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Exosomes originating from neural stem cells undergoing necroptosis participate in cellular communication by inducing TSC2 upregulation of recipient cells following spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3273-3286页

作者： Shiming Li Jianfeng Li Guoliang Chen Tao Lin Penghui Zhang Kuileung Tong Ningning Chen Shaoyu Liu Shenzhen Key Laboratory of Bone Tissue Repair and Translational Research Department of Orthopedic SurgeryThe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhenGuangdong ProvinceChina department of Orthopedic surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina department of Orthopedics and Traumatology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina department of Orthopedic surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina department of Orthopedic surgery The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

We previously demonstrated that inhibiting neural stem cells necroptosis enhances functional recovery after spinal cord *** exosomes are recognized as playing a pivotal role in neural stem cells exocrine function,their precise function in spinal cord injury remains *** investigate the role of exosomes generated following neural stem cells necroptosis after spinal cord injury,we conducted singlecell RNA sequencing and validated that neural stem cells originate from ependymal cells and undergo necroptosis in response to spinal cord ***,we established an in vitro necroptosis model using neural stem cells isolated from embryonic mice aged 16-17 days and extracted *** results showed that necroptosis did not significantly impact the fundamental characteristics or number of *** sequencing of exosomes in necroptosis group identified 108 differentially expressed messenger RNAs,104 long non-coding RNAs,720 circular RNAs,and 14 microRNAs compared with the control *** of a competing endogenous RNA network identified the following hub genes:tuberous sclerosis 2(Tsc2),solute carrier family 16 member 3(Slc16a3),and forkhead box protein P1(Foxp1).Notably,a significant elevation in TSC2 expression was observed in spinal cord tissues following spinal cord ***2-positive cells were localized around SRY-box transcription factor 2-positive cells within the injury ***,in vitro analysis revealed increased TSC2 expression in exosomal receptor cells compared with other *** assessment of cellular communication following spinal cord injury showed that Tsc2 was involved in ependymal cellular communication at 1 and 3 days post-injury through the epidermal growth factor and midkine signaling *** addition,Slc16a3 participated in cellular communication in ependymal cells at 7 days post-injury via the vascular endothelial growth factor and macrophage migration inhibitory factor signaling

关键词： cellular communication competing endogenous RNA exosomes Foxp1 necroptosis neural stem cells Slc16a3 spinal cord injury transcriptome sequencing Tsc2

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The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu Dan Liu department of Pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision Medicine Research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and Transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

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Identification of autophagy signaling network that contributes to stroke in the ischemic rodent brain via gene expression

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Neuroscience Bulletin 2015年第4期31卷 480-490页

作者： Kun Liang Lei Zhu Jinyun Tan Weihao Shi Qing He Bo Yu department of vascular surgery Huashan HospitalFudan University department of vascular surgery Shanghai Pudong Hospital

Autophagy plays a vital role in cerebral ischemia and may be a potential target for developing novel therapy for stroke. In this study, we constructed an autophagy-related pathway network by analyzing the genes related to autophagy and ischemic stroke, and the risk genes were screened. Two autophagy-related modules were significantly up-regulated and clustered to influence cerebral ischemia. Besides, three key modular genes （NFKB1, RELA, and STAT3） were revealed. With 5-fold cross validation, the ROC curves of NFKB1, RELA, and STAT3 were 0.8256, 0.8462, and 0.8923. They formed a complex module and competitively mediated the activation of autophagy in cerebral ischemia. In conclusion, a module containing NFKB1, RELA, and STAT3 mediates autophagy, serving as a potential biomarker for the diagnosis and therapy of ischemic stroke.

