1.Role and Mechanism of Cucurbitacin B in Suppressing Proliferation of Breast Cancer 4T1 Cells via Inducing Ferroptosis
Yidan RUAN ; Huizhong ZHANG ; Huating HUANG ; Pingzhi ZHANG ; Aina YAO ; Yongqiang ZHANG ; Xiaohan XU ; Shiman LI ; Jian NI ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):91-97
ObjectiveTo explore the role of cucurbitacin B (CuB) in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB(0.2, 0.4, 0.8 μmol·L-1)on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium (MTT) assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay, and the levels of lactate dehydrogenase (LDH) in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species (ROS) levels in 4T1 cells were detected by flow cytometry, and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells, solute carrier family 7 member 11 (SCL7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), transferrin receptor protein 1 (TFR1), and ferritin heavy chain 1 (FTH1). ResultsCompared with that in the blank group, the survival rate of 4T1 cells in CuB groups was significantly decreased (P<0.05), and the number of cell clones in CuB groups was significantly reduced (P<0.01). In addition, compared with that in the blank group, the leakage of LDH in cells in CuB groups was significantly increased (P<0.01), and the mitochondrial membrane potential of cells in CuB groups decreased significantly (P<0.01). Cellular ROS levels were significantly elevated in CuB groups (P<0.01). The mitochondria of cells in CuB groups were obviously wrinkled, and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group, the protein expression of p53, ACSL4, and TFR1 were significantly up-regulated in CuB groups (P<0.05), and that of SLC7A11, GPX4, and FTH1 were significantly down-regulated (P<0.05). ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53, which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe3+ and down-regulates the expression of FTH1 to reduce the ability of iron storage, resulting in an elevated free Fe2+ level. It catalyzes the Fenton reaction, generates excess ROS, imbalances the antioxidant system and iron metabolism, and then induces ferroptosis in 4T1 cells.
2.Role and Mechanism of Cucurbitacin B in Suppressing Proliferation of Breast Cancer 4T1 Cells via Inducing Ferroptosis
Yidan RUAN ; Huizhong ZHANG ; Huating HUANG ; Pingzhi ZHANG ; Aina YAO ; Yongqiang ZHANG ; Xiaohan XU ; Shiman LI ; Jian NI ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):91-97
ObjectiveTo explore the role of cucurbitacin B (CuB) in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB(0.2, 0.4, 0.8 μmol·L-1)on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium (MTT) assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay, and the levels of lactate dehydrogenase (LDH) in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species (ROS) levels in 4T1 cells were detected by flow cytometry, and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells, solute carrier family 7 member 11 (SCL7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), transferrin receptor protein 1 (TFR1), and ferritin heavy chain 1 (FTH1). ResultsCompared with that in the blank group, the survival rate of 4T1 cells in CuB groups was significantly decreased (P<0.05), and the number of cell clones in CuB groups was significantly reduced (P<0.01). In addition, compared with that in the blank group, the leakage of LDH in cells in CuB groups was significantly increased (P<0.01), and the mitochondrial membrane potential of cells in CuB groups decreased significantly (P<0.01). Cellular ROS levels were significantly elevated in CuB groups (P<0.01). The mitochondria of cells in CuB groups were obviously wrinkled, and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group, the protein expression of p53, ACSL4, and TFR1 were significantly up-regulated in CuB groups (P<0.05), and that of SLC7A11, GPX4, and FTH1 were significantly down-regulated (P<0.05). ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53, which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe3+ and down-regulates the expression of FTH1 to reduce the ability of iron storage, resulting in an elevated free Fe2+ level. It catalyzes the Fenton reaction, generates excess ROS, imbalances the antioxidant system and iron metabolism, and then induces ferroptosis in 4T1 cells.
3.Research on Difficulties and Strategies for the Use and Management of Medical Insurance Funds from the Perspective of Hospital
Ning DING ; Yidan ZHANG ; Jiahong XIA ; Ming ZHANG ; Dong XU
Chinese Hospital Management 2024;44(8):68-71
It provides a concise overview of the special rectification and daily supervision policies and measures of medical insurance since the establishment of the National Healthcare Security Administration,studies changes in medical insurance supervision fields,supervision methods,and supervision contents,and focuses on analyzing the impact of new changes in medical insurance supervision on the internal management of hospitals.Based on the practice of Union Hospital of Tongji Medical College of Huazhong University of Science and Technology,it introduces the hospital from the key areas,key departments and key mechanisms to actively respond to the above new changes in supervision,standardize the use of medical insurance fund internal management measures and their effectiveness.
