Sodium Tanshinone ⅡA Sulfonate Injection as Adjuvant Treatment for Unstable Angina Pectoris: A Meta-Analysis of 17 Randomized Controlled Trials

Objective: To systematically evaluate the effectiveness and safety of Sodium Tanshinone ⅡA Sulfonate Injection(STS) as one adjuvant therapy for treating unstable angina pectoris(UAP). Methods: Randomized controlled trials(RCTs) of UAP treated by STS were searched in the China National Knowledge Infrastructure Database(CNKI), VIP Database for Chinese Technical Periodicals(VIP), Wanfang Database, the Chinese Biomedical Literature Database(CBM), Web of Science, the Cochrane Library, Embase, and Pub Med, which from inception to January, 2016. The Cochrane Risk Assessment Tool was used to evaluate the methodological quality of the RCTs. The Review Manager 5.3 software was used to conduct the metaanalysis. Results: The results showed that 17 RCTs involving 1,372 patients were included. The meta-analysis indicated that the combined use of STS and Western medicine(WM) in the treatment of UAP can obviously improve the total effective rate [risk ratio(RR)=1.31, 95% confidence interval(CI)(1.24,1.39), P0.0001], and the total effective rate of electrocardiogram [RR=1.43, 95% CI(1.30,1.56), P0.0001], decrease the level of CRP [mean difference(MD)=–3.06, 95%CI(–3.85, –2.27), P0.00001], fibrinogen [MD=–1.03, 95% CI(–1.16, –0.89), P0.00001], and whole blood high shear viscosity [MD=–0.70, 95% CI(–0.92, –0.49), P0.00001]. Additionally, the occurrence of adverse drug reaction of the experimental group was significantly higher than that of the control group [RR=3.57, 95% CI(1.28, 9.94), P0.05]. Conclusions: Compared with WM, the combined use of STS was more effective.     

Is Chinese Herbal Medicine Effective for Elderly Isolated Systolic Hypertension? A Systematic Review and Meta-Analysis

Objective: To study the efficacy of Chinese medicine (CM) on isolated systolic hypertension. Methods: Seven electronic databases were searched for randomized controlled trials (RCTs) published until August 2015. Subgroup analyses and meta-analysis were performed to assess the efficacy and safety of the included studies. Results: A total of 24 studies, including 2,096 patients (1,058 patients in the intervention group and 1,038 in the control group), were evaluated in the final analysis. Compared with a conventional therapy used alone, CM as additional intervention was more effective on systolic blood pressure [mean difference (MD)=–0.66, 95% confidence interval (CI)=(–0.97, –0.36), P<0.00001] and significantly diminished the pulse pressure [MD=–7.49, CI=(–12.69, –2.29), P<0.00001]. However it showed no additional benefit on diastolic blood pressure [MD=1.16, CI=(0.02, 2.29), P=0.87]. Adverse events were not explicitly reported in most RCTs. Conclusions: CM might be a promising approach for the elderly with isolated systolic hypertension, while the evidence for CM employed alone was insufficient. Considering the inherent limitations of the included studies, larger high-quality RCTs with extensive follow-up should be performed to validate our findings in the future.     

Tongxinluo Capsule (通心络胶囊) for Cardiac Syndrome X: A Systematic Review and Meta-Analysis

Objective: To evaluate the efficacy and safety of Tongxinluo Capsule(通心络胶囊, TXL) for patients with cardiac syndrome X(CSX). Methods: Randomized controlled trials(RCTs) regarding TXL in the treatment of CSX were searched in Chinese Biomedicine Literature Database, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wanfang Database, Pub Med, EMBASE, Cochrane Central Register of Controlled Trial, websites of the Chinese and International Clinical Trial Registry platform up to June 30, 2015. The intervention was either TXL alone or TXL combined with conventional treatment, while the control intervention was conventional treatment with or without placebo. Data extraction, methodological quality assessment and data analyses were performed according to the Cochrane criteria. The primary outcome was a composite event of death, acute myocardial infarction(AMI), angina requiring hospitalization, revascularization, and heart failure. The secondary outcome measures were angina symptom improvement, electrocardiograph(ECG) improvement, and serum endothelin-1(ET-1) level. The adverse events were also recorded. RevMan 5.3 software was applied for data analyses. Results: Twelve RCTs(696 patients) were included. Compared with conventional treatment, the addition of TXL to conventional treatment showed some benefits on relieving angina symptoms [risk ratio(RR): 1.46, 95% confidence interval(CI)(1.25, 1.71), P0.01], and improving ECG [RR: 1.45, 95% CI(1.21, 1.74), P0.01]. The pooled result did not support a benefit of TXL on reducing the incidence of primary outcome [RR: 0.20, 95% CI(0.02, 1.61), P=0.13]. In addition, TXL decreased serum ET-1 concentration of CSX patients [standardized mean number: –1.63, 95% CI(–2.29, –0.96), P0.01]. No serious adverse events were reported. Conclusions: TXL documents potential benefits on attenuating angina symptoms, improving ECG and decreasing serum ET-1 level for CSX patients. However, more rigorous RCTs with high quality are needed to confirm its efficacy and safety.     

