Chinese herbal medicine Xinfeng Capsule in treatment of rheumatoid arthritis:study protocol of a multicenter randomized controlled trial

BACKGROUND： Rheumatoid arthritis （RA）, as a common systemic inflammatory autoimmune disease, affects approximately 1 in 100 individuals. Effective treatment for RA is not yet available because current research does not have a clear understanding of the etiology and pathogenesis of RA. Xinfeng Capsule, a patent Chinese herbal medicine, has been used in the treatment of RA in recent years. Despite its reported clinical efficacy, there are no large-sample, multicenter, randomized trials that support the use of Xinfeng Capsule for RA. Therefore, we designed a randomized, double-blind, multicenter, placebo-controlled trial to assess the efficacy and safety of Xinfeng Capsule in the treatment of RA. METHODS AND DESIGN： This is a 12-week, randomized, placebo-controlled, double-blind, multicenter trial on the treatment of RA. The participants will be randomly assigned to the experimental group and the control group at a ratio of 1：1. Participants in the experimental group will receive Xinfeng Capsule and a pharmaceutical placebo （imitation leflunomide）. The control group will receive leflunomide and an herbal placebo （imitation Xinfeng Capsule）. The American College of Rheumatology （ACR） Criteria for RA will be used to measure the efficacy of the Xinfeng Capsule. The primary outcome measure will be the percentage of study participants who achieve an ACR 20% response rate （ACR20）, which will be measured every 4 weeks after randomization. Secondary outcomes will include the ACR50 and ACR70 responses, the side effects of the medications, the Disease Activity Score 28, RA biomarkers, quality of life, and X-rays of the hands and wrists. The first four of the secondary outcomes will be measured every 4 weeks and the others will be measured at baseline and after 12 weeks of treatment. DISCUSSION： The result of this trial will help to evaluate whether Xinfeng Capsule is effective and safe in the treatment of RA. TRIAL REGISTRATION： This trial has been registered in ClinicalTrials.gov. The identifier is N CT01774877.

Science Letters:Crossover randomized controlled trial of the electronic version of the Chinese SF-36

Objectives:to verify the feasibility and reliability of the electronic version of Chinese SF-36 based on the Quality-of-Life-Recorder. Design: A crossover randomized controlled trial, comparing a paper-based and an electronic version of the Chinese SF-36, was conducted. According to generated random numbers, interviewees were asked to fill out either the electronic version or the paper version first. The second version was filled in after a pause of at least 10 min. Settings and participants: One group of 100 medical students at the School of Medicine of Zhejiang University and the other group of 50 outpatients at a clinic for general practice in Hangzhou City (China) were eventually recruited in this study. Results: The acceptance of the electronic version was good (60% of medical students and 84% of outpatients preferred the electronic version). At the level of eight-scale scores, the mean-difference for each scale (except for general health) between the two versions was less than 5%. At the level of 36 questions, the percentage of "exact agreement" ranged within 64%～99%; the percentage of "global agreement" ranged within 72%～99%; 77% of the kappa coefficients demonstrated "good/excellent agreement" and 23% of the kappa coefficients demonstrated "medium agreement". Conclusion: This study, for the first time, can provide empirical basis for the confirmation of the feasibility and reliability of the electronic version of the Chinese SF-36 and may provide an impulse towards widespread deployment of the Quality-of-Life-Recorder in Chinese populations.

Randomized trial estimating effects of hypnosis versus progressive muscle relaxation on medical students’test anxiety and attentional bias

BACKGROUND Test anxiety is prevalent among medical students and leads to impaired academic performance.Test-related attentional bias has been identified as an important maintaining factor in test-anxious individuals.AIM To evaluate whether hypnosis and progressive muscle relaxation(PMR)could modify medical college students’test anxiety and attentional bias.METHODS A total of 598 medical students were screened.The participants were divided into higher and lower test anxiety groups according to their scores on the test anxiety scale(TAS).Ninety medical college students with high TAS score were randomly assigned to a hypnosis or PMR group.Another 45 students with low TAS score were included,forming a baseline control group.The intervention was conducted weekly for 6 wk,and each session lasted approximately 30 min.The total intervention time and the number of intervention sessions for the hypnosis and PMR groups were equal.Data were collected at the pretest,posttest,and 2-mo follow-up.RESULTS Hypnosis group participants had a significantly lower TAS score at posttest(t=-21.827,P<0.001)and at follow-up(t=-14.824,P<0.001),compared to that at pretest.PMR group participants also had a significantly lower TAS score at posttest(t=-10.777,P<0.001)and at follow-up(t=-7.444,P<0.001),compared to that at pretest.At the posttest level,the hypnosis group had a significantly lower TAS score than the PMR group(t=-3.664,P<0.001).At the follow-up level,the hypnosis group also had a significantly lower TAS score than the PMR group(t=-2.943,P=0.004).Clinically significant improvement was found in both the hypnosis and PMR groups(hypnosis=64.0%;PMR=62.22%).Hypnosis was more effective than PMR in reducing test anxiety among medical college students.Hypnosis could modify attentional bias toward threatening stimuli,but PMR could not.CONCLUSION These results suggest that attentional bias plays an important role in test anxiety treatment.

