Identification and validation of potential genes for the diagnosis of sepsis by bioinformatics and 2-sample Mendelian randomization study.

This integrated study combines bioinformatics, machine learning, and Mendelian randomization (MR) to discover and validate molecular biomarkers for sepsis diagnosis. Methods include differential expression analysis, weighted gene co-expression network analysis (WGCNA) for identifying sepsis-related modules and hub genes, and functional enrichment analyses to explore the roles of hub genes. Machine learning algorithms identify 3 diagnostic genes - CD177, LDHA, and MCEMP1 - consistently highly expressed in sepsis patients. The nomogram model effectively predicts sepsis risk, supported by receiver operator characteristic (ROC) curves. Correlations between diagnostic genes and immune cell infiltration are observed. MR analysis reveals a positive causal relationship between MCEMP1 and sepsis risk. In conclusion, this study presents potential sepsis diagnostic biomarkers, highlighting the genetic association of MCEMP1 with sepsis for insights into early diagnosis.

Exploring the active components and mechanism of modified bazhen decoction in treatment of chronic cerebral circulation insufficiency based on network pharmacology and molecular docking.

Modified bazhen decoction (MBZD) is a classical Chinese medicine formula with potential efficacy in the treatment of chronic cerebral circulation insufficiency (CCCI), and its main components and potential mechanisms are still unclear. The study aimed to investigate the active ingredients and mechanism of action of MBZD in treating CCCI through network pharmacology combined with molecular docking. The chemical composition and targets of 11 Chinese herbs in MBZD were retrieved utilizing the traditional Chinese medicine systems pharmacology database and analysis platform platform, and the targets for CCCI were screened by Genecards, online mendelian inheritance in man, therapeutic target database, and comparative toxicogenomics database databases. The targets were genetically annotated with the Uniprot database. We created a compound-target network employing Cytoscape software and screened the core targets for the treatment of CCCI by CytoNCA clustering analysis; the AutoDock Vina program performed molecular docking study of crucial targets. One thousand one hundred ninety-one active compounds were obtained, 2210 corresponding targets were predicted, 4971 CCCI-related targets were obtained, and 136 intersecting genes were identified between them. The central core targets were IL6, MAPK14, signal transducer and activator of transcription 3, RELA, VEGFA, CCND1, CASP3, AR, FOS, JUN, EGFR, MAPK1, AKT1, MYC, and ESR1; gene ontology functional enrichment analysis yielded 911 gene ontology items (P < .01), while Kyoto Encyclopedia of Genes and Genomes pathway enrichment yielded 138 signal pathways (P < .01), primarily including oxidative reactions, vascular regulation, apoptosis, and PI3K-Akt signaling pathway. The molecular docking results showed that the core active component of MBZD had good binding with the main target. This research initially uncovered the mechanism of action of MBZD via multi-component-multi-target-multi-pathway for the treatment of CCCI, providing the theoretical basis for the clinical application of MBZD.

Identification of pyroptosis-related gene signature for predicting prognosis of patients with pancreatic cancer using bioinformatics.

Pancreatic cancer, a common digestive system malignancy, is dubbed the "king of cancers". The role of pyrophosis-related genes (PRGs) in pancreatic cancer prognosis is yet unknown. In pancreatic cancer and normal tissue, we discovered 9 PRGs that are expressed differently in pancreatic cancer and healthy tissue. Based on the differential expression of PRGs, 2 clusters of pancreatic cancer cases could be identified. The 2 groups had significant disparities in total survival time. The prognostic model of a 5-PRGs signature was created using least absolute shrinkage and selection operator (LASSO) method. The median risk score was used to split pancreatic cancer patients in The Cancer Genome Atlas (TCGA) cohort into 2 groups: low risk and high risk. Patients classified as low-risk had significantly higher survival rates than those classified as high-risk (P < .01). The same results were obtained by validating them against the Gene Expression Omnibus database (P = .030). Cox regression statistical analysis showed that risk score was an independent predictor of overall survival in pancreatic cancer patients. Functional enrichment analysis revealed that apoptosis, cell proliferation, and cell cycle-related biological processes and signaling pathways were enriched. Additionally, the immunological status of the high-risk group worsened. In conclusion, a novel pyroptosis-related gene signature can be used to predict pancreatic cancer patient prognosis.

Moxibustion for alleviating chemotherapy-induced gastrointestinal adverse effects: A systematic review of randomized controlled trials.

