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Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

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Neural Regeneration Research 2024年第9期19卷 2010-2018页

作者： Yan Wang Dai Li Lan Zhang Zhenyu Yin Zhaoli Han Xintong Ge Meimei Li Jing Zhao Shishuang Zhang Yan Zuo Xiangyang Xiong Han Gao Qiang Liu Fanglian Chen Ping Lei department of Geriatrics Tianjin Medical University General HospitalTianjinChina tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina tianjin Neurological Institute Tianjin Medical University General HospitalTianjinChina

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

关键词： apoptosis C/EBP homologous protein endoplasmic reticulum stress exosome inositol-requiring enzyme 1α microglia miR-124-3p neuron repetitive mild traumatic brain injury X-box binding protein 1

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Single-cell RNA sequencing reveals abnormal transcriptome signature of erythroid progenitors in pure red cell aplasia

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Genes & Diseases 2024年第1期11卷 49-52页

作者： Yumei Liu Haiyue Niu Jie Ren Zhiqin Wang Li Yan Limin Xing Zonghong Shao Rong Fu Zhigang Cai Huaquan Wang department of Hematology Tianjin Medical University General HospitalTianjin 300052China School of Basic medical Sciences Tianjin Medical UniversityTianjin 300070China

Pure red cell aplasia(PRCA)is a bone marrow failure syndrome characterized by severe anemia,reticulocytopenia,selective reduction,and even the absence of bone marrow erythroid precursors,while leukocyte and platelet counts are normal.1 Acquired PRCA can be divided into primary and secondary.Both are mediated by immune responses.Reduction in the quantity and dysfunction of committed erythroid progenitors(EPs),including burst forming uniterythroid(BFU-E)and colony forming unit-erythroid(CFU-E),may be the source of reduced erythropoiesis and needs to be elucidated.

关键词： progenitor anemia leukocyte

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Clinical outcome and prognostic factors of T4N0M0 colon cancer after R0 resection:A retrospective study

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1869-1877页

作者： Bang Liu Zhao-Xiong Zhang Xin-Yang Nie Wei-Lin Sun Yong-Jia Yan Wei-Hua Fu department of General Surgery Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China

BACKGROUND Paradoxically,patients with T4N0M0(stage II,no lymph node metastasis)colon cancer have a worse prognosis than those with T2N1-2M0(stage III).However,no previous report has addressed this issue.AIM To screen prognostic risk factors for T4N0M0 colon cancer and construct a prognostic nomogram model for these patients.METHODS Two hundred patients with T4N0M0 colon cancer were treated at tianjin medical university General Hospital between January 2017 and December 2021,of which 112 patients were assigned to the training cohort,and the remaining 88 patients were assigned to the validation cohort.Differences between the training and validation groups were analyzed.The training cohort was subjected to multi-variate analysis to select prognostic risk factors for T4N0M0 colon cancer,followed by the construction of a nomogram model.RESULTS The 3-year overall survival(OS)rates were 86.2%and 74.4%for the training and validation cohorts,respectively.Enterostomy(P=0.000),T stage(P=0.001),right hemicolon(P=0.025),irregular review(P=0.040),and carbohydrate antigen 199(CA199)(P=0.011)were independent risk factors of OS in patients with T4N0M0 colon cancer.A nomogram model with good concordance and accuracy was constructed.CONCLUSION Enterostomy,T stage,right hemicolon,irregular review,and CA199 were independent risk factors for OS in patients with T4N0M0 colon cancer.The nomogram model exhibited good agreement and accuracy.