关键词： cerebral ischemia autophagy functiona module stroke gene expression profile

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The pivotal role of microglia in injury and the prognosis of subarachnoid hemorrhage

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Neural Regeneration Research 2025年第7期20卷 1829-1848页

作者： Wenjing Ning Shi Lv Qian Wang Yuzhen Xu department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina department of Central Laboratory The Affiliated Taian City Central Hospital of Qingdao UniversityTaianShandong ProvinceChina

Subarachnoid hemorrhage leads to a series of pathological changes,including vascular spasm,cellular apoptosis,blood–brain barrier damage,cerebral edema,and white matter ***,which are the key immune cells in the central nervous system,maintain homeostasis in the neural environment,support neurons,mediate apoptosis,participate in immune regulation,and have neuroprotective *** evidence has shown that microglia play a pivotal role in the pathogenesis of subarachnoid hemorrhage and affect the process of injury and the prognosis of subarachnoid ***,microglia play certain neuroprotective roles in the recovery phase of subarachnoid *** approaches aimed at modulating microglia function are believed to attenuate subarachnoid hemorrhage *** provides new targets and ideas for the treatment of subarachnoid ***,an in-depth and comprehensive summary of the role of microglia after subarachnoid hemorrhage is still *** review describes the activation of microglia after subarachnoid hemorrhage and their roles in the pathological processes of vasospasm,neuroinflammation,neuronal apoptosis,blood–brain barrier disruption,cerebral edema,and cerebral white matter *** also discusses the neuroprotective roles of microglia during recovery from subarachnoid hemorrhage and therapeutic advances aimed at modulating microglial function after subarachnoid ***,microglia in subarachnoid hemorrhage are targeted with TLR inhibitors,nuclear factor-κB and STAT3 pathway inhibitors,glycine/tyrosine kinases,NLRP3 signaling pathway inhibitors,Gasdermin D inhibitors,vincristine receptorαreceptor agonists,ferroptosis inhibitors,genetic modification techniques,stem cell therapies,and traditional Chinese ***,most of these are still being evaluated at the laboratory *** clinical studies and data on subarachnoid hemorrhage are required to improve the treatment of subarachnoid hemor

关键词： apoptosis blood–brain barrier brain edema microglia neuroinflammation neuron neuroprotection subarachnoid hemorrhage vasoconstriction white matter injury

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A matrix metalloproteinase-responsive hydrogel system controls angiogenic peptide release for repair of cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2025年第2期20卷 503-517页

作者： Qi Liu Jianye Xie Runxue Zhou Jin Deng Weihong Nie Shuwei Sun Haiping Wang Chunying Shi department of Human Anatomy Histology and EmbryologySchool of Basic MedicineQingdao UniversityQingdaoShandong ProvinceChina department of Neurology The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina department of General Practice The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI(QK)are widely used as the most potent angiogenic factors for the treatment of multiple ischemic ***,conventional topical drug delivery often results in a burst release of the drug,leading to transient retention(inefficacy)and undesirable diffusion(toxicity)in ***,a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic *** metalloproteinase-2(MMP-2)is gradually upregulated after cerebral ***,vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG(TIMP)and customizable peptide amphiphilic(PA)molecules to construct nanofiber hydrogel ***-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in *** results indicated that PA-TIMP-QK promoted neuronal survival,restored local blood circulation,reduced blood-brain barrier permeability,and restored motor *** findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

关键词： angiogenesis biomaterial blood-brain barrier cerebral ischemia/reperfusion injury control release drug delivery inflammation QK peptides matrix metalloproteinase-2 neuroprotection self-assembling nanofiber hydrogel

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Portal vein thrombosis:Prevalence,patient characteristics and lifetime risk:A population study based on 23796 consecutive autopsies

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World Journal of Gastroenterology 2006年第13期12卷 2115-2119页

作者： Mats gren David Bergqvist Martin Bjrck Stefan Acosta Henry Eriksson Nils H Sternby department of vascular surgery uppsala university hospital UppsalaSweden departments of vascular Diseases and Pathology Lund university Malm University HospitalMalmSweden department of Medicine Sahlgrenska university hospital/stra GteborgSweden departments of vascular Diseases and Pathology Lund university MalmUniversity HospitalMalmSweden

