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应急状态下新冠流行曲线预测的方法学研究——基于北京市百度搜索和传统流感样病例监测 Article

张婷, 杨柳飏, 韩萱, 范国辉, 钱捷, 胡选成, 赖圣杰, 李中杰, 刘志敏, 冯录召, 杨维中

《工程（英文）》 2023年第31卷第12期页码 112-119 doi: 10.1016/j.eng.2023.08.006

摘要：本研究旨在利用百度搜索指数和流感样病例（ILI）监测数据，估计SARS-CoV-2的变异株奥密克戎BF.7在北京市应急状态下的传播和流行趋势。本研究创新性地提出了一种复合模型[多注意力双向门控循环单元（MABG）-易感-暴露-感染-恢复（SEIR）]，该模型利用深度学习算法（MABG）对ILI历史数据和发烧、发热、咳嗽、咽痛、退烧药、流涕等多种百度指数流感样症状相关关键词进行分析

关键词：新冠病毒感染流行曲线百度搜索引擎流感样病例深度学习传播动力学模型

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多组学导向的链霉菌1647产生的奥米克欣的发现——一组抗甲型流感病毒和冠状病毒HCoV-229E的活性类四肽化合物 Article

孙红敏, 李星星, 陈明华, 钟鸣, 李怡华, 王琨, 杜郁, 甄心, 高荣梅, 巫晔翔, 侍媛媛, 余利岩, 车永胜, 李玉环, 蒋建东, 洪斌, 司书毅

《工程（英文）》 2022年第16卷第9期页码 176-186 doi: 10.1016/j.eng.2021.05.010

摘要：链霉菌（Streptomyces sp.）1647 是20 世纪70 年代从中国南方土壤中分离的一株链霉菌，其发酵液显示优良的抗甲型流感病毒（IAV）活性，但其抗病毒活性成分始终没有得到有效的分离和结构鉴定奥米克欣B1~B4 显示出优良的抗甲型流感病毒活性，其50%抑制浓度（IC₅₀）在1 μmol·L⁻¹左右，选择指数（SI）为

关键词：多组学抗甲型流感病毒抗冠状病毒链霉菌1647 类四肽化合物

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间充质干细胞治疗人感染H7N9禽流感病毒所致急性呼吸窘迫综合征的临床研究——为新冠病毒肺炎救治提供新策略 Article

陈佳佳, 胡晨霞, 陈利军, 汤灵玲, 朱一新, 徐小微, 陈露, 高海女, 鲁晓庆, 俞亮, 戴霞红, 项春生, 李兰娟

《工程（英文）》 2020年第6卷第10期页码 1153-1161 doi: 10.1016/j.eng.2020.02.006

摘要：

2013年，H7N9病毒在哺乳动物宿主之间迅速传播，并具有人与人之间传播的风险。患者表现为重症肺炎、急性呼吸窘迫综合征（acute respiratory distress syndrome, ARDS）和呼吸衰竭。间充质干细胞（mesenchymal stem cell, MSC）移植在病毒性肺炎的治疗中有广阔的前景，并于2013年作为应急性治疗方法来治疗H7N9感染的ARDS。该研究在单中心开展，为开放式临床研究。根据自愿和知情同意的原则，17例H7N9感染的ARDS患者移植同种异体经血来源的MSC作为治疗组，44例H7N9感染的ARDS患者作为对照组。与对照组相比，MSC移植显著降低了ARDS病死率（MSC治疗组和对照组死亡率分别为17.6％和54.5％）。此外，在对4名MSC移植患者进行为期5年的随访中，未发现MSC移植产生有害影响。总体而言，该研究结果表明MSC移植显著提高了H7N9感染的ARDS的存活率，并为开展临床前和临床应用MSC治疗H7N9感染的ARDS的研究提供了理论基础。由于H7N9和2019新型冠状病毒性肺炎（coronavirus disease 2019, COVID-19）临床表现相似（如ARDS和呼吸衰竭），并继发多器官功能障碍，因此基于MSC的疗法可能为COVID-19所致的ARDS患者获益。

关键词： H7N9 间充质干细胞甲型流感急性呼吸窘迫综合征新型冠状病毒性肺炎干细胞治疗

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从H1N1血凝素序列提取的沙门氏菌传递的COBRA-HA1抗原对甲型流感亚型产生广谱保护作用 Article

