cGAS-STING信号通路与脓毒症肠屏障功能障碍相关性的研究进展

［摘要］　脓毒症的发病机制复杂。近年来研究证实，脓毒症发生时，cGAS-STING信号通路激活及作用机制对于改善脓毒症肠屏障功能障碍具有重要意义。该文就cGAS-STING信号通路的激活、cGAS-STING信号通路与脓毒症肠道炎症反应及cGAS-STING信号通路对肠屏障功能的影响作一综述。     

脓毒症并发ARDS患儿血清miR-424和miR-494表达变化及其临床意义

目的 探讨脓毒症并发急性呼吸窘迫综合征（ARDS）患儿血清微小RNA-424(miR-424)、微小RNA-494(miR-494)表达变化及其临床意义。方法 选择脓毒症并发ARDS患儿213例（并发ARDS组），病情程度：轻度54例、中度86例、重度73例，住院28天内临床结局：死亡62例、存活151例。同期另选单纯脓毒症患儿45例（单纯脓毒症组）、体检健康儿童42例（对照组）。所有研究对象入组后采集外周静脉血，离心留取血清，采用RT-qPCR法检测血清miR-424、miR-494表达。比较三组血清miR-424、miR-494表达以及不同病情程度脓毒症并发ARDS患儿血清miR-424、miR-494表达。分析脓毒症并发ARDS患儿血清miR-424、miR-494表达与氧指数（OI）的关系。采用受试者工作特征（ROC）曲线分析血清miR-424、miR-494表达对脓毒症并发ARDS患儿预后不良的预测价值。结果 对照组、单纯脓毒症组、并发ARDS组血清miR-424相对表达量依次降低，血清miR-494相对表达量依次升高（P均<0.01）。随着脓毒症并发ARDS患儿病情加...     

免疫球蛋白对脓毒症治疗效果的研究进展

本文介绍脓毒症与免疫机制的相关研究,主要从严重脓毒症和脓毒性休克的病生理机制及其自身免疫状态角度探讨补充免疫球蛋白可能的效应机制,分析通过免疫机制的干预影响难治性脓毒症预后的可能性及其机制,为预防及治疗重症脓毒症提供新的方法.     

小儿脓毒症血清C反应蛋白和心肌酶变化及临床意义

目的探讨小儿脓毒症血清中C反应蛋白(CRP)和心肌酶的变化及其临床意义。方法检测确诊的30例脓毒症患儿(脓毒症组)与28例非脓毒症患儿(对照组)血清中CRP和心肌酶的含量。结果(1)脓毒症组患儿与对照组比较血清中CRP明显升高,差异有显著性意义(P<0.01);心肌酶明显增高,差异有显著性意义(P<0.05)。(2)脓毒症组患儿治疗前后CRP、心肌酶水平间差异有显著意义(P<0.01)。结论小儿脓毒症时CRP检测可作为诊断的辅助指标,心肌酶对危重程度和预后判断有重要意义。     

脓毒症肝损伤的发病机制及治疗研究进展

脓毒症是临床常见的危重病之一，近年来由于抗生素、激素及免疫抑制剂的广泛应用，脓毒症的发病率和病死率持续升高。脓毒症早期即可诱发肝损伤，其发病机制不明，本文将近年来脓毒症肝损伤的发病机制及潜在治疗方向的进展做一阐述。     

脓毒症患儿血清胆碱酯酶、前白蛋白和C反应蛋白变化及预后的关系

目的 了解脓毒症(sepsis)患儿血清胆碱酯酶(CHE)、前白蛋白(PA) 和超敏 C反应蛋白(hsCRP)和C反应蛋白(CRP)变化特点及临床意义,探讨CHE、PA、hsCRP和CRP变化及对脓毒症患儿预后的影响.方法 对2007-01～2009-02住院的59例符合脓毒症诊断标准患儿,经治疗原发病和应用呼吸支持、液体复苏、血管活性药物、抗感染、对症治疗等处理后,依据疾病转归情况将患儿分为未愈/死亡组18例和治愈/存活组41例, 全部于入组当天及第3天检测血清CHE、hsCRP、CRP、肝功能等其他各项指标,49例同时检测血清PA,设同龄普通肺炎对照组患儿30例.结果 脓毒症患儿未愈/死亡组与治愈/存活组比较:入组当天及第3天血清CHE、PA均明显降低(均分别为P<0.05和P<0.01);hsCRP及CRP入组当天及第3天均明显增高(分别为P<0.05和P<0.01).两组分别与正常儿童比较:血清CHE、PA、均明显降低(P均＜0.01);hsCRP 未愈/死亡组较对照组增高(P＜0.01);CRP治愈/存活组及未愈/死亡组较对照组均明显增高(P均＜0.05).结论 脓毒症患儿存在不同程度血清CHE、PA降低,hsCRP及CRP增高,血清CHE、PA、hsCRP及CRP在一定程度上体现脓毒症患儿病情的危重程度,对判断脓毒症患儿预后有参考价值.     

