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Association of variants in the KIF1A gene with amyotrophic lateral sclerosis

Translational Neurodegeneration 2022年第1期11卷 235-247页

作者： Panlin Liao Yanchun Yuan Zhen Liu Xiaorong Hou Wanzhen Li Jin Wen Kexuan Zhang Bin Jiao Lu Shen Hong Jiang Jifeng Guo Beisha Tang Zhuohua Zhang Zhonghua Hu Junling Wang Hunan Key Laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangsha 410008China Department of Neurology Xiangya HospitalCentral South UniversityChangsha 410008China National clinical Research Center for Geriatric Diseases Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Hunan Province in Neurodegenerative Disorders Central South UniversityChangsha 410008China Center for Medical Genetics School of Life SciencesCentral South UniversityChangsha 410008China Engineering Research Center of Hunan Province in Cognitive Impairment Disorders Central South UniversityChangsha 410008China Hunan International Scientific and Technological cooperation Base of Neurodegenerative and Neurogenetic Diseases Changsha 410008China Hunan Provincial clinical Research Center for Critical Care Medicine Xiangya HospitalCentral South UniversityChangsha 410008China Hunan Key Laboratory of Animal Models for Human Diseases School of Life SciencesCentral South UniversityChangsha 410008China.

Background:Amyotrophic lateral sclerosis(ALS)is a devastating progressive neurodegenerative disease that affects neurons in the central nervous system and the spinal *** in many other neurodegenerative disorders,the genetic risk factors and pathogenesis of ALS involve dysregulation of cytoskeleton and neuronal ***,sen-sory and motor neuron diseases such as hereditary sensory and autonomic neuropathy type 2(HSAN2)and spastic paraplegia 30(SPG30)share several causative genes with ALS,as well as having common clinical ***1A encodes a kinesin 3 motor that transports presynaptic vesicle precursors(SVPs)and dense core vesicles and has been reported as a causative gene for HSAN2 and ***:Here,we analyzed whole-exome sequencing data from 941 patients with ALS to investigate the genetic association of KIF1A with ***:We identified rare damage variants(RDVs)in the KIF1A gene associated with ALS and delineated the clini-cal characteristics of ALS patients with KIF1A ***,these patients tended to exhibit sensory ***,the majority of these variants are located at the C-terminal cargo-binding region of the KIF1A *** examination revealed that the ALS-associated KIF1A variants located in the C-terminal region preferentially enhanced the binding of SVPs containing RAB3A,VAMP2,and *** of several disease-related KIF1A mutants in cultured mouse cortical neurons led to enhanced colocalization of RAB3A or VAMP2 with the KIF1A ***:Our study highlighted the importance of KIF1A motor-mediated transport in the pathogenesis of ALS,indicating KIF1A as an important player in the oligogenic scenario of ALS.

关键词： Amyotrophic lateral sclerosis KIF1A Axonal transport Presynaptic vesicle precursors

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A polymorphism in GAS5 promoter impacts efficacy of cytarabine-based chemotherapy in Chinese AML patients

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中国药理学与毒理学杂志 2016年第10期30卷 1077-1077页

作者： YAN Han ZHANG Dao-yu LI Xi YUAN Xiao-qing YANG Yong-long ZHU Ke-wei ZENG Hui LI Xiao-lin ZHOU Hong-hao ZHANG Wei CHEN Xiao-ping Department of clinical Pharmacology Xiangya HospitalCentral South University Institute of clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Hunan Province cooperation Innovation Center for Molecular Target New Drug Study Haikou People's Hospital and Affiliated Haikou Hospital of Xiangya Medical School Central South University Department of Hematology Xiang-Ya HospitalCentral South University

OBJECTIVE SNPs in lnc RNAs may alter the expression or secondary structure of lnc RNAs and then impact their *** lnc RNA SNPs affect the prognosis of acute myeloid leukemia(AML)remains *** search the association between lnc RNA SNPs and AML outcomes,thirty tag SNPs in GAS5,H19,MALAT1,WT1-as and SRA were genotyped in313 AML *** Survival analysis was performed in both AML patients recruited presently and GEO *** expression of GAS5 and TP63 was analyzed by real-time quantitative ***-luciferase reporter gene assay was used to confirm the interactions between GAS5 rs55829688 and *** Survival analysis indicated that rs55829688(T>C),located in GAS5 promoter,was significantly associated with the prognosis of *** average overall survival(OS)for patients with the rs55829688 CC genotype was significantly shorter than those carrying the rs55829688 T allele(P=0.018).Patients with rs55829688 CC genotype showed higher GAS5 expression in PBMCs than carriers of rs55829688T allele(P=0.025).Rs55829688 CC homozygotes also harbored a longer platelets recovery than those with rs55829688 T allele(P=0.040).In vitro study showed that GAS5 promoter harboring the rs55829688 C al ele showed marginal y increased reporter gene activity(P=0.054),and the promoter activity was increased by TP63 in a dose-dependent manner(P=0.001).Moreover,GAS5 expression was associated with AML OS in the GEO GSE12417 dataset,and GAS5 higher expression predict shorter OS(P=0.011).CONCLUSION Rs55829688 polymorphism could increase GAS5 expression by interacting with TP63 and was associated with worse OS in Chinese AML patients.