Effectiveness and safety of Jiawei Xiaoyao pill(加味逍遥丸)in the treatment of premenstrual syndrome(liver depression,spleen deficiency,and blood-heat syndrome):a multi-center,randomized,placebo-controlled trial

OBJECTIVE:To investigate the effectiveness and safety of Jiawei Xiaoyao pill(加味逍遥丸,JXP)in the treatment of symptoms associated with premenstrual syndrome(PMS).METHODS:A total of 144 regularly menstruating women with PMS were recruited at 8 sites in China from August 2017 to December 2018,and randomized to receive either a JXP or a matching placebo(12 g/d,6 g twice a day)for 3 menstrual cycles.The primary indicator was the reduced Daily Record of Severity of Problems(DRSP)scores in the luteal phase after 3 months of treatment.The safety outcomes included clinical adverse events(AEs),adverse reactions(ARs),changes in vital signs,and laboratory tests.RESULTS:JXP surpassed the placebo in reducing DRSP scores(psychological/somatic dysfunction)in the luteal phase over 3 menstrual cycles of treatment(PFAS=0.002,PPPS=0.001).Additionally,there were no significant differences in the incidence of AEs,severe AEs,withdrawal due to AEs and ARs between the two groups(all P>0.05),and no clinically significant adverse medical events related to the test drug observed.CONCLUSIONS:JXP was superior to the placebo in relieving the symptoms associated with PMS,which signified that JXP may be effective,safe,and welltolerated as an alternative therapy.

Effect and Safety of Huannao Yicong Formula(还脑益聪方) in Patients with Mild-to-Moderate Alzheimer’s Disease: A Randomized, Double-Blinded, Donepezil-Controlled Trial

Objective: To assess the effect and safety of Huannao Yicong Formula (还脑益聪方, HYF) in the treatment of patients with mild-to-moderate Alzheimer's disease (AD). Methods: Sixty patients with mild-to moderate AD were evenly randomized into HYF group and donepezil group with the random number method. Patients in the HYF group took 5 g of HYF granules twice daily and 5 mg placebo of donepezil once daily. Patients in the donepezil group took 5 mg donepezil once daily and 5 g placebo of HYF granules twice daily. The intervention lasted for 6 months. Clinical researchers, participants and statisticians were blinded to the treatment assignment throughout the study. The primary outcomes were scores of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Chinese Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Montreal Cognitive Assessment (MoCA) test and Mini-Mental State Exam (MMSE). The serum levels of acetylcholinesterase (AchE) and amyloid-β protein 42 (Aβ 42) were detected with enzyme linked immunosorbent assay kits. The scale assessments were conducted at baseline, the 3rd and 6th months of treatment, respectively. Biochemistry tests were conducted at baseline and the 6th month of treatment. Results: A total of 52 patients completed the trial, 28 in HYF group and 24 in donepezil group. Compared with the baseline, HYF and donepezil significantly decreased the total scores of ADAS-Cog and CM-SS, and significantly increased the scores of MoCA and MMSE after 6-month treatment (all P<0.01). Both treatments remarkably reduced the serum levels of AchE and Aβ 42 (both P<0.05). The CM-SS total effective rate of HYF was significantly higher than donepezil [75.00%(21/28) vs. 54.17%(13/24), P<0.05]. No severe adverse events were observed in both groups. Conclusion: HYF is effective and safe for improving the cognitive function in mild to-moderate AD patients.[Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-IOR-17011746)].

