Effects of Chinese herbal medicine Yiqi Huaju Qingli Formula in metabolic syndrome patients with microalbuminuria:a randomized placebo-controlled trial

BACKGROUND： Microalbuminuria （MAU） is a key component of metabolic syndrome （MetS） and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. OBJECTIVE： To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： Sixty patients with MetS were randomized into the Chinese herbal formula group （CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine） and control group （placebo in combination with Western medicine）. All treatments were administered for 12 weeks. MAIN OUTCOME MEASURES： Urinary microalbumin （MA）, urinary albumin-to-creatinine ratio （UACR）, 24-hour total urine protein （24-hTP）, body mass index （BMI）, waist circumference （WC）, waist-to-hip ratio （WHR）, fasting plasma glucose （FPG）, 2-hour postprandial plasma glucose （2-hPPG）, glycosylated hemoglobin （HbAlc）, homeostasis model assessment for insulin resistance （HOMA-IR）, blood lipid profile and blood pressure were observed. RESULTS： Compared with the control group, CHF treatment significantly decreased BMI （P〈0.05）, WC （P〈0.01） and WHR （P〈0.01）. Both groups had significant decreases in FPG, 2-hPPG, HbAlc, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment （P〈0.05）. Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol （TAG）, and a greater reduction in TAG was observed with CHF treatment （P〈0.05）. The level of high-density lipoprotein cholesterol did not change in the control group after treatment （P〉0.05）, whereas it significantly increased with CHF treatment （P〈0.01）. Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups （P〈0.01）. However, there was no significant difference between the two groups （P〉0.05）. CONCLUSION： Combined treatment ofYiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER： This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.

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.

Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients:A 12-week randomized placebo-controlled phase III trial with long-term extension

Background:There is a need for effective and safe therapies for psoriasis that provide sustained benefits.The aim of this study was to assess the efficacy and safety of tildrakizumab,an anti-interleukin-23p19 monoclonal antibody,for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods:In this multi-center,double-blind,phase III trial,patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned(1:1)to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4.Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12,16,and every 12 weeks thereafter.Patients in the tildrakizumab group continued with tildrakizumab at week 16,and every 12 weeks until week 52.The primary endpoint was the Psoriasis Area and Severity Index(PASI 75)response rate at week 12.Results:At week 12,tildrakizumab demonstrated significantly higher PASI 75 response rates(66.4%[73/110]vs.12.7%[14/110];difference,51.4%[95%confidence interval(CI),40.72,62.13];P<0.001)and Physician’s Global Assessment(60.9%[67/110]vs.10.0%[11/110];difference,49.1%[95%CI,38.64,59.62];P<0.001)compared to placebo.PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups,reaching maximal efficacy after 28 weeks(86.8%[92/106]vs.82.4%[89/108])and maintained up to 52 weeks(91.3%[95/104]vs.87.4%[90/103]).Most treatment-emergent adverse events were mild and not related to tildrakizumab.Conclusion:Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration:ClinicalTrials.gov,NCT05108766.

Immunomodulatory Activities of a Concentrated Fruit and Vegetable Juice Tested in a Randomized,Placebo-Controlled,Double-Blind Clinical Trial in Healthy Volunteers

22 healthy volunteers were included in a randomized, placebo-controlled pilot study in order to investigate immunomodulatory effects of a concentrated juice, containing the ingredients of a total of 80 different fruits, vegetables, herbs, mushrooms, oils, and others (Cellagon aurum?, “CA”). 11 subjects received the concentrated juice while 11 were allocated to the placebo group. Stimulated whole-blood cultures were used to assess any treatment-related changes in the response of leukocytes towards experimental immune cell activation. For each of the individuals, 5 cultures were performed either immediately before, during, or 3 days after termination of the 7 weeks treatment. Leukocyte activities were determined by measuring cytokine levels in the supernatants at the end of the 48 h of stimulation (induced by the addition of LPS + SE-B + anti-CD28 antibodies). Despite the relatively small number of volunteers, multiplexed cytokine assays revealed a typical T-cell signature of cytokines that were increased significantly in the course of CA treatment compared to placebo (GM-CSF, IFNγ, IL-4, IL-10, IL-17, TNFβ, all p 0.05). These preliminary results suggest that CA is able to support leukocyte activation, in particular that of T-lymphocytes.