关键词： growth arrest specific 5 single nucleotide polymorphism acute myeloid leukemia long non-coding RNA promoter

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Paeoniflorin Attenuates Myocardial Fibrosis in Isoprenaline-induced Chronic Heart F ailure Rats via Inhibiting P38 MA PK Pathway

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Current Medical Science 2020年第2期40卷 307-312页

作者： Mao LIU Jie FENG Qian DU Jiao AI Zhan LV Department of Cardiology Cardiovascular Research CenterAfiliated Hospital of North Sichuan Medical CollegeNanchong 637000China Department of clinical Medicine North Sichuan Medical CollegeNanchong 637000China

Paconiflorin(Pae)is a monoterpenoid glycoside compound and has many biological activitics,such as immunosuppression,anti-inflammation and anti-cell ***,the effects and mechanisms of Pae on chronic heart failure(CHF)remain *** study was conducted to assess the effects and mechanisms of Pae on myocardial fibrosis in isoprenaline(Iso)-induced CHF ***(20 mgkg)was intragastrically administrated to CHF rats for 6 *** structure and function were *** protein and mRNA levels of transforming growth factorβ1(TGF-β1)and p38 were detected.C ompared to Iso group,Pae could alleviate myocardial fbrosis and improve cardiac function in CHF *** levels of collagen volume fraction(13.75%+3.77%vs.30.97%+4.22%,P<0.001)and perivascular collagen volume area(14.32%+2.50%v8.28.31%+3.16%,P<0.001)were significantly reduced in Pae group as compared with those in Iso *** expression of TGF-BI protein(0.30+0.07 vs.0.66+0.07,P<0.05)and mRNA(3.51+0.44 vs.7.58+0.58,P<0.05)decreased significantly in Pac group as compared with that in Iso *** expression of p38 protein(0.36+0.12 vs.0.81+0.38,P<0.05)and mRNA(3.84+0.05 vs.4.40+0.17,P<0.05)also decreased markedly in Pae group as compared with that in Iso *** could attenuate myocardial fibrosis and improve cardiac function in CHF rats by down-regulating the p38 MAPK signaling pathway.

关键词： chronic heart failure paconiflorin myocardial fibrosis p38 transforming growth factorβ1

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Lung cancer burden and trends from 2000 to 2018 in China:Comparison between China and the united States

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Chinese Journal of Cancer Research 2023年第6期35卷 618-626页

作者： Yi Teng Changfa Xia Maomao Cao Fan Yang Xinxin Yan Siyi He Mengdi Cao Shaoli Zhang Qianru Li Nuopei Tan Jiachen Wang Wanqing Chen Office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Objective: This study aims to provide an analysis of the current status and trends of lung cancer incidence and mortality rates in China, comparing trends with those in the united States(U.S.).Methods: Data on lung cancer incidence and mortality rates spanning 2000 to 2018 were extracted from the China Cancer Registry Annual Report and the Surveillance, Epidemiology, and End Results database for China and the U.S., respectively. Crude incidence and mortality rates were calculated by sex and age, with age-standardized incidence rates(ASIR) and mortality rates(ASMR) calculated using the Segi-Doll world standard *** analyses employed Joinpoint regression models to determine average annual percentage change(AAPC).The study also assessed the proportion of new cases and deaths by sex and ***: In 2018, the ASIR of lung cancer for males in China was 50.72 per 100,000 and the ASMR was 39.69 per 100,000, the ASIR for females was 26.25 per 100,000 and the ASMR was 15.24 per 100,000. Both ASIR and ASMR were higher in males and the highest in the population aged 65 years and older, with the lowest among those aged 20-49 years. In China, female ASIR demonstrated an increasing trend(AAPC: 1.16%), while ASMR decreased in both sexes(AAPCs:-0.48% for males,-1.00% for females). The U.S. exhibited decreasing trends in both ASIR and ASMR across sexes and age ***: The study identified an increasing trend in lung cancer incidence among females and a decreasing mortality trend in both sexes in China. These trends are likely linked to factors such as smoking prevalence,advancements in cancer screening, and improved medical care. The findings underscore the need for tailored lung cancer prevention measures in China, particularly the reinforcement of anti-smoking policies.

