This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To investigate the influence of celastrol(CEL)on the inflammatory response of rats with endometritis by regulating high mobility group box B1(HMGB1)/receptor for advanced glycation end products(RAGE).Methods:Seventy-two SPF SD female rats were randomly grouped into normal control group(Control group),sham operation group(Sham group),Model group,low-dose CEL group(CEL-L group,CEL 20 mg/kg),high-dose CEL group(CEL-H group,CEL 40 mg/kg)and HMGB1 in-hibitor glycyrrhizic acid group(GA group,GA 2 mg/kg),12 rats in each group.A rat model of endometritis was established by intra-uterine injection of phenol mucilage.Histopathological changes of rat uterus were observed by HE staining;the levels of superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO)and prostaglandin E2(PEG2)in rat serum,and the levels of TNF-α and IL-1β in rat uterus tissue were measured by ELISA;the levels of MMP-2 and MMP-9 in rat uterus tissue were detected by immuno-histochemistry;the mRNA expression levels of HMGB1 and RAGE in rat uterus tissue were detected by RT-qPCR;the protein expres-sions of HMGB1 and RAGE in rat uterus were detected by Western blot.Results:Compared with the Sham group,the uterine tissue of the Model group was severely damaged,and the level of serum SOD and the levels of MMP-2 and MMP-9 in the uterine tissue were ob-viously decreased(P<0.05);the level of serum MDA,NO,PEG2,TNF-α and IL-1β,the expressions of HMGB1 and RAGE mRNA and protein in uterine tissue were obviously increased(P<0.05).Compared with the rats in the Model group,the changes of each in-dex of the rats in the CEL-L and CEL-H groups were opposite to the above(P<0.05).There was no obvious difference in the corre-sponding indexes between the CEL-H group and the GA group(P>0.05).Conclusion:Celastrol may reduce the inflammatory response in rats with endometritis by down-regulating the HMGB1/RAGE signaling pathway.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.