Survey and Practice of Reporting Quality of Randomized Controlled Clinical Trials on Traditional Chinese Medicine

Evidence obtained from randomized controlled trials （RCTs） has been generally accepted as the gold standard in the evaluation of clinical effectiveness. Readers need to understand the trial design, implementation, results, analysis and interpretation, so as to fully Jnderstand the results of RCTs. Thus, the investigators of RCTs have to report these items in a complete, accurate and clear manner. Since 1998, we have conducted several evaluations on the reporting quality of RCTs published in Chinese journals on traditional Chinese medicine （TCM） and results have shown that there is an urgent need for higher quality RCTs on TCM.

Systematic review and Meta-analysis of 26 randomized controlled clinical trials of Compound Danshen Dripping Pill for non-proliferating diabetic retinopathy

Objective:Diabetic retinopathy(DR) is the retinal consequence of chronic progressive diabetic microvascular leakage and occlusion.Non-proliferating diabetic retinopathy(NPDR) is the early stage of DR.It eventually occurs to some degree in all patients with diabetes mellitus.In recent years,many clinical trials have shown that Compound Danshen Dripping Pill(CDDP) may be associated with the improvement of NPDR symptoms.The aim of this study was to quantitatively summarize the association between CDDP and the therapeutic effects of NPDR.Methods:It was conducted that a systematic literature search of Pub Med,Web of Science,CNKI,VIP and Wanfang Data updated in June 2020 with the following search terms:"diabetic retinopathy° or"retinopathy° or "DR° or "NPDR°,in combination with "Compound Danshen Dripping Pill° or "Salvia miltiorrhiza° or "Danshen°.Risk ratio(RR) and weighted mean difference(WMD) with their 95% confidence interval(CI) was calculated between treatment and control groups.The sensitivity analyses were undertaken by removing each individual study when high heterogeneity appeared.Subgroup analysis,Metaregression,and publication bias analysis were also conducted.The strength of evidence was evaluated with the Grading of Recommendation,Assessment,Development,and Evaluation(GRADE) method.Results:Twenty-six RCTs involving 2047 subjects were included to conduct a Meta-analysis after screening the studies,extracting the data,and assessing the study quality.The Stata15.0 software was utilized for processing.Meta-analysis indicated that curative effects of treatment group with CDDP was significantly better than control [RR = 0.54,95% CI(0.40,0.73);moderate-quality evidence].In addition,the results showed that CDDP was significantly associated with improving retinal hemorrhages[WMD =-0.62,95% CI(-0.78,-0.46);low-quality evidence],the vision [WMD = 0.14,and 95% CI(0.09,0.19),low-quality evidence],fundus fluorescence angiography [RR = 0.37 and 95% CI(0.23,0.60);low-quality evidence],reduction of retinal microaneurysm [WMD =-3.74 and 95% CI(-4.38,-3.11);moderate-quality evidence],hemangioma volume [WMD =-3.15,95%CI(-3.45,-2.85);moderate-quality evidence],macular thickness [WMD =-5.52,95%CI =(-64.27,-48.78);low-quality evidence],mean defect [WMD =-1.65 and 95% CI(-1.95,-1.34);very low-quality evidence],fasting blooding glucose [WMD =-0.95,95% CI(-1.19,-0.70);low-quality evidence),hemoglobin A1c[WMD =-0.62,95% CI(-0.93,-0.30);low-quality evidence],high sensitive C reaction protein[WMD =-5.66,95% CI(-8.01,-3.31);low-quality evidence].Sensitivity,subgroup,and Metaregression analyses were also assessed.Conclusion:The study demonstrated that CDDP has beneficial clinical effects for treating NPDR and improve the vision.Moreover,it indicated that oral CDDP in NPDR patients led to significant regulation of serum level of fasting blooding glucose,hemoglobin A1c and high sensitive C reaction protein,which was associated with the pathogenesis of NPDR.However,high-quality and large randomized clinical trials will be needed to prove the consequence in future.

Neoadjuvant chemoradiotherapy for resectable esophageal cancer:an in-depth study of randomized controlled trials and literature review

Surgery following neoadjuvant chemoradiotherapy(NCRT) is a common multidisciplinary treatment for resectable esophageal cancer(EC). After analyzing 12 randomized controlled trials(RCTs), we discuss the key issues of surgery in the management of resectable EC. Along with chemoradiotherapy, NCRT is recommended for patients with squamous cell carcinoma(SCC) and adenocarcinoma(AC), and most chemotherapy regimens are based on cisplatin, fluorouracil(FU), or both(CF). However, taxane-based schedules or additional studies, together with newer chemotherapies, are warranted. In nine clinical trials, post-operative complications were similar without significant differences between two treatment groups. In-hospital mortality was significantly different in only 1 out of 10 trials. Half of the randomized trials that compare NCRT with surgery in EC demonstrate an increase in overall survival or disease-free survival. NCRT offers a great opportunity for margin negative resection, decreased disease stage, and improved loco-regional control. However, NCRT does not affect the quality of life when combined with esophagectomy. Future trials should focus on the identification of optimum regimens and selection of patients who are most likely to benefit from specific treatment options.

