Mechanism of new optimized Sheng-Mai-San Formula to regulate cardiomyocyte apoptosis through NMDAR pathway.

Background and objectives: Ischemic heart failure (HF) has become a disease that seriously endangers people's life and health. As a herbal formula widely used in clinical practice, new optimized Sheng-Mai-San (NO-SMS) has been shown to be significantly effective in improving cardiac function, increasing exercise tolerance, and slowing the progression of myocardial fibrosis in heart failure patients in multi-center clinical studies in various regions of China. In our previous pharmacodynamic and toxicological studies, we found that a medium-dose formulation (8.1 g of raw drug/kg) was the most effective in the treatment of heart failure, but its mechanism of action is still being investigated. The present study is exploring its relationship with cardiomyocyte apoptosis. Materials and methods: We investigated and verified this through two parts of experiments, in vivo and in vitro. Firstly, we prepared male SD rats with heart failure models by ligating the left anterior descending branch of the coronary artery (EF ≤ 50%), which were treated with NO-SMS Formula (8.1 g of raw drug/kg/d), Ifenprodil (5.4 mg/kg/d) or Enalapril (0.9 mg/kg/d) prepared suspensions by gavage for 4 weeks. The cardiac and structural changes were evaluated by echocardiography, H&E, and MASSON staining. The apoptosis of cardiomyocytes in each group was detected by Western blot, qRT-PCR, and ELISA. In vitro cell experiments include H9c2 cardiomyocyte injury induced by H2O2 and NMDA respectively, and the groups were incubated with NO-SMS and Ifenprodil-containing serum for 24 h. Apoptosis was detected by Annexin V-FITC/PI double-staining method, and the rest of the assays were consistent with the in vivo experiments. Results: Compared with the model group, the NO-SMS formula group and the Ifenprodil group could significantly improve cardiac function, delay myocardial fibrosis, reduce the expression of pro-apoptotic proteins, mRNA, and the concentration levels of Ca2+ and ROS in heart failure rats and H9c2 cardiomyocytes with H2O2 and NMDA-induced injury, which could significantly reduce the apoptosis rate of damaged cardiomyocytes and effectively inhibit the apoptosis of cardiomyocytes. Conclusion: NO-SMS Formula improved cardiac function, inhibited ventricular remodeling and cardiomyocyte apoptosis in HF rats, and its mechanism may be related to the regulation of the NMDAR signaling pathway, inhibition of large intracellular Ca2+ inward flow, and ROS production in cardiomyocytes.

Effect of optimized new Shengmai powder on exercise tolerance in rats with heart failure by regulating the ubiquitin-proteasome signaling pathway.

Introduction: Decreased exercise tolerance is a common symptom in patients with heart failure, which is closely related to protein degradation and apoptosis regulated by the ubiquitin-proteasome signaling (UPS) pathway. In this study, the effect of Chinese medicine, optimized new Shengmai powder, on exercise tolerance in rats with heart failure was investigated via the UPS pathway. Methods: The heart failure model was prepared by ligating the left anterior descending branch of the coronary artery in rats, in which the sham-operated group was only threaded and not ligated. Rats (left ventricular ejection fraction ≤ 45%) were randomly divided into the following groups: model group, YHXSMS group, Benazepril group, and proteasome inhibitor Oprozomib group, and they were administered the corresponding drugs by gavage for 4 weeks. The cardiac function of rats was evaluated by performing an echocardiography examination and a hemodynamic test and the exercise tolerance was done by conducting an exhaustive swimming test. The mechanism was revealed by TUNEL detection, immunohistochemistry, immunofluorescence analysis, Western blot, and quantitative real-time PCR. Results: The study showed that there was a decrease in cardiac function and exercise tolerance of rats in the model group and also destruction of cardiac and skeletal muscle fibers, a proliferation of collagen tissue, and an increment of apoptosis. Our study suggested that optimized new Shengmai powder could exert antiapoptotic effects on myocardial and skeletal muscle cells and improve myocardial contractility and exercise tolerance by inhibiting the overactivation of the UPS pathway, downregulating MAFbx, and Murf-1 overexpression, inhibiting the activation of the JNK signaling pathway, upregulating bcl-2 expression, and decreasing bax and caspase-3 levels. Conclusions: The study showed that the optimized new Shengmai powder could improve cardiac function and exercise tolerance in rats with heart failure through the UPS pathway.

