简介：Despitethehnpactofhighly-activemltiretroviraltherapy(HAART),manifestedasmarkedreductionsintheincidenceofopwrtunistieinfectionsinthelast5,years,respiratoryproblemsstillconstituteamajorburdenofdiseaseinthoseinfectedwithHIV.ReasonsforthisincludethelimitedavailabilityofHAART.worldwide,thefailureofsustainedviralsuppressioninupto50%ofpatientstakingHAART,failureofprophylaxisforspecificopportunisticinfectiorrs,andanincreasingnumberofpatientspresentingwithpreviouslymldiagnosedadvancedHIVinfection.

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简介：AbstractPurpose:To establish a severe blast lung injury model of goats and investigate the feasibility of lung ultrasonic score in the evaluation of blast lung injury.Methods:Twenty female healthy goats were randomly divided into three groups by different driving pressures: 4.0 MPa group (n = 4), 4.5 MPa group (n = 12) and 5.0 MPa group (n = 4). The severe blast lung injury model of goats was established using a BST-I bio-shock tube. Vital signs (respiration, heart rate and blood pressure), lung ultrasound score (LUS), PO2/FiO2 and extravascular lung water (EVLW) were measured before injury (0 h) and at 0.5 h, 3 h, 6 h, 9 h, 12 h after injury. Computed tomography scan was performed before injury (0 h) and at 12 h after injury for dynamic monitoring of blast lung injury and measurement of lung volume. The correlation of LUS with PaO2/FiO2, EVLW, and lung injury ratio (lesion volume/total lung volume*100%) was analyzed. All animals were sacrificed at 12 h after injury for gross observation of lung injury and histopathological examination. Statistical analysis was performed by the SPSS 22.0 software. The measurement data were expressed as mean ± standard deviation. The means of two samples were compared using independent-sample t-test. Pearson correlation analysis was conducted.Results:(1) At 12 h after injury, the mortality of goats was 0, 41.67% and 100% in the 4.0 Mpa, 4.5 MPa and 5.0 MPa groups, respectively; the area of pulmonary hemorrhage was 20.00% ± 13.14% in the 4.0 Mpa group and 42.14% ± 15.33% in the 4.5 MPa group. A severe lung shock injury model was established under the driving pressure of 4.5 MPa. (2) The respiratory rate, heart rate, LUS and EVLW were significantly increased, while PaO2/FiO2 was significantly reduced immediately after injury, and then they gradually recovered and became stabilized at 3 h after injury. (3) LUS was positively correlated with EVLW (3 h: r = 0.597, 6 h: r = 0.698, 9 h: r = 0.729; p < 0.05) and lung injury ratio (12 h: r= 0.884, p < 0.05), negatively correlated with PaO2/FiO2 (3 h: r =－0.871, 6 h: r =－0.637, 9 h: r =－0.658; p < 0.05).Conclusion:We established a severe blast lung injury model of goats using the BST-I bio-shock tube under the driving pressure of 4.5 MPa and confirmed that ultrasound can be used for quick evaluation and dynamic monitoring of blast lung injury.

简介：Objective:Variousnanoparticleshavebeendesignedandtestedinordertoselectoptimalcarriersfortheinhalationdeliveryofanticancerdrugstothelungs.Methods:Thefollowingnanocarrierswerestudied:micelles,liposomes,mesoporoussilicananoparticles(MSNs),polypropyleneimine(PPI)dendrimer-siRNAcomplexesnanoparticles,quantumdots(QDs),andpoly(ethyleneglycol)polymers.Allparticleswerecharacterizedusingthefollowingmethods:dynamiclightscattering,zetapotential,atomicforcemicroscopy,invitrocyto-andgenotoxicity.Invivoorgandistributionofallnanoparticles,retentioninthelungs,andanticancereffectsofliposomesloadedwithdoxorubicinwereexaminedinnudemiceafterthepulmonaryorintravenousdelivery.Results:Significantdifferencesinlunguptakewerefoundaftertheinhalationdeliveryoflipid-basedandnon-lipid-basednanoparticles.Theaccumulationofliposomesandmicellesinlungsremainedrelativelyhigheven24hafterinhalationwhencomparedwithMSNs,QDs,andPPIdendrimers.Therewerenotabledifferencesbetweennanoparticleaccumulationinthelungsandotherorgans1and3hafterinhalationorintravenousadministrations,but24hafterintravenousinjectionallnanoparticlesweremainlyaccumulatedintheliver,kidneys,andspleen.Inhalationdeliveryofdoxorubicinbyliposomessignificantlyenhanceditsanticancereffectandpreventedsevereadversesideeffectsofthetreatmentinmicebearingtheorthotopicmodeloflungcancer.Conclusion:Theresultsofthestudydemonstratethatlipid-basednanocarriershadconsiderablyhigheraccumulationandlongerretentiontimeinthelungswhencomparedwithnon-lipid-basedcarriersaftertheinhalationdelivery.Theseparticlesaremostsuitableforeffectiveinhalationtreatmentoflungcancer.

