Discussion on the Prevention and Treatment of COVID-19 Causing Lung Disease and Heart Damage Based on Lei Zhongyi's Theory of Intermingled Phlegm,Blood Stasis and Toxin

Novel coronavirus infection not only damages lung function,but also causes myocardial injury,elevated myocardial enzymes and heart failure,especially for patients with basic heart diseases who develop COVID-19,the first consideration should be the protection of cardiac function.Based on the theory of intermingled phlegm,blood stasis and toxin of heart disease put forward by Master Lei Zhongyi,the dialectical treatment thinking of COVID-19 patients from the concept of damage of phlegm,blood stasis and toxin to the heart were discussed.During the diagnosis,critical stage and recovery period of COVID-19,expectorant and blood-activating agents,heat and detoxification agents can be added to promote lung and asthma,free Bizheng and remove blood stasis,calm the heart and calm the mind,and promote the recovery of cardiopulmonary functions.

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.

Effect of programmed cell death factor 4 on the severity of coronary heart disease and coronary artery disease with blood stasis and toxin

Objective:To explore the diagnostic value of PDCD4 on the degree of arterial stenosis in"blood stasis"coronary heart disease.Methods:Select 80 patients with coronary heart disease in the Second Cardiovascular Zone of the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine in April 2020,and divide them into the"phlegm toxin"group(n=40)and the"phlegm stasis"group(n=40)based on the dialectics of traditional Chinese medicine.).Record the gender,age,smoking,and alcohol consumption of the subjects between the two groups,and detect their white blood cell count,neutrophil count,platelet count,platelet volume,platelet distribution width,blood creatinine,uric acid,cystatin,and fibrin The expression levels of original,high-sensitivity C-reactive protein,D-dimer,total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein,apolipoprotein a,apolipoprotein b,and PDCD4.Multivariate logistic regression analysis was used to screen out the risk factors that affect coronary plaque formation,and the receiver operating characteristic(ROC)curve of each index was established to evaluate the severity of coronary stenosis in patients with stasis coronary heart disease by each index and combined index Diagnostic efficiency.Results:The two groups of patients were tested in terms of gender,age,smoking,drinking,triglycerides,cholesterol,high-density lipoprotein,low-density lipoprotein,apolipoprotein-a,apolipoprotein-b,white blood cell count,neutrophil The cell count,platelet count,platelet volume width and platelet distribution width were not statistically significant(P>0.05);the expression levels of hypersensitivity-C-reactive protein,serum creatinine,cystatin,uric acid and PDCD4 were statistically significant between the two groups Difference(P<0.05),and the corresponding hypersensitivity-C-reactive protein,creatinine,cystatin,uric acid and PDCD4 expression levels in the blood stasis group were higher than those in the phlegm blood stasis group.After multivariate logistic regression analysis,the level of PDCD4 in peripheral blood[OR=31.088,95%CI(2.498,3.869)]was an independent influencing factor of the"stagnation"type of coronary heart disease,and PDCD4 was diagnosed as the"stagnation"type of coronary heart disease The area under the ROC curve(AUC)is 88.6%,95%CI(1.894,2.532)(P=0.29);the level of PDCD4 in peripheral blood is positively correlated with the number and severity of coronary artery disease,the number of coronary artery disease and stenosis The greater the degree,the higher the detection value of PDCD4,(P<0.05).Conclusion:The expression level of PDCD4 in peripheral blood is closely related to the subtype of"stasis toxin"and the severity of coronary vascular stenosis.It can be used as a quantitative diagnostic index for the diagnosis of"stasis toxin"coronary heart disease and the severity of coronary vascular stenosis.

Therapeutic effect and apoptosis mechanism of lung-tonifying and expectorant decoction on lung cancer rats with Qi deficiency and blood stasis

