CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

健脾消癌方通过PI3K/Akt信号通路抑制结肠癌血管生成的研究＊

目的 观察结肠癌HCT116细胞健脾消癌方的条件培养液对HUVEC细胞管腔形成的影响，从PI3K/Akt生物轴调控角度探讨其作用机制。方法 培养HCT116细胞，细胞设3组：对照组，健脾消癌方组（加入15%健脾消癌方含药血清）及人参皂苷Rg3组；制备HCT116细胞健脾消癌方条件培养液（分组及制备方法见实验方法），用条件培养液干预HUVEC（脐静脉内皮细胞，Human Umbilical Vein Endothelial Cells），Matrigel基质胶法检测HCT116细胞健脾消癌方条件培养液对HUVEC小管形成的影响。随后采用蛋白免疫印迹法（Western blot）检测各组HCT116细胞磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）、p-Akt、VEGF（血管内皮生长因子，Vascular endothelial growth factor）蛋白表达。最后在结肠癌HCT116荷瘤小鼠中验证健脾消癌方对肿瘤生长速度的影响，并经瘤组织VEGF蛋白表达、CD31免疫组化染色检测肿瘤内血管生成情况。结果 模型组HUVEC细胞管腔形成较空白血清组显著增加（P<0.05）；健脾消癌方组及人参皂苷Rg3组较模型组HUVEC细胞管腔形成显著减少（P<0.01）。p-Akt和VEGF蛋白表达水平模型组高于空白血清组（P<0.05），健脾消癌方组及人参皂苷Rg3组显著低于模型组（P<0.01）；PI3K、Akt蛋白表达量组间差异无统计学意义。与对照组比较，模型组荷瘤小鼠肿瘤体积显著性增大，瘤组织内VEGF表达、CD31阳性面积显著性增加，差异有统计学意义（P<0.05）；与模型组比较，健脾消癌方组及人参皂苷Rg3组荷瘤小鼠肿瘤体积显著减小，瘤组织内VEGF表达、CD31阳性面积降低，差异有统计学意义（P<0.05）。结论 健脾消癌方可抑制肿瘤的血管生成和生长，其作用机制可能与PI3K/Akt生物轴调控VEGF表达有关。     

The role of endoscopic ultrasound for portal hypertension in liver cirrhosis

Journal of Medical Ultrasonics - Chronic liver disease is still a major problem because disease progression will ultimately lead to liver cirrhosis. Portal hypertension is the hallmark in advanced...     

痛情绪相关神经递质及神经环路研究进展＊

痛情绪是指因疼痛引发的情绪和情感体验，是疾病过程中最常见的一种情绪。痛情绪相关神经机制非常复杂，但主要与单胺类神经递质、神经肽和某些神经环路有关，笔者将结合目前研究现状分别从以上两方面展开，就痛情绪相关单胺类神经递质和神经肽在受体分类、脑区通路、共疾病以及各神经递质之间的联系和痛情绪相关神经环路中各个蛋白的作用机制等方面进行探讨。