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1.
Reactive oxygen species (ROS) are involved in the pathophysiology of fulminant hepatic failure. Therefore, we developed polyethylene glycol-conjugated bovine serum albumin with multiple reduced thiols (PEG-BSA-SH) for the treatment of fulminant hepatic failure. As a long-circulating ROS scavenger, PEG-BSA-SH effectively scavenged highly reactive oxygen species and hydrogen peroxide in buffer solution. PEG-BSA-SH showed a long circulation time in the plasma after intravenous injection into mice. Fulminant hepatic failure was induced by intraperitoneal injection of lipopolysaccharide and d-galactosamine (LPS/d-GalN) into mice. The LPS/d-GalN-induced elevation of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels was significantly inhibited by a bolus intravenous injection of PEG-BSA-SH. Furthermore, the changes in hepatic lipid peroxide and hepatic blood flow were effectively suppressed by PEG-BSA-SH. In contrast, l-cysteine, glutathione, and dithiothreitol, three traditional reduced thiols, had no statistically significant effects on the serum levels of ALT or AST. These findings indicate that PEG-BSA-SH is a promising ROS scavenger and useful in the treatment of fulminant hepatic failure.  相似文献   
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To assess the influence of unknown factors in endotoxemia, a conditioned medium, achieved by the stimulation of THP1 monocytes with lipopolysaccharide (LPS) [4 h], was used for the stimulation of human umbilical vein endothelial cells (HUVECs) [16 h]. SVEP1, KIAA0247, and SRPX2 were selected after microarray analysis. To study their possible functions, siRNAs of SVEP1, KIAA0247, or SRPX2 were used for the transfection of HUVECs and cells were stimulated with conditioned medium [16 h]. Inhibition of SVEP1 expression resulted in an increase of soluble intercellular adhesion molecule (sICAM) 1 (10%) and soluble E-selectin (sE-selectin) (19%). Inhibition of SRPX2 led to an increase of sICAM (11%) and sE-selectin (14%). KIAA0247 negative HUVECs showed a decrease in monocyte chemoattractant protein (MCP) 1 of 16%. SVEP1 and SRPX2 seemed to act as regulators of ICAM1 and E-selectin shedding and influence the expression of membrane bound adhesion molecules.  相似文献   
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目的:探讨降钙素原(PCT)与白细胞介素-6(IL-6)联合检测鉴别诊断ICU患者脓毒性和非脓毒性全身炎症反应综合征(SIRS)的临床价值。方法:选择2013年~2016年入住我院ICU的100例患者,包括61例非脓毒性SIRS患者与39例脓毒症患者,同时选择同期50例健康者作对照,分别设为非脓毒性组、脓毒血症组及对照组,采用电化学发光分析法检测三组血清PCT与IL-6水平,并以PCT为2μg/L和IL-6为50 ng/L为临界值来鉴别非感染性SIRS和脓毒血症,评价联合检测的临床诊断价值。结果:非脓毒性组PCT与IL-6最大值分别为0.91±0.54μg/L、62.77±11.75 ng/L,脓毒血症组为24.49±5.00μg/L、1542.69±361.66 ng/L,对照组为0.08±0.06μg/L、3.68±1.11 ng/L,非脓毒性组与脓毒血症组PCT与IL-6最大值均显著高于对照组(P0.05);与非脓毒性组比较,脓毒血症组PCT与IL-6均显著升高(P0.05)。非脓毒性组PCT2μg/L、IL-650 ng/L的占比分别为21.31%、65.57%,脓毒血症组为92.31%、87.18%,脓毒血症组PCT2μg/L、IL-650 ng/L的占比均显著提高于非脓毒性组(P0.05)。PCT的阳性预期值、灵敏度、特异度均显著高于IL-6,而联合检测的阳性预期值、特异度显著高于IL-6及PCT,联合检测的灵敏度显著高于IL-6,P均0.05。结论:PCT与IL-6联合检测有助于脓毒性和非脓毒性SIRS的鉴别诊断。  相似文献   