A Double-Blind, Randomized, Placebo-Controlled Nutritional Study Using an Insoluble Yeast Beta-Glucan to Improve the Immune Defense System

Purpose: In a placebo-controlled, double-blind, randomized clinical trial, the effect of an insoluble yeast beta-glucan preparation on the incidences of common colds and its effect on common cold symptoms were compared to placebo. Methods: 100 healthy participants with recurring infections were randomly assigned to receive either placebo or yeast beta-glucan (Yestimun?;n = 50 each group) over a period of 26 weeks. The subjects had to document each common cold episode in a diary, and rate 6 predefined infections symptoms on a 3-point rating scale during an infection period, resulting in an infection score. The common cold episodes were confirmed by the investigators. Results: A total of 171 common cold episodes were documented. Of these, 76 were experienced by 38 subjects in the beta-glucan group and 96 were experienced by 48 subjects in the placebo group (p = 0.406). The beta-glucan group had significantly more subjects without incidences of common cold than the placebo group (15.6% vs 2.0%;p = 0.019). During the most intense infection season (first 13 weeks of the study), the beta-glucan group had significantly less infections compared to placebo (p = 0.02). Beta-glucan significantly reduced the typical cold symptoms (“sore throat and/or difficulty swallowing”, “hoarseness and/or cough” and “runny nose”) as opposed to placebo. Conclusion: The present study demonstrates a prophylactic effect of yeast beta-glucan on the occurrence of common colds as opposed to placebo. In addition, when these episodes occurred, they were from the beginning less pronounced and subsided faster.

Effects of cinnamon on perineal pain and healing of episiotomy: a randomized placebo-controlled trial

BACKGROUND： Analgesic and wound-healing effects of cinnamon, a widely used spice, have been shown in laboratory rats. However, we found no human studies in this area. OBJECTIVE： The aim of this study was to assess the effect of cinnamon on perineal pain and healing of episiotomy incision. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： In this double-blind, randomized, placebo-controlled trial, 144 postpartum women were allocated into two groups, using stratified block randomization, 1 h after completion of episiotomy repair. They received cinnamon or placebo ointment, 2 mL every 12 h for 10 d. MAIN OUTCOME MEASURES： Perineal pain and wound healing were assessed using visual analogue scale （0-10）and Redness, Edema, Ecchymosis, Discharge, Approximation scale （0-15）, respectively. General linear model was used to compare the groups on the outcomes adjusted for baseline values and stratified factors. RESULTS： Follow-up rate was 100% up to the 8 h time point in both groups, and 86% （62 of 72） in the cinnamon group and 85% （61 of 72） in the placebo group at day 10-11 after delivery. Pain score in the cinnamon group was significantly lower than that in the placebo group at （4±1） h （adjusted difference： -0.6, 95% confidence interval： -1.0 to -0.2） and （8＋1） h （-0.9, -1.4 to -0.3） after intervention, and on the 10-11th day after delivery （-1.4, -2.0 to -0.7）. Also the cinnamon group showed significantly more improvement than the control group in healing score at （8±1） h （-0.2, -0.4 to -0.04） and the 10-11th day after delivery （-1.6, -2.0 to -1.1）. CONCLUSION： Cinnamon can be used for reducing perineal pain and improving healing of episiotomy incision.