Objective:To explore the effect and specific mechanism of lung-tonifying and expectorant decoction on lung cancer rats with Qi deficiency and blood stasis,and aim to provide a new idea on treating the disease with traditional Chinese medicine based on syndrome differentiation.Methods:A total of 60 C57BL/6J male rats were included in the study.The model of Qi deficiency and blood stasis was established in 60 rats by using multiple-factor stimulation.About 10 rats were randomly taken to verify whether the model establishment was successful and the rest of 50 rats were divided into 5 groups with 10 rats each:blank control group,cisplatin group,low dose group,medium dose group and high dose group.The blank control group was treated with normal saline,and cisplatin group was treated with cisplatin while the other three groups were treated with lung-tonifying and expectorant decoction at different doses.The volume change in transplanted tumor,tumor inhibition rate,apoptosis rate,and expression of Bc1-2,Bax.cleaved caspase-3 and cleaved caspase-9 in 5 groups were compared.Results:The rapidest growth rate of transplanted tumor volume was observed in blank control group and the slowest in cisplatin group.The growth rate was gradually decreased with the increasing dose of lung-tonifying and expectorant decoction,and the difference in growth of tumor volume among groups was statistically significant(P<0.05).The cisplatin group showed the highest tumor inhibition rate,with dose-dependent increase(P<0.05).The apoptosis rate in low dose group was higher than blank control group but lower than high dose group(P<0.05).The apoptosis rate in medium dose group was significantly higher man blank control group(P).05).The apoptosis rate in high dose group was significantly higher than control group(P<0.05).The positive expression rates of Bel-2 and Bax in all groups showed statistically significant difference(P<0.05),while expression of cleaved caspase-3 and cleaved caspase-9 in 5 groups was significantly different,with dose-dependent increase(P<0.05).Conclusions:The lung-tonifying and expectorant decoction inhibits the proliferation of tumor cells by inducing and activating the cell apoptosis in treatment of lung cancer with Qi deficiency and blood stasis,probably with good clinical therapeutic effect.

Study of Interference Treatment by Xuesaitong (血塞通) Soft Capsuleon Patients of Nephrosis Syndrome with Qi Deficiency and Blood Stasisduring Dose Reducing Stage of Corticosteroid

Objective: To observe the effect of Xuesaitong (血塞通, XST) soft capsule in interference treatment on patients of nephrosis syndrome (NS) during corticosteroid (CS) dose reducing stage. Methods: Seventy-one NS patients applying prednisone and initiating dose reducing stage were randomized into trial group and control group. On the basis of conventional prednisone dose reduction of both groups, the trial group was given additionally XST, and the treatment course ended with the reduction to maintenance dose. In the course of observation, those who did not comply with the criteria of observation were excluded. Before and after the dose reduction, TCM syndrome scoring, 24 hrs urinary protein amount, blood β2-microglobulin (β2-MG), urinary β2-MG, blood fibrinogen (Fbg), plasma prothrombin time (PT), blood lipid, etc. were observed. Results: The trial group of XST could obviously lower their urinary protein amount and blood lipid level (P<0.05 or P<0.01), markedly improve the blood coagulation parameters (P<0.01), improve the TCM syndrome and CS induced adverse reaction (P<0.05 or P<0.01), also obviously reduced the recurrence rate of NS (P<0.05). Conclusion: XST could obviously improve the clinical symptoms and renal impairment parameters in NS patients during CS dose reduction stage, improve the CS induced adverse reaction and prevent the recurrence of NS.

Comparative evaluation in treating qi-yin deficiency and phlegm stasis syndrome of type 2 diabetes mellitus in a rat model

Objective:To compare the efficacy of traditional Chinese medicine (TCM),western medicine and integrative medicine in treating type 2 diabetes mellitus (T2DM) in a rat model.Methods:The T2DM rat model was established with a high-fat diet (HFD) for 35 days and a single injection of streptozotocin (STZ,30 mg/kg).The T2DM-induced rats were divided into three groups,and treated with Yiqi Yangyin Huatan (YQYYHT) granules (3.84 g/kg per day),pioglitazone (1.35 mg/kg per day) or YQYYHT granules + pioglitazone (3.84 g/kg per day+1.35 mg/kg per day) respectively for 14 days.Clinical features and behavioral changes,as well as T2DM indicators,were recorded to evaluate therapeutics effects in each treatment group.Results:The T2DM rat model expressed insulin resistance (IR),with features similar to qi-yin deficiency and phlegm stasis syndrome,including decreased cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) ratio,decreased levels of Na+-K+-ATPase,superoxide dismutase (SOD) and high density lipoprotein-cholesterol (HDL-C),and increased levels of serum triglyceride (TG),total cholesterol (TC) and low density lipoprotein (LDL-C).All three treatment groups showed significant decreases in fasting blood glucose (FBG) and fasting insulin (Fins),and improvement of TCM syndrome to different degrees.Importantly,YQYYHT improved the most of the indicators of T2DM,followed by integrative medicine and pioglitazone alone.Conclusion:Compared with western medicine or integrative medicine,prescription of TCM based on syndrome differentiation may offer more advantages in the prevention and treatment of T2DM.