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ObjectiveLow levels of selenium (Se) and glutathione peroxidase (GSHPx), a key selenoenzyme, were documented in systemic inflammatory response syndrome (SIRS) and sepsis, both associated with high mortality. Se supplementation had mixed effects on outcome. We hypothesized that Se supplementation could have a different impact on biomarkers and 28-day mortality in patients with SIRS vs. sepsis.MethodsAdult patients with SIRS or sepsis were randomized to either high-dose (Se+, n = 75) or standard-dose (Se−, n = 75) Se supplementation. Plasma Se, whole blood GSHPx activity, C-reactive protein (CRP), procalcitonin (PCT), prealbumin, albumin and cholesterol levels were measured serially up to day 14.ResultsThere was no difference in mortality between Se− (24/75) vs. Se+ group (19/75; p = 0.367) or between SIRS and septic patients (8/26 vs. 35/124; p = 0.794). There was a trend to reduced mortality in SIRS patients in the Se+ vs. Se− group (p = 0.084). Plasma Se levels increased in the Se+ group only in patients with sepsis but not in patients with SIRS. Plasma Se levels correlated with GSHPx. In SIRS/Se+ group, Se correlated only with GSHPx. In SIRS/Se− group, Se correlated with cholesterol but not with other biomarkers. In sepsis patients, Se levels correlated with cholesterol, GSHPx and prealbumin. Cholesterol levels were higher in survivors in the Se− group.ConclusionsSe levels correlated with GSHPx activity and other nutritional biomarkers with significant differences between SIRS and sepsis groups. High-dose Se supplementation did not affect mortality but a strong trend to decreased mortality in SIRS patients warrants further studies in this population.  相似文献   
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目的:探讨血必净注射液对脓毒症早期肺组织损伤的影响及其可能作用机制,为临床脓毒症时急性肺损伤的治疗提供新思路。方法:选用健康雄性S-D大鼠30只,随机分3组,即假手术组(Sham组)、盐水组(NS组)和血必净组(XBJ组)。应用盲肠结扎穿孔法(CLP)建立脓毒症大鼠模型,术后6 h处死动物,通过HE染色光镜观察组织形态学改变及透射电镜观察肺组织超微结构,测定各组肺组织湿干重比,采用RT-PCR检测肺组织内皮素-1(ET-1)、诱导型一氧化氮合酶(iNOS)、基质金属蛋白酶-9(MMP-9)、组织金属蛋白酶抑制物-1(TIMP-1)mRNA的表达。结果:XBJ组肺泡及肺间质水肿和内皮细胞超微结构改变均较NS组明显减轻。术后6 h,NS组大鼠肺组织湿干重比(W/D)显著高于Sham组(5.37±0.12 vs 4.33±0.06,P0.01),XBJ组肺组织W/D较NS组显著降低(4.67±0.09 vs 5.37±0.12,P0.05)。此外,XBJ组大鼠肺组织ET-1(0.511±0.111 vs 0.705±0.122,P0.01)、iNOS(0.456±0.075 vs 0.548±0.098,P0.05),MMP-9(0.617±0.079 vs 0.732±0.131,P0.05)、TIMP-1(0.438±0.043vs 0.515±0.049,P0.01)mRNA的表达均较NS组明显降低,而NS组大鼠肺组织ET-1(0.705±0.122 vs 0.400±0.033,P0.01)、iNOS(0.548±0.098 vs 0.334±0.027,P0.01)、MMP-9(0.732±0.131 vs 0.352±0.061,P0.01)、TIMP-1mRNA(0.515±0.049 vs 0.365±0.068,P0.01)水平均较Sham组明显升高。结论:血必净治疗对脓毒症大鼠的肺组织损伤有一定的保护作用,可能与其降低肺组织ET-1、iNOS、MMP-9、TIMP-1的表达有关。  相似文献   
7.
Community-acquired pneumonia (CAP) is a major cause of sepsis. Despite several clinical trials targeting components of the inflammatory response, no specific treatment other than antimicrobial therapy has been approved. This argued for a deeper understanding of sepsis immunopathology, in particular factors that can modulate the host response. Small non-coding RNA, for example, micro (mi)RNA, have been established as important modifiers of cellular phenotypes. Notably, miRNAs are not exclusive to the intracellular milieu but have also been detected extracellular in the circulation with functional consequences. Here, we sought to determine shifts in circulatory small RNA levels of critically ill patients with CAP-associated sepsis and to determine the influence of clinical severity and causal pathogens on small RNA levels. Blood plasma was collected