BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To...BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.展开更多
目的:鉴于脓毒症的高发病率和高病死率,早期识别高风险患者并及时干预至关重要,而现有死亡风险预测模型在操作、适用性和预测长期预后等方面均存在不足。本研究旨在探讨脓毒症患者死亡的危险因素,构建近期和远期死亡风险预测模型。方法...目的:鉴于脓毒症的高发病率和高病死率,早期识别高风险患者并及时干预至关重要,而现有死亡风险预测模型在操作、适用性和预测长期预后等方面均存在不足。本研究旨在探讨脓毒症患者死亡的危险因素,构建近期和远期死亡风险预测模型。方法:从美国重症监护医学信息数据库IV(Medical Information Mart for Intensive Care-IV,MIMIC-IV)中选取符合脓毒症3.0诊断标准的人群,按7?3的比例随机分为建模组和验证组,分析患者的基线资料。采用单因素Cox回归分析和全子集回归确定脓毒症患者死亡的危险因素并筛选出构建预测模型的变量。分别用时间依赖性曲线下面积(area under the curve,AUC)、校准曲线和决策曲线评估模型的区分度、校准度和临床实用性。结果:共纳入14240例脓毒症患者,28 d和1年病死率分别为21.45%(3054例)和36.50%(5198例)。高龄、女性、高感染相关器官衰竭评分(sepsis-related organ failure assessment,SOFA)、高简明急性生理学评分(simplified acute physiology score II,SAPS II)、心率快、呼吸频率快、脓毒症休克、充血性心力衰竭、慢性阻塞性肺疾病、肝脏疾病、肾脏疾病、糖尿病、恶性肿瘤、高白细胞计数(white blood cell count,WBC)、长凝血酶原时间(prothrombin time,PT)、高血肌酐(serum creatinine,SCr)水平均为脓毒症死亡的危险因素(均P<0.05)。由PT、呼吸频率、体温、合并恶性肿瘤、合并肝脏疾病、脓毒症休克、SAPS II及年龄8个变量构建的模型,其28 d和1年生存的AUC分别为0.717(95%CI 0.710~0.724)和0.716(95%CI 0.707~0.725)。校准曲线和决策曲线表明该模型具有良好的校准度及较好的临床应用价值。结论:基于MIMIC-IV建立的脓毒症患者近期和远期死亡风险预测模型有较好的识别能力,对患者预后风险评估及干预治疗具有一定的临床参考意义。展开更多
Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput seq...Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.展开更多
文摘BACKGROUND Liver transplantation aims to increase the survival of patients with end-stage liver diseases and improve their quality of life.The number of organs available for transplantation is lower than the demand.To provide fair organ distribution,predictive mortality scores have been developed.AIM To compare the Acute Physiology and Chronic Health Evaluation IV(APACHE IV),balance of risk(BAR),and model for end-stage liver disease(MELD)scores as predictors of mortality.METHODS Retrospective cohort study,which included 283 adult patients in the postoperative period of deceased donor liver transplantation from 2014 to 2018.RESULTS The transplant recipients were mainly male,with a mean age of 58.1 years.Donors were mostly male,with a mean age of 41.6 years.The median cold ischemia time was 3.1 hours,and the median intensive care unit stay was 5 days.For APACHE IV,a mean of 59.6 was found,BAR 10.7,and MELD 24.2.The 28-day mortality rate was 9.5%,and at 90 days,it was 3.5%.The 28-day mortality prediction for APACHE IV was very good[area under the curve(AUC):0.85,P<0.001,95%CI:0.76-0.94],P<0.001,BAR(AUC:0.70,P<0.001,95%CI:0.58–0.81),and MELD(AUC:0.66,P<0.006,95%CI:0.55-0.78),P<0.008.At 90 days,the data for APACHE IV were very good(AUC:0.80,P<0.001,95%CI:0.71–0.90)and moderate for BAR and MELD,respectively,(AUC:0.66,P<0.004,95%CI:0.55–0.77),(AUC:0.62,P<0.026,95%CI:0.51–0.72).All showed good discrimination between deaths and survivors.As for the best value for liver transplantation,it was significant only for APACHE IV(P<0.001).CONCLUSION The APACHE IV assessment score was more accurate than BAR and MELD in predicting mortality in deceased donor liver transplant recipients.
文摘目的:鉴于脓毒症的高发病率和高病死率,早期识别高风险患者并及时干预至关重要,而现有死亡风险预测模型在操作、适用性和预测长期预后等方面均存在不足。本研究旨在探讨脓毒症患者死亡的危险因素,构建近期和远期死亡风险预测模型。方法:从美国重症监护医学信息数据库IV(Medical Information Mart for Intensive Care-IV,MIMIC-IV)中选取符合脓毒症3.0诊断标准的人群,按7?3的比例随机分为建模组和验证组,分析患者的基线资料。采用单因素Cox回归分析和全子集回归确定脓毒症患者死亡的危险因素并筛选出构建预测模型的变量。分别用时间依赖性曲线下面积(area under the curve,AUC)、校准曲线和决策曲线评估模型的区分度、校准度和临床实用性。结果:共纳入14240例脓毒症患者,28 d和1年病死率分别为21.45%(3054例)和36.50%(5198例)。高龄、女性、高感染相关器官衰竭评分(sepsis-related organ failure assessment,SOFA)、高简明急性生理学评分(simplified acute physiology score II,SAPS II)、心率快、呼吸频率快、脓毒症休克、充血性心力衰竭、慢性阻塞性肺疾病、肝脏疾病、肾脏疾病、糖尿病、恶性肿瘤、高白细胞计数(white blood cell count,WBC)、长凝血酶原时间(prothrombin time,PT)、高血肌酐(serum creatinine,SCr)水平均为脓毒症死亡的危险因素(均P<0.05)。由PT、呼吸频率、体温、合并恶性肿瘤、合并肝脏疾病、脓毒症休克、SAPS II及年龄8个变量构建的模型,其28 d和1年生存的AUC分别为0.717(95%CI 0.710~0.724)和0.716(95%CI 0.707~0.725)。校准曲线和决策曲线表明该模型具有良好的校准度及较好的临床应用价值。结论:基于MIMIC-IV建立的脓毒症患者近期和远期死亡风险预测模型有较好的识别能力,对患者预后风险评估及干预治疗具有一定的临床参考意义。
基金supported by grants from Open Project of Gansu Traditional Chinese Medicine Research Center(No.zyzx-2020-10)Gansu Province Youth Science and Technology Foundation Program(No.21JR7RA652)+1 种基金Gansu Province Higher Education Research(No.2018A-049)Gansu Province Higher Education Research(No.2021B-163).
文摘Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.
