青海地区藏族肺结核患者血清SIL-2R、IFN-γ、HBD-2、MCP-1的表达及意义

目的 通过检测肺结核(tuberculosis,TB)患者血清中可溶性白介素2受体(solubleinterleukin2 receptor,SIL-2R)、γ干扰素(γ Interferon,IFN-γ)、人β-防御素-2(humanβ-defense-2,HBD-2)、单核细胞趋化蛋白-1(monocyte chemotactant protein-1,MPC-1)的表达水平,探讨其在肺结核中的作用.方法 选择藏族肺结核患者为病例组,应用双抗体夹心酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测血清中SIL-2R、IFN-γ、HBD-2、MPC-1的含量,并选择同期进行健康体检的藏族同胞为对照组,进行比较分析.结果 病例组血清中SIL-2R为(344.01±92.92) pg/ml、INF-γ为(243.84±51.40) pg/ml、HBD-2为(238.24±44.26) ng/L、MPC-1为(251.01 ±64.71) ng/L,表达水平均高于对照组,差异有统计学意义(均有P＜0.001);肺结核患者中痰菌涂片阳性组可溶性SIL-2R、IFN-γ、HBD-2、MPC-1的表达水平高于阴性组,差异有统计学意义(均有P＜0.05).结论 藏族肺结核患者血清中可溶性SIL-2R、IFN-γ、HBD-2、MPC-1的表达水平明显升高,这些细胞因子可能与肺结核病感染的程度、演变等有关.     

Acute liver injury in COVID-19 patients hospitalized in the intensive care unit: Narrative review

In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.     

Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

Solitary organ autoimmune disorders, formerly known as autoimmune pancreatitis (AIP), autoimmune sialadenitis, and autoimmune sclerosing cholangitis, are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease (IgG4-RD). AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody (Ab), accumulation of IgG4-expressing plasmacytes in the affected organs, and involvement of multiple organs. It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity. However, a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype. In addition, disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone. Therefore, it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD. Recently, we found that activation of plasmacytoid dendritic cells producing both interferon-α (IFN-α) and interleukin-33 (IL-33) mediate murine AIP and human IgG4-RD. More importantly, we provided evidence that serum concentrations of IFN-α and IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders. In this Frontier article, we have summarized and discussed biomarkers of AIP and IgG4-RD, including Igs, autoAbs, and cytokines to provide useful information not only for clinicians but also for researchers.     

Impact of cytokine storm and systemic inflammation on liver impairment patients infected by SARS-CoV-2: Prospective therapeutic challenges

Coronavirus disease 2019 (COVID-19) is a devastating worldwide pandemic infection caused by a severe acute respiratory syndrome namely coronavirus 2 (SARS-CoV-2) that is associated with a high spreading and mortality rate. On the date this review was written, SARS-CoV-2 infected about 96 million people and killed about 2 million people. Several arguments disclosed the high mortality of COVID-19 due to acute respiratory distress syndrome or change in the amount of angiotensin-converting enzyme 2 (ACE2) receptor expression or cytokine storm strength production. In a similar pattern, hepatic impairment patients co-infected with SARS-CoV-2 exhibited overexpression of ACE2 receptors and cytokine storm overwhelming, which worsens the hepatic impairment and increases the mortality rate. In this review, the impact of SARS-CoV-2 on hepatic impairment conditions we overviewed. Besides, we focused on the recent studies that indicated cytokine storm as well as ACE2 as the main factors for high COVID-19 spreading and mortality while hinting at the potential therapeutic strategies.     

