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Development of A Neonatal Mouse Model for Coxsackievirus B1 Antiviral Evaluation

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Virologica Sinica 2021年第6期36卷 1575-1584页

作者： Zhichao Yin yuanyuan Wu Rui Zhu Longfa Xu yu Lin Hongwei Yang Wenkun Fu Qiongzi Huang Dongqing Zhang Jue Wang Wei Wang Yingbin Wang Tong cheng Ningshao Xia State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesSchool of Life SciencesSchool of Public HealthXiamen UniversityXiamen 361102China

Coxsackievirus B1(CVB1) is a leading causative agent of severe infectious diseases in humans and has been reported to be associated with outbreaks of aseptic meningitis, myocarditis, and the development of chronic diseases such as type 1 diabetes mellitus(T1DM). There is no approved vaccine or effective antiviral therapy to treat CBV1 infection. And animal models to assess the effects of antiviral agents and vaccine remain limited. In this study, we established a neonatal mouse model of CVB1 using a clinically isolated strain to characterize the pathological manifestations of virus infection and to promote the development of vaccines and antiviral drugs against CVB1. One-day-old BALB/c mice were susceptible to CVB1 infection by intraperitoneal injection. Mice challenged with CVB1 at a low dose [10 median tissue culture infective dose(TCID_(50))] exhibited a series of clinical symptoms, such as inactivity, emaciation, limb weakness, hair thinning,hunching and even death. Pathological examination and tissue viral load analysis showed that positive signals of CVB1 were detected in the heart, spinal cord, limb muscle and kidney without pathological damage. Particularly, CVB1 had a strong tropism towards the pancreas, causing severe cellular necrosis with inflammatory infiltration, and was spread by viraemia. Notably, the monoclonal antibody(mAb) 6H5 and antisera elicited from CVB1-vaccinated mice effectively protected the mice from CVB1 infection in the mouse model. In summary, the established neonatal mouse model is an effective tool for evaluating the efficacy of CVB1 antiviral reagents and vaccines.

关键词： Coxsackievirus B1(CVB1) Mouse model Antiviral evaluation Neutralizing antibody

Association of heat exposure and emergency ambulance calls: A multi-city study

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Advances in Climate Change Research 2021年第5期12卷 619-627页

作者： LI Yong-Hong YE Dian-Xiu LIU yue LI Na MENG Cong-Shen WANG Yan WANG yu JIN Xin Peng BI Shilu TONG cheng Yi-Bin YAO Xiao-yuan China CDC Key Laboratory of Environment and Population Health National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijing100021China National Climate Center China Meteorological AdministrationBeijing100081China School of Public Health The University of AdelaideAdelaideSA5000Australia Shanghai Children's Medical Center School of MedicineShanghai Jiao-Tong UniversityShanghai200025China School of Public Health Institute of Environment and Population HealthAnhui Medical UniversityHefei230032China School of Public Health and Social Work Queensland University of TechnologyBrisbane4000Australia

Evidence of the impact of ambient temperatures on emergency ambulance calls (EACs) in developing countries contributes to the improvement and complete understanding of the acute health effects of temperatures. This study aimed to examine the impacts and burden of heat on EACs in China, quantify the contributions of regional modifiers, and identify the vulnerable populations. A semi-parametric generalized additive model with a Poisson distribution was used to analyze the city-specific impacts of the daily maximum temperature (Tmax) on EACs in June–August in 2014–2017. Stratified analyses by sex and age were performed to identify the vulnerable sub-populations. Meta-analysis was undertaken to illustrate the pooled associations. Further subgroup analysis, stratified by climate, latitude, and per capita disposable income (PCDI), and meta-regression analysis were conducted to explore the regional heterogeneity and quantify the contributions of possible modifiers. The city- and region-specific attributable fractions of EACs attributable to heat were calculated. Strong associations were observed between the daily Tmax and total EACs in all cities. A total of 11.7% (95% confidence interval (CI): 11.2%–12.3%) of EACs were attributed to high temperatures in ten Chinese cities, and the central region with a low level of PCDI had the highest attributable fraction of 17.8% (95% CI: 17.2%–18.4%). People living in the central region with lower PCDI, and those aged 18–44 and 0–6 years were more vulnerable to heat than the others. The combined effects of PCDI, temperature, and latitude contributed 88.6% of the regional heterogeneity. The results complemented the understanding of the burden of EACs attributable to heat in developing countries and the quantitative contribution of regional modifiers.

