穿透性胃溃疡恶变12例影像学分析

目的提高对穿透性胃溃疡恶变的影像学诊断及鉴别诊断的认识。方法经手术病理证实的12例穿透性胃溃疡恶变病例，均行胃钡餐造影，10例加行CT扫描。结果胃钡餐造影出现深大龛影12例，其中腔外龛影10例，部分腔内龛影2例，出现穿孔2例。CT见胃壁增厚8例，胃内软组织块影2例，胃外软组织块影2例，腹腔、肝门、腹膜后淋巴结肿大6例。结论胃钡餐造影对穿透性胃溃疡有良好的显示，还可以发现CT显示不理想的胃黏膜面，对估计病变的范围和溃疡、穿孔方面优于CT。但CT能清楚观察胃壁的厚度、胃外肿块、与周围脏器的关系以及胃外有无淋巴结肿大，能对判断穿透性胃溃疡有无恶变等提供更多准确的信息。     

Cross-species genetic screens identify transglutaminase 5 as a regulator of polyglutamine-expanded ataxin-1

Many neurodegenerative disorders are caused by abnormal accumulation of misfolded proteins. In spinocerebellar ataxia type 1 (SCA1), accumulation of polyglutamine-expanded (polyQ-expanded) ataxin-1 (ATXN1) causes neuronal toxicity. Lowering total ATXN1, especially the polyQ-expanded form, alleviates disease phenotypes in mice, but the molecular mechanism by which the mutant ATXN1 is specifically modulated is not understood. Here, we identified 22 mutant ATXN1 regulators by performing a cross-species screen of 7787 and 2144 genes in human cells and Drosophila eyes, respectively. Among them, transglutaminase 5 (TG5) preferentially regulated mutant ATXN1 over the WT protein. TG enzymes catalyzed cross-linking of ATXN1 in a polyQ-length–dependent manner, thereby preferentially modulating mutant ATXN1 stability and oligomerization. Perturbing Tg in Drosophila SCA1 models modulated mutant ATXN1 toxicity. Moreover, TG5 was enriched in the nuclei of SCA1-affected neurons and colocalized with nuclear ATXN1 inclusions in brain tissue from patients with SCA1. Our work provides a molecular insight into SCA1 pathogenesis and an opportunity for allele-specific targeting for neurodegenerative disorders.     

颗粒物PM10和CD4+T淋巴细胞IL-4 DNA甲基化在儿童变应性鼻炎发病机制中的研究

目的　探讨大气污染PM10对变应性鼻炎儿童CD4+T淋巴细胞IL-4基因启动子区域甲基化的表观遗传调控及相关转录水平表达的影响。方法　选择2012年上海儿童医学中心耳鼻咽喉科就诊的35例6～12岁变应性鼻炎患儿随访1年,收集血样及设立匹配对照组（30例）,进行IL-4基因启动子区域甲基化克隆测序及mRNA表达水平检测。评估PM2.5和PM10的个人综合暴露。结果　变应性鼻炎组CD4+T淋巴细胞中IL-4基因启动子区域平均甲基化程度低于对照组（P =0.038）;其中-48、+54甲基化程度有差异（P =0.041、0.032）;变应性鼻炎组IL-4转录水平升高（P =0.039）,与其平均DNA甲基化水平呈负相关（r =-0.452,P =0.032）。转录水平与对照组无显著性差异。校正后,变应性鼻炎儿童PM10暴露与其IL-4基因启动子区域甲基化程度呈负相关（r 2=0.419,β=-0.470,SD =0.781,P =0.045）。结论　变应性鼻炎儿童IL-4基因启动子区域低甲基化水平可能受到PM10影响。     

Associations between Single Nucleotide Polymorphisms of High Mobility Group Box 1 Protein and Clinical Outcomes in Korean Sepsis Patients

Purpose

High mobility group box 1 (HMGB1) plays a central role in the pathogenesis of sepsis and multiple organ dysfunction syndromes. We investigated the associations of a single nucleotide polymorphism (SNP; rs1045411) in HMGB1 with various clinical parameters, severity, and prognosis in patients with sepsis, severe sepsis, or septic shock.

Materials and Methods

We enrolled 212 adult patients followed for 28 days. All patients were genotyped for rs1045411, and the serum levels of HMGB1 and several cytokines were measured.

Results

The proportions of patients according to genotype were GG (71.2%), GA (26.4%), and AA (2.4%). Among patients with chronic lung disease comorbidity, patients with a variant A allele had higher positive blood culture rates and higher levels of various cytokines [interleukin (IL)-1β, IL-6, IL-10, IL-17, and tumor necrosis factor-α] than those with the GG genotype. In the analysis of those with diabetes as a comorbidity, patients with a variant A allele had higher blood culture and Gram-negative culture rates than those with GG genotypes; these patients also had a higher levels of IL-17. In the analysis of those with sepsis caused by a respiratory tract infection, patients with a variant A allele had higher levels of IL-10 and IL-17 (all p<0.05). This polymorphism had no significant impact on patient survival.

Conclusion

The variant A allele of rs1045411 appears to be associated with a more severe inflammatory response than the GG genotype under specific conditions.     