[Advances in N-methyl-D-aspartate Receptor Signaling Pathway and Mechanism of the Pathway-mediated Apoptosis].

N-methyl-D-aspartate receptor (NMDAR),an important ionic glutamate receptor and a ligand and voltage-gated ion channel characterized by complex composition and functions and wide distribution,plays a key role in the pathological and physiological process of diseases or stress states.NMDAR can mediate apoptosis through different pathways such as mitochondrial and endoplasmic reticulum damage,production of reactive oxygen species and peroxynitrite,and activation of mitogen-activated protein kinase and calpain.This paper reviews the structure,distribution,and biological characteristics of NMDAR and the mechanisms of NMDAR-mediated apoptosis.

Efficacy and Safety of Traditional Chinese Medicine Injections for Heart Failure With Reduced Ejection Fraction: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Background: Heart failure as an important issue in global public health, has brought a heavy economic burden. Traditional Chinese medicine injections (TCMIs) have significant effects on heart failure with reduced ejection fraction (HFrEF). However, it is difficult for clinicians to identify the differences in clinical efficacy and safety of various TCMIs. The purpose of this study is to compare the efficacy and safety of various TCMIs for treating HFrEF by conducting a Bayesian network meta-analysis (NMA) and to further provide references for clinical decision-making. Methods: The clinical randomized controlled trials of TCMIs for treating HFrEF were searched in seven database from inception to August 3rd, 2021. The Cochrane collaboration's tool was used to assess the risk of bias. NMA was performed in a Bayesian hierarchical framework. The surface under the cumulative ranking curve (SUCRA), the multi-dimensional efficacy analysis, the comparison-adjusted funnel plot, and the node-splitting analysis were conducted using R software. Results: A total of 107 eligible RCTs involving 9,073 HFrEF patients and 6 TCMIs were included. TCMIs include Huangqi injection (HQ) also called Astragalus injection, Shenfu injection (SF), Shengmai injection (SGM), Shenmai injection (SM), Xinmailong injection (XML), and Yiqifumai lyophilized injection (YQFM). The results of NMA and SUCRA showed that with conventional treatment (CT) as a common control, in terms of clinical efficacy, CT + XML was most effective in New York Heart Association cardiac functional classification efficiency, brain natriuretic peptide, and N-terminal pro-brain natriuretic peptide; the CT + SM was most effective in 6-min walking test, left ventricular end-diastolic diameter, left ventricular end-systolic diameter and cardiac output; the CT + YQFM was most effective in left ventricular ejection fraction; the CT + HQ was most effective in stroke volume; the CT + SF was most effective in Minnesota Living with Heart Failure Questionnaire. In terms of safety, there was no significant difference between CT + TCMIs and CT. Conclusion: This Bayesian network meta-analysis results show that the combination of qualified TCMIs and CT is more effective for HFrEF patients than CT alone, and CT + XML and CT + SM may be one of the potential optimal treatments. Also, the safety of these TCMIs needs to be further observed. However, due to some limitations, the conclusions need to be verified by more large-sample, double-blind, multi-center RCTs.

Protocol to study the effects of Traditional Chinese Medicine on patients with coronary heart disease showing phlegm-heat-stasis symptom pattern.

OBJECTIVE: To describe a protocol to assess the effects of Traditional Chinese Medicine (TCM) on patients with coronary heart disease (CHD) showing symptoms of phlegm-heat-stasis symptom pattern. METHODS: This is a single-blind randomized controlled trial that will be conducted in the First Teaching Hospital of Tianjin University of TCM and 60 patients with CHD showing phlegm-heat-stasis symptom pattern will be included. Patients will be randomly divided into either a treatment group (Qingre Huatan formulae + Western Medicine) or to a control group (conventional Western Medicine only) for 7-14 d. Primary patient outcomes will be vascular endothelial function and quality of life. Measurement data will be expressed as mean ± standard deviation using t-test analysis or repeated-measure variance analysis. Enumeration data will be expressed by cases and percentages, using χ2 analysis, and rank sum test will be used for ranked data. RESULTS: This study further verified the effectiveness and safety of Qingre Huatan formulae for the phlegm-heat-stasis syndrome pattern of CHD on the basis of previous studies on the characteristics of syndromes and medication rules. DISCUSSION: Phlegm-heat-stasis symptom pattern has become a common manifestation in CHD. Standardized Western medications together with TCM have been extensively used in China and have developed into a comprehensive treatment model. Our trial will help formulate recommendations for symptom maintenance and provide clinical evidence for the application of TCM for patients with CHD showing phlegm-heat-stasis symptom pattern.

