钙卫蛋白对脓毒症患者急性肾损伤的预测价值

目的探讨血清钙卫蛋白对脓毒症患者急性肾损伤(acute kidney injury, AKI)的预测价值及预后评估作用。方法本研究为前瞻性观察性研究。连续收集2018年12月1日至2020年11月30日中国康复研究中心急诊科收治的脓毒症患者, 记录患者的一般临床资料、入院24 h内急性生理与慢性健康状况评分系统Ⅱ(acute physiology and chronic health evaluation Ⅱ, APACHE Ⅱ)评分、序贯器官衰竭评分(sequential organ failure assessment, SOFA)和血清钙卫蛋白水平。根据入院7 d内是否发生AKI将患者分为AKI组和非AKI组, 比较两组钙卫蛋白及其他临床资料的差异;采用Logistic回归分析探讨脓毒症患者发生AKI的影响因素;采用受试者工作特征(receiver operating characteristic, ROC)曲线评价钙卫蛋白对脓毒症患者发生AKI的预测价值。根据28 d是否存活将AKI患者分为存活组和死亡组, 比较两组钙卫蛋白的水平。结果共入组207例脓毒症患者, 其中AKI发生...     

特发性肺纤维化患者血清淀粉样蛋白A和钙卫蛋白水平变化及临床意义研究

目的 探讨血清淀粉样蛋白A(SAA)和钙卫蛋白水平变化与特发性肺纤维化(IPF)的关系.方法 收集2016-2019年该院的IPF患者25例为IPF组,同时收集肺部其他疾病患者25例为疾病对照组和纤维支气管镜、影像学检查正常者25例为健康对照组.测定所有研究对象血清SAA和钙卫蛋白水平并进行比较,分析二者与肺功能指标的相关性.建立受试者工作特征(ROC)曲线和Kaplan-Meier生存曲线分析SAA、钙卫蛋白水平与IPF的关系.结果 IPF组SAA、钙卫蛋白水平高于疾病对照组和健康对照组(P<0.05).SAA、钙卫蛋白水平与IPF患者肺功能指标呈负相关(P<0.05),SAA水平与高密度脂蛋白呈负相关(P<0.05),与总胆固醇、低密度脂蛋白和三酰甘油呈正相关(P<0.05).SAA和钙卫蛋白联合诊断IPF的灵敏度、特异度、阳性预测值和阴性预测值均较高.Kaplan-Meier生存曲线结果提示SAA≥6.11μg/mL和钙卫蛋白≥2.39μg/mL与出院后IPF患者死亡比例升高有关.结论 IPF患者血清SAA和钙卫蛋白水平升高可能预示IPF患者肺功能不良,也与患者治疗后病死率有关.SAA和钙卫蛋白水平监测有助于IPF诊断和判断患者的临床转归.     

钙卫蛋白的临床研究进展

钙卫蛋白(calprotectin,CP)是一种主要来源于中性粒细胞和单核细胞的钙-锌结合蛋白质,其表达具有组织或细胞特异性,具有抗微生物、抗增殖、调节免疫、诱导细胞凋亡、促进肿瘤细胞生长等多种生物学功能。国外多项研究发现CP与多种临床疾病具有较好的相关性,对疾病的诊断、治疗、预示复发     

钙卫蛋白及抗中性粒细胞胞浆抗体联合检测对炎症性肠病的诊断价值研究

目的 探讨钙卫蛋白与抗中性粒细胞胞浆抗体(ANCA)联合检测对炎症性肠病(IBD)的诊断价值.方法 收集确诊为IBD的患者79例作为IBD组,腹痛、腹泻等排除IBD的患者42例作为疾病对照组,健康体检者34例作为健康对照组.分别检测血液样本中ANCA和粪便样本中钙卫蛋白的水平.结果 79例IBD患者粪便钙卫蛋白浓度为(493.86±204.18)μg/g高于疾病对照组[(71.46±60.51)μg/g]和健康对照组[(36.19±13.46)μg/g].钙卫蛋白在IBD组、疾病对照组和健康对照组中的阳性率分别为57.0%、19.0%、0.0%;ANCA在三组中的阳性率分别为63.3%、4.8%、0.0%.IBD组的钙卫蛋白、ANCA阳性率显著高于其他两组(P＜0.05).钙卫蛋白与ANCA联合检测在IBD组、疾病对照组和健康对照组中的阳性率分别为78.5%、23.8%和0.0%.结论 钙卫蛋白和ANCA联合检测可显著提高IBD的诊断率,为临床IBD的早期诊断和治疗提供可靠依据.     

