To explore the regulatory effect of Buyang Huanwu Decoction on cerebral infarction based on quantitative proteomics.

Buyang Huanwu Decoction (BYHW) contains chemical components such as ligustrazine, oxypaeoniflora, chlorogenic acid, and others. To explore the neuroprotective effect and potential target protein of BYHW in cerebral infarction (CI). A double-blind, randomized controlled trial was established and patients with CI were divided into the BYHW group (n = 35) and the control group (n = 30). To evaluate the efficacy by TCM syndrome score and clinical indicators, and to explore the changes of serum proteins by proteomics technology, so as to explore the mechanism of BYHW and potential target proteins. The study found that compared with the control group, the TCM syndrome score, including Deficiency of Vital Energy (DVE), Blood Stasis (BS), and NIHSS in the BYHW group decreased significantly (p < 0.05), and the Barthel Index (BI) score was significantly higher. A total of 99 differential regulatory proteins were identified by proteomics, which act on lipids and atherosclerosis, complement and coagulation cascade, and TNF-α signaling pathway. In addition, Elisa verified the results of proteomics and found that BYHW can reduce the neurological impairments focus on IL-1ß, IL-6, TNF-α, MCP-1, MMP-9, and PAI-1. Significance: In this study, quantitative proteomics was used in combination with liquid chromatography-mass spectrometry (LC-MS/MS) to study the therapeutic effect of BYHW on cerebral infarction (CI) and potential changes in serum proteomics. In addition, the public proteomics database was used for bioinformatics analysis, and Elisa experiment verified the results of proteomics, further clarifying the potential protection mechanism of BYHW on CI.

Differential expression profiles analysis of DNA methylation between “disease” and “syndrome” in coronary heart disease-induced unstable angina patientswith Qi deficiency and blood stasis syndrome / 数字中医药（英文）

Objective@#To explore the differential expression profiles of DNA methylation sites/regions and potential molecular mechanisms in the peripheral blood of coronary heart disease (CHD)-induced unstable angina pectoris patients with or without Qi deficiency and blood stasis syndrome, and to provide scientific evidence for the conbination of disease and syndrome.@*Methods@#According to the pre-determined inclusion and exclusion criteria, the study subjects were enrolled and divided into two groups namely CHD-induced unstable angina group (G group) and healthy control group (J group) to conduct “disease” analysis, while G group was further divided into Qi deficiency and blood stasis syndrome group (case group) and non-Qi deficiency blood stasis syndrome group (control group) to perform “syndrome” analysis. The general data and clinical information of the study subjects were collected. The peripheral venous blood was extracted on an empty stomach, and the Illumina Infinium MethylationEPIC BeadChip (850K methylation chip) was used to detect the differential expressionprofiles of DNA methylation in each group, ChAMP software (V 2.14.0) was used for the differential methylation data analysis, with a threshold of the adjusted P value (adj.P.val) < 0.01. Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) were employed for the functional and pathway enrichment analyses of related mapped genes.@*Results@#A total of 263 differentially methylated CpG positions (DMPs) were screened out between G and J groups, including 191 hypermethylated positions such as cg05845204 and cg08906898, and 72 hypomethylated positions such as cg26919182 and cg13149459. These positions were mainly mapped to 148 genes encompassing RNA binding motif protein 39 (RBM39), acetyl-CoA acyltransferase 2 (ACAA2), protein phosphatase 1 regulatory subunit 12B (PPP1R12B), and the dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2). GO functional enrichment analysis revealed that the genes of the DMPs were primarily enriched in protein localization to chromosomes, regulation of cell morphogenesis, negative regulation of calcium-mediated signals, etc. KEGG pathway analysis suggested that the genes were mainly enriched in fatty acid metabolism and endocytosis pathways. In addition, a total of 23 differential methylation regions (DMRs) were identified, with overlapping genes such as transmembrane protein 232 (TMEM232), ribosomal protein large P1 (RPLP1), peroxisomal biogenesis factor 10 (PEX10), and forkhead box N3 (FOXN3) recognized. It was found that GO functions were mainly enriched in the negative regulation of Ras protein signal transduction, small GTPase-mediated signal transduction, negative regulation, etc. A total of 1 703 differential methylation sites were screened out between case and control groups, including 444 increased methylation positions such as cg05573767 and 1 259 decreased methylationpositions such as cg19938535, and cg03893872. These positions were mapped to 1 108 genes such as ribosomal protein S6 kinase A2 (RPS6KA2), leucine rich repeat containing 16A (LRRC16A), and hedgehog acyltransferase (HHAT). According to the GO functional enrichment analysis, the genes relating to the DMPs were mainly enriched in biological functions such as transmembrane receptor protein serine/threonine kinase signaling pathway and axonogenesis. The KEGG pathway enrichment analysis suggested the involvement of Rap1 signaling pathway, adenosine 5’-monophosphate-activated protein kinase (AMPK) signaling pathway, etc. A total of 21 DMRs were identified, including 22 overlapping genes such as mucin 4 (MUC4), three prime repair exonuclease 1 (TREX1), and LIM homeobox 6 (LHX6). GO analysis demonstrated that the genes primarily participated in molecular functions such as positive regulation of transmembrane transport, regulation of fatty acid metabolism, and copper ion binding.@*Conclusion@#This study reveals the methylation patterns of DMPs and DMRs in patients with Qi deficiency and blood stasis syndrome caused by CHD-induced unstable angina pectoris. Potential epigenetic regulation of fatty acid metabolism, Rap1 signaling, and other molecular functions are involved in the development of CHD between the "disease" and "syndrome".

[Effects of Qilong Capsules on myocardial fibrosis and insufficient blood circulation in ischemic cardiomyopathy with Qi deficiency and blood stasis].

