1.Mechanisms of Traditional Chinese Medicine in Prevention and Treatment of Stroke by Regulating Ferroptosis: A Review
Mingyan WEI ; Shanze LI ; Rui HAN ; Qingbi LI ; Xingyi SUN ; Han ZHANG ; Lin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):313-321
Stroke is one of the leading causes of death and disability worldwide, ranking as the second leading cause of mortality globally and the primary cause of adult disability. Its pathological process involves complex cascade mechanisms, with high incidence and disability rates, posing a major threat to human health. According to statistics from the World Health Organization, more than 13 million new cases of stroke occur globally each year, resulting in direct medical costs and socioeconomic burdens amounting to hundreds of billions of dollars. In recent years, breakthroughs in the study of programmed cell death mechanisms have provided new insights into stroke treatment. Among them, ferroptosis, a novel form of cell death driven by iron-dependent lipid peroxidation, has attracted widespread attention in the pathological process of stroke. Ferroptosis is closely associated with iron metabolism disorders, oxidative stress, and lipid peroxidation, and exhibits unique regulatory effects in key pathological processes of stroke, such as ischemia-reperfusion injury, disruption of the blood-brain barrier, and neuronal apoptosis. It plays an important role in post-stroke neurological damage. Chinese medicine, as an essential component of traditional Chinese medicine (TCM), has demonstrated advantages in modulating ferroptosis and exerting neuroprotective effects. This review systematically summarizes current research on the neuroprotective mechanisms of Chinese medicine compound formulas and monomers through the regulation of ferroptosis pathways in post-stroke conditions, aiming to provide a basis for optimizing clinical treatment strategies and exploring new therapeutic approaches, and to offer new strategies and approaches for stroke treatment.
2.Mechanisms of Traditional Chinese Medicine in Prevention and Treatment of Stroke by Regulating Ferroptosis: A Review
Mingyan WEI ; Shanze LI ; Rui HAN ; Qingbi LI ; Xingyi SUN ; Han ZHANG ; Lin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):313-321
Stroke is one of the leading causes of death and disability worldwide, ranking as the second leading cause of mortality globally and the primary cause of adult disability. Its pathological process involves complex cascade mechanisms, with high incidence and disability rates, posing a major threat to human health. According to statistics from the World Health Organization, more than 13 million new cases of stroke occur globally each year, resulting in direct medical costs and socioeconomic burdens amounting to hundreds of billions of dollars. In recent years, breakthroughs in the study of programmed cell death mechanisms have provided new insights into stroke treatment. Among them, ferroptosis, a novel form of cell death driven by iron-dependent lipid peroxidation, has attracted widespread attention in the pathological process of stroke. Ferroptosis is closely associated with iron metabolism disorders, oxidative stress, and lipid peroxidation, and exhibits unique regulatory effects in key pathological processes of stroke, such as ischemia-reperfusion injury, disruption of the blood-brain barrier, and neuronal apoptosis. It plays an important role in post-stroke neurological damage. Chinese medicine, as an essential component of traditional Chinese medicine (TCM), has demonstrated advantages in modulating ferroptosis and exerting neuroprotective effects. This review systematically summarizes current research on the neuroprotective mechanisms of Chinese medicine compound formulas and monomers through the regulation of ferroptosis pathways in post-stroke conditions, aiming to provide a basis for optimizing clinical treatment strategies and exploring new therapeutic approaches, and to offer new strategies and approaches for stroke treatment.