脓毒症急性肾损伤研究进展

脓毒症是一个复杂的临床综合征，疾病演变过程常常导致广泛的组织损伤和多器官功能障碍（multiple organ dysfunction，MODS），特别是急性肾损伤（acute kidney injury，AKI）。其是脓毒症最常见的并发症之一，并且是死亡的独立危险因素。传统观点认为全身性低血压，肾血管收缩和局部缺血再灌注损伤是脓毒症诱导AKI的主要病理生理机制。最近研究表明，脓毒症诱导AKI发生与微血管功能障碍相关，同时伴随微粒的释放，炎症和高代谢性器官对细胞应激的能量适应。脓毒症诱导AKI的高死亡率的归因于对其病理生理学机制的不完全理解和诊断延迟。在这篇综述中，重点理解脓毒症诱导AKI的基本病理生理学机制。     

脓毒症内皮功能障碍与凝血调节机制的研究进展

脓毒症患者的病死率据统计高达25%~30%,居重症监护病房患者死亡原因的首位。研究证实,内皮细胞作为脓毒症众多发病机制的重要组成部分严重影响着疾病的进展。脓毒症时失控的炎症反应破坏了内皮细胞的生理性凝血调节机制,甚至导致弥散性血管内凝血的发生,大大增加了患者的死亡率。本文综述了脓毒症时受损的内皮细胞对凝血调节机制的影响,旨在通过检测患者体内相关的生物标志物来帮助临床医师评估患者病情,从而降低病死率。     

连续血液净化治疗小儿脓毒症的临床分析

目的:观察分析连续血液净化治疗小儿脓毒症临床效果,为连续血液净化在小儿脓毒症中的应用提供参考依据。方法:选取小儿脓毒症患儿共40例。随机将患儿分为观察组和对照组,观察组患儿采用连续血液净化治疗,对照组患儿则采用常规的治疗。结果:观察组患儿在接受治疗后其APAACHEII评分对比治疗前有明显下降,并且对比观察组患儿在接受治疗24h后患儿的评分也明显低于对照组患儿,两组数据对比,差异有统计学意义(P<0.05);观察组患儿接受治疗后其体内的白细胞数(WBC)和降钙素原(PCT)含量对比治疗前出现下降,而对照组的WBC及PCT值高于治疗前数值,差异有统计学意义。结论:连续血液净化治疗能够有效改善脓毒症患儿的感染症状,并且能够帮助其改善脏器功能,减轻患儿炎性反应。     

影响脓毒症患儿肝损伤的危险因素

目的分析影响脓毒症患儿肝损伤的危险因素及其与肝损伤程度的关系。方法选取2016年1月至2018年1月我院收治的47例脓毒症患儿为研究对象,根据是否发生肝损伤将患儿分为肝损伤组(n=16)及未损伤组(n=31)。收集患儿临床资料及血清学检查结果,采用Logistic回归分析影响患儿肝损伤的因素;利用受试者工作特征曲线(ROC)分析诊断肝损伤的效能;相关性利用Pearson及Spearman分析。结果肝损伤组患儿AST、ALT、TBil、DBil、白蛋白、INR、APACHE II评分及SOFA评分明显高于未损伤组患儿(P0.05),肝损伤组患儿C3、C4水平低于未损伤组患儿(P0.05)。进一步Logistic回归分析显示,AST、ALT、C3、C4水平为患儿发生肝损伤的独立影响因素;ROC曲线分析显示,4项指标均对肝损伤具有一定的诊断价值,联合检测诊断效能高于任一单一指标;Pearson相关性分析显示,AST与ALT呈正相关,与C3及C4呈负相关;ALT与C3及C4呈负相关。结论对于血清高AST、ALT及低C3、C4的脓毒症患儿,应该警惕其肝损伤的发生。     

Peripheral blood lymphopenia and neutrophilia in children with severe respiratory syncytial virus disease

It is not known why respiratory syncytial virus (RSV) is associated with prolonged sequelae in many children. Measles virus (also a paramyxovirus), acute stress in sepsis, and cardiac bypass all cause lymphopenia.Using a retrospective analysis of records of children in Bristol with RSV infections over 5 years, we found that children with RSV had lower lymphocyte counts than unstressed, stable children prior to cardiac surgery. Children who required intensive care had the lowest lymphocyte counts. Neutrophil counts were raised in RSV-infected children.These data may offer an insight into pathological mechanisms, and suggest new research avenues.     