4.Analysis of Research Status on Performance Assessment of Tertiary Public Hospitals Based on VOSviewer
Li WEI ; Huihui CHEN ; Jiahong XIA ; Yi-Xiang PENG ; Dong XU ; Ming ZHANG ; Ning DING ; Yidan ZHANG ; Wen CHEN ; Chang'e XIONG
Chinese Hospital Management 2024;44(9):1-4
Objective To analyze the current research status and hotspot issues of performance assessment in tertia-ry public hospitals in China,providing reference for subsequent research and practice.Methods Using"performance assessment of tertiary public hospitals"as the main keyword,a total of 520 articles were retrieved from the CNKI ac-ademic journal database from January 30,2019,to January 30,2024.After further screening of literature based on the inclusion and exclusion criteria,a total of 364 eligible articles were obtained.Visual analysis was conducted using the VOSviewer tool.Results The number of publications increased annually from 2019 to 2021,with a decline ob-served in 2022-2023."Chinese Journal of Health"published the most articles on performance assessment in tertiary public hospitals.Research institutions mainly focused on universities,health administrative departments,and hospi-tals.The hotspot clusters of research included performance assessment,public hospitals,target management,high-quality development,tertiary hospitals,and operational efficiency.Conclusion Performance assessment in tertia-ry public hospitals has received widespread attention,with rich connotations and obvious guiding effects,but further research is needed to deepen and explore related topics.
5.SWOT Analysis on the Sustainable Development of Internal Medicine Specialties under the Background of Performance Evaluation in Tertiary Public Hospital
Yidan ZHANG ; Yu HU ; Yixiang PENG ; Ming ZHANG ; Li WEI ; Ning DING ; Wen CHEN ; Dong XU
Chinese Hospital Management 2024;44(9):9-12
The performance evaluation of tertiary public hospitals aims to strengthen functional positioning,and the weight of indicators such as the proportion of surgery is relatively high in the evaluation indicators.In this con-text,some tertiary comprehensive hospitals with a high proportion of internal medicine business are facing significant challenges in sustained development.It comprehensively reviews the impact of performance evaluation indicators on the direction of internal medicine specialties,and uses SWOT analysis tools to condense the sustainable develop-ment path of tertiary public hospitals.This includes growth strategies(improving the ability to treat difficult and criti-cal diseases,undertaking scientific and educational tasks),transformational strategies(technological innovation,price approval),multiple business strategies(adjusting outpatient and inpatient structures,building specialized disease centers,etc.),and defensive strategies(reasonable diagnosis and treatment,clinical pathways),inorder to provide reference for hospital managers.
6.Research on Multi-Hospital District Homogenization Management based on Three-Level Public Hospital Performance Appraisal System
Ning DING ; Dong XU ; Ming ZHANG ; Shaoying ZENG ; Yidan ZHANG ; Li WEI ; Wen CHEN ; Yixiang PENG
Chinese Hospital Management 2024;44(9):19-22
Objective To analyze the problems existing in the homogenization management of multi-branch hospitals based on the annual performance assessment data,and provide reference for promoting the high-quality development of public hospital branch districts.Methods Based on the Performance Assessment Operation Manual of National Tertiary Public Hospitals(2022 edition),10 indicators including the proportion of discharged patients undergoing surgery and the proportion of fourth-level surgery were screened,and the functional positioning,quality and safety,revenue and expenditure structure,and cost control of 4 hospitals of a certain medical institution from 2022 to 2023 were descriptively analyzed.Results The CMI value and the proportion of discharged surgery in the main hospital were significantly better than those in the branch hospitals,and there was no significant difference in the medical quality indicators of the four hospitals,and the operation efficiency of the branch hospital with outstanding specialty characteristics was better than that of other hospitals.Conclusion Public hospitals pay more attention to the"big specialty,small comprehensive"mode in the layout of branch districts,pay more attention to the quality control management at the specialty level in medical quality management,and strengthen the benefit analysis of different hospitals in the same specialty in operation management.
7.Study on the Mechanism of the Flavonoids from the New
Liang GAO ; Yalin ZHANG ; Yuhan WU ; Jiahui SHAO ; Hui ZHANG ; Yidan SHAO ; Yaping XU ; Jianping JIANG
Chinese Journal of Modern Applied Pharmacy 2024;41(2):166-176
OBJECTIVE
To explore the mechanisms of the flavonoids from new "Zhe Eight Flavors" Quzhou Fructus Aurantii(PTFC) against hepatocellular carcinoma based on the prediction of network pharmacology and experimental verification.
