基于Clinical Trials数据库的癌性疼痛治疗药物临床试验分析

目的了解近年来癌性疼痛(癌痛)治疗药物临床试验的趋势和特点,为癌痛治疗药物的开发和临床研究提供参考依据。方法从Clinical Trials数据库中检索1987—2022年癌痛治疗药物临床试验的相关信息,从试验类型、备案时间、申报地区、癌痛类型、癌痛治疗药物等角度进行描述性分析。结果筛选出临床试验376项,由研究者发起的试验(IIT)项目数多于注册类试验(IST),其中北美洲的总项目数、IIT和IST项目数最多;试验总项目数和IST项目数先增长后回落,IIT的试验项目数稳步增长。针对慢性癌痛、爆发性癌痛和重度癌痛的研究相对较多。研究对象以阿片类药物尤其是芬太尼的占比最高。结论癌痛治疗药物临床试验对推进癌痛治疗药物治疗发挥了重要作用,未来有待进一步加强IST在新型癌痛治疗药物的研究和开展更多IIT研究,以更好地优化癌痛治疗效果。

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer:Unravelling challenges and future directions

Colorectal cancer(CRC)is a complex disease with diverse etiologies and clinical outcomes.Despite considerable progress in development of CRC therapeutics,challenges remain regarding the diagnosis and management of advanced stage metastatic CRC(mCRC).In particular,the five-year survival rate is very low since mCRC is currently rarely curable.Over the past decade,cancer treatment has significantly improved with the introduction of cancer immunotherapies,specifically immune checkpoint inhibitors.Therapies aimed at blocking immune checkpoints such as PD-1,PD-L1,and CTLA-4 target inhibitory pathways of the immune system,and thereby enhance anti-tumor immunity.These therapies thus have shown promising results in many clinical trials alone or in combination.The efficacy and safety of immunotherapy,either alone or in combination with CRC,have been investigated in several clinical trials.Clinical trials,including KEYNOTE-164 and CheckMate 142,have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab,respectively,for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC.Unfortunately,these drugs benefit only a small percentage of patients,with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients.To this end,primary and secondary resistance to immunotherapy remains a significant issue,and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response.This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC.The underlying rationale,challenges faced,and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RCTs)of non-pharmacological interventions following concussion.Methods:We searched MEDLINE,Embase,PsycInfo,CINAHL,and Web of Science up to May 2022.Two reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),Consensus on Exercise Reporting Template(CERT),and international Consensus on Therapeutic Exercise aNd Training(i-CONTENT)checklists.Additional information was sought my study authors where reporting was incomplete.Risk of bias(ROB)was assessed with the Cochrane ROB-2 Tool.RCTs examining non-pharmacological interventions following concussion.Results:We included 89 RCTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck cooling.Median scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),CERT 17/19(89%;IQR=2;range:10-19),and i-CONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),CERT 24%(5/21),and i-CONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and CERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;CERT:r_(s)=-0.44;p=0.06;i-CONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;CERT:rs=0.04;p=0.86;i-CONTENT:rs=0.12;p=0.60).Conclusion:RCTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified supervisor.Reporting completeness improved after TIDieR and CERT publication,but publication in highly cited journals and low ROB do not guarantee reporting completeness.

Factors influencing willingness to participate in ophthalmic clinical trials and strategies for effective recruitment

AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical trials.METHODS:A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center,Sun Yat-sen University,in Guangzhou,China.The survey gathered data on respondents’willingness,demographic and socioeconomic profiles,as well as their reasons and concerns regarding engagement in clinical trials.RESULTS:Of the 1078 residents surveyed(mean age 31.2±13.1y;65.8%females)in Guangzhou,749(69.5%)expressed a willingness to participate in future ophthalmic clinical trials.Specific characteristics associated with greater willingness included a younger age,lower annual income,higher education,prior participation experience,previous ophthalmic treatment,and a better understanding of clinical trials.With the exception of age,these characteristics were significantly linked to a higher willingness.The primary barrier to participation,expressed by 64.8%of those willing and 54.4%of those unwilling,was“Uncertain efficacy”.In terms of motivations,the willing group ranked“Better therapeutic benefits”(35.0%),“Professional monitoring”(34.3%),and“Trust in healthcare professionals”(33.1%)as their top three reasons,whereas the unwilling participants indicated“Full comprehension of the protocol”(46.2%)as the key facilitator.CONCLUSION:This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors.Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies.Importantly,the need for and trust in healthcare professionals stand out as powerful motivations,underscoring the importance of enhancing physician-patient relationships,adopting patient-centered communication approaches,and addressing individualized needs to improve accrual rates.

基于ClinicalTrials.gov的全球数字疗法临床试验注册现状研究

目的研究全球数字疗法临床试验注册现状,为数字疗法的临床研究及应用提供参考。方法在ClinicalTrials.gov中检索数字疗法相关临床试验,运用文献计量学方法,分析全球数字疗法临床试验的注册数量和年度变化趋势、国家/地区分布及合作情况、申办者类型及构成情况、研究类型及试验分期、适应证分类和特征。结果全球数字疗法相关临床试验共2960项,其中美国最为活跃,远超其他国家/地区,与德国同处国际合作的中心,申办者中64.79%是高校/医院,美国高校/医院表现突出。85.44%是干预性研究,大多数属于设备和行为干预,适应证集中于精神疾病、慢性病和神经系统疾病领域,包括焦虑症(109项)、抑郁症(103项)和肥胖(101项)。截至检索日期,我国数字疗法相关临床试验为143项,与美国存在较大差距。结论全球数字疗法临床试验呈现逐年增长趋势,受COVID-19大流行影响,2020年后增长显著。我国数字疗法尚处于起步阶段,全面推广及应用尚需时间。

Anti-oxidative stress treatment and current clinical trials

Oxidative stress disturbs the balance between the production of reactive oxygen species(ROS)and the detoxification biological process.It plays an important role in the development and progression of many chronic diseases.Upon exposure to oxidative stress or the inducers of ROS,the cellular nucleus undergoes some biological processes via different signaling pathways,such as stress adaption through the forkhead box O signaling pathway,inflammatory response through the IκB kinase/nuclear factor-κB signaling pathway,hypoxic response via the hypoxia-inducible factor/prolyl hydroxylase domain proteins pathway,DNA repair or apoptosis through the p53 signaling pathway,and antioxidant response through the Kelch-like ECH-associated protein 1/nuclear factor E2-related factor 2 signaling pathway.These processes are involved in many diseases.Therefore,oxidative stress has gained more attraction as a targeting process for disease treatment.Meanwhile,anti-oxidative stress agents have been widely explored in pre-clinical trials.However,only limited clinical trials are performed to evaluate the efficacy of anti-oxidative stress agents or antioxidants in diseases.In this letter,we further discuss the current clinical trials related to anti-oxidative stress treatment in different diseases.More pre-clinical studies and clinical trials are expected to use anti-oxidative stress strategies as disease treatment or dietary supplementation to improve disease treatment outcomes.

Coronary artery disease and heart failure:Late-breaking trials presented at American Heart Association scientific session 2023

