Background Acute Kidney Injury （AKI） is a common and serious complication of cardiovascular surgery. There is a need to find biomarkers that are involved in the etiology of cardiac surgery-associated acute kidney in...Background Acute Kidney Injury （AKI） is a common and serious complication of cardiovascular surgery. There is a need to find biomarkers that are involved in the etiology of cardiac surgery-associated acute kidney injury （CSA-AKI） and have an earlier response to acute kidney injury. The association between urine neutrophil gelatinase-associated lipocalin （NGAL） concentrations and AKI progression is not well established. Methods The prospective-cohort study included 1631 consecutive adult patients undergoing cardiac surgery at Fuwai Hospital between September 2012 and November 2013. AKI defined by Acute Kidney Injury Network （AKIN） criteria with a postoperative increase in plasma creatinine 〉/50% baseline or/〉0.3 mg/dL. Urine NGAL was measured us- ing latex particle-enhanced turbidimetric immunoassay. Associations between Urine NGAL levels and AKI were determined by estimating areas under receiver operating characteristic curves （AUC）. Results A total of 438 （26.9%） patients developed CSA-AKI. And the patients were divided into four groups： 1193 non-AKI patients, 368（22.6%） patients with AKIN stage I AKI, 49（3.0%） with AKIN stage 2 AKI and 21（1.3%） with AKIN stage 3 AKI. urine NGAL concentrations at surgical intensive care unit （SICU） admission were significantly related to AKI severity. The AUCs for urine NGAL were for AKIN stage 1 （0.54±0.02）, AKIN stage 2 （0.67±0.04）, and AKIN stage 3 （0.76±0.06）, respectively. Conclusions Urinary NGAL is associated with CSA-AKI and its progression, indicating their potential use as prognostic markers. Urine NGAL level measured at SICU admission predicts the development of severe AKI after cardiac surgery.展开更多
目的研究应用尿中性粒细胞明胶酶相关载脂蛋白(neutrophil gelatinase-associated apolipoprotein, NGAL)指导的集束化治疗是否能改善脓毒症相关性急性肾损伤(AKI)的预后。方法入选尿NGAL>130 ng/mL的脓毒症患者,分为标准治疗组与集...目的研究应用尿中性粒细胞明胶酶相关载脂蛋白(neutrophil gelatinase-associated apolipoprotein, NGAL)指导的集束化治疗是否能改善脓毒症相关性急性肾损伤(AKI)的预后。方法入选尿NGAL>130 ng/mL的脓毒症患者,分为标准治疗组与集束化治疗组,比较两组患者的基础临床特征及相关预后。结果①集束化治疗组与标准治疗组比较,第1天液体输入量更高[(4078±849)mL vs.(2664±828)mL,P<0.001)],而第3天液体输入量更少[(2277±733)mL vs.(3086±1056)mL,P<0.001];②集束化治疗组与标准治疗组比较,采用保护性机械通气策略的比例更高(100.0% vs. 87.9%,P<0.001),28 d内机械通气时间更长(22 d vs. 19 d,P<0.001);③集束化治疗组与标准治疗组比较,ICU住院时间更短(9.5 d vs. 10.0 d,P=0.002),肾脏替代治疗比例更低(30.9% vs. 45.5%,P=0.014)。结论集束化治疗可以缩短脓毒症相关性AKI患者的ICU住院时间,提高肾脏功能康复率。展开更多
目的探究中性粒细胞明胶酶相关脂质运载蛋白(NGAL)对脓毒症和脓毒性休克患者预后的预测作用。方法采用回顾性病例对照研究分析上海交通大学医学院附属瑞金医院急诊科2017年1月31日至2019年1月31日收治且明确诊断为脓毒症/脓毒性休克的8...目的探究中性粒细胞明胶酶相关脂质运载蛋白(NGAL)对脓毒症和脓毒性休克患者预后的预测作用。方法采用回顾性病例对照研究分析上海交通大学医学院附属瑞金医院急诊科2017年1月31日至2019年1月31日收治且明确诊断为脓毒症/脓毒性休克的84例患者,其中男性53例,女性31例;年龄18~80岁,平均(56.5±17.8)岁。根据患者的预后分为生生存组(n=62)和死亡组(n=22)。在患者入院第1天、第3天和第7天检测血浆NGAL水平,比较两组患者临床资料、实验室检查指标水平的差异,筛选出差异有统计学意义的观察指标对比,并采用pearson相关性分析比较NGAL与其他预后指标的相关性。再通过受试者工作特征曲线(ROC)曲线判断NGAL对脓毒症/脓毒性休克患者发生院内死亡和是否需行连续肾脏替代疗法(CRRT)治疗的预测价值。结果死亡组患者NGAL浓度在第1天[(2188.4±2280.8)ng/mL比(538.2±777.4)ng/mL]、第3天[(2045.5±2388.8)ng/mL比(553.8±836.4)ng/mL]和第7天[(1512.4±1840.9)ng/mL比(192.3±410.2)ng/mL]均明显高于生存组患者,差异均有统计学意义(P<0.05)。NGAL水平与序贯器官衰竭评分(Sequential Organ Failure Assessment,SOFA)(r=0.4601)、急性生理与慢性健康评分(APACHEⅡ)(r=0.37)、乳酸(r=0.41)和肌酐(r=0.48)都呈正相关性(P均<0.05)。第7天时NGAL水平对预后的预测价值[曲线下面积(AUROC)=0.85,95%CI:0.70~0.99]高于第1天(AUROC=0.71,95%CI:0.55~0.88)和第3天(AUROC=0.72,95%CI:0.55~0.88)。第3天时肌酐和NGAL对是否需行CRRT的预测价值优于第1天和第7天。入院第3天时NGAL浓度(AUROC=0.80,95%CI:0.64~0.97)与肌酐水平(AUROC=0.83,95%CI:0.68~0.97)相比,前者对患者是否需行CRRT的预测作用具有更好的特异性,但敏感度相对较低。结论对于脓毒症/脓毒性休克患者第7天时NGAL水平对预后具有很高的预测价值。与肌酐相比,NGAL对预测患者是否需行CRRT具有更高的特异性。展开更多
