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.Path analysis for the high-quality development of public hospitals assisted by new quality productive forces
Ning DING ; Yu HU ; Yidan ZHANG ; Ming ZHANG ; Dong XU
Chinese Journal of Hospital Administration 2024;40(9):651-656
Development of new quality productive forces is an inherent requirement and a crucial focus for promoting high-quality development of public hospitals. Based on Marxist productivity theory, this study elucidated the essence of new quality productive forces in the health field and its correlation with high-quality development of public hospitals. By integrating innovative developmental practices of public hospitals in China, the practical problems of new quality productive forces in promoting high-quality development of public hospitals from three aspects(production factors, production technology, and production relations) were analyzed. Furthermore, corresponding development paths were proposed, including focusing on key production factors and consolidating the talent foundation of new quality productive forces, focusing on core production technologies and accumulating advantageous momentum to promote high-quality development, and focus on new production relations and coordinate the upgrading and growth of the health industry, to provide references for accelerating the high-quality development of public hospitals.
4.Total Saponins in Paridis Rhizoma: A Review
Yibo ZHANG ; Huizhong ZHANG ; Jing FU ; Yidan RUAN ; Aina YAO ; Pingzhi ZHANG ; Xingbin YIN ; Changhai QU ; Jian NI ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(1):232-243
Paridis Rhizoma possesses the functions of clearing heat and detoxifying, alleviating swelling and relieving pain, cooling the liver and calming the convulsion. Saponins are the main active components of Paridis Rhizoma. Studies have shown that total saponins in Paridis Rhizoma have obvious inhibitory effect on solid tumors such as breast cancer, lung cancer, gastric cancer, and liver cancer and non-solid tumors such as leukemia. The saponins may exert the anti-tumor effects by inhibiting the proliferation, migration, and invasion of tumor cells, regulating cell cycle, inducing apoptotic and non-apoptotic death pathways, and regulating metabolism and tumor microenvironment. Furthermore, total saponins in Paridis Rhizoma showed anti-inflammatory, antioxidant, antimicrobial, hemostatic, and uterus-contracting activities. At the same time, they may induce apoptosis of normal cells, inflammation and oxidative stress, and metabolic disorders. In recent years, the reports of liver injury, reproductive injury, gastrointestinal injury, hemolysis, and other adverse reactions caused by total saponins in Paridis Rhizoma have been increasing. Pharmacokinetic studies have shown that there are significant differences in the metabolism of total saponins in Paridis Rhizoma administrated in different ways. Injection has a fast clearance rate, while oral administration may have hepatoenteric circulation. Meanwhile, due to the low solubility and activation of P-glycoprotein (P-gp) molecular pump, the prototype absorption, intestinal permeability, and recovery rate of total saponins in Paridis Rhizoma are poor, which affects the bioavailability. The bioavailability can be improved to some extent by preparing new dosage forms or new drug delivery systems with advanced technology. This paper reviews the pharmacological effect, pharmacokinetics, and adverse reactions of Rhizoma Paridis total saponins by searching the China National Knowledge Infrastructure (CNKI), VIP, and Web of Science with ''Rhizoma Paridis total saponins'' as the keywords, hoping to provide references for the research, development, and clinical application of such components.
