1.The molecular mechanism of liquidambaric acid inhibiting colorectal cancer by targeting TRAF6 to regulate Hippo/YAP signaling pathway
Wei-wei ZHAO ; Shi-cheng ZHENG ; Tian-yi ZHANG ; Jia-yu XIONG ; Yi QU ; Xi-song KE ; Rong YAN
Chinese Pharmacological Bulletin 2025;41(8):1463-1469
Aim To elucidate the molecular mecha-nism underlying the inhibitory effect of liquidambaric acid(LDA)targeting TNF receptor associated factor 6(TRAF6)in colorectal cancer.Methods This study employed microscale thermophoresis(MST),drug af-finity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)to confirm the direct binding of LDA to TRAF6.Additionally,we generated TRAF6 knockout colorectal cancer HCT116 cells using CRISPR/Cas9 technology,and assessed the impact of LDA on TRAF6-regulated Hippo/YAP and Wnt signaling pathways through immunofluorescence a-nalysis and TOPFlash/Renilla luciferase reporter sys-tem.Co-IP and proximity ligation assays(PLA)were conducted to investigate LDA-regulated TRAF6 pro-tein-protein interactions and elucidate molecular mech-anisms.Results The direct binding of LDA to TRAF6 was confirmed in cell lysates and living cells.LDA promoted TRAF6-dependent nuclear translocation of YAP in colorectal cancer cells,and inhibited Wnt signaling by overexpressing TRAF6.Co-IP and PLA revealed that TRAF6 formed a tripartite complex with YAP and β-catenin in colon cancer cells,where TRAF6 was a key scaffolding protein of the tripartite complex.LDA disrupted the interactions between the TRAF domain of TRAF6 and YAP,as well as YAP and β-catenin.Conclusion LDA regulates Hippo/YAP signaling pathway by targeting TRAF6 and inhib-its colorectal cancer.
2.Development of multifunctional vision examination device
Dong-chen YIN ; Yan ZHANG ; Yang WANG ; Li-hua YU ; Wei-ru SHI ; Rong-jia ZHANG
Chinese Medical Equipment Journal 2025;46(5):21-26
Objective To develop a multifunctional vision examination device for confined cabin environments to meet the requirements for detecting and collecting visual function parameters in military training and scientific research.Methods A multifunctional vision examination device was designed with a segmented mode and composed of an exmaination terminal and a control terminal.The examination terminal was composed of a sealed box,a high-definition display,an isolation baffle and a rubber eye mask.The sealed box had a fully closed structure,and the space design in the box was carried out in the form of integrating sphere;the high-definition display had a floating structure not rigidly connected with the surrounding components,and adopted a non-standard screen as the main display;the edges of the isolation baffle were sealed,and a spring washer for mechanical positioning was placed between the baffle and the sealed box.The control terminal software was programmed with C language,and there were several funcational modules involved in the software part for basic information management,function testing and summary report.Results Trials in the low-pressure chamber showed the device developed could be used for testing near vision,stereoscopic vision,contrast sensitivity,rapid dark adaptation and dark vision under the simulated altitude of 5 000 m when the examinee wore an oxygen mask,with remote operation enabled during the testing.Conclusion The multifunctional vision examination device gains advantages in light weight,high portability and compatibility with confined cabin environments,and meets the requirements for visual function testing in military training and scientific research.[Chinese Medical Equipment Journal,2025,46(5):21-26]
3.Molecular Mechanism of Premature Ovarian Insufficiency Mediated by Oxidative Stress-induced Granulosa Cell Damage
You TAN ; Shi-Yan SUI ; Bi-Rong ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(8):1137-1148
Premature ovarian insufficiency(POI),also known as premature ovarian failure(POF),is one of the major causes of female infertility.Its incidence has been increasing year by year,seriously af-fecting women's reproductive health and becoming an increasingly serious public health problem world-wide.The pathogenesis of POI is complex and may be related to genetic,immune and environmental fac-tors,but in recent years,oxidative stress(OS)has received widespread attention as a key factor that can affect the function of ovarian granulosa cells(GCs),which can lead to the occurrence of POI.Reactive oxygen species(ROS)regulate the proliferation,survival and apoptosis of GCs through multiple signaling pathways,such as PI3K-Akt,MAPK,TGF-β/Smad,Notch,etc.AMPK and mitochondrial autophagy play important roles in attenuating the ROS damage and protecting the ovarian function.Excessive ROS disrupts the autophagy and lysosomal functions,leading to the accumulation of intracellular waste prod-ucts,thus affecting the physiological function and endocrine stability of GCs.In addition,OS can in-crease the risk of POI by affecting hormone synthesis and disrupting the function of GCs,leading to an imbalance in estrogen and progesterone levels.Herein we review the mechanism of OS in POI,explore how OS affects ovarian decline through the regulation of signaling pathways and cellular functions,and provide a theoretical basis for the clinical treatment of POI,which in turn provides new research ideas for its early diagnosis and prevention.
