Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*

Objective:To evaluate the left ventricular（LV）function in heart transplant（HTx）patients with post-transplant diabetes（PTDM），and to examine the relevance of PTDM and LV function to the patient's prognosis.Methods:Two hundred and thirteen adult HTx patients who underwent echocardiography at Union Hospital，Tongji Medical College，Huazhong University of Science and Technology between January 2018 and January 2022 were prospectively included. The patients were divided into PTDM group（ n=86）and Non-PTDM group（ n=127）. LV function parameters were acquired using conventional and two-dimensional speckle-tracking echocardiography（2D-STE），and were compared between the two groups. The primary endpoints included all-cause mortality or transplant-related readmission. Results:Compared with Non-PTDM group，the LV mass of PTDM group was higher，the LV ejection fraction，LV global longitudinal strain（GLS），peak systolic global longitudinal strain rate，and early diastolic global longitudinal strain rate（dGLSr）were lower（all P＜0.05）. After a median follow-up period of 37.6（29.3）months，27 patients experienced clinical events. A multivariate analysis revealed that PTDM（ HR=2.198，95% CI=1.018-4.743， P=0.045）and low GLS（ HR=6.456，95% CI=2.889-14.426， P＜0.001）were independent predictors of adverse clinical events after adjustment for dGLSr，body mass index and age. After subdividing the two groups into 4 subgroups by the cutoff value of GLS（16.5%），the prognosis was worst for HTx patients with PTDM and low GLS. Conclusions:HTx patients with PTDM have worse LV systolic and diastolic function than those without PTDM. Management of HTx patients with PTDM may be improved using GLS guidance.

Objective The medication pattern of doctor Chen Jie in treating functional dyspepsia(FD)in children and the potential mechanism of action of core drug group were explored through data mining and network pharmacology methods.Methods The prescriptions for pediatric FD treated by doctor Chen Jie in the outpatient department of Second Affiliated Hospital of Wenzhou Medical University from January 2020 to December 2024 were collected to establish a prescription database.Excel 2019 and SPSS software were applied to statistically analyze the nature,taste,meridian tropism and frequency of drugs included in the prescriptions,and association rule analysis and cluster analysis were conducted.The potential mechanism of action of the core drug group was explored by using the network pharmacology method.Results A total of 603 prescriptions were included,involving 160 kinds of drugs,with a cumulative frequency of medication reaching 5012 times.Among them,the medicinal nature and flavour were mainly warm and sweet,and channel tropism were mainly the spleen,stomach and lung meridians.The core drug group obtained through association rules and cluster analysis was"Fuchao Baizhu-Fuling-Chenpi".Network pharmacological analysis was conducted on the core drug group,and it was found that its main components included naringenin,atractylenolide Ⅰ,atractylone,and hederagenin,as well as core genes such as AKT1,TNF,IL-6,ESR1,and IL-1β.The main enrichment pathways were lipids and atherosclerosis,advanced glycation end product-advanced glycation end product receptor signaling pathway,cancer pathway,etc..Conclusion Doctor Chen Jie's medication for treating FD in children mainly focuses on invigorating spleen and replenishing qi,regulating qi-flowing for eliminating dampness.The core drug group,"Fuchao Baizhu-Fuling-Chenpi",exerts its effects through multiple components,multiple targets and multiple pathways.

Objective The medication pattern of doctor Chen Jie in treating functional dyspepsia(FD)in children and the potential mechanism of action of core drug group were explored through data mining and network pharmacology methods.Methods The prescriptions for pediatric FD treated by doctor Chen Jie in the outpatient department of Second Affiliated Hospital of Wenzhou Medical University from January 2020 to December 2024 were collected to establish a prescription database.Excel 2019 and SPSS software were applied to statistically analyze the nature,taste,meridian tropism and frequency of drugs included in the prescriptions,and association rule analysis and cluster analysis were conducted.The potential mechanism of action of the core drug group was explored by using the network pharmacology method.Results A total of 603 prescriptions were included,involving 160 kinds of drugs,with a cumulative frequency of medication reaching 5012 times.Among them,the medicinal nature and flavour were mainly warm and sweet,and channel tropism were mainly the spleen,stomach and lung meridians.The core drug group obtained through association rules and cluster analysis was"Fuchao Baizhu-Fuling-Chenpi".Network pharmacological analysis was conducted on the core drug group,and it was found that its main components included naringenin,atractylenolide Ⅰ,atractylone,and hederagenin,as well as core genes such as AKT1,TNF,IL-6,ESR1,and IL-1β.The main enrichment pathways were lipids and atherosclerosis,advanced glycation end product-advanced glycation end product receptor signaling pathway,cancer pathway,etc..Conclusion Doctor Chen Jie's medication for treating FD in children mainly focuses on invigorating spleen and replenishing qi,regulating qi-flowing for eliminating dampness.The core drug group,"Fuchao Baizhu-Fuling-Chenpi",exerts its effects through multiple components,multiple targets and multiple pathways.

