妊娠期间脾脏T淋巴细胞的改变与鼠胚着床

应用ＦＩＴＣ标记的Ｌ３Ｔ４及Ｌｙ２单克隆抗体，及流式细胞计细胞分选，对小鼠妊娠期间脾脏Ｔ淋巴细胞亚群进行检测。结果表明，妊娠早期小鼠脾脏ＣＤ８＋淋巴细胞比例减少，在着床时尤为明显。提示脾脏Ｔ淋巴细胞数量和功能变化，参与维持正常妊娠，尤其是参与着床。     

大鼠脑皮质微血管内皮细胞培养和形态学观察

为获取较纯净脑微血管内皮细胞进行血脑屏障的病理生理研究，我们采用脑组织匀浆、过滤和酶消化技术分离大鼠脑微血管，对分离的脑微血管内皮细胞进行了体外培养和形态学观察。倒置显微镜下，细胞具有单层“卵石样”排列的典型特征、电镜观察可见细胞间连接，免疫酶技术显示，95％以上的细胞为第Ⅷ因子相关抗原反应阳性，进一步证实为血管内皮细胞。     

超氧自由基和血液粘度的相关性研究

本文对69名体检人员进行过氧化脂质(LPO)血液流变性和血脂检测,应用电子计算机和医用统计软件进行数据分析.直线回归分析表明,LPO与全血和血浆粘度无显著相关;进行多元逐步回归分析表明,LPO在全血粘度比值中则列为第3受选因子,说明LPO对血浆粘度有一定影响.     

Dual β-Catenin and γ-Catenin Loss in Hepatocytes Impacts Their Polarity through Altered Transforming Growth Factor-β and Hepatocyte Nuclear Factor 4α Signaling

Hepatocytes are highly polarized epithelia. Loss of hepatocyte polarity is associated with various liver diseases, including cholestasis. However, the molecular underpinnings of hepatocyte polarization remain poorly understood. Loss of β-catenin at adherens junctions is compensated by γ-catenin and dual loss of both catenins in double knockouts (DKOs) in mice liver leads to progressive intrahepatic cholestasis. However, the clinical relevance of this observation, and further phenotypic characterization of the phenotype, is important. Herein, simultaneous loss of β-catenin and γ-catenin was identified in a subset of liver samples from patients of progressive familial intrahepatic cholestasis and primary sclerosing cholangitis. Hepatocytes in DKO mice exhibited defects in apical-basolateral localization of polarity proteins, impaired bile canaliculi formation, and loss of microvilli. Loss of polarity in DKO livers manifested as epithelial-mesenchymal transition, increased hepatocyte proliferation, and suppression of hepatocyte differentiation, which was associated with up-regulation of transforming growth factor-β signaling and repression of hepatocyte nuclear factor 4α expression and activity. In conclusion, concomitant loss of the two catenins in the liver may play a pathogenic role in subsets of cholangiopathies. The findings also support a previously unknown role of β-catenin and γ-catenin in the maintenance of hepatocyte polarity. Improved understanding of the regulation of hepatocyte polarization processes by β-catenin and γ-catenin may potentially benefit development of new therapies for cholestasis.

