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Real-world effectiveness of early insulin therapy on the incidence of cardiovascular events in newly diagnosed type 2 diabetes

中国遗传学会“发育、遗传和疾病”研讨会

作者： Yong Zhang~1 Xue-Tao Bai~1 Yi Jin~(1,2) Min Deng~2 Yi Chen~(1,2) Huang-Ying Le~(1,2) Yah-Fang Fu~2 Xiao-Jian Sun~(1,2) Jiang Zhu~1 Zhu Chen~(1,4) Sai-Juan Chen~1 Ting Xi Liu~(1,2,3) 1.State Key Laboratory for Medical Genomics and shanghai institute of Hematology,ruijin hospital affiliated to shanghai jiao tong university school of medicine,shanghai 200025,china 2.Laboratory of Development and Diseases,institute of Health Sciences,shanghai institutes for Biological Sciences,Chinese Academy of Sciences & shanghai jiao tong university school of medicine,shanghai 20002,china 3.Model organism division,e-institutes of shanghai universities,shanghai 200025,china 4.shanghai Center for Systems Biomedicine,shanghai jiao tong university,shanghai 200240,china

We have established an in vivo model for visualizing the developmental and chemotactic movement of primitive macrophages,by generating a stable transgenic line expressing eGFP under the zebrafish lysozyme C promoter [TG(zlyz:eGFP)].We show that the earliest macrophages originate from the head mesenchyme nearby the bilateral plate mesoderm at～22 hpf,then migrate either within the head or toward the yolk sac close to the circulation *** macrophages subsequently colonize the posterior intermediate cell mass(ICM)through ***,the resident macrophages,but not the circulating macrophages,migrate rapidly to the site of inflammation induced by tail transection,with their number peaking at approximately 5-6 hours after *** hours post-injury,these recruited macrophages initiate retrograde migration from the inflamed tail back to the ICM mesenchyme,suggesting a resolution of the ***,an anti-inflammatory glucocorticoid hormone (dexamethasone)suppresses both the chemotactic and retrograde migration of macrophages during the onset and resolution of ***,the TG(zlyz:eGFP)zebrafish provides an invaluable tool not only for elucidating the pleiotropic roles of macrophages in innate immunity,tumorigenesis and organogenesis during embryogenesis,but for identifying the therapeutic small molecules against human disorders associated with deregulated migration and chemotaxis of macrophage in vivo.

关键词： A Transgenic Zebrafish Model of Macrophage Migration and Chemotaxis Model

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2953-2959页

作者： Sihui Luo Xueying Zheng Wei Bao Sheng Nie Yu Ding tong Yue Yilun Zhou Ying Hu Hua Li Qiongqiong Yang Qijun Wan Bicheng Liu Hong Xu Guisen Li Gang Xu Chunbo Chen Huafeng Liu Yongjun Shi Yan Zha Yaozhong Kong Guobin Su Ying Tang Mengchun Gong Linong Ji Fan Fan Hou Jianping Weng Department of endocrinology First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHeifeiChina institute of Public Health Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina division of Nephrology National Clinical Research Center for Kidney DiseaseState Key Laboratory of Organ Failure ResearchNanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Nephrology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina The Second Affiliated hospital of Zhejiang university school of medicine HangzhouChina Sir Run Run Shaw hospital Zhejiang University School of MedicineHangzhouChina Department of Nephrology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina The Second People’s hospital of Shenzhen Shenzhen UniversityShenzhenChina institute of Nephrology Zhongda HospitalSoutheast University School of MedicineNanjingChina Children’s hospital of Fudan university ShanghaiChina Renal Department and institute of Nephrology Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaSichuan Clinical Research Center for Kidney DiseasesChengduChina division of Nephrology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Critical Care medicine Maoming People’s HospitalMaomingChina Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City Institute of NephrologyAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina Huizhou Central People’s hospital Sun Yat-Sen UniversityHuizhouChina Guizhou Provincial People’s hospital Guizhou UniversityGuiyangChina Department of Nephrology the First People’s Hospital of FoshanFoshanChina Department of Nephrology Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospitalthe Second Clinical CollegeGuangzhou University of Chinese Medicin

early insulin therapy is capable to achieve glycemic control and restoreβ-cell function in newly diagnosed type 2 diabetes(T2D),but its effect on cardiovascular outcomes in these patients remains *** this nationwide real-world study,we analyzed electronic health record data from 19 medical centers across china between 1 January 2000,and 26 May *** included 5424 eligible patients(mean age 56 years,2176 women/3248 men)who were diagnosed T2D within six months and did not have prior cardiovascular *** Cox regression models were used to estimate the associations of early insulin therapy(defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients)with the incidence of major cardiovascular events including coronary heart disease(CHD),stroke,and hospitalization for heart failure(HF).During 17,158 persons years of observation,we documented 834 incident CHD cases,719 stroke cases,and 230 hospitalized cases for *** diagnosed T2D patients who received early insulin therapy,compared with those who did not receive such treatment,had 31%lower risk of incident stroke,and 28%lower risk of hospitalization for *** significant difference in the risk of CHD was *** found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting *** findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

