目的:探究多聚胞嘧啶结合蛋白2[poly(C)-binding protein 2,PCBP2]如何通过调节铁死亡参与大别班达病毒(Dabie Banda virus,DBV)感染后的致病过程及其作用机制。方法:以人单核细胞系THP-1为模型,采用qRT-PCR和Western blot技术检测DBV...目的:探究多聚胞嘧啶结合蛋白2[poly(C)-binding protein 2,PCBP2]如何通过调节铁死亡参与大别班达病毒(Dabie Banda virus,DBV)感染后的致病过程及其作用机制。方法:以人单核细胞系THP-1为模型,采用qRT-PCR和Western blot技术检测DBV感染的THP-1细胞中PCBP2的mRNA及蛋白表达水平。通过透射电镜观察病毒感染下的线粒体结构变化,在THP-1细胞中构建了慢病毒介导的PCBP2过表达和敲低稳转细胞系。FerroOrange荧光探针检测Fe^(2+)水平,2,7-二氯荧光素二乙酸酯(2,7-dichlorofluorescein diacetate,DCFH-DA)探针测定活性氧(reactive oxygen species,ROS)水平,Western blot检测铁死亡相关溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)和谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)蛋白表达,以评估PCBP2调控对铁死亡的影响。使用铁死亡诱导剂(RSL3、erastin)和抑制剂(Fer-1、Lip-1)处理细胞,qRT-PCR和免疫荧光检测病毒复制水平变化,探索PCBP2是否可以通过调控铁死亡影响DBV复制。结果:在DBV感染的细胞模型中,PCBP2的mRNA和蛋白表达水平显著下调,DBV感染诱导典型铁死亡特征(线粒体嵴减少、肿胀)。通过qRT-PCR和Western blot验证,PCBP2敲低和过表达的THP-1细胞系构建成功,PCBP2敲低下调了铁死亡相关基因SLC7A11和GPX4的表达,导致ROS和Fe^(2+)水平升高;相反,PCBP2过表达使得SLC7A11和GPX4的表达水平升高,ROS和Fe^(2+)的水平降低。半数组织培养感染剂量与蛋白水平的检测进一步证实:铁死亡诱导剂可部分抵消PCBP2过表达促病毒复制的效应,铁死亡抑制剂可部分逆转PCBP2敲低抑制病毒复制的效应。结论:研究发现PCBP2可以通过维持SLC7A11/GPX4系统功能抑制铁死亡,从而限制DBV复制。这不仅阐明了PCBP2在DBV感染中的调控作用,为发热伴血小板减少综合征(severe fever with thrombocytope-nia syndrome,SFTS)的发病机制提供了新见解,同时靶向PCBP2-铁死亡通路可能成为SFTS治疗的潜在策略,为抗病毒药物的研发提供新思路。展开更多
Lassa fever(LF)is an acute viral hemorrhagic illness caused by the Lassa virus(LASV),an enveloped,spherical virus belonging to the Arenaviridae family.LASV possess a single-stranded RNA genome of negative polarity and...Lassa fever(LF)is an acute viral hemorrhagic illness caused by the Lassa virus(LASV),an enveloped,spherical virus belonging to the Arenaviridae family.LASV possess a single-stranded RNA genome of negative polarity and exhibits high genetic diversity,corresponding to the geographical distribution of its seven principal distinct clades across West Africa[1].LASV was first isolated in 1969 from an American missionary nurse stationed in the rural town of Lassa,Borno State,Nigeria,following her return from a brief vacation in the United States[2].展开更多
Objective:To assess the effectiveness of intravenous immunoglobulin(IVIg)therapy in patients diagnosed with Crimean-Congo hemorrhagic fever(CCHF)disease.Methods:A single-center retrospective cohort study was conducted...Objective:To assess the effectiveness of intravenous immunoglobulin(IVIg)therapy in patients diagnosed with Crimean-Congo hemorrhagic fever(CCHF)disease.Methods:A