Ram Prasad Aganja, Amal Senevirathne, Chandran Sivasankar, John Hwa Lee

《工程（英文）》 2024年第32卷第1期页码 42-57 doi: 10.1016/j.eng.2023.08.001

摘要：

A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines. In this study, a strategy called computationally optimized broadly reactive antigen (COBRA) was used to generate a consensus sequence of the hemagglutinin globular head portion (HA1) of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed constructs. Constructs carrying different HA1 regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RdRp-dependent eukaryotic expression system, pJHL204. Recombinant protein expression was confirmed by Western blot and immunofluorescence assays. Mice immunized with the designed constructs produced a humoral response, with a significant increase in immunoglobulin G (IgG) levels, and a cell-mediated immune response, including a 1.5-fold increase in CD4⁺ and CD8⁺ T cells. Specifically, constructs #1 and #5 increased the production of interferon-γ (IFN-γ) producing CD4⁺ and CD8⁺ T cells, skewing the response toward the T helper type 1 cell (Th1) pathway. Additionally, interleukin-4 (IL-4)-producing T cells were upregulated 4-fold. Protective efficacy was demonstrated, with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer > 40 against the selected viral strains. The designed constructs conferred a broadly protective immune response, resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34, A/Brisbane/59/2007, A/California/07/2009, KBPV VR-92, and NCCP 43021 strains. This discovery revolutionizes influenza vaccine design and delivery; Salmonella-mediated COBRA-HA1 is a highly effective in vivo antigen presentation strategy. This approach can effectively combat seasonal H1N1 influenza strains and potential pandemic outbreaks.

关键词： COBRA Influenza A Salmonella Vaccine Broad spectral protection

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流感与COVID-19患者的免疫球蛋白G糖基化差异 Article

Marina Kljaković-Gašpić Batinjan, Tea Petrović, Frano Vučković, Irzal Hadžibegović, Barbara Radovani, Ivana Jurin, Lovorka Đerek, Eva Huljev, Alemka Markotić, Ivica Lukšić, Irena Trbojević-Akmačić, Gordan Lauc, Ivan Gudelj, Rok Čivljak

《工程（英文）》 2023年第26卷第7期页码 54-62 doi: 10.1016/j.eng.2022.08.007

摘要：

The essential role of immunoglobulin G (IgG) in immune system regulation and combatting infectious diseases cannot be fully recognized without an understanding of the changes in its N-glycans attached to the asparagine 297 of the Fc domain that occur under such circumstances. These glycans impact the antibody stability, half-life, secretion, immunogenicity, and effector functions. Therefore, in this study, we analyzed and compared the total IgG glycome—at the level of individual glycan structures and derived glycosylation traits (sialylation, galactosylation, fucosylation, and bisecting N-acetylglucosamine (GlcNAc))—of 64 patients with influenza, 77 patients with coronavirus disease 2019 (COVID-19), and 56 healthy controls. Our study revealed a significant decrease in IgG galactosylation, sialylation, and bisecting GlcNAc (where the latter shows the most significant decrease) in deceased COVID-19 patients, whereas IgG fucosylation was increased. On the other hand, IgG galactosylation remained stable in influenza patients and COVID-19 survivors. IgG glycosylation in influenza patients was more time-dependent: In the first seven days of the disease, sialylation increased and fucosylation and bisecting GlcNAc decreased; in the next 21 days, sialylation decreased and fucosylation increased (while bisecting GlcNAc remained stable). The similarity of IgG glycosylation changes in COVID-19 survivors and influenza patients may be the consequence of an adequate immune response to enveloped viruses, while the observed changes in deceased COVID-19 patients may indicate its deviation.

关键词：流行性感冒 COVID-19 病毒感染糖基化免疫球蛋白G 肺炎

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COVID-19大流行期间流感活动呈“断崖式”下降——佩戴口罩、人员流动变化及SARS-CoV-2干扰的作用 Article

韩莎莎, 张婷, 吕岩, 赖圣杰, 戴佩希, 郑建东, 杨维中, 周晓华, 冯录召

《工程（英文）》 2023年第21卷第2期页码 195-202 doi: 10.1016/j.eng.2021.12.011

摘要：

一般情况下，每年冬季是季节性流感高发季节，但在当前新冠病毒肺炎（COVID-19）大流行期间，全球季节性流感活动呈“断崖式”下降。为应对即将到来的流感季节，亟需弄清这种前所未有的流感低水平流行的原因。结果发现，在这些地区增加一周佩戴口罩的干预措施，流感活动可减少11.3%~35.2%。实施一周的限制人员流动措施对国际（流感活动可减少1.7%~6.5%）和国内社区（流感活动可减少1.6%~2.8%）的影响较小。探索所得出的结果对了解非药物干预措施和其他呼吸系统疾病背景下的流感演变有一定意义，有助于制定卫生政策，并可为公共卫生措施的个性化设计提供信息。

关键词：流行性感冒佩戴口罩限制人员流动 SARS-CoV-2干扰非药物干预措施