Malignant mesothelioma (MM)" is an uncommon although fatal form of cancer. The proper MM diagnosis is crucial for efficient therapy and has significant medicolegal implications. Asbestos is a carcinogenic material that poses a health risk to humans. One of the most severe types of cancer induced by asbestos is "malignant mesothelioma." Prolonged shortness of breath and continuous pain are the most typical symptoms of the condition. The importance of early treatment and diagnosis cannot be overstated. The combination "epithelial/mesenchymal appearance of MM," however, makes a definite diagnosis difficult. This study is aimed at developing a deep learning system for medical diagnosis MM automatically. Otherwise, the sickness might cause patients to succumb to death in a short amount of time. Various forms of artificial intelligence algorithms for successful "Malignant Mesothelioma illness" identification are explored in this research. In relation to the concept of traditional machine learning, the techniques support "Vector Machine, Neural Network, and Decision Tree" are chosen. SPSS has been used to analyze the result regarding the applications of Neural Network helps to diagnose MM.

Clinical multi-drug-resistant bacteria continue to be a serious health problem. Plant-derived molecules are an important source of bioactive compounds to counteract these pathogenic bacteria. In this paper, we studied the chemical composition of the methanol (80%) extract from Pithecellobium dulce seed (Hail, Saudi Arabia) and its ability to inhibit the growth of clinically relevant multi-drug-resistant bacteria. Molecular docking analysis was performed to predict the best compounds with low binding energy and high affinity to interact with two Staphylococcus aureus receptors. Data showed that P. dulce extract is a rich source of D-turanose (55.82%), hexadecanoic acid (11.56%), indole-1-acetic acid (11.42%), inositol (5.78%), and octadecanoic acid (4.36%). The obtained extract showed antibacterial activity towards tested clinical bacterial strains with MIC values ranging from 233 mg/mL for Acinetobacter baumannii to 300 mg/mL for S. aureus and Escherichia coli. Turanose interaction has resulted in -7.4 and -6.6 kcal/mol for 1JIJ and 2XCT macromolecules, while inositol showed energy values (-7.2 and -5.4 kcal/mol) for the same receptors. Multiple identified compounds showed desirable bioavailability properties indicating its great potential therapeutic use in human. Overall, current investigation highlights the possible use of P. dulce extract as a valuable source for drug development against pathogenic drug-resistant bacteria.

BACKGROUND: Long intergenic nonprotein coding RNA 1503 (LINC01503) was reportedly oncogenic in several malignancies, whereas whether it contributed to pancreatic cancer tumorigenesis and progression requires to be verified. METHODS: The expression pattern of LINC01503 was monitored via qRT-PCR assay in normal cells and cancerous pancreatic cancer cells. The introduction of silencing LINC01503 was to verify the relation between LINC01503 expression and cell growth. Then, the targeting relationship of LINC01503 to miR-1321 was confirmed by bioinformatics predication and luciferase reporter assay. In addition, luciferase reporter assays evaluated the binding of miR-1321 to the 3'-untranslated region of KLK4. Overexpressing KLK4 and inhibiting LINC01503 was introduced in tumor cells to investigate the corresponding impacts on pancreatic cancer cell proliferation and migration. RESULTS: LINC01503 and KLK4 were highly abundant in pancreatic cancer cells. Mechanistically, miR-1321 bound to LINC01503 and KLK4. Downregulating LINC01503 promoted the availability of miR-1321 in pancreatic cancer cells and thus repressed KLK4 expression. KLK4 overexpression abolished the impediment of LINC01503 depletion on cell proliferation and migration. CONCLUSION: Oncogenic function of LINC01503 was dependent on KLK4 upregulation by sponging miR-1321. Revealing the tumor-promoting property of LINC01503 in pancreatic cancer may confer new biomarkers for this malignancy.

OBJECTIVE: To evaluate whether traditional Chinese medicine compound preparations (TCMCPs) are associated with rheumatoid arthritis- (RA-) related complications (including readmission, Sjogren's syndrome, surgical treatment, and all-cause death) in patients with RA. METHODS: Clinical outcome data were retrospectively collected from patients with RA discharged from the Department of Rheumatology and Immunology of the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2009 to June 2021. The propensity score matching method was used to match baseline data. Multivariate analysis was conducted to analyze sex, age, the incidence of hypertension, diabetes, and hyperlipidemia and identify the risk of readmission, Sjogren's syndrome, surgical treatment, and all-cause death. Users of TCMCP and nonusers of TCMCP were defined as the TCMCP and non-TCMCP groups, respectively. RESULTS: A total of 11,074 patients with RA were included in the study. The median follow-up time was 54.85 months. After propensity score matching, the baseline data of TCMCP users corresponded with those of non-TCMCP users, with 3517 cases in each group. Retrospective analysis revealed that TCMCP significantly reduced clinical, immune, and inflammatory indices in patients with RA, and these indices were highly correlated. Notably, the composite endpoint prognosis for treatment failure in TCMCP users was better than that in non-TCMCP users (HR = 0.75 (0.71-0.80)). The risk of RA-related complications in TCMCP users with high-exposure intensity (HR = 0.669 (0.650-0.751)) and medium-exposure intensity (HR = 0.796 (0.691-0.918)) was significantly lower than those in non-TCMCP users. An increase in exposure intensity was associated with a concomitant decrease in the risk of RA-related complications. CONCLUSION: The use of TCMCPs, as well as long-term exposure to TCMCPs, may lower RA-related complications, including readmission, Sjogren's syndrome, surgical treatment, and all-cause death, in patients with RA.

INTRODUCTION: In recent years, the use of dashboards in healthcare has been considered an effective approach for the visual presentation of information to support clinical and administrative decisions. Effective and efficient use of dashboards in clinical and managerial processes requires a framework for the design and development of tools based on usability principles. OBJECTIVES: The present study is aimed at investigating the existing questionnaires used for the usability evaluation framework of dashboards and at presenting more specific usability criteria for evaluating dashboards. METHODS: This systematic review was conducted using PubMed, Web of Science, and Scopus, without any time restrictions. The final search of articles was performed on September 2, 2022. Data collection was performed using a data extraction form, and the content of selected studies was analyzed based on the dashboard usability criteria. RESULTS: After reviewing the full text of relevant articles, a total of 29 studies were selected according to the inclusion criteria. Regarding the questionnaires used in the selected studies, researcher-made questionnaires were used in five studies, while 25 studies applied previously used questionnaires. The most widely used questionnaires were the System Usability Scale (SUS), Technology Acceptance Model (TAM), Situation Awareness Rating Technique (SART), Questionnaire for User Interaction Satisfaction (QUIS), Unified Theory of Acceptance and Use of Technology (UTAUT), and Health Information Technology Usability Evaluation Scale (Health-ITUES), respectively. Finally, dashboard evaluation criteria, including usefulness, operability, learnability, ease of use, suitability for tasks, improvement of situational awareness, satisfaction, user interface, content, and system capabilities, were suggested. CONCLUSION: General questionnaires that were not specifically designed for dashboard evaluation were mainly used in reviewed studies. The current study suggested specific criteria for measuring the usability of dashboards. When selecting the usability evaluation criteria for dashboards, it is important to pay attention to the evaluation objectives, dashboard features and capabilities, and context of use.

