简介:NatsumeSōseki(1867-1916)sufferedfromcyclicmentaldepressionsthroughhislife,anditwaswhenhewasinthestateofthemostterribleonethathestartedhiscareerasawriterbywritingIAmaCat(1905-1906).TherearesomeevidencebyhiswifeandfriendsthatSōseki’sconditionofdiseasedramaticallyimprovedduringitsserializationonamagazine,andthewriterhimselfadmitedhumorouslyintheprefaceofotherworkthatitwashisdepressionandmaniathatenabledhimtoproduceIAmaCatandotherearlyworks.Thispaperaimsatdescribingtheprocesshowhisactofnarratinghadtherapeuticeffectsonhisstateofmindfocusingontheconstructionofcomplicitousrelationshipbetweenanimpliedauthorandreadersintheworkbytheuniquefunctionsofthefirst-‘person’narrator:ACat.Amongothers,IwillconsidertheinfluenceofLaurenceSterne’sTristramShandy(1759-1767),whichSōsekiintroducedtoJapanforthefirsttime,bydiscussingthefrequentuseofmetalepsisthatthetwoworkshaveincommon.
简介:Transcatheteraorticvalvereplacement(TAVR)isincreasinglyusedforthetreatmentofhighorveryhighsurgicalriskpatientswithsevereaorticstenosis(AS)orfailingsurgicalbioprosthesis(valve-in-valve,VIV-TAVR).InTAVR,thecollapsedtranscatheterheartvalve(THV)isintroducedusingthedeliverysysteminsertedfromthefemoralartery(preferred)orotheralternativeaccesses(transapical,transaortic,transcarotid,subclavian/transinnominateortranscaval).Thedeliverysystemisthenadvanceduntilcoaxiallyalignedwiththeaorticannulus,wheretheTHVisdeployed.Thisprocedurecanbeassociatedwithcomplicationssuchasaccesssiteinjury(vascularcomplication),paravalvarleak,cerebrovasculareventsandconductiondisturbances.However,therapidacceptanceandsuccessesobservedwithTAVRhavebeenmadepossiblethroughcarefulpatientselection,preproceduralplanning(i.e.MDCTannularsizing),THVtechnology(i.e.newgenerationvalves),andproceduraltechniques(i.e.minimalistTF-TAVRandalternativepercutaneousaccessoptions),aswellasadecreaseincomplicationsasTAVRexperiencegrows.ThoughtheresultsorongoingclinicaltrialsevaluatingTAVRinintermediatesurgicalriskpatientsarepending,itislikelythatTAVRwillsoonbeapprovedforlowerriskpatientsaswell.
简介:Thedevelopmentofcancernanotherapeuticshasattractedgreatinterestintherecentdecade.Cancernanotherapeuticshaveovercomeseverallimitationsofconventionaltherapies,suchasnonspecificbiodistribution,poorwatersolubility,andlimitedbioavailability.Nanoparticleswithtunedsizeandsurfacecharacteristicsarethekeycomponentsofnanotherapeutics,andaredesignedtopassivelyoractivelydeliveranti-cancerdrugstotumorcells.Weprovideanoverviewofnanoparticle-baseddrugdeliverymethodsandcancertherapiesbasedontumor-targetingdeliverystrategiesthathavebeendevelopedinrecentyears.
简介:Toevaluatetheeffectofatrovastatintherapyonborderlinevulnerablelesionsinpatientswithacutecoronarysyndrome(ACS).MethodsPatientswithACSunderwentcoronaryangiography(CAG)andintravascularultrasound(IVUS)investigation.Patientswithculpritvulnerableborderlinelesionswereenrolled.Nocoronaryinter-ventionwasperformedontheselesions.Allthepatientsreceivedatrovastatintherapyfor12monthsandunderwentclin-icalfollow-upalongwithIVUSfollow-up.Crosssectionarea(CSA)ofthetargetedlesion,CSAofthereferencearter-ies(extraelasticmembrane),minimallumenCSA,andplaqueareaweremeasuredatbaselineandfollow-ups.Ad-verseeventsincludedrecurrentangina,recurrentmyocardialinfarction,revascularizationanddeath.ResultsNoad-verseeventswasreportedduringfollow-upperiod.Comparedwithbaselinedata,thelevelofApoBdecreasedsignifi-cantlyattheendofthestudy(0.589±0.136g/Lvs0.681±0.132g/L,P=0.03).Boththepercentdiametersteno-sisandthepercentareastenosisdetectedbyCAGdisplayedminimalchange((62.50±10.21)%vs(54.79±12.35)%,P=0.48and(58.61±8.36)%vs(48.18+10.56)%,P=0.78).DetectedbyIVUS,theminimallu-minalCSAofthetargetedlesionincreasedsignificantly(6.32±2.42mm2vs5.63±2.51mm2,P<0.01),theplaqueareaandCSAstenosisdecreased(7.70±2.19mm2vs8.17±2.55mm2,P<0.05and56.94±8.47%vs61.4±110.34%,P<0.01).Atotalof25softplaques(50%)transformedintofibrousplaque.ConclusionsAtro-vastatintherapystabilizesborderlinevulnerableplaqueandreversesatherosclerosisprogressioninpatientswithACS.
