黄热病的再流行与世界卫生组织的消除黄热病流行战略

近年来,蚊虫传播的黄热病在非洲和南美洲地区大面积“再流行”,仅南美洲的巴西在一年时间就发现数千例黄热病确诊病例,黄热病已经在非洲和南美洲地区造成巨大的公共卫生负担。此外,在黄热病非流行国家和地区发现大量输入性病例,使得黄热病有可能在非洲和南美洲以外的地区成为“新发传染病”而在世界更大范围流行。为此,世界卫生组织制定了“消除黄热病流行（EYE）”战略,预计利用10年时间在黄热病流行地区接种13.8亿剂量黄热疫苗,以降低黄热病对国际公共卫生健康的危害。     

Interferon-induced Transmembrane Protein 3 Prevents Acute Influenza Pathogenesis in Mice

Objective Interferon-induced transmembrane protein 3(IFITM3) is an important member of the IFITM family. However, the molecular mechanisms underlying its antiviral action have not been completely elucidated. Recent studies on IFITM3, particularly those focused on innate antiviral defense mechanisms, have shown that IFITM3 affects the body's adaptive immune response. The aim of this study was to determine the contribution of IFITM3 proteins to immune control of influenza infection in vivo.Methods We performed proteomics, flow cytometry, and immunohistochemistry analysis and used bioinformatics tools to systematically compare and analyze the differences in natural killer(NK) cell numbers, their activation, and their immune function in the lungs of Ifitm3-/-and wild-type mice.Results Ifitm3-/-mice developed more severe inflammation and apoptotic responses compared to wild-type mice. Moreover, the NK cell activation was higher in the lungs of Ifitm3-/-mice during acute influenza infection.Conclusions Based on our results, we speculate that the NK cells are more readily activated in the absence of IFITM3, increasing mortality in Ifitm3-/-mice.     

基于多元统计分析的银杏叶提取物中有机酸类成分含量研究

目的建立HPLC法测定银杏叶提取物中9种小分子有机酸类成分莽草酸、儿茶素、表儿茶素、没食子酸、原儿茶酸、6-羟基犬尿喹啉酸、对羟基苯甲酸、对羟基肉桂酸、咖啡酸含量的方法,并结合多元统计分析方法比较不同厂家生产的银杏叶提取物间质量差异。方法采用Inertsil ODS-3 C_(18)(250 mm×4.6 mm,5μm)色谱柱;以乙腈-0.4%磷酸水溶液为流动相,梯度洗脱,波长切换测定(220 nm检测莽草酸、儿茶素、表儿茶素,254 nm检测没食子酸、原儿茶酸、6-羟基犬尿喹啉酸、对羟基苯甲酸,310 nm检测对羟基肉桂酸、咖啡酸),柱温40℃。结果不同厂家生产的银杏叶提取物中有机酸总含量有差异,厂家内部样品中各有机酸含量同样存在差异。经聚类分析、主成分分析、相关与回归分析等多元统计方法分析,筛选出儿茶素、没食子酸、原儿茶酸及6-羟基犬尿喹啉酸为体现样品质量差异的特征成分,同时成分间具有内在相关性。结论建立的方法操作简便、重复性好、结果可靠,可用于银杏叶提取物中有机酸类成分的质量评价。筛选出的儿茶素、没食子酸、原儿茶酸及6-羟基犬尿喹啉酸是体现质量差异的特征成分,又是具有内在关联的共性成分,为提升银杏叶提取物整体质量控制能力提供了依据,同时表明银杏叶提取物的提取工艺并不统一,企业内部工艺的稳定性也有待提高。     