The late-breaking science presented at the 2023 scientific session of the American Heart Association paves the way for future pragmatic trials and provides meaningful information to guide management strategies in coronary artery disease and heart failure(HF).The dapagliflozin in patient with acute myocardial infarction(DAPA-MI)trial showed that dapagliflozin use among patients with acute MI without a history of diabetes mellitus or chronic HF has better cardiometabolic outcomes compared with placebo,with no difference in cardiovascular outcomes.The MINT trial showed that in patients with acute MI and anemia(Hgb<10 g/dL),a liberal transfusion goal(Hgb≥10 g/dL)was not superior to a restrictive strategy(Hgb 7-8 g/dL)with respect to 30-day all-cause death and recurrent MI.The ORBITA-2 trial showed that among patients with stable angina and coronary stenoses causing ischemia on little or no antianginal therapy,percutaneous coronary intervention results in greater improvements in anginal frequency and exercise times compared with a sham procedure.The ARIES-HM3 trial showed that in patients with advanced HF who received a HeartMate 3 levitated left ventricular assist device and were anticoagulated with a vitamin K antagonist,placebo was noninferior to daily aspirin with respect to the composite endpoint of bleeding and thrombotic events at 1 year.The TEAMMATE trial showed that everolimus with low-dose tacrolimus is safe in children and young adults when given≥6 months after cardiac transplantation.Providing patients being treated for HF with reduced ejection fraction(HFrEF)with specific out-of-pocket(OOP)costs for multiple medication options at the time of the clinical encounter may reduce‘contingency planning’and increase the extent to which patients are taking the medications decided upon.The primary outcome,which was cost-informed decisionmaking,defined as the clinician or patient mentioning costs of HFrEF medication,occurred in 49%of encounters with the checklist only control group compared with 68%of encounters in the OOP cost group.

Can propensity score matching replace randomized controlled trials?

Randomized controlled trials(RCTs)have long been recognized as the gold standard for establishing causal relationships in clinical research.Despite that,various limitations of RCTs prevent its widespread implementation,ranging from the ethicality of withholding potentially-lifesaving treatment from a group to relatively poor external validity due to stringent inclusion criteria,amongst others.However,with the introduction of propensity score matching(PSM)as a retrospective statistical tool,new frontiers in establishing causation in clinical research were opened up.PSM predicts treatment effects using observational data from existing sources such as registries or electronic health records,to create a matched sample of participants who received or did not receive the intervention based on their propensity scores,which takes into account characteristics such as age,gender and comorbidities.Given its retrospective nature and its use of observational data from existing sources,PSM circumvents the aforementioned ethical issues faced by RCTs.Majority of RCTs exclude elderly,pregnant women and young children;thus,evidence of therapy efficacy is rarely proven by robust clinical research for this population.On the other hand,by matching study patient characteristics to that of the population of interest,including the elderly,pregnant women and young children,PSM allows for generalization of results to the wider population and hence greatly increases the external validity.Instead of replacing RCTs with PSM,the synergistic integration of PSM into RCTs stands to provide better research outcomes with both methods complementing each other.For example,in an RCT investigating the impact of mannitol on outcomes among participants of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial,the baseline characteristics of comorbidities and current medications between treatment and control arms were significantly different despite the randomization protocol.Therefore,PSM was incorporated in its analysis to create samples from the treatment and control arms that were matched in terms of these baseline characteristics,thus providing a fairer comparison for the impact of mannitol.This literature review reports the applications,advantages,and considerations of using PSM with RCTs,illustrating its utility in refining randomization,improving external validity,and accounting for non-compliance to protocol.Future research should consider integrating the use of PSM in RCTs to better generalize outcomes to target populations for clinical practice and thereby benefit a wider range of patients,while maintaining the robustness of randomization offered by RCTs.

Knowledge and Attitudes of Oncology Nurses Toward Clinical Trials-A Secondary Publication

Purpose:The purpose of this study was to identify the knowledge and attitudes of oncology nurses toward clinical trials and to provide evidence for the development of clinical trial education programs for oncology nurses.Methods:The study was conducted on 142 nurses who had more than six months of nursing experience working with cancer patients at a tertiary hospital in Seoul,Korea.A structured questionnaire was used to measure the knowledge and attitudes of oncology nurses toward clinical trials.Results:The participants scored an average of 15.03±3.52 out of 19 in terms of knowledge about clinical trials.In terms of attitudes toward clinical trials,the participants scored an average of 5.91±1.37 out of 8.There was a significant positive correlation between the knowledge and attitudes of the participants toward clinical trials(r=0.23,P=0.007).Conclusion:This study found that there was a relationship between the knowledge and attitudes of oncology nurses toward clinical trials.To improve the competency of oncology nurses and provide high-quality care to patients participating in clinical trials,more systematic and sustainable education is required.