粪钙卫蛋白在炎症性肠病、肠易激综合征和大肠癌鉴别诊断中的意义

目的探讨粪便钙卫蛋白在炎症性肠病(IBD)、肠易激综合征(IBS)和大肠癌(CRC)这3种消化道常见疾病鉴别诊断中的意义。方法 IBD患者30例,IBS患者20例,CRC患者30例,健康对照组20例。在结肠镜检查前1d,留取粪便标本约5g,采用ELISA方法定量检测粪便钙卫蛋白浓度。结果 IBD、IBS、CRC、健康对照组的粪钙卫蛋白浓度的中位数分别为1084.07μg/g粪便,24.45μg/g粪便,141.85μg/g粪便,21.89μg/g粪便。IBS组粪便钙卫蛋白浓度与对照组比较差异无统计学意义(P=0.13>0.05);IBD组粪便钙卫蛋白水平高于CRC患者、IBS组和健康对照组(P<0.05);CRC组粪便钙卫蛋白水平高于IBS组和健康对照组(P<0.05)。结论粪便钙卫蛋白检测作为一种非侵入性筛选试验,可为临床鉴别诊断IBD、IBS和CRC提供一种新指标。     

粪便钙卫蛋白检测在结直肠癌诊断中的作用探究

目的探讨粪便钙卫蛋白检测在结直肠癌诊断中的作用。方法选取本院2012年10月至2014年10月诊治的炎症性肠病患者246例为Ⅲ组,结直肠癌患者246例为Ⅱ组,非癌息肉患者246例为Ⅰ组,健康体检人员246例为对照组,均行粪便钙卫蛋白检测。结果Ⅰ组粪便钙卫蛋白[(145.52±4.14)μg/g]高于对照组[(18.05±3.76)μg/g],差异有统计学意义(P0.05)。Ⅱ组粪便钙卫蛋白[(557.63±24.81)μg/g]高于对照组和Ⅰ组,差异有统计学意义(P0.05)。Ⅲ组粪便钙卫蛋白[(896.50±113.57)μg/g]高于对照组、Ⅰ组和Ⅱ组,差异有统计学意义(P0.05)。结肠癌患者粪便钙卫蛋白[(205.36±31.24)μg/g]高于直肠癌患者[(126.84±19.07)μg/g],差异有统计学意义(P0.05)。B期粪便钙卫蛋白[(197.58±23.16)μg/g]高于A期[(107.36±11.25)μg/g],差异有统计学意义(P0.05)。C期粪便钙卫蛋白[(143.09±18.27)μg/g]高于A期,却低于B期,差异有统计学意义(P0.05)。D期粪便钙卫蛋白[(168.25±16.38)μg/g]高于A期和C期,却低于B期。差异有统计学意义(P0.05)。结论粪便钙卫蛋白检测可为结直肠癌临床诊断提供准确的科学依据,并且操作方便、价格低廉、患者依从性高,适用于门诊筛查,值得临床推广使用。     

粒单细胞钙卫蛋白的功能及临床意义

钙卫蛋白是近年发现的与钙结合的不均一的复合蛋白质．由2重链及1轻链构成,主要来源于嗜中性粒细胞和单核细胞,分布于粒单细胞、上皮细胞、角质细胞内及各种组织和体液中．具有抗微生物、抗增殖等多种生物学功能。本文就钙卫蛋白的结构和理化特性、分布、生物学功能及临床意义作了介绍。     