3.Rho/ROCK:key Mediator of Pulmonary Fibrosis and New Target of TCM for IPF Prevention and Treatment
Yuanyuan WU ; Kangchen LI ; Mingyan LI ; Xiling PENG ; Feifan ZHANG ; Han LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):256-265
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterized by dyspnea and progressive deterioration of lung function, which significantly impacts patients' quality of life and imposes a major burden on society. Although modern medicine has increasingly enriched the treatment options for pulmonary fibrosis, unfavorable factors such as high costs and significant side effects contribute to the persistently low survival rate of patients. Studies have shown that the occurrence and development of pulmonary fibrosis are closely related to abnormalities in multiple pathways. Among these, Rho/Rho-associated coiled-coil protein kinase (ROCK) plays a key role in the disease progression of IPF by regulating the cytoskeleton. This pathway not only transmits biochemical molecular signals that promote the progress of fibrosis but also responds to the biomechanical environment, such as the increased lung tissue stiffness caused by the deposition of extracellular matrix (ECM) during the process of pulmonary fibrosis. Therefore, research on this pathway is of great significance for the prevention and treatment of IPF. In recent years, traditional Chinese medicine (TCM) has shown remarkable effects in preventing and treating IPF. Many TCM compounds and active components can reduce the production of α-smooth muscle actin (α-SMA), CollagenⅠ (ColⅠ), ColⅢ, and inflammatory factors in lung tissue by regulating the Rho/ROCK signaling pathway. These compounds inhibit the transformation of fibroblasts (FBs) into myofibroblasts (MyoFBs), intervening in the process of pulmonary fibrosis. Based on this, the article briefly reviews relevant research from recent years, discusses the key role of the Rho/ROCK pathway in pulmonary fibrosis from an interdisciplinary perspective, and summarizes the mechanisms through which TCM regulates Rho/ROCK to prevent and treat IPF, based on resources from PubMed, CNKI, and other databases, in order to provide important references for the broader clinical application of TCM in the prevention and treatment of IPF.
4.Development of a Core Outcome Set for Clinical Evaluation of Chronic Pulmonary Heart Disease Treated with Traditional Chinese Medicine Therapy
Baihan NIU ; Mingyan ZHANG ; Zhaochen JI ; Bo PANG ; Haiyin HU ; Junhua ZHANG
Journal of Traditional Chinese Medicine 2025;66(12):1227-1232
ObjectiveTo construct an outcome set for clinical evaluation of traditional Chinese medicine (TCM) for chronic pulmonary heart disease, and to provide consensus outcomes for the evaluation of the clinical effectiveness of TCM for chronic pulmonary heart disease. MethodsWe searched randomised controlled trials of TCM for chronic pulmonary heart disease on China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (WF), VIP Chinese Science Journals Database (VIP), Chinese Biomedical Literature Service Database (SinoMed), PubMed, Cochrane Library, and Embase. We also searched Chinese Clinical Trial Registry Platform and the U.S. Clinical Trial Registry database to obtain the outcome indicators reported in the clinical research protocols of TCM for chronic pulmonary heart disease. The outcome indicators were also collected through semi-structured interviews of clinicians and patients. Then integrated the outcome indicators collected by the above methods to construct the indicator pool. Through two rounds of Delphi surveys and a consensus conference, the core outcome set for clinical evaluation of TCM for chronic pulmonary heart disease was determined. ResultsAfter screening, there were 1313 literature meeting the criteria, and 595 outcome indicators were extracted, then combined with the outcomes from semi-structured interviews which clinicians and patients concerned, finally an indicator item pool containing 369 outcome indicators were formed. After the initial screening of indicators in the pool by the steering committee, 58 indicators were established into the initial list of indicator entries. In the first round of Delphi survey, the expert coordination coefficient for the results was 0.401, and the Cronbach coefficient was 0.989. A total of 35 indicators that did not meet the criteria [<70% of the participants rated the outcome as 7~9 (critical) and the mean of the expert ratings <7] were deleted, and 23 were retained, with 7 new indicators added that were open to supplementation by the experts, resulting in a total of 30 indicators that were included in the second round of Delphi survey. In the second round of Delphi survey, the expert coordination coefficient was 0.303, and the Cronbach coefficient was 0.974, with a total of 7 indicators that did not meet the criteria being deleted, and 21 indicators being retained for the consensus conference. After the consensus meeting, the core outcome set for clinical evaluation of chronic pulmonary heart disease in two major categories, acute exacerbation stage and stable stage, was finally determined, in which there were four indicators in acute exacerbation stage: N-terminal B-type natriuretic peptide precursor (NT-proBNP), blood qi analysis, all-cause mortality rate, and complication rate; and there were eight indicators in the stable stage: pulmonary function index, six-minute walk test distance, New York cardiac function classification, all-cause mortality rate, re-hospitalisation rate, Chronic Obstructive Pulmonary Disease Assessment Test (CAT) score, Short Form 36 Health Survey (SF-36), and TCM syndrome score. ConclusionThe core outcome sets of TCM clinical evaluation in the acute exacerbation stage and stable stage are constructed, which is helpful to improve the practicability, comparability and transparency of TCM clinical research results in pulmonary heart disease.
