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Coxsackievirus B3 HFMD animal models in Syrian hamster and rhesus monkey

Virologica Sinica 2024年第2期39卷 290-300页

作者： Suqin Duan Wei Zhang Yongjie Li Yanyan Li Yuan Zhao Weihua Jin Quan Liu Mingxue Li Wenting Sun Lixiong Chen Hongjie Xu Jie Tang Jinghan Hou Zijun Deng fengmei yang Shaohui Ma Zhanlong He Institute of Medical Biology Chinese Academy of Medical Sciences Medical Primate Research Center Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research Development on Severe Infectious DiseaseKunming650118China

Coxsackievirus B3(CVB3)is the pathogen causing hand,foot and mouth disease(HFMD),which manifests across a spectrum of clinical severity from mild to severe.However,CVB3-infected mouse models mainly demonstrate viral myocarditis and pancreatitis,failing to replicate human HFMD symptoms.Although several enteroviruses have been evaluated in Syrian hamsters and rhesus monkeys,there is no comprehensive data on CVB3.In this study,we have first tested the susceptibility of Syrian hamsters to CVB3 infection via different routes.The results showed that Syrian hamsters were successfully infected with CVB3 by intraperitoneal injection or nasal drip,leading to nasopharyngeal colonization,acute severe pathological injury,and typical HFMD symptoms.Notably,the nasal drip group exhibited a longer viral excretion cycle and more severe pathological damage.In the subsequent study,rhesus monkeys infected with CVB3 through nasal drips also presented signs of HFMD symptoms,viral excretion,serum antibody conversion,viral nucleic acids and antigens,and the specific organ damages,particularly in the heart.Surprisingly,there were no significant differences in myocardial enzyme levels,and the clinical symptoms resembled those often associated with common,mild infections.In summary,the study successfully developed severe Syrian hamsters and mild rhesus monkey models for CVB3-induced HFMD.These models could serve as a basis for understanding the disease pathogenesis,conducting pre-trial prevention and evaluation,and implementing post-exposure intervention.

关键词： Coxsackievirus B3(CVB3) Hand foot and mouth disease(HFMD) Animal models Syrian hamster Rhesus monkey

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Clinical Analysis of Common Irrational Gastroenterology Medication Problems in The Gastroenterology Department

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Journal of Clinical and Nursing Research 2024年第4期8卷 149-153页

作者： fengmei Cong Chifeng Maternal and Child Health Hospital Chifeng 024000Inner MongoliaChina

Objective: To investigate and analyze the irrational problems of common gastroenterology medications applied to gastroenterology patients during treatment, and to develop and implement countermeasures. Methods: This study included 60 patients admitted to the Department of Gastroenterology from January 2021 to December 2023 who were randomly divided into a control group (conventional drug management) and an observation group (targeted drug treatment), of 30 cases each. After the implementation of different management methods, the occurrence of irrational drug use and the incidence of adverse reactions between both groups were compared and statistically analyzed. Results: The incidence of irrational medication in the observation group (13.33%) was lower than that in the control group (40.00%) (P < 0.05). The occurrence of adverse reactions in the observation group (10.00%) was lower than that of the control group (36.67%) after treatment (P < 0.05). The observation group had a higher level of satisfaction after treatment (90.00%) as compared to the control group (66.67%) (P < 0.05). Conclusion: Implementation of targeted drug treatment for gastroenterology patients reduced the incidence of irrational medication use, reduced adverse reactions, and improved patient satisfaction.

关键词： Gastroenterology Common Irrational use of drugs

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ANALYSES OF LOCATION-PRICE GAME ON NETWORKS WITH STOCHASTIC CUSTOMER BEHAVIOR AND ITS HEURISTIC ALGORITHM

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Journal of Systems Science & Complexity 2010年第4期23卷 701-714页

作者： Xiaoshan LU Jian LI fengmei yang School of Science Beijing University of Chemical Technology Beijing 100029 China School of Economics and Management Beihang University Beijing 100191 China. School of Economics and Management Beijing University of Chemical Technology Beijing 100029 China School of Science Beijing University of Chemical Technology Beijing 100029 China

In this paper,a two-stage model is developed to investigate the location strategy andthe commodity pricing strategy for a retail firm that wants to enter a spatial market with multiplecompetitive facilities,where a competitor firm is already operating as a monopoly with several outlets.Expected market shares are calculated based on the stochastic customer behavior on networks.Theauthors provide a sufficient condition for the existence of equilibrium prices in the price game for thefirst time.The existence and uniqueness of the pure strategy Nash equilibrium price with a specifiedutility function are proved in the subgame.A metaheuristic based on tabu search is proposed tosearch the optimal location-price solution of the model.In addition,the authors provide two numericalexamples to illustrate how to obtain the optimal solution and conduct sensitivity analysis.The analysisshows that the best location decision is robust for the follower firm,price game is more intense whenincomes of consumers are lower or there are more substitution products,and neither chain retail gainsfrom the price competition.