简介：AbstractThis review attempts to unveil the possible mechanisms underlying how gut lymph affects lung and further gives rise to acute respiratory distress syndrome, as well as potential interventional targets under the condition of ischemia-reperfusion injury. We searched electronic databases including PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Web of Science, and Embase to identify relevant literatures published up to December 2019. We enrolled the literatures including the Mesh Terms of "gut lymph or intestinal lymph and acute lung injury or acute respiratory distress syndrome." Gut is considered to be the origin of systemic inflammation and the engine of multiple organ distress syndrome in the field of critical care medicine, whereas gut lymph plays a pivotal role in initiation of ischemia-reperfusion injury-induced acute respiratory distress syndrome. In fact, in the having been established pathologic model of sepsis leading to multiple organ dysfunction named by Gut Lymph theory, a variety of literatures showed the position and role of changes in gut lymph components in the initiation of systemic inflammatory response, which allows us to screen out potential intervention targets to pave the way for future clinic and basic research.

简介：AbstractExtracellular vesicles (EVs) are anuclear particles composed of lipid bilayers that contain nucleic acids, proteins, lipids, and organelles. EVs act as an important mediator of cell-to-cell communication by transmitting biological signals or components, including lipids, proteins, messenger RNAs, DNA, microRNAs, organelles, etc, to nearby or distant target cells to activate and regulate the function and phenotype of target cells. Under physiological conditions, EVs play an essential role in maintaining the homeostasis of the pulmonary milieu but they can also be involved in promoting the pathogenesis and progression of various respiratory diseases including chronic obstructive pulmonary disease, asthma, acute lung injury/acute respiratory distress syndrome, idiopathic pulmonary fibrosis (IPF), and pulmonary artery hypertension. In addition, in multiple preclinical studies, EVs derived from mesenchymal stem cells (EVs) have shown promising therapeutic effects on reducing and repairing lung injuries. Furthermore, in recent years, researchers have explored different methods for modifying EVs or enhancing EVs-mediated drug delivery to produce more targeted and beneficial effects. This article will review the characteristics and biogenesis of EVs and their role in lung homeostasis and various acute and chronic lung diseases and the potential therapeutic application of EVs in the field of clinical medicine.

简介：Differentapproachesfortreatinglungcancerhavebeendevelopedovertime,includingchemotherapy,radiotherapyandtargetedtherapiesagainstactivatingmutations.Lately,betterunderstandingoftheroleoftheimmunologicalsystemintumorcontrolhasopenedmultipledoorstoimplementdifferentstrategiestoenhanceimmuneresponseagainstcancercells.Itisknownthattumorcellseludeimmuneresponsebyseveralmechanisms.Thedevelopmentofmonoclonalantibodiesagainstthecheckpointinhibitorprogrammedcelldeathprotein1(PD-1)anditsligand(PD-L1),onTcells,hasledtohighactivityincancerpatientswithlonglastingresponses.Nivolumab,anantiPD-1inhibitor,hasbeenrecentlyapprovedforthetreatmentofsquamouscelllungcancerpatients,giventhesurvivaladvantagedemonstratedinaphaseIIItrial.Pembrolizumab,anotherantiPD-1antibody,hasreceivedFDAbreakthroughtherapydesignationfortreatmentofnon-smallcelllungcancer(NSCLC),supportedbydatafromaphaseItrial.ClinicaltrialswithantiPD-1/PD-L1antibodiesinNSCLChavedemonstratedverygoodtolerabilityandactivity,withresponseratesaround20%andamediandurationofresponseof18months.

