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Early-life famine exposure,adulthood obesity patterns,and risk of low-energy fracture

Frontiers of Medicine 2024年第1期18卷 192-203页

作者： Hongyan Qi Chunyan Hu Jie Zhang Lin Lin Shuangyuan Wang Hong Lin Xiaojing Jia Yuanyue Zhu Yi Zhang Xueyan Wu Mian Li Min Xu Yu Xu Tiange Wang Zhiyun Zhao Weiqing Wang Yufang Bi Meng Dai Yuhong Chen Jieli Lu department of endocrine and metabolic diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research Center for endocrine and metabolic diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People’s Republic of ChinaShanghai National Center for Translational MedicineRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China

Malnutrition in early life increases the risk of osteoporosis,but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains *** study included 5323 community-dwelling subjects aged⩾40 years from ***-life famine exposure was identified based on the participants’birth *** obesity was assessed using the body mass index(BMI),and abdominal obesity was evaluated with the waist-to-hip ratio(WHR).Low-energy fracture was defined as fracture occurring after the age of⩾40 typically caused by falls from standing height or *** to the nonexposed group,the group with fetal,childhood,and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios(ORs)and 95%confidence intervals(CIs)of 3.55(1.57–8.05),3.90(1.57–9.71),and 3.53(1.05–11.88),respectively,but not in *** interactions were observed between fetal famine exposure and general obesity with fracture among women(P for interaction=0.0008).Furthermore,compared with the groups with normal BMI and WHR,the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture(OR,95%CI:3.32,1.17–9.40).These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.

关键词： famine obesity body mass index waist-to-hip ratio low-energy fracture

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Novel insights into immune-related genes associated with type 2 diabetes mellitus-related cognitive impairment

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World Journal of Diabetes 2024年第4期15卷 735-757页

作者： Jing Gao Ying Zou Xiao-Yu Lv Li Chen Xin-Guo Hou department of Endocrinology Qilu Hospital of Shandong UniversityCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina Institute of endocrine and metabolic diseases Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of endocrine and metabolic diseases Shandong Province Medicine&HealthJinan 250012Shandong ProvinceChina department of Endocrinology Jinan Clinical Research Center for Endocrine and Metabolic DiseaseJinan 250012Shandong ProvinceChina

BACKGROUND The cognitive impairment in type 2 diabetes mellitus(T2DM)is a multifaceted and advancing state that requires further exploration to fully ***-roinflammation is considered to be one of the main mechanisms and the immune system has played a vital role in the progression of the *** To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive *** To identify differentially expressed genes(DEGs)between T2DM and controls,we used data from the Gene Expression Omnibus database *** identify T2DM module genes,we used Weighted Gene Co-Expression Network *** the genes were subject to Gene Set Enrichment ***-protein interaction network construction and machine learning were utilized to identify three hub *** cell infiltration analysis was *** three hub genes were validated in GSE152539 via receiver operating characteristic curve *** experiments including reverse transcription quantitative real-time PCR,Western blotting and immunohistochemistry were conducted both in vivo and in *** identify potential drugs associated with hub genes,we used the Comparative Toxicogenomics Database(CTD).RESULTS A total of 576 DEGs were identified using *** taking the intersection of DEGs,T2DM module genes,and immune-related genes,a total of 59 genes associated with the immune system were ***,machine learning was utilized to identify three hub genes(H2-T24,Rac3,and Tfrc).The hub genes were associated with a variety of immune *** three hub genes were validated in *** experiments were conducted at the mRNA and protein levels both in vivo and in vitro,consistent with the bioinformatics ***,11 potential drugs associated with RAC3 and TFRC were identified based on the *** Immune-related genes that differ in expression in the hippocampus are closely linked to microgli

关键词： Bioinformatics analysis Type 2 diabetes mellitus Cognitive impairment Hippocampus Immune Microglia

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Clinical and molecular characterization of 10 Chinese children with congenital adrenal hyperplasia due to 11beta‑hydroxylase deficiency

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World Journal of Pediatrics 2024年第4期20卷 422-433页

作者： Wen‑Li Lu Xiao‑Yu Ma Jiao Zhang Jun‑Qi Wang Ting‑Ting Zhang Lei Ye Yuan Xiao Zhi‑Ya Dong Wei Wang Shou‑Yue Sun Chuan‑Yin Li Rong‑Gui Hu Guang Ning Li‑Dan Zhang department of Pediatrics Ruijin HospitalShanghai Jiao Tong University School of MedicineNo.197Ruijin 2nd RdHuangpu DistrictShanghai 200025China department of Pediatric Genetic and metabolic Endocrinology West China Second University HospitalSichuan UniversityNo.20Section 3Renmin South RoadSichuan 610041China department of endocrine and metabolic diseases Shanghai Clinical Center for Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Cancer Center School of MedicineShanghai Tenth People’s HospitalTongji UniversityYanchang Zhong Lu 301St RdJing’an DistrictShanghai 200031China

