To improve multi-environmental trial(MET)analysis,a compound method—which combines factor analytic(FA)model with additive main effect and multiplicative interaction(AMMI)and genotype main effect plus genotype-by-envi...To improve multi-environmental trial(MET)analysis,a compound method—which combines factor analytic(FA)model with additive main effect and multiplicative interaction(AMMI)and genotype main effect plus genotype-by-environment interaction(GGE)biplot—was conducted in this study.The diameter at breast height of 36 open-pollinated(OP)families of Pinus taeda at six sites in South China was used as a raw dataset.The best linear unbiased prediction(BLUP)data of all individual trees in each site was obtained by fitting the spatial effects with the FA method from raw data.The raw data and BLUP data were analyzed and compared by using the AMMI and GGE biplot.BLUP results showed that the six sites were heterogeneous and spatial variation could be effectively fitted by spatial analysis with the FA method.AMMI analysis identified that two datasets had highly significant effects on the site,family,and their interactions,while BLUP data had a smaller residual error,but higher variation explaining ability and more credible stability than raw data.GGE biplot results revealed that raw data and BLUP data had different results in mega-environment delineation,test-environment evaluation,and genotype evaluation.In addition,BLUP data results were more reasonable due to the stronger analytical ability of the first two principal components.Our study suggests that the compound method combing the FA method with the AMMI and GGE biplot could improve the analysis result of MET data in Pinus teada as it was more reliable than direct AMMI and GGE biplot analysis on raw data.展开更多
Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systemat...Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systematic review and meta-analysis examined the effect of HP treatment on clinical and laboratory parameters in NAFLD patients.Methods We conducted a literature search of the PubMed,Embase,Scopus,and Web of Science databases through Septem-ber 2023 for randomized controlled trials(RCTs)examining the effect of HP treatment on NAFLD patients versus lifestyle changes alone.The primary outcome was the change in steatosis parameters.The secondary endpoints were changes in anthropometric parameters,inflammatory markers(TNF-α),and metabolic parameters(fasting blood glucose,homeostasis model assessment of insulin resistance,AST/ALT,and lipid profile).The random effects model was used to calculate the standardized mean difference(SMD)with associated 95%confidence intervals(CIs)for our desired outcome.Results Four RCTs met our inclusion criteria.A total of 453 patients were included(mean age 42.8 years,58.5%males),228(50.3%)of whom were in the HP eradication group and 225(49.7%)of whom were in the lifestyle modification group.Compared with lifestyle modification alone,HP eradication had a significant effect on reducing liver steatosis and TNF-αlevels(SMD:-0.9;95%CI-14.67,-3.82,I^(2)=0%and SMD:-6.3;95%CI-9.04,-3.56,I^(2)=0%,respectively).No sig-nificant effect on other metabolic parameters was found.Conclusions HP eradication significantly reduced liver steatosis and TNF-αlevels in NAFLD patients.However,HP eradi-cation did not significantly affect other metabolic indices compared to lifestyle changes alone.展开更多
1.Introduction Phase Ⅱ trials are typically designed to identify promising treatment therapies that warrant further investigation in subsequent phase Ⅲ con-firmatory trials,playing a vital role in evidence generatio...1.Introduction Phase Ⅱ trials are typically designed to identify promising treatment therapies that warrant further investigation in subsequent phase Ⅲ con-firmatory trials,playing a vital role in evidence generation of drug de-velopment.The basic design features of phase II trials include interim go/no-go decisions to prevent exposing too many patients to poten-tially ineffective treatments.Appropriate go/no-go decisions and effi-cient trial designs can shorten the research duration and increase trial success rates.展开更多
OBJECTIVE:In recent years,the number of clinical research reports on acupuncture and manipulation for the treatment of greater occipital neuralgia has gradually increased,but the quality is uneven.There is currently n...OBJECTIVE:In recent years,the number of clinical research reports on acupuncture and manipulation for the treatment of greater occipital neuralgia has gradually increased,but the quality is uneven.There is currently no literature evaluating the quality of published reports,which is not conducive to the promotion of clinical use of these therapies.Therefore,this article assessed the reporting quality of randomized controlled trials on acupuncture and manipulation for greater occipital neuralgia.METHODS:Cochrane Library,PubMed,Web of Science,Embase,China National Knowledge Infrastructure(CNKI),VIP,WanFang Data,and Chinese BioMedical Literature Database(CBM)from inception to May 20,2024 were searched.The reporting quality of included randomized controlled trials was independently evaluated by two investigators using the CONSORT statement,STRICTA checklist,and Cochrane bias of risk assessment tool.A third investigator resolved any disagreement.RESULTS:A total of 62 articles were included.Based on the CONSORT statement,59.46%(22/37)of all entries had a reporting rate of less than 50%,mainly including“Identification as a randomized trial in the title(1/62,1.61%),”“How sample size was determined(7/62,11.29%),”“Implementation(1/62,1.61%),”“Blinding(1/62,1.61%),”and“Reports of Funding(4/62,6.45%).”According to the STRICTA checklist,29.41%(5/17)of all entries had a reporting rate of less than 50%,mainly including“Details of other interventions(7/58,12.07%),”“Setting and context of treatment(0/58,0%),”and“Description of participating acupuncturists(0/58,0%).”CONCLUSION:The reporting quality of randomized controlled trials on acupuncture and manipulation therapy for greater occipital neuralgia remains low.Future researchers need to make greater efforts to strictly adhere to the CONSORT statement and STRICTA checklist during trial design,implementation,and reporting.This will facilitate the standardization of research in this field and enhance the reliability and reproducibility of the research results.展开更多