Chinese Medicine for Idiopathic Parkinson's Disease: A Meta Analysis of Randomized Controlled Trials

Objective:To evaluate the efficacy of Chinese medicine(CM) adjunct to conventional medications for idiopathic Parkinson's disease(PD).Methods:Electronic English and Chinese databases including PubMed,Cochrane Library,Web of Science,Chinese Medical Current Contents,China National Knowledge Infrastructure,China Science and Technology Journal Database,Wanfang Med Database,and Traditional Chinese Medical Database System were used for key words searching in a highly sensitive search strategy.The extracted data was analyzed by the Review Manager 5.0.Results:Twelve trials involving 869 participants were included in the meta-analysis.Unified PD Rating Scale(UPDRS) I,Ⅱ,Ⅲ,Ⅳ scores and UPDRS Ⅰ-Ⅳ total scores were used to be the primary outcomes,Parkinson Disease Question-39(PDQ-39) and Scores of Chinese Medical Symptoms were the secondary outcomes.CM adjunct therapy had greater improvement in UPDRS Ⅰ[2 trials;standardized mean difference(SMD)-0.40,95%confidence interval(CI)-0.71 to-0.09;Z=2.49(P=0.01)],Ⅱ[5 trials;SMD-0.47,95%CI-0.69 to-0.25;Z=4.20(P0.01)],Ⅲ[5 trials;SMD-0.35,95%CI-0.57 to-0.13;Z=3.16(P=0.002)],Ⅳ scores[3 trials;SMD-0.32,95%CI-0.60 to-0.03;Z=2.17(P=0.03)],UPDRS Ⅰ-Ⅳ total scores[7 trials;SMD-0.36,95%CI-0.53 to-0.20;Z=4.24(P0.05)].PDQ-39 and Chinese medical symptoms compared to the conventional medication only.Conclusion:CM adjunct therapy has potential therapeutic benefits by decreasing UPDRS scores and reducing adverse effect.     

Danshen Injection as Adjuvant Treatment for Unstable Angina Pectoris: A Systematic Review and Meta-analysis

Objective: To systematically evaluate the clinical effectiveness and safety of Danshen Injection(丹参注射液, DS) as one adjuvant treatment for conventional therapy with Western medicine(WM) for unstable angina pectoris(UAP). Methods: Using literature databases, a thorough and systematic retrieval of randomized controlled trials(RCTs) comparing DS plus WM with WM was conducted from inception to April 2015. The extracted data from included studies was analyzed by Review Manager 5.2 software. The Cochrane risk of bias tool was used to assess the quality of included studies, and Begg's and Egger's tests conducted by Stata 12.0 were used to evaluate the potential presence of publication bias. Results: A total of 17 RCTs, which involving 1,433 participants, were identified and reviewed. The meta-analysis indicated that the combined use of DS and WM was significantly superior to WM alone for UAP in terms of the total effectiveness rate of angina pectoris [risk ratio(RR) =1.23, 95% confidence interval(CI): 1.17, 1.29, P0.01] and the total effectiveness rate of electrocardiogram(ECG) [RR=1.18, 95%CI: 1.06, 1.30, P=0.001]. Additionally, DS could also further reduce the content of fibrinogen, adjust blood lipid level, correct T wave inversion, and so on. Fifteen adverse drug reactions were reported in two studies, Four of which appeared in the experimental group. Conclusion: Based on the systematic review, the combined use of DS and WM was more effective than WM alone, it can be further widely used in clinic, however, there was no exact conclusion for its safety.     

