Clinical Evaluation of Multiple Inflammation Biomarkers for Diagnosis and Prognosis for Patients with Systemic Inflammatory Response Syndrome

A multiplexed biomarker bundle consisting of nine different inflammation markers was evaluated regarding their diagnostic and prognostic performances in 159 adult systemic inflammatory response syndrome (SIRS) patients enrolled at the emergency department. Fibronectin, interleukin-8 (IL-8), biotin, and neutrophil gelatinase-associated lipocalin (NGAL) were the most robust markers but were not superior to the already established markers IL-6, C-reactive protein (CRP), procalcitonin (PCT), and soluble urokinase plasminogen activator receptor (suPAR).     

Rational Drug Correction of Systemic Inflammatory Response Syndrome in Severe Experimental Heart Failure

A course of adenocine (cardiotonic drug with a pronounced cardioprotective effect) for severe experimental heart failure caused by toxic allergic myocarditis (for 10 days) more effectively restored the systolic and diastolic function of the heart and arrested systemic inflammatory response syndrome than traditional therapy with angiotensin-converting enzyme inhibitors, β-adrenoblockers, or diuretics in combination with neoton. Adenocine is characterized by a synergistic effect, and none of its ingredients alone (nicotinamide adenine dinucleotide, inosine, β-acetyldigoxin, oxyfedrine) exhibits similar effect.     

大黄对全身炎症反应综合征患者凝血功能的影响

目的 :探讨大黄对全身炎症反应综合征 (SIRS)患者凝血功能的影响机制。方法 :36例无凝血功能障碍的SIRS患者随机分为二组 ,对照组 18例给予常规抗炎及支持对症治疗 ,治疗组 18例加用生大黄粉 6 0g/天煎制后分 3次鼻饲。分别检测二组患者治疗前、治疗后 1、3、7天的血浆凝血酶原时间、血小板计数和血浆血管性假血友病因子 (vWF)含量。结果 :治疗后治疗组第 7天的检测指标与对照组比较有显著差异。结论 :大黄对SIRS患者的凝血功能有保护作用。     

Phenotypical and Functional Characterization of the Idiotype-Positive Blood B Cells in Multiple Myeloma

In this study the idiotype-positive B cells of one patient with smouldering multiple myeloma (IgG kappa) and of one patient with multiple myeloma (IgG lambda) were analysed phenotypically and functionally. As regards the expression of B cell-associated differentiation antigens and size distribution, the idiotype-positive B cells resembled normal IgG-bearing blood B cells. In functional studies the lymphocytes were cultured in vitro with Staphylococcus aureus, pokeweed mitogen, T-cell factors, or combinations of these. After culture, proliferation and differentiation of the idiotype-positive B cells were measured by autoradiography, an idiotype-specific ELISA, and a spot ELISA. The results show that idiotype-positive B cells of both patients are able to proliferate after stimulation in vitro. In contrast to their normal counterparts, however, almost no increase in the amount of secreted idiotype IgG could be induced. This suggests that the idiotype-positive blood B cells have lost some of their ability to respond to exogenous stimuli.     

老年多器官功能不全综合征患者免疫功能探讨

目的:检测老年多器官功能不全综合征(MODSE)患者的细胞免疫、体液免疫指标,了解其免疫水平及其与疾病的关系。方法:将老年患者根据诊断分为MODSE组(46例)和对照组(40例),用双/三色直接免疫荧光标记全血溶血法检测细胞免疫CD3~+、CD3~+CD4~+、CD3~+CD8~+、CD4~+/CD8~+、NK、CIK指标;用免疫比浊法检测体液免疫C3,C4,CH50,IgG,IgA,IgM指标。结果:两组患者CD3~+,NK,IgA差异有统计学意义(P<0.05)。两组免疫功能比较有明显差异:对照组CD3~+高,MODSE组NK、IgA高。结论:MODSE组患者存在免疫功能低下。     

Functional and Phenotypical Characterization of Activated T Cells from Intra-articular Sites in Inflammatory Joint Diseases

The presence of activated T lymphocytes bearing interleukin 2 (IL-2) receptors and HLA class II (Ia) antigens accompanied by impaired T cell functions such as a decreased mitogenic responsiveness are characteristic findings, especially in intra-articular sites in chronic inflammatory joint diseases. The objective of the present study was to further characterize these in vivo activated T cells by the investigation of IL-2 production and a possible T cell receptor modulation. IL-2 receptors were found to be expressed primarily in the CD4+ subset. The Ia+ subset expressing both DR and DQ antigens showed a weaker mitogen-induced response as compared to the Ia- fraction. A decreased mitogen-induced IL-2 production and a lower response to anti-CD3 monoclonal antibodies was observed with synovial T lymphocytes as compared to peripheral blood T cells. The density of the CD3 molecule, known to be closely associated with the T cell receptor, was significantly lower in intra-articular sites, while other T cell-specific surface molecules were expressed to a similar extent in both compartments. The decreased synovial T cell mitogenesis was not restored by the addition of lymphokines (IL-1 and IL-2) or blood monocytes, nor by removing CD8+ T cells. These data present further evidence for a significant T cell activation in intra-articular sites in chronic inflammatory joint diseases. The decreased expression of the CD3 glycoprotein suggests a modulation by so far unidentified antigen(s), which could also be responsible for the weak T cell response elicited by polyclonal mitogens.     

