高血压病患者血清IGFⅡ的变化

目的 :探讨胰岛素样生长因子Ⅱ (IGFⅡ )与高血压病 (EH)以及与高血压伴左室肥厚 (EH伴LVH)的关系。方法 :采用放射免疫分析 10 0例未治疗的EH患者和 5 0例正常人血清IGFⅡ水平。并用彩色多普勒诊断仪测定 10 0例EH患者的左心室重量 (LVM )。结果 :EH患者血清IGFⅡ水平明显高于正常人[(0 6 6± 0 35 )ng/ml:(0 4 4± 0 14 )ng/ml,p <0 0 1],EH伴LVH者IGFⅡ高于EH非LVH者 [(0 82± 0 4 0 )ng/ml:(0 5 4± 0 2 0 )ng/ml,p <0 0 1]。结论 :EH患者IGFⅡ水平升高 ,其升高程度与病情密切相关 ,IGFⅡ可能参与了EH心肌肥厚的形成     

三种蚊唾腺蛋白IgE亲和成分的初步分析

从我国分布较广的三种蚊中华按蚊、淡色库蚊和白纹伊蚊中分离出唾液腺 ,制成唾腺蛋白粗提物 ,再应用ELISA、竞争抑制ELISA和免疫印迹试验分析其与IgE结合的组分。结果显示三种蚊唾腺蛋白含能与IgE结合的成分 ,以白纹伊蚊反应所呈现的A值最高 ;免疫印迹在三种蚊均显示 4条阳性带 ,中华按蚊和淡色库蚊相似 ,白纹伊蚊有 3条带差异 ,但其相对分子质量为 30 0 0 0～ 310 0 0组分阳性条带均出现于三种蚊唾腺蛋白     

Construction of a risk model of steroid-induced necrosis of the femoral head and prediction of potential Chinese medicine treatments北大核心

背景:随着疾病治疗模式的改变,人们已经意识到中医药在激素性股骨头坏死治疗过程中的重要性,因此利用生物信息学从分子水平分析激素性股骨头坏死的发病机制,构建疾病风险模型,并预测具有潜在治疗作用的中药,为后期中医药治疗激素性股骨头坏死提供一定的理论依据。目的:基于生物信息学挖掘激素性股骨头坏死的竞争性内源RNA(ceRNA)调控网络,分析其在激素性股骨头坏死中的分子调控机制,预测相关疾病靶点并构建疾病风险模型,同时预测具有潜在治疗作用的中药。方法:检索GEO数据库,下载激素性股骨头坏死的矩阵文件GSE123568和基因注释文件GPL15207。借助R语言等软件分析得到差异表达的长链非编码RNA与mRNA,并通过公共数据库预测与差异表达长链非编码RNA关联的miRNA-mRNA,再将预测到的mRNA与差异表达mRNA取交集,整合得到ceRNA网络。随后采用STRING数据库和Cytoscape软件筛选关键基因,利用R语言分析关键基因的功能与相关通路,并挖掘关键ceRNA网络。最后根据关键基因构建激素性股骨头坏死的风险模型,并进行中药预测。结果与结论:(1)与健康对照相比,激素性股骨头坏死患者共有7个长链非编码RNA和1763个mRNAs存在差异表达;(2)筛选出STAT3、KAT2B、AGO4、JAK2、JAK1、PTGS2共6个关键基因;(3)关键基因所富集的功能包括对肽激素的反应、白细胞介素6介导的信号通路、细胞对白细胞介素6的反应等生物学过程,涉及JAK-STAT、脂肪细胞因子、催乳素等信号通路;(4)4种mi RNAs(mi R-135a-5p、mi R-137、mi R-17-5p、miR-20b-5p)和2种长链非编码RNA(SNHG11、C20orf197)可能在导致激素性股骨头坏死发生发展过程中发挥关键作用;(5)KAT2B最有可能是激素性股骨头坏死发生发展的风险因子;(6)郁金、淫羊藿、黄芪具备治疗激素性股骨头坏死疾病靶点的可能。通过对激素性股骨头坏死相关长链非编码RNA介导的ceRNA网络进行分析,识别出潜在的疾病靶点、信号通路及潜在治疗中药,为进一步阐明其发病机制,并为后续的实验研究提供参考依据。     

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.     

青少年罪犯的人格障碍及人格特征研究

目的:了解青少年罪犯的人格障碍分布情况及人格特征,探讨进行人格矫正改造的重要性.方法:采用人格诊断问卷(PDQ-4 )对405名男性青少年犯人进行筛查,使用明尼苏达多相人格问卷(MMPI)进行人格特征调查,并与全国常模进行比较.结果:PDO-4 筛查结果示罪犯组12型人格障碍得分均显著高于对照,MMPI结果示罪犯组F、Hs、Hy、Pd、Pa、Pt、Sc、Ma等8个量表的均分显著高于对照.结论:青少年罪犯存在多种人格特征偏移正常,部分达人格障碍,需要及时矫正治疗.     

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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