A Randomized Controlled Clinical Trial on Efficacy and Safety of Electroacupuncture on Oral Oxycodone Hydrochloride Prolonged-Release Tablets Related Constipation

Objective:To observe the efficacy and safety of electroacupuncture on oral oxycodone hydrochloride prolonged-release tablets related constipation in Qi(气)deficiency syndrome.Methods:A randomized control trial was conducted in 44 participants,who were divided into the treatment group(electroacupuncture group)and the control group(western medicine group).Two groups were treated by electroacupuncture at Zusanli(ST36),Tianshu(ST25),Zhigou(SJ6)and Shangjuxu(ST37)acupoints every day for 20 mins for 14 consecutive days and lactulose oral solution 30 ml every day for 14 consecutive days respectively.The constipation symptoms,traditional Chinese medicine(TCM)symptoms,quality of life,physical condition before and after the treatments were observed,and the safety indicators were monitored.Results:The treatment group was better than the control group in improving constipation symptom score,improving TCM symptom score and improving quality of life score,and the difference was statistically significant.There was no significant difference between the two groups in improving physical condition score.No acupuncture related adverse events were observed in the treatment group.Two patients in the control group withdrew from the study due to taking emergency defecation therapy and mild diarrhea respectively.Conclusion:Electroacupuncture is better than lactulose in the treatment of Qi deficiency constipation related to oxycodone hydrochloride prolonged-release tablets.It can significantly improve the symptoms of constipation,improve the symptoms of TCM,improve the quality of life.It is safe and effective.

Effect of Zangfu ointment and massage therapy on functional constipation:a protocol for a randomised controlled trial

Introduction:Functional Constipation(FC)is a type of functional bowel disease that is in Clinically characterized by dysportia,decreased frequency of bowel movements,or incomplete bowel movements in the absence of irritable bowel syndrome syndrome,at least 6 months before diagnosis,and symptoms within the last 3 months.At present,commonly used drugs include enema and suppositories,laxatives,microecological preparations,gastrointestinal motility drugs and other treatments.However,the effect is limited.Traditional Chinese medicine(TCM)treatment of FC has advantages.Methods:In this randomized controlled study,244 eligible patients were randomly assigned in a 1:1 ratio to a treatment group(Zangfu ointment and massage therapy+Lactulose Oral Liquid)and a control group(Lactulose Oral Liquid)for 14 days.Number of spontaneous defecation per week and First defecation time will be used as primary outcomes,and Traditional Chinese Medicine(TCM)syndrome scores and syndrome scores,PAC-QOL form will be used as secondary outcomes.Blood routine,liver function,and renal function will be used as safety outcomes.The primary and secondary outcomes will be performed at 0th,7th,and 14th day,and the safety outcomes will be performed at 0th and 14th day.Ethics and dissemination:Ethical approval has been obtained from the Committee on Health Research Ethics of the Fangshan Hospital,Beijing University of Chinese Medicine,Beijing,People's Republic of China(FZY LK-2020-010)on September 18,2020.All patients will be provided oral and written information about the trial before screening.The study results will be disseminated by peer-review publications and conference presentations.Trial registration number:ChiCTR2000038754(registered on April 14,2021).This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited,appropriate credit is given,any changes made indicated,and the use is non-commercial.STRENGTHS AND LIMITATIONS OF THIS STUDY(1)The efficacy of the Zangfu ointment and massage therapy is evaluated in a randomised,double-blind 2-week clinical trial in FC patients.(2)Form a complete and generalizable regimen for the treatment of FC(Qi stagnation)with the Zangfu ointment and massage therapy.