Protective effect of Qilong Capsules(QL) on the myocardial fibrosis and blood circulation of rats with coronary heart disease of Qi deficiency and blood stasis type was investigated. Sleep deprivation and coronary artery ligation were used to construct a disease-symptom combination model, and 60 SD rats were divided into sham operation(sham) group, syndrome(S) group, disease and syndrome(M) group and QL group randomly. The treatment group received administration of QL 0.4 g·kg~(-1)·d~(-1). Other groups were given the same amount of normal saline. The disease indexes of each group [left ventricular end diastolic diameter(LVESD), left ventricular end systolic diameter(LVEDD), left ventricular ejection fraction(LVEF), left ventricular axis shortening rate(LVFS), myocardial histopathology, platelet morphology, peripheral blood flow] and syndrome indexes(tongue color, pulse, grip power) were detected. In sham group, cardiomyocytes and myocardial fibers were arranged neatly and densely with clear structures. The tongues' color in sham were light red, and the pulse shape were regular. RGB is a parameter reflected the brightness of the image of the tongue. In the S group, the amplitude and frequency of the animal's pulse increased accompanied by decreasing R,G,B, however, the decreased R,G,B was accompanied by reduced pulse amplitude in M group. And in M group, we observed fuzzy cell morphology, hypertrophied myocytes, disordered arrangement of cardiomyocytes and myocardial fibers, reduced peripheral blood flow and increased collagen volume fraction(CVF). Increased LVESD and LVEDD, and decreased LVEF and LVFS represented cardiac function in S group was significantly lower than that in sham. In QL group, the tongue's color was red and the pulse was smooth. The myocardial fibers of the QL group were arranged neatly and secreted less collagen. It improved the blood circulation in the sole and tail, and reversed the increasing of LVEDD, LVESD and the decreasing of LVEF and LVFS of M group. Platelets in M and S group showed high reactivity, and QL could decrease aggregation risk. In conclusion, Qilong Capsules has an obvious myocardial protective effect on ischemic cardiomyopathy, which may inhibit the degree of myocardial fibrosis and reduce platelet reactivity.

[Clinical comprehensive evaluation of Qilong Capsules in treatment of ischemic stroke with Qi deficiency and blood stasis syndrome].

The present study systematically sorted out the existing research on Qilong Capsules in the treatment of ischemic stroke with Qi deficiency and blood stasis syndrome and comprehensively evaluated its clinical evidence and value to highlight the advantages and characteristics of products and provide references for the decision-making of national pharmaceutical management departments. Based on the evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, and pharmacoeconomics, the qualitative and quantitative evaluation of "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, and accessibility, as well as characteristics of traditional Chinese medicine(TCM) was performed with multi-criteria decision analysis(MCDA) mo-del using the information, such as public data, literature data, pharmaceutical research, and questionnaire survey, and CSC v2.0 was used to calculate the clinical value of Qilong Capsules. The evaluation results were grade A, B, C, or D. Spontaneous reporting system(SRS) monitoring data, literature reports, clinical trials, and other multi-source safety evidence showed that the main adverse reactions of this drug included dry mouth, nausea, and rash, and no severe adverse reactions was found. The evidence was sufficient with small and controllable known risks, and the safety was grade A. Meta-analysis showed that Qilong Capsules combined with conventional western medicine in the treatment of acute ischemic stroke was superior to the control group in improving neurological deficits, clinical total response rate, patients' activities of daily living, and hemorheological indexes. The level of evidence was high with manifest clinical significance, and the effectiveness was grade A. The results of pharmacoeconomic research showed that Qilong Capsules combined with conventional western medicine in the treatment of ischemic stroke were advantageous in cost-effectiveness as compared with conventional western medicine alone, but the incremental effect was not significant. The quality evaluation results of the economic report were comparatively clear, and the economy was grade B. Aiming at major cerebrovascular diseases in the society and giving full play to the advantages of TCM, Qilong Capsules focused on the inheritance of classics and scientific and technological innovation, and innovation was grade B. The results of the questionnaire survey showed that the technical characteristics and drug application could meet the medication needs of clinical doctors and patients, and the suitability was grade B. The price level of this drug was comparatively high and the affordability was good since the treatment cost accounted for a small proportion of disposable income. The drug accessibility was good with a wide range of drug sales, sufficient production capacity, and sustainable medicinal materials resources, and was grade B. This drug was derived from the classic prescription Buyang Huanwu Decoction with rich experience of human application, which could regulate Qi and blood circulation, and the section of TCM characteristics was grade B. Based on the evidence evaluation results of "6+1" dimensions of Qilong Capsules, the comprehensive evaluation of clinical value was class A. It is suggested that it can be transformed into relevant policy results of basic clinical medication management according to procedures.

Clinical comprehensive evaluation of Qilong Capsules in treatment of ischemic stroke with Qi deficiency and blood stasis syndrome / 中国中药杂志