简介:Themanagementofneurologicaldisordershavehugeandincreasinghumanandeconomiccosts.Despitethis,thereisascarcityofeffectivetherapeutics,andthereisanextremeurgencyfornewandrealtreatments.Inthisshortreviewweanalyzesomepromisingadvancementsinthesearchofnewbioactivemoleculestargetingneuronalnitricoxidesynthase(nNOS),anenzymedeputedtothebiosynthesisofnitricoxide(NO).Indifferentconditionsofneuronaldamages,thismoleculeisoverproduced,contributingtothepathogenesisandprogressionofneuronaldiseases.TwomainapproachestomodulatenNOSarediscussed:afirstoneconsistinginthedirectinhibitionoftheenzymebymeansofsmallorganicmolecules,whichcanbealsoactiveagainstotherdifferenttargetsinvolvedinsuchdiseases.AsecondsectionisdedicatedtomoleculesabletopreventtheformationoftheternarycomplexN-methyl-D-aspartate(NMDA)-typeglutamatereceptors,postsynapticdensity-95(PSD95)protein-nNOS,whichisnecessarytoactivatethelatterforthebiosynthesisofNO.
简介:AbstractDue to the coronavirus disease 2019 (COVID-19) pandemic, the development of antiviral drugs has attracted increasing attention. Clinical antiviral drugs show weak solubility, low bioavailability, adverse side effects, or only limited targets. With the advancement of nanotechnology and material science, biosafety nanomaterials have been constructed for drug delivery systems of antiviral disease therapy, such as liposomes, polymers, gold nanoparticles, and graphene. These nanodrug systems can either deliver synthesized antiviral drugs siRNA/miRNA and small molecular compounds, deliver bioactive large molecular drug proteins and mRNA, or show antiviral activity by themselves. Nanodelivery systems could effectively enhance the efficiency of antiviral drugs by increasing drug loading and host cell uptake with a small size and high specific surface area. This review focused on the biosafety nanomaterials used for antiviral therapy and discussed the options for the design of antiviral drugs in the future.
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简介:摘要Background and objectiveCloser monitoring and treatment is vital for pregnant carbon monoxide (CO) poisoning cases due to fetal poisoning component. Permanent damage can occur in both the mother and the baby. It may cause stillbirth even though no serious clinical symptoms occur in the mother. Hyperbaric oxygen (HBO) treatment is advised for all pregnant patients regardless of their clinical symptoms. Pregnant CO poisoning patients that received HBO treatment and their fetal status were evaluated in this study.MethodsPregnant patients poisoned with CO treated in the same hyperbaric clinic were evaluated. Pregnant patients that received HBO treatment in a multiplace chamber were evaluated in terms of clinical status, demographic structure, laboratory tests, fetal effects and progress of the fetus until birth and 6 months postpartum.ResultsA total number of 32 pregnant cases were treated. COHb values were over 20% (min 6.9- max 40.2) in 23 patients, 11 patients had a history of syncope. All patients took HBO treatment under 2.4 ATA pressure for 120 min. 3 patients received more than 1 session of HBO treatments due to fetal stress; all other cases took 1 session of HBO treatment. No spontaneous abortus occurred in early follow-ups; only 4 babies were born prematurely. 2 of the babies were lost in the early phases after birth, due to causes non-related to CO poisoning complications (cyanotic heart disease, necrotizing enterocolitis). No significant difference were observed in the comparison of laboratory results of patients with syncope and of those who did not have syncope and comparison of patients with COHb value higher than 20% and patients with COHb value lower than 20% (P>0.05).ConclusionHBO is not advisable for pregnant patients except for CO poisoning. In this study it is observed that HBO treatment under 2.4 ATA pressure for 120 min has no harmful effects on the mother and the fetus. It is observed that continuation of HBO treatment in the cases with fetal distress findings has beneficial effects. COHb levels and syncope were shown to have no significant effect on clinical symptoms and on blood tests.
简介:Precisionmedicineaimstoidentifytherightdrug,fortherightpatient,attherightdose,attherighttime,whichisparticularlyimportantincancertherapy.Problemssuchasthevariabilityoftreatmentresponseandresistancetomedicationhavebeenlongstandingchallengesinoncology,especiallyfordevelopmentofnewmedications.Solidtumors,unlikehematologicmalignanciesorbraintumors,areremarkablydiverseintheircellularoriginsanddevelopmentaltiming.Theabilityofnext-generationsequencing(NGS)toanalyzethecomprehensivelandscapeofgeneticalterationsbringspromisestodiseasesthathaveahighlycomplexandheterogeneousgeneticcompositionsuchascancer.HereweprovideanoverviewofhowNGSisabletofacilitateprecisionmedicineandchangetheparadigmofcancertherapy,especiallyforsolidtumors,throughtechnicaladvancements,moleculardiagnosis,responsemonitoringandclinicaltrials.
