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.

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.

Results of the cancer screening feasibility study in China:a multicentered randomized controlled trial of lung and colorectal cancer screening

Background:To provide an understanding of important aspects of the participant recruitment and data collec-tion,become aware of any potential problems,and obtain necessary information in order to design a large-scale randomized controlled trial(RCT)for lung cancer and colorectal cancer(CRC)screening in China.Methods:This feasibility study was a multicentered,open-label,pilot randomized trial.A total of 2696 participants who were at high risk of lung cancer were recruited from three screening centers and randomly allocated to arm 1(n=894),annual low-dose computed tomography(LDCT)plus a baseline colonoscopy;arm 2(n=902),biennial LDCT plus annual fecal immunochemical test(FIT)with OC-Sensor(OC-FIT);and arm 3(n=900),annual Insure-FIT plus Septin 9 blood test.Information on randomization,compliance,positivity rate,cancer case detection,and contamination with screening for lung cancer and CRC were collected.Results:Participant characteristics were similar across study arms.The compliance rate of annual LDCT screening in arm 1 was 86.4%(95%CI:83.9%,88.5%)at baseline(T0),and 69.0%(95%CI:65.8%,72.0%)and 70.7%(95%CI:67.6%,73.7%)at the following two rounds(T1 and T2).The compliance rates of biennial LDCT screening in arm 2 were similar to those in arm 1 in the corresponding rounds.The compliance rate was 55.5%(95%CI:52.2%,58.8%)for colonoscopy in arm 1,while the compliance rates of OC-FIT,Insure-FIT,and the Septin 9 test in arms 2 and 3 were all approximately 90%at T0,decreasing to 65%-80%at T1 and T2.The positivity rate,cancer case detection rate,and contamination rate of screening for lung cancer and CRC were also reported.Conclusion:In this pilot study,the feasibility of an RCT in China of lung cancer and CRC screening was demon-strated.

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.

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.

Evaluation of the effect of acupuncture on hand pain,functional deficits and health-related quality of life in patients with rheumatoid arthritis--A study protocol for a multicenter,double-blind,randomized clinical trial

BACKGROUND： Rheumatoid arthritis（RA） is a systemic inflammatory disease characterized by functional disability and pain. Although acupuncture is widely used, until now Western acupuncture studies on RA have not shown conclusive positive results. Acupuncture is regarded as a reflex therapy that has effects on the human autonomic nervous system. By establishing a traditional Chinese medicine（TCM） diagnosis first, the practitioner is able to choose acupoints according to the state of each individual patient.METHODS/DESIGN： We are interested if acupuncture, using a classical diagnostic procedure to allocate acupoints to the patient according to the Shang Han Lun theory, can be effective in relieving pain, improving hand function and increasing health-related quality of life in RA.The authors intend to harmonize TCM diagnosis according to clinical and genetic profiles. Patients with the TCM diagnosis of a so-called Turning Point syndrome will be followed up in a randomized, prospective, double-blind, placebo-controlled, multicenter and three-armed parallel-group study with a standardized treatment in order to optimize potential therapeutic effects of acupuncture on pain, strength and muscle function of patients with RA as well as the influence on inflammation and quality of life.DISCUSSION： The findings of this study will provide important clinical information about the feasibility and efficacy of acupuncture treatment for RA patients. In addition, it will explore the feasibility of further acupuncture research.TRIAL REGISTRATION NUMBER： Clinical Trials.gov Identifier NCT02553005.

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.

Treatment of HBV Cirrhosis with Fuzheng Huayu Tablet(扶正化瘀片)and Entecavir:Design of a Randomized,Double-Blind,Parallel and Multicenter Clinical Trial