Qishen Yiqi dripping pills for chronic ischaemic heart failure: results of the CACT-IHF randomized clinical trial.

AIMS: Qishen Yiqi dripping pills (QSYQ) may be beneficial in patients with ischaemic heart failure (IHF). We aimed to assess the efficacy and safety of QSYQ administered together with guideline-directed medical therapy in patients with IHF. METHODS AND RESULTS: This prospective randomized, double-blind, multicentre placebo-controlled study enrolled 640 patients with IHF between March 2012 and August 2014. Patients were randomly assigned to receive 6 months of QSYQ or placebo in addition to standard treatment. The primary outcome was 6 min walking distance at 6 months. Among the 638 IHF patients (mean age 65 years, 72% men), the 6 min walking distance increased from 336.15 ± 100.84 to 374.47 ± 103.09 m at 6 months in the QSYQ group, compared with 334.40 ± 100.27 to 340.71 ± 104.57 m in the placebo group (mean change +38.32 vs. +6.31 m respectively; P < 0.001). The secondary outcomes in composite clinical events, including all-cause mortality and emergency treatment/hospitalization due to heart failure, were non-significantly lower at 6 months with QSYQ compared with placebo (13% vs. 17%; P = 0.45), and the change of brain natriuretic peptide was non-significantly greater with QSYQ compared with placebo (median change -14.55 vs. -12.30 pg/mL, respectively; P = 0.21). By contrast, the Minnesota Living with Heart Failure Questionnaire score significantly improved with QSYQ compared with placebo (-11.78 vs. -9.17; P = 0.004). Adverse events were minor and infrequent with QSYQ, similar to the placebo group. CONCLUSIONS: Treatment with QSYQ for 6 months in addition to standard therapy improved exercise tolerance of IHF patients and was well tolerated.

Randomized, Double-Blinded, Multicenter, Placebo-Controlled Trial of Shenfu Injection for Treatment of Patients with Chronic Heart Failure during the Acute Phase of Symptom Aggravation (Yang and Qi Deficiency Syndrome).

BACKGROUND: Shenfu injection (SFI) has shown a remarkable therapeutic effect in patients with chronic heart failure (CHF) during the acute phase of symptom aggravation since it became commercially available in 1987. However, the therapeutic effect of SFI has not been validated in a standard clinical study. As a pilot clinical trial, this study aimed to evaluate the safety and efficacy of SFI for treatment of CHF patients during the acute phase. METHODS: A total of 160 patients experiencing acute phase CHF were enrolled in this study and randomly assigned to receive the placebo (placebo group, 150 ml glucose (GS)) or SFI (SFI group, 50 ml SFI + 100 ml GS) in addition to their standard medications for CHF treatment. The treatment lasted for 7 ± 1 days, and the follow-up continued for 28 ± 3 days after treatment. The primary endpoints were New York Heart Association (NYHA) classification and Traditional Chinese Medicine (TCM) syndrome scores. RESULTS: After 7±1 days of treatment, the efficacy of SFI according to improvements in NYHA and TCM syndrome scores in the SFI group (78.38% and 89.19%, respectively) was significantly higher than that in the placebo group (61.43% and 60.00%, respectively; P<0.05). The SFI group had a longer increase in amplitude than the placebo group (113.00 m versus 82.99 m, P<0.05). The incidence of adverse events and other safety indices showed no significant differences between the two groups. CONCLUSION: SFI combined with conventional therapy for treatment of CHF during acute symptom aggravation ameliorated the cardiac dysfunction and clinical symptoms and improved the patients' quality of life without any significant AEs compared with the conventional therapy alone.

Qishen Yiqi dripping pills for ischemic heart failure: A protocol for a prospective cohort study.

