肾透明细胞癌CYP4A11、Ki-67表达及与患者临床病理特征的关系

目的 研究细胞色素P4504A11(CYP4A11)及Ki-67在肾透明细胞癌中的表达及相关性,并探讨其与患者临床病理特征的关系.方法 采用免疫组织化学染色方法检测我院2010—2015年收治的行肾癌切除术并经病理诊断的151例肾透明细胞癌组织中CYP4A11及Ki-67的表达情况,分析CYP4A11及Ki-67的表达...     

基于网络药理学和多中心临床数据的清肺承气汤治疗腹腔感染所致急性呼吸窘迫综合征的作用机制研究

目的 采用网络药理学和多中心临床数据探讨清肺承气汤治疗腹腔感染所致急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)的作用机制.方法 通过中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Dat...     

胸腔镜下肋骨固定在严重钝性胸部损伤合并血气胸中的效果观察

目的 探讨胸腔镜下肋骨固定在严重钝性胸部损伤合并血气胸中的效果。方法 选取200例严重钝性胸部损伤合并中量以上血气胸患者作为研究对象,按照患者意愿分为对照组和研究组,每组100例。对照组采用胸腔闭式引流处理血气胸同期行肋骨固定,研究组采用胸腔镜探查同期行肋骨固定。比较2组治疗前后肺功能、炎症因子水平、心率、呼吸频率、血氧饱和度、疼痛程度和治疗效果、术后并发症发生率。结果 治疗前,2组心率、肺功能指标、呼吸频率、血氧饱和度、疼痛程度和白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)水平比较,差异无统计学意义(P>0.05)。治疗后,2组血氧饱和度、IL-6、TNF-α、CRP水平高于治疗前,心率、呼吸频率、疼痛程度低于治疗前,差异有统计学意义(P<0.05)。治疗后,研究组肺功能指标水平、血氧饱和度高于对照组,心率、呼吸频率、疼痛程度、术后并发症发生率以及IL-6、NTF-α、CRP水平低于对照组,差异有统计学意义(P<0.05)。研究组治疗总有效率为98.00%,高于对照组的72.00%,差异有统计学意义(P<0.05)。结论 胸...     

囊肿塞在颌骨囊肿袋形术后引流中的应用

目的:介绍2种囊肿塞的设计和制作特点及其在囊肿袋形术后引流中的应用。方法:根据囊肿的部位和治疗要求不同,将囊肿塞分为常规型和义齿型,分别介绍制作步骤和注意事项。结果:依囊肿造口所在区域统计,43件囊肿塞用于磨牙区32件,前磨牙区7件,前牙区4件。常规型35件,义齿型8件。所有病例中,囊肿造口保持通畅,未发现与该装置应用有关的并发症。义齿型囊肿塞具有美学和功能效果。结论:卡环固位的囊肿塞适用于颌骨囊肿的引流,义齿型囊肿塞还可以暂时修复失牙。     

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury–repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300–β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.     

Dynamic Interactions of Post Cleaved NS2B Cofactor and NS3 Protease Identified by Integrative Structural Approaches

Diseases caused by flaviviruses such as dengue virus (DENV) and West Nile Virus (WNV), are a serious threat to public health. The flavivirus single-stranded RNA genome is translated into a polyprotein which is cleaved into three structural proteins and seven non-structural proteins by the viral and cellular proteases. Non-structural (NS) protein 3 is a multifunctional protein that has N-terminal protease and C-terminal helicase domains. The NS3 protease requires co-factor NS2B for enzymatic activity and folding. Due to its essential role in viral replication, NS2B-NS3 protease is an attractive target for antiviral drugs. Despite the availability of crystal structures, dynamic interactions of the N- and C-termini of NS2B co-factor have been elusive due to their flexible fold. In this study, we employ integrative structural approaches combined with biochemical assays to elucidate the dynamic interactions of the flexible DENV4 NS2B and NS3 N- and C-termini. We captured the crystal structure of self-cleaved DENV4 NS2B₄₇NS3 protease in post cleavage state. The intermediate conformation adopted in the reported structure can be targeted by allosteric inhibitors. Comparison of our new findings from DENV4 against previously studied ZIKV NS2B-NS3 proteins reveals differences in NS2B-NS3 function between the two viruses. No inhibition of protease activity was observed for unlinked DENV NS2B-NS3 in presence of the cleavage site while ZIKV NS2B-NS3 cleavage inhibits protease activity. Another difference is that binding of the NS2B C-terminus to DENV4 eNS2B₄₇NS3Pro active site is mediated via interactions with P4-P6 residues while for ZIKV, the binding of NS2B C-terminus to active site is mediated by P1-P3 residues. The mapping of NS2B N- and C-termini with NS3 indicates that these intermolecular interactions occur mainly on the beta-barrel 2 of the NS3 protease domain. Our integrative approach enables a comprehensive understanding of the folding and dynamic interactions of DENV NS3 protease and its cofactor NS2B.     

基质金属蛋白酶-1降解兔眼增殖性玻璃体视网膜病变增殖膜的实验研究

目的：评价基质金属蛋白酶-1（MMP-1）对增殖性玻璃体视网膜病变（PVR）增殖膜的降解作用。方法：健康成年有色家兔30只,用富含血小板血浆（PRP）诱导双眼PVR模型,各组玻璃体腔注入组织型纤溶酶原激活剂（t-PA）,15 min后注入MMP-1,行PVR分级评分,光镜观察视网膜结构。结果：注药后增殖膜发生较明显降解,各时间点PVR级别与对照组相比,差异有统计学意义（P〈0.01）。结论：一定剂量的MMP-1玻璃体腔注射能对实验性PVR的增殖膜产生降解作用。     

舒洛地特对糖尿病大鼠肾脏结构及功能的影响

目的 探讨舒洛地特对链脲佐菌素(STZ)诱导的糖尿病大鼠尿白蛋白排泄率(UAER)及肾脏结构的影响.方法 33只雄性SD大鼠随机分成正常对照组、糖尿病组及舒洛地特组,每组11只.糖尿病组和舒洛地特组在空腹10h后按65mg/kg一次性腹腔内注射STZ溶液,正常对照组注射等量生理盐水,72h后尾静脉血糖≥16.7mmol/L及尿糖≥且持续3d为造模成功.其中,糖尿病组成模9只,舒洛地特组成模10只.造模成功后,舒洛地特组给予10mg/(kg·d)舒洛地特灌胃,糖尿病组和正常对照组给予等量的生理盐水灌胃,疗程12周.用药结束后次晨测24h UAER,并在光镜、电镜下观察各组大鼠肾脏组织结构的病理变化.结果 糖尿病组的24h UAER明显高于正常对照组.舒洛地特组24h UAER高于对照组,但明显低于糖尿病组,差异有统计学意义(P<0.05).与对照组相比,在光镜和电镜下,糖尿病组大鼠肾脏组织表现出明显的病理结构改变,舒洛地特组肾脏病理改变则明显减轻.结论 舒洛地特可降低糖尿病大鼠UAER,明显减轻糖尿病大鼠的肾脏病理损害,从而起到肾脏保护作用.