[Therapeutic effect of auriculotherapy with miniature bian needle on anxiety in the patients after percutaneous coronary intervention].

OBJECTIVE: To observe the effect of auriculotherapy with miniature bian needle on anxious emotion, the condition of angina pectoris attack and sleep quality in the patients with anxiety after percutaneous coronary intervention (post-PCI). METHODS: A total of 74 eligible patients of post-PCI combined with anxious depression were randomized into an auriculotherapy group (37 cases, 2 cases dropped out) and a control group (37 cases, 3 cases dropped out). In the auriculotherapy group, on the base of the conventional secondary prevention medication for coronary heart disease (CHD), auriculotherapy with miniature bian needle was supplemented. In the control group, a proper physical exercise was combined on the base of the secondary prevention medication for CHD. The duration of treatment was 4 weeks in two groups. Separately, the score of Hamilton anxiety scale (HAMA), the score Seattle angina questionnaire (SAQ) and the score of Pittsburgh sleep quality index (PSQI) were assessed in the patients of the two groups before and after treatment. RESULTS: After treatment, the score of HAMA, the score of each item of SAQ and PSQI score were all improved significantly as compared with those before treatment respectively in both the auriculotherapy group and the control group (P<0.001, P<0.05). After treatment, HAMA score, PSQI score and the scores of physical limitation (PL), anginal stability (AS), anginal frequency (AF) and treatment satisfaction (TS) in SAQ in the auriculotherapy group were all better than those in the control group (P<0.001, P<0.05). The total effective rate was 91.43% (32/35) in the auriculotherapy group, obviously higher than 58.82% (20/34) in the control group (P<0.001). CONCLUSION: Auriculotherapy with miniature bian needle effectively relieves anxious emotions and the condition of angina pectrois attack and improves sleep quality in the post-PCI patients with anxiety.

Functional suppression of Epiregulin impairs angiogenesis and aggravates left ventricular remodeling by disrupting the extracellular-signal-regulated kinase1/2 signaling pathway in rats after acute myocardial infarction.

Acute myocardial infarction (AMI), a severe consequence of coronary atherosclerotic heart disease, is often associated with high mortality and morbidity. Emerging evidence have shown that the inhibition of the extracellular-signal-regulated kinase (ERK) signaling pathway appears to protect against AMI. Epiregulin (EREG) is an autocrine growth factor that is believed to activate the MEK/ERK signaling pathway. Therefore, the aim of the present study was to determine the expression patterns of EREG in AMI and to further study its effects on AMI induced experimentally in rats focusing on angiogenesis and left ventricular remodeling. Microarray-based gene expression profiling of AMI was used to identify differentially expressed genes. To understand the biological significance of EREG and whether it is involved in AMI disease through the ERK1/2 signaling pathway, rats after AMI were treated with small interfering RNA (siRNA) against EREG, an ERK1/2 pathway inhibitor, PD98059, or both of them. The microarray data sets GSE66360 and GSE46395 showed that EREG was robustly induced in AMI. Both siRNA-mediated depletion of EREG and PD98059 treatment were shown to significantly increase infarct size and left ventricular cardiomyocyte loss and enhance left ventricular remodeling. In addition, we also found that the ERK1/2 signaling pathway was inhibited following siRNA-mediated EREG inhibition and PD98059 could enhance the effects of EREG inhibition on AMI. In conclusion, these findings highlight that the silencing of EREG inhibits angiogenesis and promotes left ventricular remodeling by disrupting the ERK1/2 signaling pathway, providing a novel therapeutic target for limiting AMI.

Shenzhu Guanxin Recipe Granules () for Improving Exercise Tolerance in Patients with Stable Angina (SERIES Trial): A Protocol of Multicenter, Randomized, Double-Blind, Placebo Parallel Controlled Clinical Trial.

