SELDI-TOF MS detection of urinary hepcidin

Hepcidin is a 25-residue hepatic peptide that regulates iron absorption from the diet and tissue iron distribution. Inappropriately low Hepcidin expression is implicated in the pathogenesis of hereditary hemochromatosis and iron-loading anemias, like the thalassemias. Increased hepcidin expression mediates iron retention in the anemias of inflammation and plays a pathogenic role in iron-refractory iron-deficiency anemia (IRIDA). Because of its clinical importance, Hepcidin is expected to be a useful biomarker for diagnosis and management of iron-related disorders. So far an ELISA for human hepcidin and SELDI-TOF-MS based approaches have been applied to monitor urinary and/or serum hepcidin levels. Here we report a modified protocol for SELDI-TOF based detection of human, urinary hepcidin. We show that CM10 Proteinchips are superior to NP20 Proteinchips commonly used in previously reported protocols to sensitively and accurately detect urinary hepcidin. Application of this modified hepcidin assay accurately detects increased hepcidin levels in the urine of sepsis patients.     

高氧在临床应用中的研究进展

氧气是人类赖以生存的物质,是人体进行新陈代谢的关键,是人体生命活动的第一需要。在人类没有发现氧气之前,其对人类生存的重要性并不为人类所知。随着人类发现氧气并意识到其对人类生存的重要性之后,人类对氧气的研究越来越深入。起初,吸入高浓度氧仅用来治疗低氧血症等呼吸相关疾病,而后,氧气发展成为临床常用的一种辅助治疗手段,可用于多个科室多种疾病的辅助治疗。本研究小组通过动物实验发现高浓度氧吸入可明显降低脓毒症小鼠的病死率,并可以改善其组织病理,炎性细胞因子等的表达变化,也可以改善脑缺血再灌注小鼠的脑梗死面积及行为学表现等。本文主要概括了高浓度氧吸入对于全身各系统的影响作用并重点阐述了高浓度氧吸入对于脓毒症以及组织缺血再灌注的治疗作用。     

微粒和血细胞在脓毒症高凝状态中的作用

目的:探讨血小板和红细胞磷脂酰丝氨酸(PS)暴露和循环微粒(MPs)在脓毒症高凝状态中的作用。方法:集10例诊断为脓毒症的患者及10例健康体检者的新鲜血;离心分离出红细胞、富血小板血浆及MPs;应用Alexa-Fluro 488-乳粘素/CD 41a/CD14、Alexa-Fluro 647-CD 235a/CD 31/CD 45标定红细胞、血小板、内皮细胞、白细胞及单核细胞来源的MPs;流式细胞仪测定红细胞和血小板的PS外翻、MPs的数量;血凝仪测定相应凝血时间。结果:相对于健康人,脓毒症患者PS外翻红细胞(3.53%vs0.53%,P0.05)和血小板(3.00%vs 0.45%,P0.05)、MPs总数(4830/μL vs 2861/μL,P0.05)及各亚型MPs均明显升高;红细胞(238.4s vs 346.8s,P0.05)、血小板(209.1s vs 335.9s,P0.05)及MPs(207.1s vs 318.2s,P0.05)的凝血时间缩短。MP数、PS+红细胞/血小板比例分别与各自凝血时间成负相关(MP:r=-0.592,P=0.006;红细胞:r=-0.565,P=0.009;血小板:r=-0.641,P=0.002)。结论:红细胞、血小板的PS暴露及循环MPs和脓毒症高凝状态的发生相关,可能对患者凝血功能检测和抗凝治疗有一定的意义。     

Deficiency of protease-activated receptor-1 limits bacterial dissemination during severe Gram-negative sepsis (melioidosis)

Protease-activated receptor-1 (PAR-1) is a G-coupled transmembrane receptor expressed by multiple cell types present in the lungs that can be activated by various proteases generated during acute inflammation. In this study we aimed to investigate the role of PAR-1 during melioidosis, a common cause of (pneumo)sepsis in Southeast Asia in a murine model of intranasal inoculation of the causative pathogen Burkholderia (B.) pseudomallei. Our results show that endogenous PAR-1 facilitates bacterial growth and dissemination during murine melioidosis, which is associated with increased cell influxes. However, these observations have no impact on survival.     

