1.Exploring Biological Characteristics of Rat Model of Atrial Fibrillation with Phlegm-heat and Blood Stasis Pattern Based on Metabolomics
Ailin HOU ; Yuxuan LIU ; Wenxi YU ; Xing JI ; Chan WU ; Dazhuo SHI ; Ying ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):245-255
ObjectiveTo establish an animal model of atrial fibrillation(AF) that accurately reflects the phlegm-heat and blood stasis(TRYZ) pathogenesis in traditional Chinese medicine. MethodsForty SPF-grade SD rats were randomly assigned using a random number table to the following groups:the control group, the TRYZ+AF group,the AF group and the TRYZ group, with ten rats in each group. The TRYZ+AF and TRYZ groups underwent a high-fat diet combined with intraperitoneal lipopolysaccharide(LPS) injection to simulate the pathological alterations of TRYZ syndrome. Groups TRYZ+AF and AF were induced with acetylcholine-calcium chloride(Ach-CaCl2) via caudal vein injection to induce AF. The control group received no intervention and was maintained under normal conditions. The modeling period lasted 3 weeks. Electrocardiography was used to assess AF episodes and duration, echocardiography evaluated left atrial dimensions and cardiac function, fully automated biochemical analyzer measured the levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C) and low-density lipoprotein cholesterol(LDL-C), hemoreometer analyzed the whole blood viscosity, plasma viscosity, and whole blood reduced viscosity, a coagulation analyzer assessed prothrombin time(PT), activated partial thromboplastin time(APTT), thrombin time(TT), and fibrinogen(FIB), enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of C-reactive protein(CRP), interleukin(IL)-1β, IL-6, IL-17, tumour necrosis factor(TNF)-α, matrix metalloproteinase-9(MMP-9), galectin-3(Gal-3), Collagen Ⅰ, and α-smooth muscle actin(α-SMA). Hematoxylin-eosin(HE) staining and Masson's trichrome staining were used to analyze pathological changes in atrial myocardium, Western blot was employed to detect MMP-9, Collagen Ⅰ and α-SMA protein expression in myocardial tissue, real-time quantitative polymerase chain reaction(Real-time PCR) evaluated fibrous factor gene expression levels. Changes in the TRYZ syndrome were assessed via body weight, tongue color[red(R), green(G), and blue(B)], and rectal temperature. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to detect differential metabolites between the control group and the TRYZ+AF group. ResultsFollowing three weeks of sustained modeling, compared with the control group, rats in the TRYZ+AF and the TRYZ groups exhibited reduced body weight, dry faeces, elevated rectal temperature, dark red tongue, decreased RGB values on the tongue surface, and markedly elevated TC and LDL-C levels(P<0.05, P<0.01). The TRYZ+AF, TRYZ, and AF groups exhibited significantly decreased TT, APTT and PT, along with markedly elevated whole blood viscosity and FIB(P<0.05, P<0.01). Rats in the TRYZ+AF and AF groups exhibited AF rhythm, markedly decreased heart rate, prolonged RR intervals, enlarged left atrium, and significantly reduced ejection fraction and shortening fraction(P<0.05, P<0.01). Serum levels of CRP, IL-1β, IL-6, IL-17, TNF-α, MMP-9, Gal-3, Collagen Ⅰ, and α-SMA were elevated in rats from the TRYZ+AF, TRYZ, and AF groups compared to the control group, with the most pronounced increase observed in the TRYZ+AF group(P<0.05, P<0.01). Histopathology revealed that the collagen fiber deposition in the atrial of rats in the TRYZ+AF, TRYZ and AF groups was higher than that in the control group(P<0.05, P<0.01). Western blot and Real-time PCR results further demonstrated that the protein and mRNA expression levels of MMP-9, Collagen Ⅰ and α-SMA in the myocardial tissue of the TRYZ+AF group were higher than those in the other three groups(P<0.05, P<0.01). Metabolomic analysis revealed 173 differentially expressed metabolites in the TRYZ+AF group and the control group, primarily enriched in pathways such as glycerophospholipid metabolism and glycolysis/gluconeogenesis. ConclusionThis study successfully establishes a rat model of AF integrated with the TRYZ syndrome, demonstrating the pathological process where the interactions of phlegm, heat and stasis jointly trigger tremor, this provides a reliable experimental tool for in-depth research into the biological basis of this disease syndrome.
