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Blocking Cyclic Adenosine Diphosphate Ribose-mediated Calcium Overload Attenuates Sepsis-induced Acute Lung Injury in Rats

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Chinese Medical Journal 2016年第14期129卷 1725-1730页

作者： Qian-Yi Peng yu Zou Li-Na Zhang Mei-Lin ai Wei Liu yu-hang ai Department of Critical Care Medicine Xiangya Hospital Central South University Changsha Hunan 410008 China Department of Anesthesia Xiangya Hospital Central South University Changsha Hunan 410008 China

Background： Acute lung injury （ALI） is a common complication of sepsis that is associated with high mortality, lntracellular Ca^2＋ overload plays an important role in the pathophysiology of sepsis-induced ALl, and cyclic adenosine diphosphate ribose （cADPR） is an important regulator of intracellular Ca^2＋ mobilization. The cluster of differentiation 38 （CD38）/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALl is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALl and whether blocking cADPR-mediated calcium overload attenuates ALl. Methods： Septic rat models were established by cecal ligation and puncture （CLP）. Rats were divided into the sham group, the CLP group, and the CLP＋ 8-bromo-cyclic adenosine diphosphate ribose （8-Br-cADPR） group. Nicotinamide adenine dinucleotide （NAD＋）, cADPR, CD38, and intracellular Ca^2＋ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor （TNF）-a, malondialdehyde （MDA） levels, and superoxide dismutase （SOD） activities were measured. Results： NAD＋, cADPR, CD38, and intracellular Ca-＋ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca^2＋ levels （P = 0.007）, attenuated lung histological injury （P = 0.023）, reduced TNF-a and MDA levels （P 〈 0.001 and P = 0.002, respectively） and recovered SOD activity （P = 0.031） in the lungs of septic rats. Conclusions： The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALl.

关键词： Acute Lung Injury Calcium Overload Cyclic Adenosine Diphosphate Ribose Sepsis

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Diagnostic and Predictive Levels of Calcium-binding Protein A8 and Tumor Necrosis Factor Receptor-associated Factor 6 in Sepsis-associated Encephalopathy： A Prospective Observational Study

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Chinese Medical Journal 2016年第14期129卷 1674-1681页

作者： Li-Na Zhang Xiao-Hong Wang Long Wu Li Huang Chun-Guang Zhao Qian-Yi Peng yu-hang ai Department of Critical Care Medicine Xiangya Hospital Central South University Changsha Hunan 410008 China Department of Anesthesiology and CrJtical Care Medicine Hunan Provincial Maternal and Child Health Care Hospital Changsha Hunan 410008 China

Background： Despite its high prevalence, morbidity, and mortality, sepsis-associated encephalopathy （SAE） is still poorly understood. The aim of this prospective and observational study was to investigate the clinical significance of calcium-binding protein A8 （S 100AS） in serum and tumor necrosis factor receptor-associated factor 6 （TRAF6） in peripheral blood mononuclear cells （PBMCs） in diagnosing SAE and predicting its prognosis. Methods： Data of septic patients were collected within 24 h after Intensive Care Unit admission fi-om July 2014 to March 2015. Healthy medical personnel served as the control group. SAE was defined as cerebral dysfhnction in the presence of sepsis that fulfilled the exclusion criteria. The biochemical indicators, Glasgow Coma Scale, Acute Physiology and Chronic Health Evaluation score II, TRAF6 in PBMC, serum S 100A8, S 10013, and neuron-specific enolase were evaluated in SAE patients afresh. TRAF6 and S 100A8 were also measured in the control group. Results： Of the 57 enrolled patients, 29 were diagnosed with SAE. The S 100A8 and TRAF6 concentrations in SAE patients were both significantly higher than that in no-encephalopathy （NE） patients, and higher in NE than that in controls （3.74 ± 3.13 vs. 1.08 ± 0.75 vs. 0.37 ± 0.14 ng/ml, P 〈 0.01 ; 3.18 ± 1.55 vs. 1.02 ± 0.63 vs. 0.47 ± 0.10, P 〈 0.01）. S 100A8 levels of 1.93 ng/ml were diagnostic of SAE with 92.90% specificity and 69.00% sensitivity in the receiver operating characteristic （ROC） curve, and the area under the curve was 0.86 （95% confidence interval [CI]： 0.76-0.95）. TRAF6-relative levels of 1.44 were diagnostic of SAE with 85.70% specificity and 86.20% sensitivity, and the area under the curve was 0.94 （95% CI： 0.88-0.99）. In addition, S 100A8 levels of 2.41 ng/ml predicted 28-day mortality of SAE with 90.00% specificity and 73.70% sensitivity in the ROC curve, and the area under the curve was 0.88. TRAF6 relative levels of 2.94 predicted 28-day mortality of SAE with 80.00% sp

