血管生成素-2及可溶性糖基化终末产物受体在脓毒症相关急性呼吸窘迫综合征发病中的作用

目的 本研究旨在探索血管生成素-2(Ang-2)及可溶性糖基化终末产物受体（sRAGE）表达在脓毒症相关急性呼吸窘迫综合征（ARDS）发病中的作用,评估其对脓毒症相关ARDS的发生起到早期预测作用。方法 收集2021年5月至2022年1月于山西白求恩医院住院的脓毒症相关ARDS患者作为研究组,脓毒症患者作为病例对照组,同期于本院体检中心进行健康体检的成人为健康对照组。追踪随访研究组患者28 d转归情况,分为存活组9例和死亡组8例。比较各组受试者Ang-2及sRAGE表达水平及实验室指标（白细胞计数、中性粒细胞计数、淋巴细胞数、中性粒细胞及淋巴细胞比值、单核细胞数及嗜酸性粒细胞数）的差异,并分析脓毒症相关ARDS发病的危险因素,以及Ang-2和sRAGE对脓毒症相关ARDS早期识别的诊断效能。结果 三组Ang-2及sRAGE表达水平比较差异均有统计学意义（分别P <0.01,P <0.05）。而且与病例对照组（3 378.06/912.67,1 343.63/334.49）及健康对照组（2 852.48/411.97,1 365.53/211.54）相比,研究组Ang-2及s...     

急性肺损伤时晚期糖基化终末产物受体变化的实验研究

目的 观察晚期糖基化终末产物受体(RAGE)在不同程度急性肺损伤(ALI)大鼠血浆和肺泡灌洗液(BALF)中的变化,探讨RAGE在判断ALI严重程度方面的价值.方法 30只SD大鼠随机分为3组:低剂量组、高剂量组和对照组.Western blot法检测BALF和血浆中RAGE相对含量,同时测定PaO2、肺组织湿干质量比值(W/D)、BALF蛋白含量、血浆和BALF中肿瘤坏死因子-α(TNF-α)水平,结合病理改变评价各组肺损伤程度.结果致伤组均出现肺损伤,高剂量组损伤更明显;与对照组比较,两致伤组血浆和BALF中RAGE含量均有所上升(P﹤0.05),且高剂量组BALF中RAGE含量又高于低剂量组(P<0.05),而血浆中RAGE含量在低剂量组与高剂量组间差异无统计学意义.结论 ALI时,BALF和血浆中RAGE水平升高,BALF中RAGE水平升高的程度可反应肺损伤的程度,RAGE可作为ALI/ARDS的预警指标.     

膝骨关节炎滑液中可溶性晚期糖基化终末产物受体水平与其病变程度的相关性

背景：研究表明骨关节炎患者关节滑液内可溶性晚期糖基化终末产物受体水平可能与关节炎病变的严重程度存在负相关,但在中国报道较少。目的：观察膝关节骨关节炎患者关节滑液内可溶性晚期糖基化终末产物受体水平与其病变严重程度的关系。方法：共纳入46名膝关节骨关节炎患者及14名健康对照者,纳入的骨关节炎患者符合美国风湿病学会骨关节炎的临床诊断标准。采用Kellgren-Lawrence的标准对膝关节骨关节炎病变严重程度进行分级,使用人可溶性晚期糖基化终末产物受体水平酶联免疫吸附试剂盒在酶标仪下检测测关节滑液的可溶性晚期糖基化终末产物受体水平。结果与结论：膝关节骨关节炎患者关节滑液可溶性晚期糖基化终末产物受体水平较健康对照组显著降低（P〈0.01）,且与膝关节骨关节炎病变严重程度呈显著独立负相关（r=-0.587,P〈0.01）。结果表明关节滑液可溶性晚期糖基化终末产物受体水平可能与膝关节骨关节炎病变的严重性和进展程度相关。     

