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Targeted metabolomics reveals the aberrant energy status in diabetic peripheral neuropathy and the neuroprotective mechanism of traditional Chinese medicine JinMaiTong

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Journal of Pharmaceutical Analysis 2024年第2期14卷 225-243页

作者： Bingjia Zhao Qian Zhang Yiqian He Weifang Cao Wei Song Xiaochun Liang Department of Traditional Chinese Medicine Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing100730China Institute of Basic Medicine sciences Chinese Academy of Medical SciencesBeijing100005China medical Research Center Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing100730China

Diabetic peripheral neuropathy (DPN) is a common and devastating complication of diabetes, for which effective therapies are currently lacking. Disturbed energy status plays a crucial role in DPN pathogenesis. However, the integrated profile of energy metabolism, especially the central carbohydrate metabolism, remains unclear in DPN. Here, we developed a metabolomics approach by targeting 56 metabolites using high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) to illustrate the integrative characteristics of central carbohydrate metabolism in patients with DPN and streptozotocin-induced DPN rats. Furthermore, JinMaiTong (JMT), a traditional Chinese medicine (TCM) formula, was found to be effective for DPN, improving the peripheral neurological function and alleviating the neuropathology of DPN rats even after demyelination and axonal degeneration. JMT ameliorated DPN by regulating the aberrant energy balance and mitochondrial functions, including excessive glycolysis restoration, tricarboxylic acid cycle improvement, and increased adenosine triphosphate (ATP) generation. Bioenergetic profile was aberrant in cultured rat Schwann cells under high-glucose conditions, which was remarkably corrected by JMT treatment. In-vivo and in-vitro studies revealed that these effects of JMT were mainly attributed to the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and downstream peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our results expand the therapeutic framework for DPN and suggest the integrative modulation of energy metabolism using TCMs, such as JMT, as an effective strategy for its treatment.

关键词： Diabetic peripheral neuropathy JinMaiTong Energy metabolism Targeted metabolomics Adenosine monophosphate-activated protein kinase

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Progress in the generation of spinal cord organoids over the past decade and future perspectives

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Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： Gang Zhou Siyuan Pang Yongning Li Jun Gao Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of International medical Service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in *** emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past *** literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal ***,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional *** qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue *** utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord ***,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational *** of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

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CD87-targeted BiTE and CAR-T cells potently inhibit invasive nonfunctional pituitary adenomas

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Science China(Life sciences) 2024年第10期67卷 2169-2185页

作者： Yuan Ren Xinjie Bao Ming Feng Bing Xing Wei Lian Yong Yao Renzhi Wang Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Recently,bispecific T-cell engagers(BiTEs)and chimeric antigen receptor-modified T cells(CAR-Ts)have been shown to have high therapeutic efficacy in hematological ***87 is highly expressed in solid tumors with an oncogenic *** assess their cytotoxic effects on invasive nonfunctioning pituitary adenomas(iNFPAs),we first examined CD87 expression and its effects on the metabolism of iNFPA *** generated CD87-specific BiTE and CAR/IL-12 T cells,and their cytotoxic effects on iNFPAs cells and in mouse models were ***87 had high expression in i NFPA tissue and cell samples but was undetected in noncancerous brain ***87×CD3 BiTE and CD87 CAR/IL-12 T-cells showed antigenic specificity and exerted satisfactory cytotoxic effects,decreasing tumor cell proliferation in vitro and reducing existing tumors in experimental ***,the above findings suggest that CD87 is a promising target for the immunotherapeutic management of iNFPAs using anti-CD87 BiTE and CD87-specific CAR/IL-12 T cells.

关键词： CD87 chimeric antigen receptor T cells invasive non-functional pituitary adenomas bispecific T cell engager Warburg effect

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Dysregulated N6-methyladenosine modification in peripheral immune cells contributes to the pathogenesis of amyotrophic lateral sclerosis

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Frontiers of Medicine 2024年第2期18卷 285-302页

作者： Di He Xunzhe Yang Liyang Liu Dongchao Shen Qing Liu Mingsheng Liu Xue Zhang Liying Cui Department of Neurology Peking Union Medical College Hospital(PUMCH)Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China medical Doctor Program Chinese Academy of Medical Science and Peking Union Medical CollegeBeijing100730China McKusick-Zhang Center for Genetic Medicine State Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic MedicinePeking Union Medical CollegeBeijing100730China Neuroscience Center Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100730China

