Host MyD88 signaling protects against acute graft-versus-host disease after allogeneic bone marrow transplantation

Recent experimental strategies to reduce graft-versus-host disease (GVHD) have focused largely on modifying innate immunity. Toll-like receptor (TLR)-driven myeloid differentiation primary response 88 (MyD88)-dependent signalling pathways that initiate adaptive immune function are also critical for the pathogenesis of GVHD. This study aimed to delineate the role of host MyD88 in the development of acute GVHD following fully major histocompatibility complex-mismatched allogeneic bone marrow transplantation (BMT). When myeloablated BALB/c MyD88 knock-out recipients were transplanted with C57BL/6 (B6) donor cells, they developed significantly more severe GVHD than wild-type (WT) BALB/c hosts. The increased morbidity and mortality in MyD88^–/– mice correlated with increased serum levels of lipopolysaccharide and elevated inflammatory cytokines in GVHD target organs. Additionally, MyD88 deficiency in BMT recipients led to increased donor T cell expansion and more donor CD11c⁺ cell intestinal infiltration with apoptotic cells but reduced proliferation of intestinal epithelial cells compared with that in WT BMT recipients. Decreased expression of tight junction mRNA in epithelial cells of MyD88^–/– mice suggested that MyD88 contributes to intestinal integrity. Cox-2 expression in the GVHD-targeted organs of WT mice is increased upon GVHD induction, but this enhanced expression was obviously inhibited by MyD88 deficiency. The present findings demonstrate an unexpected role for host MyD88 in preventing GVHD after allogeneic BMT.     

贵阳地区儿童重症社区获得性肺炎肺泡灌洗液病原及药敏分析

目的分析贵阳地区儿童重症社区获得性肺炎支气管肺泡灌洗液（BALF）病原学分布及耐药特点。方法收集989例重症社区获得性肺炎患儿临床资料，将支气管肺泡灌液采用支气管镜取出进行细菌培养、病毒以及肺炎支原体(MP)检测。结果（1）989例重症社区获得性肺炎患儿病原检出阳性716例，阳性率72.40%，细菌、病毒、支原体检出率分别33.27% （329例）、22.45%（222例）、31.45%（311例）。（2）细菌感染中的肺炎链球菌、金黄色葡萄球菌为最为常见的革兰阳性菌株(G+)；而肺炎克雷伯菌、大肠埃希菌为最为常见的革兰阴性菌株(G-)。培养菌株对青霉素类、红霉素、第1、2、3代头孢类抗生素有较高的耐药性，对头孢吡肟、拉氧头孢、哌拉西林、左氧氟沙星有较高的敏感性，对亚胺培南、万古霉素、利奈唑烷均无耐药发生。（3）病毒感染检出222例，其中呼吸道合胞病毒131例，腺病毒检测49例，流感病毒6例（A型2例，B型4例），副流感病毒36例（1型3例、2型4例、3型29例），病毒检出率以0～12月龄组最高，RSV、ADV感染主要集中在冬春季节。（4）肺炎支原体检出阳性率31.45%（311例），肺炎支原体检出率以3～5岁组最高。结论贵阳地区重症肺炎中肺炎克雷伯杆菌、肺炎链球菌、大肠埃希菌、金黄色葡萄球菌为重要的细菌病原。重要病毒为腺病毒和呼吸道病毒为主，1～12月龄组的病毒感染检出率比较高。     

The prognostic role of tumour‐infiltrating lymphocytes in oral squamous cell carcinoma: A meta‐analysis

It has been suggested that tumour‐infiltrating lymphocytes (TILs) are associated with the progression of oral squamous cell carcinoma (OSCC). However, the prognostic value of TILs is inconclusive due to the heterogeneity of immune cells within the tumour microenvironment. In this meta‐analysis, we aimed to assess the prognostic value of TILs in OSCC. The PubMed, Cochrane, Embase, Scopus and Web of Science databases were searched up to April 20, 2019, and 33 studies were ultimately included in this meta‐analysis. Our pooled meta‐analysis showed that high infiltration of CD8⁺ TILs, CD45RO⁺ TILs and CD57⁺ TILs favoured better overall survival (OS). However, high infiltration of CD68⁺ macrophages and CD163⁺ macrophages was associated with poor prognosis in OSCC. These findings suggest that CD8⁺ TILs, CD45RO⁺ TILs, CD57⁺ TILs, CD68⁺ macrophages and CD163⁺ macrophages might serve as novel prognostic factors and therapeutic targets in OSCC.