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.

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.

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.

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.

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.

Effect of Yiqi Huoxue Tongmai Method in Treating Atherosclerotic Lesions of Lower Extremity of Diabetes / 中国实验方剂学杂志

Objective:To observe the effect of Yiqi Huoxue Tongmai method in treating lower extremity atherosclerotic disease (LEAD) and on hemodynamic index and vascular endothelial function. Method:One hundred and five patients were randomly divided into control group (52 cases) and observation group (53 cases) by random number table. Patients in control group were treated for controlling blood sugar, blood fat, blood pressure and given aspirin enteric-coated tablets, 100 mg/day, cilostazol tablets, 100 mg/day, 2 times/day. In addition to the therapy of control group, patients in observation group were given modified Danggui Sini Tang and Buyang Huanwu Tang for oral and washout, 1 dose/day. The treatment course lasted for 12 weeks. Before and after treatment, ankle brachial index (ABI) was detected. And intimal thickness of shallow femoral shallower, arteriae tibialis posterior and arteriae dorsalis pedis, hardening degree, patch size and degree of stenosis were detected by color Doppler ultrasound diagnostic apparatus. Qi deficiency and blood stasis syndrome were scored. And levels of the whole blood viscosity, plasma viscosity, erythrocyte sedimentation rate (ESR), D-dimer (D-D), fibrinogen (FIB), erythrocyte electrophoresis, fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), serum 25-hydroxyvitamin D3 ([25(OH)D3]), endothelin (ET), nitric oxide (NO) and homocysteine (Hcy) were detected. Result:By the rank sum test, the clinical effect in observation group was better than that in control group (Z=2.371, PPPPPP3] and NO were higher than those in control group (PConclusion:Modified Danggui Sini Tang and Buyang Huanwu Tang can ameliorate hemodynamics and vascular endothelial function, improve ABI, relieve arteriosclerosis and narrow degrees, and alleviate clinical symptoms.

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.

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 the Regularity of Chinese Patent Medicine Prescriptions for the Qi Deficiency and Blood Stasis Syndrome / 中国药房

OBJECTIVE:To investigate the regularity of Chinese patent medicine prescriptions for Qi deficiency and blood sta-sis syndrome (QDBSS),and to provide reference for studying QDBSS diagnosis standard and new TCM for related symptoms. METHODS:Chinese patent medicine for QDBSS were collected from Chinese Pharmacopoeia (2015 edition) and Chinese Mate-ria Medica Preparation(1993 version). The regularity of Chinese patent medicine prescriptions and symptom association rule were analyzed by using TCM inheritance auxiliary system (V2.5). RESULTS:Among the 171 symptoms,chest tightness,shortness of breath,chest pain,fatigue and palpitation were common symptoms,and three groups of symptoms were included as chest tight-ness-shortness of breath-chest pain-palpitation-irregularly pulse;mouth and eye deviation-numbness of hands and feet-hemiple-gia-stiff tongue-spasm;hypomenorrhea-irregular menstruation-abdominal mass-dysmenorrheal. One hundred and thirty-one Chinese patent medicines included 304 ingredients,top 5 in the list of frequency were Astragalus membranaceus,Salvia militiorrhiza,An-gelica sinensis,Ligusticum chuanxiong,Panax ginseng. A. membranaceus- A. sinensis,L. chuanxiong-A. sinensis,S. militiorrhi-za-A. membranaceus,L. chuanxiong- A. membranaceus and L. chuanxiong-S. militiorrhiza were frequently used herbal combina-tions. A. membranaceus-A. sinensis-L. chuanxiong-S. militiorrhiza-P. ginseng-Carthamus tinctorius-Panax notoginseng was the core combination. A new prescription for QDBSS was formed (P. ginseng-Radix Paeoniae Rubra-borneol-Gastrodia elata-artificial moschus-Myristica fragrans). CONCLUSIONS:QDBSS has common symptoms which exist in many kinds of diseases,such as chest tightness,chest pain and shortness of breath;it also has the unique symptoms among various diseases. Invigorating Qi and promoting blood circulation is the basic treatment for the QDBSS. It is of significance to pay attention to"supplement by passing, combination of pass and supplement"and combine regulating Qi-flowing method with enriching blood method or aromatic warming method for QDBSS therapy according to the differ-ence of Zhengxie shengshuai.