from 13 critically ill patients with sepsis caused by CAP on intensive care unit admission and from 5 non-infectious control participants. Plasma small RNA-sequencing identified significantly altered levels of primarily mature miRNAs in CAP relative to controls. Pathways analysis of high or low abundance miRNA identified various over-represented cellular biological pathways. Analysis of small RNA levels against common clinical severity and inflammatory parameters indices showed direct and indirect correlations. Additionally, variance of plasma small RNA levels in CAP patients may be explained, at least in part, by differences in causal pathogens. Small nuclear RNA levels were specifically altered in CAP due to Influenza infection in contrast to Streptococcus pneumoniae infection. Pathway analysis of plasma miRNA signatures unique to Influenza or Streptococcus pneumoniae infections showed enrichment for specific proteoglycan, cell cycle, and immunometabolic pathways.  相似文献   
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目的:探讨脓毒症患者血清肿瘤坏死因子受体相关因子(Tumor necrosis factor receptor-related factor,TRAF)-6、单核细胞趋化蛋白(Monocyte chemotactic protein,MCP)-1、可溶性髓样细胞触发受体(Soluble myeloid cell trigger receptor,s TREM)-1、白介素(Interleukin,IL)-33水平的变化及与病情严重程度及合并急性肾损伤(acute kidney injury, AKI)的相关性。方法:选择2014年2月到2018年7月在我医院ICU病房进行诊治的脓毒症患者145例,分析脓毒症相关性急性肾损伤(sepsis-associated AKI,SAKI)的发生情况,比较SAKI和非SAKI患者血清TRAF-6、MCP-1、s TREM-1、IL-33水平,采用Pearson相关分析血清TRAF-6、MCP-1、s TREM-1、IL-33含量与APACHEⅡ评分、SOFA评分的相关性,多因素logistic回归分析脓毒症患者发生SAKI的影响因素。结果:在145例患者中,发生SAKI者69例,发生率为47.6%。SAKI组患者的年龄、性别、原发病、白细胞(white blood cell,WBC)计数、C反应蛋白(C reactive protein,CRP)、降钙素原(procalcitonin,PCT)、体重指数、BUN、Scr与eGFR值与非SAKI组患者对比差异均无统计学意义(P0.05)。SAKI组患者APACHEⅡ评分、SOFA评分血清TRAF-6、MCP-1、s TREM-1、IL-33含水平含量均显著高于非SAKI组患者(P0.05)。Pearson相关性分析显示血清TRAF-6、MCP-1、s TREM-1、IL-33水平与SAKI患者的急性生理和慢性健康Ⅱ(acute physiology and chronic health evaluation II,APACHEⅡ)评分、序贯多器官功能障碍(sequential organ failure assessment,SOFA)评分均呈显著正相关性(P0.05)。logistic回归分析显示血清TRAF-6、MCP-1、s TREM-1、IL-33水平升高均为影响SAKI发生的独立危险因素(P0.05)。结论:血清TRAF-6、MCP-1、s TREM-1、IL-33水平与脓毒症严重程度显著相关,可能作为诊断和治疗SAKI的参考指标及干预靶点。  相似文献   
9.
目的:探究脓毒症急性肾损伤患者血液净化时机选择对治疗期间微循环系统的影响。方法:选取2016年2月~2017年2月期间来我院治疗的脓毒症急性肾损伤患者200例作为研究对象,依据急性肾损伤的诊断和分级(RIFLE)标准将脓毒症急性肾损伤患者分为1期(A组,n=56)、2期(B组,n=70)、3期(C组,n=74),所有患者皆采取连续性肾脏替代疗法。观察不同时期治疗前后微循环的变化。结果:三组脓毒症急性肾损伤患者在性别、年龄、空腹血糖浓度、急性生理功能和慢性健康状况(APACHE)评分、体温、心率指标上差异无统计学意义(P0.05);治疗后,A组患者微血管流动指数低于B组和C组,而灌注血管比例、灌注血管密度及总血管密度显著高于B组和C组(P0.05);A组患者血液流态积分、襻周状态积分、管襻形态积分及总积分显著低于B组和C组(P0.05),而襻顶血管直径显著大于B组和C组(P0.05)。结论:在RLFLE诊断标准1期对脓毒症急性肾损伤患者实施血液净化,可以明显地改善治疗效果,促进微循环系统的恢复。  相似文献   
10.
目的:探讨脓毒症患者血清TOLL样受体4(TLR4)、脂联素(APN)与炎症反应和病情严重程度的关系。方法:选取2016年12月到2018年4月期间在重庆市中医院接受治疗的脓毒症患者60例作为研究组,另选取同期本院健康体检者60例作为对照组。根据急性生理及慢性健康状况Ⅱ(APACHEⅡ)评分将脓毒症患者分为高分组17例(APACHEⅡ评分≥20分)和低分组43例(APACHEⅡ评分20分)。比较两组血清中的TLR4、APN、降钙素原(PCT)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)水平,比较高分组和低分组患者血清中的TLR4、APN及炎症因子水平,分析脓毒症患者TLR4、APN的表达与炎症因子、APACHEⅡ评分的相关性。结果:研究组血清中的TLR4、PCT、TNF-α、CRP水平均明显高于对照组,APN水平明显低于对照组(P0.05)。高分组患者血清中的TLR4、PCT、TNF-α、CRP水平明显高于低分组,APN水平明显低于低分组(P0.05)。脓毒症患者TLR4的表达与PCT、TNF-α、CRP、APACHEⅡ评分呈正相关,APN的表达与PCT、TNF-α、CRP、APACHEⅡ评分呈负相关(P0.05)。结论:脓毒症患者病情越严重,TLR4水平越高,而APN水平越低,TLR4、APN可能是通过调节炎症反应来影响脓毒症患者的疾病进展。  相似文献   
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