4.Effect and mechanism of LINC00839 on the malignant biological behavior of endometrial cancer cells
Yuan-yuan SHI ; Fen TIAN ; Wei-yue ZHOU ; Mei-yan LI ; Jian-cai MA ; Ju-rong WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(1):21-27
Objective To investigate the effect of LINC00839 on the malignant biological behavior of endometrial cancer cells by regulating the miR-625-5p/cytoplasmic polyadenylation element binding protein 4 (CPEB4) axis. Methods The cancer tissues and adjacent tissues of 46 patients with endometrial cancer were obtained,endometrial cancer cells of HEC-1B,Ishikawa and RL95-2 and human endometrial epithelial cells (HEEC) were cultured in vitro,and the expression levels of LINC00839,miR-625-5p and CPEB4 in tissues and cells were detected. HEC-1B cells were divided into the HEC-1B group (conventional culture),sh-Ctrl group (transfected with sh-Ctrl),sh-LINC00839 group (transfected with shRNA-LINC00839),anti-miR-625-5p group (transfected with shRNA-LINC00839 and miR-625-5p inhibitor),and anti-NC group (transfected with shRNA-LINC00839 and inhibitor-NC). The proliferation,apoptosis,migration and invasion abilities of HEC-1B cells in each group were compared,and the expressions of CPEB4 and epithelial-mesenchymal transition (EMT) related proteins were determined. The targeting relationships between LINC00839 and miR-625-5p,and miR-625-5p and CPEB4 were analyzed. Results The mRNA expression of LINC00839 and CPEB4,as well as the positive expression rate of CPEB4 protein in endometrial cancer tissues were higher than those in adjacent tissues,and the expression of miR-625-5p was lower than that in adjacent tissues (P<0.05). Compared with HEEC cells,the expression of LINC00839 and the mRNA and protein expression of CPEB4 in Ishikawa,RL95-2 and HEC-1B cells increased (P<0.05),and the expression of miR-625-5p decreased (P<0.05). Compared with the sh-LINC00839 group and anti-NC group,the protein expression of N-cadherin,Vimentin,and CPEB4,24-hour absorbance,and migration and invasion cell numbers of HEC-1B cells in the HEC-1B group,sh-Ctrl group and anti-miR-625-5p group increased (P<0.05),while the expression of E-cadherin protein and cell apoptosis rate decreased (P<0.05). There were binding sites between LINC00839 and miR-625-5p,miR-625-5p and CPEB4,with targeting regulatory relationships. Conclusion LINC00839 is related to the malignant biological behavior of endometrial cancer cells,interference with LINC00839 expression can inhibit the proliferation,invasion and migration,and promote apoptosis of HEC-1B cells,and its mechanism may be achieved by regulating the miR-625-5p/CPEB4 axis.
