NE caused by C. perfringens.

Acute pancreatitis (AP) is an inflammatory disease of the pancreas. The severity is classified as mild (MAP), moderately severe (MSAP), or severe (SAP). In patients with SAP, organ dysfunction can occur in the early stage of the disease course, accompanied by secondary infection, with a mortality rate of 36%-50%. In the late stage SAP, infection-related complications caused by pancreatic necrotic tissue and peripancreatic effusion are the main causes of death in patients. Dysbacteriosis of intestinal microflora, barrier dysfunction of intestinal mucosa, and translocation of enteric bacteria are considered to be the main causes of infection of pancreatic necrotic tissue and peripancreatic effusion. During the past few years, increasing attention has been paid to the metabolic activities of intestinal microflora in SAP, which plays an important role in the metabolic activities of the human body. This review is aimed at bringing together the most recent findings and advances regarding the gut microbial community and associated gut microbial community metabolites and illustrating the role of these metabolites in disease progression in severe acute pancreatitis. We hope that this review will provide new ideas and schemes for the treatment of SAP in the clinical settings.

The human transmembrane protease serine 2 (TMPRSS2) protein plays an important role in prostate cancer progression. It also facilitates viral entry into target cells by proteolytically cleaving and activating the S protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the current study, we used different available tools like SIFT, PolyPhen2.0, PROVEAN, SNAP2, PMut, MutPred2, I-Mutant Suite, MUpro, iStable, ConSurf, ModPred, SwissModel, PROCHECK, Verify3D, and TM-align to identify the most deleterious variants and to explore possible effects on the TMPRSS2 stability, structure, and function. The six missense variants tested were evaluated to have deleterious effects on the protein by SIFT, PolyPhen2.0, PROVEAN, SNAP2, and PMut. Additionally, V160M, G181R, R240C, P335L, G432A, and D435Y variants showed a decrease in stability by at least 2 servers; G181R, G432A, and D435Y are highly conserved and identified posttranslational modifications sites (PTMs) for proteolytic cleavage and ADP-ribosylation using ConSurf and ModPred servers. The 3D structure of TMPRSS2 native and mutants was generated using 7 meq as a template from the SwissModeller group, refined by ModRefiner, and validated using the Ramachandran plot. Hence, this paper can be advantageous to understand the association between these missense variants rs12329760, rs781089181, rs762108701, rs1185182900, rs570454392, and rs867186402 and susceptibility to SARS-CoV-2.

The COVID-19 epidemic is spreading day by day. Early diagnosis of this disease is essential to provide effective preventive and therapeutic measures. This process can be used by a computer-aided methodology to improve accuracy. In this study, a new and optimal method has been utilized for the diagnosis of COVID-19. Here, a method based on fuzzy C-ordered means (FCOM) along with an improved version of the enhanced capsule network (ECN) has been proposed for this purpose. The proposed ECN method is improved based on mayfly optimization (MFO) algorithm. The suggested technique is then implemented on the chest X-ray COVID-19 images from publicly available datasets. Simulation results are assessed by considering a comparison with some state-of-the-art methods, including FOMPA, MID, and 4S-DT. The results show that the proposed method with 97.08% accuracy and 97.29% precision provides the highest accuracy and reliability compared with the other studied methods. Moreover, the results show that the proposed method with a 97.1% sensitivity rate has the highest ratio. And finally, the proposed method with a 97.47% F1-score rate gives the uppermost value compared to the others.

INTRODUCTION: Fracture-related infection (FRI) is a severe musculoskeletal complication in orthopedic trauma surgery, causing challenges in bony and soft tissue management. Currently, negative-pressure wound therapy (NPWT) is often used as temporary coverage for traumatic and surgical wounds, also in cases of FRI. However, controversy exists about the impact of NPWT on the outcome in FRI, specifically on infection recurrence. Therefore, this systematic review qualitatively assesses the literature on the role of NPWT in the management of FRI. METHODS: A literature search of the PubMed, Embase, and Web of Science database was performed. Studies that reported on infection recurrence related to FRI management combined with NPWT were eligible for inclusion. Quality assessment was done using the PRISMA statement and the Newcastle-Ottawa Quality Assessment Scale. RESULTS: After screening and quality assessment of 775 unique identified records, eight articles could be included for qualitative synthesis. All eight studies reported on infection recurrence, which ranged from 2.8% to 34.9%. Six studies described wound healing time, varying from two to seven weeks. Four studies took repeated microbial swabs during subsequent vacuum dressing changes. One study reported newly detected pathogens in 23% of the included patients, and three studies did not find new pathogens. CONCLUSION: This review provides an assessment of current literature on the role of NPWT in the management of soft tissue defects in patients with FRI. Due to the lack of uniformity in included studies, conclusions should be drawn with caution. Currently, there is no clear scientific evidence to support the use of NPWT as definitive treatment in FRI. At this stage, we can only recommend early soft tissue coverage (within days) with a local or free flap. NPWT may be safe for a few days as temporarily soft tissue coverage until definitive soft tissue management could be performed. However, comparative studies between NPWT and early wound closure in FRI patients are needed.

Endometrial adenocarcinoma is one of the most prevalent female reproductive tract cancers in the world, and the development of effective treatment is still the main goal of its current research. Epithelial-mesenchymal transition (EMT) plays a significant part in the occurrence and development of epithelial carcinoma, including endometrial adenocarcinoma. Recepteur d'origine nantais (RON) induces EMT and promotes proliferation, migration, and invasion in various epithelial-derived cancers, but its role in endometrial adenocarcinoma is still poorly studied. The purpose of this study is to verify the overexpression of RON in endometrial adenocarcinoma and to explore its specific roles. RON expression in tumor lesions was verified by immunohistochemical staining, HEC-1B cells were used to construct stable cell lines with RON overexpression or knockdown to investigate the effects of RON on the function of endometrial adenocarcinoma cells, and xenotransplantation experiment was carried out in nude mice to explore the effect of RON on the growth of endometrial adenocarcinoma in vivo. This study revealed that RON could promote the proliferation, migration, and invasion of HEC-1B cells and induce EMT, and these effects were regulated through the Smad pathway. RON overexpression could promote growth of endometrial adenocarcinoma cells in nude mice, while its inhibitor BMS777607 could restrict this role. RON played an important role in endometrial adenocarcinoma and had a potential to become a new therapeutic target for endometrial adenocarcinoma.

The ascendancy of coronavirus has become widespread all around the world. For the prevention of viral transmission, the pattern of disease is explored. Epidemiological modeling is a vital component of the research. These models assist in studying various aspects of infectious diseases, such as death, recovery, and infection rates. Coronavirus trends across several countries may analyze sufficiently using SIR, SEIR, and SIQR models. Across this study, we propose two modified versions of the SEIRD method for evaluating the transmission of this infectious disease in the South Asian countries, more precisely, in the south Asian subcontinent. The SEIRD model is updated further by fusing some new factors, namely, isolation for the suspected people and recovery and death of the people who are not under the coverage of healthcare schemes or reluctant to receive treatment for various catastrophes. We will investigate the influences of those ingredients on public health-related issues. Finally, we will predict and display the infection scenario and relevant elements with the concluding remarks through the statistical analysis.

Insomnia is an ordinary situation related to noticeable disability in function and quality of life, mental and actual sickness, and mishappenings. It represents more than 5.5 million appointments to family doctors every year. Nonetheless, the ratio of insomniacs who are treated keeps on being low, demonstrating the requirement for proceeding with advancement and dispersal of effective treatments. Accordingly, it becomes significant to provide a compelling treatment for clinical practice. It indicates a need for the determination of various critical viewpoints for the evaluation of insomnia along with various accessible alternatives for treatment. These alternatives incorporate both nonpharmacological therapy, specifically cognitive behavioural therapy for insomnia, and a number of pharmacological treatments like orexin antagonists, "z-drugs," benzodiazepines, selective histamine H1 antagonists, nonselective antihistamines, melatonin receptor agonists, antipsychotics, antidepressants, and anticonvulsants. Besides in individuals whose insomnia is due to restless leg syndrome, depression/mood disorder, or/and circadian disturbance, there is insignificant proof favouring the effectiveness of different prescriptions for the treatment of insomnia though they are widely used. Other pharmacological agents producing sedation should be prescribed with care for insomnia therapy because of greater risk of next-day sleepiness along with known adverse effects and toxicities. This review is also aimed at providing an update on various patents on dosage forms containing drugs for insomnia therapy.

Students have unique preferences when it comes to knowledge acquisition, information processing, retention in memory, and recall. This study is aimed at examining the preferred learning styles of medical and dental undergraduate students of Pakistan. It is also aimed at investigating the influence of gender, preclinical or clinical academic year, and academic record on the preferred learning style. A descriptive cross-sectional study was conducted in Pakistan. The learning styles of undergraduate students were identified using visual, aural, read/write, and kinesthetic (VARK) questionnaire. Students were also asked about their satisfaction towards teaching style of their teachers in institute. Descriptive statistics were done to characterize the learning styles of the students. The Fisher test and chi-square test were used to compare the learning preferences between genders and public/private sector students and among preclinical/clinical years. A p value of less than 0.05 was considered significant. A total of 1473 students participated in the study. Among the students, 39.37% preferred unimodal learning style whereas 60.62% preferred multimodal style. Kinesthetic (K) and visual (V) were the most preferred unimodal styles. The preferred learning styles of female students are aural (A), visual (V), and kinesthetic (K), whereas male students preferred visual (V) and kinesthetic more (K). Students with lower academic record chose unimodal styles in comparison to high achievers that chose multimodal styles. Students of clinical year preferred multimodal and quadmodal styles in comparison to preclinical year students. An alarming 78% of students were dissatisfied with their teacher's instructional style. Majority of students prefer multimodal learning styles over unimodal style. Gender, public/private sector, and academic record have influence on the preference of learning styles. Majority of the students are dissatisfied with their teacher's instructional style and rely on social media platforms for understanding. Academics need to adapt their teaching methods according to student preferences in order to get better graduates.