Effects of a Multivitamin/multimineral Supplement on Young Males with Physical Overtraining: A Placebo-controlled, Randomized, Double-blinded Cross-over Trial

Objective To investigate the effects of vitamin-mineral supplement on young males with physica overtraining. Methods Two hundred and forty male Chinese field artillery personnel who undertook large scale and endurance military training and were on ordinary Chinese diet were randomized to receive a multivitamin/multimineral supplement or a placebo for 1 week. After a 1-week wash-out period, a cross-over with 1 week course of a placebo or multivitamin/multimineral supplement was conducted. Blood and urine samples were analyzed for adrenal, gonadal and thyroid hormones. In addition, cellular immune parameters （CD3＋, CD3＋CD4＋, CD3＋CD8＋, CD4/CD8, CD3-CD56＋, CD3-CD19＋） were examined and psychological tests were performed before and after the training program and nutrition intervention. Results After a large scale and endurance military training, the participants showed significantly increased thyroid function, decreased adrenal cortex, testosterone and immunological function, and significantly increased somatization, anger and tension. Compared to placebo, multivitamin/ multimineral intervention showed significant effects on functional recovery of the pituitary - adrenal axis, pituitary-gonadal axis, pituitary- thyroid axis and immune system as well as psychological parameters. Conclusion High-intensity military operations have significant impacts on the psychology, physical ability and neuroendocrine-immune system in young males. Appropriate supplementation of multivitamin/multimineral can facilitate the recovery of the psychology, physical ability and neuroendocrine-immune system in young males who take ordinary Chinese diet.

Effect of an extract of Ganoderma lucidum in men with lower urinary tract symptoms： a double-blind, placebo-controlled randomized and dose-ranging study

Aim： To conduct a double-blind, placebo-controlled randomized and dose-ranging study to evaluate the safety and efficacy of the extract of Ganoderma lucidum （G. lucidum） in men with lower urinary tract symptoms （LUTS）. Methods： We enrolled male volunteers （〉 50 years） with an International Prostate Symptom Score （IPSS; questions 1-7） 〉 5 and a prostate-specific antigen （PSA） value 〈 4 ng/mL. Volunteers were randomized into groups of placebo （n = 12）, G. lucidum of 0.6 mg （n = 12）, 6 mg （n = 12） or 60 mg （n = 14）, administered once daily. Efficacy was measured as a change from baseline in IPSS and the peak urine flow rate （Qmax）. Prostate volume and residual urine were estimated by ultrasonography, and blood tests, including PSA levels, were measured at baseline and at the end of the treatment. Results： The overall administration was well tolerated, with no major adverse effects. Statistical significances in the magnitude of changes between the experimental groups were observed at weeks 4 and 8. No changes were observed with respect to Qmax, residual urine, prostate volume or PSA levels. Conclusion： The extract of G. lucidum was well tolerated and an improvement in IPSS was observed. The recommended dose of the extract of G. lucidum is 6 mg in men with LUTS.

Efficacy and safety of Xiangsha Liujunzi granules for functional dyspepsia: A multi-center randomized double-blind placebo-controlled clinical study

AIM To assess the efficacy and safety of a Chinese herbal medicine (CHM), Xiangsha Liujunzi granules, in the treatment of patients with functional dyspepsia (FD). METHODS We performed a randomized, double-blind, placebo-controlled trial with patients from three centers. Two hundred and sixteen subjects diagnosed with FD according to ROME. criteria and confirmed by upper gastrointestinal endoscopy and spleen-deficiency and Qi-stagnation syndrome were selected to receive Xiangsha Liujunzi granules or placebo for 4 wk in a 2: 1 ratio by blocked randomization. The subjects also received follow-up after the 4-wk intervention. Herbal or placebo granules were dissolved in 300 mL of water. Participants in both groups were administered 130 mL (45 degrees C) three times a day. Participants were evaluated prior to and following 4 wk of the intervention in terms of changes in the postprandial discomfort severity scale (PDSS) score, clinical global impression (CGI) scale score, hospital anxiety and depression scale (HADS) score, traditional Chinese medicine symptoms score (SS), scores of various domains of the 36-item short form health survey (SF-36), gastric emptying (GE) and any observed adverse effects. RESULTS Compared with the placebo group, patients in the CHM group showed significant improvements in the scores of PDSS, HADS, SS, SF-36 and CGI scale (P < 0.05 or P < 0.01). They also showed the amelioration in the GE rates of the proximal stomach and distal stomach (P < 0.05 or P < 0.01). CONCLUSION Xiangsha Liujunzi granules offered significant symptomatic improvement in patients with FD.

Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial

Human umbilical cord mesenchymal stem cells(hUC-MSCs)support revascularization,inhibition of inflammation,regulation of apoptosis,and promotion of the release of beneficial factors.Thus,they are regarded as a promising candidate for the treatment of intractable spinal cord injury(SCI).Clinical studies on patients with early chronic SCI(from 2 months to 1 year post-injury),which is clinically common,are rare;therefore,we will conduct a prospective,multicenter,randomized,placebo-controlled,single-blinded clinical trial at the Third Affiliated Hospital of Sun Yat-sen University,West China Hospital of Sichuan University,and Shanghai East Hospital,Tongji University School of Medicine,China.The trial plans to recruit 66 early chronic SCI patients.Eligible patients will undergo randomization at a 2:1 ratio to two arms:the observation group and the control group.Subjects in the observation group will receive four intrathecal transplantations of stem cells,with a dosage of 1×106/kg,at one calendar month intervals.Subjects in the control group will receive intrathecal administrations of 10 mL sterile normal saline in place of the stem cell transplantations.Clinical safety will be assessed by the analysis of adverse events and laboratory tests.The American Spinal Injury Association(ASIA)total score will be the primary efficacy endpoint,and the secondary efficacy outcomes will be the following:ASIA impairment scale,International Association of Neural Restoration-Spinal Cord Injury Functional Rating Scale,muscle tension,electromyogram,cortical motor and cortical sensory evoked potentials,residual urine volume,magnetic resonance imaging–diffusion tensor imaging,T cell subtypes in serum,neurotrophic factors and inflammatory factors in both serum and cerebrospinal fluid.All evaluations will be performed at 1,3,6,and 12 months following the final intrathecal administration.During the entire study procedure,all adverse events will be reported as soon as they are noted.This trial is designed to evaluate the clinical safety and efficacy of subarachnoid transplantation of hUC-MSCs to treat early chronic SCI.Moreover,it will establish whether cytotherapy can ameliorate local hostile microenvironments,promote tracking fiber regeneration,and strengthen spinal conduction ability,thus improving overall motor,sensory,and micturition/defecation function in patients with early chronic SCI.This study was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2018]-02)on March 30,2018,and was registered with ClinicalTrials.gov(registration No.NCT03521323)on April 12,2018.The revised trial protocol(protocol version 4.0)was approved by the Stem Cell Research Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University,China(approval No.[2019]-10)on February 25,2019,and released on ClinicalTrials.gov on April 29,2019.

Effect of probiotics on length of hospitalization in mild acute pancreatitis:A randomized,double-blind,placebo-controlled trial

BACKGROUND Acute pancreatitis is the leading cause of hospitalization for acute gastrointestinal disease worldwide.The effects of probiotics in mild acute pancreatitis have not been studied.We hypothesized that the administration of probiotics may accelerate the recovery of intestinal function and shorten the length of hospital stay(LOS)in patients with mild pancreatitis.AIM To investigate the value of probiotics in reducing the LOS in patients with mild acute pancreatitis.METHODS We conducted a double-blind randomized clinical trial to evaluate the effects of probiotics administered to patients with mild acute pancreatitis at a tertiary medical center.The patients were given probiotics capsules(a mixed preparation of Bacillus subtilis and Enterococcus faecium)or placebo.The primary study endpoint was the LOS.The secondary endpoints included time to abdominal pain relief,recurrent abdominal pain,and time to successful oral feeding.RESULTS A total of 128 patients were included,with 64 patients in each arm.The severity of illness and the etiological distribution of disease were similar in the two groups.There was a significant reduction in the LOS in the probiotics treatment group vs the placebo group(5.36±0.15 vs 6.02±0.17 d,P<0.05).The probiotics group was associated with a shorter time to abdominal pain relief and time to successful oral feeding(P<0.01 for both)than the placebo group.No statistical difference was found in recurrent abdominal pain between the two groups.CONCLUSION The study results showed that the administration of probiotics capsules is associated with a shorter duration of hospitalization in patients with mild acute pancreatitis.

