简介：Inthecomingyearslifeexpectancyisexpectedtoincreaseandwiththisthepercentageofthepopulationaboveage65willgrow.Patientsabove65makeupmorethantwothirdsofthosecurrentlydiagnosedwithgastrointestinalmalignancies.Availableevidencebasedmedicinedoesnotfocusontheaveragepatient,abovetheage70,encounteredineverydaypractice.Mostguidelinesandclinicaltrialsarenotdesignedtotakeintoaccountthespecialconsiderationsneededwhentreatingtheelderlysuchasfunctionalstatus,comorbidities,polypharmacy,lifeexpectancy,andsocialsupport.Themajorityofavailabledataisbasedonretrospectivereviewsorsubsetanalysesoflargerstudieswheretheelderlyrepresentafractionofthestudiedpopulation.Thisreviewfocusesonthetoxicitiesandtolerabilityofcurrentstandardtherapiesfornoncolorectalgastrointestinalmalignancies,includinggastroesophageal,pancreatic,bileductandhepatocellularcancersintheelderly.Withcarefulpatientselectionandgeriatricassessmenttheelderlycansafelybenefitfromstandardtherapiesofferedtoyoungerpatients.

简介：Lungcanceristhemostfrequentlydiagnosedcancerandaleadingcauseofcancermortalityworldwide,withadenocarcinomabeingthemostcommonhistologicalsubtype.Deeperunderstandingofthepathobiologyofnon-smallcelllungcancer(NSCLC)hasledtothedevelopmentofsmallmoleculesthattargetgeneticmutationsknowntoplaycriticalrolesinprogressiontometastaticdiseaseandtoinfluenceresponsetotargetedtherapies.Theprinciplegoalofprecisionmedicineistodefinethosepatientpopulationsmostlikelytorespondtotargetedtherapies.However,thecancergenomelandscapeiscomposedofrelativelyfew"mountains"[representingthemostcommonlymutatedgeneslikeKRAS,epidermalgrowthfactor(EGFR),andanaplasticlymphomakinase(ALK)]andavastnumberof"hills"(representinglowfrequencybutpotentiallyactionablemutations).Low-frequencylesionsthataffectadruggablegeneproductallowarelativelysmallpopulationofcancerpatientsfortargetedtherapytobeselected.

简介：Thereisalackofinvestigationintothebiologicalcharacteristicsandpreoperativesystemictherapy(PST)foroccultbreastcancer(OBC).Forthisstudy,departmentalrecordsinBreastDiseaseCenterofPekingUniversityFirstHospitalfromJanuary2008toDecember2015wereretrospectivelyreviewedtoidentifycasesofOBC.Elevencaseswereincluded,andallpatientswerefemale,withamedianageof56(range:29–75)years.Thesensitivityofmagneticresonanceimaging(MRI)was100%,andthefalsepositiveratewas33.3%.Basedonhistologicanalysisoftheaxillarynode,9(81.8%)casesweregrade3,and2(18.2%)casesweregrade2;4(36.4%)caseswere≥10%estrogenreceptor(ER)positiveand6(54.5%)humanepidermalgrowthreceptor2(HER2)positive.Ninecases(81.8%)exhibitedover30%Ki67expression.PSTwasperformedin5ofthe11cases.Thelymphnoderesponseratewas100%(5/5),butnocompleteremissionwasachieved.Inconclusion,aggressivesubtypeswerepredominantamongtheincludedcases,andPSTshouldbeconsideredforOBCtreatmentoptions.

简介：系统科学和控制论在二次世界大战以后出现在年里。这些地创造了许多新途径到工程和管理并且贡献了新想法到存在的学术地。新地也越过地的一个范围识别了类似的概念并且开始创造了系统的一个一般理论。另外，系统科学为管理复杂系统创造了许多方法，例如后勤，运筹学和计算机模拟。在1970年代，关于人口和环境平衡有担心。当前与统治正在增加担心，后来，问题的表示的率似乎比我们的机构的能力很好管理他们。这篇论文将讨论系统科学的历史，控制论，提出的问题和答案求婚，困难在在当代的大学和现在在进行之中的研究的一些令人激动的线以内发现一个家遇到了。

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简介：数据是清楚的：人类正在面对一个全球社会经济的危机。全球身体在结束neoliberal寻找答案独占性，而非自由的市场，经济，并且在在社会责任的标签下面的全身的行为的介绍。支持这个努力，在这贡献被报导关于的研究，建议社会责任的全身的感觉引起滥用的结束，社会责任，并且合适的经济前提的提升的策略，由行动的几根线支持了，所有人能触发它。

简介：Palliativeradiotherapy(pRT)isprimarilyemployedforpalliationofbonepaininpatientswithcastrate-resistantprostatecancer(CRPC).However,evidencethatpRTinfluencesprostate-specificantigenresponseinpatientswithCRPConsystemictherapyislacking.WedescribethreecasesofCRPCprogressingaftertreatmentwithdocetaxel(n=2)andabiraterone(n=1),whorespondedunusuallyafterpRTforbonepainwiththedevelopmentofasignificantbiochemicalresponseandrestorationofresponsetosystemictherapy.ThepossibilityofpRTinfluencingmetastaticdiseaseinCRPChasnotbeenpreviouslyreported,andraisesthepossibilityofradiation-inducedmodulationofanti-tumorimmuneresponsemechanismsthatmayplayaroleintherestorationofresponsetosystemictreatment.

