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Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

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Neural Regeneration Research 2025年第2期20卷 518-532页

作者： Conglin Wang Fangyuan Cheng Zhaoli Han Bo Yan Pan Liao Zhenyu Yin Xintong Ge Dai Li Rongrong Zhong Qiang Liu Fanglian Chen Ping Lei Department of geriatrics Tianjin Medical University General HospitalTianjinChina School of medicine Nankai UniversityTianjinChina Tianjin Neurological Institute TianjinChina

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor ***-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system *** this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying *** results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral ***,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory *** sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier *** with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these *** summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

关键词： AKT astrocyte blood-brain barrier cerebral edema exosomes human-induced pluripotent stem cells intracerebral hemorrhage neural stem cells neuroinflammation PI3K

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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki Kim Bum Jun Kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung Gon Kim Jun Young Choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and ***-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain *** drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system *** it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system *** this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory *** targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

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Neural Regeneration Research 2025年第1期20卷 242-252页

作者： Daiyu Hu Yuanqing Cao Chenglin Cai Guangming Wang Min Zhou Luying Peng Yantao Fan Qiong Lai Zhengliang Gao Fundamental Research Center Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghaiChina Institute of geriatrics(Shanghai University) Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong)Shanghai University School of MedicineNantongJiangsu ProvinceChina Shanghai Engineering Research Center of Organ Repair Shanghai University School of MedicineShanghaiChina Key Laboratory of Arrhythmias Ministry of EducationShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Human brain development is a complex process,and animal models often have significant *** address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and *** enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid *** involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid *** cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology *** a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental *** organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature *** exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic *** convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

关键词： cadmium cell death cell proliferation cortical development environmental toxins neural progenitor cells neurogenesis neurotoxicology organoids stem cells

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Dissecting the cell microenvironment of ovarian endometrioma through single-cell RNA sequencing

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Science China Life Sciences 2025年第1期 116-129页

作者： Jiangpeng Wu Siyu Xia Wenting Ye Yan Sun Jing Cai Fubing Yu Haiping Wen Xiuwei Yi Taikang Li Mingwei Chen Jiayun Chen Ge Song Chuanbin Yang Yali Song Jigang Wang Department of Reproductive medicine Dongguan Maternal and Child Health Care Hospital Department of Urology and Shenzhen Clinical Research Centre for GeriatricsShenzhen People's HospitalSouthern University of Science and Technology State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Centerand Institute of Chinese Materia MedicaChina Academy of Chinese Medical Sciences Reproductive medicine Center Foshan Women and Children Hospital State Key Laboratory of Antiviral Drugs School of PharmacyHenan University

Ovarian endometrioma（OE）, also known as “chocolate cysts,” is a cystic mass that develops in the ovaries due to endometriosis and is a common gynecological condition characterized by the growth of endometrial tissue outside the uterus, leading to symptoms such as dysmenorrhea, pelvic pain, and infertility. However, the precise molecular and cellular mechanisms driving this pathophysiology remain largely unknown, posing challenges for diagnosis and treatment. Here, we employed integrated single-cell transcriptomic profiling of over 52,000 individual cells from endometrial tissues of OE patients and healthy donors and identified twelve major cell populations. We identified notable alterations in cell type-specific proportions and molecular signatures associated with OE. Notably, the activation of IGFBP5+macrophages with pro-inflammatory properties, NK cell exhaustion, and aberrant proliferation of IQCG+and KLF2+epithelium are key features and may be the potential mechanisms underlying the pathogenesis of OE. Collectively, our data contribute to a better understanding of OE at the single cell level and may pave the way for the development of novel therapeutic strategies.

