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.

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.

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.

Effects of Lycii Fructus and Salviae Miltiorrhizae on the Syndrome of Deficiency with Blood Stasis in RCS(rdy-/-, p-/-) Rats with Retinitis Pigmentosa: An Intervention Study

Objective To investigate the effects of Lycii Fructus(LF,Gou Qi Zi,枸杞子)and Salviae Miltiorrhizae Radix Ex Rhizoma(SM,Dan Shen,丹参)on the syndrome of deficiency with blood stasis in the RCS(rdy-/-,p-/-)rats with retinitis pigmentosa(RP).Methods A total of 32 RCS(rdy-/-,p-/-)rats were divided into 4 groups(equal amounts of female and male rats in each group):model group treated with 0.9%normal saline,LF group treated with LF formula granules,SM group treated with SM formula granules,and LF and SM(L·S)group treated with LF and SM formula granules.Eight RCS(rdy+/+,p+/+)rats(4 males and 4 females)were treated with 0.9%normal saline to serve as blank group.The contents of E2,PG,P-Selectin,plasma viscosity,whole blood relative index of the high shear rate and fibrinogen content in plasma,and the content of cAMP and cGMP in retinal homogenate were detected.The retina was evaluated by hematoxylin-eosin staining.Results The contents of E2,PG,P-Selectin,plasma viscosity,whole blood relative index of the high shear rate,and fibrinogen content in the plasma of L·S group significantly differed from those of model group(P<0.01),but were similar to those of blank group.The contents of cAMP and cGMP in the retinal homogenate of L·S group significantly differed from those in model group(P<0.01)but were similar to those in blank group(P>0.05).Conclusions LF and SM can effectively treat retinitis pigmentosa by ameliorating the syndrome of deficiency with blood stasis.

Serum proteomic approach in patients with Qi deficiency and blood stasis syndrome in coronary heart disease:to explore therapeutic mechanism of Yiqi Huoxue decoction

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.

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.

Study on the Expression of Organic Anion Transporting Polypeptide (oatp2a1) in Rat with Spleen Deficiency Syndrome and the Exploration of Clinical Significance

Objective: to explore the mechanism of transportation and transformation of dampness by the way of the expression of organic anion transporting polypeptide (oatp) superfamily member 2a1 (oatp2a1) mRNA in rat with spleen deficiency syndrome and the significance in transportation and transformation of dampness. Methods: 32 wistar male rats were divided randomly into four groups: normal group (n = 6), normal + AA group (n = 6), spleen deficiency group (n = 10), Spleen deficiency + AA group (n = 10). After reserpine-induced spleen deficiency model was made, intragastric administration of aristolochic acid (AA) was adopted for three days, the expression of oatp2a1 mRNA were detected in the tissues of lung, liver, kidney, stomach, small intestine and large intestine in four groups by using Fluorescent Quantitative-Polymerase Chain Reaction (FQ-PCR). Results: the expression of oatp2a1 mRNA in above six tissues could be detected. The ex-pression of oatp2a1 mRNA in liver tissue of rat with spleen deficiency syndrome was up-regulated compared to normal group (P = 0.035, P < 0.05), the expression of oatp2a1 mRNA in small intestinal tissue of rat with spleen deficiency syndrome was down-regulated compared to normal group (P = 0.004, P < 0.01), the expression of oatp2a1 in intestinal tissue in normal + AA group is down-regulated compared to normal group (P = 0.032, P < 0.05). Conclusions: oatp2a1 might be one of the material basis involved in transportation and transformation of dampness. The changes of expression of oatp2a1 mRNA in small intestine, liver tissue suggests that small intestine, liver might play an important role in the transportation and transformation of dampness in the state of spleen deficiency. We further concluded that the function of spleen’s governing transportation and transformation of dampness was not only including the function of the gastrointestinal, but also part of the liver function in some degree, which needs to be further studied.