In this study, we aim to investigate retinal thickness (RT) and superficial vascular density (SVD) differences between patients with systemic sclerosis (SSc) and healthy controls (HCs) by optical coherence tomography angiography (OCTA). Sixteen patients with a definitive SSc diagnosis without clinical signs of retinopathy and 16 normal control subjects were recruited. All individuals underwent OCTA scanning to assess macular RT and SVD. We divided each image into nine subregions as the early treatment diabetic retinopathy study (ETDRS). Visual acuity (VA) was considerably different between patients with SSc (32 eyes) and control subjects (32 eyes) (p < 0.001). Compared to the control group, individuals with SSc had decreased inner RT in inner superior, outer superior, outer temporal, inner temporal, center, and inner nasal regions (p < 0.05). Outer RT was decreased in the outer and inner temporal regions, and full RT was decreased in the regions of outer superior, inner superior, inner temporal, and outer temporal, in comparison to the control group (p < 0.05). Patients with SSc had significant reduction of SVD in the inner and outer of both superior and temporal, besides outer nasal regions than controls. (p < 0.05). Moreover, SVD was significantly associated with the outer temporal region of patients suffering from SSc (p < 0.05). Diagnostic Sensitivity of RT and SVD of Inner Superior Regions in SSc, as indicated by areas under curves of the Receiver Operating Characteristic (ROC), were 0.874 (95% CI: 0.786-0.962) and 0.827 (95% CI: 0.704-0.950), respectively. In conclusion, VA may be affected by RT variations inside the macula in patients with SSc. Measuring RT with OCTA could be a useful predictor of early diagnosis.

Aging slows down the mechanisms behind skeletal muscle weakening and mobility. Increases in inflammation brought on by aging may contribute to some characteristics of sarcopenia. As a result of population aging worldwide, sarcopenia, an age-related disease, has become a huge burden on both individuals and society as a whole. The study of the morbidity mechanism and available sarcopenia treatments has received more attention. The inflammatory response may be one of the most important methods behind the pathophysiology of sarcopenia in the aged, according to the background of the study. This anti-inflammatory cytokine inhibits the ability of human monocytes and macrophages to induce inflammation as well as the production of cytokines like IL-6. Here, we investigate the association between sarcopenia and interleukin-17 (IL-17), an inflammatory cytokine in the aged. There were 262 subjects aged 61-90 years who were screened for sarcopenia in Hainan General Hospital. The subjects were divided into 45 males and 60 females aged 65-79 years (average age: 72.00 ± 4.31 years). 105 patients without sarcopenia were randomly selected among 157 participants. It included 50 males and 55 females, aged 61-76 years (mean age: 69.10 ± 4.55 years) as per the standard definition of the Asian Working Group for Sarcopenia (AWGS). The "skeletal muscle index" (SMI), "hand grip strength" (HGS), "gait speed" (GS), "biochemical indexes," "serum IL-17 level," nutritional status, and past medical history of the two groups were evaluated and compared. Compared with the participants without sarcopenia, sarcopenia patients had higher average age; less physical exercise; lower total scores of BMI, pre-ALB, IL-17, and SPPB; and a higher proportion of malnutrition risk (all P < 0.05). By "ROC curve analysis," the best critical point was IL-17 in the growth of sarcopenia. The area that comes under ROC (AUROC) value was 0.627 (95% CI = 0.552, 0.702, P = 0.002). The ideal threshold value for IL-17 to estimate sarcopenia was 18.5 pg/mL. In the unadjusted model, IL-17 was considerably linked to sarcopenia (OR = 1.123, 95% CI = 1.037-1.215, P = 0.004). After the covariate adjustment observed in the complete adjustment model (OR = 1.111, 95% CI = 1.004-1.229, P = 0.002), this significance still exists. The results of this study suggest a strong relationship between sarcopenia and IL-17. This study will look at IL-17's potential to serve as a key sarcopenia indicator. This trial is registered with ChiCTR2200022590.

PURPOSE: Malignant hyperthermia (MH) is a rare genetic disorder but one of the most severe complications of general anesthesia. The mortality rate of MH has dropped from 70% in the 1960s to 15% because of dantrolene, the only currently accepted specific treatment for MH. In this study, we retrospectively identified the optimal dantrolene administration conditions to reduce MH mortality further. METHODS: Our database performed a retrospective analysis of patients with MH clinical grading scale (CGS) grade 5 (very likely) or 6 (almost certain) between 1995 and 2020. We examined whether dantrolene administration affected mortality and compared the clinical variables associated with improved prognosis. Furthermore, a multivariable logistic regression analysis was used to identify specific variables associated with improved prognosis. RESULTS: 128 patients met the inclusion criteria. 115 patients were administered dantrolene; 104 survived, and 11 died. The mortality rate of patients who were not administered dantrolene was 30.8%, which was significantly higher than those of patients who were administered dantrolene (P = 0.047). Among patients administered dantrolene, the interval from the first sign of MH to the start of dantrolene administration was significantly longer in the deceased than in the survivors (100 min vs. 45.0 min, P < 0.001), and the temperature at the start of dantrolene administration was also significantly higher in the deceased (41.6°C vs. 39.1°C, P < 0.001). There was no significant difference in the rate of increase in temperature between the two, but there was a substantial difference in the maximum temperature (P < 0.001). The multivariable analysis also showed that the patient's temperature at dantrolene administration and interval from the first MH sign to dantrolene administration was significantly associated with improved prognosis. CONCLUSIONS: Dantrolene should be given as rapidly as possible once MH has been diagnosed. Beginning treatment at a more normal body temperature can prevent critical elevations associated with a worse prognosis.

OBJECTIVE: The aim of the study was to explore the potential mechanism of Zanthoxylum bungeanum in the treatment of diabetes mellitus (DM) using network pharmacology. METHODS: The DrugBank database and TCMSP platform were used to search for the main chemical components and their targets of Zanthoxylum bungeanum, and the genes related to diabetes mellitus were obtained from the genecards database. Import the data into the Venny 2.1.0 platform for intersection analysis to obtain the Zanthoxylum bungeanum-DM-gene dataset. The protein-protein interaction (PPI) analysis of Zanthoxylum bungeanum-DM gene was performed using the String data platform, and the visualization and network topology analysis were performed using Cytoscape 3.8.2. The KEGG pathway enrichment and biological process of GO enrichment analysis were carried out using the David platform. The active ingredients and key targets of Zanthoxylum bungeanum were molecularly docked to verify their biological activities by using Discovery Studio 2019 software. Zanthoxylum bungeanum was extracted and isolated by ethanol and dichloromethane. HepG2 cells were cultured, and cell viability assay was utilized to choose the suitable concentration of Zanthoxylum bungeanum extract (ZBE). The western blot assay was used for measuring the expression of AKT1, IL6, HSP90AA1, FOS, and JUN proteins in HepG2 cells. RESULTS: A total of 5 main compounds, 339 targets, and 16656 disease genes were obtained and retrieved, respectively. A total of 187 common genes were screened, and 20 core genes were finally obtained after further screening. The antidiabetic active ingredients of Zanthoxylum bungeanum are kokusaginin, skimmianin, diosmetin, beta-sitosterol, and quercetin, respectively. The main targets for its antidiabetic effect are AKT1, IL6, HSP90AA1, FOS, and JUN, respectively. GO enrichment analysis revealed that the biological process of Zanthoxylum bungeanum and DM is related to a positive regulation of gene expression, positive regulation of transcription, positive regulation of transcription from RNA polymerase II promoter, response to drug, positive regulation of apoptotic process, and positive regulation of cell proliferation, etc. KEGG enrichment analysis revealed that common biological pathways mainly including the phospholipase D signaling pathway, MAPK signaling pathway, beta-alanine metabolism, estrogen signaling pathway, PPAR signaling pathway, and TNF signaling pathway. Molecular docking results showed that AKT1 with beta-sitosterol and quercetin, IL-6 with diosmetin and skimmianin, HSP90AA1 with diosmetin and quercetin, FOS with beta-sitosterol and quercetin, and JUN with beta-sitosterol and diosmetin have relatively strong binding activity, respectively. Experiment verification results showed that DM could be significantly improved by downregulating the expression of AKT1, IL6, HSP90AA1, FOS, and JUN proteins after being treated at concentrations of 20 μmol/L and 40 μmol/L of ZBE. CONCLUSION: The active components of Zanthoxylum bungeanum mainly including kokusaginin, skimmianin, diosmetin, beta-sitosterol, and quercetin. The therapeutic effect of Zanthoxylum bungeanum on DM may be achieved by downregulating core target genes including AKT1, IL6, HSP90AA1, FOS, and JUN, respectively. Zanthoxylum bungeanum is an effective drug in treatment of DM related to the above targets.