关键词： Biomarker Calcium-binding Protein A8 Sepsis-associated Encephalopathy Tumor Necrosis Factor Receptor-associated Factor 6

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Involvement of phosphatase and tensin homolog-induced putative kinase 1–Parkin-mediated mitophagy in septic acute kidney injury

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Chinese Medical Journal 2019年第19期132卷 2340-2347页

作者： Xin-Gui Dai Wei Xu Tao Li Jia-Ying Lu Yang Yang Qiong Li Zhen-Hua Zeng yu-hang ai Department of Intensive Care Unit Xiangya HospitalCentral South UniversityChangshaHunan 410078China Department of Critical Care Medicine The First People's Hospital of ChenzhouChenzhouHunan 423000China Department of Critical Care Medicine Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

Background:Studies have reported mitophagy activation in renal tubular epithelial cells(RTECs)in acute kidney injury(AKI).Phosphatase and tensin homolog-induced putative kinase 1(PINK1)and E3 ubiquitin-protein ligase Parkin are involved in mitophagy regulation;however,little is known about the role of PINK1-Parkin mitophagy in septic *** we investigated whether the PINK1-Parkin mitophagy pathway is involved in septic AKI and its effects on cell apoptosis in vitro and on renal functions in ***:Mitophagy-related gene expression was determined using Western blot assay in human RTEC cell line HK-2 stimulated with bacterial lipopolysaccharide(LPS)and in RTECs from septic AKI rats induced by cecal ligation and perforation(CLP).Autophagy-related ultrastructural features in rat RTECs were observed using electron ***-and loss-of-function approaches were performed to investigate the role of the PINK1-Parkin pathway in HK-2 cell *** activators and inhibitors were used to assess the effects of mitophagy modulation on cell apoptosis in vitro and on renal functions in ***:LPS stimulation could significantly induce LC3-II and BECN-1 protein expression(LC3-II:1.72±0.05 vs.1.00±0.05,Pained unchanged in autophagy activator-treated HK-2 cells and was significantl

关键词： Sepsis Acute kidney injury Autophagy Mitophagy Phosphatase and tensin homolog-induced putative kinase 1 E3 ubiquitin-protein ligase Parkin

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Epidemiological features and risk factors of sepsis-associated encephalopathy in intensive care unit patients： 2008-2011

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Chinese Medical Journal 2012年第5期000卷 828-831页

作者： Zhang Li-na WANG Xiao-ting ai yu-hang GUO Qu-lian HUANG Li LIU Zhi-yong Vao Bo Department of Intensive Care Unit Xiangya Hospital CentralSouth University Changsha Hunan 410008 China Department of Critical Care Medicine Peking Union MedicalCollege Hospital Peking Union Medical College ChineseAcademy of Medical Sciences Beijing 100730 China

Background Encephalopathy is a common complication of sepsis, and its onset can occur at any stage of sepsis and implies worse prognosis. However, the incidence, epidemiology, and pathogenesis of sepsis-associated encephalopathy remain controversial. The purpose of this study was to investigate the epidemiological features and risk factors for sepsis-associated encephalopathy.

关键词： sepsis sepsis-associated encephalopathy epidemiology risk factor

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Boosting bidirectional sulfur conversion enabled by introducing boron-doped atoms and phosphorus vacancies in Ni2P for lithium-sulfur batteries

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Journal of Energy Chemistry 2025年第1期100卷 760-769页

作者： Lin Peng yu Bai hang Li Meixiu Qu Zhenhua Wang Kening Sun Advanced Research Institute of Multidisciplinary Science Beijing Institute of Technology Beijing Key Laboratory of Chemical Power Source and Green Catalysis School of Chemistry and Chemical Engineering Beijing Institute of Technology

Lithium-sulfur （Li-S） batteries have gained great attention due to the high theoretical energy density and low cost,yet their further commercialization has been obstructed by the notorious shuttle effect and sluggish redox ***,we supply a strategy to optimize the electron structure of Ni2P by concurrently introducing B-doped atoms and P vacancies in Ni2P （Vp-B-Ni2P）,thereby enhancing the bidirectional sulfur *** study indicates that the simultaneous introduction of B-doped atoms and P vacancies in Ni2P causes the redistribution of electron around Ni atoms,bringing about the upward shift of d-band center of Ni atoms and effective d-p orbital hybridization between Ni atoms and sulfur species,thus strengthening the chemical anchoring for lithium polysulfides （LiPSs） as well as expediting the bidirectional conversion kinetics of sulfur ***,theoretical calculations reveal that the incorporation of B-doped atoms and P vacancies in Ni2P selectively promotes Li2S dissolution and nucleation ***,the Li-S batteries with Vp-B-Ni2P-separators present outstanding rate ability of 777 m A h g-1at 5 C and high areal capacity of 8.03 mA h cm-2under E/S of 5μL mg-1and sulfur loading of 7.20 mg *** work elucidates that introducing heteroatom and vacancy in metal phosphide collaboratively regulates the electron structure to accelerate bidirectional sulfur conversion.

