中医药随机对照试验中采用真实世界数据作为对照组的研究设计及挑战

在设计随机对照试验(RCT)时,如果对照组存在患者招募和入组困难的情况,就会影响试验整体实施。近年来,真实世界数据(RWD)作为除RCT之外的数据来源,在医疗领域中发挥着越来越重要的作用。中医药RCT中可以尝试采用将RWD作为对照组的研究设计,不仅可以有效解决中医药RCT西医对照组患者入组困难的问题,同时能提供有力证据来评价中医药的疗效。倾向评分法目前已广泛应用于真实世界研究中混杂因素的处理,该文对RCT采用RWD作为对照组的这类设计中,基于倾向评分法常见的4种研究设计形式以实例分别进行了介绍,包括不对称随机分配、基于倾向评分分层法的两阶段设计、倾向评分联合复合似然法及倾向评分多种方法的联合。同时,这种设计类型也存在着方法学的挑战,包括RWD数据源必须是高质量且关键信息需要规范收集、RCT和RWD患者基线特征应该具有可比性、协变量选择时需要把所有已知与干预措施和结局相关的协变量都纳入进行分析等。在中医药领域采用这种设计时,还存在着有些RWD中医证型信息缺失、中医结局指标缺失等问题,在使用RWD时,需要根据数据实际情况决定如何分析。该文对以RWD作为RCT对照组的设计类型及面临的方法学挑战进行了介绍,期望能为研究者今后使用这类设计提供方法学借鉴。

Constitution identification model in traditional Chinese medicine based on multiple features

Objective To construct a precise model for identifying traditional Chinese medicine(TCM)constitutions;thereby offering optimized guidance for clinical diagnosis and treatment plan-ning;and ultimately enhancing medical efficiency and treatment outcomes.Methods First;TCM full-body inspection data acquisition equipment was employed to col-lect full-body standing images of healthy people;from which the constitutions were labelled and defined in accordance with the Constitution in Chinese Medicine Questionnaire(CCMQ);and a dataset encompassing labelled constitutions was constructed.Second;heat-suppres-sion valve(HSV)color space and improved local binary patterns(LBP)algorithm were lever-aged for the extraction of features such as facial complexion and body shape.In addition;a dual-branch deep network was employed to collect deep features from the full-body standing images.Last;the random forest(RF)algorithm was utilized to learn the extracted multifea-tures;which were subsequently employed to establish a TCM constitution identification mod-el.Accuracy;precision;and F1 score were the three measures selected to assess the perfor-mance of the model.Results It was found that the accuracy;precision;and F1 score of the proposed model based on multifeatures for identifying TCM constitutions were 0.842;0.868;and 0.790;respectively.In comparison with the identification models that encompass a single feature;either a single facial complexion feature;a body shape feature;or deep features;the accuracy of the model that incorporating all the aforementioned features was elevated by 0.105;0.105;and 0.079;the precision increased by 0.164;0.164;and 0.211;and the F1 score rose by 0.071;0.071;and 0.084;respectively.Conclusion The research findings affirmed the viability of the proposed model;which incor-porated multifeatures;including the facial complexion feature;the body shape feature;and the deep feature.In addition;by employing the proposed model;the objectification and intel-ligence of identifying constitutions in TCM practices could be optimized.

Meta-analysis of the efficacy and safety of Huanglian Wendan Decoction alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance

