简介：Inthepresentstudy,27multi-drugresistantstrainsofPseudomonasaeruginosawereisolatedfromclinicalspecimensinourhospitalfromJan2005toNov2005,inwhichtheresistantgenesencodingβ-lactamaseincludingTEM,SHV,OXA,PER,VEB,GES,CARB,IMP,VIM,SPM,GIM,DHAandOprD2weretestedbyPCRamplificationandsequencedbyDNAsequencer.Itwasfoundthatthedetectionratesofbla_(VEB),bla_(GES)andbla_(CARB)genesinthese27isolatesofP.aeruginosawere11.1%,11.1%and48.1%,respectively,butalmosttheoprD2genewaslacked(92.6%).Inaddition,theresistantgenesencodingTEM,SHV,OXA,PER,IMP,VIM,SPM,GIMandDHAβ-lactamasewereallnotfound.Itwasalsodemonstratedthatthesequenceofbla_(VEB)geneappearedtobeidenticaltothatofthebla_(VEB-1)(AY536743),whilethebla_(CES)andbla_(CARB)genesshared99%identitywithbla_(GES-1)(AY219651)andbla_(CARB-3)(S46063)genes.Fromtheseobservations,itisevidentthatP.aeruginosacarryingthebla_(VES),bla_(GES)andbla_(CARB)resistantgenesisolatedinourhospitalconferstheresistancetoβ-lactams,andthelossoftheoprD2genemaybetheimportantcausetodevelopresistancetoimipeneminP.aeruginosa.

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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.

简介：AbstractIn recent years, the research of immune checkpoint inhibitors has made a great breakthrough in lung cancer treatment. Currently, a variety of immune checkpoint inhibitors have been applied into clinical practice, including antibodies targeting the programmed cell death-1, programmed cell death-ligand 1, and cytotoxic T-lymphocyte antigen 4, and so on. However, not all patients can benefit from the treatment. Abnormal antigen presentation, functional gene mutation, tumor microenvironment, and other factors can lead to primary or secondary resistance. In this paper, we reviewed the molecular mechanism of immune checkpoint inhibitor resistance and various combination strategies to overcome resistance, in order to expand the beneficial population and enable precision medicine.

简介：Abstract:ChlamydiaTrachomatis(C.T.)isoneofthemostcommonpathogensofhumansexuallytransmitteddiseases.TreatmentofC.T.infectionprimarilydependsonTetracyclines,MacrolidesandQuinolones,butwiththewideuseofantibioticsanincreasingnumberofdrug-resistantChlamydiatrachomatiscaseshavebeenreported.ThisreviewsummarizestheresistantconditionsandthepossibleresistancemechanismsofC.T..

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简介：AbstractDrug resistance via drug-resistant mutations in the human immunodeficiency virus (HIV) genome is the primary cause of antiviral therapy failure. Consequently, HIV drug resistance genotyping has become a critical approach in HIV prevention and control. Compared to the Sanger sequencing technology, high-throughput sequencing (HTS) technology has superior sensitivity and timeliness, with strong detection capabilities for low-frequency mutations. With the continued advancement of HTS technologies, their prominence in HIV drug resistance detection techniques has increased accordingly. This article will review the latest developments in HTS technology and its applications in HIV drug resistance testing.

简介：AbstractBackground:After the scale-up of antiretroviral therapy (ART) for HIV infected people, increasing numbers of patients have pretreatment drug resistance (PDR). In this study, the prevalence of PDR was evaluated in adults initiating antiretroviral therapy in China.Methods:Blood samples were obtained from 1943 patients who initiated antiretroviral therapy (ART) in 2017 from 13 provinces or cities in China. Pol sequences were used to analyze drug resistance and construct transmission networks. Logistic regression model was used to estimate the potential factors associated with PDR.Results:In total, 1711 eligible patients (76.0% male; 87.8% aged ≥ 25 years) were included, of which 117 (6.8%) had PDR. The highest rates of PDR were 12.2% in Liangshan Prefecture of Sichuan and 9.3 and 8.9% in Dehong and Lincang Prefecture of Yunnan. A multivariate logistic regression analysis revealed that PDR was significantly higher among intravenous drug users (adjusted Odds Ratio (aOR) = 2.64, 95% CI: 1.57–4.44) and individuals from Liangshan, Dehong, and Lincang (aOR= 2.04, 95% CI: 1.26–3.30). In total, 754 sequences were used to generate 164 transmission networks. Five transmission networks had two or three sequences containing the same mutations, two networks contained subjects from Liangshan, and one network contained subjects from Dehong.Conclusions:Overall, the PDR prevalence was moderate, with a particularly high prevalence in areas with severe HIV epidemics. These results indicate the importance of continuous PDR monitoring in patients initiating antiretroviral therapy.