Objectives:This study aims to evaluate the current state of acupuncture randomized controlled trials(RCTs),their impact on guidelines,and future development trends,providing a reference for future re-search directions...Objectives:This study aims to evaluate the current state of acupuncture randomized controlled trials(RCTs),their impact on guidelines,and future development trends,providing a reference for future re-search directions.Methods:Search for acupuncture-related RCT articles in the Web of Science Core Collection and con-firm their guideline inclusion on Google Scholar.Analyze study characteristics to predict future research directions.Results:The analysis covered 1422 articles,reflecting a substantial rise in publications from 77 articles between 1993 and 2002 to 960 articles between 2013 and 2022.The Western Pacific region led in pub-lication numbers with 622 articles(43.7%),followed by Europe(466 articles;32.8%),Americas(250 articles;17.6%),Eastern Mediterranean(62 articles;4.4%),and Southeast Asia(22 articles;1.5%),with Africa showing a research void.Regrettably,only 29.6%(421 articles)were incorporated into guidelines.The low rate of inclusion of research results in guidelines and the uneven distribution of research fields are particularly prominent.From 1993 to 2002,there were 77 articles,among which 51(66.2%)were included in the guidelines;from 2003 to 2012,there were 385 articles,with 202(52.5%)included;from 2013 to 2022,there were 960 articles,and only 168(17.5%)were included,showing a decreasing trend in the inclusion rate year by year.Regarding geographical distribution,1167 articles were from the East-ern Hemisphere,with 326(27.9%)included;255 were from the Western Hemisphere,and 95(37.3%)were included.Regionally,179 articles(42.5%)from Europe were included,140(33.3%)from the West-ern Pacific,95(22.6%)from the Americas,6(1.4%)from the Eastern Mediterranean,and 1(0.2%)from Southeast Asia.China,the United States,and Germany were the top publishing countries,with consis-tent growth in countries like China,South Korea,Spain,Brazil,Turkey,and Iran.Noteworthy researchers such as Cesar Fernandez-de-las-Penas,Zhi-shun LIU,Jing-wen YANG,Cun-zhi LIU,Li-xing LAO,Stefan N Willich,and Benno Brinkhaus have collaborated on research in areas such as pain management,cognitive impairments,insomnia,digestive system diseases,and urinary system diseases.There has been a partic-ular increase in research focus on neck pain and myofascial trigger points.展开更多
Objective This study aimed to analyze the adverse effects(AEs)of sacituzumab govitecan(SG)through multiple sources of data to provide a reference for clinical safety management.Methods Clinical trials of SG with avail...Objective This study aimed to analyze the adverse effects(AEs)of sacituzumab govitecan(SG)through multiple sources of data to provide a reference for clinical safety management.Methods Clinical trials of SG with available safety data were retrieved and included in the pooled analysis.The adverse drug reaction(ADR)signals of SG were collected from the FDA Adverse Event Reporting System(FAERS)database.Drug interactions with SG in the DDInter database were summarized.Results A total of 6 clinical trials involving 1737 patients were included in the pooled analysis,and the most common AEs of≥grade 3 were neutropenia(46%),leukopenia(13%),and anemia(8%).In the pharmacovigilance study,1024 AE reports were extracted,and the most common toxicities of SG were hematologic and gastrointestinal.AEs not included in the drug instructions also presented high signals,such as meningitis,colitis and lymphedema.A total of 40 drugs identified could induce drug–drug interactions when they were concomitantly administered with SG.Conclusions This study provides the most comprehensive profile of SG toxicity on the basis of data from clinical trials and the FRAES and DDInter databases.Attention should be given not only to common ADRs but also to ADRs not reported in drug instructions,and potential drugs that can induce drug–drug interactions.展开更多
Central nervous system(CNS)tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-relatedmortality.Their rarity compared to adult cancers hasmade enrolling sufficient c...Central nervous system(CNS)tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-relatedmortality.Their rarity compared to adult cancers hasmade enrolling sufficient cases for clinical trials challenging.Consequently,pediatric CNS tumors were long treated with adult protocols despite distinct biological and clinical characteristics.This review examines key aspects of phase I pediatric oncology trials,including study design,primary outcomes,and pharmacological approaches,along with secondary considerations like clinical responses and ethical aspects.Firstly,we evaluated all phase I trial protocols focusing on pediatric CNS tumors with accessible results published in scientific databases(Pubmed,Scopus,Embase,Web of Science,and Google Scholar)from 1990 toNovember 2024.Secondly,we searched EudraCT and ClinicalTrials.gov on 30November 2024 for ongoing trials.Our search yielded 60 completed phase I studies and 15 trials in progress.Dividing them by chronological order revealed that study designs and the response assessments evolved as the understanding of CNS tumor biology increased.Despite advancements improving diagnosis,management,and prognostication,mortality remains high,and morbidity persists.Notably,pediatric pharmacokinetics and pharmacodynamics differ from adults,complicating trial comparisons and dosage optimization.Future efforts should focus on large-scale clinical data collection to enhance trial efficiency.展开更多
BACKGROUND Regulatory agencies are increasingly recognizing that minority trial repres-entation is inadequate,contributing to healthcare disparities.The scope of min-ority population disparities in clinical trial part...BACKGROUND Regulatory agencies are increasingly recognizing that minority trial repres-entation is inadequate,contributing to healthcare disparities.The scope of min-ority population disparities in clinical trial participation remains unclear,as previous studies have compiled enrollment data from published trials,which AIM To evaluate sex,racial and ethnic inequities in liver transplantation(LT)trials participation in the United States.METHODS We used data from completed United States liver transplant clinical trials registered and reported on the National Institute of Health(NIH)website(clincaltrials.gov).Demographic data,including race,ethnicity,sex,and age were collected.To make inferences to a larger population,95%CIs were computed for estimates in each demographic group using the Wilson method for binomial proportions.We also computed the simultaneous 95%CIs by applying a Bonferroni correction to reflect the multinomial distribution of race proportions.The numbers and percentages of racial/ethnic minority and female individuals compared with United States census data from 2010 and 2018.Secondary outcome measures were inclusion by trial funding source and year of completion.RESULTS A total of 69 United States based clinical trials involving 6990 participants were included in the analysis.Of these,35 trials(51%)were randomized,and 26(38%)were conducted across multiple United States regions.All trials reported sex,while 42(61%)reported race and 27(39%)reported ethnicity.Compared to United States census data,Asian individuals were overrepresented(9.3%;95%CI:8.1%-10.5%),whereas African American(7.8%;95%CI:6.7%-8.9%)and American Indian or Alaska Native individuals(0.4%;95%CI:0.1%-0.6%)were underrepresented.The proportion of White participants(75.9%;95%CI:74.1%-77.7%)was consistent with census estimates.Hispanic participants were underrepresented(13.3%;95%CI:12.2%-14.5%)regardless of the census year referenced.In industry-sponsored trials,Asian representation was three times higher than in the general population(15%).NIH funded trials showed overrepresentation of White participants(83.8%)and underrepresentation of Black participants(4.1%)relative to census data.Women comprised 31.1%of all participants(95%CI:30.0%-32.2%),in-dicating underrepresentation.Among trials that reported racial data,62(90%)did not include participants of American Indian or Alaska Native,Native Hawaiian,or Pacific Islander descent.CONCLUSION Our analysis indicates that women,African Americans,and Hispanic individuals are underrepresented in LT clinical trials compared to the general United States population.These results highlight the need for regulatory initiatives aimed at enhancing the inclusion of historically marginalized racial and ethnic groups in clinical re-search.展开更多
