PM2.5通过上调颗粒酶B促进IL-18表达加重肺部炎症

目的颗粒酶B促进组织炎症的作用日益引起重视,但其在PM_2.5导致的肺部炎症中是否发挥作用还不清楚,本文对在PM_2.5导致的肺部炎症中颗粒酶B的作用进行了研究。 方法第一步构建经气管滴注PM_2.5混悬液诱导大鼠肺部炎症的动物模型,实验分组为PBS组、PM_2.5(2 mg/kg)组、PM_2.5(6 mg/kg)组、PM_2.5(18 mg/kg)组。通过设置PM_2.5滴注剂量梯度,检测不同PM_2.5暴露剂量下大鼠肺组织颗粒酶B表达、病理和炎症评分,以探讨颗粒酶B表达水平与肺部炎症严重程度间有无相关性。第二步通过阻断颗粒酶B,探究在PM_2.5导致的肺部炎症中颗粒酶B是否发挥促进作用。第三步通过阻断IL-18,探究在PM_2.5导致的肺部炎症中颗粒酶B是否通过IL-18发挥作用。 结果随着PM_2.5滴注剂量升高,肺组织颗粒酶B表达增加,肺组织病理切片炎症细胞浸润和肺水肿程度加重,炎症评分增加,PM_2.5促进了肺组织颗粒酶B表达和肺部炎症;阻断颗粒酶B抑制了IL-18表达和NF-κB磷酸化,改善了PM_2.5导致的肺部炎症;阻断IL-18抑制了NF-κB磷酸化,改善了PM_2.5导致的肺部炎症。 结论PM_2.5通过上调颗粒酶B促进IL-18表达加重肺部炎症,其机制可能与激活NF-κB信号通路有关。     

A role of macrophage complement receptor CRIg in immune clearance and inflammation

Complement receptor of the immunoglobulin superfamily (CRIg), also referred to as Z39Ig and V-set and Ig domain-containing 4 (VSIG4), has recently been implicated in the clearance of systemic pathogens and autologous cells. CRIg is exclusively expressed on tissue resident macrophages and binds to multimers of C3b and iC3b that are covalently attached to particle surfaces. Next to functioning as an important clearance receptor, CRIg's extracellular domain inhibits complement activation through the alternative, but not the classical, pathway, providing a novel tool to selectively block this pathway in vivo. Here, we review a role for CRIg in immune clearance, T-cell responses and complement regulation, and discuss the implications for disease manifestation.     

EGFL7 as a novel therapeutic candidate regulates cell invasion and anoikis in colorectal cancer through PI3K/AKT signaling pathway

International Journal of Clinical Oncology - Anoikis is a form of apoptosis, which inhibits metastatic cascade and deprives cancer cells with invasive capacity. Epidermal growth factor-like...     

Safety but Limited Efficacy of Ensartinib in ROS1-Positive NSCLC: A Single-Arm,Multicenter Phase 2 Study

IntroductionSome ALK inhibitors with good inhibition of ROS1 in preclinical studies have been reported to be possibly beneficial in ROS1-positive NSCLC. In this work, we studied the efficacy and safety of ensartinib in the treatment of patients with ROS1-positive NSCLC.MethodsThe exploratory study was a phase 2, single-arm, multicenter design (NCT03608007). Patients with ROS1-positive NSCLC with a previous chemotherapy line number of less than or equal to 1 who received ensartinib at the dose of 225 mg once daily were enrolled. The primary end point was objective response rate evaluated by an investigator per Response Evaluation Criteria in Solid Tumors version 1.1.ResultsFrom June 2018 to July 2019, a total of 59 patients were enrolled at 23 centers in the People’s Republic of China. At the time of data cutoff, the median follow-up was 19.8 months (range: 0.8–22.5). The median objective response rate was 27.0 % (95 % confidence interval [CI]: 13.8–44.1) with 10 partial responses. Median duration of response was 4.8 months (95 % CI: 1.8–10.8). The median progression-free survival was 4.6 months (95 % CI: 4.0–6.4). The median overall survival was not estimable (95 % CI: 14.9–not estimable). Of four patients with brain metastases, intracranial disease control was reported in three (75.0 %, 95 % CI: 19.4–99.4). The most common treatment-related adverse events (TRAEs) were rash and liver enzyme abnormalities, with good prognosis after adjustment for dosage and concomitant medication. Most of the TRAEs were of grades 1 to 2, and incidence of grade greater than or equal to 3 TRAEs was 25.4 %.ConclusionsEnsartinib had a modest efficacy in patients with ROS1-positive NSCLC with an acceptable safety profile.     

凋亡相关基因 Bax、FasL、c - FLIP 在浆液性卵巢癌中的表达

目的:探讨凋亡相关基因Bax、Fas L、c-FLIP在浆液性卵巢癌中的表达及意义。方法:应用免疫组织化学SP法及实时定量PCR法检测卵巢浆液性囊腺瘤(16例)、交界性浆液性囊腺瘤(25例)、浆液性囊腺癌(48例)组织中Bax、Fas L、c-FLIP蛋白及mRNA的表达情况。结果:Bax、Fas L、c-FLIP在卵巢浆液性囊腺瘤组织的细胞浆中未见明显的棕黄色颗粒沉着,而在交界性浆液性囊腺瘤、浆液性囊腺癌组织的细胞浆中可见明显的棕黄色颗粒沉着,其中以浆液性囊腺癌阳性表达最高。与卵巢浆液性囊腺瘤组相比,交界性浆液性囊腺瘤、浆液性囊腺癌中Bax、Fas L、c-FLIP mRNA表达显著增高(P<0.05)。结论:Bax、Fas L、c-FLIP凋亡相关基因在卵巢癌中蛋白及mRNA的表达呈一致升高趋势,可能通过调控凋亡相关途径共同参与了卵巢癌的发生发展过程,为临床上卵巢癌防治提供新靶点。     

松质骨基质复合生物蛋白胶构建组织工程软骨的研究

目的尝试采用松质骨基质与生物蛋白胶复合材料构建组织工程软骨。方法体外培养大鼠软骨细胞,接种于松质骨基质／生物蛋白胶材料上行体外培养。采用HE、甲苯胺蓝染色免疫学检测、扫描电镜观察等方法观察所构建的组织工程软骨的特性。结果松质骨基质／生物蛋白胶组的组织学结构更接近于软骨样组织．其Ⅱ型胶原、蛋白多糖基因表达量及蛋白多糖含量明显高于松质骨基质组。结论松质骨基质／生物蛋白胶复合材料可用于构建组织工程软骨,是一种较理想的支架材料。     

现场干预在外科手术部位感染目标性监测中的作用

目的探讨现场干预对外科手术部位感染(SSI)目标性监测的作用,降低SSI发生率。方法采用干预性研究方法,对6种手术患者的手术部位感染及相关因素进行了目标性监测,对危险因素进行现场干预。结果共监测手术患者519例,SSI发生率为1.9%;手术部位感染与年龄、保温措施、ASA评分、住院天数、是否引流有关(P<0.05);其中保温措施、外科引流与手术部位感染有显著关系(P<0.01);经过现场干预,直肠、结肠手术及胆囊、胆管手术的手术部位感染率分别下降至7.1%及6.3%,单纯胆囊切除术下降至1.6%;甲状腺切除术及大隐静脉高位结扎术患者预防性抗菌药物使用率从100.0%降至<30.0%。结论术中低体温、引流、住院天数等是手术部位感染的高危因素,目标性监测中现场干预是控制这些高危因素的强有力措施。