关键词： China lung cancer incidence mortality trends

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Novel chinmedomics strategy for discovering effective constituents from ShenQiWan acting on ShenYangXu syndrome

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Chinese Journal of Natural Medicines 2016年第8期14卷 561-581页

作者： ZHOU Xiao-Hang ZHANG Ai-Hua WANG Liang TAN Yun-Long GUAN Yu HAN Ying SUN Hui WANG Xi-Jun National TCM Key Laboratory of Serum Pharmacochemistry Sino-US Chinmedomics Technology Cooperation Center Research Center of Chinmedomics (State Administration of TCM) Laboratory of Metabolomics Department of Pharmaceutical Analysis Heilongjiang University of Chinese Medicine

Elucidation of the efficacy of traditional Chinese medicine(TCM) is of importance for scientists of modern medicine to understand the value of TCM clinical experience, and it is necessary to have a biological language to scientifically describe the efficacy of TCM. With this background,Chinmedomics has been proposed by our team, which includes integrating serum pharmacochemistry and metabolomics technology, defining theory and research methods for expressing the efficacy of TCMs based on the biomarkers discovery of TCM syndrome and elucidating the efficacy of TCM formulae, discovering effective constituents, and finally elucidating the scientific value of TCM. In the present study, the innovative chinmedomics strategy was conducted to evaluate the therapeutic effects of Shen Qi Wan(SQW) acting on Shen Yang Xu(kidney-yang deficiency syndrome, KYDS). We analyzed the urine metabolic trajectory between the model and control groups, and identified the biomarkers by the multivariate analysis. We found that SQW caused significant restoration of abnormal metabolism of KYDs. Using the method of metabolomics, 17 potential urine biomarkers were analyzed through 4 repeated tests in our serial studies on SQW and KYDS. Under the premise of therapeutic efficacy, a total of 56 peaks were tentatively characterized in vivo by the use of serum pharmacochemistry. Correlation analysis between marker metabolites and in vivo constituents of SQW showed that 28 compositions had a close relationship with urine biomarkers of therapeutic effects, whichmight play a key role in the therapeutic effect of SQW. These compounds were imported into an online database to predict their targets. Twenty-three important potential targets were identified, which were related to the metabolism of steroid hormone, tryptophan utilization, and thyroid hormone. In conclusion, chinmedomics is a useful strategy for discovery of potentially effective constituents from complex TCM formulae.

关键词： Chinmedomics ShenQiWan ShenYangXu syndrome Metabolomics Serum pharmacochemistry

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An Approach to the Simultaneous Detection of Multiple Biomarkers for the Early Diagnosis of Liver Cancer Using Quantum Dot Nanoprobes

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Infectious Microbes & Diseases 2022年第1期4卷 34-40页

作者： Ningtao Cheng Jing Fu State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteRenji HospitalShanghai Jiao Tong University School of MedicineShanghaiChina International cooperation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery HospitalShanghaiChina National Center for Liver Cancer ShanghaiChina

Biomarker-based early diagnosis of liver cancer is of high clinical value for reducing the mortality ***,it has been challenging to establish early detection methods with a single biomarker such as alpha-fetoprotein(AFP)because of limited diagnostic sensitivity and ***,developing multiplexed biomarker detection assays is crucially important for early ***,simultaneous detection methods involving three or more biomarkers have been *** we suggest employing the serological biomarker panel of glypican-3(GPC3),dickkopf-1(DKK1),and AFP for liver cancer *** present a rapid simultaneous detection approach for the biomarker panel labeled with three fluorescent quantum dot nanoprobes(emission wavelengths at 565 nm,605 nm,and 655 nm).As a proof-of-concept,simultaneous fluorescence detection of the biomarker panel was demonstrated using mixed reference samples containing human recombinant GPC3,DKK1,and AFP *** simultaneous detection approach conferred a linear range of 0.625–2.5 ng·mL^(-1)for the entire biomarker panel,which merits further clinical validation for the simultaneous and accurate determination of the biomarker panel in human serum samples.