A randomized placebo-controlled trial of Chinese medicine acupoint application on gastrointestinal dysfunction after appendectomy

Background:Gastrointestinal dysfunction is one of the common complications of appendectomy,which seriously affects the postoperative recovery and clinical prognosis.Through traditional Chinese medicine acupoint application is suggested for managing postoperative gastrointestinal dysfunction,supporting evidence is weak.Here,the prospective randomized placebo-controlled study was designed to provide high-level evidence regarding whether traditional Chinese medicine acupoint application is effective on the gastrointestinal dysfunction after appendectomy.Methods:A total of 60 patients who underwent appendectomy in Dongfang Hospital Beijing University of Chinese Medicine(Beijing,China)from November 2016 to December 2017 were selected as study objects and randomly divided into control group(n=30)and observation group(n=30).Based on routine postoperative care,the acupoints Zusanli(ST36)and Yongquan(KI1)were selected.The control group was given acupoint application of traditional Chinese medicine placebo and the observation group was given acupoint application of clinical empirical Chinese medicine called Wentongliqi prescription.The course of treatment was performed on the 1st,2nd,and 3rd days after appendectomy,once a day and 4 hours each time.The primary outcome includes the time until the recovery time of bowel sounds(h),the first postoperative flatus(h)and first bowel movement time(h)on the 1st,2nd,and 3rd days after appendectomy.The secondary outcome includes clinical symptom score,life ability score and adverse reactions were observed and recorded on the 1st,2nd,and 3rd days after appendectomy.Results:After treatment,the recovery time of intestinal sound in the observation group was earlier than that in the control group(P<0.05).However,there were no significant difference between the two groups in first anal exhaust time and first bowel movement time,clinical symptom scores and life ability scores between the two groups before and after treatment(P>0.05).Conclusion:Acupoint application therapy has limited effect on the recovery of gastrointestinal dysfunction after appendectomy.Further study with large sample size is needed to confirm its therapeutic effects.

Efficacy and safety of transcutaneous auricular vagus nerve stimulation combined with conventional rehabilitation training in acute stroke patients: a randomized controlled trial conducted for 1 year involving 60 patients

Transcutaneous auricular vagus nerve stimulation(ta-VNS)is a novel noninvasive treat-ment for stroke that directly stimulates the peripheral auricular branch of the vagus nerve.There have been recent reports that ta-VNS combined with conventional rehabilitation training promotes the recovery of neurological function of patients with acute stroke.However,these were small-sample-sized studies on the recovery of neurological function in patients after percutaneous vagus nerve stimulation in the subacute and chronic phases after stroke.This double-blinded randomized controlled trial involved 60 acute ischemic or hemorrhagic stroke patients aged 18-80 years who received treatment in the Second Affiliated Hospital of Chongqing Medical University.The subjects were randomly assigned to receive ta-VNS or sham ta-VNS combined with conventional rehabilitation training.The follow-up results over 1 year revealed that ta-VNS combined with conventional rehabilitation training greatly improved the recovery of motor and sensory functions and emotional responses compared with sham ta-VNS combined with conventional rehabilitation training.There were no obvious side effects.These findings suggest that ta-VNS combined with conventional rehabilitation training for the treatment of acute ischemic or hemorrhagic stroke patients is safe and effective.

Based on the process management of traditional Chinese medicine comprehensive intervention method on outcomes in patients with mild/moderate chronic obstructive pulmonary disease:study protocol for a practical randomized controlled trial

Background:The prevalence,morbidity and mortality of chronic obstructive pulmonary disease(COPD)is very high,so it has become a public health problem.The early stage of COPD has been paid much attention before it develops severely.As well,traditional Chinese medicine has some advantages in relieving symptoms and reducing the incidence of COPD exacerbations.Methods:A practical randomized controlled trial will be designed to test the clinical effects of traditional Chinese medicine treatment according to syndrome differentiation.A total of 80 patients with mild/moderate COPD will participate in this study,40 in the treatment group and 40 in the control group.On the basis of the lifestyle intervention,traditional Chinese medicine formula granules for treatment group and the placebo simulation of traditional Chinese medicine granules for control group.The exacerbation and the improvement of pulmonary function will be used as the primary outcome measures.The improvement of clinical symptoms and signs,the quality of life and Dyspnea will be used as the secondary outcomes measures.Conclusion:We assume that the COPD patients will be benefit from therapy with Traditional Chinese medicine treatment.

