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Iron metabolism and arthritis: Exploring connections and therapeutic avenues

中华医学杂志(英文版) 2024年第14期137卷 1651-1662页

作者： Zhuo Dachun Xiao Wenze Tang Yulong Jiang Shuai Geng Chengchun Xie Jiangnan Ma Xiaobei Zhang Qing Tang Kunhai Yu Yuexin Bai Lu Zou Hejian Liu Jing Wang Jiucun department of Rheumatology Shanghai Pudong Hospital Human Phenome Institute Zhangjiang Fudan International Innovation Center Fudan University Shanghai China State Key Laboratory of genetic Engineering School of Life Science Fudan University Shanghai China department of Vascular Surgery Shanghai Pudong Hospital Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling Fudan University Pudong Medical Center Shanghai China department of Anthropology and Human genetics School of Life Sciences Ministry of Education Key Laboratory of Contemporary Anthropology Fudan University Shanghai China Division of Rheumatology Huashan Hospital State Key Laboratory of Genetic Engineering School of Life Science Fudan University Shanghai China Institute of Rheumatology Immunology and Allergy Allergy and Disease Research Center Fudan University Shanghai China Research Unit of Dissecting the Population genetics and Developing New Technologies for Treatment and Prevention of Skin Phenotypes and Dermatological Diseases (2019RU058) Chinese Academy of Medical Sciences Beijing China

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

关键词： Iron metabolism Arthritis Inflammation Immunity Rheumatoid arthritis Psoriatic arthritis Gouty arthritis

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Pathological mechanisms of amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第5期19卷 1036-1044页

作者： Yushu Hu Wenzhi Chen Caihui Wei Shishi Jiang Shu Li Xinxin Wang Renshi Xu department of Clinical Medicine Nanchang UniversityNanchangJiangxi ProvinceChina department of Neurology Jiangxi Provincial People’s HospitalNanchangJiangxi ProvinceChina department of Neurology The First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Amyotrophic lateral sclerosis refers to a neurodegenerative disease involving the motor system,the cause of which remains unexplained despite several years of ***,the journey to understanding or treating amyotrophic lateral sclerosis is still a long *** to current research,amyotrophic lateral sclerosis is likely not due to a single factor but rather to a combination of mechanisms mediated by complex interactions between molecular and genetic *** progression of the disease involves multiple cellular processes and the interaction between different complex mechanisms makes it difficult to identify the causative factors of amyotrophic lateral ***,we review the most common amyotrophic lateral sclerosis-associated pathogenic genes and the pathways involved in amyotrophic lateral sclerosis,as well as summarize currently proposed potential mechanisms responsible for amyotrophic lateral sclerosis disease and their evidence for involvement in amyotrophic lateral *** addition,we discuss current emerging strategies for the treatment of amyotrophic lateral *** the emergence of these new therapies may help to further our understanding of the pathogenic mechanisms of the disease.

关键词： amyotrophic lateral sclerosis cellular pathways disease mechanisms motor neuron neurodegenerative disease

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Independent and Combined Associations of Sleep Duration, Bedtime, and Polygenic Risk Score with the Risk of Hearing Loss among Middle-Aged and Old Chinese: The Dongfeng–Tongji Cohort Study

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Research 2024年第1期2023卷 721-733页

作者： Miao Liu Haiqing Zhang Zhichao Wang Tingting Mo Xuefeng Lai Yaling He Minghui Jiang Meian He Weijia Kong Tangchun Wu Xiaomin Zhang department of Occupational and Environmental Health Ministry of Education Key Laboratory of Environment and Healthand State Key Laboratory of Environmental Health(Incubating)School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina department of Otorhinolaryngology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina department of Epidemiology and Biostatistics School of Public HealthTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina

Evidence available on the independent and combined associations of sleep duration,bedtime,and genetic predisposition with hearing loss was *** present study included 15,827 participants from the Dongfeng–Tongji cohort *** risk was characterized by polygenic risk score(PRS)based on 37 genetic loci related to hearing *** conducted multivariate logistic regression models to assess the odds ratio(OR)for hearing loss with sleep duration and bedtime,as well as the joint association and interaction with *** showed that hearing loss was independently associated with sleeping≥9 h/night compared to the recommended 7 to9:00 *** 10:00 *** to those with bedtime>10:00 *** 11:00 p.m.,with estimated ORs of 1.25,1.27,and 1.16,respectively.