简介：Glioblastoma(GBM)isoneofthemostlethalhumancancers.GenomicanalysesdefinethemoleculararchitectureofGBMandhighlightacentralfunctionformechanistictargetofrapamycin(mTOR)signaling.mTORkinaseexistsintwomultiproteincomplexes,namely,mTORC1andmTORC2.Thesecomplexesdifferintermsoffunction,regulationandrapamycinsensitivity.mTORC1iswellestablishedasacancerdrugtarget,whereasthefunctionsofmTORC2incancer,includingGBM,remainspoorlyunderstood.ThisstudyreviewstherecentfindingsthatdemonstrateacentralfunctionofmTORC2inregulatingtumorgrowth,metabolicreprogramming,andtargetedtherapyresistanceinGBM,whichmakesmTORC2asacriticalGBMdrugtarget.

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简介：Inthepresentstudy,thedrug-resistancegenesencodingβ-lactamases,aminoglycosidemodifyingenzymes,DNAtopoisomerasesandintegronaswellastheirmolecularepidemiologywereinvestigatedbymeansofanalyzingthedrug-resistanceandmolecularepidemiologyofAcinebacterbaumanniiisolatedfromtheclinicalsamplesintwohospitalsinQiangzhouandHuzhoucityofJiangsuandZhejiangprovincefromJuly2000toMarch2005.Theminimalinhibitoryconcentrations(MICs)ofthese307isolatesweredetectedbyautomaticmicrobiologicalsystem,and35strainsagainst5-fluoro-quinoloneswereperformedbyagardilutionassay.Meanwhile,theresistantgenesin80isolateswereamplifiedbyPCRwithidentificationbyDNAsequencer.Itwasfoundthatmostofthe307isolatesofA.baumanniiwereresistanttomultipleantibioticstested,inwhichtheresistanceratesoftheisolatesagainstpiperacillin,piperacillin/tazobactam,amoxacillin/clavulanicacid,cefotaxime,ceftazidime,cefepime,gentamicin,amikacin,ciprofloxacin,chloramphenicolandsulfamethoxazole/trimethoprimwereallabove35%,butthoseofimipenemandmeropenemwerequitelow,rangedonly2.6%and3.3%.Inaddition,itwasalsodemonstratedthatthepositiveratesofTEMandSHVβ-lactamasegenesaccountedfor93.8%and22.5%respectively,andthoseoftheaminoglycoside-modifyingenzymegenesincludingaacC1,aacC2,aacC3,aacC4,aacC4A,aphA6,ant(2')-Iandant(3')Iwere58.8%,8.8%,7.5%,28.8%,45.0%,2.5%,28.8%and65.0%respectively.Themutationsinthequinolone-resistantdeterminingregion(QRDR)ofgyrAandparCgenesindicatedthatsubstitutioninSer-83residueofGyrAproteinwasmostfrequentlyoccurredamongstrainswithMICforciprofloxacinofmorethan4μg/ml,whereasadoublemutationatSer-83residueofgyrAandSer-80ofparCwasfoundinstrainswithMICofciprofloxacinofmorethan8μg/ml.Astothepositiveratesofclass1integron(IntI-1)andqacE△1-sul-1,itwasfoundtobe60.0%and77.5%respectively