外周血单核细胞SOCS-1表达与MODS患者预后关系的研究

目的了解外周血单核细胞SOCS-1表达与多器官功能障碍综合征（MODS）患者预后的关系及临床意义。方法收集24例MODS患者，并采集其外周静脉血，采用淋巴细胞分离液密度梯度离心法分离外周血单核细胞（PBMCs），分别以RT-PCR法及Western-blot法检测PBMCs中SOCS-1的基因及蛋白表达，分析其与预后及MODS评分的关系。结果MODS组中死亡患者PBMCs中的SOCS-1mRNA表达量（0.4938±0.0273）显著低于存活患者（0.5475±0.0289）（P〈0.05），SOCS-1蛋白表达量（0.7924±0.0284）显著低于存活患者（0.8406±0.0407）（P〈0.05）。MODS患者的PBMCs中的SOCS-1mRNA表达量与MODS评分呈显著的负相关关系（r=-0.723,P〈0.01），SOCS-1蛋白表达量与MODS评分呈显著的负相关关系（r=-0.534，P〈0.01）。结论在MODS中，SOCS-1的表达可能起到保护组织避免损伤的作用,SOCS-1表达的减少可能提示患者的预后不良     

Homocysteine and Laminin Are Not Prognostic Markers in Patients with Septic Inflammatory Response Syndrome

The aim of this study was to measure plasma homocysteine and laminin concentrations in patients with nonbacteremic systemic inflammatory response syndrome (SIRS) and to compare them with those of a healthy control group. Concerning laminin, significant increased concentrations could be observed in the SIRS group compared to the control group, but for homocysteine, no significance could be observed. In summary, homocysteine and laminin levels are not useful in the prediction of a patient's outcome.     

全身炎症反应综合征标准判断重症急性胰腺炎及预后的研究

目的探讨全身性炎症反应综合征(Systemic Inflammatory Response Syndrome,SIRS)在急性胰腺炎(Acute Pancreatitis,AP)中的发生情况,尝试建立修订全身性炎症反应综合征(Modified Systemic Inflammatory Response Syndrome,MSIRS)标准,应用MSIRS早期判断重症急性胰腺炎(Severe Acute Pancreatitis,SAP)及其预后. 方法收集我院1998年1月～2002年2月收治的281例急性胰腺炎的临床资料,统计分析轻型急性胰腺炎(Mild Acute Pancreatitis,MAP)和SAP患者发病48小时内的SIRS指标水平;修改SIRS标准水平,探索MSIRS标准早期判断SAP的优越性以及和SAP预后间的关系. 结果① SIRS在AP中总发生率为41.2%,其中MAP发生SIRS为18.1%,SAP则100%发生SIRS;②建立MSIRS标准:T>38℃,P>110次/min,R>22次/min,WBC>15.0×109/L,符合2项或2项以上者,判断为SAP;③与临床诊断金标准比较,MSIRS标准早期判断出SAP的敏感性、特异性、准确性、阳性预测值及阴性预测值分别为:91.9%、93.6%、93.1%、85.0%和96.7%.④SAP患者除胰腺并发症外,急性呼吸窘迫综合征(Acute Respiratory Distress Syndrome,ARDS)、多器官功能不全综合征(Multiple Organ Dysfunction Sydrome MODS)及病死率均随着符合MSIRS标准项目增多而显著升高. 结论 SIRS在AP患者中是一个具有重要意义的病理生理过程,应用MSIRS标准可以早期判断SAP,敏感性高、特异性好,并与SAP并发ARDS、MODS、及病死率有关.     