The present study systematically sorted out the existing research on Qilong Capsules in the treatment of ischemic stroke with Qi deficiency and blood stasis syndrome and comprehensively evaluated its clinical evidence and value to highlight the advantages and characteristics of products and provide references for the decision-making of national pharmaceutical management departments. Based on the evidence-based medicine, epidemiology, clinical medicine, evidence-based pharmacy, and pharmacoeconomics, the qualitative and quantitative evaluation of "6+1" dimensions of safety, effectiveness, economy, innovation, suitability, and accessibility, as well as characteristics of traditional Chinese medicine(TCM) was performed with multi-criteria decision analysis(MCDA) mo-del using the information, such as public data, literature data, pharmaceutical research, and questionnaire survey, and CSC v2.0 was used to calculate the clinical value of Qilong Capsules. The evaluation results were grade A, B, C, or D. Spontaneous reporting system(SRS) monitoring data, literature reports, clinical trials, and other multi-source safety evidence showed that the main adverse reactions of this drug included dry mouth, nausea, and rash, and no severe adverse reactions was found. The evidence was sufficient with small and controllable known risks, and the safety was grade A. Meta-analysis showed that Qilong Capsules combined with conventional western medicine in the treatment of acute ischemic stroke was superior to the control group in improving neurological deficits, clinical total response rate, patients' activities of daily living, and hemorheological indexes. The level of evidence was high with manifest clinical significance, and the effectiveness was grade A. The results of pharmacoeconomic research showed that Qilong Capsules combined with conventional western medicine in the treatment of ischemic stroke were advantageous in cost-effectiveness as compared with conventional western medicine alone, but the incremental effect was not significant. The quality evaluation results of the economic report were comparatively clear, and the economy was grade B. Aiming at major cerebrovascular diseases in the society and giving full play to the advantages of TCM, Qilong Capsules focused on the inheritance of classics and scientific and technological innovation, and innovation was grade B. The results of the questionnaire survey showed that the technical characteristics and drug application could meet the medication needs of clinical doctors and patients, and the suitability was grade B. The price level of this drug was comparatively high and the affordability was good since the treatment cost accounted for a small proportion of disposable income. The drug accessibility was good with a wide range of drug sales, sufficient production capacity, and sustainable medicinal materials resources, and was grade B. This drug was derived from the classic prescription Buyang Huanwu Decoction with rich experience of human application, which could regulate Qi and blood circulation, and the section of TCM characteristics was grade B. Based on the evidence evaluation results of "6+1" dimensions of Qilong Capsules, the comprehensive evaluation of clinical value was class A. It is suggested that it can be transformed into relevant policy results of basic clinical medication management according to procedures.

Effects of Qilong Capsules on myocardial fibrosis and insufficient blood circulation in ischemic cardiomyopathy with Qi deficiency and blood stasis / 中国中药杂志

Protective effect of Qilong Capsules(QL) on the myocardial fibrosis and blood circulation of rats with coronary heart disease of Qi deficiency and blood stasis type was investigated. Sleep deprivation and coronary artery ligation were used to construct a disease-symptom combination model, and 60 SD rats were divided into sham operation(sham) group, syndrome(S) group, disease and syndrome(M) group and QL group randomly. The treatment group received administration of QL 0.4 g·kg~(-1)·d~(-1). Other groups were given the same amount of normal saline. The disease indexes of each group [left ventricular end diastolic diameter(LVESD), left ventricular end systolic diameter(LVEDD), left ventricular ejection fraction(LVEF), left ventricular axis shortening rate(LVFS), myocardial histopathology, platelet morphology, peripheral blood flow] and syndrome indexes(tongue color, pulse, grip power) were detected. In sham group, cardiomyocytes and myocardial fibers were arranged neatly and densely with clear structures. The tongues' color in sham were light red, and the pulse shape were regular. RGB is a parameter reflected the brightness of the image of the tongue. In the S group, the amplitude and frequency of the animal's pulse increased accompanied by decreasing R,G,B, however, the decreased R,G,B was accompanied by reduced pulse amplitude in M group. And in M group, we observed fuzzy cell morphology, hypertrophied myocytes, disordered arrangement of cardiomyocytes and myocardial fibers, reduced peripheral blood flow and increased collagen volume fraction(CVF). Increased LVESD and LVEDD, and decreased LVEF and LVFS represented cardiac function in S group was significantly lower than that in sham. In QL group, the tongue's color was red and the pulse was smooth. The myocardial fibers of the QL group were arranged neatly and secreted less collagen. It improved the blood circulation in the sole and tail, and reversed the increasing of LVEDD, LVESD and the decreasing of LVEF and LVFS of M group. Platelets in M and S group showed high reactivity, and QL could decrease aggregation risk. In conclusion, Qilong Capsules has an obvious myocardial protective effect on ischemic cardiomyopathy, which may inhibit the degree of myocardial fibrosis and reduce platelet reactivity.

Meaning， Efficacy and Mechanism of Huoxin Pills in Treating Coronary Heart Disease with Qi Deficiency and Blood Stasis Syndrome / 中国实验方剂学杂志

Cardiovascular diseases， with high incidence and high mortality， belong to the category of "chest impediment and heart pain" in traditional Chinese medicine （TCM）. Chinese medicines have unique effect on the prevention and treatment of cardiovascular diseases with little side effects. Huoxin pills， one of the National Essential Drugs， is formulated based on the basic pathogenesis of weak pulse at Yang and wiry pulse at Yin and the pathological basis of myocardial ischemia and hypoxia and used for treating angina pectoris of coronary heart disease （Qi deficiency and blood stasis syndrome）. This medicine is derived from the classic famous prescription and is composed of ten precious Chinese medicinal herbs. It can replenish Qi， activate blood， and warm collaterals to diffuse impediment by enhancing myocardial contractility and cardiac output to improve micro-circulation and increase coronary blood flow， regulating immune functions， alleviating inflammation， detoxifying， and tranquilizing mind. Clinically， it is suitable for patients with angina pectoris caused by the lack of heart Yang， chest tightness， shortness of breath， palpitation， fear of cold for limbs and so on， especially for the elderly with Yang deficiency or the patients with a history of myocardial infarction. On the basis of the available research reports， this paper explains the formula meaning of Huoxin pills from the perspective of the basic pathogenesis of coronary heart disease and predicts its action targets， location and links. Furthermore， we expound the mechanism of action of Huoxin pills based on basic research and clinical evidence-based research， aiming to provide data support and evidence for the clinical application of this medicine.