Comparative Study on the Policy of Multiplicity Issues in Clinical Trials at Home and Abroad

Objective To study the content of China’s guiding principles on multiplicity issues in clinical trials,and to provide reference for the revision of China’s relevant guiding principles.Methods Based on ICH E9,the similarities and differences of the guiding principles of US Food and Drug Administration(FDA),European Medicines Agency(EMA),and National Medical Products Administration(NMPA)on the multiplicity issues in clinical trials were compared one by one.Results and Conclusion In general,NMPA guidelines are based on ICH E9,but in detail,the guidelines of FDA and EMA focus differently on the multiplicity issues.Therefore,NMPA guidelines need to be detailed and comprehensive.NMPA guidelines can be refined by referring to foreign guidelines to improve the practical guiding significance for clinical research and promote the level of domestic clinical trials in line with international standards.

Comparison of two statistical methods for handling missing values of quantitative data in Bayesian N-of-1 trials: a simulation study

Background:Missing data are frequently occurred in clinical studies.Due to the development of precision medicine,there is an increased interest in N-of-1 trial.Bayesian models are one of main statistical methods for analyzing the data of N-of-1 trials.This simulation study aimed to compare two statistical methods for handling missing values of quantitative data in Bayesian N-of-1 trials.Methods:The simulated data of N-of-1 trials with different coefficients of autocorrelation,effect sizes and missing ratios are obtained by SAS 9.1 system.The missing values are filled with mean filling and regression filling respectively in the condition of different coefficients of autocorrelation,effect sizes and missing ratios by SPSS 25.0 software.Bayesian models are built to estimate the posterior means by Winbugs 14 software.Results:When the missing ratio is relatively small,e.g.5%,missing values have relatively little effect on the results.Therapeutic effects may be underestimated when the coefficient of autocorrelation increases and no filling is used.However,it may be overestimated when mean or regression filling is used,and the results after mean filling are closer to the actual effect than regression filling.In the case of moderate missing ratio,the estimated effect after mean filling is closer to the actual effect compared to regression filling.When a large missing ratio(20%)occurs,data missing can lead to significantly underestimate the effect.In this case,the estimated effect after regression filling is closer to the actual effect compared to mean filling.Conclusion:Data missing can affect the estimated therapeutic effects using Bayesian models in N-of-1 trials.The present study suggests that mean filling can be used under situation of missing ratio≤10%.Otherwise,regression filling may be preferable.

基于ClinicalTrials.gov探讨慢性胰腺炎治疗研究新进展

慢性胰腺炎(chronic pancreatitis,CP)是指各种病因引起的胰腺慢性进行性炎症性纤维化疾病,临床表现为反复发作的上腹部疼痛和胰腺外分泌功能不全.ClinicalTrials.gov是目前国际上应用最广泛的临床试验数据库,主要包含已完成的、正在开展的和即将进行的临床研究的信息.本文通过对ClinicalTrials.gov数据库中所有于2024-06-30前注册的临床研究进行检索,筛选出最新的CP相关的临床研究,从营养支持、药物、内镜等角度整理归纳CP临床研究的方向和热点,旨在为今后CP临床研究的设计拓展新思路.

An Overview of Quality Management of Therapeutic Vaccines in Clinical Trials in China

Objective To provide suggestions and a reference for improving the quality management system of clinical trials of therapeutic vaccines and promoting the development of therapeutic vaccines in China.Methods Literature research,case study and comparative study were used to analyze the quality management system of clinical trials of therapeutic vaccines.Results and Conclusion From the perspective of the sponsor,investigators and the thirdparty technical service company,the problems such as the low efficiency of clinical trial sample preparation and the lax implementation of the protocol by hospital departments in the quality management of clinical trials of therapeutic vaccines in China were found.Then,the optimization plan for the quality management of clinical trials of therapeutic vaccines is proposed,including optimizing the preparation process of therapeutic vaccines and strengthening the training of hospital department personnel.