5.Study on core genes and potential immunological and metabolic mechanisms associated with Tongmai yangxin pills in the treatment of coronary heart disease
Junchi GUO ; Mingyan ZHANG ; Yingqiang ZHAO ; Meijuan LU
China Pharmacy 2025;36(17):2148-2153
OBJECTIVE To identify core genes associated with the treatment of coronary heart disease (CHD) with Tongmai yangxin pills, and predict their potential immunological and metabolic mechanisms. METHODS Mendelian randomization (MR) analysis was conducted using protein quantitative trait loci (pQTL) data from the UK Biobank and Icelandic,and data from genome- wide association study to screen core genes related to Tongmai yangxin pills in the treatment of CHD. Gene expression changes were further validated using transcriptomic sequencing data. Mediation analyses of immune cells and plasma metabolites were subsequently performed to explore the downstream regulatory networks of these core genes. RESULTS A total of 62 positive pQTL genes showed significant causal associations with CHD. MR analysis combined with transcriptomic sequencing validation identified three core genes FAM3D,OXT, and ENPP5-associated with Tongmai yangxin pills in the treatment of CHD. The transcriptomic sequencing results showed that after treatment with Tongmai yangxin pills, the expression levels of FAM3D and OXT were significantly reduced (P<0.01), while the expression level of ENPP5 was significantly increased (P<0.05). Mediation analyses between immune cells and plasma metabolites indicated that these genes may positively or negatively regulate CHD through immune pathways involving regulatory T cells and myeloid dendritic cells expressing CD11c and CD62L, as well as through metabolic pathways related to lipid and fatty acid metabolism, cholesterol metabolism, and bile acid metabolism. CONCLUSIONS This study identified FAM3D,OXT, and ENPP5 as core genes associated with the treatment of CHD by Tongmai yangxin pills, which may exert therapeutic effects via modulation of immune cells and plasma metabolic pathways involving fatty acids and bile acids.
6.Key points and standard status of quality evaluation of oromucosal drug delivery preparations
Liuliu YANG ; Mingyan LI ; Junqi ZHANG ; Bing WANG ; Yue SHANG ; Fang CHEN
Drug Standards of China 2024;25(3):220-226
Oromucosal drug delivery preparations offer advantages such as convenient administration,suitability for patients with dysphagia,rapid onset of action,and avoidance of first-pass metabolism in the liver.The 2020 edition of the Chinese Pharmacopoeia,EP11.0,BP2022,USP44-NF39,and JP18 all include relevant standards for the quality control of different oromucosal drug delivery systems.This article compares the differences in general re-quirements for oromucosal formulations among different countries and provides an overview of inspection items for marketed oral mucosal formulations and those documented in pharmacopoeias both domestically and internationally.Foreign pharmacopoeias include a wide range of oromucosal drug delivery formulations,with more refined quality control measures for systemic action.These findings can serve as a reference for the improvement and enhancement of standards for oromucosal drug delivery systems in China.
7.Correlation analysis of late-onset hypogonadism in a community in Beijing
Rui CHEN ; Jing ZHANG ; Mingyan ZHANG
Chinese Journal of General Practitioners 2024;23(7):716-721
Objective:To investigate the factors associated with late-onset hypogonadism (LOH) in men.Methods:This was a cross-sectional study. Male residents aged 40-75 years who attended health examinations at the Yangfangdian Community Health Service Center in Haidian District, Beijing from February 6th to June 30th, 2023 were included. The LOH group was selected based on diagnostic criteria and matched to the control group according to age. General clinical data were collected from both groups, fasting venous blood samples were taken and general health examination items were completed. Total testosterone(TT) and sex hormone-binding globulin(SHBG) levels were measured, and free testosterone(fT) were calculated. Relevant symptoms were assessed using the Chinese version of the Aging Males′ Symptoms (AMS) scale. Single and multiple factor comparative analyses were conducted to explore the factors related to LOH.Results:A total of 233 male residents from the community who met the inclusion criteria and gave informed consent were included, of whom 42 cases (18.03%) were diagnosed with LOH. After age matching, the final LOH and control groups consisted of 40 individuals each ((64.8±6.0) years vs. (62.3±8.6) years, P>0.05). There were statistically significant differences between the LOH and control groups for body mass index, waist circumference, sex hormone-binding globulin, AMS scores, and hemoglobin. The prevalence of diabetes and dyslipidemia was significantly higher in the LOH group than in the control group (both P<0.05). Multivariate logistic regression analysis showed that diabetes ( OR=4.497, 95% CI:1.291-15.664, P=0.018), dyslipidemia ( OR=8.431, 95% CI: 1.566-45.405, P=0.013), and hemoglobin level ( OR=0.923, 95% CI: 0.874-0.975, P=0.004) were significantly associated with LOH. Conclusion:Diabetes, dyslipidemia and hemoglobin levels are significantly associated with LOH.
