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Reduced clinical severity during 2022 shanghai Spring epidemic of SARS-CoV-2 omicron BA.2 variant infection——an integrated account of virus pathogenicity and vaccination effectiveness

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National Science Review 2024年第4期11卷 24-27页

作者： Xingyue Wu Yao Chen Kangli Cao Yao Shen Xueling Wu Yilin Yang Zhongshu Kuang Qingrun Li Zhenzhen Lu Yichen Jia Mian Shao Guorong Gu Xiangwei Wang Ye Yao Ying Wang Shaodie Chen Zhigao Yu Wei Wei Longfei Ding Lulu Lan Tianwen Gu Xiangyu Long Jian Sun Lingyu Xing Jiayuan Shen Yi Han Yue Luo Sucheng Mu Mengna Lin Xiaoyan Zhang Rong Zeng Jianqing Xu Guoping Zhao Lihong Huang Zhenju Song Department of Emergency Medicine Clinical Center for Bio-Therapy Department of Biostatistics and Department of UrologyShanghai Key Laboratory of Lung Inflammation and Injury Zhongshan Hospital Fudan University Department of Respiratory and Critical Care Medicine Shanghai Pudong Hospital Fudan University Department of Pulmonology Renji Hospital Shanghai Jiao Tong University School of Medicine Key Laboratory of Systems Biology Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences shanghai public health clinical center Fudan University Department of Biostatistics School of Public Health Key Laboratory of Public Health Safety of Ministry of Education and Shanghai Institute of Infectious Disease and Biosecurity School of Public Health Fudan University shanghai Institute of Immunology Department of Immunology and Microbiology Shanghai Institute of Virology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationSchool of Medicine Shanghai Jiao Tong University State Key Laboratory of Genetic Engineering Fudan Microbiome CenterSchool of Life Sciences Fudan University Bio-Med Big Data center Shanghai Institute of Nutrition and Health Chinese Academy of Sciences

The emergence of SARS-Co V-2 variant of concern omicron BA.2 led to high infection incidence rates as well as reduced severity of COVID-19 during the shanghai Spring epidemic of 2022 [1]. We assessed the role of viral pathogenicity and the effectiveness of inactivated vaccines in a retrospective observational study including 10 258 confirmed COVID-19cases identified between April and June of 2022, from four COVID-19 designated hospitals located in two areas of shanghai, namely the West Bund and the East Bund, where the populations’ demographic characteristics varied significantly (Table S1, Fig. S1).

关键词： REPLICATION

Improving the value of molecular testing:current status and opportunities in colorectal cancer precision medicine

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Cancer Biology & Medicine 2024年第1期21卷 21-28页

作者： Haiyun Li Linwei Guo Chenchen Wang Xin Hu Ye Xu Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Gastrointestinal Medical Oncology Fudan University Shanghai Cancer CenterShanghai 200032China Precision Cancer Medical center affiliated with fudan university shanghai Cancer center Shanghai 201315China

Colorectal cancer(CRC)is the second leading cause of cancer-related deaths *** radical resection with adjuvant chemotherapy remains the primary treatment choice for CRC,but the 5-year postoperative survival rate is only approximately 60%,and approximately one-third of patients with CRC experience recurrence within 2 years of ***,the transformation of high-throughput sequencing has accelerated the development of precision *** example,KRAS mutations indicate resistance to anti-epidermal growth factor receptor(EGFR)-targeted therapies in ***,molecular-guided individualized therapy has brought new promise in major clinical areas and challenges,such as novel biomarkers predicting sensitivity and resistance to immunotherapy for microsatellite stable(MSS)CRC.

关键词： cancer chemotherapy colorectal

Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1199-1208页

作者： Xinyi Yang Xu Zheng Yuqi Zhu Xiaying Zhao Jun Liu Jiangna Xun Songhua Yuan Jun Chen Hanyu Pan Jinlong Yang Jing Wang Zhimin Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Min Li Fei Peng Daru Lu Jianqing Xu Hongzhou Lu Shibo Jiang Ping Zhao Huanzhang Zhu State Key Laboratory of Genetic Engineering and Engineering Research center of Gene Technology Ministry of EducationInstitute of GeneticsSchool of Life SciencesYiwu Research InstituteFudan UniversityShanghaiChina Department of Microbiology Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Scientific Research center Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Infectious Diseases and Immunology Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Changzheng Hospital Naval Medical UniversityShanghaiChina Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghaiChina Department of Infectious Diseases and Nursing Research Institution National Clinical Research Center for Infectious DiseasesThe Third People’s Hospital of ShenzhenShenzhenGuangdongChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)causes multi-organ damage,which includes hepatic dysfunction,as observed in over 50%of COVID-19 *** I converting enzyme(peptidyl-dipeptidase A)2(ACE2)is the primary receptor for SARS-CoV-2 entry into host cells,and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2,but at extremely low ***,we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into *** address this question,we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1(ASGR1)promoted SARS-CoV-2 pseudovirus infection of HeLa *** Huh-7 cells,simultaneous knockout of ACE2 and ASGR1 prevented SARS-CoV-2 pseudovirus *** the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells,both of which barely expressed ACE2,SARSCoV-2 pseudovirus could successfully establish an ***,after treatment with ASGR1 antibody or siRNA targeting ASGR1,the infection rate significantly dropped,suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent *** confirmed that ASGR1 could interact with Spike protein,which depends on receptor binding domain(RBD)and N-terminal domain(NTD).Finally,we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal *** inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA,the infection efficiency of the live virus decreased ***,these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.

