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.

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)].

Clinical study of Guben Quyu Jiedu formula combined with western medicine on patients with acute exacerbation of chronic obstructive pulmonary disease: a double-blinded randomized controlled trial

Objective To observe the clinical effect of Guben Quyu Jiedu Formula(GQJF)combined with Western medicine on acute exacerbation of chronic obstructive pulmonary disease(AECOPD)patients with Fei-Shen deficiency and blood stasis-toxin obstructive Fei syndrome.Methods A double-blinded,randomized controlled trial was performed.Totally 60 AECOPD patients were randomly assigned to the trial group and the control group,30 in each group.All patients received routine Western medical treatment,the trial group additionally took GQJF,while those in the control group received placebo.After 10-day treatment,the changes of traditional Chinese Medicine(TCM)syndrome score,symptom integral,WBC,eosinophile granulocyte(EOS),C-reaction protein(CRP),procalcitonin(PCT),throm-belastogram(TEG)R value,K value,α angle,Ma value,arterial partial pressure of oxygen(PaO2)and arterial partial pressure of carbon dioxide(PaCO2)were compared before and after treatment.And the clinical efficacy was evaluated.Results The efficiency of TCM syndrome was 86.67%(26/30)in the trial group,which was 43.33%(13/30)in the control group,with a statistical difference between the two groups(P<0.05).All of the clinical symptoms,signs,total score and related laboratory examinations in the trial group were much better than those before the therapy(P<0.01).In the control group,cough,expectoration,panting,fever,cyanosis,chest tiredness and pain,weariness,dry rale,wet rale,insomnia,total scores,WBC,EOS,CRP,PCT,PaCO2,PaO 2 and TEG(α angle,Ma value)got better after treatment(P<0.05,P<0.01).Cough,expectoration,panting,breathless after activity,weariness,dark complexion,irritability,insomnia,total scores,EOS,CRP,PCT,PaCO2,and TEG(α angle,Ma value)in the trial group were better than the control group(P<0.05,P<0.01).Conclusion GQJF combined with Western medicine in the treatment of AECOPD(Fei-Shen deficiency and blood stasis-toxin obstructive Fei syndrome),the efficiency is superior to that of simple Western medicine treatment.

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.

Botulinum toxin type A for treating chronic low back pain:A double blinded randomized control study

BACKGROUND Low back pain(LBP)is a prevalent issue that orthopedic surgeons frequently address in the outpatient setting.LBP can arise from various causes,with stiffness in the paraspinal muscles being a notable contributor.The administration of Botulinum toxin type A(BoNT-A)has been found to alleviate back pain by relaxing these stiff muscles.While BoNT-A is approved for use in numerous conditions,a limited number of randomized clinical trials(RCTs)validate its efficacy specifically for treating LBP.AIM To study the safety and the efficacy of BoNT-A in minimizing pain and improving functional outcomes in patients of chronic LBP(CLBP).METHODS In this RCT,adults aged 18-60 years with mechanical LBP persisting for at least six months were enrolled.Participants were allocated to either the Drug group,receiving 200 Ipsen Units(2 mL)of BoNT-A,or the Control group,which received a 2 mL placebo.Over a 2-month follow-up period,both groups were assessed using the Visual Analog Scale(VAS)for pain intensity and the Oswestry Disability Index(ODI)for disability at the start and conclusion of the study.A decrease in pain by 50%was deemed clinically significant.RESULTS The study followed 40 patients for two months,with 20 in each group.A clinically significant reduction in pain was observed in 36 participants.There was a statistically significant decrease in both VAS and ODI scores in the groups at the end of two months.Nonetheless,when comparing the mean score changes,only the reduction in ODI scores(15 in the placebo group vs 16.5 in the drug group,clinically insignificant)was statistically significant(P=0.012),whereas the change in mean VAS scores was not significant(P=0.45).CONCLUSION The study concludes that BoNT-A does not offer a short-term advantage over placebo in reducing pain or improving LBP scores in CLBP patients.

