Standardized lung recruitment during high frequency and conventional ventilation: similar pathophysiologic and inflammatory responses in an animal model of respiratory distress syndrome

Objective To evaluate standardized lung recruitment strategy during both high frequency oscillation (HFO) and volume-targeted conventional ventilation (CV+V) in spontaneously breathing piglets with surfactant washout on pathophysiologic and inflammatory responses.Design Prospective animal study.Setting Research laboratory.Subjects Twenty-four newborn piglets.Interventions We compared pressure support and synchronized intermittent mandatory ventilation, both with targeted tidal volumes, (PSV+V, SIMV+V) to HFO. Animals underwent saline lavage to produce lung injury, received artificial surfactant and were randomized to one of the three treatment groups (each n=8). After injury and surfactant replacement, lung volumes were recruited in all groups using a standard protocol. Ventilation continued for 6 h.Measurements and main results Arterial and central venous pressures, heart rates, blood pressure and arterial blood gases were continuously monitored. At baseline, post lung injury and 6 h we collected serum and bronchoalveolar lavage samples for proinflammatory cytokines: IL 6, IL 8 and TNF-, and performed static pressure-volume (P/V) curves. Lungs were fixed for morphometrics and histopathologic analysis. No physiologic differences were found. Analysis of P/V curves showed higher opening pressures after lung injury in the HFO group compared to the SIMV+V group (p<0.05); no differences persisted after treatment. We saw no differences in change in proinflammatory cytokine levels. Histopathology and morphometrics were similar. Mean airway pressure (P_aw) was highest in the HFO group compared to SIMV+V (p<0.002).Conclusions Using a standardized lung recruitment strategy in spontaneously breathing animals, CV+V produced equivalent pathophysiologic outcomes without an increase in proinflammatory cytokines when compared to HFO.This study was supported in part by a grant from the Research and Education Fund of Childrens Hospitals and Clinics–St. Paul, Minnesota. Dräger Babylog supplied by Dräger Critical Care Systems, Survanta provided by Ross laboratories.     

肝素类药物防治阿尔采末病的研究进展

本文分析了阿尔采末病(AD)的病理机制,对肝素类药物神经保护机制的进展进行了综述。阐明了肝素类药物可通过调节IP3受体介导的细胞内钙释放,影响淀粉样蛋白(Aβ)沉积及其毒性、调节tau蛋白的磷酸化状态,保护胆碱能神经元等发挥神经保护作用,从而延缓AD的发生与发展。     

Retinoic acid remodels extracellular matrix (ECM) of cultured human fetal palate mesenchymal cells (hFPMCs) through down-regulation of TGF-β/Smad signaling

The regulation of extracellular matrix (ECM) by retinoic acid (RA) is interesting in light of the fact that the ECM plays an essential role in morphogenesis and palatal shelf elevation. In the current study, we explored the effect of RA overexposure on ECM and the probable mechanisms in cultured human fetal palate mesenchymal cells (hFPMCs). RA dose-dependently inhibited cell proliferation and mRNA and protein levels of ECM components fibronectin, tenascin C and fibrillin-2. Zymography revealed that MMP-2 activity was suppressed by RA. Further analysis revealed that mRNA levels of MMP2 and TIMP2 were decreased, while the MMP2/TIMP2 mRNA ratio was increased, which might facilitate the ECM degradation. Because of the pivotal role of TGF-β/Smad pathway in palatogenesis we therefore checked the effect of RA on TGF-β/Smad signaling. The results indicated RA treatment increased Smad7 expression and decreased the levels of TGF-β1, TGF-β3, TGF-β type II receptor (TβRII) and phosphorylated Smad2 and Smad3. Activation of the Smad pathways by either exogenous TGF-β3 or recombinant adenoviruses for Smad3 attenuated RA-induced inhibition of cell proliferation and ECM components and rescued the RA-altered MMP2/TIMP2 mRNA ratio. In conclusion, these findings suggested that RA overexposure inhibited cell proliferation and disrupted the ECM network through down-regulation of TGF-β/Smad pathway.     