BACKGROUND: Many patients with chronic angina experience anginal episodes despite successful recanalization, antianginal and antiischemic medications. Empirical observations suggested that Shenzhu Guanxin Recipe Granules (, SGR), a Chinese herbal compound, exerted potential impacts on increased treadmill exercise performance and angina relieve. However, there has been no systematic study to clarify the impact of SGR on exercise tolerance in patients with stable angina. The SERIES (ShEnzhu guanxin Recipe for Improving Exercise tolerance in patients with Stable angina) trial is designed to determine the effects of SGR on exercise duration, electrocardiographic (ECG) evidence of myocardial ischemia, and incidence of major adverse cardiac events (MACE) in stable anginal patients. METHODS: A total of 184 eligible patients with stable angina will be randomly assigned to receive placebo or SGR (10 g/day for 12 weeks) in a 1:1 ratio. The primary outcome will be the change from baseline in total exercise tolerance duration, time to onset of angina and ECG ischemia during exercise treadmill testing performed over a 12-week study period. The secondary outcome will include ECG measures, the occurrence and composite of MACE and the Seattle Angina Questionnaire score. Moreover, the coronary microcirculation will be evaluated to explore the possible effects in response to treatment of SGR. After the procedure, all participants will be followed up by interview at 3 and 6 months, enquiring about any cardiac events, hospitalizations, cardiac functional level and medication usage. Additionally, the occurrence of adverse events will be evaluated at each follow-up. DISCUSSION: This study may provide novel evidence on the efficacy of SGR in improving exercise tolerance and potentially reducing clinical adverse events. (Trial registration No. ChiCTR-TRC-14004504).

Systems Pharmacology Dissection of Traditional Chinese Medicine Wen-Dan Decoction for Treatment of Cardiovascular Diseases.

Cardiovascular diseases (CVDs) have been recognized as first killer of human health. The underlying mechanisms of CVDs are extremely complicated and not fully revealed, leading to a challenge for CVDs treatment in modern medicine. Traditional Chinese medicine (TCM) characterized by multiple compounds and targets has shown its marked effects on CVDs therapy. However, system-level understanding of the molecular mechanisms is still ambiguous. In this study, a system pharmacology approach was developed to reveal the underlying molecular mechanisms of a clinically effective herb formula (Wen-Dan Decoction) in treating CVDs. 127 potential active compounds and their corresponding 283 direct targets were identified in Wen-Dan Decoction. The networks among active compounds, targets, and diseases were built to reveal the pharmacological mechanisms of Wen-Dan Decoction. A "CVDs pathway" consisted of several regulatory modules participating in therapeutic effects of Wen-Dan Decoction in CVDs. All the data demonstrates that Wen-Dan Decoction has multiscale beneficial activity in CVDs treatment, which provides a new way for uncovering the molecular mechanisms and new evidence for clinical application of Wen-Dan Decoction in cardiovascular disease.

Ginsenoside Rb1 prevents homocysteine-induced EPC dysfunction via VEGF/p38MAPK and SDF-1/CXCR4 activation.

Hyperhomocystinemia (HHcy) is known as an independent risk factor for cardiovascular disease. Our previous study showed that ginsenoside Rb1, the major active constituent of ginseng, prevents homocysteine (Hcy)-induced endothelial damage. However, the role of ginsenoside Rb1 in Hcy-induced dysfunction in endothelial progenitor cells (EPCs) remains unknown. In the study, we found that ginsenoside Rb1 reversed the Hcy-induced impairment of adhesive and migratory ability in EPCs which were significantly abolished by CXCR4 antagonist AMD3100 and VEGFR2 inhibitor SU5416. Ginsenoside Rb1 significantly reversed Hcy-induced SDF-1 reduction in the supernatant and in the serum. Ginsenoside Rb1 reversed downregulation of SDF-1 and VEGFR2 protein expression, inhibition of p38MAPK phosphorylation induced by Hcy. Re-endothelialization in balloon-injured carotid arteries significantly increased with EPCs transplant, and was even better with Rb1 treatment. This effect was significantly abolished by AMD3100. AMD3100 also decreased the number of CM-DiI labeled EPCs in injured arteries. Here we show for the first time that Rb1 prevents Hcy-induced EPC dysfunction via VEGF/p38MAPK and SDF-1/CXCR4 activation. These findings demonstrate a novel mechanism of the action of Rb1 that may have value in prevention of HHcy associated cardiovascular disease.

