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基于非靶向脂质组学分析脂蛋白Rv1411c对结核分枝杆菌脂质代谢的影响

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中国防痨杂志 2024年第5期46卷 538-548页

作者：孙玉亭全舒婷孙柏旭田雪綦辉焦伟伟申阿东孙琳国家儿童医学中心/首都医科大学附属北京儿童医院/北京市儿科研究所/儿科学国家重点学科/儿科重大疾病研究教育部重点实验室/国家呼吸系统疾病临床医学研究中心/儿童呼吸道感染性疾病研究北京市重点实验室北京100045

目的:基于非靶向脂质组学探索结核分枝杆菌(Mycobacterium tuberculosis,MTB)脂蛋白Rv1411c在该菌脂质代谢中的作用。方法:构建敲除编码脂蛋白Rv1411c基因的MTB(ΔRv1411c)菌株,测定ΔRv1411c与MTB标准株H37Rv的吸光度值(A 600值)并绘... 详细信息

目的:基于非靶向脂质组学探索结核分枝杆菌(Mycobacterium tuberculosis,MTB)脂蛋白Rv1411c在该菌脂质代谢中的作用。方法:构建敲除编码脂蛋白Rv1411c基因的MTB(ΔRv1411c)菌株,测定ΔRv1411c与MTB标准株H37Rv的吸光度值(A 600值)并绘制两者生长曲线。提取ΔRv1411c与H37Rv菌液上清脂质成分,使用液相色谱-质谱(LC-MS)联用技术及非靶向脂质组学分析平台对菌株的差异脂质进行分析。采用偏最小二乘法判别分析(PLS-DA)、京都基因和基因组百科全书(KEGG)富集分析等方法分析两者的差异脂质代谢产物及差异脂质分子的富集通路。结果:通过色谱分离及质谱分析,从ΔRv1411c与H37Rv菌株中成功鉴定出归属于28种脂质亚类的460个不同的脂质分子,再通过PLS-DA模型分析获得其中归属于17种脂质亚类的158个差异脂质分子[变量权重值(VIP)>1]。以变异倍数(FC)>1.5或<0.67且P<0.05为筛选标准,共筛选出36个具有显著差异的脂质分子,其中有12个脂质分子上调,24个脂质分子下调。经KEGG通路富集分析,差异脂质代谢产物主要富集于以下8种通路,即:甘油磷脂代谢、亚麻酸代谢、α-亚麻酸代谢、糖基磷脂酰肌醇(GPI)-锚的生物合成、甘油脂代谢、鞘脂代谢、花生四烯酸代谢及不饱和脂肪酸的生物合成通路;其中又以甘油磷脂的代谢通路最为重要,其次为甘油脂代谢及糖基磷脂酰肌醇(GPI)-锚的生物合成通路。结论:脂蛋白Rv1411c可显著影响MTB的脂质代谢,可能参与MTB脂质代谢的调控。

关键词：分枝杆菌,结核脂蛋白类脂类代谢脂质组

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Low-dose versus high-dose methylprednisolone for children with severe Mycoplasma pneumoniae pneumonia (MCMP): Study protocol for a randomized controlled trial

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Pediatric Investigation 2018年第3期2卷 176-183页

作者： Baoping Xu Xiaoxia Peng Yao Yao Ju Yin Lanqin Chen Jun Liu Hao Wang Liwei Gao adong shen Kunling shen China National Clinical Research Center for Respiratory Diseases Department of Respiratory MedicineBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina Center for Clinical Epidemiology&Evidence-based Medicine Beijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina Beijing Key Laboratory of Pediatric Respiratory Infection Diseases Beijing Pediatric Research InstituteBeijing Children's HospitalCapital Medical UniversityNational Center for Children's HealthBeijingChina

