Network pharmacology-based exploration of molecular mechanisms underlying therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure with spleen Qi deficiency syndrome

BACKGROUND Chronic heart failure is a complex clinical syndrome.The Chinese herbal compound preparation Jianpi Huatan Quyu recipe has been used to treat chronic heart failure;however,the underlying molecular mechanism is still not clear.AIM To identify the effective active ingredients of Jianpi Huatan Quyu recipe and explore its molecular mechanism in the treatment of chronic heart failure.METHODS The effective active ingredients of eight herbs composing Jianpi Huatan Quyu recipe were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.The target genes of chronic heart failure were searched in the Genecards database.The target proteins of active ingredients were mapped to chronic heart failure target genes to obtain the common drugdisease targets,which were then used to construct a key chemical componenttarget network using Cytoscape 3.7.2 software.The protein-protein interaction network was constructed using the String database.Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed through the Metascape database.Finally,our previously published relevant articles were searched to verify the results obtained via network pharmacology.RESULTS A total of 227 effective active ingredients for Jianpi Huatan Quyu recipe were identified,of which quercetin,kaempferol,7-methoxy-2-methyl isoflavone,formononetin,and isorhamnetin may be key active ingredients and involved in the therapeutic effects of TCM by acting on STAT3,MAPK3,AKT1,JUN,MAPK1,TP53,TNF,HSP90AA1,p65,MAPK8,MAPK14,IL6,EGFR,EDN1,FOS,and other proteins.The pathways identified by KEGG enrichment analysis include pathways in cancer,IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,calcium signaling pathway,cAMP signaling pathway,NF-kappaB signaling pathway,AMPK signaling pathway,etc.Previous studies on Jianpi Huatan Quyu recipe suggested that this Chinese compound preparation can regulate the TNF-α,IL-6,MAPK,cAMP,and AMPK pathways to affect the mitochondrial structure of myocardial cells,oxidative stress,and energy metabolism,thus achieving the therapeutic effects on chronic heart failure.CONCLUSION The Chinese medicine compound preparation Jianpi Huatan Quyu recipe exerts therapeutic effects on chronic heart failure possibly by influencing the mitochondrial structure of cardiomyocytes,oxidative stress,energy metabolism,and other processes.Future studies are warranted to investigate the role of the IL-17 signaling pathway,PI3K-Akt signaling pathway,HIF-1 signaling pathway,and other pathways in mediating the therapeutic effects of Jianpi Huatan Quyu recipe on chronic heart failure.

Clinical Observation of the Therapeutic Effects of Wenzhong Hewei Formula in Treating Spleen and Stomach Qi Deficiency Syndrome in Internal Medicine Diseases

Objective:To observe the clinical efficacy and safety of Wenzhong Hewei Formula in treating spleen and stomach qi deficiency syndrome in internal medicine diseases.Methods:Sixty patients with spleen and stomach qi deficiency syndrome admitted to the hospital from April 2022 to June 2023 were randomly divided into observation and control groups,with 30 patients in each group.The control group received conventional internal medicine treatment,while the observation group was additionally treated with Wenzhong Hewei Formula on the basis of conventional treatment.Both groups were treated for 4 weeks.Results:The total effective rate of treatment in the observation group was higher than that of the control group(P<0.05).After treatment,the traditional Chinese medicine syndrome scores of both groups were significantly lower than before treatment,with the observation group showing a more pronounced reduction(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Wenzhong Hewei Formula can effectively improve clinical symptoms in patients with spleen and stomach qi deficiency syndrome,enhance clinical efficacy,and have a high level of safety,making it worthy of clinical promotion.

