Sublytic C5b-9 complexes induce proliferative changes of glomerular mesangial cells in rat Thy-1 nephritis through TRAF6-mediated PI3K-dependent Akt1 activation

The proliferation of glomerular mesangial cells (GMCs) and secretion of extracellular matrix (ECM) in rat Thy-1 nephritis (Thy-1N), resembling human mesangioproliferative glomerulonephritis (MsPGN), have been studied for many years, but the mechanisms, especially the role of signalling pathway activation and its regulation in GMCs triggered by sublytic C5b-9 complexes in Thy-1N rats remain largely unclear. In the study, the proliferation of GMCs and production of ECM as well as the role of PI3K/Akt and its regulation, both in GMCs induced by sublytic C5b-9 (in vitro) and in the renal tissues of rats with Thy-1N (in vivo), were determined and the results revealed that GMCs proliferation and ECM secretion, both in vitro and in vivo, were notably increased, and that PI3K/Akt1 activation and its regulation, such as TNF receptor-associated factor 6 (TRAF6)-mediated Akt1 ubiquitination and PI3K-dependent Akt1 phosphorylation, were involved in the process of Thy-1N induction. On the other hand, silence of the TRAF6, PI3K or Akt1 genes could obviously diminish the proliferative damages and urinary protein secretion of Thy-1N rats. Together, these data implicated that sublytic C5b-9 complexes in Thy-1N rats could promote GMCs proliferation and ECM production through TRAF6-mediated PI3K-dependent Akt1 activation, in which the ubiquitination and phosphorylation of the Akt1 signal molecule played an important role in the initiation and development of the proliferative changes in the rats with Thy-1N.     

外科肺活检诊断弥漫性实质性肺疾病的临床分析

目的评价外科肺活检诊断弥漫性实质性肺疾病的有效性和安全性。 方法回顾性分析南京鼓楼医院呼吸与危重症医学科2006年1月至2018年9月54例行外科肺活检的弥漫性实质性肺疾病患者的临床资料。 结果54例患者中,37例接受了电视辅助胸腔镜手术,17例接受了开胸肺活检,术后最常见的病理诊断是机化性肺炎,48例(88.9%)患者术后获得明确的诊断,术后38例(70.4%)患者根据诊断结果调整了治疗方案。术前接受小创伤肺活检未明确诊断的患者,接受外科肺活检后96%确诊。按术后有无并发症分为并发症组和无并发症二组。15例(27.8%)患者术后出现并发症,其中9例(16.7%)气胸,5例(9.3%)肺部感染,3例(5.6%)脱机困难,3例(5.6%)呼吸衰竭,1例(1.9%)术后再次插管,1例(1.9%)术后出血,1例(1.9%)进行气管切开。术后30 d病死率为1.9%,死亡原因主要是呼吸衰竭。术后并发症组和无并发症组在性别、年龄、FVC% pre、FEV₁%pre、DLCO% pre、术前PaO₂、术前激素使用情况和手术方式之间的差异没有统计学意义(P>0.05)。 结论对于结合临床病史、胸部高分辨率CT、实验室检查及小创伤肺活检资料仍诊断不明的弥漫性实质性肺疾病的患者,外科肺活检可作为最后一项有意义的检查方法,其诊断率为88.9%。外科肺活检是一项相对安全且可靠的诊断弥漫性实质性肺疾病的手段,但基础情况较差的患者,术后出现并发症的可能性较高,此类患者应尽量避免外科肺活检。     

通腑泻肺方对ALI/ARDS大鼠肺肠功能的影响

目的:观察通腑泻肺方对ALI/ARDS大鼠肺、肠功能的影响,为"肺与大肠相表里"理论提供实验证据。方法:健康SD大鼠30只,随机分为3组,正常组、模型组和治疗组,采用尾静脉注射油酸加内毒素方法造成ALI/ARDS模型,治疗组给予通腑泻肺中药,于实验第7天检测分析各组大鼠肺功能、肠屏障功能指标。结果:1)与正常组比较,模型组大鼠肺顺应性显著降低、吸气和呼气阻力显著升高(P0.01),治疗后肺顺应性、吸气阻力有所改善;2)模型组大鼠肠组织中ocdudin蛋白表达较正常组明显降低(P0.01),治疗后显著升高(P0.05);SIgA含量较正常组明显升高(P0.01),治疗后显著降低(P0.05)。结论:除肺通气功能障碍外,ALI/ARDS大鼠肠屏障功能同时受损。通腑泻肺中药能改善肺通气障碍,保护肠黏膜屏障功能。     