关键词：价格模型客户行为随机网络最佳位置博弈论启发式算法随机分析市场份额

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Immunogenicity and protective efficacy of a recombinant protein subunit vaccine and an inactivated vaccine against SARS-CoV-2 variants in non-human primates

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1170-1180页

作者： Qian He Qunying Mao Xiaozhong Peng Zhanlong He Shuaiyao Lu Jialu Zhang Fan Gao Lianlian Bian Chaoqiang An Wenhai Yu fengmei yang Yanan Zhou Yun yang Yanyan Li Yadi Yuan Xujia Yan Jinghuan yang Xing Wu Weijin Huang Changgui Li Junzhi Wang Zhenglun Liang Miao Xu Division of Hepatitis and Enterovirus Vaccines Institute of Biological ProductsNational Institutes for Food and Drug ControlNHC Key Laboratory of Research on Quality and Standardization of Biotech ProductsNMPA Key Laboratory for Quality Research and Evaluation of Biological ProductsBeijing 102629People’s Republic of China Institute of Medical Biology Chinese Academy of Medicine Sciences&Peking Union Medical CollegeKunming 650118People’s Republic of China

Emerging SARS-CoV-2 variants and the gradually decreasing neutralizing antibodies over time post vaccination have led to an increase in incidents of breakthrough infection across the world.To investigate the potential protective effect of the recombinant protein subunit COVID-19 vaccine targeting receptor-binding domain(RBD)(PS-RBD)and whole inactivated virus particle vaccine(IV)against the variant strains,in this study,rhesus macaques were immunized with PS-RBD or IV vaccine,followed by a Beta variant(B.1.351)challenge.Although neutralizing activity against the Beta variant was reduced compared with that against the prototype,the decreased viral load in both upper and lower respiratory tracts,milder pathological changes,and downregulated inflammatory cytokine levels in lung tissues after challenge demonstrated that PS-RBD and IV still provided effective protection against the Beta variant in the macaque model.Furthermore,PS-RBD-induced macaque sera possessed general binding and neutralizing activity to Alpha,Beta,Delta,and Omicron variants in our study,though the neutralizing antibody(NAb)titers declined by varying degrees,demonstrating potential protection of PS-RBD against current circulating variants of concern(VOCs).Interestingly,although the IV vaccine-induced extremely low neutralizing antibody titers against the Beta variant,it still showed reduction for viral load and significantly alleviated pathological change.Other correlates of vaccine-induced protection(CoP)like antibody-dependent cellular cytotoxicity(ADCC)and immune memory were both confirmed to be existing in IV vaccinated group and possibly be involved in the protective mechanism.

关键词： protective vaccine neutral

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Three doses of prototypic SARS-CoV-2 inactivated vaccine induce cross-protection against its variants of concern

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Signal Transduction and Targeted Therapy 2022年第3期7卷 909-917页

作者： Tianhong Xie Shuaiyao Lu Zhanlong He Hongqi Liu Junbin Wang Cong Tang Ting yang Wenhai Yu Hua Li Yun yang Hao yang Lei Yue Yanan Zhou fengmei yang Zhiwu Luo Yanyan Li Hong Xiang Yuan Zhao Jie Wang Haixuan Wang Runxiang Long Dexuan Kuang Wenjie Tan Xiaozhong Peng Qihan Li Zhongping Xie Institute of Medical Biology Chinese Academy of Medicine Sciences&Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases650118 KunmingChina The NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChina CDC102206 BeijingChina

Variants are globally emerging very quickly following pandemic prototypic SARS-CoV-2.To evaluate the cross-protection of prototypic SARS-CoV-2 vaccine against its variants,we vaccinated rhesus monkeys with three doses of prototypic SARS-CoV-2 inactivated vaccine,followed by challenging with emerging SARS-CoV-2 variants of concern(VOCs).

关键词： doses globally protection

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Pathogenic analysis of coxsackievirus A10 in rhesus macaques

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Virologica Sinica 2022年第4期37卷 610-618页

作者： Suqin Duan fengmei yang Yanyan Li Yuan Zhao Li Shi Meng Qin Quan Liu Weihua Jin Junbin Wang Lixiong Chen Wei Zhang Yongjie Li Ying Zhang Jingjing Zhang Shaohui Ma Zhanlong He Qihan Li Institute of Medical Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeYunnan Key Laboratory of Vaccine Research Development on Severe Infectious DiseaseKunming650118China Beijing Advanced Innovation Center for Soft Matter Science and Engineering College of Life Science and Technology Beijing University of Chemical TechnologyBeijing100029China