Traditional Chinese Medicine ShenZhuGuanXin Granules Mitigate Cardiac Dysfunction and Promote Myocardium Angiogenesis in Myocardial Infarction Rats by Upregulating PECAM-1/CD31 and VEGF Expression.

BACKGROUND: Myocardial infarction (MI) is the main cause of global mortality and morbidity despite the development of therapeutic approaches. ShenZhuGuanXin granules (SG) have been shown to possess cardioprotective effects against coronary heart disease (CHD). However, little is known about its specific mechanism. The present study aimed to investigate the therapeutic effect of SG in cardiac dysfunction and to demonstrate whether SG can promote myocardium angiogenesis by establishing a rat model of myocardial infarction with left anterior descending ligating. METHODS AND RESULTS: Three days after MI, rats were randomly divided into six groups: sham group (sham), MI group (MI), MI + low dose SG (SG-L) group, MI + middle dose SG (SG-M) group, MI + high dose SG (SG-H) group, and MI + compound Danshen dropping pills (CDDP) group as a positive control. Four weeks after administration, rats underwent hemodynamics and echocardiography study. Ventricle tissues were processed for histology and immunohistochemistry studies. Compared with MI group, SG treatment dose-dependently improved cardiac hemodynamic function, attenuated infarct size, increased microvessel density, and increased the expression of PECAM-1/CD31 and VEGF. CONCLUSIONS: SG dose-dependently improved cardiac hemodynamic function and attenuated infarct size by promoting angiogenesis through upregulating PECAM-1/CD31 and VEGF expression.

Effect of Shenzhu Guanxin Recipe () on patients with angina pectoris after percutaneous coronary intervention: A prospective, randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of a combination therapy using Chinese medicine (CM) Shenzhu Guanxin Recipe (, SGR) and standard Western medicine treatment (SWMT) in patients with angina pectoris after percutaneous coronary intervention (PCI). METHODS: Double-blind randomized controlled trial was used in this experimental procedure. One hundred and eighty-seven patients with coronary heart disease receiving SWMT after PCI were randomly assigned to the treatment (SGR) and control (placebo) groups. Outcome measures including angina pectoris score (APS), CM symptom score, and Seattle Angina Questionnaire (SAQ) score were evaluated in 1, 2, 3 and 12 months, and the death rate, restenosis and other emergency treatments were observed. The mixed-effects models were employed for the data analysis. RESULTS: In the treatment group, a larger within-treatment effect size (d=1.74) was found, with a 76.7% reduction in APS from pretreatment to 12-month follow-up assessment compared with the control group (d=0.83, 53.8% symptom reduction); betweentreatment (BT) effect size was d=0.66. CM symptom scores included an 18.3% reduction in the treatment group (d=0.46), and a 16.1% decrease in the control group (d=0.31); d=0.62 for BT effect size. In regard to scores of SAQ, the BT effect size of cognition level of disease was larger in the treatment group (d=0.63), followed by the level of body limitation of activity (d=0.62), condition of angina pectoris attacks (d=0.55), satisfaction level of treatments (d=0.31), and steady state of angina pectoris (d=0.30). Two cardiovascular related deaths and one incidental death were recorded in the control and treatment groups, respectively. No significant difference in any cardiovascular event (including death toll, frequency of cardiovascular hospitalization or emergency room visits) was found between the two groups. CONCLUSION: The combination therapy of SGR and SWMT is effective and safe in patients with angina pectoris after PCI when compared with SWMT alone.

A multicentre randomized clinical trial on efficacy and safety of huxin formula in patients undergoing percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) is widely used in clinical treatment of coronary artery disease. However, the effects of PCI on preventing restenosis after revascularization and improving the quality of life were not satisfying. Huxin Formula is formulated by modifying an experienced Chinese medicine formula and has been widely used in clinical practice due to its marked effects on coronary heart disease. A multicentre double-blind randomized controlled clinical trial was designed to evaluate the effects and safety of Huxin Formula in patients undergoing PCI. Our results showed that there was no significant difference between the two groups in main outcomes. For patients with ejection fraction (EF) >50%, score of the quality of life scale was higher in treatment group compared with control group. For patients with unstable angina, score of the quality of life scale in 360 days was significantly higher in treatment group compared with control group (P < 0.05). No obvious adverse reaction was found in the use of Huxin Formula. In conclusion, Huxin Formula, believed to be a safe treatment for patients after PCI, has benefits in improving the quality of life in patients with unstable angina though it failed to show superiority in primary and secondary outcomes.