A hallmark of epithelial cells is polarization, which is achieved by the orchestration of external cues, such as cellular contact, extracellular matrix, signal transduction, growth factors, and spatial organization.¹ Hepatocytes in the liver show a unique polarity by forming several apical and basolateral poles within a cell.² The apical poles of adjacent hepatocytes form a continuous network of bile canaliculi into which bile is secreted, whereas the basolateral membrane domain forms the sinusoidal pole, which secretes various components, such as proteins or drugs, into the blood circulation.³ Loss of hepatic polarity has been associated with several cholestatic and developmental disorders, including progressive familial intrahepatic cholestasis (PFIC) and primary sclerosing cholangitis (PSC).^4,5 Although the molecular mechanisms governing hepatocyte polarity have been extensively studied in the in vitro systems, there is still a significant gap in our understanding of how polarity is established within the context of tissue during development or maintained during homeostasis.^6,7 Similarly, the molecular pathways contributing to hepatic polarity are not entirely understood, and a better comprehension of hepatic polarity regulation is thus warranted.Previous studies have confirmed the role of hepatocellular junctions, such as tight and gap junctions, in the maintenance of hepatocyte polarity.^8,9 Studies done in vitro and in vivo have shown that loss of junctional proteins, such as zonula occludens protein (ZO)-1, junctional adhesion molecule-A, and claudins, lead to impairment of polarity and distorted bile canaliculi formation.10, 11, 12, 13 In addition, proteins involved in tight junction assembly, such as liver kinase B1, are also involved in polarity maintenance.¹⁴ Among adherens junction proteins, various in vitro cell culture models have confirmed the role of E-cadherin in the regulation of hepatocyte polarity, possibly through its interaction with β-catenin.^15,16 However, there is a lack of an in vivo model to study the role of adherens junction proteins in hepatocyte polarity and their misexpression contributing to various liver diseases.β-Catenin plays diverse functions in the liver during development, regeneration, zonation, and tumorigenesis.17, 18, 19 The relative contribution of β-catenin as part of the adherens junction is challenging to study because like in other tissues, γ-catenin compensates for the β-catenin loss in the liver.^20,21 To address this redundancy, we previously reported a hepatocyte-specific β-catenin and γ-catenin double-knockout (DKO) mouse model was reported.²² Simultaneous deletion of β-catenin and γ-catenin in mice livers led to cholestasis, partially through the breach of cell-cell junctions. However, more comprehensive understanding of the molecular underpinnings of the phenotype is needed.In the current study, prior preclinical findings of dual β-catenin and γ-catenin loss were extended to a subset of PFIC and PSC patients. In vivo studies using the murine model with hepatocyte-specific dual loss of β-catenin and γ-catenin showed complete loss of hepatocyte polarity compared to the wild-type controls (CONs). Loss of polarity in DKO liver was accompanied by epithelial-mesenchymal transition (EMT), activation of transforming growth factor (TGF)-β signaling, and reduced expression of hepatocyte nuclear factor 4α (HNF4α). Our findings suggest that β-catenin and γ-catenin and in turn adherens junction integrity, are critical for the maintenance of hepatocyte polarity, and any perturbations in this process can contribute to the pathogenesis of cholestatic liver disease.     

Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children

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红细胞聚集增高与纤维蛋白原的关系及其对心绞痛患者发病的影响

目的 :探讨红细胞聚集改变与纤维蛋白原的关系及其对心绞痛发病的影响。方法 :测定 80例不稳定性心绞痛患者和 40例健康人的红细胞聚集指数 (光密度法 )、红细胞变形指数 (激光衍射法 )、血浆及全血粘度 (旋转式粘度计 )和纤维蛋白原 (双缩脲法 )。结果 :不稳定性心绞痛患者红细胞聚集指数和全血粘度 ( 4 0s- 1 )及纤维蛋白原浓度均高于对照组 (P均 <0 .0 1～ 0 .0 5 ) ,且红细胞聚集指数与纤维蛋白原呈直线正相关 ,与全血粘度 ( 4 0s- 1 )无相关性。结论 :纤维蛋白原含量增加是红细胞聚集增强的主要原因之一 ;红细胞聚集能力增强导致血液高粘滞 ,与心绞痛发作有关 ;选择 10s- 1 以下切变率测定低切全血粘度 ,利于观察全血粘度与红细胞聚集的关系     

