Ki-67表达与原发性肝癌根治性切除术后行预防性肝动脉化疗栓塞患者预后的关系

目的:探讨Ki-67表达与原发性肝癌根治性切除术后行预防性TACE患者预后的关系。方法:采用回顾性队列研究,收集2014年12月—2016年1月福建医科大学孟超肝胆医院150例行原发性肝癌根治性切除术并在术后2个月内行预防性TACE患者的临床病理资料,根据术后肝癌组织病理Ki-67评分分为为低表达组(Ki-67评分≤20%,44例)和高表达组(Ki-67评分20%,106例);分析Ki-67表达量与患者临床病理因素及复发与生存的关系。结果:高表达组肿瘤多发、肿瘤包膜不完整及合并微血管癌栓患者比例明显高于低表达组(均P0.05)。Ki-67高表达与肿瘤多发、肿瘤直径大为影响无瘤生存期的独立危险因素(均P0.05);Ki-67高表达与肿瘤多发、肿瘤直径大、肿瘤包膜不完整、合并微血管癌栓为影响总生存期的独立危险因素(均P0.05);高表达组患者复发率明显高于低表达组(57.9%vs. 37.7%,χ~2=6.777,P0.05),总生存率明显低于低表达组(45.6%vs. 75.9%,χ~2=8.447,P0.05)。结论:Ki-67的表达量对肝癌根治性切除术后行预防性TACE患者的预后有显著影响,高表达者预后不良。     

程序性细胞死亡蛋白配体1在结直肠癌免疫治疗中的研究进展

近年来,抗程序性细胞死亡蛋白1(PD-1)药物在转移性结直肠癌患者错配修复缺陷治疗中的成功使得该疾病的免疫治疗得以重视。然而,失配修复缺陷的结直肠癌患者仅占结肠癌患者的一部分。目前的研究重点是将免疫治疗应用到疾病的早期阶段,包括辅助一线治疗,以及检测免疫检查点抑制剂治疗的敏感性。然而,哪些患者能够从该免疫治疗中获益仍是值得商榷的问题,因为这类药物具有自身免疫毒性。PD-1的配体之一程序性细胞死亡蛋白配体1(PD-L1)作为一种检测生物标记物,其检测可以通过免疫组化来实现。但其免疫组化的检测存在一些混杂因素,包括应用不同的检测抗体、不同的免疫组化临界值、肿瘤组织的采集准备方式不同、处理过程的不同、原发与继发的活检标本、肿瘤源性或诱导的PD-L1表达,以及肿瘤与免疫细胞的染色等。目前的结果表明,免疫组化检测肿瘤过表达PD-L1的患者在接受抗PD-L1治疗时临床效果更理想,而有些低表达的肿瘤也对该治疗有所缓解,这使PD-L1的分析中存在复杂性。阐明宿主免疫系统与肿瘤微环境的机制则能够更好地解释针对PD-L1药物是否让患者受益。     

胸腺内注射异基因抗原诱导鼠神经移植免疫耐受的实验研究

目的探讨小鼠胸腺内注射异基因抗原在同种异体异基因坐骨神经移植免疫耐受中的作用。方法自供体小鼠C57BL／6的脾细胞中提取MHC抗原注人受体鼠Balb／c小鼠胸腺内，于2周后移植供体鼠坐骨神经。48只Balb／c小鼠随机分为4组，A组（胸腺内注射组）、B组（自体神经移植组）、C组（冷冻异体神经移植组）、D组（异体神经移植加用免疫抑制剂组）。于3周后进行电生理学、组织学、免疫学检测。结果A组运动神经传导速度（38．23m／s）与D组（36．39m／s）相比无显著性差异（P〉0．05），组织学、电镜、免疫学（混合淋巴细胞培养及迟发性超敏反应）检测结果均证实B组分别优于A组、D组和C组。结论胸腺内注射异基因MHC抗原可诱导大鼠对异体坐骨神经移植的特异性免疫耐受。     

肝移植后供肝和宿主免疫学状态的变化

目的观察供肝免疫原性和宿主对供体抗原反应能力的动态改变。方法利用近交系LEW到WF的大鼠肝移植自发免疫耐受模型,取出不同时期的供肝,分别刺激长期生存的WF宿主,观察能否诱导出肝损害；另外对LEW→WF肝移植后不同时期的宿主,再次给予供体抗原刺激。结果(1)移植后第1、2天的同种移植肝,可激起长期生存的宿主出现暂时性肝损害(121±33、83±21),但第3天以后的则不能(28±9)。(2)给予供体同源的脾细胞刺激后,移植后7、14、28 d的宿主均未能诱导肝损害(56±17、66±11、61±35),但第56、84或112天的宿主均可被诱导出暂时性肝损害(98±25、158±43、330±82)。结论(1)肝移植后供肝的免疫原性在术后3 d基本消失。(2)移植术后1个月内宿主对供体抗原的刺激是处于低(无)反应状态的。     

In vivo induction of CD4+ T cell responses by antigens covalently linked to synthetic microspheres does not require adjuvant

