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Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

Neural Regeneration Research 2025年第4期20卷 1164-1177页

作者： Pengfei Wang Yuewei Bi Min Li Jiazhi Chen Zhuyong Wang Huantao Wen Ming Zhou Minjie Luo Wangming Zhang Neurosurgery Center Department of Pediatric NeurosurgeryGuangdong Provincial Key Laboratory on Brain Function Repair and RegenerationZhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

Long-term levodopa administration can lead to the development of levodopa-induced *** oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced ***,studies have reported increased oscillation power in cases of levodopa-induced ***,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced ***,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is *** found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s ***,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma *** of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum ***,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum *** findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

关键词： aperiodic components dopamine D3 receptor dorsolateral striatum functional connectivity gamma oscillations levodopa-induced-dyskinesia local field potentials neuromodulation Parkinson’s disease primary motor cortex

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Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao Deng Melissa Walker Chen Chen Heqiao Dai Qi Han Ying Ding Yongzhi Xia George Smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari Jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy department of Surgery Morehouse School of MedicineAtlantaGAUSA department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA department of pediatrics Emory UniversityAtlantaGAUSA department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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Anterior mediastinal masses and thymic cysts

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World Journal of Clinical Cases 2025年第4期13卷 1-7页

作者： ÖnerÖzdemir department of pediatric Allergy and Immunology Sakarya Research and Training HospitalSakarya University Medical FacultyAdapazarı54100SakaryaTürkiye

Cystic lesions of the anterior mediastinum in children suggest a well-known group of benign lesions that are comparatively *** cysts(TCs)are mostly positioned in the anterior mediastinum and some patients in the *** TCs classified as congenital intra-thoracic mesothelial cysts are commonly asymptomatic and have slight clinical *** TC,which can mimic another anterior mediastinal cystic tumor and is seen in adults,is more clinically *** is a sporadic mediastinal lesion thought to arise in the course of acquired *** mediastinal cysts represent 3%-6%of all mediastinal tumors and 10%-18%of radiologically reported mediastinal *** TCs are uncommon and it is hard to know their true *** 60%of cases with mediastinal TCs are asymptomatic,and the remainder of patients complains of nonspecific symptoms(e.g.,chest pain,dyspnea,or cough).The literature suggests that most cysts are benign,but an indefinite percentage may have a neoplastic process and result in significant compressive symptoms over *** symptoms of TCs vary depending on the *** addition,frequent symptoms at the appearance of enlarged benign thymic and mediastinal cysts generally contain compressive symptoms(e.g.,respiratory distress,thymic pain,and symptoms related to Horner syndrome,hoarseness,dysphonia,dyspnea,orthopnea,wheezing,and fever).Many TCs have cystic density and a neat border and are simple to diagnose with radiological ***,some TCs are hard to identify before surgery and may be misidentified as thymomas depending on their site and computed tomography *** by thoracotomy,median sternotomy,or video-assisted techniques is essential for conclusive diagnosis,management,and abolition of relapse of anterior mediastinal masses and *** examination may be required after *** the extent of the mass and the preliminary inability to make a definitiv

关键词： Mediastinal mass Thymic cyst Malignant tumor Cysts Thymoma Computer tomography

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Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua Ge Yueyang Zhao Yuanjie Liu Qinghua Zeng Qing Tang Zhifang Dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina department of Anatomy Chongqing Medical UniversityChongqingChina department of Physiology Chongqing Medical UniversityChongqingChina pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

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Towards curative therapy in gastric cancer:Faraway, so close!

