简介：AbstractBackground:The detrimental outcomes of right ventricular pacing on left ventricular electromechanical function ultimately result in heart failure, a phenomenon termed pacing-induced cardiomyopathy (PICM) in clinical research. This study aimed to validate prognostic factors that can be used to identify patients with higher susceptibility to progress to the stage of cardiomyopathy before pacemaker implantation.Methods:This observational analysis enrolled 256 patients between January 2013 and June 2016, 23 (8.98%) of whom progressed to PICM after 1 year of follow-up. A Cox proportional hazard model was used to analyze the prognostic factors associated with PICM. Dose-response analysis was used to evaluate the relationship between significant indicators in multifactor analysis and PICM.Results:The mean values of left ventricular ejection fraction before and after pacemaker implantation in 23 patients diagnosed with PICM were 62.3% and 42.7%, respectively. Univariate analysis showed that sex, atrio-ventricular block, paced QRS duration, and ventricular pacing percentage were significantly associated with PICM. In the multivariate analysis, male sex (hazard ratio: 1.20, 95% confidence interval [CI]: 1.09-1.33, P < 0.005), paced QRS duration (hazard ratio: 1.95 per 1 ms increase, 95% CI: 1.80-2.12, P < 0.001), and ventricular pacing percentage (hazard ratio: 1.65 per 1% increase, 95% CI: 1.51-1.79, P < 0.001) were independent prognostic factors associated with the development of PICM. The ventricular pacing percentage and paced QRS duration level defined by the dose-response analysis were positively associated with PICM (P < 0.05).Conclusions:Our findings indicated that paced QRS duration and ventricular pacing percentage were the most sensitive prognostic factors for PICM.

简介：Trimethyltin(TMT)isanoccupationalandenvironmentalhealthhazardbehavingasapotentneurotoxinknowntoaffectthecentralnervoussystemaswellastheperipheralauditorysystem.However,themechanismsunderlyingTMT-inducedototoxicityarepoorlyunderstood.ToelucidatetheeffectsofTMTonthecochlea,asingleinjectionof4or8mg/kgTMTwasadministeredintraperitoneallytoadultrats.Thecompoundactionpotential(CAP)thresholdwasusedtoassessthefunctionalstatusofthecochleaandhistologicaltechniqueswereusedtoassesstheconditionofthehaircellsandauditorynervefibers.TMTat4mg/kgproducedatemporaryCAPthresholdelevationof25-60dBthatrecoveredby28dpost-treatment.Althoughtherewasnohaircelllosswiththe4mg/kgdose,therewasanoticeablelossofauditorynervefibersparticularlybeneaththeinnerhaircells.TMTat8mg/kgproducedalargepermanentCAPthresholdshiftthatwasgreatestatthehighfrequencies.TheCAPthresholdshiftwasassociatedwiththelossofouterhaircellsandinnerhaircellsinthebasal,high-frequencyregionofthecochlea,considerablelossofauditorynervefibersandasignificantlossofspiralganglionneuronsinthebasalturn.Spiralganglionneuronsshowedevidenceofsomashrinkageandnuclearcondensationandfragmentation,morphologicalfeaturesofapoptoticcelldeath.TMT-induceddamagewasgreatestinthehigh-frequency,basalregionofthecochleaandthenervefibersbeneaththeinnerhaircellswerethemostvulnerablestructures.