BACKGROUND: The prognosis of ischemic heart failure (IHF) is worse than non-IHM. Improving the management of IHF remains an urgent demand. In recent years, Qishen Yiqi dripping pills (QSYQ), a type of Chinese herbal medicine (CHM), has been popular for IHF combined with standard western medicine. However, relevant scientific evidence from the real clinical practice still is insufficient. The prospective cohort study aims to assess the effectiveness and safety of QSYQ plus standard western medicine for IHF in the real clinical practice. METHODS: It is a multicenter, prospective, observational cohort study. A total of 1200 patients with IHF recruited from 84 hospitals in China will be assigned to exposure group (patients with QSYQ treatment) or non-exposed group (patients without QSYQ treatment) mainly according to patients' preference in real clinical situation. The primary outcomes include New York Heart Association (NYHA) cardiac functional classification and Minnesota Living with Heart Failure Questionnaire (MLHFQ). The secondary outcomes include composite outcomes (all-cause mortality, frequency of re-admission or emergency due to cardiovascular events), left ventricular ejection fraction and cardiothoracic ratio, symptoms and signs obtained by the 4 Tradiational Chinese Medicine (TCM) diagnostic methods. Assessments will be performed at baseline, 1st and 3rd month after enrollment. DISCUSSION: It will provide new evidence on QSYQ for IHF in real clinical practice. STUDY REGISTRATION: This study has been registered on the Chinese Clinical Trial Registry (No: ChiCTR-ONRC-14004407).

Study on syndrome differentiation and treatment in the management of chronic stable coronary artery disease to improve quality of life.

BACKGROUND: Chronic stable coronary artery disease (SCAD) is a general term for all kinds of coronary artery disease (CAD), which includes patients with chronic stable angina, old myocardial infarctions, and also stable condition after revascularization (i.e., percutaneous coronary intervention, coronary artery bypass graft). According to 2012 AHA/ACC guidelines, the objective of the treatment for SCAD is to maintain or recover patients' exercise tolerance, quality of life, and avoid complication like heart failure, so as to decrease mortality, eliminate symptoms, and avoid adverse reactions. Traditional Chinese medicine (TCM) has 2000 years of history in managing CAD and has its advantages in improving quality of life. Using scientific method to evaluate, demonstrate, and conclude the clinical curative effect of TCM is an extremely important task for both TCM and integrative Chinese and Western medicine in the treatment of CAD. METHODS: This research is to collect real effective cases from authoritative TCM cardiologists' clinic, so as to build a TCM diagnosis and treatment information database that involve 2000 patients from 32 different top-3 hospitals of china. The primary outcome includes EuroQol-5 Dimensions and Four diagnostic method of TCM, and secondary outcome includes angina score and some laboratory indexes like electrocardiograms, dynamic electrocardiogram, ultrasonic cardiogram, and treadmill exercise testing. This research uses SPSS17.0. to do the statistical analysis application. Enumeration data use χ test and measurement data which fit normality test use t test. The analysis of drugs usage in different diseases, different syndromes and different life quality effect will use principal component analysis, factorial analysis, clustering analysis. and point mutual information method, and so on. RESULTS: This research, based on past syndromes research and real clinical effective chronic SCAD cases, aim to build a TCM diagnosis and treatment information database.

Assessment of Complementary Treatment with Yiqi Fumai Lyophilized Injection on Acute Decompensated Ischemic Heart Failure (ACT-ADIHF): Rationale and Design of a Multicenter, Randomized, Controlled Trial.

BACKGROUND: Heart failure (HF) is the end stage of many heart diseases, and ischemic heart disease (IHD) is the primary cause. Yiqi Fumai lyophilized injection, a contemporary Chinese medicine preparation, widely used in the treatment of IHF patients, shows clinical efficacy on improving symptoms and cardiac function, but the quality of the current literature does not address multiple important issues. This article describes a protocol for assessment of complementary treatment with Yiqi Fumai lyophilized injection in acute decompensated IHD. METHODS: The protocol is designed as a multicenter randomized controlled trial to assess the efficacy and safety of complementary treatment with Yiqi Fumai lyophilized injection on acute decompensated IHD. This trial will be carried out in 37 hospitals in China and expected to enroll 666 inpatients with acute decompensated IHF due to coronary heart disease. On the basis of standardized western medications, patients are randomized to either the treatment group (250 ml 5% glucose / sodium injection + 5.2 g Yiqi Fumai lyophilized injection) or the control group for 7 days and follow-up for 30 ± 3 and 60 ± 3 days. The primary outcome is change in brain natriuretic peptide (BNP) concentrations. The secondary outcomes are composite endpoint, left ventricular ejection fraction, blood troponin T/I, cardiothoracic ratio, life quality scale, scores of the four traditional Chinese medicine (TCM) diagnostic methods. DISCUSSION: Standardized western medications together with TCM have been extensively used in China and have developed into a comprehensive treatment model. The trial will provide clinical research evidence for application of complementary treatment with intravenous Yiqi Fumai lyophilized injection on decompensated IHF. TRIAL REGISTRATION: This study protocol has been listed in the Chinese Clinical Trial Registry (registration number: ChiCTR-IPR-15007396, http://www.chictr.org.cn/showproj.aspx?proj=12370 ) on November 6, 2015.

