简介：AbstractBackground:Treatment of coronary bifurcation lesions remains challenging; a simple strategy has been preferred as of late, but the disadvantage is ostium stenosis or even occlusion of the side branch (SB). Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported. This prospective, multicenter, randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon (PEB) compared with regular balloon angioplasty (BA) in the treatment of non-left main coronary artery bifurcation lesions.Methods:Between December 2014 and November 2015, a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers. Patients were randomly allocated at a 1:1 ratio to a PEB group (n = 113) and a BA group (n = 109). The primary efficacy endpoint was angiographic target lesion stenosis at 9 months. Secondary efficacy and safety endpoints included target lesion revascularization, target vessel revascularization, target lesion failure, major adverse cardiac and cerebral events (MACCEs), all-cause death, cardiac death, non-fatal myocardial infarction, and thrombosis in target lesions. The main analyses performed in this clinical trial included case shedding analysis, base-value equilibrium analysis, effectiveness analysis, and safety analysis. SAS version 9.4 was used for the statistical analyses.Results:At the 9-month angiographic follow-up, the difference in the primary efficacy endpoint of target lesion stenosis between the PEB (28.7% ± 18.7%) and BA groups (40.0% ± 19.0%) was -11.3% (95% confidence interval: -16.3% to -6.3%, Psuperiority <0.0001) in the intention-to-treat analysis, and similar results were recorded in the per-protocol analysis, demonstrating the superiority of PEB to BA. Late lumen loss was significantly lower in the PEB group than in the BA group (-0.06 ± 0.32 vs. 0.18 ± 0.34 mm, P < 0.0001). For intention-to-treat, there were no significant differences between PEB and BA in the 9-month percentages of MACCEs (0.9% vs. 3.7%, P = 0.16) or non-fatal myocardial infarctions (0 vs. 0.9%, P = 0.49). There were no clinical events of target lesion revascularization, target vessel revascularization, target lesion failure, all-cause death, cardiac death or target lesion thrombosis in either group.Conclusions:In de novo non-left main coronary artery bifurcations treated with provisional T stenting, SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis.Trial registration:ClinicalTrials.gov, NCT02325817; https://clinicaltrials.gov

简介：Background:Thesafetyandefficacyofcoronaryarterybypassgrafting(CABG)andsecond-generationdrug-elutingstents(DESs)inpatientswithcoronaryarterydisease(CAD)remaincontroversial.ThereforeweaimedtocomparetheoutcomesofCADpatientstreatedwithCABGandsecond-generationDESs.Methods:WesystematicallysearchedthePubMed,CochraneLibrary,Ovid,andElsevierdatabases.Studiescomparingsecond-generationDESswithCABGinCADpatientswereincluded.RevMan5.3wasusedtoextractandpoolthedatafromtheapplicablestudies.Results:Sixtrials(N=6604participants)wereincludedinthismeta-analysis.AmongalloftheCADpatients,second-generationDESswereassociatedwithnodifferencesintherisksofall-causedeath[riskratio(RR)1.18,95%confidenceinterval(CI)0.98–1.43,P=0.09],cardiovasculardeath(RR1.14,95%CI0.81–1.59,P=0.45),myocardialinfarction(RR1.22,95%CI0.98–1.54,P=0.08),andstroke(RR0.83,95%CI0.59–1.17,P=0.29),butincreasedtherisksofrevascularization(RR1.95,95%CI1.66–2.30,P<0.001)andmajoradversecardiacandcerebrovascularevents(RR1.72,95%CI:1.31–2.26,P<0.001)whencomparedwithCABG.Conclusions:InthetreatmentofCADpatients,second-generationDESswasnotassociatedwithincreasedrisksofall-causedeath,cardiovasculardeath,myocardialinfarction,andstroke,butincreasedtherisksofrevascularizationandmajoradversecardiacandcerebrovasculareventswhencomparedwithCABG.