Association of Platelet-Activating Factor Receptor Gene rs5938 (G/T) and rs313152 (T/C) Polymorphisms with Coronary Heart Disease and Blood Stasis Syndrome in A Chinese Han Population

Objective

To explore the association of the platelet-activating factor receptor (PAFR) gene rs5938, rs313152 and rs76744145 polymorphisms with coronary heart disease (CHD) and blood stasis syndrome (BSS) of CHD in Chinese Han population.

Methods

A total of 570 CHD patients (299 with BSS and 271 with non-BSS) and 317 controls were enrolled. The PAFR gene rs5938, rs313152 and rs76744145 polymorphisms were genotyped using the multiplex SNaPshot technology. The statistical analysis was conducted using a multiple variable logistic regression model.

Results

Significant differences were detected in the genotypes frequency distributions of the rs5938 (P<0.01), but not the rs313152 (P>0.05), between the controls and CHD patients. Individuals with an rs5938 or rs313152 mutated allele had a low risk for CHD [adjusted odds ratio (aOR)=0.35, 95% confidence interval (CI): 0.23 to 0.56, P<0.01; aOR=0.65, 95% CI: 0.46 to 0.91, P<0.05, respectively]. After the CHD patients were stratified as BSS or non-BSS according to their Chinese medicine patterns, the rs5938 polymorphism mutated alleles had a significant association with a low risk for BSS of CHD (aOR=0.32, 95% CI: 0.18 to 0.57, P<0.01) and non-BSS of CHD (aOR=0.31, 95% CI: 0.17 to 0.55, P<0.01). The rs313152 polymorphism was associated with a low risk for BSS (aOR=0.51, 95% CI: 0.33 to 0.79, P<0.01), but not for non-BSS (aOR=1.22, 95% CI: 0.81 to 1.85, P<0.05). Furthermore, the interaction effect of the rs5938 and rs313152 polymorphisms for BSS of CHD was significantly based on an aOR value associated with the combination of the rs5938 GT genotype with the rs313152 TC genotype of 0.27 (95% CI: 0.1 to 0.7, P<0.01).

Conclusion

The PAFR gene rs5938 or rs313152 polymorphisms might be a potential biomarker for susceptibility to CHD, especially to BSS of CHD in Chinese Han population.

     

Gefitinib plus Fuzheng Kang'ai Formula(扶正抗癌方) in Patients with Advanced Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation:A Randomized Controlled Trial

Objective: To evaluate the effect of Fuzheng Kang'ai Formula(扶正抗癌方, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor(EGFR) mutations. Methods: A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage ⅢB/Ⅳ non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib(250 mg/day orally) plus FZKA(250 m L, twice per day, orally); 35 cases] or G group(gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival(PFS)] and secondary endpoints [median survival time(MST), objective response rate(ORR), disease control rate(DCR) and safety] were observed. Results: No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months(95% CI 3.30–21.69) vs. 8.4 months(95% CI 6.30–10.50; log-rank P0.01), MST of 21.5 months(95% CI 17.28–25.73) vs. 18.3 months(95% CI 17.97–18.63; log-rank P0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively(P0.05). The most common toxic effects in the GF group and G group were rash or acne(42.8% vs. 57.1%, P0.05), diarrhea(11.5% vs. 31.4%, P0.05), and stomatitis(2.9% vs. 8.7%, P0.05). Conclusion: Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.     