简介：Multidrug抵抗(MDR)是在癌症化疗的一个主要问题。MDR的最好已知的机制之一是ATP有约束力的盒子(ABC)的提高的表示运输ers。当人的ABC运输ers的一些成员被显示了与提高的表示引起抗药性时，另外的成员的在表示上是否能也在许多模型癌症房间线和诊所贡献抗药性，还没被知道。为介绍ABCtransporters的分析的表示的微数组和量的PCR数组的最近的开发帮助了处理这些问题。在这篇文章，有在在抗药性和chemo敏感预言识别ABCtransporter基因的ABCtransporter基因和他们的使用的有限或完整的表的各种各样的数组将被考察。

简介：AbstractBackground:Rapid and accurate detection of drug resistance in Mycobacterium tuberculosis is critical for effective control of tuberculosis (TB). Herein, we established a novel, low cost strategy having high accuracy and speed for the detection of M. tuberculosis drug resistance, using gene splicing by overlap extension PCR (SOE PCR).Methods:The SOE PCR assay and Sanger sequencing are designed and constructed to detect mutations of rpoB, embB, katG, and inhA promoter, which have been considered as the major contributors to rifampicin (RFP), isoniazid (INH), and ethambutol (EMB) resistance in M. tuberculosis. One hundred and eight M. tuberculosis isolates came from mycobacterial cultures of TB cases at Chongqing Public Health Medical Center in China from December 2018 to April 2019, of which 56 isolates were tested with the GeneXpert MTB/RIF assay. Performance evaluation of the SOE PCR technique was compared with traditional mycobacterial culture and drug susceptibility testing (DST) or GeneXpert MTB/RIF among these isolates. Kappa identity test was used to analyze the consistency of the different diagnostic methods.Results:We found that the mutations of S531L, S315T and M306V were most prevalent for RFP, INH and EMB resistance, respectively, in the 108 M. tuberculosis isolates. Compared with phenotypic DST, the sensitivity and specificity of the SOE PCR assay for resistance detection were 100.00% and 88.00% for RFP, 94.64% and 94.23% for INH, and 68.97% and 79.75% for EMB, respectively. Compared with the GeneXpert MTB/RIF, the SOE PCR method was completely consistent with results of the GeneXpert MTB/RIF, with a concordance of 100% for resistance to RFP.Conclusions:In present study, a novel SOE PCR diagnostic method was successfully developed for the accurate detection of M. tuberculosis drug resistance. Our results using this method have a high consistency with that of traditional phenotypic DST or GeneXpert MTB/RIF, and SOE PCR testing in clinical isolates can also be conducted rapidly and simultaneously for detection of drug resistance to RFP, EMB, and INH.

简介：Objective:Toexplorethereversaleffectofmifepristoneonmultidrugresistance(MDR)indrug-resistanthumanbreastcancercelllineMCF7/ADRanditsmechanisms.Methods:ExpressionofMDR1andMDR-associatedprotein(MRP)mRNAinMCF7/ADRcellswasdetectedusingreversetranscription-polymerasechainreaction(RT-PCR).WesternblottingwasusedtoassaytheproteinlevelsofP-glycoprotein(P-gp)andMRP.Intracellularrhodamine123retentionand[3H]vincristine(VCR)accumulationweremeasuredbyflowcytometryandliquidscintillationcounter,respectively.MTTreductionassaywasusedtodeterminethesensitivityofcellstotheanticanceragent,adriamycin(ADR).Additionally,aMCF7/ADRcellxenograftmodelwasestablishedtoassessthereversaleffectofmifeprisoneonMDRinMCF7/ADRcellsinvivo.Results:Miferpristonedose-dependentlydown-regulatedtheexpressionofMDR1andMRPmRNAinMCF7/ADRcells,accompaniedbyasignificantdecreaseintheproteinlevelsofP-gpandMRP.Afterexposureto5,10,and20μmol/Lmifepristone,MCF7/ADRcellsshoweda3.87-,5.81-,and7.40-foldincreaseintheaccumulationofintracellularVCR(aknownsubstrateofMRP),anda2.14-,4.39-,and5.53-foldincreaseintheretentionofintracellularrhodamine123(anindicatorofP-gpfunction),respectively.MTTanalysisshowedthatthesensitivityofMCF7/ADRcellstoADRwasenhancedby7.23-,13.62-,and20.96-foldafterincubationwithmifepristoneasabove-mentioneddosesfor96h.Invivo,mifepristoneeffectivelyrestoredthechemosensitivityofMCF7/ADRcellstoADR.After8weeksofadministrationwithADR(2mg·kg-1·d-1)aloneorincombinationwithmifepristone(50mg·kg-1·d-1),thegrowthinhibitoryrateofxenograftedtumorsinnudemicewas8.08%and37.25%,respectively.Conclusion:MifepristoneexertspotentreversaleffectsonMDRinMCF7/ADRcellsinvitroandinvivothroughdown-regulationofMDR1/P-gpandMRPexpressionandinhibitionofP-gp-andMRP-dependentdrugefflux,thusincreasing