关键词： Attributable fraction Emergency ambulance calls High temperature Regional modifiers Risk assessment

Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese

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Stroke & Vascular Neurology 2024年第4期9卷 399-406,I0044-I0065页

作者： Songchun Yang Zhijia Sun Dong Sun Canqing yu yu Guo Dianjianyi Sun yuanjie Pang Pei Pei Ling Yang Iona Y Millwood Robin G Walters Yiping Chen Huaidong Du Yan Lu Sushila Burgess Daniel Avery Robert Clarke Junshi Chen Zhengming Chen Liming Li Jun lv On behalf of the China Kadoorie Biobank Collaborative Group Department of Epidemiology&Biostatistics School of Public HealthPeking UniversityBeijingChina Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunanChina Peking University Center for Public Health and Epidemic Preparedness&Response BeijingChina Key Laboratory of Epidemiology of Major Diseases(Peking University) Ministry of EducationBeijingChina Fuwai Hospital Chinese Academy of Medical Sciences BeijingChina Medical Research Council Population Health Research Unit at the University of Oxford OxfordUK Clinical Trial Service Unit&Epidemiological Studies Unit(CTSU) Nuffield Department of Population HealthUniversity of OxfordOxfordUK NCDs Prevention and Control Department Suzhou CDCSuzhouJiangsuChina China National Center for Food Safety Risk Assessment BeijingChina State Key Laboratory of Vascular Homeostasis and Remodeling Peking UniversityBeijingChina 不详

Background and purpose Previous studies,mostly focusing on the European population,have reported polygenic risk scores(PRSs)might achieve risk stratification of *** aimed to examine the association strengths of PRSs with risks of stroke and its subtypes in the Chinese *** Participants with genome-wide genotypic data in China Kadoorie Biobank were split into a potential training set(n=22191)and a population-based testing set(n=72150).Four previously developed PRSs were included,and new PRSs for stroke and its subtypes were *** PRSs showing the strongest association with risks of stroke or its subtypes in the training set were further evaluated in the testing *** proportional hazards regression models were used to estimate the association strengths of different PRSs with risks of stroke and its subtypes(ischaemic stroke(IS),intracerebral haemorrhage(ICH)and subarachnoid haemorrhage(SAH)).Results In the testing set,during 872919 person-years of follow-up,8514 incident stroke events were *** PRSs of any stroke(AS)and IS were both positively associated with risks of AS,IS and ICH(p<0.05).The HR for per SD increment(HR_(SD))of PRSAS was 1.10(95%CI 1.07 to 1.12),1.10(95%CI 1.07 to 1.12)and 1.13(95%CI 1.07 to 1.20)for AS,IS and ICH,*** corresponding HR_(SD) of PRS_(IS) was 1.08(95%CI 1.06 to 1.11),1.08(95%CI 1.06 to 1.11)and 1.09(95%CI 1.03 to 1.15).PRS_(ICH) was positively associated with the risk of ICH(HR_(SD)=1.07,95%CI 1.01 to 1.14).PRSS_(AH) was not associated with risks of stroke and its *** addition of current PRSs offered little to no improvement in stroke risk prediction and risk *** In this Chinese population,the association strengths of current PRSs with risks of stroke and its subtypes were moderate,suggesting a limited value for improving risk prediction over traditional risk factors in the context of current genome-wide association study under-representing the East Asia

关键词： testing prediction increment

Long-term tadalafil once daily in Chinese men with erectile dysfunction:a 2-year final analysis of a post-marketing,multicenter,randomized,open-label trial

