Cellular targets of regulatory B cell-mediated suppression

Regulatory B cells (Bregs) are defined by their ability to restrain inflammatory responses both in vivo and in vitro. Interleukin 10 (IL-10) production by Bregs is thought to be central to their ability to regulate inflammation, largely due to IL-10s’ ability to suppress pro-inflammatory cytokine production by effector lymphocytes and to maintain the differentiation of regulatory T cells (Tregs). However, with an increase in available published data, it has become evident that Bregs utilize a number of suppressive mechanisms in order to alter the activation of a variety of different lymphocytes. Here, we summarize the multiplicity of cellular targets of Breg-mediated suppression and describe the mechanisms employed by Bregs to suppress chronic inflammatory responses.     

8种寄生虫病例分析

本文报道并分析8例寄生虫病例,其中包括脑裂头蚴病、眼部裂头蚴病、肺吸虫幼虫移行症、肺吸虫病、钩虫病、肝吸虫病、包虫病和广州管圆线虫病各1例。8例寄生虫病均有不同程度的误诊,其中6例在寄生虫抗体筛查检测阳性后得以确诊。因此,寄生虫病应引起临床医生的重视,抗体筛查有助于发现寄生虫病例。     

Monitoring Hepatocyte Dysfunction and Biliary Complication After Liver Transplantation Using Quantitative Hepatobiliary Scintigraphy

The significance of hepatobiliary scintigraphy (HBS) for hepatic graft function assessment was established mostly on retrospective studies and was not widely recognized due to the lack of quantitative data and variation in accuracy. This prospective study was performed to investigate the effectiveness of quantitative HBS for assessing hepatocyte dysfunction and biliary complication in liver transplant recipients.In 57 recipients who had undergone orthotopic liver transplantation, a total of 67 dynamic ^99mTc-EHIDA scans were performed and quantitative parameters including the hepatocyte extraction fraction (HEF), time to maximum hepatic radioactivity (T_max), and time for peak activity to decrease by 50% (T_1/2) were calculated. The scintigraphic results based on the 3 parameters were compared against the final diagnosis. A ROC curve analysis was carried out to identify the cutoff value of T_max for diagnosis of biliary stricture. Correlation between the parameters of postoperative HBS and conventional biochemical liver function indices were also analyzed.Quantitative ^99mTc-EHIDA HBS had an overall sensitivity of 94.12% (16/17), specificity of 93.33% (42/45), and diagnostic accuracy of 93.55% (58/62) for detecting hepatocyte dysfunction and biliary complication in liver transplant recipients. The recommended cutoff value of T_max for diagnosis of post-transplant biliary stricture was set at 15.75 min with a sensitivity of 100.0% and a specificity of 94.0%. The scintigraphic parameters (HEF, T_max) were statistically significantly associated with the conventional liver function parameters.Quantitative ^99mTc-EHIDA HBS offers a noninvasive imaging modality with high sensitivity and specificity to diagnose hepatocyte dysfunction as well as distinguish between patients with or without biliary stricture following liver transplantation. Furthermore, HEF and T_max values obtained from dynamic HBS show good correlation with conventional liver function parameters.     

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.     

DNA methylation of the ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C,and TRIM59 genes for age prediction from blood,saliva, and buccal swab samples

Many studies have reported age-associated DNA methylation changes and age-predictive models in various tissues and body fluids. Although age-associated DNA methylation changes can be tissue-specific, a multi-tissue age predictor that is applicable to various tissues and body fluids with considerable prediction accuracy might be valuable. In this study, DNA methylation at 5 CpG sites from the ELOVL2, FHL2, KLF14, C1orf132/MIR29B2C, and TRIM59 genes were investigated in 448 samples from blood, saliva, and buccal swabs. A multiplex methylation SNaPshot assay was developed to measure DNA methylation simultaneously at the 5 CpG sites. Among the 5 CpG sites, 3 CpG sites in the ELOVL2, KLF14 and TRIM59 genes demonstrated strong correlation between DNA methylation and age in all 3 sample types. Age prediction models built separately for each sample type using the DNA methylation values at the 5 CpG sites showed high prediction accuracy with a Mean Absolute Deviation from the chronological age (MAD) of 3.478 years in blood, 3.552 years in saliva and 4.293 years in buccal swab samples. A tissue-combined model constructed with 300 training samples including 100 samples from each blood, saliva and buccal swab samples demonstrated a very strong correlation between predicted and chronological ages (r = 0.937) and a high prediction accuracy with a MAD of 3.844 years in the 148 independent test set samples of 50 blood, 50 saliva and 48 buccal swab samples. Although more validation might be needed, the tissue-combined model’s prediction accuracies in each sample type were very much similar to those obtained from each tissue-specific model. The multiplex methylation SNaPshot assay and the age prediction models in our study would be useful in forensic analysis, which frequently involves DNA from blood, saliva, and buccal swab samples.     