关键词： T4N0M0 colon cancer Prognosis Multivariate analysis Nomogram Colon cancer

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Adverse effects of exposure to fine particles and ultrafine particles in the environment on different organs of organisms

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Journal of Environmental Sciences 2024年第1期135卷 449-473页

作者： Jianwei Zhang Zhao Chen Dan Shan Yang Wu Yue Zhao Chen Li Yue Shu Xiaoyu Linghu Baiqi Wang department of Occupational and Environmental Health School of Public HealthTianjin Medical UniversityTianjin 300070China department of medical Tianjin Stomatological HospitalSchool of MedicineNankai UniversityTianjin 300041China tianjin Key Laboratory of Environment Nutrition and Public HealthTianjin 300070China National Demonstration Center for Experimental Preventive Medicine Education(tianjin medical university) Tianjin 300070China

Particulate pollution is a global risk factor that seriously threatens human health.Fine particles(FPs)and ultrafine particles(UFPs)have small particle diameters and large specific surface areas,which can easily adsorb metals,microorganisms and other pollutants.FPs and UFPs can enter the human body in multiple ways and can be easily and quickly absorbed by the cells,tissues and organs.In the body,the particles can induce oxidative stress,inflammatory response and apoptosis,furthermore causing great adverse effects.Epidemiological studies mainly take the population as the research object to study the distribution of diseases and health conditions in a specific population and to focus on the identification of influencing factors.However,the mechanism by which a substance harms the health of organisms is mainly demonstrated through toxicological studies.Combining epidemiological studies with toxicological studies will provide a more systematic and comprehensive understanding of the impact of PM on the health of organisms.In this review,the sources,compositions,and morphologies of FPs and UFPs are briefly introduced in the first part.The effects and action mechanisms of exposure to FPs and UFPs on the heart,lungs,brain,liver,spleen,kidneys,pancreas,gastrointestinal tract,joints and reproductive system are systematically summarized.In addition,challenges are further pointed out at the end of the paper.This work provides useful theoretical guidance and a strong experimental foundation for investigating and preventing the adverse effects of FPs and UFPs on human health.

关键词： Fine particles Ultrafine particles Organs Adverse effect

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Ferroptosis: A therapeutic opportunity of inflammatory bowel disease

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中华医学杂志(英文版) 2024年第7期137卷 874-876页

作者： Ye Yulin Liu Limin Jing Yang Yao Shuangzhe Yang Mo Dai Xin Piao Meiyu Xu Xin Feng Zelin Wang Xiaoli Liu Yifei Miao Junming Gao Xingjie Yu Qingxiang Cao Xiaocang department of Gastroenterology and Hepatology tianjin medical university General Hospital tianjin medical university tianjin 300070 China department of Biochemistry and Molecular Biology School of Basic medical Science

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Regulation of specific abnormal calcium signals in the hippocampal CA1 and primary cortex M1 alleviates the progression of temporal lobe epilepsy

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Neural Regeneration Research 2024年第2期19卷 425-433页

作者： Feng Chen Xi Dong Zhenhuan Wang Tongrui Wu Liangpeng Wei Yuanyuan Li Kai Zhang Zengguang Ma Chao Tian Jing Li Jingyu Zhao Wei Zhang Aili Liu Hui Shen Laboratory of Neurobiology School of Biomedical EngineeringTianjin Medical UniversityTianjinChina Institute for Translational Neuroscience the Second Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Institute for Translational Brain Research Fudan UniversityShanghaiChina department of Radiology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu ProvinceChina Innovative Institute of Chinese Medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinanChina department of Anesthesiology Tianjin Medical University General HospitalTianjinChina department of Orthopaedics Tianjin Medical University General HospitalTianjinChina tianjin Eye Hospital Tianjin Eye InstituteTianjin Key Lab of Ophthalmology and Visual ScienceTianjinChina Laboratory of Neurobiology School of Basic Medical SciencesTianjin Medical UniversityTianjinChina