Effectiveness of Jinying capsule on pelvic inflammatory disease in patients with symptom pattern of damp and heat accumulation: a double-blinded, multicenter, randomized, placebo-controlled clinical trial

OBJECTIVE: To evaluate the therapeutic effectiveness and safety of Jinying capsule on pelvic inflammatory disease(PID) in patients with symptoms identified as the pattern of damp and heat accumulation in terms of Traditional Chinese Medicine(TCM).METHODS: We conducted a double-blinded, multicenter, randomized, placebo-controlled clinical trial which included 155 patients diagnosed with PID and identified as symptom pattern of damp and heat accumulation. They were randomly divided into experimental group(n = 78) and control group(n = 77) according to a random number table. The treatment lasted for a period of 28 d. The experimental group was given Jinying capsules and oral levofloxacin plus oral metronidazole for first 7 d.They continued with Jinying capsules and levofloxacin placebo and metronidazole placebo for another 7 d. For the remaining 14 d, they continued with Jinying capsules only. Whereas, the control group was treated with oral levofloxacin and metronidazole and Jinying capsule placebo for the first 14 d in the same way as the experimental group and then continued with Jinying capsule placebo only for the remaining 14 d. The clinical efficacy was assessed using McCormack scale, TCM symptom pattern scores, physicochemical indexes including white blood cell and erythrocyte sedimentation rate, C-reaction protein, smear of vaginal discharge,and pelvic ultrasound.RESULTS: Comparing McCormack scale between both groups after treatment, the difference in curative effect between both groups was significant (P = 0.0269). The cure rate of the experimental group and control group is 76.32% and 59.46% respectively at week 4. Comparing TCM symptom pattern scores between both groups before and after treatment, the differences in total effective rate were both significant(P < 0.05). The curative effect rate of experimental group is 2.63% and 13.70% of the control group at week 1(P = 0.0131), and73.33% of the experimental group and 56.94% of the control group at week 4(P = 0.0369). No significant differences were found between the two groups on the Physicochemical indexes(all P >0.05). No adverse events or reactions occurred in the experimental groups.CONCLUSION: Jinying capsule can reduce the dosage of antibiotics needed for PID treatment, and improve the symptoms in PID patients.

Effect and Safety of Kangfuyan Capsules(抗妇炎胶囊)for Relieving Chronic Pelvic Pain:A Multicenter,Randomized,Controlled,Double-Blind,Parallel-Group Clinical Trial

Objective To evaluate the effect and safety of Kangfuyan Capsules(抗妇炎胶囊)for treating pelvic inflammatory disease(PID)in patients with chronic pelvic pain(CPP)in a multicenter,randomized,controlled,double-blind,parallel-group clinical trial.Methods Totally,240 PID patients with CPP were randomized into 2 groups using a computer generated random number at a 1:1 ratio from 10 hospitals in China between September 2014 and November 2015.Patients received either oral Kangfuyan Capsules or Gongyanping Capsules(宫炎平胶囊,control);the regimen for both groups comprised 4 capsules(3 times daily)for 12 weeks,with follow-up visit 4 weeks after treatment.The visual analogue scale(VAS)scores,clinical responses,remarkable cure rates for each symptom,and quality of life scores were assessed at baseline,and after 1,2,and 3 months.Adverse events were also recorded.Results The VAS scores were significantly lower(P<0.05),whereas the clinical responses,remarkable cure rates for lower abdominal pain,uterine tenderness,adnexal mass,and adnexal tenderness,and Health-related quality of life(EQ-5D)scores were higher in the Kangfuyan group than in the control group at 3 months(P<0.05).Common treatment-related adverse events included high hepatic enzyme levels,reduced hemoglobin levels,and elevated platelet counts,although all the adverse events were either mild or moderate in severity.Conclusion Compared with Gongyanping therapy,Kangfuyan therapy yielded markedly better analgesia effects for CPP caused by PID,with obvious long-term efficacy and good safety.(Registration No.ChiCTR190022732)

Efficacy and safety of Xinfeng capsule in patients with rheumatoid arthritis:a multi-center parallel-group double-blind randomized controlled trial

OBJECTIVE:To evaluate the efficacy and safety of Xinfeng capsule in patients suffering rheumatoid arthritis(RA).METHODS:A multi-center parallel-group designed,double-blind,randomized,controlled trial was conducted.Totally 304 RA patients were assigned to two groups:one group was administered Xinfeng capsule(XFC) plus the placebo of leflunomide and the other given leflunomide(LEF) plus the placebo of XFC for twelve weeks.The clinical and laboratory parameters were compared at baseline and fourth,eighth,and twelfth weeks.RESULTS:After twelve-week treatment,patients in two groups all showed some trend of effectiveness when compared in terms of American Rheumatism Association(ACR) recommended 20%,50%,70%improvement criteria,but it was insignificant.The validity in ameliorate modified disease activity score(DAS28) and laboratory indexes as erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),rheumatoid factor(RF) were also found no difference.The score of health assessment questionnaire(HAQ),self-rating anxiety scale(SAS),self-rating depression scale(SDS) and quality of life questionnaire with rheumatoid arthritis(RAQOL)both lower than the first week and the changes showed no difference.However,the score of SDS dropped more in XFC group than in the other.A total of 147 adverse reaction cases were reported,which shows no difference between the two groups.The most common adverse reactions were hepatic impairment,anemia,leukocytopenia,epigastric discomfort and phalacrosis.CONCLUSION:XFC demonstrated better improvement in the scores of SDS and compared with those of LEF group.