粪钙卫蛋白在腹部不适患者中的诊断价值

目的评价粪钙卫蛋白在腹部不适患者中的临床诊断价值。方法收集长沙市芙蓉区红十字医院2009-2011年234例腹部不适患者,采用酶联免疫吸附试验检测粪钙卫蛋白,并进行统计学分析。结果腹部不适患者内镜下异常（n=83）的粪钙卫蛋白明显高于内镜下正常的患者（n=151）,差异有统计学意义（P〈0．01）,粪钙卫蛋白曲线下面积（AUC）为0．872（95％CI：0．85～0．91）,有明显的诊断意义,当cutoff值为50μg／g,诊断的灵敏度和特异性为71％和93％,阳性和阴性似然比为11．1和0．29,并且粪钙卫蛋白对鉴别诊断上消化道（AUC：0．721,95％CI：0．61-0．79）和结肠（AUC：0．932,95％CI：0．82～0．94）炎症也是个有用的指标,并且对结肠的诊断准确性更高（P〈0．01）,而且粪钙卫蛋白的水平与胃黏膜损害程度相关。结论粪钙卫蛋白作为一项非侵入性指标对诊断腹部不适具有良好的临床意义。     

粪便钙卫蛋白与肿瘤坏死因子-α对炎症性肠病不典型增生的影响

目的探讨粪便钙卫蛋白与肿瘤坏死因子-α(TNF-α)对炎症性肠病不典型增生的影响。方法 2010年1月至2013年12月住院确诊群体炎症性肠病(inflammatory bowel disease,IBD)患者196例,根据病理检查结果分为观察组43例与对照组156例,选取同期健康体检者86例作为正常对照组,比较三组粪钙卫蛋白及TNF-α水平。结果观察组粪钙卫蛋白水平、TNF-α水平、粪钙卫蛋白阳性率、TNF-α阳性率均高于对照组及正常对照组,差异均有统计学意义(P0.05)。结论炎症性肠病不典型增生者粪便钙卫蛋白与TNF-α显著升高,有望作为癌前病变的辅助检测指标,降低漏诊率。     

血清钙卫蛋白表达在类风湿性关节炎中的意义

目的探讨血清钙卫蛋白的表达在类风湿性关节炎(RA)中的意义。方法选取2017年10月至2018年5月该院就诊的70例RA患者,并选择该院同期体检的45例健康人作为健康对照组,比较两组受试者血清钙卫蛋白的表达水平,并分析RA患者血清钙卫蛋白水平与其临床活动度(DAS28评分)及RA实验室相关参数[C反应蛋白(CRP)、红细胞沉降率(ESR)、抗环瓜氨酸肽(CCP)抗体、类风湿因子-IgM (RF-IgM)]之间的关系。结果 RA组患者平均血清钙卫蛋白水平[(108.91±113.15)ng/mL]明显高于健康对照组[(8.33±1.98)ng/mL],差异具有统计学意义(P0.05)。低疾病活动组RA患者血清钙卫蛋白水平[(19.89±14.29)ng/mL]与健康对照组之间比较差异无统计学意义(P=0.071)。中疾病活动组RA患者和高疾病活动组RA患者血清钙卫蛋白水平分别为[(77.35±99.79)ng/mL]和[(216.39±85.83)ng/mL],均显著高于健康对照组,差异具有统计学意义(P0.05)。RA患者血清钙卫蛋白水平与28肿胀关节计数(r=0.652,P0.05),28疼痛关节计数(r=0.633,P0.05),DAS28评分(r=0.581,P0.05),RF-IgM(r=0.438,P0.05)呈正相关,而与CRP、ESR、抗-CCP抗体水平、疾病持续时间和年龄无相关性。在以DAS28为因变量的多元线性回归分析中,RA患者血清钙卫蛋白水平与DAS28评分的相关性高于CRP与ESR。结论血清钙卫蛋白水平与RA实验特异性指标和临床疾病活动度之间存在密切关系,对评估和监测RA患者病情有重要的指导和参考意义。     

Calprotectin and calgranulin C serum levels in bacterial sepsis

The aim of this study was to evaluate the serum levels of calprotectin and calgranulin C and routine biomarkers in patients with bacterial sepsis (BS). The initial serum concentrations of calprotectin and calgranulin C were significantly higher in patients with BS (n?=?66) than in those with viral infections (n?=?24) and the healthy controls (n?=?26); the level of calprotectin was found to be the best predictor of BS, followed by the neutrophil-lymphocyte count ratio (NLCR) and the level of procalcitonin (PCT). The white blood cell (WBC) count and the NLCR rapidly returned to normal levels, whereas PCT levels normalized later and the increased levels of calprotectin, calgranulin C, and C-reactive protein persisted until the end of follow-up. Our results suggest that the serum levels of calprotectin are a reliable biomarker of BS and that the WBC count and the NLCR are rapid predictors of the efficacy of antimicrobial therapy.     

