221例患者急诊血液净化及病因分析

目的了解患者急诊血液净化的病因、方式及疗效。方法分析该院2003年1月￣2005年1月行急诊血液净化的221例患者(CRF除外)的病因、方式及疗效。结果221例患者,其中男136例;平均年龄(42.86±21.15)岁,女85例;平均年龄(37.63±18.08)岁。所有患者的病因,占首位的是中毒87例(39.4%),其他依次为外科性疾病74例(33.5%)、内科性疾病46例(20.8%)和流行性出血热(epidemichemorrhagicfever,EHF)14例(6.3%)。短期血液净化后,98例治愈,104例好转,19例死亡,但死亡者的生存时间明显延长。71例MODS患者CRRT后水电解质和酸碱紊乱得到改善,抽血检测BUN、Scr、血K+(均P<0.01﹚、Na+(均P<0.05)下降,血PH、HCO3-(均P<0.01)、Cl-(P<0.05)升高。结论急诊血液净化的病因在原有中毒和ARF的基础上,新增了非肾脏疾病和MODS,提示血液净化的方式已从单纯的HD或HP扩大到多种方式联合治疗。该组成功的经验是,对不同的病例采取不同的血液净化方式,HD+HP或CRRT能缩短急性重症中毒患者的病程。对伴血小板减少或有出血的患者采用无肝素、低分子肝素或治疗后使用鱼精蛋白对抗等方法;对严重的外科性疾病如急性重症胰腺炎、大面积烧伤、严重复合性创伤、外科手术后、严重感染等患者,采用CRRT可有效地清除代谢产物,稳定内环境,提高患者的生存率。     

Is ivabradine suitable to control undesirable tachycardia induced by dobutamine in cardiogenic shock treatment?

Inotropic treatment remains the cornerstone for cardiogenic shock, an emergency that requires immediate resuscitative therapy before shock irreversibly damages vital organs. Although the sympathomimetic drug dobutamine is the most widely-used inotropic drug worldwide, it has several side effects including sinus tachycardia. Dobutamine partly restores systolic heart failure (HF); however, it increases the heart rate (HR) which counterbalances the beneficial effects. Ivabradine, a new selective I_f inhibitor, provides specific HR reduction and is indicated in stable coronary artery disease and in stable chronic HF with left ventricular dysfunction. Despite scarce data indicating beneficial effects of ivabradine in sinus tachycardia in various clinical settings, this drug remains contraindicated in acute HF. We propose that ivabradine could help to prevent the dobutamine-induced side effects, and that their combination in clinical practice could lead to pure inotropic effects, useful for the management of cardiogenic shock.     

Anti-inflammatory and organ protective effect of insulin in scalded MODS rats without controlling hyperglycemia

Background

Insulin, as an anti-inflammatory drug, could not be freely used in patients who experienced trauma according to the degree of inflammation, because of the side effect of hypoglycemia. In vivo experimental evidence is lacking concerning whether the effect is dosage dependent and whether it relies on controlling hyperglycemia.

急性脑出血后全身炎症反应综合征临床研究

目的了解急性脑出血后全身炎症反应综合征(SIRS)的发生率及其发生可能有关的因素,探讨SIRS在判断急性脑出血的病情和预后方面的临床价值.方法回顾性分析163例急性脑出血病人的临床资料,且以目前外科、危重病领域公认的SIRS、多器官功能障碍综合征(MODS)的诊断标准为依据,了解急性脑出血后SIRS和MODS的发生情况及相关问题.结果急性脑出血后SIRS的发生率为52%;出血量≤30 mL、出血破入脑室、随机血糖≥11.1 mmol/L的病人,SIRS的发生率分别较出血量＜30 mL、出血未破入脑室、随机血糖＜11.1 mmol/L的病人显著增高.脑出血后发生SIRS的病人,其MODS发生率、病死率均明显高于未发生SIRS的病人.结论急性脑出血后SIRS的发生率高,SIRS的发生提示病情危重,预后较差.     

Lipoteichoic acid may affect the pathogenesis of PBC-like bile duct damage and might be involved in systemic multifocal epithelial inflammations in chronic colitis-harboring TCRα−/−×AIM−/− mice

Background: Chronic colitis-harboring TCRα^{? / ?} × AIM^{? / ?} mice showed PBC-like bile duct damage in the liver. Bacterial infection is one of the candidates for the pathogenesis of PBC. We demonstrated that the bacterial cell wall component lipotheicoic acid (LTA) was detected at sites of inflammation around damaged bile ducts in PBC patients. The aim of this study was to investigate the pathophysiology of the liver and other organs in TCRα^{? / ?} × AIM^{? / ?} mice.

Methods: Thirteen female TCRα^{? / ?} × AIM^{? / ?} mice were sacrificed at 24 weeks of age. The liver, stomach, small intestine, colon, pancreas, kidney and spleen were studied for pathological examination. Using anti-LTA antibody as the primary antibody, an immunohistochemical study was carried out.

Results: In the liver, LTA was mainly detected in the portal area with inflammation, and some of the cytoplasm of hepatocytes. Inflammations were also observed in the stomach, intestine, pancreas and kidney. Throughout the gastrointestinal tract, from the stomach to the colon, LTA was detected in the epithelium at sites of inflammation. Furthermore, LTA was detected around both pancreatic ducts with inflammation and distal renal tubules with inflammation.

Conclusions: The development of inflammations in the liver as well as extensive organs, strongly suggests a close relationship between bile duct damage and systemic multifocal epithelial inflammations, perhaps involving bacterial LTA, in TCRα^{? / ?} × AIM^{? / ?} mice.     