Impact Evaluation of CONSORT and STRICTA Guidelines on Reporting Quality for Randomized Controlled Trials of Acupuncture Conducted in China

Objective:To evaluate and compare the reports' qualities of acupuncture randomized controlled trials(RCTs) conducted in China before and after the implementation of two guidelines,i.e.,the Consolidated Standards of Reporting Trials(CONSORT) statement and the Standards for Reporting Interventions in Controlled Trials of Acupuncture(STRICTA).Methods:Proportions of studies that reported CONSORT and STRICTA items were compared for the years before and after implementation of these two guidelines.In addition,the total score of each item's reporting were calculated and reported differences during different date ranges were compared.Results:For CONSORT items(maximum score 8),there was evidence of a slight improvement in reporting between 1994-1995 and 1999-2000 combined(2.5 + 0.6) and 2004-2005 and2009-2010 combined(3.0 ±0.9;difference 0.4,95%confidence interval,0.3 to 0.6,P0.01).For STRICTA items(maximum score 17),there was evidence that a slight improvement in reporting between 1994-1995 and 1999-2000 combined(8.6±2.1) and 2004-2005 and 2009-2010 combined(10.1 ±1.8;difference1.5,95%confidence interval,1.1 to 1.9,P0.01).Conclusion:Quality of reporting for RCTs of acupuncture treatment conducted in China have generally improved since the introduction of the STRICTA and CONSORT guidelines.     

Qingkailing Injection (清开灵注射液) for Treatment of Children Pneumonia Induced by Respiratory Syncytial Virus: A Meta-Analysis of Randomized Controlled Trials

Objective: To evaluate the efficacy and safety of Qingkailing Injection(清开灵注射液, QKL) for treatment of children pneumonia caused by respiratory syncytial virus(RSV). Methods: Randomized clinical trials(RCTs) comparing QKL with ribavirin injection in the treatment of children pneumonia induced by RSV were searched in Pub Med, Science Direct, Cochrane Library, Chinese VIP database, CNKI and Wanfang databases from their inception to March 2014. Meta-analyses were performed using RevMan 5.2 software. The methodological quality of the selected RCTs was evaluated by the Modified Jadad Score. The primary outcome measures were effective rate and the secondary outcomes were relief time of fever and cough. Results: Seven RCTs with 992 cases published from 2008 to 2013 were identified. The meta-analysis results indicated that QKL was more effective in cure rate [risk ratios(RR)=1.32, 95% CI(1.17, 1.50), P0.01], total effective rate [RR=1.07, 95% CI(1.02, 1.13), P=0.009] and less fever clearance time [mean difference=–0.73, 95% CI(–1.22, –0.23), P=0.004], compared with ribavirin injection in the treatment of RSV-induced children pneumonia. No dead case was reported in all trials. There were 3 trials mentioned adverse events, 2 reported no obvious adverse event occurred while 1 reported adverse events described as skin hypersensitivity, elevation of ALT, a mild abnormal of hepatic and renal function in both QKL and ribavirin group. Conclusions: QKL was an effective and relatively safe option for the treatment of RSV-induced children pneumonia. These therapeutic effects were promising but need to be interpreted with caution due to variations in the treatment and methodological weakness in the studies.     

Is Manipulative Therapy Clinically Necessary for Relief of Neck Pain? A Systematic Review and Meta-Analysis

Objective:To summarize and critically assess the efficacy of Eastern and Western manipulative therapies for the treatment of neck pain in adults. Methods:A search of Pub Med/MEDLINE, the Cochrane Central Register of Controlled Trials, Clinical Trials.gov, EMBASE, etc. from their inception date to January 2014 with Chinese, Japanese, and Korean databases. Two reviewers independently selected randomized controlled trials(RCTs) with negative control or blank control, extracted data and assessed methodological quality. Meta-analysis and levels of evidence were performed by Revman5.1 and Grades of Recommendations Assessment, Development and Evaluation(GRADE) approach. Results:Nineteen clinical trials with adequate randomization were included in this review, 11 of them had a low risk of bias. The primary outcome for shortterm pain had no significant differences, however, the secondary outcome, only the Numerical Pain Rating Scale(NPRS) score of intermediate-term [n=916, pooled mean differences(MD) =–0.29, P=0.02], the Neck Disability Index(NDI) score of short-term(n=1,145, pooled MD=–2.10, P0.01), and intermediate-term(n=987, pooled MD=–1.45, P=0.01) were significantly reduced with moderate quality evidence. However, it supported the minimally clinically important difference(MCID) of the Visual Analogue Scale and NPRS pain score to be 13 mm, while NDI was 3.5 points. The meta-analysis only suggested a trend in favor of manipulative therapy rather than clinical significance. Conclusions:The results do not support the existing evidences for the clinical value of Eastern or Western manipulative therapy for neck pain of short-term follow-up according to MCIDs. The limitations of our review related to blinding, allocation concealment and small sample size.     