银杏苦内酯B对重症急性胰腺炎大鼠血浆细胞因子的影响

目的:观察重症急性胰腺炎(SAP)大鼠血浆中TNF-α,血小板活化因子(PAF),IL-10, IL-12,sTNFR的水平变化及其银杏苦内酯B(BN52021)的影响.方法:实验选用Wistar♂大鼠45只,随机分成SAP模型组(SAP,n=15),BN52021治疗组(BN,n=15)和阴性对照组(NC,n=15)．前两组以50 g／L牛磺胆酸钠逆行注入主胰管制成SAP模型,NC组开腹后仅翻动十二指肠并触摸胰腺数次关腹．制模15 min后,SAP组经股静脉以5 mL／mg注射生理盐水;BN组以BN52021(5 mg／kg)代替生理盐水静注．制模后分别于1,6,12 h采血,应用ELISA技术测定血浆TNF-α,PAF,IL-10,IL-12和sTNFR水平．结果:SAP组,NC组和BN组大鼠血浆TNF-α和PAF水平相比,具有显著性差异,SAP组(746．2±374．1,82．5±35．4 ng／L)显著高于NC组(385．1±86．3．1．1±1．9 ng／L),BN组(503．7±177．9,39．9±29．9 ng／L)显著低于SAP组(P<0．05)．血浆sTNFR水平三组相比存在明显差异,SAP组(488．7±363．8 ng／L)显著高于NC组(50．0±21．0 ng／L),BN组(883．4±552．5 ng／L)显著高于SAP组(488．7±363．8 ng／L)(P<0．05)．血浆IL-12三组相比存在明显差异,SAP组(97．1±55．9 ng／L)显著高于NC组(20．4±19．4 ng／L),BN组在1 h时相点(133．5±33．4 ng／L)显著高于SAP组(55．9±14．7 ng／L)(P<0．05)．血浆IL-10三组相比不存在明显差异(P>0．05)．结论:SAP大鼠促炎细胞因子和抗炎细胞因子均显著升高．BN52021能降低血浆促炎因子含量,提高IL-12和细胞因子拮抗剂sTNFR含量．     

Cytokine-induced nitric oxide inhibits mitochondrial energy production and induces myocardial dysfunction in endotoxin-treated rat hearts

The mechanism responsible for cardiac depression in septic shock remains unknown. The present study examined whether nitric oxide (NO) overproduced by inducible NO synthase (iNOS) can inhibit aerobic energy metabolism and impair the myocardial function in endotoxin-treated rat hearts. Lipopolysaccharide (LPS) significantly decreased systolic blood pressure (BP) to 44% of control during the 48 h treatment. Hearts from control and LPS-treated rats were perfused in a Langendorff apparatus. After LPS injection, left ventricular (LV) developed pressure (LVDP) was significantly depressed, plasma NO2-/NO3- (NO(x)) concentration was markedly increased, and myocardial adenosine 5'-triphosphate (ATP), creatine phosphate (CrP), and the ratio of ATP/adenosine 5'-diphosphate were progressively decreased with time. Immunological examination showed a significant expression of iNOS protein in the LPS-treated myocytes. Aminoguanidine, an inhibitor of iNOS, significantly attenuated these LPS-induced functional and metabolic changes. Myocardial cyclic guanosine 3',5'-monophosphate (cGMP) content was significantly increased after LPS injection. Methylene blue, an inhibitor of soluble guanylate cyclase, blunted this increase in cGMP and significantly restored the LPS-induced contractile dysfunction 6 h after LPS injection. In addition, there was a significant negative correlation between LVDP and myocardial cGMP levels as well as a significant negative correlation between LVDP and plasma NO(x) levels. In contrast, 48 h after LPS injection, methylene blue no longer affected cardiac performance, and there was a significant positive correlation between LVDP and myocardial ATP content. Furthermore, the normalized activities (as a ratio of the citrate synthase activity) of mitochondrial NADH-CoQ reductase, succinate-CoQ reductase, and ATPase, were significantly inhibited, and the swelling or disruption of mitochondria cristae was seen in the 48 h LPS treatment. These LPS-induced functional and morphological disorders in the mitochondria were significantly improved by aminoguanidine. The findings suggest that sustained production of NO by iNOS leads to contractile dysfunction via cGMP in the early stage, but that it can directly impair the mitochondrial function, lower myocardial energy production, and contribute significantly to the myocardial dysfunction in the later stage of septic shock.     

