脓毒症患者血小板下降与感染性休克发生的相关性

目的：分析脓毒症患者血小板下降情况及其与感染性休克发生的相关性。方法回顾性分析45例脓毒症患者血小板正常范围内下降（同时测同一时间点的TPO水平）与感染性休克发生前后的变化,以及发生感染性休克与未发生休克的脓毒症患者血小板计数变化（同一时间TPO水平）并同APACHEⅢ（急性生理学及慢性健康状况评分系统Ⅲ）评分对比分析得出。结果脓毒症患者诊断前PLT水平为（187.7＆#177;51.73）＆#215;109/L;脓毒症诊断后PLT水平为（126.1＆#177;38.71）＆#215;109/L,二者差异具有统计学意义（t=5.743,P＜0.001）;24例脓毒症未发生休克患者PLT下降,为（49.44＆#177;49.50）＆#215;109/L;21例感染休克患者PLT水平下降,为（90.19＆#177;44.86）＆#215;109/L;二者差异具有统计学意义（t=-2.896,P＜0.001）。脓毒症患者诊断前后血小板计数下降和感染休克发生后血小板计数下降与APACHEⅢ评分均呈正相关关系（r=0.449、0.978,P＜0.001）。结论血小板计数下降作为脓毒症患者病情变化的单独风险依据,可观察抗炎与促炎平衡状态的指标,无论血小板计数在否正常范围,下降的趋势更为重要。     

CD8 T cell immunity against human respiratory syncytial virus

Human respiratory syncytial virus (HRSV) was first discovered in the 1950s, but despite decades of research, a licensed vaccine against it is not available. Epidemiological studies indicate that antibodies directed against the fusion protein (F) partially correlate with protection. In addition, an F-specific monoclonal antibody is licensed as a prophylactic treatment in children who are at high risk of developing complications following HRSV infection. Therefore, most HRSV-oriented vaccination strategies focus on inducing a humoral immune response against F. In the quest for the development of a safe HRSV vaccine, the induction of a T cell immune response has received a lot less attention. T cell immunity directed against HRSV has not been associated unequivocally with protection against HRSV and CD4⁺ T helper cell responses may even worsen disease due to HRSV. However, many studies support a protective role for CD8⁺ T cells in clearance of HRSV from the lungs. In this review we highlight the clinical and experimental evidence in favor of a CD8⁺ T lymphocyte-based vaccination strategy to protect against HRSV. First, we describe how T cell responses and T cell memory are induced in the lungs upon respiratory viral infection. HRSV has evolved mechanisms that hamper CD8⁺ T cell priming and effector functions. We appraise the information on HRSV-specific CD8⁺ T cell immunity gained from laboratory mouse studies, taking into account the advantages and limitations of this animal model and, where possible, the accordance with clinical evidence. Finally, we focus on recent efforts to develop T cell based vaccines against HRSV.     

免疫稳态与重症肌无力的目标治疗

<正>内环境的恒定是一切生命的需要,人类在长期进化过程中发展出一整套平衡调节机制,免疫平衡是其中重要组成部分。重症肌无力(MG)是慢性自身免疫性疾病,其本质是免疫失衡导致的免疫损伤。长期以来,由于重症肌无力的异质性和症状的波动性,大多数患者需长达数年的治疗[1]。因此,需     

Polarized immune responses modulated by layered double hydroxides nanoparticle conjugated with CpG

Modulation of the immune response is an important step in the induction of protective humoral and cellular immunity against pathogens. In this study, we investigated the possibility of using a nanomaterial conjugated with the toll-like receptor (TLR) ligand CpG to modulate the immune response towards the preferred polarity. MgAl-layered double hydroxide (LDH) nanomaterial has a very similar chemical composition to Alum, an FDA approved adjuvant for human vaccination. We used a model antigen, ovalbumin (OVA) to demonstrate that MgAl-LDH had comparable adjuvant activity to Alum, but much weaker inflammation. Conjugation of TLR9 ligand CpG to LDH nanoparticles significantly enhanced the antibody response and promoted a switch from Th2 toward Th1 response, demonstrated by a change in the IgG2a:IgG1 ratio. Moreover, immunization of mice with CpG-OVA-conjugated LDH before challenge with OVA-expressing B16/F10 tumor cells retarded tumor growth. Together, these data indicate that LDH nanomaterial can be used as an immune adjuvant to promote Th1 or Th2 dominant immune responses suitable for vaccination purposes.     

Ontogeny of the immune system in Acipenserid juveniles

Sturgeon aquaculture has increased considerably worldwide but little is known about their immunological development and competence in early life stages. Culture of larvae is one of the most critical stages in intensive sturgeon farming, often associated with high mortality rates. The objective of this study was to characterize the developmental morphology (light and transmission electron microscopy, LM and TEM) of the meningeal myeloid tissue, spleen and thymus in Atlantic sturgeon (Acipenser oxyrinchus oxyrinchus) from hatching until 5 months old (2895°C·day (dd)). The spleen was first visible on 541 dd larvae LM sections and the other two immune organs in 768 dd samples (approximately 400 and 600 dd after onset of feeding). Generally, younger fish had significantly higher percentages of undifferentiated cells (meningeal myeloid tissue and spleen) and effective adaptive immune competence would not be expected in these fish on the onset of feeding, but further functional immune assessment is needed.     