Acupuncture is an ancient treatment method used in traditional Chinese medicine and has been popularized worldwide.Over the past decade,there has been an increase in the amount of acupuncture research,mostly comprised...Acupuncture is an ancient treatment method used in traditional Chinese medicine and has been popularized worldwide.Over the past decade,there has been an increase in the amount of acupuncture research,mostly comprised of randomized controlled trials(RCTs)that aimed to answer the question on the efficacy of acupuncture.However,poor methodology and low replicability in these acupuncture RCTs have resulted in uncertainty about the efficacy of acupuncture.In this review,current advancements and challenges in acupuncture RCTs,regarding the methodological aspects of randomization,blinding,sham acupuncture and quality of reporting,were discussed.While there have been advancements in various aspects,current acupuncture RCTs still face pressing issues such as inadequate randomization and blinding,unviable sham acupuncture controls,and poor reporting quality.Given these limitations,this review seeks to identify the methodological problems that are responsible for these problems and to suggest solutions that could help to overcome them so as to improve the quality of future studies evaluating the efficacy of acupuncture.展开更多
BACKGROUND Systematic reviews(SRs)synthesize and evaluate data,mainly from randomized trials,which then guides the development of clinical recommendations in evidence-based medicine.However,the data and methodological...BACKGROUND Systematic reviews(SRs)synthesize and evaluate data,mainly from randomized trials,which then guides the development of clinical recommendations in evidence-based medicine.However,the data and methodological information in the included papers can often be lacking or unclear,and reviewers usually need to contact the authors of included studies for clarifications.Contacting authors is recommended,but it is unclear how often SR teams do it,or what the level of response is.AIM To investigate how often reviewers undertake contact with the authors of included randomized controlled trials(RCTs)for clarification on data and risk of bias concerns,to explore the factors that influence whether SR authors contact or do not contact the authors,and the content and level of responses.METHODS We conducted a systematic electronic database search in MEDLINE using the search string“(systematic review)”AND“(RCT OR randomized OR trial)”for articles published between 1 January 2024 and 19 February 2024,without language restrictions.Screening and data extraction was done independently by two reviewers,and conflicts resolved by a senior author.Contact authors of included SRs were contacted for clarifications.RESULTS Of the 329 included SRs,38%(n=125)explicitly mentioned contact with the authors of included studies.The remaining 62%(n=204)did not.We attempted contact with all SR teams for clarifications and received 90 responses(19.4%).Of the 50 respondents who did not explicitly mention contact in their SRs,25(50%)replied that they did make contact.We received a total of 64 responses on the level and content of information sought.The mean±SD contacts SR teams made were 10(10),replies received 5(6.7),and response waiting time 10.1(28.3)weeks.Resources,time,poor previous experience,perceived likelihood of poor response and bias concerns were reported as barriers to attempting contact.CONCLUSION The majority of SRs published in 2024 did not confirm seeking clarifying or missing information from primary study authors.However,SR teams reported that 50%of contacted primary authors respond.Additional research can clarify this rate of response and establish methods to increase the integration of this core methodological element in SRs.展开更多
Sham acupuncture,as a control intervention in acupuncture studies,has been widely conducted to eval-uate the specific effect of acupuncture.However,there was no relevant particular reporting guideline,so the reporting...Sham acupuncture,as a control intervention in acupuncture studies,has been widely conducted to eval-uate the specific effect of acupuncture.However,there was no relevant particular reporting guideline,so the reporting quality of sham acupuncture was low,which could hinder the precise understanding and interpretation of details and implementation background of sham acupuncture by researchers.In order to standardize the reporting of sham acupuncture and improve its quality,SHam Acupuncture REporting guidelines and a checklist in clinical trials(SHARE)was developed by a research team from Beijing Univer-sity of Chinese Medicine.The SAHRE standardizes the reporting of sham acupuncture from 10 categories,including brief name,rationales,details of sham acupuncture,treatment regimen of sham acupuncture,the information informed or explained to patients,practitioner information,modifications of protocol,communication between practitioner and patient,practitioner adherence and blinding.This article elab-orates the development process and key content of SHARE in order to facilitate its application by re-searchers.展开更多
BACKGROUND In randomized controlled trials(RCTs),the placebo arm has often been ignored as the attention tends to be focused on the treatment arm.We undertook a meta-analysis based on the data from the placebo arm in ...BACKGROUND In randomized controlled trials(RCTs),the placebo arm has often been ignored as the attention tends to be focused on the treatment arm.We undertook a meta-analysis based on the data from the placebo arm in RCTs of hepatocellular carci-noma(HCC),the response rates and survival status,and adverse events(AEs)were summarized and evaluated.AIM To systematically evaluate the response rates,survival status and AEs in the placebo arms of RCTs for HCC.METHODS A systematic search was performed on PubMed,Ovid MEDLINE,Embase and Cochrane Library to identify relevant trials evaluating the efficacy of drugs for the treatment of HCC,published until December 31,2023.Statistical analysis was performed using R statistical software(version 4.3.2).RESULTS A total of 18 RCTs,involving 2390 patients,met the criteria for inclusion in the meta-analysis.The pooled overall disease control rate and objective response rate in the placebo group were 38%[95%confidence interval(CI):33%-42%]and 1%(95%CI:1%-2%),respectively.Overall survival and progression-free survival in the placebo group were 7.9 months(95%CI:7.6-8.31 months)and 1.9 months(95%CI:1.6-2.1 months),respectively.The incidence of grade 3 or 4 AEs was 37%(95%CI:30%-43%).Additionally,the incidence of interruptions or dose reductions due to AEs was 20%(95%CI:13%-27%),while the incidence of treatment discontinuation due to AEs was 9%(95%CI:6%-12%).CONCLUSION Over one-third of advanced HCC patients exhibit therapy-free disease control,with placebo-arm AEs observed.These findings guide single-arm trials design and enhance patient acceptance of anticancer therapies.展开更多