Effect of Integrated Chinese and Western Medicine Therapy on Severe Hand, Foot and Mouth Disease: A Prospective, Randomized, Controlled Trial

Objective: To evaluate the efficacy and safety of Chinese medicine(CM) plus Western medicine(WM) in the treatment of pediatric patients with severe hand, foot and mouth disease(HFMD) by conducting a prospective, controlled, and randomized trial. Methods: A total of 451 pediatric patients with severe HFMD were randomly assigned to receive WM therapy alone(224 cases, WM therapy group) or CM [Reduning Injection(热毒宁注射液) or Xiyanping Injection(喜炎平注射液)] plus WM therapy(227 cases, CM plus WM therapy group) for 7–10 days, according to a web-based randomization system. The primary outcome was fever clearance time, which was presented as temperature decreased half-life time. The secondary outcomes included the rate of rash/herpes disappearance within 120 h, as well as the rate for cough, runny nose, lethargy and weakness, agitation or irritability, and vomiting clearance within 120 h. The drug-related adverse events were also recorded. Results: The temperature decreased half-life time was 40.4 h in the WM therapy group, significantly longer than 27.2 h in the CM plus WM therapy group(P0.01). Moreover, the rate for rash/herpes disappearance within 120 h was 43.6%(99/227) in the CM plus WM therapy group, significantly higher than 29.5%(66/224) in the WM therapy group(P0.01). In addition, the rate for cough, lethargy and weakness, agitation or irritability disappearance within 120 h was 32.6%(74/227) in the CM plus WM therapy group, significantly higher than 19.2%(43/224) in the WM therapy group(P0.01). No drug-related adverse events were observed during the course of the study. Conclusions: The combined CM and WM therapy achieved a better therapeutic efficacy in treating severe HFMD than the WM therapy alone. Reduning or Xiyanping Injections may become an important complementary therapy to WM for relieving the symptoms of severe HFMD.     

Comprehensive Treatment with Chinese Medicine in Patients with Advanced Non-Small Cell Lung Cancer: A Multicenter, Prospective, Cohort Study

Objective: To determine whether additional Chinese medicine(CM) could prolong survival and improve the quality of life(QOL) in patients with advanced non-small cell lung cancer(NSCLC) compared with Western medicine(WM) alone. Methods: This was a multicenter, prospective cohort study. A total of 474 hospitalized patients with stage Ⅲ–Ⅳ NSCLC were recruited and divided into 2 groups. Patients in the WM group received radiotherapy, chemotherapy, and optimal supportive therapy according to the National Comprehensive Cancer Network(NCCN) guidelines. In the integrative medicine(IM) group, individualized CM(Chinese patent medicines and injections) and WM were administered. The primary end point was overall survival, and the secondary end points were time to disease progression, adverse events, and QOL. Follow-up clinical examinations and chest radiography were performed every 2 months. Results: The median survival was 16.60 months in the IM group and 13.13 months in the WM group(P0.01). The incidences of loss of appetite, nausea, and vomiting in the IM group were significantly lower than those in the WM group(P0.05). The QOL based on Functional Assessment of Cancer Therapy-Lung in the IM group was markedly higher than that in the WM group at the fourth course(P0.05). Conclusions: Additional CM may prolong survival and improve the QOL patients with NSCLC. The adverse effects of radio-and chemotherapy may be attenuated as CM is used in combination with conventional treatments.     

Short-Term Efficacy of Treating Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Based on Cold Pattern Differentiation with Hot Herbs: A Randomized Controlled Trial

