Exosomes Derived from Glioma Cells under Hypoxia Promote Angiogenesis through Up-regulated Exosomal Connexin 43

Glioblastoma multiform (GBM) is a highly aggressive primary brain tumor. Exosomes derived from glioma cells under a hypoxic microenvironment play an important role in tumor biology including metastasis, angiogenesis and chemoresistance. However, the underlying mechanisms remain to be elucidated. In this study, we aimed to explore the role of connexin 43 on exosomal uptake and angiogenesis in glioma under hypoxia. U251 cells were exposed to 3% oxygen to achieve hypoxia, and the expression levels of HIF-1α and Cx43, involved in the colony formation and proliferation of cells were assessed. Exosomes were isolated by differential velocity centrifugation from U251 cells under normoxia and hypoxia (Nor-Exos and Hypo-Exos), respectively. Immunofluorescence staining, along with assays for CCK-8, tube formation and wound healing along with a transwell assay were conducted to profile exosomal uptake, proliferation, tube formation, migration and invasion of HUVECs, respectively. Our results revealed that Hypoxia significantly up-regulated the expression of HIF-1α in U251 cells as well as promoting proliferation and colony number. Hypoxia also increased the level of Cx43 in U251 cells and in the exosomes secreted. The uptake of Dio-stained Hypo-Exos by HUVECs was greater than that of Nor-Exos, and inhibition of Cx43 by ^37,43gap27 or lenti-Cx43-shRNA efficiently prevented the uptake of Hypo-Exos by recipient endothelial cells. In addition, the proliferation and total loops of HUVECs were remarkably increased at 24 h, 48 h, and 10 h after Hypo-Exos, respectively. Notably, ^37,43gap27, a specific Cx-mimetic peptide blocker of Cx37 and Cx43, efficiently alleviated Hypo-Exos-induced proliferation and tube formation by HUVECs. Finally, ^37,43gap27 also significantly attenuated Hypo-Exos-induced migration and invasion of HUVECs. These findings demonstrate that exosomal Cx43 contributes to glioma angiogenesis mediated by Hypo-Exos, and suggests that exosomal Cx43 might serve as a potential therapeutic target for glioblastoma.     

白塞综合征20例临床特征及心血管影像学分析

回顾性分析2018年1月—2020年8月首都医科大学附属北京安贞医院风湿免疫科治疗的白塞综合征患者20例的临床及影像学检查资料.20例患者中,男4例,女16例,平均年龄41.2岁,平均病程17.0年.超声、CT及MR检查发现心血管系统受累13例,主要表现为主动脉瓣脱垂并重度关闭不全,主动脉瘤、主动脉假性动脉瘤、主动脉溃...     

β-FIBRINOGEN PROMOTER-455 G／A （HaeⅢ） POLYMORPHISM PREDICTION OF PLASMA FIBRINOGEN BUT NOT OF ISCHEMIC CEREBROVASCULAR DISEASE

Objective The-455 G/A (HaeⅢ) polymorphism of β-fibrinogen gene influences levels of plasma fibrinogen. We further investigated whether it influences the risk of isehemie cerebrovaseular disease. Methods We accumulated 134 acute isehemic eerebrovaseular disease (ICVD) eases and compared their -455 G/A status with a control group (n=166). The β-fibrinogen gene -455 G/A polymorphism was analyzed for all subjects by PCR-RFLP with the restrictive enzyme HaeⅢ. Results Plasma fibrinogen was higher in AA homozygous participants (341mg/dL) than in participants carrying the G allele: GA (290mg/dL), GG (298mg/dL) in the control group. Plasma fibrinogen was also higher in AA homozygous patients (353mg/dL) than in eases carrying the G allele: GA (287mg/dL), GG (302mg/dL) in the ICVD group. However, there was no significant association between β-fibrinogen gene -455 G/A polymorphism and ICVD group. Conclusions Although a small effect cannot be excluded, β-fibrinogen gene -455 G/A polymorphism is an independent predictor of plasma fibrinogen, but not of isehemie cerebrovaacular disease.     

舒芬太尼对小鼠周围神经损伤后再生的影响

目的 评价舒芬太尼对小鼠单侧坐骨神经损伤后再生的影响.方法 选取健康Balb/c小鼠160只,制作单侧坐骨神经离断损伤模型.采用随机数字表法分为4组,即舒芬太尼高(H)、中(M)、低(L)剂量组和对照(B)组,H组腹腔注射舒芬太尼100 μg/(kg·d),M组50 μg/(kg·d),L组25 μg/(kg,d),B组腹腔注射0.2 ml生理盐水.连续给药7d.每组小鼠分别在给药后1、3、5d和1、2、4、8、12周8个时间点进行神经电生理测试,每个时间点每个剂量组5只小鼠.检测坐骨神经再生后神经的传导波幅及传导速度,再处死小鼠,取其坐骨神经损伤处上下0.5 cm的神经组织进行镀银染色,观察神经纤维的再生形态及免疫组化检测S-100蛋白的表达.结果 H组给药4、8、12周动作电位波幅分别为(5.13±0.20)、(24.36±0.13)、(26.17±0.44)mv,M组分别为(4.76±0.19)、(19.19±0.09)、(23.71±0.09)mv,与B组同时点[(1.99±0.18)、(13.78±0.11)、(17.90±0.66)mv]比较,差异均有统计学意义(P＜0.05).H组给药4、8、12周神经传导速度分别为(40.1±0.7)、(60.9±1.2)、(66.1±0.8)m/s,M组分别为(33.5±0.7)、(55.6±1.1)、(60.2±0.7)m/s,与B组同时点[(25.6±0.8)、(50.2±0.3)、(50.7±1.1)m/s]比较,差异均有统计学意义(P＜0.05).给药后8周镀银染色显示,H组的神经纤维排列较为整齐,很少有溶解现象;M组稍差,排列较整齐,有溶解现象;L组和B组的排列紊乱,多数神经纤维溶解.各剂量组损伤后S-100蛋白表达逐渐增加,到2周时达到高峰,然后逐渐下降.与B组比较,各时间点H、M组的S-100的表达均显著增加(P＜0.05).结论 舒芬太尼可以通过促进S-100的表达,促进周围神经损伤后的再生.     

