简介：Thedendriticcellsystemcontainsconventionaldendriticcells(DCs)andplasmacytoidpre-dendriticcells(pDCs).BothDCsandpDCsarebonemarrowderivedcells.AlthoughthecommonfunctionsofDCsareantigen-processingandT-lymphocyteactivation,theydifferinsurfacemarkers,migratorypatterns,andcytokineoutput.ThesedifferencescandeterminethefateoftheTcellstheyactivate.SeveralsubsetsofmatureDCshavebeendescribedinbothmouseandhumanandthedevelopmentalprocessesofthesespecializedDCsubsetshavebeenstudiedextensively.TheoriginalconceptthatallDCswereofmyeloidoriginwasquestionedbyseveralrecentstudies,whichdemonstratedthatinadditiontotheDCsderivedfrommyeloidprecursors,someDCscouldalsobeefficientlygeneratedfromlymphoid-restrictedprecursors.Moreover,ithasbeenshownrecentlythatbothconventionalDCsandpDCscanbegeneratedbytheFlt3expressinghemopoieticprogenitorsregardlessoftheirmyeloid-orlymphoid-origin.ThesefindingssuggestanearlydevelopmentalflexibilityofprecursorsforDCsandpDCs.ThisreviewsummarizessomerecentobservationsonthedevelopmentofDCsysteminbothhumanandmouse.

简介：今日任务蓓蒂买新手机时必须做哪些决定？会话A（赛门站在邮局里。）蓓蒂：赛门，所以我的手机出了什么问题啊？赛门：我不确定耶，蓓蒂。我看过电池，电池没问题，但你也知道这个手机很旧了。

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简介：TcellhomeostasiscommonlyreferstothemaintenanceofrelativelystableTcellnumbersintheperipherallymphoidorgans.AmongthelargenumbersofTcellsintheperiphery,Tcellsexhibitstructuraldiversity,I.e.,theexpressionofadiverserepertoireofTcellreceptors(TCRs),andfunctionaldiversity,I.e.,thepresenceofTcellsatna(I)ve,effector,andmemorydevelopmentalstages.AlthoughthehomeostasisofTcellnumbershasbeenextensivelystudied,investigationofthemechanismsunderlyingthemaintenanceofstructuralandfunctionaldiversityofTcellsisstillatanearlystage.ThefundamentalfeaturethroughoutTcelldevelopmentistheinteractionbetweentheTCRandeitherselforforeignpeptidesinassociationwithMHCmolecules.Inthisreview,wepresentevidenceshowingthathomeostasisofTcellnumberanddiversityismediatedthroughcompetitionforlimitingresources.ThenumberofTcellsismaintainedthroughcompetitionforlimitingcytokines,whereasthediversityofTcellsismaintainedbycompetitionforself-peptide-MHCcomplexes.Inotherwords,diversityoftheself-peptiderepertoirelimitsthestructural(TCR)diversityofaTcellpopulation.Wespeculatethatcognatelowaffinityself-peptides,actingasweakagonistsandantagonists,regulatethehomeostasisofTcelldiversitywhereasnon-cognateornullpeptideswhichareextremelyabundantforanygivenTCR,maycontributetothehomeostasisofTcellnumberbyprovidingsurvivalsignals.Moreover,self-peptidesandcytokinesmayformspecializednichesfortheregulationofTcellhomeostasis.

简介：AbstractBackground:Investigations of the pathogenic mechanisms in motor neurons (MNs) derived from amyotrophic lateral sclerosis (ALS) disease-specific induced pluripotent stem (iPS) cell lines could improve understanding of the issues affecting MNs. Therefore, in this study we explored mutant superoxide dismutase 1 (SOD1) protein expression in MNs derived from the iPS cell lines of ALS patients carrying different SOD1 mutations.Methods:We generated induced pluripotent stem cell (iPSC) lines from two familial ALS (FALS) patients with SOD1-V14M and SOD1-C111Y mutations, and then differentiated them into MNs. We investigated levels of the SOD1 protein in iPSCs and MNs, the intracellular Ca2+ levels in MNs, and the lactate dehydrogenase (LDH) activity in the process of differentiation into the MNs derived from the controls and ALS patients’ iPSCs.Results:The iPSCs from the two FALS patients were capable of differentiation into MNs carrying different SOD1 mutations and differentially expressed MN markers. We detected high SOD1 protein expression and high intracellular calcium levels in both the MN and iPSCs that were derived from the two SOD1 mutant patients. However, at no time did we observe stronger LDH activity in the patient lines compared with the control lines.Conclusions:MNs derived from patient-specific iPSC lines can recapitulate key aspects of ALS pathogenesis, providing a cell-based disease model to further elucidate disease pathogenesis and explore gene repair coupled with cell-replacement therapy. Incremental mutant expressions of SOD1 in MNs may have disrupted MN function, either causing or contributing to the intracellular calcium disturbances, which could lead to the occurrence and development of the disease.