2.The emerging role of lncRNA-mediated ceRNA regulatory networks in atherosclerosis-associated endothelial dysfunction
Jinwen LUO ; Min LIU ; Min LI ; Yanqiao YU ; Dazhuo SHI ; Xiaojuan MA
Chinese Journal of Arteriosclerosis 2025;33(2):169-177
Endothelial dysfunction is a pivotal contributor to atherosclerosis(As)pathogenesis.A comprehensive understanding of the mechanisms of endothelial dysfunction would provide novel insights into effective treatment of As.Recent advances in genome and transcripome technology have enabled researchers to further explore the molecular mecha-nisms of endothelial dysfunction.It has been found that the regulatory network of competitive endogenous RNA(ceRNA)mediated by long non-coding RNA(lncRNA)plays a key role in endothelial dysfunction.lncRNA acts as a"molecular sponge"for microRNA(miRNA)to block the post-transcriptional repression of miRNA on downstream target gene messen-ger RNA(mRNA)by binding to miRNA,thereby regulating the function and phenotypic conversion of endothelial cell(EC)lncRNA-miRNA-mRNA interactions are widely involved in play an essential role EC inflammatory responses,apopto-sis,autophagy,angiogenesis,and endothelial-mesenchymal transition(EndMT).Which suggests that it may be a poten-tial therapeutic targets for As.
3.Distribution of Clinical Features and Correlation Analysis between TCM Syndromes and Laboratory Indexes in 924 Cases of Atrial Fibrillation
Ailin HOU ; Yuxuan LIU ; Hongbo HUANG ; Ying ZHANG ; Dazhuo SHI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):153-158
Objective To explore the distribution of clinical features and the correlation between TCM syndromes and laboratory indicators in patients with atrial fibrillation.Methods Retrospective analysis was performed on 924 patients with atrial fibrillation who were hospitalized in Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2016 to December 2023.The distribution pattern of TCM syndromes in patients with atrial fibrillation was analyzed,and the correlation between TCM syndromes and age,gender,past history,inflammatory indicators and biochemical indicators were explored.Results The study included 924 atrial fibrillation patients,predominantly female and mostly middle-aged or elderly.The main TCM syndrome types were qi-yin deficiency syndrome,qi deficiency and blood stasis syndrome,phlegm fire disturbance syndrome and phlegm blood stasis obstruction syndrome.Correlation analysis showed that patients with qi-yin deficiency syndrome had lower total protein and globulin,and the two were negatively correlated;qi deficiency and blood stasis syndrome were positively correlated with high density lipoprotein cholesterol levels;patients with phlegm fire disturbance syndrome were mostly male,younger in age and had a higher proportion of smoking history.They were negatively correlated with gender,age,and smoking history,and positively correlated with comorbidities of coronary heart disease,white blood cells,neutrophils,total protein,albumin,and globulin;patients with phlegm blood stasis obstruction syndrome were positively correlated with creatine kinase and uric acid,with statistical significance(P<0.05).Conclusion The TCM syndrome of atrial fibrillation is mainly characterized by qi-yin deficiency,and the proportion of phlegm and fire disturbance syndrome is increasing year by year.There is a correlation between the TCM syndromes of atrial fibrillation and clinical features(gender,age,past history),laboratory indicators such as inflammatory markers(WBC,NE,SII,NLR),total proteins,globulins,high density lipoprotein cholesterol,creatine kinase and uric acid,which can provide a guide to the"differentiation of disease,syndromes and body"in the diagnosis of atrial fibrillation.
