气道压力释放通气对急性呼吸窘迫综合征患者呼吸机相关性肺损伤的影响

目的 通过测定机械通气对急性呼吸窘迫综合征（Acute Respiratory Distress Syndrome,ARDS）患者支气管肺泡灌洗液（BronchoAlveolar Lavage Fluid,BALF）与血清中肺损伤标记物的变化,明确气道压力释放通气（Airway Pressure Release Ventilation,APRV）与小潮气量保护性通气（Low Tidal Volume Protective Ventilation,LTV）对ARDS患者呼吸机相关性肺损伤（Ventilator-Induced Lung Injury,VILI）的影响。方法 收集深圳大学总医院及海南省人民医院2018-01至2019-05内ARDS住院患者40例,以随机数字法分为两组：A组21例,B组19例,A组先予APRV通气24 h,随后转为LTV 24 h;B组先予LTV 24 h,再转为APRV 24 h,比较干预治疗0 h、24 h、48 h两组患者氧合指数、呼吸力学、BALF及血清中肺泡表面活性蛋白（Pulmonary Surfactant Protein D,SP-D）、重组...     

Serum levels of soluble form of receptor for advanced glycation end products (sRAGE) are positively associated with circulating AGEs and soluble form of VCAM-1 in patients with type 2 diabetes

We have recently found that soluble form of receptor for advanced glycation end products (sRAGE) levels are positively associated with inflammatory biomarkers and the presence of coronary artery disease (CAD) in type 2 diabetic patients. Since advanced glycation end products (AGEs) up-regulate RAGE expression and endogenous sRAGE could be generated from the cleavage of cell surface RAGE, it is conceivable that sRAGE is positively associated with circulating AGEs levels in diabetes. In this study, we examined whether sRAGE were correlated to circulating levels of AGEs and soluble forms of vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in patients with type 2 diabetes. Eighty-two Japanese type 2 diabetic patients underwent a complete history and physical examination, determination of blood chemistries, sRAGE, AGEs, sVCAM-1 and sICAM-1. Multiple regression analysis revealed that serum levels of AGEs and sVCAM-1 were independently correlated with sRAGE. This study demonstrated that serum levels of sRAGE were positively associated with circulating AGEs and sVCAM-1 levels in type 2 diabetic patients. Our present observations suggest sRAGE level may be elevated in response to circulating AGEs, thus being a novel marker of vascular injury in patients with type 2 diabetes.     

Circulating advanced glycation end products (AGEs) and soluble form of receptor for AGEs (sRAGE) are independent determinants of serum monocyte chemoattractant protein-1 (MCP-1) levels in patients with type 2 diabetes

BACKGROUND: Atherosclerosis is an inflammatory disease. Monocyte chemoattractant protein-1 (MCP-1) is an essential chemokine responsible for the recruitment of monocytes to inflammatory lesions in the vasculature, an initial step of atherosclerosis. Since serum levels of MCP-1 are higher in patients with type 2 diabetes, inhibition of MCP-1 may be a novel therapeutic target for prevention of accelerated atherosclerosis in diabetes. However, little is known about the regulation and determinants of serum MCP-1 levels in patients with diabetes. In this study, we examined the determinants of serum MCP-1 levels in type 2 diabetic patients. METHODS: Eighty-six consecutive outpatients with type 2 diabetes (36 male and 50 female; mean age 68.4+/-9.6) underwent a complete history and physical examination, determination of blood chemistries, MCP-1, tumour necrosis factor-alpha, adiponectin, advanced glycation end products (AGEs), and soluble form of receptor for AGEs (sRAGE). We examined the association between MCP-1 levels and those in anthropometric, metabolic and inflammatory variables in these subjects. RESULTS: Univariate regression analysis showed that serum levels of MCP-1 were positively associated with AGEs (r=0.386, p<0.001) and sRAGE (r=0.315, p<0.001). After adjusting for age and sex, AGEs (p<0.001) and sRAGE (p<0.05) still remained significant. CONCLUSION: The results demonstrate for the first time that circulating levels of AGEs and sRAGE are independent determinants of serum MCP-1 levels in patients with type 2 diabetes. Our present observations suggest the AGEs-RAGE system may be mainly involved in the elevation of MCP-1 in type 2 diabetic patients.     

