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.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.
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.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.
8.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.
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.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.

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