Amyotrophic lateral sclerosis(ALS)is a progressive neurogenerative disorder with uncertain *** evidence implicates N6-methyladenosine(m6A)modification in ALS *** RNA immunoprecipitation sequencing(MeRIP-seq)and liquid chromatography–mass spectrometry were utilized for m6A profiling in peripheral immune cells and serum proteome analysis,respectively,in patients with ALS(n=16)and controls(n=6).The single-cell transcriptomic dataset(GSE174332)of primary motor cortex was further analyzed to illuminate the biological implications of differentially methylated genes and cell communication *** of peripheral immune cells revealed extensive RNA hypermethylation,highlighting candidate genes with differential m6A modification and expression,including C-X3-C motif chemokine receptor 1(CX3CR1).In RAW264.7 macrophages,disrupted CX3CR1 signaling affected chemotaxis,potentially influencing immune cell migration in *** proteome analysis demonstrated the role of dysregulated immune cell migration in *** type-specific expression variations of these genes in the central nervous system(CNS),particularly microglia,were *** communication between neurons and glial cells was selectively altered in ALS *** integrated approach underscores m6A dysregulation in immune cells as a potential ALS contributor.

关键词： amyotrophic lateral sclerosis N^(6)-methyladenosine epi-transcriptome proteome single cell RNA sequencing analysis CX3CR1

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Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 393-398页

作者： Mei-Zi Li Tao Guo Yun-Lu Feng Sheng-Yu Zhang Xiao-Yin Bai Xi Wu Kai Xu Ai-Ming Yang Department of Gastroenterology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China Department of Radiology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is ***,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is *** study aimed to demonstrate and identify predictors of DM control under the influence of ***:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM *** incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM *** the 52 patients with DM,CST was administered in 48 *** logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control ***:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP *** exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

关键词： Type 1 autoimmune pancreatitis Diabetes mellitus Corticosteroid therapy Predictive factor Pancreatic atrophy

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Clinical manifestations and spermatogenesis outcomes in Chinese patients with congenital hypogonadotropic hypogonadism caused by inherited or de novo FGFR1 mutations

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Asian Journal of Andrology 2024年第4期26卷 426-432页

作者： Yu-Fan Yang Hai-Lu Ma Xi Wang Min Nie Jiang-Feng Mao Xue-Yan Wu Department of Endocrinology Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China.

Fibroblast growth factor receptor 1(FGFR1)mutations are associated with congenital hypogonadotropic hypogonadism(CHH)through inheritance or spontaneous *** detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union medical college Hospital(Beijing,China)using next-generation and Sanger *** assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation *** 19 patients with FGFR1 mutations,three were recurrent,and 16 were novel *** of the novel mutations were likely pathogenic according to the American college of medical Genetics and Genomics(ACMG)guidelines,with the prevalent P366L *** majority of FGFR1 mutations was inherited(57.9%),with frameshift mutations exclusive to the de novo mutation *** inherited mutation group had a lower incidence of cryptorchidism,short stature,and skeletal *** the inherited mutation group,luteinizing hormone(LH)levels were 0.5 IU l−1,follicle-stimulating hormone(FSH)levels were 1.0 IU l−1,and testosterone levels were 1.3 nmol l−*** contrast,the de novo group had LH levels of 0.2 IU l−1,FSH levels of 0.5 IU l−1,and testosterone levels of 0.9 nmol l−1,indicating milder hypothalamus–pituitary–gonadal axis(HPGA)functional deficiency in the inherited *** inherited mutation group showed a tendency toward higher spermatogenesis *** conclusion,this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations,contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

关键词： congenital hypogonadotropic hypogonadism de novo FGFR1 inherited

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Comparative analysis of the microbiome of sympatric wintering Bean Geese,Domestic Ducks,humans,and soil at Shengjin Lake of China reveals potential public risk to human health

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Avian Research 2024年第2期15卷 279-286页

作者： Gang Liu Na Xu Chongyang Yu college of Life sciences Anhui Medical UniversityHefei 230032China