必止咳胶囊制剂工艺研究

采用正交设计,以苦杏仁中指标成分苦杏仁甙的含量为指标,对必止咳胶囊的制剂工艺条件进行试验考察,优选出最佳生产工艺路线及提取工艺条件.     

Research on Dynamic Strength and Inertia Effect of Concrete Materials Based on Large-Diameter Split Hopkinson Pressure Bar Test

The Split Hopkinson Pressure Bar (SHPB) test device is an important tool to study the dynamic characteristics of concrete materials. Inertial effect is one of the main factors that cause inaccurate results in SHPB tests of concrete materials. To solve this problem, Large-diameter SHPB tests on concrete and mortar were performed. A dynamic increase factor (DIF) model considering strain rate effect and inertia effect was established. This model provides a scientific reference for studying the dynamic mechanical properties of concrete materials. The experimental results indicate that the strain rate effect of concrete is more sensitive than that of mortar, but the inertia effect of mortar is more sensitive than that of concrete. Under the same strain rate, the energy utilization rate, average fragment size, and impact potentiality of mortar are higher than concrete.     

用整形的观念处理烧伤创面

半个世纪以来,烧伤外科学的基础研究和临床治疗发展迅速,取得了质的飞跃.     

Pan‐risk factor for a comprehensive cardiovascular health management

Cardiovascular diseases (CVDs) have become the leading cause of death in China. CVDs are mainly caused by multiple well‐known modifiable risk factors that are affected by socioeconomic and environmental determinants, lifestyle and behavioral choices, and familial and genetic predispositions. With more risk factors proved to be associated with CVD occurrence, the concept “pan‐risk factor” is proposed in this review to indicate all discovered and yet‐to‐be‐discovered CVD risk factors for comprehensive primary prevention of CVD. Recognizing more factors and their roles in CVD development and progression is the first step in reducing the ever‐increasing burden of CVD. This review is an overview of the pan‐risk factor whose associations with CVD outcomes have been established. Along with the accumulation of scientific evidence, an increasing number of risk factors will be discovered and included in the list of pan‐risk factors.     

欧盟2008～2009年CAPs抽样及检验计划报告分析

目的 研究欧盟2008～2009年CAPs抽样及检验计划报告.方法 对欧盟CAPs抽样及检验计划的相关文献和2008、2009年检验报告进行研究与分析.结果与结论 欧盟CAPs抽样及检验计划已逐渐成熟,对我国有一定的参考借鉴价值.     

慢性间歇低氧致去卵巢小鼠动脉损伤及其与硫氧还蛋白-1的关系

目的 研究雌激素在慢性间歇低氧致血管损伤中的保护作用及其与硫氧还蛋白-1( Trx-1)的关系.方法 36只成熟雌性C57/BL6J小鼠随机分为去卵巢间歇低氧(OVI)组、假手术间歇低氧(SOI)组以及对照组;前两组给予间歇低氧,而对照组间歇给予空气.28 d后,观察小鼠子宫的大小与形态并称重;主动脉弓石蜡切片进行HE染色,光学显微镜观察血管形态并测量血管壁内中膜厚度(IMT);石蜡切片行免疫组化检测Trx-1蛋白表达水平;实时荧光定量PCR检测Trx-1的mRNA相对表达量.结果 HE可见对照组主动脉弓内皮光滑,平滑肌细胞排列较整齐,未见明显异常改变;SOI组可见内皮欠连续,局灶内皮细胞聚集,主动脉弓平滑肌纤维细胞排列紊乱、肥大以及平滑肌纤维样变;OVI组除可见SOI组小鼠的上述改变加重外,另可见血管局灶内膜明显增生以及外膜增厚等改变.对照组、SOI组及OVI组的IMT分别为(38.34±1.01) μm、(50.65±2.09)μm及(64.80+4.31)μm,三组间两两比较差异具有统计学意义(P＜0.01).SOI组(8.59±0.83)及OVI组(5.14±1.01)小鼠胸主动脉Trx-1mRNA相对表达量显著高于对照组(0.18±0.13),差异具有显著统计学意义(P＜0.001);对照组、SOI组及OVI组小鼠主动脉弓Trx-1蛋白表达的累积光密度分别为(0.84±0.10)×103、(6.60±0.45)×103及(2.76±0.28)×103,三组间两两比较差异均具有显著统计学意义(P＜0.001).结论 CIH可导致主动脉弓血管壁形态改变,去卵巢可加重CIH所致主动脉弓的损害,而Trx-1蛋白表达的降低可能参与了此过程.