帕金森病患者血清中sRAGE水平及其临床意义

目的 检测帕金森病（PD）患者外周血中可溶性晚期糖基化终产物受体（sRAGE）的含量变化,并初步探讨其与PD的关系.方法 采用双抗体夹心ELISA法测定100例PD组患者与100例对照组（同期体检健康者）血清中sRAGE的含量并进行比较.结果 PD组血清sRAGE水平（767.44±18.21） pg/ml低于健康对照组（792.78±41.48） pg/ml,差异有统计学意义（t=-5.59,P＜0.01）.PD患者不同严重程度组间血清sRAGE水平,由轻到重sRAGE水平呈下降趋势,但组间差异无统计学意义（F=1.28,P＞0.05）.相同年龄段间PD组与健康对照组血中sRAGE表达水平比较,50-60岁和60-70岁年龄段两组间差异有统计意义（t分别为4.65,3.07;P＜0.01）.结论 PD组血清中sRAGE水平明显低于健康对照组,特别在50-70岁年龄段,且其水平与PD严重程度无明显相关性,推测sRAGE可能通过竞争结合晚期糖基化终产物受体（RAGE）的配体减弱后者的病理作用,可能在PD中起潜在保护作用.     

RAGE、sRAGE在结肠癌中的表达及其临床意义

目的：本研究通过检测结肠癌组织晚期糖基化终末产物受体（ the receptor for advanced glycation end product,RAGE）和血清可溶性RAGE（ soluble RAGE,sRAGE）的表达水平,探讨其在结肠癌发生、发展过程中的作用及其临床意义。方法：本研究纳入49例非糖尿病结肠癌（ I、II、III期）患者,以免疫组织化学评分法（ immunohistochemical score,IHS）评价结肠癌RAGE表达水平,以ELISA法检测患者外周血血清sRAGE浓度。结果：结肠癌组织RAGE表达水平（IHS为1.24±0.48）显著高于癌周组织（IHS为0.50±0.25）（P﹤0.05）, III期（IHS为1.42±0.51）显著性高于I期（IHS为1.01±0.35）（P﹤0.05）和II期（IHS为1.11±0.42）（P﹤0.05）;低分化结肠癌组织（IHS为1.58±0.49）显著高于中分化（IHS为1.08±0.45）（P﹤0.05）和高分化结肠癌组织（IHS为1.02±0.27）（P﹤0.05）。结肠癌患者血清sRAGE表达水平术前、术后分别为（344.77±68.06）ng/L、（265.43±76.85）ng/L,二者相比有显著性差异（ P ﹤0.05）,而且分别与健康志愿者 sRAGE （149.97±30.12）ng/L相比有显著性差异（ P﹤0.05）,但sRAGE表达水平与TNM分期、结肠癌组织分化程度没有关联。结肠癌组织RAGE高表达患者术前血清sRAGE浓度（415.02±85.08）ng/L高于中表达（334.26±44.56）ng/L和低表达（335.95±78.48）ng/L患者（P﹤0.05）。结论：结肠癌组织RAGE表达水平与分化程度呈负相关趋势,与TNM分期呈正相关趋势,作为术后诊断指标有一定的临床意义。血清sRAGE浓度与结肠癌组织RAGE表达水平呈正相关趋势,但与TNM分期和结肠癌组织分化程度没有关联,作为术前诊断指标仅能代表结肠癌风险,但无法考量结肠癌的恶性程度和进展情况。     

Pregnancy-associated plasma protein A (PAPP-A) and soluble receptor for advanced glycation end products (sRAGE) – intra- and inter-individual variability in chronic hemodialysis patients

Background. Dialysis patients are at high risk of cardiovascular complications. Pregnancy-associated plasma protein A (PAPP-A) as well as sRAGE (soluble receptor for advanced glycation end products) are new biomarkers related to cardiovascular disease. The aim of our study was to describe their intra- and inter-individual variability. Methods. The studied group consisted of 21 chronic hemodialysis patients. PAPP-A, sRAGE and selected routine parameters were measured monthly during a 1-year prospective study. Results. Our results show high intra-individual variability of both PAPP-A and sRAGE. Both PAPP-A and sRAGE were closely linked to serum transferrin levels. Additionally, sRAGE was significantly associated with leukocyte count and haemoglobin. Conclusion. Our study demonstrates high intra-individual variability of PAPP-A and sRAGE in stable clinical status. This finding could be helpful for further evaluation of the significance of PAPP-A and sRAGE in chronic kidney disease.     