全身炎症反应综合征标准判断重症急性胰腺炎及预后的研究

目的　探讨全身性炎症反应综合征 (SystemicInflammatoryResponseSyndrome,SIRS)在急性胰腺炎 (AcutePan creatitis,AP)中的发生情况 ,尝试建立修订全身性炎症反应综合征 (ModifiedSystemicInflammatoryResponseSyndrome ,MSIRS)标准 ,应用MSIRS早期判断重症急性胰腺炎 (SevereAcutePancreatitis,SAP)及其预后 .方法　收集我院 1998年 1月～ 2 0 0 2年 2月收治的 2 81例急性胰腺炎的临床资料 ,统计分析轻型急性胰腺炎 (MildAcutePancreatitis,MAP)和SAP患者发病 48小时内的SIRS指标水平 ;修改SIRS标准水平 ,探索MSIRS标准早期判断SAP的优越性以及和SAP预后间的关系 .结果　①SIRS在AP中总发生率为 41.2 % ,其中MAP发生SIRS为 18.1% ,SAP则 10 0 %发生SIRS ;②建立MSIRS标准 :T >38℃ ,P >110次 /min ,R >2 2次 /min ,WBC >15 .0× 10 9/L ,符合 2项或 2项以上者 ,判断为SAP ;③与临床诊断金标准比较 ,MSIRS标准早期判断出SAP的敏感性、特异性、准确性、阳性预测值及阴性预测值分别为 :91.9%、93.6 %、93.1%、85 0 %和 96 .7% .④SAP患者除胰腺并发症外 ,急性呼吸窘迫综合征 (AcuteRespiratoryDistressSyndrome ,ARDS)、多器官功能不全综合征 (MultipleOrganDysfunctionSydromeMODS)及病死率均随着符合M     

炎症反应对急性冠脉综合征患者血小板活性及预后的影响

目的:观察急性冠脉综合征(ACS)患者炎症反应与血小板活性的关系及对预后的影响。方法:348例ACS患者根据是否合并全身炎症反应综合征(SIRS)分为SIRS组(n=128)及对照组(n=220)。两组均给予标准的冠心病二级预防及冠状动脉介入(PCI)治疗。比较两组患者术前血小板最大聚集率(mPAR)、超敏C反应蛋白(hs-CRP)、血清可溶性CD40L(sCD40L)、血清基质金属蛋白酶-9(MMP-9)等指标的差异,分析两组各种炎症因子水平与mPAR的相关性,并比较术后30天两组不良事件的发生率。结果:SIRS组患者mPAR、hs-CRP、sCD40L、MMP-9均明显高于对照组(P均<0.01);两组hs-CRP、sCD40L、MMP-9水平与mPAR之间均呈正相关(P<0.01)。术后30天,SIRS组患者不良事件发生率高于对照组(P<0.01)。结论:炎症反应可能是导致血小板活化的原因之一,合并SIRS的ACS患者预后较差。     

老年多器官衰竭患者外周血白细胞糖皮质激素受体改变及其意义

应用放射配体结合法检测老年多器官衰竭（MOFE）患者外周血单个核白细胞（MNL）糖皮质激素受体（GR）的结合量，并与成年人多器官衰竭（MOF）和单一器官衰竭进行比较。结果显示MOFE患者MNL的GR结合量明显降低，而血浆皮质醇（F）则升高。单一器官衰竭时，MNL的GR结合容量也下降，但幅度较MOFE时小。实验结果提示，GR的改变参与MOF的病理生理过程，检测GR可作为判断MOF严重程度的指标和监测GR改变可以指导合理用药。     

乌司他丁联合血必净对烧伤后脓毒症患者凝血功能及全身炎性反应的影响研究

目的 研究乌司他丁、血必净联合治疗对烧伤后脓毒症凝血功能及全身炎性反应影响。方法 回顾分析2016年6月~2018年6月在我院诊治的146例烧伤后脓毒症患者临床资料,随机分为对照组和观察组,各73例。对照组采用常规综合治疗,观察组在对照组基础上采用乌司他丁联合血必净治疗,观察两组治疗患者治疗前后凝血功能及全身炎性反应情况。结果 治疗后,观察组凝血酶原时间（PT）、纤维蛋白原（FIB）、血纤维蛋白原降解产物（FDP）、部分凝血活酶时间（APTT）、凝血酶时间（TT）均优于对照组,差异均有统计学意义（P＜0.05）;观察组TNF-α、IL-6、IL-10、CRP水平改善优于对照组,差异有统计学意义（P＜0.05）。结论 乌司他丁、血必净联合治疗对烧伤后脓毒症可以改善凝血功能,减轻炎性反应,促进患者的康复。     

Natural Killer Cells Promote Tissue Injury and Systemic Inflammatory Responses During Fatal Ehrlichia-Induced Toxic Shock-Like Syndrome

