小儿脓毒血症血清NT-proBNP、CRP、IL-10及TNF-α水平变化及其与预后的关系

［摘要］ 目的分析小儿脓毒血症血清氨基末端脑钠肽前体（N-terminal pro-brain natriuretic peptide,NT-proBNP）、C反应蛋白（C-reactive protein,CRP）、白细胞介素10（interleukin-10,IL-10）及肿瘤坏死因子α（tumor necrosis factor-α,TNF-α）水平变化及其与预后的关系。 方法选取脓毒症患儿80例（观察组）及同期健康体检儿童30例（对照组）,比较2组入院5 d内血清NT-proBNP、CRP、IL-10及TNF-α水平,分析不同病情脓毒症患儿上述指标,依据脓毒症患儿28 d预后情况将其分为预后良好组、预后不良组,对比其入院5 d内平均血清NT-proBNP、CRP、IL-10及TNF-α水平,分析NT-proBNP、CRP、IL-10及TNF-α水平对小儿脓毒症死亡的预测价值。 结果观察组入院第1 天至第5 天血清NT-proBNP、CRP及TNF-α水平呈先升高后降低趋势,而IL-10呈先降低后升高趋势,且观察组第1 d血清NT-proBNP、CRP及TNF-α水平高于对照组,而IL-10水平低于对照组（P＜0.05）;脓毒症休克患儿入院5 d内平均NT-proBNP、CRP及TNF-α高于一般脓毒症、严重脓毒症患儿,而IL-10低于一般脓毒症、严重脓毒症患儿（P＜0.05）;预后良好组入院5 d内平均NT-proBNP、CRP及TNF-α水平低于预后不良组,而IL-10高于预后不良组（P＜0.05）;NT-proBNP预测脓毒症患儿死亡的ROC曲线下面积为0868,大于CRP、IL-10及TNF-α。 结论脓毒症患儿入院5 d内NT-proBNP、CRP、IL-10及TNF-α水平发生明显变化,且与预后有密切关系,应加以监测。     

乌司他丁联合丹红注射液对脓毒症患者的疗效以及对sTREM-1、HBP水平及th17/treg的影响

目的乌司他丁联合丹红注射液对脓毒症患者的疗效以及对可溶性髓样细胞触发受体1(soluble triggering receptor exprssed on myeloid cells 1,sTREM-1）、肝素结合蛋白（heparin-bindingprotein,HBP）水平和辅助性T细胞17(T help cell 17,Th17)/调节性T细胞(T regular cell,Treg)的影响。 方法选取脓毒症患者120例,根据随机数字表法分为对照组和观察组各60例。对照组采用常规方式联合乌司他丁治疗,观察组在对照组基础上注射丹红注射液。比较两组治疗后的临床疗效,治疗前后急性生理学与慢性健康状况（Acute Physiology And Chronic Health Evaluation Ⅱ,APACHEⅡ）评分、血清HBP和sTREM-1水平、T细胞亚群、凝血功能指标及不良反应情况。 结果治疗7 d后,观察组有效率为90.00%（54/60）,明显高于对照组75.00%（45/60）,差异有统计学意义(χ2=4.490,P=0.034)。两组APACHEⅡ评分组间、时点间和组间·时点间比较差异均有统计学意义（P＜0.05）。治疗后,两组血清HBP和sTREM-1水平低于治疗前（P＜0.05）,观察组血清HBP和sTREM-1水平显著低于对照组（P＜0.05或P＜0.01）。治疗后,两组Th17和Treg（CD4+ CD25+、CD4+ CD25high）表达率显著低于治疗前（P＜0.05）,观察组Th17和Treg（CD4+ CD25+、CD4+ CD25high）表达率显著低于对照组（P＜0.05或P＜0.01）。治疗后,两组较治疗前血小板计数(platelet count,PLT)和纤维蛋白原(fibrinogen,FIB)均升高,凝血酶原时间(prothrombin time,PT)、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)和凝血酶时间(thrombin time,TT)均降低（P＜0.05）;观察组较对照组PLT和FIB均显著升高,PT、APTT和TT均显著降低（P＜0.01）。两组不良反应发生率差异无统计学意义（χ2=0.260,P=0.609）。 结论乌司他丁联合丹红注射液对脓毒症患者的疗效显著,能够有效调节sTREM-1、HBP水平及Th17/Treg表达率,改善免疫、凝血功能,促进预后。     