Interleukin-18 (IL-18) is an inflammatory cytokine that has been linked to energy homeostasis and psychiatric symptoms such as depression and cognitive impairment. We previously revealed that deficiency in IL-18 led to hippocampal abnormalities and resulted in depression-like symptoms. However, the impact of IL-18 deficiency on other brain regions remains to be clarified. In this study, we first sought to confirm that IL-18 expression in neural cells can be found in human brain tissue. Subsequently, we examined the expression of genes in the prefrontal cortex of Il18 -/- mice and compared it with gene expression in mice subjected to a chronic mild stress model of depression. Extracted genes were further analyzed using Ingenuity® Pathway Analysis, in which 18 genes common to both the chronic mild stressed model and Il18 -/- mice were identified. Of those, 16 were significantly differentially expressed between Il18+/+ and Il18 -/- mice. We additionally measured protein expression of α-2-HS-glycoprotein (AHSG) and transthyretin (TTR) in serum and the brain. In the prefrontal cortex of Il18 -/- mice, TTR but not AHSG was significantly decreased. Conversely, in the serum of Il18 -/- mice, AHSG was significantly increased but not TTR. Therefore, our results suggest that in IL-18-deficit conditions, TTR in the brain is one of the mediators causally related to depression, and AHSG in peripheral organs is one of the regulators inducing energy imbalance. Moreover, this study suggests a possible "signpost" to clarify the molecular mechanisms commonly underlying the immune system, energy metabolism, neural function, and depressive disorders.

Neutrophil cytoplasmic factor 1/2/4 (NCF1/2/4) belongs to the NADPH oxidase complex, which is a cytoplasmic component, and its polymorphism is the main factor related to autoimmune diseases, which is probably caused by the regulation of peroxide. They also play a role in tumor growth and metastasis. This research is aimed at evaluating the biological function and prognostic role of NCF1, NCF2, and NCF4 genes in kidney renal clear cell carcinoma (KIRC) by using multiple online bioinformatics website, including Oncomine, GEPIA, UALCAN, Kaplan-Meier Plotter, TIMER, TISIDB, cBioPortal, LinkedOmics, GeneMANIA, and DAVID databases. The mRNA levels of NCFs were higher in KIRC tissues than in normal tissues. The overexpression of NCFs was significantly correlated with advanced pathological grades and individual cancer stages in KIRC. Meanwhile, the expressions of NCFs played an important role in the tumorigenesis and progression of KIRC. Prognostic value analysis suggested that high transcription levels of NCF1/4 were associated with poor overall survival in KIRC patients. In addition, results from the LinkedOmics database showed that the KEGG pathway related to NCFs mainly focused on immune activation and immune regulation function. NCF genetic alterations, including copy number amplification, missense mutation, and deep deletion, could be found through the cBioPortal database. Further, NCF expression was significantly correlated with infiltration levels of various immune cells as well as immune signatures. Protein-protein interaction network and enrichment analysis of NCF1/2/4 in KIRC showed that NCF coexpressed genes mainly associated with diverse immune marker sets showed significance. Overall, these results indicated that NCFs could be prognostic biomarkers as well as effective targets for diagnosis in KIRC.

Diabetic gastroparesis (DGP) is a serious and chronic complication of long-standing diabetes mellitus, which brings a heavy burden to individuals and society. Traditional Chinese medicine (TCM) is considered a complementary and alternative therapy for DGP patients. Huanglian (Coptidis Rhizoma, HL) and Banxia (Pinelliae Rhizoma, BX) combined as herb pair have been frequently used in TCM prescriptions, which can effectively treat DGP in China. In this article, a practical application of TCM network pharmacological approach was used for the research on herb pair HL-BX in the treatment of DGP. Firstly, twenty-seven potential active components of HL-BX were screened from the TCMSP database, and their potential targets were also retrieved. Then, the compound-target network and PPI network were constructed from predicted common targets, and several key targets were found based on the degree of the network. Next, GO and KEGG enrichment analyses were conducted to obtain several significantly enriched terms. Finally, the experimental verification was made. The results demonstrated that network pharmacological approach was a powerful means for identifying bioactive ingredients and mechanisms of action for TCM. Network pharmacology provided an effective strategy for TCM modern research.

Bombyxin, as an insulin-like insect hormone, was discovered in the silkmoth Bombyx mori. It can regulate the metabolism of trehalose and glycogen in Bombyx mori, but whether it has glucose absorption and glycogen synthesis effect on mammalian cells was not clear. BombyxinII (BbxII) and mutant BbxII (mBbxII) genes were cloned into pcDNA3.1(+) vector, respectively; then, gene vectors were transfected into 293FT cells using Lipofectamine 2000. Levels of mRNA and protein expression of BbxII and mBbxII were detected by PCR and Western blot in 293FT cells, respectively. Glucose consumption and glycogenesis were determined by glucose oxidase-peroxidase (GOD-POD) and periodic acid-Schiff (PAS) staining in HepG2 cells; the PI3K signaling pathway was inhibited with wortmannin S1952 in HepG2 cells. Result showed that BbxII and mBbxII genes were being successfully expressed in 293FT cells, respectively. The expression protein of BbxII gene is 10kd pre-bombyxinII, and yet, the expression protein of mBbxII gene is 4kd mature bombyxinII. Only the 4kd bombyxinII showed increased glucose uptake and glycogenesis in HepG2 cells, and the ability of increasing glucose uptake was equal to the human insulin (10 nM). PI3K-wortmannin S1952 inhibitor can decrease the glycogen synthesis induced by bombyxin II protein in HepG2 cells. In conclusion, mature bombyxin II may adjust glucose absorption and glycogen synthesis in HepG2 cells through the PI3K signaling pathway.

Ferroptosis is a mode of regulated cell death that depends on iron and plays pivotal roles in regulating various biological processes in human cancers. However, the role of ferroptosis in gastric cancer (GC) remains unclear. In our study, a total of 2721 differentially expressed genes (DEGs) were filtered based on The Cancer Genome Atlas (TCGA) (n = 375) dataset. Weighted gene coexpression network (WGCNA) analysis was then used and identified 7 modules, of which the blue module with the most significant enrichment result was selected. By taking the intersections of the blue module and ferroptosis-related genes (FRGs), we obtained 23 common genes. Functional analysis was performed to explore the biological function of the genes of interest, and with univariate Cox regression (UCR) analysis, survival genes were screened to construct a prognostic model based on 3 genes (SLC1A5, ANGPTL4, and CGAS), which could play a role in predicting the survival of GC patients. UCR and multivariate Cox regression (MCR) analysis revealed that the prognostic index could be used as an independent prognostic indicator and validated using another GSE84437 dataset. Notably, patients in the high-risk group had higher mutation frequencies, such as TTN and TP53. TIMER analysis demonstrated that the risk score strongly correlated with macrophage and CD4+ T cell infiltration. In addition, the high- and low-risk groups illustrated different distributions of different immune statuses. Furthermore, the low-risk group had a higher immunophenoscore (IPS), which meant a better response to immune checkpoint inhibitors (ICIs). Finally, gene set enrichment analysis (GSEA) revealed several significant pathways involved in GC. In this study, a novel FRG signature was built that could predict GC prognosis and reflect the status of the tumor immune microenvironment.

BACKGROUND: HIV/AIDS is becoming more prevalent over time, resulting in a considerable number of deaths. In 2017, 36.9 million (35.1 million adults) people worldwide were living with HIV, 1.8 million people were newly infected with HIV, and 940 000 people died from AIDS-related illnesses. Mining workers are at a high risk of contracting HIV and infecting others, and effective prevention is a critical. OBJECTIVE: To assess HIV preventive behaviors and associated factors among gold mining workers in Dima district, southwest Ethiopia, 2019. METHODS AND MATERIALS: A community-based cross-sectional study was conducted from November 1st to 30th, 2019. A convenience sampling technique was used to get mining workers for the interview.The data were collected through face-to-face interviews. The collected data were coded and entered into EpiData version 4.2.0.101, cleaned, and analyzed using SPSS version 21 statistical software. A binary logistic regression was conducted to determine the association using odds ratios at 95% confidence intervals. A P value of less than 0.05 considered the level of significance for HIV preventive behaviors. RESULTS: From a total of 455 mining worker, 279 (61.3%) of them have good practices of HIV prevention. Factors associated with good preventive practice were not alcohol drinkers (AOR = 2.86, 95% CI: 1.30-6.29), not chew khat (AOR = 2.09, 95% CI: 1.09-4.02), having good knowledge about HIV (AOR = 1.81, CI: 1.16-2.83), favorable attitude towards HIV prevention (AOR = 4.76, 95% CI: 3.02-7.49), and high perceived susceptibility to HIV (AOR = 2.63, 95% CI: 1.63-4.24). CONCLUSION: Only about 61% of the mining workers in the study area were practiced HIV preventive behaviors. Not alcohol drinkers, having good knowledge about HIV, having a favorable attitude toward HIV prevention, and having high perceived susceptibility to HIV were factors associated with the practice of HIV preventive behaviors. Efforts have to be made by local governments and other concerned bodies to increase preventive behavior.

Imperata cylindrica is traditionally used to cure several diseases including cancer, wounds, and hypertension. The present study was designed to investigate the anticancer activity of the methanolic root extract of I. cylindrica (IC-MeOH). The water-soluble tetrazolium-1 and colony formation assays were used to check the proliferation ability of the cells. Cell apoptosis and cell cycle were measured by flow cytometry-based fluorescence-activated cell sorting. The ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) analysis was used for the metabolites profiling of IC-MeOH. Based on high-mass accuracy, spectral data, and previous reports, tentative compound identifications were assigned. Our findings revealed that IC-MeOH inhibited the proliferation of HeLa and CaSki cells. The plant extract was also found to induce a concentration- and time-dependent apoptosis and cell cycle arrest in the G0/G1 phase (IC50 value) in CaSki cell line. Analysis of IC-MeOH permitted the identification of 10 compounds already reported for their anticancer activity, epicatechin, curcumin, (-)-yatein, caffeic acid, myricetin, jatrorrhizine, harmaline, cinnamaldehyde, dobutamine, and syringin. In conclusion, IC-MeOH is a rich source of cytotoxic metabolites that inhibits human cervical cancer proliferation via apoptosis and cell cycle arrest.

Entamoeba histolytica is the causative agent of amoebiasis, and Entamoeba dispar is its noninvasive morphological twin. Entamoeba invadens is a reptilian parasite. In the present study, Western blot, phosphatase activity, immunofluorescence, and bioinformatic analyses were used to identify PP2C phosphatases of E. histolytica, E. dispar, and E. invadens. PP2C was identified in trophozoites of all Entamoeba species and cysts of E. invadens. Immunoblotting using a Leishmania mexicana anti-PP2C antibody recognized a 45.2 kDa PP2C in all species. In E. histolytica and E. invadens, a high molecular weight element PP2C at 75 kDa was recognized, mainly in cysts of E. invadens. Immunofluorescence demonstrated the presence of PP2C in membrane and vesicular structures in the cytosol of all species analyzed. The ~75 kDa PP2C of Entamoeba spp. shows the conserved domain characteristic of phosphatase enzymes (according to in silico analysis). Possible PP2C participation in the encystation process was discussed.