Objective: To evaluate the clinical efficacy and safety of Yinchen Zhufu Decoction(茵陈术附汤, YCZFD) in the treatment of acute-on-chronic liver failure caused by hepatitis B virus(HBV-ACLF) with cold pattern in Chinese medicine(CM). Methods: This is a multi-center randomized controlled trial of integrative treatment of CM and Western medicine(WM) for the management of HBV-ACLF patients. A total of 200 HBV-ACLF patients with cold pattern were equally randomly assigned to receive YCZFD and WM(integrative treatment) or WM conventional therapy alone respectively for 4 weeks. The primary end point was the mortality for HBV-ACLF patients. Secondary outcome measures included Model for End-Stage Liver disease(MELD) score, liver biochemical function, coagulation function and complications. Adverse events during treatment were reported. Results: The mortality was decreased 14.28% in the integrative treatment group compared with WM group(χ2=6.156, P=0.013). The integrative treatment was found to significantly improve the MELD score(t=2.353, P=0.020). There were statistically significant differences in aspartate transaminase, total bilirubin, indirect bilirubin, direct bilirubin and prothrombin time between the two groups(P0.05 or P0.01). The complications of ascites(χ2=9.033, P=0.003) and spontaneous bacteria peritonitis(χ2=4.194, P=0.041) were improved significantly in the integrative treatment group. No serious adverse event was reported. Conclusions: The integrative treatment of CM and WM was effective and safe for HBV-ACLF patients with cold pattern in CM. The Chinese therapeutic principle "treating cold pattern with hot herbs" remains valuable to the clinical therapy.(Trial registration No. Chi CTR-TRC-10000766)     

Chinese Herbal Medicine Xingnaojing Injection (醒脑静注射液) for Hypoxic Ischemic Encephalopathy in Newborns: A Systematic Review and Meta-Analysis

Objectives: To evaluate the efficacy and safety of Chinese herbal medicine Xingnaojing Injection(醒脑静注射液) for newborns with hypoxic ischemic encephalopathy(HIE). Methods: Literature was identified by searching the Pub Med, EMBASE, Cochrane Library, Cochrane Central, and four Chinese literature databases from the establishment of database to October in 2013. Relevant reference lists were also screened. Two reviewers independently evaluated the methodological quality of included studies. We also conducted the meta-analysis. Results: Thirteen trials involving 1,169 patients were included. There was no trial reported death or disability at the end of follow-up period. Meta-analysis of 4 trials(n=371) showed that there was no significant difference in the reduction of mortality [risk ratios(RR)=0.48, 95% confidence intervals(CI, 0.21, 1.13), P=0.09] between the Xingnaojing and control groups. Meta-analysis of 5 trials(n=359) showed that there was significant difference in reducing the major neurodevelopmental disability [RR=0.36, 95% CI(0.19, 0.66), P=0.001]. Meta-analysis of 6 trials(n=447) showed that there was a significant difference in the author self-defined symptom improvement [RR=1.25, 95% CI(1.14, 1.37), P0.01]. No fatal side-effects were reported. Conclusion: Based on the limited evidence, the routine use of Xingnaojing Injection for treatment of HIE in newborns is not recommended. Further well-conducted trials are justified.     

Cohort Study on Prognosis of Patients with Metastatic Colorectal Cancer Treated with Integrated Chinese and Western Medicine

Objective: To investigate the efficacy of integrated Chinese and Western medicine(IM) in the treatment of metastatic colorectal cancer(m CRC) in a cohort study.Methods: The survival outcome of patients receiving IM was compared with that of patients receiving Western medicine alone.The study design was adopted with "continuous administration of Chinese medicine for 3 months" as the exposure factor.Patients who met this exposure factor were assigned to the IM cohort(Group A,110 patients).Patients who did not meet this exposure factor were assigned to the Western medicine cohort(Group B,225 patients).The overall survival(OS),progression-free survival(PFS),and 1 st year,2 nd year,and 3 rd year survival in the two cohorts were compared.Results: The median OS in Group A and B were 18 months [95% confidence interval(CI) 15–21] and 16 months(95% CI 14–18),respectively,and the median PFS in Group A and B were 6 months(95% CI 4–7) and 5 months(95% CI 4–6),respectively.No statistically significant differences were observed between the groups(P=0.186,P=0.223).Group A demonstrated significantly longer OS and PFS than Group B in the following subgroups: female patients,patients with lesions in the right half of the colon,and those who received first-line treatment(P0.05).In the subgroup of elderly patients(age65 years),the OS in Group A was longer than that in Group B(P0.05).Conclusion: IM could prolong the survival of patients with m CRC.(Registry No.Chi CTR-IOR-17010497)     

Effect of Kuanxiong Aerosol(宽胸气雾剂)on Patients with Angina Pectoris:A Non-inferiority Multi-center Randomized Controlled Trial

