Comparing the mechanism of four classic Gualou-Xiebai prescriptions for cardiovascular diseases with phlegm and blood stasis syndrome based on molecular network modeling

Background:Four classical Traditional Chinese Medicine prescriptions,namely Gualou Xiebai Baijiu decoction,Gualou Xiebai Banxia decoction(GLXBBX),Zhishi Xiebai Guizhi decoction(ZSXBGZ)and Danlou prescription(DL),have been frequently used for treatment of phlegm and blood stasis syndrome(PBSS)-related cardiovascular diseases.However,its therapeutic mechanism has not been clearly elucidated.This study aimed to explore PBSS and its molecular mechanism,clarify and compare the mechanisms of four prescriptions in treating PBSS-related diseases.Method:In this study,we collected four prescriptions’compounds,predicted therapeutic targets,and enriched pathways which were based on network pharmacology.Then,we analysed the commen and different mechanisms by combing the network of components,targets and pathways.Finally,molecular docking was engaged to assess the binding potential of key compounds and hub targets.Results:We showed that four prescriptions’intersection genes(VEGFA,SRC,EGFR,etc.)were commonly enriched in PI3K-AKT signaling pathway,HIF-1 signaling pathway,etc.In addition,platelet activation and cAMP signaling pathway were singly enriched from the GLXBBX through unique compounds 12,13-epoxy-9-hydroxynonadeca-7,10-dienoic acid and Cyclo(L-tyrosyl-L-phenylalanyl).These bioactive compounds may exert GLXBBX’s unique pharmacological pathways via involving in mediating PPARA,PTGER3,etc.Sphingolipid signaling pathway was singly enriched from the ZSXBGZ through unique compounds tetramethoxyluteolin,ergosterol peroxide,etc.These bioactive compounds could mediate ADORA1,ADORA3 and TNFRSF1A to regulate ZSXBGZ’s unique pharmacological pathways.AMPK signaling pathway was singly enriched from the DL through unique compounds kaempferol,evofolinb,ethyl acid and aureusidin.These bioactive compounds were involved in mediating the main targets of AMPK signaling pathway,such as TNF,TNFRSF1A,etc.Conclusions:Our research demonstrated that GLXB-prescriptions involved in almost all pathological stages of PBSS-related cardiovascular diseases by modulating high-frequency shared pathways and targets mainly through key compounds(quercetin,mandenol,sitosteryl acetate and luteolin,etc.),for example,participate in the process of atherosclerosis,lipid metabolism,inflammation,immune response,thrombosis,inhibit inflammatory factors and platelet aggregation,regulate immune function,vascular function,oxidative stress.In addition to common pharmacological efficacies,there could also be specificities among GLXB prescriptions due to different compounds.For example,GLXBBX tends to regulate the function of vascular and endothelial barrier,prevent thrombosis.ZSXBGZ tends to regulate lipid metabolism and protect the heart from lipid accumulation.DL tends to maintain energy homeostasis and improve inflammation.

A Clinical Study on the Treat ment of Chronic Pelvic Inflammation of Qi-stagnation with Blood Stasis Syndrome by Penyanqing Capsule (盆炎清胶囊)

Objective： To observe the clinical efficacy of Penyanqing Capsule （盆炎清胶囊, PYQC） in treating pelvic inflammation of Qi-stagnation with blood stasis syndrome. Methods： The randomized, single blinded, parallel positive drug controlled method was adopted, with 82 patients assigned into two groups by envelop method. The 42 patients in the treated group received PYQC 3 times a day, 4 capsules each time taken orally; the 40 patients in the control group were given orally Fuyankang tablets （妇炎康片, FYKT） 3 times a day, 6 tablets each time. The therapeutic course for both groups was 2 months, and 2 courses of treatment were given successively to observe the comprehensive effect, changes of symptoms and signs before and after treatment. The effects of PYQC on hemorrheological character in part of the patients and on the pathogenetic chlamydia and mycoplasma were also observed. Results： The total effective rate in the treated group was 83.3%, which was insignificantly different from that in the control group （77.5%, P〉0.05）. However, PYQC could significantly lower the hemorrheologic indexes in patients and showed definite influence on the pathogenetic chlamydia and mycoplasma. Conclusion： PYQC has good therapeutic effect in treating chronic pelvic inflammation of Qi-stagnation with blood stasis syndrome, and showed definite effect on chlamydia and mycoplasma.

