1.Construction and Application Evaluation of an Integrated Traditional Chinese and Western Medicine Risk Prediction Model for Readmission in Patients with Stable Angina of Coronary Heart Disease:A Prospective Study Based on Real-World Clinical Data
Wenjie HAN ; Mingjun ZHU ; Xinlu WANG ; Rui YU ; Guangcao PENG ; Qifei ZHAO ; Jianru WANG ; Shanshan NIE ; Yongxia WANG ; Jingjing WEI
Journal of Traditional Chinese Medicine 2025;66(6):604-611
ObjectiveBy exploring the influencing factors of readmission in patients with stable angina of coronary heart disease (CHD) based on real-world clinical data, to establish a risk prediction model of integrated traditional Chinese and western medicine, in order to provide a basis for early identification of high-risk populations and reducing readmission rates. MethodsA prospective clinical study was conducted involving patients with stable angina pectoris of CHD, who were divided into a training set and a validation set at a 7∶3 ratio. General information, traditional Chinese medicine (TCM)-related data, and laboratory test results were uniformly collected. After a one-year follow-up, patients were classified into a readmission group and a non-readmission group based on whether they were readmitted. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for readmission. A risk prediction model of integrated traditional Chinese and western medicine was constructed and visualized using a nomogram. The model was validated and evaluated in terms of discrimination, calibration, and clinical decision curve analysis. ResultsA total of 682 patients were included, with 477 in the training set and 205 in the validation set, among whom 89 patients were readmitted. Multivariate logistic regression analysis identified heart failure history [OR = 6.93, 95% CI (1.58, 30.45)], wiry pulse [OR = 2.58, 95% CI (1.42, 4.72)], weak pulse [OR = 3.97, 95% CI (2.06, 7.67)], teeth-marked tongue [OR = 4.38, 95% CI (2.32, 8.27)], blood stasis constitution [OR = 2.17, 95% CI (1.06, 4.44)], phlegm-stasis mutual syndrome [OR = 3.64, 95% CI (1.87, 7.09)], and elevated non-high-density lipoprotein cholesterol [OR = 1.30, 95% CI (1.01, 1.69)] as influencing factors of readmission. These factors were used as predictors to construct a nomogram-based risk prediction model for readmission in patients with stable angina. The model demonstrated moderate predictive capability, with an area under the receiver operating characteristic curve (AUC) of 0.818 [95% CI (0.781, 0.852)] in the training set and 0.816 [95% CI (0.779, 0.850)] in the validation set. The Hosmer-Lemeshow test showed good calibration (χ² = 4.55, P = 0.80), and the model's predictive ability was stable. When the threshold probability exceeded 5%, the clinical net benefit of using the model to predict readmission risk was significantly higher than intervening in all patients. ConclusionHistory of heart failure, teeth-marked tongue, weak pulse, wiry pulse, phlegm-stasis mutual syndrome, blood stasis constitution, and non-high-density lipoprotein cholesterol are influencing factors for readmission in patients with stable angina of CHD. A clinical prediction model was developed based on these factors, which showed good discrimination, calibration, and clinical utility, providing a scientific basis for predicting readmission events in patients with stable angina.
2.Improvement effects and mechanism of total secondary ginsenosides on hypertrophic changes in cardiomyocytes
Bin LI ; Jia LI ; Zhongjie YUAN ; Mingjun ZHU ; Shiyang XIE ; Yuan GAO ; Rui YU ; Xinlu WANG
China Pharmacy 2025;36(12):1430-1435
OBJECTIVE To investigate the ameliorative effects and potential mechanism of total secondary ginsenosides (TSG) on hypertrophic changes of primary cardiomyocytes stimulated by angiotensin Ⅱ (Ang Ⅱ). METHODS Primary cardiomyocytes were isolated from the hearts of neonatal SD rats and divided into the following groups: control group, AngⅡ group (2 µmol/L), TSG group (7.5 µg/mL), PFK-015 group [6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase 3 (PFKFB3) inhibitor, 10 nmol/L], and TSG+PFK-015 group (TSG 7.5 µg/mL+PFK-015 10 nmol/L). The surface area, protein synthesis, energy metabolism-related indicators [free fatty acid (FFA), coenzyme A (CoA), acetyl coenzyme A (acetyl-CoA)], and the expressions of glycolysis-related factors [hypoxia-inducible factor 1α (HIF-1α), glucose transporter protein 4 (GLUT-4), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase 1 (PDK1) and PFKFB3] in primary cardiomyocytes of each group were measured. RESULTS Compared with the control group, the surface area of primary cardiomyocytes and protein synthesis were significantly increased, the content of FFA, protein and mRNA expressions of HIF-1α, LDHA, PDK1 and PFKFB3 were significantly increased or up-regulated in the AngⅡ group, while the contents of CoA and acetyl-CoA, the protein and mRNA expressions of GLUT-4 were significantly decreased or down-regulated (P<0.05). Compared with the AngⅡ group, both TSG group and PFK-015 group showed significant improvements in these indexes, with the TSG+PFK-015 group generally demonstrating superior effects compared to either treatment alone (P<0.05). CONCLUSIONS TSG can reduce the surface area of AngⅡ-induced primary cardiomyocytes, decrease protein synthesis, and inhibit their hypertrophic changes. These effects may be related to improving energy metabolism and the inhibition of glycolysis activity.
