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简介：Cholesterolcrystalshavelongbeenrecognizedaspartofatheroscleroticplaques.Theyhavebeenvisualizedbylightmicroscopyasemptyspacesorimprintswherecrystalswereoncepresentandthendissolvedbytissueprocessing.Thus,untilnow,theirroleinatherosclerosisandplaquerupturehadbeenconsideredtobeinert.However,bytheprocessingoftissuewithoutethanolitwaspossibletovisualizetheirextensivenessandpotentialroleintissueinjury.Also,itwasdemonstratedthatcholesterolexpandsinvolumewhencrystallizingfromtheliquidtothesolidstate,whichisthepresumedcauseofplaquerupturebysharp-tippedcrystalsgrowingoutoftheplaque'snecroticcore.Specifically,inpatientswhodiedofmyocardialinfarction,allculpritcoronarylesionshadextensivecholesterolcrystalsperforatingthefibrouscapandintima,whilethosepatientswhodiedofothercausesandhadplaquesdidnothavecrystalsperforatingthecapandintima.Additionally,cholesterolcrystalstravelingdownstreamfromtheplaquerupturesitecanscrapetheendotheliumandpromotevasospasm.Moreover,cholesterolcrystalslodgingintothemusclecantriggeraninflammationwithnecrosisindependentofcirculatorycompromiseorischemia.Thesefindingssuggestthatcholesterolcrystalscouldplayacriticalroleinplaquerupture,aswellasvascularandmyocardialinjury.

简介：Objective:Toobservetheeffectofacupunctureonsimpleobesityandcellularhemorheology.Methods:Thirty-twocasesofsimpleobesitypatientswereenrolledintothisstudy.AcupointsoftheStomachMeridianandSpleenMeridianasZhongwan(中脘CV12),Liangmen(梁门ST21),Tianshu(天枢ST25),Guanyuan(关元CV4),etc.werepunctured,oncedailyinthefirst5days,andonceeveryotherdayafterwards,with10sessionsbeingatherapeuticcourse.Beforetreatmentandafter3coursesoftreatment,thebodyweight,waistline,weightindex,serumcholesterol(CH),triglycerideandaggregationindexofredbloodcell(RBC)weredetected.Results:Afteracupuncturetreatment,alltheindexesofbodyweight,waistline,weightindex,serumCH,triglycerideandaggregationindexofRBCdecreasedsignificantlyincomparisonwiththoseofpre-treatment(P<0.05).Conclusion:Acupuncturecanapparentlyimprovecellularhemorheology,reducebodyweight,serumcholesterolandTGlevelsinsimpleobesitypatients.

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简介：3-hydroxy-3-methylglutaryl辅酶a(HMGCoA)reductase生产mevalonate，在胆固醇和必需品的合成的重要中介非甾醇isoprenoids。reductase通过被甾醇并且非调停的多重机制服从于反馈控制的过高的数量mevalonate的甾醇结束产品新陈代谢。这里，我将讨论为reductase的控制使一机制清楚些的最近的进展，它包含酶的快速的降级。某些甾醇的累积触发reductase的绑定到endoplasmic(嗯)膜蛋白质叫了Insig-1和Insig-2。在联系膜的ubiquitin连接酶的招募的Reductase-Insig有约束力的结果叫了gp78，它开始reductase的ubiquitination。这ubiquitination是为reductase从的识别和降级的应尽的反应嗯由cytosolic26Sproteasomes的膜。因此，reductase的加速甾醇的降级代表一般细胞的进程(嗯联系降级)怎么被用来控制一条重要新陈代谢的小径(胆固醇合成)的一个例子。

简介：In2014theAmericanCollegeofCardiology/AmericanHeartAssociationissuedfournewguidelinesforcardiovasculardiseasepreventionthatfocusedoncardiovascularriskassessment,lifestylemanagement,obesitymanagement,andbloodcholesterolmanagement.Thedevelopmentofanatheroscleroticcardiovasculardiseaseriskcalculatorformedthebasisoftheriskassessmentguideline,andthelifestylemanagementguidelinefocusedonrecommendinganevidence-baseddietarypattern.Thebloodcholesterolmanagementguidelinespecificallyidentifiedfourgroupsofpatientsshowntobenefitfrommoderate-intensityorhigh-intensitystatintherapyfrompreviousclinicaltrialsandabandonedtheuseofspecificlow-densitylipoprotein(LDL)cholesterol(LDL-C)goallevelsonthebasisofthelackofclinicaltrialevidence.Therecommendationsfortreatmentwithmoderate-intensityorhigh-intensitystatintherapyarebasedonrigorousevidencefromrandomizedclinicaltrials.Guidancehassincebeenprovidedfortheuseofnonstatintherapies,includingcholesterolabsorptioninhibitorandproproteinconvertasesubtilisin/kexintype9monoclonalantibodytherapywhenadequatereductionofLDL-Clevelsisnotachievedwithmaximallytoleratedstatintherapy.TherecentdevelopmentandapplicationofthesetherapieshaveresultedinremarkablereductionsinLDL-Clevelsthatarewelltolerated,andpreliminaryoutcomedataarepromisinginshowingsubstantialatheroscleroticcardiovasculardiseaseeventreductionsbeyondstatintherapy.