基于ClinicalTrials数据库分析抗凝血药妊娠期相关临床试验注册及方法学设计特点

目的:针对ClinicalTrials临床试验注册平台,探讨抗凝血药妊娠期应用相关临床试验注册及方法学设计特点。方法:依据抗凝血药及妊娠相关关键词,通过对ClinicalTrials临床试验注册平台进行检索,对题目及干预措施进行初选,根据注册内容进行筛选并提取相关信息,分析注册数量、研究阶段、国家/地区、研究类型等注册特点,评估涉及药物种类、妊娠相关疾病、观察结局、盲法、样本量等方法学设计特点。结果:通过双人检索及筛选,最终纳入109项抗凝血药妊娠期相关研究,我国共涉及19项相关研究。研究设计中以干预性研究为主,同时平行对照研究的研究目的以应用抗凝血药预防及治疗血栓性疾病为主。有50项研究应用盲法,以针对研究者及患者设盲较多。阿司匹林、肝素及低分子肝素涉及的研究分别有70、50项,涉及疾病中妊娠期高血压疾病及子痫、复发性流产、血栓类疾病的研究数量居前3位。已完成的临床研究中,平均样本量、时间跨度分别为780例、3.9年,终止、撤回及暂停的研究分析凸显了前期实验性研究及中期评估对于研究的重要性。结论:通过对ClinicalTrials平台临床研究特点及方法学设计进行分析,能够有效针对我国抗凝血药妊娠期临床试验设计及管理提供借鉴及参考。

基于ClinicalTrials.gov数据库分析骨肉瘤临床试验注册现状

目的 分析全球骨肉瘤临床试验注册情况,了解该领域研究现状和发展态势,为骨肉瘤研究和临床诊治提供新的信息。方法 通过采集2001—2021年期间在美国ClinicalTrials.gov注册平台注册的骨肉瘤临床试验数据,从区域分布、年度趋势、试验进展、研究类型、临床分期、参与机构数量等进行多方面的统计分析。结果 2001—2021年间,全球骨肉瘤临床试验共注册514项,主要集中在北美洲和欧洲;其中干预性临床试验有416项(80.9%),药物相关治疗占87.0%(362/416),抗肿瘤药物研究有127种;显示已完成干预性临床试验仅147项(35.3%),其中已发表论文71项(48.3%),公布试验结果 33项(46.5%)。与2001—2011年相比,2012—2021年间在亚洲地区注册的骨肉瘤干预性临床试验比例从6.1%(10/163)增加到15.0%(38/253),招募前注册从1.2%(2/163)增加到43.9%(111/253),但Ⅱ期临床试验数量在这2个时间段依旧占比最大,分别为46.0%(75/163)和37.9%(96/253)。结论 全球大多数骨肉瘤研究为干预性临床试验,主要集中在药物相关治疗,抗肿瘤药物仍然是骨肉瘤药物干预研究的首选。亚洲地区注册的干预性临床试验较之前明显增加,但研究质量和数量与北美洲、欧洲地区差异仍较大。

Characteristics of Xiao Chai Hu decoction based on randomized controlled trials: A bibliometric analysis

