First report of liver transplantation in Blau syndrome: The challenges faced in this rare granulomatous liver disease

Blau syndrome is a rare autoinflammatory granulomatous disease caused by variants in the NOD2 gene, classically presenting in childhood. Hepatic manifestations are recognized including cholestasis and granulomatous liver disease. We describe a novel NOD2 gene variant c.1471A > C, p.(Met491Leu) in an adult who developed cirrhotic complications despite selective immunotherapy, including recurrent esophageal bleeding and spontaneous bacterial peritonitis which resulted in liver transplantation. He required a second liver transplant as his first graft failed due to ischemic cholangiopathy. Disease recurrence has been observed (hitherto unreported). Of 84 patients with Blau syndrome treated with antibody therapy, five hepatic cases responded to anti-TNF therapy, with promising results if instigated before decompensation occurs. We report the first case of liver transplantation for Blau syndrome in an adult with a novel NOD2 variant. Blau related liver disease can reoccur post transplantation and is an important consideration for any future graft.Lay summaryBlau syndrome is a rare immune disease which presents in childhood. We describe the first liver transplant for this condition following development of progressive liver disease in adulthood. The patient had a newly described variant in the Blau gene (NOD2). We discuss the effectiveness of antibody therapy currently being used to control the disease, and the role of liver transplantation in Blau syndrome.     

抗体依赖的增强作用在传染性疾病中的研究新进展

抗体依赖的增强作用(ADE)是指某些病毒特异性抗体(一般多为非中和抗体)与病毒结合后,通过其Fc段与某些表面表达FcR的细胞结合从而介导病毒内吞和复制,增强病毒感染的过程。本文概述了ADE在呼吸道合胞病毒、登革病毒、流感病毒等几种传染性疾病中的相关研究发现,借鉴ADE在几种病毒传染性疾病中发生的情况,探讨新型冠状病毒肺炎发生ADE的可能性及其作用机制,期望为新型冠状病毒肺炎发病机制、重症治疗和疫苗研发提供一些见解。     

沙利度胺治疗原发性骨髓纤维化临床疗效观察

目的探讨沙利度胺治疗原发性骨髓纤维化(IMF)的临床有效性。方法IMF患者10例,剂量150mg/d,同时羟基脲1.0~3.0mg/d仍维持治疗。根据治疗前后血液学指标白细胞计数、血红蛋白测定、血小板计数和肝脾大小测定的变化及腹胀和下肢浮肿的改善来评定疗效。结果10例脾大患者,9例明显缩小,其中7例巨脾患者5例缩小更显著;2例肝大患者2例恢复正常;5例白细胞升高患者,1例明显降低,2例恢复正常;6例轻中度贫血患者,1例有所上升,2例贫血纠正;4例血小板升高患者,1例明显降低,3例恢复正常。9例腹胀患者,4例好转,3例消失;7例双下肢浮肿患者,2例好转,4例消失。10例IMF患者中,仅2例出现轻度不良反应。结论沙利度胺治疗原发性骨髓纤维化有一定疗效。     

Nucleus classification in histology images using message passing network

Identification of nuclear components in the histology landscape is an important step towards developing computational pathology tools for the profiling of tumor micro-environment. Most existing methods for the identification of such components are limited in scope due to heterogeneous nature of the nuclei. Graph-based methods offer a natural way to formulate the nucleus classification problem to incorporate both appearance and geometric locations of the nuclei. The main challenge is to define models that can handle such an unstructured domain. Current approaches focus on learning better features and then employ well-known classifiers for identifying distinct nuclear phenotypes. In contrast, we propose a message passing network that is a fully learnable framework build on classical network flow formulation. Based on physical interaction of the nuclei, a nearest neighbor graph is constructed such that the nodes represent the nuclei centroids. For each edge and node, appearance and geometric features are computed which are then used for the construction of messages utilized for diffusing contextual information to the neighboring nodes. Such an algorithm can infer global information over an entire network and predict biologically meaningful nuclear communities. We show that learning such communities improves the performance of nucleus classification task in histology images. The proposed algorithm can be used as a component in existing state-of-the-art methods resulting in improved nucleus classification performance across four different publicly available datasets.     

