简介:AbstractAlbumin solutions derived from human plasma have demonstrated clinical benefits as intravenous fluid therapy in clinical settings such as liver disease, sepsis, intensive care, and surgery. For all plasma-derived medicinal products, there is a potential risk from pathogens, including relevant blood-borne viruses, emerging viruses, and prion proteins. To minimize the risk of transmissible infections, the production of human albumin solutions includes rigorous donor selection and plasma testing, and effective pathogen removal and inactivation methods such as fractionation and pasteurization. Compliance with international pharmacopeial standards for purity and prekallikrein activator and aluminum content is crucial, as is post-marketing pharmacovigilance for the continuous monitoring of adverse events. This review focuses on the effectiveness of manufacturing methods in the production of plasma-derived albumin, to ensure the safety of hyperoncotic solutions for volume expansion. We evaluated evidence identified through online database (PubMed) searches and from unpublished sources, on the manufacturing and pathogen safety of plasma-derived albumin solutions. The results confirmed the already established and evolving pathogen reduction capacity of the reviewed manufacturing methods. Up-to-date post-marketing pharmacovigilance data and log10 reduction factors for known and emerging pathogens during albumin production are included. Towards the goal of ever-increasing clinical safety, potential areas of improvement, such as compliance rates for the completion of donor health questionnaires, are also discussed. Taken together, the current manufacturing and pathogen reduction steps result in albumin products of greater purity than previous-generation products, with a high margin of pathogen safety against known and emerging pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
简介:StabilizedorChebyshevexplicitmethodshavebeenwidelyusedinthepasttosolvestiffordinarydifferentialequations.MakinguseofspecialpropertiesofChebyshev-likepolynomials,thesemethodshavefavorablestabilitypropertiescomparedtostandardexplicitmethodswhileremainingexplicit.Anewclassofsuchmethods,calledROCK,introducedin[Numer.Math.,90,1-18,2001]hasrecentlybeenextendedtostiffstochasticdifferentialequationsunderthenameS-ROCK[C.R.Acad.Sci.Paris,345(10),2007andCommun.Math.Sci,6(4),2008].InthispaperwediscusstheextensionoftheS-ROCKmethodstosystemswithdiscretenoiseandproposeanewclassofmethodsforsuchproblems,theT-ROCKmethods.Onemotivationforsuchmethodsisthesimulationofmulti-scaleorstiffchemicalkineticsystemsandsuchsystemsarethefocusofthispaper,butournewmethodscouldpotentiallybeinterestingforotherstiffsystemswithdiscretenoise.TwoversionsoftheT-ROCKmethodsarediscussedandtheirstabilitybehaviorisanalyzedonatestproblem.ComparedtotheT-leapingmethod,asignificantspeed-upcanbeachievedforsomestiffkineticsystems.Thebehavioroftheproposedmethodsaretestedonseveralnumericalexperiments.
简介:基因治疗为癌症的治疗提供一条新途径。编码immunostimulatorycytokines的基因的转移与显著成功被使用了在动物消除癌症。然而,在有这策略的病人的临床的试用限制了功效。因此,基因转移向量系统的改进是必要的。混合病毒的向量,与鼠科的IL-12或记者LacZ基因由SFVreplicon组成,被构造。这混合向量在vitro并且在vivo在HCC显示出表示的特性和高水平。在一个老鼠orthotropic肝肿瘤模型,没有伴随毒性,由有mIL-12基因的混合向量的确定的肿瘤的治疗导致了一项强壮的反肿瘤活动。随后,助手依赖者侵入人体气管粘膜的病菌包含mifepristone(RU486)的向量可诱导的系统被构造为控制并且人的interleukin的肝特定的表示12(hIL-12)(HD-Ad/RUhIL-12)并且鼠标IL-12(mIL-12)(HD-Ad/RUmIL-12)。数据证明hIL-12的高、支撑的浆液层次能被继续RU486的管理达到每12或24h。hIL-12的重复正式就职能被获得在上,至少在HD-Ad/RUhIL-12的单个注射以后的48个星期的一个时期。肝转移与的处理HD-Ad/RUmIL-12,正RU846在所有动物导致了完全的肿瘤回归。然后,不同cytokine基因被插入到有条件的replicative侵入人体气管粘膜的病菌向量(也叫的oncolytic侵入人体气管粘膜的病菌)。在肿瘤房间的侵入人体气管粘膜的病菌的复制将杀死肿瘤房间和版本病毒,它感染包围肿瘤房间。由oncolytic侵入人体气管粘膜的病菌的cytopathic效果和transgene的生物效果的联合将施加强壮的反肿瘤活动。向量的这些新类型可以为癌症基因治疗提供一个有势力和安全工具。
简介:Inthispaper,standardandeconomicalcascadicmultigridmethodsareconsideredforsolvingthealgebraicsystemsresultingfromthemortarfiniteelementmethods.Bothcascadicmultigridmethodsdonotneedfullellipticregularity,sotheycanbeusedtotacklemoregeneralellipticproblems.Numericalexperimentsarereportedtosupportourtheory.