Propranolol has been used in the first-line therapy of infantile hemangioma (IH) for a number of years; however, the mechanisms through which propranolol regulates IH are not yet fully understood. In the present study, microRNA (miRNA/miR) sequencing analysis was performed to identify differentially expressed miRNAs in human umbilical vascular endothelial cells (HUVECs) treated with propranolol. Cell viability and apoptosis were detected using CCK-8 assay and flow cytometry, respectively. Cell migration was assessed using wound healing, Transwell, and tube formation assays. Methylation-specific PCR was then used to investigate the promoter methylation status. The levels of oxidative stress indicators, including superoxide dismutase, glutathione, and malondialdehyde were also detected. Finally, cell cycle analysis was performed using flow cytometry and western blotting. It was observed that propranolol induced the upregulation of miR-206 in HUVECs, which was caused by demethylation of the miR-206 promoter. Moreover, propranolol significantly inhibited the proliferation of HUVECs by inducing apoptosis, while these phenomena were reversed by miR-206 antagomir. VEGFA was found to be a target gene of miR-206. In addition, propranolol notably inhibited the migration and induced G1 arrest of the HUVECs, whereas these results were eliminated by miR-206 antagomir. Collectively, the findings of the present study demonstrated that propranolol may inhibit the proliferation and migration in HUVECs via modulating the miR-206/VEGFA axis. These findings suggest a novel mechanism through which propranolol suppresses the progression of IH.

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus causing substantial morbidity and mortality worldwide. We performed a cross-sectional investigation of SARS-CoV-2 clusters in Suzhou to determine the transmissibility of the virus among close contacts and to assess the demographic and clinical characteristics between index and secondary cases. METHODS: We review the clustered patients with SARS-CoV-2 infections in Suzhou between 22 January and 29 February 2020. The demographic and clinical characteristics were compared between index and secondary cases. We calculated the basic reproduction number (R 0) among close contacts with SLI model. RESULTS: By 22 February, 87 patients with SARS-CoV-2 infection were reported, including 50 sporadic and 37 clustered cases, who were generated from 13 clusters. On admission, 5 (20.8%) out of 24 secondary cases were asymptomatic. The male ratio of index cases was significantly higher than that of secondary cases. Additionally, the index cases were more likely to have fever and increased CRP levels than the secondary cases. The R 0 values of clusters displayed a significantly declining trend over time for all clusters. The relative risk of infection in blood-related contacts of cases versus unrelated contacts was 1.60 for SARS-CoV-2 (95% CI: 0.42-2.95). CONCLUSIONS: In conclusion, SARS-CoV-2 has great person-to-person transmission capability among close contacts. The secondary cases are more prone to have mild symptoms than index cases. There is no increased RR of secondary infection in blood relatives versus unrelated contacts. The high rate of asymptomatic SARS-CoV-2 infections highlights the urgent need to enhance active case finding strategy for early detection of infectious patients.

Genome-wide omics technology boosts deep interrogation into the clinical prognosis and inherent mechanism of pancreatic oncology. Classic LASSO methods coequally treat all candidates, ignoring individual characteristics, thus frequently deteriorating performance with comparatively more predictors. Here, we propose a wavelet-based deep learning method in variable selection and prognosis formulation for PAAD with small samples and multisource information. With the genomic, epigenomic, and clinical cohort information from The Cancer Genome Atlas, the constructed five-molecule model is validated via Kaplan-Meier survival estimate, rendering significant prognosis capability on high- and low-risk subcohorts (p value < 0.0001), together with three predictors manifesting the individual prognosis significance (p value: 0.0012~0.024). Moreover, the performance of the prognosis model has been benchmarked against the traditional LASSO and wavelet-based methods in the 3- and 5-year prediction AUC items, respectively. Specifically, the proposed model with discrete stationary wavelet base (bior1.5) overwhelmingly outperformed traditional LASSO and wavelet-based methods (AUC: 0.787 vs. 0.782 and 0.721 for the 3-year case; AUC: 0.937 vs. 0.802 and 0.859 for the 5-year case). Thus, the proposed model provides a more accurate perspective, but with less predictor burden for clinical prognosis in the pancreatic carcinoma study.

BACKGROUND: Increasing evidence demonstrated that long noncoding RNA (lncRNA) could affect inflammatory tumor immune microenvironment by modulating gene expression and could be used as a biomarker for HBC-related hepatocellular carcinoma (HCC) but still needs further research. The aim of the present study was to determine an lncRNA signature for the diagnosis of HBV-related HCC. METHODS: HBV-related HCC expression profiles (GSE55092, GSE19665, and GSE84402) were abstracted from the GEO (Gene Expression Omnibus) data resource, and R package limma and RobustRankAggreg were employed to identify common differentially expressed genes (DEGs). Using machine learning, optimal diagnostic lncRNA molecular markers for HBV-related HCC were identified. The expression of candidate lncRNAs was cross-validated in GSE121248, and an ROC (receiver operating characteristic) curve of lncRNA biomarkers was carried out. Additionally, a coexpression network and functional annotation was built, after which a PPI (protein-protein interaction) network along with module analysis were conducted with the Cytoscape open source software. RESULT: A total of 38 DElncRNAs and 543 DEmRNAs were identified with a fold change larger than 2.0 and a P value < 0.05. By machine learning, AL356056.2, AL445524.1, TRIM52-AS1, AC093642.1, EHMT2-AS1, AC003991.1, AC008040.1, LINC00844, and LINC01018 were screened out as optional diagnostic lncRNA biosignatures for HBV-related HCC. The AUC (areas under the curve) of the SVM (support vector machine) model and random forest model were 0.957 and 0.904, respectively, and the specificity and sensitivity were 95.7 and 100% and 94.3 and 86.5%, respectively. The results of functional enrichment analysis showed that the integrated coexpressed DEmRNAs shared common cascades in the p53 signaling pathway, retinol metabolism, PI3K-Akt signaling cascade, and chemical carcinogenesis. The integrated DEmRNA PPI network complex was found to be comprised of 87 nodes, and two vital modules with a high degree were selected with the MCODE app. CONCLUSION: The present study identified nine potential diagnostic biomarkers for HBV-related HCC, all of which could potentially modulated gene expression related to inflammatory conditions in the tumor immune microenvironment. The functional annotation of the target DEmRNAs yielded novel evidence in evaluating the precise functions of lncRNA in HBV-related HCC.

BACKGROUND: Nontechnical skills are necessary for clinicians' safe performance and prevention of errors in the operating room. Educational intervention is a useful way to improve these skills, which are a vital area for improvement. Circulating nurses are surgical team members whose work depends heavily on using nontechnical skills. This study is aimed at assessing the effect of an educational intervention on the improvement of circulating nurses' nontechnical skills. METHODS: This semiexperimental study was conducted on 300 circulating nurses divided into the intervention and no intervention groups each containing 150 participants. The nontechnical skills were assessed using the circulating practitioners' list of nontechnical skills. Then, the intervention group received training regarding these skills, and the two groups were evaluated again. After all, the data were entered into the SPSS 24 software and were analyzed using descriptive statistics and Wilcoxon and Mann-Whitney tests. Furthermore, Kendall's tau, independent sample t-test, and one-way ANOVA were used for assessment of relationship between median scores and demographics. RESULTS: The results revealed a significant improvement in the scores of all domains of nontechnical skills in the intervention group (p < 0.05). The highest and lowest improvements were observed in teamwork (42%) and situational awareness (16.7%), respectively. After the intervention, the scores of some of the behaviors were still below the average level or were not improved significantly. CONCLUSIONS: Circulating nurses' nontechnical skills can be improved by educational interventions. However, regarding the low scores or no improvements in the scores of some behaviors, other intervention types such as policymaking and correcting the existing hierarchies in the operating room can be useful to complete the educational interventions.

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by polydactyly, obesity, rod-cone dystrophy, and mental retardation. Twenty-one genes have been identified as causing BBS. This study collected a BBS pedigree from two patients and performed whole-exome sequencing on one patient. We identified a novel homozygous variant c.1114C>T (p.Q372X) in the BBS9 of the two siblings. This variant was confirmed and completely cosegregated with the disease of this family by Sanger sequencing. We report a novel homozygous variant c.1114C>T in the BBS9 gene in a Chinese family.

OBJECTIVES: Urethral tissue reconstruction for hypospadias is challenging for urologists. In this study, bovine acellular dermal matrix (ADM) patch loading with collagen-binding vascular endothelial growth factor (CBD-VEGF) was used to repair the urethral injury in beagles. METHODS: The safety and effectiveness of the scaffold implantation were carefully evaluated by comparing among the urethral injury control group, ADM implantation group, and ADM modified with CBD-VEGF implantation group during 6 months. Urodynamic examination, urethral angiography, and pathological examination were performed to evaluate the recovery of urethral tissue. RESULTS: Stricture, urethral diverticulum, and increased urethral closure pressure were observed in the control group. Fistula was observed in one animal in the ADM group. By contrast, no related complications or other adverse situations were observed in animals treated with ADM patch modified with CBD-VEGF. The average urethra diameter was significantly smaller in the control animals than in scaffold implantation groups. Pathological examination revealed more distribution of proliferative blood vessels in the animals treated with ADM modified with CBD-VEGF. CONCLUSIONS: Overall, ADM patches modified with CBD-VEGF demonstrated an optimized tissue repair performance in a way to increase tissue angiogenesis and maintain urethral function without inducing severe inflammation and scar formation.

Isopimaric acid (IPA) exhibits a diverse array of pharmacological activities, having been shown to function as an antihypertensive, antitumor, antibacterial, and hypocholesterolemic agent. However, few studies of the pharmacokinetics of IPA have been performed to date, and such analyses are essential to explore the in vivo mechanisms governing the biological activity of this compound. As such, we herein designed a selective LC-MS approach capable of quantifying serum IPA levels in model rats using an Agilent HC-C18 column (250 mm × 4.6 mm, 5 μm) via isocratic elution with a mobile phase composed of methanol 0.5% formic acid (91 : 9, v/v) at a 1 mL/min flow rate. Ion monitoring at m/z 301.2 [M-H]- was used to quantify IPA levels in plasma samples from these rats, while internal standard (IS) levels were assessed at m/z 455.3 [M-H]-. After validation, this approach was employed to conduct a pharmacokinetic analysis of rats administered IPA via the oral (p.o. 50, 100, or 200 mg/kg) and intravenous (i.v. 5 mg/kg) routes. Analyses of noncompartmental pharmacokinetic parameters revealed that IPA underwent secondary absorption following oral administration to these animals, with the two tested oral doses (50 and 100 mg/kg) being associated with respective absolute bioavailability values of 11.9% and 17.5%. In summary, this study may provide a foundation for future efforts to explore the mechanistic basis for the pharmacological activity of IPA, offering insights to guide its subsequent clinical utilization.