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Asian Journal of Andrology 2024年第3期26卷 282-287页

作者： Hui Jiang Lian-Ming Zhao Su Yan Ji-Hong Liu Zhao-Hui Zhu Jin-Dan Luo yu-Tian Dai Fu-Biao Li Hao-cheng Lin Zhi-Chao Zhang Department of Urology Peking University First HospitalBeijing 100000China Department of Urology Peking University Third HospitalBeijing 100191China Department of Urology Peking Union Medical College HospitalBeijing 100730China Department of Urology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Urology Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Urology The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Departmentof Andrology Nanjing Drum Tower HospitalNanjing 210008China Department of Andrology The First Hospital of Jilin UniversityChangchun 130021China Andrology Center Department of UrologyPeking University First HospitalBeijing 100034China

The long-term safety and effectiveness of once-daily tadalafil is crucial,but limited data are available in Chinese patients witherectile dysfunction(ED).In this post-marketing,multicenter,randomized,open-label trial with 2-year follow-up,635 ED caseswere randomized to receive daily oral tadalafil 2.5 mg or 5 mg for 3 months,of whom 580 continued once-daily tadalafil 5 mg for21 ***-emergent adverse events in the 12-month and 24-month period were similar,with the most common beingviral upper respiratory tract infection,upper respiratory tract infection,and *** improvement from baseline inthe International Index of Erectile Function-Erectile Function(IIEF-EF)score was detected at month 12(least squares mean[LSM]change:7.9,95%confidence interval[CI]:7.5–8.4,P<0.001)and was maintained to month 24(LSM change:8.6,95%CI:8.1–9.0,P<0.001).The proportions of patients regaining normal erectile function(IIEF-EF score≥26)were 43.7%and 48.0%at months 12 and 24,*** Assessment Questionnaire results showed improved erection function in 97.5%ofpatients and improved ability to engage in sexual activity in 95.9%of patients at month 12;these values were 96.1%and 95.0%at month 24,*** quality of sexual life score based on the Sexual Life Quality Questionnaire(SLQQ)was increased by52.2%at month 12 and by 55.3%at month 24(both P<0.001).The treatment satisfaction score determined by SLQQ(mean±standard deviation)was 62.4±21.0 at month 12 versus 65.9±20.2 at month ***-year daily application of tadalafil 5mg in Chinese men with ED showed a favorable safety profile and durable improvement in sexual performance and satisfaction.

关键词： clinical trial erectile dysfunction long-term safety once-daily dosing tadalafil

Influencing Factors and Improvement Strategies for Indoor Air Quality and Human Thermal Comfort in a Convenience Store

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Health 2018年第2期10卷 215-227页

作者： yu-Chieh Chen Shih-yu Chang Chung-Hao cheng Chin-Ching Wu Department of Public Health Chung Shan Medical University Taiwan Department of Public Health China Medical University Taiwan

Indoor air quality has received increased attention. Surveying human thermal comfort and evaluating indoor airflow and ventilation can improve the integrity assessment of the indoor environment. In this study, indoor air quality measurements and spatial assessments were performed in a convenience store on a campus. The computational fluid dynamics model was used to simulate the indoor airflow and explore the spatial distribution of the CO2 concentration. The results showed the CO2 concentration easily surpassed the standard value during the weekdays and accumulated in short flows and dead zones. In the condition of no-building alterations, the preferred improvement strategy is to modify the air supply angle to 30°.