膝骨关节炎滑液中可溶性晚期糖基化终末产物受体水平与其病变程度的相关性

背景:研究表明骨关节炎患者关节滑液内可溶性晚期糖基化终末产物受体水平可能与关节炎病变的严重程度存在负相关,但在中国报道较少。目的:观察膝关节骨关节炎患者关节滑液内可溶性晚期糖基化终末产物受体水平与其病变严重程度的关系。方法:共纳入46名膝关节骨关节炎患者及14名健康对照者,纳入的骨关节炎患者符合美国风湿病学会骨关节炎的临床诊断标准。采用Kellgren-Lawrence的标准对膝关节骨关节炎病变严重程度进行分级,使用人可溶性晚期糖基化终末产物受体水平酶联免疫吸附试剂盒在酶标仪下检测测关节滑液的可溶性晚期糖基化终末产物受体水平。结果与结论:膝关节骨关节炎患者关节滑液可溶性晚期糖基化终末产物受体水平较健康对照组显著降低(P<0.01),且与膝关节骨关节炎病变严重程度呈显著独立负相关(r=-0.587,P<0.01)。结果表明关节滑液可溶性晚期糖基化终末产物受体水平可能与膝关节骨关节炎病变的严重性和进展程度相关。     

晚期糖基化终末产物的临床检测进展

晚期糖基化终末产物（AGE）已被证实与衰老及其相关性疾病有关。因此,AGE的临床检测对于以上慢性疾病的早期预测和干预以及长期监测具有重要价值。现有多种AGE的检测方法,但由于AGE具有高度异质性,结构复杂,临床上尚缺乏标准化的检测方法。该文简要概述目前AGE的检测方法及其优缺点,以期为AGE的临床检测指明未来方向。     

晚期糖基化终末产物受体对原发性肝癌患者根治术后复发转移及死亡的预测价值

目的观察原发性肝癌患者癌组织晚期糖基化终末产物受体(receptor for advanced glycation end product, RAGE)表达变化,探讨其预测原发性肝癌患者根治术后复发转移及死亡的价值。方法 134例原发性肝癌患者,均行肝癌根治术,术后给予辅助性肝动脉化疗栓塞治疗、分子靶向治疗或免疫治疗等。取手术切除癌组织及癌旁组织,采用免疫组织化学法检测RAGE阳性表达率,比较不同临床病理特征肝癌患者RAGE阳性表达率。对134例患者随访5年,记录术后复发转移及死亡情况,比较RAGE阳性表达与阴性表达者术后5年无病生存期、复发转移率及病死率。以术后5年复发转移及死亡者为预后不良组,其余为预后良好组,比较预后不良组与预后良好组一般临床资料和RAGE阳性表达率;多因素Cox回归分析原发性肝癌患者根治术后复发转移及死亡的影响因素。结果肝癌组织RAGE阳性表达率(64.9%)高于癌旁组织(15.7%)(χ²=5.678,P=0.021)。134例患者中RAGE阳性表达87例,肿瘤直径≥5 cm(79.7%)、病理分级低分化(84.6%)、有微血管侵犯(80...     

晚期糖基化终末产物的检测和临床意义

晚期糖基化终末产物（advancedglycosylationendprodrcts,AGEs）在糖尿病慢性并发症发病中起重要作用。近年AGEs作为监视伴慢性并发症糖尿病病人治疗效果的一项重要指标,正被认识并在临床应用。本文介绍AGEs的形成过程、化学结构、检测方法和临床意义。     

糖基化终末代谢产物及其受体与动脉粥样硬化的关系及抑制剂的研究进展

正随着人类社会文明的发展,随之而来的各种慢性疾病成为了困扰世界各国的公共健康问题,尤其糖尿病的患病率呈逐年增加趋势。糖尿病的各种大血管和微血管病变成为患者致残率和致死率增加的重要原因,这是因为糖尿病患者的持续高血糖状态导致晚期糖基化终末产物(advanced glycation end products,AGEs)明显增加,该产物与糖基化终末产物受体(receptor of advanced     