Detection of circulating lipopolysaccharide-bound monocytes in children with gram-negative sepsis

The possibility that gram-negative sepsis can be diagnosed by detection of lipopolysaccharide (LPS) bound on the surface of monocytes in the circulation of patients with gram-negative sepsis was investigated. Peripheral monocytes were analyzed by flow cytometer and an anti-LPS monoclonal antibody in 3 groups: children with gram-negative sepsis, children with gram-positive sepsis, and healthy children. LPS-bound monocytes were found in all patients with gram-negative sepsis but not in children with gram-positive sepsis or in healthy children. Therefore, the flow cytometry method developed for this study may be a novel method for diagnosing gram-negative sepsis.     

Global fibrinolytic capacity in pediatric patients with sepsis and disseminated intravascular coagulation.

There are many complex pathophysiologic changes of the coagulation system in sepsis. The fibrinolytic system was evaluated in septic children using the global fibrinolytic capacity (GFC), a new technique reflecting the overall fibrinolytic activity. The study consisted of 24 children with sepsis, 36 children with sepsis plus disseminated intravascular coagulation (DIC), and 20 healthy age-matched control individuals. Compared with controls, 86% of sepsis patients and 87% of sepsis plus DIC patients had decreased GFC levels. Between the sepsis plus DIC and sepsis groups there was no significant difference in terms of GFC levels. While 19 patients (52.7%) died in the sepsis plus DIC group, only three patients (12.5%) died in the sepsis group. When survivors and nonsurvivors were compared in terms of coagulation tests, there were significant differences for protein C, antithrombin, platelet, fibrinogen, aspartate aminotransferase, alanine aminotransferase, prothrombin time, and white blood cell values. In conclusion, the level of GFC reduced in most of the pediatric sepsis patients but no difference was observed between patients with sepsis and patients with sepsis plus DIC. While inhibition of fibrinolysis is an important finding in sepsis, the mortality is mainly associated with the presence of end-organ damage and the status of coagulation parameters.     

Immunoglobulins in Adult Sepsis and Septic Shock

For more than 30?years, intravenously administered immunoglobulins (ivIG) have been used to treat primary and secondary syndromes of immune deficiency. Increasing insight into pathomechanisms of severe sepsis and septic shock have led to the implementation of ivIG therapy in the strategies for adjunctive therapy in sepsis in both adults and children. Direct antitoxic effects, as well as indirect immunomodulatory mechanisms of ivIG have been described in the literature and were the basis for the rationale to use these substances in life-threatening infections and hyperinflammatory states. Several clinical trials have been performed, most of them as minor, investigator-initiated protocols. This review summarizes the results of clinical investigations and systematic meta-analyses that have implications for the development of therapeutic strategies, and international guidelines for the management of severe sepsis and septic shock in adult patients.     

The epidemiology of severe sepsis in children in the United States

Despite extensive research into the etiology and treatment of severe sepsis, little is known about its epidemiology in children. We sought to determine the age- and sex-adjusted incidence, outcome, and associated hospital costs of severe sepsis in United States children using 1995 hospital discharge and population data from seven states (24% of the United States population). Of 1,586,253 hospitalizations in children who were 19 years old or less, 9,675 met International Classification of Diseases, 9th revision, clinical modification-based severe sepsis criteria or 42,364 cases of pediatric severe sepsis per year nationally (0.56 cases per 1,000 population per year). The incidence was the highest in infants (5.16 per 1,000), fell dramatically in older children (0.20 per 1,000 in 10 to 14 year olds), and was 15% higher in boys than in girls (0.60 versus 0.52 per 1,000, p < 0.001). Hospital mortality was 10.3%, or 4,383 deaths nationally (6.2 per 100,000 population). Half of the cases had underlying disease (49.0%), and over one-fifth (22.9%) were low-birth-weight newborns. Respiratory infections (37%) and primary bacteremia (25%) were the most common infections. The mean length of stay and cost were 31 days and $40,600, respectively. Estimated annual total costs were 1.97 billion US dollars nationally. Severe sepsis is a significant health problem in children and is associated with the use of extensive healthcare resources. Infants are at highest risk, especially those with a low birth weight.     

