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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

Effect of Tip Flange on Tip Leakage Flow of Small Axial Flow Fans

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Journal of Thermal science 2014年第1期23卷 45-52页

作者： ZHANG Li JIN Yingzi JIN Yuzhen The Province Sky Lab of Fluid Transmission technology Zhejiang Sci-Tech University

Aerodynamic performance of an axial flow fan is closely related to its tip clearance leakage flow. In this paper, the hot-wire anemometer is used to measure the three dimensional mean velocity near the blade tips. Moreover, the filtered N-S equations with finite volume method and RNG k-s turbulence model are adopted to carry out the steady simulation calculation of several fans that differ only in tip flange shape and number. The large eddy simulation and the FW-H noise models are adopted to carry out the unsteady numerical calculation and aerodynamic noise prediction. The results of simulation calculation agree roughly with that of tests, which proves the numerical calculation method is *** effects of tip flange shapes and numbers on the blade tip vortex structure and the characteristics are analyzed. The results show that tip flange of the fan has a certain influence on the characteristics of the fan. The maximum efficiencies for the fans with tip flanges are shifted towards partial flow with respect to the design point of the dattun fan. Furthermore, the noise characteristics for the fans with tip flanges have become more deteriorated than that for the datum fan. Tip flange contributes to forming tip vortex shedding and the effect of the half-cylinder tip flange on tip vortex shedding is obvious. There is a distinct rela- tionship between the characteristics of the fan and tip vortex *** research results provide the profitable reference for the internal flow mechanism of the performance optimization of small axial flow fans.

关键词： Tip Flange Tip Leakage Flow Small Axial Flow Fan Performance

Skewed CD39/CD73/adenosine pathway contributes to B-cell hyperactivation and disease progression in patients with chronic hepatitis B

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Gastroenterology Report 2021年第1期9卷 49-58,I0002页

作者： Shuang-Nan Zhou Ning Zhang Hong-Hong Liu Peng Xia Chao Zhang Jin-Wen Song Xing Fan Ming Shi Lei Jin Ji-Yuan Zhang Fu-Sheng Wang Medical School of Chinese PLA BeijingP.R.China Infectious Disease Treatment and Research Center The Fifth Medical Center of Chinese PLA General HospitalBeijingP.R.China Liver transplatation Center The Fifth Medical Center of ChinesePLA General HospitalBeijingP.R.China Department of Integrated TCM&Western Medicine The Fifth Medical Center of Chinese PLA General HospitalBeijingP.R.China International Center for Liver Disease Treatment The Fifth Medical Center of Chinese PLA General HospitalBeijingP.R.China

Background:The mechanisms underlying B-cell hyperactivation in patients with chronic hepatitis B virus(HBV)infection remain largely *** present study assessed the clinical characteristics of the CD39/CD73/adenosine pathway in patients with chronic hepatitis B(CHB).Methods:We examined CD39 and CD73 expression and adenosine production by B-cells from 202 HBV-infected patients.B-cell-activation phenotypes were assessed by flow cytometry after CpG+CD40 ligand stimulation with or without blockade and activation of the adenosine ***:CD39 and CD73 expression on circulating B-cells was decreased in CHB patients with high HBV DNA,HBeAg positivity,high HBsAg levels,and active liver inflammation,and was hierarchically restored in complete responders according to HBeAg seroconversion or HBsAg ***,CD39 and CD73 expression on activated memory and tissue-like memory B-cell subsets in complete responders was not increased despite effective antiviral ***,CD39 and CD73 expression on intra-hepatic B-cells was decreased in inflammatory *** vitro,B-cells from CHB patients showed a markedly reduced capacity to generate CD39/CD73-dependent extracellular adenosine and expressed increased levels of activation markers after adenosine-production ***,metformin significantly reduced activation-marker expression via regulating AMP-activated protein ***:The skewed CD39 and CD73 expression on B-cells was associated with a high viral burden,liver inflammation,and antiviral efficacy in CHB patients,and the skewed CD39/CD73/adenosine pathway contributed to B-cell *** of the CD39/CD73/adenosine pathway using metformin may represent a therapeutic option to reverse HBVinduced immune pathogenesis.