Construction of Rat Model of Hepatic Fibrosis with Blood Stasis Syndrome Integrated with Traditional Chinese Medicine(TCM)Syndrome and Western Medicine Disease

[ Objective ] According to the theory of blood stasis in traditional Chinese medicine （ TCM）, the animal modeling method of hepatic fibrosis integrated with pathology and symptoms was explored and improved, to construct a new type of rat model of hepatic fibrosis with blood stasis syndrome integrated with tradition- al Chinese and westem medicine. [ Method] The hepatic fibrosis model of blood stasis with blood stasis syndrome was constructed by jointing multi factors, inclu- ding intragastric administration of ethanol, high fat and low protein feeding, joint injection of dimethylnitrosamine （DMN）, bovine serum albumin （BSA） and nor- epinephrine （NE）. The modeling method was further compared with traditional CC14 single-factor modeling method from the aspects of mortality, blood stasis syn- drome of TCM, syndrome grading, general morphology of liver pathology, liver function changes, as well as expression levels of three kinds of collagen （type I and type III collagen, a-SMA） determined by immunohistochemical staining method, and four items of rat hepatic fibrosis （HA, P3NP, LN, CIV content） determined by radio enzyme immunoassay. [ Result ] In blood stasis group, （ 1 ） the mortality of rats was 20% ; （2） model rats appeared typical blood stasis syndromes of TCM such as ecchymosis, dark purple tongue, loose stool, and blood stasis syndrome grading was high; （3） fibrosis changes of liver such as dark white surface, dense gray nodules and brittle texture were observed in general morphological examination; （4） serological liver function tests found that ALT and AST of model rats, as well as TBIL, DBIL and IBIL contents increased significantly; （5） immunohistochemical staining demonstrated that the expression levels of three kinds of collagen （type I and type III collagen, ot-SMA） increased significantly; （6） four items of rat serum hepatic fibrosis, HA, P3NP, LN, CIV content, increased significantly; （7） the above results in blood stasis syndrome model group （except morality and liver function） were higher than those in CC14 modeling group, and the difference was statistically significant （P 〈 0.05 ）. [ Conclusion ] The new improved modeling method effectively reduces high mortality in traditional CC 14 modeling method. In addition to low mortality, the model animal has dual characteristics of disease in western medicine and syndrome in TCM. It is consistent with the pathological characteristics of hepatic fibrosis in western medicine when according with the basic characteristics of blood stasis syndrome in TCM.

Effect of Gualou Xiebai Banxia decoction combined with Danshen Decoction on clinical efficacy of unstable angina with phlegm and blood stasis syndrome

Objective:To observe the clinical efficacy and safety of Gualou Xiebai Banxia decoction combined with Danshen decoction on unstable angina(UA)with phlegm and blood stasis syndrome.Method:Eighty patients with UA were randomly divided into treatment group(40 cases)and control group(40 cases)by random number table.The control group was given conventional western medicine treatment,and the experimental group was given Gualou Xiebai Banxia decoction and Danshen decoction on the basis of the control group.Both groups were treated for 4 weeks.Before and after treatment,the angina attacks,dosage of nitroglycerin,traditional Chinese medicine syndrome score,quality of life score,blood lipid,coagulation index and clinical total efficacy were observed and recorded.Results:After 4 weeks of treatment,the attack times and duration of angina in the two groups were both decreased compared with those before treatment.And the treatment group was more significantly reduced than the control group,the difference was statistically significant(p<0.05);the consumption of nitroglycerin of the treatment group was 90.0%,which was better than 67.5%of the control group,the difference was statistically significant(p<0.05);the total effective rate of the treatment group was 90%,which was better than 65%of the control group,the difference was statistically significant(p<0.05);the traditional Chinese medicine(TCM)syndrome score of the experimental group was lower than that of the control group,the differences was significant(p<0.05).The improvement of low density lipoprotein(LDL-C),total cholesterol(TC)and prothrombin time(PT)in the experimental group was better than that in the control group(p<0.05).During the study,there were no obvious adverse reactions in both groups.Conclusion:Gualou Xiebai Banxia decoction combined with Danshen decoction can effectively relieve the attack of angina and the consumption of nitroglycerin,improve clinical symptoms,regulate blood lipid and blood flow state,and improve the quality of life of patients with UA,with good clinical efficacy 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

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 disease 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,biological pathway and protein interaction of the different proteins were analyzed by bioinformatics,so as to identify the molecular 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 syndrome 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.

