Background The tumor suppressor FBW7 is the substrate recognition component of the SCF E3-ubiquitin ligase complex that mediates proteolytic degradation of various oncogenic proteins. However, the role of FBW7 in ovarian cancer progression remains inadequately understood. Methods IP-MASS, co-IP, immunohistochemistry, and western blotting were used to identify the potential substrate of FBW7 in ovarian cancer. The biological effects of FBW7 were investigated using in vitro and in vivo models. LC/MS was used to detect the m6A levels in ovarian cancer tissues. MeRIP-Seq and RNA-Seq were used to assess the downstream targets of YTHDF2. Results We unveil that FBW7 is markedly down-regulated in ovarian cancer tissues and its high expression is associated with favorable prognosis and elevated m6A modification levels. Consistently, ectopic FBW7 inhibits ovarian cancer cell survival and proliferation in vitro and in vivo, while ablation of FBW7 empowers propagation of ovarian cancer cells. In addition, the m6A reader protein, YTHDF2, is identified as a novel substrate for FBW7. FBW7 counteracts the tumor-promoting effect of YTHDF2 by inducing proteasomal degradation of the latter in ovarian cancer. Furthermore, YTHDF2 globally regulates the turnover of m6A-modified mRNAs, including the pro-apoptotic gene BMF. Conclusions Our study has demonstrated that FBW7 suppresses tumor growth and progression via antagonizing YTHDF2-mediated BMF mRNA decay in ovarian cancer.

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Background: Elderly patients undergoing hip fracture repair surgery are at increased risk of delirium due to aging, comorbidities, and frailty. But current methods for identifying the high risk of delirium among hospitalized patients have moderate accuracy and require extra questionnaires. Artificial intelligence makes it possible to establish machine learning models that predict incident delirium risk based on electronic health data.Methods: We conducted a retrospective case-control study on elderly patients (≥65 years of age) who received orthopedic repair with hip fracture under spinal or general anesthesia between June 1, 2018, and May 31, 2019. Anesthesia records and medical charts were reviewed to collect demographic, surgical, anesthetic features, and frailty index to explore potential risk factors for postoperative delirium. Delirium was assessed by trained nurses using the Confusion Assessment Method (CAM) every 12 h during the hospital stay. Four machine learning risk models were constructed to predict the incidence of postoperative delirium: random forest, eXtreme Gradient Boosting (XGBoosting), support vector machine (SVM), and multilayer perception (MLP). K-fold cross-validation was deployed to accomplish internal validation and performance evaluation.Results: About 245 patients were included and postoperative delirium affected 12.2% (30/245) of the patients. Multiple logistic regression revealed that dementia/history of stroke [OR 3.063, 95% CI (1.231, 7.624)], blood transfusion [OR 2.631, 95% CI (1.055, 6.559)], and preparation time [OR 1.476, 95% CI (1.170, 1.862)] were associated with postoperative delirium, achieving an area under receiver operating curve (AUC) of 0.779, 95% CI (0.703, 0.856).The accuracy of machine learning models for predicting the occurrence of postoperative delirium ranged from 83.67 to 87.75%. Machine learning methods detected 16 risk factors contributing to the development of delirium. Preparation time, frailty index uses of vasopressors during the surgery, dementia/history of stroke, duration of surgery, and anesthesia were the six most important risk factors of delirium.Conclusion: Electronic chart-derived machine learning models could generate hospital-specific delirium prediction models and calculate the contribution of risk factors to the occurrence of delirium. Further research is needed to evaluate the significance and applicability of electronic chart-derived machine learning models for the detection risk of delirium in elderly patients undergoing hip fracture repair surgeries.

The long-term follow-up data confirms the role of CCRT as a treatment of locoregionally advanced NPC. Oxaliplatin can be considered as an alternative optional therapeutic regimen for these patients due to its high efficiency and low toxic effect.