Abnormal expression and significance of circ-CBLB/miR-486-5p in patients with rheumatoid arthritis of spleen deficiency and dampness excess type

Objective:To explore the abnormal expression and significance of circ-CBLB/miR-486-5p in patients with rheumatoid arthritis of spleen deficiency and dampness excess type.Methods:The 30 healthy individuals included in the method were from the Physical Examination Center of Anhui Provincial Hospital of Traditional Chinese Medicine,and the 60 rheumatoid arthritis patients included were from the First Affiliated Hospital of Anhui University of Traditional Chinese Medicine.The disease activity score of patients with rheumatoid arthritis was evaluated using VAS score and DAS28 score,joint symptoms and spleen deficiency syndrome score were evaluated using graded quantification method,immune inflammation indicators were detected using relevant instruments,inflammatory cytokines were detected using ELISA method,macrophage markers were detected using FCM method,and pathway gene expression was detected using RT-qPCR;Evaluate the predictive effect of circ-CBLB and miR-486-5p on disease activity in rheumatoid arthritis using ROC curves.Results:(1)miR-486-5p,CD14^(+)CD86^(+),ESR,CRP,RF,Anti CCP Ab,IL-6,TNF in patients with rheumatoid arthritis-αThe levels of circ-CBLB,CD14^(+)CD163^(+),IL-4,and IL-10 were significantly higher than those of healthy individuals;(2)The expression level of circ-CBLB in patients with rheumatoid arthritis is positively correlated with CD14^(+)CD163^(+),and negatively correlated with miR-486-5p and CD14^(+)CD86^(+);The expression level of miR-486-5p is negatively correlated with CD14^(+)CD163^(+)and positively correlated with CD14^(+)CD86^(+);There is a negative correlation between CD14^(+)CD86^(+)and CD14^(+)CD163^(+);ESR is negatively correlated with circ-CBLB,and positively correlated with miR-486-5p,CD14^(+)CD86^(+),CRP;CRP is negatively correlated with circ-CBLB,CD14^(+)CD163^(+),and positively correlated with CD14^(+)CD86^(+),ESR;(3)The expression level of circ-CBLB in patients with rheumatoid arthritis is negatively correlated with joint tenderness,morning stiffness,lack of qi and lazy speech,and postprandial abdominal distension score;The expression level of miR-486-5p is positively correlated with the scores of joint tenderness and decreased appetite.(4)The ROC curve shows that in terms of circ-CBLB,ESR,CRP,VAS,and DAS28 AUC are 0.662(P=0.032),0.658(P=0.035),0.516(P=0.830),and 0.791(P=0.000),respectively.In terms of miR-486-5p,ESR,CRP,VAS,and DAS28 AUC were 0.566(P=0.385),0.511(P=0.883),0.592(P=0.223),and 0.727(P=0.003),respectively.Conclusion:The abnormal expression of circ CBLB and miR-486-5p in peripheral blood mononuclear cell of patients with rheumatoid arthritis of spleen deficiency and dampness excess type is related to inflammatory polarization markers,immune inflammation,disease activity,joint symptoms and spleen deficiency syndrome of rheumatoid arthritis,and the low expression of circ CBLB and high expression of miR-486-5p have certain predictive value for disease activity of rheumatoid arthritis.

Study on the Characteristics of Gut Microbiota in Chronic Hepatitis B(CHB)Patients with Damp Heat Syndrome and Liver Depression and Spleen Deficiency Syndrome

Objective:This study was designed to explore the characteristics of gut microbiota in CHB patients with two most common traditional Chinese medicine(TCM)Syndromes—damp heat syndrome and liver depression and spleen deficiency syndrome.Methods:According to the diagnostic criteria of Western medicine,TCM and screening exclusion criteria,65 cases of CHB with damp heat syndrome and 28 cases of CHB with liver depression and spleen deficiency syndrome were finally included in the study.All the basic information was gathered and the fresh fecal samples were collected for 16S rDNA sequencing.16S rDNA of gut microbiota was sequenced using Illumina hiseq 2,500 high-throughput sequencing platform.Based on the optimized sequence,Operational Taxonomic Units(OTU)clustering analysis and taxonomic annotation were carried out.Results:The difference in relative abundance of gut microbiota was significant between damp heat syndrome and liver depression and spleen deficiency syndrome in CHB patients.Cyanobacteria was only found in damp heat syndrome.The relative abundance of Erysipelotrichia and Subdoligranulum were higher in liver depression and spleen deficiency syndrome,while the relative abundance of Rhodospirillales,Alphaproteobacteria and Lachnospira were higher in the damp heat syndrome.LDA Effect Size(LEfSe)analysis showed that Lachnospira,Olsenella and Subdoligranulum had significant difference in species among the two TCM syndromes.Conclusion:The different characteristics of gut microbiota in the two TCM syndromes of CHB patients may play an important role in syndrome formation of TCM,which provides a new field of vision for the accurate diagnosis and treatment of TCM.