single-center retrospective cohort study was conducted on hospitalized patients with confirmed severe CCHF at a tertiary care hospital in Turkey between 2010 and 2022.Cases were categorized into two groups based on whether they received IVIg therapy,with the treatment plan determined by the primary healthcare provider.The clinical,epidemiological,and laboratory parameters of these patients were evaluated.Demographic,laboratory findings,platelet counts on the day of IVIg indication and the third day,bleeding status during follow-up beyond 24 hours after IVIg administration,and prognosis recorded in patient information forms were retrieved.Results:72 patients were included in the analysis,with IVIg administered to 42 cases(58.3%)and not given to 30 cases(41.7%).Among the patients,37(51.4%)were female.Fever(65.3%)was the most common clinical presentation.The overall mortality rate was 19.4%,and IVIg administration did not significantly impact overall survival outcomes(P=0.48).On Day 3 following IVIg administration or indication,the platelet count was higher in the IVIg-treated group compared to the non-treated group(P=0.02).Furthermore,during follow-up beyond 24 hours after IVIg administration,bleeding was observed in 19.0%of the IVIg-treated group,compared to 46.6% in the non-treated group(P=0.01).Conclusions:This study underscores the potential advantages of IVIg therapy in managing severe CCHF.Although IVIg administration did not significantly affect overall survival,it was associated with earlier improvement in platelet counts and a notable reduction in bleeding complications.These findings indicate that IVIg may serve as an adjunctive treatment in CCHF,particularly for addressing hemorrhagic manifestations.展开更多
目的评估2019年海南省登革热患者的疾病与经济负担,并比较全国各省份登革热单位伤残调整寿命年(disability-adjusted life years,DALY)经济成本的差异,为量化登革热疾病与经济负担、制定区域精准的疾病防控策略和资源配置提供科学依据...目的评估2019年海南省登革热患者的疾病与经济负担,并比较全国各省份登革热单位伤残调整寿命年(disability-adjusted life years,DALY)经济成本的差异,为量化登革热疾病与经济负担、制定区域精准的疾病防控策略和资源配置提供科学依据。方法本研究采用回顾性分析,基于海南省人民医院2019年确诊的330例登革热患者的就诊信息,估算全省368例报告病例的疾病和经济负担。通过系统文献检索,汇总中国其他地区登革热经济负担数据,计算各省单位DALY经济成本,并比较地区间差异。结果在330例登革热患者中,人均DALY负担为0.03人年,总经济负担的M(P_(25),P_(75))为1822.11(162.61,2601.74)元,其中直接经济负担的M(P_(25),P_(75))为1513.03(162.61,2144.84)元,间接经济负担的M(P_(25),P_(75))为219.28(0,438.56)元。2019年海南省登革热病例的全省总DALY负担为11.33人年。全省估计总经济负担为670536.48(95%UI:575537.30~751654.70)元,其中直接经济负担为556795.04(95%UI:488810.70~626089.40)元,间接经济负担为80695.04(95%UI:53797.92~107592.20)元。全省估算单位DALY经济成本为59182.39元。在我国登革热经济负担研究涉及的地区(广东、浙江、广西、云南和重庆)中,广东省的单位DALY经济成本和人均经济负担均为最高。结论海南省登革热患者的经济负担严重,应通过扩大医保覆盖范围、完善异地医保结算来减轻患者的直接经济负担。全国各省间登革热患者的经济负担存在较大差异,因此登革热防控与补偿政策应结合区域特点,优化资源配置。展开更多