简介：客观：为了调查抵抗和颠倒的机制，在导致cisplatin的multidrug抵抗ligustrazine和cyclosporinA完成卵巢的癌症房间线3Ao/cDDP。方法：用每周期在30mgcisplatin从临床的化疗计算的相应剂量，我们建立了3Ao/cDDP，3Ao每次在10渭g/ml在常规间隔并且反复暴露了到cisplatin的高级集中24个小时。LRP，MRP，P-gp，GST蟺和TopoII的表情是与FCM检测的份量上。为药抵抗颠倒，没有cytotoxicity，cyclosporinA和ligustrazine在最大的剂量单身地或在联合被管理。抑制率被MTT试金决定。结果：3Ao/cDDP在4.5个月以后被建立，与抵抗因素1.6它类似于临床的抵抗度。MRP和P-gp的低表示层次在3Ao和3Ao/cDDP被发现(P>0.05)，并且在3Ao/cDDP的LRP和GST蟺表示层次比在3Ao的那些显著地高(P<0.005andP<0.05，分别地)，并且在3Ao/cDDP的TopoII显著地更低对3Ao(P<0.05)。cDDP的抑制率是20.807卤0.015%，加ligustrazine的cDDP27.421卤0.07%(P>0.05对cDDP)，加cyclosporinA的cDDP49.635卤0.021%(P<0.01对cDDP)，并且加ligustrazine和cyclosporinA的cDDP58.861卤0.014%(P<0.01对cDDP)。结论：3Ao/cDDP，由cisplatin导致了并且由为上皮的卵巢的癌症模仿临床的化疗的特征建立了，是为cisplatinresistanceinvitro的调查的一个理想的模型。在3Ao/cDDP的Cisplatin抵抗能被说明为由更高的LRP，GST蟺和更低的TopoII表示并且没与MRP或P-gp被联系。Ligustrazine没在A能颠倒的cisplatin抵抗，而是cyclosporin上有重要颠倒效果抵抗有效地。

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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：43个米饭变化的DNA碎片被放大，11份教材基于植物的抵抗基因类似物(RGA)设计了，并且变化的强风抵抗被接种与33识别从云南省收集的Magnaporthegrisea孤立，中国。聚类结果与0.6117的一个关联系数揭示了在强风抵抗和DNA乐队之间的重要关联(α=0.01)，显示抵抗分析基于接种与那基于聚类分析的RGA-PCR与一致。关联系数，然而，从0.1701～0.535取决于教材。五份教材，S1/AS3，S1INV/S2INV，XLRRFor/XLRR加快，Pto-Kin1IN/Pto-Kin2在，和NLRRFor/NLRR加快可能被申请在他们的乐队数字和多型性的考虑的强风抵抗鉴定，和他们有强风抵抗的关联系数是0.5305，0.4898，0.4059，0.3719和0.3524分别地。而且，除了二个高度易受影响的变化，CO39和Lijiangxintuanheigu的indica和装饰用的梨树米饭，能被11份教材很好分类。