关键词： hepatitis B virus B-lymphocyte CD39 5’-nucleotidase lymphocyte activation

Safety validation of decision trees for hepatocellular carcinoma

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World Journal of Gastroenterology 2015年第31期21卷 9394-9402页

作者： Xian-Qiang Wang Zhe Liu Wen-Ping Lv Ying Luo Guang-Yun Yang Chong-Hui Li Xiang-Fei Meng Yang Liu Ke-Sen Xu Jia-Hong Dong Department of Hepatobiliary Surgery Qilu HospitalShandong University Department of Hepatobiliary Surgery PLA General Hospital

AIM: To evaluate a different decision tree for safe liver resection and verify its ***: A total of 2457 patients underwent hepatic resection between January 2004 and December 2010 at the Chinese PLA General Hospital,and 634 hepatocellular carcinoma(HCC) patients were eligible for the final analyses. Post-hepatectomy liver failure(PHLF) was identified by the association of prothrombin time 50 μmol/L(the "50-50" criteria),which were assessed at day 5 postoperatively or later. The Swiss-Clavien decision tree,Tokyo University-Makuuchi decision tree,and Chinese consensus decision tree were adopted to divide patients into two groups based on those decision trees in sequence,and the PHLF rates were ***: The overall mortality and PHLF rate were 0.16% and 3.0%. A total of 19 patients experienced PHLF. The numbers of patients to whom the SwissClavien,Tokyo University-Makuuchi,and Chinese consensus decision trees were applied were 581,573,and 622,and the PHLF rates were 2.75%,2.62%,and 2.73%,respectively. Significantly more cases satisfied the Chinese consensus decision tree than the Swiss-Clavien decision tree and Tokyo University-Makuuchi decision tree(P < 0.01,P < 0.01); nevertheless,the latter two shared no difference(P = 0.147). The PHLF rate exhibited no significant difference with respect to the three decision ***: The Chinese consensus decision tree expands the indications for hepatic resection for HCC patients and does not increase the PHLF rate compared to the Swiss-Clavien and Tokyo UniversityMakuuchi decision trees. It would be a safe and effective algorithm for hepatectomy in patients with hepatocellular carcinoma.

关键词： Hepatectomy Liver failure Decision tree

Effect of Steam Dilution on the MILD Combustion Characteristics of Methane in a Model Combustor

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Journal of Thermal science 2023年第2期32卷 822-836页

作者： ZHU Ziru XIONG Yan LIU Zhigang ZHANG Zhedian Key Laboratory of Advanced Energy and Power Institute of Engineering ThermophysicsChinese Academy of SciencesBeijing 100190China University of Chinese Academy of sciences Beijing 100049China

Moderate or Intense Low-oxygen Dilution(MILD)combustion has low emission potential in gas *** present work has investigated the performance of MILD combustion with parallel-jet burner arrangement in dry and steam-diluted *** combustion tests were conducted in atmospheric pressure at various equivalence ratios from LBO(Lean Blow Out)to near-stoichiometric conditions and steam-to-air mass ratios from 0 to 0.2.A simplified chemical reactors network(CRN)model based on MILD combustion concept has been established to study the effect of steam dilution on different pathways of NO *** experimental results show that under the same adiabatic flame temperature,the reaction zone gradually moves downstream with the increase of steam *** the high steam content(0.2 kg/kg),the reaction zone is widely distributed,and the distribution of reaction intensity in the reaction zone is more *** average lift-off height of reaction zone is proportional to the steam *** the steam content of 0.2 kg/kg,the average lift-off height reaches 2.5 times that of the dry conditions,which brings the risk of *** the adiabatic flame temperature of 1650–1900 K,the emissions of NOxare below 3×10–6(at 15%O2,dry)when the steam content varies from 0 to 0.2 kg/kg,which indicates the ultra-low emissions can be obtained under large changes in steam *** the inlet temperature of 381 K,as the steam content increases,the Prompt NO is dominant in the total NO *** dilution results in a smaller operating range with lower CO *** the steam content reaches 0.2 kg/kg,compared to the dry condition,the carbon monoxide emission increases *** addition,the LBO equivalence ratio of combustion with larger steam content is significantly higher.

关键词： MILD combustion steam dilution chemical reactors network(CRN) NOx emissions

Evaluation of a novel choanoid fluidized bed bioreactor for future bioartificial livers

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World Journal of Gastroenterology 2014年第22期20卷 6869-6877页

作者： Cheng-Bo Yu Xiao-Ping Pan Liang Yu Xiao-Peng Yu Wei-Bo Du Hong-Cui Cao Jun Li Ping Chen Lan-Juan Li States Key Laboratory for Diagnosis and Treatment of Infectious Diseases First Affiliated HospitalSchool of MedicineZhejiang University Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases

AIM: To construct and evaluate the functionality of a choanoid-fluidized bed bioreactor (CFBB) based on microencapsulated immortalized human hepatocytes.