目的了解北京市2021—2023年发热伴血小板减少综合征(severe fever with thrombocytopenia syndrome,SFTS)的流行病学特征,为北京市防控该疾病提供依据。方法收集分析SFTS病例的个案资料,对阳性样本进行全基因测序,并进行遗传进化分析...目的了解北京市2021—2023年发热伴血小板减少综合征(severe fever with thrombocytopenia syndrome,SFTS)的流行病学特征,为北京市防控该疾病提供依据。方法收集分析SFTS病例的个案资料,对阳性样本进行全基因测序,并进行遗传进化分析。结果2021—2023年,北京市共报告9例本地感染病例,发病时间均在5—10月。男性6例,女性3例,年龄分布在40~<70岁,职业以农民为主。病例分布在5个区,平谷区发病数最多,有5例,存在一定的地域聚集性,平谷区还发生1起动物传人的聚集性疫情。测序及遗传进化分析结果显示,北京市的病例分属于A基因型和B基因型,未发现重配毒株。结论北京市SFTS病例为散发病例,有一定的地域聚集性,流行毒株为A基因型和B基因型。展开更多
文摘目的:探究多聚胞嘧啶结合蛋白2[poly(C)-binding protein 2,PCBP2]如何通过调节铁死亡参与大别班达病毒(Dabie Banda virus,DBV)感染后的致病过程及其作用机制。方法:以人单核细胞系THP-1为模型,采用qRT-PCR和Western blot技术检测DBV感染的THP-1细胞中PCBP2的mRNA及蛋白表达水平。通过透射电镜观察病毒感染下的线粒体结构变化,在THP-1细胞中构建了慢病毒介导的PCBP2过表达和敲低稳转细胞系。FerroOrange荧光探针检测Fe^(2+)水平,2,7-二氯荧光素二乙酸酯(2,7-dichlorofluorescein diacetate,DCFH-DA)探针测定活性氧(reactive oxygen species,ROS)水平,Western blot检测铁死亡相关溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)和谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)蛋白表达,以评估PCBP2调控对铁死亡的影响。使用铁死亡诱导剂(RSL3、erastin)和抑制剂(Fer-1、Lip-1)处理细胞,qRT-PCR和免疫荧光检测病毒复制水平变化,探索PCBP2是否可以通过调控铁死亡影响DBV复制。结果:在DBV感染的细胞模型中,PCBP2的mRNA和蛋白表达水平显著下调,DBV感染诱导典型铁死亡特征(线粒体嵴减少、肿胀)。通过qRT-PCR和Western blot验证,PCBP2敲低和过表达的THP-1细胞系构建成功,PCBP2敲低下调了铁死亡相关基因SLC7A11和GPX4的表达,导致ROS和Fe^(2+)水平升高;相反,PCBP2过表达使得SLC7A11和GPX4的表达水平升高,ROS和Fe^(2+)的水平降低。半数组织培养感染剂量与蛋白水平的检测进一步证实:铁死亡诱导剂可部分抵消PCBP2过表达促病毒复制的效应,铁死亡抑制剂可部分逆转PCBP2敲低抑制病毒复制的效应。结论:研究发现PCBP2可以通过维持SLC7A11/GPX4系统功能抑制铁死亡,从而限制DBV复制。这不仅阐明了PCBP2在DBV感染中的调控作用,为发热伴血小板减少综合征(severe fever with thrombocytope-nia syndrome,SFTS)的发病机制提供了新见解,同时靶向PCBP2-铁死亡通路可能成为SFTS治疗的潜在策略,为抗病毒药物的研发提供新思路。
文摘Lassa fever(LF)is an acute viral hemorrhagic illness caused by the Lassa virus(LASV),an enveloped,spherical virus belonging to the Arenaviridae family.LASV possess a single-stranded RNA genome of negative polarity and exhibits high genetic diversity,corresponding to the geographical distribution of its seven principal distinct clades across West Africa[1].LASV was first isolated in 1969 from an American missionary nurse stationed in the rural town of Lassa,Borno State,Nigeria,following her return from a brief vacation in the United States[2].
