Background:Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute...Background:Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear.Methods:C57BL/6 wild-type mice were assigned to sham,lipopolysaccharide (LPS) + vehicle,LPS + acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups.Mice were given intraperitoneal (IP) injections of LPS.Drugs were IP injected 1 h before LPS administration.Mice were sacrificed 16 h after LPS administration,and AMs were isolated.Western blot analysis for active caspase-1 and cleaved caspase-3,evaluation of lung injury and a cytokine release analysis were performed.AMs were treated with LPS and adenosine triphosphate (ATP);caspase-l-dependent cell death was evaluated using flow cytometry;the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosomes were examined by immunofluorescence.Results:The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group.In the ex vivo study,the caspase-1/propidium iodide-positive cells,caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation.The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death.Ac-YVAD-CMK also reduced the lung injury,pulmonary edema and total protein in bronchoalveolar lavage fluid (BALF).In addition,Ac-YVAD-CMK significantly inhibited interleukin-β (IL-lβ) release both in serum and BALF and reduced the levels of IL-18,tumor necrosis factor-α (TNF-α),High Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS.Conclusions:This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury.These 展开更多
Background:Blood glucose control is closely related to type 2 diabetes mellitus(T2DM)prognosis.This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China ...Background:Blood glucose control is closely related to type 2 diabetes mellitus(T2DM)prognosis.This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network(EN)with a machine-learning algorithm to predict glycemic control.Methods:Basic information,biochemical indices,and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017.An EN regression was used to address variable collinearity.Then,three common machine learning algorithms(random forest[RF],support vector machine[SVM],and back propagation artificial neural network[BP-ANN])were used to simulate and predict blood glucose status.Additionally,a stepwise logistic regression was performed to compare the machine learning models.Results:The well-controlled blood glucose rate was 45.82%in North China.The multivariable analysis found that hypertension history,atherosclerotic cardiovascular disease history,exercise,and total cholesterol were protective factors in glycosylated hemoglobin(HbAlc)control,while central adiposity,family history,T2DM duration,complications,insulin dose,blood pressure,and hypertension were risk factors for elevated HbAlc.Before the dimensional reduction in the EN,the areas under the curve of RF,SVM,and BP were 0.73,0.61,and 0.70,respectively,while these figures increased to 0.75,0.72,and 0.72,respectively,after dimensional reduction.Moreover,the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models(the sensitivity and accuracy of logistic were 0.52 and 0.56;RF:0.79,0.70;SVM:0.84,0.73;BP-ANN:0.78,0.73,respectively).Conclusions:More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications.The EN and machine learning algorithms are alternative choices,in addition to the traditional logistic展开更多
目的系统评价老年综合评估对预防老年患者护理不良事件发生的干预效果。方法计算机检索中国知网、万方、中国生物医学文献数据库、PubMed、Cochrane、Embase、EBSCO、Medline、Web of Science,检索时间为建库截至2019年6月。收集所有关...目的系统评价老年综合评估对预防老年患者护理不良事件发生的干预效果。方法计算机检索中国知网、万方、中国生物医学文献数据库、PubMed、Cochrane、Embase、EBSCO、Medline、Web of Science,检索时间为建库截至2019年6月。收集所有关于老年综合评估对老年患者护理不良事件影响的随机对照试验。由2名研究员按照纳入和排除标准独立筛选文献并提取资料,运用RevMan 5.3进行Meta分析,Stata 15进行Begg秩相关分析。结果最终纳入13篇随机对照实验,总计26241例患者。Meta分析结果显示:老年综合评估能够降低老年患者跌倒发生率(OR=0.42,95%CI:0.34~0.54,P<0.01)、降低患者非计划拔管发生率(OR=0.19,95%CI:0.08~0.47,P<0.01),患者住院压疮发生率(OR=0.62,95%CI:0.38~1.00,P=0.05)未显著降低。结论与常规护理评估相比,老年综合评估能够降低老年患者跌倒发生率和非计划拔管发生率,但不能降低老年患者住院压疮发生率。展开更多
基金The author thanks the National Natural Science Foundation of China (No. 81470266).