Exploring the biological mechanism of qi deficiency syndrome with chronic obstructive pulmonary disease(COPD)based on integrated pharmacology

Objective:To explore the potential biological mechanism of chronic obstructive pulmonary disease(COPD)qi deficiency syndrome,we used the integrated pharmacology network computing platform and carried out experimental verification.Methods:Using an integrated pharmacology strategy to analyze the potential biological targets of COPD qi deficiency syndrome.Based on the established qi deficiency syndrome rat model of COPD,the biological targets of lung and skeletal muscle were detected by electron microscopy,adenosine triphosphate(ATP)content assays,and western blotting.Results:According to the integrated pharmacological results,it was found that the locations of cell components related to COPD qi deficiency syndrome were mainly mitochondria.Electron microscopy results using lung tissue showed that mitochondria in the lipopolysaccharide(LPS group)and pulmonary instillation of LPS combined with cigarette smoke(LPStCS group)were swollen,deformed,and fragmented,with disappearing or broken crista.Results also showed that the total content of ATP in the lung and skeletal muscle of both groups was significantly lower than that in the control group at the 12th week(P<.05).At the 12th week,the expression of dynamin-related protein 1(DRP1)and mitofusin 1(MFN1)protein was significantly difference than that of the control group(P<.05).At the 10th and 14th weeks,changes in fission and fusion proteins in mitochondria of the lung and skeletal muscle were further detected.There was also a significant difference in the expression between the two groups compared to that in the control group at the 10th week and 14th week(P<.05).Conclusion:These findings suggest that the changes in mitochondrial morphology and ATP content and the unbalanced expression of DRP1 and MFN1 might be the key mechanisms underlying qi deficiency syndrome in rats with COPD.

Symptom characteristics and prevalence of qi deficiency syndrome in people of varied health status and ages: A multicenter cross-sectional study

Objective:Aging caused by a deficiency syndrome can be found in ancient and modern traditional Chinese medicine literature.Qi deficiency syndrome(QDS)is a vital factor in the aging process.This study aimed to establish a full-scale trial to evaluate the prevalence,symptom severity,frequency,and distribution of QDS in different age groups and varying health status to elucidate the role of qi deficiency in the aging process and deterioration of health.Methods:This cross-sectional study was conducted in four hospitals in China,and data from 1220 participants were included.The participants,aged between 20 and 79 years,completed questionnaires that recorded prevalence of QDS and severity or frequency of relevant symptoms,then were interviewed by investigators.We used frequency analysis and chi-squared tests to perform comparative analysis of prevalence in different age and health groups;we used a ranksum tests for quantitative analysis of symptoms severity and frequency scores;we performed a regression analysis of correlation between syndrome occurrence and potential factors using nonconditional binary logistic stepwise regression of numerical variables.P<0.05 was considered statistically significant.Results:Prevalence,symptom severity and frequency scores of QDS showed a rising trend when physical condition worsened,rather than when age increased.Health status,fatigue,shortness of breath or no desire to talk,spontaneous sweating,swollen tongue with teeth marks on side,and deficient and weak pulse,rather than increasing age were contributing factors to this syndrome.Distribution of QDS in certain health and age stages showed remarkable irregularities.Conclusions:Qi deficiency may be a contributing factor for sub-health(sub-optimal health)and chronic diseases rather than aging.It may play a crucial role in chronic disease pathogenesis of young and middle-aged people,and in sub-health pathogenesis of older adults.Recognition of the warning signs and symptoms of QDS may lead to early intervention and prevention of subhealth,and chronic diseases.

Study on the Biological Basis of Qi, Blood, and Vessel in Immune Thrombocytopenia Patients With Syndrome of Qi Failing to Govern Blood Based on the Theory of Qi and Blood