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简介：Redbloodcells(RBC)’flickeringpresentthedynamicpropertiesofthecytomembrane.Itscomplexitycouldbeusedforaginganalysisortheevaluationforthestoragequality.Theflickeringactivityisakindofreversibleperpendicularmotionofthespecifiedpixel.Therefore,thecomplexityanalysisdependsonthereliabledetectionoftemporalvariationforthegray-scalevaluesfromeachpixelofthecells.Inthispaper,weimprovedourpreviousworkonthescreeningofthehorizontaldriftedcellswithasurfacebasedoncellregistrationmethodandtheeffectofGSMexposuretothedynamicpropertiesoftheRBCsintermsofmulti-scalesampleentropywaspresentedinthepaper.

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简介：Cancercelldormancyisthemaincauseofcancerrecurrenceandfailureoftherapyasdormantcellsevadenotonlytheanticancerdrugsbutalsothehostimmunesystem.Thesedormantcellsveilthemselvesfromdetectionbyimagingand/orusingbiomarkers,whichimposesanadditionalproblemintargetingsuchcells.Asimilarformofhibernationprocessknownasencystationisstudiedindetailforpathogenicunicellulareukaryoticmicroorganisms.Byexaminationusingmicroarraygeneexpressionprofiles,immunocytochemistrytools,andsiRNAsduringtheprocessofencystation,understandingthecovertfeaturesofcancercelldormancyasproposedcouldbepossible.Thisknowledgecanbeextendedtodormantcancercellstouncoverthemechanismsthatunderliethisghost,yetdangerousstateofhumancancers.Weproposeastrategytoinducedormancyandexitthisstatebyapplicationofknowledgegainedfromtheencystationinductionandretrievalprocessesinpathogeniceukaryoticmicroorganisms.Giventhatearlydetectionandcharacterizationofdormantmalignanttumorcellsisimportantasageneralstrategytomonitorandpreventthedevelopmentofovertmetastaticdisease,thishomologymayenablethedesignoftherapiesthatcouldeitherawakethedormantcellfromdormancytomakeitavailablefortherapiesorprolongsuchaphasetomakecancerappearasachronicdisease

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简介：AbstractFecal microbiota transplantation (FMT) has been used as a core therapy for treating dysbiosis-related diseases by remodeling gut microbiota. The methodology and technology for improving FMT are stepping forward, mainly including washed microbiota transplantation (WMT), colonic transendoscopic enteral tubing (TET) for microbiota delivery, and purified Firmicutes spores from fecal matter. To improve the understanding of the clinical applications of FMT, we performed a systematic literature review on FMT published from 2011 to 2021. Here, we provided an overview of the reported clinical benefits of FMT, the methodology of processing FMT, the strategy of using FMT, and the regulations on FMT from a global perspective. A total of 782 studies were included for the final analysis. The present review profiled the effectiveness from all clinical FMT uses in 85 specific diseases as eight categories, including infections, gut diseases, microbiota–gut–liver axis, microbiota–gut–brain axis, metabolic diseases, oncology, hematological diseases, and other diseases. Although many further controlled trials will be needed, the dramatic increasing reports have shown the promising future of FMT for dysbiosis-related diseases in the gut or beyond the gut.