Objectification on Metabolomics of Different Traditional Chinese Medicine Syndromes in Patients with Coronary Heart Disease and Angina Pectoris / 世界科学技术-中医药现代化

This study was aimed to investigate potential biomarkers in different traditional Chinese medicine (TCM) syndromes of angina pectoris of coronary heart disease (CHD) by using metabolomic technology,and to explore the objective law of different TCM syndromes of CHD.Endogenous metabolites in serum and urine from the healthy group,and patients with DHD angina pectoris patients of the syndrome of Qi deficiency and blood stasis,as well as the syndrome of Qi deficiency,blood stasis and phlegm turbidity were detected by the liquid chromatography-mass spectrometry (LC-MS).Metabolic profiles were analyzed by the principal component analysis (PCA) and the orthogonal partial least squares discriminant analysis (OPLS-DA).The results showed that in PCA,the healthy group,Qi deficiency and blood stasis group,as well as the Qi deficiency,blood stasis and phlegm turbidity group can be obviously distinguished.Potential biomarkers in the Qi deficiency and blood stasis syndrome contained aspartyl methionine and cysteine sulfinic acid.Potential biomarkers in the Qi deficiency,blood stasis and phlegm turbidity syndrome contained hippuric acid,amino glucose,fructosamine and triglyceride.The objective performance of Qi deficiency syndrome was the absence of biotin,lysyl tyrosine,phosphatidylglycerol and glycocholic acid.It was concluded that through the new metabolomic technology,different endogenous metabolites in the syndrome of Qi deficiency and blood stasis,as well as the syndrome of Qi deficiency,blood stasis and phlegm turbidity of patients with DHD angina pectoris were detected.It provided ideas for the clinical practice of prevention,diagnosis and treatment of different TCM syndromes.

Analysis of on medication rules for Qi-deficiency and blood-stasis syndrome of chronic heart failure based on data mining technology / 中国中药杂志

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.

Study on the Effect of Safflower Injection on the Regulation of Genes related to Qi-deficiency and Blood Stasis Syndrome in Rats / 现代生物医学进展

Objective:To establish two differential gene expression profiles of qi-deficiency and blood stasis syndrome before or after safflower injection treatment by using gene chip technology;compared and analyzed to ensure the effective genes that are responsible for the therapeutic effects of safflower injection against qi-deficiency and blood stasis syndrome in rats.Furthermore,speculated the effect mechanism of the therapeutic genes.Methods:Fifteen SD rats were randomly divided into 3 groups (n=5):control group,model group,and medication group.Qi-deficiency and blood stasis model was established by subjecting the rats to hunger and fatigue for two weeks.After a week of the modeling,safflower injection (100 mg/kg/d) was administered daily via the tail vein for 7 days in medication group,and the rats in model group were injected with saline of the same volume.Control group received normal feeding.At the end of the experiment,rats were killed and whole blood was collected to evaluate the blood stream change and extract mRNAs in blood samples.Qualified mRNAs were reverse transcribed into cDNA which was then used in gene chip hybridization.The genes regulated by safflower injection were determined by the fluorescence signal and the functional mechanisms of safflower injection were confirmed by further querying genealogy databases and reviewing literatures.Results:After two weeks of the modeling,the whole blood viscosity under various shear rates was significantly increased in the model rats which showed faint,blood stasis and weight loss,indicating that the model is made successfully.The increased whole blood viscosity and qi-deficiency and blood stasis syndrome were obviously reversed by safflower injection treatment.Compared with the control group,252 genes up-regulated while 54 genes down-regulated in model group;compared with the model group,196 genes up-regulated while 32 genes down-regulated.Among these,16 differentially expressed genes were involved in inflammation and immune response.Conclusions:Safflower injection was effective in treating qi deficiency and blood stasis syndrome,which was achieved by regulating inflammation related genes.