Background The clinical manifestations of nonclassical 11beta-hydroxylase deficiency are very similar to those of nonclassical 21-hydroxylase *** this study,we investigated the relationship between the clinical and molecular features of congenital adrenal hyperplasia caused by 11beta-hydroxylase deficiency and reviewed the related literature,which are expected to provide assistance for the clinical diagnosis and analysis of congenital adrenal *** Clinical data for 10 Chinese patients diagnosed with congenital adrenal hyperplasia in our hospital from 2018 to 2022 were retrospectively *** examined the effects of gene mutations on protease activity and constructed threedimensional structure prediction models of *** We describe 10 patients with 11beta-hydroxylase gene mutations(n=5,46,XY;n=5,46,XX),with 10 novel mutations were *** patients received treatment at an early stage,with an average age of 2.08±1.66 years,whereas male patients received treatment significantly later,at an average age of 9.77±3.62 *** most common CYP11B1 pathogenic variant in the Chinese population was found to be c.1360C>*** mutations lead to spatial conformational changes that affect protein *** Our study found that there was no significant correlation between each specific mutation and the severity of clinical *** patients with the same gene pathogenic variant may have mild or severe clinical *** correlation between genotype and phenotype needs further ***-dimensional protein simulations may provide additional support for the physiopathological mechanism of genetic mutations.

关键词： 11β-hydroxylase deficiency CYP11B1 Enzymatic activity Phenotype-genotype correlation Threedimensional protein simulations

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Multi-omics analyses of G6PD deficiency variants in Chinese population

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Journal of Genetics and Genomics 2024年第1期51卷 100-104页

作者： He Ji Jiahuan Chen Peide Huang Zhimin Feng Weining Hu Mengyao Dai Xiaohui Sun Xiao Jin Guangquan Chen Guang Ning Lin Li Weiqing Wang Yanan Cao department of endocrine and metabolic diseases Shanghai Institute of Endocrine and Metabolic DiseasesNational Clinical Research Centre for Metabolic DiseasesState Key Laboratory of Medical GenomicsResearch Unit of Clinical and Basic Research on Metabolic Diseases of Chinese Academy of Medical SciencesRuijin Yangtze River Delta Health InstituteWuxi Branch of Ruijin HospitalRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China National Research Center for Translational Medicine National Key Scientific Infrastructure for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China SJTU-BGI Innovation Research Center Shanghai 200240China BGI-ShenZhen ShenzhenGuangdong 518083China

Glucose-6-phosphate dehydrogenase(G6PD)deficiency is one of the most prevalent hereditary and X-linked enzyme disorders caused by the pathogenetic G6PD(NM_001042351.2)variants(Yang et al.,2016).The clinical manifestations of G6PD deficiency offer a wide spectrum of diverse disease phenotypes(Hecker et al.,2013).Investigations of prevalence and molecular epidemiology demonstrate that G6PD deficiency affects over 400 milion individuals worldwide and leads to thousands of deaths annually(Mortality and Causes of Death,2015).

关键词： al. G6PD epidemiology

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Analysis of an adult diabetes mellitus caused by a rare mutation of the gene:A case report

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World Journal of Clinical Cases 2024年第19期12卷 3942-3949页

作者： Wen-Xuan Li Li-Li Xu Chuan-Feng Liu Bing-Zi Dong Yun-Yang Wang department of endocrine and metabolic diseases The Affiliated Hospital of Qingdao UniversityQingdao 266003Shandong ProvinceChina

BACKGROUND This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence,featuring a unique mutation in the peroxisome proliferator-activated receptor gamma(PPARG)*** Access Statement:Research data supporting this publication are available from the NN repository at ***/download/.CASE SUMMARY The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family ***,high-throughput sequencing was conducted to analyze the PPARG genes of the patient,her siblings,and their *** results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy,accompanied by insulin resistance and ***,these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation *** results from the gene detection process demonstrated a heterozygous mutation of guanine(G)at position 284 in the coding region of exon 2 of PPARG,which replaced the base adenine(A)(exon2c.284A>***95Cys).This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated ***,both of her siblings harbored a nucleotide heterozygous variation at the same site,and both were diagnosed with *** The PPARG gene mutation,particularly the ***95Cys mutation,may represent a newly identified subtype of maturity-onset diabetes of the *** subtype is characterized by insulin resistance and lipid metabolism disorders.