Induced arousal following zolpidem treatment in a vegetative state after brain injury in 7 cases Analysis using visual single photon emission computerized tomography and digitized cerebral state monitor

BACKGROUND： Several studies have reported the use of zolpidem for induced arousal after permanent vegetative states. However, changes in brain function and EMG after zolpidem treatment requires further investigation. OBJECTIVE： To investigate the effect of zolpidem, an unconventional drug, on inducing arousal in patients in a permanent vegetative state after brain injury using visual single photon emission computerized tomography and digitized cerebral state monitor. DESIGN： A self-controlled observation. SETTING： Shenzhen People＇s Hospital. PARTICIPANTS： Seven patients in a permanent vegetative state were selected from the Department of Neurosurgery, Shenzhen People＇s Hospital from March 2005 to May 2007. The group included 5 males and 2 females, 24-55 years of age, with a mean age of 38.5 years. All seven patients had been in a permanent vegetative statement for at least six months. The patient group included three comatose patients, who had sustained injuries to the cerebral cortex, basal ganglia, or thalamus in motor vehicle accidents, and four patients, who had suffered primary/secondary brain stem injury. Informed consents were obtained from the patients＇ relatives. METHODS： The patients brains were imaged by ^99Tc^m ECD single photon emission computerized tomography prior to treatment with zolpidem [Sanofi Winthrop Industrie, France, code number approved by the State Food ＆ Drug Administration （SFDA） J20040033, specification 10 mg per tablet. At 8：00 p.m., 10 mg zolpidem was dissolved with distilled water and administered through a nasogastric tube at 1 hour before and after treatment and 1 week following treatment, respectively. Visual analysis of cerebral perfusion changes in the injured brain regions before and after treatment was performed. Simultaneously, three monitoring parameters were obtained though a cerebral state monitor, which included cerebral state index, electromyographic index, and burst suppression index. MAIN OUTCOME MEASURES： Comparison of the three brain function indices, cerebral perfusion in the areas of brain injury, and clinical indices before and after treatment. RESULTS： All seven patients were included in the final analysis. （1） Following treatment, the parameters of cerebral state index and electromyographic index were significantly higher than before treatment （P 〈 0.05）. The burst suppression index was significantly lower than before treatment （P 〈 0.05）. （2） Cerebral perfusion in areas of brain injury improved significantly in all subjects compared to before treatment. CONCLUSION： The findings of visual single photon emission computerized tomography and digitized cerebral state monitor reveal that Zolpidem appears to be an effective treatment for restoring brain function to certain patients in a permanent vegetative state.

Chinese Medicine Sequential Therapy Improves Pregnancy Outcomes after Surgery for Endometriosis-Associated Infertility: A Multicenter Randomized Double-blind Placebo Parallel Controlled Clinical Trial

Objective:To evaluate the efficacy and safety of Chinese medicine(CM)improving pregnancy outcomes after surgery for endometriosis-associated infertility.Methods:A multicenter,randomized,doubleblind placebo parallel controlled clinical trial was designed.A total of 202 patients who had laparoscopy for endometriosis-associated infertility with qi stagnation and blood stasis syndrome were included and randomly divided into the CM treatment group and placebo control group at a ratio of 1:1 using a central block randomization from May 2014 to September 2017,101 patients in each group.The two groups received continuous intervention at 1–5 days after surgery,for 6 menstrual cycles.Before ovulation,the CM group was treated Huoxue Xiaoyi Granule(活血消异颗粒);after ovulation,Bushen Zhuyun Granule(补肾助孕颗粒)was involved.The control group was treated with placebo.Transvaginal ultrasonography was performed every menstrual cycle during the treatment,and female hormone levels in the follicular and luteal phases were measured during the 1 st,3 rd and 6 th menstrual cycles.The analysis was continued until pregnancy.The primary outcomes were clinical pregnancy rate and pregnancy outcome,and the secondary outcomes were follicular development and endometrial receptivity.Safety evaluations were performed before and after treatment.Results:(1)Clinical pregnancy and live birth rates:the clinical pregnancy and live birth rates of the CM group were significantly higher than those of the placebo group[44.6%(45/101)vs.29.7%(30/101),34.7%(35/101)vs.20.8%(21/101),both P<0.05].(2)Follicle development:the incidence of dominant follicles,rate of cumulative cycle ovulation,and rate of cumulative cycle mature follicle ovulation were significantly higher in the CM group than those in the placebo group[93.8%(350/373)vs.89.5%(341/381),80.4%(275/342)vs.69.1%(253/366),65.8%(181/275)vs 56.1%(142/253),P<0.05 or P<0.01]).The incidence of cumulative cycle luteinized unruptured follicle syndrome was significantly lower in the CM group than in the placebo group[11.7%(40/342)vs.17.8%(65/366),P<0.05).(3)Endometrial receptivity:after treatment,both endometrial types and endometrial blood flow types in the CM group were mainly types A and B,while those in the placebo group were mainly types B and C,with a significant difference between the two groups(both P<0.05).(4)Adverse events:the incidence of adverse events between the two groups was not significantly different(P>0.05).Conclusion:Strategies for activating blood circulation-regulating Gan(Liver)-tonifying Shen(Kidney)sequential therapy can effectively improve the clinical pregnancy rate and live birth rate of endometriosis-associated infertility with qi stagnation and blood stasis after laparoscopy,improve follicular development,promote ovulation,improve endometrial receptivity,while being a safe treatment option.(Trial registration No.NCT02676713).