Optimization of synergistic drug combinations of different sparganins against blood stasis syndrome

Background:Blood stasis syndrome is one of the major syndromes in the development of chronic conditions in traditional Chinese medicine.Blood stasis syndrome is closely related to microcirculation dysfunction and thrombosis.Trigonaceae,as a representative traditional Chinese medicine for promoting blood circulation and removing blood stasis,there are many studies on its anticoagulant,antiplatelet aggregation and antithrombotic effects.Methods:Optimization of sparganin compounds,comprising sparganin A,sparganin B,and sparganin C for the characterization of drug pair effects against blood stasis syndrome was carried out.Ternary quadratic regression orthogonal combination design was carried out in a mouse model of blood stasis syndrome.The concentrations of thromboxane B2,plasminogen activator inhibitor 1,fibrinogen,and endothelin 1 were evaluated by enzyme linked immunosorbent assay.Thymus,hepatic,and spleen indices were also assessed.The outcomes of the evaluations aided in identifying optimum parameter values for the most favorable precipitation against blood stasis syndrome.Subsequently,Cytoscape 3.7.1 was used for network pharmacology to predict the key targets of sparganins and disease.Results:After sparganin A,sparganin B,and sparganin C treatment,hepatic had a downward trend,while spleen indices and thymus had an upward trend.Compared with the model group,thromboxane B2,endothelin 1,plasminogen activator inhibitor 1,and fibrinogen were decreased(P<0.05).The blood stasis syndrome model regression equation was extremely significant,and the correlation coefficient of R was 0.939,indicating that sparganin A,sparganin B and sparganin C were positively correlated at all levels.According to the dosage of these three factors and test results,the equation was fitted and the maximum values of the three sparganin in the corresponding dose range were obtained as follows:A=0.2982 mg/10g,B=0.1438 mg/10g,C=0.0417 mg/10g.Thus,the optimum parameters were found to be 0.298:0.144:0.042 for synergistic drug combinations of sparganin compounds sparganin A,sparganin B,and sparganin C in blood stasis syndrome.The possible key targets of sparganins included matrix metalloproteinase 9,plasminogen,proto-oncogene tyrosine-protein kinase src,and akt serine/threonine kinase 1 in blood stasis syndrome.Conclusion:Our study for the first time found two novel cyclic peptide compounds sparganin B and sparganin C have an anti-blood stasis effect,and speculated sparganins key targets included matrix metalloproteinase 9,plasminogen,proto-oncogene tyrosine-protein kinase src,and akt serine/threonine kinase 1 in blood stasis syndrome.

Clinical observation on efficacy of compound of warming yang, descending turbidity and dredging collaterals in the treatment of diabetic kidney disease with Yin-Yang deficiency and blood stasis syndrome

Objective:To observe the clinical efficacy of compound of owarming yang,descending turbidity and dredging collaterals in the treatment of diabetic kidney disease with yin-yang deficiency and blood stasis syndrome.Methods:Seventy-six patients of diabetic kidney disease with yin-yang deficiency and blood stasis syndrome were randomly divided into observation group and control group,thirty-eight cases in each group.The control group was given conventional western medicine treatment,while the observation group took compound of owarming yang,descending turbidity and dredging collaterals orally on the basis of conventional western medicine treatment.The course of treatment covered for one month.Before and after treatment,we observed the scores of traditional Chinese medicine symptoms,indicators of renal function[serum creatinine(Scr),blood urea nitrogen(BUN),microalbuminuria(MALB)],indicators of glucose metabolism[fasting plasma glucose(FPG),2-hour postprandial blood glucose(2hPG),glycosylated hemoglobin(HbAlc)],indicators of hemorheology[plasma viscosity(PV),platelet aggregation rate(PAR),fibrinogen(FIB)],Cystatin-C(Cys-C),C-reactive protein(CRP)in the two groups.Results:After treatment,the clinical effect of the observation group was significantly better than the control group(P<0.05).The scores of traditional Chinese medicine symptoms,indicators of renal function(Scr、BUN、UAER),indicators of glucose metabolism(FPG、2hPG、HbAlc),indicators of hemorheology(PV、PAR、FIB),Cys-C and CRP in the two groups were decreased significantly compared with those before treatment(P<0.05),and the decrease in the observation group was superior to that in the control group(P<0.05).Conclusion:Compound of warming yang,descending turbidity and dredging collaterals has remarkable efficacy in treating of diabetic kidney disease patients with yin-yang deficiency and blood stasis syndrome by alleviating clinical symptoms,glucose metabolism,renal function and microcirculatory disturbance,and the mechanism related to alleviation of microinflammation.