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简介：AbstractBackground:The mechanism and characteristics of early and late drug-eluting stent in-stent restenosis (DES-ISR) have not been fully clarified. Whether there are different outcomes among those patients being irrespective of their repeated treatments remain a knowledge gap.Methods:A total of 250 patients who underwent initial stent implantation in our hospital, and then were readmitted to receive treatment for the reason of recurrent significant DES-ISR in 2016 were involved. The patients were categorized as early ISR (<12 months; E-ISR; n = 32) and late ISR (≥12 months; L-ISR; n = 218). Associations between patient characteristics and clinical performance, as well as clinical outcomes after a repeated percutaneous coronary intervention (PCI) were evaluated. Primary composite endpoint of major adverse cardiac events (MACEs) included cardiac death, non-fatal myocardial infarction (MI), or target lesion revascularization (TLR).Results:Most baseline characteristics are similar in both groups, except for the period of ISR, initial pre-procedure thrombolysis in myocardial infarction, and some serum biochemical indicators. The incidence of MACE (37.5% vs. 5.5%; P < 0.001) and TLR (37.5% vs. 5.0%; P < 0.001) is higher in the E-ISR group. After multivariate analysis, E-ISR (odds ratio [OR], 13.267; [95% CI 4.984-35.311]; P < 0.001) and left ventricular systolic dysfunction (odds ratio [OR], 6.317; [95% CI 1.145-34.843]; P = 0.034) are the independent predictors for MACE among DES-ISR patients in the mid-term follow-up of 12 months.Conclusions:Early ISR and left ventricular systolic dysfunction are associated with MACE during the mid-term follow-up period for DES-ISR patients. The results may benefit the risk stratification and secondary prevention for DES-ISR patients in clinical practice.

简介：BackgroundCreatinekinase-MB(CK-MB)elevationafterpercutaneouscoronaryintervention(PCI)hasbeenassociatedwithincreasedriskformortality.Althoughmoststudieshavedefinedperiproceduralmyocardialinfarction(pMI)asanelevationinCK-MB>3×upperlimitofnormal(ULN),useofdifferentCK-MBassaysandvariationinsite-specificdefinitionsoftheULNmaylimitthevalueofsuchrelativethresholds.MethodsandResultsWeuseddatafromthemulticenterEvaluationofDrug-ElutingStentsandIschemicEvents(EVENT)registrytoexaminetheimpactofvariationsinsite-specificthresholdsforCK-MBelevationontheincidenceofpMIaswellastherelationshipbetweenabsolutepeaklevelsofCK-MBafterPCIand1-yearmortality.Thestudycohortconsistedof6347patientswhounderwentnonemergentPCIandhadnormalCK-MBatbaseline.Acrossthe59studycenters,theULNforCK-MBrangedfrom2.6to10.4ng/mL(median,5.0ng/mL),andtherewasaninverserelationshipbetweenthesite-specificULNandtheincidenceofpMI(definedasCK-MBelevation>3×ULN).AlthoughanypostprocedureelevationofCK-MBwasassociatedwithanadverseprognosis,incategoricalanalyses,onlyCK-MB≥50ng/mLwasindependentlyassociatedwithincreased1-yearmortality(hazardratio,4.71;95%confidenceinterval,2.42to9.13;P<0.001).SplineanalysisusingpeakCK-MBasacontinuousvariablesuggestedagraded,nonlinearrelationshipwith1-yearmortality,withaninflectionpointat≈30ng/mL.ConclusionsAmongunselectedpatientsundergoingPCI,thereisagradedrelationshipbetweenCK-MBelevationafterPCIand1-yearmortalitythatisparticularlystrongforlargeCK-MBelevations(>30to50ng/mL).FuturestudiesthatincludepMIasaclinicalendpointshouldconsiderusingacorelaboratorytoassessCK-MB(toensureconsistency)andraisingthethresholdfordefiningpMIabovecurrentlevels(toenhanceclinicalrelevance).