创伤后感染致多器官功能障碍综合征患者血清β-hBD-2、OPN、pro-ADM和NPt水平的变化

目的：探讨多器官功能障碍综合征（multipleorgandysfunctionsyndrome,MODS）患者的炎症感染病理过程中炎性介质水平的变化。方法：血清人类B防御素-2（humanB．defensin-2,β—hBD-2）、骨桥蛋白（osteopontin,OPN）和新蝶呤（neoptefin,NPt）采用酶联免疫分析法（ELISA）测定,肾上腺髓质素前体（pro-adrenomeduUin,pro—ADM）检测采用化学免疫发光法。结果：四项血清标志物测定结果分别显示,对照组和确诊时组B-hBD-2、OPN、pro-ADM、NPt四种血清炎症介质标志水平均显著高于正常人组（P〈0．05,P〈0．01）,出院前组β-hBD-2、OPN水平显著高于正常人组,另两项指标均与正常人组比较无显著性差异（P均〉0．05）;同时确诊时组与对照组比较β—hBD-2、OPN、pro-ADM三项指标水平也显著升高（P〈0．05,P〈0．01）,NPt水平患者组呈略高,但无统计学意义（P〉0．05）;出院前组β-hBD-2、OPN、pro-ADM、NPt四种血清炎症介质标志水平均显著低于确诊时组（P〈0．05,P〈0．01）。结论：MODS患者的炎症感染病理过程中炎性介质水平显著升高,其测定对于临床抗感染治疗提供重要价值。     

PD-L1 blockade improves immune dysfunction of spleen dendritic cells and T-cells in zymosan-induced multiple organs dysfunction syndromes

This research is to investigate the role of tolerant spleen dendritic cells (DC) in multiple organs dysfunction syndromes (MODS) at late stage. Tolerant DC and MODS were induced by intraperotineal injection of zymosan. The immunity of DC was determined by examining interleukin (IL)-10, IL-12, IL-2, major histocompatibility complex (MHC), CD86, programmed death (PD-1), programmed death ligand 1 (PD-L1), paired immunoglobulin-like receptor B (PIR-B) or T-cell proliferation in serum, spleen homogenate, DC culture or DC/T-cell co-culture. The PD-L1/PD-1 pathway was blocked using PD-L1 antibody. The IL-12p70 in serum, spleen homogenate and DC culture supernatant were decreased at 5 d and 12 d after zymosan injection while the IL-12p40 and IL-10 were increased. The expression of MHC, cluster of differentiation 86 (CD86), PD-1 and PD-L1 in spleen DCs were increased at early stage after zymosan injection. At 5 d and 12 d, the expression of MHC and CD86 was reduced while the expression of PD-1, PD-L1 and PIR-B was increased, accompanied with decreased proliferation of T-cell and decrease of IL-2 in spleen and serum. Application of PD-L1 antibody improved the above changes. At late stage of MODS mice induced by zymosan, the expression of co-stimulators and inhibitors in spleen DCs was imbalanced to form tolerant DCs which reduced the activation of T-cells. PD-L1 antibody improved the immune tolerance of DCs through intervening PD-1/PD-L1 pathway, and attenuated the inhibition of T-cell activities by tolerant DCs and the immune inhibition.     

MK2 plays an important role for the increased vascular permeability that follows thermal injury

We previously reported Rho kinase is involved in vessel hyper-permeability caused by burns. Here we further explore the Rho kinase downstream signaling, it is found that its specific inhibitor Y27632 significantly diminishes the activation of JNK and p38 MAPKs but not ERK that induced by serum from burned rats (burn-serum). JNK activation was found involved in the expression of HUVEC adhesion molecules following thermal injury, although not in the process of stress fiber formation. Inhibition of various MAPKs by specific inhibitors showed that SB203580 (inhibitor of p38), but neither SP600125 (inhibitor of JNK) nor PD98059 (inhibitor of ERK), abolish activation of the p38 downstream kinase MK2. Demonstration of stress fibers by fluorescent-labeled phalloidin showed that inhibition of MK2, either by its specific inhibitor or by dominant negative adeno-viral-carried constructs, significantly reduced burn-serum-induced HUVEC stress-fiber formation, while inhibition of another downstream p38 MAPK kinase, PRAK, had no such effects. Transfection of dominant negative adeno-viral MK2 (Ad-MK2(A)) significantly inhibited thermal injury-induced blood vessel hyper-permeability in rats and, moreover, prolonged the survival of burned rats beyond 72 h following thermal injury. One of the mechanisms behind these phenomena is that Ad-MK2(A) causes a significant depression of burn-serum-induced HSP27-phosphorylation, while the adeno-viral transported dominant negative PRAK (Ad-PRAK(A)) does not block. Although the effect of blockade of MK2 through its adeno-viral approach requires further study and investigation of alternatives to know for sure, we may have found a new pathway behind thermal-injury-induced blood vessel hyper-permeability, namely: Rho kinase > p38 > MK2 > HSP27.     

The Role of Complement,C5a and Its Receptors in Sepsis and Multiorgan Dysfunction Syndrome

Sepsis continues to be a major clinical problem that is difficult to treat, as the pathophysiology of the disease is still unclear. Despite promising experimental strategies, therapeutic interventions have been largely unsuccessful. There is now increasing evidence that the disturbance of innate immunity during sepsis and multiorgan dysfunction syndrome (MODS) may be linked to uncontrolled activation of the complement system. Especially, the powerful anaphylatoxin C5a seems to play a key role in the development of immune paralysis. In this review, we describe our present understanding of the role of complement in the inflammatory response during sepsis and MODS.