关键词： ACE2 infection glycoprotein

Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

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Biomedical and Environmental Sciences 2024年第2期37卷 170-177页

作者： GU Wen Fei SHI Xia MA Xin YU Jun Lei XU Jin Chuan QIAN Cheng Cheng HU Zhi Dong ZHANG Hui shanghai public health clinical center Fudan UniversityShanghai 201508China School of Laboratory Medicine and Life Science Wenzhou Medical UniversityWenzhou 325000ZhejiangChina Department of Laboratory Medicine Zhejiang Putuo HospitalZhoushan 316100ZhejiangChina Zhongshan Hospital Fudan UniversityShanghai 200032China

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the shanghai public health clinical center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological *** assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),*** on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),*** examination showed the highest sensitivity but lowest ***,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of *** with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower *** combination of histopathology with Xpert showed the best performance characteristics.

关键词： Extrapulmonary tuberculosis Diagnosis Biopsy Histopathological examination Puncture samples

METTL5 promotes gastric cancer progression via sphingomyelin metabolism

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1925-1946页

作者： Ya-Qiong Zhang Jian Li Zhe Qin De-Ming Li Fang-Zhou Ye Song-Hua Bei Xiao-Hong Zhang Li Feng Endoscopy center Minhang Hospital Affiliated to Fudan UniversityShanghai 201100China

BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden *** studies have reported that N6-methyladenosine(m6A)is closely related to tumor ***5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of ***,its aberrant regulation in GC has not been fully *** To excavate the role of METTL5 in the development of *** METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry,western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical *** tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays,colony formation assays,scratch healing assays,transwell assays and flow *** tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor *** EpiQuik m6A RNA Methylation Quantification Kit was used for m6A ***,liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism,which was confirmed by Enzyme-linked immunosorbent assay and rescue *** addition,we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell *** Our research revealed substantial upregulation of METTL5,which suggested a poor prognosis of GC *** METTL5 expression indicated distant lymph node metastasis,advanced cancer stage and pathological *** increased level of METTL5 correlated with a high degree of m6A ***5 markedly promotes the proliferation,migration,and invasion of GC cells in ***5 also promotes the growth of GC in animal ***5 knockdown resulted in significant changes in sphingomyelin metabolism,which implies that METTL5 may impact the development of GC via sphin

关键词： Gastric cancer METTL5 Sphingomyelin metabolism Cisplatin

Genetic mutation of Tas2r104/Tas2r105/Tas2r114 cluster leads to a loss of taste perception to denatonium benzoate and cucurbitacin B

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Animal Models and Experimental Medicine 2024年第3期7卷 324-336页

作者： Bowen Niu Lingling Liu Qian Gao Meng-Min Zhu Lixiang Chen Xiu-Hua Peng Boying Qin Xiaohui Zhou Feng Li Department of Laboratory Animal Science Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Biology College of Life SciencesShanghai Normal UniversityShanghaiPeople's Republic of China

Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic *** taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in ***:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the ***,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder *** real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste *** to taste substance was also studied using twobottle preference ***:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 *** results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant *** qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant *** two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of *** addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB ***:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.

关键词： bitter taste receptor CRISPR/Cas9 genetic mutation two-bottle preference test type 2 taste receptors(Tas2rs)

Evaluation of antibody responses in healthy individuals receiving SARS-CoV-2 inactivated vaccines

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Biosafety and health 2024年第3期6卷 153-164页

作者： Ziyu Liu Liyan Cai Man Xing Nan Qiao Jiaojiao Liu Xuejun Li Chiyu Zhang Naijun Tang Zhelong Xu Yingying Guo Renfei Lu Dongming Zhou Department of Pathogen Biology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Physical examination center Affiliated Nantong Hospital 3 of Nantong UniversityNantong 226000China shanghai public health clinical center Fudan UniversityShanghai 201508China Department of Occupational and Environmental health School of Public HealthTianjin Medical UniversityTianjin 300070China clinical Laboratory Affiliated Nantong Hospital 3 of Nantong UniversityNantong 226000China

Inactivated coronavirus disease 2019(COVID-19)vaccines such as CoronaVac and BBIBP-CorV have been widely used in ***,more investigation is still needed to understand antibodies'duration and effectiveness against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants in the real *** this study,575 participants who had been vaccinated with two or three doses of the inactivated vaccine were *** samples were collected and tested for anti-spike IgG and neutralizing antibodies against SARS-CoV-2(original strain,Dela,and Omicron).Unsurprisingly,a third dose of the vaccine significantly enhanced antibody responses against SARS-CoV-2 and its ***,despite a booster dose,the neutralizing antibody levels against Omicron,particularly the BA.5.2 subvariant,remained *** was no sex bias,but an age bias was ***,the predominant IgG subclass antibodies were IgG1 and IgG2,with a much lower level of *** the booster shot,the ratio of IgG4 to IgG1 significantly *** observation of IgG1 to the IgG4 class switch after repeated inactivated vaccinations underscores the importance of continuous monitoring of subclass antibody *** clinical investigations are required to understand the implications of this class switch for optimizing immunization strategies.