8.Exploring the influencing factors of stroke and constructing a nomogram prediction model in Chinese middle-aged and older population
Jin LI ; Hou HOU ; Yaxin WANG ; Xin ZHANG ; Zhenqiang SONG ; Mingyan SUN
Chinese Journal of Arteriosclerosis 2024;32(10):865-871
Aim To explore the related influencing factors of stroke in middle-aged and elderly population in China,and to construct a nomogram prediction model to provide more personalized reference for the prevention and treat-ment of stroke.Methods This study included 13 063 participants from the China Health and Retirement Tracking Survey project.This project conducted a cross-sectional survey in 2011 using a multi-stage sampling method,targeting in-dividuals aged 45 and above from 150 counties and 450 communities(villages)in 28 provinces(autonomous regions and municipalities).Detailed data were collected on participants'socio-demographic characteristics,physical measurements,health status,healthcare utilization,household income,and expenditure.The study participants were followed up to as-sess stroke in 2013,2015,and 2018.Univariate and multivariate Cox regression analyses were employed to identify the factors associated with stroke incidence and to construct a nomogram predictive model.Results During the follow-up,774 participants developed to stroke.Multivariate Cox regression results showed that older age(HR=1.028,95%CI:1.019-1.038),being single(HR=1.295,95%CI:1.031-1.626),smoking(HR=1.264,95%CI:1.074-1.489),abnormal body mass index(HR=1.204,95%CI:1.020-1.420),hypertension(HR=2.200,95%CI:1.855-2.609)and diabetes(HR=1.483,95%CI:1.117~1.970)were the risk factors affecting the incidence of stroke,high levels of annual per capita expenditure(HR=0.783,95%CI:0.642-0.953)are antagonistic factors in the incidence of stroke.The nomogram constructed based on the above factors had good predictive performance,and its area under the curve(AUC)was about 0.700.Conclusion Old age,being single,smoking,abnormal body mass index,history of hypertension and diabetes are independent risk factors for stroke,the nomogram constructed based on these factors can help predict the incidence rate of stroke.
9.Diagnosis of Two-Dimensional Speckle Tracking Automatic Functional Imaging of Postsystolic Shortening in Ischemia with Non-Obstructive Coronary Arteries
Ying LI ; Dandan SUN ; Zhiyan QIN ; Yuhui YANG ; Huihui ZHANG ; Mingyan DING ; Hanzhang ZHAO
Chinese Journal of Medical Imaging 2024;32(10):1000-1004,1006
Purpose To investigate the diagnostic value of postsystolic shortening in ischemia with non-obstructive coronary arteries(INOCA).Materials and Methods A total of 85 INOCA patients admitted to People's Hospital of Liaoning Province from May 2020 to December 2022 were selected and divided into two groups according to the ratio of distal diastolic average blood velocity of left anterior descending branch before and after treatment obtained by thymosidine load echocardiography(coronary flow velocity reserve,CFVR):CFVR<2.0 was in the coronary microvascular dysfunction(CMD)group(n=40),and CFVR≥2.0 was in the control group(n=45).Conventional echocardiographic parameters of all enrolled subjects were measured:left ventricular end-diastolic diameter index(LVEDDI),left ventricular end-diastolic volume index(LVEDVI),left ventricular end-systolic volume index(LVESVI),left ventricular ejection fraction(LVEF),early and late mitral valve diastolic blood flow velocity(E,A),E/A,average velocity of mitral valve annulus and interventricular septum in early diastolic(e')and E/e'on the wall and septal side were measured.The global longitudinal strain(GLS)and the post systolic index(PSI)of the left ventricle were measured by two-dimensional speckle tracking automated functional imaging.The differences of echocardiographic parameters,GLS and PSI between CMD group and control group were observed.The relationship between CFVR and PSI in CMD group was analyzed.Results There were no significant differences in LVEDDI,LVEDVI,LVESVI,LVEF,E,A,E/A,e',E/e'and GLS between control group and CMD group(t=-0.577-1.472,P>0.05).There was a statistically significant difference in PSI increase between CMD group and control group(t=-5.370,P<0.05).There was a good correlation between CFVR and PSI in CMD group(r=-0.486,P<0.05).The receiver operator characteristic curve showed that the area under the curve predicted by PSI for CMD was 0.786,the sensitivity was 68.0%,and the specificity was 77.8%.Conclusion PSI has good application value in evaluating left ventricular systolic function in INOCA patients,and can detect left ventricular systolic function injury in such patients at an early stage.