[Chronic heart failure due to Qi deficiency and blood stasis and intervention mechanism of Compound Renshen Buqi Granules:a proteomics-based study].

Compound Renshen Buqi Granules have been widely used to treat chronic heart failure(CHF) due to Qi deficiency and blood stasis, but the mechanism of action remains unclear. This paper explored the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules based on quantitative proteomics for uncovering the biological basis. SD rats were divided into the normal control(N) group, normal+Compound Renshen Buqi Granules(ND) group, model(M) group, model+Compound Renshen Buqi Granules(D) group, and positive control(Y) group. The rat model of CHF due to Qi deficiency and blood stasis was established by ligation of the left anterior descending(LAD) coronary artery and chronic sleep deprivation. The rats in the ND group and D group were provided with Compound Renshen Buqi Granules, while those in the Y group received valsartan. Six weeks later, the serum was sampled and the data-dependent acquisition(DDA) was employed for the non-targeted quantitative proteomics analysis of the differences in protein expression among groups, followed by the targeted analysis of differentially expressed proteins(DEPs) generated by data-independent acquisition(DIA). Compared with the N group, the rats in the M group pre-sented with decreased body weight, grip strength, and pulse amplitude and increased RGB value on the tongue surface. The pathomorphological examination revealed inflammatory cell infiltration, cell degeneration and necrosis, tissue fibrosis, etc. After the intervention with Compound Renshen Buqi Granules, multiple indicators were reversed. As demonstrated by proteomics results, there were 144 and 111 DEPs found in the M group and ND group in comparison with the N group. Compared with the M group, 107 and 194 DEPs were found in the D group and the Y group, respectively. Compared with the ND group, 119 DEPs were detected in the D group. As illustrated by DIA-based verification, the quantitative results of six proteins in each group were consistent with those by DDA. The syndrome indicators and pathomorphological examination results demonstrated that the protein expression profile of rats with CHF due to Qi deficiency and blood stasis changed obviously. However, Compound Renshen Buqi Granules were able to reverse the differential expression of immune proteins to regulate CHF of Qi deficiency and blood stasis syndrome, which has provided clues for figuring out the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules.

Chronic heart failure due to Qi deficiency and blood stasis and intervention mechanism of Compound Renshen Buqi Granules:a proteomics-based study / 中国中药杂志

Compound Renshen Buqi Granules have been widely used to treat chronic heart failure(CHF) due to Qi deficiency and blood stasis, but the mechanism of action remains unclear. This paper explored the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules based on quantitative proteomics for uncovering the biological basis. SD rats were divided into the normal control(N) group, normal+Compound Renshen Buqi Granules(ND) group, model(M) group, model+Compound Renshen Buqi Granules(D) group, and positive control(Y) group. The rat model of CHF due to Qi deficiency and blood stasis was established by ligation of the left anterior descending(LAD) coronary artery and chronic sleep deprivation. The rats in the ND group and D group were provided with Compound Renshen Buqi Granules, while those in the Y group received valsartan. Six weeks later, the serum was sampled and the data-dependent acquisition(DDA) was employed for the non-targeted quantitative proteomics analysis of the differences in protein expression among groups, followed by the targeted analysis of differentially expressed proteins(DEPs) generated by data-independent acquisition(DIA). Compared with the N group, the rats in the M group pre-sented with decreased body weight, grip strength, and pulse amplitude and increased RGB value on the tongue surface. The pathomorphological examination revealed inflammatory cell infiltration, cell degeneration and necrosis, tissue fibrosis, etc. After the intervention with Compound Renshen Buqi Granules, multiple indicators were reversed. As demonstrated by proteomics results, there were 144 and 111 DEPs found in the M group and ND group in comparison with the N group. Compared with the M group, 107 and 194 DEPs were found in the D group and the Y group, respectively. Compared with the ND group, 119 DEPs were detected in the D group. As illustrated by DIA-based verification, the quantitative results of six proteins in each group were consistent with those by DDA. The syndrome indicators and pathomorphological examination results demonstrated that the protein expression profile of rats with CHF due to Qi deficiency and blood stasis changed obviously. However, Compound Renshen Buqi Granules were able to reverse the differential expression of immune proteins to regulate CHF of Qi deficiency and blood stasis syndrome, which has provided clues for figuring out the pathogenesis of CHF due to Qi deficiency and blood stasis and the intervention mechanism of Compound Renshen Buqi Granules.

Effect on Treatment of Addition and Subtraction Therapy of Zhuyu Zhixuetang to Chronic Endometritis with Syndrome of Qi Deficiency and Blood Stasis / 中国实验方剂学杂志

