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Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology

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Biomedical and Environmental Sciences 2024年第4期37卷 387-398页

作者： ZHAO Zi Jin CHEN Xiao Ping HUA Shao Wei LI Feng Yu ZHAO Meng XING Chen Hao WANG Jie TIAN Feng Yu ZHANG Rui Qing LYU Xiao Na HAN Zhi Qiang WANG Yu Xin LI Hong Yi SHEN Xin Xin MA Xue Jun TIE Yan Qing Graduate School Hebei North UniversityZhangjiakou 075000HebeiChina department of Clinical laboratory Hebei General HospitalShijiazhuang 050051HebeiChina National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases NHC Key Laboratory of Medical Virology and Viral DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China department of Clinical laboratory Pathology Diagnostic Center Shiyan General HospitalShiyan 442000HubeiChina Graduate School Hebei Medical University Shijiazhuang 050031HebeiChina

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification *** study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with *** Recombinant plasmids were used to evaluate the assay *** blood influenza bacteria were used for the specific *** and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)*** analysis was used to evaluate the consistency between the two *** The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial *** M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

关键词： Staphylococcus aureus Pseudomonas aeruginosa Acinetobacter baumannii Human Mannan-binding lectin protein Bloodstream infection Recombinase-aided PCR assay Multiple detection

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TEA domain transcription factor 1(TEAD1)induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1209-1220页

作者： Shuai Song Xiaokai Zhang Zihang Huang Yongchao Zhao Shuyang Lu Linqi Zeng Fengze Cai Tongyao Wang Zhiqiang Pei Xinyu Weng Wei Luo Hao Lu Zilun Wei Jian Wu Peng Yu Li Shen Xiaochun Zhang Aijun Sun Junbo Ge department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghaiChina State Key laboratory of Cardiology Zhongshan HospitalFudan UniversityShanghaiChina Key laboratory of viral Heart Diseases National Health CommissionShanghaiChina Key laboratory of viral Heart Diseases Chinese Academy of Medical SciencesShanghaiChina National Clinical Research Center for Interventional Medicine ShanghaiChina department of cardiac surgery Zhongshan HospitalFudan UniversityShanghaiChina Institutes of Biomedical Sciences Fudan UniversityShanghaiChina Shanghai Institute of Hypertension Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and ***,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely *** analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l *** investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure *** TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre *** and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac ***,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 ***1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 ***,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 *** conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.

关键词： TEAD1 expression Wnt4

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To Analyze the Sensitivity of RT-PCR Assays Employing S Gene Target Failure with Whole Genome Sequencing Data during Third Wave by SARS-CoV-2 Omicron Variant

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Advances in Microbiology 2024年第5期14卷 247-255页

作者： Pooja Patel Yogita Mistry Monika Patel Summaiya Mullan viral Research and Diagnostic laboratory Department of Microbiology Government Medical college Surat India

Introduction: Omicron is a highly divergent variant of concern (VOCs) of a severe acute respiratory syndrome SARS-CoV-2. It carries a high number of mutations in its spike protein hence;it is more transmissible in the community by immune evasion mechanisms. Due to mutation within S gene, most Omicron variants have reported S gene target failure (SGTF) with some commercially available PCR kits. Such diagnostic features can be used as markers to screen Omicron. However, Whole Genome Sequencing (WGS) is the only gold standard approach to confirm novel microorganisms at genetically level as similar mutations can also be found in other variants that are circulating at low frequencies worldwide. This Retrospective study is aimed to assess RT-PCR sensitivity in the detection of S gene target failure in comparison with whole genome sequencing to detect variants of Omicron. Methods: We have analysed retrospective data of SARS-CoV-2 positive RT-PCR samples for S gene target failure (SGTF) with TaqPath COVID-19 RT-PCR Combo Kit (ThermoFisher) and combined with sequencing technologies to study the emerged pattern of SARS-CoV-2 variants during third wave at the tertiary care centre, Surat. Results: From the first day of December 2021 till the end of February 2022, a total of 321,803 diagnostic RT-PCR tests for SARS-CoV-2 were performed, of which 20,566 positive cases were reported at our tertiary care centre with an average cumulative positivity of 6.39% over a period of three months. In the month of December 21 samples characterized by the SGTF (70/129) were suggestive of being infected by the Omicron variant and identified as Omicron (B.1.1.529 lineage) when sequence. In the month of January, we analysed a subset of samples (n = 618) with SGTF (24%) and without SGTF (76%) with Ct values Conclusions: During the COVID-19 pandemic, it took almost more than 15 days to diagnose infection and identify pathogen by sequencing technology. In contrast to that molecular assay provided qu