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简介：Withtheadventofmoderntechniques,drugs,andmonitoring,generalanesthesiahascometobeconsideredanunlikelycauseofharm,particularlyforhealthypatients.Whilethisislargelytrue,newlyemergingclinicalandlaboratorystudieshavesuggestedthatexposuretoanestheticagentsduringearlychildhoodmayhavelong-lastingadverseeffectsoncognitivefunction.Thisconcernhasbeenthefocusofintensestudyinthefieldof

简介：AbstractNormal pregnancy is associated with dramatically increased estrogen biosynthesis whose role is believed to raise uterine blood flow to facilitate the bi-directional maternal-fetal exchanges of gases (O2 and CO2), to deliver nutrients, and exhaust wastes to support fetal development and survival. Constrained uterine blood flow in pregnancy is a leading cause of preeclampsia with fetal growth restriction, rendering investigations of uterine hemodynamics to hold a high promise to inform pathways as targets for therapeutic interventions for preeclampsia. The mechanisms of estrogen-induced uterine vasodilation in pregnancy have long been attributed to enhanced endothelium production of nitric oxide, but clinical trials targeting this pathway that dominates uterine hemodynamics have achieved no to little success. Emerging evidence has recently shown a novel proangiogenic vasodilatory role of hydrogen sulfide in regulating uterine hemodynamics in pregnancy and preeclampsia, provoking a new field of perinatal research in searching for alternative pathways for pregnancy disorders especially preeclampsia and intrauterine growth restriction. This minireview is intended to summarize the nitric oxide pathway and to discuss the emerging hydrogen sulfide pathway in modulating estrogen-induced uterine vasodilation in pregnancy and preeclampsia.

简介：ObjectivesIschemiainducedarrhythmia(ventriculartachycardia/ventricularfibrillation)isoneofthemajorcausesofdeath.Potassiumchannelschangearelikelytoberesponsiblefortheischemia-relatedarrhythmias.Cardiacpotassiumcurrentisthemajoroutwardcurrentinvolvedincardiacrepolarization.Thepropertiesofpotassiumchannelshavebeenintensivelystudied.Here,weinvestigatedtheassociationbetweenischemiainducedarrhythmiaandpotassiumchannelsgeneticvariations.Methods23patientswithventriculartachycardia/ventricularfibrillationinducedbyischemiawereselectedasobjects.5MLperipheralbloodweretakenfromeachperson,fromwhichDNAwasextractedus-ingastandardenzymaticphenol-chloroformmethod.Candidategenes(HERG、KCNJ2、KCNQ1、Mink、Mirp1、Kir2.1、KV4.3、Kir3.1、KV1.5、Kir6.1、Kir6.2、Kir2.1)Werescreenedforpotassiumchannelsgenemutationswithdirectsequencingmethods.ResultsHere4potassiumchannelsgenemutationshavebeendiscovered.InthegenecodingfortheATP-sensitiveK~+channelssubunitKir6.2,thereisachangefromvalinetoisoleucineatthepositionof326(V326I).Attheposition448,argininesubstitutesproline(P448R)intheKC-NQ1gene.InthegeneKCNJ2twomutationshavebeenfound(P156L,Q193H).ConclusionsThisstudyimplicatedthatthereisahighrelationshipbetweenischemiainducedarrhythmiaandthemutationofpotassiumchannels.Inordertoidentifythepreciselyrelationshipthereisneedfunctionalanalysis.

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简介：AbstractWith the increasing use of immune checkpoint inhibitors (ICI) including anti-cytotoxic T lymphocyte associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) in cancers, ICI-induced type 1 diabetes has been reported throughout the world. In this review, we aim to summarize the characteristics of this disease and discuss the mechanism of it. As an immune-related adverse event, type 1 diabetes developed after the administration of anti-PD-1 or anti-PD-ligand 1 (PD-L1) in the combination with or without anti-CTLA-4. It usually presented with acute onset, and 62.1% of the reported cases had diabetic ketoacidosis. Only a third of them had positive autoantibodies associated with type 1 diabetes. Susceptible HLA genotypes might be associated. T-cell-stimulation by blocking of the interaction of PD-1 and PD-L1 in pancreatic β cells was the main mechanism involved in the pathology. Insulin was the only effective treatment of ICI-induced type 1 diabetes. In conclusions, ICI-induced type 1 diabetes is a potentially life-threating adverse event after the immunotherapy of cancers. Screening and early recognition is important. Further investigation of the mechanism may help to better understand the pathology of type 1 diabetes.