Increased Chondrocyte Apoptosis in Kashin-Beck Disease and Rats Induced by T-2 Toxin and Selenium Deficiency

Objective To investigate chondrocyte apoptosis and the expression of biochemical markers associated with apoptosis in Kashin-Beck disease（KBD） and in an established T-2 toxin-and selenium（Se） deficiency-induced rat model. Methods Cartilages were collected from the hand phalanges of five patients with KBD and five healthy children. Sprague-Dawley rats were administered a selenium-deficient diet for 4 weeks prior to T-2 toxin exposure. The apoptotic chondrocytes were observed by terminal deoxynucleotidyl transferase d UTP nick end labeling staining. Caspase-3, p53, Bcl-2, and Bax proteins in the cartilages were visualized by immunohistochemistry, their protein levels were determined by Western blotting, and m RNA levels were determined by real-time reverse transcription polymerase chain reaction. Results Increased chondrocyte apoptosis was observed in the cartilages of children with KBD. Increased apoptotic and caspase-3-stained cells were observed in the cartilages of rats fed with normal and Se-deficient diets plus T-2 toxin exposure compared to those in rats fed with normal and Se-deficient diets. Caspase-3, p53, and Bax proteins and m RNA levels were higher, whereas Bcl-2 levels were lower in rats fed with normal or Se-deficiency diets supplemented with T-2 toxin than the corresponding levels in rats fed with normal diet. Conclusion T-2 toxin under a selenium-deficient nutritional status induces chondrocyte death, which emphasizes the role of chondrocyte apoptosis in cartilage damage and progression of KBD.

Preliminary molecular basis of Danggui-buxue-tang on Qi deficiency and blood stasis syndrome

Objective To study the molecular biology mechanism of Danggui-buxue-tang on tonifying Qi and controlling blood circulation through modulation the immune functional genes.Methods Rats were randomly divided into control group,model group,and Danggui-buxue-tang group.Effect of Dang-guibuxue-tang on mRNA expressions of IL-1β,TNF-α,HSP-70,NF-κB,p38MAPK and JNK in blood cells of rats with Qi deficiency and blood stasis were measured with real-time fluorescent quantitative-PCR at 5th,14th and 28th day.And that in artery wall were determined at the 28th day.NF-κB/p65 and p-c-jun protein expressions in rat artery wall were detected by western blotting as well.Results In model group,TNF-α,IL-1β,NF-κB,HSP-70,p38MAPK and JNK mRNA expression in blood cell increased significantly compared with control group.Compared with model group,mRNA expression of IL-1βand JNK decreased significantly;TNF-α decreased at 5th,14th day;HSP-70,p38MAPK decreased at 14th,28th day;NF-κB decreased at 28th day.In model group,TNF-α,IL-1β,NF-κB,p38MAPK and JNK mRNA expression in artery increased compared with control group,excluded HSP-70,and that in Danggui-buxue-tang group decreased significantly.In model group,NF-κB/p65 and p-c-jun protein expression in artery increased compared with control group,and that in Danggui-buxue-tang group decreased significantly.Conclusions The effects of Dang-guibuxue-tang on Qi deficiency and blood stasis syndrome was brought from the regulating of cytokine network at multi-link and multi-target,NF-κB,p38MAPK and JNK signal transduction pathways included.Through which the immune system and whole body reached to a functional balance status.

Effect of Chanfukang(Chinese Medicine)on Endothelin and Nitric Oxide in Postpartum Cows with Qi Deficiency and Blood Stasis

