简介：Whyundertakeclinicaltrials?Beforeanewtreatmentcanbewidelyusedonpatients,itmustbeproventobesafeandeffective.Clinicaltrialsareumeansofconductingexperimentsonhumanstoyieldreliableresults.Forthisreason,theyareinthebestinterestsofpatients,clinicians,pharmaceuticalcompaniesandsocietyasawbele.

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简介：Howtodesignclinicaltrialsformedicaldevicesisaproblemplaguingtheindustrytoday.Astherearemanydifferencesinclinicaltrialsofmedicaldevicesanddrugs.Thispaperdescribesthedifferencesofthetwopointsfromtheperspectivsofdefinitionofmedicaldevicesanddrugs,scope,phasing,subjectsanddesignofclinicaltrialsindetails,aimingtohelptherelatedpersonnelmakescientificdecisionswhileconductingclinicaltrialdesignformedicaldevices.

简介：Accordingtothemostrecentepidemiologicaldata,theprevalenceofhypertensionrangedfromabout25%inChineselivingeitherinthemainlandorinTaiwanandKoreans,toapproximately40%inMongolians.Thecontrolrateofhypertensionwasabout35%inKoreansandJapanese,24%inMongolians,andlessthan10%inChinese.Fourplacebo-controlledtrialsinChinaunequivocallyprovedthatantihypertensivetherapymaypreventstrokeandothercardiovascularcomplicationsinhypertensionorpatientswithahistoryofstrokeortransientischemicattack.Fouractively-controlledtrialsinJapandidnotshowsignificantdifferencebetweenvariousclassesorcombinationsofantihypertensivedrugs.TwotrialsthatcomparedintensivewithlessintensivebloodpressurecontrolinelderlyJapanesehypertensivepatientsdidnotshowfurtherbenefitofcontrollingsystolicbloodpressuretoalevelbelow140mmHgincomparisonwithbloodpressurecontroltoalevelof140mmHgorabove.Thesetrialsthatcomparedvariousclassesofantihypertensivedrugsorintensivewithlessintensivebloodpressurecontroloftenhadsmallsamplesizeandhenceinadequatepowertodetectmodestormoderatebenefit.ThereisstillaneedforhighqualityoutcometrialdatainEastAsians.

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简介：AbstractFibroblast growth factor 21 (FGF21) is a fasting or stress inducible metabolic hormone produced mainly in the liver. It plays important roles in regulating both glucose and lipid homeostasis via interacting with a heterodimeric receptor complex comprising FGF receptor 1 (FGFR1) and β-klotho (KLB). For the past decade, great effort has been made on developing FGF21 derivatives or specific FGF21 receptor agonists into therapeutic agents for various metabolic disorders including type 2 diabetes (T2D), obesity, and more importantly, nonalcoholic fatty liver disease (NAFLD). Here we have reviewed FGF21 gene and protein structures, its expression pattern, cellular signaling cascades that mediate FGF21 production and function. We have then summarized the six clinical trials utilizing four FGF21 analogues. Finally, two recent literatures on the development of GLP-1 and FGF21 dual agonists were presented briefly.

简介：Theimplementationofmolecularprofilingtechnologiesinoncologydeepensourknowledgeforthemolecularlandscapesofcancerdiagnoses,identifyingaberrationsthatcouldbelinkedwithspecifictherapeuticvulnerabilities.Inparticular,thereisanincreasinglistofmolecularlytargetedanticanceragentsundergoingclinicaldevelopmentthataimtoblockspecificmolecularaberrations.Thisleadstoaparadigmshift,withanincreasinglistofspecificaberrationsdictatingthetreatmentofpatientswithcancer.Thisparadigmshiftimpactsthefieldofclinicaltrials,sincetheclassicalapproachofhavingclinico-pathologicaldiseasecharacteristicsdictatingthepatients'enrolmentinoncologytrialsshiftstowardstheimplementationofmolecularprofilingasprescreeningstep.Inordertofacilitatethesuccessfulclinicaldevelopmentofthesenewanticancerdrugswithinspecificmolecularnichesofcancerdiagnoses,therehavebeendevelopednew,innovativetrialdesignsthatcouldbeclassifiedasfollows:i)longitudinalcohortstudiesthatimplement(ornot)'nested'downstreamtrials,2)studiesthatassesstheclinicalutilityofmolecularprofiling,3)'master'protocoltrials,iv)'basket'trials,v)trialsfollowinganadaptivedesign.Inthepresentarticle,wereviewtheseinnovativestudydesigns,providingrepresentativeexamplesfromeachcategoryandwediscussthechallengesthatstillneedtobeaddressedinthiseraofnewgenerationoncologytrialsimplementingmolecularprofiling.Emphasisisputonthefieldofbreastcancerclinicaltrials.