5.Cost-effectiveness and mortality risk impact on elderly health management of essential public health services:A case study in Henan Province
Zhi-ping GUO ; Rong-mei LIU ; Neng-guang DAI ; Yi LI ; Tong JIN ; Qiu-ping ZHAO ; Hao SHI ; Chun-rong BAO ; Yan-qing MIAO
Chinese Journal of Health Policy 2025;18(11):17-24
Objective:To evaluate the cost-effectiveness and impact on mortality of health management services for the elderly aged 65 years and older in national essential public health service project.Methods:Based on the data of county-level medical institutions in Henan Province from 2019 to 2024,the Random Forest Method was used to construct a counterfactual framework to predict the hospitalization expenses under the unmanaged scenario,and then the cost-benefit ratio(BCR)and net income were calculated.Time-dependent Cox proportional hazards model was used to evaluate the effect of health management on all-cause mortality and cardiovascular and cerebrovascular disease mortality in the elderly.Results:A total of 962 955 elderly patients were included,451 119(46.85%)were included in the management group.The average hospitalization cost of the management group was significantly lower than that of the non-management group(P<0.05).Except for 2020-2021,BCRS in 2019 and 2022-2024 were 6.34,2.05,4.45 and 6.60,respectively.The risk of all-cause death was reduced by 76.96%,and the risk of cardiovascular and cerebrovascular death was reduced by 75.57%in the elderly patients included in the management group compared with those not included in the management group.Suggestions:It is necessary to establish a health outcomes-based evaluation system and promote the transformation and upgrading of the service model from single chronic disease management to"integrated health services with multi-disease management".
6.The molecular mechanism of liquidambaric acid inhibiting colorectal cancer by targeting TRAF6 to regulate Hippo/YAP signaling pathway
Wei-wei ZHAO ; Shi-cheng ZHENG ; Tian-yi ZHANG ; Jia-yu XIONG ; Yi QU ; Xi-song KE ; Rong YAN
Chinese Pharmacological Bulletin 2025;41(8):1463-1469
Aim To elucidate the molecular mecha-nism underlying the inhibitory effect of liquidambaric acid(LDA)targeting TNF receptor associated factor 6(TRAF6)in colorectal cancer.Methods This study employed microscale thermophoresis(MST),drug af-finity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)to confirm the direct binding of LDA to TRAF6.Additionally,we generated TRAF6 knockout colorectal cancer HCT116 cells using CRISPR/Cas9 technology,and assessed the impact of LDA on TRAF6-regulated Hippo/YAP and Wnt signaling pathways through immunofluorescence a-nalysis and TOPFlash/Renilla luciferase reporter sys-tem.Co-IP and proximity ligation assays(PLA)were conducted to investigate LDA-regulated TRAF6 pro-tein-protein interactions and elucidate molecular mech-anisms.Results The direct binding of LDA to TRAF6 was confirmed in cell lysates and living cells.LDA promoted TRAF6-dependent nuclear translocation of YAP in colorectal cancer cells,and inhibited Wnt signaling by overexpressing TRAF6.Co-IP and PLA revealed that TRAF6 formed a tripartite complex with YAP and β-catenin in colon cancer cells,where TRAF6 was a key scaffolding protein of the tripartite complex.LDA disrupted the interactions between the TRAF domain of TRAF6 and YAP,as well as YAP and β-catenin.Conclusion LDA regulates Hippo/YAP signaling pathway by targeting TRAF6 and inhib-its colorectal cancer.