BACKGROUND: Coronary heart disease (CHD) is the most prevalent disease with an unelucidated pathogenetic mechanism and is mediated by complex molecular interactions of exosomes. Here, we aimed to identify differentially expressed exosome genes for the disease development and prognosis of CHD. METHOD: Six CHD samples and 32 normal samples were downloaded from the exoRbase database to identify the candidate genes in the CHD. The differentially expressed genes (DEGs) were identified. And then, weighted gene correlation network analysis (WGCNA) was used to investigate the modules in coexpressed genes between CHD samples and normal samples. DEGs and the module of the WGCNA were intersected to obtain the most relevant exosome genes. After that, the function enrichment analyses and protein-protein interaction network (PPI) were performed for the particular module using STRING and Cytoscape software. Finally, the CIBERSORT algorithm was used to analyze the immune infiltration of exosome genes between CHD samples and normal samples. RESULT: We obtain a total of 715 overlapping exosome genes located at the intersection of the DEGs and key modules. The Gene Ontology enrichment of DEGs in the blue module included inflammatory response, neutrophil degranulation, and activation of CHD. In addition, protein-protein networks were constructed, and hub genes were identified, such as LYZ, CAMP, HP, ORM1, and LTF. The immune infiltration profiles varied significantly between normal controls and CHD. Finally, we found that mast cells activated and eosinophils had a positive correlation. B cell memory had a significant negative correlation with B cell naive. Besides, neutrophils and mast cells were significantly increased in CHD patients. CONCLUSION: The underlying mechanism may be related to neutrophil degranulation and the immune response. The hub genes and the difference in immune infiltration identified in the present study may provide new insights into the diagnostic and provide candidate targets for CHD.

The coronavirus disease 2019 (COVID-19) pandemic poses a special risk for both immunosuppressed patients, especially transplant recipients. Although the knowledge about this infection is growing, many uncertainties remain, particularly regarding the kidney. Kidney transplant recipients (KDRs) should be considered immunocompromised hosts since a potential risk for infection, comorbidity, and immunosuppression exposure exists. Additionally, the management of immunosuppressive agents in KDRs remains challenging. Potential drug interactions with immunosuppressive treatment escalated the risk of unwanted side effects. In this review, we aimed to attain an augmented awareness and improved management immunosuppressant for COVID-19 KDRs.

This study is aimed at evaluating the binding effect of Acacia etbaica gum in granule and tablet formulations using paracetamol as a model drug. Some physicochemical properties of the purified gum such as pH, the presence of tannin and dextrin, solubility, viscosity, loss on drying, total ash value, water solubility index, swelling power, moisture sorption, and powder flow properties were investigated. Paracetamol granules were prepared using wet granulation method at 2%, 4%, 6%, and 8% w/w of the Acacia etbaica gum and compared with granules prepared with reference binders (PVP K-30 and Acacia BP) in similar concentrations. The granules were characterized for bulk and tapped densities, compressibility index and Hausner ratio, angle of repose, flow rate, and friability. Finally, the prepared granules were compressed into tablets and evaluated for different tablet characteristics: weight uniformity, thickness, diameter, crushing strength, tensile strength, friability, disintegration time, and in vitro release profile. The physicochemical characterization revealed that tannins and dextrin are absent in the gum, and the gum has acidic pH. Both the moisture content and total ash values were within the official limits. Furthermore, the gum was found to be soluble in cold and hot water but insoluble in organic solvent and exhibited a shear thickening viscosity profile and excellent flow properties with excellent compressibility. The granules prepared with the gum of Acacia etbaica and reference binders showed good particle size distribution and excellent flow and compressibility properties. All the prepared tablets passed pharmacopeial specifications with respect to their uniformity of weight, thickness, and disintegration time. Tablets formulated with Acacia etbaica gum and acacia BP meet the compendial specification for friability at binder concentrations more than 2%. Drug release properties of all the batches formulated with Acacia etbaica, PVP, and acacia BP complied with the pharmacopeial specification. It can be concluded that the gum of Acacia etbaica could be explored as an alternative excipient for its binder effect in granule and tablet formulations.

Toxoplasmosis is a global threat with significant zoonotic concern. The present in silico study was aimed at determination of bioinformatics features and immunogenic epitopes of a tyrosine-rich oocyst wall protein (TrOWP) of Toxoplasma gondii. After retrieving the amino acid sequence from UniProt database, several parameters were predicted including antigenicity, allergenicity, solubility and physico-chemical features, signal peptide, transmembrane domain, and posttranslational modifications. Following secondary and tertiary structure prediction, the 3D model was refined, and immunogenic epitopes were forecasted. It was a 25.57 kDa hydrophilic molecule with 236 residues, a signal peptide, and significant antigenicity scores. Moreover, several linear and conformational B-cell epitopes were present. Also, potential mouse and human cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL) epitopes were predicted in the sequence. The findings of the present in silico study are promising as they render beneficial characteristics of TrOWP to be included in future vaccination experiments.

Alzheimer's disease (AD) is known as a critical neurodegenerative disorder. It worsens as symptoms concerning dementia grow severe over the years. Due to the globalization of Alzheimer's disease, its prevention and treatment are vital. This study proposes a method to extract substantial gene complexes and then introduces potential drugs in Alzheimer's disease. To this end, a protein-protein interaction (PPI) network was utilized to extract five meaningful gene complexes functionally interconnected. An enrichment analysis to introduce the most important biological processes and pathways was accomplished on the obtained genes. The next step is extracting the drugs related to AD and introducing some new drugs which may be helpful for this disease. Finally, a complete network including all the genes associated with each gene complex group and genes' target drug was illustrated. For validating the proposed potential drugs, Connectivity Map (CMAP) analysis was accomplished to determine target genes that are up- or downregulated by proposed drugs. Medical studies and publications were analyzed thoroughly to introduce AD-related drugs. This analysis proves the accuracy of the proposed method in this study. Then, new drugs were introduced that can be experimentally examined as future work. Raloxifene and gentian violet are two new drugs, which have not been introduced as AD-related drugs in previous scientific and medical studies, recommended by the method of this study. Besides the primary goal, five bipartite networks representing the genes of each group and their target miRNAs were constructed to introduce target miRNAs.

Alzheimer's disease (AD) and epilepsy are neurological disorders that affect a large cohort of people worldwide. Although both of the two diseases could be influenced by genetic factors, the shared genetic mechanism underlying the pathogenesis of them is still unclear. In this study, we aimed to identify the shared genetic networks and corresponding hub genes for AD and epilepsy. Firstly, the gene coexpression modules (GCMs) were constructed by weighted gene coexpression network analysis (WGCNA), and 16 GCMs were identified. Through further integration of GCMs, genome-wide association studies (GWASs), and expression quantitative trait loci (eQTLs), 4 shared GCMs of AD and epilepsy were identified. Functional enrichment analysis was performed to analyze the shared biological processes of these GCMs and explore the functional overlaps between these two diseases. The results showed that the genes in shared GCMs were significantly enriched in nervous system-related pathways, such as Alzheimer's disease and neuroactive ligand-receptor interaction pathways. Furthermore, the hub genes of AD- and epilepsy-associated GCMs were captured by weighted key driver analysis (wKDA), including TRPC1, C2ORF40, NR3C1, KIAA0368, MMT00043109, STEAP1, MSX1, KL, and CLIC6. The shared GCMs and hub genes might provide novel therapeutic targets for AD and epilepsy.

The posterior interosseous nerve (PIN) innervates the posterior compartment muscle of the forearm and is a continuation of the deep branch of the radial nerve. The anatomic descriptions of PIN vary among different authors. This study investigated the distribution patterns of PIN and its relationships to the supinator muscle. This study investigated which nerves innervate the posterior compartment muscles of the forearm, the radial nerve, and the PIN, using 28 nonembalmed limbs. Also, the points where the muscle attaches to the bone were investigated. The measured variables in this study were measured from the most prominent point of the lateral epicondyle of the humerus (LEH) to the most distal point of the radius styloid process. For each specimen, the distance between the above two points was assumed to be 100%. The measurement variables were the attachment area of the supinator and branching points from the radial nerve. The attachment points of the supinator to the radius and ulna were 47.9% ± 3.6% and 31.5% ± 5.2%, respectively, from the LEH. In 67.9% of the specimens, the brachioradialis and extensor carpi radialis longus (ECRL) were innervated by the radial nerve before superficial nerve branching, and the extensor carpi radialis brevis (ECRB) innervated the deep branch of the radial nerve. In 21.4% of the limbs, the nerve innervating the ECRB branched at the same point as the superficial branch of the radial nerve, whereas it branched from the radial nerve in 7.1% of the limbs. In 3.6% of the limbs, the deep branch of the radial nerve branched to innervate the ECRL. PIN was identified as a large branch without divisions in 10.7% and as a deep branch innervating the extensor digitorum in 14.3% of the limbs. The anatomic findings of this study would aid in the diagnosis of PIN syndromes.

OBJECTIVE: To evaluate the effect of prepregnancy lymphocyte active immunotherapy on unexplained recurrent miscarriage, pregnancy success rate, and maternal-infant outcome. METHODS: A total of 124 patients with recurrent miscarriage admitted to our hospital from January 2018 to December 2020 were selected as the research objects and divided into the experimental group and the control group according to the random number table method, with 62 patients in each group. The experimental group was treated with lymphocyte active immunotherapy, and the control group was given conventional treatment. The pregnancy success rate, estrogen indexes, hemorheology indexes, and psychological state of the two groups were compared. RESULTS: The experimental group garnered a notably higher pregnancy success rate and a prominently lower miscarriage rate than the control group (P < 0.05). Better results of self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed in the experimental group, as compared to the control group (P < 0.05). The experimental group yielded more desirable results in terms of treatment satisfaction, estrogen indexes, and hemorheology indexes in comparison with the control group (P < 0.05). CONCLUSION: The use of lymphocyte active immunotherapy for patients with unexplained recurrent miscarriage can significantly increase the pregnancy success rate, optimize the maternal-infant outcome, drive down the miscarriage rate, and ameliorate the patient's estrogen levels and hemorheology indicators, which is worthy of promotion and application in clinical practice.

