简介：AbstractBackground:After neoadjuvant chemotherapy (NAC), non-pathological complete response of breast cancer patients can benefit from tailored adjuvant chemotherapy. However, it is difficult to select patients with poorer prognosis for additional adjuvant chemotherapy to maximize the benefits. Our study aimed to explore whether the subtypes of tumor-infiltrating lymphocytes (TILs) in residual tumors (RT) is related to the prognosis of triple-negative breast cancer (TNBC) after NAC.Methods:Data from patients with primary TNBC consecutively diagnosed at the Breast Disease Center of Peking University First Hospital from 2008 to 2014 were retrieved, and the cases with RT in the breast after NAC were enrolled. TILs subtypes in RT were observed by double-staining immunohistochemistry, and counted with the median TILs value per square millimeter as the cut-off to define high versus low TILs density in each subtype. The relationships between the TIL density of each subgroup and the clinicopathological characteristics of the RT after NAC patients were analyzed by Fisher exact test. Disease-free survival (DFS) and overall survival (OS) were analyzed by the Kaplan-Meier method and log-rank statistics.Results:A total of 37 eligible patients were included in this study, and the median follow-up period was 50 months (range 17–106 months). There was no significant correlation between the infiltrate density of CD4+, CD8+, CD20+, and CD68+ lymphocytes and clinic-pathological characteristics. Significantly better prognosis was observed in patients with high CD4+-TILs (DFS: P = 0.005, OS: P = 0.021) and high CD8+-TILs (DFS: P = 0.018) and low CD20+-TILs (OS: P = 0.042). Further analysis showed that patients with CD4+/CD20+ ratio greater than 1 (DFS: P = 0.001, OS: P = 0.002) or CD8+/CD20+ ratio greater than 1 (DFS: P = 0.009, OS: P = 0.022) had a better prognosis.Conclusions:Subtypes of TILs in RT is a potential predictive biomarker of survival in TNBC patients after NAC.

简介：Objective:Tostudytheexpressionofdendriticcellsinhumanrenalcellcarcinomaandexplorethecause,sotorevealthemechanismofescapingimmunesurveillanceinRCC.Methods:TheexpressionsofCD83+DCS,CD1a+DCS,VEGFandTGF-β1intumoral,peritumoralandnormalkidneytissuesofRCCin30casesweredetectedbyimmunohistochemistryusingstreptavidin/peroxidese(SP)Results:CD83+DCSweremainlylocatedintheperitumoralareas;whereasCD1a+DCS、weremainlyretainedwithinthecancernests.ThenumberofCD83+DCSwasinverselycorrelatedwiththeclinicalstage(P<0.05);buttherewerenosignificantcorrelationsbetweenthenumberofCD1a+DCS、andtheclinicalstage(P>0.05).TheexpressionsofCD83+DCSandCD1a+DCShavesignificantdifferencebetweenthetumoral,peritumoralandnormalkidneytissues(P<0.001).TheexpressionofVEGFandTGF-β1weresignificantlylowerinsampleswithhighlyinfiltratingCD83+DCS(P<0.05);WhereasCD1a+DCSwerenot(P>0.05).Conclusion:DChasthetendencytogatheringintumor,butbecauseoftheimmunosuppressivecytokins,forexampleVEGFandTGF-β1,inhibitsthematurationofDC,therearelessmatureTIDCS(CD83+TIDCS)inthetumoraltissues,theyaremainlylocatedintheperitumoralareas.ThismaycontributetothemechanismofescapingimmunesurveillanceinRCC.

简介：Ｔ－ＬＹＭＰＨＯＣＹＴＥＭＥＤＩＡＴＥＤＴＵＭＯＲＣＥＬＬＤＥＳＴＲＵＣＴＩＯＮＩＮＶＩＶＯＡＳＳＯＣＩＡＴＩＮＧＷＩＴＨＡＳＰＥＣＩＦＩＣＦＥＡＴＵＲＥ　ＯＦ　ＡＰＯＰＴＯＳＩＳＹｕＤａ鱼达；ＹａｎｇＨｕａ杨骅；ＺｈｅｎｇＳｈｕ郑树；ＷａｎｇＸｉａ...