OBJECTIVE: This systematic review aims to assess whether moxibustion is effective and safe for gastrointestinal adverse effects, a common and thorny issue arising from chemotherapy. METHODS: Seven electronic databases were searched up to August 28, 2021, to identify randomized controlled trials (RCTs) comparing moxibustion versus non-moxibustion treatments for various gastrointestinal adverse effects after chemotherapy. The Karnofsky performance status (KPS) and quality of life scores and the incidence of moxibustion-related adverse events were also investigated. Effects in meta-analyses were measured by risk ratios (RRs) or mean differences (MDs). RESULTS: Thirty-two RCTs (n = 2990) were included. Compared to the controls, moxibustion significantly reduced the incidences of nausea/vomiting (RR 0.70, 95% CI 0.61-0.79), severe nausea/vomiting (RR 0.39, 95% CI 0.29-0.51), diarrhoea (RR 0.56, 95% CI 0.38-0.82), constipation (RR 0.59, 95% CI 0.44-0.78), and abdominal distension (RR 0.60, 95% CI 0.46-0.78). The KPS (MD 7.53, 95% CI 3.42-11.64) and quality of life (MD 8.88, 95% CI 0.96-16.80) scores were also significantly improved after moxibustion. The results did not support a benefit of moxibustion on inappetence (RR 0.69, 95% CI 0.40-1.22) or abdominal pain (RR 0.60, 95% CI 0.28-1.30). All adverse events related to moxibustion were mild. CONCLUSIONS: Moderate-to very-low-quality evidence suggests that moxibustion may be safely used as an adjuvant treatment after chemotherapy to reduce the incidences of nausea and vomiting, diarrhoea, constipation, and abdominal distension and improve the performance status and quality of life in patients with malignant tumours. Its effects on abdominal pain and inappetence are uncertain.

Identification of key genes and microRNAs for multiple sclerosis using bioinformatics analysis.

ABSTRACT: To better understand the molecular mechanism underlying the pathogenesis of multiple sclerosis (MS), we aimed to identify the key genes and microRNAs (miRNA) associated with MS and analyze their interactions. Differentially expressed genes (DEGs) and miRNAs (DEMs) based on the gene miRNA dataset GSE17846 and mRNA dataset GSE21942 were determined using R software. Next, we performed functional enrichment analysis and constructed a protein-protein interaction network. Data validation was performed to ensure the reliability of hub genes. The miRNA-mRNA regulatory network was constructed. In total, 47 DEMs and 843 DEGs were identified. Protein-protein interaction network analysis identified several hub genes, including JUN, FPR2, AKT1, POLR2L, LYZ, CXCL8, HBB, CST3, CTSZ, and MMP9, especially LYZ and CXCL8. We constructed an miRNA-mRNA regulatory network and found that hsa-miR-142-3p, hsa-miR-107, hsa-miR-140-5p, and hsa-miR-613 were the most important miRNAs. This study reveals some key genes and miRNAs that may be involved in the pathogenesis of MS, providing potential targets for the diagnosis and treatment of MS.

Using bioinformatics approach identifies key genes and pathways in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis is a chronic and irreversible respiratory disease with a high incidence worldwide and no specific treatment. Currently, the etiology and pathogenesis of this disease remain largely unknown. In main purpose of this study, bioinformatics analysis was used to uncover key genes and pathways related to idiopathic pulmonary fibrosis (IPF). Gene expression profiles of GSE2052 and GSE35145 were obtained. After combining the 2 chip groups; then, we normalized the data, eliminating batch difference. R software was used to process and to screen differentially expressed genes (DEGs) between the IPF and normal tissues. Then, functional enrichment analysis of these DEGs was carried out, and a protein-protein interaction network (PPI) was also constructed. A total of 276 DEGs (152 up and 134 down-regulated genes) were identified in the IPF lung samples. The PPI network was established with 227 nodes and 763 edges. The top 10 hub genes were CAM1, CDH1, CXCL12, JUN, CTGF, SERPINE1, CXCL1, EDN1, COL1A2, and SPARC. Analyzing the PPI network modules with close interaction, the 3 key modules in the whole PPI network were screened out. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched for the module containing DEGs contained the viral protein interaction with cytokine and the cytokine receptor, the TNF signaling pathway, and the chemokine signaling pathway. The identified key genes and pathways may play an important role in the occurrence and development of IPF, and may be expected to be biomarkers or therapeutic targets for the diagnosis of IPF.

Fourteen small molecule and biological agents for psoriatic arthritis: A network meta-analysis of randomized controlled trials.