Evaluation of the Potential Inhibitory Activity of A Combination of L.Acidophilus,L.Rhamnosus and L.Sporogenes on Helicobacter Pylori：A Randomized Double-Blind Placebo-Controlled Clinical Trial

Objective： To investigate whether three strains of probiotics, L. acidophilus, L. rhamnosus, and L. sporogenes, had significant inhibitive effects on Helicobacter pylori（H. pylori）. Methods： This is a 4-week, randomly assigned, parallel-group, doubled-blind, and placebo-controlled study. Fifty patients with a positive H. pylori infection urea breath test（△UBT） result 〉 10% and without ulcer symptoms were randomized into a treatment group and a placebo group by a computer generated allocation sheet with 1：1. These subjects took one capsule of probiotics or placebo twice daily. The primary measurement was the change in △UBT values. Results： The △UBT values during the 4-week treatment period and the 2-week follow-up period were not significantly different between the treatment group and the placebo group, indicating that the inhibitive effects on H. pylori were comparable between both groups. The monocyte count（%） was 5.77±1.11 in the treatment group versus 5.09±1.12 in the placebo group（P=0.044）, and the basophile count was 0.55±0.32 in the treatment group versus 0.36±0.23 in the placebo group（P=0.024） at week 2 of the treatment period, both of which reached statistical significance. The monocyte count was 5.75±1.26 in the treatment group and 4.72±0.99 in the placebo group at the end of the follow-up period（P=0.003）. Conclusions： There was no significant inhibitive effects of the three probiotic strains（L. acidophilus, L. rhamnosus, and L. sporogenes） on H. pylori. Probiotics can not play the same role as antibiotics in the eradication of H. pylori, the role of probiotics is likely to be important as adjuvant to the triple or quadruple therapy for H. pylori, especially in resistance cases.

Efficacy of Huadananshen mistura on insomnia: a randomized, double-blind, placebo-controlled, and multi-center clinical trial

OBJECTIVE: To evaluate the effect of Huadananshen mistura in clinical treatment of Chinese patients with insomnia. METHODS: In this randomized, double-blind, placebo-controlled, multi-center study, 244 patients with insomnia were randomly assigned to a placebo group, a low-dose (10 mL/day), or a high-dose (20 mL/day) mistura group. Efficacy was assessed by using the sleep dysfunction rating scale (SDRS) and Clinical Global Impression-Improvement (CGI-I) scores. Safety and tolerability assessments included emergent adverse events, laboratory tests, and electrocardiograms. RESULTS: Total SDRS scores decreased in all three groups, and there were significant differences between the placebo group and the lowand high-dose mistura groups (P=0.000). CGI-I ratings in the lowand high-dose mistura groups were sig-nificantly better than that of the placebo group (P= 0.000). Incidences of rebound insomnia were similar in all three groups (placebo group: 6.94% , low-dose mistura group: 12.99% , and high-dose mistura group: 10.96% ; P=0.475). The efficacy of Huadananshen mistura in the lowor high-dose group was significantly better than that of the placebo group (P=0.000), but with no significant difference found between the lowand high-dose mistura groups (P=0.887). The rates of adverse events were similar in the three groups (placebo 2.44% , low-dose mistura 0%, and high-dose mistura 5%; P=0.088). CONCLUSION: Huadananshen mistura is an effective and generally well-tolerated hypnotic medicine for the treatment of Chinese patients with insomnia.