Analysis of herbs-combination of Professor Yang Su-qing in the treatment of psoriasis vulgaris with blood stasis syndrome

Objective:To explore Professor Yang Suqing’s experience in treating blood stasis syndrome of psoriasis vulgaris and analyze the characteristics of its prescription;Methods:Outpatient prescriptions for the treatment of psoriasis vulgaris with blood stasis syndrome were selected and extracted traditional Chinese medicine for standardized processing.Then analyze the data by using set visualization analysis and Apriori algorithm.Results:A total of 149 traditional Chinese herbs were extracted.Among them,and the top 12 commonly used herbs with frequency>30 were Licorice,Saposhnikovia,Schizonepeta tenuifolia,Angelica sinensis,Paeonia lactiflora,Ligusticum chuanxiong,Rehmannia glutinosa,Cicada slough,Oyster and Keel through the set visualization analysis,herbs association rules analysis,and herbs combination analysis.Saposhnikovia,Liquorice,Schizonepeta tenuifolia,Angelica sinensis and Paeonia Alba are the most commonly used combination of herbs by Professor Yang Suqing in the treatment of blood stasis syndrome of psoriasis vulgaris.Conclusion:In addition to invigorating blood circulation and removing blood stasis herbs,which are preferred for the treatment of blood stasis syndromes,Saposhnikovia and Schizonepeta tenuifolia,etc.,are used to synergistically exert the functions of invigorating blood circulation and removing blood stasis and eliminating wind expression,with remarkable efficacy.

Blood stasis syndrome:clinical multi-omics research and related problems

Multi-omics is a biological analysis approach in which the data sets are multiple"omics",such as genomics,transcriptomics,proteomics,metabolomics.Multiomics can be used in the detection,diagnosis,treatment,and prognosis of diseases as a kind of potential biomarker.Blood stasis syndrome(BSS)is a common syndrome in traditional Chinese medicine(TCM).Multi-omics can reflect the change of BSS as a whole.Thus,the purpose of this manuscript was to fully review the clinical multi-omics research and related problems of BSS.We found that the multi-omics of BSS reflected many pathophysiological processes through regulating vascular endothelial cells,vasodilation and contraction,oxidative stress,thrombosis,angiogenesis,platelet aggregation,lipid metabolism,inflammatory response,immune and coagulation function,energy balance,amino acid metabolism,and so forth.Many potential biomarkers of BSS were found in multi-omics and some promoting blood circulation Chinese medicines(PBCCMs)could well regulate the abnormal biomarkers and make them return to the normal level.

Clinical Nursing Intervention of Moxibustion on Abdominal Distension Symptoms in Heart Failure (Heart and Kidney Yang Deficiency and Blood Stasis Blocking Collaterals Syndrome)

Objective:To investigate the clinical nursing intervention effect of moxibustion on abdominal distension symptoms in heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome).Methods:62 patients with heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome)admitted to our hospital from February 2023 to February 2024 were selected and divided into the observation group(n=31)and the control group(n=31)by using the random numerical table method.The control group adopted conventional nursing interventions,and the observation group received the nursing program of the control group with the addition of moxibustion nursing interventions.The nursing effectiveness,quality of life scores,and nursing satisfaction were compared between the two groups.Results:The nursing effectiveness of the observation group was significantly higher than the control group(P<0.05);the quality of life score of the observation group was significantly higher than the control group(P<0.05);the nursing satisfaction of the observation group was significantly higher than that of the control group(P<0.05).Conclusion:The use of moxibustion nursing intervention in patients with heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome)can effectively relieve the symptoms of abdominal distension,improve patients'quality of life,and increase nursing satisfaction,which has promotion and application values.