3.A Cross-Sectional Study of Secondary Prevention Status and Influencing Factors of Stable Angina in 1061 Patients with Coronary Heart Disease
Rui YU ; Yingqiang ZHAO ; Peng LI ; Jianru WANG ; Xinlu WANG ; Qifei ZHAO ; Yuan GAO ; Hongxin GUO ; Mingjun ZHU
Journal of Traditional Chinese Medicine 2024;65(20):2126-2134
ObjectiveTo investigate the current status of secondary prevention of stable angina in patients with coronary heart disease in three regions of China, namely Henan Province, Xinjiang Uygur Autonomous Region, and Tianjin City, and analyze the the influencing factors. MethodsA cross-sectional study was conducted to include patients with stable angina with coronary heart disease in Henan, Tianjin and Xinjiang from August 10, 2020 to March 14, 2021. General information, traditional Chinese medicine (TCM) syndrome elements, prescriptions and other data of patients were collected, and clinical characteristics, blood pressure, blood lipid and blood glucose of patients were analyzed; the patients were divided into groups according to whether their blood pressure, blood lipid and blood glucose were up to standard. With the most common syndrome element as the main variable, region, age and gender as covariables, Logistic regression equation was incorporated to analyze the influencing factors for the patients' blood pressure, blood lipid and blood glucose being up to standard. ResultsA total of 1061 coronary heart disease patients with stable angina were included, including 658 in Henan, 210 in Xinjiang, and 193 in Tianjin. The clinical characteristics of patients in the three regions showed statistical different in age, sex, disease course, complication, blood pressure, blood lipid, blood glucose, smoking, drinking, living habits, and medication treatment (P<0.05 or P<0.01). For the included patients, qi deficiency (79.55%, 844/1061) and blood stasis (39.96%, 424/1061) were the main syndrome elements. The overall compliance rate of blood pressure was 48.89% (506/1035), blood lipids 12.68% (133/1049) and blood glucose 48.18% (504/1046). Qi deficiency was the independent factor affecting the blood pressure of coronary heart disease patients with stable angina combined with hypertension (P = 0.029,95%CI [1.048, 2.369]), and the independent factors influencing the blood lipid standard of coronary heart disease patients with stable angina (P = 0.011, 95%CI [1.133, 2.646]), but not the independent factors affecting blood glucose standard in coronary heart disease patients with diabetes (P>0.05). ConclusionCoronary artery disease patients with stable angina have geographical variability in clinical characteristics and distribution of TCM syndrome elements, and the overall control of blood pressure, blood lipids, and blood glucose is poor, and qi deficiency syndrome is an independent risk factor affecting the control of blood pressure and blood lipids.
4.A Review of Researches on Traditional Chinese Medicine for Prevention and Treatment of Common Cardio-vascular Diseases during 2021 to 2023
Yongxia WANG ; Jia ZHENG ; Qiaozhi LI ; Xinlu WANG ; Rui YU ; Jingyuan MAO ; Boli ZHANG ; Mingjun ZHU
Journal of Traditional Chinese Medicine 2024;65(11):1189-1195
This study searched the clinical researches on traditional Chinese medicine (TCM) for cardiovascular diseases registered in Chinese Clinical Trial Registry and the US Clinical Trial Registry, the cardiovascular disease-related studies funded by the National Natural Science Foundation of China, as well as those published in China National Knowledge Infrastructure (CNKI), Wanfang database, VIP.com, China Biology Medicine disc (CBMdisc), Embase, Medline, Cochrane Library, and other databases published cardiovascular disease-related studies from 1 January 2021 to 30 June 2023. In order to analyse and evaluate the research progress of TCM treatment for coronary heart disease, hypertension, heart failure, and arrhythmia, this study aimed at recent research hotspots and research direction. It is found that the research on TCM for cardiovascular diseases was gradually deepening and the high-quality evidence continued to emerge. It is believed that studies related to the prevention and treatment of common cardiovascular diseases by TCM reflected the multi-angle integration of modern technology and pattern differentiation and treatment, closer integration of clinical and basic research, and further optimisation of pattern identification and interventions. On this basis, the research programme and implementation process should be further standardized, and the translation of research results should be emphasized to promote the standardized application and promotion of TCM diagnosis and treatment of cardiovascular diseases.