Pay-it-forward gonorrhea and chlamydia testing among men who have sex with men in China:a study protocol for a three-arm cluster randomized controlled trial

Background:Gonorrhea and chlamydia testing rates are poor among Chinese men who have sex with men(MSM).A quasi-experimental study suggested that a pay-it-forward strategy increased dual gonorrhea/chlamydia testing among MSM.Pay-it-forward offers an individual a gift(e.g.,a free test)and then asks the same person if they would like to give a gift to another person.This article reports the protocol of a randomized controlled trial to evaluate dual gonorrhea/chlamydia test uptake and other outcomes among MSM in three arms-a pay-it-forward arm,a pay-what-you-want arm,and a standard of care arm.Methods:Three hundred MSM will be recruited at three HIV testing sites in Guangzhou and Beijing.Testing sites include two hospital-based MSM sexually transmitted diseases clinics and one MSM community-based organization.Eligible participants will be born biologically male,aged 16 years or older,reporting previous anal sex with another man,having never participated in the pay-it-forward program,without previous gonorrhea and chlamydia testing in the past 12 months,and residing in China.Following a cluster randomized design,every cluster of ten participants will be randomly allocated into one of three arms:(1)a pay-it-forward arm in which men are offered free gonorrhea and chlamydia testing and then asked whether they would like to donate("pay it forward")toward testing for future testers;(2)a pay-what-you-want arm in which men are offered free testing and told to decide how much to pay after receiving the test;(3)a standard of care arm in which men can pay the full price for dual gonorrhoea and chlamydia testing.The primary outcome is dual gonorrhoea/chlamydia testing as verified by administrative records.Secondary outcomes include incremental cost per test,incremental cost per diagnosis,community connectedness,and social cohesion.Primary outcome will be calculated for each arm using intention-to-treat and compared using one-sided 95%confidence intervals with a margin of 20%increase defined as superiority.Discussion:This study will examine the pay-it-forward strategy in comparison to the standard of care in improving test uptake for gonorrhea and chlamydia.We will leverage the cluster randomized controlled trial to provide scientific evidence on the potential effect of pay-it-forward.Findings from this study will shed light on novel intervention methods for increasing preventive health service utilization and innovate ways to finance it among communities.Trial registration:ClinicalTrials.gov,NCT03741725.Registered on 12 November 2018.

Efficacy of Zhenjingdingzhi decoction in treating insomnia with Qi-deficiency of heart and gallbladder:a randomized,double-blind,controlled trial

OBJECTIVE: To evaluate the clinical efficacy of Zhenjingdingzhi decoction in treating insomnia with Qi-deficiency of heart and gallbladder.METHODS: We conducted a double-blind,randomized,controlled trial involving 100 patients with insomnia of Qi-deficiency of heart and gallbladder.Patients were randomly divided into the treatment group(n = 50) and the control group(n = 50) according to a random number table. The treatment group was given Zhenjingdingzhi decoction,while the control group was treated with Suanzaoren decoction. the pharmacological treatment lasted for 8weeks. The clinical efficacy was assessed by using Spiegel scale,Pittsburgh sleep quality index(PSQI)and Traditional Chinese Medicine(TCM) syndrome scores.RESULTS: Comparing Spiegel scores between the two groups at 4 and 8 weeks,the differences in curative effect between the two groups were both significant(both P < 0.05). The total effective rate was46% in the treatment group and 27.7% in the control group at 4 weeks,and 80% and 53.2% at 8weeks,respectively; After 8 weeks,PSQI scores showed that the total effective rates differed significantly between the two groups(P < 0.01): 84% in the treatment group and 59.6% in the control group; In improving sleep quality and sleep duration,the curative effect of the treatment group was better than that of the control group(P < 0.05).TCM syndrome,especially insomnia and palpitation,was improved better in the treatment group after 8 weeks as compared to that in the control group(P < 0.05). The total effective rate of the two groups was 84% and 66%,respectively.CONCLUSION: Zhenjingdingzhi decoction is effective and safe for the treatment of insomnia with Qi-deficiency of heart and gallbladder,especially for improving sleep quality and sleep duration.

Gravid oviposition sticky trap and dengue non-structural 1 antigen test for early surveillance of dengue in multi-storey dwellings: study protocol of a cluster randomized controlled trial