关键词： SARS-CoV-2 S Gene Target Failure Whole Genome Sequencing Omicron

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PCK1 attenuates tumor stemness via activating the Hippo signaling pathway in hepatocellular carcinoma

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Genes & Diseases 2024年第4期11卷 340-352页

作者： Rui Liu Yi Liu Wenlu Zhang Guiji Zhang Zhirong Zhang Luyi Huang Ni Tang Kai Wang Key laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China department of Clinical laboratory Sichuan Clinical Research Center for CancerSichuan Cancer Hospital&InstituteSichuan Cancer CenterAffiliated Cancer Hospital of University of Electronic Science and Technology of ChinaChengduSichuan 610041China

Liver cancer stem cells were found to rely on glycolysis as the preferred metabolic *** carboxylase 1(PCK1),a gluconeogenic metabolic enzyme,is down-regulated in hepatocellular carcinoma and is closely related to poor *** onco-genesis and progression of tumors are closely related to cancer stem *** is not completely clear whether the PCK1 deficiency increases the stemness of hepatoma cells and promotes the oncogenesis of hepatocellular ***,the results showed that PCK1 inhibited the self-renewal property of hepatoma cells,reduced the mRNA level of cancer stem cell markers,and inhibited ***,PCK1 increased the sensitivity of hepatocellular carci-noma cells to ***,we found that PCK1 activated the Hippo pathway by enhancing the phosphorylation of YAP and inhibiting its nuclear *** reduced the stemness of hepatoma cells and promoted the pro-apoptotic effect of ***,combined treatment with verteporfin and sorafenib may be a potential anti-tumor strat-egy in hepatocellular carcinoma.

关键词： Cancer stem cells Chemoresistance Gluconeogenesis Hepatocellular carcinoma YAP

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Preparation and immunoprotective effects of a virus-like particle candidate vaccine of the dominant epidemic D3 genotype coxsackievirus A6 in China

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Biosafety and Health 2024年第1期6卷 28-34页

作者： Xiaoliang Li Xizhu Xu Jichen Li Huanhuan Lu Congcong Wang Rui Wang Jinbo Xiao Ying Liu Yang Song Jingdong Song Qiang Sun Yong Zhang department of Public Health and Health Administration Shandong First Medical UniversityJinan 250117China National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases(NITFID) National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China National Polio laboratory WHO WPRO Regional Polio Reference LaboratoryNational Health Commission Key Laboratory for BiosafetyNational Health Commission Key Laboratory for Medical VirologyNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBejing 102206China department of Medical Microbiology Weifang Medical UniversityWeifang 261053China