The prescription rule analysis of the New Theory on Spleen Dampness Syndrome by Academician TONG Xiaolin

Objective To analyze the basic characteristics,drug features,prescription rules,and drug-symptom relationships of patients in the splenic deficiency and impairment stage,by data mining of medical records under the New Theory on Spleen Dampness Syndrome(Pi Dan Xin Lun,《脾瘅新论》).Methods Medical records listed in the“New Theory on Spleen Dampness Syndrome-Under-standing and Treatment of Metabolic Syndrome from the Perspective of Traditional Chinese Medicine”,and which were diagnosed with the spleen dampness syndrome at the splenic de-ficiency and impairment stage,during January 2004 and December 2016 were selected.These patients’data,including basic information,clinical symptoms,laboratory examination res-ults,traditional Chinese medicine(TCM)and western medicine diagnoses,treatment meth-ods,prescriptions,etc.,were collected.The collected data were subsequently compiled into a medical record database using the Epidata 3.1 data management software,followed by the use of Apriori algorithm provided in the SPSS Modeler 14.2 statistical software to investigate the association rules between drug-drug,drug-symptom,and drug-western medicine indices.Results(i)A total of 51 medical records were included,involving 17 types of syndromes.Among them,the top three with frequency≥3 included“Phlegm and blood stasis,and thoracic obstruction”“Deficiency-weakness of the spleen Qi,and static blood blocking collat-erals”,and“Deficiency-weakness of the spleen Qi,and static blood blocking collaterals”.Al-ternatively,of the 14 treatment methods,the top three treatments with frequency of≥3 in-cluded“Activating Yang and eliminating turbidity,and removing phlegm and dredging chan-nel blockage”“Strengthening the spleen and benefiting Qi,and eliminating phlegm to activ-ate the channels”,and“Warming Yang and benefiting Qi,and expelling cold to remove ob-structions”.Among the 15 prescriptions,the top three used with frequency≥3 included Huangqi Guizhi Wuwu Tang(黄芪桂枝五物汤),Gualou Xiebai Banxia Tang(瓜蒌薤白半夏汤),and Ganjiang Huangqin Huanglian Renshen Tang(干姜黄芩黄连人参汤).Lastly,of the 83 drugs used for a total of 476 times,those with frequency≥15 included Huanglian(Coptid-is Rhizoma),Huangqi(Astragali Radix),Jiudahuang(Wine-processed Rhei Radix et Rhizoma),Jixueteng(Spatholobi Caulis),Shengjiang(Zingiberis Rhizoma Recens),Huangqin(Scutellariae Radix),and Guizhi(Cinnamomi Ramulus).(ii)For the drug-drug associations,under the criteria of support≥15%and confidence=100%,seven second-order association rules,seven third-order rules,and six fourth-order roles were identified.The top-ranking rule of each was“Huangqin(Scutellariae Radix)→Huanglian(Coptidis Rhizoma)”“Ganjiang(Zingiberis Rhizoma)+Huangqin(Scutellariae Radix)→Huanglian(Coptidis Rhizoma)”,and“Baishao(Paeoniae Radix Alba)+Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatho-lobi Caulis)→Huangqin(Scutellariae Radix)”,respectively.Alternatively,the drug-symptom associations were analyzed under the criteria of support≥5%and confidence=100%,which derived eight second-order association rules,31 third-order rules,and 30 fourth-order rules.The top-ranking association rule of each order was“Huangqi(Astragali Radix)→Limb ed-ema”“Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatholobi Caulis)→Limb numbness and pain”,and“Guizhi(Cinnamomi Ramulus)+Jixueteng(Spatholobi Caulis)+Huangqi(As-tragali Radix)→Limb numbness and pain”,respectively.Similarly,the drug-western medi-cine index associations were investigated under the criteria of support≥5%and confidence=100%,and five second-order association rules,16 third-order rules,and 16 fourth-order rules were identified.In this category,the top-ranking association rule of each order was“Qinpi(Fraxini Cortex)→Uric acid”“Huanglian(Coptidis Rhizoma)+Ganjiang(Zingiberis Rhizoma)→Glycated hemoglobin”,and“Huanglian(Coptidis Rhizoma)+Ganjiang(Zing-iberis Rhizoma)+Huangqin(Scutellariae Radix)→Glycated hemoglobin”,respectively.Conclusion Through association rule mining,this study objectively and quantitatively demonstrated the drug-drug,drug-symptom,and drug-physicochemical index associations of patients with the spleen dampness syndrome at the splenic deficiency and impairment stage treated by Academician TONG Xiaolin.The results indicated that treatment for these patients adopted the“state-target”syndrome differentiation method.The drug combination was characterized by“small prescriptions”,targeting both the patient’s symptoms and signs(syndrome target)and western medicine indices(treatment target).This study could provide references for future research on the academic thoughts and medical experience of Academi-cian TONG Xiaolin.