Macrophages, dendritic cells or B lymphocytes have been shownto play a major role in the presentation of soluble antigensto CD4⁺ T cells. In contrast, the capacity of these cells topresent particulate antigens such as bacterial or parasiticantigens to T cells remains controversial. To investigate thisquestion, well defined particulate antigens were prepared bycovalent linkage of proteins or peptides to 1 µm in diametersynthetic microspheres. The T cell immunogenicity of such particulateantigens was analyzed in vitro and in vivo. In vitro, a solubleprotein such as hen egg lysozyme (HEL) coupled to beads stimulateda strong proliferative T cell response of lymph node cells fromHEL-primed mice or of specific T cell hybridomas. HEL coupledto beads was presented to the specific T cell hybridomas bysplenocytes or by peritoneal macrophages, but not by lymphomaB cells. Immunization of mice with several different proteinantigens or with a synthetic peptide covalently linked to beadsinduced strong CD4⁺ T cell responses in the absence of adjuvant.The strong in vivo immunogenicity of proteins coupled to beadsdid not result from a non-specific adjuvant effect of beadssince covalent linkage of the antigen to beads was strictlyrequired to induce T cell responses in the absence of adjuvant.In vivo treatment by carrageenan showed that macrophages arerequired for the in vivo stimulation of T cell responses bythese particulate antigens. Thus, these results demonstratedthe role of phagocytic cells, especially macrophages, for invivo presentation of particulate antigens. These particulateantigens represent an interesting approach for the developmentof new vaccines, and for the in vivo analysis of the role ofvarious antigen presenting cells in T cell activation and differentiation.     

Antigen Presentation By Class I Major Histocompatibility Complex Molecules: A Context for Thinking About HLA-G

PROBLEM: There is substantial data that support the efficacy of paternal leukocyte immunization (PLI) for the treatment of alloimmune mediated miscarriage; however, there is confusion regarding the laboratory test that should be performed to determine levels of maternal anti-paternal leukocyte antibodies (MAPLA). METHOD: Popular methodologies employed include: 1) microcytotoxicity (MCX), 2) mixed lymphocyte culture (MLC), and 3) cell flow cytometry crossmatch (FCXM). Cell flow cytometry crossmatch correlates well with the more difficult MLC assay although the former proves the more sensitive study. This work compares the MCX assays with FCXM. The study group consisted of ten women who had a history of three or more spontaneous abortions (SABs). All ten had very low levels (<10%) of MAPLA as measured by FCXM. Following PLI all subjects demonstrated elevated levels (>50%) of MAPLA by FCXM. At 12 weeks gestation, sera were simultaneously measured for MAPLA by MCX and FCXM. RESULTS: Although all ten patients had very high levels of MAPLA by FCXM during pregnancy, five of ten had antibodies to HLA Class I and two of ten had antibodies to HLA Class II paternal antigens by MCX. Furthermore, all patients who were positive by MCX to paternal Class I antigens were also positive to Class I antigens not seen in either parent. Both patients who were positive by MCX to paternal Class II antigens were also positive to maternal Class II antigens. Notable is that all ten women eventually delivered healthy infants. CONCLUSION: Based on this preliminary study, the MCX assay is neither sensitive or reliable enough to determine the need and/or to monitor the effectiveness of PLI. Flow cytometry should be the modality of choice when determining the need for alloimmunotherapy and to monitor the effectiveness of treatment.     

树突状细胞的移行与递呈抗原作用的实验研究

借助异硫氰酸荧光素（ＦＩＴＣ）的可显示性，将其作为抗原免疫ＣＢＡ小鼠，以观察树突状细胞的移行及其抗原递呈方式与功能。结果表明，经ＦＩＴＣ两次刺激后（皮内），移行至局部淋巴结的树突状细胞数明显高于对照组（Ｐ＜０．０５）。ＦＡＣＳ的分析结果亦表明，局部淋巴结内的树突状细胞荧光阳性率显著增高，且荧光显微镜观察呈现不均一的膜荧光，提示该细胞的抗原递呈方式为单纯膜结合型，而无内在化过程。ＣｏｎＡ刺激的淋巴细胞增殖反应及ＦＩＴＣ特异性刺激的细胞增殖反应则分别体现了树突状细胞抗原递呈作用的后效应。     

多种底物在免疫金银染色检测抗核抗体试验中的联合应用

将多种底物联合应用于免疫金银染色检测ANA试验,与各底物单独应用比较,可明显改善检测的敏感性与核型显示。其中,两种鼠脏器印片联合应用的结果可与Hep-2细胞的结果相当,三种及四种鼠脏器印片联合应用的结果可与Hep-2细胞和一种鼠脏器印片联合应用的结果相当,且均不使正常人ANA阳性率明显升高。     

Medical management of chronic pancreatitis

慢性胰腺炎的临床表现包括疼痛、脂肪泻和糖尿病。在西方国家，慢性胰腺炎最常见的病因是酗酒。70％以上的病人在就诊时有疼痛的临床表现，而且，这些患者中又有75％以上会在几年之后出现疼痛减轻或完全消失。对于所有的慢性胰腺炎的病人来说，均应排除非胰源性疼痛和胆道梗阻、胰腺假性囊肿等胰腺局部并发症。应建议所有慢性胰腺炎病人戒烟、戒酒。阿片类镇痛剂仅应用于治疗疼痛严重的病人。尽管有报道认为胰酶替代治疗有助于止痛，但是，对于已经确诊的慢性胰腺炎病人来说，该疗法无效。激素类药物进行腹腔神经丛阻滞术可能有助于病人度过剧烈疼痛期。顽固性疼痛是进行胰液引流或胰腺切除的适应证。建议应用适量胰酶替代联合(或不联合)制酸剂治疗营养不良。慢性胰腺炎导致的糖尿病与原发性糖尿病的治疗原则相似。