晚期糖基化终末产物受体与肿瘤的关系

晚期糖基化终末产物受体（receptor for advanced glycation end products,RAGE）是细胞表面分子免疫球蛋白超家族成员之一,属多配体受体,其通过与细胞表面不同配体结合发挥效应,广泛研究表明：RAGE参与糖脂代谢、细胞增殖与分化、炎症反应等生理病理过程。     

Soluble receptor for advanced glycation end products predicts 28-day mortality in critically ill patients with sepsis

Abstract

Objective. Multiple biomarkers are used to assess sepsis severity and prognosis. Increased levels of the soluble receptor for advanced glycation end products (sRAGE) were previously observed in sepsis but also in end-organ injury without sepsis. We evaluated associations between sRAGE and (i) 28-day mortality, (ii) sepsis severity, and (iii) individual organ failure. Traditional biomarkers procalcitonin (PCT), C-reactive protein (CRP) and lactate served as controls. Methods. sRAGE, PCT, CRP, and lactate levels were observed on days 1 (D1) and 3 (D3) in 54 septic patients. We also assessed the correlation between the biomarkers and acute respiratory distress syndrome (ARDS), acute kidney injury (AKI) and acute heart failure. Results. There were 38 survivors and 16 non-survivors. On D1, non-survivors had higher sRAGE levels than survivors (p = 0.027). On D3, sRAGE further increased only in non-survivors (p < 0.0001) but remained unchanged in survivors. Unadjusted odds ratio (OR) for 28-day mortality was 8.2 (95% CI: 1.02–60.64) for sRAGE, p = 0.048. Receiver operating characteristic analysis determined strong correlation with outcome on D3 (AUC = 0.906, p < 0.001), superior to other studied biomarkers. sRAGE correlated with sepsis severity (p < 0.00001). sRAGE showed a significant positive correlation with PCT and CRP on D3. In patients without ARDS, sRAGE was significantly higher in non-survivors (p < 0.0001) on D3. Conclusion. Increased sRAGE was associated with 28-day mortality in patients with sepsis, and was superior compared to PCT, CRP and lactate. sRAGE correlated with sepsis severity. sRAGE was increased in patients with individual organ failure. sRAGE could be used as an early biomarker in prognostication of outcome in septic patients.     

血浆可溶性髓样细胞触发受体-1对脓毒症早期诊断的价值及预后意义

目的 探讨血浆可溶性髓样细胞触发受体-1(soluble triggering receptor expressed on myeloid cells-1,sTREM-1)对脓毒症早期诊断的价值及预后意义。方法 采用前瞻性病例对照研究。将2009年5月至2010年6月天津医科大学第二医院重症监护病房( ICU)收治的56例系统性炎症反应综合征(SIRS)患者,根据2001年国际脓毒症会议诊断标准分为脓毒症组32例、SIRS组24例,同时收集非SIRS患者25例作为对照组,根据28 d转归将脓毒症组分为生存组和死亡组两个亚组。入院24h内测定血常规、血气分析、血生化、降钙素原（PCT）、C反应蛋白(CRP),记录最高体温(T),进行急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分;采用酶联免疫吸附法(ELISA)检测sTREM-1水平。采用SPSS 16.0统计分析软件进行数据处理,计量资料采用方差或Kruskal-Wallis H检验,相关性分析采用Spearman相关系数。结果 血浆sTREM-1水平脓毒症组高于SIRS组及对照组[分别为250.9 (195.8 ～ 354.3) ng/L、103.6(89.4～166.2)ng/L、33.6 (26.2 ～43.0) ng/L,P＜0.01],死亡组高于生存组[分别为360.5 (262.2 ～434.5)ng/L、204.1（175.0～269.6）ng/L,P＜0.01];脓毒症组患者血浆sTREM-1水平与APACHEⅡ评分呈正相关(r,=0.426,P=0.032);sTREM-1 ROC曲线下面积为0.935,高于PCT、CRP。结论 血浆sTREM-1水平对脓毒症早期诊断有一定意义,早期sTREM-1水平升高与不良预后相关。     