Cavum septum pellucidum and first-episode psychosis: A meta-analysis.

OBJECTIVES: To investigate the prevalence and changes of cavum septum pellucidum (CSP) in first-episode psychosis (FEP) patients. METHODS: Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify eligible studies comparing FEP patients and healthy controls from inception to Feb 29, 2016. RESULTS: Ten cross-sectional studies and three longitudinal studies reported in ten articles met our criteria. Our meta-analysis found no significant differences in the prevalence of either "any CSP" (OR = 1.41; 95% CI 0.90-2.20; p = 0.13; I2 = 52.7%) or "large CSP" (OR = 1.10; 95% CI 0.77-1.58; p = 0.59; I2 = 24.1%) between FEP patients and healthy controls. However, the heterogeneity analysis of the prevalence of "any CSP" suggested bias in outcome reporting. CONCLUSIONS: The results based on current evidence suggest it is unclear whether "any CSP" is a risk factor for FEP due to the heterogeneity of the studies. There is insufficient evidence to support that "large CSP" is a possible risk factor for FEP.

Western medication plus Traditional Chinese Medicine preparations in patients with chronic heart failure: a prospective, single-blind, randomized, controlled, and multicenter clinical trial.

OBJECTIVE: To assess the efficacy and safety in patients with chronic heart failure (CHF) of Western medication plus Traditional Chinese Medicine (TCM) preparations. METHODS: This prospective, single-blind, randomized, controlled, and multicenter clinical trial began on September 17, 2008, and was completed on June 25, 2011. A total of 340 inpatients, aged 40-79 years, with exacerbating CHF from 10 hospitals were enrolled and randomly allocated within 24 h of admission. The trial included three intervention periods. During hospitalization, the control group received western medication for CHF and the treatment group received Danhong injection with Shenfu injection or Shenmai injection. After discharge, all patients were treated with Qiliqiangxin capsules and Buyiqiangxin tablets or a placebo for 6 months. After the 6-month intervention, both groups received only continuous western medication. The primary endpoint was all-cause mortality. The efficacy assessments were as follows: B-type natriuretic peptide (BNP), Lee's HF score, the 6-minute walking test (6MWT), left ventricular ejection fraction (LVEF), and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The safety assessments were as follows: blood and urine routine examination, hepatic and renal function, electrolytes in blood and adverse events. RESULTS: Compared with the control group, the treatment group showed a 30.99% reduction in all-cause mortality and an improved survival rate. The treatment group showed greater improvement in 6MWT (P = 0.02) than the control group on discharge, after 12-month follow-up, there was a time-group interaction for MLHFQ (P = 0.03). Incidence rate of adverse events and other relevant safety indexes were not statistically significant between the two groups. CONCLUSION: Western medication plus TCM treatment can increase 6-minute walking distance (improve exercise tolerance) and quality of life with heart failure patients.

[Analysis of Medication Laws for Chinese Medicine Treating Hypertension Patients with Yin Defi- ciency Yang Hyperactivity Syndrome Based on Literatures].