Temporal lobe epilepsy is a multifactorial neurological dysfunction syndrome that is refractory,resistant to antiepileptic drugs,and has a high recurrence rate.The pathogenesis of temporal lobe epilepsy is complex and is not fully understood.Intracellular calcium dynamics have been implicated in temporal lobe epilepsy.However,the effect of fluctuating calcium activity in CA1 pyramidal neurons on temporal lobe epilepsy is unknown,and no longitudinal studies have investigated calcium activity in pyramidal neurons in the hippocampal CA1 and primary motor cortex M1 of freely moving mice.In this study,we used a multichannel fiber photometry system to continuously record calcium signals in CA1 and M1 during the temporal lobe epilepsy process.We found that calcium signals varied according to the grade of temporal lobe epilepsy episodes.In particular,cortical spreading depression,which has recently been frequently used to represent the continuously and substantially increased calcium signals,was found to correspond to complex and severe behavioral characteristics of temporal lobe epilepsy ranging from gradeⅡto gradeⅤ.However,vigorous calcium oscillations and highly synchronized calcium signals in CA1 and M1 were strongly related to convulsive motor seizures.Chemogenetic inhibition of pyramidal neurons in CA1 significantly attenuated the amplitudes of the calcium signals corresponding to gradeⅠepisodes.In addition,the latency of cortical spreading depression was prolonged,and the above-mentioned abnormal calcium signals in CA1 and M1 were also significantly reduced.Intriguingly,it was possible to rescue the altered intracellular calcium dynamics.Via simultaneous analysis of calcium signals and epileptic behaviors,we found that the progression of temporal lobe epilepsy was alleviated when specific calcium signals were reduced,and that the end-point behaviors of temporal lobe epilepsy were improved.Our results indicate that the calcium dynamic between CA1 and M1 may reflect specific epileptic behaviors corresponding to diff

关键词： Ca^(2+) calcium signals chemogenetic methods hippocampus primary motor cortex pyramidal neurons temporal lobe epilepsy

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Advances in the molecular genetics of parathyroid tumors

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Chinese medical Journal 2024年第3期137卷 376-378页

作者： Liwei Zhao Xianghui He department of General Surgery Tianjin Medical University General HospitalTianjin 300052China

To the Editor:Parathyroid tumors are endocrine tumors that can lead to disorders of calcium and phosphorus metabolism and involve multiple organ systems.In the past,the genetics of parathyroid tumors have been well established,and the significant roles of genes such as MEN1,CDC73,and CCND1 in the process of parathyroid tumorigenesis have been identified and confirmed[Table 1].However,with further research and the widespread use of sequencing technology,“new”roles for“old”genes and new pathogenic mechanisms have been discovered.

关键词： metabolism tumors parathyroid

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Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

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Neural Regeneration Research 2024年第4期19卷 900-907页

作者： Haoshuai Tang Junjin Li Hongda Wang Jie Ren Han Ding Jun Shang Min Wang Zhijian Wei Shiqing Feng department of Othopaedics Tianjin Medical University General Hospital International Science and Technology Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General Hospital tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General Hospital department of Othopaedics Qilu Hospital of Shandong UniversityShandong University Centre for OthopedicsAdvanced Medical Research InstituteShandong University Orthopedic Research Center of Shandong university&Advanced medical Research Institute Cheeloo College of MedicineShandong University

Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

关键词： axon growth collagen exosome human umbilical cord mesenchymal stem cells hyaluronic acid muscular atrophy nerve guidance conduits peripheral nerve regeneration

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Interaction between adolescent sleep rhythms and gender in an obese population

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World Journal of Clinical Cases 2024年第1期12卷 86-94页

作者： Nan-Nan Wu Guo-Li Yan Hong-Yu Zhang Ling Sun Min Hou Guang-Ming Xu department of Laboratory Medicine Tianjin Chest HospitalTianjin 300222China Mental Health Center of tianjin medical university Tianjin Anding HospitalTianjin 300222China department of Child and Adolescent Psychology Mental Health Center of Tianjin Medical UniversityTianjin 300222China