Decreased plasma levels of soluble receptor for advanced glycation endproducts (sRAGE) in patients with nonalcoholic fatty liver disease

Objectives

Levels of soluble receptor for advanced glycation endproducts (sRAGE) have been linked to several components of the metabolic syndrome. We tested the hypothesis that plasma levels of sRAGE may be associated with non-alcoholic fatty liver disease.

Design and methods

We enrolled subjects with definite nonalcoholic steatohepatitis (NASH, n = 40), borderline NASH (n = 8), simple fatty liver (n = 9) and healthy controls (n = 14). Plasma levels of sRAGE were measured by ELISA.

Results

Concentrations of sRAGE were significantly lower in patients with definite NASH (1080 ± 392 pg/mL, P < 0.01) and borderline NASH (1050 ± 278 pg/mL, P < 0.05) compared to controls (1480 ± 387 pg/mL). Levels of sRAGE were significantly and inversely correlated with ALT (r = − 0.30, P < 0.05) and AST (r = − 0.23, P < 0.05).

Conclusion

Plasma levels of sRAGE are significantly reduced in definite and borderline NASH.     

Targeting the receptor for advanced glycation end products (RAGE) in type 1 diabetes

Type 1 diabetes (T1D) is one of the most common chronic diseases manifesting in early life, with the prevalence increasing worldwide at a rate of approximately 3% per annum. The prolonged hyperglycaemia characteristic of T1D upregulates the receptor for advanced glycation end products (RAGE) and accelerates the formation of RAGE ligands, including advanced glycation end products, high-mobility group protein B1, S100 calcium-binding proteins, and amyloid-beta. Interestingly, changes in the expression of RAGE and these ligands are evident in patients before the onset of T1D. RAGE signals via various proinflammatory cascades, resulting in the production of reactive oxygen species and cytokines. A large number of proinflammatory ligands that can signal via RAGE have been implicated in several chronic diseases, including T1D. Therefore, it is unsurprising that RAGE has become a potential therapeutic target for the treatment and prevention of disease. In this review, we will explore how RAGE might be targeted to prevent the development of T1D.     

急性呼吸窘迫综合征患者血管外肺水指数动态变化与预后的关系

目的分析急性呼吸窘迫综合征(ARDS)患者血管外肺水指数(EVLWI)的变化特点,探讨其在ARDS患者液体管理中的指导意义以及对预后评估的价值。方法采用回顾性研究的方法 ,将2011年1月至12月收住湖州市第一人民医院重症监护室(ICU)的24例ARDS患者根据临床转归分为存活组(16例)与死亡组(8例),观察两组患者的临床特点,运用脉搏指示持续心输出量监护仪进行血流动力学监测。结果两组患者入住ICU第1天的一般情况、平均动脉压、中心静脉压(CVP)、氧合指数、血乳酸水平、心排指数和EVLWI差异均无统计学意义(P均>0.05)。从第1天到第3天,存活组氧合指数逐天上升,EVLWI、血乳酸值逐天降低,而死亡组三个指标均逐天降低,三个指标在两组间有统计学意义(P均<0.05)。另EVLWI与氧合指数呈明显负相关(r=-0.46,P<0.01),而EVLWI与CVP无明显相关性(r=-0.11,P=0.146)。第3天的EVLWI与预后的接受者操作特性曲线下面积为0.738±0.069,当EVLWI>8.5ml/kg时,预后评价的敏感度为85.3%,特异度为56.8%。结论 EVLWI的动态变化可用于评估治疗效果和患者预后,EVLWI可能是客观评价肺毛细血管渗漏的指标之一。     