Cancer is characterized by abnormal cell growth and proliferation, which are both diagnostic indicators of the disease. When cancerous cells enter one organ, there is a risk that they may spread to adjacent tissues and eventually to other organs. Cancer of the cervix of the uterus often initially manifests itself in the uterine cervix, which is located at the very bottom of the uterus. Both the growth and death of cervical cells are characteristic features of this condition. False-negative results provide a significant moral dilemma since they may cause women to get an incorrect diagnosis of cancer, which in turn can result in the woman's premature death from the disease. False-positive results do not raise any significant ethical concerns; but they do require a patient to go through an expensive and time-consuming treatment process, and they also cause the patient to experience tension and anxiety that is not warranted. In order to detect cervical cancer in its earliest stages in women, a screening procedure known as a Pap test is often performed. This article describes a technique for improving images using Brightness Preserving Dynamic Fuzzy Histogram Equalization. To individual components and find the right area of interest, the fuzzy c-means approach is applied. The images are segmented using the fuzzy c-means method to find the right area of interest. The feature selection algorithm is the ACO algorithm. Following that, categorization is carried out utilizing the CNN, MLP, and ANN algorithms.

Cigarette smoking is a significant risk factor for chronic and atherosclerotic vascular disease that causes preventable considerable morbidity and mortality worldwide. This study is aimed at comparing inflammation and the levels of oxidative stress biomarkers in elderly subjects. The authors recruited the participants (1281 older adults) from the Birjand Longitudinal of Aging study. They measured oxidative stress and inflammatory biomarkers serum levels in the 101 cigarettes and 1180 nonsmokers. The mean age of smokers was 69.3 ± 7.95 years, and most were male. The most percentage of male cigarette smokers have lower body mass index (BMI) (≤19 kg/m2). Females have higher BMI categories than males (P ≤ 0.001). The percentage of diseases and defects was different between cigarette and non-cigarette smoker adults (P ≤ 0.01 to P ≤ 0.001). The total white blood cells, neutrophils, and eosinophils were significantly higher in cigarettes compared to non-cigarette smokers (P ≤ 0.001). Besides, cigarette consumers' percentage of hemoglobin and hematocrit compared to other aged people was significantly different (P ≤ 0.001). However, biomarkers of oxidative stress and antioxidant levels were not significant differences between the two senior groups. Cigarette smoking in older adults was associated with increased inflammatory biomarkers and cells, but it did not find a significant difference in oxidative stress markers. Longitudinal prospective studies may help illuminate the mechanisms inducing oxidative stress and inflammation due to cigarette smoking in each gender.

Despite the recent advancement of treatment strategies, cancer ranks 2nd among the causes of death globally. Phytochemicals have gained popularity as an alternate therapeutic strategy due to their nontoxic nature. Here, we have investigated the anticancer properties of guttiferone BL (GBL) along with four known compounds previously isolated from Allanblackia gabonensis. The cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The study was extended for the assessment of the effect of GBL in PA-1 cells apoptosis induction, cell cycle distribution, and change in mitochondrial membrane potential using flow cytometry, Western blot analysis, and real-time PCR. Among the five tested compounds, GBL displayed significant antiproliferative effects against all tested human cancer cells (IC50 < 10μM). Moreover, GBL exhibited no significant cytotoxicity towards normal ovarian epithelial cell line (IOSE 364) up to 50 μM. GBL induced sub-G0 cell cycle arrest and significant upregulation of cell cycle regulatory proteins of ovarian cancer cell PA-1. Furthermore, GBL induced its apoptosis as depicted by the accumulation of cells both at the early and late apoptotic phase in Annexin V/PI assay. In addition, it decreased the PA-1 mitochondrial membrane potential and promoted upregulation of caspase-3, caspase-9, and Bax and downregulation of Bcl-2. GBL also showed a dose-dependent inhibition of PA-1 migration. Altogether, this study reveals that guttiferone BL, studied herein for the first time, exhibits efficient antiproliferative activity by the induction of apoptosis through the mitochondrial-dependent pathway. Its investigation as a therapeutic agent against human cancers especially ovarian cancer should be envisaged.

BACKGROUND: No pan-cancer study has been conducted till date to explore the comprehensive oncogenic roles of pyruvate kinase M2 (PKM2). METHODS: TCGA, TIMER, GEPIA, UALCAN, STRING, and other databases were used to analyze the expression, prognostic roles, epigenetic variants, and possible oncogenic mechanisms of PKM2. Proteomic sequencing data and PRM were applied to validate. RESULTS: PKM2 showed higher expression in majority of cancers, the expression being significantly correlated with the clinical stage. Higher expression of PKM2 was associated with lower OS and DFS in several cancers, such as MESO and PAAD. In addition, the epigenetic variation of PKM2, including gene alteration, mutation type and sites, DNA methylation, and phosphorylation, showed diversity in different cancers. All four methods indicated that PKM2 is positively associated with the immune infiltration of tumor-associated fibroblasts, such as in THCA, GBM, and SARC. Further mechanistic exploration suggested that the ribosome pathway might play an essential role in the regulation of PKM2, and interestingly, four out of ten hub genes were found to be highly related to OS in several cancers. Finally, in thyroid cancer specimen, we validated the expression and potential mechanisms by proteomic sequencing and PRM validation. CONCLUSION: In the majority of cancers, the higher expression of PKM2 was highly associated with poor prognosis. Further molecular mechanism exploration implied that PKM2 might serve as a potential target for cancer survival and immunotherapy by regulating the ribosome pathway.

RNA viruses have been the most destructive due to their transmissibility and lack of control measures. Developments of vaccines for RNA viruses are very tough or almost impossible as viruses are highly mutable. For the last few decades, most of the epidemic and pandemic viral diseases have wreaked huge devastation with innumerable fatalities. To combat this threat to mankind, plant-derived novel antiviral products may contribute as reliable alternatives. They are assumed to be nontoxic, less hazardous, and safe compounds that have been in uses in the beginning of human civilization. In this growing COVID-19 pandemic, the present review amalgamates and depicts the role of various plant products in curing viral diseases in humans.

OBJECTIVE: The diagnosis of primary malignant melanoma of the esophagus (PMME) before treatment is essential for clinical decision-making. However, PMME may be misdiagnosed as esophageal squamous cell carcinoma (ESCC) sometimes. This research is aimed at devising a radiomics nomogram model of CT for distinguishing PMME from ESCC. METHODS: In this retrospective analysis, 122 individuals with proven pathologically PMME (n = 28) and ESCC (n = 94) were registered from our hospital. PyRadiomics was applied to derive radiomics features from plain and enhanced CT images after resampling image into an isotropic resolution of 0.625 × 0.625 × 0.625 mm3. The diagnostic efficiency of the model was evaluated by an independent validation group. RESULTS: For the purpose of differentiation between PMME and ESCC, a radiomics model was constructed using 5 radiomics features obtained from nonenhanced CT and 4 radiomics features derived from enhanced CT. A radiomics model including multiple radiomics features showed excellent discrimination efficiency with AUCs of 0.975 and 0.906 in the primary and validation cohorts, respectively. Then, a radiomics nomogram model was developed. The decision curve analysis has shown remarkable performance of this nomogram model for distinguishing PMME from ESCC. CONCLUSIONS: The proposed radiomics nomogram model based on CT could be used for distinguishing PMME from ESCC. Moreover, this model also contributed to helping clinicians determine an appropriate treatment strategy for esophageal neoplasms.

