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.Annual review of basic research on lung transplantation of China in 2024
Jier MA ; Junmin ZHU ; Lan ZHANG ; Xiaohan JIN ; Xiangyun ZHENG ; Senlin HOU ; Zengwei YU ; Yaling LIU ; Haoji YAN ; Dong TIAN
Organ Transplantation 2025;16(3):386-393
Lung transplantation is the optimal treatment for end-stage lung diseases and can significantly improve prognosis of the patients. However, postoperative complications such as infection, rejection, ischemia-reperfusion injury, and other challenges (like shortage of donor lungs) , limit the practical application of lung transplantation in clinical practice. Chinese research teams have been making continuous efforts and have achieved breakthroughs in basic research on lung transplantation by integrating emerging technologies and cutting-edge achievements from interdisciplinary fields, which has strongly propelled the development of this field. This article will comprehensively review the academic progress made by Chinese research teams in the field of lung transplantation in 2024, with a focus on the achievements of Chinese teams in basic research on lung transplantation. It aims to provide innovative ideas and strategies for key issues in the basic field of lung transplantation and to help China's lung transplantation cause reach a higher level.
4.Pathogenesis and Treatment of Atopic Dermatitis from the Theory of Pathogens Intruding Eight Weak Areas
Zhengwen TENG ; Nan LI ; Sai ZHANG ; Xiaohan HANG ; Fengchuan ZHANG ; Yuanwen LI
Journal of Traditional Chinese Medicine 2025;66(15):1548-1552
Based on the discussion of "eight weak areas" in The Inner Canon of Yellow Emperor (《黄帝内经》), combined with the typical rash manifestations of atopic dermatitis, it is believed that atopic dermatitis is mostly deficiency-excess complex, and that pathogens intruding eight weak areas are the core of its pathogenesis. The external cause is exterior deficiencies, with heat, wind, dampness and other pathogenic qi attacking. The heart, lungs, kidneys out of balance, and excess pathogen are the internal cause, in which fire constraint and excessive heat are the basis of the disease, the wind invading leads to the progress of the changes, dampness obstructing channels and colla-terals make the condition persistent. Internal and external pathogens combination and retention result to the course of the disease lingering and difficult to cure. The internal treatment is to regulate zang-fu organs, and the formula could use self-prescribed modified Qingrun Tongluo Decoction (清润通络汤), clearing heart and reducing fire in order to clear the heat and cool the blood, moistening lungs and generating metal to consolidate the exterior and dispel the wind, and nourishing kidneys and draining water to dispel the dampness and activate the collaterals. The external treatment applies maceration, fire acupuncture, wrapping to dredge the eight weak areas and regulate qi and blood in channel, so as to expel pathogens.
5.Research focus and future trend of Chinese hospital supply chain management: a literature review based on bibliometric analysis
Baoyang DING ; Zheng LIU ; Wei HAO ; Liujin ZHANG ; Xiaohan YANG ; Qiang SUN
Chinese Journal of Hospital Administration 2024;40(1):53-58
Objective:To reveal the research hotspots in hospital supply chain management in China and explore how supply chain management can facilitate the high-quality development of public hospitals.Methods:Bibliometric analysis method was employed, retrieving the Chinese literature on hospital supply chain management from 2000 to 2022 from CNKI, WeiPu, and WanFang databases. Descriptive analysis and cluster analysis of high-frequency keywords were conducted.Results:Through cluster analysis of 34 high-frequency keywords in the 1 113 Chinese literature, it was found that current research on hospital supply chain management mainly focused on 7 research hotspots: big data information systems, procurement management, risk management, refined management, inventory management, supplier management, and traceability management.Conclusions:Future research could focus on construction of hospital supply chain performance evaluation systems, digital technology-driven supply chain transformation and upgrading, enhancing hospital supply chain resilience under risks, and sustainable supply chain management.
6.Application and progress of radiomics in bone and soft tissue tumors
Xiaohan ZHANG ; Yao ZHANG ; Linfeng AI ; Tian LI ; Hao XIONG
China Medical Equipment 2024;21(1):199-204
Bone and soft tissue tumors are diverse and with complicated histologic components and significantly divergent biological behaviors.Conventional imaging examinations,such as CT,magnetic resonance imaging(MRI)and positron emission tomography(PET),are limited to the identification of anatomical structures and abnormal signals,which are difficult to meet the qualitative requirements of imaging.With the improvement of digitalization in hospitals and medical institutions,the introduction of electronic medical records and the improvement of computational power,modern intelligent medical treatment gradually evolves to the combination of human brain,big data and artificial intelligence.Researchers are committed to mining deeper image data information,and radiomics came into being.Radiomics is a method of extracting and analyzing subvisual quantitative features from medical images and quantifying tumor heterogeneity through modeling,which is of great significance in the accurate diagnosis and treatment of bone and soft tissue tumors.
