Objective:To identify the association between serum albumin levels and disease severity among adult patients with dengue in China's Mainland.Methods:This retrospective cohort study analyzed the data of adult patie...Objective:To identify the association between serum albumin levels and disease severity among adult patients with dengue in China's Mainland.Methods:This retrospective cohort study analyzed the data of adult patients(aged≥18 years)hospitalized with laboratory-confirmed dengue in a tertiary center for infectious diseases from 2013 to 2019 in China's Mainland.Serum albumin levels were estimated and compared between patients with severe dengue and non-severe dengue.Additionally,the association between serum albumin levels and severe dengue was evaluated using a generalized linear model[relative risks(RR)].Multivariate logistic regression analysis was performed to identify the potential predictors of severe dengue.Results:Overall,1568 patients were included in this study.Of these patients,34(2.17%)developed severe dengue.The median serum albumin levels were significantly lower in patients with severe dengue than that in those with non-severe dengue(33 g/L vs.37 g/L,P<0.001).After adjustment for age,sex,and comorbidities,hypoalbuminemia(RR 4.877,95%CI 2.193-11.461,P<0.001)was found to be a predictor of severe dengue.Serum albumin levels(OR 1.303,95%CI 1.161-1.462,P<0.001)and age(OR 1.038,95%CI 1.017-1.061,P<0.001)were significant risk factors for severe dengue.The area under the curve for serum albumin levels to distinguish severe dengue was 0.787.Conclusions:Lower serum albumin levels were significantly associated with disease severity in adult patients with dengue.Hypoalbuminemia on admission resulted in at least a four-fold increased risk of severe dengue.展开更多
Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiolog...Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance.Methods: Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics.Results: The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2-6%, 0.8-2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics.Conclusions: The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically.展开更多
Dear Editor,Dengue infections are caused by all four serotypes of dengue virus(DENV1–4).In recent years it has been confirmed that DENV-1 and DENV-2 are co-circulated in Guangzhou,Guangdong,China(Lai et al.2015;Luo e...Dear Editor,Dengue infections are caused by all four serotypes of dengue virus(DENV1–4).In recent years it has been confirmed that DENV-1 and DENV-2 are co-circulated in Guangzhou,Guangdong,China(Lai et al.2015;Luo et al.2017).DENV-2 strains were imported from Thailand and Indonesia(Luo et al.2017;Zhao et al.2014,2016),and had become the second local circulated serotype in Guangzhou.展开更多
Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-relat...Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases,and found new-onset in suli n resista nee,hyperglycemia,and decreased HDL-C in these patie nts.Mecha nistically,SARS-CoV-2 infecti on in creased the expression of RE1-silencing transcription factor(REST),which modulated the expression of secreted metabolic factors including myeloperoxidase,apelin,and myostatin at the transcriptional level,resulting in the perturbation of glucose and lipid metabolism.Furthermore,several lipids,including(±)5-HETE,(±)12-HETE,propionic acid,and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation,especially in insulin resistance.Taken together,our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19,and further illustrated the underlying mechanisms,providing potential therapeutic targets for COVID-19-induced metabolic complications.展开更多
Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus(DENV).DENV causes a febrile illness,severe forms including hemorrhagic fevers and shock with fatalit...Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus(DENV).DENV causes a febrile illness,severe forms including hemorrhagic fevers and shock with fatalities in humans.DENV-2 is frequently associated with severe dengue infections and epidemics.DENV-2 strains from Guangdong,China,have not been characterized to compare the phylogenetics and pathogenicity of different DENV-2 subgenotype strains in both vitro and vivo.A total of 22 patients tested to be DENV-2 positive and were enrolled in this study,22 complete genomes were obtained by virus isolation and high-throughput sequencing.Phylogenetic and single amino polymorphism(SAP)analysis indicated that two major subgenotypes(A and C)of DENV-2 Cosmopolitan were prevalent in Guangdong in 2018.The apparent change of major subgenotypes of DENV-2 circulating in Guangdong indicated the diversity of DENV-2 strains,including endemic genotype and imported genotype.It alerted the risk of cross-border transmission of DENV.A significant difference in replication rate was observed in C6/36 between different DENV-2 strains,although growth kinetics comparison of different DENV-2 Cosmopolitan subgenotypes showed similar profiles.DENV-2 subgenotypes(A and C)replicated efficiently in IFNAR−/−C57BL/6 mice,and subgenotype A of Cosmopolitan infected mice showed increased weight loss and delayed viral clearance compared with the subgenotype C group.DENV-2 prevalent in Guangdong in 2018 showed apparent genetic and pathogenicity diversity in both vitro and vivo,indicating the necessity of molecular surveillance and exploration of the relationship between its pathogenicity and clinical characteristics.展开更多
基金supported by Special Program of Science and Technology of Guangdong Province(Grant No.:2013A020229001)the Major Program of Guangzhou Healthcare Collaborative Innovation(Grant No.:201803040006)Basic and applied basic research project jointly funded by the University of Guangzhou(Grant No.:2023A03J0810).
