Mitochondrial­associated endoplasmic reticulum membrane interference in ovarian cancer (Review).

The mitochondria­associated endoplasmic reticulum (ER) membrane (MAM), serving as a vital link between the mitochondria and ER, holds a pivotal role in maintaining the physiological function of these two organelles. Its specific functions encompass the participation in the biosynthesis and functional regulation of the mitochondria, calcium ion transport, lipid metabolism, oxidative stress and autophagy among numerous other facets. Scientific exploration has revealed that MAMs hold potential as effective therapeutic targets influencing the mitochondria and ER within the context of cancer therapy. The present review focused on elucidating the related pathways of mitochondrial autophagy and ER stress and their practical application in ovarian cancer, aiming to identify commonalities existing between MAMs and these pathways, thereby extending to related applications of MAMs in ovarian cancer treatment. This endeavor aimed at exploring new potential for MAMs in clinically managing ovarian cancer.

Machine learning developed an intratumor heterogeneity signature for predicting prognosis and immunotherapy benefits in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma is a kind of epithelial cell malignancy with high mortality. Intratumor heterogeneity (ITH) is involved in tumor progression, aggressiveness, treatment resistance, and disease recurrence. METHODS: Integrative machine learning procedure including 10 methods (random survival forest, elastic network, Lasso, Ridge, stepwise Cox, CoxBoost, partial least squares regression for Cox, supervised principal components, generalized boosted regression modeling, and survival support vector machine) was performed to construct an ITH-related signature (IRS) for cholangiocarcinoma. Single cell analysis was performed to clarify the communication between immune cell subtypes. Cellular experiment was used to verify the biological function of hub gene. RESULTS: The optimal prognostic IRS developed by Lasso method served as an independent risk factor and had a stable and powerful performance in predicting the overall survival rate in cholangiocarcinoma, with the AUC of 2-, 3-, and 4-year ROC curve being 0.955, 0.950 and 1.000 in TCGA cohort. low IRS score indicated with a lower tumor immune dysfunction and exclusion score, lower tumor microsatellite instability, lower immune escape score, lower MATH score, and higher mutation burden score in cholangiocarcinoma. Single cell analysis revealed a strong communication between fibroblasts, microphage and epithelial cells by specific ligand-receptor pairs, including COL4A1-(ITGAV+ITGB8) and COL1A2-(ITGAV+ITGB8). Down-regulation of BET1L inhibited the proliferation, migration and invasion as well as promoted apoptosis of cholangiocarcinoma cell. CONCLUSION: Integrative machine learning analysis was performed to construct a novel IRS in cholangiocarcinoma. This IRS acted as an indicator for predicting the prognosis and immunotherapy benefits of cholangiocarcinoma patients.

Correlation Between Pre-Operative Sleep Disturbance and Post-Operative Pain in Patients With Rotator Cuff Tear.

Objectives: This study aims to investigate the relationship between preoperative sleep disturbance and postoperative pain in patients with a rotator cuff tear, and to provide a theoretical basis for taking corresponding interventions to alleviate postoperative pain in patients with rotator cuff tear. Methods: A total of 87 patients, who had undergone shoulder arthroscopy due to rotator cuff injury in Hunan Provincial People's Hospital from January to October 2021, were selected as the research subjects. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of patients with rotator cuff tears. All patients were divided into the low sleep quality group (PSQI score >7 points, n = 61) and the high sleep quality group (PSQI score ≤7 points, n = 26). Postoperative pain was assessed by using the Numerical Rating Scale (NRS). General clinical data of the patients were collected 1 day, 2 days, and 1 month after surgery. Univariate and multivariate analyses of influencing factors were performed in patients with moderate or above pain at 1 month after surgery. Results: The score of postoperative pain of patients in the high sleep quality group was significantly lower than that of patients in the low sleep quality group (P < 0.05). A total of 35 patients (40.2%) had moderate or above pain 1 month after surgery, including 5 patients (19.2%) in the high sleep quality group and 30 patients (49.2%) in the low sleep quality group. The incidence rate of the low sleep quality group was significantly higher than that of the high sleep quality group (P = 0.009). After controlling confounding factors, preoperative sleep disturbance of patients was still independently associated with the occurrence of moderate or above pain 1 month after surgery (OR = 3.794, 95% CI: 1.261-11.409, P = 0.018). Conclusion: Preoperative sleep disturbance can increase the risk of postoperatively moderate or above pain threshold in patients with rotator cuff tear. Paying more attention to and actively improving preoperative sleep disturbance can effectively promote postoperative pain management in patients with rotator cuff tears.