关键词： Middle hearing fen

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A genetic variant study of bortezomib-induced peripheral neuropathy in Chinese multiple myeloma patients

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Oncology Research 2024年第5期32卷 955-963页

作者： YAN ZHANG HEYANG ZHANG JING WANG XIN WEI YI QU FENG XU LIJUN ZHANG department of Hematology The First Affiliated Hospital of China Medical UniversityShenyang110001China

Background:Bortezomib results in peripheral neuropathy(PN)in approximately 50%of patients,during multiple myeloma(MM)treatment,a complication known as Bortezomib-induced peripheral neuropathy(BIPN).The drug response varies among *** factor may play an important role in ***:A nextgeneration sequencing(NGS)panel containing 1659 targets from 233 genes was used to identify risk variants for developing BIPN in 204 MM patients who received bortezomib *** expression of MTHFR and ALDH1A1 in 62 peripheral blood samples was detected by real-time quantitative PCR(RT-qPCR).Serum homocysteine(Hcy)levels were detected in 40 samples by chemiluminescent microparticle immunoassay(CMIA).Results:Compared with the non-BIPN group(n=89),a total of 8 significantly associated single nucleotide polymorphisms(SNPs)were identified in the BIPN group(n=115):MTHFR(rs1801131,rs1801133,rs17421511),EPHX1(rs1051740),MME(rs2016848),ALDH1A1(rs6151031),HTR7(rs1935349)and CYP2A6(rs8192720).The mRNA expression level of MTHFR in newly diagnosed patients with peripheral neuritis after treatment(NP group)was lower than that of newly diagnosed patients without peripheral neuritis after treatment(NnP group)(1.70±0.77 vs.2.81±0.97,p=0.009).Serum Hcy levels were significantly higher in BIPN group than in non-BIPN group(11.66±1.79μmol/L vs.8.52±3.29μmol/L,p=0.016)and healthy controls(11.66±1.79μmol/L vs.8.55±2.13μmol/L,p≤0.001).Conclusion:CYP2A6,EPHX1,MTHFR,ALDH1A1,HTR7,MME and BIPN are linked in Chinese MM *** is more likely to occur in patients with lower MTHFR mRNA expression,which might result in higher serum Hcy levels.

关键词： Multiple Myeloma Peripheral neuropathy Bortezomib Bortezomib-induced peripheral neuropathy Next-generation sequencing MTHFR Serum Hcy

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Engineering of ovarian tissue for ovarian dysfunctions:A review

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Asian pacific Journal of Reproduction 2024年第1期13卷 3-11页

作者： Aliya Zhylkybekova Gulbakit KKoshmaganbetova Myltykbay SRysmakhanov Nurgul Abdullayevna Abenova Nadiar Maratovich Mussin Asset Askerovich Kaliyev Mahdi Mahdipour Amin Tamadon department of Evidence-Based Medicine and Scientific Management West Kazakhstan Marat Ospanov Medical UniversityAktobeKazakhstan department of Surgery and Urology No.2 West Kazakhstan Medical UniversityAktobeKazakhstan department of Surgery and Transplantation Aktobe Medical CenterAktobeKazakhstan department of Internal Diseases West Kazakhstan Marat Ospanov Medical UniversityAktobeKazakhstan Stem Cell Research Center Tabriz University of Medical SciencesTabrizIran department of Reproductive Biology Faculty of Advanced Medical SciencesTabriz University of Medical SciencesTabrizIran department for Scientific Work West-Kazakhstan Marat Ospanov Medical UniversityAktobeKazakhstan