BACKGROUND Nutritional psychiatry is a rapidly expanding field of research,with mounting evidence suggesting that nutritional factors may play a role in the development of psychiatric disorders.AIM To examine the leve...BACKGROUND Nutritional psychiatry is a rapidly expanding field of research,with mounting evidence suggesting that nutritional factors may play a role in the development of psychiatric disorders.AIM To examine the level of evidence for nutritional psychiatry.METHODS A scoping review was conducted to assess the current state of nutritional psychiatry,including a search for randomized controlled trials(RCTs).RESULTS The review identified a total of seven papers,with many concentrating on the relationship between depression and the gut microbiome.A salient issue that emerged from this review was the paucity of sample size in many studies.The inherent complexity of nutritional studies,characterized by a multitude of potential factors and exposures that often act as confounders,poses significant challenges to the development of effective RCT designs.The analysis revealed that probiotics,though demonstrating efficacy,exhibited a modest effect size.CONCLUSION Conducting RCTs with effective markers is imperative from these studies.The implementation of Mendelian randomization and the investigation of mechanisms in basic research are essential complementary approaches.展开更多
The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research ...The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research indicates the aberrant expression of diverse tyrosine kinases(TKs)within this cancer,contributing significantly to tumor cell proliferation,survival,invasion,and migration.The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies,given their pivotal roles in tumor initiation,progression,and advancement.Intensive investigations have focused on various monoclonal antibodies(mAbs)and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR),cellular mesenchymal-epithelial transition factor(c-MET),human epidermal growth factor receptor 2(HER2),among others,for combating TNBC.These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents.Despite these advances,a substantial terrain of unexplored potential lies within the realm of TK-targeted therapeutics,which hold promise in reshaping the therapeutic landscape.This review summarizes the various TK-targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC,dissecting the outcomes and revelations stemming from diverse clinical investigations.A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBC for the maximum efficiency of TK-targeted therapeutics,either as standalone treatments or a combination.Moreover,our observation highlights that the outcomes of TK-targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort,emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.展开更多
The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation...The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome,Muckle-Wells syndrome,and familial cold autoinflammatory syndrome 1.To date,a great effort has been made to decode the underlying mechanisms of NLRP3 activation.The priming and activation of NLRP3 drive the maturation and release of active interleukin(IL)-18 and IL-1βto cause inflammation and pyroptosis,which can significantly trigger many diseases including inflammatory diseases,immune disorders,metabolic diseases,and neurodegenerative diseases.The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials.Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields.In this minireview,we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways.We then reviewed the molecular and cellular pathways of NLRP3 in many diseases,including obesity,diabetes,and other metabolic diseases.In addition,we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy.Finally,clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.展开更多
Traditional Medicine(TM),particularly Traditional Chinese Medicine(TCM),is an indispensable component of the global healthcare system,offering unique insights to modern medical science.Clinical efficacy is the bedrock...Traditional Medicine(TM),particularly Traditional Chinese Medicine(TCM),is an indispensable component of the global healthcare system,offering unique insights to modern medical science.Clinical efficacy is the bedrock for the inheritance and development of TM.To meet the growing demand for high-quality healthcare,it is imperative to integrate TM with modern technology to address the issue of insufficient evidence for the efficacy of TM.展开更多
基金supported by State Key Laboratory of Tree Genetics and Breeding(Northeast Forestry University)(K2013204)co-financed with NSFC project(31470673)Guangdong Science and Technology Planning Project(2016B070701008)
文摘To improve multi-environmental trial(MET)analysis,a compound method—which combines factor analytic(FA)model with additive main effect and multiplicative interaction(AMMI)and genotype main effect plus genotype-by-environment interaction(GGE)biplot—was conducted in this study.The diameter at breast height of 36 open-pollinated(OP)families of Pinus taeda at six sites in South China was used as a raw dataset.The best linear unbiased prediction(BLUP)data of all individual trees in each site was obtained by fitting the spatial effects with the FA method from raw data.The raw data and BLUP data were analyzed and compared by using the AMMI and GGE biplot.BLUP results showed that the six sites were heterogeneous and spatial variation could be effectively fitted by spatial analysis with the FA method.AMMI analysis identified that two datasets had highly significant effects on the site,family,and their interactions,while BLUP data had a smaller residual error,but higher variation explaining ability and more credible stability than raw data.GGE biplot results revealed that raw data and BLUP data had different results in mega-environment delineation,test-environment evaluation,and genotype evaluation.In addition,BLUP data results were more reasonable due to the stronger analytical ability of the first two principal components.Our study suggests that the compound method combing the FA method with the AMMI and GGE biplot could improve the analysis result of MET data in Pinus teada as it was more reliable than direct AMMI and GGE biplot analysis on raw data.
