Background: Vascular dementia (VaD) is a degenerative cerebrovascular disease that leads to progressive decline of patients' cognitive ability and memory. Yizhi Tongmai (YZTM) decoction is an empirical prescription first formulated by Professor Guomin Si. Our previous experiments proved the effectiveness of this prescription in the treatment of VaD. In this study, we aimed to use network pharmacology and molecular docking technology to systematically explain the potential anti-VaD mechanism of YZTM.Methods: We identified the core compounds of YZTM and their potential targets through the TCMSP, BATMAN, and SwissTargetPrediction databases. Then, we identified the molecular targets of YZTM in VaD using the Online Mendelian Inheritance in Man and GeneCards databases. The common targets of YZTM and VaD were screened out, and then the pathways of these target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery v6.8. Molecular docking was used to verify the relationship between the core compounds and proteins.Results: Through network pharmacology analysis, we discovered that the 5 core compounds in YZTM exert an anti-VaD effect. The potential mechanism of YZTM anti-VaD may be through inhibiting the NLRP3 inflammasome, TNF signaling pathway, and toll-like receptor signaling pathways. Subsequently, key compounds were docked with related proteins in the NLRP3 inflammasome (NLRP3, ASC, caspase-1, interleukin-18, and interleukin-1 β) using molecular docking technology. The compounds were found to spontaneously bind to the proteins.Conclusions: YZTM may exert an anti-VaD effect through inhibition of the NLRP3 inflammasome.In addition, TNF signaling pathway and toll-like receptor signaling pathway may also be its underlying mechanism. The application of network pharmacology and molecular docking technology may provide a novel method for research of Chinese herbal medicine. YZTM may also provide a complementary treatment option for patients with VaD

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.

Background: Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) therapy may experience further damage to the vascular endothelium, leading to increased inflammatory response and in-stent thrombosis. In many clinical studies, sodium tanshinone IIA sulfonate injection (STS) has been found to reduce inflammatory factors and enhance vascular endothelial function in patients with ACS while improving the prognosis of PCI. However, to date, there has been no systematic review assessing the effectiveness and safety of STS on inflammatory factors and vascular endothelial function.Purpose: The aim of this study is to systematically review the effects of STS on inflammatory factors and endothelial function in patients with ACS treated with PCI.Methods: Until October 2022, eight literature databases and two clinical trial registries were searched for randomized controlled trials (RCTs) investigating STS treatment for ACS patients undergoing PCI. The quality of the included studies was assessed using the Cochrane Risk Assessment Tool 2.0. Meta-analysis was performed using RevMan 5.4 software.Results: Seventeen trials met the eligibility criteria, including 1,802 ACS patients undergoing PCI. The meta-analysis showed that STS significantly reduced high-sensitivity C-reactive protein (hs-CRP) levels (mean difference [MD = −2.35, 95% CI (−3.84, −0.86), p = 0.002], tumor necrosis factor-alpha (TNF-α) levels (standard mean difference [SMD = −3.29, 95%CI (−5.15, −1.42), p = 0,006], matrix metalloproteinase-9 (MMP-9) levels [MD = −16.24, 95%CI (−17.24, −15.24), p < 0.00001], and lipid peroxidation (LPO) levels [MD = −2.32, 95%CI (−2.70, −1.93), p < 0.00001], and increased superoxide dismutase (SOD) levels [SMD = 1.46, 95%CI (0.43, 2.49), p = 0,006] in patients with ACS. In addition, STS significantly decreased the incidence of major adverse cardiovascular events (relative risk = 0.54, 95%CI [0.44, 0.66], p < 0.00001). The quality of evidence for the outcomes was assessed to be very low to medium.Conclusion: STS can safely and effectively reduce the levels of hs-CRP, TNF-α, MMP-9, and LPO and increase the level of SOD in patients with ACS treated with PCI. It can also reduce the incidence of adverse cardiovascular events. However, these findings require careful consideration due to the small number of included studies, high risk of bias, and low to moderate evidence. In the future, more large-scale and high-quality RCTs will be needed as evidence in clinical practice.

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: Subclinical hypothyroidism (SCH) can increase the risk of heart failure (HF) clinically. However, thyroxine therapy for patients with HF and SCH has the risk of developing tachyarrhythmias. At present, there is no sufficient evidence-based medical evidence for levothyroxine in the therapy of this situation, and the treatment issue is still controversial. Therefore, our meta-analysis aims to assess the effectiveness and safety of thyroxine therapy for patients with HF and SCH. Methods: We searched the related randomized controlled trials that have been published in the following 7 electronic databases: PubMed, Cochrane Library, EMBASE, Chongqing VIP, China National Knowledge Infrastructure, Chinese biomedical literature database, and Wan Fang database. The treatment group was treated with routine HF therapy plus thyroxine, while the control group was treated with HF routine therapy. Main outcome measures effective rate and New York Heart Association classification; Secondary outcome measures included: left ventricular ejection fraction, quality of life score, brain natriuretic peptide / N-terminal pro brain natriuretic peptide, 6-minute walk test, and adverse events. After screening studies and extracting data, we will use Cochrane collaborative tools to evaluate the risk of bias to assess the methodological quality of the included randomized controlled trials. We will use STATA 14.0 software for data synthesis and statistical analysis. Both subgroup analysis and sensitivity analysis will be used to detect potential sources of heterogeneity. In addition, we will use sensitivity analysis to test the stability of the outcomes. If possible, we will perform a funnel chart and Eggers test evaluate publication bias. The quality of the evidence will be evaluated through the grades of recommendations assessment, development, and evaluation system. Results: Our findings will be published in peer-reviewed journals. Conclusion: This research will provide evidence about the efficacy and safety of thyroxine in the treatment of patients with HF and SCH. Objective to provide evidence-based medicine basis for thyroxine treatment of patients with SCH and HF. Registration number: INPLASY2020100062.