[Literature study on the syndrome diagnosis and classification of coronary artery disease].

To investigate the application of diagnosis methods for coronary artery disease (CAD) and the status quo of its syndrome typing. The literature content analysis was used in this study. The frequency statistics was performed by comprehensively collecting CAD (thoracic obstruction) syndrome typing correlated literatures, designing content analysis tables, extracting information such as typing methods, typing elements, and syndrome typing, and so on. Results showed that blood stasis, yin deficiency, qi deficiency, yang deficiency, phlegm turbidity, and other syndrome elements extensively exist in literatures concerning CAD syndrome typing. Modem doctors prefer to use syndrome typing of qi, blood, jinye, and eight principles in syndrome typing of CAD more frequently. The asthenia in origin and asthenia in superficiality has been widely recognized as the basic syndrome of CAD.

Effect of Huxin Formula on reverse cholesterol transport in ApoE-gene knockout mice.

OBJECTIVE: To observe the effect of Huxin Formula on expressions of the chief reverse cholesterol transport (RCT) associated genes, caveolin-1 and scavenger receptor-BI (SR-BI) in ApoE-gene knockout [ApoE (-/-)] mice. METHODS: Thirty ApoE (-/-) mice of 4-6 weeks old were randomly divided into three groups (A-C). After being fed with high-fat diet for 16 weeks, they were treated with HXF (1 mL/100 g), pravachol (0.3 mg/100 g), and saline in equal volume respectively for 16 weeks successively; in addition, a blank group was set up with 10 C57BL/6J mice of 6-week old received 16-week high-fat feeding and saline treatment. Animals were sacrificed at the termination of the experiment, their paraffin sections of aortic tissue were used to measure the size of plaque, expressions of cavolin-1 and SR-BI were detected by immunological histochemical method. RESULTS: As compared with the blank group, levels of caveolin-1 and SR-BI were increased in Groups A and B (P<0.01); but the increase in Group A was more significant than that in Group B (P<0.05). The plaque/aorta area ratio decreased significantly in Groups A and B, but showed insignificant difference between the two groups. CONCLUSION: HXF could obviously increase the expressions of RCT associated genes, caveolin-1 and SR-BI, promote the RCT process, so as to reduce the formation of aorta atherosclerotic plaque in ApoE (-/-) mice.

Activated nuclear factor-kappaB and increased tumor necrosis factor-alpha in atrial tissue of atrial fibrillation.

OBJECTIVES: To depict the interaction between atrial fibrillation (AF) and inflammatory reaction, studies were taken to measure the activity of NF-kappaB in myocardium, the concentration of regional inflammatory factors and the pathological process of the right atrium in patients with AF. DESIGN: Patients with valvular disease with AF or sinus rhythm (SR) were recruited and compared. Before the extracorporal circulation, about 250 mg tissue of right atrium was collected for pathological examination. The activity of NF-kappaB in myocardium was measured by electrophoretic mobility shift assay (EMSA), and the concentration of cardiac tissue interleukin-6 (IL-6) and tumor necrosis factor (TNF-alpha) was determined by radioimmuoassay. RESULTS: Patients with valvular disease with AF exhibited higher NF-kappaB activity, higher concentration of TNF-alpha and IL-6, severe lymphomonocyte infiltration, and more fibrosis than those patients with valvular disease with SR. There were significant positive correlations among NF-kappaB activity and levels of TNF-alpha and IL-6 and collagen volume fraction. CONCLUSIONS: This study proved the presence of inflammation in atrial myocardium by triggering inflammatory reaction.

The guanine-nucleotide-exchange factor BopE from Burkholderia pseudomallei adopts a compact version of the Salmonella SopE/SopE2 fold and undergoes a closed-to-open conformational change upon interaction with Cdc42.