OBJECTIVE: To analyze medication laws of Chinese medicine (CM) treatment in hypertension patients with yin deficiency yang hyperactivity syndrome. METHODS: China National Knowledge Infrastructure (CNKI, Jan. 1979-Dec 2014), Chinese Scientific Journals Database (VIP, Jan 1989-Dec2014), Chinese Biomedical Literature Database (CBM, Jan.1978-Dec.2014), Wanfang Database (Jan 1990-Dec 2014) were retrieved by using "hypertension", "CM", "Chinese herbs", "syndrome" as keywords. Totally 149 literatures concerning CM treatment for hypertension patients with yin deficiency yanghyperactivity syndrome were included in this study. The herbs database was established by SPSS20.0,and correlation laws were analyzed by SAS9.3. With the Pajek3.1, results were presented visually withcomplex networks. RESULTS: There were 149 literatures including 131 kinds of herbs with 1,598 frequencies. The conventional compatibility program of herbs for asthenic yin and predominant yang syndrome of hypertension were two toothed achyranthes root, tall gastrodia rhizome, Cassia obtusifolia L., eucommiabark, baikal skullcap root, and so on, about 29 kinds. Of them, core herbs were two toothed achyranthes root, tall gastrodia rhizome, Cassia obtusifolia L., poria, prepared rhizome of rehmannia, oriental water-plantain tuber, asiatic cornelian cherry fruit, Uncariae Rhynchophylla, common yam rhizome, the rootbark of the peony tree, and so on. CONCLUSION: Medication laws of CM treatment in hypertension patientswith yin deficiency yang hyperactivity syndrome obtained by analysis of complex networks reflected thetherapeutics of nourishing yin to suppress yang, which could further provide reference for clinical studies.

[Scientific Evaluation of TCM Clinical Outcomes Rating Scale for Heart Failure Based on Patients Report].

OBJECTIVE: To evaluate the reliability, validity, and responsiveness of traditional Chinese medicine (TCM) clinical outcomes rating scale for heart failure (HF) based on patients' report. METHODS: TCM clinical outcomes rating scale for HF (TCM-HF-PRO) were evaluated based on 340 HF patients' report from multiple centers. The completion of the investigation was recorded. Cronbach's α coefficient and split-half reliability were used for reliability analysis, and factor analysis was used to assess the construct validity of the rating scale. Pearson correlation analysis was then used for criterion validity analysis. Discriminant analysis was used to assess the responsiveness of the scale. All 340 HF patients having complete TCM-HF-PRO data were assigned to the treatment group and the control group by central randomization. The total TCM-HF-PRO scores of the two groups were compared using paired t-test to reflect the longitude responsiveness of the scale before treatment and at week 2 after treatment. RESULTS: (1) The recycling rate of the scale was 100.0%. One of them was not filled completely, which was rejected thereby. So the completion rate was 99.7%. The completion time for TCM-HF-PRO scale ranged 15 to 25 min. (2) The Cronbach's α coefficient of rating scale was 0.903, split-half reliability was 0.844 and 0.849. (3) Confirmatory factor analysis showed that 7 factors and items formed according to maximum load factor basically coincided with the construct of the rating scale, 7 factors accumulated contribution rate was 43.8%. TCM clinical outcomes rating scale for HF based on patients' report was relatively better correlated with the Minnesota living with HF questionnaire (r = 0.726, P < 0.01). (4) Discriminant analysis showed that the rating scale correctly classified more than 78.8% of case studies having confirmed initial differential diagnosis by experts. The total scale of the rating scale decreased more in the two group after treatment, with significant difference as compared with before treatment (P < 0.01. CONCLUSION: TCM clinical outcomes rating scale for HF based on patients' report had good reliability, validity and responsiveness, hence it could be used to assess clinical efficacy for HF patients.

Clinical assessment of Shenfu injection loading in the treatment of patients with exacerbation of chronic heart failure due to coronary heart disease: study protocol for a randomized controlled trial.