5.Effectiveness of TCM Health Management for Myocardial Infarction based on Tertiary Management System: A Single-arm Cohort Study of 255 Patients
Hongxin GUO ; Mingjun ZHU ; Rui YU ; Xingyuan LI ; Guangcao PENG ; Xinlu WANG ; Jianru WANG ; Bin LI ; Qifei ZHAO ; Yongxia WANG
Journal of Traditional Chinese Medicine 2024;65(8):821-829
ObjectiveTo evaluate the efficacy of TCM health management based on tertiary management system for patients with myocardial infarction (MI). MethodsA total of 277 patients with non-acute MI were enrolled and given comprehensive TCM health management strategies including health education, lifestyle adjustment, risk factors control, medication and TCM appropriate techniques management through a tertiary management system with "the patient as the core, village/community physicians as the main executive body, and tertiary TCM hospital specialists as the leading body", for a period of 12 months by using a prospective single-arm cohort study. Through patient reporting and medical records surveys, various indicators before and after 12-month management were collected and compared. The primary efficacy indicators were readmission rate and recurrent exacerbation rate, and the secondary efficacy indicators included disease awareness-related indicators, lifestyle behavior-related indicators, cardiovascular risk factor-related indicators and Canadian cardiovascular society (CCS) cardiac function classification. ResultsA total of 255 patients completed the study and were included in the final analysis. The recurrent exacerbation and readmission rates of patients after management were 23.14% (59 cases) and 20.25% (49 cases), respectively, significantly lower than 36.08% (92 cases) and 53.72% (130 cases) before management (P<0.05). Except for knowledge on diabetes diagnostic criteria with no significant difference before and after management (P>0.05), awareness of other knowledge with regard to the prevention and treatment of cardiovascular and cerebrovascular diseases were improved after management (P<0.01), as well as the total score (P<0.01). In terms of daily life behaviors, the rates of salty diet, sweet diet and greasy diet were significantly lower than baseline, while the rate of moderate exercise was significantly higher (P<0.05 or P<0.01); the rates of ongoing smoking and vigorous exercise were not significantly changed (P>0.05). For cardiovascular risk factors, patients' total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, total depression assessment scale score, and total anxiety assessment scale score were significantly reduced after management (P<0.01). Systolic blood pressure and body mass index (BMI) were both higher after management (P<0.05 or P<0.01), and there was no statistically significant difference in diastolic blood pressure (P>0.05). In terms of the cardiovascular disease risk factors reaching the standard levels, the rate of LDL cholesterol <1.8 mmol/L significantly increased (P<0.01), while the rate of BMI <24 kg/m2 and the rate of systolic blood pressure <140 mmHg both decreased significantly (P<0.05 or P<0.01) from baseline; the diastolic blood pressure and rate of fasting glucose <7.0 mmol/L were not significantly changed (P>0.05). The patients' CCS cardiac function classification was significantly reduced (P<0.05). ConclusionTCM health management based on the tertiary management system can enhance MI patients' awareness of the disease, change poor lifestyle habits, reduce risk factors such as blood lipids and blood glucose, improve anxiety and depression, increase activity tolerance, and reduce their recurrence exacerbation and readmission rates, which is worthy of clinical promotion.