文摘Objective:To assess the effectiveness of intravenous immunoglobulin(IVIg)therapy in patients diagnosed with Crimean-Congo hemorrhagic fever(CCHF)disease.Methods:A single-center retrospective cohort study was conducted on hospitalized patients with confirmed severe CCHF at a tertiary care hospital in Turkey between 2010 and 2022.Cases were categorized into two groups based on whether they received IVIg therapy,with the treatment plan determined by the primary healthcare provider.The clinical,epidemiological,and laboratory parameters of these patients were evaluated.Demographic,laboratory findings,platelet counts on the day of IVIg indication and the third day,bleeding status during follow-up beyond 24 hours after IVIg administration,and prognosis recorded in patient information forms were retrieved.Results:72 patients were included in the analysis,with IVIg administered to 42 cases(58.3%)and not given to 30 cases(41.7%).Among the patients,37(51.4%)were female.Fever(65.3%)was the most common clinical presentation.The overall mortality rate was 19.4%,and IVIg administration did not significantly impact overall survival outcomes(P=0.48).On Day 3 following IVIg administration or indication,the platelet count was higher in the IVIg-treated group compared to the non-treated group(P=0.02).Furthermore,during follow-up beyond 24 hours after IVIg administration,bleeding was observed in 19.0%of the IVIg-treated group,compared to 46.6% in the non-treated group(P=0.01).Conclusions:This study underscores the potential advantages of IVIg therapy in managing severe CCHF.Although IVIg administration did not significantly affect overall survival,it was associated with earlier improvement in platelet counts and a notable reduction in bleeding complications.These findings indicate that IVIg may serve as an adjunctive treatment in CCHF,particularly for addressing hemorrhagic manifestations.
文摘目的评估2019年海南省登革热患者的疾病与经济负担,并比较全国各省份登革热单位伤残调整寿命年(disability-adjusted life years,DALY)经济成本的差异,为量化登革热疾病与经济负担、制定区域精准的疾病防控策略和资源配置提供科学依据。方法本研究采用回顾性分析,基于海南省人民医院2019年确诊的330例登革热患者的就诊信息,估算全省368例报告病例的疾病和经济负担。通过系统文献检索,汇总中国其他地区登革热经济负担数据,计算各省单位DALY经济成本,并比较地区间差异。结果在330例登革热患者中,人均DALY负担为0.03人年,总经济负担的M(P_(25),P_(75))为1822.11(162.61,2601.74)元,其中直接经济负担的M(P_(25),P_(75))为1513.03(162.61,2144.84)元,间接经济负担的M(P_(25),P_(75))为219.28(0,438.56)元。2019年海南省登革热病例的全省总DALY负担为11.33人年。全省估计总经济负担为670536.48(95%UI:575537.30~751654.70)元,其中直接经济负担为556795.04(95%UI:488810.70~626089.40)元,间接经济负担为80695.04(95%UI:53797.92~107592.20)元。全省估算单位DALY经济成本为59182.39元。在我国登革热经济负担研究涉及的地区(广东、浙江、广西、云南和重庆)中,广东省的单位DALY经济成本和人均经济负担均为最高。结论海南省登革热患者的经济负担严重,应通过扩大医保覆盖范围、完善异地医保结算来减轻患者的直接经济负担。全国各省间登革热患者的经济负担存在较大差异,因此登革热防控与补偿政策应结合区域特点,优化资源配置。
文摘目的了解北京市2021—2023年发热伴血小板减少综合征(severe fever with thrombocytopenia syndrome,SFTS)的流行病学特征,为北京市防控该疾病提供依据。方法收集分析SFTS病例的个案资料,对阳性样本进行全基因测序,并进行遗传进化分析。结果2021—2023年,北京市共报告9例本地感染病例,发病时间均在5—10月。男性6例,女性3例,年龄分布在40~<70岁,职业以农民为主。病例分布在5个区,平谷区发病数最多,有5例,存在一定的地域聚集性,平谷区还发生1起动物传人的聚集性疫情。测序及遗传进化分析结果显示,北京市的病例分属于A基因型和B基因型,未发现重配毒株。结论北京市SFTS病例为散发病例,有一定的地域聚集性,流行毒株为A基因型和B基因型。