Zishenpingchan granules for the treatment of Parkinson＇s disease：a randomized,double-blind,placebo-controlled clinical trial

Levodopa preparations remain the preferred drug for Parkinson＇s disease.However,long-term use of levodopa may lead to a series of motor complications.Previous studies have shown that the combination of levodopa and Zishenpingchan granules（consisting of Radix Rehmanniae preparata,Lycium barbarum,Herba Taxilli,Rhizoma Gastrodiae,Stiff Silkorm,Curcuma phaeocaulis,Radix Paeoniae Alba,Rhizoma Arisaematis,Scorpio and Centipede） can markedly improve dyskinesia and delay the progression of Parkinson＇s disease,with especially dramatic improvements of non-motor symptoms.However,the efficacy of this combination has not been confirmed by randomized controlled trials.The current study was approved by the Hospital Ethics Committee and was registered in the Chinese Clinical Trial Register（registration number：Chi CTR-INR-1701194）.From December 2014 to December 2016,128 patients（72 males and 56 females,mean age of 65.78 ± 6.34 years） with Parkinson＇s disease were recruited from the Department of Neurology of Longhua Hospital and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine in China.Patients were equally allocated into treatment and control groups.In addition to treatment with dopamine,patients in treatment and control groups were given Zishenpingchan granules or placebo,respectively,for 24 weeks.Therapeutic efficacy was assessed using the Unified Parkinson＇s Disease Rating Scale,on-off phenomenon,Hoehn-Yahr grade,Scales for Outcomes in Parkinson＇s disease–Autonomic,Parkinson＇s disease sleep scale,Hamilton Anxiety Scale,Hamilton Depression Scale,Mini-Mental State Examination,and the Parkinson＇s Disease Quality of Life Questionnaire.Artificial neural networks were used to determine weights at which to scale these parameters.Our results demonstrated that Zishenpingchan granules significantly reduced the occurrence of motor complications,and were useful for mitigating dyskinesia and non-motor symptoms of Parkinson＇s disease.This combination of Chinese and Western medicine has the potential to reduce levodopa dosages,and no obvious side effects were found.These findings indicate that Zishenpingchan granules can mitigate symptoms of Parkinson＇s disease,reduce toxic side effects of dopaminergic agents,and exert synergistic and detoxifying effects.

New botanical drug, HL tablet, reduces hepatic fat as measured by magnetic resonance spectroscopy in patients with nonalcoholic fatty liver disease: A placebo-controlled, randomized, phase Ⅱ trial

AIM To evaluate the efficacy and safety of HL tablet extracted from magnolia officinalis for treating patients with nonalcoholic fatty liver disease(NAFLD).METHODS Seventy-four patients with NAFLD diagnosed by ultrasonography were randomly assigned to 3 groups given high dose(400 mg) HL tablet, low dose(133.4 mg) HL tablet and placebo, respectively, daily for 12 wk. The primary endpoint was post-treatment change of hepatic fat content(HFC) measured by magnetic resonance spectroscopy. Secondary endpoints included changes of serum aspartate aminotransferase, alanine aminotransferase(ALT), cholesterol, triglyceride, free fatty acid, homeostasis model assessment-estimated insulin resistance, and body mass index(BMI).RESULTS The mean HFC of the high dose HL group, but not of the low dose group, declined significantly after 12 wk of treatment(high dose vs placebo, P = 0.033; low dose vs placebo, P = 0.386). The mean changes of HFC from baseline at week 12 were-1.7% ± 3.1% in the high dose group(P = 0.018),-1.21% ± 4.97% in the low dose group(P = 0.254) and 0.61% ± 3.87% in the placebo group(relative changes compared to baseline, high dose were:-12.1% ± 23.5%, low dose:-3.2% ± 32.0%, and placebo: 7.6% ± 44.0%). Serum ALT levels also tended to decrease in the groups receiving HL tablet while other factors were unaffected. There were no moderate or severe treatment-related safety issues during the study.CONCLUSION HL tablet is effective in reducing HFC without any negative lipid profiles, BMI changes and adverse effects.

Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial

AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy.RESULTSSitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% &#x000b1; 0.4% vs 7.9% &#x000b1; 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 &#x000b1; 3.5 &#x003bc;g/mL vs 3.9 &#x000b1; 2.7 &#x003bc;g/mL, P = 0.06) and triglyceride levels (1.26 &#x000b1; 0.43 mmol/L vs 2.80 &#x000b1; 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol/L, P = 0.19) but did trend towards improved adiponectin levels only (mean difference, 0.60 &#x003bc;g/mL, P = 0.095). No significant changes in anthropometrics, liver enzymes, other adipocytokines, lipid profile, thrombosis parameters, or adipose distribution were demonstrated. The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment, and the Spearman correlation coefficients ranged from r = 0.819 (baseline) to r = 0.878 (post-treatment), P = 0.002.CONCLUSIONSitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis.

Low-level laser acupuncture reduces postoperative pain and morphine consumption in older patients with total knee arthroplasty: A randomized placebo-controlled trial

Background: Patients commonly develop postoperative pain after total knee arthroplasty(TKA).Acupuncture-related techniques and low-level laser therapy could be beneficial for pain management for older individuals.Objective: To examine the effect of low-level laser acupuncture(LA) in reducing postoperative pain, painrelated interference in daily life, morphine consumption, and morphine-related side effects in older patients with knee osteoarthritis who underwent TKA.Design, setting, participants and intervention: A single-blind randomized placebo-controlled trial was conducted. Patients(N = 82) were recruited and randomly assigned via a computer-generated list to the LA group or a placebo group. The LA group received low-level laser therapy at Sanyinjiao(SP6), Taixi(KI3),Kunlun(BL60), Fengshi(GB31), Futu(ST32) and Neiguan(PC6) after TKA, while the placebo acupuncture group received the same treatment procedure without laser energy output.Main outcome measures: The primary outcome was postoperative pain intensity, and it was measured at baseline and hours 2, 6, 10, 24, 48 and 72 after TKA. The secondary outcomes, including relative pain,postoperative pain-related interference in daily life and morphine consumption, were measured at hours24, 48 and 72 after TKA.Results: Generalized estimating equations revealed significant between-group differences in pain intensity(P = 0.01), and trend differences in pain intensity for the LA group starting at hours 10 to 72(P < 0.05)and morphine consumption at hours 48 and 72(P < 0.05). The changes in pain-related interference in daily life were significant(P < 0.05) at 72 h, with the exception of the parameters for worst pain, mood,and sleep. Nausea and vomiting side effects from morphine had significant between-group differences at hours 10 and 24(P < 0.05).Conclusion: Low-level LA gradually reduced older patients’ postoperative pain intensity and morphine consumption within the first 72 h after their TKA for osteoarthritis. Low-level LA may have benefits as an adjuvant pain management technique for clinical care.Trial registration: ClinicalTrials.gov registration number NCT03995446.