OBJECTIVE: Ulcerative colitis is an intestinal condition that severely affects the life quality of a patient. Jiawei Zhengqi powder (JWZQS) has some therapeutic benefits for ulcerative colitis. The current study investigated the therapeutic mechanism of JWZQS for ulcerative colitis using a network pharmacology analytical approach. METHODS: In this study, network pharmacology was used to investigate the potential mechanism of JWZQS in treating ulcerative colitis. The common targets between the two were identified, and a network map was created with the Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses of JWZQS was performed using the Metascape database. Protein-protein interaction networks (PPI) was created to screen core targets and main components, and molecular docking was conducted between the main components and core targets. The expression levels of IL-1β, IL-6, and TNF-α were detected in animal experiments. Their effect on the NF-κB signaling pathway and the protective mechanism of JWZQS on the colon by tight junction protein were investigated. RESULTS: There were 2127 potential ulcerative colitis targets and 35 components identified, including 201 non-reproducible targets and 123 targets shared by drugs and diseases. Following the analysis, we discovered 13 significant active components and 10 core targets. The first 5 active ingredients and their corresponding targets were molecularly docked, and the results showed a high level of affinity. GO analysis showed that JWZQS participate in multiple biological processes to treat UC. KEGG analysis showed that JWZQS may be involved in regulating multiple pathways, and the NF-κB signaling pathway was selected for analysis and verification. JWZQS has been shown in animal studies to effectively inhibit the NF-κB pathway; reduce the expression of IL-1β, TNF-α, and IL-6 in colon tissue; and increase the expression of ZO-1, Occludin, and Claudin-1. CONCLUSION: The network pharmacological study provides preliminary evidence that JWZQS can treat UC through multiple components and targets. JWZQS has been shown in animal studies to effectively reduce the expression levels of IL-1β, TNF-α, and IL-6, inhibit the phosphorylation of the NF-κB pathway, and alleviate colon injury. JWZQS can be used in clinical, but the precise mechanism of UC treatment requires further investigation.

Yiqi Yangyin Decoction (YYD) is a classic traditional Chinese medicine (TCM) formulation to treat lung cancer in clinic. Nevertheless, the active ingredients, key targets, and molecular mechanisms for YYD are still poorly understood. This study is focused on elucidating the pharmacological mechanism of YYD in non-small-cell lung cancer (NSCLC) by using a combined network pharmacology approach and biological experiment validation. Online bioinformatics tools showed that 40 bioactive compounds and 229 putative targets of YYD were associated with anti-NSCLC activity. Protein-Protein Interaction (PPI) network demonstrated AKT1, SRC, JUN, TP53, and EGFR as the top five key targets for YYD against NSCLC. Through enrichment analysis, YYD was found to affect cell proliferation and apoptosis in NSCLC possibly by PI3K-AKT signaling. Molecular docking confirmed a strong binding between the main compounds (quercetin or luteolin) and EGFR. As demonstrated by CCK-8, EdU, and colony formation assays, we found a significant inhibition of YYD on cell proliferation. Moreover, YYD treatment induced cell cycle arrest by affecting p53, p21, and cyclin D1 expression. YYD administration enhanced apoptosis by changing the expression of cleaved caspase-3, Bax, and Bcl-2. Mechanistically, YYD resulted in a significant inactivation of EGFR-PI3K-AKT signaling. Furthermore, EGFR activator significantly reversed YYD-mediated proliferation inhibition and apoptosis. YYD also showed an inhibitory effect on tumor growth in mice. Together, YYD might target the EGFR-PI3K-AKT pathway to repress NSCLC progression.

The prospective, simple randomized study assesses the effect of focused extracorporeal shock wave therapy (f-ESWT) on pain intensity and calcification size compared to the application of ultrasound physical therapy in treating patients with calcar calcanei. A total of 124 patients diagnosed with calcar calcanei were consecutively included in the study. The patients were divided into two groups: the experimental group (n = 62), which included the patients treated with f-ECWT, and the control group (n = 62), consisting of patients treated with the standard ultrasound therapy method. The experimental group's patients received ten therapy applications spaced seven days apart. The patients in the control group had ten ultrasound treatments on ten consecutive days over two weeks. All patients in both groups were tested using the Visual Analog Scale (VAS) to measure pain intensity before the beginning and at the end of treatment. The size of the calcification was assessed in all patients. The study hypothesizes that f-ESWT reduces the pain and the size of the calcification. Pain intensity reduction was registered in all patients. The calcification size in patients in the experimental group was reduced from the initial range of 2 mm-15 mm, to a content of 0.0 mm-6.2 mm. The calcification size in the control group ranged from 1.2 to 7.5 mm, without any change. None of the patients experienced any adverse reactions to the therapy. Patients treated with standard ultrasound therapy did not have a statistically significant reduction in the calcification size. In contrast, the patients in the experimental group treated with f-ESWT showed a substantial decrease in the calcification size.

OBJECTIVES: To evaluate the success rate of bone grafts and implants carried out at the Latin American Institute for Research and Dental Education (ILAPEO), considering the following: (i) the different pure bone substitutes (autogenous, xenogeneic, and alloplastic), (ii) the presurgical bone height, and (iii) how the treatment is compromised when membrane perforation occurs during sinus lift in maxillary sinus surgeries. Material and Methods. The initial sample comprised 1040 records of maxillary sinus lifting surgeries. After evaluation, the final sample retained 472 grafts performed using the lateral window technique with a total of 757 implants. The grafts were divided into 3 groups: (i) autogenous bone (n = 197), (ii) xenogenous bovine bone (n = 182), and (iii) alloplastic material (n = 93). One calibrated examiner classified the sample into two groups based on the residual bone height (<4 mm and ≥4 mm) of the area of interest measured on parasagittal sections of tomographic images. Data on membrane perforation occurrences in each group were collected; qualitative variables were described using frequency, expressed as percentages. The Chi-square test was used to analyze the success of the graft types and the survival rate of the implants as a function of the grafted material and the residual bone height. The Kaplan-Meier survival analysis was used to calculate the survival rate of bone grafts and implants according to the classifications adopted in this retrospective study. RESULTS: The success rate of grafts and implants was 98.3% and 97.2%, respectively. There was no statistically significant difference in the success rate among the different bone substitutes (p = 0.140). Only 8 grafts (1.7%) and 21 implants (2.8%) failed. There was a greater success rate for both grafts (96.5%) and implants (97.4%) when the bone height was ≥4 mm. The success rate in the 49 sinuses in which the membrane was perforated was 97.96% for the grafts and 96.2% for the implants. The follow-up periods after rehabilitation ranged from 3 months to 13 years. CONCLUSIONS: Within the limitations of the data analyzed in this retrospective study, maxillary sinus lift was a viable surgical technique that enabled implant placement with a predictable long-term success rate, regardless of the type of material used. The presence of membrane perforation did not interfere with the success rate obtained for grafts and implants.

PURPOSE: To investigate changes in corneal densitometry (CD) and visual quality following small incision lenticule extraction (SMILE) and laser epithelial keratomileusis (LASEK) in patients with mild-to-moderate myopia. METHODS: A retrospective analysis was performed on 24 and 25 patients (46 eyes each) who underwent SMILE and LASEK, respectively, for mild-to-moderate myopia. The visual quality and CD values were recorded. Using the Pentacam Scheimpflug system, CD values were collected in three concentric optical zones at the depths of the anterior, central, and posterior layers. Efficacy, safety, predictability, corneal wavefront aberrations, and QoV scores were measured to evaluate visual quality. A correlation analysis was performed between changes in CD and clinical characteristics. RESULTS: There were no statistical differences in efficacy and safety indices between the two groups. At 3 months postoperatively, a pronounced reduction in several zones was observed in the LASEK group (p < 0.05), whereas no obvious change was observed in the SMILE group. There were obvious changes in the CD values in several zones in the SMILE and LASEK groups (p < 0.05) after 1 year. The magnitude of the CD changes in the anterior and central corneal layers was smaller in the SMILE group than in the LASEK group (all p < 0.05). Lower HOAs, spherical aberration, and horizontal comas of the anterior and whole corneal surfaces were observed in the SMILE group. QoV scores were similar between the two groups. CONCLUSION: CD decreased in the SMILE and LASEK groups after 1 year; there was a smaller reduction in SMILE than in LASEK. SMILE and LASEK did not differ significantly in terms of safety and effectiveness in correcting mild-to-moderate myopia.