简介：AbstractBackground:To analyze clinically and radiologically the surgical outcome like residual disease, progression of disease, recurrence, disabilities, event-free survival (EFS), and mortality of different infra-tentorial tumor subtypes in children and adults of a strictly non-migratory and ethnic population.Methods:The 410 histologically proved, out of 589, infra-tentorial brain tumor patients were analyzed clinically and by the imaging post-surgically in a single tertiary center for an ethnic region. In this analytico-observational study, retrospectively postoperative records of 589 infra-tentorial brain tumors from November 1998 to December 2018 (20 years) were retrieved, scrutinized, and compiled. The post-operative clinic-radiological records of 410 patients with proved histopathological examination results were included. Statistical law of variance was applied where-ever necessary.Results:The 63.2% of the all 410 operated infra-tentorial brain tumors were males while females predominated in meningiomas and pineoblastomas. About 31.7% infra-tentorial tumors were children (below 18 years). About 54.1% cases were histologically malignant. The residual tumors comprised 40.2% and symptoms of disease-progression occurred in 10.9%. The tumor recurrence occurred in 14.3% while 6.0% patients developed severe disability. The overall mortality was 11.4% but 18.9% in malignant tumors. The event-free survival (EFS) for all the patients was 66.0%, patients with malignancies had 47.7% and benign group had 87.7%.Conclusion:The study, surgical outcome of infra-tentorial brain tumor subtypes in children and adults (approx. 1/3rd of patients being children), conducted in a tertiary center at a remote land-locked location with non-migratory ethnic population as its catchment area, has a significant epidemiological value for the community and the region.

简介：AbstractBackground:The dermoscopic features of rosacea have already been reported. However, the current findings are incomplete, and little is known about phymatous rosacea. Hence, this study aimed to summarize and compare the dermoscopic features and patterns of three rosacea subtypes (erythematotelangiectatic [ETR], papulopustular [PPR], and phymatous [PHR]) in the Chinese Han population and to evaluate whether these features differ with patients’ genders, ages, and durations.Methods:Dermoscopic images of 87 rosacea patients were collected in non-polarized and polarized dermoscopy contact modes at 20-fold magnification. Dermoscopic features, including vessels, scales, follicular findings, and other structures, were summarized and evaluated.Results:The reticular linear vessels and red diffuse structureless areas of ETR were distinctive. For PPR, red diffuse structureless areas, reticular linear vessels, yellow scales, follicular plugs, and follicular pustules were typical dermoscopic criteria. The common dermoscopic features of PHR were: orange diffuse structureless areas, linear vessels with branches, perifollicular white color, orange focal structureless areas, and white lines. The following features statistically differed among the three rosacea subtypes: reticular linear vessels (P < 0.001), unspecific linear vessels (P= 0.005), linear vessels with branches (P < 0.001), yellow scales (P = 0.001), follicular plugs (P < 0.001), perifollicular white color (P < 0.001), red diffuse structureless areas (P = 0.022), orange diffuse structureless areas (P < 0.001), red focal structureless areas (P = 0.002), orange focal structureless areas (P = 0.003), white lines (P < 0.001), follicular pustules (P < 0.001), and black vellus hairs (P < 0.001).Conclusions:The dermoscopic patterns of ETR are red diffuse structureless areas and reticular linear vessels. For PPR, the pattern comprehends combinations of red diffuse structureless areas, reticular linear vessels, yellow scales, follicular plugs, and follicular pustules. Meanwhile, PHR is characterized by remarkable orange diffuse structureless areas, linear vessels with branches, perifollicular white color, orange focal structureless areas, and white lines.

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简介：为neovascular在诊断和预后调查neutrophil-to-lymphocyte比率(NLR)和platelet-to-lymphocyte比率(PLR)的地方年龄相关的有斑点的退化(AMD).METHODSOne百个AMD病人和100健康控制在学习被包括。血样品从静脉的血被获得，它被用于平淡的分析，并且这些样品被使遭到完成血计数。NLR被定义为淋巴细胞的数字划分的嗜中性的计数，并且PLR被定义为lymphocytes.RESULTSNo的数字划分的血小板计数统计上重要的差别以人口统计的特征在考虑下面在二个组之间被观察(P>0.05)。在耐心的组的平均NLR被发现在健康控制组比那显著地高(P<0.05)。平均PLR作为与控制组相比在耐心的组是显著地更高的(P<0.05)。当最好改正的视觉尖酸(BCVA)增加了，NLR和PLR减少了(在49.8%和63.0%点的重要否定关联，分别地)而当中央有斑点的厚度(CMT)增加了，NLR和PLR增加了(在59.3%和70.0%点的重要积极关联，分别地).CONCLUSIONNLR和PLR层次作为与健康控制相比在neovascularAMD病人之中是更高的组。NLR和PLR层次被发现与BCVA并且直接相反地成正比与CMT成正比。

简介：AsanewmemberofIAP(inhibitorsofapoptosisprotein)family,survivinhaspotentanti-apoptoticactivities,andinvolvesinthemitosisandangiogenesis.Researcheshavedemonstratedthatsurvivingisatumor-specificanti-apoptoticfactor,expressedinfetaltissues,andcommonhumancancers,whilenotinnormal,terminallydifferentiatedadulttissues.Theoverexpressionofsurvivinintumortissuesiscorrelatedwithpoorprognosisofthepatients.Survivincanbeusedasaprognosticfactorandanewtargetintumortargetingtherapy.