Objective:To discuss clinical effect of Zhuyu Zhixuetang to chronic endometritis （CE） with syndrome of Qi deficiency and blood stasis and to study improvement effect to pregnancy outcome. Method:One hundred and forty-four patients were randomly divided into two groups， patients in control group were 72 cases and in observation group were 72 cases. In control group， 66 patients completed the therapy because of 4 falling off or missing visit and 2 eliminated， and in observation group， 65 patients completed the therapy because of 3 falling off or missing visit and 5 eliminated. In two groups. anti-infection treatment was gicen to patients. Patients in control group got Fuke Qianjin Pian， 6 tablets/time， 3 times/day. Patients in observation group got Zhuyu Zhixuetang， 1 dose/day. The treatment was continued for 3 months and the follow up was recorded for 6 months. Before and after treatment， changes of menstrual volume， period and cycle were recorded. And hysteroscopy and color Doppler ultrasound of vagina were made， and endometrial morphology and endometrial receptivity were evaluated ［endometrial thickness， resistance index （RI）， pulsation index （PI） and blood flow index （FI）］ were evaluated， and pathology of endometrial were tested. And scores of syndrome of Qi deficiency and blood stasis were graded， levels of interleukin-1 <italic>β</italic> （IL-1<italic> β</italic>）， IL-6 and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and T-lymphoid subsets （CD3⁺， CD4⁺， CD8⁺） in peripheral blood were measured. Pregnancy and miscarriage were recorded and the safety was evaluated. Result:After treatment， menstrual volume， menstrual period， cycle and complete normal rate of menstruation in observation group were all higher than those in control group （<italic>P</italic><0.05）. Endometrial thickness and FI were more than those in control group （<italic>P</italic><0.01）， RI and PI were lower than RI and PI in control group （<italic>P</italic><0.01）. And compared with control group， levels of IL-1<italic>β</italic>， IL-6， TNF-<italic>α</italic> and CD8⁺were less （<italic>P</italic><0.01）. And levels of CD3⁺， CD4⁺ and CD4⁺/ CD8⁺ were higher than the data in control group （<italic>P</italic><0.01）. During 6 months follow-up， pregnancy rate in observation group was 46.97% （31/66） was higher than 27.69% （18/65） in control group （<italic>χ</italic>²=5.197， <italic>P</italic><0.05）. Total effective rate of endometrial morphology was 96.97% （64/66） higher than 86.15% （56/65） in control group （<italic>χ</italic>²=4.981， <italic>P</italic><0.05）. Total effective rate endometrial pathology was 95.45% （63/66） higher than 84.62% （55/65） in control group （<italic>χ</italic>²=4.304， <italic>P</italic><0.05）. Total effective rate of comprehensive clinical effect was 93.94% （62/66） higher than 81.54% （55/65） in control group （<italic>χ</italic>²=4.696， <italic>P</italic><0.05）. There was no adverse reactions related to traditional Chinese medicine. Conclusion:Zhuyu Zhixuetang can regulate menstruation， relieve clinical symptoms， improve endometrial morphology under hysteroscopy， regulate systemic and local immune inflammatory response， improve CP， thus improve pregnancy outcome， with better comprehensive effect and safety.

Correlations Between Severity of Heart Failure Related to Coronary Heart Disease of Qi Deficiency and Blood Stasis Syndrome and Biological Indexes / 中国实验方剂学杂志

Objective:To explore the correlations of the severity of heart failure related to coronary heart disease arising from Qi deficiency and blood stasis with cardiac function indexes， energy metabolism indexes， coagulation function indexes， and inflammatory factors， in order to provide a scientific basis for further research on the biological foundation of this disease. Method:Two hundred patients with heart failure related to coronary heart disease of Qi deficiency and blood stasis syndrome were collected and then classified into mild， moderate and severe groups according to their scores of Qi deficiency and blood stasis syndrome. Meanwhile， 40 healthy persons confirmed by physical examination during the same period were included into the control group. Such biological indexes as cardiac function indexes， energy metabolism indexes， coagulation function indexes， and inflammatory factors were determined in patients of each group for comparison. Then the Spearman rank correlation analysis was conducted to figure out the correlations between differential indexes and the severity of Qi deficiency and blood stasis syndrome， followed by the determination of risk factors for the severity of Qi deficiency and blood stasis syndrome by ordered logistic regression analysis. Result:The cardiac function indexes， energy metabolism indexes， coagulation function indexes， and inflammatory factors in patients with heart failure related to coronary heart disease arising from Qi deficiency and blood stasis varied significantly. There were significant statistical differences in the levels of N-terminal pro-B-type natriuretic peptide （NT-ProBNP）， 6-minute walk test （6MWT）， heart-type fatty acid-binging protein （H-FABP）， prothrombin time （PT）， activated partial thromboplastin time （APTT）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， and nitric oxide （NO） among the mild， moderate， and severe groups （<italic>P</italic><0.05）. The severity of Qi deficiency and blood stasis syndrome was positively correlated with NT-ProBNP （<italic>r</italic>=0.144）， PT （<italic>r</italic>=0.173）， and APTT （<italic>r</italic>=0.144）， but negatively with 6MWT （<italic>r</italic>=-0.287）. The 6MWT［odds ratio（OR）=0.995， 95% confidence interval（CI） 0.991-0.998），<italic>P</italic><0.01］ and APTT（OR=1.088，95%CI 1.021-1.157，<italic>P</italic><0.01） were independent risk factors affecting the severity of heart failure related to coronary heart disease arising from Qi deficiency and blood stasis. Conclusion:The severity of heart failure related to coronary heart disease of Qi deficiency and blood stasis syndrome is closely related to NT-ProBNP， 6MWT， H-FABP， PT， APTT， TNF-<italic>α</italic>， and NO. Moreover， 6MWT and APTT can be used as independent risk factors to evaluate the severity of patients with heart failure related to coronary heart disease due to Qi deficiency and blood stasis.

Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction / 中国药理学与毒理学杂志

OBJECTIVE To explore the curative effect and mechanism of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. METHODS The patients with coronary heart dis?ease of Qi deficiency and blood stasis syndrome were treated with Yiqi Huoxue decoction for 3 months, and the changes of cardiac function were observed. 61 serum samples (including 29 cases of disease group and 32 cases of Yiqi Huoxue expression group) were analyzed by non labeled proteomics. The disease group was used as the control group, and the protein with expression level difference of more than 1.2 folds (P<0.05) was screened. The molecular function, biologi?cal pathway and protein interaction of the different proteins were analyzed by bioinformatics, so as to identify the molecu?lar and biological pathway of Yiqi Huoxue decoction in the treatment of coronary heart disease with Qi deficiency and blood stasis syndrome. RESULTS Clinical treatment found that Yiqi Huoxue decoction can improve TCM syndrome score and left ventricular ejection fraction, regulate blood glucose and blood lipid levels, prolong thrombin time, and improve heart function. The results of proteomic quantitative analysis showed that there were 69 proteins with different expression levels in the disease group. Bioinformatics analysis results showed that Yiqi Huoxue decoction may regulate ApoA1, alpha-2 and other proteins to act on HDL assembly, platelet degradation, PI3K Akt signaling pathway, and then play a therapeutic role in coronary heart disease with Qi deficiency and blood stasis syndrome. CONCLUSION Yiqi Huoxue decoction can effectively improved the heart function decline caused by Qi deficiency and blood stasis syn?drome of coronary heart disease. It mainly act on energy metabolism and platelet activation pathway by activating HDL assembly and platelet degradation signal pathway proteins. This study can provide reference for the follow-up treatment mechanism of Qi deficiency and blood stasis syndrome of coronary heart disease.

Investigation of Invigorating Qi and Activating Blood Circulation Prescriptions in Treating Qi Deficiency and Blood Stasis Syndrome of Ischemic Stroke Patients: Study Protocol for a Randomized Controlled Trial.

Ischemic stroke (IS) is characterized by high morbidity and high mortality. The integration of Traditional Chinese medicine (TCM) and western medicine has shown promising benefits in relieving symptoms, promoting neurological recovery, and improving the quality of life of patients with IS. In TCM, Qi-deficiency along with blood-stasis (QDBS) syndrome is one of the common types of IS that is treated by invigorating Qi and activating blood circulation. In TCM theory, improving the corresponding degree of prescription-syndrome correlation (PSC) is helpful to improve clinical efficacy. In this study, we intend to use similar prescriptions that invigorate Qi and activate blood circulation: Buyang Huanwu granules (BHG), Naoxintong capsules (NXTC), and Yangyin Tongnao granules (YTG). The goal is to evaluate their level of PSC inpatients with IS with QDBS syndrome and find relevant biomarkers to provide an objective basis for precise treatment of TCM and improve the clinical therapeutic effects. A multicenter, randomized, double-blinded, and placebo-controlled intervention trial will be conducted in IS patients with QDBS syndrome, followed by an add-on of Chinese patent medicine. A total of 160 subjects will be randomly assigned to the BHG, NXTC, YTG, and placebo groups in a 1:2:1:1 allocation ratio. All subjects will undergo 28 days of treatment and then followed for another 180 days. The primary outcome is the changes in the National Institutes of Health Stroke Scale score after 28 days of medication. The secondary outcomes include the modified Rankin scale score, activity of daily living scale score, and TCM symptom score. Data will be analyzed in accordance with a predefined statistical analysis plan. Ethical approval of this trial has been granted by the Research Ethics Committee of the First Affiliated Hospital of Zhejiang Chinese Medical University (ID: 2017-Y-004-02). Written informed consent of patients will be required. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR1800015189), and the results will be disseminated to the public through peer-reviewed journals and academic conferences.

Effect of Zhongfeng Xingnao Liquid on Neurological Recovery of Patients with Ischemic Stroke at Early Recovery / 中国实验方剂学杂志

<b>Objective::To discuss the effect of Zhongfeng Xingnao liquid on neurological recovery of patients of ischemic stroke with Qi deficiency and blood stasis syndrome at early recovery, and the mechanisms of anti-inflammation, neuroprotection and improvement of microcirculation. <b>Method::One hundred and twenty-eight patients were randomly divided into control group (64 cases) and observation group (64 cases) by random number table. Both groups’ patients got atorvastatin, 10 mg/days, aspirin enteric-coated tablets, 100 mg/days, and control of blood pressure and blood sugar, and modern rehabilitation training. Patients in control group orally got Zhongfeng Xingnao liquid, 25 mL/time, 3 times/days. The course of treatment was 90 days. And before and after treatment, national institutes of health neurological deficiency (NIHSS), Barthel index, improvement Rankin scale, brunel balance scale (BBA), Fugl-Meyer scale (FMA), Qi deficiency and blood stasis syndrome (SS-QOL) were scored. And levels of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-alpha), homocysteine (Hcy), serum cystatin C (Cys-C), platelet aggregation rate (ADP) and fibrinogen (FIB) were detected. <b>Result::The clinical efficacy in observation group was better than that in control group (<italic>Z</italic>=1.981, <italic>P</italic><0.05). At different time points after treatment, scores of NIHSS and Qi deficiency and blood stasis syndrome were lower than those in control group (<italic>P</italic><0.05), whereas scores of Barthel index, FMA, BBA and SS-QOL were higher than those in control group (<italic>P</italic><0.01). Degrees of disability and dyskinesia in observation group was lighter than those in control group (<italic>Z</italic>=1.932, <italic>P</italic><0.05). Degree of dyskinesia was lighter than that in control group (<italic>Z</italic>=2.149, <italic>P</italic><0.05). And level of BDNF was higher than that in control group (<italic>P</italic><0.01), while levels of TNF-<italic>α</italic>, Hcy, Cys-C, ADP and FIB were lower than those in control group (<italic>P</italic><0.01). <b>Conclusion::In addition to the routine comprehensive rehabilitation measures of western medicine, Zhongfeng Xingnao liquid can promote recovery of nerve function defect of patients of cerebral infarction with Qi deficiency and blood stasis syndrome at convalescence, is beneficial for rehabilitation of patients and improving the quality of life, with certain effects in resisting inflammation, improving microcirculation and protecting nerves, and better efficacy than simple western medicine treatment.