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简介：AbstractImmunotherapy has become the mainstay for lung cancer treatment, providing sustained therapeutic responses and improved prognosis compared with those obtained with surgery, chemotherapy, radiotherapy, and targeted therapy. It has the potential for anti-tumor treatment and killing tumor cells by activating human immunity and has moved the targets of anti-cancer therapy from malignant tumor cells to immune cell subsets. Two kinds of immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), are the main targets of current immunotherapy in lung cancer. Despite the successful outcomes achieved by immune checkpoint inhibitors, a small portion of lung cancer patients remain unresponsive to checkpoint immunotherapy or may ultimately become resistant to these agents as a result of the complex immune modulatory network in the tumor microenvironment. Therefore, it is imperative to exploit novel immunotherapy targets to further expand the proportion of patients benefiting from immunotherapy. This review summarizes the molecular features, biological function, and clinical significance of several novel checkpoints that have important roles in lung cancer immune responses beyond the CTLA-4 and PD-1/PD-L1 axes, including the markers of co-inhibitory and co-stimulatory T lymphocyte pathways and inhibitory markers of macrophages and natural killer cells.

简介：肺上皮是在各种各样的肺疾病的肺损坏的主要地点。上皮的房间apoptosis被认为是在各种各样的肺疾病的起始的事件。发信号的Apoptosis古典主义地由二条原则小径组成。一个人是从死亡受体结扎的一条直接小径到caspase串联激活和房间死亡。象药，放射，传染代理人和反应的氧种类那样的压力触发的另外的小径被线粒体调停。Endoplasmic蜂窝胃也被显示了是细胞器调停apoptosis.Epithelial房间死亡被改变过程跟随，它由组成上皮并且成纤维细胞激活，cytokine生产，凝结小径的激活，neoangiogenesis，re-epithelialization和fibrosis.Epithelial和间充质的相互作用在这些过程起重要作用。apoptosis由新奇策略发信号和它的规定的进一步的理解可以对各种各样的肺疾病导致有效治疗。我们在apoptosis发信号的理解考察最近的进展并且在肺改变讨论apoptosis的参与。

简介：FromNovember1,2013,TranslationalLungCancerResearch(TLCR)isofficiallyendorsedbytheSpanishLungCancerGroup(Figure1).ThisisameaningfulmilestoneforTLCRasanacknowledgmentofitsexpansionanddedicationtolungcancerresearchandwilltremendouslyadvanceitscontinuedexplorationinthefield.SinceitwaslaunchedinMay2013,TLCRhasbeendedicatedtoprovidingcutting-edgefindingsintherapidly

简介：AIM:TopreparepolylacticacidmicrospheresofErythromycinforLungtargeting.METHEDS:Theorthogonaltestdesignwasusedtooptimizethetechnology,ofpreparation.Thecharacterofthemicrospheres,drugreleaseinvitro,stabilityandtissuedistributionwereexaminedRESULTS:TheErythromycinpolylacticacidmicrosphereswasregularinitsmorphology.DrugwasenvelopedinmicrospheresbutnotphysicallymixedwithPDLLA.Theaverageparticlesizewas11.65μnwithover94%ofthemicrospheresbeingintherangeof5～20trn;Thedrugloadingandtheincorporationefciencywere18%and60%respectively.Themicrosphereswerestableforthreemonthat4℃androomtemperature.TheinvitroreleasepropertiescouldbeexpressedbytheHiguchi'sequation:y=28.067+3.8515t11/2(r=0.9834).Comparingwithinjection,thedruginmicrosphereswasmoreconcentratedinlungtissue.CONCLUSION:Erythromycinpolylacticacidmicrospheresshowedsignificantsustainedreleaseandlungtargeting.

简介：LyingatthesouthernfootofMountJishiinJishishanCountyborderingGansuandQinghaiProvinces,Hor-sTag-lungMonastery(thereafterabbreviatedtosTag-lungMonastery)isawell-knownTibetanBuddhistmonasterybuiltintheearlyperiodofTibetanBuddhism.Ithasahistoryofmorethan400yearsandwasaffiliatedwithbKra-shis-lhun-poMonastery.Its