7.Development of multifunctional vision examination device
Dong-chen YIN ; Yan ZHANG ; Yang WANG ; Li-hua YU ; Wei-ru SHI ; Rong-jia ZHANG
Chinese Medical Equipment Journal 2025;46(5):21-26
Objective To develop a multifunctional vision examination device for confined cabin environments to meet the requirements for detecting and collecting visual function parameters in military training and scientific research.Methods A multifunctional vision examination device was designed with a segmented mode and composed of an exmaination terminal and a control terminal.The examination terminal was composed of a sealed box,a high-definition display,an isolation baffle and a rubber eye mask.The sealed box had a fully closed structure,and the space design in the box was carried out in the form of integrating sphere;the high-definition display had a floating structure not rigidly connected with the surrounding components,and adopted a non-standard screen as the main display;the edges of the isolation baffle were sealed,and a spring washer for mechanical positioning was placed between the baffle and the sealed box.The control terminal software was programmed with C language,and there were several funcational modules involved in the software part for basic information management,function testing and summary report.Results Trials in the low-pressure chamber showed the device developed could be used for testing near vision,stereoscopic vision,contrast sensitivity,rapid dark adaptation and dark vision under the simulated altitude of 5 000 m when the examinee wore an oxygen mask,with remote operation enabled during the testing.Conclusion The multifunctional vision examination device gains advantages in light weight,high portability and compatibility with confined cabin environments,and meets the requirements for visual function testing in military training and scientific research.[Chinese Medical Equipment Journal,2025,46(5):21-26]
8.The study of 18F-fluorodeoxyglucose PET-CT dual-modality habitat imaging in predicting epidermal growth factor receptor mutation status of lung adenocarcinoma
Rong NIU ; Jinbao FENG ; Jianxiong GAO ; Xinyu GE ; Yan SUN ; Yunmei SHI ; Yuetao WANG ; Xiaonan SHAO
Chinese Journal of Radiology 2025;59(4):409-417
Objective:To explore the value of 18F-fluorodeoxyglucose ( 18F-FDG) PET-CT dual-modality habitat imaging technology in predicting the epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma. Methods:This study was designed as a cross-sectional study. Clinical and imaging data of 403 patients with lung adenocarcinoma who underwent 18F-FDG PET-CT imaging with definitive EGFR results from January 2018 to April 2022 at the Third Affiliated Hospital of Soochow University were retrospectively analyzed.The patients were divided into a development set (282 cases) and a validation set (121 cases) using a stratified random sampling method at a 7∶3 ratio. An adaptive clustering algorithm was used to segment the regions of interest, forming different habitats and obtaining derived parameters. Independent samples t-test or Mann-Whitney U test were used to compare clinical, imaging indicators, and habitat-derived parameters between EGFR mutant and wild-type patient. The clinical, imaging indicators, and habitat-derived parameters that showed statistically significant differences in univariate analysis were included in multivariate logistic regression to construct clinical and clinical-habitat combined models, respectively. The receiver operating characteristic curve and area under the curve (AUC) were used to evaluate the model′s ability to predict EGFR mutations in lung adenocarcinoma. Additionally, the net reclassification index (NRI) was employed to assess the model′s classification improvement capability. Results:There were 249 cases of EGFR mutation and 154 cases of wild type. The optimal number of habitats was two, namely Habitat 1 and Habitat 2. The parameters included in the clinical model were smoking history, bronchial sign, pleural indentation sign, and tumor diameter. The parameters incorporated into the clinical-habitat combined model were smoking history, bronchial sign, pleural indentation sign, Habitat 2, and Habitat 1 voxel count. In the development set, the AUCs for predicting EGFR mutations in lung adenocarcinoma using the clinical model and the clinical-habitat combined model were 0.723 and 0.733, respectively, with no statistically significant difference ( Z=0.60, P=0.549); In the validation set, the AUCs were 0.684 and 0.715, respectively, with no statistically significant difference ( Z=1.32, P=0.186). The accuracy (0.694) and specificity (0.609) of the clinical-habitat combined model in the validation set were slightly higher than those of the clinical model (0.686 and 0.565, respectively). NRI analysis confirmed that the clinical-habitat combined model improved the correct classification of EGFR wild-type lung adenocarcinoma by 10.9% compared to the clinical model ( P=0.018). Conclusion:18F-FDG PET-CT dual-modality habitat imaging technology can be used to analyze the microenvironment of lung adenocarcinoma and has the potential in non-invasively predicting EGFR mutation status, providing an important basis for personalized and accurate treatment of patients with lung adenocarcinoma.