Implant-associated infections remain one of the main problems in the treatment of open tibia fractures. The role of systemic antibiotic prophylaxis is now agreed and accepted; nevertheless, recent literature also seems to emphasize the importance of local antibiotic therapy at the fracture site. Several therapeutic strategies have been proposed to overcome this new need. Antibiotic-coated nails play crucial role in this, allowing both infection prevention and favoring the fracture stabilization. We describe the outcome of patients with open diaphyseal tibia fracture treated either with a standard uncoated nail or a gentamicin-coated nail from January 2016 to December 2018 at our second level emergency-urgency department. Primary outcomes were infection rate and bone union rate. Other outcomes reported are reoperation rate, time between injury and nailing, and safety of antibiotic nail. Numerical variables were tabulated using mean, standard deviation, minimum, maximum, and number of observations. Categorical variables were tabulated using number of observations. 23 patients treated with uncoated nail and 23 patients treated with antibiotic-coated tibia nail were included in the study and were evaluated for a minimum follow-up of 18 months. Among the 46 patients, 9 were Gustilo-Anderson type I, 21 type II, and 16 type III open fracture. Regarding the bone healing rate at 12 months, 16 fractures in the first group and 18 in the second were completely healed. 4 infections were found in the first group (3 superficial surgical site infection and 1 osteomyelitis) and 3 superficial infections in the second one. No adverse events have been recorded with antibiotic-coated nails. In this unicentric retrospective study observed no deep wound infections and good fracture healing in the use of antibiotic-coated nails. Antibiotic nails have been shown to play a role in the treatment of fractures in critically ill patients with severe soft tissue damage.

BACKGROUND: Septic patients often require mechanical ventilation due to respiratory dysfunction, and effective ventilatory strategies can improve survival. The effects of the combination of permissive hypoxia and hyperoxia avoidance for managing mechanically ventilated patients are unknown. This study examines these effects on outcomes in mechanically ventilated septic patients. METHODS: In a retrospective before-and-after study, we examined adult septic patients (aged ≥18 years) requiring mechanical ventilation at a university hospital. On April 1, 2017, our mechanical ventilation policy changed from a conventional oxygenation target (SpO2: ≥96%) to more conservative targets with permissive hypoxia (SpO2: 88-92% or PaO2: 60 mmHg) and hyperoxia avoidance (reduced oxygenation for PaO2 > 110 mmHg). Patients were divided into a prechange group (April 2015 to March 2017; n = 83) and a postchange group (April 2017 to March 2019; n = 130). Data were extracted from clinical records and insurance claims. Using a multiple logistic regression model, we examined the association of the postchange group (permissive hypoxia and hyperoxia avoidance) with intensive care unit (ICU) mortality after adjusting for variables such as Sequential Organ Failure Assessment (SOFA) score and PaO2/FiO2 ratios. RESULTS: The postchange group did not have significantly lower adjusted ICU mortality (0.67, 0.33-1.43; P = 0.31) relative to the prechange group. However, there were significant intergroup differences in mechanical ventilation duration (prechange: 11.0 days, postchange: 7.0 days; P = 0.01) and ICU stay (prechange: 11.0 days, postchange: 9.0 days; P = 0.02). CONCLUSIONS: Permissive hypoxia and hyperoxia avoidance had no significant association with reduced ICU mortality in mechanically ventilated septic patients. However, this approach was significantly associated with shorter mechanical ventilation duration and ICU stay, which can improve patient turnover and ventilator access.

White spot lesions (WSLs) are one of the adverse effects of fixed orthodontic treatments. They are the primary sign of caries, which means inhibiting this process by antibacterial agents will reverse the procedure. The current study tested the surface modification of nickel-titanium (NiTi) wires with ZnO nanoparticles (NPs), as antimicrobial agents. As the morphology of NPs is one of the most critical factors for their properties, the antibacterial properties of different morphologies of ZnO nanostructures coated on the NiTi wire were investigated. For the preparation of ZnO nanostructures, five coating methods, including chemical vapor deposition (CVD), chemical precipitation method, polymer composite coating, sol-gel synthesis, and electrospinning process, were used. The antibacterial activity of NPs was assessed against Streptococcus mutans by the colony counting method. The obtained results showed that all the samples had antibacterial effects. The antibacterial properties of ZnO NPs were significantly improved when the specific surface area of particles increased, by the ZnO nanocrystals prepared via the CVD coating method.

Dental caries is a multifactorial disease mainly caused by cariogenic bacteria commonly found in the oral cavity. Dental caries may cause demineralization of the tooth, cavitation, hypersensitivity, pulp inflammation, and even tooth loss if left untreated. Saliva secreted in the oral cavity can serve as a tool for identification of biomarkers for early detection of diseases. In the present study, differential expression of salivary proteins from 33 dental caries patients was compared with 10 control subjects. The unstimulated saliva was analyzed by 12% SDS-PAGE and two-dimensional gel electrophoresis. Gelatin and casein zymography was performed to check for protease activity. Also, salivary IgAs from both groups were compared by sandwich ELISA technique. Dental caries patient's saliva showed decreased caseinolytic and increased gelatinolytic activity probably due to metalloproteases and cathepsins. Mean salivary levels of sIgA were also significantly higher (p < 0.018) in dental caries saliva samples. The 2D electrophoresis profile of both the groups showed regions on gel with visually detectable alterations in protein expression. The present study is among the few initial studies in the locality for identification of protein differences in saliva from dental caries patients and has demonstrated a good potential to identify alterations. However, a large population-based analysis is required to validate these findings to be translated as a tool for indicative applications.

PURPOSE: Studying the cytokine profiles in influenza A pneumonia could be helpful to better understand the pathogenesis of the disease and predict its prognosis. Patients and Methods. Patients with influenza A pneumonia (including 2009H1N1, H1N1, H3N1, and H7N1) hospitalized in six hospitals from January 2017 to October 2018 were enrolled (ClinicalTrials.gov ID, NCT03093220). Sputum samples were collected within 24 hours after admission and subsequently analyzed for cytokine profiles using a Luminex assay. RESULTS: A total of 35 patients with influenza A pneumonia were included in the study. The levels of IL-6, IFN-γ, and IL-2 were increased in patients with severe influenza A pneumonia (n =10) (P = 0.002, 0.009, and 0.008, respectively), while those of IL-5, IL-25, IL-17A, and IL-22 were decreased compared to patients with nonsevere pneumonia (P = 0.0001, 0.009, 0.0001, and 0.006, respectively). The levels of IL-2 and IL-6 in the nonsurvivors (n = 5) were significantly higher than those in the survivors (P = 0.043 and 0.0001, respectively), while the levels of IL-5, IL-17A, and IL-22 were significantly lower (P = 0.001, 0.012, and 0.043, respectively). The IL-4/IL-17A ratio has the potential to be a good predictor (AUC = 0.94, P < 0.05, sensitivity = 88.89%, specificity = 92.31%) and an independent risk factor (OR, 95% CI: 3.772, 1.188-11.975; P < 0.05) for intermittent positive pressure ventilation (n = 9). CONCLUSION: Significant dysregulation of cytokine profiles can be observed in patients with severe influenza A pneumonia.

Familial Mediterranean fever (FMF) is the most prevalent autoinflammatory disease. Typical findings are recurrent fever attacks with serositis, skin rash, and synovitis. FMF is caused by mutations in the MEFV gene, encoding pyrin protein. Pyrin functions in innate immunity and triggers inflammation via inflammatory mediators' production and acts as the primary regulatory component of the inflammasome. On the other hand, various miRNAs play crucial roles in the pathogenesis of different types of cancers and immune-related and neurodegenerative diseases. However, their association with FMF is still unclear. Therefore, in this study, we assessed the roles of selected thirteen miRNAs associated with immune functions. We recruited genetically diagnosed 28 FMF patients and 28 healthy individuals. The expression profiling of the miRNAs was determined by qRT-PCR and normalized to SNORD61. Our analysis revealed that miR-34a-5p, miR-142-3p, miR-216a-5p, miR-340-5p, miR-429, and miR-582-5p were upregulated, whereas miR-107, miR-569, and miR-1304-5p were downregulated in the FMF patients. Among them, miR-107 was found to be the most remarkable in M694V homozygous mutants compared to other homozygous mutants. During clinical follow-up of the patients with M694V mutation, which is closely related to amyloidosis, evaluation of mir-107 expression might be crucial and suggestive. Our results showed that miRNAs might serve a function in the pathogenesis of FMF. Further studies may provide novel and effective diagnostic and therapeutic agents that target examined miRNAs. Targeting miRNAs in FMF seems to be promising and may yield a new generation of rational therapeutics and diagnostic or monitoring tools enabling FMF treatment.

Expression and immunolocalization of Substance P (SP)/Neurokinin-1 Receptor (NK-1R) in breast carcinoma (BC) patients and its association with routine proliferative markers (ER, PR, HER2/neu, and Ki-67) were evaluated. A cross-sectional study was performed on 34 cases of BC. There were 23 cases of group A (grade III), 8 of group B (grade II), and only 3 cases of group C (grade I). All samples were then processed for SP and NK-1R immunohistochemistry for few cases. 14/23 cases (61%) of group A, 7/8 cases (88%) of group B, and 2/3 (67%) cases of group C were SP positive. Overall, strong staining (≥10% tumor cells), labeled as "+3," was observed in 9/14 (64.2%) cases of group A and 1/8 (12.5%) cases of group B. Moderate staining labelled as "+2" (in ≥10% tumor cells) was observed in 3/14 (21.4%) cases of group A and 4/8 (50%) cases of group B. Weak positive staining "+1" was observed in only 2/14 (14.28%) cases of group A, 2/8 (25%) cases of group B, and all 2/2 (100%) cases of group C. SP and NK-1R are overexpressed in breast carcinomas, and there is significant association between the grade of tumor and their overexpression.

Chronic inflammation affects bone metabolism and accelerates bone loss. This study is aimed at analyzing the prevalence of low bone mineral density (LBMD) in patients with untreated Takayasu's arteritis (TA) and risk factors. Forty untreated TA patients were enrolled, including 38 premenopausal women and 2 men before 50 years old. The control group included 60 age- and gender-matched healthy persons. Bone mineral density (BMD) of lumbar vertebrae and hip in patients with TA and the control group was measured by the dual-energy X-ray method. Serum 25OHD and β-CTX were also measured. The lumbar BMD of TA patients (0.89 ± 0.11 g/cm2) was significantly lower than that of the healthy control (0.97 ± 0.11 g/cm2). The prevalence of LBMD at the lumbar spine (17.50%) was significantly higher than that of the control group (3.33%). However, there was no significant difference at the hip. The 25OHD of TA patients was lower than that of healthy controls, while the level of β-CTX was higher. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in patients with LBMD were higher than those in patients with normal BMD. According to univariate correlation analysis, there was a significant negative correlation between LDL-C and lumbar BMD. Binary logistic regression analysis showed that LDL-C was an important factor affecting the occurrence of LBMD in patients with TA (OR = 25.269, P = 0.02). Our result reveals bone loss in TA patients, which hints the relationship among inflammation, lipid metabolism, and bone metabolism.