Donor lung ventilation and inflation during the warm ischemia could attenuate ischemia-reperfusion injury (IRI) after lung transplantation. Hydrogen sulfide (H2S), as a kind of protective gas, has demonstrated the antilung IRI effect. This study is aimed at observing the different methods of administering H2S in the setting of warm ischemia, ventilation, and inflation on the lung graft from a rat non-heart-beating donor. After 1 h of cardiac arrest, donor lungs in situ were inflated with 80 ppm H2S (FS group), ventilated with 80 ppm H2S (VS group), or deflated (control group) for 2 h. Then, the lung transplantation was performed after 3 h cold ischemia. The rats without ischemia and reperfusion were in the sham group. Pulmonary surfactant in the bronchoalveolar lavage fluid was measured in donor lung. The inflammatory response, cell apoptosis, and lung graft function were assessed at 3 h after reperfusion. The lung injury was exacerbated in the control group, which was attenuated significantly after the H2S treatment. Compared with the FS group, the pulmonary surfactant in the donor was deteriorated, the lung oxygenation function was decreased, and the inflammatory response and cell apoptosis were increased in the graft in the VS group (P < 0.05). In conclusion, H2S inflation during the warm ischemia phase improved the function of lung graft via regulating pulmonary surfactant stability and decreased the lung graft IRI via decreasing the inflammatory response and cell apoptosis.

Traditional Chinese medicines (TCM) play an important role in the control and treatment of several animal diseases. Penthorum chinense Pursh (PCP) is a famous plant for its use in traditional medication practice and therapeutic effects in numerous pathological conditions. In China, PCP is utilized for both food and medication due to numerous bioactivities. PCP is widely administered in prevention and treatment of traumatic injury, edema, and liver diseases with functions of reducing swelling, support diuresis, blood stasis, and mitigation symptoms of excessive alcohol intake. Recently, PCP highlighted for research trials in various fields including pharmacology, pharmacognosy, cosmeceuticals, nutraceuticals, and pharmaceuticals due to medicinal significance with less toxicity and an effective ethnomedicine in veterinary practice. PCP contains diverse important ingredients such as flavonoids, organic acids, coumarins, lignans, polyphenols, and sterols that are important bioactive constituents of PCP exerting the therapeutic benefits and organ-protecting effects. In veterinary, PCP extract, compound, and phytochemicals/biomolecules significantly reversed the liver and kidney injuries, via antioxidation, oxidative stress, apoptosis, mitochondrial signaling pathways, and related genes. PCP water extract and compounds also proved in animal and humans' clinical trial for their hepatoprotective, antiaging, nephroprotective, anti-inflammatory, antidiabetic, antibacterial, antiapoptotic, immune regulation, and antioxidative stress pathways. This updated review spotlighted the current information on efficiency and application of PCP by compiling and reviewing recent publications on animal research. In addition, this review discussed the toxicology, traditional use, comparative, and clinical application of PCP in veterinary practices to authenticate and find out new perspectives on the research and development of this herbal medicine.

OBJECTIVES: This study is aimed at developing a screening tool that could evaluate the upper airway obstruction on lateral cephalograms based on deep learning. METHODS: We developed a novel and practical convolutional neural network model to automatically evaluate upper airway obstruction based on ResNet backbone using the lateral cephalogram. A total of 1219 X-ray images were collected for model training and testing. RESULTS: In comparison with VGG16, our model showed a better performance with sensitivity of 0.86, specificity of 0.89, PPV of 0.90, NPV of 0.85, and F1-score of 0.88, respectively. The heat maps of cephalograms showed a deeper understanding of features learned by deep learning model. CONCLUSION: This study demonstrated that deep learning could learn effective features from cephalograms and automated evaluate upper airway obstruction according to X-ray images. Clinical Relevance. A novel and practical deep convolutional neural network model has been established to relieve dentists' workload of screening and improve accuracy in upper airway obstruction.

This study investigated the influence of two different devices with lower torso sports training in patients with asthma. Patients with asthma (n = 300) aged 55-60 years with FEV1/FVC ratio < 65%, who were repeatedly admitted to a pulmonary rehabilitation centre, participated. Patients were evaluated and randomized into two groups (experimental group 1; EXP-1, n = 150, who applied a conventional threshold loading device, and experimental group 2; EXP-2, n = 150, who used an innovative respiratory training device). Patients were included only if they met the global criteria for asthma. The experimental intervention period lasted 10 weeks with 3 weekly training sessions lasting 30-40 min. The maximal inspiratory pressure (PI, max), pulmonary function test, baseline dyspnoea index (BDI), oxygen saturation, and 6 min walking test (6MWT) performance were all measured at baseline and postintervention. Also, an assessment of the 1 min repeated exercise performance (leg extension and leg press) was performed. Moreover, St. George Respiratory Questionnaire was used to quantify the quality of life (SGRQ). Statistical analysis displayed significant favourable effects on 6MWT, leg press, and FRV1, for patients using both devices (EXP-1 and EXP-2, respectively) with lower torso athletic training. The other variables, weight SPO2 and SGRO, also showed no significant change in neither EXP-1 nor EXP-2. Thus, the new respiratory training device (EXP-2) appeared to be as effective as the conventional threshold loading device (EXP-1). In conclusion, our findings demonstrated beneficial effects of combining respiratory training with athletic training in asthma patients. Additionally, the validity of a unique respiratory training device for asthma patients was confirmed.

BACKGROUND: The IL-12/IFN-γ axis pathways play a vital role in the control of intracellular pathogens such as Salmonella typhi. OBJECTIVE: The study is aimed at using whole exome sequencing (WES) to screen out genetic defects in IL-12/IFN-γ axis in patients with recurrent typhoid fever. METHODS: WES using next-generation sequencing was performed on a single patient diagnosed with recurrent typhoid fever. Following alignment and variant calling, exomes were screened for mutations in 25 genes that are involved in the IL-12/IFN-γ axis pathway. Each variant was assessed by using various bioinformatics mutational analysis tools such as SIFT, Polyphen2, LRT, MutationTaster, and MutationAssessor. RESULTS: Out of 25 possible variations in the IL-12/IFN-γ axis genes, only 2 probable disease-causing mutations were identified. These variations were rare and include mutations in IL23R and ZNFX I. Other pathogenic mutations were found, but they were not considered likely to cause disease based on various mutation predictors. CONCLUSION: Applying WES to the patient with recurrent typhoid fever detects variants that are not much important as other genes in the IL-12/IFN-γ axis. Results of the current study suggest that a large population sizes would be needed to examine the functional relevance of IL-12/IFN-γ axis genes with recurrent typhoid fever.

