B vitamins and bone health: a meta-analysis with trial sequential analysis of randomized controlled trials.

Our study showed that B vitamins did not have significant effect on fracture incidence, bone mineral density, and bone turnover markers. However, the research data of B vitamins on bone mineral density and bone turnover markers are limited, and more clinical trials are needed to draw sufficient conclusions. PURPOSE: The objective of this study was to identify the efficacy of B vitamin (VB) (folate, B6, and B12) supplements on fracture incidence, bone mineral density (BMD), and bone turnover markers (BTMs). METHODS: A comprehensive search was performed in PubMed, MEDLINE, EMBASE, Cochrane databases, and ClinicalTrials.gov up to September 4, 2023. The risk of bias was assessed according to Cochrane Handbook and the quality of evidence was assessed according to the GRADE system. We used trial sequential analysis (TSA) to assess risk of random errors and Stata 14 to conduct sensitivity and publication bias analyses. RESULTS: Data from 14 RCTs with 34,700 patients were extracted and analyzed. The results showed that VBs did not significantly reduce the fracture incidence (RR, 1.06; 95% CI, 0.95 - 1.18; p = 0.33; I2 = 40%) and did not affect BMD in lumbar spine and femur neck. VBs had no significant effect on bone specific alkaline phase (a biomarker for bone formation), but could increase the serum carboxy-terminal peptide (a biomarker for bone resorption) (p = 0.009; I2 = 0%). The TSA showed the results of VBs on BMD and BTMs may not be enough to draw sufficient conclusions due to the small number of sample data included and needed to be demonstrated in more clinical trials. The inability of VBs to reduce fracture incidence has been verified by TSA as sufficient. Sensitivity analysis and publication bias assessment proved that our meta-analysis results were stable and reliable, with no significant publication bias. CONCLUSIONS: Available evidence from RCTs does not support VBs can effectively influence osteoporotic fracture risk, BMD, and BTMs. TRIAL REGISTRATION: PROSPERO registration number: CRD42023427508.

Identification and validation of RNA methylation-related alternative splicing gene signature for low-grade glioma to predict survival and immune landscapes.

BACKGROUND: Low-grade glioma (LGG) is a crucial pathological type of glioma. The present study aimed to explore multiple RNA methylation regulator-related AS events and investigate their prognostic values in LGG. METHODS: The prognostic model for low-grade glioma was established using the LASSO regression analysis. To validate prognostic value, we performed Kaplan-Maier survival analysis, ROC curves and nomograms. The ESTIMATE algorithm, the CIBERSORT algorithm and the ssGSEA algorithm were utilized to explore the role of the immune microenvironment in LGG. Subsequently, we then used GO, KEGG and GSEA enrichment analysis to explore the functional roles of these genes. In addition, we employed the GDSC database to screen potential chemotherapeutic agents. RESULTS: Eight RNA methylation related AS events were involved in construct a survival and prognosis model, which had good ability of independent prediction for patients with LGG. Patients in the high-risk group had shorter life expectancy and higher mortality, while patients in the low-risk group had a better prognosis. We constructed a nomogram which showed an excellent predictive performance for individual OS. The risk score exhibited a close correlation with some immune cells and expression of immune checkpoints. Patients in high-risk group were characterized by immunosuppressive microenvironment and poor response to immunotherapy, and were sensitive to more chemotherapeutic drugs. Pathway and functional enrichment analyses further confirmed that significant differences existed in immune landscape between the two subgroups. CONCLUSION: The prognostic RNA methylation-related alternative splicing signature constructed could constitute a promising prognostic biomarker, which could serve to optimize treatment regimens.