Objective:To evaluate the left ventricular（LV）function in heart transplant（HTx）patients with post-transplant diabetes（PTDM），and to examine the relevance of PTDM and LV function to the patient's prognosis.Methods:Two hundred and thirteen adult HTx patients who underwent echocardiography at Union Hospital，Tongji Medical College，Huazhong University of Science and Technology between January 2018 and January 2022 were prospectively included. The patients were divided into PTDM group（ n=86）and Non-PTDM group（ n=127）. LV function parameters were acquired using conventional and two-dimensional speckle-tracking echocardiography（2D-STE），and were compared between the two groups. The primary endpoints included all-cause mortality or transplant-related readmission. Results:Compared with Non-PTDM group，the LV mass of PTDM group was higher，the LV ejection fraction，LV global longitudinal strain（GLS），peak systolic global longitudinal strain rate，and early diastolic global longitudinal strain rate（dGLSr）were lower（all P＜0.05）. After a median follow-up period of 37.6（29.3）months，27 patients experienced clinical events. A multivariate analysis revealed that PTDM（ HR=2.198，95% CI=1.018-4.743， P=0.045）and low GLS（ HR=6.456，95% CI=2.889-14.426， P＜0.001）were independent predictors of adverse clinical events after adjustment for dGLSr，body mass index and age. After subdividing the two groups into 4 subgroups by the cutoff value of GLS（16.5%），the prognosis was worst for HTx patients with PTDM and low GLS. Conclusions:HTx patients with PTDM have worse LV systolic and diastolic function than those without PTDM. Management of HTx patients with PTDM may be improved using GLS guidance.

Objective:To investigate the impact of body mass index (BMI) on the postoperative complications of open pancreaticoduodenectomy (OPD).Methods:The preoperative, operative and postoperative data of 234 patients who underwent OPD in the Department of the Hepatobiliary and Pancreatic Surgery of First Affiliated Hospital affiliated to Naval Medical University from January 2015 to June 2016 were analyzed retrospectively. According to the Asian BMI standard, the patients were divided into three groups: underweight group (BMI<18.5 kg/m 2, n=32), normal weight group (18.5 kg/m 2≤BMI<23.0 kg/m 2, n=110) and overweight group (BMI≥23.0 kg/m 2, n=92). Normal weight group was compared with underweight group and overweight group, respectively, to analyze the relationship between BMI and intraoperative parameters and major postoperative complications of OPD. Results:The incidence of diabetes in underweight group was lower than that in normal weight group, and the proportion of ASA score 3 in underweight group was higher than that in normal weight group, and there were significantly statistical differences (both P value <0.05). There was no significant difference on the other variables between underweight group, normal weight group and overweight group. The operation time, intraoperative hemorrhage volume >800 ml and intraoperative blood transfusion rate were not statistically different between underweight group and normal weight group, but overweight group had obviously higher intraoperative blood transfusion rate than normal weight group and the difference was statistically significant ( P<0.05). Underweight group had more postoperative intraperitoneal hemorrhage and postoperative blood transfusion rate than normal weight group, and the readmission rate in underweight group was less than that in normal weight group; the incidence of clinically related-post operative pancreatic fistula, postoperative infection, gastrointestinal bleeding and delayed gastric emptying in overweight group were significantly higher than those in normal weight group, and there were significantly statistical differences (all P value <0.05). In underweight group, normal weight group and overweight group, the average length of hospital stay were 9.9 days, 11.3 days, 15 days, and the total hospitalization expenses were 63663.04 yuan, 66241.78 yuan and 80484.31 yuan, respectively. Conclusions:Compared to normal weight patients, the difficulty of OPD in underweight patients does not increase, while the difficulty of OPD in overweight patients increases. Underweight and overweight could both increase the postoperative complications of OPD to some extent.

Cognitive reserve referred to the cumulative flexibility of an individual's cognitive processes,whereas accurately assessing an individual's cognitive reserve and intervening was important for preventing the occurrence of cognitive dysfunction as well as promoting cognitive health.This article reviewed the main contents and applications of cognitive reserve assessment tools,and compared the characteristics and limitations of each assessment tool.The purpose was to provide ideas for the development of cognitive reserve assessment tools suitable for China's cultural background and population characteristics,and to provide a basis for accurately assessing the current status of China's cognitive reserve and formulating targeted cognitive reserve enhancement programs.