Objective To evaluate the efficacy and safety of Huanglian Wendan Decoction(黄连温胆汤,HLWDD)alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance in recent 10 years.Methods The randomized controlled trials of HLWDD alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance from January 1,2012 to April 1,2022 were searched in China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP),Wanfang Database,China BioMedical Literature Database(CBM),PubMed,Web of Science,Embase,and Cochrane Library databases.After being screening,the included literature was analyzed to evaluate the effective rate,Pittsburgh Sleep Quality Index(PSQI)score,traditional Chinese medicine(TCM)syndrome score,and adverse reactions of HLWDD on insomnia caused by phlegm-heat internal disturbance.The subgroup analyzed the effect of HLWDD after different treatment courses,and compared the therapeutic effects of HLWDD alone and HLWDD combined with western medicine.Results Twenty-seven randomized controlled trials were finally included,with a total of 2395 patients.The results of the meta-analysis showed that the curative effect of HLWDD alone or combined with the western medicine group was better than that of the western medicine group[RR=1.14,95%CI(1.06,1.22),P=0.000].The PSQI score[SMD=-0.31,95%CI(-0.42,-0.20),P=0.000],TCM syndrome score[SMD=-0.40,95%CI(-0.67,-0.12),P=0.005],and adverse reaction rate[RR=0.21,95%CI(0.15,0.29),P=0.000]of HLWDD alone or combined with western medicine group were significantly reduced compared with the western medicine group.The subgroup’s analysis showed that the curative effect of HLWDD alone or combined with western medicine group of 4 weeks treatment course was better than that of the western medicine group[RR=1.14,95%CI(1.03,1.26),P<0.05].The TCM syndrome score of HLWDD alone or combined with the western medicine group of 4 weeks treatment course decreased more obviously than that of the western medicine group[SMD=-0.60,95%CI(-0.96,-0.25),P<0.05].There were no significant differences between HLWDD alone or combined with western medicine group and western medicine group with different treatment courses based on PSQI score and adverse reaction rate.Based on the effective rate,the comparison between the HLWDD alone group and the western medicine group[RR=1.09,95%CI(1.00,-1.20)P<0.05],and between the HLWDD combined with western medicine group and the western medicine group[RR=1.15,95%CI(1.03,1.29),P<0.05]was the same.PSQI score[SMD=-0.44,95%CI(-0.59,-0.30),P<0.05]and TCM syndrome score[SMD=-1.10,95%CI(-1.59,-0.61),P<0.05]of HLWDD combined with western medicine group were significantly lower than those of the western medicine group.There were no significant differences of adverse reaction rate between HLWDD alone group[RR=0.08,95%CI(0.04,0.17),P<0.05]and HLWDD combined with western medicine group[RR=0.36,95%CI(0.24,0.53),P<0.05].Conclusion HLWDD alone or combined with western medicine is an effective treatment for insomnia caused by phlegm-heat internal disturbance,which has a high effective rate,significantly reduced PSQI score and TCM syndrome score,and favorable safety.The best course of treatment is 4 weeks.

The Mechanism of Action of Qihuang Jiangtang Capsule in the Treatment of Type 2 Diabetes Based on Network Pharmacology and Molecular Docking Technology

Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule(QHJTC)in the treatment of type 2 diabetes mellitus(T2DM)through network pharmacology and molecular docking.Methods The active components of materia medica in the formula of QHJTC were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine.The targets related to the active components were obtained via PubChem database.The targets related to T2DM were retrieved through the GeneCards database.The targets corresponding to the active components and diabetes mellitus were uploaded to the Venn diagrams website to get the Venn diagram,and the intersecting targets were the potential targets of QHJTC in treating T2DM.The active components and potential targets were imported into Cytoscape 3.7.2 software to construct the active component–potential target network,and the key compounds and targets were screened by the Network Analyzer module in the Tools module.The potential targets were imported into the STRING database to obtain the interaction relationships,so as to analyze and construct the protein–protein interaction(PPI)network by Cytoscape 3.7.2 software.The intersecting targets were introduced into Metascape for gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The top 20 signaling pathways obtained by the KEGG pathway enrichment analysis and the related targets and the corresponding targets were analyzed by using Cytoscape 3.7.2 software to construct the“active component–important target-key pathway network”for the intervention of T2DM with QHJTC.The molecular docking of active components and core targets was performed with AutoDock software.Results A total of 237 active components and 281 related targets were obtained from QHJTC,as well as 1362 T2DM targets and 155 potential targets of QHJTC in treating T2DM.There were 32 key components and 49 key targets identified by the active component–potential target network topology analysis.There were 471 terms obtained from GO functional enrichment analysis,among which 248 related to biological processes,125 related to molecular functions,and 98 related to cellular components.There were 299 signaling pathways obtained from KEGG pathway enrichment analysis.The active components of QHJTC were found spontaneously binding to the core targets.Conclusions QHJTC can treat T2DM through multi-components,multi-targets,and multi-pathways.

