目的:通过分析儿童结核性脑膜炎(tuberculous meningitis,TBM)患者的临床特征和预后相关的危险因素,为儿童TBM高危患者的早期识别和干预提供有效依据。方法:回顾性收集2013年1月1日至2023年12月31日上海市(复旦大学附属)公共卫生临床中...目的:通过分析儿童结核性脑膜炎(tuberculous meningitis,TBM)患者的临床特征和预后相关的危险因素,为儿童TBM高危患者的早期识别和干预提供有效依据。方法:回顾性收集2013年1月1日至2023年12月31日上海市(复旦大学附属)公共卫生临床中心首次诊断为TBM儿童患者的资料。根据门诊和电话相结合的方式,采用改良兰金量表(modified Rankin scale,mRS)评估儿童TBM抗结核治疗12个月后的神经系统结局,比较预后良好和预后不良两组患儿的临床特征,采用单因素和多因素分析识别和预后不良相关的因素。结果:研究共纳入TBM儿童患者91例,其中,62例预后良好,29例预后不良。患儿年龄的中位数(四分位数)为3.00(1.00,8.00)岁,51例为男性患儿。入院时预后不良组发生肌力异常(12/29,41.38%)、神志不清(16/29,55.17%)、脑积水(17/29,58.62%)的比例均高于预后良好组[分别为(9/62,14.52%)、(13/62,20.97%)和(22/62,35.48%)](χ^(2)=8.032,P=0.005;χ^(2)=10.647,P<0.001;χ^(2)=4.319,P=0.038);发生咳嗽≥2周(4/29,13.79%)和咳痰(1/29,3.45%)的比例则低于预后良好组[分别为(21/62,33.87%)、(13/62,20.97%)](χ^(2)=3.997,P=0.046;χ^(2)=4.659,P=0.031);预后不良组的格拉斯哥昏迷量表(Glasgow Coma Scale,GCS)评分比预后良好组更低(13和15;Z=-4.190,P<0.001),英国医学研究委员会(Medical Research Council,MRC)疾病分期差异具有统计学意义(χ^(2)=22.327,P<0.001)。此外,预后不良组的脑脊液(cerebrospinal fluid,CSF)乳酸脱氢酶含量[中位数(四分位数):60.00(29.50,128.00)IU/L]、使用外脑室引流术(7/29,24.14%)以及机械通气(19/29,65.52%)的比例均高于预后良好组[分别为39.50(20.75,64.00)IU/L、(2/62,3.23%)、(25/62,40.32%)](Z=-2.100,P=0.036;χ^(2)=9.696,P=0.002;χ^(2)=5.022,P=0.025)。多因素logistic分析结果显示入院神志不清(OR=3.690;95%CI:1.045~13.034;P=0.043)和使用外脑室引流(OR=8.041;95%CI:1.064~60.760;P=0.043)是儿童TBM患者预后不良的独立危险因素。结论:预后不良儿童TBM患者更多表现为严重神经系统症状(如肌力异常、低GCS评分)、脑积水及CSF乳酸脱氢酶升高,且机械通气需求更高。而预后良好组呼吸道症状(如咳嗽、咳痰)更突出,可能提示早期就诊或疾病较轻。入院神志不清、外脑室引流是提示预后不良的独立危险因素。展开更多
The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tum...The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tumors.However,its underlying mechanisms remain elusive.In this work,we explore the role of receptor-interacting protein 1(RIP1)which plays a crucial role in the process of cell death,in metformin-induced anticancer activities in lung cancer.Metformin inhibits lung cancer cell proliferation in a dose-dependent manner and promotes apoptotic cell death,as evidenced by metformin-induced PARP and caspase cleavage.Furthermore,the pan-caspase inhibitor z-VAD-fmk reverses metformin-induced cell death.Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels(0 vs 80 mmol/L,100%vs 20%,100%vs 15%).Additionally,co-immunoprecipitation and immunofluorescence results reveal that metformin may suppress RIP1 expression in an Hsp70-dependent manner,as metformin promotes Hsp70 degradation,and Hsp70 endogenously interacts with RIP1.Subsequent CCK-8,flow cytometry,and Western blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3βaxis.Consistently,results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight.Collectively,these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo,providing novel strategy for lung cancer administration.展开更多
碳青霉烯类耐药革兰阴性菌(CRGNB)的广泛播散是一个全球性的公共卫生问题。CRGNB临床分离株通常呈现广泛耐药或全耐药,对其感染的抗菌治疗方案有限、死亡率高。由感染病临床诊疗、临床微生物、临床药理、医院感染控制及指南方法学等多...碳青霉烯类耐药革兰阴性菌(CRGNB)的广泛播散是一个全球性的公共卫生问题。CRGNB临床分离株通常呈现广泛耐药或全耐药,对其感染的抗菌治疗方案有限、死亡率高。由感染病临床诊疗、临床微生物、临床药理、医院感染控制及指南方法学等多学科专家组成的指南制定小组,根据现有科学证据制定了本临床实践指南,以解答有关CRGNB检测、抗菌治疗及感染预防控制的系列临床优先问题。本指南聚焦于碳青霉烯类耐药肠杆菌目细菌、碳青霉烯类耐药鲍曼不动杆菌和碳青霉烯类耐药铜绿假单胞菌,从当前临床实践的角度提出16个临床问题,采用人群、干预、对照及预后(population,intervention,comparator,outcomes,PICO)格式转换为研究问题,全面收集和综合分析相关研究证据。采用推荐的分级、评估、制定与评价(grading of recommendations,assessment,development and evaluation,GRADE)方法评估相应干预措施的证据体质量、效益及风险,从而制定推荐意见或建议。随机对照临床试验及系统评价获得的结果被优先用于治疗相关临床问题的推荐证据。在缺乏随机对照临床试验的情况下,观察性研究、非对照研究和专家意见被考虑作为补充证据。推荐意见分为强推荐或弱推荐(有条件推荐)。结合中国的临床实践经验,本指南同时提出实施建议,便于指南推荐意见的临床实施。本指南对耐药菌感染诊疗相关的临床医师等多学科专业人员具有参考价值。展开更多
文摘目的:通过分析儿童结核性脑膜炎(tuberculous meningitis,TBM)患者的临床特征和预后相关的危险因素,为儿童TBM高危患者的早期识别和干预提供有效依据。方法:回顾性收集2013年1月1日至2023年12月31日上海市(复旦大学附属)公共卫生临床中心首次诊断为TBM儿童患者的资料。根据门诊和电话相结合的方式,采用改良兰金量表(modified Rankin scale,mRS)评估儿童TBM抗结核治疗12个月后的神经系统结局,比较预后良好和预后不良两组患儿的临床特征,采用单因素和多因素分析识别和预后不良相关的因素。结果:研究共纳入TBM儿童患者91例,其中,62例预后良好,29例预后不良。患儿年龄的中位数(四分位数)为3.00(1.00,8.00)岁,51例为男性患儿。入院时预后不良组发生肌力异常(12/29,41.38%)、神志不清(16/29,55.17%)、脑积水(17/29,58.62%)的比例均高于预后良好组[分别为(9/62,14.52%)、(13/62,20.97%)和(22/62,35.48%)](χ^(2)=8.032,P=0.005;χ^(2)=10.647,P<0.001;χ^(2)=4.319,P=0.038);发生咳嗽≥2周(4/29,13.79%)和咳痰(1/29,3.45%)的比例则低于预后良好组[分别为(21/62,33.87%)、(13/62,20.97%)](χ^(2)=3.997,P=0.046;χ^(2)=4.659,P=0.031);预后不良组的格拉斯哥昏迷量表(Glasgow Coma Scale,GCS)评分比预后良好组更低(13和15;Z=-4.190,P<0.001),英国医学研究委员会(Medical Research Council,MRC)疾病分期差异具有统计学意义(χ^(2)=22.327,P<0.001)。此外,预后不良组的脑脊液(cerebrospinal fluid,CSF)乳酸脱氢酶含量[中位数(四分位数):60.00(29.50,128.00)IU/L]、使用外脑室引流术(7/29,24.14%)以及机械通气(19/29,65.52%)的比例均高于预后良好组[分别为39.50(20.75,64.00)IU/L、(2/62,3.23%)、(25/62,40.32%)](Z=-2.100,P=0.036;χ^(2)=9.696,P=0.002;χ^(2)=5.022,P=0.025)。