BACKGROUND: Acute exacerbation is a common cause of hospitalization in patients with chronic heart failure, and coronary heart disease is the most common cause. Shenfu injection, a Traditional Chinese Medicine injection, widely used in the adjuvant treatment of patients with acute exacerbation of chronic heart failure, shows some treatment effect in improving the symptoms and the quality of life, but it lacks the rigorous clinical evaluation of research reports. This paper describes the protocol for the clinical assessment of Shenfu injection loading in the treatment of patients with acute exacerbation of chronic heart failure. METHODS: This protocol adopts the design of a prospective, randomized, multicenter, blind imitation, placebo-controlled trial to assess the efficacy and safety of Shenfu injection loading in the treatment of patients with acute exacerbation of chronic heart failure due to coronary heart disease. The research will be carried out in 12 hospitals in China and is expected to enroll 160 inpatients with acute exacerbation of chronic heart failure due to coronary heart disease (yang and qi deficiency syndrome). On the basis of the conventional therapy of western medicine, patients will be randomized to either the treatment group (100 ml 5% glucose injection + 50 ml Shenfu injection) or the control group (150 ml 5% glucose injection) for 7 ± 1 days and follow-up for 28 ± 3 days. The primary outcomes are New York Heart Association cardiac function classification and Traditional Chinese Medicine syndromes. The secondary outcomes are left ventricular ejection fraction, brain natriuretic peptide level, Lee's heart failure score, 6-minute walking distance, and the incidence and readmission rate of cardiovascular events (including the emergency rate due to acute exacerbation of chronic heart failure). DISCUSSION: This trial will assess the effect of loading Shenfu injection in the treatment of patients with acute exacerbation of chronic heart failure caused by coronary heart disease (yang-qi deficiency syndrome) on the symptoms and signs of heart failure, exercise tolerance, and other aspects, and observe its influence on the short-term prognosis with follow-up. The results of the study will provide clinical research evidence for application of Shenfu injection in the treatment. TRIAL REGISTRATION: This trial was registered on 26 December 2012 at the Chinese Clinical Trials Register (Identifier: ChiCTR-TRC-12002857 ).

[Expert survey for Chinese medicine syndrome characteristics of different clinical types of coronary artery disease based on the Delphi method].

OBJECTIVE: To carry out expert survey for traditional Chinese medicine (TCM) syndrome characteristics of different clinical types of coronary artery disease (CAD). METHODS: By using Delphi method, we carried out two rounds of nationwide expert surveys for modern TCM characteristics of syndrome elements and syndrome types of CAD. RESULTS: Based on expert consensus, qi deficiency, blood stasis, phlegm turbidity, qi deficiency blood stasis, and intermingled phlegm and blood stasis are common TCM syndromes for different clinical types of CAD. Of them, qi stagnation, blood stasis, phlegm turbidity, heat accumulation, cold coagulation, yang deficiency, deficiency of both qi and yang were more often seen in patients with unstable angina than in those with stable angina. Qi deficiency, yin deficiency, and deficiency of both qi and yin were less seen. We could see more excess syndrome and less deficiency syndrome (such as qi deficiency, yin deficiency, etc.) in acute ST-segment elevation myocardial infarction (STEMI) than acute non-ST-segment elevation myocardial infarction (NSTEMI). Qi deficiency, blood stasis, water retention, yang deficiency, phlegm turbidity, yin deficiency, Xin-qi deficiency, and qi deficiency blood stasis induced water retention are the most common TCM syndrome types of CAD heart failure (HF). Blood deficiency, yin deficiency, heat accumulation, deficiency of both Xin and Pi, deficiency of both qi and blood, deficiency of both qi and yin, yin deficiency and fire hyperactivity were more often seen in CAD arrhythmias. CONCLUSIONS: TCM syndrome distributions of different clinical types of CAD have common laws and individual characteristics. Results based on the expert consensus supplied evidence and support for clinical diagnosis and treatment of CAD.

[Effect of complementary treatment of Chinese drugs on myocardial perfusion patients with acute myocardial infarction after coronary intervention: a systematic review].

OBJECTIVE: To systematically review the safety and efficacy of routine Western medicine (WM) plus Chinese drugs for no-flow or slow flow after coronary revascularization. METHODS: CNKI, VIP, CBM, Wanfang Data, PubMed, The Cochrane Library, EMBase, and other relevant databases were electronically searched. Literatures were also manually retrieved from related journals. Randomized control trials of treating no-flow or slow flow patients after coronary revascularization by routine WM treatment plus Chinese drugs were retrieved. The quality of retrieved literature was assessed by methods from Cochrane Handbook. Valid data were extracted and analyzed by meta-analysis using RevMan5. 1.0 Software. Results Totally 5 trials including 526 patients with poor general quality were included. RESULTS: of meta-analyses showed that compared with the routine WM treatment group, additional use of Chinese drugs could improve thrombolysis in myocardial infarction (TIMI) [RR =0. 16, 95% Cl (0.07, 0.34), P < 0.01]; reduce elevated ST segment significantly [RR = 0.59, 95% CI (0.44, 0.79), P = 0. 00031]; in- crease regional myocardial blood flow (P < 0.01) and myocardial perfusion scores (P = 0.0109, P = 0.0115); and improve left ventricular ejection fraction (LVEF) under dobutamine stress state (P = 0.041). Only one trial covered a 6-month follow-up study. There was no statistical difference in the mortality, recurrent myocardial infarction, or revascularization between the two groups. There was no statistical difference in adverse event or safety indicators between the two groups. CONCLUSIONS: Compared with the WM treatment, complementary Chinese drugs could reduce occurrence of no-flow or slow flow after coronary revascularization, and further improve clinical efficacy. But larger and higher quality clinical trials are necessary for further evidence.

