Objective To explore the effects of combined exposure to bisphenol A (BPA) and high-fat diet on liver lipid metabolism and hepatocyte senescence in mice, and to elucidate the potential mechanisms of the onset and development of non-alcoholic fatty liver disease (NAFLD). Methods Specific pathogen free C57BL/6J mice were randomly divided into six groups, with 10 mice with equal numbers of each sex in each group. The mice in the control group and the simple BPA group were fed with regular diet, while others four groups of mice were fed with high-fat diet. At the same time, the mice in the simple BPA group were intragastric administered with BPA at a dose of 50 μg/kg body weight, while the mice in the low-, medium- and high-dose BPA+high-fat groups were intragastric administered with BPA at doses of 5, 50 and 500 μg/kg body weight respectively. The mice in the control group and the high-fat group were intragastric administered with the same volume of corn oil once per day for 90 consecutive days. Liver tissues were subjected to hematoxylin-eosin (HE) and Oil Red O staining. Liver coefficients and lipid-stained area ratios were calculated. Serum level of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic biochemical analyzer. The hepatic tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 levels were quantified by enzyme-linked immunosorbent assay. The relative expression of cholesterol regulatory element binding protein 1 (SREBP1), CCAAT enhancer binding protein α, P16, and phosphorylated histone H2AX (γ-H2AX) in liver tissues was detected using Western blotting. The interaction effect of the combined exposure to BPA and high-fat diet was observed based on the result of mice in the control group, the simple high-fat group, the simple BPA group, and the medium-dose BPA group+high-fat group (the combined exposure group) using a 2×2 factorial design. The results of mice in the simple high-fat group and the low-, medium-, and high-dose BPA+high-fat groups were used to observe the effect of BPA exposure dose under high-fat diet conditions. Results i) The interactive effect of combined exposure to BPA and high fat. The HE and Oil Red O staining results indicated that the combined exposure to BPA and high-fat diet successfully established NAFLD in mice. The interactive effect of combined exposure to BPA and high-fat diet on serum ALT activity and the relative expression of P16 in the liver tissue of female mice, as well as the serum ALT and AST activities and the relative expression of SREBP1 in the liver tissue of male mice was significant (all P<0.05). Specifically, the serum ALT activity of male mice in the combined exposure group was higher than that in the simple high-fat group (P<0.05), while the ALT activity in the serum of female mice in the combined exposure group was lower than that in the simple BPA group (P<0.05). The relative expression of SREBP1 protein in the liver tissue of male mice in the combined exposure group was higher than that in the control group, the simple high-fat group, and the simple BPA group (all P<0.05). For the other indicators, there were no significant differences in the interactive effect of combined exposure to BPA and high-fat diet (all P>0.05). ii) Dose effects of BPA exposure. The HE and Oil Red O staining result showed that the degree of vacuolar steatosis in the liver of female and male mice of medium- and high-dose BPA + high-fat groups was aggravated, and the range of inflammatory cell infiltration was expanded when compared with same-sex mice in the simple high-fat group. The serum ALT activity and the fat stained area ratio, as well as the relative expression of P16 in liver tissue of female mice in high-dose BPA + high-fat group increased (all P<0.05), while the level of IL-10 in liver tissue decreased (P<0.05), compared with the female mice in simple high-fat group. The serum ALT activity, the TNF-α level in liver tissue, and the relative expression of SREBP1, P16 and γ-H2AX proteins in liver tissue of male mice in high-dose BPA + high-fat group increased (all P<0.05), while the IL-6 level in liver tissue decreased (P<0.05), compared with the male mice in simple high-fat group. For the female or male mice in the low- and medium-dose BPA + high-fat groups, only some of the above indicators showed significant changes (all P<0.05). Conclusion The combined exposure to BPA and high-fat diet has a synergistic effect on the onset and development of NAFLD. The mechanism may be related to inducing cellular senescence and modulation of lipid synthesis pathways, thereby affecting liver steatosis. The exposure dose of BPA may affect the synergistic effect.

Objective To observe the incidence and prognosis of respiratory failure in patients after cardiac surgery,and the risk factors were analyzed.Methods A total of 559 patients who underwent cardiac surgery were enrolled in Tongji Hospital,Tongji Medical College of Huazhong University of Science and Technology from July 2020 to November 2023.Clinical data were extracted through the hospital information system(HIS).This included general data such as gender,age,body mass index(BMI),smoking history,alcohol history,comorbidities,and basic disease data like occurrence of respiratory tract infection in the past 1 month before surgery,preoperative use of antimicrobial drugs,ejection fraction,operation time,cardiopulmonary bypass time,intraoperative blood transfusion,nasogastric tube indwelling,nosocomial infection,secondary thoracotomy,preoperative white blood cell count(WBC),length of intensive care unit(ICU)stay,secondary intubation and tracheostomy,discharge diagnosis,and outcome.The patients were divided into two groups according to whether or not they had expiratory failure.The difference of the above data between the two groups was compared.Multivariate Logistic regression was used to analyze the risk factors of respiratory failure in patients after cardiac surgery,the prediction model was constructed based on the above risk factors,and the receiver operator characteristic curve(ROC curve)was drawn to analyze the predictive value of the prediction model for patients with respiratory failure.Results The incidence of respiratory failure in patients after cardiac surgery was 7.51%(42 cases).Multivariate Logistic regression analysis showed that intraoperative blood transfusion>2000 mL,nasogastric tube,and nosocomial infection were risk factors for respiratory failure in patients after cardiac surgery[odds ratio(OR)and 95%confidence interval(95%CI)were 4.136(1.794-9.535),3.162(1.454-6.878)and 3.488(1.262-9.638),all P<0.05].The ROC curve analysis showed that the prediction model had a certain predictive value for the occurrence of respiratory failure in patients after cardiac surgery[area under the curve(AUC)=0.738,95%CI was 0.658-0.818,P<0.001].The length of ICU stay of patients in the group with respiratory failure was significantly longer than that in the group without respiratory failure(hours:8.16±7.62 vs.4.52±3.95),the secondary intubation rate[80.95%(34/42)vs.0(0/517)]and the tracheostomy rate[88.10%(37/42)vs.0(0/517)]were significantly higher than those in the non-respiratory failure group,and the recovery/improvement rate was significantly lower than that in the non-respiratory failure group[59.52%(25/42)vs.90.13%(466/517)],the differences were statistically significant(all P<0.05).Conclusions Patients with intraoperative blood transfusion>2000 mL,nasogastric tube inserted,and nosocomial infection are the high-risk groups for respiratory failure after cardiac surgery.Medical staff should strengthen the identification of high-risk groups and actively take intervention measures to improve the prognosis of patients.