Objective:To explore the characteristics of Xiao Chai Hu(XCH)decoction in randomized controlled trials(RCTs)using a bibliometric method.Methods:Seven databases including PubMed,Web of Science,Embase,Cochrane library,China National Knowledge Infrastructure(CNKI),Chinese Scientific Journal Database(VIP)and Wanfang database were retrieved from inception to May 27,2022.In the study,XCH decoction(or modified)used alone or combined with conventional Western medicine as an intervention measure was included.The basic characteristics,funding support,relevant diseases,intervention methods,and adverse events(AEs)were analyzed.Data analysis was performed using SPSS 26.0 software.Results:A total of 813 RCTs were included,published from 1989 to 2022.There was only one Englishlanguage literature with the recent impact factor of 5.374.There were 147 studies were from Chineselanguage core journals,with the highest impact factor of 2.414.Only 6.15%of the literatures mentioned funding support.96.31%of the included literature reported the statistical significance of using XCH decoction.The diseases treated mainly included chronic hepatitis B(9.35%),cough variant asthma(5.66%),dizziness(5.54%),bile reflux gastritis(4.43%),and fever(4.18%).However,the overall research design of the included literature was poor,and large sample size,multicenter RCTs are needed.The incidence of AEs of XCH decoction alone was 8.86%,which was significantly lower than that of conventional Western medicine treatment.The combination of XCH decoction and conventional Western medicine treatment could reduce the incidence of AEs,and no serious adverse event was reported.Conclusion:Although the included studies show that XCH decoction is widely used,and has good efficacy and few AEs.Due to the low quality of the included RCTs,there may be some bias,and its rational use based on the specific conditions is recommended in clinical practice.

Short-term outcomes of single-incision compared to multi-port laparoscopic gastrectomy for gastric cancer:A meta-analysis of randomized controlled trials

Objective:Single-incision laparoscopic sugery has emerged as a safe and less invasive approach to conventional multi-port laparoscopy.The present meta-analysis aimed to assess the collective outcomes of single-incision laparoscopic gastrectomy(SILG)compared to multi-port laparoscopic gastrectomy(MLG)for gastric cancer.Methods:A PRISMA-compliant systematic review of randomized controlled trials(RCTs)that compared SILG and MLG for gastric cancer in PubMed and Scopus through January 2023 was conducted.The main outcomes of the review were complications,postoperative pain,conversion to open surgery,hospital stay,and recovery.Results:Three RCTs including 301 patients(61.8%male)were incuded.A total of 151 patients underwent SILG,and 150 underwent MLG.SILG was associated with a shorter operative time(WMD=-16.39,95%CI:=27.38 to=5.40,p=0.003;2=0%)and lower pain scores at postoperative day 3(WMD=-1.18,95%CI:=2.27 to=0.091,p=0.033;I^(2)=99%)than MLG.There were no statistically significant differences between the two groups in es timated blood loss(WMD=-16.95,95%CI:-35.84 to 1.95,p=0.078;I^(2)=82%),complications(OR=0.71,95%Cl:0.36 to 1.42,p=0.337;I^(2)=0%),conversion to open surgery(OR=0.33,95%C:0.01 to 8.38,p=0.504),hospital stay(WMD=0.72,95%CI:-0.92 to 2.36,p=0.056;P=84%),time to first flatus(WMD=0.06,95%CI:=0.14 to 0.26,p=0.566;I^(2)=0%),time to first defecation(WMD=-0.14,95%CI:=0.46 to 0.18,p=0.392;I^(2)=0%),or time to first oral intake(WMD=0.37,95%a:=0.75 to 1.49,p=0.520;I^(2)=94%).Conclusions:SILG is associated with shorter operative times and less early postoperative pain than MLG.The odds of complications,blood loss,hospital stay,and gastrointestinal recovery were similar between the two procedures.

Unveiling the hidden world of gut health:Exploring cutting-edge research through visualizing randomized controlled trials on the gut microbiota

