Background The association between triglyceride and prostate cancer (PCa) has been reported in observational studies. However, the causality from triglyceride on PCa remained unknown. Method Two-sample Mendelian randomization (MR) was performed with triglyceride genome-wide association study (GWAS) data from 177,861 individuals and GWAS summary statistics of PCa from 463,010 individuals. Then, 48 single nucleotide polymorphisms (SNPs) of triglyceride were used as instrumental variables (IVs) to conduct MR analysis on PCa. Inverse‐variance weighted (IVW), Weighted median, MR‐Egger regression, Simple mode and Weighted mode were used for MR analysis. To verify the sensitivity of the data, heterogeneity test, pleiotropy test and leave-one-out sensitivity test were performed. Results Association for an effect of triglyceride on PCa risk was found in IVW (odds ratio [OR]: 1.002, 95% confidence interval (CI): 1.000–1.004, p = 0.016). However, opposing results were observed using the weighted median (OR: 1.001, 95% CI: 0.999–1.003, p = 0.499) and MR‐Egger (OR: 0.999, 95% CI: 0.995–1.002, p = 0.401) approach. After MRPRESSO, the same result was obtained by using IVW method (OR: 1.002, 95% CI: 1.001–1.004, p = 0.004). Conclusions The large MR analysis indicated that the potential causal effect of triglyceride on PCa. The odds of PCa would increase with high levels of triglyceride.

Background Cuproptosis-related genes (CRGs) have been recently discovered to regulate the occurrence and development of various tumors by controlling cuproptosis, a novel type of copper ion-dependent cell death. Although cuproptosis is mediated by lipoylated tricarboxylic acid cycle proteins, the relationship between cuproptosis-related long noncoding RNAs (crlncRNAs) in bladder urothelial carcinoma (BLCA) and clinical outcomes, tumor microenvironment (TME) modification, and immunotherapy remains unknown. In this paper, we tried to discover the importance of lncRNAs for BLCA. Methods The BLCA-related lncRNAs and clinical data were first obtained from The Cancer Genome Atlas (TCGA). CRGs were obtained through Coexpression, Cox regression and Lasso regression. Besides, a prognosis model was established for verification. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, gene ontology (GO) analysis, principal component analysis (PCA), half-maximal inhibitory concentration prediction (IC50), immune status and drug susceptibility analysis were carried out. Results We identified 277 crlncRNAs and 16 survival-related lncRNAs. According to the 8-crlncRNA risk model, patients could be divided into high-risk group and low-risk group. Progression-Free-Survival (PFS), independent prognostic analysis, concordance index (C-index), receiver operating characteristic (ROC) curve and nomogram all confirmed the excellent predictive capability of the 8-lncRNA risk model for BLCA. During gene mutation burden survival analysis, noticeable differences were observed in high- and low-risk patients. We also found that the two groups of patients might respond differently to immune targets and anti-tumor drugs. Conclusion The nomogram with 8-lncRNA may help guide treatment of BLCA. More clinical studies are necessary to verify the nomogram.

Bladder urothelial carcinoma (BLCA) is the most common malignancy of the urinary tract, with a wide range of clinical symptoms and prognosis. Disulfidptosis is newly identified cell death method and closely associated with BLCA progression, prognosis, and treatment outcome. Currently, we need to construct a new prognostic model of disulfidptosis-related long noncoding RNAs (drlncRNAs) to improve the treatment strategy of BLCA. Methods The data of BLCA samples were obtained from The Cancer Genome Atlas (TCGA), then 10 unique disulfidptosis-related genes (DRGs) were obtained from the research papers. The differences between the two groups showed in this study were used to create the “disulfidptosis-related long noncoding RNAs score” (disulfidptosis-score) prognostic model. Results We identified two groups of drlncRNAs with high and low disulfidptosis scores in this study. Patients with low disulfidptosis scores had a better overall survival rate compared to those with high scores in bladder cancer, and the high disulfidptosis score subtype exhibited more active malignant pathways related to cancer than the low score subtype. We found that the low disulfidptosis-score subgroup had better prognosis than the high disulfidptosis-score subgroup. The expression of mutation burden (TMB) was much higher in the low disulfidptosis-score group than in the high disulfidptosis-score group. The low disulfidptosis-score subgroup of patients exhibited significantly higher proportions of plasma cells, T cells CD8, and Tregs, while the high-risk subgroup had a greater abundance of Macrophages M0 and Macrophages M2. The disulfidptosis-score showed a strong correlation with the sensitivity of chemotherapeutic drugs, and patients in the low disulfidptosis-score group were more likely to exhibit an immune response and respond positively to immunotherapy. Additionally, we developed a nomogram to enhance the accuracy of the disulfidptosis-clinical score. Conclusion Based on our investigation of disulfidptosis-score in BLCA, disulfidptosis-score may have an important role in TME, prognosis, and drug sensitivity. We also investigated the significance of the disulfidoptosis-score in relation to immunotherapy and immune response, providing a basis for improving prognosis and responding to immunotherapy among patients with BLCA.

Background Risk factors for urolithiasis have not been identified. Here, we aimed to identify potentially causal risk factors driving the risk of urolithiasis. Methods Two sets of instrumental variables were used for analysis, derived from publicly available databases. Summary-level statistical data for urolithiasis were obtained from the MRC-IEU Consortium and UK biobank (Neale Lab). Mendelian randomization (MR) was conducted to identify causal risk of urolithiasis. Finally, the results of the two databases were combined and a meta-analysis was performed. Results In the MRC-IEU consortium, the odds of urolithiasis increased per 1-SD increase of body mass index (BMI) (OR = 1.0016, 95% CI:1.0004–1.0029, p = 0.010), triglycerides (OR = 1.0016, 95% CI:1.0003–1.0029, p = 0.017), adiponectin (OR = 1.0027, 95% CI:1.0003–1.0050, p = 0.024), and body fat percentage (OR = 1.008, 95% CI:1.0001–1.0161, p = 0.047). In addition, alcohol intake also increased the incidence of urolithiasis (OR = 1.0030, 95% CI:1.0009–1.0051, p = 0.005). In the UK biobank, the odds of urolithiasis increased per 1-SD increase of waist circumference (OR = 1.0215, 95% CI:1.0061–1.0372, p = 0.008) and body fat percentage (OR = 1.0239, 95% CI:1.0043–1.0440, p = 0.020). Surprisingly, we found that the risk of urolithiasis decreased with increasing hip circumference (OR = 0.9954, 95% CI:0.9915–0.9992, p = 0.017). In a meta-analysis of MR results, higher BMI (OR = 1.0016, 95% CI:1.0004–1.0027, p = 0.009), waist circumference (OR = 1.0073, 95% CI:1.0020–1.0126, p = 0.007), adiponectin (OR = 1.0026, 95% CI:1.0008–1.0043, p = 0.004), triglycerides (OR = 1.0015, 95% CI:1.0004–1.0026, p = 0.008) and body fat percentage (OR = 1.0104, 95% CI:1.0030–1.0178, p = 0.006) increased the risk of urolithiasis. Furthermore, alcohol intake also increased the incidence of urolithiasis (OR = 1.0033, 95% CI:1.0012–1.0053, p = 0.002). Conclusions Our MR study found that higher BMI, triglycerides, waist circumference, adiponectin, body fat percentage, and alcohol intake increased the risk of urolithiasis.