关键词： Variant of concern(VOC) Inactivated vaccines Serological study IgG subclasses Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)

Higher ambient temperatures may worsen obstructive sleep apnea:A nationwide smartwatch-based analysis of 6.2 million person-days

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Science Bulletin 2024年第13期69卷 2114-2121页

作者： Anni Li Qingli Zhang Yuan Yao Xinlei Zhu Cong Liu Yutao Guo Haidong Kan Renjie Chen School of public health Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology AssessmentFudan UniversityShanghai 200032China Ministry of Education-shanghai Key Laboratory of Children’s Environmental health Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Pulmonary Vessel and Thrombotic Disease Sixth Medical CenterChinese PLA General HospitalBeijing 100048China Institute for Hospital Management Research Chinese PLA General HospitalBeijing 100048China Children’s Hospital of fudan university National Children’s Medical CenterShanghai 201102China School of public health Hengyang Medical SchoolUniversity of South ChinaHengyang 421001China

Obstructive sleep apnea(OSA)is a serious type of sleep disorder that can lead to cardiometabolic and neurocognitive *** utilized smart device-based photoplethysmography technology to collect sleep data from the Chinese population from 2019 to *** lag nonlinear models combined with a generalized nonlinear model or a linear mixed effects model were used to investigate the shortterm associations between daily temperature and indicators of OSA *** included a total of 6,232,056 d of sleep monitoring data from 51,842 participants with moderate to severe risk of OSA from 313 Chinese *** relationships between ambient temperature and OSA exacerbation,apneahypopnea index(AHI),and minimum oxygen saturation(MinSpO_(2))were almost linear and present only on the same *** temperatures were associated with a greater risk of OSA exacerbation,with an 8.4%(95%confidence interval(CI):7.6%–9.3%)increase per 10℃increase in temperature.A 10℃increase in daily temperature corresponded to an AHI increase of 0.70 events/h(95%CI:0.65–0.76)and a MinSpO_(2)decrease of 0.18%(95%CI:0.16%–0.19%).Exposure to elevated temperatures during the night can also lead to adverse *** effects of higher temperatures on OSA severity were stronger among men,participants with a body mass index24 kg/m2,those aged 45 years and older,individuals with a history of hypertension and diabetes,and during the cold *** large-scale,nationwide,longitudinal study provides robust evidence suggesting that higher ambient temperatures may immediately worsen OSA.

关键词： Obstructive sleep apnea Temperature Apnea-hypopnea index Oxygen saturation Smart device

The risk of mpox importation and subsequent outbreak potential in Chinese mainland: a retrospective statistical modelling study

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Infectious Diseases of Poverty 2024年第1期13卷 63-73页

作者： Xiaowei Deng Yuyang Tian Junyi Zoul Juan Yang Kaiyuan Sun Hongjie Yu School of public health Key Laboratory of Public Health SafetyMinistry of EducationFudan UniversityShanghai 200032China Division of International Epidemiology and Population Studies Fogarty International CenterNational Institutes of HealthBethesdaMDUSA

Background The 2022-2023 mpox(monkeypox)outbreak has spread rapidly across multiple countries in the non-endemic region,mainly among men who have sex with men(MSM).In this study,we aimed to evaluate mpox's importation risk,border screening effectiveness and the risk of local outbreak in Chinese *** We estimated the risk of mpox importation in Chinese mainland from April 14 to September 11,2022 using the number of reported mpox cases during this multi-country outbreak from *** and the international air-travel data from Official Aviation *** constructed a probabilistic model to simulate the effectiveness of a border screening scenario during the mpox outbreak and a hypothetical scenario with less stringent quarantine *** we further evaluated the mpox outbreak potential given that undetected mpox infections were introduced into men who have sex with men,considering different transmissibility,population immunity and population *** We found that the reduced international air-travel volume and stringent border entry policy decreased about 94% and 69% mpox importations *** the quarantine policy,15-19% of imported infections would remain *** a case of mpox is introduced into active MSM population with almost no population immunity,the risk of triggering local transmission is estimated at 42%,and would rise to>95% with over six *** Our study demonstrates that the reduced international air-travel volume and stringent border entry policy during the COvID-19 pandemic reduced mpox importations ***,the risk could be sub-stantially higher with the recovery of air-travel volume to pre-pandemic *** could emerge as a public health threat for Chinese mainland given its large MSM community.

关键词： Mpox(Monkeypox) Importation risk International air travel Statistical modelling Men who have sex with men