Effect of <i>Lactobacillus brevis</i>SBC8803 on Gamma-Glutamyl Transferase in Japanese Habitual Drinkers: A Double-Blind, Placebo-Controlled Study

A randomized, double-blind, placebo-controlled clinical trial in Japanese habitual drinkers was conducted to evaluate the efficacy of Lactobacillus brevis SBC8803 to alleviate adverse effect of alcohol. Subjects who drank habitually and had moderately higher levels of gamma-glutamyl transferase (GGT) (50 - 100 IU/L) were enrolled. The levels of transaminases in these subjects were almost within normal levels (aspartate transaminase (AST) <30 IU/L and alanine transaminase (ALT) <40 IU/L). Either the capsules containing placebo (n = 23) or 130 mg (4.0 × 1010 colony-forming units) of live L. brevis SBC8803 (n = 22) per day were administered for the continuous eight weeks (56 days). During the period, the subjects both in test group and placebo groups have kept each drinking behavior as usual. Regarding lipid metabolism, triacylglycerol (TG) levels in the male test group significantly decreased at week 4 as compared with week 0. Biomarkers of hepatocytes-damage;AST and ALT levels showed no significant differences between the pla- cebo and test groups at both weeks 4 and 8. Oxidative stress marker;GGT at weeks 4 was significantly lower in the test group than that in the placebo group (p = 0.017), but not at weeks 8. However, taking a reduced rate of GGT at weeks 8 comparing with that at week 0, that in the test group showed larger value comparing with that in the placebo group. These data about TG and GGT suggest that, although efficacy of L. brevis SBC8803 is limited in this study, intake of the probiotic may alleviate alcoholic influence in lipid metabolism and oxidative stress.

The Efficacy and Safety of a Patent Pending Combination of Ginger and Goldenrod Extracts on the Management of Cold Symptoms: A Randomized, Double-Blind Controlled Trial

Objective: In a randomized, double-blind, exploratory, active-controlled trial, the efficacy and safety of a patent-pending combination of Ginger and Goldenrod extracts (BDI-630) in alleviating cold symptoms in community-dwelling adults was compared to a combination of standardized amounts of Echinacea (EC) components. Methods: 44 healthy adults, experiencing new onset of cold symptoms were randomly assigned to receive either BDI-630 (900 mg) or EC (500 mg) twice daily for 10 days. The severity of cold symptoms and the quality of life was assessed by self-reporting of subjects using the Wisconsin Upper Respiratory Symptom Survey (WURSS-21? 2004). Results: The intent-to-treat population (ITT) consisted of 44 subjects (n = 22 for BDI-630;n = 22 for EC). The modified ITT (mITT) population consisted of 40 subjects, excluding four subjects with major protocol deviations related to inclusion/exclusion criteria and/or use of prohibited drugs from the efficacy analysis (n = 3 for BDI-630 and n = 1 for EC). Results indicated a sig-nificant difference between the two groups: the superiority of BDI-630 over EC was particularly noticeable between Day 1 and Day 7, as demonstrated by a 14-fold difference of the mean percentage of change of total score from baseline in the mITT population. Adverse events (AEs) following the intake of BDI-630 were mostly limited to mild gastrointestinal intolerance in less than 10% of the subjects. Conclusions: BDI-630 was shown to be more effective than EC in alleviating cold symptoms in the adult population, particularly during the first 7 days of treatment. BDI-630 was very well tolerated by all subjects.

EFFECT OF ADDED DIETARY CALCIUM ON ESOPHAGEAL EPITHELIAL-CELL PROLIFERATION IN SUBJECTS AT HIGH RISK FOR ESOPHAGEAL CANCER: A DOUBLE-BLIND INTER-VENTION STUDY

A randomized double-blind intervention trial was carried determine whether oral calcium supplementation could lower the proliferation of epithelial cells of the esophagus. 41 subjects identified with precancerous lesions by histopathology were randomized to receive oral supplementation of their conventional diets with 0.6 g of calcium as calcium carbonate or placebo. Both at the entry to the study and at the end of the treatment, seven months later, the subjects were examined, with an emphasis on the frequency and distribution of proliferating epithelial cells of the esophagus. Patterns of cell proliferation was defined by dividing the esophageal epithelium into cell columns oriented perpendicularly to the basal cell layer and by comparing the numbers and fractions of tritiated thymidine-labeled epithelial cells in the various cell columns and cell compartments.Before dietary supplementation with calcium, the profile of proliferating epithelial cells in the esophageal compartments in calcium group is similar to that in the placebo group, which is comparable to that previously observed in subjects with high risk for esophageal cancer. Seven months after supplementation having been started, in calcium group, proliferation was significantly reduced and the profile of the esophageal columns approached to that previously observed in subjects at low risk for esophageal cancer, however, in the placebo group, the proliferation and profile maintain at the same level as that before supplementation. Our findings indicate that oral calcium supplementation induces a more quiescent equilibrium in epithelial-cell proliferation in the esophageal mucosa of the subjects at high-risk for esophageal cancer, similar to that observed in subjects at low risk.