Cation-π interaction is an electrostatic interaction between a cation and an electron-rich arene.It plays an essential role in many biological systems as a vital driving force for protein folding,stability,and recept...Cation-π interaction is an electrostatic interaction between a cation and an electron-rich arene.It plays an essential role in many biological systems as a vital driving force for protein folding,stability,and receptor-ligand interaction/recognition.To date,the discovery of most cation-π interactions in proteins relies on the statistical analyses of available three-dimensional(3D)protein structures and corresponding computational calculations.However,their experimental verification and quantification remain sparse at the molecular level,mainly due to the limited methods to dynamically measure such a weak non-covalent interaction in proteins.Here,we use atomic force microscopy-based single-molecule force spectroscopy(AFM-SMFS)to measure the stability of protein neutrophil gelatinase-associated lipocalin(also known as NGAL,siderocalin,lipocalin 2)that can bind iron through the cation-π interactions between its three cationic residues and the iron-binding tri-catechols.Based on a site-specific cysteine engineering and anchoring method,we first characterized the stability and unfolding pathways of apo-NGAL.Then,the same NGAL but bound with the iron-catechol complexes through the cation-π interactions as a holo-form was characterized.AFM measurements demonstrated stronger stabilities and kinetics of the holo-NGAL from two pulling sites,F122 and F133.Here,NGAL is stretched from the designed cysteine close to the cationic residues for a maximum unfolding effect.Thus,our work demonstrates high-precision detection of the weak cation-π interaction in NGAL.展开更多
文摘Background Acute Kidney Injury （AKI） is a common and serious complication of cardiovascular surgery. There is a need to find biomarkers that are involved in the etiology of cardiac surgery-associated acute kidney injury （CSA-AKI） and have an earlier response to acute kidney injury. The association between urine neutrophil gelatinase-associated lipocalin （NGAL） concentrations and AKI progression is not well established. Methods The prospective-cohort study included 1631 consecutive adult patients undergoing cardiac surgery at Fuwai Hospital between September 2012 and November 2013. AKI defined by Acute Kidney Injury Network （AKIN） criteria with a postoperative increase in plasma creatinine 〉/50% baseline or/〉0.3 mg/dL. Urine NGAL was measured us- ing latex particle-enhanced turbidimetric immunoassay. Associations between Urine NGAL levels and AKI were determined by estimating areas under receiver operating characteristic curves （AUC）. Results A total of 438 （26.9%） patients developed CSA-AKI. And the patients were divided into four groups： 1193 non-AKI patients, 368（22.6%） patients with AKIN stage I AKI, 49（3.0%） with AKIN stage 2 AKI and 21（1.3%） with AKIN stage 3 AKI. urine NGAL concentrations at surgical intensive care unit （SICU） admission were significantly related to AKI severity. The AUCs for urine NGAL were for AKIN stage 1 （0.54±0.02）, AKIN stage 2 （0.67±0.04）, and AKIN stage 3 （0.76±0.06）, respectively. Conclusions Urinary NGAL is associated with CSA-AKI and its progression, indicating their potential use as prognostic markers. Urine NGAL level measured at SICU admission predicts the development of severe AKI after cardiac surgery.
