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Cuproptosis, a newly discovered form of programmed cell death, plays a vital role in the occurrence and development of tumors. However, the role of cuproptosis in the bladder cancer tumor microenvironment remains unclear. In this study, we developed a method for predicting the prognostic outcomes and guiding the treatment selection for patients with bladder cancer. We obtained 1001 samples and survival data points from The Cancer Genome Atlas database and Gene Expression Omnibus database. Using cuproptosis-related genes (CRGs) identified in previous studies, we analyzed CRG transcriptional changes and identified two molecular subtypes, namely high- and low-risk patients. The prognostic features of eight genes (PDGFRB, COMP, GREM1, FRRS1, SDHD, RARRES2, CRTAC1, and HMGCS2) were determined. The CRG molecular typing and risk scores were correlated with clinicopathological features, prognosis, tumor microenvironment cell infiltration characteristics, immune checkpoint activation, mutation burden, and chemotherapy drug sensitivity. Additionally, we constructed an accurate nomogram to improve the clinical applicability of the CRG_score. qRT-PCR was used to detect the expression levels of eight genes in bladder cancer tissues, and the results were consistent with the predicted results. These findings may help us to understand the role of cuproptosis in cancer and provide new directions for the design of personalized treatment and prediction of survival outcomes in patients with bladder cancer.

Context Limited information was available on detailed associations of low-density lipoprotein cholesterol (LDL-C) with all-cause and cause-specific mortality in older adults. Methods This prospective cohort study included a representative sample of 211 290 adults aged 65 or older who participated in Shenzhen Healthy Aging Research 2018-2019. The vital status of the participants by December 31, 2021, was determined. We estimated the hazard ratios (HR) with 95% confidence intervals for all-cause or cause-specific mortality using multivariable Cox proportional hazards models and Cox models with restricted cubic spline (RCS). Results The median follow-up time was 3.08 years. A total of 5333 participants were confirmed to have died. Among them, 2037 cardiovascular disease (CVD) deaths and 1881 cancer deaths occurred. Compared to those with LDL-C of 100 to 129 mg/dL, the all-cause mortality risk was significantly higher for individuals with LDL-C levels that were very low (<70 mg/dL) or low (70-99 mg/dL). Compared with individuals with the reference LDL-C level, the multivariable-adjusted HR for CVD-specific mortality was 1.338 for those with very low LDL-C levels (< 70 mg/dL), 1.437 for those with high LDL-C levels (160 mg/dL ≤ LDL-C < 190 mg/dL), and 1.489 for those with very high LDL-C levels (≥190 mg/dL). Low LDL-C levels (70-99 mg/dL) and very low LDL-C levels (<70 mg/dL) were also associated with increased cancer mortality and other-cause mortality, respectively. The results from an RCS curve showed similar results. Conclusion Considering the risk of all-cause mortality and cause-specific mortality, we recommended 100 to 159 mg/dL as the optimal range of LDL-C among older adults in China. [ABSTRACT FROM AUTHOR]

Evidence that long-term exposure to ambient air pollution increases mortality among older adults, particularly those residing in low-level air pollution locations, remains scarce. This study investigated the potential links between long-term low-level air pollution exposure and mortality among Chinese older adults. A population-based study with 317,464 individuals aged ≥ 65 years was conducted in Shenzhen, China during 2018 and 2020. Logistic regression models were used to analyze the associations between long-term exposure to air pollution and all-cause mortality, as the primary outcome, as well as non-accidental, cancer and cardiovascular mortality. Significant associations of PM 1 , PM 2.5 , PM 10 , SO 2 , CO, and O 3 exposures with a higher risk of all-cause mortality were found. Adjusted odds ratio (OR) for each 1 μg/m3 increment was 1.49 [95% confidence interval (CI): 1.46, 1.53] for PM 1 , 1.30 (1.27, 1.32) for PM 2.5 , 1.05 (1.04, 1.06) for PM 10 , 5.84 (5.39, 6.32) for SO 2 , 1.04 (1.04, 1.05) for CO, and 1.02 (1.00, 1.03) for O 3 , respectively. Long-term PM 1 , PM 2.5 , PM 10 , SO 2 , and CO exposures also elevated the risks of non-accidental, cancer and cardiovascular mortality. Long-term low-level air pollution exposure was associated with an increased mortality risk among Chinese older adults. [ABSTRACT FROM AUTHOR]