Background:Dengue is a global disease,transmitted by the Aedes vectors.In 2018,there were 80615 dengue cases with 147 deaths in Malaysia.Currently,the nationwide surveillance programs are dependent on Aedes larval surveys and notifications of lab-confirmed human infections.The existing,reactive programs appear to lack sensitivity and proactivity.More efficient dengue vector surveillance/control methods are needed.Methods:A parallel,cluster,randomized controlled,interventional trial is being conducted for 18 months in Damansara Damai,Selangor,Malaysia,to determine the efficacy of using gravid oviposition sticky(GOS)trap and dengue non-structural 1(NS1)antigen test for early surveillance of dengue among Aedes mosquitoes to reduce dengue outbreaks.Eight residential apartments were randomly assigned into intervention and control arms.GOS traps are set at the apartments to collect Aedes weekly,following which dengue NS1 antigen is deteaed in these mosquitoes.When a dengue-positive mosquito is detected,the community will be advised to execute vector search-and-destroy and protective measures.The primary outcome concerns the the percentage change in the(i)number of dengue cases and(ii)durations of dengue outbreaks.Whereas other outcome measures include the change in density threshold of Aedes and changes in dengue-related knowledge,attitude and practice among cluster inhabitants.Discussion:This is a proactive and early dengue surveillance in the mosquito vector that does not rely on notification of dengue cases.Surveillance using the GOS traps should be able to efficiently provide sufficient coverage for multistorey dwellings where population per unit area is likely to be higher.Furthermore,trapping dengue-infected mosquitoes using the GOS trap,helps to halt the dengue transmission carried by the mosquito.It is envisaged that the results of this randomized controlled trial will provide a new proactive,cheap and targeted surveillance tool for the prevention and control of dengue outbreaks.Trial registration:This is a parallel-cluster,randomized controlled,interventional trial,registered at ClinicalTrials.gov(ID:NCT03799237),on 8th January 2019(retrospectively registered).

Rhus coriaria L. increases serum apolipoprotein-A1 and high-density lipoprotein cholesterol levels： a double-blind placebo-controlled randomized clinical trial

Background： Lipid-lowering effect ofRhus coriaria L. （Rhus） has been investigated in multiple animal stud- ies with promising results. Nonetheless, its clinical efficacy has not been adequately examined. Objective： The aim of this study was to evaluate the lipid-lowering effects of Rhus among patients with hyperlipidemia. Design, setting, participants and interventions： The study was designed as a two-arm, double-blind placebo-controlled randomized clinical trial, using a parallel design. Eighty patients with primary hyper- lipidemia were randomly assigned to receive Rhus capsules or placebo for 6 weeks. Main outcome measures： The serum lipid levels, apolipoprotein-A1 （Apo-A1） and apolipoprotein-B （Apo-B） were measured. Results： Mean serum high-density lipoprotein cholesterol （HDL-C） and Apo-Al levels were significantly increased in the Rhus group, compared with the placebo group, after 6 weeks of intervention （P= 0.001）. The analysis of covariance test including age, gender, body mass index （BMI）, and smoking as co-variables revealed that the increase in HDL-C and Apo-A1 levels remained significant, and increases in HDL-C were dependent on the increase in Apo-A1 levels. No significant difference was observed between Rhus and placebo groups in terms of mean reductions in total cholesterol, low-density lipopro- tein cholesterol and triglyceride levels; however, more significant improvement was observed among obese patients （BMI≥ 30 kg/m^2）. Conclusion： The study showed significant increases in HDL-C and Apo-Al levels in response to Rhus sup- plementation in patients with hyperlipidemia. Trial registration： ClinicalTrials.gov ID： NCT02295293.

Double-blinded,randomized clinical trial of Gegen Qinlian decoction pinpoints Faecalibacterium as key gut bacteria in alleviating hyperglycemia

Background:Accumulating evidence suggests that metabolic disorders,including type 2 diabetes mellitus(T2DM),can be treated with traditional Chinese medicine formulas,such as the Gegen Qinlian decoction(GQD).This study elucidates the mechanisms by which gut microbes mediate the anti-diabetic effects of GQD.Methods:We conducted a double-blind randomized clinical trial involving 120 untreated participants with T2DM.During the 12-week intervention,anthropometric measurements and diabetic traits were recorded every 4 weeks.Fecal microbiota and serum metabolites were measured before and after the intervention using 16S rDNA sequencing,liquid chromatography-mass spectrometry,and Bio-Plex panels.Results:Anti-diabetic effects were observed in the GQD group in the human trial.Specifically,glycated hemoglobin,fasting plasma glucose,and two-hour postprandial blood glucose levels were significantly lower in the GQD group than in the placebo group.Additionally,Faecalibacterium was significantly enriched in the GQD group,and the short-chain fatty acid levels were higher and the serum inflammation-associated marker levels were lower in the GQD group compared to the placebo group.Moreover,Faecalibacterium abundance negatively correlated with the levels of serum hemoglobin,fasting plasma glucose,and pro-inflammatory cytokines.Finally,the diabetes-alleviating effect of Faecalibacterium was confirmed by oral administration of Faecalibacterium prausnitzi(DSMZ 17677)in T2DMmousemodel.Conclusions:GQD improved type 2 diabetes primarily by modulating the abundance of Faecalibacterium in the gut microbiota,alleviating metabolic disorders and the inflammatory state.