关键词： nanomedical detection early cancer diagnosis liver cancer multiplex fluoroassay of biomarkers quantum dots simultaneous biomarker detection

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DNMT3A genetic polymorphisms predict disease prognosis in R882 mutation negative AML patients

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中国药理学与毒理学杂志 2016年第10期30卷 1067-1067页

作者： YUAN Xiao-qing ZHNG Dao-yu YAN Han YANG Yong-long ZHU Ke-wei ZHOU Hong-hao ZENG Hui CHEN Xiao-ping Department of clinical Pharmacology Xiangya HospitalCentral South University Institute of clinical Pharmacology Central South University Hunan Key Laboratory of Pharmacogenetics Department of Pharmacy Haikou People' s Hospital and Affiliated Haikou Hospital of Xiangya Medical SchoolCentral South University Department of Hematology Xiangya Hospital Central South University Hunan Province cooperation Innovation Center for Molecular Target New Drug Study

OBJECTIVE To evaluate the association between DNA(cytosine-5)-methyltransferase 3 alpha(DNMT3A)genetic polymorphisms and the disease prognosis of R882 mutation negative acute myeloid leukemia(AML)*** DNMT3A 11 SNPs(rs11695471,rs2289195,rs734693,rs2276598,rs1465825,rs7590760,rs13401241,rs7581217,rs749131,rs41284843 and rs7560488)were genotyped using a MassA RRAY platform or Sanger sequencing method in 317 diagnostic non-FABM3 AML patients without R882 mutation from southern *** patients underwent combined chemotherapy with cytarabine and *** survival(OS)and Disease-free survival(DFS)as major end points were *** prognostic(median OS and DFS)evaluations were performed by Kaplan-Meier curve and Cox′s proportional hazard *** We found that the rs2289195 G>A SNP could act as a poor prognostic predictor independently(HR=0.442,P=0.035 for OS;HR=0.431,P=0.031 for DFS),while the rs1465825 T>C SNP and rs7590760 G>C SNP appeared to predict independently poor prognosis for both OS(HR=1.453,P=0.037 for rs1465825;HR=1.584,P=0.063 for rs7590760)and DFS(HR=1.459,P=0.057 for rs1465825;HR=1.965,P=0.017for rs7590760).However,no significant associations between other DNMT3A polymorphisms and prognosis(OS in conjunction with DFS)were *** DNMT3A polymorphisms may be potential predictive markers for AML prognosis in R882 mutation negative patients,which might improve prognostic stratification of AML.

关键词： DNMT3A polymorphism AML prognosis

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clinical effect of manual reduction of humeroradial joint in the treatment of typeⅠ-Ⅲfresh Monteggia fracture in children

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Chinese Journal of Traumatology 2020年第4期23卷 233-237页

作者： Yin-Qiang Cao Jia-Zhong Deng Yuan Zhang Xiao-Wei Yuan Tao Liu Jun Li Xiang Li Pan Gou Ming Li Xing Liu Department of Orthopedics Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChinaInternational Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of PediatricsChildren's Hospital of Chongqing Medical UniversityChongqingChina Cangxi Social Insurance Hospital Guangyuan CitySichuan ProvinceChina

Purpose:To evaluate the efficacy of closed reduction on the humeroradial joint in the treatment of Bado typeⅠ,ⅡandⅢfresh Monteggia fractures in children and investigate the effect of clinical factors,including Bado classification,age and time of treatment on the success rate of closed ***:We retrospectively studied the data of childrenclinical *** data were collected and reviewed to assess the reduction of the humeroradial *** of the elbow joint and forearm was evaluated and risk factors related to the failure of reduction were *** successful manual reduction was analyzed from three aspects,respectively Bado fracture type(Ⅰ,Ⅱ,Ⅲ),patient age(6 years)and time interval from injury to treatment(group A,3 days).Results:Altogether 88 patients were employed in this study,including 58 males(65.9%)and 30 females(34.1%)aged from 1 to 10 *** were 29 cases(33.0%)of Bado typeⅠMonteggia fractures,16(18.2%)typeⅡand 43(48.7%)typeⅢ.Successful manual reduction was achieved in 79 children(89.8%)at the last *** failed 9 patients received open *** criteria showed 100%goodexcellent rate for all the *** success rate of manual reduction was 89.7%,87.5%and 90.7%in Bado typeⅠ,ⅡandⅢcases,respectively,revealing no significant differences among different Bado types(x2=0.131,p=0.937).Successful closed reduction was achieved in 13 toddlers(13/13,100%),38 preschool children(28/42,90.5%)and 28 school-age children(28/33,84.8%),suggesting no sig