血清 presepsin（sCD14-ST）对脓毒症早期诊断价值及预后意义

目的：探讨血清可溶性白细胞分化抗原14亚型（sCD14-ST,presepsin）对脓毒症早期诊断价值及预后意义。方法采用前瞻性研究方法,于2014年1月至2015年6月收集患者80例,根据脓毒症诊断标准分为脓毒症组50例、非感染性系统性炎症反应综合征组（systemic inflammatory response syndrome,SIRS）30例,同期选择25例健康查体者作为对照组;根据28 d 预后将脓毒症组分为生存组35例和死亡组15例。入院第1、3、7天晨时取血,动态观察血清presepsin、降钙素原（procalciton,PCT）、可溶性髓系细胞表达的触发受体-1（soluble myeloid cells expressing triggering receptor-1,sTREM-1）、C 反应蛋白（C-reactive protein,CRP）和白介素-6（interleukin 6,IL-6）水平。结果（1）脓毒症组患者入院第1 天血清 presepsin 高于 SIRS 组及对照组[912.0（563.5,1514.8）pg／mLvs.462.0（334.0,556.0）pg／mL vs.120.0（70.2,320.1）pg／mL,P ＜0.05];（2）第1 天 presepsin 的 ROC 曲线下面积（AUC）高于 PCT、sTREM-1、CRP、IL-6,当其截断值为672.5 pg／mL 时,其诊断脓毒症的敏感度为80％,特异度为96.7％,presepsin、PCT 和 sTREM-1三个指标联测明显诊断效能提高;（3）生存组随着病情好转,血清 presepsin、PCT、sTREM-1和 IL-6逐渐下降至正常水平,均低于同时点死亡组（P ＜0.05）,上述指标在死亡组无显著下降趋势（P ＞0.05）;（4）presepsin 预测脓毒症结局的 AUC 高于 PCT、sTREM-1, presepsin、PCT 和 sTREM-1三个指标联测明显提高预后判断能力。结论血清 presepsin 是脓毒症早期诊断的一个较好指标,其敏感度和特异度高于其他炎性指标,与疾病严重程度相关,与 PCT和 sTREM-1联测能够提高脓毒症早期诊断和和死亡风险预测。     

High plasma levels of the soluble receptor for advanced glycation endproducts in patients with symptomatic carotid atherosclerosis

Background  Advanced glycation endproducts (AGEs), particularly carboxymethyl(lysine)-adducts (CML), exert part of their cellular effects by binding to a receptor, named receptor for AGEs (RAGE). The soluble form of this receptor (sRAGE) has been shown to have an athero-protective role. We hypothesized the existence of a relationship between the AGE–RAGE axis and the occurrence of symptoms related to carotid atherosclerosis in nondiabetic conditions.
Materials and methods  We evaluated plasma levels of CML and sRAGE (by ELISA), and tissue levels (tAGEs and tRAGE, semiquantitatively, by immunohistochemistry) in endarterectomy carotid plaque tissue in 29 nondiabetic patients. At the time of surgery, 10 patients were asymptomatic and 19 were symptomatic.
Results  Plasma levels of sRAGE were higher in symptomatic patients than in asymptomatic patients [median (interquartile range): 676 (394–858) pg mL⁻¹ vs. 347 (284–479) pg mL⁻¹, P  = 0·009]. In symptomatic patients, plasma levels of sRAGE correlated positively with CML ( r  = 0·60, P  < 0·01), C-reactive protein (CRP) ( r  = 0·618, P  < 0·01) and fibrinogen ( r  = 0·522, P <0·005), while in asymptomatic patients, no correlation was observed. Although tissue and plasma levels of AGEs and RAGE did not correlate between each other, tAGEs and tRAGE were also positively correlated only in symptomatic patients (χ² = 8·93, P  = 0·003).
Conclusions  Plasma levels of sRAGE are higher in symptomatic than asymptomatic carotid atherosclerosis. Higher levels of sRAGE in symptomatic patients may be markers of a higher degree of vascular inflammation in such patients.     

