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 compare the effect of palliative mitral valve surgeries and medication therapies for secondary non-ischemic mitral regurgitation. Methods The clinical data of patients with non-ischemic functional mitral regurgitation treated in our hospital between 2009 and 2019 were retrospectively analyzed. Patients with a left ventricular ejection fraction (LVEF)＜40% underwent a dobutamine stress test, and a positive result was determined when the LVEF improved by more than 15% compared to the baseline value. Positive patients were divided into a surgery group and a medication group. The surgery group underwent surgical mitral valve repair or replacement, while the medication group received simple medication treatment. Follow-up on survival and cardiac function status through outpatient or telephone visits every six months after surgery, and patients underwent cardiac ultrasound examination one year after surgery. The main research endpoint was a composite endpoint of all-cause death, heart failure readmission, and heart transplantation, and the differences in cardiac function and cardiac ultrasound parameters between the two groups were compared. Results Ultimately 41 patients were collected, including 28 males and 13 females with an average age of 55.5±11.1 years. Twenty-five patients were in the surgery group and sixteen patients in the medication group. The median follow-up time was 16 months, ranging 1-96 months. The occurrence of all-cause death in the surgery group was lower than that in the medication group (HR=0.124, 95%CI 0.024-0.641, P=0.034). The difference between the two groups was not statistically significant in the composite endpoint (HR=0.499, 95%CI 0.523-1.631, P=0.229). The New York Heart Association (NYHA) grade of the surgery group was better (NYHA Ⅰ-Ⅱ accounted for 68.0% in the surgury group and 18.8% in the medication group, P<0.01) as well as the grade of mitral valve regurgitation (87.5% of the patients in the medication group had moderate or above regurgitation at follow-up, while all the patients in the surgery group had moderate below regurgitation, P<0.01). There was no statistical difference in preoperative and follow-up changes in echocardiograph parameters between the two groups (P＞0.05). Conclusion For non-ischemic functional mitral regurgitation, if the cardiac systolic function is well reserved, mitral valve surgery can improve survival and quality of life compare to simple medication therapy.

OBJECTIVE To study the correlation between penetration enhancement effect and transepidermal water loss(TEWL)values of essential oils(EOs)from traditional Chinese medicine(TCM).METHODS The amount of 3 kinds of glycosides(geniposide,gentiopicroside,paeoniflorin)and their oil-water partition coefficient were determined by HPLC.The penetration enhancement effect of the five EOs from Gaoliangjiang(Alpiniae Officinarum Rhizoma,AOR),Ganjiang(Zingiberis Rhizoma,ZR),Bohe(Menthae Haploca-lycis Herba,MHH),Hujiao(Piperis Fructus,PF)and Wuzhuyu(Euodiae Fructus,EF)on geniposide,gentiopicroside,and paeoniflor-in were performed by the modified Franz diffusion cell method with the abdominal skin of rats.The TEWL values were measured to evalu-ate the effect of the five EOs on the skin barrier function of rats.The correlation between penetration enhancement effect of EOs and their effect on skin barrier function was investigated by correlation analysis.RESULTS AOR oil,ZR oil,MHH oil,and PF oil could im-prove the absorption of the three glycosides and reduce skin barrier function of rats.The results of correlation analysis showed that the penetration enhancement effect of EOs was significantly related to TEWL values following dermal administration of EOs.CONCLUSION TEWL measurement technology provides a more convenient method for the selection of penetration enhancers.

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.

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 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.

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 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.

ObjectiveTo observe the clinical efficacy and mechanism of Tongnao Yizhi Formula （通脑益智方， TYF） in treating vascular cognitive impairment no dementia （VCIND） with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome. MethodsNinety-two VCIND patients with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome were randomly divided into control group （42 cases） and treatment group （52 cases）. Both groups received routine basic treatment. The control group was given donapezil hydrochloride capsules orally， 5 mg each time， once at night， while the treatment group was given TYF orally， 1 dose per day. Both groups were treated continuously for 3 months. The scores of Mini-Mental State Examination （MMSE）， Vascular Dementia Assessment Scale-Cognitive Subscale （VaDAS-Cog）， Activity of Daily Living Scale （ADL）， and TCM syndrome scores （the primary symptoms such as sluggish thinking， forgetfulness， temperament changes， and language confusion， and secondary symptoms such as weakness of waist and knees， dizziness and headache， occasional tinnitus， fatigue， heaviness of limbs， insomnia and irritability， poor appetite and abdominal distension， numbness of face） were observed before and after treatment in both groups. The changes in gut microflora diversity and flora abundance structure as well as fecal short-chain fatty acids （SCFAs） levels including acetic acid， propionic acid， butyric acid， isobutyric acid， isovaleric acid， valeric acid， and caproic acid were compared between groups. The feces of 20 healthy subjects in the same period were included as reference. Safety was evaluated during the study. ResultsAfter treatment， both groups exhibited significant increases in MMSE scores and decreases in VaDAS-cog scores （P＜0.05 or P＜0.01）， and ADL scores in the treatment group significantly increased （P＜0.05）. Scores of symptoms including sluggish thinking， forgetfulness， temperament change， language confusion， heaviness of limbs， insomnia， irritability， poor appetite， abdominal distension， and facial numbness as well as the total score significantly decreased in both groups after treatment （P＜0.05 or P＜0.01）. When compared between groups， the treatment group showed substantial reductions in scores of weakness of waist and knees， tinnitus， fatigue， heaviness of limbs， insomnia， irritability， loss of appetite and abdominal distension （P＜0.05 or P＜0.01）. The gut microflora diversity analysis showed that the Shannon index of the treatment group significantly increased after treatment （P＜0.05）.PCoA analysis and ANOSIM test indicated significant differences between groups， suggesting changes in microflora species （P＜0.01）. After treatment， the relative abundance of Bacteroidetes and Fusobacteria in the treatment group increased， while the relative abundance of Actinobacteria， Verrucomicrobia and Cyanobacteria decreased （P＜0.05）； the relative abundance of Faecalibacterium prausnitzii， Bifidobacterium， Lactobacillus， and Ruminococcus increased significantly （P＜0.05）. Compared to the the gut microflora species diversity of the healthy people， it is indicated that the gut microflora structure in the treatment group was close to that of the healthy people， while there was no such trend in the control group. In the treatment group， acetic acid， propionic acid， and butyric acid in the treatment group were all higher after treatment （P＜0.05 or P＜0.01）. ConclusionsTYF can improve the cognitive ability and quality of life of VCIND patients with spleen and kidney depletion， phlegm and stasis obstructing collaterals syndrome， and this improvement may be related to regulating intestinal microecology.

Periodontology is one of the important disciplines in oral clinical medicine, which covers a wide range of subjects and intersects with many basic disciplines. Under the environment of the implementation of modular teaching in Shanghai Jiao Tong University School of Medicine, the assessment method with separate propositions for the teaching and research section is still adopted. There is a mismatch between the assessment mode and the curriculum setting; the basic subject propositions are difficult to be combined with clinical cases; the knowledge point assessment is single, and the students' ability to integrate the knowledge points cannot be assessed. The development and construction of the comprehensive examination database for periodontology was based on curriculum integration, gathering the teaching backbones of various disciplines, focusing on periodontology, radiating all related disciplines, unifying the proposition outline, proposition type, proposition principle, combining with relevant knowledge points of various disciplines based on clinical cases, and tried to apply to clinical students majoring in stomatology. The use of the examination database promotes students' ability to flexibly apply theoretical knowledge to clinical case analysis, further promotes the reform of modular teaching, lays a solid foundation for future clinical work, and meanwhile provides an important basis for directions of the teaching and research section.