[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.

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.

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.

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.

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.

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.

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.

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 of Yiqi Huoxue Recipe on Vascular Endothelial Function in Rats with Qi Deficiency and Blood Stasis Syndrome / 中国实验方剂学杂志

Objective: To explore the changes and benefits of vascular endothelial cell function in rats with qi deficiency and blood stasis syndrome, and the effect of Yiqi Huoxue recipe (YQHXF) of such changes. Method: Rats were randomly divided into blank control group, Qi deficiency and blood stasis group, and YQHXF high and low dose groups (5.54,2.77 g·kg-1). A small platform of water environment was used to make the rats stand for a long-term with irregular and incomplete sleep deprivation, 16 h per day for six weeks, so that both mentality and labor of rats were consumed to establish qi deficiency and blood stasis rat models. From the fifth week, intragastric administration was given for 2 weeks, until end of the experiment. Then levels of endothelin-1(ET-1), von willebrand factor (vWF), vascular cell adhesion molecule-1(VCAM-1), intercellular adhesion molecule (ICAM-1), P-selectin,interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in rat plasma were detected by enzyme-linked immunosorbent assay (ELISA) and nitric oxide (NO) was detected by nitrate reductase assay. Result:Compared with blank control group, rats in Qi deficiency and blood stasis group showed rough and dark hair, with significantly decreased body weight and pulse amplitude (PPPα were abnormally increased after sleep deprivation (PPPPPPPConclusion:Sleep deprivation can induce the formation of Qi deficiency and blood stasis syndrome in rats, and lead to vascular endothelial dysfunction. YQHXF has the function of protecting the vascular endothelium. It can improve the Qi deficiency and blood stasis symptoms in rats with Qi deficiency and blood stasis syndrome by regulating the secretion of vascular endothelial active substances, reducing cell adhesion and inhibiting inflammation.

Guanxinjing capsule in the treatment of chronic stable angina: study protocol for a randomized controlled trial.

BACKGROUND: Stable angina is a common cardiovascular disease with high mortality and a poor prognosis. Although there are various interventions against stable angina, none are able to significantly reduce the mortality rate. Guanxinjing capsule (GXJ) is made from the classical Chinese prescription Xuefuzhuyutang (). Both basic research and clinical studies have shown that GXJ can relieve the symptoms of angina, but currently, the effects of GXJ lack high-quality clinical evidence. The aim of this study was to evaluate the clinical effectiveness and safety of GXJ compared with placebo. METHODS/DESIGN: This multicentre, blinded, randomized trial will be conducted with a total of 120 participants diagnosed with chronic stable angina (Qi deficiency and blood stasis syndrome). Using a central randomization system, participants will be randomized (1:1) into groups receiving either GXJ or placebo for 8 weeks. After a 2-week run-in period, eligible patients will receive either GXJ or placebo (4 pills, three times daily) for 8 weeks in addition to conventional treatment. The primary outcomes include changes in the total exercise time on exercise tolerance tests and changes in the integral scores of angina symptoms. The secondary outcome measures include changes in the maximal estimated workload, changes in time to a 1 mm ST-segment depression or raise, changes in the time to onset of angina during exercise tolerance testing, changes in the total score of traditional Chinese medicine syndrome, and changes in the total score of the Generalized Anxiety Disorder 7-item assessment between baseline and week 8. Other outcome measures will also be assessed. All exercise tolerance tests use a standard Bruce multistage exercise test protocol. Adverse events will be monitored throughout the trial. DISCUSSION: This study will investigate whether GXJ can alleviate clinical symptoms, increase the angina-free walking time, and improve quality of life in patients with chronic stable angina (Qi deficiency and blood stasis syndrome). The results of this study will provide clinical evidence for the application of GXJ to the treatment of stable angina. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800014258 . Registered on 2 January 2018.

[Quantitative proteomic research of biological basis of Buyang Huanwu decoction therapy for cerebral infarction combined with Qi-deficiency and blood-stasis syndrome].

Chinese medicine Buyang Huanwu decoction (BYHW) is widely used in treating cerebral infarction combined with Qi-deficiency and blood-stasis syndrome, but the pharmacological basis is still not clear. This study aims to uncover the biological basis of BYHW therapy for cerebral infarction combined with Qi-deficiency and blood-stasis syndrome using label-free proteomic technology. Using Qi deficiency and blood stasis rat cerebral infarction model as the research object, the protein expression of rat brain tissue was compared among the sham operation group, the model group and the drug group. Quantitative analysis of the 3 groups of tissue samples detected 3 959, 3 996 and 4 055 proteins in the sham operation group, the model group and the drug group, respectively. Take model group as the control group, 391 proteins were identified to be upregulated or downregulated for more than 2 folds. Biological analysis and functional enrichment of the differentially expressed proteins revealed that BYHW may treat cerebral infarction combined with Qi-deficiency and blood-stasis syndrome through energy metabolism, nervous system and several signal pathways. This study preliminarily revealed the pharmacological mechanism of BYHW at the protein level, and provided a molecular basis for clinical treatment and traditional Chinese medicine research on cerebral infarction combined with Qi-deficiency and blood-stasis syndrome.

The efficacy and safety of Jiedu Tongluo granules for treating post-stroke depression with qi deficiency and blood stasis syndrome: study protocol for a randomized controlled trial.