关键词： Carbon Dioxide Computational Fluid Dynamics Simulation Ventilation

Bites from the same dog,different outcomes for two patients:a case report

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Infectious Diseases of Poverty 2017年第1期6卷 963-966页

作者： Xue-Yong Huang Xing-Le Li Shu-yu Wu yu-Lei Gu Xin-Jun lv John David Klena Bian-Li Xu Henan Center for Disease Control and Prevention ZhengzhouChina Henan Key Laboratory of Pathogenic Microorganisms ZhengzhouChina Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine XinxiangChina International Emerging Infections Program United States Centers for Disease Control and PreventionBeijingChina Global Disease Detection Branch Division of Global Health ProtectionCenter for Global HealthUnited States Centers for Disease Control and PreventionAtlantaGAUSA The First Affiliated Hospital of Zhengzhou University ZhengzhouChina Chinese Center for Disease Control and Prevention BeijingChina

Background:Rabies is a serious reemerging zoonosis in *** present human rabies cases are primarily diagnosed based on clinical *** presentation:In August 2012,a woman and her son were attacked by a stray dog in Henan,*** son received rabies postexposure prophylaxis(wound treatment followed by vaccine,no immunoglobulin),however,the mother did *** infection was subsequently laboratory confirmed in the mother and she died in December;her son is alive and healthy after 2 years of ***:This report documents that the timely utilization of postexposure prophylaxis is a required measure in preventing rabies after exposure to an animal bite.

关键词： China Encephalitis Neglected diseases Rabies Rabies atypical manifestations Rabies laboratory diagnosis Rabies postexposure prophylaxis Zoonosis

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Construction and Secretory Expression of β-Galactosidase Gene from Lactobacillus Bulgaricus in Lactococcus Lactis

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Biomedical and Environmental Sciences 2012年第2期25卷 203-209页

作者： ZHANG Wen WANG Chuan HUANG cheng yu yu Qian LIU Heng Chuan ZHANG Chao Wu PEI Xiao Fang Department of Nutrition and Food Hygiene West China School of Public Health Sichuan University Chengdu 610041 Sichuan China Department of Medical Technology West China School of Public Health Sichuan University Chengdu 610041 Sichuan China Central Hospital of Sichuan Petroleum Bureau Chengdu 610213 Sichuan China

Objective This study is to examine the secretion effects of β-galactosidase in Lactococcus *** The usp45 and β-galactosidase genes were cloned and inserted into plasmid pMG36e to obtain the recombinant plasmid *** recombinant plasmid was transformed into both Escherichia coli DH5α and *** *** enzyme activity,gene sequencing,SDS-PAGE and hereditary stability were assessed and *** The lacZ gene inserted into plasmids pMG36e-usp-lacZ was 99.37% similar to the GenBank sequence,and SDS-PAGE revealed an evident idio-strap at 116 KDa between *** MG1363/pMG36eusp-lacZ in both supernatant and cell samples.β-Galactosidase activity measured 0.225 U/mL in *** pMG36e-usp-lacZ transformants,and its secretion rate was 10%.The plasmid pMG36e-usp-lacZ appeared more stable in *** The authors concluded that these new recombinant bacteria well expressed and secreted β-galactosidase,indicating that the β-galactosidase expression system was successfully constructed,and this might provide a new solution for management of lactose intolerance specifically and promote the use of gene-modified organisms as part of the food-grade plasmid in general.

关键词： Gene constructs Gene expression Secretory expression β-Galactosidase Lactococcus lactis

Identification of novel loci influencing refractive error in East Asian populations using an extreme phenotype design

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Journal of Genetics and Genomics 2022年第1期49卷 54-62页

作者： Xiaotong Han Tianzi Liu Xiaohu Ding Jialin Liu Xingyan Lin Decai Wang Moeen Riaz Paul N.Baird Zhi Xie yuan cheng Yi Li yuki Mori Masahiro Miyake Hengtong Li Ching-yu cheng Changqing Zeng Kyoko Ohno-Matsui Xiangtian Zhou Fan Liu Mingguang He State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510000China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China University of Chinese Academy of Sciences Beijing 100101China School of Public Health and Preventive Medicine Monash UniversityMelbourne 3800Australia Department of Surgery OphthalmologyFaculty of MedicineDentistry and Health SciencesThe University of MelbourneMelbourneVictoria 3010Australia Department of Ophthalmology and Visual Science Tokyo Medical and Dental UniversityTokyo 113-8510Japan Singapore Eye Research Institute Singapore National Eye Centre 168751Singapore Department of Ophthalmology Yong Loo Lin School of MedicineNational University of Singapore 119077Singapore Centre for Quantitative Medicine Duke-NUS Medical School 169857Singapore School of Optometry and Ophthalmology and Eye Hospital Wenzhou Medical UniversityWenzhouZhejiang 325035China State Key Laboratory of Optometry Ophthalmology and Vision ScienceWenzhouZhejiang 325035China