文摘Objective Helicobacter pylori(HP)infection is associated with non-alcoholic fatty liver disease(NAFLD)and insulin resistance;however,the correlation between HP eradication and NAFLD remains controversial.This systematic review and meta-analysis examined the effect of HP treatment on clinical and laboratory parameters in NAFLD patients.Methods We conducted a literature search of the PubMed,Embase,Scopus,and Web of Science databases through Septem-ber 2023 for randomized controlled trials(RCTs)examining the effect of HP treatment on NAFLD patients versus lifestyle changes alone.The primary outcome was the change in steatosis parameters.The secondary endpoints were changes in anthropometric parameters,inflammatory markers(TNF-α),and metabolic parameters(fasting blood glucose,homeostasis model assessment of insulin resistance,AST/ALT,and lipid profile).The random effects model was used to calculate the standardized mean difference(SMD)with associated 95%confidence intervals(CIs)for our desired outcome.Results Four RCTs met our inclusion criteria.A total of 453 patients were included(mean age 42.8 years,58.5%males),228(50.3%)of whom were in the HP eradication group and 225(49.7%)of whom were in the lifestyle modification group.Compared with lifestyle modification alone,HP eradication had a significant effect on reducing liver steatosis and TNF-αlevels(SMD:-0.9;95%CI-14.67,-3.82,I^(2)=0%and SMD:-6.3;95%CI-9.04,-3.56,I^(2)=0%,respectively).No sig-nificant effect on other metabolic parameters was found.Conclusions HP eradication significantly reduced liver steatosis and TNF-αlevels in NAFLD patients.However,HP eradi-cation did not significantly affect other metabolic indices compared to lifestyle changes alone.
基金funded by Beijing Nova Program(grant number:20230484277)National Natural Science Foundation of China(grant number:82303955).
文摘1.Introduction Phase Ⅱ trials are typically designed to identify promising treatment therapies that warrant further investigation in subsequent phase Ⅲ con-firmatory trials,playing a vital role in evidence generation of drug de-velopment.The basic design features of phase II trials include interim go/no-go decisions to prevent exposing too many patients to poten-tially ineffective treatments.Appropriate go/no-go decisions and effi-cient trial designs can shorten the research duration and increase trial success rates.
文摘OBJECTIVE:In recent years,the number of clinical research reports on acupuncture and manipulation for the treatment of greater occipital neuralgia has gradually increased,but the quality is uneven.There is currently no literature evaluating the quality of published reports,which is not conducive to the promotion of clinical use of these therapies.Therefore,this article assessed the reporting quality of randomized controlled trials on acupuncture and manipulation for greater occipital neuralgia.METHODS:Cochrane Library,PubMed,Web of Science,Embase,China National Knowledge Infrastructure(CNKI),VIP,WanFang Data,and Chinese BioMedical Literature Database(CBM)from inception to May 20,2024 were searched.The reporting quality of included randomized controlled trials was independently evaluated by two investigators using the CONSORT statement,STRICTA checklist,and Cochrane bias of risk assessment tool.A third investigator resolved any disagreement.RESULTS:A total of 62 articles were included.Based on the CONSORT statement,59.46%(22/37)of all entries had a reporting rate of less than 50%,mainly including“Identification as a randomized trial in the title(1/62,1.61%),”“How sample size was determined(7/62,11.29%),”“Implementation(1/62,1.61%),”“Blinding(1/62,1.61%),”and“Reports of Funding(4/62,6.45%).”According to the STRICTA checklist,29.41%(5/17)of all entries had a reporting rate of less than 50%,mainly including“Details of other interventions(7/58,12.07%),”“Setting and context of treatment(0/58,0%),”and“Description of participating acupuncturists(0/58,0%).”CONCLUSION:The reporting quality of randomized controlled trials on acupuncture and manipulation therapy for greater occipital neuralgia remains low.Future researchers need to make greater efforts to strictly adhere to the CONSORT statement and STRICTA checklist during trial design,implementation,and reporting.This will facilitate the standardization of research in this field and enhance the reliability and reproducibility of the research results.