Drotrecogin alfa (recombinant human activated protein C) for the treatment of severe sepsis

BACKGROUND: The search for a life-preserving drug to treat sepsis has increased understanding of the pathogenesis of the process but produced little in the way of successful treatments. The prospective, randomized, double-blind, placebo-controlled, Phase III, multicenter Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial suggested that drotrecogin alfa--recombinant human activated protein C--significantly improved 28-day mortality rates in acute sepsis (P = 0.005). OBJECTIVES: The goals of this drug review were to summarize the recent findings regarding the pathogenesis of sepsis and septic shock, as well as the results of select immunomodulator drug trials, and to offer a comprehensive review of the mechanism of action, pharmacokinetic profile, efficacy and safety profile, and pharmacoeconomics of drotrecogin alfa. METHODS: The English-language literature was searched using the EMBASE and MEDLINE databases. In EMBASE, the subject headings drotrecogin, activated protein C, and sepsis were used to search publications from 1980 through September 2002. In MEDLINE, the MeSH heading protein C and subject heading sepsis were used to search publications from 1966 through September 2002. Published abstracts of recent meetings and proceedings of the US Food and Drug Administration were also reviewed. RESULTS: Drotrecogin alfa mimics the endogenous protein depleted during acute sepsis. Its activity as an antithrombotic, anti-inflammatory, and profibrinolytic agent appears to diminish the negative outcomes of acute sepsis, notably mortality at 28 days. The results of the PROWESS trial support this finding. A bleeding risk was noted during Phase II and III trials despite efforts to exclude those patients at high risk of bleeding. CONCLUSIONS: Drotrecogin alfa is the first adjunctive agent for the treatment of sepsis to display clinically and statistically significant effects on mortality rates at 28 days. Many questions remain regarding which patients are ideal candidates for treatment. New research and treatment guidelines are necessary to address these questions.     

病毒性脓毒症的研究进展与启发

脓毒症是一种由宿主反应失调引起的危及生命器官功能障碍的感染,具有复杂的生理和病理变化^[1]。近年来,人们对脓毒症的研究取得了很大进展,但对不同类型病原体引起的脓毒症差异研究尚少,大多数是针对细菌性脓毒症的研究。随着新型冠状病毒(COVID-19)的暴发,病毒性脓毒症再次引起人们关注。因此,了解病毒性脓毒症的常见病毒类型、发病机制的主要特征、临床表现、诊断、治疗等方面,能进一步调整后续诊疗策略,改善患者预后状况,有效降低临床病死率。     

Microvascular endothelial dysfunction: a renewed appreciation of sepsis pathophysiology

Severe sepsis, defined as sepsis associated with acute organ dysfunction, results from a generalized inflammatory and procoagulant host response to infection. Coagulopathy in severe sepsis is commonly associated with multiple organ dysfunction, and often results in death. The molecule that is central to these effects is thrombin, although it may also have anticoagulant and antithrombotic effects through the activation of Protein C and induction of prostacyclin. In recent years, it has been recognized that chemicals produced by endothelial cells play a key role in the pathogenesis of sepsis. Thrombomodulin on endothelial cells coverts Protein C to Activated Protein C, which has important antithrombotic, profibrinolytic and anti-inflammatory properties. A number of studies have shown that Protein C levels are reduced in patients with severe infection, or even in inflammatory states without infection. Because coagulopathy is associated with high mortality rates, and animal studies have indicated that therapeutic intervention may result in improved outcomes, it was rational to initiate clinical studies.     