7.Analysis of image features of fundus blood vessel in healthy human eye based on deep learning techniques
Mengyu HUI ; Jinglin SHI ; Xiaohan YU ; Jian LI ; Yan ZHANG ; Zhengli TANG ; Shanghai YU ; Yue GAO ; Ping LIU ; Hua ZHANG
International Eye Science 2024;24(10):1542-1550
AIM:To explore the fundus vascular characteristics of healthy individuals based on deep learning techniques, with a view to discovering the range of normal values of the fundus arteries and veins, as well as the relationship between physiological factors, such as gender, age, body mass index(BMI), blood pressure, and fundus vasculature characteristics.METHODS:Fundus images of healthy people were taken from a professional fundus camera, and the subject's blood pressure and laboratory test was collected. Additionally, the fundus arteries and veins were segmented by the improved U-Net model, and the color, morphology and Haralick texture features of the vessels were extracted from computer vision technology.RESULTS:A total of 4 487 cases fundus images were taken and 326 cases with healthy and clear fundus images were screened, including 200 males and 126 females. There were differences in the morphology, color, and textural characteristics of the left and right eyes, as well as of the fundus arterioles and veins, with a mean vessel width(width)of 1.146 in the arteries and 1.430 in the veins, and an arteriovenous ratio about 4:5. Fundus artery and vein characteristics in healthy individuals of different ages(21-30, 31-40, 41-50): compared with the healthy population aged 21-30 and 31-40 years, arterial and venous inverse difference moment(idm), f12 and venous angular second moment(asm)values increased, and arterial and venous contrast(con), entropy(ent), difference entropy(den), and venous sum entropy(sen)values decreased in 41-50 years. Compared with the 21-30 years age group, arterial f12 values increased and venous con values decreased in 31-40 years(all P<0.05). Fundus vascular characteristics of healthy individuals of different sexes: compared with male, fundus arterial and venous sum average(sav), sum variance(sva)values, arterial curved values, and venous b mean, bsd, variance(var), sen, ent values increased in female, while venous area value of female decreased(all P<0.05). There were no statistically significant differences in fundus arteriosus and venous features in healthy subjects with different levels of BMI(all P>0.05). Fundus characteristics of healthy people with different degrees of blood pressure: there were statistically significant differences in fundus arteriosus area, width, and venous con, idm, dva, and den values between the normal blood pressure and high blood pressure groups(all P<0.05).CONCLUSION: The characteristics of the left and right eyes as well as the fundus arteries and veins differ in healthy individuals and correlate with physiological factors such as gender, age and blood pressure, which have the value of a potential microcirculation marker.
8.Preparation and evaluation of in situ film of compound iodine oral spray for promoting oral ulcer repair
Xiaojun ZHANG ; Shanqin HUANG ; Xiaohan GUO ; Mengfei JI ; Yan SHEN ; Daquan CHEN
Journal of China Pharmaceutical University 2024;55(6):775-782
In this study, a new in situ film of compound iodine oral spray was prepared by in situ gel technology, which was used to exert sustained-release effect for promoting the repair of oral ulcer wounds. Firstly, the formulation and process of the spray solution were optimized according to the spray state and film-forming time. The drug-liquid mixing ratio was evaluated by film-forming time and drug film adhesion. The drug content, stability, pH, and spraying effect of compound iodine oral spray prepared by the optimal formulation were investigated; and the physicochemical properties, including film formation time, solubility, hygroscopicity, moisture retention and in vitro release of drug film were evaluated. In addition, the biocompatibility of the film-forming materials and proliferation ability of drug film were investigated by cell experiment. Through the rabbit oral ulcer model, the in vivo film-forming and repair-promoting effects of compound iodine oral spray were evaluated. The results showed that the pH of liquid A and liquid B prepared were 6.21±0.02 and 6.42±0.03, respectively, which were in line with the normal pH range of oral mucosa; liquid A and liquid B had good stability and spray state; the iodine content in solution B was (1.96±0.01) mg/mL; the in situ membrane formation time in vitro and in the oral cavity were (118.3±3.6) s and (133.3±4.6) s, respectively; the 24-hour dissolution rate was (87.31±1.74)%, the moisture absorption rate was (124.17±7.13)%, and the moisture retention rate was (26.85±2.50)%; the iodine content in the oral spray was (47.42±0.39) mg/g, with good flexibility and adhesion, as well as some slow-release effect. In cell experiment, the film-forming materials showed good biocompatibility and growth promotion ability. The results of the rabbit oral ulcer experiment showed that the compound iodine oral spray could rapidly form a film in vivo and significantly promote the repair of oral ulcer. In conclusion, the compound iodine oral spray in situ film with a stable preparation process can effectively promote the repair of oral ulcer wounds, which provides a new idea for the research of novel oral mucosa formulations, with a good prospect of transfer.