10.Effects of brusatol on the malignant biological behavior of ovarian cancer cells by regulating SPHK1/S1P/S1PR3 signaling pathway
Mingyan ZHONG ; Fan YANG ; Haizhen LI ; Qi ZHAN ; Wei ZHANG
China Pharmacy 2024;35(16):1991-1997
OBJECTIVE To investigate the effects of brusatol on the malignant biological behavior of ovarian cancer cells by regulating the sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor 3 (S1PR3) signaling pathway. METHODS Human ovarian cancer cell strain SKOV-3 were randomly divided into control group, brusatol group, SPHK1 overexpression group, brusatol+blank load group, brusatol+SPHK1 overexpression group. The cell viability, colony formation rate, the number of migration and invasion, apoptosis rate, the expressions of cell proliferation-related proteins [myelocytomatosis viral oncogene homolog (C-myc)], apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax)], epithelial mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin) and SPHK1, S1P, S1PR3 proteins were all detected in each group. Transplanted tumor model of nude mice was constructed by using SKOV-3 cells and randomly separated into control group, brusatol low-dose, medium-dose and high-dose groups, SPHK1 overexpression group, high- dose brusatol+blank load group, and high-dose brusatol+SPHK1 overexpression group; the growth of transplanted tumors were detected. The nude mice model of SKOV-3 transplantation tumor was randomly divided into control group, brusatol group, SPHK1 overexpression group, brusatol+blank load group, and brusatol+SPHK1 overexpression group; the proliferation and apoptosis of transplanted tumor tissue, the expressions of EMT-related Δ 基金项目江西省中医药管理局科技计划项目(No.2023B0762) *第一作者 副主任药师 。研究方向 :药学研究及药理学 。E- proteins and SPHK1/S1P/S1PR3 signaling pathway proteins mail:jsgj2023@126.com were detected in each group. RESULTS Cell experiments in # 通信作者 主任医师,硕士。研究方向:妇科及妇科肿瘤学。E- vitro had shown that compared with the control group, the cell mail:11638199@qq.com viability, clone formation rate, migration number, invasion 中国药房 2024年第35卷第16期 China Pharmacy 2024 Vol. 35 No. 16 · 1991 · number, protein expressions of C-myc, Bcl-2, N-cadherin, SPHK1, S1P and S1PR3 were decreased significantly in brusatol group (P<0.05), while the apoptosis rate, protein expressions of Bax and E-cadherin were increased significantly (P<0.05); overexpression of SPHK1 could weaken the effects of brusatol on the above indicators in SKOV-3 cells. Mice experiments in vivo had shown that compared with the control group, the transplanted tumor volumes of nude mice in the brusatol low-dose, medium- dose and high-dose groups were decreased significantly in a dose-dependent manner after 21 days of intervention (P<0.05). Brusatol of high dose could also significantly reduce the protein expressions of C-myc, Bcl-2, N-cadherin, SPHK1, S1P and S1PR3 in transplanted tumor tissue of nude mice (P<0.05), and significantly increase the protein expressions of Bax and E- cadherin (P<0.05); overexpression of SPHK1 could weaken the effects of brusatol on the above indicators in transplanted tumor tissue of nude mice. CONCLUSIONS Brusatol can inhibit the proliferation, cloning, EMT, migration and invasion of ovarian cancer cells, and induce their apoptosis by down-regulating the expression of SPHK1/S1P/S1PR3 signaling pathway. It can also inhibit the growth of ovarian cancer cells in nude mice, ultimately suppressing their malignant biological behavior and exerting significant anti-cancer effects on ovarian cancer.

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