The gut microbiota of migratory waterbirds is affected by various complex factors,including cross-species transmission,which increases the risk of pathogen spreading among sympatric animals and poses a potential public health risk to *** this study,we investigated the microbial communities of wintering Bean Geese(Anser fabalis),Domestic Ducks(*** domesticus),humans,and soil using high-throughput sequencing of the 16S rRNA gene region in Shengjin Lake,*** total,6,046,677 clean reads were obtained,representing 41,119 operational taxonomic units(OTUs)across the four *** dominant microbial phyla were the Proteobacteria,Firmicutes,Bacteroidota,and *** Sorensen similarity index and alpha and beta diversity results showed that the gut microbial communities of Bean Geese and Domestic Ducks were more similar to those of the other *** analysis revealed that Faecalibacterium prausnitzii,Pseudomonas fragi,and Bradyrhizobium elkanii were hubs of the three major *** common microbiomes were iden-tified in Bean Geese,Domestic Ducks,humans,and soil in Shengjin Lake.A total of 96 potential pathogens were identified among the four groups,with 20 specific potentially pathogenic microbiomes found in the gut of Bean *** of these pathogens are responsible for significant financial losses in the poultry industry and pose risks to human *** pneumoniae,Morganella morganii,Escherichia coli,and Ralstonia insidiosa are potential core pathogens found in the four groups at Shengjin Lake that can cause diseases in humans and an-imals and facilitate cross-species transmission through various ***,humans are at risk of con-tracting these pathogens from migratory birds because of their frequent contact with domestic ***,further studies are required to explore the potential pathogenic species and transmission pathways among sympatric wintering Bean Geese,Domestic Ducks,humans,and soil.

关键词： Microbiome Migratory waterbird Pathogens Poultry Sympatric species

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Heat stress induced hepatocyte apoptosis in largemouth bass Micropterus salmoides via IRE1α/TRAF2/ASK1/JNK pathway

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Journal of Oceanology and Limnology 2024年第3期42卷 988-1000页

作者： Xuqian ZHAO Wenjia MAO Zijie LIN Qufei LING School of Biology and Basic medical sciences Suzhou Medical College of Soochow UniversitySuzhou 215000China

Heat stress(HS)has been shown to adversely affect fish livers and can lead to extensive *** investigate the relationship between endoplasmic reticulum(ER)stress and HS-induced apoptosis in fish livers,we isolated and cultured primary hepatocytes of largemouth bass,Micropterus salmoides by trypsin method,then established an in-vitro model of liver cells under HS(35℃).The contents of lactic dehydrogenase(LDH)and hydrogen peroxide(H2O2)were determined to evaluate the effects of HS on hepatocyte injury and oxidative ***-qPCR was performed to discover the key genes in unfolded protein response(UPR)pathways involved at different HS *** inhibitor 4-PBA and IRE1αinhibitor 4μ8C were used to further investigate the effects of HS on IRE1αapoptosis pathway in *** show that HS led to significant increases in the release of LDH,the content of H2O2,and the expressions of oxidative protein folding genes(ero1αand pdi)under HS,suggesting severe hepatocyte injury and oxidative stress happened in heat-stressed largemouth bass *** continuous activation of IRE1αpathway genes(grp78,grp94,atf6,perk,eif2a,atf4,chop,ire1α,traf2,ask1,jnk1,and jnk2)indicated that HS led significantly to ER *** particular,the mRNA expression levels of ER stress-related genes(grp78,grp94,atf6,perk,ire1α,chop,jnk1,and jnk2)in the high temperature(HT)+4-PBA group and the HT+4μ8C group were significantly down-regulated under *** 4μ8C treatment,the expression levels of apoptosis-related genes(caspase-2,caspase-3,caspase-6,caspase-7,caspase-8,caspase-9,and caspase-10)and LDH content were significantly decreased,whereas the cell survival rate was significantly increased when given 4-PBA or 4μ8C *** findings demonstrate that HS could induce liver apoptosis of largemouth bass through the IRE1αpathway,which may act as a key switch mediating liver apoptosis of largemouth bass under HS.