简介：Theobjectiveofthissystematicreviewwastoassesstheeffectivenessofspinalmanipulationsasatreatmentoptionforcervicogenicheadaches.SevendatabasesweresearchedfromtheirinceptiontoFebruary2011.Allrandomizedtrialswhichinvestigatedspinalmanipulationsperformedbyanytypeofhealthcareprofessionalfortreatingcervicogenicheadachesinhumansubjectswereconsidered.Theselectionofstudies,

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简介：Anewendophyticantagonisticfungus,ChaetomiumspiraleND35fromPopulustomentosa,wasreported.Thebio-controltrialsofC.spiraleND35againsttheValsaCankerofapplewerepreliminarilyinvestigated.TheresultsofdualcultureonPDAplateshowedthatC.spiraleND35wascapableofstrongantagonismagainstValsaceratosperma,andforinhibitingthemycelialgrowthofV.ceratosperma,.thecrudeextractofliquidcultureofcornsteeppowderbrothwasmoreeffectivethanthatoneofmaltextractbroth(MEB).Theresultsofbio-controlingreenhouseandfieldindicatedthatthediseaseincidenceofappletreetreatedwithC.spiraleND35waslowersignificantlythanthattreatedbyothermethods.There-isolationexperimentsuggestedthatC.spiraleND35couldcolonizeinstemsandbranchesofappletreessuccessfully,andtheND35colonizationrateofthetreatmentwithsolidwheatbranculturewashigherthanthatofcornsteeppowderbroth,butthefieldexperimentresultthecontroleffectofliquidcultureofC.spiraleND35wasbetterthanthatofsolidculture.

简介：AbstractBackground:Pioglitazone may be beneficial in the treatment of psoriasis. However, based on the effectiveness and safety considerations, it has not been widely used. To fully evaluate the strength of evidence supporting psoriasis treatment with pioglitazone, we conducted a meta-analysis of existing published studies.Methods:PubMed, Ovid, Cochrane Library, Google Scholar, and Web of Science databases were systematically searched before February 2019. Randomized controlled trials (RCTs) of pioglitazone administration compared with placebo, administered to patients with psoriasis for at least 10 weeks, and published in English were included. Quality of the included RCTs was identified by the modified Jadad scale. The quality of evidence for each outcome was evaluated using the GRADEpro Guideline Development Tool online software. Primary outcomes were proportion of patients showing psoriasis area and severity index (PASI) score improvement (<75%) and the mean percent change in PASI score from baseline to the end of treatment. Dichotomous data were analyzed using odds ratios (ORs) corresponding to the 95% confidence interval (CI), whereas continuous variables, expressed as mean and standard deviation, were analyzed using the mean differences (MD) with the 95% CI.Results:Six RCTs were analyzed. Meta-analysis showed that pioglitazone reduced the PASI scores in patients with psoriasis compared with the control group when administered at 30 mg per day (P < 0.001, MD = -3.82, 95% CI = -5.70, -1.93) and at 15 mg per day (P = 0.04, MD = -3.53, 95% CI = -6.86, -0.20). The PASI-75 of the pioglitazone group was significantly higher than that of the control group at 30 mg per day (P < 0.001, OR = 8.30, 95% CI = 3.99, 17.27) and at 15 mg per day (P = 0.03, OR = 2.96, 95% CI = 1.08, 8.06). No statistically significant differences in total adverse events were observed between the groups. There were no significant differences in common adverse reactions such as weight gain and elevated liver enzymes between the two pioglitazone groups.Conclusions:Use of pioglitazone in the current treatment of psoriasis is beneficial. The therapeutic effect of the daily 30 mg dose may be greater than that of the 15 mg dose per day with no significant change in the frequency of adverse reactions.