Coxsackievirus A10(CV-A10)is one of the etiological agents associated with hand,foot and mouth disease(HFMD)and also causes a variety of illnesses in humans,including pneumonia,and myocarditis.Different people,particularly young children,may have different immunological responses to infection.Current CV-A10 infection animal models provide only a rudimentary understanding of the pathogenesis and effects of this virus.The characteristics of CV-A10 infection,replication,and shedding in humans remain unknown.In this study,rhesus macaques were infected by CV-A10 via respiratory or digestive route to mimic the HFMD in humans.The clinical symptoms,viral shedding,inflammatory response and pathologic changes were investigated in acute infection(1–11 day post infection)and recovery period(12–180 day post infection).All infected rhesus macaques during acute infection showed obvious viremia and clinical symptoms which were comparable to those observed in humans.Substantial inflammatory pathological damages were observed in multi-organs,including the lung,heart,liver,and kidney.During the acute period,all rhesus macaques displayed clinical signs,viral shedding,normalization of serum cytokines,and increased serum neutralizing antibodies,whereas inflammatory factors caused some animals to develop severe hyperglycemia during the recovery period.In addition,there were no significant differences between respiratory and digestive tract infected animals.Overall,all data presented suggest that the rhesus macaques provide the first non-human primate animal model for investigating CV-A10 pathophysiology and assessing the development of potential human therapies.

关键词： Coxsackievirus A10(CV-A10) Hand Foot and mouth disease(HFMD) Non-human primate model Rhesus macaque Pathogenic analysis

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新质生产力三维创新生态系统及水平测度分析

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云南财经大学学报 2024年第6期40卷 1-14页

作者：祝志勇杨凤梅李维莉西南大学经济管理学院重庆400715 西华师范大学招生就业处四川南充637009

新质生产力是由技术颠覆性突破、生产要素创新性配置、产业深度转型升级而催生的当代先进生产力;一切利用新技术提升生产力水平驱动高质量发展的领域,都属于新质生产力的应用范畴。从创新生态系统角度构建新质生产力的评价指标体系,利... 详细信息

新质生产力是由技术颠覆性突破、生产要素创新性配置、产业深度转型升级而催生的当代先进生产力;一切利用新技术提升生产力水平驱动高质量发展的领域,都属于新质生产力的应用范畴。从创新生态系统角度构建新质生产力的评价指标体系,利用熵值法、Kernel密度估计法和空间Markov链法进行实证分析。研究结论如下:首先,新质生产力在微观层面表现为新质人才、新质生产单元和新质企业组织;在中观层面表现为新质产业部门、新质产业链、新质创新网络、新质产业集群;在宏观层面表现为国家科技创新政策体系。其次,基于新质生产力的三个维度,构建新质生产力的综合指标体系,通过熵值法测度发现,中国新质生产力总体水平较低,但呈逐年增长趋势,东部地区新质生产力水平远高于中部、西部和东北地区。最后,利用Kernel密度估计法和空间Markov链法分析可知,新质生产力发展不均衡问题较为凸显,空间效应也是影响新质生产力发展的重要因素。

关键词：新质生产力科技创新熵值法 Kernel密度估计空间Markov链

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融合有效掩膜和局部增强的遮挡行人重识别

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计算机工程与应用 2024年第11期60卷 156-164页

作者：王小檬梁凤梅太原理工大学信息与计算机学院山西晋中030600

在监控系统中行人经常会被各种障碍物遮挡,使得遮挡行人重识别仍然是一个长期存在的挑战。最近一些基于Transformer和外部语义线索的方法都改善了特征的表示和相关性能,但仍存在表示弱和语义线索不可靠等问题。为解决上述问题,提出了一... 详细信息

在监控系统中行人经常会被各种障碍物遮挡,使得遮挡行人重识别仍然是一个长期存在的挑战。最近一些基于Transformer和外部语义线索的方法都改善了特征的表示和相关性能,但仍存在表示弱和语义线索不可靠等问题。为解决上述问题,提出了一种基于Transformer的新方法。引入了一种有效的掩膜生成方式,可靠的掩膜可以使模型不依赖外部语义线索并实现自动对齐。提出了一种基于平均注意力分数的序列重建模块,可以更有效地关注前景信息。提出了局部增强模块,获得了更鲁棒的特征表示。比较了所提方法和现有的各种方法在Occluded-Duke,Occluded-ReID,Partial-ReID,Market-1501数据集上的性能。Rank-1准确率分别达到了72.3%、84.8%、86.5%和95.6%,mAP精度分别为62.9%、83.2%、76.4%和89.9%,实验结果表明所提模型性能较其他先进网络有所提升。