757例体检人群血脂水平调查分析

目的 :了解“健康”体检人群不同年龄组的血脂水平。方法 :对75 7例体检人群的血清甘油三酯 (TG)、总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL C) ,按年龄分组 ,采用SPSS10 .0软件进行统计分析。结果 :2 0～ 2 9岁组的TG (1.2 8± 0 .63mmol/L)与 3 0～ 3 9岁组(1.5 6± 0 .78mmol/L)和 40～ 49岁组 (1.5 1± 0 .79mmol/L)均有显著性差异 (P <0 .0 1) ;其它各组间无显著性差异。 2 0～ 2 9岁组的TC (4 .5 8± 0 .88mmol/L)与 3 0～ 3 9岁组 (4 .97± 0 .97mmol/L)、40～ 49岁组 (5 .0 0± 1.0 3mmol/L)、5 0～ 5 9岁组 (5 .0 0± 1.0 4mmol/L)、60～ 69岁组 (5 .0 7± 0 .96mmol/L)均有显著性差异 (P <0 .0 1);其它各组间无显著性差异。HDL C水平 70～ 77岁组均显著高于其它各年龄组 ,而其它各年龄组间无统计学差异。TG ,TC ,HDL C的异常率分布在各年龄组间无统计学差异 (P >0 .0 5 )。结论 :75 7例体检人群血脂水平呈升高趋势 ,中青年人群更为明显 ,应当提倡文明饮食和健康的生活方式 ,加强健康教育     

脊髓损伤后神经修复过程中的细胞微环境北大核心

背景:以往的研究显示单一改变脊髓损伤区域某一基因表达或者某一细胞的状态,对脊髓损伤后功能恢复无显著影响,而大量证据表明调控脊髓损伤后紊乱的细胞微环境是神经功能恢复的关键因素。目的:对脊髓损伤前后细胞微环境的生物学特性,包括多种细胞之间的相互调控以及细胞外组分对损伤神经修复的作用和机制进行综述。方法:由第一作者检索PubMed及Web of Science数据库,英文检索词为“spinal cord injury,glial cell,neuron,immune cell,neural stem cell,extracellular matrix,cytokine,extracellular vesicle,regeneration”。文献检索的时间范围为2000年1月至2021年12月,最终筛选出64篇文献进行分析。结果与结论:①脊髓损伤后,在细胞微环境的细胞组分中,占比最高的胶质细胞间的相互作用,以及与神经元的相互调控作用最为关键。②在脊髓损伤后的细胞外组分中,利用生物相容性良好的水凝胶模仿天然细胞外基质,可有效模拟和重建损伤区域内的细胞微环境,促进轴突伸长。③在脊髓损伤后的细胞外调节因子中,促炎因子如肿瘤坏死因子α和白细胞介素1β等加剧了细胞微环境的炎症反应,应用受体抑制剂或阻断相关通路抑制上述促炎因子的表达是一种有效的治疗方法,同时在脊髓微环境中增加白细胞介素10等抗炎因子的表达,抑制损伤区域炎症发展的研究也陆续出现。④最近被重视起来的细胞外囊泡作为传递信息的载体在细胞微环境中也发挥了重要作用。⑤文章揭示了脊髓损伤后细胞微环境中的包括细胞组分和细胞外组分之间的多组相互调控关系,证实了细胞微环境中各组分之间所发挥的神经修复作用并不是孤立的。     

细胞内抗原免疫金银染色技术的改进

为解决细胞内抗原应用免疫金银法染色时背景过重的问题,建立了甘氨酸二次阻断的处理方法,效果较好。     

EB病毒感染与中线恶性网织细胞增多症

使用一个针对ＥＢ病毒编码的小分子ＲＮＡ（ＥＢＥＲ）的寡核苷酸探针对１９例中线恶性网织细胞增多症病变组织进行了原位杂交检测，并配合免疫表型分析。结果为：（１）本组病例中１８／１９例（９４．７％）的病变组织中的异形淋巴样细胞表达Ｔ细胞分化抗原。ＣＤ３阳性１５例，ＵＣＨＬ１阳性９例，其中二者均阳性６例，但各例中的异形淋巴样细胞均未表达Ｂ细胞及组织细胞分化抗原；（２）ＥＢＥＲ原位杂交检测的阳性数高（１５／