Exploring the medication pattern and mechanism of action of traditional Chinese medicine in treating polycystic ovary syndrome with kidney deficiency and blood stasis based on data mining and network pharmacology

Background:Using network pharmacology to explore the potential molecular mechanism of traditional Chinese medicine in treating polycystic ovary syndrome(PCOS)with kidney deficiency and blood stasis syndrome.Method:Collect the related literature materials of PCOS with kidney deficiency and blood stasis syndrome treated by traditional Chinese medicine in four databases in recent ten years,extract the information of prescriptions and complete the frequency analysis.Traditional Chinese Medicine Systems Pharmacology Database was used to screen out the effective components.Use Online Mendelian Inheritance in Man and other databases to screen PCOS disease targets.The intersection targets obtained by clustering prescription and PCOS disease targets were submitted to STRING database for protein-protein interaction network analysis,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes pathways were analysed by Metascape.Result:There are 155 kinds of traditional Chinese medicines used in the literature.The most commonly utilized ones are Cuscutae Semen,Angelicae Sinensis Radix,and Rehmanniae Radix Praeparata.The results of the cluster analysis indicated that the plants most commonly found throughout the prescription were Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.GO results show that biological processes include cell reaction to organic nitrogen compounds and cell reaction to nitrogen compounds.The functional display of GO molecule includes cytokine receptor binding,signal receptor regulator activity and so on.Kyoto Encyclopedia of Genes and Genomes results show that the possible mechanisms of action are cancer pathway,an endocrine resistance signal pathway.Conclusion:Through data mining,the cluster prescription for PCOS with kidney deficiency and blood stasis syndrome is Leonuri Herba,Lycopi Herba,Dipsaci Radix,etc.The network pharmacology research of cluster prescription shows that the main drug components for treating PCOS with kidney deficiency and blood stasis syndrome are quercetin,kaempferol,luteolin,tanshinone IIA,etc.,which act on PTGS2,NCOA2,and other targets,and treat PCOS with kidney deficiency and blood stasis syndrome through cancer and endocrine resistance.

Platelet proteomics and its advanced application for research of blood stasis syndrome and activated blood circulation herbs of Chinese medicine

The development of novel and efficient antiplatelet agents that have few adverse effects and methods that improve antiplatelet resistance has long been the focus of international research on the prevention and treatment of cardiovascular and cerebrovascular diseases.Recent advances in platelet proteomics have provided a technology platform for high-quality research of platelet pathophysiology and the development of new antiplatelet drugs.The study of blood stasis syndrome(BSS)and activated blood circulation of traditional Chinese medicine(TCM)is one of the most active fields where the integration of TCM and western medicine in China has been successful.Activated blood circulation herbs(ABC herbs)of Chinese medicine are often used in the treatment of BSS.Most ABC herbs have antiplatelet and anti-atherosclerosis activity,but knowledge about their targets is lacking.Coronary heart disease(CHD),BSS,and platelet activation are closely related.By screening and identifying activated platelet proteins that are differentially expressed in BSS of CHD,platelet proteomics has helped researchers interpret the antiplatelet mechanism of action of ABC herbs and provided many potential biomarkers for BSS that could be used to evaluate the clinical curative effect of new antiplatelet drugs.In this article the progress of platelet proteomics and its advanced application for research of BSS and ABC herbs of Chinese medicine are reviewed.

Effect and Safety of Hydroxysafflor Yellow A for Injection in Patients with Acute Ischemic Stroke of Blood Stasis Syndrome: A Phase Ⅱ , Multicenter, Randomized, Double-Blind, Multiple-Dose, Active-Controlled Clinical Trial

Objective:To assess the effect and safety of Hydroxysafflor Yellow A for Injection(HSYAI)in treating patients with acute ischemic stroke(AIS)and blood stasis syndrome(BSS).Methods:A multicenter,randomized,double-blind,multiple-dose,active-controlled phaseⅡtrial was conducted at 9 centers in China from July 2013 to September 2015.Patients with moderate or severe AIS and BSS were randomly assigned to low-,medium-,high-dose HSYAI groups(25,50 and 70 mg/d HSYAI by intravenous infusion,respectively),and a control group(Dengzhan Xixin Injection(灯盏细辛注射液,DZXXI)30 mL/d by intravenous infusion),for 14 consecutive days.The primary outcome was the Modified Rankin Scale(mRS)score 1 at days 90 after treatment.The secondary outcomes included the National Institute of Health Stroke Scale(NIHSS)score 1,Barthel Index(BI)score 95,and BSS score reduced 30%from baseline at days 14,30,60,and 90 after treatment.The safety outcomes included any adverse events during 90 days after treatment.Results:Of the 266 patients included in the effectiveness analysis,66,67,65 and 68 cases were in the low-,medium-,and high-dose HSYAI and control groups,respectively.The proportions of patients in the medium-and high-dose HSYAI groups with mRS score 1 at days 90 after treatment were significantly larger than the control group(P<0.05).The incidences of favorable outcomes of NIHSS and BI at days 90 after treatment as well as satisfactory improvement of BSS at days 30 and 60 after treatment in the medium-and high-dose HSYAI groups were all significantly higher than the control group(P<0.05).No significant difference was reported among the 4 groups in any specific adverse events(P>0.05).Conclusions:HSYAI was safe and well-tolerated at all doses for treating AIS patients with BSS.The medium(50 mg/d)or high dose(75 mg/d)might be the optimal dose for a phaseⅢtrial.