简介:Inthepastdecade,anincreasedamountofclinically-orientedresearchinvolvingimmunotoxinshasbeenpublished.Immunotoxinsareagroupofartificially-madecytotoxicmoleculestargetingcancercells.Thesemoleculescomposedofatargetingmoiety,suchasaligandoranantibody,linkedtotoxinmoiety,whichisatoxinwitheithertruncatedordeletedcell-bindingdomainthatpreventsitfrombindingtonormalcells.Immunotoxinscanbedividedintotwocategories:chemicallyconjugatedimmunotoxinsandrecombinantones.Theimmunotoxinsofthefirstcategoryhaveshownlimitedefficacyinclinicaltrialsinpatientswithhematologicmalignanciesandsolidtumors.Withinthelastfewyears,single-chainimmunotoxinsprovideenhancedtherapeuticefficacyoverconjugatedformsandresultinimprovedantitumoractivity.Inthisreview,webrieflyillustratethedesignoftheimmunotoxinsandtheirapplicationsinclinicaltrials.Cellular&MolecularImmunology.2005;2(2):106-112.
简介:IntroductionThereisnowanewwaytotreathypercholesterolemia,usingamonoclonalantibody(Evolocumab)thatbindstoandinhibitsPCSKA9.MostphysiciansknowthetermPCSK9buthavenoideawhatPCSK9standsfor(includingme).MypurposeforwritingthiseditorialistoeducatemyselfonwhatPCSK9isandwhatitdoes.MyhopeisthatIcanperhapseducatethosereadingthisdocumentaswell.
简介:BioscienceMethods(ISSN1925-1920)isanopenaccess,peerreviewedjournalpublishedonlinebyBioPublisher.Thejournalpublishesallthelatestandoutstandingresearcharticles,lettersandreviewsinallareasofbioscience,therangeoftopicsincluding(butarenotlimitedto)technologyreview,techniqueknow-how,labtool,statisticalsoftwareandknown
简介:BioscienceMethods(ISSN1925-1920)isanopenaccess,peerreviewedjournalpublishedonlinebyBioPublisher.Thejournalpublishesallthelatestandoutstandingresearcharticles,lettersandreviewsinallareasofbioscience,therangeoftopicsincluding(butarenotlimitedto)technologyreview,techniqueknow-how,labtool,statisticalsoftwareandknown
简介:BioscienceMethods(ISSN1925-1920)isanopenaccess,peerreviewedjournalpublishedonlinebyBioPublisher.Thejournalpublishesallthelatestandoutstandingresearcharticles,lettersandreviewsinallareasofbioscience,therangeoftopicsincluding(butarenotlimitedto)technologyreview,techniqueknow-how,labtool,statisticalsoftwareandknowntechnologymodification.Casestudiesontechnologiesforgenediscoveryandfunction
简介:CascadicmultigridtechniqueformortarWilsonfiniteelementmethodofhomogeneousboundaryvalueplanarlinearelasticityisdescribedandanalyzed.FirstthemortarWilsonfiniteelementmethodforplanarlinearelasticitywillbeanalyzed,andtheerrorestimateunderL2andH1normisoptimal.Thenacascadicmultigridmethodforthemortarfiniteelementdiscreteproblemisdescribed.Suitablegridtrans-feroperatorandsmootheraredevelopedwhichleadtoanoptimalcascadicmultigridmethod.Finally,thecomputationalresultsarepresented.
简介:Coronaryarterydisease(CAD)istheleadingcauseofdeathworldwide,butbecauseofseveralfactors,oneofwhichisantiplatelettherapy,themortalityrateshavesteadilydeclined.However,womencontinuetoexperiencehigherCADmortalityratesthanmen.Thismaybeexplainedbydifferencesincomorbidities,increasedtimetopresentation,higherbleedingrates,anddifferencesinmanagement.Therearenumerouslandmarktrialsinthefieldofantiplatelettherapy;however,womenareconsistentlyunderrepresentedinthesetrials.Theresultsofthesetrialsrevealthatwomenexperiencethesamebenefitasmenfromantiplatelettherapybutexperiencehigherbleedingrates;thereforebleeding-reductionstrategiesareimperativeinthispatientpopulation.ThisreviewprovidesanoverviewoftheavailableevidenceonCADinwomenanditsimplicationsforantiplateletmedications.