[ Objective] To observe effect of Chanfukang on vascular endothelial cells of postpartum cows with Oi deficiency and Blood stasis, and to explore the treatment mechanism of Chanfukang. [Method] A total of 58 cows were assigned to four groups. The cows in group 1 and group 2 suffered from Qi deficiency and Blood stasis. The cows in group 1 were gavaged with Chanfukang （0.5 g/kg-BW, 5 d） at 12 h post partum, but the cows in group 2 were not treated. The cows in group 3 were healthy and gavaged with Chanfukang （0.4 g/kg.BW, 5 d） at 12 h post partum. Cows in group 4 were healthy control cows. The plasma endothelin （ET） concentration and serum nitric oxide （NO） concentration were determined before and after parturition, respectively. [ Result ] The plasma ET concentration and serum NO concentration were significantly higher in the cows with Qi deficiency and Blood stasis than in the healthy control cows （P 〈 0.05）. The NO concentration decreased on Day 10 post partum in the cows with Qi deficiency and Blood stasis, but it was still higher than that in the healthy control cows. After taking Chanfukang for 7 d, the ET concentration and NO concentration decreased, and no significant difference was found between the cows with Qi deficiency and Blood stasis treated with Chanfukang and the healthy control cows. [ Conclusion] Chanfukang may relieve Qi deficiency and Blood stasis of postpartum cows through decreasing plasma ET concentration and serum NO concentration.

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.

Yiqi Huoxue Decoction in the treatment of Qi and yin deficiency and stasis type diabetic nephropathy in stageⅢ and its effect on VEGF and TGF-β1

Objective:To observe the efficacy of Yiqi Huoxue Decoction in the treatment of patients with diabetic nephropathy(DN)stageⅢwith qi and yin deficiency and stasis and its effects on vascular endothelial growth factor(VEGF)and transforming growth factor-β(TGF-β1).Methods:Sixty patients with stage DN of Qi-yin deficiency and stasis type DN who were treated in the Endocrinology Department of the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine from September 2018 to December 2019 were selected as the research subjects.The remainder method was used to divide them into 30 cases in the observation group and 30 cases in the control group.Patients in both groups were referred to the guidelines and expert consensus for general treatment of DN(hypogl-ycemic,antihypertensive,lipid-lowering,etc.).The control group was given pancreatic kallikrein enteric-coated tablets orally once,120U,3 times a day,and the observation group was given The traditional Chinese medicine Yiqi Huoxue Decoction was taken orally,one dose daily,twice a day in the morning and evening;the two groups intervened continuously for 8 weeks.Detect blood FPG,PBG,HbA1c,β2-MG,BUN,SCr,VEGF,TGF-β1,and urine mALB and UACR levels before and after treatment,and calculate eGFR before and after treatment in both groups;observe changes in TCM syndrome scores in the two groups,Compare its clinical efficacy.Results:After 8 weeks of treatment,the total clinical effective rate of patients in the observation group was 93.3%,which was significantly different from the control group of 76.6%(P<0.05);the TCM syndrome scores in the observation group were significantly lower than those before treatment and in the control group(P<0.05);The levels of FPG,HbA1c,PPG,mALB,β2-MG,UACR,VEGF,and TGF-β1 in the observation group were significantly lower than those in the control group,with significant differences(P<0.05).The levels of SCr and BUN in the observation group were significantly lower.Compared with before treatment,eGFR increased,but there was no signi-ficant difference(P>0.05).Conclusion:Yiqi Huoxue Decoction for the treatment of patients with DN typeⅢqi-yin deficiency and stasis type,not only helps to lower blood sugar levels,improve TCM syndromes,but also can reduce early renal damage,reduce urine albumin,and delay kidney function It may be further worsened and has better safety.The mechanism may be related to reducing the levels of VEGF and TGF-β1,thereby delaying the fibrosis of tubulointerstitial scar and inhibi-ting glomerular capillary sclerosis.

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.

On the Treatment of Kidney Fibrosis from the Theory of Internal Deficiency of Qi and the Coexistence of Phlegm and Blood Stasis

Traditional Chinese medicine believes that the etiology and pathogenesis of renal fibrosis are characterized by deficiency of the lung,spleen and kidney,and phlegm,blood stasis,dampness and poison.The positive and the evil can influence each other and cause and effect each other,forming the pathological characteristics of the deficiency,the deficiency,the deficiency and the reality.Chinese medicine treatment of the disease has its unique advantages,external and internal injury equal emphasis,correction and dispelling evil and regulation.From the point of view of"deficiency of qi and coexistence of phlegm and blood stasis",the treatment of renal fibrosis can provide theoretical basis for the treatment of the disease.