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简介：AbstractBackground:Acute kidney injury (AKI) is a common and serious complication following lung transplantation (LTx), and it is associated with high mortality and morbidity. This study assessed the incidence of AKI after LTx and analyzed the associated perioperative factors and clinical outcomes.Methods:This retrospective study included all adult LTx recipients at the China-Japan Friendship Hospital in Beijing between March 2017 and December 2019. The outcomes were AKI incidence, risk factors, mortality, and kidney recovery. Multivariate analysis was performed to identify independent risk factors. Survival analysis was presented using the Kaplan-Meier curves.Results:AKI occurred in 137 of the 191 patients (71.7%), with transient AKI in 43 (22.5%) and persistent AKI in 94 (49.2%). AKI stage 1 occurred in 27/191 (14.1%), stage 2 in 46/191 (24.1%), and stage 3 in 64/191 (33.5%) of the AKI patients. Renal replacement therapy (RRT) was administered to 35/191 (18.3%) of the patients. Male sex, older age, mechanical ventilation (MV), severe hypotension, septic shock, multiple organ dysfunction (MODS), prolonged extracorporeal membrane oxygenation (ECMO), reintubation, and nephrotoxic agents were associated with AKI (P < 0.050). Persistent AKI was independently associated with preoperative pulmonary hypertension, severe hypotension, post-operative MODS, and nephrotoxic agents. Severe hypotension, septic shock, MODS, reintubation, prolonged MV, and ECMO during or after LTx were related to severe AKI (stage 3) (P < 0.050). Patients with persistent and severe AKI had a significantly longer duration of MV, longer duration in the intensive care unit (ICU), worse downstream kidney function, and reduced survival (P < 0.050).Conclusions:AKI is common after LTx, but the pathogenic mechanism of AKI is complicated, and prerenal causes are important. Persistent and severe AKI were associated with poor short- and long-term kidney function and reduced survival in LTx patients.

简介：AbstractLung cancer continues to be the leading cause of cancer-related death in the world, which is classically subgrouped into two major histological types: Non-small cell lung cancer (NSCLC) (85% of patients) and small-cell lung cancer (SCLC) (15%). Tumor location has been reported to be associated with the prognosis of various solid tumors. Several types of cancer often occur in a specific region and are more prone to spread to predilection locations, including colorectal cancer, prostate cancer, gastric cancer, ovarian cancer, cervical cancer, bladder cancer, lung tumor, and so on. Besides, tumor location is also considered as a risk factor for lung neoplasm with chronic obstructive pulmonary disease/emphysema. Additionally, the primary lung cancer location is associated with specific lymph node metastasis. And the recent analysis has shown that the primary location may affect metastasis pattern in metastatic NSCLC based on a large population. Numerous studies have enrolled the "location" factor in the risk model. Anatomy location and lobe-specific location are both important in prognosis. Therefore, it is important for us to clarify the characteristics about tumor location according to various definitions. However, the inconsistent definitions about tumor location among different articles are controversial. It is also a significant guidance in multimode therapy in the present time. In this review, we mainly aim to provide a new insight about tumor location, including anatomy, clinicopathology, and prognosis in patients with lung neoplasm.

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简介：Immunotherapyhasbecomeakeystrategyforcancertreatment,andtwoimmunecheckpoints,namely,programmedcelldeath1(PD-1)anditsligand(PD-L1),haverecentlyemergedasimportanttargets.TheinteractionblockadeofPD-1andPD-L1demonstratedpromisingactivityandantitumorefficacyinearlyphaseclinicaltrialsforadvancedsolidtumorssuchasnon-smallcelllungcancer(NSCLC).ManycelltypesinmultipletissuesexpressPD-L1aswellasseveraltumortypes,therebysuggestingthattheligandmayplayimportantrolesininhibitingimmuneresponsesthroughoutthebody.Therefore,PD-L1isacriticalimmunomodulatingcomponentwithinthelungmicroenvironment,butthecorrelationbetweenPD-L1expressionandprognosisiscontroversial.MoreevidenceisrequiredtosupporttheuseofPD-L1asapotentialpredictivebiomarker.ClinicaltrialshavemeasuredPD-L1intumortissuesbyimmunohistochemistry(IHC)withdifferentantibodies,buttheassessmentofPD-L1isnotyetstandardized.Somecommercialantibodieslackspecificityandtheirreproducibilityhasnotbeenfullyevaluated.FurtherstudiesarerequiredtoclarifytheoptimalIHCassayaswellastopredictandmonitortheimmuneresponsesofthePD-1/PD-L1pathway.