基金Supported by the National Natural Science Foundation of China:82074529Guangdong Province Famous Traditional Chinese Medicine Inheritance Studio Construction Project:Guangdong Traditional Chinese Medicine Office Letter 2023_108+1 种基金Sanming Project of Medicine in Shenzhen:SZZYSM202108013Hainan General Hospital Science and Technology Start-up Fund for Braught-in Talents:YJRC2022001。
文摘Objectives:This study aims to evaluate the current state of acupuncture randomized controlled trials(RCTs),their impact on guidelines,and future development trends,providing a reference for future re-search directions.Methods:Search for acupuncture-related RCT articles in the Web of Science Core Collection and con-firm their guideline inclusion on Google Scholar.Analyze study characteristics to predict future research directions.Results:The analysis covered 1422 articles,reflecting a substantial rise in publications from 77 articles between 1993 and 2002 to 960 articles between 2013 and 2022.The Western Pacific region led in pub-lication numbers with 622 articles(43.7%),followed by Europe(466 articles;32.8%),Americas(250 articles;17.6%),Eastern Mediterranean(62 articles;4.4%),and Southeast Asia(22 articles;1.5%),with Africa showing a research void.Regrettably,only 29.6%(421 articles)were incorporated into guidelines.The low rate of inclusion of research results in guidelines and the uneven distribution of research fields are particularly prominent.From 1993 to 2002,there were 77 articles,among which 51(66.2%)were included in the guidelines;from 2003 to 2012,there were 385 articles,with 202(52.5%)included;from 2013 to 2022,there were 960 articles,and only 168(17.5%)were included,showing a decreasing trend in the inclusion rate year by year.Regarding geographical distribution,1167 articles were from the East-ern Hemisphere,with 326(27.9%)included;255 were from the Western Hemisphere,and 95(37.3%)were included.Regionally,179 articles(42.5%)from Europe were included,140(33.3%)from the West-ern Pacific,95(22.6%)from the Americas,6(1.4%)from the Eastern Mediterranean,and 1(0.2%)from Southeast Asia.China,the United States,and Germany were the top publishing countries,with consis-tent growth in countries like China,South Korea,Spain,Brazil,Turkey,and Iran.Noteworthy researchers such as Cesar Fernandez-de-las-Penas,Zhi-shun LIU,Jing-wen YANG,Cun-zhi LIU,Li-xing LAO,Stefan N Willich,and Benno Brinkhaus have collaborated on research in areas such as pain management,cognitive impairments,insomnia,digestive system diseases,and urinary system diseases.There has been a partic-ular increase in research focus on neck pain and myofascial trigger points.
基金supported by grants from the National Natural Science Foundation of China(82200212)and(81902934).
文摘Objective This study aimed to analyze the adverse effects(AEs)of sacituzumab govitecan(SG)through multiple sources of data to provide a reference for clinical safety management.Methods Clinical trials of SG with available safety data were retrieved and included in the pooled analysis.The adverse drug reaction(ADR)signals of SG were collected from the FDA Adverse Event Reporting System(FAERS)database.Drug interactions with SG in the DDInter database were summarized.Results A total of 6 clinical trials involving 1737 patients were included in the pooled analysis,and the most common AEs of≥grade 3 were neutropenia(46%),leukopenia(13%),and anemia(8%).In the pharmacovigilance study,1024 AE reports were extracted,and the most common toxicities of SG were hematologic and gastrointestinal.AEs not included in the drug instructions also presented high signals,such as meningitis,colitis and lymphedema.A total of 40 drugs identified could induce drug–drug interactions when they were concomitantly administered with SG.Conclusions This study provides the most comprehensive profile of SG toxicity on the basis of data from clinical trials and the FRAES and DDInter databases.Attention should be given not only to common ADRs but also to ADRs not reported in drug instructions,and potential drugs that can induce drug–drug interactions.
文摘Central nervous system(CNS)tumors are the most common solid tumors in pediatric patients and the leading cause of childhood cancer-relatedmortality.Their rarity compared to adult cancers hasmade enrolling sufficient cases for clinical trials challenging.Consequently,pediatric CNS tumors were long treated with adult protocols despite distinct biological and clinical characteristics.This review examines key aspects of phase I pediatric oncology trials,including study design,primary outcomes,and pharmacological approaches,along with secondary considerations like clinical responses and ethical aspects.Firstly,we evaluated all phase I trial protocols focusing on pediatric CNS tumors with accessible results published in scientific databases(Pubmed,Scopus,Embase,Web of Science,and Google Scholar)from 1990 toNovember 2024.Secondly,we searched EudraCT and ClinicalTrials.gov on 30November 2024 for ongoing trials.Our search yielded 60 completed phase I studies and 15 trials in progress.Dividing them by chronological order revealed that study designs and the response assessments evolved as the understanding of CNS tumor biology increased.Despite advancements improving diagnosis,management,and prognostication,mortality remains high,and morbidity persists.Notably,pediatric pharmacokinetics and pharmacodynamics differ from adults,complicating trial comparisons and dosage optimization.Future efforts should focus on large-scale clinical data collection to enhance trial efficiency.