Serum AGEs and sRAGE levels are not related to vascular complications in patients with prediabetes

BackgroundWhile hyperglycemia has a key role in the pathogenesis of microvascular complications of diabetes, it is just one of the many factors contributing to macrovascular damage. The aim of the present study is to investigate the link between serum pentosidine and sRAGE levels and vascular complications in patients with prediabetes compared to normal glucose tolerance controls with obesity.MethodsIn this study were included 76 patients with mean age 50.7 ± 10.7 years, divided into two age and BMI-matched groups – group 1 with obesity without glycemic disturbances (n = 38) and group 2 with obesity and prediabetes (n = 38).ResultsThere was no significant difference in pentosidine and sRAGE levels between patients with obesity and prediabetes. Patients with hypertension had lower levels of sRAGE compared to nonhypertensive subjects. sRAGE showed a weak negative correlation to blood glucose on 60th min of OGTT and HOMA index. There was no correlation between sRAGE and pentosidine levels and the markers of micro- and macrovascular complications. There was no difference in sRAGE and pentosidine levels between patients with and without endothelial dysfunction.Conclusions: sRAGE and pentosidine levels are similar in patients with obesity with and without prediabetes and do not correlate to the markers of micro- and macrovascular complications.     

The promoter polymorphisms of receptor for advanced glycation end products were associated with the susceptibility and progression of sepsis

Receptor for advanced glycation end products (RAGE) is considered a major pattern recognition receptor, which plays an important role in the development of sepsis. Increasing evidence showed an association between RAGE polymorphisms and the susceptibility to several inflammatory‐related diseases. However, little is known about the clinical relationship between RAGE polymorphisms and sepsis. In this study, we analyzed the association of sepsis with three functional RAGE gene polymorphisms (rs1800624, rs1800625 and rs2070600) in a Chinese Han population (372 sepsis cases and 400 healthy controls). Significant differences were observed in the rs1800624 and rs1800625 genotype/allele distributions between the sepsis and controls, but no significant difference was observed in the rs2070600 genotype/allele. Moreover, our results also revealed a significant difference in the genotype/allele frequencies of the rs1800624 and rs1800625 polymorphisms between the sepsis and severe sepsis subtypes, the rs1800624 TT or rs1800625 TT genotype carriers exhibited a significant increase in RAGE mRNA, sRAGE, TNF‐α and IL‐6 expression compared with the rs1800624 AT/AA or rs1800625 CT/CC carriers in sepsis patients. Overall, this study might provide valuable clinical evidence between the RAGE gene polymorphisms and the risk or the development of sepsis.     

Advanced glycation endproducts (AGEs): Pharmacological inhibition in diabetes

AGE inhibitors may act by various mechanisms at different steps of advanced glycation endproduct (AGE) formation (depending on oxidative stress and/or carbonyl stress) and AGE-mediated damage: trapping of reactive dicarbonyl species; antioxidant activity by transition metal chelation; other antioxidant activity including free radical scavenging; AGE cross-link breaking; AGE receptor (RAGE) blocking; RAGE signaling blocking; glycemia reduction by anti-diabetic therapy; aldose reductase inhibition; shunting of trioses-P towards the pentose-P pathway by transketolase activation. Most of the inhibitors have several sites of action. Practically one can distinguish drugs specifically developed as AGE inhibitors or AGE breakers; RAGE and receptor signaling blockers; other therapeutic compounds which were found subsequently to possess also AGE inhibitor activity, including dietary antioxidants. Encouraging results obtained in studies of various AGE inhibitors, conducted in vitro and in diabetic animals, are summarized in this review. However most of the clinical trials have been more or less disappointing, in part because of side effects; the long-term therapeutic interest of the most recently developed AGE inhibitors or breakers remains to be demonstrated in diabetes.