Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of H...Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.展开更多
Introduction: Adenovirus infections are associated with significant morbidity and mortality among immunocompromised hosts. Adenovirus pneumonia is a rare and often fatal disease in patients with AIDS. Case Report: We ...Introduction: Adenovirus infections are associated with significant morbidity and mortality among immunocompromised hosts. Adenovirus pneumonia is a rare and often fatal disease in patients with AIDS. Case Report: We report a case of a 28-year-old woman with advanced HIV/AIDS, who developed pneumonia four weeks after initiation of highly active antiretroviral therapy (HAART). Despite empiric antibiotics, the patient developed worsening hypoxemia and progressive pneumonia on chest x-ray. Culture data from a bronchoalveolar lavage (BAL) was negative for bacteria, fungi, pneumocystis jirovecii, but was positive for adenovirus detected by PCR. After transfer to a tertiary care hospital intensive care unit, a repeat BAL confirmed the presence of adenovirus by immunohistochemical staining. Tissue samples sent for histopathology revealed 'smudge cells'. Serum adenovirus viral load was 1.6 × 105 copies/mL. Intravenous cidofovir, 1 mg/kg/day, was initiated and scheduled three times a week. The patient exhibited remarkable improvement and was discharged to home in stable condition after four doses of cidofovir treatment. Discussion: Prior to our case, the few published accounts of HIV patients with adenovirus pneumonia treated with cidofovir have all resulted in death. Our case is distinct from these cases by the lack of concomitant pulmonary infection and the initiation of HAART prior to presentation. Conclusion: To our knowledge, we present the first case of adenovirus pneumonia in a patient with AIDS successfully treated with cidofovir. Our case suggests that limited and low dose cidofovir may be an efficacious approach to treat adenovirus pneumonia among HIV patients, especially those established on HAART.展开更多
目的:系统评价急性缺血性脑卒中相关性肺炎评分(AIS-APS)评分对缺血性脑卒中病人卒中相关性肺炎(SAP)的预测价值。方法:检索中国知网、万方数据库、维普数据库、中国生物医学文献数据库、PubMed、Web of Science、EMbase、the Cochrane ...目的:系统评价急性缺血性脑卒中相关性肺炎评分(AIS-APS)评分对缺血性脑卒中病人卒中相关性肺炎(SAP)的预测价值。方法:检索中国知网、万方数据库、维普数据库、中国生物医学文献数据库、PubMed、Web of Science、EMbase、the Cochrane Library、Wiley等数据库关于使用AIS-APS评分预测缺血性脑卒中发生SAP风险的相关文献,检索时限为建库至2023年5月31日。采用诊断准确性研究质量评估工具(QUADAS-2)进行文献质量评价,运用Stata 17.0软件进行Meta分析。结果:最终纳入14篇文献进行Meta分析,涉及7117例病人。Meta分析结果显示,AIS-APS预测缺血性脑卒中病人发生SAP风险合并灵敏度为0.82[95%CI(0.74,0.88)],合并特异度为0.73[95%CI(0.66,0.80)],合并阳性似然比为3.08[95%CI(2.53,3.76)],合并阴性似然比为0.25[95%CI(0.18,0.34)],合并DOR为2.52[95%CI(2.20,2.84)],合并优势比为12.40[95%CI(9.01,17.06)]。AIS-APS预测缺血性脑卒中SAP的综合受试者工作特征曲线(SROC)的曲线下面积(AUC)为0.84[95%CI(0.81,0.87)]。Deek′s漏斗图分析显示,纳入文献无发表偏倚(P=0.73),范根图显示该评分在临床适用性良好。结论:现有证据表明,AIS-APS评分对缺血性脑卒中病人发生SAP风险具有一定的预测价值,可对临床病人进行初步筛查,识别发生SAP高风险病人,以便做出进一步的预防与治疗。展开更多