微滴式数字PCR和实时荧光定量PCR对新型冠状病毒肺炎患者不同时间血便尿中核酸检测结果初步探讨

目的 分析微滴式数字PCR(droplet digital PCR, ddPCR)和实时荧光定量PCR(quantitative real-time PCR,qPCR)的核酸检测结果,比较两种方法检测各类样本的差异性,为改进新型冠状病毒核酸检测方案提供数据支持。 方法 利用ddPCR和qPCR技术对已经确诊的3例新型冠状病毒肺炎患者发病不同时间的全血、尿液、粪便共22份标本进行新型冠状病毒核酸检测。 结果 两种方法对人保守区域基因扩增结果一致:全血标本信号最强,尿液次之,粪便最少;ddPCR在1份全血,1份尿液,5份粪便中检出ORF-1ab和N基因的阳性微滴,qPCR仅在3份粪便中检出上述基因,漏检的3个标本基因拷贝数平均浓度为128 copies/ml;ddPCR在发病<5、5~15、>15 d的各类标本中都有检出,qPCR检出以中晚期为主;重症病例用ddPCR均可测到阳性微滴,qPCR检测的各类标本均为阴性;轻症病例的各类标本中qPCR只有粪便核酸检测阳性,ddPCR检出率高于qPCR。 结论 ddPCR可以有效克服qPCR 灵敏度不足的难题,是对qPCR 的有益补充,尤其是针对病毒载量比较低的血液、尿液和可疑的粪便或肛拭子标本,适用于早期感染的判断及患者治愈后出院诊断。     

1H nuclear magnetic resonance-based metabolic profiling of cerebrospinal fluid to identify metabolic features and markers for tuberculosis meningitis

BackgroundTuberculosis meningitis (TBM) is the most severe form of tuberculosis, and currently lacks efficient diagnostic approaches. Metabolomics has the potential to differentiate patients with TBM from those with other forms of meningitis and meningitis-negative individuals. However, no systemic metabolomics research has compared the cerebrospinal fluid (CSF) of these patients.Methods¹H nuclear magnetic resonance (NMR) was used for CSF metabolic profiling. Principal component analysis and orthogonal signal correction-partial least squares-discriminant analysis (OPLS-DA) were used to screen for important variables. The Human Metabolome Database was used to identify metabolites, and MetaboAnalyst 4.0 was used for pathway analysis and over-representation analysis.ResultsOPLS-DA modeling could distinguish TBM from other forms of meningitis, and several significantly changed metabolites were identified. Additionally, 23, 6, and 21 metabolites were able to differentiate TBM from viral meningitis, bacterial meningitis, and meningitis-negative groups, respectively. Pathway analysis indicated that these metabolites were mainly involved in carbohydrate and amino acid metabolism, and over-representation analysis indicated that some of these pathways were over-represented.ConclusionsThe metabolites identified have the potential to serve as biomarkers for TBM diagnosis, and carbohydrate and amino acid metabolism are perturbed in the CSF of patents with TBM. Metabolomics is a valuable approach for screening TBM biomarkers. With further investigation, the metabolites identified in this study could aid in TBM diagnosis.     

The roles of prostaglandin E2 and D2 in lipopolysaccharide-mediated changes in sleep

When living organisms become sick as a result of a bacterial infection, a suite of brain-mediated responses occur, including fever, anorexia and sleepiness. Systemic administration of lipopolysaccharide (LPS), a common constituent of bacterial cell walls, increases body temperature and non-rapid eye movement (NREM) sleep in animals and induces the production of pro-inflammatory prostaglandins (PGs). PGE₂ is the principal mediator of fever, and both PGE₂ and PGD₂ regulate sleep–wake behavior. The extent to which PGE₂ and PGD₂ are involved in the effect of LPS on NREM sleep remains to be clarified. Therefore, we examined LPS-induced changes in body temperature and NREM sleep in mice with nervous system-specific knockouts (KO) for the PGE₂ receptors type EP₃ or EP₄, in mice with total body KO of microsomal PGE synthase-1 or the PGD₂ receptor type DP, and in mice treated with the cyclooxygenase (COX) inhibitor meloxicam. We observed that LPS-induced NREM sleep was slightly attenuated in mice lacking EP₄ receptors in the nervous system, but was not affected in any of the other KO mice or in mice pretreated with the COX inhibitor. These results suggest that the effect of LPS on NREM sleep is partially dependent on PGs and is likely mediated mainly by other pro-inflammatory substances. In addition, our data show that the main effect of LPS on body temperature is hypothermia in the absence of nervous system EP₃ receptors or in the presence of a COX inhibitor.