阻断局部肾素-血管紧张素-醛固酮系统不同环节对大鼠肺间质纤维化肿瘤坏死因子α表达的影响

目的:观察阻断肾素-血管紧张素-醛固酮系统不同环节对实验性肺纤维化大鼠肺组织肿瘤坏死因子α的影响。方法:实验于2005-08/2006-08在南华大学附属第一医院临床研究所及南华大学医学院组胚、生理实验室完成。取6周龄SD大鼠50只,随机分为正常对照组、模型组、卡托普利组、螺内酯组和氯沙坦组,每组10只。正常对照组气管内注入生理盐水,其他40只SD大鼠气管内注入博莱霉素5mg/kg复制肺纤维化模型。次日胃管内灌注血管紧张素转换酶抑制剂卡托普利60mg/kg(卡托普利组)、血管紧张素Ⅱ的Ⅰ型受体阻断剂氯沙坦10mg/kg(氯沙坦组)、醛固酮受体拮抗剂螺内酯100mg/kg(螺内酯组)、等量生理盐水(模型组和正常对照组),1次/d。各组动物均于给药后第28天处死,通过苏木精-伊红染色和Mallory染色观察肺组织病理变化,用免疫组织化学法和图像分析系统定量检测肺组织肿瘤坏死因子α的表达。结果:41只大鼠进入结果分析。①肿瘤坏死因子α蛋白表达:模型组高于正常对照组(166.82±4.14,61.44±1.94,P<0.01),卡托普利组、氯沙坦组、螺内酯组低于模型组(107.50±4.60,113.64±8.47,118.00±7.14,P<0.01),各用药组间无差异。②模型组肺泡炎程度、肺纤维化程度显著高于正常对照组(P<0.01,0.05),卡托普利组、氯沙坦组、螺内酯组较模型组好转(P<0.01),各用药组间无差异。结论:肺局部肾素-血管紧张素-醛固酮不同环节可能通过刺激肺部肿瘤坏死因子α表达而发挥致纤维化作用,阻断其不同环节可阻止肿瘤坏死因子α水平升高,抑制肺纤维化形成。     

Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia

Introduction  

This study sought to assess the prognostic value of the kinetics of procalcitonin (PCT), C-reactive protein (CRP) and clinical scores (clinical pulmonary infection score (CPIS), Sequential Organ Failure Assessment (SOFA)) in the outcome of ventilator-associated pneumonia (VAP) at an early time point, when adequacy of antimicrobial treatment is evaluated.     

1，1－二烷基－4－（3－溴丙酰基）－哌嗪溴化物的合成及生物活性研究

设计合成了七种新的１，１－二烷基－４－（３－溴丙酰基）哌嗪季铵盐溴化物，通过ＩＲ，￣１ＨＮＭＲ和元素分析证实其结构。初步生物活性试验结果表明，Ⅵａ，Ⅵｃ和Ⅵｅ～ｇ有明显的镇痛活性，Ⅵｅ～ｇ还有较好的抗氧化ＳＯＤ活性，但未发现有抗肿瘤作用。     

脑损伤后高血糖对大鼠血-脑屏障通透性的影响

目的 :研究脑损伤后高血糖对大鼠血 脑屏障通透性的影响。方法 :雄性Wistar大鼠 4 0只 ,随机分为 4组 :正常对照组 (Ⅰ组 ) ,高血糖组 (Ⅱ组 ) ,脑损伤后正常血糖组 (Ⅲ组 ) ,脑损伤后高血糖组 (Ⅳ组 )。应用流体冲击装置制作大鼠脑损伤模型 ,然后分别对高血糖及正常血糖组的血 脑屏障结构的损伤的标记物伊文蓝含量进行测定。结果 :在相同脑损伤的情况下 ,高血糖组的伊文蓝含量明显高于正常血糖组 (P <0 .0 1) ;同时以上 2组的伊文蓝含量均高于正常对照组及高血糖组 (无脑损伤组 ,P <0 .0 0 1) ;而正常对照组与高血糖组的伊文蓝含量无明显差异 (P >0 .0 5 )。结论 :脑损伤后高血糖使大鼠血 脑屏障通透性增高     