Pharmacokinetics of traditional Chinese syndrome and recipe:a hypothesis and its verification(Ⅰ)

AIM To propose a hypothesis defining theabsorption,distribution,metabolism andelimination of traditional Chinese recipe（TCR）-component in blood of healthy subjects andpatients,and estimate its correctness.METHODS The pharmacokinetics（PK）of samedose of drug was studied in the animal model oftraditional Chinese syndrome（S）and healthyanimals.The classification,terminology,concept and significance of the hypothesis wereset forth with evidence provided in the presentstudy.The hypotheses consisted of traditionalChinese syndrome PK（S-PK）and traditionalChinese recipe PK（R-PK）.Firstly,the observedtetramethylpyrazine（TMP）PK in healthy,chronically reserpinized rats（rat model ofspleen deficiency syndrome,RMSDS）andRMSDS treated with Sijunzi decoction（SJZD）forconfirmation were used to verify S-PK; secondly,the ferulic acid（FA）PK in healthy andhigh molecular weight dextran（HMWD）-inducedrabbit model with blood stasis syndrome（RDBSS）was also used to verify S-PK;andlastly,TMP PK parameters in serum of healthyrats after orally taken Ligusticum wallichii（LW）,LW and Salvia miltiorrhiza（LW&SM）decoctions were compared to verify R-PK.RESULTS The apparent first-order absorption[Ka,（13.61±2.56）h-1,area under the blooddrug concentration-time curve[AUC,（24.88±9.76）μg.h-1mL-1],maximum drug concentration[Cmax,（4.82±1.23）μg·mL-1]of serum TMP inRMSDS were increased markedly（P【0.05）compared with those[Ka=（5.41±1.91）h-1,AUC=（5.20±2.57）μg·h-1·mL-1,Cmax=（2.33±1.77）μg·mL-1]of healthy rats（HR）.Theapparent first-order rate constant for α and βdistribution phase[α=（0.38±0.09）h-1,β=（0.06±0.03）h-1,the apparent first-orderintercompartmental transfer rate constants[K10=（0.24±0.07）h-1,K12=（0.11±0.02）h-1,K21=（0.11±0.02）h-1]of serum TMP in RMSDS weredecreased significantly（P【0.01）comparedwith those[K10=（0.88±0.20）h-1,K12=（1.45±0.47）h-1,K21=（0.72±0.22）h-1]of HR.However,no apparent differences occurredbetween HR and RMSDS treated with SJZD.Theserum FA concentration and its AUC[（5.6690±2.3541）μg·h-1·mL-1] in RMBSS were also higherthan those[AUC=（2.7566±0.8232）μg·h-1·mL-1]of healthy rabbits（P【0.05）.The Ka（11.51±2.82）h-1,AUC（0.84±0.17）μg·h-1·mL-1of LW & SM-derived TMP in serum weremuch lower（P【0.05）than those[Ka=（19.58±4.14）h-1,AUC=（1.27±0.26）μg·h-1·mL-1]ofLW-derived TMP in serum after oral decoctions.CONCLUSION The SDS and blood stasissyndrome state could affect significantly thepharmacokinetic parameters of drugs and theabnormal SDS pharmacokinetic parameters couldbe normalized by SJZD.The combination ofChinese medicine in TCR could reciprocallyaffect the pharmacokinetic parameters of othercomponents absorbed into the systemiccirculation.These results support the S-and R-PK hypothesis.