4.The emerging role of lncRNA-mediated ceRNA regulatory networks in atherosclerosis-associated endothelial dysfunction
Jinwen LUO ; Min LIU ; Min LI ; Yanqiao YU ; Dazhuo SHI ; Xiaojuan MA
Chinese Journal of Arteriosclerosis 2025;33(2):169-177
Endothelial dysfunction is a pivotal contributor to atherosclerosis(As)pathogenesis.A comprehensive understanding of the mechanisms of endothelial dysfunction would provide novel insights into effective treatment of As.Recent advances in genome and transcripome technology have enabled researchers to further explore the molecular mecha-nisms of endothelial dysfunction.It has been found that the regulatory network of competitive endogenous RNA(ceRNA)mediated by long non-coding RNA(lncRNA)plays a key role in endothelial dysfunction.lncRNA acts as a"molecular sponge"for microRNA(miRNA)to block the post-transcriptional repression of miRNA on downstream target gene messen-ger RNA(mRNA)by binding to miRNA,thereby regulating the function and phenotypic conversion of endothelial cell(EC)lncRNA-miRNA-mRNA interactions are widely involved in play an essential role EC inflammatory responses,apopto-sis,autophagy,angiogenesis,and endothelial-mesenchymal transition(EndMT).Which suggests that it may be a poten-tial therapeutic targets for As.
5.Distribution of Clinical Features and Correlation Analysis between TCM Syndromes and Laboratory Indexes in 924 Cases of Atrial Fibrillation
Ailin HOU ; Yuxuan LIU ; Hongbo HUANG ; Ying ZHANG ; Dazhuo SHI
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):153-158
Objective To explore the distribution of clinical features and the correlation between TCM syndromes and laboratory indicators in patients with atrial fibrillation.Methods Retrospective analysis was performed on 924 patients with atrial fibrillation who were hospitalized in Xiyuan Hospital of China Academy of Chinese Medical Sciences from January 2016 to December 2023.The distribution pattern of TCM syndromes in patients with atrial fibrillation was analyzed,and the correlation between TCM syndromes and age,gender,past history,inflammatory indicators and biochemical indicators were explored.Results The study included 924 atrial fibrillation patients,predominantly female and mostly middle-aged or elderly.The main TCM syndrome types were qi-yin deficiency syndrome,qi deficiency and blood stasis syndrome,phlegm fire disturbance syndrome and phlegm blood stasis obstruction syndrome.Correlation analysis showed that patients with qi-yin deficiency syndrome had lower total protein and globulin,and the two were negatively correlated;qi deficiency and blood stasis syndrome were positively correlated with high density lipoprotein cholesterol levels;patients with phlegm fire disturbance syndrome were mostly male,younger in age and had a higher proportion of smoking history.They were negatively correlated with gender,age,and smoking history,and positively correlated with comorbidities of coronary heart disease,white blood cells,neutrophils,total protein,albumin,and globulin;patients with phlegm blood stasis obstruction syndrome were positively correlated with creatine kinase and uric acid,with statistical significance(P<0.05).Conclusion The TCM syndrome of atrial fibrillation is mainly characterized by qi-yin deficiency,and the proportion of phlegm and fire disturbance syndrome is increasing year by year.There is a correlation between the TCM syndromes of atrial fibrillation and clinical features(gender,age,past history),laboratory indicators such as inflammatory markers(WBC,NE,SII,NLR),total proteins,globulins,high density lipoprotein cholesterol,creatine kinase and uric acid,which can provide a guide to the"differentiation of disease,syndromes and body"in the diagnosis of atrial fibrillation.