5.Active Ingredients of Chinese Medicines Induce Ferroptosis in Tumor Cells: A Review
Huizhong ZHANG ; Yibo ZHANG ; Jing FU ; Huating HUANG ; Yidan RUAN ; Xingbin YIN ; Changhai QU ; Jian NI ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(9):245-253
Ferroptosis, a new form of programmed cell death different from apoptosis, necrosis, and autophagy, is closely associated with a variety of physiological and pathological processes. Iron-mediated accumulation of reactive oxygen species is the main inducement of ferroptosis, the mechanism of which is related to intracellular lipid metabolism, iron metabolism, and antioxidant defense pathways. Multiple signaling axes and regulators jointly regulate the occurrence and disruption of ferroptosis. Studies have demonstrated that ferroptosis regulates the growth and proliferation of tumor cells. Inducing ferroptosis in tumor cells can control the growth, metastasis, and multi-drug resistance of tumors. Therefore, the effect and mechanism of ferroptosis on tumor cells have become a hot topic in anti-cancer research. As the research advances, a variety of ferroptosis inducers has been used in the clinical chemotherapy for cancers and demonstrate significant efficacy. Accordingly, the development of ferroptosis-inducing anticancer drugs has become a new research direction for tumor treatment. Some active ingredients such as lycorine, oleanolic acid, dihydroartemisinin, pseudolaric acid B, and ophiopogonin B of Chinese medicines can induce ferroptosis in tumor cells via lipid metabolism, iron metabolism, system Xc-, and GPX4/GSH to regulate the development of tumors, demonstrating a promising prospect in clinical treatment. Based on the theory of the mechanism of ferroptosis, this paper reviews the research progress in ferroptosis induced by active ingredients of Chinese medicines in tumor cells and describes the metabolic regulatory network of ferroptosis from signaling pathways and regulatory factors, providing new strategies for applying active ingredients of Chinese medicines in the treatment of tumors.
6.Mechanism of Polyphyllin Ⅱ in Induction of Ferroptosis in Hepatocellular Carcinoma HepG2 Cells
Huizhong ZHANG ; Jian NI ; Hulinyue PENG ; Yibo ZHANG ; Xiaohan XU ; Shiman LI ; Yidan RUAN ; Yongqiang ZHANG ; Pingzhi ZHANG ; Aina YAO ; Ying WANG ; Xiaoxu DONG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(17):105-112
ObjectiveTo investigate the induction of ferroptosis by polyphyllin Ⅱ (PPⅡ) in hepatocellular carcinoma HepG2 cells and its underlying mechanism. MethodThe effect of PPⅡ (0, 1.5, 3.0, 4.5, 6.0, 9.0, 18.0 mg·L-1) on the in vitro proliferation of HepG2 cells was assessed using the methyl thiazolyl tetrazolium (MTT) assay. Colony formation ability of HepG2 cells was evaluated through a colony formation assay. Cell migration ability was assessed via a scratch assay. Lactate dehydrogenase (LDH) content in HepG2 cells was measured using a kit. Reactive oxygen species (ROS) levels in HepG2 cells were observed using a fluorescence inverted microscope. Malondialdehyde (MDA), glutathione (GSH), and free Fe2+ content in HepG2 cells were detected using respective kits. The mitochondrial ultrastructure in HepG2 cells was observed by transmission electron microscopy. The expression of ferroptosis-related proteins p53, solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), long-chain acyl-CoA synthetase 4 (ACSL4), and transferrin receptor 1 (TFR1) in HepG2 cells was detected using Western blot. ResultCompared with the control group, the PPⅡ treatment groups showed significantly decreased survival rate of HepG2 cells in a dose-dependent manner (P<0.01), significantly reduced number of cell colonies (P<0.01), significantly shortened scratch healing distance, inverse correlation of the migration distance with drug concentration (P<0.01), significantly increased LDH leakage in cells (P<0.01), significantly enhanced relative fluorescence intensity of intracellular ROS, and significantly increased accumulation of lipid peroxide MDA (P<0.01), decreased intracellular GSH content with increasing drug concentration (P<0.01), and significantly enhanced fluorescence intensity of FeRhoNox-1 in cells (P<0.01). Moreover, cells exhibited vacuolation, and mitochondria showed significant shrinkage with reduced or even disappeared cristae. Compared with the results in the control group, the expression of p53, ACSL4, and TFR1 proteins significantly increased, while the expression of SLC7A11 and GPX4 proteins significantly decreased in the PPⅡ treatment groups (P<0.05). ConclusionIn summary, PPⅡ induces ferroptosis in HepG2 cells by regulating the p53/SLC7A11/GPX4 signaling axis, promoting ACSL4 expression and Fe3+ uptake, leading to an imbalance in the antioxidant system.
7.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.
8.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.
9.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.
10.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.

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