1,6-二磷酸果糖对体外循环患者血浆细胞因子的影响

目的　探讨 1,6-二磷酸果糖 (FDP)减轻体外循环 (CPB)术后全身炎症反应的临床效果。方法　将 3 8例心脏直视手术患者随机分为实验组 2 0例 ,对照组 18例。实验组在常规 CPB预充液中加入 FDP2 0 0 m g/kg,对照组不用 FDP。于手术开始前 (T0 )、 CPB结束后即刻 (T1)、CPB结束后 3小时 (T2 )、 6小时 (T3)及 2 4小时 (T4)分别抽取桡动脉血 ,采用 EL ISA法测定血浆肿瘤坏死因子 (TNF-α)、白介素 -6(IL-6)、白介素 -8(IL-8) ,用硫代巴比妥酸比色法测定血浆丙二醛 (MDA)。结果　两组术前血浆 TNF-α、IL-6、IL-8、MDA浓度无差异 ,CPB结束后均已明显升高 (P <0 .0 5) ,CPB后 3小时 TNF-α、 IL -6、 IL -8达高峰 ,6小时开始下降 ,MDA在 6小时达高峰 ,2 4小时 TNF-α、 MDA恢复到接近术前水平 (P >0 .0 5) ,IL -6、 IL -8仍高于术前 (P <0 .0 5)。实验组血浆 TNF-α、 IL -6、 IL -8浓度在 T1、 T2 、 T3均明显低于对照组 (P <0 .0 1) ,MDA浓度在 T1、 T2 (P <0 .0 5)和 T3 (P <0 .0 1)均明显低于对照组 ,血浆 IL -6、 IL -8在 T4也均低于对照组 (P <0 .0 1,P <0 .0 5)。结论　 CPB术后血浆 TNF-α、IL-6、IL-8、MDA浓度明显升高 ,在 CPB预充液中加入 FDP可明显降低 CPB术后TNF-α、 IL-6、 IL-8及 MDA的浓度 ,     

尼古丁对人树突状细胞的激活及其与急性冠状动脉综合征的关系

目的:研究尼古丁对人树突状细胞(DC)功能的影响及其与急性冠状动脉综合征(ACS)发病的关系.方法:观察体外尼古丁对DC功能的作用以及11例正常对照者(正常对照组)与45例ACS者(ACS组)发病时及戒烟后DC的功能状态.流式细胞仪检测DC CD86的表达;混合淋巴反应检测DC对T淋巴细胞的刺激作用;酶联免疫吸附法(ELISA)测定混合淋巴反应上清液中细胞因子水平.结果:与正常对照组比较,ACS时DC表面CD86的表达明显增高,对T淋巴细胞刺激的能力增强;致炎细胞因子分泌增多;DC CD86的表达与日吸烟量正相关(r=0.63,P＜0.01);平均戒烟5个月后,DC功能接近正常;体外尼古丁亦能明显刺激DC的功能,呈浓度依赖性.结论:①ACS时DC明显激活;②戒烟后DC功能可迅速恢复;③尼古丁可能是ACS时DC激活的刺激因素之一.     

IL-27 and autoimmune rheumatologic diseases: The good,the bad,and the ugly

The footprint of cytokines is evident in almost every biological process, such as development, as well as the pathogenesis of the different diseases, immune responses to pathogens, etc. These small proteins are categorized into different functional classes; for instance, they can play a pro-inflammatory or anti-inflammatory role in different situations, or they can confer a polarization to the immune system. Interleukin (IL)-27 is a member of the IL-12 family. Antigen-presenting cells are the primary source of IL-27 production, which exerts its effects by bindings to the IL-27 receptor expressed on the surface of target cells. Interaction of IL-27 and IL-27 receptor leads to activation of the JAK-STAT and p38 MAPK signaling pathways. Most studies focused on the inflammatory effects of this cytokine, but gradually anti-inflammatory effects were also revealed for this cytokine, which changed the traditional perception of the function of this cytokine. The functionality of IL-27 in the pathogenesis of rheumatic diseases has been attributed to a double-blade sword. Hence, novel therapeutic approaches have been devised targeting IL-12 family that has been accompanied with promising results. In this review, we focused on the inflammatory and anti-inflammatory properties of IL-27 in different autoimmune rheumatologic diseases and its plausible therapeutic potentials.