Effects of Depth of Needle Insertion with Risperidone Long-Acting Injectable in Persons with Schizophrenia: A Randomized Double-Blind Study

In some cases, if the insertion depth is shallower than expected, intramuscular (IM) injection of risperidone long-acting injectable (RLAI) may not penetrate the muscle fascia. However, if needle insertion depth is deeper than anticipated, needle penetration may cause damage to nerves, arteries and veins. Few clinical studies were done to evaluate the depth of needle length insertion reaching the intended gluteal muscle. The aim of this study was to evaluate the suitable depth of injecting RLAI. Twenty-six patients with schizophrenia were treated with RLAI, and randomly divided into two groups: 50 mm needle inserted group (Group-D, deep insertion, n = 13) and 20 mm needle insertion group (Group-S, shallow insertion, n = 13). For Group-S, the needle length was marked with a spacer at exactly 20 mm. Injections were performed by the psychiatrist or nurse, alternating between the two gluteal sites by double-cross method every two weeks. Clinical psychotic symptoms and injection site reactions were recorded throughout the study period. Experienced psychologists who were blinded from the needle-length experimental variable evaluated patients’ psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS) every two weeks. The plasma 9-hydroxyrisperidone (9-OH-RIS) concentrations were measured every two weeks;comparison data were determined on the 8th week and the 14th week. No significant difference was observed in 9-OH-RIS concentrations, psychotic symptoms, injection site skin reactions of subjects in both groups. However, in Group-D, injection site adverse reactions were confirmed in two subjects (15%). In Group-S, injection site reactions were confirmed in six subjects (46%). Although effective 9-OH-RIS concentrations were obtained with the insertion using both depth, it was concluded that the 50 mm insertion length was more suitable for dorsogluteal IM injections in adult patients with schizophrenia as demonstrated by the incidence of local adverse skin reactions.

Shexian Bupleurum Alleviates Insomnia and Improves Symptoms of Anxiety and Depression:A Randomized Double-Blind Placebo-Controlled Clinical Trial

Objective:To observe the clinical efficacy of Shexian bupleurum on insomnia based on evaluation scales and polysomnogram(PSG).Methods:A total of 260 patients suffering from insomnia admitted to the outpatient department of Handan Central Hospital were included in a randomized,double blind,placebo-controlled trial.The patients were randomly divided into two groups:a control group(receiving placebo,n=150),and an intervention group(receiving Shexian bupleurum treatment,n=110).The clinical trial lasted for 4 weeks.The Pittsburgh Sleep Quality Index(PSQI),Insomnia Severity Index(ISI),Patient Health Questionnaire(PHQ)-9,Generalized Anxiety Disorder(GAD)-7,17 items of Hamilton Depression Scale(HAMD-17),and Hamilton Anxiety Scale(HAMA)were used to evaluate the patients at baseline as well as two weeks and four weeks after treatment;the Treatment Emergent Symptom Scale(TESS)was used to evaluate adverse reactions;polysomnography(PSG)was used to monitor and analyze their sleep characteristics at baseline and four weeks after treatment.Results:The PSQI,ISI,PHQ-9,HAMD-17,and HAMA scores of the intervention group significantly decreased compared to the control group,while the total sleep time,rapid eye movement sleep latency,stage 2 sleep,deep sleep,rapid eye movement sleep,and sleep efficiency of the intervention group significantly increased compared to the control group.The PHQ-9 score of the control group only decreased two weeks after treatment(p<0.05)compared to the intervention group.In addition,there were no obvious adverse events in both the intervention group and the control group.Conclusion:Shexian bupleurum not only improves sleep quality,but also relieves depression and anxiety in patients who suffer from insomnia.