BACKGROUND The obesity rate of adolescents is gradually increasing,which seriously affects their mental health,and sleep plays an important role in adolescent obesity.AIM To investigate the relationship between sleep rhythm and obesity among adolescents and further explores the interactive effect of sleep rhythm and gender on adolescent obesity,providing a theoretical basis for developing interventions for adolescent obesity.METHODS Research data source tianjin Mental Health Promotion Program for Students.From April to June 2022,this study selected 14201 students from 13 middle schools in a certain district of tianjin as the research subject using the convenient cluster sampling method.Among these students,13374 accepted and completed the survey,with an effective rate of 94.2%.The demographic data and basic information of adolescents,such as height and weight,were collected through a general situation questionnaire.The sleep rhythm of adolescents was evaluated using the reduced version of the morningness-eveningness questionnaire.RESULTS A total of 13374 participants(6629 females,accounting for 49.56%;the average age is 15.21±1.433 years)were analyzed.Among them,the survey showed that 2942 adolescent were obesity,accounting for 22%and 2104 adolescent were overweight,accounting for 15.7%.Among them,1692 male adolescents are obese,with an obesity rate of 25.1%,higher than 18.9%of female adolescents.There is a statistically significant difference between the three groups(χ2=231.522,P<0.000).The obesity group has the smallest age(14.94±1.442 years),and there is a statistical difference in age among the three groups(F=69.996,P<0.000).Obesity rates are higher among individuals who are not-only-child,have residential experience within six months,have family economic poverty,and have evening-type sleep(P<0.05).Logistic regression analysis shows a correlation between sleep rhythm and adolescent obesity.Evening-type sleep rhythm can increase the risk of obesity in male adolescents[1.250(1.067-1.468)],but the effect on fema

关键词： Adolescent Obesity Sleep rhythm Gender Interaction

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Gestational diabetes mellitus combined with fulminant type 1 diabetes mellitus, four cases of double diabetes: A case report

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World Journal of Clinical Cases 2024年第4期12卷 787-794页

作者： Hui Li Yun Chai Wei-Hong Guo Yu-Meng Huang Xiao-Na Zhang Wen-Li Feng Qing He Jin Cui Ming Liu department of Endocrinology and Metabolism Tianjin Medical University General HospitalTianjin 300052China

BACKGROUND Fulminant type 1 diabetes mellitus(FT1DM)that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM(PF),always without history of abnormal glucose metabolism.Here,we present four patients who developed FT1DM during treatment but were first diagnosed with gestational diabetes mellitus(GDM).CASE SUMMARY The clinical data of four patients with GDM combined with FT1DM admitted to our hospital between July 2018 and April 2021 were collected,and the patients and their infants were followed up.All patients were diagnosed with GDM during the second trimester and were treated.The blood glucose level elevated suddenly during the third trimester and then were diagnosed with FT1DM.Two patients had an insulin allergy,and two had symptoms of upper respiratory tract infection before onset.One patient developed ketoacidosis,and three developed ketosis.Two patients had cesarean section deliveries,and two had vaginal deliveries.The growth and development of the infants were normal.C-peptide levels were lower than those at onset,suggesting progressive impairment of islet function.The frequencies of the DRB109:01,DQB103:03,DQA103:02,DPA101:03,DPA102:02,DPB105:01,DRB401:03,G 01:01,and G 01:04 human leukocyte antigen(HLA)-G alleles were high in the present study.CONCLUSION In comparison with pregnancy-associated FT1DM(PF),patients with GDM combined with FT1DM had an older age of onset,higher body mass index,slower onset,fewer prodromal symptoms,and less acidosis.The pathogenesis may be due to various factors affecting the already fragileβ-cells of GDM patients with genetically susceptible class II HLA genotypes.We speculate that GDM combined with FT1DM during pregnancy,referred to as“double diabetes,”is a subtype of PF with its own unique characteristics that should be investigated further.

关键词： Fulminant type 1 diabetes mellitus Gestational diabetes mellitus Pregnancy-related fulminant type 1 diabetes mellitus Double diabetes Case report

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