Influence of Tiaopi Huxin Decoction on Ventricular Remodeling and Prognosis of Chronic Heart Failure Based on Theory of Heart Spleen Correlation / 中国实验方剂学杂志

Objective:To observe clinical effect of Tiaopi Huxin decoction to chronic heart failure (CHF) and to study mechanism of action of anti-inflammatory and anti ventricular remodeling.Method:One hundred and forty patients were randomly divided into control group (70 cases) and observation group (70 cases) by random number table. And during the study, there were four patients for falling off and missing visit, two eliminated patients in control group, and 64 patients finished the study, and there were six patients for falling off and missing visit in observation group, so 64 patients finished the study. Two groups of patients got losartan potassium tablets, 50 mg/time, 1 time/day, metoprolol tablets, 200 mg/time, 1 time/day, spironolactone tablets, 20-40 mg/time, 1 time/day, control group Jingshe Yiqi granule 1 bag/time,3 times/day,flushed with boiling water, patients in observation group added Tiaopi Huxin decoction, 1 dose/day. The courses of treatment were 12 weeks. Before and after treatment, left ventricular ejection fraction (LVEF), left ventricular end diastolic dimension (LVEDd), leftventricular end-stolic diameter (LVEDs), stroke volume (SV), cardiac output (CO) and ratio of peak value of early diastolic velocity of mitral valve and peak velocity of late diastolic mitral valve (E/A) were recorded by echocardiography. And scores of Lee's heart failure, Qi deficiency and blood stasis, Minnesota Heart Failure Quality of life questionnaire (MLHFQ) and 6 minutes' walking test（6 MWT）were graded. And levels of N-terminal B-type natriuretic peptide (NT-proBNP), galactose lectin-3, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-17, transforming growth factor (TGF) - β and matrix metalloproteinase-9 (MMP-9) were detected.Result:After treatment, LVEDd and LVEDs were lower than that in control group (P<0.05). LVEF, SV, CO and E/A were higher than those in control group (P<0.05). And scores of Lee's heart failure, Qi deficiency blood stasis and MLHFQ were lower than those in control group (P<0.01). And 6 MWT was more than that in control group (P<0.01). And levels of NT-proBNP, galactose lectin 3, IL-17, IL-6, TNF-α, TGF-β and MMP-9 were lower than those in control group (P<0.01). Effect of cardiac function was better than that in control group (Z=2.191, P<0.05).Conclusion:On the basis of conventional western medicine treatment and according to theory of heart and spleen, Tiaopi Huxin decoction can improve the clinical symptoms and signs of heart failure, and it had effect of anti-inflammatory, and can improve ventricular remodeling, improve the exercise tolerance and quality of life of patients, improve the prognosis of heart failure, and its clinical effect is better than that of Western medicine alone.

Effect of Adjuvant Therapy of Huayu Pills on Neurological Recovery of Patients with Acute Cerebral Infarction / 中国实验方剂学杂志

Objective:To observe the effects of adjuvant therapy of Huayu pills on neurological recovery of patients with acute cerebral infarction (ACI) and syndrome of Qi deficiency and blood stasis, and to investigate its mechanism of action for antioxidation, anti-inflammation and improvement of microcirculation. Method:One hundred and forty patients were randomly divided into control group (70 cases) and observation group (70 cases) by random number table. During the study period, there were 3 drop-out cases, 2 excluded cases, and 65 completed cases in the control group. There were 1 drop-out cases, 4 excluded case, and 65 completed cases in the observation group. Western medicine was given in both groups. Patients in control group additionally got oral administration of Xiaoshuang Tongluo tablets, 6 tablets/time, 3 times/day. The patients in observation group got oral administration of Huayu pills, 5 g/time, 2 times/days. The treatment course was 4 weeks in both groups. Before the treatment, and at the second and fourth week after treatment, scores of national institute of health stroke scale (NIHSS) were graded. Before and after treatment, scores of functional independent measures (FIM) scale, fugl-meyer assessment of motor function (FMA), Qi deficiency and blood stasis syndrome were graded. Disability/mortality and safety were discussed after treatment. Levels of the whole blood viscosity (BV), plasma viscosity (PV), platelet aggregation rate (PAG), fibrinogen (FIB), P-selectin (CD62p), D-dimer (D-D), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), lipid peroxide (PLO), homocysteine (Hcy), tumor necrosis factor -α (TNF-α), serum cystatin C (Cys-C) and hypersensitive C-reactive protein (hs-CRP) were detected both before and after treatment. Result:In the analysis of rank sum test, clinical efficacy in observation group was better than that in control group (Z=2.131, P<0.05). At the second and fourth week after treatment, scores of NIHSS, Qi deficiency and blood stasis, as well as levels of NO, PLO, MDA, Hcy, Cys-C, hs-CRP, TNF-α, BV, PV, PAG, FIB, CD62 p and D-D in observation group were lower than those in control group (P<0.01), while levels of FIM, FMA and SOD were all higher than those in control group (P<0.01). Conclusion:Based on the comprehensive treatment of Western medicine, adjuvant therapy of Huayu pills can improve the degree of nerve function defect, improve the ability of exercise and daily life, reduce the degree of disability, improve the microcirculation and hemorheology, reduce the inflammatory reaction, eliminate oxygen free radicals, and relieve the oxidative stress injury in patients with ACI and Qi deficiency and blood stasis syndrome, and the clinical efficacy is better than that of Western medicine alone.