BACKGROUND: The comparative efficacy and safety of small molecule and biological agents in the treatment of psoriatic arthritis (PsA) remain unknown. OBJECTIVES: To compare the efficacy and safety of 14 small molecule and biological agents by network meta-analysis (NMA). METHODS: Relevant randomized controlled trials involving biological treatments for PsA were identified by searching PubMed, Cochrane Library, EMBASE, Web of Science, and Clinicaltrials.gov and by manual retrieval, up to June 2018. NMA was conducted with Stata 14.0 based on the frequentist method. Effect measures were odds ratios (ORs) with 95% confidence intervals (CIs). Intervention efficacy and safety were ranked according to the surface under the cumulative ranking curve (SUCRA). RESULTS: A total of 30 studies involving 10,191 adult subjects were included. According to NMA, ≥ 20% improvement in modifed American College of Rheumatology response criteria (ACR20) response, Psoriasis Area and Severity Index 75 (PASI75) response, and serious adverse events rate (SAEs) were observed. In direct comparisons, most of the biologics performed better than placebo in terms of ACR20 response rate and PASI75 response rate. Additionally, all medicines were comparable to placebo in terms of SAEs except secukinumab. In terms of mixed comparisons, with regard to the ACR20 response, etanercept (ETN) and infliximab (IFX) were more effective than golimumab (GOL), with ORs of 3.33 (95% CI: 1.17-9.48) and 1.24 (95% CI: 0.61-2.52), respectively. For PASI75 response, IFX was superior to certolizumab pegol (OR = 10.08, 95% CI: 1.54-75.48). In addition, these medicines were comparable to each other in terms of SAEs. ETN and IFX were shown to have the most favorable SUCRA for achieving improved ACR20 and PASI75 responses, respectively, while ABT-122 exhibited the best safety according to the SUCRA for SAEs. Considering both the efficacy (ACR20, PASI75) and safety (SAEs), GOL, ETN, and IFX are the top 3 treatments. CONCLUSIONS AND IMPLICATIONS: Direct and indirect comparisons and integrated results suggested that the 3 anti- tumor necrosis factor -α biologics (GOL, ETN, and IFX) can be considered the best treatments for PsA after comprehensive consideration of efficacy and safety.

Efficacy and safety of oral traditional Chinese patent medicine for chronic cerebral circulation insufficiency patients: A protocol for a systematic review and network meta-analysis.

BACKGROUND: Chronic cerebral circulation insufficiency (CCCI) is a common clinical cerebrovascular disease, especially among middle-aged and elderly patients, which seriously endangers their quality of life and physical and mental health. At present, Oral traditional Chinese patent medicine (OTCPM) is widely used in the treatment of CCCI in China, but its actual efficacy and safety lack of evidence-based evidence. Therefore, we will screen out the most effective OTCPM through a systematic review and network meta-analysis to provide a reliable theoretical basis for clinical decisions. METHODS: We will search electronic databases to collect relevant RCT studies from inception to October 2019. Those electronic databases include PubMed, Cochrane Library, Web of Science, EMBASE, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), and Wan-fang database. Only randomized clinical trials (RCTs) concerned any OTCPM treatments for CCCI will be collected. The included studies will no restrictions on language or publication year. There were no publication year or language for the included literature. Risk bias tools will assess the quality of the included literature. A Bayesian NMA will be performed to combine the direct and indirect comparisons of TCPMs interventions. The surface under the cumulative ranking curve (SUCRA) will be drawn to display the hierarchy of each TCPMs treatment. All statistical analyses will be implemented using R v3.5.2. and GeMTC v1.4.3.We will publish this systematic review in academic journals. Since this literature review will not involve directly contacting patients, ethical approval and informed consent are not required. TRIAL REGISTRATION NUMBER: CRD42019123878.

Effectiveness of Perioperative Auricular Therapy on Postoperative Pain after Total Hip Arthroplasty: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Auricular therapy (AT) is a conventional therapy in traditional Chinese medicine. However, the effectiveness of perioperative AT in pain treatment after total hip arthroplasty (THA) is still controversial. Nine randomised controlled trials (RCTs) involving 605 patients who have undergone THA with or without AT from inception to March 2018 were collected and included in this study by searching more than 12 databases (e.g., PubMed, Excerpta Medica Database, and Cochrane Library). A random-effects model that pooled seven articles showed that the visual analogue scale (VAS) in the AT group was lower than that of the control group at each postoperative time point in patients after THA, except at the time points of 6 and 36 h. The intraoperative body mass-adjusted fentanyl amount in the AT group was also lower than that of the control group in two trials. The other outcomes (time to first analgesic request and incidence of postoperative nausea and vomiting, perioperative bradycardia, and transitory hypotension) showed insignificant difference. Then, subgroup analysis showed similar results to those of the total articles with the term "VAS". Regression analysis found that the prolonged time after the operation decreased the difference in VAS between the two groups. Although all the outcomes were assessed as very low to low in the GRADE system, evidence on the effectiveness of perioperative AT in pain treatment after total hip replacement was positive.