Metformin treatment reduces the incidence of osteoporosis: a two-sample Mendelian randomized study.

It remains unclear whether the association between metformin and osteoporosis (OP) risk is causal. This two-sample Mendelian randomization (MR) study suggests a causal relationship between metformin treatment and a decrease in OP and fracture incidence, as well as an increase in bone mineral density (BMD) in the lumbar spine, femoral neck, and heel. Nonetheless, no significant causal effect is observed on forearm BMD. PURPOSE: We utilize a MR approach to investigate the association between metformin treatment and the risk of OP. METHODS: Metformin treatment was selected as exposures. Outcomes included OP; BMD at the forearm (FA), femoral neck (FN), and lumbar spine (LS); estimated heel bone mineral density (eBMD); and fracture. Summary statistics for exposures and outcomes were obtained from corresponding genome-wide association studies. Inverse variance-weighted (IVW) analysis was mainly applied; the weighted median (WM), penalized weighted median (PWM), maximum likelihood (ML), and MR-Egger regression (MR-Egger) method were also used to obtain robust estimates. A series of sensitivity analyses including Cochran's Q test, MR-Egger regression, leave-one-out analysis, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) were used to detect pleiotropy or heterogeneity. RESULTS: In the main analysis, IVW estimates demonstrated that metformin treatment had a definite causal effect on the risk of OP (odds ratio (OR): 0.859, 95% CI: 0.774-0.953, P = 0.004), LS-BMD (OR: 1.063, 95% CI: 1.023-1.105, P = 0.002), FN-BMD (OR: 1.034, 95% CI: 1.000-1.069, P = 0.049), eBMD (OR: 1.035, 95% CI: 1.023-1.047, P ≤ 0.001), and fracture(OR: 0.958, 95% CI: 0.928-0.989, P = 0.008). However, it did not have an effect on FA-BMD(OR: 1.050, 95% CI: 0.969-1.138, P = 0.237). CONCLUSIONS: This study indicated that metformin treatment is significantly associated with a reduction in the risk of OP, fracture and higher LS-BMD, FN-BMD, and eBMD. However, there was no significant association with FA-BMD.

Identification of a new risk score model based on hypoxia and EMT-related genes for predicting lung squamous cell carcinoma prognosis.

A complicated analysis of the prognostic characteristics of lung squamous cell carcinoma (LUSC) is needed. The aim of this study was to develop a risk score model to predict immunotherapeutic response and prognosis for patients with LUSC. A hypoxia and epithelial-mesenchymal transition-related risk score model was developed for prediction of LUSC. The correlation between risk score and clinical characteristics was determined. The single sample gene set enrichment analysis algorithm was utilized to determine the abundance of cell infiltration in tumor immune microenvironment in LUSC. The predictive value of risk score model in response to immunotherapy was evaluated. A hypoxia and epithelial-mesenchymal transition-related risk score model was constructed. This risk score model was correlated with the overall survival of LUSC. Patients with low-risk presented a high survival possibility. The high-risk group was involved in ECM receptor interaction, complement and coagulation cascades, intestinal immune network for IgA production. Finally, patients with low-risk score had significant clinical benefit. The risk score model was constructed to predict immunotherapeutic response and prognosis for patients with LUSC. In addition to identifying LUSC patients with poor survival, the results provide more information for the immune immunotherapy and microenvironment for LUSC.