Xi-Feng-Hua-Shi granules for diarrhea-predominant irritable bowel syndrome:protocol for a randomized,double-blind,placebo-controlled multi-center clinical trial

Background:Irritable bowel syndrome(IBS)is a common functional bowel disorder that can severely affect the quality of life of patients.Limited drugs have been reported for modern medical IBS treatment.The advantages of traditional Chinese medicine(TCM)treatment are gradually becoming prominent.Xi-Feng-Hua-Shi granules have been clinically used for diarrhea-predominant IBS(IBS-D)treatment for many years in TCM practice.Thus,this study aimed to further verify the effectiveness and safety of Xi-Feng-Hua-Shi(XFHS)granules in IBS-D treatment through a randomized,double-blind,placebo-controlled multi-center clinical trial and provide high-quality evidence for its effectiveness and safety in treatment,as well as provide a basis for clinical rational drug use and explore new clinical IBS-D treatment plans.Methods:A randomized,double-blind,placebo-controlled multi-center clinical trial will be performed in 23 hospitals.A total of 300 participants will be randomly divided into the experimental group(prescribed with XFHS granules)and the control group(prescribed with the placebo granules),with 150 participants in each group.The appearance,shape,color,and taste of the placebo granules are the same as those of XFHS granules.All participants will receive a 4-week treatment and a 6-month follow-up.The primary outcome is the overall clinical efficacy;the secondary outcomes are the IBS-Symptom Severity Score(IBS-SSS),TCM Syndrome Evaluation,and the IBS-Quality of Life(IBS-QoL)score,mental state assessment,and recurrence rate.Outcome measures(including primary and secondary outcome measures)are collected at baseline,as well as 2,4,16,and 28 weeks post-intervention.Discussion:This randomized,placebo-controlled,multi-center trial may provide high-quality evidence for the clinical XFHS granule efficacy in IBS-D treatment.Additionally,this study will conduct safety evaluations to provide a basis for clinical rational drug use.

Modulation of postoperative immune and inflammatory response by immune-enhancing enteral diet in gastrointestinal cancer patients

AIM: To evaluate if the administration of an enteral diet supplemented with glutamine, arginine and omega-3-fatty acids modulates inflammatory and immune responses after surgery. METHODS: A prospective randomized double-blind, clinical trial was performed. Forty-eight patients with gastrointestinal cancer were randomized into two groups, one group was given an isocaloric and isonitrogenous standard diet and the other was fed with the supplemented diet with glutamine, arginine and omega-3-fatty acids. Feedings were started within 48 hours after operation, and continued until day 8. All variables were measured before operation and on postoperative day 1 and 8. Immune responses were determined by phagocytosis ability, respiratory burst of polymorphonuclear cells, total lymphocytes lymphocyte subsets, nitric oxide, cytokines concentration, and inflammatory responses by plasma levels of C-reactive protein, prostaglandin E2 level. RESULTS: Tolerance of both formula diets was excellent.There were significant differences in the immunological and inflammatory responses between the two groups. In supplemented group, phagocytosis and respiratory burst after surgery was higher and C-reactive protein level was lower (P【0.01) than in the standard group. The supplemented group had higher levels of nitric oxide, total lymphocytes, T lymphocytes, T-helper cells, and NK cells. Postoperative levels of IL-6 and TNF-alpha were lower in the supplemented group (P 【0.05). CONCLUSION: It was clearly established in this trial that early postoperative enteral feeding is safe in patients who have undergone major operations for gastrointestinal cancer. Supplementation of enteral nutrition with glutamine, arginine, and omega-3-fatty acids positively modulated postsurgical immunosuppressive and inflammatory responses.

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.

Efficacy of therapeutic ultrasound vs sham ultrasound on pain and physical function in people with knee osteoarthritis: A meta-analysis of randomized controlled trials

AIM: To determine the efficacy of therapeutic ultrasound vs sham for improving pain and physical function immediately post-intervention in people with knee osteoarthritis(OA). METHODS: We hand searched meta-analyses on the topic published in 2010 and updated the search in three electronic databases(MEDLINE, EMBASE, CINAHL) January 1, 2009 to September 5, 2013 to identify relevant studies. The inclusion criteria were human randomized controlled trials published in the English language in which active therapeutic ultrasound was compared tosham ultrasound, data for people with knee OA were reported separately, participants were blinded to treatment allocation and outcomes assessed before and after treatment included pain, self-reported physical function and performance-based physical function. Two reviewers independently screened titles and abstracts retrieved in the search to identify trials suitable for full text review. Data extraction and risk of bias assessment of the identified trials were completed independently by two reviewers. Pooled analyses were conducted using inverse-variance random effects models.RESULTS: We screened 1013 titles and abstracts. Meta-analysis of pain outcomes from 5 small trials(281 participants/OA knees) showed that, compared to sham ultrasound, therapeutic ultrasound improves pain [standardized mean difference(SMD)(95%CI) =-0.39(-0.70--0.08); P = 0.01] but not physical function [self-reported in 3 trials(130 participants/OA knees): SMD(95%CI) =-0.21(-0.55-0.14), P = 0.24; walking performance in 4 trials(130 participants/OA knees): SMD(95%CI) =-0.11(-0.59-0.37), P = 0.65). For the walking performance outcome, the dispersion of the estimated effects exceeded that expected due to sampling error(χ2 = 8.37, P = 0.04, I 2 = 64%). Subgroup analyses of three trials that administered high dose ultrasound improved the consistency(I2 = 28%) but the treatment effect remained insignificant.CONCLUSION: Meta-analyzed double-blind placebocontrolled randomized trials provide low-strength evidence that therapeutic ultrasound decreases knee OA pain and very low-strength evidence that it does not improve physical function.