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简介：BackgroundPriorrandomizedtrialshaveshownreducedbleedingwithbivalirudincomparedwithunfractionatedheparin(UFH)inpatientsundergoingpercutaneouscoronaryintervention(PCI).However,itisnotknownifthisbenefitisalsopresentwhenUFHdosesaremoretightlycontrolled(asmeasuredbyactivatedclot-tingtime,ACT).MethodsandResultsPatientsenrolledintheEVENT(EvaluationofDrug-ElutingStentsandIschemicEvents)registry,weredividedinto3groups,basedontheantithromboticdrugusedduringPCI(UFHmonotherapy,UFH+glycoproteinIIb-IIIareceptorinhibitor[GPI],orbivalirudinalone).Propensityscorematchingwasusedtoadjustformeasuredcovariates(89variables)andtocomparebivalirudinversusUFHmonotherapyandbivalirudinversusUFH+GPIgroups.TheUFHgroupswerestratifiedbasedonACTachieved(optimalACTdefinedas250-300forUFHmonotherapyand200-250whenGPIwasalsoused).Theprimarybleedingoutcomewasin-hospitalcompositebleeding,definedaseventsofaccesssitebleeding,ThrombolysisInMyocardialInfarctionmajor/minorbleeding,ortransfusion.Primary(in-hospitaldeath/myocardialinfarction)andsecondaryischemicoutcomes(death/MI/unplannedrepeatrevascularizationat12months)werealsoevaluated.Propensityscorematchingyielded3022patientsfortheUFHmonotherapyversusbivalirudincomparisonand3520patientsfortheUFH+GPIversusbivalirudincomparison.BivalirudinusewasassociatedwithnumericallylowerbleedingratesatallcategoriesofachievedACTwhencomparedwithUFH(low,optimal,highACT:2.5%versus4.7%,1.9%versus6.0%,3.1%versus4.8%,respectively)orheparin+GPIgroups(low,optimal,highACT:0.0%versus2.7%,2.7%versus5.2%,2.4%versus6.1%,respectively)andwasnotassociatedwithanystatisticallysignificantincreaseineitherprimaryorsecondaryischemicoutcomes.ConclusionsAmongunselectedpatientsundergoingPCI,bivalirudinuseduringPCIwasassociatedwithalowerriskofbleedingatall

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简介：TheobjectiveofthisstudyistoexploreapotentiallyeffectivetrainingmethodforthehospitalprofessionalstoeducatedrugusersandtoenhancetheirknowledgeofHIVinfection.Onehundredandsixtyonesubjects,whocamefrom13differentprovincesandwereadmittedinadrugreliefhospitalinBeijing,wererecruitedforthisstudy.Theaverageageofthesesubjectswas35.21±6.24yearold.Theaveragenumbersofyearsfordrugaddictionwere7years,andtheaveragenumbersofdrugrelieftreatmentreceivedinthepastwas5.5times.ThelevelofAIDSknowledgeofthesesubjects,includingpathogenicfactors,sourceofinfection,routeoftransmissionandpreventivemeasures,wereevaluatedbeforeandafterreceivingtheAIDSeducationaltrainingtothesedrugusers.Ourresultsshowedthattherewasastatisticallysignificantincrease(P＜0.01)intheknowledgeofHIVinfectionandpreventionamongthesesubjects.PositiveattitudeandbehavioraltendenciestowardHIVpreventionwerealsoimproved.Therefore,itisimperativeforthemedicalprofessionalstoincorporateAIDSeducationintodrugrelieftreatmenttoachievethemaximumeffectontheknowledgeofAIDSandimprovementofpositiveattitudesandbehaviorstowardHIVpreventionamongdrugusers.

简介：Drugdevelopmentinoncologyisundergoingasubstantialshiftnowadays.Thedriversforthisaremulti-factorial.Ontheoneside,drugdevelopmentisperformedmorerationallythanever,profitingfromthescientificadvancesinmolecularbiologyingeneralandtheelucidationofthevarious'omes'fromgenometometabolomeinparticular.Ontheotherside,itisbasedonenormoustechnologicalprogress,e.g.,inthefieldofgenome

简介：人被自然选择进化到目前在自然生物圈中的地位，因故人的生命是坚强的。于是，作为自然的主宰，人创造了许多是自然原本没有的“东西”，这些人为的“东西”既给纯朴的自然描绘上了华丽的色彩，同时也给自然带来了不少的灾难，源于这些灾难，人的生命随时随地都可能发生“差错”，这又折射出人生命的脆弱。为了保护自己，人便创造了医学，也发明了药物，以便能在这许许多多的“差错”之中拯救人的生命于危验。

简介：INTRODUCTIONSincetheirintroductioninmid-1980s,polyamidoamide(PAMAM)dendrimershaveattractedconsiderableattentionbecauseoftheiruniquestructuresandproperties.Accordingtopreliminarystudiesinanimals,PAMAMdendrimersarenon-immunogenic,verylowinvivotoxicityandcanbeexcretedbyurineandfeces.

简介：AnewclassofcrosslinkingpolyphosphatesweresynthesizedandcharacterizedbyIR^1HNMR,^31PNMRspectroscopyaswellaselementalanalysis.InvitrodegradationofthepolyphosphatesobtainedandthereleaseofantineoplasticdrugMethotrexate(MTX)andcontraceptiveLevonorgestrel(LNG)byusingthesepolymersasmatrixwerestudied.ZeroorderreleaseratewasobservedinthecaseofLNGrelease.