医疗机构中药药物警戒体系建设指南

由中国中医科学院中医临床基础医学研究所与北京中医药大学东方医院牵头,中华中医药学会归口管理的《医疗机构中药药物警戒体系建设指南》团体标准于2024年1月16日于全国团体标准信息平台公布,标准号T/CACM 1563.2-2024。借鉴欧盟药物警戒法规以及国际人用药品注册技术协调会(ICH)的二级指导原则,在充分考虑中药自身特点基础上,明确医疗机构建设中药药物警戒体系的相关制度和流程,包括建设中药药物警戒信息平台、配备人员、制定各种规章制度、全链条监测中药(包括中药饮片、颗粒剂、中成药、院内制剂、上市前中成药等)药品不良反应等,形成符合中药特点的医疗机构中药药物警戒体系,在不同级别医疗机构中,可根据医疗机构职业范围和实际情况进行适当调整。从而更好地开展中药药物警戒工作,保障用药安全。该团体标准经组内外专家多轮征求意见,最终形成了适用于医疗机构以及医疗相关单位进行药物警戒活动的指南性文件。

Overview of the systematic reviews of premature ovarian insufficiency treated with acupuncture

Objective:To assess the reliability of the methodological quality and outcome measures of systematic reviews(SR)/meta-analysis of premature ovarian insufficiency(POI) treated with acupuncture.Methods:SR/meta-analysis of POI treated with acupuncture were searched on POI from the databases including PubMed,Web of Science,EMBase,the Cochran Library,Chinese biomedical literature database(SinoMed),China journal full-text database(CNKI),Wanfang data knowledge service platform(Wanfang)and VIP information Chinese periodical service platform(VIP),from inception to 1 st May 2021.Using A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2) scale and Grades of Recommendations Assessment,Development and Evaluation(GRADE) system,the methodological quality and outcome measures of the included studies were appraised.Results:Ten articles of SR/meta-analysis were included,published from 2015 to 2020.Using AMSTAR 2,5 articles of SR/meta-analysis were rated as critical low quality in methods,3 articles as low quality,and2 articles as moderate quality.The results of GRADE showed that among the 50 outcomes the quality of evidence of 22 outcomes was very low,that of 25 outcomes was low and that of 3 outcomes was moderate.Conclusion:The methodological quality and the reliability of outcome measures were not high in existing SR/meta-analysis on POI treated with acupuncture,which may affect the translation of the SR/metaanalysis findings into clinical practice.It is necessary to further strengthen the methodological quality and reporting standard of SR/meta-analysis,as well as the robustness of design and implementation of randomized controlled trials(RCTs),in order to generate high quality evidences for clinical decision-making and practice.

Analysis on the outcomes in randomized controlled trials of perimenopausal syndrome treated with acupuncture and moxibustion

Objective:To search systematically the application situation of the outcomes in the randomized controlled trials(RCTs) of perimenopausal syndrome treated with acupuncture and moxibustion so as to provide the foundation for the core outcome sets in treatment of periomenopausal syndrome with acupuncture and moxibustion.Methods:The articles of RTCs on perimenopausal syndrome treated with acupuncture and moxibustion were searched in China National knowledge Infrastructure(CNKI),Wanfang Data Knowledge Service Platform(Wanfang),VIP Chinese Journal Service Platform(VIP),Pubmed,Excerpt medica database(Embase)and Cochrane central register of controlled trials(CENTRAL) databases from January 1,2010 to December31,2020.Two reviewers screened the articles,extracted data and analyzed the application of outcomes in the eligible trials independently.Results:A total of 9391 articles were retrieved initially and 79 articles of them were eligible,including 43 articles in English and 36 articles in Chinese.115 outcomes were involved totally and collected according to 7 outcome domains,of which,the effective rate was the outcome with the highest use frequency.35 articles reported adverse events and 17 articles reported the effect in followup.Conclusion:At present,the outcomes of RCTs on perimenopausal syndrome in treatment with acupuncture and moxibustion are big in divergence,absent in normalization and lack of indicators for long-term prognosis and economics outcomes,as well as have the issues on the incomplete reports on the differentiation between the primary and the secondary outcomes,safety indicators and followup outcomes.It needs to construct the core outcome sets in line with the characteristics of acupuncture-moxibustion discipline so as to improve the quality of clinical trials of acupuncture and moxibustion.