PI3K抑制剂对急性胰腺炎细胞因子和组织病理学评分的影响

目的:研究磷脂酰肌醇-3激酶(phosphatidylino-sitol 3-kinase,P13K)/丝/苏氨酸激酶(ser-ine threonine kinase,Akt)信号通路抑制剂渥曼青霉素(wortmannin)对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠细胞因子[肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-1β(interleukin-1β,IL-1β)、IL-6]转录和表达以及胰腺组织病理评分的影响,探讨其对SAP大鼠的保护作用.方法:将60只SD大鼠随机分为重症急性胰腺炎组(S组)、假手术组(C组)、生理盐水组(NS组)、溶剂(DMSO)对照组(R组)、PI3K/Akt抑制剂wortmannin组(W组).采用改良的Aho法制作SAP模型,分别在造模3、6h后抽血并处死大鼠,收集胰腺组织.采用酶联免疫吸附试验(ELISA)检测血清细胞因子(TNF-α、IL-1β、IL-6)表达.Real-time PCR方法检测胰腺组织细胞因子(TNF-α、IL-1β、IL-6)mRNA转录水平变化,并常规HE染色进行胰腺组织病理评分,同时观察各组腹水量、血清及腹水淀粉酶的变化.结果:S组和R组大鼠术后3、6h的腹水量、血清及腹水淀粉酶水平、胰腺组织病理评分较C组和NS组差异有统计学意义(P<0.05);W组的腹水量、血清及腹水淀粉酶水平、胰腺组织病理评分较同时段的S组和R组有所降低,差异有统计学意义(P<0.05).与C组和NS组相比,S组和R组大鼠术后3、6h的血清细胞因子TNF-α、IL-1β、IL-6表达水平和胰腺组织内TNF-α、IL-1β、IL-6mRNA转录水平差异有统计学意义(P<0.05);W组的上述指标均低于S组和R组,差异有统计学意义(P<0.05).结论:PI3K抑制剂wortmanin通过抑制PI3K/Akt信号转导通路下调SAP大鼠细胞因子(TNF-α、IL-1β、IL-6)的转录和表达水平,减轻胰腺组织的病理损伤,对SAP大鼠具有保护作用.     

上海市松江区中心医院2010--2012年住院药房抗生素使用情况分析

目的了解上海市松江区中心医院住院药房抗生素的使用情况,为临床合理用药提供参考。方法统计2010---2012年住院药房抗生素的消耗金额、用药总剂量、限定日剂量（DDD）、用药天数、用药频率（DDDS）、日均费用（DDC）、药物利用指数（DUI）以及抗生素使用率、抗生素使用强度（AUD）等,分析临床应用情况。结果3年来上海市松江区中心医院抗生素使用率和使用强度都超过了卫生部的相关标准,但呈现下降趋势。结论住院药房对抗生素的用药基本合理,但个别药物DUI〉1,存在不合理使用情况,应进一步加强对抗生素使用的监督管理,防止少数抗生素的滥用。     

长期有效控制血压改善高危高血压患者的肾功能

目的对《1999WHO/ISH高血压治疗指南》(《指南》)危险分层为高危和极高危组的患者单用或联合使用《指南》推荐的一线降压药,以血压<140/90mmHg作为目标血压,观察长期有效控制血压对高危高血压患者肾功能的影响。方法患者763例确定危险分层入选后,随机进入目标治疗组(n=382)和对照组(n=381)。目标治疗组在高血压专科门诊定期随访,按5步法治疗方案,直到达到或接近目标血压为止。对照组在普通门诊治疗。测定基线和治疗后的血清肌酐浓度并计算肾小球滤过率。结果两组患者的基线特征无明显差异。在平均4.4年随访期间,目标治疗组平均收缩压/舒张压为(133.8±6.6)/(79.7±5.5)mmHg,明显低于对照组[(151.7±12.7)/(87.7±8.0)mmHg,P<0.01]。尽管两组治疗强度不同,但两组间使用各类抗高血压药物的比例相似。共有526例患者复查血清肌酐1次以上。目标治疗组(n=304)血清肌酐由(90.9±29.1)降至(87.0±26.1)μmol/L,下降4.5%(P=0.006);对照组(n=222)则由(91.6±30.1)增至(96.4±46.4)μmol/L,增加5.2%(P=0.074),两组间治疗后比较,差异有非常显著意义(P<0.01)。目标治疗组血清肌酐清除率由(67.5±21.9)升至(70.0±22.3)mL/(min.1.73m2),升高4.5%(P=0.019);对照组则无明显变化[(66.9±24.2)vs(67.3±27.6)mL/(min.1.73m2),P=0.737]。结论与一般治疗相比,长期严格控制血压能降低高危高血压患者的血清肌酐,并提高血清肌酐清除率。     

肿瘤坏死因子-α诱导红细胞衰亡的研究

目的 探讨肿瘤坏死因子-α（TN F-α）在红细胞衰亡中的作用.方法 将分离的小鼠红细胞经TNF-α（1 ng/ml）处理6、12、24、48、72 h或在不同质量浓度（0.1、1、10 ng/ml）处理24h后,利用流式细胞仪检测红细胞前向散射（FSC）值的变化、红细胞膜磷脂酰丝氨酸（PS）和神经酰胺的标记率.结果 经TNF-α处理后的小鼠红细胞较对照组于24h后出现FSC减小（（81.5±1.02）％比（87.6±0.55）％,P＜0.05）,膜的PS外露水平和神经酰胺含量增加（（5.5±1.07）％比（2.7±0.17）％,（2.1±0.23）％比（0.7±0.26）％）,差异均有统计学意义（P＜0.01）,且随着时间的推移变化趋势更加明显.结论 TNF-α可诱导红细胞体积缩小,促进红细胞膜PS外露以及神经酰胺的增加,是红细胞衰亡的触发因素.