Condition dependence and the maintenance of genetic variance in a sexually dimorphic black scavenger fly

The maintenance of genetic variation in traits under strong sexual selection is a longstanding problem in evolutionary biology. The genic capture model proposes that this problem can be explained by the evolution of condition dependence in exaggerated male traits. We tested the predictions that condition dependence should be more pronounced in male sexual traits and that genetic variance in expression of these traits should increase under stress as among‐genotype variation in overall condition is exposed. Genetic variance in female and nonsexual traits should, by contrast, be similar across environments as a result of stabilizing selection on trait expression. The relationship between the degree of sexual dimorphism, condition dependence and additive genetic variance (V_a) was assessed for two morphological traits (body size and relative fore femur width) affecting male mating success in the black scavenger fly Sepsis punctum (Diptera: Sepsidae) and for development time (a nonsexual trait often correlated with body size). We compared trait expression between the sexes for two cross‐continental populations that differ in degree of sexual dimorphism (Ottawa and Zurich). Condition dependence was indeed most pronounced in males of the strongly dimorphic Zurich population (males larger), and V_a was similar for males and females unless the trait was strongly sex specific and condition dependent. Contrary to prediction, however, V_a primarily increased under food limitation in both sexes, and genetic variance in fore femur width was low to nil, perhaps depleted by putatively strong sexual selection. Solely for body size of Zurich males, V_a increased more in males than females at limited food, in accordance with the predictions of the genic capture model. Overall therefore, quantitative genetic evidence in support of the model was inconsistent and weak at best.     

乌司他丁联合连续性血液净化治疗重症脓毒症临床研究

目的：研究连续性血液净化联合乌司他丁对重症脓毒症患者炎症反应的影响及其临床疗效。方法：70例重症脓毒症患者随机分为对照组（n=22例）、CBP组（n=23例）和CBP＋乌司他丁组（n=25例）,其中对照组采用经典治疗方案,CBP组在此基础上加用连续性血液净化,CBP＋乌司他丁组在CBP组基础上加用乌司他丁治疗。观察比较患者病情发展,分别于治疗前后进行血液生化指标、凝血功能检测和动脉血气分析,ELISA法检测血清CRP水平。结果：①与对照组和CBP组相比,CBP＋鸟司他丁纽患者病死率、ICU住院时间、MODS发生率均明显下降（P〈0．05）。②经过治疗,CBP＋乌司他丁组患者APACHEⅡ评分降至15．46±3．96,与对照组（18．06±4．25）和CBP组（17．14±5．55）比较差异有统计学意义（P〈0．05）。③治疗后,患者BUN、HR降低程度依次为CBP＋乌司他丁组〉CBP组〉对照组,组问比较差异有显著性（P〈0．05）,而治疗前后PH值、HCO3-、MAP比较差并不明显（P〉0．05）。④CBP＋乌司他丁纽血清CRP含量下降,WBC数量减少,其变化程度明显大于CBP组和对照组（P〈0．05）。⑤对照组、CBP组和CBP＋乌司他丁组患者PT、TT和APTT时间延长,血小板数量下降,其中CBP＋鸟司他丁组PT、APTT时间短于CBP组和对照组（P〈0．05）。结论：连续性血液净化联合乌司他丁可有效抑制脓毒症患者炎症反应,缓解病情,改善患者预后。     

