Background:The number of studies describing the use of metformin in gestational diabetes mellitus (GDM) is increasing, and metformin is considered an acceptable and economic alternative to insulin in many countries. Because metformin can pass through the placenta, it is necessary to continuously assess the maternal and fetal impact of metformin compared with insulin in pregnancy. Methods and findings:We systematically searched PubMed, Embase, Medline, ClinicalTrials.gov, and the Cochrane database (from database inception to 10 February 2020) for randomized controlled trials (RCTs) that treatment with metformin versus insulin for GDM. Two reviewers independently assessed the articles, and conflicts were resolved by a third reviewer.Main results: Twenty-seven RCTs (n = 4568 participants) were included for quantitative analyses in the meta-analysis. Metformin improved maternal outcomes, reduced the incidence of preeclampsia (p<0.00001; risk ratio (RR)=0.52; confidence interval (95% CI) [0.40, 0.67]), macrosomia (p<0.00001; RR=0.62; 95% CI [0.51, 0.76]). Metformin did not increase the incidence of premature delivery (p=0.78; RR=96; 95% CI [0.61, 1.45]), small for gestational age (SGA) (p=0.72; RR=1.06; 95% CI [0.76, 1.49]). As for neonatal outcomes, metformin reduced the incidence of neonatal hypoglycemia (p<0.00001; RR=0.56; 95% CI [0.48, 0.64]), neonatal intensive care unit admission (p=0.001; RR=0.78; 95% CI [0.67, 0.91]). Conclusions:According to our analysis of the literature, several adverse maternal and neonatal outcomes are reduced with the use of metformin. Metformin may have potential benefits for the mother and fetus. This meta-analysis protocol was registered with PROSPERO under registration number CRD42019148484.

Objective. This study aimed to analyze the cuproptosis-related long non-coding RNA (lncRNA) in patients with bladder urothelial carcinoma (BLCA), construct a prognostic model, and screen its potential drugs. Methods. The transcriptome expression and clinical and mutation burden data related to BLCA were downloaded from The Cancer Genome Atlas database. The prognostic lncRNAs were screened using univariate Cox and Lasso regression analyses, and then included in the multifactor risk ratio model. The risk score of each sample was calculated based on the prognostic model formula, and the patients were divided into high- and low-risk groups for survival difference analysis. Clinically relevant receiver operating characteristic (ROC) curve, C-index principal component analysis, and clinical data statistics were used to evaluate the predictive power of the model. The risk-differential lncRNAs were functionally enriched. We calculated the tumor mutation burden of risk lncRNAs, and survival and the Tumor Immune Dysfunction and Exclusion analyses for high- and low-risk groups. Finally, immunocorrelation analysis and potential drug screening were performed. Results. Eleven lncRNAs with independent prognostic significance were screened out to construct the prognostic model. Survival analysis showed a significant difference in survival between the high- and low-risk groups. The areas under the ROC curve at 1, 3, and 5 years were 0.711, 0.679, and 0.713, respectively. The discrimination between the lncRNA high- and low-risk groups in the constructed model was the most obvious. The risk-differential lncRNAs were closely related to immunity. The treatment drugs with high sensitivity were screened based on the IC50 value. Conclusion. The 11 cuproptosis-related lncRNAs may serve as molecular biomarkers and therapeutic targets for BLCA.

No abstract