简介：Wepresentherethedevelopmentofcholesterol(Chol)-modifieddendrimersystemfortargetedchemotherapyoffolate(FA)receptor-expressingcancercells.Inourstudy,poly(amidoamine)(PAMAM)dendrimersofgeneration5(G5)werefunctionalizedstepby-stepwithChol,fluoresceinisothiocyanate(FI),andFAviaapoly(ethyleneglycol)(PEG)spacer(PEG-FA),andthenacetamidetoshieldtheirremainingsurfaceamines.ThesynthesizedG5.NHAc-Chol-FI-PEG-FA(forshort,G5-CFPF)dendrimerswereutilizedtoencapsulate10-hydroxycamptothecin(HCP),ahydrophobicanticancerdrug.WefindthateachG5-CFPFdendrimercanencapsulate13.8HCPmolecules.ThecomplexesshowaslowerreleaseprofilesofHCPinapH-dependentmannerthanthecontrolcomplexesformedusingthesamedendrimerswithoutCholunderthesameconditions.ThankstothetargetingroleplayedbyFA,thecomplexesdisplayaspecificinhibitionefficacytoFAreceptor-expressingcervicalcancercells.ThedesignedChol-modifieddendrimersmaybeadoptedasapromisingcarrierforapplicationintargetedcancertherapy.

简介：BackgroundAnimalmodelsofhyperlipidemiawereestablishedbyfeedingrabbitswithhigh-cholesteroldiet,andthechangesinstructureandfunctionofcellmembraneinrabbitswerealsoreducedbyhyperlipidemia.Thus,thealternationsinerythrocytemembranelipidperoxidation(EMLP)andfluidityinrabbitsinducedbyhigh-cholesteroldietwereresearchedbyus.MethodsFourteenrabbitsweresubjectedtohigh-cholesteroldiet(cholesterol2g/d)andtheother14rabbitstocommondieteverydayforconsecutivetwomonths,plasmatotalcholesterol(TC),andbloodlipidsaswellasEMLPandfluidityweremeasuredbeforeandafterthefeeding.ResultsComparedwiththefeedingbefore,levelsofTCandlowdensitylipoproteincholesterol(LDL-C)weresignificantlyraised,thoseoferythrocytemembranelowdensitylipoproteincholesterol(MLDL-C),membraneconjugateddiene(MCD),erythrocytemalonaldehyde(RMDA)weresignificantlyincreased,whilethoseoferythrocytesuperoxidedismutase(R-SOD),membranefluidity(M-Flu)andmembranehighdensitylipoprotein-cholesterol(MHDL-C)weresignificantlydecreasedinexperimentalgroup,andtherewerenochangesincontrolgroup.ConclusionsHigh-cholesteroldietinduceslipidperoxidationandlowerfluidityoferythrocytemembrane.

简介：Aseriesofglucose-cholesterolderivatives8a-8easligandsforbraintargetingliposomesweresynthesized.Thepreparationofcompound6involvedtemporaryprotectionofglucosewithchlorotrimethylsilicaneandhexamethyldisilazanefollowedbyselectivelyhydrolyzed.Theknowncholesteryltosylate1werecoupledtoethyleneglycolstoaffordalcohol2a-2e.Substitutionanddeprotectionofalcohol2a-2efurnishedtheacids4a-4e,whichwascondensedwithcompound6togetcompounds7a-7e,andthenwasdeprotectedintetrahydrofuranwithTFAtoobtainthetitlecompounds.Asamodeldrug,tegafurwasentrappedbyliposomescoupledwith8b,andpreliminaryinvivoevaluationshown8bcouldenhancetheabilityofliposomesdeliveringtegafuracrossthebloodbrainbarrier.