Huoxiang Zhengqi Oral Liquid (HZOL) is a classic Chinese patent medicine used in China for more than 1,000 years in treating gastrointestinal and respiratory diseases. Clinically applied HZOL in early respiratory disease stages can reduce the proportion of lung infection patients that progress to severe acute lung injury (ALI). However, few pharmacological studies evaluated its level of protection against ALI. We explored mechanisms of HZOL against ALI by employing network pharmacology, molecular docking, and rat experiments. Firstly, network pharmacology prediction and published biological evaluation of active ingredients of HZOL suggested that HZOL exerted the protective effect in treating ALI mainly in the areas of regulation of cell adhesion, immune response, and inflammatory response and closely related to the NF-κB pathway. Secondly, molecular docking results demonstrated that imperatorin and isoimperatorin combined well with targets in the NF-κB pathway. Finally, ALI rats induced by lipopolysaccharides (LPS) were used to validate prediction after pretreatment with HZOL for 2 weeks. Results confirmed that lung and colon injury occurred in ALI rats. Furthermore, HZOL exerts anti-inflammatory effects on LPS-induced ALI and gut injury by repairing lung and colon pathology, reducing and alleviating pulmonary edema, inhibiting abnormal enhancement of thymus and spleen index, modulating hematologic indices, and increasing levels of total short-chain fatty acids (SCFAs) in the cecum. Additionally, abnormal accumulation of inflammatory cytokines IL-6, IL-1β, TNF-α, and IFN-γ in serum and bronchoalveolar lavage fluid was significantly reduced after pretreating with HZOL. Furthermore, HZOL downregulated the expression of TLR4, CD14, and MyD88 and phosphorylation of NF-κB p65 in lung tissue. Altogether, HZOL was found to exert an anti-inflammatory effect regulation by increasing levels of SCFAs, inhibiting the accumulation of inflammatory cytokines, and attenuating the activation of the TLR4/NF-κB p65 pathway. Our study provided experimental evidences for the application of HZOL in preventing and treating ALI.

OBJECTIVES: Delayed cerebral ischemia (DCI) contributes to poor aneurysm prognosis. Subarachnoid hemorrhage and DCI have irreversible and severe consequences once they occur; therefore, early prediction and prevention are important. We investigated the risk factors for postoperative complications of DCI in patients with aneurysmal subarachnoid hemorrhage (aSAH) requiring mechanical ventilation in intensive care and validated a prediction model. METHODS: We retrospectively analyzed patients with aSAH who were treated in a French university hospital neuro-ICU between January 2010 and December 2015. The patients were randomized into a training group (144) and verification groups (60). Nomograms were validated in the training and verification groups, where receiver operating characteristic curve analysis was used to verify model discrimination; calibration curve and Hosmer-Lemeshow test were used to determine model calibration; and decision curve analysis (DCA) was used to verify clinical validity of the model. RESULTS: External ventricular drain (EVD), duration of mechanical ventilation, and treatment were significantly associated in the univariate analysis; EVD and rebleeding were significantly associated with the occurrence of DCI after aSAH. Binary logistic regression was used to select five clinicopathological characteristics to predict the occurrence of DCI in patients with aSAH requiring mechanical ventilation nomograms of the risk of DCI. Area under the curve values for the training and verification groups were 0.768 and 0.246, with Brier scores of 0.166 and 0.163, respectively. Hosmer-Lemeshow calibration test values for the training and verification groups were x 2 = 3.824 (P = 0.923) and x 2 = 10.868 (P = 0.285), respectively. Calibration curves showed good agreement. DCA indicated that the training and verification groups showed large positive returns in the broad risk range of 0-77% and 0-63%, respectively. CONCLUSIONS: The predictive model of concurrent DCI in aSAH has theoretical and practical values and can provide individualized treatment options for patients with aSAH who require mechanical ventilation.

BACKGROUND: Despite of having improved endodontic file designs as well as the reinforced metal alloy file structure, intracanal endodontic file separation (EFS) is still a very problematic and worrisome dental incident, which usually occurs without any visible signs of permanent deformation. Further, there have been conflicting reports regarding the clinical significance of leaving separated files within root canals. AIMS: The aim of this study was to look into the current perceptions and awareness about file separation during endodontic treatment among the dental house officers (DHOs). MATERIALS AND METHODS: A novel validated questionnaire comprising of 15 close-ended questions was distributed anonymously via Google Forms through email to 1100 DHOs across Pakistan. The questionnaire consisted of two parts: the first component (Section I) collected demographic data and the second component (Section II) investigated the causes of EFS during root canal treatment. Following the completion of socioeconomic information, including age and gender, the DHOs were asked to answer a few questions about the various reasons for endodontic instrument fracture. RESULTS: A total of 800 responses were recorded, with an effective rate of 72.8%. The majority of the DHOs (p value < 0.001) perceived that endodontic instrument fracture occurred in the posterior (61.5%) and apical third of the canal (50.5%) and in older permanent dentition (67.3%), possibly due to patient anxiety (62%). Better choice of instrument (61.15%), operators' experience (95.3%), knowledge (87.5%), and proper root canal cleaning (91.1%) are believed to be the vital steps in reducing endodontic file separation/fracture. Furthermore, majority of them (p value < 0.001) perceived that stainless steel was a superior alloy for filing instruments. Manual files tend to be more prone to fractures due to repeated use than rotary files. CONCLUSION: This study demonstrated that young DHOs had adequate knowledge and awareness regarding the potential predisposing factors and handling techniques for EFS. This study thereby provides an evaluating tool to access the insights of the current perceptions and awareness of DHOs concerning EFS.

The combination of traditional Chinese medicine (TCM) and Western medicine is a promising method for treating rheumatoid arthritis (RA). Combining the two fully exploits the advantages of Western and TCM to treat RA and has the potential to greatly improve the therapeutic effect on RA. In this study, we developed a combination drug training set by using 16 characteristic variables based on the characteristics of small molecules of TCM ingredients and Food and Drug Administration-certified combination drug data downloaded from the DrugCombDB database. Furthermore, we compared the prediction and classification abilities of five models: the k-nearest neighbors, naive Bayes, support vector machine, random forest, and AdaBoost algorithms. The random forest model was selected as the classification and prediction model for Western and TCM and Western combination drugs. We collected data for 41 small molecules of TCM ingredients from the Traditional Chinese Medicine Systems Pharmacology database and 10 small molecule drugs commonly used in anti-RA treatment from the DrugBank database. Combinations of Western and TCM for anti-RA treatment were screened. Finally, the CellTiter-Glo method was used to determine the synergy of these combinations, and the 15 most predicted drug combinations were carried out experimental verification. Myricetin, rhein, nobiletin, and fisetin had high synergy with celecoxib, and rhein had high synergy with hydroxychloroquine. The preliminary findings of this study can be further applied for practical clinical anti-RA combined treatment strategies and serve as a reference for clinical treatment of RA with integrated Western and TCM.

[This retracts the article DOI: 10.1155/2022/7478373.].

The current study assessed the detection of virulence genes and drug resistance among Klebsiella pneumoniae isolates from Iran. During 2018 to 2020, 52 K. pneumoniae isolates were obtained from patients at Iran hospitals. By disk diffusion method, the antimicrobial susceptibility of K. pneumoniae isolates was assessed, and ESBL-producing K. pneumoniae isolates were detected by CDDT method. PCR analysis was done to detect virulence genes (iucB, iutA, iroN, kfu, allS, fimH, ybtS, mrkD, and entB); ESBL-encoding genes (bla TEM, bla PER, bla CTX-M, bla VEB, and bla SHV); and class D (bla OXA-48), class B (bla VIM, bla NDM, and bla IMP), and class A (bla KPC and bla GES) carbapenemase genes. Among all isolates, 84.6%, 13.5%, and 1.9% isolates were multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant (PDR), respectively. Also, 84.6% were ESBL-producing and 71.2%, 53.8%, 40.4%, and 9.6% of all isolates were carrying bla TEM, bla SHV, bla CTX-M, and bla OXA-48 genes, respectively. Six isolates (11.5%) were positive for bla NDM gene. In contrast, no isolates were positive for the presence of bla KPC, bla IMP, and bla VIM. Virulence factor genes including iucB, iutA, iroN, kfu, allS, fimH, ybtS, mrkD, and entB were carried by 24%, 46.2%, 25%, 11.5%, 17.3%, 86.5%, 75%, 88.5%, and 100% isolates, respectively. This study evaluated the distribution and prevalence of virulence factor genes among K. pneumoniae isolates. The treatment of these infections is challenging due to the existence of particular virulence factors and the rise of antibiotic resistance. Therefore, the current study accentuates the necessity of finding new and efficient solutions for stopping the increase of antibiotic resistance.