关键词： Choanoid Fluidized bed Bioreactor Immortalized human hepatocytes Bioartificial liver

PD0325901, an ERK inhibitor, enhances the efficacy of PD-1 inhibitor in non-small cell lung carcinoma

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Acta Pharmaceutica Sinica B 2021年第10期11卷 3120-3133页

作者： Min Luo Yuhui Xia Fang Wang Hong Zhang Danting Su Chaoyue Su Chuan Yang Shaocong Wu Sainan An Suxia Lin Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteSun Yat-sen University Cancer CenterGuangzhou 510060China Pharmacy College Guangzhou Medical UniversityGuangzhou 510182China

ERK pathway regulated the programmed death ligand-1(PD-L1)expression which was linked to the response of programmed death-1(PD-1)/PD-L1 blockade *** it is deducible that ERK inhibitor could enhance the efficacy of PD-1 inhibitor in cancer *** this study,PD0325901,an oral potent ERK inhibitor,strongly enhanced the efficacy of PD-1 antibody in vitro and in vivo models in non-small cell lung carcinoma(NSCLC)***,PD0325901 or shRNA-ERK1/2 significantly downregulated the PD-L1 expression in NSCLC cells and increased the CD3+T cells infiltration and functions in tumor *** was a positive correlation between the p-ERK1/2 expression and PD-L1 expression in patients with *** the patients with low p-ERK1/2 expression were observed a high response rate of PD-1/PD-L1 blockage *** results demonstrate that PD0325901,an ERK inhibitor,can enhance the efficacy of PD-1 blockage against NSCLC in vitro and in vivo *** the combination of ERK inhibitor such as PD0325901 and PD-1/PD-L1 blockage is a promising regimen and encouraged to be further confirmed in the treatment of patients with NSCLC.

关键词： ERK1/2 PD-L1 PD-1 PD0325901 NSCLC Immunotherapy Targeted therapy Combination therapy

Morbidity Analysis of the Notifiable Infectious Diseases in China,2018

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China CDC weekly 2019年第4期1卷 47-53页

作者： Shuaibing Dong Xiang Ren Cuihong Zhang Mengjie Geng Yuliang Zhu Lusha Shi Lijie Zhang Zhongjie Li Liping Wang Division of Infectious Disease Key Laboratory of Surveillance and Early Warning on Infectious DiseaseChina CDCBeijingChina Fuyang CDC AnhuiChina Heilongjiang CDC HeilongjiangChina Complex Systems Research Center Shanxi UniversityShanxiChina

Introduction Notifiable infectious disease surveillance is important for understanding the trends in morbidity for certain diseases,especially detection of acute infectious disease outbreaks and changing epidemiology.A web-based reporting system was deployed in January 2004,which has improved data collection and speed *** report provides an updated analysis for reports published in 2013 and *** Data from the national Notifiable Disease Reporting System(NNDRS)was *** NNRDS shows data from 39 notifiable diseases split into three categories(A,B,and C)based on severity and importance.A descriptive analysis was conducted to analyze the morbidity of notifiable diseases in *** In 2018,the morbidity of national notifiable diseases was 559.41 per 100,000 population,an increase of 12.88% compared with the average of 2015–*** proportion of laboratory confirmed cases was 36.22%,which decreased 4.03% compared with the average of that in the recent three *** transmitted by direct contact/fecal–oral transmission accounted for the largest proportion,49.37% of the total reported cases,followed by the respiratory transmitted diseases,blood-borne/sexually transmitted diseases,and the zoonotic and vectorborne diseases with a proportion of 25.18%,24.60%,and 0.85%,*** descriptive analysis showed that the viral-infected cases accounted for 73.78% of the totals,followed by the bacterialinfected and parasitic *** The national morbidity of notifiable infectious diseases showed increases in 2018,mostly due to higher morbidity of category C diseases,such as HFMD,infectious diarrhea,and influenza,and these diseases need to be further prioritized in disease control and prevention *** confirmed cases remain low and need to be improved to improve data quality.

关键词： Diseases epidemiology prevention

Noncanonical NF-κB Signaling Pathway in Liver Diseases

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 81-89页

作者： Qianhui Chen Xinyu Lu Xiaoyong Zhang State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis ResearchDepartment of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina Hepatology Unit Shenzhen HospitalSouthern Medical UniversityShenzhenGuangdongChina

The noncanonical NF-κB signaling pathway is an important branch of NF-κB *** is involved in regulating multiple important biological processes,including inflammation and host immune response.A central adaptor protein of the noncanonical NF-κB pathway is NF-κB-inducing kinase(NIK),which activates the downstream kinase IKKαto process p100 to p52,thereby forming the RelB/p52 heterodimer to initiate the expression of target ***,many specific inhibitors and monoclonal antibodies targeting or triggering this pathway are being developed and tested for various diseases,including cancers,autoimmune diseases,and virus *** that aberrant activation of the noncanonical NF-κB pathway is frequently observed in various liver diseases,targeting this pathway may be a promising therapeutic strategy to alleviate liver ***,activation of this pathway may contribute to the antiviral immune response and promote the clearance of persistent hepatotropic virus ***,we review the role of the noncanonical NF-κB pathway in the occurrence and development of different liver diseases,and discuss the potency and application of modulating the noncanonical NF-κB pathway for treatment of these liver diseases.

关键词： Noncanonical NF-κB pathway NF-κB-inducing kinase Liver inflammation Immune responses Liver diseases