OBJECTIVE To investigate the effects and potential mechanism of persimmon leaf （PL） extract against ferroptosis induced by H2O2 in IEC-6 cells. METHODS Using IEC-6 cells as object， the effects of ferroptosis inhibitor ferrostatin-1 on IEC-6 cell viability induced by H2O2 were investigated； IEC-6 cells were divided into control group， H2O2 group， H2O2+PL 25 μg/mL group and H2O2+PL 50 μg/mL group. The levels of oxidant stress indexes [content of malondialdehyde （MDA）， activity of superoxide dismutase （SOD）， and levels of reactive oxygen species （ROS）]， mitochondrial membrane potential （MMP） as well as mRNA and protein expressions of nuclear factor-erythroid-2 related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， NADPH/quinone oxidoreductase-1 （NQO-1）， cystine/glutamate anti-porter （xCT）， glutathione peroxidase 4 （GPX4） and ferritin heavy chain （FTH） were detected. RESULTS Ferroptosis inhibitor ferrostatin-1 could significantly increase the survival rate of H2O2-induced cells （P＜ 0.01）. Compared with the control group， MDA content， ROS level， mRNA expressions of Nrf2 and NQO-1 as well as protein expressions of Nrf2 and HO-1 were increased or up-regulated significantly， while SOD activity， MMP， mRNA expressions of xCT， GPX4 and FTH as well as protein expressions of GPX4 and FTH were decreased or down-regulated significantly （P＜0.01 or P＜0.05）. Compared with the H2O2 group， oxidative stress Δ indexes of H2O2+PL 25， 50 μg/mL groups were reversed to different extents， MMP level was increased significantly， as well as mRNA and protein expressions of Nrf2， HO-1， NQO-1，xCT， GPX4 and FTH were up-regulated to different extents；there were statistical significances in some indexes between groups （P＜0.01 or P＜0.05）. CONCLUSIONS PL extract can alleviate mitochondrial membrane damage and abnormal accumulation of ROS caused by H2O2， which may be related to the inhibition of ferroptosis by activating the Nrf2/HO-1 signaling pathway.

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 explore the effects of CDP-diacylglycerol synthase 1(CDS1)on autophagy and amyloid deposition in hippocampal neurons of mice and the related mechanism.Methods Congo red and immunohistochemical staining were used to observe the amyloid deposition in hippocampus of amyloid precursor protein(APP)/presenilin 1(PS1)double-transgenic mice.Lentivirus-mediated overexpression of APP was induced in HT22 cells,and Congo red staining was used to observe the amyloid deposition in HT22 cells.The protein expression levels of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ and P62 in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were detected by Western blotting.The differential protein CDS1 was screened based on the hippocampal proteomics results of APP/PS1 double-transgenic mice.The expression of CDS1 protein in hippocampal tissue of APP/PS1 transgenic mice and APP-overexpressed HT22 cells was detected by Western blotting.After lentivirus-mediated APP overexpression in HT22 cells,CDS1 was overexpressed,and the protein expression levels of LC3-Ⅱ and P62 were detected by Western blotting.Results β-amyloid protein(Aβ)was deposited in the hippocampus of APP/PS1 mice and in HT22 cells overexpressing APP.The levels of LC3-Ⅱ and P62 protein in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were significantly increased.A differential metabolic pathway,glycerophospholipid metabolic pathway,was screened by Kyoto Encyclopedia of Genes and Genomes pathway analysis in the proteomic results of APP/PS1 double-transgenic mice,and the differential protein CDS1 was obtained.Compared with wild-type C57BL/6 mice,APP/PS1 double-transgenic mice exhibited a significantly decrease in CDS1 protein expression in the hippocampus(0.46±0.07 vs 1.00±0.25,P＜0.01).Similarly,lentivirus-mediated overexpression of APP in HT22 cells resulted in decreased CDS1 protein levels compared to cells infected with empty viral vector controls(0.68±0.18 vs 1.00±0.13,P＜0.01).The autophagy flow of nerve cells was significantly restored after the CDS1 overexpression in APP-overexpressed HT22 cells(LC3-Ⅱ:1.00±0.15 vs 0.21±0.05,P＜0.01;P62:1.00±0.16 vs 0.67±0.10,P＜0.01),and Aβ deposition was significantly decreased.Conclusion Downregulation of CDS1 expression can induce dysfusion of autophagosome and lysosome,promoting amyloid deposition in hippocampus of mice with Alzheimer's disease.