关键词： Diabetes Gene mutation Maturity-onset diabetes of the young Peroxisome proliferator-activated receptor gamma Lipid metabolism

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Has the open surgical approach in colorectal cancer really become uncommon?

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1485-1492页

作者： Maria Cariati Giuseppe Brisinda Maria Michela Chiarello department of Surgery Azienda Sanitaria Provinciale di CrotoneCrotone 88900Italy Abdominal and endocrine metabolic Medical and Surgical Sciences Fondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy department of Surgery Azienda Sanitaria Provinciale di CosenzaCosenza 87100Italy

Colorectal cancer is the third most common cancer in the *** is man-datory to treat patients with colorectal *** colorectal cancer be treated in laparoscopy?Scientific literature has validated the oncological quality of laparo-scopic approach for the treatment of patients with colorectal *** non-inferiority trials with good remote control have answered positively to this long-debated *** as 1994,first publications demonstrated technical feasibility and compliance with oncological imperatives and,as far as short-term outcomes are concerned,there is no difference in terms of mortality and post-operative morbidity between open and minimally invasive surgical approaches,but only longer operating times at the beginning of the ***,from 2007 onwards,long-term results were published that demonstrated the ab-sence of a significant difference regarding overall survival,disease-free survival,quality of life,local and distant recurrence rates between open and minimally in-vasive *** this editorial,we aim to summarize the clinical and technical aspects which,even today,make the use of open surgery relevant and necessary in the treatment of patients with colorectal cancer.

关键词： Colorectal cancer Laparoscopy Laparoscopic colorectal resection Bowel obstruction Bowel perforation Advanced colorectal cancer

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Large-scale manufacturing of functional single-atom ink for convenient glucose sensing

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Nano Research 2024年第8期17卷 7256-7263页

作者： Muyu Yan Xiaofei Zhu Can Xiong Xiao Han Zhenggang Xue Yuen Wu department of Endocrinology Institute of Endocrine and Metabolic DiseasesThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Deep Space Exploration Laboratory University of Science and Technology of ChinaHefei 230026China NEST Laboratory Department of PhysicsDepartment of ChemistryCollege of ScienceShanghai UniversityShanghai 200444China Center of Advanced Nanocatalysis(CAN) Department of Applied ChemistryUniversity of Science and Technology of ChinaHefei 230026China

Printing techniques hold great potential in the manufacture of electronics such as sensors,micro-supercapacitors,and flexible ***,developing large-scale functional conductive inks with appropriate rheological properties and active components still remains a ***,through optimizing the formulations of ink,iron single sites supported N-doped carbon black(Fe_(1)-NC)inks can serve as both conductive electrodes and high-reactive catalysts to realize convenient glucose detection,which pronouncedly reduces the dosage of enzyme and simplifies the sensors *** detail,utilizing in-situ pyrolysis method,Fe_(1)-NC single-atom catalysts(SACs)are prepared in bulk(dekagram-level).The batched Fe_(1)-NC SACs materials can be uniformly mixed with modulated ink to realize the screen printing with high resolution and ***,the whole scalable preparation and ink-functional process can be extended to various metals(including Co,Ni,Cu,and Mn).The introduction of highly active Fe_(1)-NC sites reduces the amount of enzyme used in glucose detection by at least 50%,contributing to the cost reduction of *** strategy in harnessing the SACs onto the carbon inks thus provides a broad prospect for the low-cost and large-scale printing of sensitive sensing devices.

关键词： large-scale manufacturing single-atom inks screen printing glucose sensing low enzyme dosage

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Analysis of the electron transfer pathway in small laccase by EPR and UV-vis spectroscopy coupled with redox titration

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Magnetic Resonance Letters 2024年第3期4卷 52-59页

作者： Lu Yu Aokun Liu Jian Kuang Ruotong Wei Zhiwen Wang Changlin Tian High Magnetic Field Laboratory Hefei Institutes of Physical ScienceChinese Academy of SciencesHefei230031China department of Endocrinology Institute of Endocrine and Metabolic DiseaseThe First Affiliated Hospital of USTCDivision of Life Sciences and MedicineHefei National Research Center for Physical Sciences at the MicroscaleJoint Center for Biological Analytical ChemistryAnhui Engineering Laboratory of Peptide DrugAnhui Laboratory of Advanced Photonic Science and TechnologyUniversity of Science and Technology of ChinaHefei230026China