简介：ObjectivesToanalyzethesix-minutewalktest(6MWT)andgasexchangeof5hearttransplantationpatientsandtoapproachthevariationtendencyofexercisetolerance,oxygenuptake(VO2)andheartratechronotropicresponse.Methods5casesofhearttransplantationpatients(age25～52years)wereundertaken6MWT6～30monthsafteroperation,synchronizinggasexchangingparametersweremeasuredbywirelessportableremotesensingK4B2gasanalyzer,51normalcontrolswerecompared.ResultsThesix-minutewalkdistance(6MWD)of5patientswere(592.6±26.7)m(558～625)m,theascendingtendencyduringexercisewasslower,themaximumheartrateswere80%±6%ofage-predictingmaximalheartrate,lowerthannormalcontrol(86%);theendpointVO2/kgwere(21.8±1.4)mL/min·kg(19.94～23.60)mL/min·kg.ConclusionsThe6WMDandVO2of5patientsreachednormalrange,buttheheartratechronotropicresponseandVO2ascendingtendencywereslowerthanthoseofnormalcontrols.

简介：Neuroendocrinetumors(NET)areaheterogeneousgroupofcancers,withindolentbehavior.Themostcommonprimaryoriginisthegastro-intestinaltractbutcanalsoappearinthelungs,kidneys,adrenals,ovariesandotherorgans.Ingeneral,NETisusuallydiscoveredinthemetastaticphase(40%-80%).Theliveristhemostcommonorganinvolvedwhenmetastasesoccur(40%-93%),followedbybone(12%-20%)andlung(8%-10%).Anumberofdifferenttherapeuticoptionsareavailableforthetreatmentofhepaticmetastasesincludingsurgicalresection,transplantation,ablation,trans-arterialchemoembolization,chemotherapyandsomatostatinanalogues.Recently,moleculartargetedtherapieshavebeenused,usuallyincombinationwithothertreatmentoptions,toimproveoutcomesinpatientswithmetastases.ThisarticleemphasizesontheroleofsurgeryinthetreatmentoflivermetastasesfromNET.

简介：Onetosixpercentofpatientswithmicroscopiccolitisarerefractorytomedicaltreatment.Theeffectoffaecalmicrobiotatransplantation(FMT)inactivecollagenouscolitis(CC)has,tothebestofourknowledge,neverbeenreportedbefore.Here,wereporttheeffectofrepeatedFMTinapatientwithCC.Thepatientpresentedwithseveresymptomsincludingprofusediarrheaandprofoundweightloss.Althoughsherespondedtobudesonideinthebeginning,shebecamegraduallyrefractorytomedicaltreatment,andwasthereforetreatedwithFMT.Thepatientremainedinremissionfor11moafterthethirdfaecaltransplantation.Theimmunomodulatoryeffectofthetherapywasevaluatedusingflowcytometry,whichshowedalterationsintheprofileofintraepithelialandlaminaproprialymphocytesubsetsafterthesecondtransplantation.OurobservationsindicatethatFMTcanhaveaneffectinCC,whichsupportthehypothesisthatluminalfactors,influencingtheintestinalmicrobiota,areinvolvedinthepathogenesisofCC.

简介：Withimprovementsintheirsurgicalandmedicalmanagement,thenumberofpatientswithcongenitalheartdisease(CHD)reachingadulthoodhasincreasedoverthelastdecade.AsthepopulationofadultCHDpatientscontinuestorise,anincreasingnumberofthesepatientswillrequireevaluationforhearttransplantation.ItisimportanttorecognizeadvancedheartfailureandotherassociatedcomplicationsearlyinthiscohortofcomplexpatientsforearlyreferraltoanadultCHDspecialist.Asthesepatientspresentwithuniquechallengesbecauseoftheirmultiplecomorbiditiesandcomplexanatomy,thereneedstobeacarefulselectionprocessfortransplantationtooptimizetheutilizationofdonororgans.