TGF-β对 AngⅡ调节人成纤维细胞 Toll 样受体2表达中的影响

目的：研究生长转化因子β（ transforming growth factor beta ,TGF-β）在血管紧张素Ⅱ（ AngiotensinⅡ,AngⅡ）对体外培养的人成纤维细胞（HT-1080）toll样受体2（toll like receptor 2,TLR2）调控中的作用。方法取处于对数生长期的成纤维细胞,分为5组：空白对照组、阴性对照组,AngⅡ刺激组、TGF-β刺激组、TGF-β抑制剂Decorin＋AngⅡ共刺激组。给药后采用实时定量PCR检测各组细胞内TLR2基因的表达量,并对各组结果进行统计分析。结果AngⅡ作用组中TLR2的表达量高于空白对照组（ P ＜0．05）;TGF-β组中低浓度（0．1、0．01μg/L）促进细胞内TLR2的表达,且表达量高于空白对照组,高浓度（1．0、10μg/L）抑制TLR2的表达,且表达量低于空白对照组（ P ＜0．05）;TGF-β抑制剂Decorin和AngⅡ联合作用组中TLR2的表达量高于空白对照组,且最高表达量高于其他各组（ P ＜0．05）。结论 AngⅡ能够上调HT-1080中TLR2的表达量;TGF-β高浓度时抑制HT-1080中TLR2表达量,低浓度时促进TLR2的表达;在TGF-β低浓度时可与AngⅡ协同促进HT-1080中TLR2的表达。     

亚低温联合促红细胞生成素治疗对重型颅脑创伤患者脑脊液β-淀粉样蛋白表达的影响

目的 研究亚低温治疗（MHT）联合促红细胞生成素（EPO）治疗对重型颅脑创伤（sTBI）患者脑脊液中β-淀粉样蛋白的影响.方法 将120例sTBI患者按随机数字表法将患者分为对照（常规治疗）组、MHT组、EPO组和MHT＋ EPO组,每组30例.对照组给予常规治疗,MHT组、EPO组、MHT ＋EPO组在对照组治疗的基础上,分别给予MHT（32 ～ 35℃并维持1～7d）、EPO（静脉注射75 ～ 100 IU/kg,每周3次）以及MHT＋ EPO进行相同疗程的治疗,采用酶联免疫吸附试验（ELISA）测定各组患者治疗前和治疗后第1、3、7天脑脊液中β-淀粉样蛋白水平变化,观察治疗前后颅内压、3个月后格拉斯哥昏迷量表（GCS）评分、6个月后格拉斯哥预后量表（GOS）评分以及远期生活质量评估量表（KPS）评分的变化.结果 治疗7d内各组患者均无丢失病例.治疗第1、3、7天后,MHT组、EPO组和MHT＋ EPO组颅内压值及其脑脊液β-淀粉样蛋白水平均明显降低,而MHT＋ EPO组患者颅内压和β-淀粉样蛋白水平较其他3组明显下降（P＜0.01）.3个月后,MHT＋ EPO组GCS评分明显高于其他3组[（11.1±1.4）分比（7.6±1.1）、（9.5±1.4）、（9.5±0.9）分]（P＜0.01）.6个月后,MHT＋ EPO组GOS评分[（4.3±0.7）分比（3.1 ±1.0）、（3.8±1.0）、（3.8±0.8）分]和KPS评分[（76±14）分比（54±11）、（63±16）、（64±13）分]也明显高于对照组、MHT组和EPO组（P＜0.01）.结论 亚低温联合EPO治疗能明显降低sTBI患者脑脊液β-淀粉样蛋白水平,改善患者神经功能及预后.     