文摘BACKGROUND Regulatory agencies are increasingly recognizing that minority trial repres-entation is inadequate,contributing to healthcare disparities.The scope of min-ority population disparities in clinical trial participation remains unclear,as previous studies have compiled enrollment data from published trials,which AIM To evaluate sex,racial and ethnic inequities in liver transplantation(LT)trials participation in the United States.METHODS We used data from completed United States liver transplant clinical trials registered and reported on the National Institute of Health(NIH)website(clincaltrials.gov).Demographic data,including race,ethnicity,sex,and age were collected.To make inferences to a larger population,95%CIs were computed for estimates in each demographic group using the Wilson method for binomial proportions.We also computed the simultaneous 95%CIs by applying a Bonferroni correction to reflect the multinomial distribution of race proportions.The numbers and percentages of racial/ethnic minority and female individuals compared with United States census data from 2010 and 2018.Secondary outcome measures were inclusion by trial funding source and year of completion.RESULTS A total of 69 United States based clinical trials involving 6990 participants were included in the analysis.Of these,35 trials(51%)were randomized,and 26(38%)were conducted across multiple United States regions.All trials reported sex,while 42(61%)reported race and 27(39%)reported ethnicity.Compared to United States census data,Asian individuals were overrepresented(9.3%;95%CI:8.1%-10.5%),whereas African American(7.8%;95%CI:6.7%-8.9%)and American Indian or Alaska Native individuals(0.4%;95%CI:0.1%-0.6%)were underrepresented.The proportion of White participants(75.9%;95%CI:74.1%-77.7%)was consistent with census estimates.Hispanic participants were underrepresented(13.3%;95%CI:12.2%-14.5%)regardless of the census year referenced.In industry-sponsored trials,Asian representation was three times higher than in the general population(15%).NIH funded trials showed overrepresentation of White participants(83.8%)and underrepresentation of Black participants(4.1%)relative to census data.Women comprised 31.1%of all participants(95%CI:30.0%-32.2%),in-dicating underrepresentation.Among trials that reported racial data,62(90%)did not include participants of American Indian or Alaska Native,Native Hawaiian,or Pacific Islander descent.CONCLUSION Our analysis indicates that women,African Americans,and Hispanic individuals are underrepresented in LT clinical trials compared to the general United States population.These results highlight the need for regulatory initiatives aimed at enhancing the inclusion of historically marginalized racial and ethnic groups in clinical re-search.
基金supported by the National High-Level Chinese Medicine Hospital Clinical Research Funding(No.DFGZRB-2024GJRC015)。
文摘Acupuncture is an ancient treatment method used in traditional Chinese medicine and has been popularized worldwide.Over the past decade,there has been an increase in the amount of acupuncture research,mostly comprised of randomized controlled trials(RCTs)that aimed to answer the question on the efficacy of acupuncture.However,poor methodology and low replicability in these acupuncture RCTs have resulted in uncertainty about the efficacy of acupuncture.In this review,current advancements and challenges in acupuncture RCTs,regarding the methodological aspects of randomization,blinding,sham acupuncture and quality of reporting,were discussed.While there have been advancements in various aspects,current acupuncture RCTs still face pressing issues such as inadequate randomization and blinding,unviable sham acupuncture controls,and poor reporting quality.Given these limitations,this review seeks to identify the methodological problems that are responsible for these problems and to suggest solutions that could help to overcome them so as to improve the quality of future studies evaluating the efficacy of acupuncture.
文摘BACKGROUND Systematic reviews(SRs)synthesize and evaluate data,mainly from randomized trials,which then guides the development of clinical recommendations in evidence-based medicine.However,the data and methodological information in the included papers can often be lacking or unclear,and reviewers usually need to contact the authors of included studies for clarifications.Contacting authors is recommended,but it is unclear how often SR teams do it,or what the level of response is.AIM To investigate how often reviewers undertake contact with the authors of included randomized controlled trials(RCTs)for clarification on data and risk of bias concerns,to explore the factors that influence whether SR authors contact or do not contact the authors,and the content and level of responses.METHODS We conducted a systematic electronic database search in MEDLINE using the search string“(systematic review)”AND“(RCT OR randomized OR trial)”for articles published between 1 January 2024 and 19 February 2024,without language restrictions.Screening and data extraction was done independently by two reviewers,and conflicts resolved by a senior author.Contact authors of included SRs were contacted for clarifications.RESULTS Of the 329 included SRs,38%(n=125)explicitly mentioned contact with the authors of included studies.The remaining 62%(n=204)did not.We attempted contact with all SR teams for clarifications and received 90 responses(19.4%).Of the 50 respondents who did not explicitly mention contact in their SRs,25(50%)replied that they did make contact.We received a total of 64 responses on the level and content of information sought.The mean±SD contacts SR teams made were 10(10),replies received 5(6.7),and response waiting time 10.1(28.3)weeks.Resources,time,poor previous experience,perceived likelihood of poor response and bias concerns were reported as barriers to attempting contact.CONCLUSION The majority of SRs published in 2024 did not confirm seeking clarifying or missing information from primary study authors.However,SR teams reported that 50%of contacted primary authors respond.Additional research can clarify this rate of response and establish methods to increase the integration of this core methodological element in SRs.
文摘Sham acupuncture,as a control intervention in acupuncture studies,has been widely conducted to eval-uate the specific effect of acupuncture.However,there was no relevant particular reporting guideline,so the reporting quality of sham acupuncture was low,which could hinder the precise understanding and interpretation of details and implementation background of sham acupuncture by researchers.In order to standardize the reporting of sham acupuncture and improve its quality,SHam Acupuncture REporting guidelines and a checklist in clinical trials(SHARE)was developed by a research team from Beijing Univer-sity of Chinese Medicine.The SAHRE standardizes the reporting of sham acupuncture from 10 categories,including brief name,rationales,details of sham acupuncture,treatment regimen of sham acupuncture,the information informed or explained to patients,practitioner information,modifications of protocol,communication between practitioner and patient,practitioner adherence and blinding.This article elab-orates the development process and key content of SHARE in order to facilitate its application by re-searchers.
