Immunisation with the BCG and DTPw vaccines induces different programs of trained immunity in mice

In addition to providing pathogen-specific immunity, vaccines can also confer nonspecific effects (NSEs) on mortality and morbidity unrelated to the targeted disease. Immunisation with live vaccines, such as the BCG vaccine, has generally been associated with significantly reduced all-cause infant mortality. In contrast, some inactivated vaccines, such as the diphtheria, tetanus, whole-cell pertussis (DTPw) vaccine, have been controversially associated with increased all-cause mortality especially in female infants in high-mortality settings. The NSEs associated with BCG have been attributed, in part, to the induction of trained immunity, an epigenetic and metabolic reprograming of innate immune cells, increasing their responsiveness to subsequent microbial encounters. Whether non-live vaccines such as DTPw induce trained immunity is currently poorly understood. Here, we report that immunisation of mice with DTPw induced a unique program of trained immunity in comparison to BCG immunised mice. Altered monocyte and DC cytokine responses were evident in DTPw immunised mice even months after vaccination. Furthermore, splenic cDCs from DTPw immunised mice had altered chromatin accessibility at loci involved in immunity and metabolism, suggesting that these changes were epigenetically mediated. Interestingly, changing the order in which the BCG and DTPw vaccines were co-administered to mice altered subsequent trained immune responses. Given these differences in trained immunity, we also assessed whether administration of these vaccines altered susceptibility to sepsis in two different mouse models. Immunisation with either BCG or a DTPw-containing vaccine prior to the induction of sepsis did not significantly alter survival. Further studies are now needed to more fully investigate the potential consequences of DTPw induced trained immunity in different contexts and to assess whether other non-live vaccines also induce similar changes.     

Interleukin-11 Overexpression and M2 Macrophage Density are Associated with Angiogenic Activity in Proliferative Diabetic Retinopathy

ABSTRACT

Purpose

To investigate the expression of IL-11 and its receptor IL-11Rα and to quantify density of CD163⁺ M2 macrophages in proliferative diabetic retinopathy (PDR).     

单孔胸腔镜下肺癌术后胸腔引流时间的影响因素分析北大核心

目的:探讨单孔胸腔镜下肺癌手术术后胸腔引流时间的影响因素。方法:本研究采用回顾性分析方法,回顾我院2018年01月至2019年12月原发性肺癌患者经单孔胸腔镜手术治疗的病例199例。按照术后胸腔引流时间分为两组,Ⅰ组(术后胸腔引流时间<5天)和Ⅱ组(术后胸腔引流时间≥5天)。对于影响术后胸腔引流时间的可能因素在两组间先采用单因素分析的方法筛选,再将筛选出来的对术后胸腔引流时间可能有意义的影响因素进行二项Logistic多因素回归分析。结果:经单因素分析及二项Logistic多因素回归分析结果显示:年龄≥60岁、手术部位、肺段切除术、胸膜粘连、手术时间≥180 min、术后早期下床活动是术后胸腔引流时间的独立影响因素(P<0.05)。结论:对于具有多个延长术后胸腔引流时间的独立影响因素的患者,应制定个体化管理方案,尽可能减少术后胸腔引流时间,减少住院天数,加快患者康复。     

Progress in Targeting the TGFβ Pathway

Signaling by the transforming growth factor-β (TGF-β) superfamily is important in the regulation of hematopoiesis and is dysregulated in myelodysplastic syndromes (MDS), contributing to ineffective hematopoiesis and clinical cytopenias. TGF-β, activins and growth differentiation factors exert inhibitory effects on red cell formation by activating canonical SMAD2/3 pathway signaling. SMAD2/3 overactivation is seen in numerous subtypes of MDS. Furthermore, reduced levels of inhibitory SMAD7 are

References

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Caveolin-1 in skin aging – From innocent bystander to major contributor

Caveolin-1 (Cav-1) appears to be both a pathophysiological contributor and a target in different inflammatory and hyperproliferative skin conditions as well as in skin aging. Skin fibroblasts demonstrate an up-regulation of Cav-1 expression both in chronological and UV-induced aging, and such an up-regulation was observed both in vitro and in vivo. Typical alterations in aging skin involve a reduction of the dermis thickness, a significant expansion of the dermal white adipose tissue as well as modifications of the content and distribution of hyaluronan, impairment of autophagic flux, a reduction of collagen expression and an increase in tissue inflammation. All of these phenomena can be connected with changes in Cav-1 expression in the aging skin. Modified expression of Cav-1 can also significantly influence the mechanical properties of individual skin layers, thus changing the total mechanical stability of the layered composite skin/WAT, leading to typical structural modifications of the skin surface in the aging skin. Selective reduction of Cav-1 expression has the potential to exert anti-aging effects on the skin.     