Cell death in sepsis: a matter of how, when, and where

Dysregulated cell death in several tissues is intimately involved in the pathogenesis of sepsis and contributes to multiple organ failure. Whether cell death during sepsis occurs by necrosis or apoptosis may depend on the cell type as well as the disease stage and is therefore a matter of intense debate. While lymphocyte apoptosis contributes to immunosuppression in sepsis, recent evidence suggests that necrosis of hepatocytes predominates in septic patients with liver dysfunction and correlates with poor survival. These distinct modes of cell death might have different consequences for the inflammatory response but are also critical for therapeutic interventions and the disease outcome. Understanding the complexity of death processes employing recently available serum biomarkers of cell death could lead to novel therapeutic approaches and assist in the steering of sepsis treatment.     

高迁移率族蛋白B1与脓毒症认知功能障碍关系的研究进展

脓毒症幸存者出院后常出现远期的记忆力下降、认知障碍、生活质量下降，甚至死亡等不利结局，给家庭和社会造成极大的经济及精神负担。近年来，脓毒症认知功能障碍越来越成为医学研究关注的热点，高迁移率族蛋白B1（HMGB1）作为关键晚期炎症介质参与了脓毒症发病过程，并且与脓毒症认知功能障碍存在密切关系。但HMGB1介导脓毒症认知功能障碍机制尚不清楚。目前认为其主要通过介导炎症反应及神经炎症，血脑屏障的破坏，氧化应激和小胶质细胞的激活，海马体的炎性损伤四个方面参与脓毒症认知功能损伤。未来亟待进一步探索HMGB1介导脓毒症与脓毒症后认知障碍的确切关系及其具体信号通路，进而为脓毒症及脓毒症认知功能障碍的防治开辟新的干预靶点。     

Improved assay for fecal calprotectin

Fecal calprotectin is a marker of inflammatory and neoplastic disease in the lower gastrointestinal tract. A new fecal sample preparation procedure for the measurement of calprotectin has been developed, with higher calprotectin yield and lower contamination risk. Changes in the new method compared to the original [Roseth AG, Fagerhol MK, Aadland E, Schonsby H. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand J Gastroenterol 1992;27(9):793-798] are smaller sample size, higher dilution of the sample, presence of dissociating agents in the extraction solution and procedure performed in closed disposable tubes. The extraction yield was 78% (41-100%) of total calprotectin, giving an overall five-fold increase compared to the original method. Samples with high calprotectin values were increased to a slightly higher degree, than low calprotectin samples, thus improving the separation between high and low calprotectin levels. Median calprotectin level in healthy subjects was 26 microg/g. Pathological samples with pancolitis showed levels up to 30000 microg/g. The mean C.V. (coefficient of variation) in blended feces was lower than that of unblended, suggesting uneven distribution of calprotectin. However, no significant difference between spot measurements was found when five samples from each of 47 stools were measured. Thus measurements of calprotectin in fecal samples were accurate and reproducible. No interference with foods or relevant oral pharmaceuticals or nutraceuticals was found.     

脓毒症与铁代谢的研究进展

脓毒症是一种由感染引起的常见的全身炎症反应综合征,具有高发病率和高病死率的特征,已成为重要的公共健康问题之一。脓毒症及其发病机制和治疗也一直是研究重点。2016年,脓毒症被重新定义为由宿主对感染的反应失调引起的危及生命的器官功能障碍模式。近年来,针对脓毒症患者的免疫反应及代谢变化开展了大量临床及实验研究,其中铁代谢与脓毒症的关系也是研究重点之一。铁在调节免疫功能和微生物生长方面有着关键作用,已有研究证明铁代谢的变化会影响感染的风险。本文旨在对铁代谢与脓毒症及脓毒症诱导的多器官功能障碍的关系等作简要概述,以期对脓毒症的预后预测及治疗提供新的方向。     

Levels of calprotectin (leukocyte L1 protein) during apheresis.

The plasma concentration of calprotectin was measured before, during and after apheresis in patients with Guillain-Barré Syndrome (GBS), Waldenstr?m's syndrome or hypercholesterolaemia and in healthy donors of platelets. Increased calprotectin levels were found after plasma exchange in the Waldenstr?m's syndrome patients, probably caused by release of the protein from activated leukocytes. The decreased calprotectin values observed in the other patients, may be due to plasma dilution. Unexpectedly, the GBS patients were found to have high initial calprotectin levels in plasma but not in cerebrospinal fluid. In donors, normal and unchanged calprotectin concentrations were found throughout.