关键词：遮挡行人重识别原型掩膜特征注意力机制平均注意力分数局部增强 Transformer

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眼外肌转位改良Yokoyama术治疗高度近视眼限制性内斜视的临床效果

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中华眼科杂志 2024年第1期60卷 72-77页

作者：杨莎单凤梅李洁冯雪莹王富华山东第一医科大学附属眼科研究所、山东第一医科大学附属眼科医院(山东省眼科医院)山东省眼科学重点实验室-省部共建国家重点实验室培育基地、山东第一医科大学眼科学院济南250021

目的探讨眼外肌转位改良Yokoyama术治疗高度近视眼限制性内斜视的临床效果。方法回顾性病例系列研究。收集2017年2月至2022年2月在山东第一医科大学附属眼科医院就诊,接受眼外肌转位改良Yokoyama术治疗高度近视眼限制性内斜视的患者。... 详细信息

目的探讨眼外肌转位改良Yokoyama术治疗高度近视眼限制性内斜视的临床效果。方法回顾性病例系列研究。收集2017年2月至2022年2月在山东第一医科大学附属眼科医院就诊,接受眼外肌转位改良Yokoyama术治疗高度近视眼限制性内斜视的患者。术中充分分离上直肌及外直肌,于肌腹中央纵向钝性剖开向后延伸至肌止点后12~14 mm,将上直肌颞侧及外直肌上方1/2肌腹交叉转位固定到对侧肌肉止点,同时联合内直肌后退。于术后1周、1个月、3个月和6个月复诊,记录患者眼位、眼球运动、代偿头位改善情况,同视机检查客观斜视度数,眼眶CT检查眼外肌和眼球位置的改变,同时记录手术并发症。结果共纳入患者5例(8只眼),其中女性4例(7只眼),男性1例(1只眼);年龄(63±11)岁,眼轴长度(34.58±2.25)mm,术中内直肌后退(7.6±2.3)mm。所有患者术前眼位均为内下转位,角膜映光点水平范围为+15~>+45°,垂直范围为+15~+45°;外转及上转明显受限,运动受限程度均为-3(-4~-1)级。3例双眼患病和1例单眼患病患者代偿头位明显,1例单眼患病患者无代偿头位。术前眼眶CT提示上直肌向鼻侧移位、外直肌向下方移位,眼球从肌锥的颞上方疝出。术后6个月,所有患者眼位基本正位,同视机检查客观斜视度数水平范围为-4~+7°,垂直范围为0~+6°。所有患者眼球运动均明显改善,外转运动程度为-1级(-2~-1)、上转运动程度为-2级(-3~-1);代偿头位消失;眼眶CT提示眼球位于肌锥内;无眼前节缺血、肌肉粘连、病情复发、继发性青光眼、球壁刺穿等严重并发症发生。结论眼外肌转位改良Yokoyama术治疗高度近视眼限制性内斜视初步临床效果较好。

关键词：近视内斜视动眼肌眼外科手术

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直接进样-高效液相色谱-串联质谱法快速检测饮用水中草铵膦、草甘膦及其代谢物氨甲基膦酸

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分析试验室 2024年第5期43卷 687-692页

作者：方力邱凤梅浙江省海产品健康危害因素关键技术研究重点实验室舟山市疾病预防控制中心舟山316021 浙江省舟山市普陀区疾病预防控制中心舟山316100

建立了高效液相色谱串联三重四极杆质谱(HPLC-MS/MS)定量检测饮用水中草铵膦、草甘膦及其代谢产物氨甲基膦酸的方法。水样直接经亲水PTFE膜过滤,以50 mmol/L甲酸铵(pH 3.0)为流动相,Acclaim Trinity Q1色谱柱分离,电喷雾离子化(ESI-)、... 详细信息

建立了高效液相色谱串联三重四极杆质谱(HPLC-MS/MS)定量检测饮用水中草铵膦、草甘膦及其代谢产物氨甲基膦酸的方法。水样直接经亲水PTFE膜过滤,以50 mmol/L甲酸铵(pH 3.0)为流动相,Acclaim Trinity Q1色谱柱分离,电喷雾离子化(ESI-)、选择反应监测(SRM)模式检测,外标法定量,总运行时间仅为5 min。草甘膦、氨甲基膦酸和草铵膦在10.0~1000μg/L浓度范围内存在较好的线性关系,相关系数大于0.999,其定量限分别为5.0,5.0和10.0μg/L;目标化合物日内和日间加标回收率分别为92.7%~102.1%和89.3%~99.9%,日内与日间相对标准偏差(RSD)均小于7.7%。该方法能满足水源水和饮用水中草铵膦、草甘膦及其代谢物氨甲基膦酸的应急检测或日常检测要求。

关键词：草甘膦氨甲基膦酸草铵膦饮用水液相色谱-串联质谱

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