This review explores tissue engineering as a potential solution for reproductive health issues in women caused by genetic or acquired diseases,such as premature ovarian failure or *** loss of ovarian function can lead to infertility,osteoporosis,and cardiovascular *** replacement therapy is a common treatment,but it has limitations and *** review focuses on two main approaches in tissue engineering:scaffold-based(3D printing,electrospinning,decellularization)and scaffold-free(stem cell transplantation,organoid cultivation).Both approaches show promise in preclinical studies for creating functional ovarian *** include vascularization,innervation,long-term function,and *** these challenges,tissue engineering offers a potential avenue for restoring fertility and hormone balance in women with ovarian dysfunction.

关键词： Female gonads Tissue engineering Estrogen Reproductive system

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Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs

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Journal of Animal Science and Biotechnology 2024年第1期15卷 108-126页

作者： Tianqi Duo Xiaohong Liu Delin Mo Yu Bian Shufang Cai Min Wang Ruiqiang Li Qi Zhu Xian Tong Ziyun Liang Weilun Jiang Shiyi Chen Yaosheng Chen Zuyong He State Key Laboratory of Biocontrol School of Life SciencesSun Yat-Sen UniversityGuangzhou 510275GuangdongChina department of Pharmacology(the State‑Province Key Laboratories of Biomedicine‑Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Hunan Provincial Key Laboratory for genetic Improvement of Domestic Animal College of Animal Science and TechnologyHunan Agricultural UniversityChangsha 410128China

Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat ***-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat *** favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig *** improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) *** We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote *** We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling *** study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing.

关键词： CBE3 IGF2 Intramuscular fat Meat production PI3K-AKT/AMPK ZBED6

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Hotspots and trends of risk factors in gastric cancer: A visualization and bibliometric analysis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2200-2218页

作者： Meng Li Ning Gao Shao-Li Wang Yu-Feng Guo Zhen Liu department of Gastroenterology Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijing 100053China department of Acupuncture and Moxibustion Guang'anmen HospitalChina Academy of Chinese Medical SciencesBeijing 100053China

BACKGROUND The lack of specific symptoms of gastric cancer(GC)causes great challenges in its early *** it is essential to identify the risk factors for early diagnosis and treatment of GC and to improve the survival *** To assist physicians in identifying changes in the output of publications and research hotspots related to risk factors for GC,constructing a list of key risk factors,and providing a reference for early identification of patients at high risk for *** Research articles on risk factors for GC were searched in the Web of Science core collection,and relevant information was extracted after *** literature was analyzed using Microsoft Excel 2019,CiteSpace V,and VOSviewer *** A total of 2514 papers from 72 countries and 2507 research institutions were ***(n=1061),National Cancer Center(n=138),and Shoichiro Tsugane(n=36)were the most productive country,institution,or author,*** research hotspots in the study of risk factors for GC are summarized in four areas,namely:Helicobacter pylori(***)infection,single nucleotide polymorphism,bio-diagnostic markers,and GC risk prediction *** In this study,we found that *** infection is the most significant risk factor for GC;single-nucleotide polymorphism(SNP)is the most dominant genetic factor for GC;bio-diagnostic markers are the most promising diagnostic modality for *** risk prediction models are the latest current research *** conclude that the most important risk factors for the development of GC are *** infection,SNP,smoking,diet,and alcohol.

关键词： Gastric cancer Risk factor Bibliometric Research hotspots VOSviewer

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genetically predicted waist circumference and risk of atrial fibrillation

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Chinese medical Journal 2024年第1期137卷 82-86页