Background:Severe Mycoplasma pneumoniae pneumonia(MPP)may develop with long-term pulmonary outcomes despite treatment with *** treatment with glucocorticoids can improve this outcome,though the optimal dosage is *** aim of this study was to investigate the effects of low-and high-dose methylprednisolone in reducing the percentage of long-term pulmonary outcomes for children with severe ***:A randomized,single-blind,parallel-controlled,multicenter clinical trial,methylprednisolone for children with severe *** pneumonia(MCMP),is being conducted in *** patients(≤18 years of age,expected number=402)admitted to the hospital with a clinical diagnosis of severe MPP and fulfilling inclusion and exclusion criteria are randomized(ratio of 1:1)to either a low-dose(2 mg/kg/d)or high-dose(10 mg/kg/d)methylprednisolone treatment group for 3 days followed by tapering of methylprednisolone over 12 days and combined with *** primary composite outcome will be incidence of atelectasis,bronchiectasis,or bronchiolitis obliterans at 6-months after *** outcomes include recovery time of patient temperature,proportion of pulmonary lesions absorbed,changes of mucosa identified by bronchoscopy,length of hospital stay,pulmonary function and number of participant(s)needing intensive *** will be made at baseline,post-treatment and at 1-month,3-month and 6-month ***:This is the first randomized clinical trial designed to evaluate the safety and efficacy of low-versus high-dose methylprednisolone for reducing long-term pulmonary outcomes in pediatric patients with severe *** results of this study will provide scientific evidence to guide clinical practice for the treatment of severe *** registration:This study is registered at ***(NCT02303587).

关键词： Glucocorticoids Severe Mycoplasma pneumoniae pneumonia Children

A Multicenter Study of Viral Aetiology of Community-Acquired Pneumonia in Hospitalized Children in Chinese Mainland

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Virologica Sinica 2021年第6期36卷 1543-1553页

作者： Yun Zhu Baoping Xu Changchong Li Zhimin Chen Ling Cao Zhou Fu Yunxiao Shang Aihuan Chen Li Deng Yixiao Bao Yun Sun Limin Ning Shuilian Yu Fang Gu Chunyan Liu Ju Yin adong shen Zhengde Xie Kunling shen Laboratory of Infection and Virology Beijing Pediatric Research InstituteBeijing Key Laboratory of Pediatric Respiratory Infection DiseasesResearch Unit of Critical Infection in ChildrenChinese Academy of Medical Sciences2019RU016Beijing Children's HospitalCapital Medical UniversityKey Laboratory of Major Diseases in ChildrenMinistry of EducationNational Clinical Research Center for Respiratory DiseasesNational Center for Children's HealthBeijing 100045China Department of Respiratory Diseases I Beijing Children's HospitalCapital Medical UniversityNational Clinical Research Center for Respiratory DiseasesNational Center for Children's HealthBeijing 100045China The 2nd Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou 325027China The Children's Hospital of Zhejiang University School of Medicine Hangzhou 310005China Children's Hospital Capital Institute of Pediatrics Beijing 100020China Children's Hospital of Chongqing Medical University Chongqing 400015China shengjing Hospital of China Medical University Shenyang 110004China The First Affiliated Hospital of Guangzhou Medical University Guangzhou 510120China Guangzhou Women and Children's Medical Center Guangzhou 510623China Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200092China Yinchuan Women and Children Healthcare Hospital Yinchuan 750000China Children's Hospital of Changchun Changchun 130000China The 2nd Affiliated Hospital of Harbin Medical University Harbin 150086China Baoding Children's Hospital Baoding 071051China Laboratory of Respiratory Diseases Beijing Key Laboratory of Pediatric Respiratory Infection DiseasesBeijing Pediatric Research InstituteBeijing Children's HospitalCapital Medical UniversityKey Laboratory of Major Diseases in ChildrenMinistry of EducationNational Clinical Research Center for Respiratory DiseasesNational Center for Children's HealthBeijing 100045China Beijing Children's Hospital Capital Medical UniversityNationa

Community-acquired pneumonia(CAP) is one of the leading causes of morbidity and mortality in children *** this study,we aimed to describe the aetiology of viral infection of pediatric CAP in Chinese *** November2014 to June 2016,the prospective study was conducted in 13 *** hospitalized children under 18 years old who met the criteria for CAP were *** throat swabs or nasopharyngeal aspirates(NPAs) were collected which were then screened 18 respiratory viruses using multiplex PCR *** pathogens were present in 56.6%(1539/2721) of the enrolled cases,with the detection rate of single virus in 39.8% of the cases and multiple viruses in 16.8% of the *** most frequently detected virus was respiratory syncytial virus(RSV)(15.2%,414/2721).The highest detection rate of virus was in <6-month-age group(70.7%,292/413).RSV,human metapneumovirus(HMPV),human parainfluenza viruses(HPIVs) and influenza B virus(Flu B) showed the similar prevalence patterns both in north and south China,but HPIVs,Flu A,human bocavirus(HBoV),human adenovirus(HAdV) and human coronaviruses(HCoVs) showed the distinct circulating patterns in north and south *** enterovirus/human rhinovirus(HEV/HRV)(27.6%,27/98),HBoV(18.4%,18/98),RSV(16.3%,16/98) and HMPV(14.3%,14/98) were the most commonly detected viruses in severe pneumonia cases with single virus *** conclusion,viral pathogens are frequently detected in pediatric CAP cases and may therefore play a vital role in the aetiology of *** was the most important virus in hospitalized children with CAP in Chinese mainland.