重度妊娠高血压综合征患者脑灌注压变化及其临床意义

目的 :通过检测重度妊娠高血压综合征 (妊高征 )脑灌注压变化 ,探讨脑灌注压变化与头痛症状的关系。方法 :选择重度妊高征 6 9例为实验组 ,正常晚期妊娠妇女 10 0例为对照组 ,采用Aaslid评估脑灌注压方法检测脑灌注压 ,评价妊高征患者脑灌注压变化及与头痛症状的关系。结果 :重度妊高征患者中异常脑灌注压患者明显多于正常脑灌注压患者 (P <0 .0 5 )。严重头痛和轻中度头痛患者脑灌注压均异常 ,且均以脑灌注压增高为多 (P<0 .0 5 )。在脑灌注压增高组中 ,严重头痛组脑灌注压明显高于轻中度头痛组 (P <0 .0 5 ) ;而在脑灌注压减低组中 ,严重头痛组脑灌注压又显著低于轻中度头痛组和无头痛症状组 (P <0 .0 5 )。 3组重度妊高征间平均动脉压比较无显著差异 (P >0 .0 5 )。无头痛症状组有脑灌注压正常和脑灌注压轻度降低 2种状态。结论 :高脑血流灌注状态和低脑血流灌注状态均可导致妊高征脑损害。高脑灌注压和低脑灌注压均是妊高征患者头痛发生的病理生理机制。高脑灌注压是妊高征头痛症状的主要原因 ,高脑灌注压患者更有发生子痫的危险     

A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function

Dietary protein restriction has been reported to delay the need for renal replacement therapy in clinical trials and meta-analyses. However, less clear is what effect dietary protein has on the rate of decline in renal function. We pooled the results of 13 randomized controlled trials (n = 1,919 patients) and found that dietary protein restriction reduced the rate of decline in estimated glomerular filtration rate by only 0.53 mL/min/yr (95% confidence interval [CI], 0.08 to 0.98 mL/min/yr). We also used weighted regression analysis to determine the reasons for the differences in the results of these 13 randomized trials along with 11 other nonrandomized controlled trials (n = 2,248 patients). The effect of dietary protein restriction (glomerular filtration rate decline in treatment minus control) was substantially less in randomized versus nonrandomized trials (regression coefficient, -5.2 mL/min/yr; 95% CI, -7.8 to -2.5 mL/min/yr; P < 0.05) and relatively greater among diabetic versus nondiabetic patients (5.4 mL/min/yr; 95% CI, 0.3 to 10.5 mL/min/yr; P < 0.05), while there was a trend toward a greater effect with each additional year of follow-up (2.1 mL/min/yr; 95% CI, -0.05 to 4.2 mL/min/yr; P = NS). However, the number of diabetic patients studied was small and the duration of follow-up was short in most trials. No other patient or study characteristics altered the effect of dietary protein restriction on the rate of decline in renal function. Thus, although dietary protein restriction retards the rate of renal function decline, the relatively weak magnitude of this effect suggests that better therapies are needed to slow the rate of renal disease progression.     