Objective: To investigate the biological basis of qi, blood and vessel in immune thrombocytopenia(ITP) patients with syndrome of qi failing to govern blood(SQFGB) based on traditional Chinese medicine.Methods: A total of 52 ITP patients with SQFCB were enrolled and divided into bleeding group(38 cases) and non-bleeding group(14 cases).Bleeding group was further divided into mild qi deficiency group(25 cases) and moderate/severe qi deficiency group(13 cases) based on Chinese Medicine syndrome score.20 healthy volunteer were recruited as control group.The count of platelet(PLT) was taken as the blood related indicator.The expressions of cytokines including IL-1β, IL-17 A, TNF-α, CD40 L, and TGF-β, detected by Aim Plex Multiple Immunoassays for Flow, were taken as the qi related indicators.The expressions of VEGF-A, detected by Aim Plex Multiple Immunoassays for Flow and NO, NOS, and ET-1 detected by ELISA, were taken as the vessel related indicators.Results: As compared to the control group, the count of PLT, taken as the blood related indicator, was significantly lower in ITP group patients with SQFCB(P<0.05).The expression levels of IL-17 A and TNF-α, taken as the qi related indicators, were significantly higher, while those of CD40 L, IL-1β, and TGF-β, also taken as the qi related indicators, were significantly lower in ITP patients with SQFCB, respectively(P<0.05).The expression levels of NO and ET-1, taken as the vessel related indicators, were significantly higher, while the expression levels of NOS and VEGF-A also taken as the vessel related indicators, were significantly lower in ITP patients with SQFCB, respectively(P<0.05).The count of PLT, taken as the blood related indicator, was significantly lower in moderate/severe group than those in mild group(P<0.05).The expression levels of CD40 L and TGF-β, taken as the qi related indicators, were also significantly lower in moderate/severe group than those in mild group, respectively(P<0.05).Conclusion: The count of PLT might be the biological basis of blood.The expressions of NO, NOS, ET-1 and VEGF-A might be the biological basis of vessel.The expressions of IL-1β, IL-17 A, TNF-α, TGF-β, and CD40 L may be the biological basis of qi.The expressions of CD40 L and TGF-β could reflect the degree of qi deficiency in ITP patients based on the theory of qi and blood.

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.

Study on syndrome differentiation based on pharmacology of syndrome management system-a case of Qi and Yin deficiency syndrome

Taking the Qi and Yin deficiency syndrome as an example,the research method of pharmacology of syndrome management system was proposed.By means of text mining,systematic pharmacology and target analysis,to attempt to reveal the essence of the corresponding syndrome by studying the drugs and targets of Qi and Yin deficiency.Fourteen Chinese herbs treating Qi and Yin deficiency were retrieved and used more than 30 times,and 9,317 related targets were predicted.The common targets of action were 85.Topological analysis was carried out by using degree centrality,closeness centrality and betweenness centrality to confirm that estrogen receptor(ESR1),tumor necrosis factor(TNF),D(2)dopamine receptor(DRD2),vitamin D3 receptor(VDR),glucocorticoid receptor(NR3C1),acetylcholinesterase(ACHE)and endothelin-1(EDN1)were highly correlated with Qi and Yin deficiency syndrome.Through the target to find Qi and Yin deficiency syndrome corresponding to 17 categories of diseases.A new idea was provided for studying the biological essence of TCM clinical syndrome differentiation.

Pharmacological effects of Paeoniflorin and Albiflorin on IL-3, GM-CSF, IL-6 and TNF-α in the rats of syndrome of stagnation of liver qi and blood deficiency

Objective： To observe the effect of paeoniflorin （PF）, albiflorin （AF） on the hemogram, visceral index and hematopoiesis cytokine in the rats of syndrome of stagnation of liver qi and blood deficiency, and to discuss the material base and mechanism of effect of nourishing blood and smoothing the liver of Baishao （Radix Paeoniae Alba）. Methods： Male SD rats were randomly divided into groups according to the sucrose preference test and body weight （n = 12）. Except the normal control, the other groups were treated with the chronic stress stimulation combined with radiation respectively to establish the model of syndrome of stagnation of liver qi and blood deficiency. The body weight, visceral index and the quantity of Leucocyte, Red Blood Cells, Hemoglobin in peripheral hemogram were monitored, then plasma and serum were separated. Radioimmunoassay was used to analyze the levels of Lnterleukin-3, Granulocyte-macrophage Colony-stimulating Factor, Lnterleukin-6 and Tumor Necrosis Factor-α in plasma. Results： Compared with that of model group, 30 mg·kg^-1 PF and 30 mg·kg^-1 AF of the weight, spleen index, quantity of Leucocyte were increased significantly （P 〈 0.05, P 〈 0.01）. The results of Radioimmunoassay showed that the levels of Interleukin-3 increased （P 〈 0.05, P 〈 0.05） and the levels of Tumor Necrosis Factor-α decreased in both 30 mg·kg^-1 PF and 30 mg·kg^-1 AF groups （P 〈 0.05, P 〈 0.05）. Conclusion： The effect of PF and AF on the regulation of bone marrow hematopoietic system and immune system play a role in the blood of rats with syndrome of stagnation of liver qi and blood deficiency, which suggests that both of them are the main active ingredients of nourishing blood and smoothing the liver of Baishao.