关键词： ovary high-throughput sequencing transcriptomics gene expression analysis ligand-receptor analysis

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Heterogeneity of chronic obstructive pulmonary disease:from phenotype to genotype

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Frontiers of medicine 2013年第4期7卷 425-432页

作者： Xu Chen Xiaomao Xu Fei Xiao Key Laboratory of geriatrics Beijing Institute of Geriatrics Department of Respiratory medicine Beijing HospitalMinistry of HealthBeijing 100730China

Chronic obstructive pulmonary disease(COPD)is one of the leading causes of morbidity and mortality throughout the world and is mainly characterized by persistent airflow *** that multiple systems other than the lung can be impaired in COPD patients,the traditional FEV1/FVC ratio shows many limitations in COPD diagnosis and *** heterogeneities are found in terms of clinical manifestations,physiology,imaging findings,and inflammatory reactions in COPD patients;thus,phenotyping can provide effective information for the prognosis and ***,phenotypes are often based on symptoms or pathophysiological impairments in late-stage COPD,and the role of phenotypes in COPD prevention and early diagnosis remains *** shortcoming may be overcome by the potential genotypes defined by the heterogeneities in certain *** review briefly describes the heterogeneity of COPD,with focus on recent advances in the correlations between genotypes and *** potential roles of these genotypes and phenotypes in the molecular mechanisms and management of COPD are also elucidated.

关键词： chronic obstructive pulmonary disease heterogeneity phenotype genotype prediction

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Moxibustion enables protective effects on rheumatoid arthritis-induced myocardial injury via transforming growth factor beta1 signaling and metabolic reprogramming

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Journal of Traditional Chinese medicine 2023年第6期43卷 1190-1199页

作者： WANG Miao ZHU Yan ZHAO Hui ZHAO Hongfang the geriatrics Anhui University of Traditional Chinese MedicineHefei 230031China the geriatrics the Second Hospital Affiliated of Anhui University of Traditional Chinese MedicineHefei 230061China

OBJECTIVE:To examine the effects of moxibustion on myocardial injury and myocardial metabolomics in rats with rheumatoid arthritis(RA)based on the transforming growth factor beta1(TGF-β1)/Smads signaling ***:One hundred rats were treated with saline[normal control(NC)group]or complete Freund’s adjuvant(CFA)by right plantar injection for the RA model group,and the latter were randomly divided into 4 *** wilfordii polyglycoside tablets(雷公藤多苷片,TPT)have anti-inflammatory and are widely used in the clinical treatment of RA,therefore serving as a positive control *** days post injection rats were given TPT tablet(TPT group),acupuncture therapy(APT group),and moxibustion treatment(MOX group)for 15 consecutive days,while NC group and model group were equally grasped and fixed and received normal *** joint swelling scores and arthritis index(AI)were evaluated in each group before the CFA challenge,therapy and after receiving *** ultrastructure was observed by electron ***-linked immunosorbent assay was used to detect cardiac troponin I(cTnI)levels in rat myocardial *** reverse transcription polymerase chain reaction and Western blotting analysis were used to measure the mRNA and protein levels of TGF-βsignaling molecules including TGF-β1,Smad2,Smad3,Smad4,and *** metabolomics was analyzed using gas chromatography-mass ***:Compared with model group,RA model rats receiving TPT,acupuncture,or moxibustion therapy all showed reduced joint swelling scores and AI(all P<0.01)and improved myocardial damage,whereas rats treated with moxibustion were found to be more ***,the expressions of cTnI,TGF-β1,Smad2,Smad3,and Smad4 were found to be elevated in model rat group in contrast to NC rats and were significantly downregulated in TPT,APT and MOX group when compared with model group,while the levels of Smad7 showed the opposite result(all P<0.01).Moreover,

关键词： moxibustion arthritis rheumatoid transforming growth factor beta1 smad proteins signal transduction myocardial injury metabolomics

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Exhaled breath analysis in hepatology: State-of-the-art and perspectives

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World Journal of Gastroenterology 2019年第30期25卷 4043-4050页

作者： Antonio De Vincentis Umberto Vespasiani-Gentilucci Anna Sabatini Raffaele Antonelli-Incalzi Antonio Picardi unit of Clinical medicine and Hepatology Unit of GeriatricsDepartment of MedicineCampus Bio-Medico University HospitalRome 00128Italy unit of Electronics for sensor systems Department of EngineeringUniversity Campus Bio-Medico of RomeRome 00128Italy

Liver disease is characterized by breath exhalation of peculiar volatile organic compounds(VOCs).Thanks to the availability of sensitive technologies for breath analysis,this empiric approach has recently gained increasing attention in the context of hepatology,following the good results obtained in other fields of *** the first studies that led to the identification of selected VOCs for pathophysiological purposes,subsequent research has progressively turned towards the comprehensive assessment of exhaled breath for potential clinical *** VOC patterns were found to discriminate subjects with liver cirrhosis,to rate disease severity,and,eventually,to forecast adverse clinical outcomes even beyond existing *** results suggest that breath analysis could be useful also for detecting and staging hepatic encephalopathy and for predicting steatohepatitis in patients with nonalcoholic fatty liver ***,clinical translation is still hampered by a number of methodological limitations,including the lack of standardization and the consequent poor comparability between studies and the absence of external validation of obtained *** the low-cost and easy execution at bedside of the new technologies(e-nose),larger and well-structured studies are expected in order to provide the adequate level of evidence to support VOC analysis in clinical practice.