多因素logistic分析结果显示入院神志不清(OR=3.690;95%CI:1.045~13.034;P=0.043)和使用外脑室引流(OR=8.041;95%CI:1.064~60.760;P=0.043)是儿童TBM患者预后不良的独立危险因素。结论:预后不良儿童TBM患者更多表现为严重神经系统症状(如肌力异常、低GCS评分)、脑积水及CSF乳酸脱氢酶升高,且机械通气需求更高。而预后良好组呼吸道症状(如咳嗽、咳痰)更突出,可能提示早期就诊或疾病较轻。入院神志不清、外脑室引流是提示预后不良的独立危险因素。
文摘The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tumors.However,its underlying mechanisms remain elusive.In this work,we explore the role of receptor-interacting protein 1(RIP1)which plays a crucial role in the process of cell death,in metformin-induced anticancer activities in lung cancer.Metformin inhibits lung cancer cell proliferation in a dose-dependent manner and promotes apoptotic cell death,as evidenced by metformin-induced PARP and caspase cleavage.Furthermore,the pan-caspase inhibitor z-VAD-fmk reverses metformin-induced cell death.Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels(0 vs 80 mmol/L,100%vs 20%,100%vs 15%).Additionally,co-immunoprecipitation and immunofluorescence results reveal that metformin may suppress RIP1 expression in an Hsp70-dependent manner,as metformin promotes Hsp70 degradation,and Hsp70 endogenously interacts with RIP1.Subsequent CCK-8,flow cytometry,and Western blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3βaxis.Consistently,results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight.Collectively,these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo,providing novel strategy for lung cancer administration.
文摘碳青霉烯类耐药革兰阴性菌(CRGNB)的广泛播散是一个全球性的公共卫生问题。CRGNB临床分离株通常呈现广泛耐药或全耐药,对其感染的抗菌治疗方案有限、死亡率高。由感染病临床诊疗、临床微生物、临床药理、医院感染控制及指南方法学等多学科专家组成的指南制定小组,根据现有科学证据制定了本临床实践指南,以解答有关CRGNB检测、抗菌治疗及感染预防控制的系列临床优先问题。本指南聚焦于碳青霉烯类耐药肠杆菌目细菌、碳青霉烯类耐药鲍曼不动杆菌和碳青霉烯类耐药铜绿假单胞菌,从当前临床实践的角度提出16个临床问题,采用人群、干预、对照及预后(population,intervention,comparator,outcomes,PICO)格式转换为研究问题,全面收集和综合分析相关研究证据。采用推荐的分级、评估、制定与评价(grading of recommendations,assessment,development and evaluation,GRADE)方法评估相应干预措施的证据体质量、效益及风险,从而制定推荐意见或建议。随机对照临床试验及系统评价获得的结果被优先用于治疗相关临床问题的推荐证据。在缺乏随机对照临床试验的情况下,观察性研究、非对照研究和专家意见被考虑作为补充证据。推荐意见分为强推荐或弱推荐(有条件推荐)。结合中国的临床实践经验,本指南同时提出实施建议,便于指南推荐意见的临床实施。本指南对耐药菌感染诊疗相关的临床医师等多学科专业人员具有参考价值。