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.

Chinmedomics facilitated quality-marker discovery of Sijunzi decoction to treat spleen qi deficiency syndrome

Sijunzi decoction (SJZD) is a Chinese classical formula to treat spleen qi deficiency syndrome (SQDS) and has been widely used for thousands of years.However,the quality control (QC) standards of SJZD are insufficient.Chinmedomics has been designed to discover and verify bioactive compounds of a variety of formularapidly.In this study,we used Chinmedomics to evaluate the SJZD's efficacy against SQDS to discover the potential quality-markers (q-markers) for QC.A total of 56 compounds in SJZD were characterized in vitro,and 23 compounds were discovered in vivo.A total of 58 biomarkers were related to SQDS,and SJZD can adjust a large proportion of marker metabolites to normal level and then regulate the metabolic profile to the health status.A total of 10 constituents were absorbed as effective ingredients that were associated with overall efficacy.We preliminarily determined malonyl-ginsenoside Rb2 and ginsenoside Ro as the q-markers of ginseng;dehydrotumulosic acid and dihydroxy lanostene-triene-21-acid as the q-markers of poria;glycyrrhizic acid,isoglabrolide,and glycyrrhetnic acid as the q-markers of licorice;and 2-atractylenolide as the q-marker of macrocephala.According to the discovery of the SJZD q-markers,we can establish the quality standard that is related to efficacy.

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

Clinical Observation of Qi Deficiency Syndrome in72 Patients with Chronic Obstructive Pulmonary DiseaseTreated with Yiqi Mianyi Granule (益气免疫冲剂)

Seventy-two patients of chronic obstructive pulmonary disease (COPD) of Qi deficiency syn-drome with abnormal immune indices were treated with Yiqi Mianyi Granule (YQMYG) and the efficacy wascompared with that of 30 cases treated with Zhenqi fuzheng Granule (ZQFZG) for control. Results showedthat the markedly effective rate of symptomatic improvement ot Qi deficiency in YQMYG group was 65. 3%,the total effective rate 93. 1 % . 88. 6% of the immune indices lower than normal were corrected and 43. 7%ot them were normalized, while for indices that were higher than normal the rate were 78. 2 % and 52 . 9% re-spectively. These results suggested that YQMYG could improve symptom of Qi Deficiency markedly,strengthen cellutar immunity and regulate immune dysfunction. its therapeutic efficacy was obvfously superiorto ZQFZG ( P < 0 . 05 ).

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.

Clinical observation on acupuncture treatment for constipation due to intestinal qi stagnation

