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B-cell lymphoma-2 phosphorylation at Ser70 site-related autophagy mediates puerarin-inhibited the apoptosis of MC3T3-E1 cells during osteoblastogenesis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 27-34页

作者： LI Xi LIN Xiangquan CHEN Dongdong LIU Hui the Third Clinical medical college Fujian Medical University Department of Orthopedics Fuzhou Second HospitalFuzhou 350007China

OBJECTIVE:To explore the relationship between autophagy and apoptosis regulated by puerarin during ***:In this study,the effects of puerarin on the autophagic activity and apoptosis level of osteoblast precursors(MC3T3-E1 cells)was ***,the roles of puerarin on B-cell lymphoma-2(Bcl-2)phosphorylation at different sites in osteoblast precursors were *** effect of puerarin on the interaction between Bcl-2 and autophagy regulatory molecule or pro-apoptotic molecule was also investigated using Co-immunoprecipitation *** addition,the effect of puerarin on mitochondrial membrane potential of osteoblast precursors was also identified by mitochondrial membrane potential fluorescence probe ***:Our results showed that puerarin can promote the autophagic activity and apoptosis level of *** addition,puerarin promoted Bcl-2phosphorylation at Ser70 site,and the dissociation of Bcl-2-Beclin1 ***,puerarin could enhance the binding of Bcl-2-Bcl-2-Associated X(Bax)complex in MC3T3-E1 ***,puerarin increased the mitochondrial membrane potential of MC3T3-E1 ***:Therefore,puerarin promotes Beclin1into autophagy flux through Bcl-2 phosphorylation at Ser70,thereby enhancing autophagy of osteoblast precursors,which mediates its anti-apoptotic role during ***,the dissociation of Bcl-2-Beclin1 complex is conducive to the binding of Bcl-2-Bax complex,which resists the apoptosis of osteoblast precursors via the increased mitochondrial membrane potential.

关键词： puerarin osteoblasts autophagy apoptosis lymphoma B-cell

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

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

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World Journal of Gastroenterology 2024年第8期30卷 855-862页

作者： Li-Hui Wang Bin-Bin Su Sheng-Shu Wang Guan-Chao Sun Kun-Ming Lv Yi Li Hui Shi Qian-Qian Chen college Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology Second Medical Center of Chinese PLA General HospitalBeijing 100853China Institute of Geriatrics The 2nd Medical CenterBeijing Key Laboratory of Aging and GeriatricsNational Clinical Research Center for Geriatrics DiseasesSecond Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse *** its risk factors is crucial to understanding the etiology,prevention,and management of the *** occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(***)infection,and metabolic *** To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,*** infection,and metabolic syndrome on reflux *** Outpatients attending the second medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively *** patients’basic information,test results,gastroscopy results,*** test results,and IgG-mediated food intolerance results were *** logistic regression analysis was used to analyze risk factors for reflux *** mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on *** infection affecting reflux *** A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,*** infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,*** analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was *** infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on *** infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on *** infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intol

关键词： Gastroesophageal reflux Esophagitis Food intolerance Metabolic syndrome Helicobacter pylori Chemokines

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

The advantages of multi-level omics research on stem cell-based therapies for ischemic stroke

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Neural Regeneration Research 2024年第9期19卷 1998-2003页

作者： Yiqing Wang Chuheng Chang Renzhi Wang Xiaoguang Li Xinjie Bao 4+4 Doctor medical Program Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of Neurosurgery Peking Union Medical College HospitalPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina beijing Key Laboratory for Biomaterials and Neural Regeneration School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina

Stem cell transplantation is a potential therapeutic strategy for ischemic stroke. However, despite many years of preclinical research, the application of stem cells is still limited to the clinical trial stage. Although stem cell therapy can be highly beneficial in promoting functional recovery, the precise mechanisms of action that are responsible for this effect have yet to be fully elucidated. Omics analysis provides us with a new perspective to investigate the physiological mechanisms and multiple functions of stem cells in ischemic stroke. Transcriptomic, proteomic, and metabolomic analyses have become important tools for discovering biomarkers and analyzing molecular changes under pathological conditions. Omics analysis could help us to identify new pathways mediated by stem cells for the treatment of ischemic stroke via stem cell therapy, thereby facilitating the translation of stem cell therapies into clinical use. In this review, we summarize the pathophysiology of ischemic stroke and discuss recent progress in the development of stem cell therapies for the treatment of ischemic stroke by applying multi-level omics. We also discuss changes in RNAs, proteins, and metabolites in the cerebral tissues and body fluids under stroke conditions and following stem cell treatment, and summarize the regulatory factors that play a key role in stem cell therapy. The exploration of stem cell therapy at the molecular level will facilitate the clinical application of stem cells and provide new treatment possibilities for the complete recovery of neurological function in patients with ischemic stroke.

关键词： ischemic stroke mesenchymal stem cells metabolomics multilevel omics neural stem/progenitor cells neuroinflammation pathophysiology proteomics stem cell therapy transcriptomes

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

Effect of a systemic intervention combined with a psychological intervention in stroke patients with oropharyngeal dysfunction

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World Journal of Psychiatry 2024年第6期14卷 904-912页

作者： Jie Song Jian-Dong Wang Di Chen Jing Chen Jin-Feng Huang Mao Fang second Ward Department of NeurologyThe Second Affiliated Hospital of Qiqihar Medical CollegeQiqihar 161006Heilongjiang ProvinceChina Third Ward Department of NeurologyThe Second Affiliated Hospital of Qiqihar Medical CollegeQiqihar 161006Heilongjiang ProvinceChina

BACKGROUND Stroke frequently results in oropharyngeal dysfunction(OD),leading to difficulties in swallowing and eating,as well as triggering negative emotions,malnutrition,and aspiration pneumonia,which can be detrimental to ***,routine nursing interventions often fail to address these issues *** and psychological interventions can improve dysphagia symptoms,relieve negative emotions,and improve quality of ***,there are few clinical reports of systemic interventions combined with psychological interventions for stroke patients with *** To explore the effects of combining systemic and psychological interventions in stroke patients with *** This retrospective study included 90 stroke patients with OD,admitted to the second Affiliated Hospital of Qiqihar medical college(January 2022–December 2023),who were divided into two groups:regular and *** function grading(using a water swallow test),swallowing function[using the standardized swallowing assessment(SSA)],negative emotions[using the selfrating anxiety scale(SAS)and self-rating depression scale(SDS)],and quality of life(SWAL-QOL)were compared between groups before and after the intervention;aspiration pneumonia incidence was *** Post-intervention,the coalition group had a greater number of patients with grade 1 swallowing function compared to the regular group,while the number of patients with grade 5 swallowing function was lower than that in the regular group(P<0.05).Post-intervention,the SSA,SAS,and SDS scores of both groups decreased,with a more significant decrease observed in the coalition group(P<0.05).Additionally,the total SWAL-QOL score in both groups increased,with a more significant increase observed in the coalition group(P<0.05).During the intervention period,the total incidence of aspiration and aspiration pneumonia in the coalition group was lower than that in the control group(4.44%vs 20.00%;P<0.05).CONCLUSION Systemic int

关键词： Stroke Oropharyngeal dysfunction Systemic interventions Psychological intervention Curative effect Negative emotion

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

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 P<5×10^(-8)).The data of WC(from the Genetic 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