Natural herbal medicine Lianhuaqingwen capsule anti-influenza A （H1N1） trial： a randomized, double blind, positive controlled clinical trial

Background The 2009 influenza A （H1N1） virus infection is associated with the high risk of severe complications and is spreading more rapidly throughout the world than other reported seasonal influenzas. This study aimed to evaluate the efficacy and safety of the nature herbal medicine Lianhuaqingwen capsule （LHC） in patients infected with influenza A （H1N1） virus. Methods A total of 244 patients aged 16-65 years confirmed with influenza A （H1N1） virus infection by the real time RT-PCR were randomized to one of two treatment groups of 122 patients each. Each group assigned to receive either LHC or Oseltamivir for five days and observation for seven days. The patients were enrolled within 36 hours of illness onset if they had an axillary temperature of ≥37.4℃ and with at least one of the following symptoms： nasal obstruction, runny nose, cough, sore throat, fatigue, headache, myalgia, chills and sweating. The primary end point was the duration of illness. Results Of 244 patients, 240 （98.36%） patients with a median age 21 years completed the study between October 24, 2009 and November 23, 2009. There were no significant overall differences between LHC treated and Oseltamivir treated patients in the median duration of illness （LHC 69 hours vs. Oseltamivir 85 hours P 〉0.05） or the median duration of viral shedding （LHC 103 hours vs. Oseltamivir 96 hours, P 〉0.05）. However, it was worthwhile to note that LHC significantly reduced the severity of illness and the duration of symptoms including fever, cough, sore throat, and fatigue （P〈0.05）. Both study medications were well tolerated. No drug related serious adverse events occurred during the study. Conclusions Compared with Oseltamivir, LHC achieved a similar therapeutic effectiveness reduction of the duration of illness and duration of viral shedding. Therefore, LHC might be an alternative therapeutic measure for influenza A （H1N1） virus infections.

Effects of Interactive Dynamic Scalp Acupuncture on Motor Function and Gait of Lower Limbs after Stroke:A Multicenter,Randomized,Controlled Clinical Trial

Objective:To evaluate the effects of interactive dynamic scalp acupuncture(IDSA),simple combination therapy(SCT),and traditional scalp acupuncture(TSA)on motor function and gait of the lower limbs in post-stroke hemiplegia patients.Methods:A total of 231 patients with post-stroke hemiplegia was randomly divided into IDSA(78 cases),SCT(78 cases),and TSA(75 cases)groups by a random number table.Scalp acupuncture(SA)and lower-limb robot training(LLRT)were both performed in the IDSA and SCT groups.The patients in the TSA group underwent SA and did not receive LLRT.The treatment was administered once daily and 6 times weekly for 8 continuous weeks,each session lasted for 30 min.The primary outcome measures included Fugl-Meyer Assessment of the Lower Extremity(FMA-LE),Berg Balance Scale(BBS),Modified Barthel Index(MBI),and 6-min walking test(6 MWT).The secondary outcome measures included stride frequency(SF),stride length(SL),stride width(SW),affected side foot angle(ASFA),passive range of motion(PROM)of the affected hip(PROM-H),knee(PROM-K)and ankle(PROM-A)joints.The patients were evaluated before treatment,at 1-and 2-month treatment,and 1-,and 2-month follow-up visits,respectively.Adverse events during 2-month treatment were observed.Results:Nineteen patients withdrew from the trial,with 8 in the IDSA group,5 in the SCT group,and 6 in the TSA group.The FMA-LE,BBS,6 MWT and MBI scores in the IDSA group were significantly increased after 8-week treatment and2 follow-up visits compared with the SCT and TSA groups(P<0.05 or P<0.01).Compared with pre-treatment,the grade distribution of BBS and MBI scores in the 3 groups were significantly improved at 1,2-month treatment and 2 follow-up visits(P<0.05 or P<0.01).The SF,PROM-H,PFOM-K and PROM-A in the IDSA group was significantly increased compared with the SCT and TSA groups after 8-week of treatment(P<0.05 or P<0.01).Compared with the SCT group,ASFA of the IDSA group was significantly reduced after 8-week of treatment(P<0.05).SF,SL,PROM-K and PROM-A were significantly increased at the 2 nd follow-up visit whereas the ASFA was significantly reduced in the IDSA group compared with the SCT groups at 1 st follow-up visit(P<0.05 or P<0.01).The SF was significantly increased in the SCT group compared with the TSA group after 8-week treatment(P<0.05).Compared with the TSA group,PROM-K,PROM-A were significantly increased at the 2 nd follow-up visit(P<0.05).Conclusions:The effects of IDSA on lower-limb motor function and walking ability of post-stroke patients were superior to SCT and TSA.The SCT was comparable to TSA treatment,and appeared to be superior in improving the motion range of the lower extremities.(Registration No.ChiCTR1900027206)