BACKGROUND: Post-stroke depression (PSD) is the most common psychiatric complication after a stroke. The most frequently used antidepressants are selective serotonin receptor inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), however, these exhibit a series of side effects. Traditional Chinese medicine has been used to treat PSD with few side effects. The aim of this study is to evaluate the efficacy and safety of Jiedu Tongluo granules for treating PSD with qi deficiency and blood stasis syndrome. METHODS: The planned study is a double-blind, randomized, placebo-controlled pilot trial. Eighty participants will be randomly assigned to receive either treatment or placebo. The treatment group will receive Jiedu Tongluo granules (JDTLG) with conventional treatment, and the placebo group will receive placebo with conventional treatment for 8 weeks. The primary outcome is the effectiveness of JDTLG on depression after 8 weeks treatment, which is defined as a decrease of 50% or more in 17-item Hamilton Depression Scale (HAMD-17) score or clinical recovery (score < 7). Secondary outcomes are improvement in neurological function, degree of independence, activities of daily living, and TCM syndrome at each visit, which will be measured with National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Barthel Index (BI) and TCM scale, respectively. Interleukin (IL)-6, IL-8, and small-molecule metabolites will be monitored to explore the mechanism of action of JDTLG on PSD. Safety measures include vital signs, results of electrocardiography, laboratory index (full blood count, kidney and liver function tests) and adverse events. DISCUSSION: The purpose of this trial is to evaluate the therapeutic effects and safety of JDTLG in individuals with PSD with concomitant qi deficiency and blood stasis syndrome. If successful, the outcome of this trial will provide a viable treatment option for PSD patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03147053 . Registered on 27 April 2017.

Quantitative proteomic research of biological basis of Buyang Huanwu decoction therapy for cerebral infarction combined with Qi-deficiency and blood-stasis syndrome / 中国中药杂志

Chinese medicine Buyang Huanwu decoction (BYHW) is widely used in treating cerebral infarction combined with Qi-deficiency and blood-stasis syndrome, but the pharmacological basis is still not clear. This study aims to uncover the biological basis of BYHW therapy for cerebral infarction combined with Qi-deficiency and blood-stasis syndrome using label-free proteomic technology. Using Qi deficiency and blood stasis rat cerebral infarction model as the research object, the protein expression of rat brain tissue was compared among the sham operation group, the model group and the drug group. Quantitative analysis of the 3 groups of tissue samples detected 3 959, 3 996 and 4 055 proteins in the sham operation group, the model group and the drug group, respectively. Take model group as the control group, 391 proteins were identified to be upregulated or downregulated for more than 2 folds. Biological analysis and functional enrichment of the differentially expressed proteins revealed that BYHW may treat cerebral infarction combined with Qi-deficiency and blood-stasis syndrome through energy metabolism, nervous system and several signal pathways. This study preliminarily revealed the pharmacological mechanism of BYHW at the protein level, and provided a molecular basis for clinical treatment and traditional Chinese medicine research on cerebral infarction combined with Qi-deficiency and blood-stasis syndrome.

[Analysis of on medication rules for Qi-deficiency and blood-stasis syndrome of chronic heart failure based on data mining technology].

To analyze the medication features and the regularity of prescriptions of traditional Chinese medicine in treating patients with Qi-deficiency and blood-stasis syndrome of chronic heart failure based on modern literature. In this article, CNKI Chinese academic journal database, Wanfang Chinese academic journal database and VIP Chinese periodical database were all searched from January 2000 to December 2015 for the relevant literature on traditional Chinese medicine treatment for Qi-deficiency and blood-stasis syndrome of chronic heart failure. Then a normalized database was established for further data mining and analysis. Subsequently, the medication features and the regularity of prescriptions were mined by using traditional Chinese medicine inheritance support system(V2.5), association rules, improved mutual information algorithm, complex system entropy clustering and other mining methods. Finally, a total of 171 articles were included, involving 171 prescriptions, 140 kinds of herbs, with a total frequency of 1 772 for the herbs. As a result, 19 core prescriptions and 7 new prescriptions were mined. The most frequently used herbs included Huangqi(Astragali Radix), Danshen(Salviae Miltiorrhizae Radix et Rhizoma), Fuling(Poria), Renshen(Ginseng Radix et Rhizoma), Tinglizi(Semen Lepidii), Baizhu(Atractylodis Macrocephalae Rhizoma), and Guizhi(Cinnamomum Ramulus). The core prescriptions were composed of Huangqi(Astragali Radix), Danshen(Salviae Miltiorrhizae Radix et Rhizoma) and Fuling(Poria), etc. The high frequent herbs and core prescriptions not only highlight the medication features of Qi-invigorating and blood-circulating therapy, but also reflect the regularity of prescriptions of blood-circulating, Yang-warming, and urination-promoting therapy based on syndrome differentiation. Moreover, the mining of the new prescriptions provide new reference and inspiration for clinical treatment of various accompanying symptoms of chronic heart failure. In conclusion, this article provides new reference for traditional Chinese medicine in the treatment of chronic heart failure.

Relationship between two blood stasis syndromes and inflammatory factors in patients with acute coronary syndrome.

OBJECTIVE: To investigate the relationship between inflammatory factors and two Chinese medicine (CM) syndrome types of qi stagnation and blood stasis (QSBS) and qi deficiency and blood stasis (QDBS) in patients with acute coronary syndrome (ACS). METHODS: Sixty subjects with ACS, whose pathogenesis changes belongs to qi disturbance blood stasis syndrome, were divided into 2 groups: 30 in the QSBS group and 30 in the QDBS group. The comparative analysis on them was carried out through comparing general information, coronary angiography and inflammatory factors including intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40) and lipoprotein-associated phospholipase A2 (Lp-PLA2). RESULTS: Compared with the QSBS group, Lp-PLA2 and YKL-40 levels in the QDBS group showed no-significant difference (P>0.05); ICAM-1 was significantly higher in the QDBS group than in the QSBS group in the pathological processes of qi disturbance and blood stasis syndrome of ACS (P<0.05). CONCLUSIONS: Inflammatory factor ICAM-1 may be an objective basis for syndrome typing of QSBS and QDBS, which provides a research direction for standardization research of CM syndrome types.