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Objective To systematically evaluate the efficacy and safety of insulin Icodec in the treatment of type 2 diabetes mellitus (T2DM) in order to provide evidence-based guidance for the rational clinical use of drug. Methods The databases of PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang and VIP were searched by computer to identify randomized controlled trials (RCT) comparing the efficacy and safety of insulin Icodec (trial group) versus placebo or other hypoglycemic agents (control group) in the treatment of T2DM were collected from the date of database inception to August 2023. The efficacy indexes included: glycated hemoglobin A1c (HbA1c) level, HbA1c compliance rate (HbA1c<7%), fasting plasma glucose (FPG) level, body weight level, time in range (TIR) percentage. Safety indicators included: incidence of hypoglycemia events, incidence of injection site reactions, incidence of drug allergic reactions, and incidence of serious adverse events. Two evaluators independently screened the literature, extracted data from the literature and assessed the risk of bias of the studies included, and performed a meta-analysis of the data using RevMan 5.4 software. Results Seven studies with a total of 3 286 patients were included. The results of meta-analysis showed that compared with the control group, insulin Icodec reduced HbA1c (WMD=-0.16%, 95%CI -0.26%-0.07%, P<0.01), increased the rate of HbA1c compliance (OR=1.50, 95%CI 1.29-1.74, and decreased HbA1c compliance (WMD=-0.16%, 95%CI -0.26%-0.07%, P<0.01). However, there was no statistically significant difference between the two groups in reducing FPG levels (WMD=-0.05 mmol/L, 95%CI -0.29-0.20 mmol/L, P=0.71), and it increased the body weight of patients (WMD=0.52 kg, 95%CI 0.22-0.82 kg, P<0.01), but increased the percentage of TIR in patients (WMD=5.86%, 95%CI 2.02%-9.70%, P=0.003). In terms of safety, although the incidence of hypoglycemic events (OR=1.37, 95%CI 1.17-1.61, P<0.01) was higher in the insulin Icodec group than in the control group, the incidence of anaphylaxis was higher in insulin Icodec group than in the control group (OR=0.91, 95%CI 0.64-1.31, P=0.62), injection site reaction (OR=1.03, 95%CI 0.63-1.66, P=0.92) and incidence of serious adverse events (OR=0.97, 95%CI 0.75-1.24, P=0.79), there was no significant difference between insulin Icodec and control groups. Conclusions Insulin Icodec can lower HbA1c levels in patients and increase the rate of HbA1c compliance without increasing the incidence of injection site reactions, allergic events and serious adverse events. [ABSTRACT FROM AUTHOR]

Background: It is reported that the Ixeris chinensis has high medicinal value, but there are few reports about its potential molecular mechanism. We used a network pharmacology approach to predict the active ingredients, targets of action and possible interventions in diseases of Ixeris chinensis ., Methods: We employed various databases and software to predict the active ingredients, target genes, protein interactions, signaling pathways, network diagrams, and molecular docking of Ixeris chinensis . Simultaneously, we searched multiple Chinese and English databases and conducted meta-analyses of five randomized controlled trials., Results: The analysis results revealed 12 effective components, including apigenin β -sitosterol, baicalin, baicalein, and luteolin; and selected 40 key targets, including AKT1, TNF, EGFR, ESR1, SRC, among others. GO analysis generated 225 biological processes, 39 cellular components, and 65 molecular functions; KEGG analysis revealed 103 signaling pathways. Molecular docking results indicated that the main active components of Ixeris chinensis can bind well with key targets. Five randomized controlled trials were included. Meta-analysis showed that Ixeris extract can effectively reduce animal blood lipid levels., Conclusion: This study revealed the main active ingredients and key targets of Ixeris chinensis , analyzed the signaling pathways of potential targets, conducted disease prediction, and performed molecular docking prediction, providing a basis for research on the pathways of Ixeris treatment for related diseases and subsequent new drug development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ni, Ma, Qiao, Guo, Ruan, Wang and Yang.)

Background: Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty liver disease (NAFLD), one of the most prevalent chronic liver diseases. The effectiveness of bariatric surgery in treating NASH and preventing or even reversing liver fibrosis has been demonstrated in numerous clinical studies, but the underlying mechanisms and crucial variables remain unknown., Methods: Using the GSE135251 dataset, we examined the gene expression levels of NASH and healthy livers. Then, the differentially expressed genes (DEGs) of patients with NASH, at baseline and one year after bariatric surgery, were identified in GSE83452. We overlapped the hub genes performed by protein-protein interaction (PPI) networks and DEGs with different expression trends in both datasets to obtain key genes. Genomic enrichment analysis (GSEA) and genomic variation analysis (GSVA) were performed to search for signaling pathways of key genes. Meanwhile, key molecules that regulate the key genes are found through the construction of the ceRNA network. NASH mice were induced by a high-fat diet (HFD) and underwent sleeve gastrectomy (SG). We then cross-linked the DEGs in clinical and animal samples using quantitative polymerase chain reaction (qPCR) and validated the key genes., Results: Seven key genes (FASN, SCD, CD68, HMGCS1, SQLE, CXCL10, IGF1) with different expression trends in GSE135251 and GSE83452 were obtained with the top 30 hub genes selected by PPI. The expression of seven key genes in mice after SG was validated by qPCR. Combined with the qPCR results from NASH mice, the four genes FASN, SCD, HMGCS1, and CXCL10 are consistent with the biological analysis. The GSEA results showed that the 'cholesterol homeostasis' pathway was enriched in the FASN, SCD, HMGCS1, and SQLE high-expression groups. The high-expression groups of CD68 and CXCL10 were extremely enriched in inflammation-related pathways. The construction of the ceRNA network obtained microRNAs and ceRNAs that can regulate seven key genes expression., Conclusion: In summary, this study contributes to our understanding of the mechanisms by which bariatric surgery improves NASH, and to the development of potential biomarkers for the treatment of NASH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Deng, Sun, Bai, Wang and Yang.)