Coxsackievirus A6 of the D3a genotype(CVA6 D3a)is a primary pathogen causingmainland of China's hand,foot,and mouth disease(HFMD).viral‐like particle(VLP)vaccines represent a potential candidate vaccine to prevent *** study collected Anti‐CVA6 D3a VLPs serum from BALB/c female mice immunized using CVA6 D3a *** neutralizing antibody levels were compared against the representative 14‐JX2018(D3a)and N4‐YN2015(D3b)strains between the antisera of different immune *** immunoprotective effect of anti‐CVA6 D3a VLPs against these strains was monitored using pathological sections and immuno-histochemical results of lung and skeletal muscle tissues in seven‐day‐old Institute of Cancer Research(ICR)*** protection against different branches of viruses was evaluated in 7‐day‐old(serum passive immune protection)and 14‐day‐old(VLPs active immune protection)neonatal ICR mice ***‐neutralizing antibody levels were positively correlated with the number of immunizations and higher against 14‐JX2018 than against N4‐***,these levels were significantly higher with abdominal injection than intramuscular *** immunized serum of 7‐day‐old ICR mice inoculated three times was 100%protected against CVA6 D3a 14‐JX2018(lethal titer:106.25 TCID 50)and CVA6 D3b N4‐YN2015(lethal titer:105.25TCID 50)fatal attacks,*** ICR mice that have completed two active immunizations for 14 days,both CVA6 D3a 14‐JX2015(challenge titer:108.25 TCID 50)and CVA6 D3b N4‐YN2015(challenge titer:107.25 TCID 50)were used for the challenge,and the mice were able to ***,the CVA6 D3a VLPs prepared in this study are a potential vaccine candidate for CVA6,as it has the optimal protective effect against both CVA6 D3a and D3b evolutionary branches viruses.

关键词： Coxsackievirus A6 D3 genotype Virus‐like particle Immunoprotective effect

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Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling

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Genes & Diseases 2024年第5期11卷 470-483页

作者： Zhirong Zhang Jiayao Yang Rui Liu Jing Ma Kai Wang Xiaojun Wang Ni Tang Key laboratory of Molecular Biology for Infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

Cancer stem cells(CSCs)play a crucial role in tumor initiation,recurrence,metastasis,and drug ***,the current understanding of CSCs in hepatocellular carcinoma(HCC)remains *** a comprehensive analysis of the database,it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR),a critical enzyme involved in cholesterol synthesis,is up-regulated in HCC tissues and liver ***,high expression of HMGCR is associated with a poor prognosis in patients with ***,HMGCR promotes the stemness and metastasis of HCC both in vitro and in *** screening various signaling pathway inhibitors,we have determined that HMGCR regulates stemness and metastasis by activating the Hedgehog signaling in ***,HMGCR positively correlates with the expression of the Smoothened receptor and facilitates the nuclear translocation of the transcriptional activator GLI family zinc finger *** of the Hedgehog pathway can reverse the stimulatory effects of HMGCR on stemness and metastasis in ***,simvastatin,an FDA-approved cholesterol-lowering drug,has been shown to inhibit stemness and metastasis of HCC by targeting *** together,our findings suggest that HMGCR promotes the regeneration and metastasis of HCC through the activation of Hedgehog signaling,and simvastatin holds the potential for clinical suppression of HCC metastasis.

关键词： Cancer stem cells Hedgehog Hepatocellular carcinoma Metastasis Statin

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Seroprevalence of neutralizing antibodies against HFMD associated enteroviruses among healthy individuals in Shanghai,China,2022

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Virologica Sinica 2024年第4期39卷 694-698页

作者： Jiayu Wang Wencheng Wu Wei Wang Jingyi Zhang Jianwei Xiao Mingyi Cai Jiaying Guo Run Li Shuangli Zhu Wanju Zhang Min Chen Zheng Teng Microbiology department Shanghai Municipal Center for Disease Control and PreventionShanghai200336China Microbiology department Yangpu Municipal Center for Disease Control and PreventionShanghai200090China Microbiology department Jing’an Municipal Center for Disease Control and PreventionShanghai200070China Microbiology department Changning Municipal Center for Disease Control and PreventionShanghai200050China WHO WPRO Regional Polio Reference laboratory NHC Key Laboratory for BiosafetyNHC Key Laboratory for Medical VirologyNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing102206China

Dear Editor,Hand,foot and mouth disease(HFMD)is one of the most common infectious diseases,particularly in the Asia-Pacific *** the past two decades,HFMD rises to prominence for its heavy burden,with over one million cases reported *** 2013,enterovirus A71(EV-A71)and Coxsackievirus A16(CVA16)were the main pathogens leading to HFMD in the mainland of China(Yang et al.,2017).In recent years,non-EV-A71-non-CVA16 other enteroviruses,such as Coxsackievirus A6(CVA6),Coxsackievirus A10(CVA10)and Coxsackievirus A4(CVA4),were frequently reported and replaced EV-A71 and CVA16 becoming the major causative agents of HFMD(Zhou et al.,2021;Wang et al.,2022).