A DOUBLE BLIND OBSERVATION FOR THERAPEUTIC EFFECTS OF THE TONG LUO KAI BI TABLETS ON RHEUMATOID ARTHRITIS

The therapeutic effects of the Tong Luo Kai Bi Tablets [symbol: see text] in 120 patients with rheumatoid arthritis were observed in this clinical trial by the randomized double blind method. Both the observed group and the control group each had 60 patients. In the observed group treated with the Tong Luo Kai Bi Tablets, 1 case (1.7%) was cured clinically, 27 cases (45.0%) improved markedly, 26 cases (43.3%) improved, with a total effective rate of 90.0%. In the control group treated with Rheumatic Semen Strychni Tablets [symbol: see text], no case was cured, 16 cases (26.7%) improved markedly, 33 cases (55.0%) improved, with a total effective rate of 81.7%. Statistical data showed the Tong Luo Kai Bi Tablets had much better therapeutic effectiveness clinically than the Rheumatic Semen Strychni Tablets (P

A systematic review and meta-analysis for platelet-rich plasma in treatment of knee osteoarthritis

Objective:Knee osteoarthritis(KOA)is a common chronic joint disease that usually occurs in older people,and injuries articular cartilage and cartilage proliferation. Studies have shown that platelet-rich plasma(PRP),as one of non-surgical treatments,is used to alleviate the symptoms of patients with KOA,becoming popular with doctors. In this study,the purpose was to investigate the effects of platelet-rich plasma on the level of pain and function in patients with KOA. Methods:The Pubmed,Cochrane Library,Embase,and Medline were investigated from 2005 through May 2020. All randomized double-blind controlled trials on the effect of PRP injections for KOA were included. Outcome indicators included the Western Ontario and McMaster Universities Arthritis Index(WOMAC)and the Knee Osteoarthritis Outcome Score(KOOS)for function,the visual analogue scale(VAS)for pain,and adverse events(AEs). Review Manager 5.3 was used to calculate these outcome indicators. Results:In this study,(1)Seven studies met the eligibility criteria,including 250 patients in the experiment(PRP)group and 230 patients in the control(no PRP)group.(2)Meta-analysis results showed that the WOMAC scores were differed significantly between the PRP and no PRP groups at the 6 months follow-up(MD=9.63,95%CI:3.29 to 15.96,P=0.003),and 12 months follow-up(MD=3.85,95%CI:2.66 to 5.04,P<0.000 01)(P<0.05). In a comparison of KOOS function scores at the 6 months follow-up,PRP improved knee function scores more than no PRP(MD=8.63,95%CI:0.85 to 16.42,P=0.03)(P<0.05). PRP injections reduced pain more effectively than no PRP injections in patients with KOA at 3,6 months of follow-up,and the VAS pain score showed a significant difference(SMD=0.88,95%CI:0.13 to 1.62,P=0.02)(SMD=0.85,95%CI:0.11 to 1.59,P=0.002)(P<0.05). However,adverse events(AEs)were all not significantly different(RR=0.96,95%CI:0.65 to 1.40,P=0.82)(P>0.05).(3)Results showed that PRP has significant advantages in pain relief and functional improvement. Conclusion:In improving knee function and relieving pain,PRP showed superiority to other non-surgical treatments in long-term follow-up from well-designed double-blind trials. Due to the limited quality and data,more high-quality multi-center studies are required.