Human monocytotropic ehrlichiosis is caused by Ehrlichia chaffeensis, a Gram-negative bacterium lacking lipopolysaccharide. We have shown that fatal murine ehrlichiosis is associated with CD8⁺T cell-mediated tissue damage, tumor necrosis factor-α, and interleukin (IL)-10 overproduction, and CD4⁺Th1 hyporesponsiveness. In this study, we examined the relative contributions of natural killer (NK) and NKT cells in Ehrlichia-induced toxic shock. Lethal ehrlichial infection in wild-type mice induced a decline in NKT cell numbers, and late expansion and migration of activated NK cells to the liver, a main infection site that coincided with development of hepatic injury. The spatial and temporal changes in NK and NKT cells in lethally infected mice correlated with higher NK cell cytotoxic activity, higher expression of cytotoxic molecules such as granzyme B, higher production of interferon-γ and tumor necrosis factor-α, increased hepatic infiltration with CD8αCD11c⁺ dendritic cells and CD8⁺T cells, decreased splenic CD4⁺T cells, increased serum concentrations of IL-12p40, IL-18, RANTES, and monocyte chemotactic protein-1, and elevated production of IL-18 by liver mononuclear cells compared with nonlethally infected mice. Depletion of NK cells prevented development of severe liver injury, decreased serum levels of interferon-γ, tumor necrosis factor-α, and IL-10, and enhanced bacterial elimination. These data indicate that NK cells promote immunopathology and defective anti-ehrlichial immunity, possibly via decreasing the protective immune response mediated by interferon-γ producing CD4⁺Th1 and NKT cells.Human monocytotropic ehrlichiosis (HME) is an emerging tick-borne and a life threatening illness caused by Ehrlichia chaffeensis, an obligatory intracellular bacterium.^1,2 HME can manifest as either mild disease with nonspecific flu-like symptoms or severe and fatal disease that presents as toxic shock-like syndrome, multi-organ failure, or adult respiratory distress syndrome.^2,3,4,5,6 Severe HME in immunocompetent patients is thought to be due to immune-mediated pathology, which is attributed to severe inflammation in the absence of large quantities of ehrlichiae in the tissues.⁴ Doxycycline treatment is most effective if administered early in the course of illness.^1,7 The lack of complete understanding of the pathogenic mechanisms of Ehrlichia-induced toxic shock-like syndrome is a major limitation in successful management of these patients. Ehrlichia muris and Ixodes ovatus Ehrlichia (IOE), which are closely related to each other and to E. chaffeensis, stimulate protective or pathogenic immune responses, respectively, in C57BL/6 mice.^8,9 Intradermal (i.d.) and intraperitoneal (i.p.) infection with a high dose of IOE induces mild and fatal disease, respectively.⁹ Using these models, we and others have shown that antigen-specific interferon (IFN)-γ producing CD4⁺Th1 cells and IgG2a antibodies play important roles in protective immunity against Ehrlichia.^4,10,11 In contrast, fatal murine ehrlichiosis, which recapitulates the pathological and laboratory manifestations of fatal HME is associated with a suppressed or weak CD4⁺Th1 immune response, marked lymphopenia, high levels of serum tumor necrosis factor (TNF)-α and interleukin (IL)-10, and severe liver injury, characteristics consistent with toxic shock syndrome.^4,5,12 β₂m^−/− mice, which are deficient in CD8⁺T cells and natural killer T (NKT) cells, are resistant to fatal IOE-induced toxic shock when compared with wild-type and TAP^−/− mice that are deficient in only CD8⁺T cells, suggesting that CD8⁺T cells mediate immunopathology and fatal ehrlichiosis.¹² Interestingly, absence of NKT cells in CD1d^−/− mice did not protect mice from fatal ehrlichiosis even though their absence prevented the development of liver injury and systemic inflammation.¹³ LPS-lacking Ehrlichia can directly stimulate IFN-γ production by NKT cells in a CD1 days-dependent, but toll-like receptor 4-independent, manner.¹⁴ Further studies showed that NKT cells are critical for clearance of the bacterial burden in vivo, which may account for death of CD1d^−/− mice following lethal ehrlichial infection.¹³NK cells are abundant in the liver, able to produce high levels of pro- and anti-inflammatory cytokines, and play an important role in innate immunity to microbial pathogens.¹⁵ NK cells contribute to the capacity of CD8⁺T cells to produce IFN-γ and to lyse Listeria monocytogenes- and Mycobacterium tuberculosis-infected monocytes.^16,17 Cross talk between NK cells and dendritic cells (DC) is essential for maturation of DC and activation of NK cells. IL-12, IL-15, and IL-18 produced by activated macrophages or mature DC activate cytotoxic NK cells and stimulate their IFN-γ production, which in turn promotes the expansion of CD4⁺Th1 cells.^{17,18,19,20,21,22,23,24} While NK cells play a protective role in some viral infections, NK cells cause hepatocyte apoptosis in models of viral hepatitis.^25,26The current study was undertaken to specifically delineate the contributions of NK cells and NKT cells to the immunopathogenesis of Ehrlichia-induced toxic shock-like syndrome using animal models of nonlethal and lethal ehrlichiosis caused by i.d. and i.p inoculation of IOE, respectively. Our data provide a new finding suggesting that NK cells contribute to severe tissue injury and suppressed protective immunity during infection with these LPS-lacking, obligately intracellular bacteria.