Effects of body-resistance strengthening and tumor-suppressing granules on immune adhesion function of red blood cells and expression of metastasis protein CD44 in tumor cells of patients with esophageal carcinoma

AIM： To investigate the effects of Fuzheng Yiliu granules （body-resistance strengthening and tumor-suppressing granules） in patients with esophageal carcinoma. METHODS： We compared the immune adherent properties of red blood cells （RBCs）, the expression of metastasis protein CD44, and the metastasis inhibition factor nm23, in esophageal carcinoma tumor cells of patients before and after radiotherapy in the presence and absence of orally administered Fuzheng Yiliu granules. Sixty-three hospitalized patients with esophageal carcinoma were treated with standard radiotherapy and randomly divided into treatment group （n = 30） treated with both radiotherapy and Fuzheng Yiliu granules and control group （n = 33） given radiotherapy only. Blood samples and tumor tissue were obtained before and after 21 d of treatment. The rosette rates for complement receptor type 3b （C3bRR） and immune complex receptor （ICRR） on RBCs were measured by erythrocyte immunological methods. Expression of CD44 and rim23 in tumor tissue sections was determined by immunohistochemical staining with monoclonal antibodies CD44v6 ad nm23H-1, respectively. RESULTS： The positivity of RBC-C3bRR before and after 21 d of treatment increased from 7.78% ± 1.59% to 10.03% ± 2.01% in the double treatment group, while it changed only slightly from 7.18% ± 1.29% to 7.46% ± 1.12% in the radiotherapy group. The positive rate for RBC-ICRR decreased from 37.68% ± 2.51% to 22.55% ± 1.65% after the double treatment, and from 37.28% ± 2.41% to 24.69% ± 1.91% in radiotherapy group at the same time points. The difference in erythrocyte immune adherent function between the two groups was significant （P 〈 0.01, t-test）. The CD44^± - cases were reduced from 21 （70.00%） to 12 （40.00%） after treatment with Fuzheng Yiliu granules, whereas the CD44^± -cases （69.70%） in the radiotherapy group remained unchanged. The difference between the treatment （40.00%） and control （69.70%） groups was significant （P 〈 0.05）. Although the nm23^± -cases were increased from 4 （13.33%） to 6 （20.00%） in the double treatment group and from 6 （18.18%） to 7 （21.21%） in the radiotherapy group, the difference was not significant （P 〉 0.05）. CONCLUSION： Fuzheng Yiliu granules enhance the immune adhesion function of RBCs and reduce the number of CD44^± -cells in esophageal carcinoma patients, suggesting a potential role of these Chinese herbals in suppression of invasion and metastasis of malignant cells. However, this anti-metastatic effect has yet to be validated in vivo.

Efficacy and safety of Hemoheal cream in patients with hemorrhoids:a randomized double-blind placebo controlled clinical trial

OBJECTIVE:To evaluate the efficacy and safety of Hemoheal cream,an anti-hemorrhoid herbal preparation,(inspired by Persian medicine literatures in a double-blind,randomized placebo-controlled trial.METHODS:Hemoheal cream consists of aqueous extract of Allium ampeloprasum L.,Commiphora mukul(Hook.Ex Stocks)Engl and the oil of Sesamum indicum L.Fifty-two patients with symptomatic hemorrhoids were randomized to receive hemoheal cream or placebo for 3 weeks.The patients were evaluated before and after the intervention in terms of the severity of anal irritation,bleeding,anal itching,pain,defecation discomfort and swelling sense,and overall subjective improvement(%),as well as any reported adverse events.RESULTS:The results showed that after 3 weeks of treatment,distribution of anal irritation,bleeding,pain as well as swelling sense were significantly different(P<0.05),while the analysis showed no significant differences between two groups for anal itching and defecation discomfort(P>0.05).Furthermore,a significant difference was observed between the overall subjective improvement of Hemoheal cream and placebo groups(P=0.012).One patient in the treatment group complained of rashes on the application site.CONCLUSION:The present study showed a positive effect of Hemoheal cream in improving clinical signs and symptoms in patients with hemorrhoids.