简介：AbstractSystemic sclerosis (SSc) is characterized by immune dysfunction, vasculopathy, chronic fibrosis of skin and internal organs with complex etiology. With the rapid development and the application in biomedicine of epigenetics, accumulating evidence has shown that epigenetics plays an important role in the pathogenesis of SSc. Environmental factors via epigenetics are needed to trigger and maintain for the disease in the subjects with genetic predisposition to SSc. The role of epigenetics in the pathogenesis of SSc includes hypermethylation of the promoter region of nitric oxide synthase and bone morphogenetic protein receptors II, up-regulation of histone deacetylases 4 and 5 expression, and down-regulation of miR-193b and miR-152 in endothelial cells inducing vascular dysfunction; DNA hypermethylation and hypoacetylation of histone H3 and H4 in Friend leukemia virus integration 1 and Kruppel-like factor 5 genes, and the abnormal expression of miR-29, miR-129-5p and miR-135b in fibroblasts causing excessive fibrosis; DNA hypomethylation in the promoter regions of CD11a and CD70 genes in CD4+T cells resulting in immune dysfunction. Studies on the role of epigenetics in SSc are of great significance for better understanding the pathogenic machanism of SSc, which is helpful to find new molecular targets for treating SSc, and consequently, improve the prognosis of SSc.

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：考生进入高三后，紧张的情绪会逐渐加深，每天可以听20-30分钟音乐舒缓一下情绪。

简介：Theworldpost-9/11ischaracterisedbyuncertainty,fearandsuspicion.Psychologicalconfrontationsamplifiedbythemassmediahaveevencometodominatephysicalengagementsbetweenwarringparties.Dramatheoryprovidesapowerfulframeworkforunderstandingtheseinteractionsinmuchthewaythatgametheorywasabletosupportstrategymakingbyautonomousplayersinalessinter-connectedera.Amodelofthe'normal'processleadingtodramaticresolutionisanessentialfeatureofthedramatheoryapproachandisdescribedhere.Howeverthisprocesscanbederailedorfailinmanyways.Thispaperreviewsmanyofthesesystemicpathologiesandillustratessomeofthemthroughconsiderationofthreehigh-profilecases.Theconclusionisthatitisimportanttorecogniseandpossiblytousepathologicalbehaviorasanelementofacharacter'sinteractionstrategy.

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简介：AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease with extreme heterogeneity and potentially involvement of any organ or system. Numerous unanswered questions and challenges in SLE always prompt further exploration. In 2019, great progress in various aspects of SLE emerged. Both the classification criteria and management recommendation for SLE were updated. New promising medications have been widely developed and tested, although subsequent clinical studies are warranted. As an emerging number of most notable studies in SLE were published in both clinical area and basic research in 2019, we aim to summarize the highest quality data on SLE regarding novel insights of pathogenesis, updated recommendations, hot-spot issues on clinical manifestations, new understanding of disease prognosis, and most importantly, the therapeutic advances in SLE in this review.

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.

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简介：AbstractIntroduction:Primary systemic amyloidosis is characterized by clonal plasma cell disorder, and its signs and symptoms are various and complex, damage to the skin and mucous membrane is often more likely to attract attention.Here we reported a case of a 61-year-old male patient who presented with topical mucocutaneous lesion, as well unusual skin vegetations.Case presentation:A 61-year-old man was hospitalized due to repeated burning sensation on his back, multiple ecchymosis, and skin vegetations. Through a series of examinations (mainly including skin histopathology, bone marrow cytology, bone marrow flow cytometry, immunofixation electrophoresis), Primary systemic amyloidosis was diagnosed, but multiple myeloma could not be diagnosed. Subsequently, he received chemotherapy. In the half-year follow-up, there was no significant change in his symptoms and signs.Discussion:In this case, in addition to the typical skin damage of primary amyloidosis, the multiple skin vegetations in the buttocks, abdomen, and arms are particularly noteworthy. According to the histopathology and Immunohistochemistry of the skin vegetation, we infer that the formation mechanism of these skin vegetation is lymphatic obstruction caused by amyloid, which leads to lymphatic dilatation, lymph leakage, and dermal edema.Conclusion:Primary systemic amyloidosis is a rare disease, which is often difficult to diagnose. We should be alert to those atypical skin features so as not to delay diagnosis.