Objective:To analyze the current status of clinical trials of Chinese materia medica for the purpose of registration in China; To provide reference for the research and development of new TCM drugs.Methods:Clinical trials of Chinese materia medica/natural medicine registered in Drug Clinical Trial Registration and Information Disclosure Platform were retrieved from inception to December 31, 2024. Excel 2019 software was used to input and analyze the data such as the number of registered clinical trials, date of first publication, study status, field of indication, trial phases, sponsors, group leader, and design types.Results:A total of 1 137 Chinese materia medica clinical trials had been registered, accounting for 4.12% of the total number registered on the platform. Phase Ⅱ clinical trials accounted for the highest proportion (58.8%), and 99.7% of clinical trials conducted domestically. The sponsors were predominantly domestically pharmaceutical enterprises. These 1 137 clinical trials of Chinese materia medica clinical trials involved 752 drug categories, 28 dosage forms, and 796 varieties (the same class of drugs had different drug dosage forms), with capsules being the most common. The indications primarily focused on respiratory, digestive, cardio-cerebrovascular, neuropsychiatric, gynecological diseases. The group leader of clinical trials was distributed in 28 provinces, among which the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine as the group leader, undertook the most clinical trials of TCM. 89.9% of the clinical trials adopted the randomized controlled trial design, and only 31.9% of the clinical trials purchased insurance for the subjects.Conclusion:The research and development of new TCM drugs has entered a phase of vigorous development. Further efforts are still needed in establishing systematic guidelines for Chinese materia medica clinical trials, accelerating the internationalization of TCM, exploring innovative dosage forms and indications, and strengthening the protection of participants' rights.

Objective:To systematically review and integrate the caring experience of caregivers of lung transplant patients.Methods:Qualitative studies on the caregiving experience of caregivers of lung transplant patients were searched by computer from PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disc, China National Knowledge Infrastructure and Wanfang data, and the search period was from establishment of the databases to April 30, 2023. The qualitative research quality evaluation criteria (2016 edition) of the Joanna Briggs Institute Evidence Based Health Care Center in Australia were used to evaluate the quality of the included literature, and the Meta-synthesis was used to integrate the literature results.Results:A total of ten articles were included, and 33 clear research results were extracted, which were summarized into eight new categories, and finally summarized into four integrated results, such as heavy burden experience, strong demand, positive experience and satisfaction with the medical service system.Conclusions:Medical workers should attach importance to and pay attention to the burden and needs of caregivers of lung transplant patients, provide professional and emotional support to caregivers, improve their caring ability and quality, and ultimately improve the quality of life of lung transplant patients.

ObjectiveTo investigate the effect of supplemented Buyang Huanwutang on kidney tissue， nuclear factor-κB （NF-κB） pathway， and fibrosis factors in diabetic kidney disease （DKD） mice. MethodA total of 24 db/db mice （11-12 weeks old） were randomized into the model group （equivalent volume of distilled water， once/day， 8 weeks）， supplemented Buyang Huanwutang group （16.0 g·kg^-1， once/day， 8 weeks）， and irbesartan group （13.5 mg·kg^-1， once/day， 8 weeks） after adaptive feeding for 1 week and positive urinary protein monitoring， with 8 in each group. Another 8 db/m mice （11-12 weeks old） were included in the normal group （equivalent volume of distilled water， once/day， 8 weeks）. Then samples were collected， and the levels of fasting blood glucose （FBG）， total cholesterol （TC）， triglyceride （TG）， blood urea nitrogen （BUN）， serum creatinine （SCr）， and urinary microalbumin （mALB） were detected. The mRNA expression of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and monocyte chemoattractant protein-1 （MCP-1） was determined by real-time polymerase chain reaction （Real-time PCR）. The expression of nuclear factor-κB （NF-κB）， NF-κB inhibitor α （IκBα）， phosphorylated IκBα （p-IκBα）， transforming growth factor-β₁ （TGF-β₁）， α-smooth muscle actin （α-SMA）， and fibronectin （FN） in kidney tissue was measured by Western blot. The expression of NF-κB in renal tissue was detected by immunofluorescence. The pathological changes of kidney were observed under light microscope. ResultCompared with the normal group， the model group showed glomerular hypertrophy， increase in extracellular matrix， thickening of basement membrane， small cystic lumen， interstitial inflammatory cell infiltration， and some interstitial fibrosis （P<0.01）. Moreover， the model group had higher content of FBG， mALB， TC， TG， BUN， and SCr （P<0.01）， higher expression of inflammatory factors TNF-α， IL-1β， and MCP-1， and fibrosis-related proteins TGF-β₁， α-SMA， and FN （P<0.01）， and stronger activation of NF-κB pathway in renal tissue （P<0.01） than the normal group. Compared with the model group， supplemented Buyang Huanwutang alleviated the pathological injury in kidney （P<0.01）， decreased the content of mALB， TC， and TG， the content of BUN and SCr （P<0.01）， and the content of TNF-α， IL-1β， and MCP-1 （P<0.05， P<0.01）， and inhibited the activation of NF-κB pathway and the expression of fibrosis factors in renal tissue （P<0.05， P<0.01）， but had no significant effect on blood glucose level. ConclusionBy inhibiting NF-κB pathway and the expression of fibrosis factors in renal tissue， supplemented Buyang Huanwutang can exert anti-inflammatory and anti-fibrosis effect and alleviate the pathological damage in kidney tissue， thereby protecting the kidney.