Pathological Mechanism of “Phlegm, Blood stasis, Toxin ”in a Rabbit Model of Carotid Atherosclerosis Based on Gut Microbiota-host Metabolism Interactions

Background:In Traditional Chinese Medicine(TCM)theory,"phlegm,blood stasis and toxin"are the pathogenesis of carotid atherosclerosis(CAS).The rabbit carotid atherosclerosis(CAS),which is induced by high-cholesterol diet combined with carotid artery balloon injury,is a classic model for studying CAS.Many studies indicate that gut microbiota and host metabolic disorders are involved in the pathogenesis of rabbit CAS.However,the TCM pathological features and syndromes of this classic rabbit CAS model have not been reported.Objective:To explore the pathogenesis of the rabbit CAS model and its TCM syndrome types from the perspective of"phlegm,blood stasis,and toxin".Methods:Twelve male New Zealand white rabbits were randomly divided into NC group and CAS group according to their body weight,followed by feeding of basic feed and a 1%high cholesterol diet,respectively.After two weeks,the rabbits in the CAS group underwent common carotid artery(CCA)balloon injury,while the rabbits in the NC group underwent only CCA separation without balloon injury.The two groups received differential feed postoperatively for six more weeks,after which,changes in lipids,hemorheology,inflammation,oxidative stress,and CAS phenotypes were analyzed.In addition,the colon contents and serum were collected for 16S rRNA sequencing and ^(1)H-NMR metabonomic analysis.Results:The CAS rabbits were observed to form noticeable abnormalities in lipid metabolism and blood rhe-ology,a sharp increase in oxidative stress levels,excessive release of inflammatory factors and apparent CAS plaque formation.Furthermore,10 specific gut microbiota(such as Akkermansia muciniphila,Barnesiellaceae and Faecalibacterium)and 14 characteristic metabolites(such as trimethylamine oxide,acetic acid and L-carnitine)were identified in the CAS rabbits,which were significantly related to the CAS phenotypes.The pathway func-tion analysis showed that the gut microbiota and its metabolites mainly affected cholesterol metabolism,energy metabolism,inflammation and oxidative stress.Conclusion:The rabbit CAS model conforms to the“phlegm,blood stasis and toxin damage”theory.The gut microbiota and host metabolic disorders of the CAS rabbits interact and promote internal and external toxins,aggravating the progression of CAS.Our study provided experimental evidence for the application of this model in the TCM-based research of CAS.

Study on the Tongue Manifestations for the Blood-Stasis and Toxin Syndrome in the Stable Patients of Coronary Heart Disease

Objective： To explore the tongue manifestations for the blood-stasis and toxin syndrome in the stable patients of coronary heart disease （CHD） according to the acute cardiovascular events （ACEs） in one-year follow-up which based on the pathogenesis hypothesis of ＂blood-stasis and toxin causing catastrophe＂. Methods： Totally 254 stable CHD cases were enrolled after diagnosed by coronary angiography, their tongue appearances were recorded by the digital camera of uniform type, 29 cases with ACEs during one-year follow-up were assigned in ACEs group. The non-ACEs were matched in proportion of 2：1 according to the gender, age （± 2.5 years）, diabetes mellitus history and previous acute coronary syndrome hospitalization history in the non-ACEs group, and 54 cases were eligibly included. The differences of tongue appearance between the ACEs and non-ACEs group were compared. Results： Fifteen cases manifested with bluish tongue （including bluish-grounding or bluish purple tongue）, among which 11 cases （37.9%） in the ACEs group and four cases （7.4%） in the non-ACEs group, and there was significant difference （P〈0.002）. Twenty six cases showed yellow tongue coating in the non-ACEs group, which was significantly higher than that in the ACEs group （48.1 vs. 10.3%, P=0.001）. The tongue of sticky greasy coating was more frequently occurred in the non-ACEs group than that in the ACEs group （66.7% vs. 41.4%, P=0.026）. The proportion of purplish-red sublingual vessel was higher in the ACEs group than that in the non-ACEs group （41.4% vs. 20.4%, P=0.041）. Odd ratio （OR） analysis showed that the patients with bluish tongue, purplish-red sublingual vessel, dry-greasy or dirty greasy coating were more likely to experience ACEs during one- year follow-up （OR： 11.67, 95%CI： 3.34-40.81, P〈0.001; OR： 2.76, 95%CI： 1.02-7.44, P〈0.05; OR： 3.12, 95%, CI： 0.89-10.92, P=0.066）. Conclusions： The bluish tongue （including bluish-grounding or bluish purple tongue） and purplish-red sublingual vessel were potential tongue manifestations of blood-stasis and toxin. The tongue coating changing from sticky greasy to dry greasy or dirty greasy was also probably a tongue manifestation of ＂transforming toxin＂, which need demonstration by further study.

