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chinese medical Journal 2024年第8期137卷 883-886页

作者： Xiaoshuang Wang Jing Wang Tao Cheng institute of Basic medical sciences Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China

The institute of Basic medical sciences(IBMS)is a global leader in biomedical research and advanced medical *** year(2023)marks the 65^(th)anniversary of its foundation at the chinese academy of medical sciences(CAMS)and School of Basic Medicine(SBM)of the peking union medical college(PUMC).In the beginning,the IBMS and SBM incorporated the premedical departments of the PUMC,which was established by the Rockefeller Foundation in *** then,these departments have been committed to undertakingrstrate medical science research in China.

关键词： Basic IBMS foundation

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

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

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

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

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

Neg-Entropy Mechanism as a Target for Natural Medicines

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Engineering 2024年第7期38卷 11-12页

作者： Tian-Le Gao Hui-Hui Guo Jian-Dong Jiang institute of Materia Medica Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Current strategies for drug discovery research mainly focus on molecular targets,in which structure biology plays a central role,such as the detailed mechanism of a drug-target *** principle of this approach is the presumed molecular mechanism or genetic background of the disease being *** this approach has brought progress in understanding the mode of action for some drugs,most prevalent illnesses-especially chronic diseases-are multifactorial and present with a group of symptoms,as is often the case in cardiovascular diseases,metabolic disorders,cancers,and so *** newly emerging term“multi-morbidity”(i.e.,multiple co-occurring diseases)describes a grand challenge for this strategy,and successful drug intervention for multimorbidity should be multifaceted[1].So,our research team has shifted its attention to a new direction that views the disease as a whole instead of a single-molecule abnormality,and focusing on drugs with multiple targets.

关键词： drugs diseases cardiovascular

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

Transcranial Magneto-Acoustic Stimulation Attenuates Synaptic Plasticity Impairment through the Activation of Piezo1 in Alzheimer’s Disease Mouse Model

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Research 2024年第1期2023卷 81-95页

作者： Fangxuan Chu Ruxin Tan Xin Wang Xiaoqing Zhou Ren Ma Xiaoxu Ma Ying Li Ruixu Liu Chunlan Zhang Xu Liu Tao Yin Zhipeng Liu institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China Tianjin institutes of Health Science Tianjin301600China Neuroscience Center Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing100730China

The neuropathological features of Alzheimer’s disease include amyloid *** emerging evidence suggests that Piezo1,a mechanosensitive cation channel,plays a critical role in transforming ultrasound-related mechanical stimuli through its trimeric propeller-like structure,but the importance of Piezo1-mediated mechanotransduction in brain functions is less ***,apart from mechanical stimulation,Piezo1 channels are strongly modulated by *** assume that Piezo1 may play a role in converting mechanical and electrical signals,which could induce the phagocytosis and degradation of Aβ,and the combined effect of mechanical and electrical stimulation is superior to single mechanical ***,we design a transcranial magneto-acoustic stimulation(TMAS)system,based on transcranial ultrasound stimulation(TUS)within a magnetic field that combines a magnetoacoustic coupling effect electric field and the mechanical force of ultrasound,and applied it to test the above hypothesis in 5xFAD *** tests,in vivo electrophysiological recordings,Golgi–Cox staining,enzyme-linked immunosorbent assay,immunofluorescence,immunohistochemistry,real-time quantitative PCR,Western blotting,RNA sequencing,and cerebral blood flow monitoring were used to assess whether TMAS can alleviate the symptoms of AD mouse model by activating Piezo1.

关键词： stimulation Alzheimer Piezo1

Cervical cancer prevention in China: where are we now, and what's next?

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cancer Biology & Medicine 2024年第3期21卷 213-217页

作者： Huijiao Yan Qiankun Wang Youlin Qiao School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical CollegeBejing 100730China Department of cancer Epidemiology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBejing 100021China

Cervical cancer(CC) epidemiology CC, the fourth most frequently diagnosed malignancy in women worldwide, is a major global health challenge, particularly in low-resource regions. Approximately 88.1% of the 604,000 CC new cases occurred in low-and middle-income countries in 2020, and more than 90% of the 342,000 CC deaths occurred in low-and middle-income countries in 2020~1.

关键词： prevention Cervical epidemiology