Study of establishing disease-syndrome combined with animal model for immune thrombocytopenic purpura without additional conditions

Objective:To explore the feasibility of establishing the disease-syndrome combined animal model for immune thrombocytopenic purpura(ITP)without additional conditions.Methods:Three batches of data related to the ITP model mice obtained by replication at different time were analyzed,and whether the APS-injected model mice replicated through the passive immune modeling method could simulate the pathogenesis and clinical characteristics of human ITP was evaluated according to the differentiation criteria for diseasesyndrome combined model.Results:The APS-injected replicated ITP model mice possessed the following traits:(1)Compared with the normal group,the platelet count was significantly decreased,and coagulation time was significantly increased in the model group(P<.01).(2)Compared with the normal group,the medullary thrombocytogenous megakaryocytes were significantly decreased(P<.05,.01,.001).(3)The APS-injected sites and other parts of the model mice had spontaneous hemorrhage.(4)Behavioral changing signs were observed 1 week after the modeling(i.e.low activity,delayed activity,poor appetite,skin petechia/hemorrhage and spontaneous hemorrhage at the injected sites or other parts),and were getting more and more severe.Conclusion:According to the syndrome differentiation criteria for disease-syndrome combined model of ITP,the APS-injected animal model of ITP replicated through the passive immune modeling method without additional conditions possesses the characteristics of disease-syndrome combined model.It provides an ideal tool for the development of traditional Chinese medicine pharmacology experiment.

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.

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.

Efficacy of Modified Qufeng Runmian Powder(加减祛风润面散)on Acne Vulgaris with Syndromes of Dampness and Blood Stasis:A Multicenter,Randomized,Double-Blind,Placebo-Controlled Clinical Trial

Objective:To evaluate the efficacy and safety of a Chinese medicine(CM)Modified Qufeng Runmian Powder(加减祛风润面散,MQFRMP)for the treatment of acne vulgaris with CM syndromes of dampness and blood stasis.Methods:In this multicenter,randomized,double-blind,placebo-controlled clinical trial,220 acne vulgaris patients with CM syndrome of dampness and blood stasis were included and randomly assigned using a central area group random design to receive either MQFRMP or the placebo,with 110 cases in each group.MQFRMP or a placebo at 145 g/bag were administered once daily for 4 weeks,respectively.The primary index of efficacy was the effective rate according to the acne severity score(ASS).The secondary indices of efficacy included the changes in the dermatology life quality index(DLQI)score,VISIA scores(spots,pores,brown spots,porphyrins and red areas)and skin assessment(skin p H,sebum amount and hydration)according to a SOFT skin multianalyzer.Results:(1)Follow-up:a total of 204 patients completed the follow-up,with 103 in the treatment group and 101 in the control group.(2)Effective rate:the total effective rate of the treatment group was significantly higher than the control group[83.5%(86/103)vs.31.7%(32/101),P<0.01)]with 95%confidence interval of 39.3%–66.4%.(3)DLQI:DLQI scores were significantly decreased the treatment and control groups(both P<0.01),but the treatment group was more obvious than the placebo group(P<0.01).(4)VISIA scores:the scores of spots,brown spots and red areas in the treatment group decreased compared with baseline(P<0.05).In the control group,the scores of brown spots and pores decreased compared with baseline(P<0.05).The improvement was more obvious in the treatment group than in the control group for all items(P<0.05).(5)Skin assessment:the p H and sebum score in the both groups decreased drastically compared with the baseline(all P<0.01),however,the improvement was more obvious in the treatment group than in the control group(P<0.01).The hydration amount in the two groups showed no statistically significant difference compared with the baseline(both P>0.05).(6)Safety:two cases of mild drug allergy were observed in the treatment group.Conclusion:MQFRMP was effective and safe for the treatment of acne vulgaris with syndromes of dampness and blood stasis.(No.ChiCTR1900020479).