Metabonomic phenotype and identification of “heart blood stasis obstruction pattern” and “qi and yin deficiency pattern” of myocardial ischemia rat models

The traditional Chinese medicine concepts of "Xinxueyuzuzheng (heart blood stasis obstruction pattern)" and "Qiyinliangxuzheng (qi and yin deficiency pattern)" for myocardial ischemia rat models were constructed in the present study. Endogenous metabolites in rat plasma were analyzed using the GC/TOF-MS-based metabonomic method. Significant metabolic differences were observed between the control and two model groups, and the three groups were distinguished clearly by pattern recognition. Compared with those of the control, the levels of hydroxyproline, threonic acid, glutamine and citric acid were strikingly up or down-regulated in model rats. The metabolites contributing most to the classification between the two "pattern" rats were identified, such as valine, serine, threonine, ornithine, hydroxyproline, lysine, 2-hydroxybutanoic acid, 3-hydroxybutanoic acid, galactofuranose and inositol. These compounds were indicated as the potential biomarkers. The results suggested that the two "patterns" are involved in dysfunction in oxidative stress, energy metabolism and amino acid metabolism. These findings also provided the substantial foundation for exploring the scientific connotation of these two "Zhengxing (pattern types)" of myocardial ischemia, and "Bianzheng (pattern identification)".

Energy Metabolism Disorder and Myocardial Injury in Chronic Myocardial Ischemia with Qi Deficiency and Blood Stasis Syndrome Based on 2-DE Proteomics

Objective： To inquire the characteristic proteins in chronic myocardial ischemia by testing twodimensional electrophoresis （2-DE） map to explore the possible inherent pathological mechanism and the therapeutic intervention of qi deficiency and blood stasis syndrome. Methods： Ameroid constrictor ring was placed on the first interval of left anterior descending coronary artery to prepare chronic myocardial ischemia model on Chinese miniature swine. Animals were randomly divided into sham group and model group with 10 animals in each group, respectively. The dynamic symptoms observation of the four diagnostic information was collected from 0 to 12 weeks. Echocardiography was employed to evaluate cardiac function and the degree of myocardial ischemia, 2-DE and matrix-assisted laser desorption/ionization-time of flight mass spectrometry （MALDI-TOF-MS） were used to carry out proteomics research on animals. Enzyme-linked immunosorbent assay was applied to identify the relevant differential proteins on chronic myocardial ischemia with qi deficiency and blood stasis syndrome. Results： The preliminary study found that at the 12th week, chronic myocardial ischemia with qi deficiency and blood stasis syndrome model was established stably. Compared with the sham group, there were 8 different proteins down-regulated, 22 proteins up-regulated significantly. After validated by MALDI- TOF-MS/MS, 11 protein spots were identified. Distinct proteins were mainly associated with energy metabolism and myocardial structural injury, including isocitrate dehydrogenase 3 （NAD＋） alpha, NADH dehydrogenase （NAD） Fe-S protein 1, chain A （crystal structure of aidose reductase by binding domain reveals a new Nadph）, heat shock protein 27 （HSP27）, oxidoreductase （NAD-binding protein）, antioxidant protein isoform, cardiac troponin T （cTnT）, myosin （myosin light polypeptide）, cardiac alpha tropomyosin, apolipoprotein A- I and albumin. Conclusion： Down-regulated energy metabolism disorder mediated by NADH respiratory chain and myocardial injury may be the pathogenesis of myocardial ischemia with qi deficiency and blood stasis syndrome. These proteins may be the potential diagnostic marker（s） for qi deficiency and blood stasis syndrome, finally provided new clues for new therapeutic drug target of Chinese medicine

Efficacy of Yangyin Yiqi Huoxue Granule (养阴益气活血颗粒) in Treatment of Ischemic Stroke Patients with Qi-Yin Deficiency and Blood Stasis Syndrome: A Randomized, Double-Blind, Multicenter, Phase-2 Clinical Trial