ARDS“肺肠同病”的病理特征与通腑泻肺中药作用机制的实验研究

目的:在"肺与大肠相表里"理论指导下,观察ARDS"肺肠同病"的病理特征及通腑泻肺中药的作用机制,为"肺肠同病"的临床治疗提供实验依据。方法:健康wistar大鼠30只,随机分为3组,正常组、模型组和治疗组,采用尾静脉注射油酸加内毒素方法造成ARDS模型,治疗组给予通腑泻肺中药,于实验第7天检测分析各组大鼠肺功能、肺脏局部及全身炎症因子、肠黏膜屏障功能及肺肠组织黏膜免疫等指标。结果:1)与正常组比较,模型组大鼠肺顺应性显著降低、吸气和呼气阻力显著升高(P0.01),治疗后肺顺应性、吸气阻力有所改善。2)模型组大鼠血浆D-乳酸、DAO含量较正常组明显升高(P0.01)。治疗后二者含量显著降低(P0.01)。3)模型组大鼠血清及BALF中TNF-α、IL-1β、IL-6、IL-10含量较正常组均明显升高(P0.01)。治疗后血清TNF-α、IL-1β含量明显降低(P0.01),BALF中TNF-α、IL-1β和IL-6含量明显降低(P0.01)。4)模型组大鼠肺与肠组织SIgA含量较正常组明显升高(P0.01),治疗后显著降低(P0.05)。结论:1)肺通气功能障碍、肠黏膜屏障功能受损、全身及肺脏局部炎症反应水平明显升高、肺肠组织黏膜免疫的同步反应是ARDS"肺肠同病"的主要病理特征;2)通腑泻肺中药具有肯定的疗效,其作用机制在于改善肺通气和肠黏膜屏障功能、调节炎性因子表达及肺肠黏膜免疫应答。     

Oxygen-enhanced magnetic resonance imaging of the brain: a rodent model

Oxygen-enhanced MRI has been shown to be a viable alternative to hyperpolarized gases for pulmonary imaging. The changes in the relaxation times due to hyperoxic conditions in the blood pool induced by inhalation of pure oxygen have produced sufficient signal changes for imaging applications. This is a safe and low-cost alternative for contrast-enhanced imaging. The application of oxygen-enhanced MRI in brain imaging has been much less studied. In this study, we investigated the changes in the relaxation times in the brain due to inhalation of pure oxygen in a rodent model. We also assessed the effects of reduced blood flow due to hyperoxic conditions. Despite the reduced blood flow, significant changes in T1, T2, and T2* relaxation times were detected. We conclude that oxygen-enhanced MRI can be used in rodent models of disease.     

A task-based analysis of machinery entanglement injuries among Western Canadian farmers

Machinery entanglements are a leading cause of hospitalized injury on Canadian farms. This study evaluates the role farm tasks play in the occurrence of machinery entanglement events. A retrospective case series of 41 entanglement injuries involving 35 farm-machinery types was assembled. Only a few limited tasks were implicated in the majority of entanglements. These tasks were as follows: (1) field adjustments of machinery; (2) product handling and conveyance; and (3) driveline attachments and servicing. Hazards inherent and common to these tasks affected the behavior of farmers, leading to entanglements. This study establishes a need to identify hazards and assess risks associated with different tasks involving the use of farm machinery under actual field situations. Systemic changes are required to improve existing machinery safety practices through engineering, work methods, and work practice modifications. In addition to design solutions, occupational health and safety strategies should consider activities associated with hazardous situations to inform the content of injury prevention efforts.     