Background Antiviral therapy can lead to regression of fibrosis in chronic hepatitis B(CHB),but it has a limited effect on cirrhosis.Chinese medicines(CMs),particularly Fuzheng Huayu Tablet(扶正化瘀片,FZHY),have an antifibrotic effect in patients with CHB.Objective To observe the safety and efficacy of adjunctive FZHY in patients with hepatitis B virus(HBV)cirrhosis,this study was designed as a randomized,placebo-controlled,double-blind,parallel assignment,multicenter trial at 20 centers in China.The total 700 naive patients will be enrolled with compensate cirrhosis due to HBV,and randomly assigned into 2 groups,receiving entecavir(0.5 mg,daily)and FZHY placebo(1.6 g,3 times a day),or entecavir(0.5 mg,daily)and FZHY(1.6 g,3 times a day),respectively.The primary endpoint was histological improvement at week 48.The secondary outcome is the decline values of liver fibrosis using the noninvasive methods from baseline to week 48 in each arm of the study.Adverse events such as stomach upset,headache,fatigue,dizziness,nausea will be strictly recorded.Discussion Through this study,we hope to generate a solid evidence for the therapeutic strategy of HBV cirrhosis with a combination of anti-viral such as ETV and anti-fibrotic herbal product such as FZHY.Protocol version:Version 1.3,Date:2014.12.4.Trial registration number:NCT02241590.

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 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)

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.

Efficacy of acupuncture and moxibustion in treating Bell’s palsy: a multicenter randomized controlled trial in China

Background Bell’s palsy involves acute facial paralysis due to inflammation of the facial nerve. Acupuncture and moxibustion (acu-moxi) is beneficial in treating facial palsy. In order to verify the efficacy of acu-moxi on Bell’s palsy, a randomized single-blind, multicenter clinical trial was performed.Methods A total of 480 patients from four clinical centers were involved in this trial, of whom 439 completed the trial and 41 did not. All patients were randomly assigned to either the control group or to one of two treatment groups. The control group was treated with prednisone, vitamin B_1, vitamin B_ 12, and dibazole; the treatment groups were treated either with acu-moxi alone or in combination with prednisone, Vitamin B_1, vitamin B_ 12, and dibazole. Symptoms and signs, the House-Brackmann scale, and facial disability index (FDI) scores were assessed and determined both pre- and post-treatment to evaluate the effectiveness of the treatment methods.Results The characteristics of the control and two treatment groups were comparable without statistically significant differences before treatment. There were significant differences between the control and treatment groups after treatment (χ2=15.265, P=0.018). According to evaluations based on the House-Brackmann scale and FDI scores, the effectiveness of treatment in the two treatment groups was better than in the control group and was most effective in patients receiving acu-moxi treatment alone (Z=-2.827, P=0.005). Conclusion The efficacy of acu-moxi treatment for Bell’s palsy is verified scientifically.

Effectiveness of ZiYin Xiehuo granules and Zishen Qinggan granules on partial precocious puberty in girls: a multicenter, randomized, single-blind, controlled trial

OBJECTIVE: To evaluate the effect of ZiYin Xiehuo granules(ZYXH) and Zishen Qinggan granules(ZSQG) on partial precocious puberty(PPP).METHODS: This was a multicenter, randomized, single-blind, positive-controlled trial. A total of 143 pa-tients were assigned to either the ZYXH group or the ZSQG group using a random number table. The ZYXH group received ZYXH three times daily for 6 months and the ZSQG group received ZSQG three times daily for 6 months. Mammary nucleus diameter; the results of uterus, ovarian, and maximum follicle measures; and Chinese medicine symptom pattern scores were compared at baseline and after 3 months and 6 months of treatment.RESULTS: After 3 months' treatment, there were no significant differences between the two groups in mammary nucleus index changes(left 3.4 ± 3.1 vs3.5 ± 3.1, P = 0.790; right 3.0 ± 2.9 vs 3.6 ± 3.0, P =0.719). The uterine volume in the ZYXH group was smaller than that in the ZSQG group(2.1 ± 1.6 vs2.6 ± 2.2, P = 0.006). There were no significant between-group differences in ovarian volume and maximum follicular diameter on either side(ovarian volume: left 1.2 ± 0.7 vs 1.3 ± 0.6, P = 0.8; right1.2 ± 0.7 vs 1.4 ± 1.1, P = 0.984; maximum follicular diameter: left 3.9 ± 1.7 vs 3.5 ± 2.2, P = 0.158; right3.5 ± 1.7 vs 3.9 ± 2.1, P = 0.314).CONCLUSION: ZYXH granules and ZSQG granules both affected the size of the mammary nucleus in girls with PPP, and improved Chinese medicine symptom patterns. ZYXH granules showed slight advantages over ZSQG granules in terms of the decrease in the size of the uterus, ovaries, and ovarian follicles.

Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer(ESWN 01):a prospective randomized,multicenter,open-labeled phase 3 trial

Background:The benefit of systemic treatments in esophageal squamous cell carcinoma(ESCC)which has pro-gressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established.We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum-or taxane-based chemotherapy.Methods:We conducted a prospective randomized,multicenter,open-label,phase 3 trial in 15 centers across China.Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC,and were randomly assigned(ratio,1:1)to receive either irinotecan plus S-1(intravenous infusion of irinotecan[160 mg/m2]on day 1 and oral S-1[80-120 mg]on days 1-10,repeated every 14 days)or oral S-1 monotherapy(80-120 mg/day on days 1-14,repeated every 21 days)using a central computerized minimization procedure.The primary endpoint was progression-free survival(PFS).Results:Between December 23,2014 and July 25,2016,we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen(n=61)or S-1 monotherapy(n=62).After a median follow-up of 29.2 months(95%confidence interval[CI]17.5-40.9 months),the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group(3.8 months[95%CI 2.9-4.3 months]vs.1.7 months[95%CI 1.4-2.7 months],hazard ratio=0.58,95%CI 0.38-0.86,P=0.006).The objective response rates were 24.6%in the irinotecan plus S-1 group and 9.7%in the S-1 monotherapy group(P=0.002).The patients in the irinotecan plus S-1 group presented with increased rates of grade 3-4 leukopenia(16.4%vs.0%),neutropenia(14.8%vs.1.6%),and nausea(4.9%vs.0%).No significant difference in grade 3-4 diarrhea and no treatment-related deaths were observed in both groups.Conclusions: The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC.

Treatment of Psoriasis Vulgaris with Medicated Thread Moxibustion of Zhuang Medicine:A Multicenter Randomized,Parallel Controlled Trial

Objective:To explore the efficacy and safety of Zhuang medicine medicated thread moxibustion(ZMTM)on psoriasis vulgaris.Methods:A multicenter,randomized,parallel controlled clinical trial was designed.A total of 241 outpatients with psoriasis vulgaris were randomly divided into a control group(120 cases)and a treatment group(121 cases)using a central block randomization from June 2015 to May 2018.The control group was treated with Western medicines alone including pidotimod dispersible tablets,vitamin B compound tablets,and compound cod liver oil-zinc oxide ointment.The treatment group was treated with ZMTM every 2 days combined with Western medicines.The two groups received continuous intervention for 30 days.The primary outcome was Psoriasis Area and Severity Index(PASI),and the secondary outcomes included Itch Rating Scale,Dermatology Quality of Life Index(DLQI),Hamilton Anxiety Rating Scale(HAMA),as well as PASI response rate.Meanwhile,adverse events were evaluated during the whole clinical trial.Follow-up was carried out 30 days after treatment.Results:There were 5 cases of shedding in this trial.In intention-to-treat analysis,236 cases were included and each group contained 118 cases.On the 30th and 60th days,PASI scores of patients in each group were significantly lower than that at baseline(P<0.01)and the PASI score reduction of the treatment group was greater than that of the control group(P<0.01).Itch Rating Scale,DLQI,and HAMA scale were decreased in both groups after treatment,and the treatment group showed a better therapeutic effect(P<0.01).The response rates of PASI 50 and 75 were significantly higher than those in the control group[81.4%(96/118),43.2%(51/118)vs.41.5%(49/118),11.0%(13/118),respectively,P<0.05].During follow-up,the improvements in scores of PASI,Itch Rating Scale,DLQI,and HAMA of the treatment group were significantly greater than those of the control group(P<0.01).The response rates of PASI 50 and 75 in the treatment group were significantly higher than those in the control group,respectively(both P<0.05).No obvious adverse reaction was found in either group.Conclusion:ZMTM combined with Western medicines showed a better therapeutic effect in the treatment of psoriasis vulgaris without obvious adverse reaction.(Trial Registration No.ChiCTR-IOR-16008159)