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

Screening the effective components in treating dampness stagnancy due to spleen deficiency syndrome and elucidating the potential mechanism of Poria water extract

Poria is an important medicine for inducing diuresis to drain dampness from the middle energizer.However,the specific effective components and the potential mechanism of Poria remain largely unknown.To identify the effective components and the mechanism of Poria water extract(PWE)to treat dampness stagnancy due to spleen deficiency syndrome(DSSD),a rat model of DSSD was established through weight-loaded forced swimming,intragastric ice-water stimulation,humid living environment,and alternate-day fasting for 21 days.After 14 days of treatment with PWE,the results indicated that PWE increased fecal moisture percentage,urine output,D-xylose level and weight;amylase,albumin,and total protein levels;and the swimming time of rats with DSSD to different extents.Eleven highly related components were screened out using the spectrum-effect relationship and LC-MS.Mechanistic studies revealed that PWE significantly increased the expression of serum motilin(MTL),gastrin(GAS),ADCY5/6,p-PKAα/β/γcat,and phosphorylated cAMP-response element binding protein in the stomach,and AQP3 expression in the colon.Moreover,it decreased the levels of serum ADH,the expression of AQP3 and AQP4 in the stomach,AQP1 and AQP3 in the duodenum,and AQP4 in the colon.PWE induced diuresis to drain dampness in rats with DSSD.Eleven main effective components were identified in PWE.They exerted therapeutic effect by regulating the AC-cAMP-AQP signaling pathway in the stomach,MTL and GAS levels in the serum,AQP1 and AQP3 expression in the duodenum,and AQP3 and AQP4 expression in the colon.

Clinical Observation on 34 Cases of Chronic Atrophic Gastritis Treated with Shenlian Twelve Flavors

[Objectives]The research aimed to observe the curative effect of Shenlian Twelve Flavors in treating CAG patients with spleen deficiency and blood stasis toxin.[Methods]66 cases of CAG patients with spleen deficiency and blood stasis toxin were selected,32 cases in the control group and 34 cases in the observation group were generated according to the random number table method.The control group was treated with Moluodan;the observation group was treated with Shenlian Twelve Flavors.After treatment,the effective rate,TCM symptom score,gastroscopic score,pathological score,serum gastrin 17(G-17)level,and adverse reactions were compared between the two groups.[Results]The total effective rates of control group and observation group were 84.37%and 91.18%,respectively,and there was no statistical significance between the two groups(P>0.05).For the improvement of TCM symptom score,both groups were improved significantly compared with that before treatment,and observation group was better than control group(P<0.05).For the improvement of gastroscopic score,both groups were improved compared with that before treatment,and observation group was better than control group(P<0.05).For the improvement of pathological scores,both groups were improved compared with that before treatment,but there was no statistical significance between the two groups(P>0.05).[Conclusions]Shenlian Twelve Flavors has definite clinical efficacy in the treatment of CAG with spleen deficiency and blood stasis toxin.It could improve clinical symptoms,delay pathological progress,and regulate the level of G-17.There is no obvious adverse reaction,and it is worthy of clinical reference.

Relationship between Two Blood Stasis Syndromes and Inflammatory Factors in Patients with Acute Coronary Syndrome

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

益心泰颗粒对慢性心衰(心气虚兼血瘀水停证)大鼠AMPK、PGC-1α的影响

目的观察益心泰颗粒对慢性心力衰竭(CHF)(心气虚兼血瘀水停证)大鼠AMPK、PGC-1α的影响。方法采用丙硫氧嘧啶灌胃及阿霉素腹腔注射复制CHF(心气虚兼血瘀水停证)模型大鼠,将造模成功大鼠分为模型组与益心泰低、中、高剂量组和曲美他嗪组;另设正常对照组。灌胃4周后观察心肌组织病理结构,检测LVEF、血清NT-proBNP及心肌组织FFA、ATP/AMP、LAC、pAMPK、AMPK、PGC-1α水平。结果与模型组比较,益心泰颗粒低、中、高剂量组及曲美他嗪组LVEF、心肌组织ATP/AMP值、心肌组织p-AMPK、AMPK、PGC-1α相对灰度值均明显升高(P<0.05或P<0.01),血清NT-proBNP及心肌组织FFA、LAC明显降低(P<0.05或P<0.01)。结论益心泰颗粒能促进慢性心力衰竭(心气虚兼血瘀水停证)大鼠AMPK、PGC-1α表达,改善心肌能量代谢。