Expression of interferon-alpha／beta receptor protein in liver of patients with hepatitis C virus-related chronic liver disease

ABM: To study the expression of interferon-alpha/beta (IFN-α/β) receptor protein in liver of patients with hepatitis C virus (HCV)-related chronic liver disease and its clinical significance. METHODS: A total of 181 patients with HCV-related chronic liver disease included 56 with HCV-related liver cirrhosis (LC) and 125 with chronic hepatitis C (CHC). CHC patients were treated with five megaunits of interferon-α1b six times weekly for the first 2 weeks and then every other day for 22 wk. The patients were divided into interferon (IFN) treatment-responsive and non-responsive groups, but 36 patients lost follow-up shortly after receiving the treatment. The expression of IFN-α/β receptor (IFN-α/βR) protein in liver of all patients was determined with immunofluorescence. RESULTS: In liver of patients with HCV-related chronic liver disease, the expression of IFN-α/βR protein in liver cell membrane was stronger than that in cytoplasm and more obvious in the surroundings of portal vein than in the surroundings of central vein. Moreover, it was poorly distributed in hepatic lobules. The weak positive, positive and strong positive expression of IFN-α/βR were 40% (50/125), 28% (35/125), 32% (40/125), respectively in CHC group, and 91.1% (51/56), 5.35% (3/56), and 3.56% (2/56), respectively in LC group. The positive and strong positive rates were higher in CHC group than in LC group (P<0.01). In IFN treatment responsive group, 27.8% (10/36) showed weak positive expression; 72.2% (26/36) showed positive or strong positive expression. In the non-responsive group, 71.7% (38/53) showed weak positive expression; 28.3% (15/53) showed positive or strong positive expression. The expression of IFN-α/βR protein in liver was more obvious in IFN treatment responsive group than in non-responsive group. CONCLUSION: Expression of IFN-α/βR protein in liver of patients with HCV-related chronic liver disease is likely involved in the response to IFN treatment.     

Smads在日本血吸虫病小鼠肝纤维化形成过程中的表达

目的　从转录水平研究参与转化生长因子β1(transforminggrowthfactor beta 1,TGF β1)信号传导的Smads分子在日本血吸虫病小鼠肝纤维化形成过程中的表达。　方法　以日本血吸虫尾蚴感染BALB/c小鼠形成肝纤维化动物模型,分别于感染后第 8、12、16和24周取小鼠肝组织 ,作病理学检测,观察肝纤维化程度,采用逆转录聚合酶链反应(RT PCR)的方法检测模型组和正常组小鼠肝组织中Smad2、Smad3、Smad4和Smad7的mRNA水平。　结果　Smad 2mRNA水平在感染12周后表达下降(P<0.05),16周后恢复正常,2 4周后再次下降(P<0.05)。Smad 3mRNA水平在感染后 16周开始明显升高 ,达正常水平的2倍(P<0.05)。Smad4和Smad7的mRNA水平在肝纤维化形成过程中与正常组比较无明显差异。　结论　Smad3促进肝纤维化形成。Smad2对肝纤维化形成具有双效性 ,即感染初期属于促进因子 ,感染后期属于抑制因子。     

同型半胱氨酸和β2撇蛋白检测在糖尿病肾病早期诊断中的意义

目的：探讨同型半胱氨酸和β2-微球蛋白检测技术在临床上早期诊断糖尿病肾病中的意义和价值。方法：选择2012年2月-2013年8月本院确诊的63例糖尿病肾病患者为观察组,选择同时期57例在本院进行健康体检者为对照组,采集血液样本后利用循环酶法和乳胶增强免疫比浊法,在全自动生化分析仪上分别对两组血液样本中同型半胱氨酸和β2-微球蛋白水平进行检测并比较,同时也对血清学指标尿素和肌酐含量进行了测定和比较。结果：观察组同型半胱氨酸、β2-微球蛋白、尿素和肌酐含量均明显高于对照组（t=29.5302、17.4914、44.8168、9.0717,P〈0.01）;处于糖尿病肾病Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期患者的同型半胱氨酸和β2-微球蛋白含量呈递增性增加;处于糖尿病肾病Ⅱ期、Ⅲ期和Ⅳ期患者的同型半胱氨酸和β2-微球蛋白含量明显高于糖病肾病Ⅰ期患者,差异均有统计学意义（t=8.5199、9.8964、15.3487,P〈0.01;t=3.0382、7.6056、7.0711,P〈0.01）。结论：联合检测患者同型半胱氨酸和β2-微球蛋白水平有助于糖尿病肾病的早期诊断,检测结果能够为临床上糖尿病肾病患者治疗提供参考依据,值得在临床上推广和应用。