脑静脉畸形的MRI表现及其诊断价值

目的 探讨脑静脉畸形的MRI表现，评价各成像序列的诊断价值。资料与方法 搜集经临床手术证实的脑静脉畸形8例进行回顾性分析，所有患者均进行了常规MRI平扫及3D-MOTSA MRA检查。6例行Gd-DTPA增强T1WI，其中3例行3D-MOTSA增强MRA检查。结果 小脑4例，额叶、顶叶、枕叶共4例。5例MRI平扫引流静脉为长T1短T2流空信号，3例呈长T1低信号、长T2高信号。扩张的髓静脉为网状及条状长T1低信号、长T2高信号，增强扫描呈“海蛇头”样改变，即多条髓静脉呈辐射状汇入粗大的引流静脉。3D-MOTSA MRA检查显示部分引流静脉，髓静脉显示较少。3D-MOTSA增强MRA检查引流静脉全程显示，髓静脉显示数目多。结论 MRI能明确诊断脑静脉畸形的合并症，弥补脑血管造影的不足，3D-MOTSA增强MRA检查可取代脑血管造影。     

颗粒松质骨压紧植骨全髋关节置换术治疗创伤性髋关节炎的疗效

目的探讨颗粒松质骨压紧植骨全髋关节置换术(THA)治疗髋臼骨折继发创伤性髋关节炎的疗效。方法1998年12月-2005年5月,对15例髋臼骨折继发创伤性髋关节炎患者行颗粒松质骨压紧植骨THA,所有患者髋臼假体均采用骨水泥固定,颗粒骨均取自体骨,术后24h后开始被动活动,3个月后开始全负重锻炼。临床随访采用Harris髋关节评分(HSS)系统评分,对任何原因引起髋臼假体翻修均视为临床失败。根据Conn等影像学评价法观察颗粒骨长人情况,根据DeLee的三区法测量臼杯、骨水泥与移植骨间的界面宽度,臼杯的移位程度则依据其相对于泪点间线的距离而定。结果14例患者获得平均4．3年(1．0-7．5年)随访,HHS评分由术前平均42分(10-62分)提高到随访结束时平均84分(58-98分)。1例髋部有轻度疼痛,无患者行翻修手术。大部分髋部恢复了其正常的旋转中心,仅有2例高出对侧0．8 mm。大多数患者影像学表现稳定,2例在Ⅰ区和Ⅲ区出现进行性增宽的透亮带,1例在Ⅲ区出现非进行性增宽的透亮带。1例臼杯假体在术后7年出现明显移位(6 mm),但并没有行翻修手术。结论颗粒骨压紧植骨技术作为一种生物学髋臼重建方法,其联合THA治疗髋臼骨折后继发创伤性关节炎伴髋臼缺损的疗效令人满意,能够恢复髋关节的正常解剖和功能活动。     

腺病毒介导MDA-7/IL-24选择性杀伤肝癌 细胞HepG2的研究

目的 ：观察MDA-7/IL-24基因对肝癌的选择性杀伤作用，为肝癌的基因治疗提供理论基础。 方法 ：将携带人MDA-7/IL-24基因的腺病毒Ad.mda-7感染人正常肝细胞L02和肝癌细胞HepG2;用RT-PCR法观察MDA-7/IL-24基因的表达;ELISA方法检测细胞培养上清液中MDA-7/IL-24蛋白的浓度;4甲基偶氮唑蓝染色法（MTT）及Hoechst染色观察MDA-7/IL-24对肝癌细胞的生长抑制和杀伤作用;Annexin-V和PI双染后流式细胞仪检测2种细胞的凋亡;用流式细胞仪检测细胞周期。 结果 ：复制缺陷型腺病毒能介导外源基因MDA-7/IL-24在肝癌细胞株HepG2和正常细胞L02中的高效表达;细胞培养上清液中有MDA-7/IL-24蛋白的表达; MDA-7/IL-24能明显抑制肝癌细胞生长并可促进肝癌细胞的凋亡;MDA-7/IL-24阻滞肝癌细胞于G2/M期，能选择性杀伤肝癌细胞而对正常的肝细胞无阻滞作用和毒性作用。结论 ：复制缺陷型重组腺病毒载体Ad.mda-7能介导MDA-7/IL-24基因在人肝癌细胞中高效表达，促使细胞增殖阻滞及诱导肿瘤细胞凋亡，选择性地杀伤肝癌细胞HepG2，而对正常肝细胞L02无任何毒性作用。