文摘BACKGROUND In randomized controlled trials(RCTs),the placebo arm has often been ignored as the attention tends to be focused on the treatment arm.We undertook a meta-analysis based on the data from the placebo arm in RCTs of hepatocellular carci-noma(HCC),the response rates and survival status,and adverse events(AEs)were summarized and evaluated.AIM To systematically evaluate the response rates,survival status and AEs in the placebo arms of RCTs for HCC.METHODS A systematic search was performed on PubMed,Ovid MEDLINE,Embase and Cochrane Library to identify relevant trials evaluating the efficacy of drugs for the treatment of HCC,published until December 31,2023.Statistical analysis was performed using R statistical software(version 4.3.2).RESULTS A total of 18 RCTs,involving 2390 patients,met the criteria for inclusion in the meta-analysis.The pooled overall disease control rate and objective response rate in the placebo group were 38%[95%confidence interval(CI):33%-42%]and 1%(95%CI:1%-2%),respectively.Overall survival and progression-free survival in the placebo group were 7.9 months(95%CI:7.6-8.31 months)and 1.9 months(95%CI:1.6-2.1 months),respectively.The incidence of grade 3 or 4 AEs was 37%(95%CI:30%-43%).Additionally,the incidence of interruptions or dose reductions due to AEs was 20%(95%CI:13%-27%),while the incidence of treatment discontinuation due to AEs was 9%(95%CI:6%-12%).CONCLUSION Over one-third of advanced HCC patients exhibit therapy-free disease control,with placebo-arm AEs observed.These findings guide single-arm trials design and enhance patient acceptance of anticancer therapies.
文摘BACKGROUND Nutritional psychiatry is a rapidly expanding field of research,with mounting evidence suggesting that nutritional factors may play a role in the development of psychiatric disorders.AIM To examine the level of evidence for nutritional psychiatry.METHODS A scoping review was conducted to assess the current state of nutritional psychiatry,including a search for randomized controlled trials(RCTs).RESULTS The review identified a total of seven papers,with many concentrating on the relationship between depression and the gut microbiome.A salient issue that emerged from this review was the paucity of sample size in many studies.The inherent complexity of nutritional studies,characterized by a multitude of potential factors and exposures that often act as confounders,poses significant challenges to the development of effective RCT designs.The analysis revealed that probiotics,though demonstrating efficacy,exhibited a modest effect size.CONCLUSION Conducting RCTs with effective markers is imperative from these studies.The implementation of Mendelian randomization and the investigation of mechanisms in basic research are essential complementary approaches.
基金supported by the Department of Biotechnology(DBT),Government of India(BT/556/NE/U-Excel/).
文摘The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research indicates the aberrant expression of diverse tyrosine kinases(TKs)within this cancer,contributing significantly to tumor cell proliferation,survival,invasion,and migration.The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies,given their pivotal roles in tumor initiation,progression,and advancement.Intensive investigations have focused on various monoclonal antibodies(mAbs)and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR),cellular mesenchymal-epithelial transition factor(c-MET),human epidermal growth factor receptor 2(HER2),among others,for combating TNBC.These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents.Despite these advances,a substantial terrain of unexplored potential lies within the realm of TK-targeted therapeutics,which hold promise in reshaping the therapeutic landscape.This review summarizes the various TK-targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC,dissecting the outcomes and revelations stemming from diverse clinical investigations.A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBC for the maximum efficiency of TK-targeted therapeutics,either as standalone treatments or a combination.Moreover,our observation highlights that the outcomes of TK-targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort,emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.
文摘The nucleotide-binding domain,leucine-rich repeat,and pyrin domain-containing protein 3(NLRP3)inflammasome is a critical modulator in inflammatory disease.Activation and mutation of NLRP3 can cause severe inflammation in diseases such as chronic infantile neurologic cutaneous and articular syndrome,Muckle-Wells syndrome,and familial cold autoinflammatory syndrome 1.To date,a great effort has been made to decode the underlying mechanisms of NLRP3 activation.The priming and activation of NLRP3 drive the maturation and release of active interleukin(IL)-18 and IL-1βto cause inflammation and pyroptosis,which can significantly trigger many diseases including inflammatory diseases,immune disorders,metabolic diseases,and neurodegenerative diseases.The investigation of NLRP3 as a therapeutic target for disease treatment is a hot topic in both preclinical studies and clinical trials.Developing potent NLRP3 inhibitors and downstream IL-1 inhibitors attracts wide-spectrum attention in both research and pharmaceutical fields.In this minireview,we first updated the molecular mechanisms involved in NLRP3 inflammasome activation and the associated downstream signaling pathways.We then reviewed the molecular and cellular pathways of NLRP3 in many diseases,including obesity,diabetes,and other metabolic diseases.In addition,we briefly reviewed the roles of NLRP3 in cancer growth and relative immune checkpoint therapy.Finally,clinical trials with treatments targeting NLRP3 and its downstream signaling pathways were summarized.
文摘Traditional Medicine(TM),particularly Traditional Chinese Medicine(TCM),is an indispensable component of the global healthcare system,offering unique insights to modern medical science.Clinical efficacy is the bedrock for the inheritance and development of TM.To meet the growing demand for high-quality healthcare,it is imperative to integrate TM with modern technology to address the issue of insufficient evidence for the efficacy of TM.