6.Screening and experimental validation of hub genes for myocardial isch-emia-reperfusion injury based on bioinformatics
Jianru WANG ; Xingyuan LI ; Shiyang XIE ; Yanling CHENG ; Hongxin GUO ; Mingjun ZHU ; Rui YU
Chinese Journal of Pathophysiology 2024;40(3):473-483
AIM:Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury(MIRI).METHODS:Firstly,the rat MIRI related dataset GSE122020,E-MEXP-2098,and E-GEOD-4105 were downloaded from the database.Secondly,differentially expressed genes(DEGs)were screened from each dataset using the linear models for microarray data(limma)package,and robust DEGs were filtered using the robust rank aggregation(RRA)method.In addition,the surrogate variable analysis(SVA)package was used to merge all datas-ets into one,and merged DEGs were screened using the limma package.The common DEGs were obtained by taking the intersection of the two channels of DEGs.Next,the protein-protein interaction(PPI)network of common DEGs was con-structed,and the hub genes were identified using the density-maximizing neighborhood component(DMNC)algorithm.The receiver operating characteristic curve(ROC)was plotted to evaluate the diagnostic performance of the hub gene.Then,the mRNA and protein expression levels of hub genes were detected in the rat MIRI model,and the literature re-view analysis was carried out on the involvement of hub genes in MIRI.Finally,the gene set enrichment analysis(GSEA)was performed on hub gene to further reveal the possible mechanism in mediating MIRI.RESULTS:A total of 143 robust DEGs and 48 merged DEGs were identified.After taking the intersection of the two,48 common DEGs were obtained.In the PPI network of common DEGs,5 hub genes were screened out,namely MYC proto-oncogene bHLH transcription fac-tor(MYC),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),caspase-3(CASP3),and plasminogen activator urokinase receptor(PLAUR).The ROC results showed that the area under the curve values for all hub genes were greater than 0.8.MYC,PTGS2,CASP3,and PLAUR showed high mRNA and protein expression in rat MIRI,while there was no difference in mRNA and protein expression for HMOX1.The literature review revealed that among the 5 hub genes,only PLAUR has not been reported to be involved in MIRI.The GSEA results for PLAUR indicat-ed that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway,P53 signaling pathway,Toll-like receptor signaling pathway,apoptosis,and fatty acid metabolism.CONCLUSION:MYC,PTGS2,CASP3,HMOX1,and PLAUR are involved in the pathological process of MIRI.PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling,P53 signaling,Toll like receptor signaling,cell apoptosis,and fatty acid metabolism.The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI.
7.Exploring the Core Medication and Efficacy Evaluation of Hypoxic Pulmonary Hypertension Based on the Traditional Chinese Medicine Inheritance Assistance Platform
Zhengwei DONG ; Min ZHANG ; Yun DING ; Zuoying XING ; Rui YU ; Mengyi ZHAO ; Guanwei FAN ; Yongxia WANG ; Mingjun ZHU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(8):2016-2022
Objective To investigate the core drugs of traditional Chinese medicine(TCM)for the treatment of hypoxic pulmonary hypertension(HPH),and to verify the drug efficacy by hypoxia combined with Su5416(Hypoxia+Su5416,HySu)-induced PH mouse model.Methods Relevant literatures on TCM treatment of HPH in China Knowledge Network,Wanfang,Weipu were collected,screened and set up a database through the nerf criteria,and inputted into the software of traditional Chinese medicine inheritance assistance platform(V2.5)for the excavation of medication law.The HySu-PH mouse model was established,and the core drugs were evaluated for drug efficacy through force exhaustion exercise running table,blood oxygen saturation,right ventricular pressure,and right heart hypertrophy index test.Results The 102 relevant formulas for the treatment of HPH were screened,involving a total of 158 traditional Chinese medicines,and the top 5 drug frequencies were Salvia miltiorrhiza,Rhizoma Chuanxiong,Astragalus membranaceus,Draba hebecarpa,and Angelica sinensis,with the highest use of blood-activating and blood-stasis removing drugs,and deficiency-tonifying drugs in the categories of drugs used,and Salvia miltiorrhiza was the core drug used.HySu-PH mouse models were constructed and given 2 weeks of treatment with the danshen preparation Danshen injection.Danshen injection significantly elevated body weight(P<0.01),oxygen saturation(P<0.05),displacement of exhaustion(P<0.01),and duration of exhaustion(P<0.05),and lowered the right ventricular systolic blood pressure(P<0.01)and the right cardiac hypertrophy index(P<0.01).Conclusion Salvia miltiorrhiza is a core drug for the treatment of HPH,and the danshen preparation Danshen injection can effectively treat HySu-PH.
