ObjectiveTo explore the mechanism of renal tubular epithelial cell apoptosis induced by endoplasmic reticulum stress in rats with intermittent hypoxia (IH) and the intervention effect of losartan.MethodsSixty SPF grade healthy male SD rats were randomly divided into four groups (15 rats in each group), namely as group A (control group), group B (IH group), group C (IH+losartan group), and group D (IH+saline group). The group C and D were intraperitoneally injected with losartan 30 mg/kg and the same dose of saline 30 minutes daily before the experiment, and then the group B, C and D were placed in the intermittent hypoxia chamber. After 6 weeks of modeling, serum of the rats was sampled to detect the renal function. Hematoxylin-eosin staining was used to observe histomorphological changes of the kidney; transmission electron microscopy was used to observe ultrastructural changes of the kidney; TUNEL was used to detect apoptotic index of the renal tubular epithelial cells; and RT-PCR method was used to detect expressions of caspase-12, JNK and CHOP mRNA in the kidney.ResultsThe differences of renal function among these four groups were statistically significant (all P<0.05). Hematoxylin-eosin staining and transmission electron microscopy showed the histomorphological and ultrastructural changes of the kidneys in group B, C and D compared with group A, and the damages in group B and D were more significant. TUNEL results showed that the apoptotic index of renal tubular epithelial cells in group B and D was significantly higher than that in group A (P<0.01), while that in group C was significantly lower than that in group B and D (all P<0.01). RT-PCR results showed that caspase-12, JNK and CHOP mRNA expressions were significantly higher in group B and D than those in group A (all P<0.01); caspase-12 mRNA expression was significantly lower in group C than that in group B and D (P<0.01; P<0.05); and CHOP mRNA expression was significantly lower in group C than that in group B and D (all P<0.01).ConclusionsIH may induce apoptosis of renal tubular epithelial cells by activating endoplasmic reticulum stress through caspase-12, JNK and CHOP. Losartan has protective effects on the kidney of rats with intermittent hypoxia. Its mechanism may be related to the inhibition of apoptotic pathways mediated by endoplasmic reticulum stress.
Objective To investigate the prevalence of water-loss dehydration on admission among older patients with hip fractures and to develop a machine learning-based risk prediction model. Methods A retrospective cohort study was conducted in older patients with hip fractures admitted to the Third Hospital of Hebei Medical University between January and December 2024. Ten machine learning algorithms were used to develop prediction models. Model performance was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), accuracy, sensitivity, specificity, and F1 score. Shapley additive explanations (SHAP) were applied to interpret the optimal model. Results A total of 529 patients were included, of whom 165 patients (31.2%) had water-loss dehydration. The random forest model showed the best overall performance, with ROC-AUC values of 0.862 [95% confidence interval (CI) (0.825, 0.899)] in the training set and 0.831 [95%CI (0.762, 0.899)] in the internal validation set. In the internal validation set, the accuracy, sensitivity, specificity, and F1 score were 0.744, 0.800, 0.718, and 0.661, respectively. SHAP analysis showed that time from injury to admission, history of diabetes, and history of previous surgery made the greatest contributions to model predictions. Conclusions Water-loss dehydration is common on admission among older patients with hip fractures. The random forest model demonstrated good performance in internal validation and may support early risk stratification for dehydration in this population. Further external validation is warranted.