Objective: To evaluate the effect and safety of Kuanxiong Aerosol(宽胸气雾剂, KA) on patients with angina pectoris. Methods: Block randomization was performed to randomly allocate 750 patients into KA(376 cases) and control groups(374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA(0.6 m L per spray). The control group received 1 sublingual nitroglycerin tablet(NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment(1, 2, 3, 4, 5, and 5 min). Logistic regression analysis was performed to observe the factors influencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society(CCS) classes of angina. Results: The 5-min remission rates in the KA and control groups were not significantly different(94.41% vs. 90.64%, P0.05). The angina CCS class significantly influenced the rate of remission (95% confidence interval = 0.483–0.740, P0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSⅠ and Ⅳ subgroups(P0.05), while they were significantly better for KA in the CCSⅡ and Ⅲ subgroups(P0.05 or P0.01). Furthermore, the incidence of adverse reactions was significantly lower in the KA group than in the control group for the CCSⅡ and Ⅲ subgroups(9.29% vs. 26.22%, 10.13% vs. 20.88%, P0.05 or P0.01). Conclusions: KA is not inferior to NT in the remission of angina. Furthermore, in CCSⅡ and Ⅲ patients, KA is superior to NT, with a lower incidence of adverse reactions.     

Contribution of Water and Lipid Soluble Substances in the Relaxant Effects of Tymus Vulgaris Extract on Guinea Pig Tracheal Smooth Muscle in Vitro

Objective:To examine the relaxant effects of hydro-ethanolic,macerated aqueous(MA) and lipidfree macerated aqueous(LFMA) extract of Tymus vulgaris on tracheal chains of guinea pigs.Methods:The relaxant effects of five cumulative concentrations of each extract(0.4,0.8,1.2,1.6 and 2.0 g/100 mL) were compared with saline as negative control and five cumulative concentrations of theophylline(0.1,0.2,0.4,0.6 and 0.8 mmol/L) on precontracted tracheal smooth muscle of guinea pig with 60 mmol/L KCI(group 1) and 10 μmol/L methacholine(group 2,n=6 for each group).Results:In group 1 all concentrations of theophylline,three higher concentrations of hydro-ethanolic,two concentrations of LFMA and last concentration of MA extracts showed significant relaxant effects compared with that of saline(P0.05 or P0.01).Two lower concentrations of LFMA and all concentrations of MA except higher one caused contraction compared with saline(P0.05 or 0.01).In group 2 experiments,all concentrations of theophylline,hydro-ethanolic,MA and LFMA extracts showed significant relaxant effects compared to that of saline(P0.05 or P0.01).In both groups,the relaxant effect of all concentrations of hydro-ethanolic extract were significantly higher than most concentrations of others(P0.05 or P0.01).The relaxant effect of different concentrations of three extracts were significantly greater in group 2 compared with group 1 experiments(all P0.01).There were significantly positive correlations between the relaxant effects and concentrations for theophylline and ail extracts in both groups(P0.05 or P0.01).Conclusion:Hydro-ethanolic extract has a potent weaker relaxant effect for other extracts from Tymus vulgaris on tracheal chains of guinea pigs.     

Synchronous Dynamic Research on Respiratory and Intestinal Microflora of Chronic Bronchitis Rat Model

Objectives

To investigate the mechanism of the Chinese medicine theory that Fei (Lung) and Dachang (Large Intestine) are exteriorly and interiorly related via synchronous observation on the dynamic changes of the respiratory and intestinal microflora.

Methods

Forty specific pathogen free Sprague-Dawley rats were selected and randomly divided into blank (10 rats) and chronic bronchitis model groups (30 rats). The blank group rats were put into the smoke-free environment and the model group rats were put into the smoke environment in order to establish pulmonary disease (chronic bronchitis) model. Then the corresponding changes of the respiratory and intestinal microflflora of the model on 20th, 50th and 70th days were synchronously observed.