AIM： TO assess the lifetime cumulative incidence of portal venous thrombosis （PVT） in the general population. METHODS： Between 1970 and 1982, 23 796 autopsies, representing 84% of all in-hospital deaths in the Malmo city population, were performed, using a standardised protocol including examination of the portal vein. PVT patients were characterised and the PVT prevalence at autopsy, an expression of life-time cumulative incidence, assessed in high-risk disease categories and expressed in terms of odds ratios and 95% CI. RESULTS： The population prevalence of PVT was 1.0%. Of the 254 patients with PVT 28% had cirrhosis, 23% primary and 44% secondary hepatobiliary malignancy, 10% major abdominal infectious or inflammatory disease and 3% had a myeloproliferative disorder. Patients with both cirrhosis and hepatic carcinoma had the highest PVT risk, OR 17.1 （95% CI 11.1-26.4）. In 14% no cause was found; only a minority of them had developed portal-hypertension-related complications. CONCLUSION： In this population-based study, PVT was found to be more common than indicated by previous clinical series. The markedly excess risk in cirrhosis and hepatic carcinoma should warrant an increased awareness in these patients for whom prospective studies of directed intervention might be considered.

关键词： Epidemiology Venous thrombosis Portal hypertension Cirrhosis Gastrointestinal cancer

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Enhancing postoperative pain control by surgically-initiated rectus sheath block in abdominal aortic aneurysm open repair: A case report

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World Journal of Clinical Cases 2025年第6期13卷 41-47页

作者： Kuan-Hua Chen Ming-Yuan Kang Yi-Ting Chang Sheng-Yang Huang Yung-Szu Wu Center for Cardiovascular Disease Taichung Veterans General HospitalTaichung 407219TaiwanChina department of Anesthesiology Taichung Veterans General HospitalTaichung 407219TaiwanChina Division of Pediatric surgery Department of SurgeryTaichung Veterans General HospitalTaichung 407219TaiwanChina School of Medicine National Yang Ming Chiao Tung UniversityTaipei 112304TaiwanChina department of Post-Baccalaureate Medicine National Chung Hsing UniversityTaichung 402202TaiwanChina

BACKGROUND Abdominal aortic aneurysm(AAA)repair often involves significant postoperative pain,traditionally managed with systemic opioids,which can cause undesirable side *** case report explores the novel use of a surgically-initiated rectus sheath block with a catheter-over-needle assembly for pain management in AAA *** SUMMARY A 67-year-old female with hypertension and previous aortic dissection underwent elective open repair of an infrarenal AAA,which had grown from 3.4 cm to 4.3 cm over 14 months.A rectus sheath block was initiated surgically for postoperative pain *** patient reported low pain scores and did not require systemic intravenous opioids,enabling early ambulation and discharge on postoperative day seven without *** preventing complications of systemic opi-oids,the method indicating a promising direction for postoperative pain management in major vascular *** Surgically-initiated rectus sheath block as a valuable tool for managing postoperative pain in AAA repair.

关键词： Abdominal aortic aneurysm Postoperative pain management Rectus sheath block Surgical anesthesia Opioid-sparing techniques Case report

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Increased apoptosis and decreased density of medial smooth muscle cells in human abdominal aortic aneurysms

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Chinese Medical Journal 2003年第10期116卷 1549-1552页

作者：张健 Jan Schmidt Eduard Ryschich Hardy Schumacher Jens R Allenberg department of vascular surgery the First Affiliated HospitalChina Medical University department of vascular surgery University of Heidelberg School of Medicine

Objective To determine the increase of apoptosis and the decrease of smooth muscle cells (SMCs) density in human abdominal aortic aneurysms (AAA). Methods In situ terminal transferase-mediated dUTP nick end labeling (TUNEL) was employed to detect apoptosis of SMCs in patients with AAA (n=25) and normal abdominal aortae (n=10). Positive cells were identified by specific cell marker in combination with immunohistochemistry. Meanwhile SMC counting was performed by anti-α-actin immunohistostaining to compare the SMC density. Results TUNEL staining revealed that there was significantly increased apoptosis in AAAs (average 8.6%) compared with normal abdominal aortae (average 0.95%, P <0.01). Double staining showed that most of these cells were SMCs. Counting of α-actin positive SMCs revealed that medial SMC density of AAAs (37.5±7.6 SMCs /HPF) was reduced by 79.1% in comparison with that of normal abdominal aortae (179.2±16.1 SMCs /HPF,P <0.01). Conclusions Significantly increased SMCs of AAA bear apoptotic markers initiating cell death. Elevated apoptosis may result in a decreased density of SMCs in AAA,which may profoundly influence the development of AAA.