6.Intervention of traditional Chinese patent medicine based on syndrome differentiation in female patients after percutaneous coronary intervention due to acute coronary syndrome: a nationwide multicenter prospective cohort study
Ruina BAI ; Feng GU ; Yajie CAI ; Song SHENG ; Qiaoning YANG ; Ruixi XI ; Lizhi LI ; Dazhuo SHI
Chinese Journal of Cardiology 2024;52(9):1073-1080
Objective:To evaluate the efficacy and safety of discriminative application of Chinese patent medicines in female patients after percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS).Methods:The study population was from the Chinese Patent Medicine (CPM) trial. CPM trial was a multicenter prospective cohort study, which enrolled patients from 40 centers in mainland China between February 2012 and December 2015, with the discriminative use of Chinese patent medicines as the exposure factor. Female patients with ACS after PCI who completed 36-month follow-up were included in this analysis, and were divided into a conventional treatment group (using conventional western medicine recommended by the guidelines) and a group with the discriminative use of proprietary Chinese medicines (on the basis of conventional western medicine treatment, discriminative use of Qishen Yiqi dropping pills for Qi deficiency and blood stasis syndrome, Guanxin Danshen dropping pills for blood stasis syndrome, and Danlou tablets for phlegm and blood stasis syndrome combined with the conventional western medicine). The primary endpoint event was a composite endpoint event including cardiovascular death, nonfatal myocardial infarction, and emergency revascularization surgery. Secondary endpoint events were composite endpoint events including readmission for ACS, heart failure, stroke, and other thrombotic events. Adverse events were collected. Cox proportional risk model was used to assess the effect of discriminatory application of Chinese patent medicine on endpoint events, and sensitivity analysis was performed by comparing the results with propensity score matching analysis.Results:A total of 748 female ACS post-PCI patients were included in the analysis, aged (63.2±8.3) years. There were 370 patients in the group of discriminative application of Chinese patent medicines and 378 patients in the conventional treatment group. There were 37 cases (10.0%) and 58 cases (15.3%) of primary endpoint events in the discriminatory application of Chinese patent medicines group and the conventional treatment group, respectively. Cox analysis showed that the risk of primary endpoint in the discriminatory application of Chinese patent medicines group was lower than that in the conventional treatment group after adjusting for confounding factors (adjusted HR=0.62, 95% CI 0.40-0.96, P=0.031). There were 38 (10.3%) and 57 (15.1%) cases of secondary endpoint events in the two groups, respectively. Cox regression analysis showed that the risk of secondary endpoint events in the discriminatory application of Chinese patent medicine group was lower than that in the conventional treatment group after adjusting for confounders (adjusted HR=0.56, 95% CI 0.37-0.87, P=0.001). The results of propensity score matching analysis also showed that Chinese patent medicines based on discriminatory application could reduce the risk of primary endpoint ( HR=0.62,95% CI 0.40-0.97 ,P=0.033) and second endpoint ( HR=0.56, 95% CI 0.37-0.87, P=0.009) significantly. There was no significant difference in adverse events between the two groups (12.4% (46/370) vs. 10.3% (39/378), P=0.362). Conclusion:On the basis of conventional western medicine treatment, discriminatory application of Chinese patent medicines can reduce the risk of endpoints in female patients after PCI due to ACS without significant adverse effects.