The Effectiveness of Diamel in the Treatment of Type 2 Diabetic Patients Receiving Insulin Therapy: A Randomized, Controlled Clinical Trial

Aims/Introduction: Effectiveness of Diamel? on the biochemical variables: fasting blood glucose, postprandial glucose, cholesterol, triglycerides, and glycosylated haemoglobin [HbA1c] in type-2 diabetic patients receiving insulin terapy. Diamel is a natural product composed of trace elements: amino acids, vitamins, cranberry extract, and lettuce extract that have been activated by means of a magnetization process. Materials and methods: Randomized, doubleblind, comparator-controlled clinical trial. A central randomization centre used computer generated tables to allocate treatments. 116 patients suffering from type-2 diabetes mellitus treated with insulin at the Diabetes Care Centre in Pinar del Rio (Cuba), were recruited and randomly. The subjects were separated into two groups: Group A (n = 59), who were administered Diamel and Group B (n = 57) using placebo. The clinical and biochemical variables were assessed for 24 weeks. Results: Two subjects were excluded from the Diamel treatment group during the clinical trial. From the statistical point of view, a significant drop in the levels of the baseline glucose, postprandial glucose, glycated haemoglobin, and triglycerides was observed in the group taking Diamel (Group A). There was observed an increase in insulin requirements and in waist circumference in the subjects of Group B There was not reported any severe or serious adverse reactions during this clinical trial. Conclusion: Diamel (nutritional supplement) together with the administration of insulin in type-2 diabetic patients is useful to optimize the biochemical variables (baseline and postprandial glucose, Hb A1C, plus triglycerides), as well as to prevent the increase of insulin requirements at medium-term.

A slight glance at peer review

In order to ensure that the highest quality of literature is published, most journals utilize a peer review process for manuscripts submitted. Although the primary purpose for this process is to filter out "bad science", the process is not perfect. While there is a general consensus among researchers and clinicians that something must be done to improve upon the method for properly vetting manuscripts, there are conflicting opinions on how to best implement new policies. In this paper, we discuss the most well-supported suggestions to improve the process, with the hopes of increasing rigor and reproducibility, ensuring double-blinding, developing set guidelines, offering early training to reviewers, and giving reviewers better feedback and recognition for their work.

Inter-Toe Cracks: A Cosmetic Response versus Excipient. Efficacy and Tolerance Evaluation

A randomized, monocentric, double-blind, intra-individual excipient-controlled comparative study was performed to evaluate the efficacy and tolerance of an active peptide (laminin 5 fragment [LN-5]) formulated in cosmetic balm, versus excipient in inter-toe cracks. Two products were tested on 10 healthy volunteers. Each of them suffered from this particular superficial wound characterized by a peeling off a skin tab between at least two inter-toe spaces. The duration of this study belonged of 28 days with an intermediate visit to D14. Initial and outcome evaluation was performed using a 4-grade-scale depending on the severity of the inter-toe cracks. Tolerance and healing were assessed using macrophotographs. At D14 and D 28, the difference of cure between the 2 treatments was in favor of the peptide active product. The clinical score showed a best efficiency of the active compared with the excipient;indeed a significant difference between D28 and D0 was observed for the active ingredient. Active product repairs more quickly inter-toes cracks than the excipient and we noted the complete disappearance of the “severe” and “moderate” stages from the 14th day. This study showed clearly a fast (in 14 days) and beneficial effect of the application of LN-5 compared with the excipient, on the cutaneous repair of inter-toes cracks. Since LN-5 fragment is capable of producing immediate biological activity and reinforcing the dermal-epidermal junction, it can accelerate tissue repair.

A double-blind,placebo-controlled study of traditional Chinese medicine sarsasapogenin added to risperidone in patients with negative symptoms dominated schizophrenia

Objective To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. Methods The trial was a double-blind, placebo-controlled, parallel- group design. The eligible patients were randomized into 2 treatment groups： sarsasapogenin group （sarsasapogenin plus risperidone for 8 weeks, n = 41） and placebo group （risperidone only for 8 weeks, n = 39）. At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Nega- tive Symptoms Scale （PANSS）, Wechsler Memory Scale （WMS）, modified Chinese Wechsler Adult Intelligence Scale （mWAIS）, Clinical Global Impression （CGI） and Brief Psychiatry Rating Scale （BPRS）. The study period for each subject was 8 weeks and duration of overall trial was 2 years. Results Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. Conclusion Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.