简介：Objective:Todetecttheexistenceofimmunetoleranceinducedbygamma-rayirradiation.Methods:Peritonealcellswereharvestedfrommicesubjectedto5Gy60Cogamma-raytotalbodyirradiationat3d,7d,15dand30d,thentheircounts,morphologicalchangesandIL-12geneexpressionwereinvestigated.Results:Afterirradiation,theperitonealcellsweresharplyreduced,thecellmorphologyshiftedfromround-liketopolymorphicandfusiformwithsomeprocesses,expressionofIL-12p35wasseriouslysuppressed,whilethatofIL-12p40greatlyenhanced.Conclusion:Ourdatahighlysuggestthatthegamma-rayirradiationcouldpotentiallyinducedendriticcell(DC)commitmentandimmunetolerance.

简介：Objective:toobserveeffectofendothelin-1(ET-1)onhepaticdamageinducedbyendotoxin.Methods:atotalof90ratswererandomlydividedintocontrolgroup(groupc),endotoxintreatedgroup(groupLPS)andendotoxinplusET-1antibodytreatedgroup(groupLEA).AnobservationwasdoneonthechangesofET-1concentration,andtranscriptionandexpressionofET-1mRNA.Plasmaglutamicpyruvictransaminaseenzyme(GPT),hepaticlactatedehydrogenase(LDH),adenosinetriphosphate(ATP)andmalondialdehyde(MDA)werealsoobservedat3,6,9,12,24hoursaftersaline,endotoxin(10mg·kg^-1)andET-1antibody(dalubine1:2000,2ml·kg^-1)administration.Results:TheresultsindicatedthattheconcentrationofplasmaandhepaticET-1andexpressionofET-1mRNAinliversignificantlyincreasedfollowingendotoxemia.ThehepaticET-1levelswereinverselycorrelatedwiththeATPconcentration,andpositivelyrelatedtotheMDAconcentration.ET-1antibodycouldpartiallyprotecttheliveragainstdamageinducedbyendotoxin.Conclusions:Theseresultssuggestthatendotoxinmay,ontranscriptionandtranslationlevel,leadtoanincreaseofET-1insynthesis.ET-1maycontributetohepaticdamageduringendotoxemia.

简介：Objective:Toobservethetherapeuticeffectofoculo-acupuncturetherapyinthetreatmentofcerebralinfarctioninducedhemiplegia.Methods:58casesofstrokepatientswererandomlydividedintotreatmentgroup(n=30)andcontrolgroup(n=28).Intreatmentgroup,onthebasisofmedicationplusrehabilitationtreatment,patientsvoluntarilyacceptedoculo-acupuncturetherapy(acupunctureofUpper-JiaoAreaandLower-JiaoArea).Incontrolgroup,patientsonlyacceptedmedicationandrehabilitationtreatment.ThetherapeuticeffectwasevaluatedwithBrunstrom's6-stagesAssessingMethod.Results:After24sessionsoftreatment,theratiosofthediseasedlimbsreachingstageⅥandmoreinfunctionalactivityinthepatientsoftreatmentgroupincreasedfrom16.7%(upper-limb)and20.0%(lower-limb)beforetreatmentto70.0%and90.0%respectively;whileincontrolgroup,thoseratiosoftheupperandlowerlimbsincreasedfrom10.7%and28.6%beforetreatmentto39.2%and60.7%separately.Therewasasignificantdifferencebetweentwogroupsinthetherapeuticeffect(P＜0.05).Conclusion:Oculo-acupunctureplusmedicationissuperiortosimplemedicationtreatmentinimprovingfunctionalactivityofthehemiplegiclimbs.