Effectiveness and Safety of Acupoint Application of Guan Xin Su He Pill (冠心苏合丸) for Patients with Chronic Stable Angina Pectoris: A Multi-Center, Randomized Controlled Trial

Objective To assess the clinical effectiveness of acupoint application(AP)of Guan Xin Su He Pill(冠心苏合丸,GXSHP)for patients with chronic stable angina pectoris(CSAP).Methods This study was carried out in 3 local hospitals in Chengdu,China.After baseline evaluation,eligible patients were randomly assigned to the placebo application for acupoints(PAA)group or the herbal application for acupoints(HAA)group.Patients in the HAA group underwent AP with herbal powder,which was mainly GXSHP,and patients in the PAA group underwent AP with sham drugs.For each treatment session,unilateral acupoints including Neiguan(PC 6),Danzhong(RN 17),Xinshu(BL 15)and Jueyinshu(BL 14),were stimulated for both groups.AP was performed 3 times a week with a 2-day interval for 4 weeks.The primary outcome was the frequency of angina pectoris attacks per week,while the secondary outcomes included angina pain intensity measured by the Visual Analogue Scale(VAS),dose of rescue oral drugs(nitroglycerin),scores on the Seattle Angina Questionnaire(SAQ),Self-Rating Anxiety Scale scores(SAS)and Self-Rating Depression Scale scores(SDS).Clinical outcomes were measured at week 0,4 and 8.The safety of AP of GXSHP treatment for CSAP were assessed.Results A total of 121 patients were enrolled.Baseline characteristics were comparable across the 2 groups.After treatment,the angina attack numbers in the HAA group were significantly reduced from 11.00 to 4.81(P<0.05).While,for PAA group,the angina frequency was not significantly improved(baseline 10.55;post-treatment 11.05).The HAA group had significantly fewer angina attacks than the PAA group(P<0.05).Pain intensity measured by VAS in HAA group was significantly reduced from 4.06 to 3.02(P<0.05).While,for PAA group,the VAS was significantly increased(baseline 3.62;post-treatment 3.96;P<0.05).Clinical outcomes showed better improvement after treatment in the HAA group than in the PAA group in terms of oral administration of rescue drugs,SAS,SDS and SAQ scores(P<0.05).The adverse events were also reported.Conclusion AP of GXSHP is a safe and effective treatment for CSAP patients(Registration No.NCT02029118).

A Randomized Controlled Trial of Adjunctive Bunchang Naoxintong Capsule (步长脑心通胶囊) Versus Maintenance Dose Clopidogrel in Patients with CYP2C19*2 Polymorphism

Objective：To determine the impact of adjunctive Buchang Naoxintong Capsule（步心脑心通胶囊,NXT） on dual antiplatelet therapy in patients with cytochrome P450 2C19＊2（CYP2C19＊2） polymorphism undergoing percutaneous coronary intervention（PCI）.Methods：Ninety patients with CYP2C19＊2 polymorphism were enrolled,and their genotypes were confirmed by polymerase chain reaction（PCR）.The patients were randomly assigned to receive either adjunctive NXT（triple group,45 cases） or dual antiplatelet therapy（dual group,45 cases） using a computer-generated randomization sequence and sealed envelopes.Platelet function was assessed at baseline and 7 days after treatment with conventional aggregometry.Subsequent major adverse cardiovascular events（MACE,including sudden cardiac arrest and acute coronary syndrome） were recorded during a 12-month followup.Results：Baseline platelet function measurements were similar in both groups.After 7 days,percent inhibitions of maximum platelet aggregation and late platelet aggregation were significantly greater in the triple versus dual group（42.3%±16.0%vs.20.8%±15.2%,P〈0.01,and 54.7%±18.3%vs.21.5%±29.2%,P〈0.01,respectively）.During the 12-month follow-up,the rate of subsequent MACE（6/45） was significantly lower in the triple group compared with the dual group（14/45;P〈0.05）.Conclusion：Adjunctive NXT to maintenance dose clopidogrel（75 g） could enhance the antiplatelet effect and decrease subsequent MACE in patients with the CYP2C19＇2polymorphism undergoing PCI.