关键词： Children Community-acquired pneumonia Multicenter study Viral aetiology Multiplex PCR assay

Severe cases of BCGosis-susceptible primary immunodeficiency diseases identified by next-generation sequencing:Implications for adjustment of BCG vaccination timing in China

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Journal of Genetics and Genomics 2020年第4期47卷 229-232页

作者： Gang Liu Haijuan Xiao Linlin Liu Lingyun Guo Ruolan Guo Xuyun Hu Chanjuan Hao Jingang Gui Weiwei Jiao Fang Xu adong shen Wei Li Department of Infectious Disease Beijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China Beijing Pediatric Research Institute Genetics and Birth Defects Control CenterBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China

The World Health Organization(WHO)recommends neonatal Bacillus Calmette-Guerin(BCG)vaccination in countries with a high prevalence of tuberculosis(TB),which has been practiced in more than 150 countries(WHO,2004).The prevalence of TB is a serious condition in China,ranking as the second in the high epidemic countries globally(WHO,2018).China initiated a neonatal BCG vaccination program in 1986 and reached an average vaccination rate of 99%in 2016 with a great success in preventing the incidence of TB(WHO,2018).

关键词： vaccination neonatal diseases

宏基因组测序在儿童呼吸道感染性疾病研究中的应用

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中华实用儿科临床杂志 2020年第10期35卷 783-786页

作者：徐放申阿东国家儿童医学中心首都医科大学附属北京儿童医院北京市儿科研究所儿科学国家重点学科国家呼吸系统疾病临床医学研究中心儿科重大疾病研究教育部重点实验室儿童呼吸道感染性疾病研究北京市重点实验室北京100045

呼吸道感染性疾病严重威胁儿童健康,早期明确病原可为疾病的诊断和治疗奠定基础。宏基因组测序是一种不依赖于培养,直接对临床样品进行测序,并给出全部微生物序列信息的技术。宏基因组测序从病原微生物的检测、微生物组学、微生物与宿... 详细信息

呼吸道感染性疾病严重威胁儿童健康,早期明确病原可为疾病的诊断和治疗奠定基础。宏基因组测序是一种不依赖于培养,直接对临床样品进行测序,并给出全部微生物序列信息的技术。宏基因组测序从病原微生物的检测、微生物组学、微生物与宿主基因相互作用等方面为儿童呼吸道感染性疾病病原微生物的研究提供了十分重要的研究方法。现从宏基因组测序流程、在儿童呼吸道感染性疾病中的应用及国内外研究进展等方面进行阐述。

关键词：呼吸道感染性疾病高通量测序宏基因组测序

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儿童结核病药物治疗现状及进展

中华实用儿科临床杂志 2020年第10期35卷 753-758页

作者：焦伟伟申阿东国家儿童医学中心首都医科大学附属北京儿童医院北京市儿科研究所儿科学国家重点学科国家呼吸系统疾病临床医学研究中心儿科重大疾病研究教育部重点实验室儿童呼吸道感染性疾病研究北京市重点实验室北京100045

结核病是严重危害儿童健康的重要疾病。近年来,国内外制定和更新了多个结核病治疗相关指南和共识,结合最新的循证医学证据,提出了许多结核病药物治疗的新观点,但目前针对儿童结核病药物治疗的指南和共识较少,现依据现有的证据,就我国儿... 详细信息

结核病是严重危害儿童健康的重要疾病。近年来,国内外制定和更新了多个结核病治疗相关指南和共识,结合最新的循证医学证据,提出了许多结核病药物治疗的新观点,但目前针对儿童结核病药物治疗的指南和共识较少,现依据现有的证据,就我国儿童敏感结核病和耐药结核病可行的药物治疗方案进行阐述。

关键词：结核病儿童抗结核药物治疗

氟喹诺酮类药物在儿科呼吸系统感染性疾病中的应用

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中华实用儿科临床杂志 2020年第10期35卷 766-769页