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简介：Electrophoresis,chromatography,immunoassay,sequencingandothertimeconsumingap-proacheshavebeendevelopedtodetermineDNAbasemismatching,oxidativelesionorstrandbreaks.Sometimes,however,onlyqualitativeinformationisenoughtodecidewhethermutationhashappenedtoDNAanditsextent.Convolutionspectrometry(CS),anewtechniquetodiscoverultrafmedifferenceonultraviolet(UV)absorptionofdifferentsubstances,isoriginallyemployedtofindoutanysubtlemutationofDNAinducedbyUVradiation.Muta-tiveDNAiscomparedwithegocriteriabasedonthespectraoftheformerDNA,anydifferenceisquantitativelyex-pressedbydispersion(5).Visiblechangescannotbeobservedonsecond-derivativespectrauntilthemutationgets5upto11.48%.DimethylsulfoxideisanintensifierofUV254nminducedDNAmutationandprotectorat365nm,whichissimplyconfirmedbyincreasinganddecreasing5.Everyconvolutionproceduretakeslessthan1min.Convolutionspectrometryprovidesafast,simple,sensitiveandinexpensivealternativetodetermineDNAmutation,andtoscreenanti-mutationalmedicines.

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简介：Introduction:Theabsenceofvertigoduringthecalorictest,despitearobustresponse,hasbeensuggestedtorepresentacentralvestibularsystemphenomenon.Thepurposeofthisinvestigationwastodeterminetheprevalenceofabsentcaloric-inducedvertigoperceptioninanunselectedgroupofpatientsandtoassesspossiblepredictingvariables.Methods:Prospectiveinvestigationof92unselectedpatientswhounderwentcalorictesting.Inclusioncriteriawerethateachpatientgenerateamaximumslowphasevelocity(maxSPV)
15deg/secandacaloricasymmetryof10%.Followingthecaloric,patientswereasked,“Didyouhaveanysensationofmotion?”Results:Resultsshowed75%ofpatientsreportedmotionwithameanageof56.51yearscomparedtoameanageof66.55inthe25%ofpatientsreportinganabsenceofmotion.Alogisticregressionwasperformedandtheoverallmodelwasstatisticallysignificantaccountingfor29%ofthevarianceincaloricperception.ThesignificantpredictorvariableswerepatientageandmaxSPVofthecaloricresponse.Theeffectsizeforbothvariableswassmallwithanoddsratioof.9formaxSPVand1.06forage.Conclusions:ThecurrentinvestigationshowedthatbothageandmaxSPVofthecaloricresponseweresignificantpredictorsofvertigoperceptionduringthecaloricexam.However,theassociationbetweenageandcaloricperceptionisnotconclusive.Althoughthereisevidencetosuggestthatthesefindingsrepresentage-relatedchangesinthecentralprocessingofvestibularsystemstimulation,thereareadditionalunmeasuredfactorsthatinfluencetheperceptionofcaloric-inducedvertigo.

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简介：Anti-androgentherapyistheleadingtreatmentforadvancedprostatecancerandiscommonlyusedforneoadjuvantoradjuvanttreatment.Bicalutamideisanon-steroidalanti-androgen,usedduringtheinitiationofandrogendeprivationtherapyalongwithaluteinizinghormone-releasinghormoneagonisttoreducethesymptomsoftumor-relatedflaresinpatientswithadvancedprostatecancer.Assideeffects,bicalutamidecancausefatigue,gynecomastia,anddecreasedlibidothroughcompetitiveandrogenreceptorblockade.Additionally,althoughnotascommon,drug-inducedliverinjuryhasalsobeenreported.Herein,wereportacaseofhepatotoxicitysecondarytobicalutamideuse.Typically,bicalutamideinducedhepatotoxicitydevelopsafterafewdays;however,inthiscase,hepaticinjuryoccurred5moaftertreatmentinitiation.Basedonthisrarecaseofdelayedliverinjury,werecommendcarefulmonitoringofliverfunctionthroughoutbicalutamidetreatmentforprostatecancer.