关键词： cardiovascular treatment nationwide

Sumoylation of hypoxia inducible factor-1α and its significance in cancer

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Science china(Life Sciences) 2014年第7期57卷 657-664页

作者： LI Jie XU Ying jiao HuiKe WANG Wei MeI Zhu CHeN GuoQiang Department of Pathophysiology Chemical Biology Division of Shanghai Universities E-InstitutesKey Laboratory of Cell Differentiation and Apoptosis of Ministry of EducationShanghai Jiao Tong University School of Medicine institute of Health Sciences Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine

Hypoxia-inducible factor-1(HIF-1)is a key heterodimeric transcription factor for the cellular adaptive response to hypoxia,a common feature of the microenvironment in solid *** transcriptional activity,protein stabilization,protein-protein interactions and cellular localization of HIF-1α,an oxygen-sensitive subunit of HIF-1,are mainly modulated by various post-translational ***,we reported that polycomb chromobox 4(Cbx4)governs the transcriptional activity of HIF-1αby enhancing its sumoylation at K391 and K477,through which Cbx4 potentiates angiogenesis of hepatocellular *** review summarizes the current knowledge of HIF-1α sumoylation and its roles in the pathogenesis of cancer.

关键词： HIF-1α sumoylation cancer

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Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling

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蛋白质与细胞:英文版 2023年第8期14卷 603-617页

作者： Min Wei Yanping Sun Shouzhen Li Yunuo Chen Longfei Li Minghao Fang Ronghua Shi Dali tong Jutao Chen Yuqian Ma Kun Qu Mei Zhang Tian Xue division of Life Sciences and medicine Department of OphthalmologyThe First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefei 230026China Hefei National Research Center for Physical Sciences at the Microscale Neurodegenerative Disorder Research CenterCAS Key Laboratory of Brain Function and DiseaseUniversity of Science and Technology of ChinaHefei 230026China division of Life Sciences and medicine School of Life SciencesUniversity of Science and Technology of ChinaHefei 230026China Center for excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100864China

Light adaptation enables the vertebrate visual system to operate over a wide range of ambient *** of phototransduction in photoreceptors is considered a major mechanism underlying light ***,various types of neurons and glial cells exist in the retina,and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic ***,we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in *** results demonstrated that,in addition to photoreceptors,other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark ***,Müller glial cells(MGs)were identified as hub cells for intercellular interactions,displaying complex cell‒cell communication with other retinal ***,light increased the transcription of the deiodinase Dio2 in MGs,which converted thyroxine(T4)to active triiodothyronine(T3).Subsequently,light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light *** cones specifically express the thyroid hormone receptor Thrb,they responded to the increase in T3 by adjusting light *** of the expression of Dio2 specifically in MGs decreased the light responsive ability of *** results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.

关键词： single cell Müller glial cells intercellular communication light/dark adaptation thyroid hormone signaling

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Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques

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Protein & Cell 2023年第1期14卷 69-73页

作者： Dali tong Mei Zhang Yunru Yang Han Xia Haiyang tong Huajun Zhang Weihong Zeng Muziying Liu Yan Wu Huan Ma Xue Hu Weiyong Liu Yuan Cai Yanfeng Yao Yichuan Yao Kunpeng Liu Shifang Shan Yajuan Li Ge Gao Weiwei Guo Yun Peng Shaohong Chen Juhong Rao Jiaxuan Zhao Juan Min Qingjun Zhu Yanmin Zheng Lianxin Liu Chao Shan Kai Zhong Zilong Qiu Tengchuan Jin Sandra Chiu Zhiming Yuan Tian Xue First Affiliated hospital of USTC School of Life SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China Hefei National Research Center for Physical Sciences at the Microscale Neurodegenerative Disorder Research CenterCAS Key Laboratory of Brain Function and DiseaseCAS Key Laboratory of Innate Immunity and Chronic DiseaseBiomedical Sciences and Health Laboratory of Anhui ProvinceUniversity of Science and Technology of ChinaHefei 230026China State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Center for Biosafety Mega-Science Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China Hefei institutes of Physical Science Chinese Academy of SciencesHefei 230031China Anhui institute of Pediatric Research Anhui Provincial Children's HospitalHefei 230051China Chinese Academy of Sciences Center for excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Department of Clinical Laboratory First Affiliated Hospital of Anhui Medical UniversityHefei230022China institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Dear editor,Coronavirus disease 2019(COVID-19)is a highly infectious respiratory disease that continues to pose a serious global public health *** disease shows a high infection rate,long incubation period,and rapidly emerging variants,which have led to its rapid spread worldwide(Krammer 2020).Many vaccines have been developed for the control of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),the virus responsible for COVID-19,including vaccines based on messenger RNA(mRNA)(Polack et al.2020),viral vectors(Zhu et al.2020),recombinant proteins(Yang et al.2020),and inactivated SARS-CoV-2(Zhang et al.2021).