The plant B3 gene superfamily contains a large number of transcription factors playing a vital role in both vegetative growth and reproductive development in plants. Although several B3 genes have been well studied, molecular functions of the B3 genes in olive are largely unknown. In our study, a total of 200 B3 genes were identified in olive genome based on RNA-seq and comparative genomic analyses and further classified into five groups (i.e., REM, RAV, LAV, HSI, and ARF) based on phylogenetic analysis. Results of gene structure and motif composition analyses revealed diversified functions among these five groups of B3 genes. Results of genomic duplication and syntenic analyses indicated the gene expansion in the B3 genes. Results of gene expression based on both transcriptomics and relative expression revealed the tissue-biased expression patterns in B3 genes. The results of the comparative expression analysis of B3 genes between two olive cultivars with high and low oil contents identified several potential REM genes which may be involved in oil biosynthesis in olive. Based on the comprehensive characterization of the molecular structures and functions of B3 genes in olive genome, our study provided novel insights into the potential roles of B3 transcription factors in oil biosynthesis in olive and lays the groundwork for the functional explorations into this research field.

BACKGROUND AND AIMS: In recent years, various studies have been conducted worldwide to investigate the relationship between receiving the flu vaccine with acute cerebrovascular accident or stroke and its hospitalization in the elderly; however, the results of these studies are contradictory. Therefore, this study was aimed at investigating the relationship between receiving the flu vaccine with stroke and its hospitalization in the elderly. METHODS: This study is a systematic review and meta-analysis of studies examining the relationship between receiving the flu vaccine with stroke and its hospitalization in the elderly during the years 1980 to 2021 which have been published in ISI Web of Science, Scopus PubMed, Cochrane, Science Direct, Google Scholar, and Embase. All analyses were performed by Stata 15, and the significance level in this study was considered <0.05. RESULTS: In the systematic search, 3088 articles were retrieved, considering the study criteria; finally, 14 studies were included in the meta-analysis. Based on the results of the meta-analysis, the odds ratio (OR) of occurrence and hospitalization of stroke compared to the nonvaccinated group in vaccine recipients is equal to 0.84 (95% confidence interval (CI): 0.78-0.90, P value ≤ 0.001). Publication bias was not observed in this study (P value = 0.101). CONCLUSION: Getting the flu vaccine can reduce the risk of occurrence and hospitalization of stroke in the elderly by 16% (10%-22%). Therefore, receiving this vaccine as a preventive intervention for stroke in the elderly may be promising.

Functional Movement Screen (FMS) is a tool used to assess fundamental movement patterns. There are relationships between musculoskeletal fitness (MSF) and a FMS. However, there is limited data regarding the multidimensional associations between these two constructs. This study is aimed at investigating the associations and detailed structures of FMS components and MSF components and identifying a deeper detailed structure of their relations to physical fitness. The study sample included 114 physically active men with an average body height of 1.81 ± 0.07 (cm), body weight of 80.61 ± 9.49 (kg), and a BMI of 24.65 ± 2.46 (kg/m2). Each participant performed a FMS test, sit-and-reach (S&R) test, sit-ups (ABS) evaluation, balance evaluation on an AMTI platform, handgrip strength (HG) testing, and standing broad jump (SBJ) ability. The Kendall's Tau correlation was performed to identify simple associations between FMS and MSF. Cluster analysis was used to determine the multidimensional nature of the relationships. In the vast majority, a positive correlation was observed suggesting that a high level of MSF improved FMS test results. A cluster analysis revealed 4 separate clusters. Shoulder mobility (SM) was identified as a single cluster. A strong similarity was observed between SBJ and trunk stability push-up (TSPU) forming a second cluster. This cluster joined to another consisting of the S&R test and active straight leg raise (ASLR) test. The last cluster consisted of HG and hurdle step (HS). These results confirmed that FMS and MSF tests measure the same constructs-a foundation for an individual's motor coordination, muscle strength, postural stability, and dynamic balance. This knowledge could be helpful in effectively enhancing physical performance based on combining similar constructs to accelerate the achievement of established goals.

Genetic variations (mutation, crossing over, and recombination) act as a source for the gradual alternation in phenotype along a geographic transect where the environment changes. Posttranslational modifications (PTMs) predicted modifications successfully in different and the same species of living organisms. Protein diversity of living organisms is predicted by PTMs. Environmental stresses change nucleotides to produce alternations in protein structures, and these alternations have been examined through bioinformatics tools. The goal of the current study is to search the diversity of genes and posttranslational modifications of protease serine endopeptidase in various strains of Sordaria fimicola. The S. fimicola's genomic DNA was utilized to magnify the protease serine endopeptidase (SP2) gene; the size of the product was 700 and 1400 base pairs. Neurospora crassa was taken as the reference strain for studying the multiple sequence alignment of the nucleotide sequence. Six polymorphic sites of six strains of S. fimicola with respect to N. crassa were under observation. Different bioinformatics tools, i.e., NetPhos 3.1, NetNES 1.1 Server, YinOYang1.2, and Mod Pred, to search phosphorylation sites, acetylation, nuclear export signals, O-glycosylation, and methylation, respectively, were used to predict PTMs. The findings of the current study were 35 phosphorylation sites on the residues of serine for protease SP2 in SFS and NFS strains of S. fimicola and N. crassa. The current study supported us to get the reality of genes involved in protease production in experimental fungi. Our study examined the genetic biodiversity in six strains of S. fimicola which were caused by stressful environments, and these variations are a strong reason for evolution. In this manuscript, we predicted posttranslational modifications of protease serine endopeptidase in S. fimicola obtained from different sites, for the first time, to see the effect of environmental stress on nucleotides, amino acids, and proteases and to study PTMs by using various bioinformatics tools. This research confirmed the genetic biodiversity and PTMs in six strains of S. fimicola, and the designed primers also provided strong evidence for the presence of protease serine endopeptidase in each strain of S. fimicola.

BACKGROUND: Stomach adenocarcinoma (STAD) has an extremely high fatality rate worldwide, and survival after metastasis is extremely poor. Cytokine-like protein 1 (CYTL1) has prognostic significance in various tumors. We aimed to explore the impact and underlying molecular mechanisms of CYTL1 in STAD through bioinformatics analysis. METHODS: We used R software to analyze CYTL1 expression in STAD samples (n = 375) and normal samples (n = 32) in The Cancer Genome Atlas database. Kaplan-Meier analysis was used to verify the relationship between CYTL1 expression and overall survival (OS) and disease-specific survival (DSS) based on the clinical characteristics and subgroups of patients with STAD. Furthermore, univariate and multivariate Cox regression analyses were used to verify the outcome variables of OS and DSS in patients with STAD. Receiver operating characteristic curves were used to test the predictive power of CYTL1. The biological functions and signaling pathways of CYTL1 were determined using gene set enrichment analysis (GSEA), and the immune infiltration patterns of CYTL1 and correlation of immune-related markers were analyzed using single-sample GSEA (ssGSEA) and an estimate algorithm. RESULTS: In our research, low CYTL1 expression (tumor vs. normal) was noted in patients with STAD. High CYTL1 expression was detrimental to OS and DSS and had good diagnostic performance (AUC = 0.731). In the subtype analysis of STAD, T3 and T4 stages, N0 and N1 stages, M0 stage, gender (female), and age (≤65 years) showed different performances between OS and DSS. Univariate and multivariate Cox analyses identified CYTL1 as an independent factor, and logistic regression analysis indicated that CYTL1 was associated with M stage (OR = 3.406) and sex (OR = 1.535). GSEA of the differential genes of CYTL1 showed the possible involvement of immunity. ssGSEA and estimation algorithms were used to further evaluate whether immune cells were closely related to CYTL1 expression, and many markers of immune cells also had statistical significance with the expression of CYTL1. CONCLUSION: CYTL1 may, thus, act as an independent prognostic factor for STAD and regulate STAD progression by affecting the immune microenvironment.