简介:Objective:Tostudytheprotectiveeffectofischemicpreconditioning(Ⅰ-pre)andischemicpostconditioning(Ⅰ-post)againstischemia/reperfusion(I/R)injuryinrat'sliver.Methods:UsingratmodelofhepaticsegmentalI/Rinjury,ratsweredividedinto5groups:GroupA(shamgroup),GroupB(I/Rinjury),GroupC(Ⅰ-pregroup),GroupD(Ⅰ-postgroup)andGroupE(combinedtreatmentofⅠ-preandⅠ-post).Serumalanineaminotransferase(ALT),aspartateaminotransferase(AST),malondiaidehyde(MDA),glutathione(GSH),superoxidedismutase(SOD),glutathioneperoxidase(GSH-Px)andmyeloperoxidase(MPO)inhepatictissuesweredetermined,respectively.Inaddition,7days'survivalofGroupsB,C,DandEwereevaluated.Results:ComparedwithGroupB,GroupsC,DandEexhibitedsignificantlydecreasedALTandASTrelease,minimizedtissueinjury,suppressedvaluesofMDAandMPO,increasedactivitiesofSOD,GSH-PxandGSH(P<0.05),aswellasimprovedanimalsurvival.ThedifferencesamongGroupsC,DandEwerenotstatisticallysignificant.Conclusions:Ⅰ-pre,Ⅰ-postandcombinedtherapyofⅠ-preandⅠ-posthaveprotectiveeffectagainsthepaticI/Rinjury,whichiscorrelatedwithitsfunctionofreducingtheproductionofreactiveoxygenspecies,maintainingtheactivitiesofantioxidantsystemsandsuppressingneutrophilsrecruitment.NoadditiveeffectcanbeobtainedinGroupE.
简介:AbstractGastric cancer, which has a high incidence and poor prognosis, remains a therapeutic challenge. Recently, neoadjuvant therapy has attracted increasing attention due to high recurrence rate and low survival rate after resection in most patients with advanced stage. Clinical trials show that neoadjuvant approaches confer a significant survival advantage for resectable locally advanced gastric cancer. The specific advantages of chemoradiotherapy compared with chemotherapy have not been clarified; optimal regimens and cycles, particularly in the preoperative setting, should be studied further; and trials aimed at determining the role of targeted and immunological therapies should be conducted.
简介:Objective:Laser-inducedCoulombexplosionofgoldnanoparticlesforbreastcancerhasbeenstudiedbynanophotolysistechnique.Thisstudyaimedtoinvestigatewhetherlaser-inducedbubbleformationduetoCoulombexplosioncanprovideaneffectiveapproachforselectivedamageofbreastcancerwithgoldnanoparticles.Method:Numericalmethodinvolveslaser-inducedCoulombexplosionofgoldnanoparticles.Differentparametersrelatedtonanophotolysissuchaslaserfluence,tumordepth,clusterradius,laserpulseduration,andbubbleformationisstudiednumerically.NumericalsimulationwasperformedusingMatlab.Results:Thegoldnanoparticlesof10,20,30,40,and50nminradiuscouldpenetrateintotumor1.14,1.155,1.189,1.20and1.22cmindepthrespectively.Themaximumpenetrationdepthintumorcouldbeobtainedwithnanoparticlesof50nmradius.Shortlaserpulseof40nswithnanoparticlesof10nmradiuscouldpenetrateintotumor1.14cmindepth.Bubbleswitharadiusof9μmcouldeffectivelykillbreastcancercellswithoutdamaginghealthyones.Thebubbleradiusincreasedfrom4to9μmwithanincreaseinpulsedurationintherangeof10to30ns.Conclusions:Goldnanoparticleswithincreasingradiusandbubbleformationforselectivedamageofbreastcancercellsaresuccessfullyprobed.Thepresentcalculatedresultsarecomparedwithotherexperimentalfindings,andgoodcorrelationisfoundbetweenthepresentworkandpreviousexperimentalvalues.Itwasdemonstratedthatbubbleformationintumormayfurtherincreasetheefficacyofbreastcancertreatment.
简介:Thecomplexityofacancer,suchascellheterogeneity,andtheexistenceofhypoxia,stromalcellsandstemcellshaspresent,theuseofconventionaltherapies,suchaschemo/radiotherapyislimited,andonlytherapiesthataresofarpreventedsuccessfuldevelopmentandtreatmentofpatientssufferingfromthelaterstagesofcancers.Atfocusedonutilizingthepatient'simmuneresponsetocombatagainstthediseaseappeartobethemostreliableandpromising.Twodecadesago,cytokineswerediscoveredtobeabletoactivatetheimnunesystemsandmountananti-tumourresponse.Then,dendriticcellswerehailedasthemostsignificantregulatorsofimmunityandareemployedinavarietyofcancermanagementschemes.Thisreviewintroducescurrentdevelopmentinthefield,focusingoncombinationofthecomponentsoftherapidlygrowingfieldsofimmunotherapyandgenetransfer/therapy,providingusefulandsignificantdetailedinformationforreadersofcellularandmolecularimmunology.Cellular&MolecularImmunology.