关键词： aneurysm muscle,snooth cells apoptosis

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Hepatocellular carcinoma recurrence after liver transplant:An Australian single-centre study

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World Journal of Transplantation 2025年第1期15卷 105-114页

作者： Matthew G Garas Luis Calzadilla-Bertot Briohny W Smith Luc Delriviere Byron Jaques Lingjun Mou Leon A Adams Gerry C MacQuillan George Garas Gary P Jeffrey Michael C Wallace Medical School University of Western AustraliaNedlands 6009Western AustraliaAustralia department of Hepatology Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia department of surgery Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia

BACKGROUND Hepatocellular carcinoma(HCC)is a leading cause of cancer-related deaths *** transplantation(LT)offers the most effective *** recurrence is the strongest risk factor that decreases post-LT survival in patients transplanted for *** rate of HCC recurrence is generally reported as 8%-20%in the *** predictors of HCC have already been researched,however,to our knowledge there are no published studies on this topic using Australian *** To determine the rate and identify predictors of HCC recurrence in a contemporary Western Australian LT *** We performed a retrospective cohort study of all liver transplants in patients with HCC at Sir Charles Gairdner hospital between 2006 and *** was collected from various health record databases and included recipient demographics,serum biochemistry,radiology,operation notes,explant histopathology and details of *** survival of HCC patients post-LT,stratified for recurrence,was calculated by Kaplan Meier *** and multivariate Cox regression was used to determine predictors of HCC recurrence *** Between 1/1/2006 and 12/31/2021,119 patients were transplanted with HCC.8.4%of subjects developed recurrent HCC after LT with median follow-up time of 5.4 *** median time to recurrence was 2.9 years±0.75 *** comparing baseline characteristics,a greater proportion of subjects with recurrence had common characteristics on explant histopathology,including>3 viable nodules(P=0.001),vascular invasion(P=0.003)and poorly differentiated HCC(P=0.03).Unadjusted survival curves showed lower 1-year,3-year,5-year and 10-year survival rates in subjects with HCC recurrence compared to those without HCC recurrence(90%vs 92%,70%vs 88%,42%vs 80%,14%vs 76%,respectively;log rank P<0.001).CONCLUSION HCC recurrence was low at 8.4%in this contemporary Australian cohort,however it significantly impacted post-LT *** studies are requir

关键词： Liver cancer Recurrence Liver transplantation Hepatocellular carcinoma Predictors Post-transplant survival Australian data

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Multiple liver metastases of unknown origin:A case report

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 233-238页

作者： Ying-Jin Wang Ze-Chuan Liu Jian Wang Yin-Mo Yang department of Hepatobiliary Pancreatic surgery Peking University First HospitalBeijing 100034China department of Interventional and vascular surgery Peking University First HospitalBeijing 100034China

BACKGROUND The liver is the most common site of digestive system tumor metastasis,but not all liver metastases can be traced back to the primary *** it is unusual,syphilis can impact the liver,manifesting as syphilitic hepatitis with inflammatory nodules,which might be misdiagnosed as *** SUMMARY This case report involves a 46-year-old female who developed right upper abdominal pain and intermittent low fever that persisted for more than three *** definitive diagnosis of a tumor had been made in the past decades,but signs of multiple liver metastases were recognized after a computed tomo-graphy scan without evidence of primary *** positive serological tests for syphilis and a biopsy of the liver nodules,a diagnosis of hepatic syphilis was made and confirmed with follow-up nodule reduction after anti-syphilis *** Clinicians must be aware of the possibility that syphilis can cause hepatic inflam-matory masses,especially when liver metastasis is suspected without evidence of primary lesions.A definitive diagnosis should be established in conjunction with a review of the patient’s medical history for accurate therapeutic intervention.

关键词： Syphilitic hepatitis Liver nodules Liver metastasis Treponema pallidum Case report

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