Despite advances in diabetes care, impaired diabetic wound healing remains a significant clinical problem. The present study was aimed at developing a novel cream based on Ginkgo biloba extract and investigating its wound healing effect on full-thickness wounds in diabetic rats. The topical formulated oil-in-water emulsion-based cream contains Ginkgo biloba aqueous extract in an amount of about 1% to 5% as an active agent. The prepared formula was subjected to physicochemical assessment and pharmacotechnical characterization. Eighteen alloxan-induced diabetic rats completing full-thickness excisional skin wounds were randomly divided into three groups topically treated with either a normal saline (control group), the reference drug ("Cytol Centella cream®"), and cream based on the Ginkgo biloba extract. The response to treatment was assessed by macroscopic, qualitative, and quantitative histopathological analysis. The prepared formula showed good physicochemical properties. The rheological behavior of the prepared cream followed a non-Newtonian pseudoplastic pattern at different storage temperatures. The cream, which is a macroemulsion with uniform size distribution, remained stable for 6 months. Skin tolerance studies confirmed the compatibility of the cream with the skin. During the experimental trial, the cream based on the Ginkgo biloba-treated group showed significant improvements over the control and reference groups for both general wound appearance and healing dynamics. This increased rate of closure of wounds in diabetic rats was associated with increased collagen synthesis. Our findings showed that the cream could be a promising and innovative topical treatment with Ginkgo biloba extract for the management of acute diabetic wounds.

BACKGROUND: Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is inevitable in EGFR-mutant non-small-cell lung cancer (NSCLC) patients. A germline 2903 bp deletion polymorphism of Bcl-2-like protein 11 (BIM) causes reduced expression of proapoptotic BH3-only BIM protein and blocks TKI-induced apoptosis of tumor cells. Yet the association between the deletion polymorphism and response to EGFR-TKI treatment remains inconsistent among clinical observations. Thus, we performed the present meta-analysis. METHODS: Eligible studies were identified by searching PubMed, Embase, and ClinicalTrials.gov databases prior to March 31, 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) of progression-free survival (PFS) and overall survival (OS) and odds ratios (ORs) and 95% CIs of objective response rate (ORR) and disease control rate (DCR) were calculated by using a random effects model. Sensitivity, metaregression, and publication bias analyses were also performed. RESULTS: A total of 20 datasets (3003 EGFR-mutant NSCLC patients receiving EGFR-TKIs from 18 studies) were included. There were 475 (15.8%) patients having the 2903-bp intron deletion of BIM and 2528 (84.2%) wild-type patients. BIM deletion predicted significantly shorter PFS (HR = 1.35, 95% CI: 1.10-1.64, P = 0.003) and a tendency toward an unfavorable OS (HR = 1.22, 95% CI: 0.99-1.50, P = 0.068). Patients with deletion polymorphism had lower ORR (OR = 0.60, 95% CI: 0.42-0.85, P = 0.004) and DCR (OR = 0.59, 95% CI: 0.38-0.90, P = 0.014) compared with those without deletion. CONCLUSION: BIM deletion polymorphism may confer resistance to EGFR-TKIs and can be used as a biomarker to predict treatment response to EGFR-TKIs in EGFR-mutant NSCLC patients from Asian populations.

Aging is characterized by a progressive inability to maintain homeostasis, self-repair, renewal, performance, and fitness of different tissues throughout the lifespan. Senescence is occurring following enormous intracellular or extracellular stress stimuli. Cellular senescence serves as an antiproliferative process that causes permanent cell cycle arrest and restricts the lifespan. Senescent cells are characterized by terminal cell cycle arrest, enlarged lysosome, and DNA double-strand breaks as well as lipofuscin granularity, senescence-associated heterochromatin foci, and activation of DNA damage response. Curcumin, a hydrophobic polyphenol, is a bioactive chemical constituent of the rhizomes of Curcuma longa Linn (turmeric), which has been extensively used for the alleviation of various human disorders. In addition to its pleiotropic effects, curcumin has been suggested to have antiaging features. In this review, we summarized the therapeutic potential of curcumin in the prevention and delaying of the aging process.

The applications of 3D printing technology in health care, particularly orthopedics, continue to broaden as the technology becomes more advanced, accessible, and affordable worldwide. 3D printed models of computed tomography (CT) and magnetic resonance image (MRI) scans can reproduce a replica of anatomical parts that enable surgeons to get a detailed understanding of the underlying anatomy that he/she experiences intraoperatively. The 3D printed anatomic models are particularly useful for preoperative planning, simulation of complex orthopedic procedures, development of patient-specific instruments, and implants that can be used intraoperatively. This paper reviews the role of 3D printing technology in orthopedic surgery, specifically focusing on the role it plays in assisting surgeons to have a better preoperative evaluation and surgical planning.

Several studies have suggested that coatomer protein complex subunit beta 2 (COPB2) may act as an oncogene in various cancer types. However, no systematic pan-cancer analysis has been performed to date. Therefore, the present study analyzed the potential oncogenic role of COPB2 using TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus) datasets. The majority of the cancer types overexpressed the COPB2 protein, and its expression significantly correlated with tumor prognosis. In certain tumors, such as those found in breast and ovarian tissues, phosphorylated S859 exhibited high expression. It was found that mutations of the COPB2 protein in kidney and endometrial cancers exhibited a significant impact on patient prognosis. It is interesting to note that COPB2 expression correlated with the number of cancer-associated fibroblasts in certain tumors, such as cervical and endocervical cancers and colon adenocarcinomas. In addition, COPB2 was involved in the transport of substances and correlated with chemotherapy sensitivity. This is considered the first pan-tumor study, which provided a relatively comprehensive understanding of the mechanism by which COPB2 promotes cancer growth.

A new master-slave binary grey wolf optimizer (MSBGWO) is introduced. A master-slave learning scheme is introduced to the grey wolf optimizer (GWO) to improve its ability to explore and get better solutions in a search space. Five high-dimensional biomedical datasets are used to test the ability of MSBGWO in feature selection. The experimental results of MSBGWO are superior in terms of classification accuracy, precision, recall, F-measure, and number of features selected when compared to those of the binary grey wolf optimizer version 2 (BGWO2), binary genetic algorithm (BGA), binary particle swarm optimization (BPSO), differential evolution (DE) algorithm, and sine-cosine algorithm (SCA).

OBJECTIVES: In this study, the cytotoxic responses of six different over-the-counter mouthwashes on L929 cells were analyzed by two different techniques: the traditional colorimetric tetrazolium-based reduction assay (MTT) and the modern impedance-based real-time cell analysis (RTCA) system to investigate their biocompatibility in vitro. Thus, the investigation of the antiproliferative effects of the specified materials via different techniques is vital to reach this goal. MATERIALS AND METHODS: First, L929 mouse fibroblasts were exposed to the dilutions of mouthwashes for 2 minutes. After incubation, the tetrazolium reduction method was used to assess the metabolic viability of cells measured by colorimetric MTT assay and morphological inspection of cells was performed via phase-contrast microscopy. Furthermore, the effect of each mouthwash on the proliferation, morphology, and adhesion of L929 cells was monitored continuously by a noninvasive and label-free RTCA system for 140 h. RESULTS: Our data showed that all of the mouthwashes had varying cytotoxic effects on fibroblasts compared to the control group in MTT assay. In addition to that, RTCA technology has provided the growth kinetic profiles that can be used to analyze if the treatment is causing antimitotic or DNA-damaging effect on cells. Thus, analysis via this system can tell us the mechanism of toxicity behind the cell growth inhibition in vitro. Here, we found that only mouthwash 1 moderately maintained the viability of the L929 cells, yet displaying antimitotic effects and the other mouthwashes (mouthwash 2-mouthwash 6) showed toxicity via DNA-damaging effects. CONCLUSIONS: Of the six types of mouthwash tested, the most biocompatible result was obtained from a mouthwash containing alcohol (i.e., mouthwash 1). On the other hand, sodium fluoride- (NaF-) and cetylpyridinium chloride- (CPC-) containing mouthwash (i.e., mouthwash 2) showed the most cytotoxic effect.

Erratum for Biomed Res Int. 2021 May 24;2021:8836243.

In recent years, almost every country in the world has struggled against the spread of Coronavirus Disease 2019. If governments and public health systems do not take action against the spread of the disease, it will have a severe impact on human life. A noteworthy technique to stop this pandemic is diagnosing COVID-19 infected patients and isolating them instantly. The present study proposes a method for the diagnosis of COVID-19 from CT images. The method is a hybrid method based on convolutional neural network which is optimized by a newly introduced metaheuristic, called marine predator optimization algorithm. This optimization method is performed to improve the system accuracy. The method is then implemented on the chest CT scans with the COVID-19-related findings (MosMedData) dataset, and the results are compared with three other methods from the literature to indicate the method's performance. The final results indicate that the proposed method with 98.11% accuracy, 98.13% precision, 98.66% sensitivity, and 97.26% F1 score has the highest performance in all indicators than the compared methods which shows its higher accuracy and reliability.

BACKGROUND: The aim of this study was to identify potential key genes, proteins, and associated interaction networks for the development of lung cancer in nonsmoking women through a bioinformatics approach. METHODS: We used the GSE19804 dataset, which includes 60 lung cancer and corresponding paracancerous tissue samples from nonsmoking women, to perform the work. The GSE19804 microarray was downloaded from the GEO database and differentially expressed genes were identified using the limma package analysis in R software, with the screening criteria of p value < 0.01 and ∣log2 fold change (FC) | >2. RESULTS: A total of 169 DEGs including 130 upregulated genes and 39 downregulated were selected. Gene Ontology and KEGG pathway analysis were performed using the DAVID website, and protein-protein interaction (PPI) networks were constructed and the hub gene module was screened through STING and Cytoscape. CONCLUSIONS: We obtained five key genes such as GREM1, MMP11, SPP1, FOSB, and IL33 which were strongly associated with lung cancer in nonsmoking women, which improved understanding and could serve as new therapeutic targets, but their functionality needs further experimental verification.