关键词： Lithium sulfur batteries

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经皮扩张气管套管导入术在重度颅脑外伤中的应用

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中南大学学报（医学版） 2005年第6期30卷 736-737页

作者：龚华张丽娜艾宇航中南大学湘雅医院麻醉科ICU 长沙410008

重度颅脑外伤病人合并呼吸功能障碍常见,如处理不当则可成为致死原因.气管切开术是抢救危重患者常用的外科手术之一,包括传统的气管切开术和经皮扩张气管套管导入术(percutaneous dilatational tracheostomy,PDT)等,后者在国外已广泛采... 详细信息

重度颅脑外伤病人合并呼吸功能障碍常见,如处理不当则可成为致死原因.气管切开术是抢救危重患者常用的外科手术之一,包括传统的气管切开术和经皮扩张气管套管导入术(percutaneous dilatational tracheostomy,PDT)等,后者在国外已广泛采用,且主要用于危重患者的抢救[1],目前国内报道不多.2004年2月至2005年2月,笔者对20例重度颅脑损伤患者行PDT,并与同期20例传统的气管切开术进行比较,现将结果报告如下.

关键词：经皮扩张气管套管导入术重度颅脑外伤气管切开术

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超声与颅内压监测和脑血流动力学评估

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中国实用内科杂志 2017年第8期37卷 686-689页

作者：张丽娜艾宇航中南大学湘雅医院重症医学科湖南长沙410008

超声可以通过中线结构位移、视神经鞘直径、经颅多普勒频谱形态和测量数值定性定量监测颅内压力改变。经颅多普勒超声或经颅彩色多普勒超声可实时监测脑血流特征,尤其是可提供脑血管反应性和脑血管自动调节功能的重要信息。重症超声通... 详细信息

超声可以通过中线结构位移、视神经鞘直径、经颅多普勒频谱形态和测量数值定性定量监测颅内压力改变。经颅多普勒超声或经颅彩色多普勒超声可实时监测脑血流特征,尤其是可提供脑血管反应性和脑血管自动调节功能的重要信息。重症超声通过颅内压监测和脑血流调节功能评估与反映脑代谢活动的颈静脉球血氧饱和度、反映脑电及功能活动的持续脑电图监测从不同层面提供信息,共同组成脑血流动力学监测的重要内容,帮助临床准确评估颅脑血流动力学指导治疗和协助预后判断。

关键词：重症超声颅内压视神经鞘直径颅脑血流动力学脑血流调节功能

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大脑状态指数和脑电双频谱指数对ICU患者镇静深度的评价

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中国现代医学杂志 2013年第3期23卷 92-96页

作者：罗翠竹艾宇航中南大学湘雅医院重症医学科湖南长沙410008

目的对靶控输注丙泊酚镇静的ICU患者,评价大脑状态指数（CSI）和脑电双频谱指数（BIS）在监测镇静深度的准确性以及年龄因素对其的影响。方法 Ramsay评分为1的ICU患者,排除中枢神经系统病变、休克以及高脂血症者。按年龄分为两组：A组... 详细信息

目的对靶控输注丙泊酚镇静的ICU患者,评价大脑状态指数（CSI）和脑电双频谱指数（BIS）在监测镇静深度的准确性以及年龄因素对其的影响。方法 Ramsay评分为1的ICU患者,排除中枢神经系统病变、休克以及高脂血症者。按年龄分为两组：A组（年龄20~64岁,16例）和B组（年龄〉64岁,15例）。均以丙泊酚靶控输注镇静,监测并记录各时间点（见正文）平均动脉压、心率、BIS值、CSI值和Ramsay评分,并记录靶控输注系统预测的效应部位浓度值（Ce）。比较Ce、BIS值和CSI值与Ramsay评分值有无相关性,以及Ce与BIS值和CSI值的相关性,并且比较BIS和CSI在老年患者和中青年患者中有无差异。结果随着Ce的增加,Ramsay评分值逐渐升高,CSI值和BIS值逐渐降低,Ramsay评分值、CSI值和BIS值均与Ce有良好的相关性;CSI值和BIS值均与Ramsay评分值有良好的相关性;与中青年患者比较,老年患者CSI值差异具有显著性（P〈0.05）,两组患者BIS值差异无显著性（P〉0.05）。结论靶控输注丙泊酚镇静,CSI和BIS一样能预测ICU患者意识状态的变化;同一个Ramsay评分等级,老年人组CSI值较中青年组低。