文摘Background:Pyroptosis is the term for caspase-l-dependent cell death associated with pro-inflammatory cytokines.The role of alveolar macrophage (AM) pyroptosis in the pathogenesis of the acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains unclear.Methods:C57BL/6 wild-type mice were assigned to sham,lipopolysaccharide (LPS) + vehicle,LPS + acetyl-tyrosyl-valyl-alanyl-aspartyl-chloromethylketone (Ac-YVAD-CMK) and LPS + Z-Asp-Glu-Val-Asp-fluoromethylketone groups.Mice were given intraperitoneal (IP) injections of LPS.Drugs were IP injected 1 h before LPS administration.Mice were sacrificed 16 h after LPS administration,and AMs were isolated.Western blot analysis for active caspase-1 and cleaved caspase-3,evaluation of lung injury and a cytokine release analysis were performed.AMs were treated with LPS and adenosine triphosphate (ATP);caspase-l-dependent cell death was evaluated using flow cytometry;the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) pyroptosomes were examined by immunofluorescence.Results:The expression of activated caspase-1 in AMs was enhanced following LPS challenge compared with the sham group.In the ex vivo study,the caspase-1/propidium iodide-positive cells,caspase-1 specks and ASC pyroptosomes were up-regulated in AMs following LPS/ATP stimulation.The specific caspase-1 inhibitor Ac-YVAD-CMK inhibited the activation of caspase-1 and pyroptotic cell death.Ac-YVAD-CMK also reduced the lung injury,pulmonary edema and total protein in bronchoalveolar lavage fluid (BALF).In addition,Ac-YVAD-CMK significantly inhibited interleukin-β (IL-lβ) release both in serum and BALF and reduced the levels of IL-18,tumor necrosis factor-α (TNF-α),High Mobility Group Box 1 (HMGB1) in BALF during LPS-induced ALI/ARDS.Conclusions:This study reported AM pyroptosis during LPS-induced ALI/ARDS in mice and has demonstrated that Ac-YVAD-CMK can prevent AM-induced pyroptosis and lung injury.These
基金This study was supported by grants from the Ministry of Education of the Humanities and Social Science Project(No.17YJAZH048)the National Natural Science Foundation of China(No.81803333).
文摘Background:Blood glucose control is closely related to type 2 diabetes mellitus(T2DM)prognosis.This multicenter study aimed to investigate blood glucose control among patients with insulin-treated T2DM in North China and explore the application value of combining an elastic network(EN)with a machine-learning algorithm to predict glycemic control.Methods:Basic information,biochemical indices,and diabetes-related data were collected via questionnaire from 2787 consecutive participants recruited from 27 centers in six cities between January 2016 and December 2017.An EN regression was used to address variable collinearity.Then,three common machine learning algorithms(random forest[RF],support vector machine[SVM],and back propagation artificial neural network[BP-ANN])were used to simulate and predict blood glucose status.Additionally,a stepwise logistic regression was performed to compare the machine learning models.Results:The well-controlled blood glucose rate was 45.82%in North China.The multivariable analysis found that hypertension history,atherosclerotic cardiovascular disease history,exercise,and total cholesterol were protective factors in glycosylated hemoglobin(HbAlc)control,while central adiposity,family history,T2DM duration,complications,insulin dose,blood pressure,and hypertension were risk factors for elevated HbAlc.Before the dimensional reduction in the EN,the areas under the curve of RF,SVM,and BP were 0.73,0.61,and 0.70,respectively,while these figures increased to 0.75,0.72,and 0.72,respectively,after dimensional reduction.Moreover,the EN and machine learning models had higher sensitivity and accuracy than the logistic regression models(the sensitivity and accuracy of logistic were 0.52 and 0.56;RF:0.79,0.70;SVM:0.84,0.73;BP-ANN:0.78,0.73,respectively).Conclusions:More than half of T2DM patients in North China had poor glycemic control and were at a higher risk of developing diabetic complications.The EN and machine learning algorithms are alternative choices,in addition to the traditional logistic
文摘目的系统评价老年综合评估对预防老年患者护理不良事件发生的干预效果。方法计算机检索中国知网、万方、中国生物医学文献数据库、PubMed、Cochrane、Embase、EBSCO、Medline、Web of Science,检索时间为建库截至2019年6月。收集所有关于老年综合评估对老年患者护理不良事件影响的随机对照试验。由2名研究员按照纳入和排除标准独立筛选文献并提取资料,运用RevMan 5.3进行Meta分析,Stata 15进行Begg秩相关分析。结果最终纳入13篇随机对照实验,总计26241例患者。Meta分析结果显示:老年综合评估能够降低老年患者跌倒发生率(OR=0.42,95%CI:0.34~0.54,P<0.01)、降低患者非计划拔管发生率(OR=0.19,95%CI:0.08~0.47,P<0.01),患者住院压疮发生率(OR=0.62,95%CI:0.38~1.00,P=0.05)未显著降低。结论与常规护理评估相比,老年综合评估能够降低老年患者跌倒发生率和非计划拔管发生率,但不能降低老年患者住院压疮发生率。