Internal challenge to clinical trial project management: strategies for managing investigator compliance.

BACKGROUND: Managing compliance in a clinical research, especially in a multi-centre randomized clinical trial (MRCT) is vital. We now feel the need to take a look at the once overlooked area of investigator compliance as it may provide resources necessary for producing satisfactory trial outcomes. OBJECTIVES: To analyze investigator performance and examine their adherence behavior using data collected and information gained from the MISPS-TCM, a Chinese national research project. METHODS: Four researchers were responsible for collecting relevant information and investigating the compliance behavior of participants in MISPS-TCM. The Data Management Committee of MISPS-TCM offered us the number of withdrawal at each site and other site information. Reports on investigator compliance events were provided by the Monitoring Committee. Records of any misconduct of or errors made by the investigator were collected from the Center's daily management diary. Other information sources included trial managers and investigators at the Center or at different sites of the study. RESULTS: Investigator compliance can be an important determinant of trial outcomes and the degree of compliance may have detrimental effects on the reliability of findings of an MRCT, directly or indirectly. CONCLUSIONS: Trial managers of future MRCTs should take a firm grip on investigator compliance from the following aspects. First, physicians should be provided with more opportunities. Second, we created and recommended the 'Five Step Method' for evaluating investigators. Third, measures must be taken to secure investigator compliance. Fourth, evaluation of investigator compliance in an MRCT needs to be made.

[Application and evaluation of Chinese medicine in treatment of chronic heart failure].

Chinese medicine (CM) has been widely used in treatment of chronic heart failure (CHF) and a large number of researches has been done on its clinical application. Through the analysis and assessment of these literatures, CM syndromes and corresponding treatment regimens for heart failure (CF) could be better understood and used in clinics. This will provide guidelines for the treatment of HF and further elevate higher standards of research.

[Routine western medicine treatment plus qishen yiqi dripping pill for treating patients with chronic heart failure: a systematic review of randomized control trials].

OBJECTIVE: To systematically review the safety and efficacy of Qishen Yiqi Dripping Pill (QYDP) as a complementary treatment for chronic heart failure (CHF) patients. METHODS: CNKI, VIP, Wanfang Data, PubMed and Cochrane Library were retrieved for papers on randomized control trials of treating CHF patients by routine western medical treatment plus QYDP. The quality of inclusive literatures was assessed by methods from Cochrane Handbook. Valid data were extracted and analyzed by Meta-analysis using RevMan 5.1.0 Software. RESULTS: Totally 17 trials and 1840 patients in line with standard were included. Results of Meta-analysis showed, compared with the routine Western medical treatment group, additional use of QYDP could decrease re-admission rate [RR = 0.52, 95% CI (0.33, 0.81), P = 0.004] and the mortality rate, improve the clinical efficacy [RR = 1.18, 95% CI (1.12, 1.25), P < 0.01] and cardiac function [RR = 1.18, 95% CI (1.10, 1.27),P < 0.01], increase left ventricular ejection fraction (LVEF) [WMD = 5.57, 95% CI (4.16, 6.97), P < 0.01] of CHF patients. Subgroup analysis of LVEF showed that additional use of QYDP could further improve LVEF [ WMD = 8.34, 95% CI (6.23, 10.45), P < 0.01] of CHF patients and increase the distance of their 6-min walk test [WMD = 94.39, 95% CI (71.89, 116.89), P < 0.01]. But there was no statistical difference in plasma brain natriuretic peptide (BNP) between the two groups. No obvious adverse reaction and liver or kidney damage was reported during the trial. CONCLUSIONS: Compared with the Western medical treatment, additional use of QYDP was safe and could further improve clinical efficacy. However, larger and high-quality clinical trials are necessary for further evidence.