乳酸和APACHE II 评分在评估老年脓毒症患者预后中的应用

目的:研究乳酸和急性生理学及慢性健康状况评分(APACHE Ⅱ评分)对老年脓毒症患者预后的评估作用。方法:老年脓毒症患者96例,按照入院时血乳酸值分成升高者60例,乳酸正常者36例,比较两组的病死率、休克、机械通气和MODS发生率、APACHE Ⅱ评分的区别;根据APACHE Ⅱ评分(<15、15～24、≥25)分为3组,比较每组患者的病情和预后区别。结果:乳酸升高组老年脓毒症患者的机械通气、休克发生率、MODS发生率、APACHE Ⅱ评分明显大于乳酸正常组(P<0.05),病死率明显上升(28.3%vs 2.7%),(P=0.005);随着APACHE Ⅱ评分增高,患者病情逐渐加重,休克发生率和住院病死率明显升高,(P<0.05),患者乳酸水平也明显增高(P<0.05)。结论:血乳酸和APACHE Ⅱ评分都可以评估老年脓毒症患者病情严重和预后,两者升高提示预后差。     

不同预后脓毒症患者血清降钙素原、C反应蛋白与凝血功能指标和APACHE Ⅱ评分的关系分析

目的:探讨不同预后脓毒症患者血清降钙素原(PCT)、C反应蛋白(CRP)与凝血功能指标和急性生理和慢性健康状况评分系统Ⅱ(APACHEⅡ)评分的关系。方法:回顾性分析2015年1月至2019年1月期间深圳市第二人民医院重症医学科收治的160例脓毒症患者(脓毒症组)与在深圳市第二人民医院接受住院治疗的160例非脓毒症患者(非脓毒症组)的临床资料,根据脓毒症组患者住院28d后的预后情况分为存活组118例和死亡组42例,比较脓毒症组和非脓毒症组以及死亡组和存活组患者血清PCT和CRP水平、APACHE II评分以及凝血功能指标,采用Pearson相关性回归分析脓毒症患者血清降钙素原和CRP水平与APACHEⅡ评分以及凝血功能指标相关性。结果:与非脓毒症组相比,脓毒症组的血清PCT和CRP水平以及APACHEⅡ评分明显升高,凝血酶原时间(PT)和部分凝血活酶时间(APTT)明显延长(均P<0.05)。与存活组相比,死亡组的血清PCT和CRP水平以及APACHEⅡ评分明显升高,而PT和APTT均明显延长(均P<0.05)。Pearson相关性回归分析结果显示,血清PCT和CRP水平与APACHEⅡ评分、PT及APTT均呈正相关(均P<0.05)。结论:脓毒症患者血清PCT和CRP水平异常升高,APACHEⅡ评分及凝血功能指标均与血清PCT和CRP水平呈正相关,检测血清PCT和CRP水平有助于评估脓毒症患者的预后。     

脓毒症患者中可溶性髓样细胞触发受体1、降钙素原、核因子κB水平与肠道菌群失调的相关性

本研究旨在探讨脓毒症患者中血清可溶性髓样细胞触发受体1(soluble myeloid cell trigger receptor 1,sTREM1)、降钙素原(procalcitonin,PCT)、核因子κB(nuclear factor­κB,NF­κB)水平与肠道菌群失衡的相关性。将2016年5月-2019年6月重庆市綦江区人民医院消化内科收治的86例脓毒症患者纳入脓毒症组,同期收治的未并发脓毒症患者50例纳入非脓毒症组,同期到本院进行体检的健康人50例纳入对照组,比较3组之间肠道菌群α多样性、肠道菌群含量,以及血清sTREM1、PCT、NF­κB水平的差异,并进行Spearman相关性分析。结果显示,脓毒症组Ace指数、Chao指数、Shannon指数显著低于非脓毒症组和对照组,Simpson指数显著高于非脓毒症组和对照组(P<0.05);脓毒症组类杆菌、双歧杆菌含量显著低于非脓毒症组和对照组,肠球菌、大肠埃希菌、葡萄球菌含量显著高于非脓毒症组和对照组(P<0.05);脓毒症组血清sTREM1、PCT、NF­κB水平显著高于非脓毒症组和对照组(P<0.05)。Spearman相关性分析显示,脓毒症患者中sTREM1、PCT、NF­κB水平与Ace指数、Chao指数、Shannon指数均呈负相关(P<0.05),与Simpson指数呈正相关(P<0.05)。结果提示,脓毒症患者中血清sTREM1、PCT、NF­κB水平与肠道菌群失衡有关联。