OBJECTIVE: To evaluate the role of prostate-specific antigen density (PSAD) in different Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1) categories to avoid an unnecessary biopsy in transition zone (TZ) patients with PSA ranging from 4 to 20 ng/mL. MATERIALS AND METHODS: In this retrospective and single-center study, 333 biopsy-naïve patients with TZ lesions who underwent biparametric magnetic resonance imaging (bp-MRI) were analyzed from January 2016 to March 2020. Multivariate logistic regression analyses were performed to determine independent predictors of clinically significant prostate cancer (cs-PCa). The receiver operating characteristic (ROC) curve was used to compare diagnostic performance. RESULTS: PI-RADS v2.1 and PSAD were the independent predictors for TZ cs-PCa in patients with PSA 4-20 ng/mL. 0.9% (2/213), 10.0% (7/70), and 48.0% (24/50) of PI-RADS v2.1 score 1-2, 3, and 4-5 had TZ cs-PCa. However, for patients with PI-RADS v2.1 score 1-2, there were no obvious changes in the detection of TZ cs-PCa (0.8% (1/129), 1.3% (1/75), and 0.0% (0/9)) combining with different PSAD stratification (PSAD < 0.15, 0.15-0.29, and ≥0.30 ng/mL/mL). For patients with PI-RADS v2.1 score ≥ 3, the TZ cs-PCa detection rate significantly varied according to different PSAD stratification. A PI-RADS v2.1 score 3 and PSAD < 0.15 and 0.15-0.29 ng/mL/mL had 8.6% (3/35) and 3.7% (1/27) of TZ cs-PCa, while a PI-RADS v2.1 score 3 and PSAD ≥ 0.30 ng/mL/mL had a higher TZ cs-PCa detection rate (37.5% (3/8)). A PI-RADS v2.1 score 4-5 and PSAD <0.15 ng/mL/mL had no cs-PCa (0.0% (0/9)). In contrast, a PI-RADS v2.1 score 4-5 and PSAD 0.15-0.29 and ≥0.30 ng/mL/mL had the highest cs-PCa detection rate (50.0% (10/20), 66.7% (14/21)). It showed the highest AUC in the combination of PI-RADS v2.1 and PSAD (0.910), which was significantly higher than PI-RADS v2.1 (0.889, P = 0.039) or PSAD (0.803, P < 0.001). CONCLUSIONS: For TZ patients with PSA 4-20 ng/mL, PI-RADS v2.1 score ≤ 2 can avoid an unnecessary biopsy regardless of PSAD. PI-RADS v2.1 score ≥ 3 may avoid an unnecessary biopsy after combining with PSAD. PI-RADS v2.1 combined with PSAD could significantly improve diagnostic performance.

OBJECTIVE: This study was designed to probe into the changes and clinical significance of GRP78 and miR-495-3p in renal failure (RF) patients during high-flux dialysis (HFD) combined with hemoperfusion (HP). METHODS: Sixty-five RF patients and 74 health check-ups who were admitted in our hospital from March 2015 to February 2017 were prospectively selected, and the related characteristics were retrospectively collected for analysis. GRP78 and miR-495-3p were detected in RF patients at admission (before treatment), 12 weeks after treatment (during treatment), 24 weeks after treatment (after treatment), and the control group at admission, and the relationship between the two and the occurrence, efficacy, and recurrence of RF was analyzed. RESULTS: Before treatment, the GRP78 mRNA level in RF patients was higher than that in health check-ups, while the miR-495-3p level was lower (P < 0.05). GRP78 mRNA in RF patients was lower than that before treatment and was the lowest after treatment. On the contrary, miR-495-3p was higher than that before treatment and was the highest after treatment (P < 0.05). The two had a significant effect on predicting RF before treatment, efficacy of patients, and their recurrence after treatment (all P < 0.001). CONCLUSION: GRP78 decreased during the treatment of high-flux hemodialysis (HF-HD) combined with systemic HP in RF patients, while miR-495-3p increased. Both of them have a good reference value for RF occurrence, treatment results, and recurrence.

OBJECTIVE: This study is aimed at identifying stemness-related genes in pancreatic ductal adenocarcinoma (PDAC). METHODS: The RNA-seq data of PADC patients were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. The mRNA expression-based stemness index (mRNAsi) and epigenetically regulated mRNAsi (EREG-mRNAsi) of PADC patients were evaluated. The mRNAsi-related gene sets in PADC were identified by weighted gene coexpression network analysis (WGCNA). The key genes were further analyzed using functional enrichment analysis. The Kaplan-Meier survival analysis and the Cox proportional hazards model were used to evaluate the prognostic value of the key genes. Prognostic hub genes were used to establish nomograms. The receiver operating characteristic (ROC) curves, concordance index (C-index), and calibration curves were used to assess the discrimination and accuracy of the nomogram. Finally, these results were validated in the Gene Expression Omnibus (GEO) database. RESULTS: A total of 36 key genes related to mRNAsi were identified by WGCNA. A prognostic gene signature compromising seven genes (TPX2, ZWINT, UBE2C, CCNB2, CDK1, BUB1, and BIRC5) was established to predict the overall survival (OS) of PADC patients. The Cox regression analysis revealed that the risk score was an independent prognostic factor for PADC. Patients were then divided into the high-risk and low-risk groups. The ROC curves, C-index, and calibration curves indicated good performance of the prognostic signature in the TCGA and GEO datasets. Moreover, the nomogram incorporating clinical parameters showed better sensitivity and specificity for predicting the OS of PADC patients. CONCLUSION: The stemness-related prognostic model successfully predicted the OS of PADC patients and could be used for the treatment of PADC.

BACKGROUND: Male infertility is a main clinical problem that affects about 7% of all men worldwide. Many patients with male infertility are caused by a reduced antioxidant capacity of semen. Several antioxidant supplements, especially vitamin E, are proposed to help male infertility treatment. This project was goaled to study the effects of oral synthetic vitamin E (400 IU/day) for eight weeks on betterment of semen parameters and pregnancy rate. METHODS: After dropping the cases, 124 infertile couples with a male factor who were admitted to the IVF program were included. The male patients with idiopathic abnormal motility and/or morphology were randomized into two groups: 61 receiving vitamin E and 63 as the control group receiving placebo for eight weeks. The pretreatment semen parameters of both groups were compared with those of posttreatment. The pregnancy outcomes were considered between the two groups. RESULTS: There were no significant differences statistically between before and after treatment in the term of sperm volume, count, motility, and morphology. Furthermore, the IVF outcomes of the two groups were not different significantly, either. Interestingly, the percent of normal sperm in the placebo group was significantly decreased after eight weeks. CONCLUSION: Vitamin E supplementation might neutralize free radical activity to keep sperm from more oxidative damages. Further studies regarding the influence of higher acceptable doses of vitamin E on semen characteristics and fertility rates are needed. This study was registered as a two-arm, blinded, randomized, placebo-controlled clinical trial (IRCTID: IRCT2014020616506N1, 2014-03-18).

This study is aimed at developing coriander oil into a nanoemulgel and evaluating its antimicrobial and anticancer effects. Coriander (Coriandrum sativum) oil was developed into a nanoemulgel by using a self-nanoemulsifying technique with Tween 80 and Span 80. Hydrogel material (Carbopol 940) was then incorporated into the nanoemulsion and mixed well. After this, we evaluated the particle size, polydispersity index (PDI), rheology, antimicrobial effect, and cytotoxic activity. The nanoemulsion had a PDI of 0.188 and a particle size of 165.72 nm. Interesting results were obtained with the nanoemulgel against different types of bacteria, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 2.3 μg/ml, 3.75 μg/ml, and 6.5 μg/ml, respectively. In addition, the half-maximal inhibitory concentration (IC50) of the nanoemulgel when applying it to human breast cancer cells (MCF-7), hepatocellular carcinoma cells (Hep3B), and human cervical epithelioid carcinoma cells (HeLa) was 28.84 μg/ml, 28.18 μg/ml, and 24.54 μg/ml, respectively, which proves that the nanoemulgel has anticancer effects. The development of C. sativum oil into a nanoemulgel by using a self-nanoemulsifying technique showed a bioactive property better than that in crude oil. Therefore, simple nanotechnology techniques are a promising step in the preparation of pharmaceutical dosage forms.

BACKGROUND: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. RESULTS: Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. CONCLUSIONS: There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

BACKGROUND: Radiation using conventional X-ray is associated with exposure of radiosensitive organs and typically requires the use of protection. This study is aimed at evaluating the use of bismuth shielding for radiation protection in pediatric pelvic radiography. The effects of the anteroposterior and lateral bismuth shielding were verified by direct measurements at the anatomical position of the gonads. METHODS: Radiation doses were measured using optically stimulated luminescence dosimeters (OSLD) and CIRS ATOM Dosimetry Verification Phantoms. Gonad radiographs were acquired using different shields of varying material (lead, bismuth) and thickness and were compared with radiographs obtained without shielding to examine the effects on image quality and optimal reduction of radiation dose. All images were evaluated separately by three pediatric orthopedic practitioners. RESULTS: Results showed that conventional lead gonadal shielding reduces radiation doses by 67.45%, whereas dose reduction using one layer of bismuth shielding is 76.38%. The use of two layers of bismuth shielding reduces the dose by 84.01%. Using three and four layers of bismuth shielding reduces dose by 97.33% and 99.34%, respectively. Progressively lower radiation doses can be achieved by increasing the number of bismuth layers. Images obtained using both one and two layers of bismuth shielding provided adequate diagnostic information, but those obtained using three or four layers of bismuth shielding were inadequate for diagnosis. CONCLUSIONS: Bismuth shielding reduces radiation dose exposure providing appropriate protection for children undergoing pelvic radiography. The bismuth shielding material is lighter than lead, making pediatric patients more comfortable and less apt to move, thereby avoiding repeat radiography.

Colorectal cancer is a high death rate cancer until now; from the clinical view, the diagnosis of the tumour region is critical for the doctors. But with data accumulation, this task takes lots of time and labor with large variances between different doctors. With the development of computer vision, detection and segmentation of the colorectal cancer region from CT or MRI image series are a great challenge in the past decades, and there still have great demands on automatic diagnosis. In this paper, we proposed a novel transfer learning protocol, called CST, that is, a union framework for colorectal cancer region detection and segmentation task based on the transformer model, which effectively constructs the cancer region detection and its segmentation jointly. To make a higher detection accuracy, we incorporate an autoencoder-based image-level decision approach that leverages the image-level decision of a cancer slice. We also compared our framework with one-stage and two-stage object detection methods; the results show that our proposed method achieves better results on detection and segmentation tasks. And this proposed framework will give another pathway for colorectal cancer screen by way of artificial intelligence.