The global "myopia boom" has raised significant international concerns. Despite a higher myopia prevalence in Asia, previous large-scale genome-wide association studies(GWASs) were mostly based on European descendants. Here, we report a GWAS of spherical equivalent(SE) in 1852 Chinese Han individuals with extreme SE from Guangzhou(631 0.00 D) and Wenzhou(593 -1.75 D), followed by a replication study in two independent cohorts with totaling 3538 East Asian individuals. The discovery GWAS and meta-analysis identify three novel loci, which show genome-wide significant associations with SE, including 1 q25.2 FAM163 A, 10 p11.22 NRP1/PRAD3, and 10 p11.21 ANKRD30 A/MTRNR2 L7, together explaining 3.34% of SE variance. 10 p11.21 is successfully *** allele frequencies of all three loci show significant differences between major continental groups(P < 0.001). The SE reducing(more myopic) allele of rs10913877(1 q25.2 FAM163 A) demonstrates the highest frequency in East Asians and much lower frequencies in Europeans and Africans(EAS = 0.60,EUR = 0.20, and AFR = 0.18). The gene-based analysis additionally identifies three novel genes associated with SE, including EI24, LHX5, and ARPP19. These results provide new insights into myopia pathogenesis and indicate the role of genetic heterogeneity in myopia epidemiology among different ethnicities.

关键词： Extreme phenotype Genome-wide association study Population heterogeneity Refractive error East Asian population Prediction

Metformin promotes angiogenesis and functional recovery in aged mice after spinal cord injury by adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway

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Neural Regeneration Research 2023年第7期18卷 1553-1562页

作者： Jin-yun Zhao Xiao-Long Sheng cheng-Jun Li Tian Qin Run-Dong He Guo-yu Dai Yong Cao Hong-Bin Lu Chun-yue Duan Jian-Zhong Hu Department of Spine Surgery and Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Key Laboratory of Organ Injury Aging and Regenerative Medicine of Hunan ProvinceChangshaHunan ProvinceChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan ProvinceChina Hunan Engineering Research Center of Sports and Health ChangshaHunan ProvinceChina Department of Sports Medicine Research Centre of Sports MedicineXiangya HospitalCentral South UniversityChangshaHunan ProvinceChina

Treatment with metformin can lead to the recovery of pleiotropic biological activities after spinal cord ***,its effect on spinal cord injury in aged mice remains *** the essential role of angiogenesis during the regeneration process,we hypothesized that metformin activates the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway in endothelial cells,thereby promoting microvascular regeneration in aged mice after spinal cord *** this study,we established young and aged mouse models of contusive spinal cord injury using a modified Allen *** found that aging hindered the recovery of neurological function and the formation of blood vessels in the spinal *** with metformin promoted spinal cord microvascular endothelial cell migration and blood vessel formation in ***,intraperitoneal injection of metformin in an in vivo model promoted endothelial cell proliferation and increased the density of new blood vessels in the spinal cord,thereby improving neurological *** role of metformin was reversed by compound C,an adenosine monophosphate-activated protein kinase inhibitor,both in vivo and in vitro,suggesting that the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway likely regulates metformin-mediated angiogenesis after spinal cord *** findings suggest that metformin promotes vascular regeneration in the injured spinal cord by activating the adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway,thereby improving the neurological function of aged mice after spinal cord injury.

关键词： adenosine monophosphate-activated protein kinase/endothelial nitric oxide synthase pathway angiogenesis aged mice compound C metformin spinal cord injury