简介:Wehavereviewedthegenetherapyingastrointestinaldiseases^[1].GastriccanceriscommoninChina^(2-20),anditsearlydiagnosisandtreatmentarestilldifficultuptonow^(13-36).Theex-pressionofanexogenousgeneintroducedbygenetherapyintopa-tientswithgliomascanbemonitorednon-invasivelybypositron-emissiontornography^[4].
简介:质子放射疗法在hepatocellular癌(HCC)的治疗看见了一个增加的角色。历史上,外部横梁放射疗法由于毒性的高发生在HCC起了一个很有限的作用到包围正常结构。把放射的高剂量送到肿瘤的能力是在在HCC改进结果的一个关键因素。在光子放射疗法的进展改进了剂量一致并且允许剂量逐步上升到肿瘤。然而,尽管有这些进展,仍然有一个大量正常的肝,在处理期间收到可观的放射剂量。一旦他们进入身体,质子横梁没沿着横梁路径有出口剂量。质子放射疗法的固有的物理属性提供一个方法当避免过多的放射到留下的肝时,经由剂量逐步上升最大化肿瘤控制,因此增加的生物有效性。在这评论,我们在HCC为质子放射疗法讨论物理属性和基本原理。我们也关于为HCC的处理使用质子放射疗法的临床的结果考察最近的文学。
简介:Advancedagebringsahigherincidenceofthrombosis-relateddiseases.Althoughantithrombotictherapysignificantlyreducestheriskofischemicevents,relativelyhigherbleedingratesresultinincreasedmortalityandworseprognosisintheelderly.Thusthebenefitsandharmsofantithromboticdrugsshouldtobecarefullyevaluated.Inthisreview,wesummarizecurrentevidenceandupdatedguidelinesregardingantithrombotictherapyintheagingpopulation.
简介:ChinahasrecognizedthethreatofHIVtoitspopulationandrespondedwithanationalantiretroviraltreatment(ART)program.However,highARTfailureratesandthespreadofresistancewithinpopulationsareimportantrealitiestoconsiderwhendevelopingandmanagingARTprogramsinChinaandworldwide.Conceptswhichwilldefinetreatmentsuccessandlocalandnationalprogrammaticgoalsare1)accesstoART,2)durabilityofARTatthepatientlevel,3)scalabilityoftreatmentmodalities,andthe4)sustainabilityoftheprogramatthecommunityornationallevel.Inthefaceoflimitedresources,ChinamustalsoconsiderwhentostartARVtherapy,whichagentstouse,whentoswitchthem,andhowtotreathighlyexperiencedpatientswithdrugresistance.TheoptimalARVregimentostartwithischangingfrequentlywiththeintroductionofnewagentsandthepresentationofnewdata.Currently,aregimenincludingtenofovir,emtricitabineorlamivudineandanonnucleosidereversetranscriptaseinhibitorappearstohaveoptimalcharacteristicstotreatHIV/AIDSinChina.However,criticaltoallofthesechoicesistheevaluationofprogramsimplementedtoinsurewidescalesuccess.Chinahaswiselybegunthisprocessofevaluatingtheperformanceoflocalprogramsthroughsystematicmonitoringandevaluationoftreatmentoutcomes.Thiswillallowregimensandprogramsthatworktobeexpanded,andprogramswithhighfailureratestobeeliminated.Intheend,evidencebaseddatasupportingtreatmentstrategieswillallowChinatosuccessfullyconfrontitsAIDSepidemicearlyandpreventitstragicconsequences
简介:AbstractIncreasing numbers of targeted drugs are used in hormone receptor (HR)-positive metastatic breast cancer (MBC) to overcome or delay resistance to endocrine therapy. This study will systemically review the progress made in endocrine therapy combined with targeted therapy in the treatment of HR-positive MBC. From the "AI (aromatase inhibitor) era" represented by aromatase inhibitors, we have gradually entered the "post-AI era" represented by fulvestrant. Under the guidance of research on the molecular mechanism of endocrine therapy resistance, the "combination of endocrine therapy and targeted therapy" era is approaching. The development of drugs that target endocrine therapy resistance has concentrated on cyclin-dependent kinase 4/6 inhibitors, histone deacetylase inhibitors, and inhibitors of drug targets in the phosphatidylinositol 3 kinase-protein kinase B-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway, providing new strategies for HR-positive MBC. Exploring biomarkers to guide the more precise use of targeted drugs in endocrine therapy for MBC is the focus of current and future research.