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World Journal of Gastroenterology 2015年第41期21卷 11609-11620页

作者： Marília Cravo Catarina Fidalgo Rita Garrido Tania Rodrigues Gon?alo Luz Carolina Palmela Marta Santos Fábio Lopes Rui Maio Gastroenterology department Surgery and Oncology ClinicsHospital Beatriz Angelo

Although recent diagnostic and therapeutic advances have substantially improved the survival of patients with gastric cancer(GC), the overall prognosis is still poor. Surgery is the only curative treatment and should be performed in experienced centers. Due to high relapse following surgery, complementary and systemic treatment aimed at eradicating micrometastasis should be performed in most cases. Cytotoxic treatments are effective in downstaging locally advanced cancer, but different sensitivities and toxicities probably exist in different GC subtypes. Current treatment protocols are based primarily on clinical data and histological features, but molecular biomarkers that would allow for the prediction of treatment responses are urgently needed. Understanding how host factors are responsible for inter-individual variability of drug response or toxicity will also contribute to the development of more effective and less toxic treatments.

关键词： Gastric cancer Multidisciplinary treatment Therapeutic strategies Curative surgery

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Therapeutic effect of oridonin on mice with prostate cancer

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Asian Pacific Journal of Tropical Medicine 2016年第2期9卷 182-185页

作者： Ming Ming Feng-Yin Sun Wen-Tong Zhang Ji-Ke Liu department of pediatric Surgery Qilu Hospital of Shandong University department of pediatric Surgery Taian City Central Hospital department of pediatric Surgery Liaocheng Hospital

Objective: To investigate the therapeutic effect and the related mechanism of oridonin on mice with prostate cancer. Methods: Sixty BALB/C male nude mice were selected. A model of RM-1 cell transplantation tumor of prostate cancer was built by the subcutaneous inoculation of RM-1 cells. After that, those 60 experimental mice were randomly divided into groups A, B and C. Each group had 20 mice. Mice in group A were treated with 0.2 m L of normal saline(0.9%) by intraperitoneal injection once a day; mice in group B received intraperitoneal injection of 1.875 mg/m L of oridonin once a day; and mice in group C received intraperitoneal injection of 7.5 mg/m L of oridonin once a day. Mice in the three groups were treated uninterruptedly for 5 weeks and were all killed. Then, tumors were excised and weighed to calculate their growth inhibitory rate, volume increment and anti-tumor rate. Thymus and spleen of mice in the three groups were collected to calculate the thymus and spleen index. Immunohistochemical staining was applied to observe the expression of caspase-3 in prostate cancer tissue of mice of the three groups. Results: The qualities and volume increment of tumors in groups B and C were significantly lower than those of group A(P 0.05). Immumohistochemical staining revealed that the caspase-3 protein in prostate cancer tissue of mice of group A expressed negatively with colourless or light-colored karyon; while the caspase-3 protein in prostate cancer tissue of mice of group B expressed positively with dark-colored karyon, ce

关键词： Oridonin Prostate cancer RM-1 cells Caspase-3

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Growth-inhibitory Effects of Curcumin on Ovary Cancer Cells and Its Mechanisms

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2004年第1期24卷 55-58页

作者：郑丽端童强松吴翠环 department of Pathology department of pediatric Surgery

To study the growth inhibitory effects of curcumin on human ovary cancer A2780 cells in vitro and its molecular mechanisms, the growth inhibition rates of A2780 cancer cells, after being treated with 10 μmol/L-50 μmol/L curcumin for 6-24 h, were examined by MTT method. The morphological changes of cancer cells were observed under inversion microscopy. Cellular apoptotic rates were determined by using TUNEL. The protein expression levels of bcl 2, p53 and MDM2 in cancer cells were examined by SP immunohistochemistry. After being treated by various concentrations of curcumin, the growth of cancer cells was inhibited significantly. Some cancer cells presented characteristic morphological changes of apoptosis. The rates of apoptosis were 6.41 % -28.48 % ( P <0.01). The expression of bcl 2 and p53 was decreased, which depended on the action time ( P <0.01). There were no obvious changes in MDM2 expression. It was concluded that curcumin could significantly inhibit the growth of ovary cancer cells. The induction of apoptosis by down re gulating the expression of bcl 2 and p53 was probably one of its molecular mechanisms.