BACKGROUND The gut microbiota plays a crucial role in gastrointestinal and overall health.Randomized clinical trials(RCTs)play a crucial role in advancing our knowledge and evaluating the efficacy of therapeutic interventions targeting the gut microbiota.AIM To conduct a comprehensive bibliometric analysis of the literature on RCTs involving the gut microbiota.METHODS Using bibliometric tools,a descriptive cross-sectional investigation was conducted on scholarly publications concentrated on RCTs related to gut microbiota,spanning the years 2003 to 2022.The study used VOSviewer version 1.6.9 to examine collaboration networks between different countries and evaluate the frequently employed terms in the titles and abstracts of the retrieved publications.The primary objective of this analysis was to identify key research areas and focal points associated with RCTs involving the gut microbiota.RESULTS A total of 1061 relevant articles were identified from the 24758 research articles published between 2003 and 2022.The number of publications showed a notable increase over time,with a positive correlation(R2=0.978,P<0.001).China(n=276,26.01%),the United States(n=254,23.94%),and the United Kingdom(n=97,9.14%)were the leading contributing countries.Københavns Universitet(n=38,3.58%)and Dankook University(n=35,3.30%)were the top active institutions.The co-occurrence analysis shows current gut microbiota research trends and important topics,such as obesity interventions targeting the gut microbiota,the efficacy and safety of fecal microbiota transplantation,and the effects of dietary interventions on humans.CONCLUSION The study highlights the rapid growth and importance of research on RCTs that involve the gut microbiota.This study provides valuable insight into research trends,identifies key players,and outlines potential future directions in this field.Additionally,the co-occurrence analysis identified important topics that play a critical role in the advancement of science and provided insights into future research directions in this field.

Clinical Non-inferiority Trial on Treatment of Coronary Heart Disease Angina Pectoris of Xin-blood Stasis Syndrome Type with Lyophilized Salvia Salt of Lithospermic Acid Powder for Injection

Objective： To evaluate the effectiveness and safety of lyophilized Salvia salt of lithospermic acid powder for injection （SSLA） in treating coronary heart diseases angina pectoris （CHD-AP） of Xin-blood stasis syndrome type, and to conduct the non-inferiority trial with Danshen injection （丹参注射液, DSI） as positive control. Methods： An non-inferiority clinical layered, segmented, randomized, and blinded trial on three parallel and multiple centered groups was conducted in 480 patients with stable effort angina grade Ⅰ , Ⅱand Ⅲ, who had two or more times of attack every week. The 240 patients in test group A were treated with SSLA 200 mg added in 250 ml of 5% glucose solution for intravenous dripping every day; the 120 patients in test group B were treated with SSLA but the dosage doubled; and the 120 patients in the control group were treated with DSI 20 ml daily in the same method as SSLA was given. The clinical effectiveness and safety were evaluated after the patients were treated for 14 days. Results： The results showed that the markedly effective rate in test groups A, B and control group was 37.45 %, 36.75 % and 30.09 % respectively, while the total effective rate in them was 88.09%, 89.74% and 67.26% respectively. Statistical significance was shown in comparisons of the therapeutic effect between control group with test group A and test group B, with that in the two test groups superior to that in the control group, and non-inferiority trial showed eligibility （P〈0.01）. Adverse reaction appeared in 8 patients in the test groups and 2 in the control group. Conclusion： SSLA has definite therapeutic effect in treating patients with CHD-AP, with its effect not inferior to that of DSI, and no evident toxic-adverse reaction.

帕金森病步态异常非药物康复循证研究:基于ClinicalTrials.gov数据库分析

目的了解非药物疗法治疗帕金森病步态异常的相关临床试验进展。方法检索临床试验注册平台ClinicalTrials.gov建库至2022年10月25日注册的有关非药物疗法治疗帕金森病步态异常的临床试验。两名研究人员独立对试验进行筛选,收集相关信息并对数据根据PICOS原则进行分析,包括注册时间、注册数量、样本量、干预措施、主要结局指标、研究设计等。结果最终纳入临床试验218项。近年来该领域临床试验注册数呈上升趋势。大部分临床试验的样本量<100例(93.6%),主要为21~30例。主要干预措施为神经调控技术,虚拟现实技术、机器人辅助训练技术也逐渐被采用。主要结局指标为评定量表、评定问卷和运动测试。试验设计以随机平行对照试验为主(111项,50.9%)。结论非药物疗法治疗帕金森病步态异常的临床试验注册数逐年增加,随着科学技术的发展,虚拟现实技术、机器人辅助训练技术等新的治疗方法可能成为研究主流。