关键词： respiratory acute

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A single-cell transcriptome atlas of the aging human and macaque retina

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National Science Review 2021年第4期8卷 48-65页

作者： Wenyang Yi Yufeng Lu Suijuan Zhong Mei Zhang Le Sun Hao Dong Mengdi Wang Min Wei Haohuan Xie Hongqiang Qu Rongmei Peng Jing Hong Ziqin Yao Yunyun tong Wei Wang Qiang Ma Zeyuan Liu Yuqian Ma Shouzhen Li Chonghai Yin Jianwei Liu Chao Ma Xiaoqun Wang Qian Wu Tian Xue eye Center at The First Affiliated hospital of USTC Hefei National Laboratory for Physical Sciences at the MicroscaleSchool of Life Sciences Division of Life Sciences and Medicine University of Science and Technology of China State Key Laboratory of Brain and Cognitive Science Institute of Brain-Intelligence TechnologyBioland Laboratory Institute of Biophysics Chinese Academy of Sciences university of Chinese Academy of Sciences State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal University IDG/McGovern institute for Brain Research Beijing Normal University Neurodegenerative Disorder Research Center CAS Key Laboratory of Brain Function and DiseaseUniversity of Science and Technology of China Department of Ophthalmology Beijing Key Laboratory of Restoration of Damaged Ocular Nerve Peking University Third Hospital Chinese Academy of Medical Sciences & Peking Union Medical College State Key Laboratory of Brain and Cognitive Science Institute of Brain-Intelligence Technology (Shanghai)Bioland Laboratory (Guangzhou) Institute of Biophysics Chinese Academy of Sciences institute for Stem Cell and Regeneration Chinese Academy of Sciences Advanced Innovation Center for Human Brain Protection Beijing Institute for Brain DisordersCapital Medical University Center for excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences National Resource Center for Non-Human Primates(Kunming) Primate Research Center at IBP(Beijing) Chinese Academy of Sciences

The human retina is a complex neural tissue that detects light and sends visual information to the ***, the molecular and cellular processes that underlie aging primate retina remain unclear. Here, we provide a comprehensive transcriptomic atlas based on 119 520 single cells of the foveal and peripheral retina of humans and macaques covering different ages. The molecular features of retinal cells differed between the two species, suggesting distinct regional and species specializations of the human and macaque retinae. In addition, human retinal aging occurred in a region-and cell-type-specific manner. Aging of human retina exhibited a foveal to peripheral gradient. MYO9A~-rods and a horizontal cell subtype were greatly reduced in aging retina, indicating their vulnerability to aging. Moreover, we generated a dataset showing the cell-type-and region-specific gene expression associated with 55 types of human retinal disease, which provides a foundation to understanding of the molecular and cellular mechanisms underlying human retinal diseases. Such datasets are valuable to understanding of the molecular characteristics of primate retina, as well as molecular regulation of aging progression and related diseases.

关键词： single-cell RNA sequencing primate retina aging cell heterogeneity age-related disease cell-cell communication

USP7 deubiquitinates and stabilizes NOTCH1 in T-cell acute lymphoblastic leukemia

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Signal Transduction and Targeted Therapy 2018年第1期3卷 52-61页

作者： Huizhuang Shan Xiangyun Li Xinhua Xiao Yuting Dai Jinyan Huang Junjun Song Meng Liu Li Yang Hu Lei Yin tong Li Zhou Hanzhang Xu Yingli Wu Hongqiao International institute of medicine Shanghai Tongren Hospital/Faculty of Basic MedicineChemical Biology Division of Shanghai Universities E-InstitutesKey Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of EducationShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Hematology Rui-Jin HospitalShanghai Jiao Tong University School of MedicineNo.197Ruijin Er RoadShanghaiChina shanghai university of medicine&Health Sciences No.279Zhouzhu RoadShanghaiChina Department of Hematology Shanghai First People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

T-cell acute lymphoblastic leukemia(T-ALL)is a highly aggressive leukemia that is primarily caused by aberrant activation of the NOTCH1 signaling *** studies have revealed that posttranslational modifications,such as ubiquitination,regulate NOTCH1 stability,activity,and ***,the specific deubiquitinase that affects NOTCH1 protein stability remains ***,we report that ubiquitin-specific protease 7(USP7)can stabilize ***7 deubiquitinated NOTCH1 in vivo and in vitro,whereas knockdown of USP7 increased the ubiquitination of ***7 interacted with NOTCH1 protein in T-ALL cells,and the MATH and UBL domains of USP7 were responsible for this *** of USP7 significantly suppressed the proliferation of T-ALL cells in vitro and in vivo,accompanied by downregulation of the NOTCH1 protein ***,pharmacologic inhibition of USP7 led to apoptosis of T-ALL *** importantly,we found that USP7 was significantly upregulated in human T-ALL cell lines and patient samples,and a USP7 inhibitor exhibited cell cytotoxicity toward primary T-ALL cells,indicating the clinical relevance of these ***,our results demonstrate that USP7 is a novel deubiquitinase that stabilizes ***,USP7 may be a promising therapeutic target in the currently incurable T-ALL.

关键词： ubiquitin USP7 lymphoblastic