Objective:To explore the independent risk factors of poor healing of surgical incisions in patients with drainage tube removal after thoracic and abdominal surgery and establish a risk prediction model for poor healing of surgical incisions.Methods:Using the convenient sampling method, a total of 545 patients who underwent thoracic and abdominal surgery in the Affiliated Hospital of Qingdao University were selected from July to December 2020. The patients were divided into the poor wound healing group ( n=87) and the non-incision poor healing group ( n=458) according to whether they had poor wound healing. Logistic regression analysis was used to analyze the risk factors of poor healing of surgical incisions and build a risk prediction model. The receiver operating characteristic (ROC) area under the curve was used to test the model to predict the effect and 230 patients were selected to verify the model prediction effect. Results:In this study, 5 factors including duration of exudation, serum albumin, incision infection, the volume of exudation during catheterization and catheterization time were finally included to construct a risk prediction model. The model formula was Z=4.608+4.855× duration of exudation +3.173× serum albumin +3.739× infection of the incision +2.271×the volume of exudation during catheterization + 0.466× catheterization time. The area under ROC curve of this model was 0.773 (95% CI: 0.678 - 0.868). The maximum value of Youden index was 0.549, the sensitivity was 0.742 and the specificity was 0.807. Conclusions:The risk prediction model of poor incision healing after drainage tube removal for patients undergoing thoracic and abdominal surgery can better predict the risk of poor incision healing and provide a basis for clinical medical staff to take preventive management measures for high-risk patients in time.

Objective To investigate the clinical effect of percutaneous transhepatic drainage combined with sequential percutaneous nephroscopy for necrosectomy and drainage in the treatment of refractory liver abscess after transcatheter arterial embolization (TACE). Methods A retrospective analysis was performed for three patients with refractory liver abscess after TACE in The Affiliated 3201 Hospital of Xi'an Jiaotong University School of Medicine from January 2018 to December 2020, and among the three patients, one had the formation of liver abscess after TACE for hepatic metastases after pancreaticoduodenectomy, one had liver abscess after repeated TACE for massive hepatocellular carcinoma, and one had secondary liver abscess after TACE for traumatic hepatic rupture. All three patients received percutaneous transhepatic drainage and sequential percutaneous nephroscopy for the treatment of refractory liver abscess, and their specific treatment process was summarized. Results All three patients were diagnosed with refractory liver abscess based on CT, routine blood test, procalcitonin, blood culture, and clinical manifestation. Percutaneous transhepatic catheterization under the guidance of conventional ultrasonography or CT and effective antibiotics had an unsatisfactory therapeutic effect, and after sequential percutaneous nephroscopy was performed for necrosectomy and drainage, liver abscess was cured and the patients had good prognosis. Conclusion For refractory liver abscess after TACE, when routine puncture treatment has an unsatisfactory therapeutic effect or a patient cannot tolerate surgical operation, percutaneous transhepatic drainage combined with sequential percutaneous nephroscopy is safe and effective in the treatment of refractory liver abscess.

Objective To investigate the clinical effect of two-step percutaneous transhepatic choledochoscopic lithotomy (PTCSL) in the treatment of complex hepatolithiasis. Methods A retrospective analysis was performed for the clinical data of 118 patients with complex hepatolithiasis who were admitted to 3201 Hospital of Xi'an Jiaotong University Health Science Center from January 2018 to June 2020, and according to the surgical procedure, they were divided into PTCSL group with 60 patients and surgery group with 58 patients. All patients were followed up for half a year to 3 years via telephone and outpatient service. The two groups were compared in terms of general information, perioperative indicators (including time of operation, intraoperative blood loss, incision length, time to first flatus and time to first defecation after surgery, time to extraction of abdominal drainage tube, and length of hospital stay), changes in liver function and inflammatory indicators, postoperative complications (bile leakage, acute cholangitis, wound infection, and venous thrombosis of lower extremities), stone clearance rate and recurrence rate, and quality of life. The two-independent-samples t -test was used for comparison of continuous data between two groups; the paired t -test was used for comparison between different periods of time within group; the chi-square test was used for comparison of categorical data between two groups. Results Compared with the surgery group, the PTCSL group had significantly shorter time of operation, time to first flatus and time to first defecation after surgery, and time to extraction of abdominal drainage tube, a significantly lower intraoperative blood loss, and a significantly shorter incision length (all P < 0.05). On day 1 after surgery, both groups had significant reductions in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ( P < 0.05) and a significant increase in white blood cell count (WBC) ( P < 0.05), and the PTCSL group had significantly lower levels of ALT, AST, and WBC than the surgery group (all P < 0.05). Compared with the surgery group, the PTCSL group had significantly lower incidence rates of postoperative bile leakage (5.0% vs 17.2%, P < 0.05), acute cholangitis (3.3% vs 13.8%, P < 0.05), wound infection (1.7% vs 10.3%, P < 0.05), and venous thrombosis of lower extremities (1.7% vs 12.1%, P < 0.05). Compared with the surgery group, the PTCSL group had a significantly higher stone clearance rate (58.3% vs 37.9%, P < 0.05) and a significantly lower long-term stone recurrence rate (10.0% vs 20.7%, P < 0.05). The PTCSL group had significantly higher quality of life scores than the surgery group (all P < 0.05). Conclusion For the treatment of complex hepatolithiasis, two-step PTCSL can effectively remove stones, with the advantages of fast postoperative recovery, low recurrence rate and incidence rate of complications, and high quality of life, and therefore, it is an effective alternative surgical procedure.