Autophagy contributes to BMP type 2 receptor degradation and development of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is characterised by an increase in mean pulmonary arterial pressure which almost invariably leads to right heart failure and premature death. More than 70% of familial PAH and 20% of idiopathic PAH patients carry heterozygous mutations in the bone morphogenetic protein (BMP) type 2 receptor (BMPR2). However, the incomplete penetrance of BMPR2 mutations suggests that other genetic and environmental factors contribute to the disease. In the current study, we investigate the contribution of autophagy in the degradation of BMPR2 in pulmonary vascular cells. We demonstrate that endogenous BMPR2 is degraded through the lysosome in primary human pulmonary artery endothelial (PAECs) and smooth muscle cells (PASMCs): two cell types that play a key role in the pathology of the disease. By means of an elegant HaloTag system, we show that a block in lysosomal degradation leads to increased levels of BMPR2 at the plasma membrane. In addition, pharmacological or genetic manipulations of autophagy allow us to conclude that autophagy activation contributes to BMPR2 degradation. It has to be further investigated whether the role of autophagy in the degradation of BMPR2 is direct or through the modulation of the endocytic pathway. Interestingly, using an iPSC-derived endothelial cell model, our findings indicate that BMPR2 heterozygosity alone is sufficient to cause an increased autophagic flux. Besides BMPR2 heterozygosity, pro-inflammatory cytokines also contribute to an augmented autophagy in lung vascular cells. Furthermore, we demonstrate an increase in microtubule-associated protein 1 light chain 3 beta (MAP1LC3B) levels in lung sections from PAH induced in rats. Accordingly, pulmonary microvascular endothelial cells (MVECs) from end-stage idiopathic PAH patients present an elevated autophagic flux. Our findings support a model in which an increased autophagic flux in PAH patients contributes to a greater decrease in BMPR2 levels. Altogether, this study sheds light on the basic mechanisms of BMPR2 degradation and highlights a crucial role for autophagy in PAH. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

生物黏附材料壳聚糖的黏附性能

目的:考察壳聚糖与黏蛋白的相互作用,评价壳聚糖黏附性能的影响因素。方法:于2006-07/12在中国科学院大连化学物理研究所生物医用材料工程实验室完成。将壳聚糖溶液与黏蛋白溶液混合,用紫外分光光度计测定溶液混合前后紫外吸收值的变化,表征壳聚糖的黏附性能。①调节反应溶液的pH值(1.0,3.0,5.0),考察环境pH对壳聚糖黏附性能的影响。②改变反应温度(4,25,37℃),考察环境温度对壳聚糖黏附性能的影响。③选择不同相对分子质量(48000,124000,230000)的壳聚糖,考察壳聚糖相对分子质量对其黏附性能的影响。④选择不同脱乙酰度(56%,67%,97%)的壳聚糖,考察壳聚糖脱乙酰度对其黏附性能的影响。⑤使用不同种类(I-S型及Ⅲ型)黏蛋白,考察黏蛋白中唾液酸含量对壳聚糖黏附性能的影响。结果:①环境介质pH由1.2升至5.0时,壳聚糖黏附性能随之显著升高。②壳聚糖黏附性能随着温度的升高而显著增强。③壳聚糖相对分子质量对于壳聚糖黏附无显著影响。④壳聚糖脱乙酰度增加,其黏附性能显著增强。⑤I-S型黏蛋白与壳聚糖的作用较之Ⅲ型黏蛋白与壳聚糖的相互作用明显增强。结论:壳聚糖的黏附受环境pH、温度、壳聚糖及黏蛋白两种分子电荷密度的显著影响;在酸性环境下增大环境pH值、升高环境温度、增加壳聚糖的脱乙酰度和增加黏蛋白中唾液酸的含量,均有利于壳聚糖的黏附。     

Enterobacter cloacae causing pneumatocele in a neonate

Pneumatocele formation, a cyst-like rarefaction that develops within the lung parenchyma, is an unusual complication of pneumonia in the neonate. It has been reported to occur with Staphlococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae , and Pseudomonas aeruginosa infections. We describe a case of a premature neonate with pneumonia and subsequent pneumatocele formation caused by Enterobacter cloacae     

HM-PAO非对映立体异构体的核磁共振鉴定及立体异构纯度的测定

本文报道外消旋和内消旋六甲基丙二胺肟(HM-PAO)在一些常见溶剂中的¹H和¹³C化学位移。利用它们的¹³CNMR谱或氯仿中的¹HNMR谱,可以方便地鉴定这两个性质非常近似的非对映立体异构体。研究结果还表明,利用常规的全去偶¹³CNMR谱可以测定外消旋体在这两种异构体混合物中的立体异构纯度。