整合素α5β1在苯妥英钠促进大鼠PDLSCs和BMMSCs黏附于牙骨质中的作用

目的 探讨在苯妥英钠(Phenytoin,PHT)促进大鼠牙周膜干细胞(Rat periodontal ligament stem cells,rPDLSCs)、大鼠骨髓间充质干细胞(Rat Bone Marrow Mesenchymal Stem Cells,rBMMSCs)黏附于牙骨质过程中,整合素α5β1(Integrin α5β1)起到的作用。方法 提取大鼠BMMSCs和PDLSCs,培养并纯化。通过细胞鉴定后,将获得的两种细胞各分为4组:40 mg/L PHT处理组、40 mg/L PHT+整合素α5抗体处理组、40 mg/L PHT+整合素β1抗体处理组、PBS处理组,每组细胞放入置有牙骨质片的96孔板处理4 h后,检测黏附于牙骨质片上的细胞量并做以比较。最后,利用qRT-PCR和Western blot检测40 mg/L PHT组与对照组细胞的整合素α5、β1亚基的mRNA与蛋白表达量。结果 40 mg/L PHT可促进rBMMSCs及rPDLSCs黏附于牙骨质片,加入整合素α5、β1抗体后,均明显抑制了40 mg/L PHT对rBMMSCs、rPDLSCs黏附于牙骨质的促进作用(P＜0.01)。qRT-PCR、Western-blot结果显示PHT处理组的整合素α5、β1亚基表达量高于空白对照组(P＜0.05)。结论 40 mg/L PHT能促进rBMMSCs、rPDLSCs黏附于牙骨质,该作用与整合素α5β1的表达上调密切相关。     

甲状腺功能减退与子宫内膜癌的相关性分析

 目的 探讨甲状腺功能减退与子宫内膜癌（EC）的关系及EC患者癌组织分化程度和雌激素受体（ER）、孕激素受体（PR）的表达与甲状腺功能之间的关系。方法 选取2015年1月—2018年7月我院收治的EC患者113例，同时随机选取年龄与EC组相匹配的此段时间内我院健康体检的妇女156例作为对照组，检测血清促甲状腺激素（TSH）、甲状腺激素（FT4）。比较两组间甲状腺功能减退的患病率，并利用免疫组织化学法测定EC患者手术切除标本的癌组织中ER、PR的表达，分析EC患者癌组织分化程度及癌组织中ER、PR的表达与甲状腺功能之间的相关性。结果 EC组甲状腺功能减退的患病率较对照组高（P<0.000）。低分化EC患者的TSH高于中分化EC患者（P=0.025）。EC手术切除标本的癌组织中ER、PR阳性与阴性患者的TSH、FT4差异无统计学意义（P>0.05）。结论 甲状腺功能减退与EC具有相关性。     

喉癌患者PAC-1、CD62P表达与临床病理特征和复发的关系

目的探讨喉癌患者血小板表面血小板膜糖蛋白Ⅱb/Ⅲa纤维蛋白原受体(PAC-1)、血小板P-选择素(CD62P)阳性表达率以及与患者临床病理特征和复发的关系。方法选取2014年1月~2015年12月间在我院耳鼻喉科手术治疗的116例喉癌患者,随访≥2年,并选取同期在我院体检的健康人群60例为对照组,采用流式细胞仪检测法检测外周血PAC-1和CD62P阳性率,并分析与临床病理特征、复发的关系。结果喉癌患者PAC-1和CD62P阳性表达率分别为(17.82±1.76)%和(22.87±3.13)%,明显高于健康人群(P<0.05);而且在喉癌患者PAC-1表达和CD62P表达呈正相关性(r=0.238,P<0.05)。T3-T4分期或N2-N3分期患者PAC-1和CD62P阳性表达率高于T1-T2分期或N0-N1分期患者(P<0.05)。另外远处转移组PAC-1和CD62P阳性表达率高于未发生转移组(P<0.05);随访期间有24例患者复发,复发率为20.69%。复发喉癌患者PAC-1、CD62P阳性表达率分别为(17.02±0.85)%和(21.84±1.17)%,明显高于未复发的喉癌患者(P<0.05)。经Logistics回归分析,PAC-1和CD62P是喉癌患者复发的独立危险因素(P<0.05)。结论PAC-1和CD62P阳性表达率与喉癌患者T分期、淋巴结转移和远处转移密切相关,同时可作为喉癌局部复发、区域淋巴结转移、远处转移的预测指标。