关键词： Children Monteggia fracture Manual reduction

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Emergence of plasmid-mediated tigecycline resistance tet(X4)gene in Enterobacterales isolated from wild animals in captivity

Science in One Health

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Science in One Health 2024年第1期3卷 134-139页

作者： Lei Lei Panfeng Xiong Zelin Yan Yanyan Zhang Yuchen Wu Gongxiang Chen Houhui Song Rong Zhang Key Laboratory of Applied Technology on Green-Eco-healthy Animal Husbandry of Zhejiang Province Zhejiang Provincial Engineering Laboratory for Animal Health Inspection&Internet TechnologyZhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health ManagementChina-Australia Joint Laboratory for Animal Health Big Data AnalyticsCollege of Animal Science and Technology&College of Veterinary MedicineZhejiang Agriculture and Forestry UniversityHangzhouZhejiang 311300China Department of clinical Laboratory The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang 310009China

Background:Over the past few decades,antimicrobial resistance(AMR)has emerged as a global health challenge in human and veterinary *** on AMR genes in captive wild animals has ***,the presence and molecular characteristics of tet(X)-carrying bacteria in these animals remain ***:Eighty-four samples were collected from captive wild ***(X)variants were detected using polymerase chain reaction and the isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass *** isolated strains were subjected to antimicrobial susceptibility testing and wholegenome *** virulence of an Escherichia coli strain carrying enterotoxin genes was assessed using a Galleria mellonella larval ***:We isolated two tet(X4)-positive *** strains and one tet(X4)-positive Raoultella ornithinolytica *** susceptibility tests revealed that all three tet(X4)-carrying bacteria were sensitive to the 13 tested antimicrobial agents,but exhibited resistance to ***,one tet(X4)-carrying *** strain producing an enterotoxin had a toxic effect on *** ***-genome sequencing analysis showed that the two tet(X4)-carrying *** strains had more than 95%similarity to tet(X4)-containing *** strains isolated from pigs and humans in ***:The genetic environment of tet(X4)closely resembled that of the plasmid described in previous *** study identified tet(X4)-positive strains in wildlife and provided valuable epidemiological data for monitoring drug *** identification of enterotoxin-producing *** strains also highlights the potential risks posed by virulence genes.

关键词： Wild animal tet(X4) Enterobacterales Enterotoxin Tigecycline resistance Epidemiology

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Universal MOF nanozyme-induced catalytic amplification strategy for label-free electrochemical immunoassay

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Chinese Chemical Letters 2024年第11期35卷 290-293页

作者： Ruixin Liu Feng Shi Yanping Xia Haibing Zhu Jiawen Cao Kai Peng Chuanli Ren Juan Li Zhanjun Yang School of Chemistry and Chemical Engineering Yangzhou UniversityYangzhou 225002China clinical Medical College of Yangzhou University Northern Jiangsu People's Hospital Affiliated to Yangzhou UniversityYangzhou UniversityYangzhou 225001China

Label-free immunoassay is confronted with a great challenge that its insufficient sensitivity for low concentration analytes,which can be assigned to the low catalytic efficiency of modified materials towards electroactive ***,a universal MOF nanozyme-induced catalytic amplification strategy was proposed for constructing highly sensitive label-free electrochemical ***,the synthesized Cu Fe-MOF nanozyme with superior peroxidase(POD)-like activity,regarding as a MOF nanozyme model,can catalyze hydrogen peroxide to produce hydroxyl radicals(·OH),which can efficiently oxidize electroactive probe(such as 1,2-phenylenediamine(o-PD))accompanying with intense electrochemical *** of MOF nanozyme on the electrode and capture of antibodies for binding target antigens hinder the catalytic process of MOF nanozyme toward o-PD,resulting in a gradual decrease in electrochemical signal with increasing target antigen concentration,enabling quantitative label-free ***,a highly sensitive label-free immunosensor using MOF nanozyme-induced catalytic amplification achieved effective detection of Immunoglobulin G(Ig G)with a wide linear range of 0.001-50 ng/mL and low detection limit of 0.45 pg/*** work proposes a promising nanozyme-induced catalytic amplification strategy for the development of label-free electrochemical immunoassay.

关键词： MOF nanozyme Catalytic amplification POD-like Label-free Electrochemical immunosensor

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