Correlation of Platelet and Coagulation Function with Blood Stasis Syndrome in Coronary Heart Disease: A Systematic Review and Meta-Analysis

Objective To investigate the correlation of platelet and coagulation function with blood stasis syndrome(BSS)in coronary heart disease(CHD).Methods The protocol for this meta-analysis was registered on PROSPERO(CRD42019129452).PubMed,Excerpta Medica Database(Embase),the Cochrane Library,and China National Knowledge Infrastructure(CNKI)were searched from inception to 1st June,2020.Trials were considered eligible if they enrolled BSS and non-BSS(NBSS)patients with CHD and provided information on platelet and coagulation function.The platelet function,coagulation function,and fibrinolytic activity were compared between the BSS and NBSS groups.Forest plots were generated to show the SMDs or ESs with corresponding 95%CIs for each study.Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity.Results The systematic search identified 1,583 articles.Thirty trials involving 10,323 patients were included in the meta-analysis.The results showed that mean platelet volume,platelet distribution width,platelet aggregation rate,platelet P selectin,fibrinogen,plasminogen activator inhibitor-1(PAI-1),thromboxane B2(TXB2),6-keto-prostaglandin F1alpha(6-keto-PGF1α),and TXB2/6-keto-PGF1αwere higher in the BSS group than in the NBSS group(P<0.05 or P<0.01).Activated partial thromboplastin time was lower in the BSS group than in the NBSS group in the acute phase of CHD(P<0.01).The R and K values in thromboelastography and tissue plasminogen activator(t-PA)and t-PA/PAI-1 were lower in the BSS group than in the NBSS group(all P<0.01).No difference was found in the results of platelet count,plateletcrit,maximum amplitude,von Willebrand factor,prothrombin time,thrombin time,international normalized ratio,etc.between groups.Conclusions Increased platelet function,hypercoagulability,and decreased fibrinolytic activity were found among CHD patients with BSS.

Study on Correspondence between Prescription and Syndrome and the Essence of Phlegm and Blood Stasis Syndrome in Coronary Heart Disease Based on Metabonomics

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine.Until now,due to limitations of the methods available,the progress towards understanding such complicated systems has been slow.Metabonomics encompasses the dynamics,composition and analysis of metabolites,enabling the observation of changes in the metabolic network of the human body associated with disease.Being from the point of view of the whole organism,metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level.Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease（CHD）,which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs.The fundamental differences of material between the two also need to be interpreted.The authors consider that we can use the method of combining a disease（in this case CHD）with associated syndromes（phlegm and blood stasis syndrome）to select patients with phlegm and blood stasis syndrome of CHD,and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra.Meanwhile,we can study the syndrome in CM,observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome,in order to validate the material fundament in the progress of syndrome formation and their differences.This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria,but will also offer a new approach of studying the essence for a syndrome using metabonomics.

Association of Platelet-Activating Factor Receptor Gene rs5938(G/T) and rs313152(T/C) Polymorphisms with Coronary Heart Disease and Blood Stasis Syndrome in A Chinese Han Population