脓毒症所致ARDS患者血浆肺表面活性蛋白D水平及其临床意义

目的探讨脓毒症所致急性呼吸窘迫综合征（ARDS）患者血浆肺表面活性蛋白-D（SP—D）水平动态变化的临床意义及其与临床特征的相关性。方法前瞻性研究脓毒症患者不同病程阶段血浆样本,于2012年1月至2012年10月入住重症医学科的40例患者纳入研究。根据收集血浆时患者是否符合ARDS诊断分为系统性炎症反应综合征（SIRS）组（即对照组）与ARDS组。ARDS组根据柏林ARDS诊断标准分为轻度、中度、重度3个亚组,ARDS重度患者临终前再次采集血浆样本,纳入ARDS临终组,运用酶联免疫吸附法测定各组血浆样本的SP—D水平,再结合患者的临床特征进行相关分析。结果ARDS轻度组的SP—D的血浆水平高于SIRS组（0．723±0．153rig／ml比0．510±0．187ng／ml,P〈0．05）;随着ARDS病情加重,血浆SP—D水平呈进行性升高（ARDS轻度组比中度组0．723±0．153．g／ml比1．043±0．198ng／ml,P〈0．05;中度组比重度组：1．043±0．198ng／ml比1．343±0．186ng／ml。P〈0．05）。临终组较ARDS重度组,SP—D水平无显著差异（1．343±0．186ng／ml比1．398±0．216ng／ml,P〉0．05）。血浆SP—D水平Pa02／FiO2呈负相关（r值为-0．436,P〈0．05）,与AaDO2、SOFA评分和APACHEII评分呈正相关（r值分别为0．314、0．321和0．453,P〈0．05）。结论检测脓毒症患者血浆SP—D水平有助于脓毒症所致ARDS的早期诊断。     

Receptors for advanced glycation end products (RAGE) is associated with microvessel density and is a prognostic biomarker for clear cell renal cell carcinoma

The receptor for advanced glycation end products (RAGE) is involved in a variety of biological processes, including tumorigenisis. Previous studies have demonstrated that RAGE regulates the neo-angiogenesis related downstream molecule – vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we investigated the potential relationship between RAGE, VEGFR-2 and angiogenesis in 80 renal cell carcinoma (RCC) patients. Real-time quantitative PCR and ELISA analysis were used to explore the RAGE and VEGFR-2 gene expression levels and the protein of VEGFR-2 expression. Meanwhile, angiogenesis was detected by the semi-quantification of endothelial cell marker CD34 combined with caldesmon, which was detected by microvessel density (MVD) technique and immunohistochemistry. Tumors were classified as low or high RAGE-expressing using the median as the cut-off. Immunofluorescence staining for RAGE protein was performed as well. Additionally, the median gene expression levels of VEGFR-2 in the tumors were significantly lower expressing low levels of RAGE expression, 0.34 (95% CI, 0.28–0.39) compared to the expressing high levels of RAGE expression, 0.45 (95% CI, 0.29–0.61), (P = 0.03). The median MVD was significantly lower in the tumors expressing low levels of RAGE, 6.5 (95% CI, 6.21–7.43), compared to the expressing high levels, 7.9 (95% CI, 6.25–8.93), (P < 0.01). Further, a positive association was certified with VEGFR-2 protein levels, P = 0.07. Besides, RCC with high levels of RAGE expression are associated with high VEGFR-2 mRNA/protein levels and a higher density of microvessels; conversely, Kaplan–Meier survival analysis suggests that a significant correlation of elevated RAGE expression with decreased overall survival and metastasis-free survival. Our results establish that RAGE was identified as a potential prognostic biomarker for disease prognosis of RCC.