Electroacupuncture in Treatment of Acute Gastrointestinal Injury in Patients with Severe Traumatic Brain Injury:A Multicenter Randomized Controlled Trial

Objective: To evaluate whether electroacupuncture(EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury(TBI) complicocted by acute gastrointestinal injury(AGI). Methods: This multicenter, single-blind trial included patients with TBI and AGI admitted to 5Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli(ST 36), Shangjuxu(ST 37), Xiajuxu(ST 39), Tianshu(ST 25), and Zhongwan(RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily,for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid(D-lac), diamine oxidase(DAO), lipopolysaccharide(LPS), motilin(MTL) and gastrin(GAS), intra-abdominal pressure(IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure(GIF),Glasgow Coma Scale(GCS), Acute Physiology and Chronic Health Evaluation(APACHE Ⅱ), Sequential Organ Failure Assessment(SOFA), and Multiple Organ Dysfunction Syndrome(MODS), mechanical ventilation time,intense care unit(ICU) stay, and the incidence of hospital-acquired pneumonia. Results: The 28-d mortality in the acupuncture group was lower than that in the control group(22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE Ⅱ, SOFA, MODS scores, D-lac,DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency(all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 in the EA group(all P<0.05). Conclusion: Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI.(Registration No. ChiCTR2000032276)

Multicenter randomly controlled trial on acupoint injection therapy with Chinese herbal medicines for oculomotor paralysis

Objective To evaluate the clinical effect of acupoint injection therapy for paralysis of oculomotor nerve with Chinese herbal medicines. Methods A total number of 456 patients from 3 centers with paralysis of oculomotor nerve were randomly divided into an acupoint injection group and a control group with 228 cases each. Patients in the acupoint injection group were treated with injection of Chinese herbal medicines to Jingming （晴明 BL 1）, Yangbai （阳白GB 14}, Sibai （四白 ST 24 Tongziliao （瞳子髎 GB I） on the affected side, and Ganshu （肝俞 BL 18） on both sides, Compound Angelica Injection was the main drug, and the corresponding acupoints and other injection drugs were also used according to differentiation of syndrome. Patients in the control group were treated with common western medicine. The treatment was given once a day, 10 times constituted one course with 3 days of interval. After 3 courses, the effect was assessed. TCM syndrome score, eyeball movement degree, the sizes of oculi rimae and pupil of the two groups were recorded before and after treatment. Results The effective rate of acupoint injection group was 91.7% （209/228）, and that of the control group was 73.6% （168/228）. There was statistical significance in comparing the difference between the two groups （P〈0.05）. TCM syndrome scores of the two groups after the treatment became less obviously than those before the treatment （P〈0.01, P〈0.05）, the score of acupoint injection group was more reduced than that of the control group （P〈0.05）. Eyeball movement degree and oculi rimae were enlarged and the pupil reduced in the affected eye in both groups after the treatment Call P〈0.05）. The musculus rectus medialis for the eyeball movement in the acupoint injection group was more improved than that of the control group, and the oculi rimae was bigger in the acupoint injection group than that in the control group （both P〈0.05）. Conclusion Acupoint injection therapy with Chinese herbal medicines has assured effect on the treatment of oculomotor paralysis.

A PROSPECTIVE STUDY TO EVALUATE THE SAFETY AND EFFICACY USING REMOVING BLOOD STASIS HERBALS FOR PATIENTS WITH INTRACRANIAL HEMORRHAGE OF HYPERACUTE STAGE AND RELATIVE FACTORS OF HEMATOMA ENLARGEMENT(A MULTICENTER PROSPECTIVE RANDOMIZED DOUBLE-BLIND PLACEBO

The aim was to investigate whether using a removing blood stasis method in hyperacute intracranial hemorrhage stage can lead to hematoma enlargement and its clinical efficacy.A multicenter retrospective randomized double-blind placebo-controlled clinical study.We recruited patients aged 18 years or older and presenting at less than 6 h from symptom onset in 8 research centers.All the patients

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.