Objective: To explore the association of the platelet-activating factor receptor(PAFR) gene rs5938, rs313152 and rs76744145 polymorphisms with coronary heart disease(CHD) and blood stasis syndrome(BSS) of CHD in Chinese Han population. Methods: A total of 570 CHD patients(299 with BSS and 271 with non-BSS) and 317 controls were enrolled. The PAFR gene rs5938, rs313152 and rs76744145 polymorphisms were genotyped using the multiplex SNaP shot technology. The statistical analysis was conducted using a multiple variable logistic regression model. Results: Significant differences were detected in the genotypes frequency distributions of the rs5938(P<0.01), but not the rs313152(P>0.05), between the controls and CHD patients. Individuals with an rs5938 or rs313152 mutated allele had a low risk for CHD [adjusted odds ratio(aOR)=0.35, 95% confidence interval(CI): 0.23 to 0.56, P<0.01; aOR=0.65, 95% CI: 0.46 to 0.91, P<0.05, respectively]. After the CHD patients were stratified as BSS or non-BSS according to their Chinese medicine patterns, the rs5938 polymorphism mutated alleles had a significant association with a low risk for BSS of CHD(aOR=0.32, 95% CI: 0.18 to 0.57, P<0.01) and non-BSS of CHD(aOR=0.31, 95% CI: 0.17 to 0.55, P<0.01). The rs313152 polymorphism was associated with a low risk for BSS(aOR=0.51, 95% CI: 0.33 to 0.79, P<0.01), but not for non-BSS(aOR=1.22, 95% CI: 0.81 to 1.85, P>0.05). Furthermore, the interaction effect of the rs5938 and rs313152 polymorphisms for BSS of CHD was significantly based on an aOR value associated with the combination of the rs5938 GT genotype with the rs313152 TC genotype of 0.27(95% CI: 0.1 to 0.7, P<0.01). Conclusion: The PAFR gene rs5938 or rs313152 polymorphisms might be a potential biomarker for susceptibility to CHD, especially to BSS of CHD in Chinese Han population.

Efficacy and Safety of Guihuang Formula in Treating Type Ⅲ Prostatitis Patients with Dampness-Heat and Blood Stasis Syndrome: A Randomized Controlled Trial

Objective: To observe the efficacy and safety of Guihuang Formula(GHF) in treating patients with type Ⅲ prostatitis and Chinese medicine syndrome of dampness-heat and blood stasis. Methods: Sixty-six type Ⅲ prostatitis patients with dampness-heat and blood stasis syndrome were randomly divided into the treatment group(GHF) and the control group(tamsulosin) using a random number table, with 33 cases each group. The treatment group received GHF twice a day, and the control group received tamsulosin 0.2 mg once daily before bedtime. Patients in both groups received treatment for 6 weeks and was followed up for 2 weeks. The outcomes included the National Institute of Health Chronic Prostatitis Symptom Index(NIH-CPSI) score, Chinese Medicine Symptoms Score(CMSS), expressed prostatic secretions(EPS) and adverse events(AEs). Results: After treatment, the NIH-CPSI total score and domain scores of pain discomfort, urination and quality of life decreased significantly from the baseline in both groups(P<0.05). The CMSS score decreased in both groups(P<0.05). The white blood cell(WBC) count decreased and lecithin body count increased in both groups(P<0.05). GHF showed a more obvious advantage in reducing the pain discomfort and quality of life domain scores of NIH-CPSI, reducing the CMSS score, increasing the improvement rate of the WBC and lecithin body counts, compared with the control group(P<0.05). There were no significant differences in decreasing urination domain score of NIH-CPSI between two groups(P>0.05). In addition, no serious AEs were observed. Conclusion: GHF is effective in treating type Ⅲ prostatitis patients with dampness-heat and blood stasis syndrome without serious AEs.(Registration No. ChiCTR1900026966)

Blood Stasis Syndrome of Coronary Heart Disease:A Perspective of Modern Medicine

The medical community as a whole is attempting to start preventive therapy for coronary heartdisease （CHD） patients earlier in life. However, the main limitations of such interventions are drug resistanceand adverse reactions. Additionally, traditional biomarker discovery methods for CHD focus on the behavior ofindividual biomarkers regardless of their relevance. These limitations have led to attempting novel approachesto multi-dimensionally investigate CHD and identify safe and efficacious therapies for preventing CHD. Recently,the benefit of Chinese medicine （CM） in CHD has been proven by increasing clinical evidence. More importantly,linking CM theory with modern biomedicine may lead to new scientific discoveries. According to CM theory,all treatments for patients should be based on patients＇ syndromes. A recent epidemiological investigation hasdemonstrated that blood stasis syndrome （BSS） is the major syndrome type of CHD. BSS is a type of complexpathophysiological state characterized by decreased or impeded blood flow. Common clinical features ofBSS include a darkish complexion, scaly dry skin, and cyanosis of the lips and nails, a purple or dark tonguewith purple spots, a thready and hesitant pulse, and stabbing or pricking pain fixed in location accompaniedby tenderness, mass formation and ecchymosis or petechiae. The severity of BSS is significantly correlatedwith the complexity of coronary lesions and the degree of stenosis, and is an important factor affecting theoccurrence of restenosis after percutaneous coronary intervention. The mechanisms of BSS of CHD patientsshould be investigated from a modern medicine perspective. Although many studies have attempted toexplore the biomedical mechanisms of BSS of CHD, from hemorheological disorders to inflammation andimmune responses, the global picture of BSS of CHD is still unclear. In this article, the current status of studiesinvestigating the biomedical mechanisms of BSS of CHD and future perspectives are discussed.