A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Study of the Effects of Tongxinluo Capsules in Acute Coronary Syndrome Patients with High On-Treatment Platelet Reactivity

Background： High platelet reactivity （HPR） during clopidogrel treatment predicts postpercutaneous coronary intervention （PCI） ischemic events strongly and independently. Tongxinluo capsules （TCs） are a traditional Chinese medicine formulation used as antiplatelet treatment. However, its efficacy against HPR is not known. The aim of the present study was to evaluate the effects of TCs in acute coronary syndrome （ACS） patients with HPR. Methods： This multicenter, randomized, double-blind, placebo-controlled study prospectively analyzed 136 ACS patients with HPR who underwent PCI. The patients were enrolled from November 2013 to May 2014 and randomized to receive placebo or TCs in addition to standard dual antiplatelet therapy （DAPT） with aspirin and clopidogrel. The primary end points were the prevalence of HPR at 30 days and the mean change in P2YIz reaction units （PRUs） between baseline and 30 days. Survival curves were constructed with Kaplan-Meier estimates and compared by log-rank tests between the two groups. Results： Both groups had a significantly reduced prevalence of HPR at 30 days versus baseline, but the TC group, compared with the placebo group, had greater reduction （ 15.8% vs. 24.8%, P = 0.013）, especially among patients with one cytochrome P450 2C 19 loss of function （LOF） allele （χ2 = 2.931, P = 0.047）. The TC group also had a lower prevalence of HPR （33.3% vs. 54.2%, t - 5.284, P 0.022） and superior performance in light transmittance aggregometry and higher levels of high-sensitivity C-reactive protein （hsCRP）, but the composite prevalence ofischemic events did not differ significantly （χ2 = 1.587, P = 0.208）. Conclusions： In addition to standard DAPT with aspirin and clopidogrel, TCs further reduce PRU and hsCRP levels, especially in patients carrying only one LOF allele. The data suggest that TCs could be used in combination therapy for ACS patients with HPR undergoing PCI.

Effects of Qizhukangxian granules on idiopathic pulmonary fibrosis:a randomized,double blind,placebo-controlled and multicenter clinical pilot trial

OBJECTIVE:To evaluate the effects of Qizhukangxian granules(QG)on idiopathic pulmonary fibrosis(IPF).METHODS:This is a randomized,double blind,placebo-controlled and multicenter clinical pilot trial.Six medical centers in Tianjin,China,participated in the study.A total of 120 IPF patients were enrolled and randomized into two groups,with 60 patients in each group.The treatment group was treated with QG,while the control group received a Qizhukangxian placebo.The pharmacological treatment lasted for 48 weeks from the enrollment date.The indexes of patients were recorded on the admission day and at the end of the 24th and 48th weeks.Data were analyzed to study the effects of QG;forced vital capacity,change in forced vital capacity and maximal 6-min walk test(6MWT)distance were the primary endpoints.Secondary endpoints were percentage of patients with episodes of acute exacerbation of IPF,pulmonary function,changes in pulse oxygen saturation during the 6MWT,dyspnea score,St.George's respiratory questionnaire score,arterial blood gas analyses and the total Traditional Chinese Medicine symptom pattern score.RESULTS:After 24 weeks of treatment,QG showed greater efficacy than the placebo in certain parameters,including the dyspnea score,Traditional Chinese Medicine symptom pattern score and some indicators in the St.George's respiratory questionnaire score.Analysis of the indexes obtained from all patients at the end of the 48th week showed that the therapeutic effects in the treatment group were significantly better than those in the control group because remarkable differences were observed in most of the primary and secondary endpoints between the two groups,except for the maximal distance of the 6MWT and arterial blood gas analyses.No adverse reaction was observed in either group during the 48-week trial treatment period.CONCLUSION:QG could effectively treat IPF patients by ameliorating pulmonary function,improving the quality of life and lowering the percentage of acute exacerbations.