完全性左束支阻滞的临床意义探讨

目的：探讨完全性左束支阻滞（complete left bundle branch block,CLBBB）的临床意义。方法：对常规心电图检查为CLBBB的162例住院患者的动态心电图、超声心动图及冠状动脉造影检查结果进行回顾性分析。结果：动态心电图显示：97例患者合并各种类型心律失常。超声心动图显示：111例发生不同程度左房、左室肥大及心脏瓣膜病变,左室射血分数（LVEF）≤50%者80例。37例冠脉造影显示：以左前降支为主的单支及多支病变16例。结论：CLBBB多发生于老年患者,常见于器质性心脏病,主要为高血压、冠心病、退行性心脏瓣膜病、扩张性心肌病等,且多伴发各种类型心律失常,易导致心功能不全。临床应对CLBBB尤其是新发的CLBBB患者进行动态心电图及超声心动图评估,必要时行冠脉造影及心脏电生理检查以明确原因,及时采取治疗措施。     

MDSC subtypes and CD39 expression on CD8+ T cells predict the efficacy of anti-PD-1 immunotherapy in patients with advanced NSCLC

The major suppressive immune cells in tumor sites are myeloid derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs), and Treg cells, and the major roles of these suppressive immune cells include hindering T-cell activities and supporting tumor progression and survival. In this study, we analyzed the pattern of circulating MDSC subtypes in patients with non-small cell lung cancer (NSCLC) whether those suppressive immune cells hinder T-cell activities leading to poor clinical outcomes. First, we verified PMN-MDSCs, monocytic-MDSCs (M-MDSCs), and Treg cells increased according to the stages of NSCLC, and MDSCs effectively suppressed T-cell activities and induced T-cell exhaustion. The analysis of NSCLC patients treated with anti-PD-1 immunotherapy demonstrated that low PMN-MDSCs, M-MDSCs, and CD39⁺CD8⁺ T cells as an individual and all together were associated with longer progression free survival and overall survival, suggesting PMN-MDSCs, M-MDSCs, and CD39⁺CD8⁺ T cells frequencies in peripheral blood might be useful as potential predictive and prognostic biomarkers.     

胃肠外营养支持治疗慢性阻塞性肺病29例

用胃肠外营养支持治疗29例慢性阻塞性肺病患者并设对照组，临床结果表明胃肠外营养支持治疗能改善慢性阻塞性肺病患者的营养状况，增加体重和提高白蛋白；能弥补慢性阻塞性肺病病人的微量元素缺乏；能增强慢性阻塞性肺病病人的细胞免疫和体液免疫功能，以上结果与对照组比较有极显著性差异（P＜0.001）。     

Decorin‐expressing adenovirus decreases collagen synthesis and upregulates MMP expression in keloid fibroblasts and keloid spheroids

Decorin is a natural transforming growth factor‐β1 (TGF‐β1) antagonist. Reduced decorin synthesis is associated with dermal scarring, and increased decorin expression appears to reduce scar tissue formation. To investigate the therapeutic potential of decorin for keloids, human dermal fibroblasts (HDFs) and keloid‐derived fibroblasts (KFs) were transduced with decorin‐expressing adenovirus (dE1‐RGD/GFP/DCN), and we examined the therapeutic potential of decorin‐expressing Ad for treating pathologic skin fibrosis. Decorin expression was examined by immunofluorescence assay on keloid tissues. HDFs and KFs were transduced with dE1‐RGD/GFP/DCN or control virus, and protein levels of decorin, epidermal growth factor receptor (EGFR) and secreted TGF‐β1 were assessed by Western blotting and ELISA. And type I and III collagen, and matrix metalloproteinase‐1 (MMP‐1) and matrix metalloproteinase‐3 (MMP‐3) mRNA levels were measured by real‐time RT‐PCR. Additionally, we immunohistochemically investigated the expression levels of the major extracellular matrix (ECM) proteins in keloid spheroids transduced with dE1‐RGD/GFP/DCN. Lower decorin expression was observed in the keloid region compared to adjacent normal tissues. After treatment with dE1‐RGD/GFP/DCN, secreted TGF‐β1 and EGFR protein expressions were decreased in TGF‐β1‐treated HDFs and KFs. Also, type I and III collagen mRNA levels were decreased, and the expression of MMP‐1 and MMP‐3 mRNA was strongly upregulated. In addition, the expression of type I and III collagen, fibronectin and elastin was significantly reduced in dE1‐RGD/GFP/DCN‐transduced keloid spheroids. These results support the utility of decorin‐expressing adenovirus to reduce collagen synthesis in KFs and keloid spheroid, which may be highly beneficial in treating keloids.     

Complementary role of CD4+ T cells and secondary lymphoid tissues for cross-presentation of tumor antigen to CD8+ T cells

MHC class I-restricted tumor antigens can be presented to CD8+ T cells by two distinct pathways: via direct and indirect presentation. The relative contribution of these two pathways toward the initial activation of tumor antigen-specific CD8+ T cells and their subsequent tumor rejection is still vigorously debated. Using a tumor model able to dissect the relative contributions of direct and indirect presentation, we show unequivocally the inefficiency of direct presentation and the essential requirement of indirect presentation for the priming of naive tumor antigen-specific T cells leading to tumor rejection. Moreover, we characterize the essential environment under which indirect presentation occurs, and find efficient cross-priming of tumor-specific CD8+ T cells in the complete absence of secondary lymphoid tissues. The independence of this process from local lymph nodes is compromised, however, in the absence of CD4+ T cell help. Therefore, our paper demonstrates that effective immune protection against tumors requires the cross-priming of CD8+ T cells under conditions that require either CD4+ T cell help, or draining lymph nodes.