Differential Proteomics Analysis of Endometriosis in Blood Stasis Syndrome

Objective： To investigate the innate characters of 3 endometriosis （EMT） syndromes, blood stasis （BS）, qi stagnation and blood stasis （QSBS） as well as Shen （Kidney） deficiency and blood stasis （KDBS） in terms of proteomics, lay a molecular biological basis for the differentiation of various blood stasis syndromes of EMT, establish a EMT microscopic syndrome differentiation and diagnosis system in terms of proteomics, discover the evolution principles and therapeutic targets of these EMT syndromes, and search their significant molecular markers and genetic intervention targets. Methods： Six specimens from the ectopic and entopic endometrium tissues of patients with EMT in each syndrome, BS, QSBS as well as KDBS, in the early proliferative phase of the menstrual cycle, and 6 specimens from normal endometrium tissues in the early proliferative phase of the menstrual cycle were obtained. Three groups were formed in each syndrome by mixing two random specimens in equal amount, and then their respective two-dimensional electrophoresis graphs were obtained after total protein extraction. Finally, the detected differences in protein expression were identified through matrix-assisted laser desorption Ionization-time of flight mass spectrometry （MALDI-TOF/MS） and protein database. Results： The results of differential proteins expressed in each syndrome were shown as follows： BS syndrome had 2 differential proteins in entopic endometrium and 1 differential protein in ectopic endometrium; KDBS syndrome had 3 in entopic endometrium and 3 in ectopic endometrium; and QSBS syndrome had 3 in entopic endometrium and 4 in ectopic endometrium. It was found out that annexin was highly expressed in both entopic and ectopic endometrium of KDBS syndrome; and myosin light chain 3 was highly expressed in both entopic and ectopic endometrium of QSBS syndrome. Conclusion： There are differential protein expressions among the 3 EMT syndromes, which might be the inner origin of syndrome characters, and these differential proteins might be the candidate biomarkers for the pathogenesis of various EMT syndromes.

Biomedical Mechanisms of Blood Stasis Syndrome of Coronary Heart Disease by Systems Biology Approaches

The prevalence of coronary heart disease （CHD） is increasing, and has been a severe burden on society and family worldwide. New ideas need to be achieved for developing more efficacious and safe therapies to treat CHD. Chinese medicine （CM） uses multicomponent drugs to prevent disease and ameliorate symptoms based on patients＇ different syndromes. The benefit of CM in CHD has recently been proven by increasing clinical evidence. More importantly, linking CM syndrome differentiation and biomedical diagnosis might provide innovative thinking for treating CHD. According to epidemiological investigations, blood stasis syndrome （BSS） is the major type of syndrome in CHD. Investigating the biomedical mechanisms of BSS of CHD is a topic of CM research. Because the holistic perspective of systems biology is well matched with CM, the application of omics techniques and other integrative approaches appears inherently appropriate. A wide range of omics techniques, including transcriptomics and proteomics, have been used in studies of BSS of CHD to search for a common ground of understanding. These approaches could be useful for understanding BSS of CHD from clinical and biological viewpoints. Nevertheless, current studies mainly contain results from a single approach, and they have not achieved the holistic, systematic and integrative concept of system biology. Therefore, we discuss the progress and challenges in exploring the biomedical mechanisms of BSS of CHD by systems biology approaches. With further development of systems biology, a better platform to study BSS of CHD may be provided, and biomarkers for BSS of CHD and therapeutic targets may be found. The study of BSS of CHD by systems biology approaches will also be beneficial for developing personalized treatment for BSS of CHD patients.