METHODS
From TCMSP, TCMID, ETCM, BATMAN-TCM and SwissTargetPrediction databases, the potential target proteins of PTFC, including naringin, narirutin and neohesperidin were collected. Based on the GeneCards, CTD, Disgenet, and OMIM databases, a set of target proteins for hepatocellular carcinoma was constructed. Taking the intersection of potential target proteins of PTFC and target proteins of hepatocellular carcinoma, key target proteins were obtained and a protein-protein interaction network was established. Besides, GO function and KEGG pathway enrichment analysis on the core target proteins was performed and a Compounds-Targets-Pathways-Disease network was constructed. Through proliferation, cloning, wound healing, and migration experiments, the effects of PTFC on the viability of HepG2 liver cancer cells were analyzed. Using fluorescence probe staining the impacts of PTFC on the mitochondrial membrane potential and apoptosis of HepG2 were observed. Finally, the validation of the regulatory effect of PTFC on the key predicted target PRKCA were carried out through RT-qPCR.
RESULTS
Based on network pharmacology, a total of 217 potential target proteins for PTFC were screened, with 59 intersecting target proteins related to diseases, including ALB, ESR1, PRKCA, and others. GO functional and KEGG pathway enrichment analysis revealed that the PTFC target proteins were involved in 193 biological processes and 13 cancer-related signaling pathways. Experimental results demonstrated that PTFC could impact the proliferation, cloning, wound healing, and migration abilities of liver cancer cells, leading to a decrease in mitochondrial membrane potential and promoting cell apoptosis. The results of RT-qPCR confirmed a significant downregulation of PRKCA expression by PTFC, validating the predictions made by network pharmacology analysis.
CONCLUSION
This study has revealed the potential molecular mechanism of PTFC treating hepatocellular carcinoma via the PRKCA target, laying the foundation for clinical application of PTFC.
8.Research on Difficulties and Strategies for the Use and Management of Medical Insurance Funds from the Perspective of Hospital
Ning DING ; Yidan ZHANG ; Jiahong XIA ; Ming ZHANG ; Dong XU
Chinese Hospital Management 2024;44(8):68-71
It provides a concise overview of the special rectification and daily supervision policies and measures of medical insurance since the establishment of the National Healthcare Security Administration,studies changes in medical insurance supervision fields,supervision methods,and supervision contents,and focuses on analyzing the impact of new changes in medical insurance supervision on the internal management of hospitals.Based on the practice of Union Hospital of Tongji Medical College of Huazhong University of Science and Technology,it introduces the hospital from the key areas,key departments and key mechanisms to actively respond to the above new changes in supervision,standardize the use of medical insurance fund internal management measures and their effectiveness.
9.Analysis of Research Status on Performance Assessment of Tertiary Public Hospitals Based on VOSviewer
Li WEI ; Huihui CHEN ; Jiahong XIA ; Yi-Xiang PENG ; Dong XU ; Ming ZHANG ; Ning DING ; Yidan ZHANG ; Wen CHEN ; Chang'e XIONG
Chinese Hospital Management 2024;44(9):1-4
Objective To analyze the current research status and hotspot issues of performance assessment in tertia-ry public hospitals in China,providing reference for subsequent research and practice.Methods Using"performance assessment of tertiary public hospitals"as the main keyword,a total of 520 articles were retrieved from the CNKI ac-ademic journal database from January 30,2019,to January 30,2024.After further screening of literature based on the inclusion and exclusion criteria,a total of 364 eligible articles were obtained.Visual analysis was conducted using the VOSviewer tool.Results The number of publications increased annually from 2019 to 2021,with a decline ob-served in 2022-2023."Chinese Journal of Health"published the most articles on performance assessment in tertiary public hospitals.Research institutions mainly focused on universities,health administrative departments,and hospi-tals.The hotspot clusters of research included performance assessment,public hospitals,target management,high-quality development,tertiary hospitals,and operational efficiency.Conclusion Performance assessment in tertia-ry public hospitals has received widespread attention,with rich connotations and obvious guiding effects,but further research is needed to deepen and explore related topics.
10.SWOT Analysis on the Sustainable Development of Internal Medicine Specialties under the Background of Performance Evaluation in Tertiary Public Hospital
Yidan ZHANG ; Yu HU ; Yixiang PENG ; Ming ZHANG ; Li WEI ; Ning DING ; Wen CHEN ; Dong XU
Chinese Hospital Management 2024;44(9):9-12
The performance evaluation of tertiary public hospitals aims to strengthen functional positioning,and the weight of indicators such as the proportion of surgery is relatively high in the evaluation indicators.In this con-text,some tertiary comprehensive hospitals with a high proportion of internal medicine business are facing significant challenges in sustained development.It comprehensively reviews the impact of performance evaluation indicators on the direction of internal medicine specialties,and uses SWOT analysis tools to condense the sustainable develop-ment path of tertiary public hospitals.This includes growth strategies(improving the ability to treat difficult and criti-cal diseases,undertaking scientific and educational tasks),transformational strategies(technological innovation,price approval),multiple business strategies(adjusting outpatient and inpatient structures,building specialized disease centers,etc.),and defensive strategies(reasonable diagnosis and treatment,clinical pathways),inorder to provide reference for hospital managers.


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