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 observe the effect of electroacupuncture (EA) at different time points during the perioperative period on the recovery of gastrointestinal function after gastrointestinal malignant neoplasms surgery. Methods: Sixty-three patients who needed radical surgery for gastrointestinal tumors were randomized into a control group, treatment group 1 (postoperative EA group), and treatment group 2 (intraoperative and postoperative EA group). The control group received surgery and conventional Western medicine treatment, and treatment groups 1 and 2 received additional EA treatment at different time points. The initial flatus time after the surgery, visual analog scale (VAS) score at different time points after the surgery, the proportion of using patient-controlled analgesia (PCA) after the surgery, and the times of adding analgesics were observed in the three groups. Results: The initial flatus time after the surgery was earlier in treatment groups 1 and 2 than in the control group (P<0.05); the difference between treatment groups 1 and 2 was statistically insignificant (P>0.05). The VAS score was lower in treatment group 2 than in the control group at 6, 12, 24, and 72 h after the surgery (P<0.05); the VAS score was lower in treatment group 1 than in the control group only at 72 h after the surgery (P<0.05). There were no significant differences in the rate of using PCA among the three groups (P>0.05). Regarding the times of adding analgesics, it was less in treatment group 2 than in the control group at 12 h after the surgery (P<0.05). Conclusion: Either EA during and after the surgery or only after the surgery can hasten the initial flatus and boost the recovery of gastrointestinal function in patients after radical resection of gastrointestinal neoplasms. Successive EA during and after the surgery should be superior to postoperative EA regarding the analgesic effect after the surgery.

Objective To investigate the application of real-time gray-scale contrast enhanced ultrasound (CEUS)imaging in the diagnosis of fallopian tube obstruction.Methods Forty-six females with infertility in the period of 3-7 days after menses were inspected by transvaginal CEUS,and the transmission of contrast agents in the fallopian tubes was observed.Then they were inspected by routine iodic X-ray salpingography.Later the value of real-time gray-scale CEUS in diagnosis of fallopian tube was evaluated.Results The sensitivity of CEUS indiagnosis of fallopian tubal unobstruction,obstruction and open without freely was 92.0%,87.1%,36.4%respectively;the specificity was 85.7%,96.7%,93.7%;the accurate was 89.1%,93.5%,84.7%;the Kappa was 0.78,0.85,0.16 with X-ray salpingography.The concordance was 83.7% between CEUS and X-ray salpingography.Conclusions There were no significant difference between CEUS and X-ray salpingography in diagnosis of fallopian tube unobstruction or obstruction,and the former method is safer and more convenient that is suitable to become an valuable method in inspecting of infertility.