有创机械通气重症肺炎患儿的临床特征及死亡危险因素分析

目的 探讨有创机械通气重症肺炎患儿的临床特征及死亡患儿的危险因素.方法 采用回顾性研究,收集2011年1月至2014年12月因需有创机械通气入住天津市儿童医院PICU的重症肺炎患儿资料,分析其年龄分布、病原学特点、机械通气情况、并发症及基础疾病情况,对死亡相关因素进行单因素分析及多因素分析.结果 共214例患儿符合标准纳入研究,其中男134例,女80例,总病死率6.17%.病原学检出率16.36%.死亡组患儿中位年龄大于生存组(4个月比2个月,P=0.039),年龄超过1岁患儿所占比例更高(21.43%比15.8%,P<0.001).脑病和电解质紊乱是有创机械通气重症肺炎患儿常见并发症,构成比分别为11.68%和8.41%.贫血、心脏病、呼吸系统发育异常位列基础疾病前3位(29.91%、14.49%、9.35%).Logistic多元回归分析显示,患儿发病年龄大于1岁(OR值1.019,95%CI 1.003~1.030,P=0.019),合并急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)(OR值7.254,95%CI 1.581~33.277,P=0.011),患有心脏病(OR值0.47,95%CI 0.273~0.810,P=0.007)是有创机械通气重症肺炎患儿死亡的危险因素. 结论 在救治需有创通气重症肺炎患儿时,对于年龄大于1岁、合并ARDS或患有心脏病的患儿要加强监护,积极治疗原发病,防治ARDS,必要时可行心脏手术以改善预后,降低需有创通气重症肺炎患儿的病死率.     

GCN5调控sublytic C5b⁃9诱导大鼠肾小球系膜细胞表达Cyclin D1及致SOX9的乙酰化修饰

目的：探讨GCN5调控sublytic C5b?9刺激大鼠肾小球系膜细胞（glomerular mesangial cell,GMC）诱导Cyclin D1基因表达以及GCN5乙酰化修饰SOX9转录因子的作用。方法：先用Western blot检测Thy?1肾炎（Thy?1 nephritis,Thy?1N）大鼠的肾组织和sublytic C5b?9 刺激的GMC中GCN5、SOX9和Cyclin D1的表达。然后分别将pIRES2?GCN5过表达和shGCN5小干扰质粒或将这些质粒与Cyclin D1启动子质粒行不同组合转染GMC,用荧光素酶报告基因实验和real?time PCR、Western blot检测过表达或沉默GCN5后对Cyclin D1表达的影响。同时用免疫共沉淀（Co?IP）和Western blot检测sublytic C5b?9刺激或分别转染GCN5过表达和酶活性突变质粒（ΔGCN5）的GMC中SOX9的乙酰化修饰。结果：Thy?1N大鼠肾组织和sublytic C5b?9刺激的GMC中GCN5、SOX9、Cyclin D1蛋白水平均明显上调,而过表达GCN5基因能上调Cyclin D1的启动子活性、mRNA和蛋白表达;敲低GCN5表达则得到了相反的结果。此外,sublytic C5b?9刺激和过表达GCN5基因促进了SOX9的乙酰化修饰,而沉默GCN5后则降低了SOX9的乙酰化水平。结论：GCN5可上调GMC中Cyclin D1的表达,并促进SOX9的乙酰化修饰。     

幽门螺杆菌感染与慢性荨麻疹相关性研究

目的 探究幽门螺杆菌感染(Helicobacter pylori,Hp)与慢性荨麻疹(chronic urticaria,CU)相关性,为CU患者提供更有效的诊疗策略.方法 选取2015年6月至2017年12月在柳州市人民医院皮肤科门诊确诊慢性荨麻疹患者290例作为实验组,另选取本院健康体检者310名作为对照组.应用14C呼气试验检测实验组和对照组Hp感染情况,将慢性荨麻疹Hp阳性患者113例分为A(n=55)、B(n=58)两组,A组行常规治疗荨麻疹方案,B组在A组基础上联合抗Hp标准四联疗法治疗,比较实验组和对照组Hp检测结果,比较A组和B组临床疗效.结果 实验组阳性率为39.0％,明显高于对照组的29.7％,差异有统计学意义(P<0.05);B组治疗总有效率为67.2％,高于A组的47.3％,差异具有统计学意义(P<0.05).结论 Hp感染与慢性荨麻疹有一定相关性,针对Hp的检测和治疗可为慢性荨麻疹患者的临床诊疗提供重要参考.