关键词：清醒镇静二异丙酚脑电描记术

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重度颅脑外伤后早期肠内营养对胃黏膜pHi、Pg-aCO_2的影响

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中华神经外科杂志 2007年第6期23卷 455-457页

作者：马新华张丽娜艾宇航赵双平龚华中南大学湘雅医院ICU 长沙410008

目的探讨重度脑外伤后早期肠内营养对胃黏膜监测的影响。方法40例重度脑外伤患者(GCS≤8分)分为两组,每组20例:一组给予早期肠内营养,另一组给予全静脉营养。入室当天插入Tonometer导管监测胃黏膜pH值(pHi)、胃黏膜表面CO2张力和动脉血... 详细信息

目的探讨重度脑外伤后早期肠内营养对胃黏膜监测的影响。方法40例重度脑外伤患者(GCS≤8分)分为两组,每组20例:一组给予早期肠内营养,另一组给予全静脉营养。入室当天插入Tonometer导管监测胃黏膜pH值(pHi)、胃黏膜表面CO2张力和动脉血CO2之差(Pg-aCO2),抽动脉血监测乳酸值,连续监测7d,比较第1天和第7天患者乳酸值、pHi、Pg-aCO2。结果第1天两组间比较差异无统计学意义;第7天早期肠内营养组pHi显著大于全静脉营养组,Pg-aCO2显著小于全静脉营养组,乳酸值两组比较无统计学差异。结论早期肠内营养显著增加pHi,降低Pg-aCO2值,对胃肠黏膜具有保护作用。

关键词：胃黏膜pH值胃黏膜CO2张力肠内营养乳酸

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血必净促进内毒素／脂多糖刺激调节性T淋巴细胞凋亡并介导辅助性T淋巴细胞漂移的作用

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中华烧伤杂志 2009年第2期25卷 106-110页

作者：戴新贵姚咏明艾宇航于燕解放军总医院第一附属医院全军烧伤研究所北京100037 中南大学湘雅医院重症医学科

目的了解血必净注射液促进LPS刺激CD4^＋CD25^＋调节性T淋巴细胞（Treg细胞）凋亡过程及介导辅助性T淋巴细胞（Th）漂移的调节作用。方法免疫磁珠法分选获得大鼠脾脏CD4^＋CD25^＋Treg细胞，分为常规培养对照组、抗CD3／CD28组、抗CD3／... 详细信息

目的了解血必净注射液促进LPS刺激CD4^＋CD25^＋调节性T淋巴细胞（Treg细胞）凋亡过程及介导辅助性T淋巴细胞（Th）漂移的调节作用。方法免疫磁珠法分选获得大鼠脾脏CD4^＋CD25^＋Treg细胞，分为常规培养对照组、抗CD3／CD28组、抗CD3／CD28＋LPS组、抗CD3／CD28^＋血必净组和抗CD3／CD28＋LPS＋血必净组，培养3d后应用流式细胞术检测Treg细胞凋亡率及叉头翼状螺旋转录因子3（Foxp3）表达。将CD4^＋CD25^＋Treg细胞与CD4^＋CD25^-T淋巴细胞1：1培养，伴刀豆球蛋白A刺激68h，检测上清液中Th1分泌的γ干扰素（IFN-γ）、Th2分泌的IL-4、Th17分泌的IL-17水平。结果抗CD3／CD28＋LPS＋血必净组Treg细胞凋亡率为（45．14±2．7）％，明显高于抗CD3／CD28＋LPS组[（29．4±1．6）％，P〈0．01]；2组Foxp3平均荧光强度分别为95±9、140±18，差异有统计学意义（P〈0．01）。同时，抗CD3／CD28＋LPS＋血必净组IFN-γ分泌水平显著高于抗CD3／CD28＋LPS组（P〈0．01），IL4则呈相反变化（P〈0．05），抗CD3／CD28＋LPS＋血必净组IFN-γ／IL-4较对照组升高（P〈0．01）；抗CD3／CD28＋血必净组IL-17分泌水平较抗CD3／CD28组明显下降（P〈0．05）。结论CD4^＋CD25^＋Treg细胞活化介导了Th1向Th2功能性极化；血必净对LPS诱导的T淋巴细胞免疫功能有重要调节作用，可促进CD4^＋CD25^＋Treg细胞凋亡并介导Th2向Th1漂移，从而缓解细胞免疫抑制状态。

关键词：内毒素类脓毒症 T淋巴细胞调节性 T淋巴细胞辅助诱导血必净注射液

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