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简介：Smoothened(SMO)是表明小径的刺猬的一个重要成员。我们为RNA干扰构造了特定的recombinantlentiviral向量，指向SMO基因(NM_005631)观察它在人的雄激素敏感的前列腺癌症房间线的SMO表示，房间增长和房间周期上的效果，LNCaP，并且在雄激素无关的前列腺癌症房间线，PC3。四个siRNA序列被设计并且插入了到lentiviral向量pGCSIL-GFP构造四recombinant向量。有最高的介入效率的向量是有在293T房间包装向量(pHelper1.0和pHelper2.0)为分别地感染LNCaP和PC3房间线由liposome装配lentivirus粒子的co-transfected。SMOmRNA，肿瘤房间增长和房间周期的表示水平被量的实时聚合酶链反应(qRT-PCR)测量，3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)试金和流动cytometry分别地。顺序结果证明recombinantlentiviral向量成功地被构造。pGCSIL-GFP-723有最高的介入效率，在co-transfection，LNCaP和PC3房间与排队以后的命名Lv-SIL-SMO723被感染。与控制组相比，显著地显示出的结果减少了(P<0.05)LNCaP和PC3，S阶段房间的更低的吝啬的百分比和G2/M的更高吝啬的百分比的SMOmRNA表情分阶段执行房间，以及显然减缓增长(P<0.01)在感染的组的LNCaP。然而，PC3的增长没被改变(P>0.05)。在结论，recombinantlentivirus粒子能压制SMO表示，在LNCaP和PC3房间线调整房间周期并且显著地禁止LNCaP房间然而并非PC3房间的增长。

简介：AbstractIntroduction:Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy, and its pathogenesis might relate to ultraviolet light and Merkel cell polyomavirus infection. MCC in the Chinese population is uncommon.Here, we present a case of MCC that occurred based on widespread actinic keratosis (AK) in a Chinese female.Case report:An 82-year-old woman presented with two rapidly enlarging and rupture lesions on the face for 1 year. Biopsy was suggestive of squamous cell carcinoma (SCC) on the forehead and MCC on the left cheek. The patient had a history of generalized AK for 3 years. The lesion on the left cheek was also revealed as an AK by histopathological examination 1 year ago. Complete surgical resection was performed to remove the two malignancies.Discussion:The co-occurrence of AK, SCC, and MCC in a Chinese woman is unusual. Immunohistopathological examination is vital for correct diagnosis. The three tumors, in this case, may originate from two different precursor cells and are affected by the same carcinogen. Alternatively, they may come from the same pluripotent epidermal stem cells, and chronic exposure to ultraviolet light and Merkel cell polyomavirus lead to the formation of different types of tumors. The coexist of MCC with other cutaneous tumors provided a train of thought for exploring the origin of MCC.Conclusion:We reported a rare co-existence phenomenon of MCC associated with AK and SCC. Hence, long-term follow-up and early treatment are imperative for patients with premalignant lesions, such as widespread AK.

简介：ＴＣＥＬＬＲＥＣＥＰＴＯＲＧＥＮＥＲＥＡＲＲＡＮＧＥＭＥＮＴＡＮＡＬＹＳＩＳＩＮＴＨＥＰＲＩＭＡＲＹＣＵＴＡＮＥＯＵＳＴＣＥＬＬＬＹＭＰＨＯＭＡＱｉｕＢｉｎｇｓｅｎ邱丙森ＷａｎｇＰｉｎｇ１王平ＧａｏＨｏｎｇｙａｎｇ２高红阳ＳｈａｎｇＹｉｆｅｉ２...

简介：在发炎和白血球过多症之间的潜在的交叉连接有一段时间被讨论了，但是支持这教义的试验性的证据是少见的。特别地，由煽动性的调停人理解为proto-oncogenic生长因素表情的潜在的upregulation负责的机制是重要的。这里，我们调查了高度煽动性的cytokineinterleukin-1贝它的能力(IL-1β；)到导致干细胞因素(SCF)的生产，它是在造血的myeloid细胞的恶意的转变之上控制尖锐myeloid白血球过多症的前进的一个主要造血的生长因素。我们发现了那人的IL-1β；在MCF-7人的上皮的乳癌房间和那导致了SCF的表示/分泌物这个过程取决于组织缺氧可诱导的因素1(HIF-1)抄写建筑群。我们也表明了phosphatidylinositol-3kinase(PI-3K)的一个关键角色rapamycin(mTOR)的/mammalian目标在IL-1β的小径；导致的HIF-1α；在MCF-7房间的累积。重要地，mTOR也被发现在IL-1β起一个作用；导致的SCF生产。而且，为IL-1β的积极关联的一个趋势；并且在健康人的施主的血浆的SCF层次被观察。总的来说，我们的结果表明那IL-1β；，它通常衔接天生、适应的免疫，通过PI-3K/mTOR小径和HIF-1抄写建筑群导致主要haematopoietic/proleukaemic生长因素SCF的生产。这些调查结果强烈支持在发炎和尖锐myeloid白血球过多症之间的串音。