简介：Thegeneralprinciplefortumorcellstoescapefromimmunesurveillanceistopreventtumorantigensfrombeingrecognizedbytheimmunesystem.Manymethodshavebeendevelopedtoincreasetheimmunogenecityofthetumorcells.Themostefficientmethodsareabletoforcetumorcellstopresenttheirowntumorantigenstotheimmunesystem.StimulatingThcellsbyconvertingtumorcellsintoMHCclassⅡ+/Ii-antigenpresentingcellsisoneofthemostefficienttechnologies.Usingantisensemethods,wesuppresstheexpressionoftheIiproteinthatnormallyco-expresseswithMHCclassⅡmoleculesandblockstheantigenicpeptidebindingsiteofMHCclassⅡmoleculesduringsynthesisintheendoplasmicreticulum.Insuchtumorcells,the'unprotected'MHCclassⅡmoleculespickupendogenoustumorantigenicpeptides,whichhavebeentransportedintotheERforbindingtoMHCclassⅠmolecules.SimultaneouspresentationoftumorantigensbybothMHCclassⅠandⅡmoleculesgeneratesarobustandlong-lastinganti-tumorimmuneresponse.MHCclassⅡ+/Ii-tumorcellsarepotenttumorcellvaccinesandalsocureasignificantnumberofanimalswithrenalandprostatetumors.Wehavedevelopedanalogoushumangenevectorsthataresuitableformostpatientsandcancers.

简介：Tumor-targetingantibodieswereinitiallydefinedasagroupoftherapeuticmonoclonalantibodies(mAb)thatrecognizetumor-specificmembraneproteins,blockcellsignaling,andinducetumor-killingthroughFc-driveninnateimmuneresponses.However,inthepastdecade,ampleevidencehasshownthattumor-targetingmAb(TTmAb)eradicatestumorcellsviaactivationofcytotoxicTcells(CTLs).Inthisreview,wespecificallyfocusonhowTTmAbsinduceadaptiveanti-tumorimmunityanditspotentialincombinationtherapywithimmunecytokines,checkpointblockade,radiation,andenzymetargetedsmallmoleculedrugs.ExploringthemechanismsofthesepreclinicalstudiesandretrospectiveclinicaldatawillsignificantlybenefitthedevelopmentofhighlyefficientandspecificTTmAb-orientedanti-tumorremedies.

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简介：AbstractBackground:Previous evidence suggests inflammation may be a double-edged sword with cancer-promoting and cancer suppressing function. In this study, we explore the impact of local and systemic inflammation on cancer growth.Methods:Female BALB/C mice were subcutaneously implanted with foreign body (plastic plates) to build up a local inflammation and intraperitoneally injected with PolyIC or lipopolysaccharides (LPS) to build up a systemic inflammation, followed by subcutaneous injection of 5 × 105 colon cancer cells. Immunohistochemistry and enzyme linked immunosorbent assay were utilized to detect the Ki67 and interleukin (IL) 6, IL-1β, and monocyte chemoattractant protein-1 expression in the tumor tissues and serum, respectively. The distributions of immune cells and expression of toll-like receptors (TLRs) were evaluated by flow cytometry (FCM) and quantitative real time-polymerase chain reaction.Results:The results showed that local inflammation induced by foreign body implantation suppressed tumor growth with decreased tumor weight (P = 0.001), volume (P = 0.004) and Ki67 index (P < 0.001). Compared with the control group, myeloid-derived suppressive cells sharply decreased (P = 0.040), while CD4+ T cells slightly increased in the tumor tissues of the group of foreign body-induced local inflammation (P = 0.035). Moreover, the number of M1 macrophages (P = 0.040) and expression of TLRs, especially TLR3 (P < 0.001) and TLR4 (P < 0.001), were significantly up-regulated in the foreign body group. Contrarily, tumor growth was significantly promoted in LPS or PolyIC-induced systemic inflammation (P = 0.009 and 0.006). FCM results showed M1 type macrophages (P = 0.017 and 0.006) and CD8+ T cells (P = 0.031 and 0.023) were decreased, while M2 type macrophages (P = 0.002 and 0.007) were significantly increased in tumor microenvironment of LPS or PolyIC-induced systemic inflammation group. In addition, the decreased expression of TLRs was detected in LPS or PolyIC group.Conclusions:The foreign body-induced local inflammation inhibited tumor growth, while LPS or PolyIC-induced systemic inflammation promoted tumor growth. The results suggested that the different outcomes of tumor growth might be attributed to the infiltration of anti-tumor or pro-tumor immune cells, especially M1 or M2 type macrophages into tumor microenvironment.