作者：孙琳徐保平申阿东申昆玲国家儿童医学中心首都医科大学附属北京儿童医院北京市儿科研究所儿科学国家重点学科国家呼吸系统疾病临床医学研究中心儿科重大疾病研究教育部重点实验室儿童呼吸道感染性疾病研究北京市重点实验室北京100045 首都医科大学附属北京儿童医院呼吸科北京100045

出于安全性的考虑,喹诺酮类药物在儿童中的应用比较谨慎。目前大多数的观点认为儿童不应禁用喹诺酮类药物。在临床实际应用中,在充分评估风险和获益的情况下,针对重症感染、耐多药病原菌感染等可酌情使用。因此,现就氟喹诺酮类抗菌药物... 详细信息

出于安全性的考虑,喹诺酮类药物在儿童中的应用比较谨慎。目前大多数的观点认为儿童不应禁用喹诺酮类药物。在临床实际应用中,在充分评估风险和获益的情况下,针对重症感染、耐多药病原菌感染等可酌情使用。因此,现就氟喹诺酮类抗菌药物在儿科重症、耐药呼吸系统感染性疾病治疗中的应用、对关节和软骨的损害及安全性分析、药代动力学研究、在儿童中的耐药情况进行阐述,以期为儿童重症和耐药感染性疾病的治疗提供参考。

关键词：氟喹诺酮儿科呼吸感染性疾病安全性耐药

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结核病疫苗研发进展及挑战

中华实用儿科临床杂志 2020年第10期35卷 721-725页

作者：李洁琼申阿东国家儿童医学中心首都医科大学附属北京儿童医院北京市儿科研究所儿科学国家重点学科国家呼吸系统疾病临床医学研究中心儿科重大疾病研究教育部重点实验室儿童呼吸道感染性疾病研究北京市重点实验室北京100045

结核病(TB)是严重威胁儿童健康的重要疾病,世界卫生组织报道,2018年全球新发TB患者1000万,死亡人数高达124万,其中儿童TB新发人数约为112万,死亡数约为17.3万。"发现、治疗所有病例以终止TB"的行动指出,有效的疫苗接种是对传染病最有效... 详细信息

结核病(TB)是严重威胁儿童健康的重要疾病,世界卫生组织报道,2018年全球新发TB患者1000万,死亡人数高达124万,其中儿童TB新发人数约为112万,死亡数约为17.3万。"发现、治疗所有病例以终止TB"的行动指出,有效的疫苗接种是对传染病最有效的控制措施。儿童TB由于临床症状不典型,早期诊断困难,导致治疗延误,因此早期疫苗接种对于预防儿童TB显得更为重要。然而目前全球广泛使用的唯一TB疫苗——卡介苗存在免疫持续时间有限、保护作用不明确、可引发卡介苗病等问题,新型疫苗的研发势在必行。现就TB疫苗研究进展及存在的挑战进行阐述,为加强疫苗研发,并解决现有问题提供指导。

关键词：结核病疫苗进展挑战

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结核分枝杆菌乙胺丁醇耐药机制的研究进展

遗传 2016年第10期38卷 910-917页

作者：王婷焦伟伟申阿东首都医科大学附属北京儿童医院北京市儿科研究所儿童呼吸道感染性疾病研究北京市重点实验室教育部儿科重大疾病研究重点实验室北京100045

耐多药结核病的出现和流行对结核病的防控造成了严重威胁。乙胺丁醇（Ethambutol,EMB）是一线抗结核药物,常与异烟肼、利福平等联合应用,还可用于耐药结核病的治疗。但近年来EMB耐药形势严峻,我国复治结核病患者中EMB耐药率已达17.2%,... 详细信息

耐多药结核病的出现和流行对结核病的防控造成了严重威胁。乙胺丁醇（Ethambutol,EMB）是一线抗结核药物,常与异烟肼、利福平等联合应用,还可用于耐药结核病的治疗。但近年来EMB耐药形势严峻,我国复治结核病患者中EMB耐药率已达17.2%,并呈上升趋势;耐多药结核病患者中,EMB耐药率约为51.3%-66.7%,情况不容乐观。明确EMB耐药的产生机制对于有效防控EMB耐药率的上升、充分发挥EMB的作用十分重要,因此本文对结核分枝杆菌EMB的耐药现状、EMB的作用机制及其耐药产生机制方面的研究进展进行了综述。

关键词：结核分枝杆菌乙胺丁醇耐药