Animal Model of Qi Deficiency and Blood Stasis Syndrome / 中国实验方剂学杂志

The study of traditional Chinese medicine(TCM) syndrome model started late but developed rapidly. In recent years, with the deepening of the study of TCM diseases and prescriptions, to develop the modernization of TCM, the study of TCM syndrome model has been required to be more specific and went deeper. Qi deficiency and blood stasis syndrome, as a common clinical syndrome type, often occurs in cardiovascular and cerebrovascular diseases, digestive system diseases, chronic kidney disease, cancer and other diseases. With the increase in the aging of population in China, the research on Qi deficiency and blood stasis syndrome has become a hot topic in the field of TCM due to the physical characteristics of the elderly people with multiple Qi deficiency and blood stasis. The animal models of Qi deficiency and blood stasis syndrome established in recent years were classified into pathological model, etiological model and combined disease and syndrome model. By observing the macroscopical representation, limb behavior and hemorheology of experimental animals in line with the theory of TCM, this paper evaluates the method of modeling, and provides ideas and reference for the method of modeling for Qi-deficiency and blood-stasis syndrome. The research on the model of Qi-deficiency and blood-stasis syndrome should follow the thought of cause-pulse-syndrome-treatment, namely etiology-external manifestation-pathological mechanism-syndrome differentiation and treatment, and combine the study on the TCM syndrome model with modern science, so as to standardize the development of modeling methods and build relatively improved animal models of Qi deficiency and blood stasis, and provide model support for exploring the pathogenesis of Qi deficiency and blood stasis syndrome and new treatment ideas in the future.

Effect Research Antiventricular Remodeling of Qili Qiangxin Capsules in Treating Dilated Cardiomyopathy / 中国实验方剂学杂志

Objective:To discuss the effect of Qili Qiangxin capsules on cardiac function, myocardial fibrosis and ventricular remodeling of patients with dilated cardiomyopathy (DCM) and Yang Qi deficiency and blood stasis syndrome. Method:One hundred and seven patients were randomly divided into control group (53 cases) and observation group (54 cases) by random number table. Patients in control group got metoprolol succinate sustained-release tablet, 47.5 mg/time, 1 time/day, sacubitril valsartan sodium tablets, 50 mg/time, 1 time/day, hydrochlorothiazide tablets, 20 mg/time, 1 time/day, and spironolactone tablets, 20 mg/time, 1 time/day. In addition to the therapy of control group, patients in observation group were also given Qili Qiangxin capsules, 4 granules/time, 3 times/days. A course of treatment was 6 months. Before and after treatment, levels of left ventricular end-diastolic diameter (LVEDd), left ventricular ejection fraction (LVEF), left ventricular end systolic diameter (LVESD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left ventricular myocardial mass (LVM) and left ventricular myocardial mass index (LVMI) were recorded by echocardiography. The classification of cardiac function was recorded by New York College of Cardiology (NYHA). Lee's heart failure and Yang Qi deficiency and blood stasis syndrome were scored. And levels of N-terminal B-type natriuretic peptide (NT-proBNP), soluble ST2 (sST2), galectin-3 (galectin-3), angiotensin-Ⅱ(Ang-Ⅱ), matrix metalloproteinase-2 (MMP-2), MMP-9, matrix metalloproteinase inhibitor-1 (TIMP-1), type I procollagen carboxy-terminal peptide (PIP) and type I collagen carboxy-terminal cross-linking peptide (CITP) were detected. Result:After treatment, levels of LVEDd, LVESD, IVST, LVPWT, LVM and LVMI were lower than those in control group (PPZ=2.031, PPPConclusion:In addition to the routine western medicine, Qili Qiangxin capsules can relieve clinical symptoms, degree of heart failure of DCM patients and ventricular remodeling, ameliorate heart function, regulate levels of sST2, galectin-3, MMPs and Ang-Ⅱ, inhibit myocardial fibrosis, and delay heart failure.

Influence of Shengmaiyin Combined with Xuefu Zhuyu Tang on Hypercoagulable State Caused by Non-small Cell Lung Cancer / 中国实验方剂学杂志

Objective:To observe influence of dialectical addition and subtraction of Shengmaiyin combined with Xuefu Zhuyu Tang on fibrinolytic activity and coagulation active factor of patients with non-small cell lung cancer at hypercoagulable state. Method:One hundred and eighty patients were randomly divided into control group (58 cases) and observation group (60 cases) by random number table. Patients in control group got low molecular weight heparins calcium injection by subcutaneous injection for 3 weeks, 1.0 mL (5 000 AXa unit)/time, 1 time/day, and oral aspirin enteric-coated tablets, 100 mg/time, 1 time/day. Patients in observation group got dialectical addition and subtraction of Shengmaiyin combined with Xuefu Zhuyu Tang, 1 dose/day. A course of treatment was 8 weeks. And activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), platelet (PLT), fibrinogen (FIB), D-dimer (D-D), plasma tissue plasminogen activator (t-PA), plasminogen activator inhibitor in plasma-1 (PAI-1), von willebrand factor (vWF), P-selectin, basic fibroblast growth factor (bFGF), transforming growth factor (TGF), vascular endothelial growth factor (VEGF) were detected. And before and after treatment, scores of Qi deficiency and blood stasis syndrome and hemorheological indices were detected. Result:After treatment, APTT, PT and TT in observation group were longer than those in control group. Levels of PLT, D-D and PAI-1 were lower than those in control group (PPPPPPPConclusion:Dialectical addition and subtraction of Shengmaiyin combined with Xuefu Zhuyu Tang can ameliorate hypercoagulable state of NSCLC, relieve clinical symptoms, and can regulate fibrinolytic activity and coagulation activity factors, so it can mitigate dangers caused by deep venous thrombosis of NSCLC.