Tetralogy of Fallot (TOF) is one of the most common cyanotic congenital heart diseases (CHD) worldwide; however, its pathogenesis remains unclear. Recent studies have shown that circular RNAs (circRNAs) act as “sponges” for microRNAs (miRNAs) to compete for endogenous RNA (ceRNA) and play important roles in regulating gene transcription and biological processes. However, the mechanism of ceRNA in TOF remains unclear. To explore the crucial regulatory connections and pathways of TOF, we obtained the human TOF gene, miRNA, and circRNA expression profiling datasets from the Gene Expression Omnibus (GEO) database. After data pretreatment, differentially expressed mRNAs (DEmRNAs), microRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) were identified between the TOF and healthy groups, and a global triple ceRNA regulatory network, including circRNAs, miRNAs, and mRNAs based on the integrated data, was constructed. A functional enrichment analysis was performed on the Metascape website to explore the biological functions of the selected genes. Then, we constructed a protein-protein interaction (PPI) network and identified seven hub genes using the cytoHubba and MCODE plug-ins in the Cytoscape software, including BCL2L11, PIK3R1, SOCS3, OSMR, STAT3, RUNX3, and IL6R. Additionally, a circRNA–miRNA–hub gene subnetwork was established, and its enrichment analysis results indicated that the extrinsic apoptotic signaling pathway, JAK-STAT signaling pathway and PI3K-Akt signaling pathway may be involved in the pathogenesis of TOF. We further identified the hsa_circ_000601/hsa-miR-148a/BCL2L11 axis as a crucial signaling pathway axis from the subnetwork. This study provides a novel regulatory network for the pathogenesis of TOF, revealing the possible molecular mechanisms and crucial regulatory pathways that may provide new strategies for candidate diagnostic biomarkers or potential therapeutic targets for TOF.

Introduction: Epidural analgesia (EA) is the most widely used intervention for the reduction of labor pain; however, it is contra-indicated for patients with spinal deformity or allergy to anesthetics and may be refused by parturients. As a noninvasive and nonnarcotic analgesic intervention, transcutaneous electrical acupoint stimulation (TEAS) has gained increasing attention in recent years. Therefore, we performed a network meta-analysis to compare the efficacy and safety of TEAS and EA as measured by visual analog scale score, the failure rate of natural delivery, adverse events, and Apgar scores. Methods: Relevant randomized controlled trials (RCTs) from four electronic databases (PubMed, EMBASE, Web of Science, and Cochrane CENTRAL) and clinical trials.gov were searched from inception until September 4, 2022. A random effects model was used during analysis, and outcomes were evaluated as standard mean difference (SMD), odds ratio (OR), and 95% confidence intervals (CrI) using STATA (version SE15.0), R (version 3.6.1), and ADDIS (version 1.16.8) software. Results: Ten RCTs comprising 1214 parturients were identified by screening. Six RCTs compared TEAS and controls, three compared EA and controls, and one compared TEAS and EA. No heterogeneity was found within the four outcomes. There was no significant difference in any outcomes between interventions or control treatments in terms of SMD, OR, and CrI. Combined with the highest surface under the cumulative ranking curve score, TEAS demonstrated possible better effects in the aspects of analgesic efficacy and safety under certain circumstances. Conclusions: TEAS may be a potential alternative for parturients as a simple, noninvasive, and non-pharmacological intervention compared with EA in terms of analgesic efficacy and safety for mothers and neonates.

Background: Irritable bowel syndrome (IBS) is the most common gastrointestinal disease worldwide, with diarrhea-predominant irritable bowel syndrome (IBS-D) being the prevalent subtype. However, its pathogenesis remains unclear. Research has increasingly focused on identifying genetic factors in the mechanisms underlying IBS. Objective: We aimed to explore key gene nodes and potential microRNA–mRNA regulatory pairs of IBS-D using bioinformatics methods. Methods: We downloaded the GSE36701 microarray dataset from the Gene Expression Omnibus database and obtained 1358 differentially expressed mRNAs by analyzing mRNA profiles using the GEO2R analysis tool. Based on our previous study, we used TargetScan, miTarBase, and miRDB to predict the downstream genes of three known microRNAs (hsa-let-7b-5p, hsa-miR-19b-3p, and hsa-miR-20a-5p), and the microRNA–mRNA regulatory network was visualized using Cytoscape. Results: A total of 795 downstream target genes were found in TargetScan, miRTarBase, and miRDB databases, and 50 candidate genes were obtained. The Metascape and STRING databases were used to perform enrichment analysis and construct a protein–protein interaction network of candidate genes. Finally, we constructed a network of 3 microRNAs and 50 candidate mRNAs, among which 28 negative relationship pairs and 5 key axes (hsa-miR-20a-5p/VEGFA, hsa-let-7b-5p/MSN, hsa-let-7b-5p /PPP1R16B, hsa-19b-3p/ITGA2, and hsa-19b-3p/PIK3R3) were identified. Conclusion: We report five novel microRNA–mRNA regulatory axes in IBS-D pathogenesis and speculated that PIK3R3, negatively regulated by hsa-miR-19b-3p, may regulate NF-κB production through the PI3K/Akt pathway, which accounts for the occurrence of clinical symptoms in IBS-D patients. Our findings may offer key biomarkers for IBS-D diagnosis and treatment.