BopE is a type III secreted protein from Burkholderia pseudomallei, the aetiological agent of melioidosis, a severe emerging infection. BopE is a GEF (guanine-nucleotide-exchange factor) for the Rho GTPases Cdc42 (cell division cycle 42) and Rac1. We have determined the structure of BopE catalytic domain (amino acids 78-261) by NMR spectroscopy and it shows that BopE(78-261) comprises two three-helix bundles (alpha1alpha4alpha5 and alpha2alpha3alpha6). This fold is similar to that adopted by the BopE homologues SopE and SopE2, which are GEFs from Salmonella. Whereas the two three-helix bundles of SopE(78-240) and SopE2(69-240) form the arms of a 'Lambda' shape, BopE(78-261) adopts a more closed conformation with substantial interactions between the two three-helix bundles. We propose that arginine and proline residues are important in the conformational differences between BopE and SopE/E2. Analysis of the molecular interface in the SopE(78-240)-Cdc42 complex crystal structure indicates that, in a BopE-Cdc42 interaction, the closed conformation of BopE(78-261) would engender steric clashes with the Cdc42 switch regions. This implies that BopE(78-261) must undergo a closed-to-open conformational change in order to catalyse guanine nucleotide exchange. In an NMR titration to investigate the BopE(78-261)-Cdc42 interaction, the appearance of additional peaks per NH for residues in hinge regions of BopE(78-261) indicates that BopE(78-261) does undergo a closed-to-open conformational change in the presence of Cdc42. The conformational change hypothesis is further supported by substantial improvement of BopE(78-261) catalytic efficiency through mutations that favour an open conformation. Requirement for closed-to-open conformational change explains the 10-40-fold lower k(cat) of BopE compared with SopE and SopE2.

[Cluster analysis on TCM syndromes in 319 coronary artery disease patients for establishment of syndrome diagnostic figure].

OBJECTIVE: To explore the diagnostic figures for TCM syndrome typing in coronary heart disease (CHD) patients. METHODS: A retrospective investigation was carried out in 319 CHD patients hospitalized from Jan. 2004 to Dec. 2004 in authors' hospital. Through cluster analysis, descriptive statistics and frequency normalization in combination of clinical observation, the diagnostic figures of TCM syndromes were obtained. RESULTS: The figures for qi deficiency syndrome were: primary symptoms: chest pain and stuffiness, secondary symptoms: tiredness, short breath, poor appetite, light colored tongue, deep and thready pulse; for qi deficiency with phlegm and blood stasis syndrome: primary symptoms: chest stuffiness and pain, secondary symptoms: tiredness, insomnia, palpitation, obesity, dark red tongue, string and slippery pulse; for turbid-phlegm blocking collateral syndrome: primary symptoms: chest stuffiness, secondary symptoms: cough, expectoration with much white sputum, tiredness, short breath and poor appetite, light colored tongue with white greasy coating, slippery pulse. CONCLUSION: Research on diagnostic criteria for TCM syndrome typing could be established upon clinical epidemiologic survey and statistic analysis in combining with specialists' suggestions to primarily set the referrence figures.

[Analysis on TCM syndrome distribution laws in 319 patients with coronary heart disease].

OBJECTIVE: To study TCM syndrome distribution laws in patients with coronary heart diseases (CHD) by epidemiological investigation. METHODS: A clinical survey was carried out in 319 inpatients with CHD, whose diagnosis was confirmed by coronary arteriography, in the authors' hospital from January 2004 to December 2004. The TCM syndrome distribution laws were analyzed, and the relationship of coronary arteriographic picture with TCM syndrome elements, common symptoms, pulse and tongue figures, as well as the correlation between syndrome typing and blood-lipid levels were analyzed, too. RESULTS: Qi deficiency was the most popular syndrome in patients with CHD (87.1%), blood stasis syndrome and phlegm retention syndrome took the second place, accounting for 79.9% and 78.7% respectively. No significant difference was shown in comparison of tongue and pulse figures with the affected branches of coronary artery, the dark-pale tongue with white greasy fur and taut-slippery pulse being the dominance in patients. The blood-lipid levels in patients with various TCM syndrome types were similar, showing insignificant difference. CONCLUSION: The TCM pathogenesis of CHD takes qi deficiency as the core, blood stasis and phlegm retention as the important pathologic products.