7.Prediction Study on Potential Chinese materia medica for the Treatment of coronary microvascular dysfunction
Chunlin ZHU ; Dazhuo SHI ; Kangkang WEI ; Lina MIAO ; Jie GAO
International Journal of Traditional Chinese Medicine 2024;46(2):222-228
Objective:To predict Chinese materia medica that may prevent and treat coronary microvascular dysfunction (CMD) by identifying disease core targets.Methods:CMD- related targets were obtained through GeneCards and OMIM databases. Subnetworks were extracted by using MCODE plugin in Cytoscape 3.9.1. Core targets of subnetworks were obtained by using cytoNCA plugin. GO function and KEGG pathway enrichment analysis for core targets were performed by using Metascape. Coremine Medical database was used to match targets with Chinese materia medica. Obtained Chinese materia medica was screened, and their properties and tastes, meridians and efficacy categories were under statistics.Results:Totally 3 859 disease-related targets were screened and five subnetworks were obtained. An in-depth study of MCODE1 yielded ten core targets, including IL-1β, IL6, TNF, STAT3, AKT1, ACTB, VEGFA, GAPDH, TP53, and ALB. GO functional enrichment analysis showed that these core targets were mainly involved in biological processes, such as positive regulation of gene expression, positive regulation of transcription, DNA template, and negative regulation of gene expression. KEGG pathway enrichment analysis identified 67 signaling pathways, including the AGEs-RAGE signaling pathway, HIF-1 signaling pathway, adipocytokine signaling pathway, fluid shear stress, and atherosclerosis. The researchers identified 36 kinds of Chinese materia medica associated with the ten core targets, including Salviea Miltiorrhizae Radix et Rhizoma, Chuanxiaong Rhizoma, Carthami Flos, Paeoniae Radix Rubra, Coptidis Rhizoma, Ginseng Radix et Rhizoma, Ophiopogonis Radix, Schisandrae Chinensis Fructus, Cinnamomi Cortex, Nelumbinis Semen, and Valerianae Jatamansi Rhizoma et Radix among 880 herbs.Conclusion:This study predicts 36 kinds of Chinese materia medica that have the effect of preventing and treating CMD, which can provide research ideas for the development of new drugs.
8.Analysis of the Nature,Flavor and Combination Characteristics of the Two-herb Compound Formulas inTreatise on Cold Damage and Miscellaneous Diseases (《伤寒杂病论》)
Ying ZHANG ; Yihan ZHAO ; Qinghua SHANG ; Ruina BAI ; Wenhui DUAN ; Jianpeng DU ; Zhuye GAO ; Zhonghui JIANG ; Dazhuo SHI
Journal of Traditional Chinese Medicine 2024;65(22):2378-2382
Based on the natures and flavors of herbal medicinals recorded in Shen Nong's Classic of the Materia Medica (《神农本草经》); Miscellaneous Records of Famous Physicians (《名医别录》), this study analyzed the characte-ristics of the natures, flavors and combination of medicinals of the two-herb compound formulas in Treatise on Cold Damage and Miscellaneous Diseases (《伤寒杂病论》).Finally, 31 compound formulas were included, and it was found that the nature and flavor of the herbs in these two-herb compound formulas are closely related to the functions of the compound formulas, such as the common pairing of the acrid and the sweet herbs to warm yang and transform qi, the acrid and the bitter herbs in pairs to regulate and harmonize cold and heat, the sweet and the bitter in pairs to remove dampness and clear heat, the acrid and the acrid in pairs to arrest vomiting and direct qi downward, and the sour and the sweet in pairs to slow the urgent and relieve pain. Regardless of the deficiency or excess nature of the disease, the corresponding two-herb compound formulas often aim to reinforce healthy qi while eliminating pathogenic factors, with some formulas showcasing a unique correspondence between the disease pattern and the symptoms addressed.