简介：Thisworkaimstoinvestigatetheeffectsofdosingregimentsondrugdeliveryinsolidtumorsandtovalidatethemwithexperimentsonrats.Thelumpedparametermodelsofpharmacokineticsandofdrugdeliveryintumorweredevelopedtosimulatetimecoursesofaveragedrugconcentration(Ct)oftumorinterstitiumintwotypesofdosingregiments(i.e.,single-shotandtriple-shotones).Thetworegimentswereperformedviaantitumordrug,hydroxycamptothecin(HCPT),onrats,tomeasurethedrugconcentrationinthetumor.Thesimulationsofthedrugconcentrationinthetumorofthetwodosingregimentswereconductedandcomparedwiththeexperimentaldataonrats.Thecoefficientsinthemodelswereinvestigated.Itisconcludedthatthetriple-shotmethodismoreeffectivethanthatofsingle-shotinjection.Thepresentlumped-parametermodelisquantitativelycompetentfordrugdeliveryinsolidtumor.

简介：AlatticeBoltzmannnumericalmodelingmethodwasdevelopedtopredictskinconcentrationaftertopicalapplicationofadrugontheskin.ThemethodisbasedonD2Q9latticespacesassociatedwiththeBhatnagar-Gross-Krook(BGK)collisiontermtosolvetheconvection-diffusionequation(CDE).Asimulationwascarriedoutindifferentrangesofthevalueofbound,whichisrelatedtoskincapillaryclearanceandthevolumeofdiffusionduringapercutaneousabsorptionprocess.Whenatypicaldrugisusedontheskin,thevalueofcorrespondstotheamountofdrugabsorbedbythebloodandtheabsorptionofthedrugaddedtotheskin.Theeffectofwasstudiedforwhentheregionofskincontactisalinesegmentontheskinsurface.

简介：Colorectalcancer（CRC）isthethirdmostcommoncancerdiagnosedworldwideinhumanbeings.Surgery,chemotherapy,radiotherapyandtargetedtherapiesaretheconventionalfourapproacheswhicharecurrentlyusedforthetreatmentofCRC.Thesitespecificdeliveryofchemotherapeuticstotheirsiteofactionwouldincreaseeffectivenesswithreducingsideeffects.Targetedoraldrugdeliverysystemsbasedonpolysaccharidesarebeinginvestigatedtotargetanddeliverchemotherapeuticandchemopreventiveagentsdirectlytocolonandrectum.Site-specificdrugdeliverytocolonincreasesitsconcentrationatthetargetsite,andthusrequiresalowerdoseandhenceabridgedsideeffects.Somenoveltherapiesarealsobrieflydiscussedinarticlesuchasreceptor（epidermalgrowthfactorreceptor,folatereceptor,wheatgermagglutinin,VEGFreceptor,hyaluronicacidreceptor）basedtargetingtherapy;colontargetedproapoptoticanticancerdrugdeliverysystem,genetherapy.EventhoughgoodtreatmentoptionsareavailableforCRC,theultimatetherapeuticapproachistoaverttheincidenceofCRC.ItwasalsofoundthatCRCscouldbepreventedbydietandnutritionsuchascalcium,vitaminD,curcumin,quercetinandfishoilsupplements.ImmunotherapyandvaccinationareusednowadayswhichareshowingbetterresultsagainstCRC.

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简介：AbstractThe low success rates in the treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant TB (XDR-TB), which account for 55% and 34% respectively, led the WHO to conclude that MDR/XDR-TB is a serious public health crisis. However, the virulence of MDR/XDR-Mycobacterium Tuberculosis(Mtb) has not been analyzed in details, which could provide a specific guidance for the control and prevention. In this review, we discuss different aspects of MDR/XDR-Mtb virulence and its relationship to fitness cost by probing the following questions: (1) what mediates the virulence of MDR/XDR-Mtb? (What is the relationship between fitness and virulence of Mtb? (2) Is it possible that drug-resistant Mtb(DR Mtb) can show higher fitness? (3) What is the definite effect on fitness of each drug-resistant mutant? (4) What other important factors affecting fitness in the mutant strain? (5) How to study the virulence of a large number of DR Mtb?And what prevention and control measures will be taken in the future, especially for the high virulent DR Mtb? We therefore summarized the congruent relationship between drug resistance and fitness from the global response-related genes to antibiotic resistance-contributing mutation, provided methods to explore the virulence of DR Mtb. This review may offer some critical information and concise guide to creating strategies for the prevention and control of drug-resistant Mtb.

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