8.Exploring the Mechanism of Salvia Miltiorrhiza in the Treatment of Hypoxic Pulmonary Hypertension Based on Network Pharmacology and Experimental Validation
Zhengwei DONG ; Min ZHANG ; Huan ZHAO ; Zuoying XING ; Rui YU ; Guanwei FAN ; Yongxia WANG ; Mingjun ZHU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(8):2023-2029
Objective Based on the pre-existing basis of effective treatment of hypoxia combined with Su5416-induced hypoxic pulmonary hypertension(HPH)by Salvia miltiorrhiza,to investigate the mechanism of Salvia miltiorrhiza in the treatment of HPH.Methods Using a network pharmacology approach to obtain the key pathways of Salvia miltiorrhiza for the treatment of HPH.The active ingredients of Salvia miltiorrhiza were collected to obtain the targets of the active ingredients.HPH disease targets were collected to obtain the intersection of Salvia miltiorrhiza component targets and HPH disease targets.Protein-Protein Interaction Networks(PPIs)were constructed and KEGG analysis was performed to obtain the key pathways of Salvia miltiorrhiza for HPH.Then used molecular biology to validate the key pathways.Results The 81 targets of Salvia miltiorrhiza for the treatment of HPH were obtained by network pharmacology,and PPI showed that drug component-disease common core targets included ATK1,TNF,EGFR,IL6,ESR1,and KEGG-enriched Pathway mainly included PI3K-AKT signaling pathway,HIF-1 signaling pathway,MAKP signaling pathway,TNF signaling pathway,JAK-STAT signaling pathway and so on.Molecular biological assays showed that Salvia miltiorrhiza had the effect of reducing lung tissue fibrosis and inhibiting the PI3K/AKT signalling pathway in HySu-PH mice.Conclusion Salvia miltiorrhiza has the effect of attenuating pulmonary fibrosis,and its mechanism of action is related to the inhibition of the PI3K/Akt signalling pathway.
9.Analysis of risk factors and establishment of prediction model for immune checkpoint inhibitor related myocarditis and major adverse cardiovascular events
Rui LU ; Jing LU ; Yi LIAO ; Wenjie LUO ; Min WANG ; Mingjun LU
Chinese Journal of Cardiology 2024;52(11):1290-1295
Objectives:To explore the risk factors of major adverse cardiovascular events (MACEs) in immune checkpoint inhibitor (ICI) related myocarditis and establish a predictive model.Methods:This was a retrospective case-control study. Tumor patients diagnosed with ICI related myocarditis in the First Affiliated Hospital of Guangzhou Medical University from May 2019 to August 2023 were selected and divided into non-MACE group and MACE group based on whether MACE occurred. Clinical and imaging data of the two groups were collected. Univariate and multivariate logistic regression models were used to analyze the risk factors for MACE in patients with ICI related myocarditis. According to the results of multivariate logistic regression analysis, R 4.1.0 software was used to construct the MACE risk prediction model for these patients and draw a nomogram. The receiver operating characteristic curve was used to evaluate the prediction ability of the prediction model.Results:A total of 35 patients with ICI related myocarditis, aged (63.9±8.2) years, were included, including 28 males (80%). There were 18 patients in the non-MACE group and 17 patients in the MACE group. Multivariate logistic regression analysis showed that elevated neutrophil to lymphocyte ratio ( OR=1.115, 95% CI 1.007-1.235, P=0.036) and ST-T segment changes ( OR=24.942, 95% CI 1.239-502.194, P=0.036) were risk factors for MACE in patients with ICI related myocarditis. The receiver operating characteristic curve indicated that the area under the curve of the prediction model was 0.967 (95% CI 0.916-1.000, P<0.001), with a sensitivity of 88.2% and specificity of 100%, demonstrating good predictive ability. Conclusion:Elevated neutrophil to lymphocyte ratio and ST-T segment change are independent risk factors for MACE in patients with ICI related myocarditis. Risk prediction model based on the above two indicators can assist in the early identification and individualized intervention of ICI related myocarditis patients.
10.Study on value-based medical insurance access and pricing methods of multi-indication drugs
Yingcheng WANG ; Yao WU ; Lan YANG ; Mingjun RUI ; Hongchao LI
China Pharmacy 2023;34(2):179-184
OBJECTIVE To discuss medical insurance access and pricing methods for multi-indication drugs. METHODS The access situation of multi-indication drugs in China’s medical insurance negotiation over the years was sorted out. Referring to the economic theory of value-based pricing and the relevant experience of other countries, five applicable pricing methods of 3 categories for multi-indication drug in China were summarized. Taking ceftazidime-avibactam(CAZ-AVI) as an example, cost- utility analyses were performed for different indications, and appropriate pricing methods were applied. RESULTS & CONCLUSIONS All multi-indication drugs in China adopted a single pricing method. The pricing methods that could be explored include product-based pricing, such as single pricing based on the lower-value indication or mixed/weighted single pricing; indication-based pricing, such as developing a new agreement for single pricing under different discounts and listing with different brands and pricing of the same medicine for different indications; and compensation for access restrictions. Each method has its advantages and limitations. The case of CAZ-AVI showed that it is necessary to estimate the value of each indication for multi- indication drugs, and comprehensively consider appropriate access conditions and pricing methods based on value. Although single pricing is simple to operate, it is different to reflect the value entirely. The indication-based pricing and compensation for access restrictions all depend on the information collection system and the cooperation of multiple departments. China is supposed to carry out the value-based pricing of multi-indication drugs and constantly explore reasonable access methods to improve overall social welfare.

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