International patient registry on acupuncture therapy for premature ovarian insufficiency:Challenges and opportunities

Premature ovarian insufficiency（POI） affects seriously physical and mental health of the patients. Studies show that acupuncture may be promising in treating POI. yet evidence is insufficient. International patient registry, one form of observational study, is designed for evaluating effectiveness and safety of acupuncture in real-world clinical settings. We will face a series of opportunities and challenges. The opportunities are as follows：（1） Interdisciplinary cooperation can improve the effect of acupuncture for POI.（2） The protocol for acupuncture to treat POI has room for improvement.（3） The patient registry study can make up the shortcomings of randomized controlled trials.（4） The patient registry study can collect real-world data and explore responses of different populations to acupuncture and can be the foundation for the successive studies. International patient registry may face technological, ethical and financial challenges, while the established International Patient Registry Platform of Acupuncture-Moxibustion（www.amreg.org：8082/v3） is actively responding to these challenges. Till now there have been more than 300 patients of POI enrolled on this platform.

Transcutaneous auricular vagus nerve stimulation for impaired glucose tolerance:a randomized controlled trial Protocol

Background:impaired glucose tolerance(IGT)is the early stage of diabetes and it would be deteriorated to type 2 diabetes mellitus(T2 DM)easily if no intervention provided.In western medicine,drug therapy assisted with the intervention of lifestyle is predominated.However,drug therapy brings serious side effect and high prices,while lifestyle intervention is difficult to be insisted on by patients.Therefore,a green and effective intervention mode is urgently needed.Transcutaneous auricular vagus nerve stimulation(taVNS)is a noninvasive and green therapeutic method based on the theory of traditional Chinese medicine(TCM),which can regulate glucose metabolism and reduce blood glucose,but the clinical effect of it has not been clarified yet at present.Hence,this randomized controlled trial(RCT)aims at exploring the effectiveness and safety of taVNS in the treatment of IGT.Methods:a total of 158 patients with IGT will be randomized into a taVNS group and a transcutaneous non-auricular vagus nerve stimulation(tnVNS)group,79 cases in each one.In the taVNS group and the tnVNS group,electric stimulation would be applied to Yidan(胰胆pancreas and gallbladder,CO11)and Pi(脾spleen,CO13)on auricular concha and Jian(肩shoulder SF4,5)on auricular rim respectively.The electric stimulation parameters would be the same in the patients of two groups,for 30 min in each treatment,twice a day,6 weeks as one course and 2 courses of treatment required totally.In week 0,6 and 12 of intervention,the effectiveness indicators would be determined,i.e.fasting plasma glucose(FPG),2 h plasma glucose(2 hPG)and glycosylated hemoglobin(HbA1c)successively.On week 0 and 12,body mass index(BMI)would be calculated,respiration,pulse and blood pressure would be recorded separately.Discussion:through observing the regulatory effect of taVNS on FPG,2 hPG,HbAlc and BMI as well as the adverse reactions,the effectiveness and safety of taVNS in treatment of IGT would be evaluated.This study will provide a safe,effective,convenient and nontoxic side effect intervention for clinical treatment of IGT and prevention from the occurrence and development of T2DM.

Psychosomatic skin disease treated by acupuncture and moxibustion

Based on the theory of "regulating body" integrated with "regulating mind",following the principle of "treating the body and mind simultaneously,treating both symptoms and root causes",Prof.Shao-jun WANG adopts flexibly the different techniques,including body acupuncture,wrist-ankle acupuncture,umbilical acupuncture,fire needling,moxibustion,and cupping,etc.for the treatment of psychosomatic skin diseases.According to the manifestations of skin diseases in different stages,she adopts different acupuncture and moxibustion techniques for the comprehensive treatment of psychosomatic skin diseases,including senile pruritus,alopecia areata,neurodermatitis,eczema,urticaria,and acne,on the basis of syndrome differentiation and different acupoint selections,and achieves good results.