Toll-like receptor signaling in neonatal sepsis and inflammation: a matter of orchestration and conditioning

Altered neonatal Toll-like receptor (TLR) function is hypothesized to contribute to the heightened susceptibility to infection and perpetuated inflammation in term and preterm neonates, clinically evident in neonatal sepsis and increased rates of inflammatory disorders. Current data indicate that basal TLR expression in term neonates equals adult expression patterns, while expression in preterm infants seems to increase, depending on gestational age. Regarding TLR signaling, some studies suggest TLR incompetence in neonates associated with impaired pro-inflammatory responses, others describe neonatal TLR function well developed and allude to its hyper-inflammation tendency. We discuss the competing positions and considerable limitations of research approaches and conclude that neonatal innate immunity is not generally less able to respond to TLR stimulation. Moreover, we describe pre-conditioning factors other than immaturity having a comparable impact. In the long term, better understanding of the complex interplay of pre- and postnatal conditions and maturation-dependent neonatal TLR function may provide new therapeutic approaches.     

The Role of Complement,C5a and Its Receptors in Sepsis and Multiorgan Dysfunction Syndrome

Sepsis continues to be a major clinical problem that is difficult to treat, as the pathophysiology of the disease is still unclear. Despite promising experimental strategies, therapeutic interventions have been largely unsuccessful. There is now increasing evidence that the disturbance of innate immunity during sepsis and multiorgan dysfunction syndrome (MODS) may be linked to uncontrolled activation of the complement system. Especially, the powerful anaphylatoxin C5a seems to play a key role in the development of immune paralysis. In this review, we describe our present understanding of the role of complement in the inflammatory response during sepsis and MODS.     

Late brain alterations in sepsis‐survivor rats

Central nervous system (CNS) dysfunction secondary to sepsis is characterized by long‐term cognitive impairment. It was observed that oxidative damage, energetic metabolism impairment, and cytokine level alteration seen in early times in an animal model of sepsis may persist for up to 10 days and might be associated with cognitive damage. In order to understand these mechanisms, at least in part, we evaluated the effects of sepsis on cytokine levels in the cerebrospinal fluid (CSF), oxidative parameters, and energetic metabolism in the brain of rats at both 30 and 60 days after sepsis induction by cecal ligation and perforation (CLP). To this aim, male Wistar rats underwent CLP with “basic support” or were sham‐operated. Both 30 and 60 days after surgery, the CSF was collected and the animals were killed by decapitation. Then, the prefrontal cortex, hippocampus, striatum, and cortex were collected. Thirty days after surgery, an increase of IL‐6 level in the CSF; an increase in the thiobarbituric acid‐reactive species (TBARS) in prefrontal cortex and a decrease in hippocampus, striatum, and cortex; a decrease of carbonyl protein formation only in prefrontal cortex and an increase in striatum; and an increase in the complex IV activity only in hippocampus were observed. Sixty days after sepsis, an increase of TNF‐α level in the CSF; a decrease of TBARS only in hippocampus; an increase of carbonyl protein formation in striatum; and a decrease of complex I activity in prefrontal cortex, hippocampus, and striatum were observed. These findings may contribute to understanding the role of late cognitive impairment. Further studies may address how these findings interact during sepsis development and contribute to CNS dysfunction. Synapse 67:786–793, 2013. © 2013 Wiley Periodicals, Inc.