关键词： Exhaled breath analysis Electronic nose Gas chromatography Breath print Liver cirrhosis Nonalcoholic fatty liver disease Hepatic encephalopathy

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Risk of stroke after acute myocardial infarction among Chinese

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Chinese Medical Journal 2001年第2期114卷 98-99页

作者： Ping-WingNG Wai-KwongCHAN Patrick Kwok-Leung K WAN Department of medicine and geriatrics United Christian Hospital Hong Kong China

Following an acute myocardial infarction (AMI), patients have an increased risk of stroke. Estimates of risk are mainly derived from AMI treatment trials or secondary prevention studies. The reported incidence of stroke in Caucasians in the early phase after AMI ranged from 0.5% to 2.5%.1-3 Similar assessment of risk in the Chinese population is lacking. As thrombolytic therapy becomes standard treatment for AMI, there is concern that there may be an increase in haemorrhagic stroke complicating AMI treatment, especially since haemorrhagic stroke is more common in Asian populations.

关键词： Aged Cerebrovascular Accident China Female Humans Male Myocardial Infarction Risk Factors

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Concurrent stenoses: A common etiology of stroke in Asians

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World Journal of Clinical Cases 2014年第6期2卷 201-205页

作者： Bik Ling Man Yat Pang Fu Department of medicine and geriatrics Tuen Mun Hospital

Atherosclerosis of cerebral vessels is a common cause of stroke. Racial differences in the distribution of cerebrovascular occlusive disease are well *** stenosis is more common in Caucasians,while intracranial stenosis is more common in Asians,Hispanics and African-Americans. Concurrent atherosclerosis of extracranial and intracranial vessels is common in Asians. The incidence of concurrent stenoses ranges from 10% to 48% in patients with symptomatic cerebrovascular disease. The long-term prognosis of these patients is poor and they are at high risk of further vascular events or death. The purpose of this review is to examine the epidemiology, risk factors,stroke mechanism and genetics of concurrent stenoses and to discuss strategies for treatment.

关键词： Atherosclerosis Concurrent stenosis Stroke Asians

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Multidisciplinary treatment of a patient with necrotizing fasciitis caused by Staphylococcus aureus: A case report

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World Journal of Clinical Cases 2019年第21期7卷 3595-3602页

作者： Li-Qian Xu Xin-Xiu Zhao Pei-Xia Wang Ji Yang Yun-Mei Yang Department of geriatrics The First Affiliated Hospital College of Medicine Zhejiang University

BACKGROUND Necrotizing fasciitis is a severe bacterial skin infection that spreads quickly and is characterized by extensive necrosis of the deep and superficial fascia resulting in the devascularization and necrosis of associated *** of high morbidity and mortality,accurate diagnosis and early treatment with adequate antibiotics and surgical intervention are *** timely identification and treatment of complications are necessary to improve survival of *** SUMMARY We report a case of necrotizing fasciitis caused by Staphylococcus aureus in a patient using high doses of glucocorticoid and suffering from secondary diabetes *** was admitted to our hospital due to redness and oedema of the lower *** admission,necrotizing fasciitis caused by Staphylococcus aureus was considered,and he was discharged after B-ultrasound drainage and multiple surgical *** the process of treatment,multiple organ functions were damaged,but with the help of multi-disciplinary treatment,the patient got better *** The key to successful management of necrotizing fasciitis is an early and accurate *** method of using vacuum sealing drainage in postoperative patients can keep the wound dry and clean,reduce infection rate,and promote wound *** collaboration is a vital prerequisite for successful treatment.

关键词： Necrotizing fasciitis Surgical debridement Vacuum sealing drainage Multidisciplinary treatment Case report

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