BACKGROUND: Lysine crotonylation (Kcr) is a newly identified posttranslational modification type regulated by various enzymes and coenzymes, including lysine crotonyltransferase, lysine decrotonylase, and binding proteins. However, the role of Kcr regulators in head and neck squamous cell carcinoma (HNSCC) remains unknown. The aim of this study was to establish and validate a Kcr-related prognostic signature of HNSCC and to assess the clinical predictive value of this signature. METHODS: The mRNA expression profiles and clinicopathological data from The Cancer Genome Atlas (TCGA) database were downloaded to explore the clinical significance and prognostic value of these regulators in HNSCC. The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to generate the Kcr-related prognostic signature for HNSCC. Subsequently, the GSE65858 dataset from the Gene Expression Omnibus (GEO) database was used to validate the signature. The prognostic value of the signature was evaluated using the Kaplan-Meier survival, receiver operating characteristic (ROC) curve, and univariate and multivariate Cox regression analyses. RESULTS: We established a nine-gene risk signature associated with the prognosis of HNSCC based on Kcr regulators. High-risk patients demonstrated significantly poorer overall survival (OS) than low-risk patients in the training (TCGA) and validation (GEO) datasets. Then, the time-dependent receiver operating characteristic (ROC) curve analysis showed that the nine-gene risk signature was more accurate for predicting the 5-year OS than other clinical parameters, including age, gender, T stage, N stage, and histologic grade in the TCGA and GEO datasets. Moreover, the Cox regression analysis showed that the constructed risk signature was an independent risk factor for HNSCC. CONCLUSION: Our study identified and validated a nine-gene signature for HNSCC based on Kcr regulators. These results might contribute to prognosis stratification and treatment escalation for HNSCC patients.

OBJECTIVE: Hyperandrogenaemia and insulin resistance (IR) are the main characteristics of polycystic ovary syndrome (PCOS). Here, we study to find appropriate markers predicting IR and hyperandrogenaemia of women with PCOS in northwest China. METHODS: According to body mass index (BMI), 953 patients with PCOS were divided into two groups. All the patients underwent physical examination and ultrasonography and collected elbow vein blood. Their BMI, waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), LAP, VAI, homeostasis model assessment index of insulin resistance (HOMA-IR), and free androgen index (FAI) were calculated. Each group (normal weight and obesity/overweight) was further divided into two subgroups according to their HOMA-IR and FAI: the IR+ subgroup/IR- subgroup and FAI+ subgroup/FAI- subgroup. Furthermore, we compared the clinical indices, hormone levels, and metabolic makers separately between these groups. The correlations between these parameters and HOMA-IR or FAI were tested; sensitivity, specificity, and receiver-operating characteristic (ROC) curves were calculated. RESULTS: In the obesity/overweight group, the VAI (best cut-off value: 2.27, area under the curve (AUC) = 0.699) and LAP (best cut-off value: 45.54, AUC = 0.680) were sensitive predictors of IR (sensitivity = 72% and sensitivity = 67%). Additionally, the VAI (best cut-off value: 2.13, AUC = 0.624) and LAP (best cut-off value: 51.18, AUC = 0.582) were sensitive predictors of FAI (sensitivity = 87% and sensitivity = 64%). In the normal weight group, BMI could preferably predict HOMA-IR (AUC = 0.717, best cut-off value: 21.62) and HOMA-IR could preferably predict FAI (best cut-off value: 2.11, AUC = 0.648). CONCLUSION: Our data indicated that the VAI and LAP may contribute to the early identification of IR and hyperandrogenaemia in the obesity/overweight patients of PCOS. In normal weight PCOS, BMI was a better predictor to IR, and HOWA-IR was a better predictor to FAI.

Antimicrobial resistance (AMR) is a significant public health issue in Bangladesh like many other developing countries where data on resistance trends are scarce. Moreover, the existence of multidrug-resistant (MDR) Escherichia coli exerts an ominous effect on the poultry sector. Therefore, the current systematic review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was conducted to find out the AMR scenarios in E. coli isolates sourced from poultry and poultry environments in Bangladesh between 2010 and 2021. Following the PRISMA guidelines, a total of 17 published scientific articles were selected for this systematic review. This review revealed that 18 out of 64 districts in Bangladesh reported E. coli in poultry, having a higher prevalence (combined prevalence: 69.3%, 95% confidence interval, CI: 67.3-71%). Moreover, the prevalence ranged from 24.3% to 100%. This review found that E. coli isolates showed resistance to 14 antimicrobial classes and 45 different antimicrobial agents, including the last-line (reserve group) antibiotics and banned antimicrobial categories for the treatment of infections in agricultural animals. Phenotypic resistance of E. coli against penicillins and beta-lactamase inhibitors (20.2%-100%), cephalosporins (1.9%-100%), fluoroquinolones (5.98%-100%), aminoglycosides (6%-100%), tetracyclines (17.7%-100%), carbapenems (13.6%-72.7%), macrolides (11.8%-100%), polymyxins (7.9%-100%), phenicols (20%-97.2%), sulfa drugs (44.7%-100%), cephamycins (21.4%-48.8%), nitrofurans (21.4%-63.2%), monobactams (1.2%), and glycylcyclines (2.3%) was recorded in the last decades in Bangladesh. Also, 14 articles reported MDR E. coli in poultry, including a 100% MDR in nine articles and a 92.7% (95% CI: 91.2-94%) combined percentage of MDR E. coli isolates. Twenty-four different AMR genes encoding resistance to beta-lactams (bla TEM, bla CTX-M-1, bla CTX-M-2, bla CTX-M-9, bla OXA-1, bla OXA-47, bla SHV, and CITM), colistin (mcr1 and mcr3), fluoroquinolones (qnrB and qnrS), tetracyclines (tetA, tetB, and tetC), sulfonamides (sulI and sulII), trimethoprim (dfrA1), aminoglycosides (rmtB), streptomycin (aadA1), gentamicin (aac-3-IV), erythromycin (ereA), and chloramphenicol (catA1 and cmlA) were detected in E. coli isolates. The presence of MDR E. coli and their corresponding resistance genes in poultry and poultry environments is an alarming issue for all health communities in Bangladesh. We suggest a regular antimicrobial surveillance program with a strong One Health approach to lessen the hazardous effects of AMR E. coli in poultry industries in Bangladesh.

BACKGROUND: Celiac disease (CD) is an autoimmune genetic disorder in which gluten protein causes inflammation of the intestinal enterocytes. CD diagnosis in most cases is delayed or mistreated due to its varied clinical features. We aimed to evaluate the protein profile imbalance in different CD groups of children, which could help aid in the diagnosis and proper management of the disease. Methodology. This was a cross-sectional study with a nonrandom purposive sampling technique. All samples were taken from tertiary care hospitals of Hyderabad, Pakistan. In total, there were 175 children (age 3-15 years) divided into five equal groups (n = 35), namely, group A (control), group B (celiac diagnosed), group C (celiac-like symptoms), group D (celiac with type 1 diabetes mellitus), and group E (type 1 diabetes mellitus only). Clinical symptoms and laboratory parameters were analyzed among all the groups. Sera proteins, albumin, globulins, and transferrin levels were evaluated and compared with healthy individuals. RESULTS: The albumin in serum of celiac groups B and C was 3.0 g/dl and 2.8 g/dl, respectively. While in diabetic patients with CD, it is 2.7 g/dl. The globulin levels were raised among all the celiac groups with typical GIT symptoms. The highest transferrin was observed in group B, celiac patients with severe anemia. Patients were not on GFD, hence had no or less recovery and had chronic symptoms of celiac. CONCLUSION: The misdiagnosis and poor management of celiac leads to chronic villous atrophy with imbalance in metabolic profile. Serum analysis of albumin, globulins, and transferrin may help in the diagnosis and proper management of the disease to recover the celiac symptoms.