Chinese herbal medicine for chronic heart failure:a multicenter,randomized,double-blind,placebo-controlled trial

Objective:The purpose of this study was to assess the efficacy and safety of Chinese herbal medicine(CHM)in the treatment of chronic heart failure(CHF)patients according to syndrome differentiation.Methods:In this multicenter,randomized,double-blind,placebo-controlled clinical trial,a total of 220 CHF patients were assigned to receive CHM or placebo granules without decoction according to syndrome differentiation in addition to their standard western treatment for 4 weeks.The change in the left ventricular ejection fraction(LVEF)was the primary outcome,and the changes in the TCM syndrome scores(TCM-SS)and New York Heart Association functional classification(NYHA-FC)were the secondary outcomes.

Ruyi Zhenbao Pills for Patients with Motor and Sensory Dysfunction after Stroke: A Double-Blinded, Randomized Placebo-Controlled Clinical Trial

Objective: To evaluate the efficacy and safety of Tibetan medicine Ruyi Zhenbao Pills(RZPs) in the treatment of patients with motor and sensory dysfunction after stroke. Methods: A total of 120 convalescent stroke patients hospitalized in the Rehabilitation Department of Guangdong Provincial Hospital of Chinese Medicine from June 2017 to December 2019 were enrolled in this trial. Patients were assigned to control(60 cases) and research(60 cases) groups by computer random assignment. All patients received internal treatment and modern rehabilitation training. On this basis, the research group was given oral RZPs for 4 weeks, while the control group was given oral placebo. The primary outcome was motor function of the affected side evaluated by simplified FuglMeyer Motion Assessment Scale(FMA-M). The secondary outcomes included sensory function, activity of daily living(ADL), quality of life, balance function, and pain, which were assessed by Fugl-Meyer Sensory Assessment Scale(FMA-S), Modified Barthel Index(MBI), Special Scale of the Quality of Life(SS-QOL), Berg Balance Scale(BBS), and Visual Analogue Scale(VAS), respectively. All of the assessments were performed before treatment, and 4 and 8 weeks after treatment. Vital signs, liver and kidney functions, routine blood test, blood coagulation profile, and routine urinalysis of patients were monitored. Results: After 4-week treatment, the FMA-M, BBS and FMA-S scores in the research group significantly increased compared with the control group(P<0.05). At 8-week follow-up, the BBS and MBI scores in the research group were higher than the control group(P<0.05). There was no statistical difference between the 2 groups in the SS-QOL and VAS scores at 4 and 8 weeks(P>0.05). Moreover, after treatment, there was no significant difference in vital signs, liver and kidney functions, blood coagulation function, blood routine and urinalysis between the 2 groups(P>0.05). Conclusion: RZPs improved limb motor, balance, and sensory functions of stroke patients during recovery period with good safety.(Trial registration No. NCT04029701)

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction(CODE-AAMI):Protocol for a Randomized Placebo-Controlled Trial

Background:Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction(AAMI)is an important factor in occurrence of heart failure which additionally results in poor prognosis.Therefore,the treatment of ventricular remodeling needs to be further optimized.Compound Danshen Dripping Pills(CDDP),a traditional Chinese medicine,exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.Objective:This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.Methods:This study is a multi-center,randomized,doubleblind,placebo-controlled,parallel-group clinical trial.The total of 268 patients with AAMI after primary percutaneous coronary intervention(pPCI)will be randomly assigned 1:1 to the CDDP group(n=134)and control group(n=134)with a follow-up of 48 weeks.Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction(STEMI),with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI,and the control group treated with a placebo simultaneously.The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction(LVEF),left ventricular end-diastolic volume index(LVEDVI),and left ventricular end-systolic volume index(LVESVI).The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide(NT-proBNP)level,arrhythmias,and cardiovascular events(death,cardiac arrest,or cardiopulmonary resuscitation,rehospitalization due to heart failure or angina pectoris,deterioration of cardiac function,and stroke).Investigators and patients are both blinded to the allocated treatment.Discussion:This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI.Patients in the CDDP group will be compared with those in the control group.If certified to be effective,CDDP treatment in AAMI will probably be advised on a larger scale.(Trial registration No.NCT05000411)