简介：BackgroundThisstudytestedthehypothesisthatmoderatealcoholintakeexertsitscardioprotectiveeffectmainlythroughanincreaseintheserumlevelofhigh-densitylipoproteincholesterol.MethodsandResultsIntheCohortofNorway(CONOR)study,149729adultparticipants,recruitedfrom1994to2003,werefollowedbylinkagetotheCauseofDeathRegistryuntil2006.Atrecruitment,questionnairedataonalcoholintakewerecollected,andtheconcentrationofhigh-densitylipoproteincholesterolinserumwasmeasured.UsingCoxregression,wefoundthattheadjustedhazardratioformenfordyingfromcoronaryheartdiseasewas0.52(95%confidenceinterval,0.39-0.69)whenconsumingalcoholmorethanonceaweekcomparedwithneverorrarely.Theratiochangedonlyslightly,to0.55(0.41-0.73),aftertheregressionmodelincludedtheserumlevelofhigh-densitycholesterol.Forwomen,thecorrespondinghazardratioswere0.62(0.32-1.23)and0.68(0.34-1.34),respectively.ConclusionsAlcoholintakeisrelatedtoareducedriskofdeathfromcoronaryheartdiseaseinthefollow-upofalarge,population-basedNorwegiancohortstudywithextensivecontrolforconfoundingfactors.Ourfindingssuggestthattheserumlevelofhigh-densitycholesterolisnotanimportantintermediatevariableinthepossiblecausalpathwaybetweenmoderatealcoholintakeandcoronaryheartdisease.

简介：Take-homeMessages.TherecentlypublishedACC/AHAcholesterolguidelinesrecommendfixed-dosestatintherapyforthoseatrisk,andalthoughnotrecommendedasfirstlinetherapy,nonstatintherapiesarerecommendedwhenlessthananticipatedtherapeuticresponsetostatintherapyoccursorwhenpatientsarenotabletotoleratestatintherapy.Nonstatincholesterol-loweringdrugsshowntoreduceatheroscleroticcardiovasculardisease(ASCVD)eventsinrandomizedcontrolledtrials(RCTs)arepreferred.Noevidencewasfoundtosupporttheuseofspecificlow-densitylipoprotein(LDL)-cholesteroltargetlevels.

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简介：BackgroundMonocytetohighdensitylipoproteinratio(MHR)hasbeenconsideredasanovelparameterrelatedwithadverserenalandcardiovascularoutcomes.InthisstudyweinvestigatedtheassociationofMHRwithmajoradverseclinicalevents(MACEs)inpatientswithtype2diabetesmellitus(T2DM)undergoingelectivepercutaneouscoronaryintervention(PCI).MethodsConsecutiveT2DMpatientstreatedwithelectivePCIwereprospectivelyrecruitedbetweenJuly2008-January2016inDepartmentofCardiologyofPanyuCentralHospital.Subjectswerecategorizedintotwogroups:aspatientswhodevelopedMACEs(MACEs+)andpatientswhodidnotdevelopMACEs(MACEs-)duringhospitalization.MACEsweredefinedasthecompositeendpoints,includingall-causemortality,oracuteheartfailure,ortargetvesselrevascularization,orstrokeorrecurrentangina.ResultsAtotalof418patientswereincludedinthestudy.64patientsdevelopedMACEs(15.3%).IntheMACEs(+)patients,monocyteswerehigher(1.12[0.78-1.42]vs.0.72[0.68-0.92]109/L,P<0.01)andHDLcholesterollevelswerelower(0.87[0.72-1.21]vs.0.96[0.81-1.11]mmol/L,P<0.01).Inaddition,MHRwassignificantlyhigherintheMACEs(+)group(1.12[0.91-2.09]vs.0.73[0.54-0.93]109mmol/L,P<0.01).ThecutoffvalueofMHRforpredictingMACEswas22,withasensitivityof81%andaspecificityof75.1%(areaunderthecurve0.79,P<0.001).Inmultivariatelogisticregressionanalysis,MHRremainedanindependentfactorcorrelatedwithMACEs(OR=3.97,95%CI=1.38-11.5,P<0.01).ConclusionHigherMHRlevelsmaypredictMACEsdevelopmentafterelectivePCIinT2DMpatients.

简介：AbstractDespite overwhelming evidence from large randomized clinical trials supporting a clear benefit of low-density lipoprotein cholesterol (LDL-C) lowering therapy on the primary and secondary prevention of atherosclerotic cardiovascular disease, data from epidemiological and clinical observations demonstrated an increased incidence of hemorrhagic stroke in patients with low LDL-C exposure (<70 mg/dL), especially among East Asians. Meanwhile, emerging studies have reported a paradoxical phenomenon in which hypercholesterolemia is associated with better short-term outcomes in acute coronary syndrome patients, the "lipid paradox." The underlying mechanism for these two closely connected clinical observations is not clear. This review aimed to summarize the evolution and clinical implications of these two low LDL-C related concepts, and proposed a "double-hit" hypothesis that may help explain these phenomena. It is worth noting that in the era of increasing use of high-intensity LDL-C lowering and dual antiplatelet strategies in atherosclerotic cardiovascular disease in patients receiving percutaneous coronary intervention, balancing the risk of thrombosis with bleeding complication should be a priority in clinical practice. Our hypothesis may raise clinicians’ awareness to identify potential high risk patients with low LDL-C (<70 mg/dL), especially among East Asians.