Objective： To compare the different therapeutic effects of acupuncture and Phenolphthalein for constipation due to intestinal qi stagnation. Methods： A total of 50 patients with constipation due to intestinal qi stagnation were randomly divided into an acupuncture group and a medication group by the random digital table, 25 cases in each group. The patients in the acupuncture group were treated by puncturing Gongsun（SP 4）, Sanyinjiao（SP 6）, Taichong（LR 3）, Zusanli（ST 36）, Shangjuxu（ST 37）, Hegu（LI 4）, Lieque（LU 7）, and Tianshu（ST 25）, once every day, and 7 d as one course, for continuous 3 courses; while the patients in the medication group were given Phenolphthalein, 7 d as one course, for continuous 3 courses. Compared the Cleveland clinic constipation score（CCS） between the two groups after one course, 3 courses and 3 months after the treatment, as well as the frequency of defecation within one week. Results： After one week of treatment, CCS scores and frequency of defecation per week were significantly changed in both groups compared with those before treatment（P〈0.05）, and CCS scores and frequency of defecation per week were improved more significantly in the patients of the medication group than in those of the acupuncture group（P〈0.01）. After 3 weeks of treatment, CCS scores and frequency of defecation per week were significantly changed in both groups compared with those before treatment（P〈0.05）, and CCS scores and frequency of defecation per week were improved more significant in the patients of the acupuncture group than in those of the medication group（P〈0.05）. Three months after the end of treatment, CCS scores and frequency of defecation per week were significantly changed in both groups compared with those before treatment（P〈0.05）, and CCS scores and frequency of defecation per week were improved more significantly in the patients of the acupuncture group than in those of the medication group（P〈0.05）. Conclusion： Acupuncture and medication are effective in the treatment of constipation due to intestinal qi stagnation. Their short-term therapeutic effect is similar, but the long-term therapeutic effect is better in the acupuncture group than in the medication group.

Long-Term Follow-Up of Chinese Herbal Medicines Combined with Conventional Treatment in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention: A Multicenter Randomized Controlled Trial

Objective： To evaluate the prognosis effect of Chinese herbal medicines（CHMs） for benefiting qi and activating blood circulation adjunctive to conventional treatment in patients with acute coronary syndrome（ACS） after percutaneous coronary intervention（PCI）. Methods： A total of 702 patients with ACS who underwent PCI were enrolled and randomly assigned to receive conventional treatment plus CHMs for benefiting qi and activating blood circulation（treatment group, 351 cases） or conventional treatment alone（control group, 351 cases） for 6 months. Six months later, all patients received conventional treatment alone. Follow-ups were scheduled at 6th, 12 th, 18 th, 24 th month after enrollment in April 2008, and the final follow-up visit was during September 2011 and November 2011. The primary endpoint was the composite of cardiac death, nonfatal myocardial infarction or revascularization（PCI or coronary artery bypass grafting）; and the secondary endpoint was the composite of re-admission for ACS, congestive heart failure, nonfatal stroke or other thrombus events. Results： A total of 621（88.59%） patients completed 35.4±3.8 months follow-up, while 80（11.41%） patients withdrew from the trial（41 in the treatment group and 39 in the control group）. The incidence of primary endpoint was 5.7%（20 patients） in the treatment group versus 10.86%（38 patients） in the control group [relative risk（RR）： 0.53; 95% confidence interval（CI）： 0.30, 0.88; P=0.013; absolute risk reduction（ARR）： –0.052, 95% CI： –0.06, 0.01]. The incidence of secondary endpoint was 5.98%（21 patients） in the treatment group versus 10.28%（36 patients） in control group（RR： 0.58, 95% CI： 0.33, 0.97, P=0.037; ARR： –0.043, 95% CI： 0.06, 0.01）. Most of the primary and secondary endpoints were occurred in 18 months（84.50% in the treatment group versus 78.10% in the control group）. Conclusion： CHMs for benefiting qi and activating blood circulation adjunctive to conventional treatment improved clinical outcomes for patients with ACS after PCI in long-term follow-up.

Pulse changes in patients with cervical spondylosis before and after acupuncture treatment