The Lepidopteran endoribonuclease-U domain protein P102 displays dramatically reduced enzymatic activity and forms functional amyloids

Hemocytes of Heliothis virescens (F.) (Lepidoptera, Noctuidae) larvae produce a protein, P102, with a putative endoribonuclease-U domain. In previous works we have shown that P102 is involved in Lepidopteran immune response by forming amyloid fibrils, which catalyze and localize melanin deposition around non-self intruders during encapsulation, preventing harmful systemic spreading. Here we demonstrate that P102 belongs to a new class of proteins that, at least in Lepidoptera, has a diminished endoribonuclease-U activity probably due to the lack of two out of five catalytically essential residues. We show that the P102 homolog from Trichoplusia ni (Lepidoptera, Noctuidae) displays catalytic site residues identical to P102, a residual endoribonuclease-U activity and the ability to form functional amyloids. On the basis of these results as well as sequence and structural analyses, we hypothesize that all the Lepidoptera endoribonuclease-U orthologs with catalytic site residues identical to P102 form a subfamily with similar function.     

盐酸戊乙奎醚对粘连性肠梗阻大鼠肠黏膜免疫屏障的保护作用

目的 探讨盐酸戊乙奎醚(PHC)对粘连性肠梗阻(AIO)大鼠肠黏膜免疫屏障功能的影响及可能机制.方法 将60只SD大鼠分为正常组(N组)、假手术组(S组)、生理盐水组(NS组)及盐酸戊乙奎醚组(P2、P4、P8组).建立AIO模型.正常组不予处理,生理盐水组及假手术组均给予0.4 ml生理盐水,PHC组按0.2、0.4、0.8 mg/kg配成0.4 ml,于术后第7d开始连续肌注7d.ELISA法测量血清中IL-4、IL-10含量以及肠内容物中分泌型免疫球蛋白A(sIgA)含量.结果 与S组、NS组比较,P2、P4、P8组血清IL-4[(19.34±2.87),(23.85±2.72),(27.89±2.71) vs (6.18±1.42),(8.37±2.69) ng/L)]、IL-10[(118.93±20.78),(121.61±24.932),(127.41±22.61) vs (78.19±19.41),(42.72±21.31) ng/L]以及肠内容物中sIgA含量(0.64±0.089,0.99±0.093,1.02±0.12 vs 0.41±0.06,0.14±0.03 ng/L)均有明显增高,差异均有统计学意义(均P＜ 0.05).与P2组比较,P4、P8组IL-4与sIgA水平升高更为明显,差异均有统计学意义(P＜ 0.05).结论 中、高剂量PHC对AIO大鼠肠黏膜的免疫屏障有一定保护作用,且以高剂量更为显著,其机制可能与增加抗炎因子释放和抑制炎性因子产生有关.     

低热量营养支持对肝癌术后营养和免疫功能的影响

目的:比较低热量肠内、外营养支持对肝癌术后营养和免疫功能的影响.方法:将49例可切除肝癌的病人随机分为两组,术后第2 d始分别接受低热量肠内营养(HEN组)和低热量肠外营养(HPN组),比较两组术后的免疫和营养指标.结果:HEN组术后前清蛋白、转铁蛋白、IgA、IgG、IgM下降幅度小,CD3和CD4/CD8易恢复至术前水平,与HPN组比较,差异有显著性意义(P＜0.05).结论:HEN支持有利于肝癌术后营养和免疫功能的改善.     

IFNγ signaling integrity in colorectal cancer immunity and immunotherapy

The majority of colorectal cancer patients are not responsive to immune checkpoint blockade (ICB). The interferon gamma (IFNγ) signaling pathway drives spontaneous and ICB-induced antitumor immunity. In this review, we summarize recent advances in the epigenetic, genetic, and functional integrity of the IFNγ signaling pathway in the colorectal cancer microenvironment and its immunological relevance in the therapeutic efficacy of and resistance to ICB. Moreover, we discuss how to target IFNγ signaling to inform novel clinical trials to treat patients with colorectal cancer.     

子宫内膜异位症与肠道菌群失衡关系的研究进展

子宫内膜异位症（endometriosis,EMs）是一种妇科常见的激素依赖性疾病,高发于育龄期女性。该病虽是一种良性疾病,但具有黏附、侵袭和转移等恶性肿瘤的性质,且容易反复发作,严重影响女性患者日常生活和身心健康。EMs具体发病机制尚不明确,但已有研究证明肠道菌群失衡在其发病过程中起重要作用。肠道菌群失衡影响EMs发病可能与参与免疫调控、脂多糖生成、影响炎症因子及血管生成素释放、参与性激素代谢等机制有关。综述目前对肠道菌群失衡参与EMs发病的相关途径及机制的最新研究进展。