简介：TheEditor’sNote:RecentlyabooktitledADepictionofTrialsofStrengthBetweenChinaandtheUSwaspublishedinBeijing.ItiseditedandmainlywrittenbyProfessorChenFengofChinaInstituteofContemporaryInternationalRelations.Fouryoungresearcherofthesameinstitutealsoparticipatedinthewriting.Afterthebookwaspublished,ithasevokedstrongrepercussionsbothathomeandabroad.Itsfirsteditionhasalreadybeensoldoutandthesecondedi-tionhasrushedthroughprint.Foreignpressandnewsagenciesalsopaymuchattentiontothebookandhavemadequiteafewcomments.Someforeignexpertsandscholarshaveaskedthepublishinghouseortheauthorstosendthemacopyofthebook.Someoverseaspublish-inghousehaveevenproposedtopurchasethebook’scopyright.A-gainstthisbackdrop,membersoftheeditorialdepartmentofthisjour-nalhashadaspecialinterviewwithProfessorChenFengtoaskabouthismotivetowritethebookandsomeotherrelatedmatters.Belowisabriefrecordoftheinterview.

简介：AbstractBackground:Recent evidence has shown that prophylactic antibiotic treatment in patients with acute pancreatitis is not associated with a significant decrease in mortality or morbidity. The use and efficacy of prophylactic antibiotic treatment in acute pancreatitis remain controversial. This meta-analysis was conducted to assess whether antibiotic prophylaxis is beneficial in patients with acute pancreatitis.Methods:We searched randomized controlled trials (RCTs) of prophylactic use of antibiotics using Medline (PubMed), Embase, the Cochrane Library, and Web of Science. The data were analyzed using Review Manager 5.3 software. We performed pooled analyses for infected pancreatic necrosis, mortality, surgical intervention, and non-pancreatic infection. Odds ratios (ORs) from each trial were pooled using a random or fixed effects model, depending on the heterogeneity of the included studies. Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity, when necessary.Results:Totally, 11 RCTs involving 747 participants were included, with an intervention group (prophylactic use of antibiotics, n = 376) and control group (n = 371). No significant differences were found regarding antibiotic prophylaxis with respect to incidence of infected pancreatic necrosis (OR, 0.74; 95% confidence interval [CI], 0.50–1.09; P = 0.13), surgical intervention (OR, 0.92; 95% CI, 0.62–1.38; P = 0.70), and morality (OR, 0.71; 95% CI, 0.44–1.15; P = 0.16). However, antibiotic prophylaxis was associated with a statistically significant reduction in the incidence of non-pancreatic infection (OR, 0.59; 95% CI, 0.42–0.84; P = 0.004).Conclusions:Prophylactic antibiotics can reduce the incidence of non-pancreatic infection in patients with AP.

简介：AbstractBackground:Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).Methods:A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool.Results:In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07-1.26, P < 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26-2.17, P < 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04-1.32, P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10-1.42, P < 0.001), and Candida infection (Peto OR: 2.64, 95% CI: 1.48-4.71, P = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-α inhibitors (Peto OR: 1.38, 95% CI: 1.13-1.68, P = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08-2.22, P = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14-1.69, P = 0.001); higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26-9.55, P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38-2.91, P < 0.001); higher risk of URTI for TNF-α inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05-1.78, P= 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08-2.36, P = 0.018); higher risk of nasopharyngitis for TNF-α inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05-1.90, P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09-2.05, P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01-1.82, P = 0.044); higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03-4.62, P = 0.043); higher risk of Candida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31-4.84, P= 0.006).Conclusions:This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, and Candida infection, which should be paid attention to in our clinical practice.

简介：AbstractBackground:Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials.Methods:This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation.Results:We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the realworld inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population.Conclusions:The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.

简介：AbstractAntiviral therapy with antiviral agents is a very important component of treatment for the 2019 novel coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is important to clarify how to evaluate efficacy and safety of antiviral agents in treatment of COVID-19 during the pandemic of this disease. We need to answer the following questions: do we still need to use rigorously designed randomized controlled clinical trials (RCTs)? Or, will it be enough if we use loosened criteria, observational studies or even retrospective case series and case reports? The answer is "No, we still need to use the strictly designed preferably blinded multicenter RCTs to evaluate the antiviral agents." In this article, we reviewed almost all the RCT reports on monotherapies and combined therapies with antiviral agents for COVID-19, and found that among the reports on monotherapies, only remdesivir, and among combined antiviral agents, only the combined regimen with interferon-β1b, lopinavir-ritonavir and ribavirin were effective and safe based on evidences from RCTs. The results of five RCTs for chloroquine or hydroxychloroquine consistently showed that they were ineffective and unsafe in the treatment of COVID-19, especially at larger doses. Many aspects in the design of the clinical trials may be related to success or failure of a trial and the relevant factors need to be analyzed, discussed and emphasized from the specific requirements and considerations of antiviral therapies. We hope such discussions be of certain use in designing clinical trials for pediatric antiviral therapies.