文摘Objective:To identify the association between serum albumin levels and disease severity among adult patients with dengue in China's Mainland.Methods:This retrospective cohort study analyzed the data of adult patients(aged≥18 years)hospitalized with laboratory-confirmed dengue in a tertiary center for infectious diseases from 2013 to 2019 in China's Mainland.Serum albumin levels were estimated and compared between patients with severe dengue and non-severe dengue.Additionally,the association between serum albumin levels and severe dengue was evaluated using a generalized linear model[relative risks(RR)].Multivariate logistic regression analysis was performed to identify the potential predictors of severe dengue.Results:Overall,1568 patients were included in this study.Of these patients,34(2.17%)developed severe dengue.The median serum albumin levels were significantly lower in patients with severe dengue than that in those with non-severe dengue(33 g/L vs.37 g/L,P<0.001).After adjustment for age,sex,and comorbidities,hypoalbuminemia(RR 4.877,95%CI 2.193-11.461,P<0.001)was found to be a predictor of severe dengue.Serum albumin levels(OR 1.303,95%CI 1.161-1.462,P<0.001)and age(OR 1.038,95%CI 1.017-1.061,P<0.001)were significant risk factors for severe dengue.The area under the curve for serum albumin levels to distinguish severe dengue was 0.787.Conclusions:Lower serum albumin levels were significantly associated with disease severity in adult patients with dengue.Hypoalbuminemia on admission resulted in at least a four-fold increased risk of severe dengue.
基金This study was supported by the National Key R&D Program of China(2020YFC120104)the National Institutes of Health+3 种基金the USA(AI136850)the National Natural Science Foundation of China(82072311)the Guang‑zhou Synergy Innovation Key Program for Health(201803040006 and 201508020263)the Guangzhou International Science and Technology Cooperation Program(2012J5100026).
文摘Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance.Methods: Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics.Results: The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2-6%, 0.8-2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics.Conclusions: The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically.
基金supported by funds from 2017 Guangzhou major projects of collaborative innovation in health care(201704020229)the State Key Laboratory of Pathogen and Biosecurity(SKLPBS1839)。
文摘Dear Editor,Dengue infections are caused by all four serotypes of dengue virus(DENV1–4).In recent years it has been confirmed that DENV-1 and DENV-2 are co-circulated in Guangzhou,Guangdong,China(Lai et al.2015;Luo et al.2017).DENV-2 strains were imported from Thailand and Indonesia(Luo et al.2017;Zhao et al.2014,2016),and had become the second local circulated serotype in Guangzhou.
基金This study was supported by the joint emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology of China,Guangdong Science and Technology Department and Guangzhou Municipal Science and Technology Bureau(2020B111108001)Guangdong Science and Technology Department(2020B121206001&2020B1212030004)The funders had no role in study design,data collection and analysis,or preparation of the manuscript.
文摘Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases,and found new-onset in suli n resista nee,hyperglycemia,and decreased HDL-C in these patie nts.Mecha nistically,SARS-CoV-2 infecti on in creased the expression of RE1-silencing transcription factor(REST),which modulated the expression of secreted metabolic factors including myeloperoxidase,apelin,and myostatin at the transcriptional level,resulting in the perturbation of glucose and lipid metabolism.Furthermore,several lipids,including(±)5-HETE,(±)12-HETE,propionic acid,and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation,especially in insulin resistance.Taken together,our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19,and further illustrated the underlying mechanisms,providing potential therapeutic targets for COVID-19-induced metabolic complications.
基金funded by grants from the National Key Research and Development Program of China(2020YFC1200100,2018YFC1200100,2018ZX10301403)the Guangdong Provincial Department of Science and Technology(2020A1515010911,201803040006,2019B030316028)+2 种基金National Natural Science Foundation of China(81772191,91842106 and 8181101118,32000658)National Key Technology R&D Program(2018YFC1311900)Guangzhou Medical University High-level University Innovation Team Training Program(Guangzhou Medical University released[2017]No.159).
文摘Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus(DENV).DENV causes a febrile illness,severe forms including hemorrhagic fevers and shock with fatalities in humans.DENV-2 is frequently associated with severe dengue infections and epidemics.DENV-2 strains from Guangdong,China,have not been characterized to compare the phylogenetics and pathogenicity of different DENV-2 subgenotype strains in both vitro and vivo.A total of 22 patients tested to be DENV-2 positive and were enrolled in this study,22 complete genomes were obtained by virus isolation and high-throughput sequencing.Phylogenetic and single amino polymorphism(SAP)analysis indicated that two major subgenotypes(A and C)of DENV-2 Cosmopolitan were prevalent in Guangdong in 2018.The apparent change of major subgenotypes of DENV-2 circulating in Guangdong indicated the diversity of DENV-2 strains,including endemic genotype and imported genotype.It alerted the risk of cross-border transmission of DENV.A significant difference in replication rate was observed in C6/36 between different DENV-2 strains,although growth kinetics comparison of different DENV-2 Cosmopolitan subgenotypes showed similar profiles.DENV-2 subgenotypes(A and C)replicated efficiently in IFNAR−/−C57BL/6 mice,and subgenotype A of Cosmopolitan infected mice showed increased weight loss and delayed viral clearance compared with the subgenotype C group.DENV-2 prevalent in Guangdong in 2018 showed apparent genetic and pathogenicity diversity in both vitro and vivo,indicating the necessity of molecular surveillance and exploration of the relationship between its pathogenicity and clinical characteristics.