Clinical efficacy of low-dose emetine for patients with COVID-19:a real-world study

Objective:Emetine,an isoquinoline alkaloid that is enriched at high concentrations in the lung,has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019(COVID-19).Methods:In this real-world study,63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province,China from February to March 2020.Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial,and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study.The medication course of emetine was less than 10 days.The main symptoms and adverse reactions of all patients were observed and recorded.The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10.Secondary outcomes included axillary temperature,transcutaneous oxygen saturation,and respiratory frequency recovery.The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20,2019(approval No.PJ2020-03-19)and was registered with the Chinese Clinical Trial Registry on February 20,2019(registration number:ChiCTR2000030022).Results:The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital.The axillary body temperature,respiratory rate,and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures.The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect.The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures.Conclusion:Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects,suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.

Jinye Baidu granule for wind-warmth lung-heat disease(heat in the lung-wei)： protocol for a randomized, double-blind, parallel, controlled trial

OBJECTIVE: To observe the curative effect of Jinye Baidu granule in the treatment of fever and swollen and sore throat caused by wind-warmth lung-heat disease(heat in the lung-wei) to further identify the indications.METHODS: This randomized, double-blind, parallel, controlled trial will include patients with acute upper respiratory infection and wind-warmth lung-heat disease(heat in the lung-wei). Patientswith serious bacterial infection(white blood cell count > 12 × 10~9, neutrophils > 80%) will be excluded. Patients will be divided into three categories(blocks) according to their condition: fever only, a swollen and sore throat, and combined fever plus a swollen and sore throat. Patients within each of the three blocks will be further divided into a treatment group and a control group via stratified blocked randomization. The treatment group will be treated with Jinye Baidu granule, and the control group will be treated with Fufang Shuanghua granule. The primary outcome measure will be body temperature recovery time for patients with fever, throat symptom score for patients with a swollen and sore throat, and body temperature recovery time and throat symptom score for patients with combined fever plus a swollen and sore throat. Routine blood testing, urine testing, liver function, kidney function and ECG data of all patients will be collected as safety indices before and after enrollment, and adverse events will be recorded during the whole trial course.CONCLUSION: This study protocol will include stratified block analysis according to patients' symptoms, and identify the accurate clinical indications of Jinye Baidu granule. It will also enable safety evaluation from laboratory indices and adverse events, which will provide reliable evidence for clinical treatment.

Calcium dobesilate for diabetic retinopathy: a systematic review and meta-analysis

Many randomized clinical controlled trials have confirmed the efficacy and safety of calcium dobesilate in treating diabetic retinopathy(DR).This systematic review critically evaluated the evidence that links calcium dobesilate to DR.In this fixed-effects meta-analysis,a total of 221 pertinent English-language articles published between January 1975 and October 2013 were identified.Systematic searches of PUBMED,Springer Link and the Cochrane Clinical Trials Database were conducted using the keywords "diabetic retinopathy" and "calcium dobesilate".The extracted information included the study design,inclusion and exclusion criteria,setting,sample size,participant mean age,treatment regime,mean change in best corrected visual acuity,laboratory parameters,capillary fragility,intraocular pressure and fundus manifestations based on the findings of fluorescent angiography.The summary statistics indicated that calcium dobesilate was significantly associated with improving retinal microaneurysms(RR: 0.62,95%CI: 0.42?0.90,P=0.01),retinalhemorrhages(RR: 0.39,95% CI: 0.17?0.88,P=0.02); exudates(RR: 0.31,95% CI: 0.12?0.81,P=0.02),reduction of whole blood viscosity(MD: ?0.57 CP,95% CI: ?0.75 to ?0.38,P<0.001),plasma viscosity(MD: ?0.36 CP,95% CI: ?0.63 to ?0.09,P=0.01) and blood cholesterol(MD: ?0.48 mg m L?1,95% CI: ?0.64?0.33,P<0.00001).Intraocular pressure was also significantly reduced(MD: ?5.59 mm Hg,95% CI: ?6.69 to ?4.50,P<0.00001).The results indicate that calcium dobesilate effectively treats DR at the systematic and local ocular levels.

Toward Evidence-Based Chinese Medicine：Status Quo,Opportunities and Challenges

How to test the treatments of Chinese medicine（CM） and make them more widely accepted by practitioners of Western medicine and the international healthcare community is a major concern for practitioners and researchers of CM.For centuries,various approaches have been used to identify and measure the efficacy and safety of CM.However,the high-quality evidence related to CM that produced in China is still rare.Over the recent years,evidence-based medicine（EBM） has been increasingly applied to CM,strengthening its theoretical basis.This paper reviews the past and present state of CM,analyzes the status quo,challenges and opportunities of basic research,clinical trials,systematic reviews,clinical practice guidelines and clinical pathways and evidence-based education developed or conducted in China,pointing out how EBM can help to make CM more widely used and recognized worldwide.