OBJECTIVE： To study changes in pulse diagram parameters （PDP） in patients with cervical spondylosis （CS） before and after acupuncture treatment, explore the characteristics of PDP and the relationship between PDP changes and therapeutic effectiveness, and provide evidence for outcome prediction and objective evaluation of CS treatment before and after acupuncture treatment. METHODS： Patients with CS were treated with acupuncture and measured with a pulse acquisition device based on image （PADBI） before the first and after the tenth acupuncture sessions. Changes in PDP from before until after the acupuncture sessions and patient impressions were analyzed to judge the effect of acupuncture treatment for. RESULTS： The PDP values in effective patients were closer to normal values. This indicated that Qi stagnation and blood stasis of the patients was improved. The PDP changes from before to after the first acupuncture treatment were more obvious than those from before to after the tenth acupunc- ture treatment. This result indicates that the speed of symptom improvement decreased significantly after several acupuncture courses. Analysis of correlation between efficacy and PDP showed that the changes in PDP in five patients was abnormal, which mainly manifested as values of hl, u, p, Pp, and tl, and no significant changes or differences were increased with standard values. This indicated that the symptoms of CS were not improved in these patients. CONCLUSION; PADBI can provide evidence for outcome prediction of acupuncture treatment in patients with CS. PADBI can provide evidence for objective evaluation of acupuncture treatment of CS.

Effect of Chaihushugan San on expression of the Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in the hippocampi of perimenopausal rats induced by immobilization stress

OBJECTIVE: We wished to study the impact of Chaihushugan San(CSS) on the behavior of perimenopausal rats with liver-Qi stagnation(LQS) and to investigate the effect of CSS on signal transduction of the Raf/mitogen-activated protein kinase(MEK)/extracellular signal-regulated kinase(ERK) cascade in the hippocampi of rats induced by immobilization.METHODS: Twenty 52-week-old female rats were divided into two groups by the random number table method: model control group(MCG) and CSS group(CSSG), with 10 rats in each group.Ten-week-old female rats were used as the normal control group(NCG). CSS effects were assessed using rats exposed to immobilization stress by measuring body weight and sucrose consumption, serum hormone levels, and observing performance in the open field test(OFT). Molecular mechanisms were examined by measuring the effect of CSS on expression of Raf1, MEK1/2 and ERK1/2 m RNA in hippocampi using quantitative real-time polymerase chain reaction and by measuring levels of these proteins and related phospho-proteins using Western blotting.RESULTS: Perimenopausal rats with LQS had decreased locomotor activity; reduced sucrose consumption; and increased serum levels of corticotropin releasing hormone(CRH) and corticosterone(CORT). Activation of hippocampal Raf/MEK/ERK cascade was suppressed significantly in the MCG,and activation was increased after 21 days of CSS treatment.CONCLUSION: CSS has significant effects upon relief of the symptoms of LQS in immobilization-induced rats. The mechanism underlying this action might(at least in part) be mediated by reversal of disruption of the Raf/MEK/ERK pathway.

Serum Low-Density Lipoprotein and Heart Rate Related to the Effectiveness in the Treatment of Angina Pectoris with Two Similar Chinese Medicine Herbal Formulae

Objective： To explore the effectiveness related indicators which might help identify the indications of Tongxinluo Capsule （通心络胶囊） and Kangxin Capsule （康欣胶囊） targeting on qi deficiency and blood stasis pattern in Chinese medicine （CM） in the treatment of angina pectoris. Methods： The data from a multicenter, randomized and double-blinded study conducted at 5 centers in China were obtained for the analysis. A total of 239 patients with angina pectoris and CM syndrome of qi deficiency and blood stasis were randomly assigned in a 1：1 ratio to Tongxinluo Capsule group （119 cases） and Kangxin Capsule group （120 cases）. Angina effectiveness and electrocardiogram （ECG） improvement were selected as the therapeutic outcomes. Results： After a 4-week treatment, the effective rates of Tongxinluo Capsule and Kangxin Capsule were 43.70% and 25.00%, respectively （P〈0.05）. Serum low-density lipoprotein （LDL） level was found to influence the effectiveness of Tongxinluo Capsule which had higher effective rate in the patients with lower level of LDL. Heart rate was found to influence the effectiveness in the patients treated with Kangxin Capsule which had higher effective rate in the patients with heart rate ≤80 beats/min. Conclusion： LDL level and heart rate were the indicators which help indentify the indications of Tongxinluo Capsule and Kangxin Capsule, respectively, in the treatment of angina pectoris with CM syndrome of qi deficiency and blood stasis.