9.Value of serum free light chain in the prognosis evaluation of patients with chronic lymphocytic leukemia
Hui WANG ; Rong WANG ; Erfu XIE ; Xiaojiao SHI ; Lei FAN ; Chun QIAO ; Hairong QIU ; Yan WANG
Chinese Journal of Laboratory Medicine 2025;48(1):142-148
Objective:To explore the prognostic value of serum free light chain in chronic lymphocytic leukemia patients.Methods:Retrospective cohort study was conducted. One hundred and fifty-six newly diagnosed chronic lymphocytic leukemia(CLL) patients in the first affiliated hospital of Nanjing Medical University from January 2016 to December 2020 were included in the retrospective analysis. Among them, there were 106 males and 50 females, with a median age of 60.7 (53.4, 66.0) years old.Serum sample was collected, serum free light chains were detected, and patients were divided into a treatment group (106 cases) and a follow-up group (50 cases) based on the presence of treatment indications.The threshold of serum free light chain(sFLC) was defined by the reference range of the instruction manual and ROC curve. Three indicators were used, including sFLCR, sFLC(κ+λ) and sFLC(κ-λ). Patients were divided into normal sFLCR group ( n=61)and abnormal group( n=95), as well as sFLC (κ+λ) low value group ( n=88) and high value group ( n=68), and sFLC (κ-λ) low value group ( n=64) and high value group ( n=92).The abnormal group and high value group were enrolled as the experimental group, while the normal group and low value group were enrolled as control group. Chi-square test and Fisher′s exact test were used to compare the clinical data, cytogenetics, and molecular biology characteristics of patients in two groups, Kaplan-Meier method was used to analyze the median treatment-free survival (TFS) of the patients, and Cox regression was used to screen the prognostic factors of the patients. Results:The proportion of Rai stage Ⅰ-Ⅳ ( χ2=8.16, P<0.05 and χ2=7.63, P<0.05 and χ2=5.45, P<0.05), Binet stage B-C( χ2=4.11, P<0.05 and χ2=9.43, P<0.05 and χ2=7.34, P<0.05), β 2-microglobulin>3.5 mg/L( χ2=5.13, P<0.05 and χ2=18.3, P<0.05 and χ2=12, P<0.05), ATM gene mutation rate( χ2=6.21, P<0.05 and χ2=4.88, P<0.05 and χ2=5.19, P<0.05), and immunoglobulin heavy chain variable region (IGHV) mutation free rate ( χ2=18.9, P<0.05 and χ2=24.6, P<0.05 and χ2=10.4, P<0.05)in the experimental group were significantly higher than that in control group 1 ( P<0.05). Multivariate analysis indicated that sFLC(κ+λ) ( HR=1.615,95% CI 1.012-2.576, P=0.044), β 2-microglobulin>3.5 mg/L( HR=2.103,95% CI 1.356-3.262, P=0.001) and TP53 deletion and/or mutation( HR=1.892,95% CI 1.082-3.308, P=0.025) were independent prognostic factors affecting the patients time to first treatment(TFT). Conclusions:Serum free light chains can predict the risk of early treatment and have good prognostic significance in newly diagnosed CLL patients.
10.Molecular Mechanism of Premature Ovarian Insufficiency Mediated by Oxidative Stress-induced Granulosa Cell Damage
You TAN ; Shi-Yan SUI ; Bi-Rong ZHANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(8):1137-1148
Premature ovarian insufficiency(POI),also known as premature ovarian failure(POF),is one of the major causes of female infertility.Its incidence has been increasing year by year,seriously af-fecting women's reproductive health and becoming an increasingly serious public health problem world-wide.The pathogenesis of POI is complex and may be related to genetic,immune and environmental fac-tors,but in recent years,oxidative stress(OS)has received widespread attention as a key factor that can affect the function of ovarian granulosa cells(GCs),which can lead to the occurrence of POI.Reactive oxygen species(ROS)regulate the proliferation,survival and apoptosis of GCs through multiple signaling pathways,such as PI3K-Akt,MAPK,TGF-β/Smad,Notch,etc.AMPK and mitochondrial autophagy play important roles in attenuating the ROS damage and protecting the ovarian function.Excessive ROS disrupts the autophagy and lysosomal functions,leading to the accumulation of intracellular waste prod-ucts,thus affecting the physiological function and endocrine stability of GCs.In addition,OS can in-crease the risk of POI by affecting hormone synthesis and disrupting the function of GCs,leading to an imbalance in estrogen and progesterone levels.Herein we review the mechanism of OS in POI,explore how OS affects ovarian decline through the regulation of signaling pathways and cellular functions,and provide a theoretical basis for the clinical treatment of POI,which in turn provides new research ideas for its early diagnosis and prevention.

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