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简介：AbstractPurpose:The poor prognosis in patients with floating knee injuries is mainly contributed to articular involvement (Fraser's type II). This study aims to evaluate and compare the functional outcomes among different Fraser's type II floating knee injuries after surgical management.Methods:Twenty-seven patients with Fraser's type II floating knee injuries (54 fractures) between September 2014 and December 2015 were enrolled prospectively in this study and were distributed according to Fraser's floating knee classification into three different groups as type IIA (ipsilateral femoral shaft and tibial intra-articular involvement, n = 11), type IIB (ipsilateral tibial shaft and femoral intra-articular involvement, n = 9) and type IIC (both femoral and tibial intra-articular involvement, n = 7). The differences among the groups were evaluated and compared. The functional outcomes of these injuries at one year were analyzed using Knee Injury and Osteoarthritis Outcome Score (KOOS) which covers 5 subscales of pain, other symptoms, activities of daily living, sports and recreation, and quality of life. The result was also compared with standardized age-sex matched healthy population using paired samples t-test.Results:All the patients were male, and the injury mechanism was solely roadside accident. The mean age was 29.8 years and injury severity score 17.9 (comparable in all the three groups). Most injuries were observed on the right side (20 cases, 74.1%). Based on paired samples t-test, the KOOS score of patients with Fraser's type IIA was found to be better than that of type IIB and type IIC. Compared with the reference age-sex matched control group, patients with Fraser's type IIB and IIC fractures had significantly lower mean score in all KOOS subscales (all p < 0.01). However, Fraser's type IIA only revealed significant difference regarding the subscales of activities of daily living (p < 0.0001), sports and recreation (p < 0.0001), and quality of life (p < 0.0001).Conclusion:The results of this study show that patients with Fraser's type IIA fractures had a better functional outcome as compared to those with type IIB and IIC fractures. This might be due to the open intra-articular involvement of the distal femur of the latter two fracture types.

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简介：ＴＵＭＯＲＮＥＣＲＯＳＩＳＦＡＣＴＯＲ－αＡＬＴＥＲＳＰＲＯＴＥＩＮＭＥＴＡＢＯＬＩＳＭＡＮＤＣＥＬＬ－ＣＹＣＬＥＫＩＮＥＴＩＣＳＩＮＭＡＬＩＧＮＡＮＴＴＵＭＯＲＹｅＳｈｅｎｇｌｏｎｇ叶胜龙；ＴａｎｇＺｈａｏｙｏｕ汤钊猷；ＢｒｕｃｅＲＢｉｓｔｒｉａｎ...

简介：AbstractBackground:Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Large tumor suppressor 1 (LATS1) and large tumor suppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice.Methods:Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between Lats1 or Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student’s t test.Results:Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ± 54,384.796 vs. 221,149.4 ± 42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ± 347.856 vs. 3249.763 ± 370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ± 99,721.86 vs. 467,127.8 ± 89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ± 1518.01 vs. 5327.437 ± 873.297, P = 0.502) heterozygotes were not impaired. Moreover, the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes (Lats1: P = 0.654; Lats2: P = 0.152).Conclusion:These results indicate that a single allele of Lats1 or Lats2 may be sufficient for normal hematopoiesis.

简介：Tumormetastasisisthedominantcauseofdeathincancerpatients.However,themolecularandcellularmechanismsunderlyingtumormetastasisarestillelusive.Theidentificationofproteinmoleculeswiththeirexpressionscorrelatedtothemetastaticprocesswouldhelptounderstandthemetastaticmechanismsandthusfacilitatethedevelopmentofstrategiesforthetherapeuticinterventionsandclinicalmanagementofcancer.Proteomicsisasystematicresearchapproachaimingtoprovidetheglobalcharacterizationofproteinexpressionandfunctionundergivenconditions.Proteomictechnologyhasbeenwidelyusedinbiomarkerdiscoveryandpathogeneticstudiesincludingtumormetastasis.Thisarticleprovidesabriefreviewoftheapplicationofproteomicsinidentifyingmolecularfactorsintumormetastasisprocess.Thecombinationofproteomicswithotherexperimentalapproachesinbiochemistry,cellbiology,moleculargeneticsandchemistry,togetherwiththedevelopmentofnewtechnologiesandimprovementsinexistingmethodologieswillcontinuetoextenditsapplicationinstudyingcancermetastasis.

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