Objective To establish an artificial intelligence(AI)diagnostic model for the histopathologic diagnosis of extramammary Paget's disease(EMPD)and to evaluate its efficiency for the diagnosis and differential diagnosis of EMPD.Methods All non-tumor skin disease patients who underwent skin tissue biopsy in Department of Dermatology of First Affiliated Hospital of Army Medical University from September 2003 to February 2023 were recruited,and their pathological data were collected,including EMPD,Bowen's disease(BD),squamous cell carcinoma(SCC),and epidermal hyperplasia and hypertrophy.With EMPD as the main research subject,the histopathological images of BD,SCC,and non-tumor skin diseases were included in the study.The histopathological data of 4 types of diseases was classified and diagnosed by ResNet101 and DenseNet121 deep learning neural networks,and the performance of these models was evaluated.Results The AUC values of the ResNet101 diagnostic model for the diagnosis of EMPD,BD,SCC and non-tumor skin diseases on the images at x20 magnification were 0.97,0.98,1.00 and 0.96,respectively,with an accuracy of 0.925±0.011,while the AUC values on the images at x40 magnification were 1.00,0.99,1.00 and 0.97,respectively,with an accuracy of 0.943±0.017.The AUC values of the DenseNet121 diagnostic model for the diagnosis of 4 diseases on the images at x20 magnification were 0.98,0.95,0.99 and 1.00,respectively,with an accuracy of 0.912±0.034,while the AUC values on the images at x40 magnification were 0.99,0.96,1.00 and 1.00,respectively,with an accuracy of 0.971±0.012.Our results indicated that the histopathologic diagnostic model could effectively differentiate EMPD from BD,SCC and non-tumor skin diseases at low power magnification.The FLPOs of ResNet101 was 786.6 M,and the parameter was 4.5 M;The FLPOs of DensNet121 was 289.7 M,and the parameter was 0.8M.Conclusion Our AI diagnostic model is of good effectiveness in the diagnosis and differential diagnosis of EMPD.DenseNet121 is recommended as the dermatopathological diagnostic model of this study.

Objective To observe the value of deep learning(DL)models for automatic classification of echocardiographic views.Methods Totally 100 patients after heart transplantation were retrospectively enrolled and divided into training set,validation set and test set at a ratio of 7∶2∶1.ResNet18,ResNet34,Swin Transformer and Swin Transformer V2 models were established based on 2D apical two chamber view,2D apical three chamber view,2D apical four chamber view,2D subcostal view,parasternal long-axis view of left ventricle,short-axis view of great arteries,short-axis view of apex of left ventricle,short-axis view of papillary muscle of left ventricle,short-axis view of mitral valve of left ventricle,also 3D and CDFI views of echocardiography.The accuracy,precision,recall,F1 score and confusion matrix were used to evaluate the performance of each model for automatically classifying echocardiographic views.The interactive interface was designed based on Qt Designer software and deployed on the desktop.Results The performance of models for automatically classifying echocardiographic views in test set were all good,with relatively poor performance for 2D short-axis view of left ventricle and superior performance for 3D and CDFI views.Swin Transformer V2 was the optimal model for automatically classifying echocardiographic views,with high accuracy,precision,recall and F1 score was 92.56％,89.01％,89.97％and 89.31％,respectively,which also had the highest diagonal value in confusion matrix and showed the best classification effect on various views in t-SNE figure.Conclusion DL model had good performance for automatically classifying echocardiographic views,especially Swin Transformer V2 model had the best performance.Using interactive classification interface could improve the interpretability of prediction results to some extent.

Objective:To investigate the chain mediation effect of psychological flexibility and dyadic coping between perceived social support and family function in parents of pediatric liver transplant recipients.Methods:Totally 320 parents of pediatric liver transplant recipients who were treated at the Department of Pediatric Organ Transplantation, Tianjin First Central Hospital from April to October 2023 were selected by convenience sampling. The participants were surveyed using a general information questionnaire, the Perceived Social Support Scale (PSSS), the Acceptance and Action Questionnaire-Ⅱ (AAQ-Ⅱ), the Dyadic Coping Inventory (DCI), and the Family APGAR Index (APGAR). Pearson correlation analysis was used to examine the relationships between perceived social support, psychological flexibility, dyadic coping, and family function in these parents. Structural equation modeling (SEM) was performed using Amos 26.0 to analyze the chain mediation effect of psychological flexibility and dyadic coping between perceived social support and family function, with the Bootstrap method used for model testing.Results:A total of 320 questionnaires were distributed, with 312 valid responses, yielding a response rate of 97.50% (312/320). The scores for the 312 parents were as follows: PSSS (59.29±15.64), AAQ-Ⅱ (20.35±9.07), DCI (124.64±32.65), and APGAR (6.98±2.74). Family function was positively correlated with perceived social support and dyadic coping ( P<0.01), and perceived social support was positively correlated with dyadic coping ( P<0.01). Psychological flexibility was negatively correlated with family function, perceived social support, and dyadic coping ( P<0.01). SEM results showed that psychological flexibility and dyadic coping had a significant chain mediation effect between perceived social support and family function, with a mediation effect value of 0.059. The chain mediation effect of psychological flexibility and dyadic coping accounted for 13.81% of the total effect (0.059/0.427) . Conclusions:Perceived social support directly affects family function in parents of pediatric liver transplant recipients and also indirectly influences family function through the chain mediation effect of psychological flexibility and dyadic coping.