[Study on TCM syndrome differentiation rules in coronary artery bypass grafting patients during peri-operation period].

OBJECTIVE: To study the TCM syndrome differentiation rules in coronary artery bypass grafting (CABG) patients during peri-operation period. METHODS: According to the Guideline for Clinical Trail of Traditional Chinese New Drugs and experience of Professor DENG Tie-tao, the standard of TCM syndrome differentiation for CABG patients was established, with which 161 CABG patients were classified before and two weeks after CABG operation. RESULTS: Before CABG, the qi stagnation and blood stasis syndrome type was the type most commonly seen (46.0%), the next in turn was the phlegm stagnation type (24.8%), the yang-qi deficiency type (15.5%), and the yin-blood deficiency type (13.7%). While after CABG, the phlegm stagnation syndrome type was the most frequently occurred one (35.9%), then in turn was the yang-qi deficiency type (30.8%), the yin-blood deficiency type (21.2%) and the qi stagnation with blood stasis type (12.2%). CONCLUSION: For patients before CABG, the pathological characteristic is mostly the deficiency in root with excess in superficiality, and the commonest syndrome is the qi stagnation with blood stasis type. For patients after CABG, both deficiency and excess is the pathological characteristic, the Xin-qi and Xin-yang deficiency syndrome the commonest type, and with phlegm as the main pathologic factor.

[Trial study on DENG Tie-tao's coronary heart disease capsules in improving patients' quality of life].

OBJECTIVE: To assess the efficacy of the Coronary Heart Disease (CHD) Capsules worked out by Prof. Deng --in improving quality of life of CHD patients of qi deficiency with phlegm and blood stasis syndrome. METHOD: According to the WHO's diagnosis criteria of CHD, a total of 93 stable angina patients were divided into 3 groups using the single blinded method. The groups were evenly distributed into CHD Capsule treated group (CHDC), isosorbide dinitrate control group (ID), and Compound Prescription Danshen Droplet Pills control group (CPDDP). Two courses of treatment lasting for 6 months were given. During the courses of treatment, the following parameters were observed: clinical symptoms of angina pectoris, ECG change, treadmill exercise test, 36 items in short form of health survey (SF-36) and Seattle Angina Questionnaire (SAQ) scale. RESULTS: After 6 months of treatment, all the three groups showed good curative effect in angina pectoris, ECG and treadmill exercise test, differences between them had no statistical significance. The CHDC group showed a better result in nitro-glycerine stopping or alleviation rate and in improving symptoms than the other groups (P < 0.05). The general health, vitality, role-emotional, mental health and reported health transition in the CHDC group were significantly better than those in the control groups (P < 0.05). The scores in physiological functioning role, physiological function and pain alleviation were not different among the three groups. CONCLUSION: Prof. DENG Tie-tao's CHDC is effective in treating CHD with qi deficiency, phlegm and blood stasis and also in improving the quality of life. CHDC is more suitable to be used in long-term treatment than isosorbide dinitrate. The SF-36 and SAQ can be used to appraise the curative effect of traditional Chinese medicine agents for CHD angina pectoris.

Evolution of the genetic triplet code via two types of doublet codons.

Explaining the apparent non-random codon distribution and the nature and number of amino acids in the 'standard' genetic code remains a challenge, despite the various hypotheses so far proposed. In this paper we propose a simple new hypothesis for code evolution involving a progression from singlet to doublet to triplet codons with a reading mechanism that moves three bases each step. We suggest that triplet codons gradually evolved from two types of ambiguous doublet codons, those in which the first two bases of each three-base window were read ('prefix' codons) and those in which the last two bases of each window were read ('suffix' codons). This hypothesis explains multiple features of the genetic code such as the origin of the pattern of four-fold degenerate and two-fold degenerate triplet codons, the origin of its error minimising properties, and why there are only 20 amino acids.