目的探究活动性肺结核患者血清核苷酸结合寡聚化结构域蛋白2(nucleotide-binding oligomerization domain 2,NOD2)、自噬相关蛋白16样蛋白1(autophagy related protein 16 like protein 1,ATG16L1)水平与病情、预后的关系。方法选择2020...目的探究活动性肺结核患者血清核苷酸结合寡聚化结构域蛋白2(nucleotide-binding oligomerization domain 2,NOD2)、自噬相关蛋白16样蛋白1(autophagy related protein 16 like protein 1,ATG16L1)水平与病情、预后的关系。方法选择2020年1月—2022年1月在陕西省结核病防治院治疗的110例活动性肺结核患者作为活动性肺结核组,同一时间在本院进行健康体检的60名健康人作为健康对照组。ELISA法检测血清NOD2、ATG16L1水平。将活动性肺结核组分为轻度组、中度组和重度组,通过标准化治疗后根据疗效分为预后良好组和预后不良组,分析NOD2、ATG16L1水平与病情及预后的关系。分析活动性肺结核患者血清NOD2与ATG16L1水平的相关性。用ROC曲线评估NOD2、ATG16L1对活动性肺结核患者预后的评估价值,Cox回归分析活动性肺结核患者预后的影响因素。结果活动性肺结核组血清NOD2、ATG16L1水平明显高于健康对照组(P<0.05),且随着病情的加重,NOD2、ATG16L1水平呈上升趋势(P<0.05)。活动性肺结核患者血清NOD2与ATG16L1水平呈正相关(r=0.360)。与预后良好组比较,预后不良组血清NOD2、ATG16L1水平明显升高(P<0.05)。ROC曲线显示,NOD2、ATG16L1水平预测活动性肺结核患者预后的曲线下面积分别为0.878(95%CI:0.814~0.941)和0.815(95%CI:0.731~0.900)。患者病情、血清NOD2、ATG16L1水平均是活动性肺结核患者预后不良的危险因素(P<0.05)。结论活动性肺结核患者血清NOD2、ATG16L1水平高表达,与病情发展密切相关,可在一定程度上预测患者的预后。展开更多
Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the...Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.展开更多
Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestin...Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.展开更多
文摘目的探究活动性肺结核患者血清核苷酸结合寡聚化结构域蛋白2(nucleotide-binding oligomerization domain 2,NOD2)、自噬相关蛋白16样蛋白1(autophagy related protein 16 like protein 1,ATG16L1)水平与病情、预后的关系。方法选择2020年1月—2022年1月在陕西省结核病防治院治疗的110例活动性肺结核患者作为活动性肺结核组,同一时间在本院进行健康体检的60名健康人作为健康对照组。ELISA法检测血清NOD2、ATG16L1水平。将活动性肺结核组分为轻度组、中度组和重度组,通过标准化治疗后根据疗效分为预后良好组和预后不良组,分析NOD2、ATG16L1水平与病情及预后的关系。分析活动性肺结核患者血清NOD2与ATG16L1水平的相关性。用ROC曲线评估NOD2、ATG16L1对活动性肺结核患者预后的评估价值,Cox回归分析活动性肺结核患者预后的影响因素。结果活动性肺结核组血清NOD2、ATG16L1水平明显高于健康对照组(P<0.05),且随着病情的加重,NOD2、ATG16L1水平呈上升趋势(P<0.05)。活动性肺结核患者血清NOD2与ATG16L1水平呈正相关(r=0.360)。与预后良好组比较,预后不良组血清NOD2、ATG16L1水平明显升高(P<0.05)。ROC曲线显示,NOD2、ATG16L1水平预测活动性肺结核患者预后的曲线下面积分别为0.878(95%CI:0.814~0.941)和0.815(95%CI:0.731~0.900)。患者病情、血清NOD2、ATG16L1水平均是活动性肺结核患者预后不良的危险因素(P<0.05)。结论活动性肺结核患者血清NOD2、ATG16L1水平高表达,与病情发展密切相关,可在一定程度上预测患者的预后。
基金grants from the National Natural Science Foundation of China (No.81573745and No.8160140274)Beijing Municipal Natural Science Foundation (No.7172066) Beijing Development Foundation of Traditional Chinese Medicine (QN2016-23).
文摘Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.
文摘Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient's site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.