Tolerability of a Proprietary Larch Arabinogalactan Extract: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial in Healthy Subjects

In a placebo-controlled, double-blind, randomized clinical trial, the tolerability of a proprietary larch arabinogalactan preparation (ResistAidTM) was investigated. METHODS: 199 healthy participants were randomly assigned to receive either placebo (n = 98) or an arabinogalactan preparation (n = 101) over a period of 12 weeks. As safety parameters the total number of adverse events, changes in various biochemical and laboratory parameters as well as the global evaluation of tolerability by investigator and subjects compared to placebo were evaluated. RESULTS: In total 16 adverse events were observed in 16 subjects, with no difference between the arabinogalactan and the placebo group (p = 0.935). There were no differences in the mean changes of the measured biochemical and laboratory parameters. The tolerability of the arabinogalactan extract was rated as “very good” or “good” by the investigators for 99% of the subjects and by 98% subjects in self-assessment with no statistical differences to placebo. CONCLUSION: The measured parameters as well as the evaluation of the tolerability by the investigators and the subjects demonstrate a very good tolerance profile of the proprietary arabinogalactan extract with no differences to placebo when taken for 12 weeks.

A multicenter randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of rhubarb in treating acute exacerbation of chronic obstructive pulmonary disease of the syndrome type phlegm-heat obstructing the lungs

Objective:To observe the clinical efficacy and safety of oral administration of the traditional Chinese herb rhubarb to treat acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Method:This was a multicenter randomized double-blinded placebo controlled study that took place in 7 provinces of China that enrolled 244 patients(aged 18e80 years)who had acute exacerbation of COPD with the traditional Chinese syndrome pattern of phlegm-heat obstructing lung.Participants were divided into experimental and control groups.The experimental group received 4.5 g of rhubarb granules twice daily and the control group received placebo granules.Both groups also received conventional Western therapy consisting of oxygen therapy,an antibiotic,expectorant,and a bronchodilator.Treatment lasted 10 days.Symptom scores for cough,sputum volume and color,wheezing and chest tightness before treatment and on days 3,5,7,and 10 during the treatment were recorded.Lung function,arterial blood gas and levels of serum inflammatory factors,interleukin-4(IL-4),interleukin-8(IL-8),and interleukin-10(IL-10)and tumor necrosis factor-alpha(TNF-a),before and after treatment were measured.Results:The sample size of the full analysis set(FAS)was 244 participants,and the sample size of per protocol set(PPS)was 235.Following 10 days’treatment,symptom scores of the experimental group were markedly lower than those of the placebo group(FAS:mean difference
1.67,95%CI:e2.66 to
0.69,P Z 0.001;PPS:mean difference
1.55,95%CI:
2.56 to
0.54,P Z 0.003).Lung function in the experimental group was significantly higher than in the placebo group(FEV1,FAS:mean difference 0.12,95%CI:0.06 to 0.18;P<0.001;PPS:mean difference 0.12,95%CI 0.05 to 0.18;P<0.001.FVC:FAS:mean difference 0.16,95%CI:0.06 to 0.26;P Z 0.002;PPS:mean difference 0.16,95%CI 0.05 to 0.26;P Z 0.003.FEV1%,FAS:mean difference 5.95,95%CI:3.36 to 8.53;P<0.001;PPS:mean difference 5.92,95%CI 3.28 to 8.56;P<0.001.).PaO2,PaCO2,as well as serum inflammatory factors were also improved when compared to the placebo group.There were no significant differences in the incidence rate of adverse reaction between the two groups.Conclusions:Compared with placebo,rhubarb granules significantly reduced symptom scores,improved blood oxygen level,controlled systemic inflammatory response,without significant adverse effects.Thus,rhubarb may be a beneficial adjuvant method for treating the phlegm-heat obstructing the lung syndrome pattern of AECOPD.