The epidermal-dermal (ED) and dermal-subcutaneous (DS) junctions are the most prominent skin interfaces, which are known to be of primary importance in different dermatological and aesthetic conditions. These interfaces are strongly modified in aging skin, and their effective targeting can lead to improvement of skin appearance in aging and by cellulite. Application of radiofrequency (RF) currents to the skin can selectively produce mechanical stress on these interfaces. Here, we assess the stresses induced by RF currents of different frequencies on EDJ and DSJ and discuss possible applications of the interfacial therapy in aesthetic medicine.

PURPOSE: The finite element analysis method was used to explore the biomechanical stability of a novel locking plate for thoracolumbar burst fracture fusion fixation. METHODS: The thoracolumbar CT imaging data from a normal volunteer was imported into finite software to build a normal model and three different simulated surgical models (the traditional double-segment fixation model A, the novel double-segment fixation model B, and the novel single-segment fixation model C). An axial pressure (500 N) and a torque (10 Nm) were exerted on the end plate of T12 to simulate activity of the spine. We recorded the range of motion (ROM) and the maximum stress value of the simulated cages and internal fixations. RESULTS: Model A has a larger ROM in all directions than model B (flexion 5.63%, extension 38.21%, left rotation 46.51%, right rotation 39.76%, left bending 9.45%, and right bending 11.45%). Model C also has a larger ROM in all directions than model B (flexion 555.63%, extension 51.42%, left rotation 56.98%, right rotation 55.42%, left bending 65.67%, and right bending 59.47%). The maximum stress of the cage in model A is smaller than that in model B except for the extension direction (flexion 96.81%, left rotation 175.96%, right rotation 265.73%, left bending 73.73%, and right bending 171.28%). The maximum stress value of the internal fixation in model A is greater than that in model B when models move in flexion (20.23%), extension (117.43%), and left rotation (21.34%). CONCLUSION: The novel locking plate has a smaller structure and better performance in biomechanical stability, which may be more compatible with minimally invasive spinal tubular technology.

BACKGROUND: Countries need vital statistics for social and economic planning. World Health Organization (WHO) recommends at least 80% coverage to use registration data on births and deaths for social and economic planning. However, registration remains low in developing countries. National coverage for Kenya in 2014 was 62.2% for births and 45.7% for deaths, with wide regional differentials. Kilifi County in the coastal region in Kenya reported rates below the national coverage at 56% for births and 41% for deaths in 2013. OBJECTIVE: To determine level of knowledge and practice and reasons for low coverage of birth and death in Kilifi County. METHOD: This is a descriptive cross-sectional study that employed multistage cluster random sampling procedure to select a sample of 420 households from which household heads and women with children below five years old were surveyed. RESULTS: Out of the 420 households sampled, about all respondents (99%) were aware of birth registration while death was 77%. Their main sources of information were assistant chiefs at 77% for both birth and death registration and family and friends at 67% for deaths and 52% for births. Coverage for birth registration was 85% and death 63%. More deaths occurred at home (55%) than in hospital (44%) while 55% of deliveries occurred in hospital and 44% at home. Main reasons for not registering death were ignorance (77%) and transport and opportunity cost (21%) while for birth registration were ignorance (42%), travel and opportunity cost (41%), lack of identification documents (9%), and home deliveries (7%). CONCLUSION: Registration of birth and death has improved in Kilifi County. The drivers are legal and requirements to access social rights. Reasons for not registering are ignorance and opportunity costs. Community should be sensitized on the importance of registration, address home deliveries and deaths, and increase efficiency in registration. Further research is recommended to determine the severity of teenage pregnancy and orphanhood in the county.

The prevalence of inflammatory-mediated and oxidative stress-associated diseases is increasing worldwide, creating an increasing demand for novel sources of anti-inflammatory agents and antioxidants. This study was focused on determining the in vitro arachidonate 5-lipoxygenase (A5-LOX), xanthine oxidase (XO), hyaluronidase and oxidative burst inhibitory activities, and antioxidant properties of Ravi, Rawana, and Oshadha finger millet varieties using ethanolic and methanolic extracts. Among all extracts, the methanolic extract of Oshadha exhibited the highest A5-LOX (IC50 value: 484.42 μg/ml) and XO (IC50 value: 764.34 μg/ml) inhibitory activities. All extracts showed less than 50% hyaluronidase inhibitory activity at 1 mg/ml concentration. Methanolic extracts showed moderate inhibitory potential on reactive oxygen species (ROS) generated from whole blood phagocytes, with IC50 values ranging between 26.9 and 27.7 μg/ml, when compared to ibuprofen (IC50 value: 11.18 μg/ml). All extracts showed potent inhibition of ROS produced from polymorphonuclear neutrophils isolated from human blood when compared to ibuprofen (IC50 value: 2.47 μg/ml) and IC50 values of methanolic and ethanolic extracts ranged from 0.29 to 0.47 μg/ml and 1.35 to 1.70 μg/ml, respectively. All extracts had significantly high amounts of phenolic compounds including flavonoids and the potential to scavenge 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic) acid (ABTS) cation, 2,2-diphenyl-1-picryl-hydrazyl (DPPH), and oxygen radicals. Besides, they were able to reduce metal ions and chelate metal ions terminating radical generating reactions. This is the first report of A5-LOX, XO, hyaluronidase, and oxidative burst inhibitory properties of any extract of any finger millet variety cultivated in Sri Lanka. The findings revealed the potential of using these finger millet extracts as natural sources of anti-inflammatory drug candidates. Additionally, the findings indicated that Ravi, Rawana, and Oshadha varieties are good sources of antioxidants. Therefore, consumption of these finger millet varieties on a regular basis may play an important role in the prevention and dietary management of oxidative stress-associated diseases.

Breast cancer diagnosis is a critical step in clinical decision making, and this is achieved by making a pathological slide and gives a decision by the doctors, which is the method of final decision making for cancer diagnosis. Traditionally, the doctors usually check the pathological images by visual inspection under the microscope. Whole-slide images (WSIs) have supported the state-of-the-art diagnosis results and have been admitted as the gold standard clinically. However, this task is time-consuming and labour-intensive, and all of these limitations make low efficiency in decision making. Medical image processing protocols have been used for this task during the last decades and have obtained satisfactory results under some conditions; especially in the deep learning era, it has exhibited the advantages than those in the shallow learning period. In this paper, we proposed a novel breast cancer region mining framework based on deep pyramid architecture from multilevel and multiscale breast pathological WSIs. We incorporate the tissue- and cell-level information together and integrate these into a LSTM model for the final sequence modelling, which successfully keeps the WSIs' integration and is not mentioned by the prevalence frameworks. The experiment results demonstrated that our proposed framework greatly improved the detection accuracy than that only using tissue-level information.

Multiantimicrobial-resistant Escherichia coli isolates are a global human health problem causing increasing morbidity and mortality. Genes encoding antimicrobial resistance are mainly harbored on mobile genetic elements (MGEs) such as transposons and plasmids as well as integrons, which enhance their rapid spread. The aim of this study was to characterize 83 multiantimicrobial-resistant E. coli isolates recovered from healthy broiler chickens. Among 78 tetracycline-resistant isolates, the tetA, tetB, and tetC genes were detected in 59 (75.6%), 14 (17.9%), and one (1.2%) isolates, respectively. The sul1, sul2, and sul3 genes were detected 31 (46.2%), 16 (23.8%), and 6 (8.9%) isolates, respectively, among 67 sulfonamide-resistant isolates. The PCR-based replicon typing method showed plasmids in 29 isolates, IncFIB (19), IncI1-Iγ (17), IncF (14), IncK (14), IncFIC (10), IncP (8), IncY (3), IncHI2 (1), and IncX (1). The class 1 and 2 integrons were detected in 57 and 2 isolates, respectively; one isolate harbored both integrons. Seven and one gene cassette arrays were identified in class 1 and class 2 integrons, respectively. Our findings show that multiantimicrobial-resistant E. coli isolates from chickens serve as reservoirs of highly diverse and abundant tet and sul genes and plasmid replicons. Such isolates and MGEs pose a potential health threat to the public and animal farming.

In patients of oral cavity or oropharyngeal cancers, resection of the tumor and reconstruction of the defect may reduce the framework, add a bulky flap, alter the tissue flexibility, and contribute to postoperative obstructive sleep apnea (OSA). Postoperative OSA and the potential consequences may decrease the survival rate and reduce patients' quality of life. It is unclear whether the surgery is associated with postoperative OSA. Here, we compared the polysomnographies (PSGs) before and after the surgery in 15 patients of oral cavity or oropharyngeal cancers (out of 68 patients of head and neck cancers) without a chemo- or radio-therapy. Each patient received the second PSG before the start of any indicated adjuvant therapy to prevent its interference. There were 14 men and 1 woman, with a mean age and a standard deviation (SD, same in the following) of 56.2 ± 12.8 years. There were 6 tongue cancers, 5 buccal cancers, 2 tonsil cancer, 1 lower gum cancer, and 1 trigone cancer. The results show that the surgery changed sleep parameters insignificantly in apnea-hypopnea index (AHI), mean oxyhemoglobin saturation of pulse oximetry (SpO2), minimum SpO2, mean desaturation, and desaturation index but increased mean heart rate in the patients with free flaps. These results hint that the effect of surgery on developing OSA was small in this sample, with a longer plate or a larger framework for a bulkier free flap. It needs future studies with a large sample size to generalize this first observation.

Our aim was to explore the effects of dietary and behavior interventions on lipometabolism caused by an unhealthy high-fat diet and the best method to rebuild lipid homeostasis of this lifestyle. Apart from normal diet rats, 34 rats were fed with high-fat emulsion for 4 weeks and then intervened for another 4 weeks. Eight of them were classified into high-fat control group, and 9 were sorted into high-fat diet with rice vinegar group. Meanwhile, 10 were put into high-fat diet in swimming group, and 7 were just for refeeding normal diet group. Then, the data of body weight was recorded and analyzed. Indexes of serum samples were tested by kits. AMPKα, HNF1α, and CTRP6 in pancreas, liver, cardiac, and epididymis adipose tissues were detected by western blot. According to our experiments, swimming and refeeding groups reflected a better regulation on lipid homeostasis mainly by upregulating the expression of pancreas AMPKα. To be more specific, the refeeding rats showed lower T-CHO (P < 0.001) and LDL-C (P < 0.05), but higher weight gain (P < 0.001), insulin level (P < 0.01), and pancreas AMPKα (P < 0.01) than high-fat control rats. Compared with rats intervened by swimming or rice vinegar, they showed higher weight gain (P < 0.001), insulin level (P < 0.01), and HNF1α, but lower of CTRP6. In summary, refeeding diet functioned better in regulating the lipometabolic level after high-fat diet. Whatever approach mentioned above we adopted to intervene, the best policy to keep the balance of lipid homeostasis is to maintain a healthy diet.