目的研究麻杏解毒合剂对冠状病毒肺炎模型小鼠炎性因子表达的影响,基于p38MAPK/AP-1通路研究其疗效机制。方法60只昆明种(KM)小鼠随机分成空白对照组、模型组、p38MAPK抑制剂组及麻杏解毒合剂高、中、低剂量组,每组10只。采用模拟寒湿...目的研究麻杏解毒合剂对冠状病毒肺炎模型小鼠炎性因子表达的影响,基于p38MAPK/AP-1通路研究其疗效机制。方法60只昆明种(KM)小鼠随机分成空白对照组、模型组、p38MAPK抑制剂组及麻杏解毒合剂高、中、低剂量组,每组10只。采用模拟寒湿环境、表达h ACE2的重组腺相关病毒转导、SARS-CoV-2spike假病毒气管内给药建立小鼠冠状病毒肺炎模型。检测各组小鼠血清炎性因子、肺组织病理改变、肺组织p38MAPK、c-jun、c-fos的mRNA水平和蛋白表达情况。结果与空白对照组比较,模型组小鼠血清炎性因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)的表达均显著升高(P<0.01),肺组织炎性改变明显,c-fos m RNA水平和p-p38、c-fos、c-jun蛋白表达均显著增加(P<0.05)。与模型组比较,麻杏解毒合剂高、中剂量组小鼠血清炎性因子显著降低(P<0.01或P<0.05),小鼠肺组织炎性损伤明显减轻,同时肺组织中c-fos的mRNA水平和p-p38、c-fos的蛋白表达均显著下调(P<0.05)。结论麻杏解毒合剂能降低病毒性肺炎模型小鼠血清炎性因子水平,减轻肺组织炎性损伤,其疗效机制与抑制p38MAPK蛋白的磷酸化,下调AP-1通路mRNA及蛋白表达有关。展开更多
Background: Lower respiratory tract infection (LRTI) is a main cause of hospitalization in infants and children. These patients’ nasopharyngeal swabs more frequently contain respiratory syncytial virus (RSV) than hum...Background: Lower respiratory tract infection (LRTI) is a main cause of hospitalization in infants and children. These patients’ nasopharyngeal swabs more frequently contain respiratory syncytial virus (RSV) than human adenovirus (HAdV) in cold seasons;recent data suggest that oropharyngeal swabs more frequently contain HAdV than RSV. Knowing more about virus detection with oropharyngeal swabs, seasonal fluctuations and age-related distribution of RSV and HAdV would help treat children hospitalized for LRTI more effectively. We investigated the seasonal virus-related frequency (as assessed by oropharyngeal swabs) and environmental and clinical features in infants and children hospitalized for LRTI from autumn to spring. Methods: We studied 98 subjects hospitalized for LRTI in our Pediatric Unit, from November 2006 to May 2007. RSV and HAdV in oropharyngeal swabs were assessed by real-time polymerase chain reaction (PCR) assay. Results: PCR assays more frequently detected HAdV (29.6% of patients) than RSV (25.5%). The seasonal incidence also differed (RSV, narrow peak in December and HAdV, wide peak from April to May). Most patients infected with RSV were aged 2 yrs or younger (23/25: 88%);no difference was found in age between subjects who tested HAdV-positive (13/29: 45%) or undetectable-virus (23/44: 52%). Bronchiolitis was more frequently associated with RSV than HAdV or undetectable-virus oropharyngeal swabs. No difference was found in risk factors (school attendance, atopic parents, exposure to cigarette smoking, home dampness or exposure to animals) or clinical features (vital parameters or duration of hospital stay) among the three viral groups. Conclusions: Our findings show a high frequency of HAdV-positive oropharyngeal swabs during acute LRTIs in infants and children and differences in the seasonal distribution of RSV and HAdV in Rome.展开更多
基金supported by the National Natural Science Foundation of China(No.82073617)Joint Research Fund for Beijing Natural Science Foundation and Haidian Original Innovation(No.L202007)+1 种基金Fundamental Research Funds for the Central Universities and Peking University Health Science Center(No.BMU2021YJ041)Peking University Medicine Fund of Fostering Young Scholars'Scientific&Technological Innovation(No.BMU2021PY005).
文摘Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.