Effect of a Traditional Chinese Medicine combined therapy on adolescent idiopathic scoliosis:a randomized controlled trial

OBJECTIVE:To evaluate the effectiveness of a combined Traditional Chinese Medicine(TCM) therapy versus conventional treatment on adolescent idiopathic scoliosis.METHODS:One hundred twenty outpatients with mild and moderate adolescent idiopathic scoliosis were randomly divided into a TCM group(TCMG)and a brace group(CG).TCMG patients underwent Daoyin,Tuina,and acupotomology therapies.CG patients were treated with a Milwaukee brace.Each patient's Cobb angle was measured after 12 and 24 months of treatment,and pulmonary function was determined after 12 months of treatment.Average electromyogram(AEMG) ratio of the surface electromyogram was measured after 6 and 12 months of treatment and followed-up after 18 and 24 months.RESULTS:The Cobb angle significantly decreased in both groups after 12 months of treatment compared with before treatment(P< 0.05).The percentages of original Cobb angle in TCMG and CG were51.4%and 47.8%(P > 0.05) after 12 months and62.5%and 34.7%(P < 0.05) after 24 months,respectively.Pulmonary function significantly improved after 12 months in TCMG(P < 0.05) but significantly decreased in CG(P < 0.05).The AEMG ratio was significantly lower(P < 0.01) and tended to remain at1 after stopping treatment in TCMG,but increased in CG(P<0.05).CONCLUSION:TCM combined therapy can prevent the progression of scoliosis.The AEMG ratio is a promising index that could replace radiography in the evaluation of treatment effect and progression in scoliosis.

Effects of Feiwei granules in the treatment of idiopathic pulmonary fibrosis:a randomized and placebo-controlled trial

OBJECTIVE： To document the therapeutic effects of Feiwei granules （FGs） for idiopathic pulmonary fi-brosis （IPF）.METHODS： One hundred cases with IPF were ran- domized into the treatment group （80） and control group （20）. Both groups were given basic treat- ment with prednisone. The treatment group was given FGs, and the control group was given Jinshui- bao capsules （JCs）. Treatment lasted for 6 months. The Medical Research Council Dyspnea Scale （MRCDS）, the Saint George＇s Hospital Respiratory Questionnaire （SGHRQ）, pulmonary function, the Traditional Chinese Medicine Syndrome Score （TC- MSS）, 6-min walking test （6MWT） and blood gas analyses were recorded before the study as well as 3 months and 6 months after treatment.RESULTS： FGs showed greater efficacy than the control in certain parameters between before the study and 6 months, and between 3 months and 6 months, in the MRCDS, some indicators in the SGHRQ, and the TCMSS. There were no significant differences between the treatment group and con- trol group in the remainder of the indices evaluat- ed. In the treatment group, there were significant differences in before and after treatment in the MRCDS, SGHRQ, TCMSS and 6MWT.

Efficacy of Wuda Granule on Recovery of Gastrointestinal Function after Laparoscopic Bowel Resection:A Randomized Double-Blind Controlled Trial

Objective:To evaluate the efficacy and safety of Wuda Granule(WDG)on recovery of gastrointestinal function after laparoscopic bowel resection in the setting of enhanced recovery after surgery(ERAS)-based perioperative care.Methods:A total of 108 patients aged 18 years or older undergoing laparoscopic bowel resection with a surgical duration of 2 to 4.5 h were randomly assigned(1:1)to receive either WDG or placebo(10 g/bag)twice a day from postoperative days 1-3,combining with ERAS-based perioperative care.The primary outcome was time to first defecation.Secondary outcomes were time to first flatus,time to first tolerance of liquid or semi-liquid food,gastrointestinal-related symptoms and length of stay.Subgroup analysis of the primary outcome according to sex,age,tumor site,surgical time,histories of underlying disease or history of abdominal surgery was undertaken.Adverse eventse were observed and recorded.Results:A total of 107patients[53 in the WDG group and 54 in the placebo group;61.7±12.1 years;50 males(46.7%)]were included in the intention-to-treat analysis.The patients in the WDG group had a significantly shorter time to first defecation and flatus[between-group difference-11.01 h(95%CI-20.75 to-1.28 h),P=0.012 for defecation;-5.41 h(-11.10 to 0.27 h),P=0.040 for flatus]than the placebo group.Moreover,the extent of improvement in postoperative gastrointestinal-related symptoms in the WDG group was significantly better than that in the placebo group(P<0.05).Subgroup analyses revealed that the benefits of WDG were significantly superior in patients who were male,or under 60 years old,or surgical time less than 3 h,or having no history of basic disease or no history of abdominal surgery.There were no serious adverse events.Conclusion:The addition of WDG to an ERAS postoperative care may be a viable strategy to enhance gastrointestinal function recovery after laparoscopic bowel resection surgery.(Registry No.ChiCTR2100046242)