Bacterial small laccases(SLAC) are promising industrial biocatalysts due to their ability to oxidize a broad range of substrates with exceptional thermostability and tolerance for alkaline p H. Electron transfer between substrate, copper centers, and O2is one of the key steps in the catalytic turnover of SLAC. However, limited research has been conducted on the electron transfer pathway of SLAC and SLAC-catalyzed reactions, hindering further engineering of SLAC to produce tunable biocatalysts for novel applications. Herein, the combinational use of electron paramagnetic resonance(EPR) and ultraviolet-visible(UV-vis) spectroscopic methods coupled with redox titration were employed to monitor the electron transfer processes and obtain further insights into the electron transfer pathway in SLAC. The reduction potentials for type 1 copper(T1Cu), type 2 copper(T2Cu) and type 3copper(T3Cu) were determined to be 367 ± 2 mV, 378 ± 5 m V and 403 ± 2 mV,respectively. Moreover, the reduction potential of a selected substrate of SLAC, hydroquinone(HQ), was determined to be 288 mV using cyclic voltammetry(CV). In this way, an electron transfer pathway was identified based on the reduction potentials. Specifically,electrons are transferred from HQ to T1Cu, then to T2Cu and T3Cu, and finally to ***, superhyperfine splitting observed via EPR during redox titration indicated a modification in the covalency of T2Cu upon electron uptake, suggesting a conformational alteration in the protein environment surrounding the copper sites, which could potentially influence the reduction potential of the copper sites during catalytic processes. The results presented here not only provide a comprehensive method for analyzing the electron transfer pathway in metalloenzymes through reduction potential measurements, but also offer valuable insights for further engineering and directed evolution studies of SLAC in the aim for biotechnological and industrial applications.

关键词： Electron paramagnetic resonance Redox titration Electron transfer Reduction Potential Small laccase

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Idebenone alleviates doxorubicin-induced cardiotoxicity by stabilizing FSP1 to inhibit ferroptosis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2581-2597页

作者： Hongliang Qiu Sihui Huang Yuting Liu Libo Liu Fengming Guo Yingying Guo Dan Li Xianfeng Cen Yajie Chen Meng Zhang Yan Che Man Xu Qizhu Tang department of Cardiology Renmin Hospital of Wuhan UniversityWuhan 430060China Hubei Key Laboratory of metabolic and Chronic diseases Wuhan 430060China

Doxorubicin(DOX)-mediated cardiotoxicity can exacerbate mortality in oncology patients,but related pharmacotherapeutic measures are relatively *** was recently identified as a major mechanism of DOX-induced ***,a novel ferroptosis inhibitor,is a well-described clinical drug widely ***,its role and pathological mechanism in DOX-induced cardiotoxicity are still *** this study,we demonstrated the effects of idebenone on DOX-induced cardiotoxicity and elucidated its underlying mechanism.A single intraperitoneal injection of DOX(15 mg/kg)was administrated to establish DOX-induced *** results showed that idebenone significantly attenuated DOX-induced cardiac dysfunction due to its ability to regulate acute DOX-induced Fe^(2+)and ROS overload,which resulted in *** and BLI further revealed that idebenone's anti-ferroptosis effect was mediated by ***,idebenone increased FSP1 protein levels but did not affect Fsp1 mRNA levels in the presence of *** could form stable hydrogen bonds with FSP1 protein at K355,which may influence its association with *** results confirmed that idebenone stabilized FSP1 protein levels by inhibiting its ubiquitination *** conclusion,this study demonstrates idebenone attenuated DOX-induced cardiotoxicity by inhibiting ferroptosis via regulation of FSP1,making it a potential clinical drug for patients receiving DOX treatment.

关键词： Idebenone DOX-induced cardiotoxicity Ferroptosis FSP1 Ubiquitination Lipid peroxidation Iron overload Clinical translation

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Gut microbial-host-isozymes are new targets for diseases

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Science China(Life Sciences) 2024年第7期67卷 1525-1527页

作者： Zhiwei Zhang Kai Wang Changtao Jiang department of Physiology and Pathophysiology School of Basic Medical SciencesState Key Laboratory of Female Fertility PromotionCenter for Reproductive MedicinePeking UniversityBeijing 100191China Center for Obesity and metabolic disease Research School of Basic Medical SciencesState Key Laboratory of Vascular Homeostasis and RemodelingPeking UniversityBeijing 100191China

Gut microbiota can interact with the host through lots of media including small molecular metabolites and proteins(Cani,2019;Fan and Pedersen,2021;Krautkramer et al.,2021).Recently,a new interaction pattern was identified,i.e.,gut microbiota can mimic the function of the host by producing a variety of enzymes with functions homologous to host enzymes.

关键词： diseases pattern

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