关键词： curcumin ovary cancer gene expression apoptosis

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Opportunistic screening for atrial fibrillation with a single lead device in geriatric patients

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Journal of Geriatric Cardiology 2020年第3期17卷 149-154,I0008页

作者： Lennaert AR Zwart Rene WMM Jansen Jacob H Ruiter Tjeerd Germans Suat Simsek Martin EW Hemels department of Geriatric Medicine North West ClinicsWilhelminalaanAlkmaarthe Netherlands department of Geriatric Medicine Dijklander HospitalMaelsonstraatHoornthe Netherlands department of Cardiology North West ClinicsWilhelminalaanAlkmaarthe Netherlands department of Internal Medicine North West ClinicsWilhelminalaanAlkmaarthe Netherlands department of Cardiology Rijnstate HospitalArnhemthe Netherlands department of Cardiology Radboud University Medical CentreGeert Grooteplein ZuidNijmegenthe Netherlands

Objective To determine the diagnostic yield of repeated screening for atrial fibrillation(AF)among geriatric *** A pragmatic prospective cohort study into applying opportunistic screening for AF with a handheld single lead ECG device(SLD)in a geriatric *** patients of 65 years old and older visiting the geriatric outpatient clinic were eligible for inclusion.A 12 lead ECG was performed,followed by measurements with the SLD during every visit to the geriatric outpatient clinic.A frailty index was based on the accumulation of deficits *** 478 patients were *** were excluded if they did not give informed consent(17 patients),had a pacemaker or implantable cardioverter defibrillator(20 patients),or had incomplete medical files(two patients).After exclusion,439 patients participated in this *** mean age was 78 years(range 65 to 100 years),54%were *** was known in 89 patients(20%),first detected on the baseline ECG in four patients(1%)and first detected with the SLD in 20 patients(5%)during follow up *** of the SLD was 90.0%,specificity 99.0%,negative predictive value 99.7%,and positive predictive value 73.5%.Most patients(82%)with AF were frail and 53%were severely *** Repeated screening in geriatric patients has a five times higher diagnostic yield than usual *** was easily combined with usual *** of the positive predictive value of 73.5%,it remains necessary to confirm AF with a 12 lead ECG or 24-h Holter monitoring.

关键词： Atrial fibrillation Frailty Geriatric patients Opportunistic screening The elderly

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Distal femoral extension and shortening osteotomy as a part of multilevel surgery in children with cerebral palsy

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World Journal of pediatrics 2017年第4期13卷 353-359页

作者： Matthias C.M.Klotz Klemens Hirsch Daniel Heitzmann Michael W.Maier Sebastien Hagmann Thomas Dreher department of Orthopedic and Trauma Surgery Heidelberg University ClinicsHeidelbergGermany

Background:There are several reports describing an increase in anterior pelvic tilt after hamstring lengthening in children with cerebral palsy (CP).Distal femoral extension and shortening osteotomy (DFESO) is an alternative treatment for correction of flexed knee gait,but investigations analyzing outcome and influence on adjacent joint are few in the *** purpose of this study was to analyze the influence of DFESO on knee and pelvis in children with ***,it was of interest if an additional patellar tendon advancement (PA) influences ***:In this retrospective study,31 limbs of 22 children (GMFCS Ⅰ-Ⅲ;mean age:12.1±3.1 years),who received DFESO were included and kinematic parameters (knee,pelvis) measured by 3-D-gait analysis were compared before and at least 1 year after surgery (mean follow-up period:15.6 months).Results:After surgery,during stance phase minimum knee flexion improved significantly by 20.5° (P<0.001) and mean anterior pelvic tilt increased by 4.0 degrees (P=0.045).In 16 limbs,the postoperative increase in maximum anterior pelvic tilt was more than 5°.Limbs who received an additional PA showed the biggest increase in anterior pelvic ***:DFESO is an effective method for correction of flexed knee gait in children with ***,the results of this study indicate that DFESO may lead to an increase in anterior pelvic tilt,which may lead to a recurrence of flexed knee *** this context,PA seemed to aggravate the effect on the pelvis.

关键词： cerebral palsy femoral extension osteotomy motion analysis

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