作者： Wenting Wang Jiang-shan Tan Jingyang Wang Wei Xu Liting Bai Yu Jin Peng Gao Peiyao Zhang Yixuan Li Yanmin Yang Jinping Liu department of Cardiopulmonary Bypass State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China department of Anaesthesiology Second Affiliated HospitalHainan Medical CollegeHaikouHainan 570311China State Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Introduction:Observational studies have revealed an association between waist circumference(WC)and atrial fibrillation(AF).However,it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk ***,the causal role of WC in AF is *** study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization(MR)***:In our two-sample MR analysis,the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study(GWAS)of WC(42 single nucleotide polymorphisms with a genetic significance of Pgenetic Investigation of ANthropometric Traits consortium,containing 232,101 participants)and the data of AF(from the European Bioinformatics Institute database,containing 55,114 AF cases and 482,295 controls)were used to assess the causal role of WC on *** different approaches(inverse variance weighted[IVW],MR-Egger,and weighted median regression)were used to ensure that our results more ***:All three MR analyses provided evidence of a positive causal association between high WC and *** WC was suggested to increase the risk of AF based on the IVW method(odds ratio[OR]=1.43,95%confidence interval[CI],1.30-1.58,P=2.51×10^(-13)).The results of MR-Egger and weighted median regression exhibited similar trends(MR-Egger OR=1.40[95%CI,1.08-1.81],P=1.61×10^(-2);weighted median OR=1.39[95%CI,1.21-1.61],P=1.62×10^(-6)).MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and ***:Our findings suggest that greater WC is associated with an increased risk of *** measures to reduce WC may help prevent the occurrence of AF.

关键词： genetically predicted Waist circumference Atrial fibrillation Mendelian randomization

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Discovery of CCDC188 gene as a novel genetic target for human acephalic spermatozoa syndrome

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Protein & Cell 2024年第9期15卷 704-709页

作者： Jing Wang Hui-Juan Jin Yi Lu Zi-Han Wang Teng-Yan Li Lan Xia Hong-Jun Li Bin-Bin Wang Su-Ren Chen department of medical genetics and Developmental Biology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Key Laboratory of Cell Proliferation and Regulation Biology Ministry of EducationDepartment of BiologyCollege of Life SciencesBeijing Normal UniversityBeijing 100875China Graduate School Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China department of Urology Peking Union Medical College HospitalBeijing 100005China Center for genetics National Research Institute of Family PlanningBeijing 100081China NHC Key Laboratory of Reproductive Health Engineering Technology Research(NRIFP) Beijing 100081China

Dear Editor,Male infertility is a widespread health problem and affects approximately 6%–8%of the male population(Jiao et al.,2021).Acephalic spermatozoa syndrome(ASS),a rare but severe type of teratozoospermia,is ch... 详细信息

关键词： al. infertility finally

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Temporal-spatial Generation of Astrocytes in the Developing Diencephalon

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Neuroscience Bulletin 2024年第1期40卷 1-16页

作者： Wentong Hong Pifang Gong Xinjie Pan Zhonggan Ren Yitong Liu Guibo Qi Jun-Liszt Li Wenzhi Sun Woo-Ping Ge Chun-Li Zhang Shumin Duan Song Qin department of Anatomy Histology and EmbryologySchool of Basic Medical SciencesFudan UniversityShanghai 200032China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China Chinese Institute for Brain Research Beijing 102206China School of Basic medical Sciences Capital Medical UniversityBeijing 100069China department of Molecular Biology University of Texas Southwestern Medical CenterDallasTexas 75390-9148USA department of Neurobiology Key Laboratory of Medical Neurobiology of Ministry of Health of ChinaZhejiang University School of MedicineHangzhou 310058China State Key Laboratory of medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghai 200032China

tAstrocytes are the largest glial population in the mammalian ***,we have a minimal understanding of astrocyte development,especially fate specification in different regions of the *** lineage tracing of the progenitors of the third ventricle(3V)wall via in-utero electroporation in the embryonic mouse brain,we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V ***,radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types:radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the *** genetic fate mapping analysis,we reveal that the first population of astrocytes appears along the zona incerta in the *** occurs at an early time point in the dorsal region relative to that in the ventral region of the developing *** transcriptomic analysis of the region-specific 3V wall and lateral ventricle(LV)wall,we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal ***,these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.

关键词： Radial glia Astrocyte specification Lineage tracing Diencephalon Third ventricle

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