High-mobility group box-1 protein,lipopolysaccharide-binding protein,interleukin-6 and C-reactive protein in children with community acquired infections and bacteraemia: a prospective study

Introduction  

Even though sepsis is one of the common causes of children morbidity and mortality, specific inflammatory markers for identifying sepsis are less studied in children. The main aim of this study was to compare the levels of high-mobility group box-1 protein (HMGB1), Lipopolysaccharide-binding protein (LBP), Interleukin-6 (IL-6) and C-reactive protein (CRP) between infected children without systemic inflammatory response syndrome (SIRS) and children with severe and less severe sepsis. The second aim was to examine HMGB1, LBP, IL6 and CRP as markers for of bacteraemia.     

Risk of infection in hospitalised children with systemic lupus erythematosus: a 10-year follow-up

The objective of this study was to investigate infection and sepsis in hospitalised children with systemic lupus erythematosus (SLE). Between 1991 and 2000 we reviewed 72 episodes of suspected infection in 42 children with SLE from all hospitalised children with SLE at a medical center in Taiwan. Data comprised clinical and laboratory characteristics of SLE at the time of infection. Infections were identified and categorised as minor or major. A total of 125 patients (110 girls, 15 boys) were admitted 557 times. Forty-two patients had infections, giving an infection rate of 33.6%. There were a total of 72 infections including 20 proven infections; 61 cases of these were minor infections and 11 cases of these were major infections (10 cases were sepsis). Four patients died because of sepsis. By univariate analysis, major infection (sepsis) was significantly associated with a high SLE disease activity index score, lower complement levels and higher anti-DNA titres. In conclusion, our data confirm that infection is common in hospitalised children with SLE. Sepsis, most frequent in major infections, is associated with disease activity and causes significant mortality. These facts should be borne in mind when children with SLE are hospitalised.     

Differential Paradigms in Animal Models of Sepsis

Sepsis is a serious clinical problem involving complex mechanisms which requires better understanding and insight. Animal models of sepsis have played a major role in providing insight into the complex pathophysiology of sepsis. There have been various animal models of sepsis with different paradigms. Endotoxin, bacterial infusion, cecal ligation and puncture, and colon ascendens stent peritonitis models are the commonly practiced methods at present. Each of these models has their own advantages and also confounding factors. We have discussed the underlying mechanisms regulating each of these models along with possible reasons why each model failed to translate into the clinic. In animal models, the timing of development of the hemodynamic phases and the varied cytokine patterns could not accurately resemble the progression of clinical sepsis. More often, the exuberant and transient pro-inflammatory cytokine response is only focused in most models. Immunosuppression and apoptosis in the later phase of sepsis have been found to cause more damage than the initial acute phase of sepsis. Likewise, better understanding of the existing models of sepsis could help us create a more relevant model which could provide solution to the currently failed clinical trials in sepsis.     

Pediatric Sepsis: Preparing for the Future Against a Global Scourge

Sepsis is a leading cause of morbidity and mortality among children worldwide. As consensus statements emerge regarding early recognition and goal-directed management of sepsis, scrutiny should be given to the unique characteristics of sepsis in children. Pediatric patients are not small adults! Sepsis epidemiology, pathophysiology, and management strategy can vary significantly from those for adults. Herein, we describe the epidemiology of pediatric sepsis, in both resource-rich and resource-poor worlds, and discuss how the pathophysiology of pediatric sepsis differs from that for adults. We discuss the timeline of management of pediatric sepsis, studying how discoveries over the past 50?years have changed the way sepsis is treated. Finally, we discuss the future of pediatric sepsis. We focus on approaches that carry the most substantive impact on the global burden of disease.     

MicroRNA与脓毒症作用机制研究进展

脓毒症指是指宿主对感染产生的失控反应,并出现危及生命的器官功能障碍,是临床危重患者死亡的重要病因之一,其主要病理生理机制包括机体失控的炎性反应、凝血和免疫功能障碍,涉及细胞内多条信号传导通路的活化和分子机制.MicroRNA(miRNA)是一类长度约为21~25个核苷酸序列的内源性非编码RNA,通过转录后水平抑制靶基因表达及调节免疫细胞的分化,进而调控脓毒症的发生发展.因此深入研究microRNA与脓毒症的作用机制,可为预防与治疗脓毒症开拓新的思路.本文就目前已研究较为清楚的几种miRNA与脓毒症作用机制作一简要综述.