文摘Introduction: Adenovirus infections are associated with significant morbidity and mortality among immunocompromised hosts. Adenovirus pneumonia is a rare and often fatal disease in patients with AIDS. Case Report: We report a case of a 28-year-old woman with advanced HIV/AIDS, who developed pneumonia four weeks after initiation of highly active antiretroviral therapy (HAART). Despite empiric antibiotics, the patient developed worsening hypoxemia and progressive pneumonia on chest x-ray. Culture data from a bronchoalveolar lavage (BAL) was negative for bacteria, fungi, pneumocystis jirovecii, but was positive for adenovirus detected by PCR. After transfer to a tertiary care hospital intensive care unit, a repeat BAL confirmed the presence of adenovirus by immunohistochemical staining. Tissue samples sent for histopathology revealed 'smudge cells'. Serum adenovirus viral load was 1.6 × 105 copies/mL. Intravenous cidofovir, 1 mg/kg/day, was initiated and scheduled three times a week. The patient exhibited remarkable improvement and was discharged to home in stable condition after four doses of cidofovir treatment. Discussion: Prior to our case, the few published accounts of HIV patients with adenovirus pneumonia treated with cidofovir have all resulted in death. Our case is distinct from these cases by the lack of concomitant pulmonary infection and the initiation of HAART prior to presentation. Conclusion: To our knowledge, we present the first case of adenovirus pneumonia in a patient with AIDS successfully treated with cidofovir. Our case suggests that limited and low dose cidofovir may be an efficacious approach to treat adenovirus pneumonia among HIV patients, especially those established on HAART.
文摘目的研究麻杏解毒合剂对冠状病毒肺炎模型小鼠炎性因子表达的影响,基于p38MAPK/AP-1通路研究其疗效机制。方法60只昆明种(KM)小鼠随机分成空白对照组、模型组、p38MAPK抑制剂组及麻杏解毒合剂高、中、低剂量组,每组10只。采用模拟寒湿环境、表达h ACE2的重组腺相关病毒转导、SARS-CoV-2spike假病毒气管内给药建立小鼠冠状病毒肺炎模型。检测各组小鼠血清炎性因子、肺组织病理改变、肺组织p38MAPK、c-jun、c-fos的mRNA水平和蛋白表达情况。结果与空白对照组比较,模型组小鼠血清炎性因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)的表达均显著升高(P<0.01),肺组织炎性改变明显,c-fos m RNA水平和p-p38、c-fos、c-jun蛋白表达均显著增加(P<0.05)。与模型组比较,麻杏解毒合剂高、中剂量组小鼠血清炎性因子显著降低(P<0.01或P<0.05),小鼠肺组织炎性损伤明显减轻,同时肺组织中c-fos的mRNA水平和p-p38、c-fos的蛋白表达均显著下调(P<0.05)。结论麻杏解毒合剂能降低病毒性肺炎模型小鼠血清炎性因子水平,减轻肺组织炎性损伤,其疗效机制与抑制p38MAPK蛋白的磷酸化,下调AP-1通路mRNA及蛋白表达有关。
文摘Background: Lower respiratory tract infection (LRTI) is a main cause of hospitalization in infants and children. These patients’ nasopharyngeal swabs more frequently contain respiratory syncytial virus (RSV) than human adenovirus (HAdV) in cold seasons;recent data suggest that oropharyngeal swabs more frequently contain HAdV than RSV. Knowing more about virus detection with oropharyngeal swabs, seasonal fluctuations and age-related distribution of RSV and HAdV would help treat children hospitalized for LRTI more effectively. We investigated the seasonal virus-related frequency (as assessed by oropharyngeal swabs) and environmental and clinical features in infants and children hospitalized for LRTI from autumn to spring. Methods: We studied 98 subjects hospitalized for LRTI in our Pediatric Unit, from November 2006 to May 2007. RSV and HAdV in oropharyngeal swabs were assessed by real-time polymerase chain reaction (PCR) assay. Results: PCR assays more frequently detected HAdV (29.6% of patients) than RSV (25.5%). The seasonal incidence also differed (RSV, narrow peak in December and HAdV, wide peak from April to May). Most patients infected with RSV were aged 2 yrs or younger (23/25: 88%);no difference was found in age between subjects who tested HAdV-positive (13/29: 45%) or undetectable-virus (23/44: 52%). Bronchiolitis was more frequently associated with RSV than HAdV or undetectable-virus oropharyngeal swabs. No difference was found in risk factors (school attendance, atopic parents, exposure to cigarette smoking, home dampness or exposure to animals) or clinical features (vital parameters or duration of hospital stay) among the three viral groups. Conclusions: Our findings show a high frequency of HAdV-positive oropharyngeal swabs during acute LRTIs in infants and children and differences in the seasonal distribution of RSV and HAdV in Rome.