Objective To evaluate the efficacy and safety of Yangyin Yiqi Huoxue Granule(养阴益气活血颗粒,YYHG)in the treatment of ischemic stroke(IS)patients with qi-yin deficiency and blood stasis syndrome(QYDBSS),and to explore its effective dosage.Methods The total of 288 patients were randomly assigned to the YYHG high-dose,YYHG low-dose,positive control(administered Xiaoshuantong Granule,XSTG,消栓通颗粒),or placebo control(administered inert granule)groups(72 cases per group)by software-drived competitive block randomization.The trial was conducted for a 28-day period,with a 180-day follow-up period.The primary outcome was the comprehensive curative evaluation,and secondary outcomes were the National Institute of Health Stroke Scale(NIHSS)score,Barthel activities of daily living(ADL)index score,the quality of life index(QLI)score,and the Chinese medicine syndrome(CMS)score.All analyses were done on an intention-to-treat basis.The clinical safety was also assessed.Results The total of 288 participants were recruited between June 1,2008 and September 30,2009,and 287 patients received intervention;the treatment groups were well balanced at baseline.The comprehensive cure rates of YYHG high-dose,low-dose,positive and placebo control groups were 63.38%,31.94%,36.11%and 6.14%,respectively;there was a statistical difference between the two groups(P<0.01),while the high-dose YYHG treatment group was significantly higher than the other 3 groups(P<0.01).The improvement of NIHSS,ADL,QLI and CMS scores of the YYHG high-dose and low-dose groups was significantly better than that of the positive control group and the placebo control group(P<0.05).In terms of improving the classification of the NIHSS scale and the assessment of the ADL scale,the YYHG high-dose group was significantly better than the other three groups(P<0.05),and the YYHG low-dose group was better than the placebo control group(P<0.01).At the same time,except for the QLI score,the high-dose group was better than the low-dose group(P<0.05).In terms of safety,adverse reactions after YYHG treatment were generally mild(3.78%),and no serious adverse reactions have been reported.Conclusion YYHG is safe and effective in the treatment of IS patients with QYDBSS.

Metabonomics analysis of the urine of rats with Qi deficiency and blood stasis syndrome based on NMR techniques

Metabonomics analysis of the urine of rats with Qi deficiency and blood stasis syndrome has been performed by comparison with those of normal rats based on NMR techniques. The relative contents of formate,creatinine,2-oxoglutarate(2-OG) ,citrate,taurine,trimethylamine-N-oxide(TMAO) ,succinate and hippurate in the urine of the rats with Qi deficiency and blood stasis syndrome have been changed. These results have provided evidence for understanding the mechanism and the therapy of Qi defi-ciency and blood stasis syndrome.

Variations of energy metabolism and adenosine Triphosphatase activity in gastric mucosa in chronic atrophic gastritis rats with Qi deficiency and blood stasis syndrome and effect of Zhiweifangbian capsule

OBJECTIVE: To study the effects of Zhiweifangbian (ZWFB) capsule on lactic dehydrogenase (LDH), succinic dehydrogenase (SDH) and ATPase activities in gastric mucosa of chronic atrophic gastritis (CAG) rats with Qi deficiency and blood stasis syndrome. METHODS: Totally 90 rats were randomly divided into 2 groups: normal group (n=10) and modelgroup (n=80). The CAG rat model of Qi deficiency and blood stasis type was induced by synthetic methods. After modeling for 12 weeks and the successful CAG model was determined, the CAG model rats were divided by random number table into model group (MG), ZWFB high-dose group (ZWFBH), ZWFB middle-dose group (ZWFBM), ZWFB low-dose group (ZWFBL) and Weimeisu group (WM), 9 rats in each group. The rats in the normal and model groups were intragastrically administrated with distilled water, 10 mL/kg every day; the ZWFB high-dose group with ZWFB, 0.6 g/ kg -1 · d -1 ; the ZWFB middle-dose group with ZWFB, 0.3 g/kg -1 · d -1 ; the ZWFB low-dose group with ZWFB, 0.15 g/kg -1 · d -1 , and the WM group with suspension of WM , 0.25 g/kg -1 · d -1 . The treatment was given for 90 consecutive days. Then general survival states were observed and the activities of LDH, SDH, Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase in gastric mucosa tissue were detected. RESULTS: Compared with the normal group, activity of LDH in the gastric mucosa (P<0.05) and activities of SDH, Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase significantly decreased in the normal group (P<0.05). Compared with the model group the activity of LDH decreased and activities of SDH, Na + -K + -ATPase and Ca 2+ -Mg 2+ -ATPase significantly increased in the high dose ZWFB group (P<0.05). CONCLUSION: ZWFB capsule can promote energy metabolism and ATPase activity in the gastric mucosa cell, so as to protect the function of the gastric mucosa cell.