9.Cost-utility analysis of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous NSCLC
Wenxiang JU ; Yingying ZHAO ; Luolan LU ; Xiaohan ZHANG ; Aizong SHEN
China Pharmacy 2024;35(11):1357-1362
OBJECTIVE To evaluate the cost-effectiveness of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous non-small cell lung cancer (NSCLC) from the perspective of China’s health system. METHODS A dynamic Markov model was established based on BEVERLY study data, with a cycle of 3 weeks, a research deadline until 99% of patients die, and an annual discount rate of 5%. The model outputs were total cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). Taking 3 times China’s per capita gross domestic product (GDP) in 2023 as the willingness-to-pay (WTP) threshold, the cost-utility analysis was used to evaluate the cost-effectiveness of bevacizumab combined with erlotinib (observation group) versus erlotinib alone (control group) in the first-line treatment of advanced EGFR mutant non-squamous NSCLC, and the single factor sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The results of the basic analysis showed that compared with the erlotinib therapy plan, ICER of bevacizumab combined with erlotinib was 1 452 243.01 yuan/QALY, which was more than 3 times China’s per capita GDP in 2023 (268 074 yuan/QALY) as the WTP threshold, indicating that bevacizumab combined with erlotinib was not cost-effective. The results of single factor sensitivity analysis showed that the cost of bevacizumab, the utility value of progression-free survival and progressed disease status had a great influence on the results. The results of probability sensitivity analysis showed that when the WTP threshold was 1 740 000 yuan/QALY, the probability of cost-effective of bevacizumab combined with erlotinib plan was 50%. CONCLUSIONS Compared with erlotinib alone, bevacizumab combined with erlotinib is not cost-effective in the first-line treatment of advanced EGFR mutant non-squamous NSCLC, when using 3 times China’s per capita GDP in 2023 as the WTP threshold.
10.Cost-utility analysis of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous NSCLC
Wenxiang JU ; Yingying ZHAO ; Luolan LU ; Xiaohan ZHANG ; Aizong SHEN
China Pharmacy 2024;35(11):1357-1362
OBJECTIVE To evaluate the cost-effectiveness of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous non-small cell lung cancer (NSCLC) from the perspective of China’s health system. METHODS A dynamic Markov model was established based on BEVERLY study data, with a cycle of 3 weeks, a research deadline until 99% of patients die, and an annual discount rate of 5%. The model outputs were total cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER). Taking 3 times China’s per capita gross domestic product (GDP) in 2023 as the willingness-to-pay (WTP) threshold, the cost-utility analysis was used to evaluate the cost-effectiveness of bevacizumab combined with erlotinib (observation group) versus erlotinib alone (control group) in the first-line treatment of advanced EGFR mutant non-squamous NSCLC, and the single factor sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The results of the basic analysis showed that compared with the erlotinib therapy plan, ICER of bevacizumab combined with erlotinib was 1 452 243.01 yuan/QALY, which was more than 3 times China’s per capita GDP in 2023 (268 074 yuan/QALY) as the WTP threshold, indicating that bevacizumab combined with erlotinib was not cost-effective. The results of single factor sensitivity analysis showed that the cost of bevacizumab, the utility value of progression-free survival and progressed disease status had a great influence on the results. The results of probability sensitivity analysis showed that when the WTP threshold was 1 740 000 yuan/QALY, the probability of cost-effective of bevacizumab combined with erlotinib plan was 50%. CONCLUSIONS Compared with erlotinib alone, bevacizumab combined with erlotinib is not cost-effective in the first-line treatment of advanced EGFR mutant non-squamous NSCLC, when using 3 times China’s per capita GDP in 2023 as the WTP threshold.

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