文摘目的研究应用尿中性粒细胞明胶酶相关载脂蛋白(neutrophil gelatinase-associated apolipoprotein, NGAL)指导的集束化治疗是否能改善脓毒症相关性急性肾损伤(AKI)的预后。方法入选尿NGAL>130 ng/mL的脓毒症患者,分为标准治疗组与集束化治疗组,比较两组患者的基础临床特征及相关预后。结果①集束化治疗组与标准治疗组比较,第1天液体输入量更高[(4078±849)mL vs.(2664±828)mL,P<0.001)],而第3天液体输入量更少[(2277±733)mL vs.(3086±1056)mL,P<0.001];②集束化治疗组与标准治疗组比较,采用保护性机械通气策略的比例更高(100.0% vs. 87.9%,P<0.001),28 d内机械通气时间更长(22 d vs. 19 d,P<0.001);③集束化治疗组与标准治疗组比较,ICU住院时间更短(9.5 d vs. 10.0 d,P=0.002),肾脏替代治疗比例更低(30.9% vs. 45.5%,P=0.014)。结论集束化治疗可以缩短脓毒症相关性AKI患者的ICU住院时间,提高肾脏功能康复率。
文摘目的探究中性粒细胞明胶酶相关脂质运载蛋白(NGAL)对脓毒症和脓毒性休克患者预后的预测作用。方法采用回顾性病例对照研究分析上海交通大学医学院附属瑞金医院急诊科2017年1月31日至2019年1月31日收治且明确诊断为脓毒症/脓毒性休克的84例患者,其中男性53例,女性31例;年龄18~80岁,平均(56.5±17.8)岁。根据患者的预后分为生生存组(n=62)和死亡组(n=22)。在患者入院第1天、第3天和第7天检测血浆NGAL水平,比较两组患者临床资料、实验室检查指标水平的差异,筛选出差异有统计学意义的观察指标对比,并采用pearson相关性分析比较NGAL与其他预后指标的相关性。再通过受试者工作特征曲线(ROC)曲线判断NGAL对脓毒症/脓毒性休克患者发生院内死亡和是否需行连续肾脏替代疗法(CRRT)治疗的预测价值。结果死亡组患者NGAL浓度在第1天[(2188.4±2280.8)ng/mL比(538.2±777.4)ng/mL]、第3天[(2045.5±2388.8)ng/mL比(553.8±836.4)ng/mL]和第7天[(1512.4±1840.9)ng/mL比(192.3±410.2)ng/mL]均明显高于生存组患者,差异均有统计学意义(P<0.05)。NGAL水平与序贯器官衰竭评分(Sequential Organ Failure Assessment,SOFA)(r=0.4601)、急性生理与慢性健康评分(APACHEⅡ)(r=0.37)、乳酸(r=0.41)和肌酐(r=0.48)都呈正相关性(P均<0.05)。第7天时NGAL水平对预后的预测价值[曲线下面积(AUROC)=0.85,95%CI:0.70~0.99]高于第1天(AUROC=0.71,95%CI:0.55~0.88)和第3天(AUROC=0.72,95%CI:0.55~0.88)。第3天时肌酐和NGAL对是否需行CRRT的预测价值优于第1天和第7天。入院第3天时NGAL浓度(AUROC=0.80,95%CI:0.64~0.97)与肌酐水平(AUROC=0.83,95%CI:0.68~0.97)相比,前者对患者是否需行CRRT的预测作用具有更好的特异性,但敏感度相对较低。结论对于脓毒症/脓毒性休克患者第7天时NGAL水平对预后具有很高的预测价值。与肌酐相比,NGAL对预测患者是否需行CRRT具有更高的特异性。
基金This work was funded by the Fundamental Research Funds for the Central Universities(No.14380259)Natural Science Foundation of Jiangsu Province(No.BK20200058)+1 种基金the National Natural Science Foundation of China(Nos.21771103 and 21977047)computational resources from computing facilities of the High-Performance Computing Center(HPCC)of Nanjing University。
文摘Cation-π interaction is an electrostatic interaction between a cation and an electron-rich arene.It plays an essential role in many biological systems as a vital driving force for protein folding,stability,and receptor-ligand interaction/recognition.To date,the discovery of most cation-π interactions in proteins relies on the statistical analyses of available three-dimensional(3D)protein structures and corresponding computational calculations.However,their experimental verification and quantification remain sparse at the molecular level,mainly due to the limited methods to dynamically measure such a weak non-covalent interaction in proteins.Here,we use atomic force microscopy-based single-molecule force spectroscopy(AFM-SMFS)to measure the stability of protein neutrophil gelatinase-associated lipocalin(also known as NGAL,siderocalin,lipocalin 2)that can bind iron through the cation-π interactions between its three cationic residues and the iron-binding tri-catechols.Based on a site-specific cysteine engineering and anchoring method,we first characterized the stability and unfolding pathways of apo-NGAL.Then,the same NGAL but bound with the iron-catechol complexes through the cation-π interactions as a holo-form was characterized.AFM measurements demonstrated stronger stabilities and kinetics of the holo-NGAL from two pulling sites,F122 and F133.Here,NGAL is stretched from the designed cysteine close to the cationic residues for a maximum unfolding effect.Thus,our work demonstrates high-precision detection of the weak cation-π interaction in NGAL.