9.A Prospective Cohort Study on the Risk of Major Adverse Cardiovascular Events in Patients with Coronary Heart Disease after Percutaneous Coronary Intervention with Blood-invigorating and Stasis-dissolving Medicinals
Lintong YU ; Shiyi TAO ; Xiaojuan MA ; Jie GAO ; Hua QYU ; Yu YANG ; Bingchang CHEN ; Dazhuo SHI
Journal of Traditional Chinese Medicine 2024;65(18):1895-1902
ObjectiveTo explore the impact of blood-invigorating and stasis-dissolving medicinals combined with conventional western medicine on the major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). MethodsA prospective cohort study was conducted to collect data on consecutive cases of CHD after PCI. According to whether blood-invigorating and stasis-dissolving medicinals were used, the cases were divided into a Chinese herbal medicinals (CHM) group and control group. The primary outcome was the incidence of MACE one year after PCI, while the secondary outcomes included TCM syndrome score and echocardiography left ventricular ejection fraction (LVEF). Logistic regression analysis was performed to explore the influencing factors of MACE. ResultsA total of 844 patients who met the criteria were included, with 617 in the CHM group and 227 in the control group. The main blood-invigorating and stasis-dissolving medicinals being used were Danshen (Radix et Rhizoma Salviae Miltiorrhizae, 46.35%), Chuanxiong (Rhizoma Chuanxiong, 45.87%), and Chishao (Radix Paeoniae Rubra, 42.30%). After a median follow-up of 12.73 months, the incidence of MACE in the CHM group (142/617, 23.01%) was significantly lower than that in the control group (68/227, 29.96%) with significant difference (OR=0.70, 95%CI 0.50 to 0.98, P = 0.04). The LVEF of the CHM group [(60.06±6.13)%] was higher than that of the control group [(58.27±7.36)%] with significant difference (t = 0.356, P<0.01). The TCM syndrome score in the CHM group decreased to 12.66±4.47, while that in the control group increased to 13.81±3.88, with the results favoring the CHM group (t = 2.78, P<0.01). Univariate analysis showed correlations between the incidence of MACE after PCI and the use of blood-invigorating and stasis-dissolving medicinals, LVEF, usage of renin-angiotensin-aldosterone system (RAAS) inhibitors, TCM syndrome score, and usage of β blockers (P<0.05). Multivariate analysis showed that the use of blood-invigorating and stasis-dissolving medicinals was significantly associated with the reduction of MACE (P<0.01), while the baseline LVEF decline, TCM syndrome score increase, no use of RAAS inhibitors or β blockers were the risk factors of MACE after PCI (P<0.05). ConclusionThe use of blood-invigorating and stasis-dissolving medicinals based on the conventional western medicine can reduce the risk of MACE one year after PCI of CHD, improve the TCM syndromes and protect heart function.
10.Influence of Chinese medicinals with functions of activating blood and re-moving toxicity on inflammatory markers and blood fat in patients with acute coronary syndrome after percutaneous coronary intervention
Ming GUO ; Zhuye GAO ; Peili WANG ; Dazhuo SHI
Journal of Beijing University of Traditional Chinese Medicine 2018;41(5):423-427
Objective To observe the influence of routine statins drugs combined with Guanxin Danshen (Coronary Salvia Root)Gutta Pills and Chuanxinlian(Andrographitis)Tablet on serum inflammatory markers and blood fat in patients with acute coronary syndrome(ACS)after percutaneous coronary inter-vention(PCI).Methods ACS patient(n=40)were randomly divided into control group and treatment group(each n=20)after PCI.The control group was treated with basic therapy of Western medicine and statins,and treatment group was additionally given Guanxin Danshen Gutta Pills and Chuanxinlian Tablet for 30 d.The levels of serum high sensitivity C-reactive protein(hs-CRP), tumor necrosis factor-α (TNF-α)and blood fat were detected by using ELISA,and integrals of blood stasis pattern were calculat-ed.Results The levels of hs-CRP and TNF-αdecreased significantly in 2 groups after treatment(P<0.05 or P<0.01), and difference between 2 groups had statistical significance after treatment(P<0.01).The level of serum total cholesterol(TC)decreased significantly and level of high-density lipo-protein-cholesterol(HDL-C increased in treatment group(P<0.05).The integrals of blood stasis pat-tern decreased significantly in treatment group after treatment(P<0.01).Conclusion Guanxin Dan-shen Gutta Pills and Chuanxinlian Tablet,with effects of activating blood and removing toxicity,can fur-ther reduce the levels of inflammatory markers, hs-CRP and TNF-α, relieve blood stasis and assist to control blood fat in patients with ACS after PCI.

Result Analysis
Print
Save
E-mail