关键词： enterovirus HFMD al.

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More common RNAemia in the early stage of severe SARS-CoV-2 BF.7.14 infections in pediatric patients

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Biosafety and Health 2024年第1期6卷 5-11页

作者： Yu Sun Runan Zhu Yang Pan Ri De Shuang Liu Liping Jia Bing Lv Xiaoyun Li Dongmei Chen Yao Yao Dong Qu Daitao Zhang Linqing Zhao laboratory of Virology Bejing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBejing 100020China Institute for Infectious Disease and Endemic Disease Control Bejing Center for Disease Control and Prevention Beijing 100013China department of Intensive Care Unit Affiliated Children's Hospital of Capital Institute of PediatricsBeijing 100020China

The risk factors of severe infections in children during the severe acute respiratory syndrome coronavirus 2(SARS‐CoV‐2)outbreak in Beijing remain ***‐CoV‐2‐positive children admitted to the intensive care unit(ICU)with collected plasma specimens were enrolled and screened for common pathogens using capillary electrophoresis‐based multiplex PCR from December 12,2022,to January 24,*** SARS‐CoV‐2 subvariants were identified using next‐generation *** was positive for two(positive;P),one(suspicious;S),or no(negative;N)SARS‐CoV‐2 genes were classified as plasmatic RNA‐positive(RNAemia;P+S)or without RNAemia(N).Clinical and laboratory data of the enrolled cases were then collected and *** 34 enrolled children included 26 males and 24 younger than three *** were negative for other respiratory ***.7.14(18/29)was the predominant *** loads in respiratory specimens,hours from symptom onset to the first respiratory specimen collection(time‐variable),with comorbidities and BF.7.14 and BA.5.2 distributions were significantly different in P vs.N and RNAemia *** RNAemia *** most cases,the T lymphocyte ratios decreased,while the cytokine level and the B lymphocyte ratio *** time variables were 2.22±2.05 and 4.00±2.49 days in BF.7.14 and BA.5.2 infections,*** conclusion,SARS‐CoV‐2 was more likely to cause severe infections among males aged≤3 years old with comorbidities during the SARS‐CoV‐2 outbreak in Beijing,while RNAemia is more common in children at the early stage of severe BF.7.14 infections,and most had high cytokine levels and B‐cell activation.

关键词： Severe SARS‐CoV‐2 infection Pediatric patients Risk factor RNAemia BF.7.14

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A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells(TCR-T cells)against hepatocellular carcinoma

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2215-2230页

作者： Wei Zhu Zhiming Zhang Jinzhang Chen Xiaolan Chen Lei Huang Xiaoyong Zhang Xuan Huang Na Ma Weikang Xu Xuan Yi Xinyu Lu Xin Fu Siwei Li Guoheng Mo Yiyue Wang Guosheng Yuan Mengya Zang Qi Li Xiaotao Jiang Yajing He Sha Wu Yukai He Yongyin Li Jinlin Hou State Key laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis ResearchDepartment of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouChina Institute of Cellular Medicine Newcastle University Medical SchoolNewcastleUK department of Pathology The First People’s Hospital of FoshanFoshanChina Dermatology Hospital Southern Medical UniversityGuangzhouChina department of Immunology School of Basic Medical SciencesSouthern Medical UniversityGuangzhouChina Microbiome Medicine Center Department of Laboratory MedicineZhujiang HospitalSouthern Medical UniversityGuangzhouChina Key laboratory of Proteomics of Guangdong Province Demonstration Center for Experimental Education of Basic Medical Sciences of ChinaGuangzhouChina Medical College of Georgia Augusta University112015th StreetAugustaGAUSA

Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma(HCC)are urgently *** common cytokine receptorγchain(γc)family cytokines such as IL-2,IL-7,IL-15 and IL-21 play fundamental roles in T cell development,differentiation and effector *** study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell *** antitumor function of AFP-specific T cell receptor-engineered T cells(TCR-T)was augmented by exogenous IL-21 in vitro and in ***-21 enhanced proliferation capacity,promoted memory differentiation,downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation.A novel engineered IL-21 receptor was established,and TCR-T armed with the novel engineered IL-21 receptors(IL-21R-TCR-T)showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ***-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in ***-21R-TCR-T exhibited a less differentiated,exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen *** novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic *** novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

关键词： hepatocellular TCR utilize

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Epidemiological Characteristics of Human Parainfluenza Viruses Infections-China,2019-2023

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China CDC weekly 2024年第12期6卷 235-241,I0003,I0004页

作者： Yixuan Gao Yingwei Ma Daxing Feng Feng Zhang Biao Wang Xiaoqing Liu Bing Zhu Hui Xie Linqing Zhao Xiaoru Long Ying Chen Bing Wang Jie Jiang Zhen Zhu Yan Zhang Aili Cui Baicheng Xia Naiying Mao National Key laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Precision Medicine Research Center Children’s Hospital of ChangchunChangchun CityJilin ProvinceChina Henan Provincial Center for Disease Control and Prevention Zhengzhou CityHenan ProvinceChina laboratory of viral Diseases Qingdao Municipal Centre for Disease Control and PreventionQingdao CityShandong ProvinceChina Virus laboratory Gansu Provincial Center for Disease Control and PreventionLanzhou CityGansu ProvinceChina Jiangxi Provincial Center for Disease Control and Prevention Nanchang CityGansu ProvinceChina Virus laboratory Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina Institute for Immunization and Prevention Beijing Center for Disease Prevention and ControlAcademy for Preventive MedicineInstitute of Tuberculosis Control Research and PreventionBeijingChina laboratory of Virology Beijing Key Laboratory of Etiology of Viral Diseases in ChildrenCapital Institute of PediatricsBeijingChina department of Infection Children’s Hospital of Chongqing Medical UniversityChongqingChina Inner Mongolia Autonomous Region Comprehensive Center for Disease Control and Prevention Hohhot CityInner Mongolia Autonomous RegionChina Shenyang Prefecture Center for Disease Control and Prevention Shenyang CityLiaoning ProvinceChina

Introduction:A retrospective study based on sentinel surveillance was conducted in 10 provinciallevel administrative divisions(PLADs)in China to enhance the understanding of the epidemiological characteristics of human parainfluenza viruses(HPIVs).Methods:From January 2019 to June 2023,respiratory specimens were collected from individuals with acute respiratory infections(ARIs)and screened for four HPIVs serotypes and other common respiratory viruses using multiplex real-time polymerase chain reaction(PCR).This study analyzed the association of HPIVs infections with seasonal patterns,geographical distribution,demographic profiles,clinical features,and co-infection ***:During the study period,a total of 12,866 ARIs were *** overall detection rate of HPIVs was 6.15%,varying from 5.04%in 2022 to 9.70%in *** median age of HPIVs-infected patients was 3 ***2 was more prevalent among individuals aged 5–17 years(42.57%),while HPIV4 was more common in those over 65 years(12.24%).HPIV3(54.16%)and HPIV1(27.18%)were the predominant serotypes,and their prevalence exhibited significant seasonal fluctuations postcoronavirus disease 2019(COVID-19)*** peak of HPIV3 shifted three months later in 2020 compared to 2019 and returned to a summer peak *** peaks of HPIV1 were observed in 2021 following the peak of ***,coinfections were frequent in HPIVs cases(overall rate:22.12%),with human rhinovirus being the most common co-infecting ***:The prevalence of HPIVs in China was predominantly due to HPIV3 and HPIV1,and their seasonal patterns were altered by pandemic ***,continuous surveillance of HPIVs is essential.

关键词： prevalence seasonal Human

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