Results

The respiratory tract microflflora showed an increase in the total aerobic and Staphylococcus aureus and reduced anaerobic amount signifificantly on 20th day in the respiratory tract microflflora (P<0.05 or 0.01). On 50th day, total aerobic, total anaerobic amount and bififidobacterium signifificantly increased (P<0.05). On 70th day, Staphylococcus aureus reduced and lactobacillus increased signifificantly (P<0.01). The intestinal microflflora showed an increase in the total aerobic, Clostridium perfringens, enterobacter and enterococcus significantly increased on 20th day (P<0.05 or 0.01). Staphylococcus aureus on 50th day increased significantly (P<0.05). Total aerobic and enterococcus increased, total anaerobic and Clostridium perfringens reduced signifificantly on 70th day (P<0.05 or 0.01).

Conclusion

The microecosystem of respiratory tract and intestine of rat model during the pathological process showed a dynamic disorder, indicating an interaction between the lung and large intestine which may be one of the connotations as they exteriorly and interiorly related.

     

Efficacy and Safety of Quxie Capsule (祛邪胶囊) in Metastatic Colorectal Cancer: A Double-Blind Randomized Placebo Controlled Trial

Objective:To verify the efficacy and safety of Quxie Capsule(祛邪胶囊) in patients with metastatic colorectal cancer(mC RC).Methods:The present study was a randomized,double-blind,placebo-controlled trial.Sixty patients with mC RC were randomized into two groups at a 1:1 ratio by sealed envelope.The treatment group received conventional therapy combined with Quxie Capsule for 3 months.The control group was treated with conventional therapy combined with placebo for 3 months.Main outcome measures were overall survival(OS) and progression-free survival(PFS).Subgroup analysis was performed according to age,right or left-sided disease,and second-line therapy to determine the differences in PFS and OS between the two groups.Patients were followed up every 3 months until Dec 31 st 2016.Results:The median OS was 23 months in the treatment group [95% confidence interval(CI):15–not calculated] vs.14 months in the control group(95% CI:11–22,P=0.060).The OS of the treatment group tended to be longer than that of the control group(P0.05).In the subgroups of patients 65 years old,left-sided colon,and 2 nd-line therapy,the treatment group showed a significant survival benefit compared with the control group(P=0.006,0.038,0.013,respectively).There were no significant differences between the two groups in PFS(P0.05).Safety analysis showed no severe hematological toxicity or liver and renal function injury in the treatment group.Conclusions:Quxie Capsule showed good safety and efficacy,and could prolong the OS of patients with mC RC.     

Effects of Modified Qing'e Pill (加味青娥丸) on Expression of Adiponectin, Bone Morphogenetic Protein 2 and Coagulation-Related Factors in Patients with Nontraumatic Osteonecrosis of Femoral Head

Objective: To observe the regulation of Chinese herbal medicine, Modified Qing'e Pill(加味青娥丸, MQEP), on the expression of adiponectin, bone morphogenetic protein 2(BMP2), osteoprotegerin(OPG) and other potentially relevant risk factors in patients with nontraumatic osteonecrosis of the femoral head(ONFH). Methods: A total of 96 patients with nontraumatic ONFH were unequal randomly divided into treatment group(60 cases) and control group(36 cases). The treatment group were treated with MQEP while the control group were treated with simulated pills. Both groups were given caltrate D. Six months were taken as a treatment course. Patients were followed up every 2 months. The levels of plasma adiponectin, BMP2, OPG, von Willebrand factor(vWF), von Willebrand factor cleaving protease(vWF-cp), plasminogen activator inhibitor 1(PAI-1), tissue plasminogen activator(tPA), C-reactive protein(CRP), blood rheology, bone mineral density(BMD) of the femoral head and Harris Hip Score were measured before and after treatment. Results: After 6 months of treatment, compared with the control group, patients in the treatment group had significantly higher adiponectin and BMP2 levels(P0.01 and P=0.013, respectively), lower vWF, PAI-1 and CRP levels(P=0.019, P0.01 and P0.01, respectively), and lower blood rheology parameters. BMD of the femoral neck, triangle area and Harris Hip Score in the treatment group were significantly higher than those in the control group. Moreover, plasma adiponectin showed a positive association with BMP2(r=0.231, P=0.003) and a negative association with PAI-1(r=–0.159, P0.05). Conclusions: MQEP may play a protective role against nontraumatic ONFH by increasing the expression of adiponectin, regulating bone metabolism and improving the hypercoagulation state, which may provide an experimental base for its clinical effects.