关键词： heat stress Micropterus salmoides endoplasmic reticulum stress apoptosis oxidative stress

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Differential expression of miRNAs and mRNAs in the livers of largemouth bass Micropterus salmoides under heat stress

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Journal of Oceanology and Limnology 2024年第2期42卷 594-608页

作者： Xuqian ZHAO Zijie LIN Caijuan LI Hao ZHU Lingling LI Wenjia MAO Qufei LING School of Biology and Basic medical sciences Suzhou Medical College of Soochow UniversitySuzhou 215000China

Global warming threatens freshwater ecosystems and compromises fish *** elucidate the role of miRNAs in the livers of heat stressed largemouth bass,juvenile fish was subject to heat stress under 37°*** mRNA-seq and miRNA-seq were conducted on the liver tissues under control and heat stress *** gene expression analysis and enrichment analysis were performed on mRNA and miRNA expression profiles.A total of 406 differentially expressed genes(DEGs)were discovered,of which 212 were up-regulated and 194 were *** of the DEGs were significantly implicated in the regulation of“protein processing in endoplasmic reticulum”,“proteasome”,“steroid biosynthesis”,and“ornithine decarboxylase inhibitor activity”*** addition,47 differentially expressed miRNAs(DEMs)were identified in largemouth bass livers under heat stress,including 21 up-regulated and 25 down-regulated miRNAs.A negatively regulated miRNA-mRNA network including 12 miRNAs and 19 mRNAs was constructed with DEMs involved in“protein degradation”,“calcium ion regulation”,“cell apoptosis”,and“lipid metabolism”.Moreover,this study indicated novel-miR-144 activated the IRE1 signaling pathway by targeting txndc5 to induce liver apoptosis in largemouth bass under heat *** study revealed the involvement of miRNA regulation in largemouth bass in response to heat stress.

关键词： heat stress largemouth bass miRNA-mRNA interaction

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Long-term prognosis and its associated predictive factors in patients with eosinophilic gastroenteritis

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World Journal of Gastroenterology 2024年第2期30卷 146-157页

作者： Kai-Wen Li Ge-Chong Ruan Shuang Liu Tian-Ming Xu Ye Ma Wei-Xun Zhou Wei Liu Peng-Yu Zhao Zhi-Rong Du Ji Li Jing-Nan Li Department of Gastroenterology Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China Department of Allergy Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China Department of Pathology Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China Department of Radiology Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100730China Affairs Office Chinese Academy of Medical Sciences and Peking Union Medical College Hospital(West campus)Beijing 100032China

BACKGROUND Eosinophilic gastroenteritis(EGE)is a chronic recurrent disease with abnormal eosinophilic infiltration in the gastrointestinal *** remain the most common treatment ***,disease relapse and glucocorticoid dependence remain notable *** date,few studies have illuminated the prognosis of EGE and risk factors for disease *** To describe the clinical characteristics of EGE and possible predictive factors for disease relapse based on long-term *** This was a retrospective cohort study of 55 patients diagnosed with EGE admitted to one medical center between 2013 and *** records were collected and ***-Meier curves and log-rank tests were conducted to reveal the risk factors for long-term relapse-free survival(RFS).RESULTS EGE showed a median onset age of 38 years and a slight female predominance(56.4%).The main clinical symptoms were abdominal pain(89.1%),diarrhea(61.8%),nausea(52.7%),distension(49.1%)and vomiting(47.3%).Forty-three(78.2%)patients received glucocorticoid treatment,and compared with patients without glucocorticoid treatments,they were more likely to have elevated serum immunoglobin E(IgE)(86.8%vs 50.0%,P=0.022)and descending duodenal involvement(62.8%vs 27.3%,P=0.046)at *** a median follow-up of 67 mo,all patients survived,and 56.4%had at least one *** variables at baseline might have been associated with the overall RFS rate,including age at diagnosis24 kg/m^(2)(HR 0.3922,95%CI:0.1916-0.8027,P=0.014),disease duration from symptom onset to diagnosis>3.5 mo(HR 2.4725,95%CI:1.220-5.0110,P=0.011),vomiting(HR 3.1259,95%CI:1.5246-6.4093,P=0.001),total serum IgE>300 KU/L at diagnosis(HR 0.2773,95%CI:0.1204-0.6384,P=0.022)and glucocorticoid treatment(HR 6.1434,95%CI:2.8446-13.2676,P=0.003).CONCLUSION In patients with EGE,younger onset age,longer disease c

关键词： Eosinophilic gastroenteritis Prognosis Relapse Glucocorticoid Glucocorticoid dependence

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