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The combination of eddy thermal effect of biodegradable magnesium with immune checkpoint blockade shows enhanced efficacy against osteosarcoma

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Bioactive Materials 2023年第7期25卷 73-85页

作者： Jun Ge Nailin Yang Yuqi Yang Hao Yu Xiaoyuan Yang Yingjie Wang Tianyi Wang Shuning Cheng Yuanjie Wang Zhihui Han Yun Teng Jun Zou Huilin Yang Liang Cheng department of Orthopedic Surgery The First Affiliated Hospital of Soochow UniversitySuzhouJiangsuChina Institute of functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory for Carbon-Based Functional Materials&DevicesSoochow UniversitySuzhouJiangsuChina department of neurosurgery The First Affiliated Hospital of Soochow UniversitySuzhouJiangsuChina

Osteosarcoma(OS)patients have a poor prognosis due to its high degree of heterogeneity and high rate of metastasis.Magnetic hyperthermia therapy(MHT)combined with immunotherapy is an effective strategy to treat solid and metastatic tumors.Here,we combined biodegradable magnesium(Mg)macroscale rods,which acted as an eddy thermo-magnetic agent under a low external alternating magnetic field,and immunotherapy to achieve a radical cure for OS.The eddy thermal effect(ETE)of the Mg rods(MgR)showed outstanding cytotoxic effects and enhanced the maturation of dendritic cells(DCs),and the mild MHT induced the immunogenic cell death(ICD)in the OS cells.Combined with immune checkpoint blockade(ICB)therapy,we obtained an excellent curative effect against OS,and a further evaluation demonstrated that the local MHT induced by the MgR increased T cells infiltration and the polarization of M1 macrophages.Interestingly,the biodegradable MgR also promoted bone osteogenesis.Our work highlighted the uneven ETE mediated by the biodegradable MgR induced a comprehensive immunologic activation in the OS tumor microenvironment(TME),which would inspire the application of MHT for the effective treatment of OS.

关键词： Osteosarcoma Eddy thermal effect Magnesium rods(MgR) Osteosarcoma therapy Tumor microenvironment(TME) immunotherapy

Independent temporal lobe epilepsy in patients with tuberous sclerosis complex

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Pediatric Investigation 2022年第1期6卷 23-28页

作者： Tinghong Liu Jing Ding Shaohui Zhang Yangshuo Wang Jinshan Xu Liu Yuan Feng Zhai Guojun Zhang Shuli Liang department of functional neurosurgery Key Laboratory of Major Disease in ChildrenMinistry of EducationBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijingChina department of Neurology Zhongshan HospitalFudan UniversityShanghaiChina department of neurosurgery Fourth Medical CenterPLA General HospitalBeijingChina

Tuberous sclerosis complex(TSC)is a rare disease that involves multiple organs,including the brain;approximately 80%-90%of TSC patients exhibit TSC-associated epilepsy.Independent temporal lobe epilepsy(TLE),TSC-unrelated epilepsy,is particularly rare in patients with TSC.Here,we describe three patients with TSC with independent TLEs that were confirmed by stereo-electroencephalography(EEG),postoperative pathological findings,and seizure outcome at follow-up.The patients were retrospectively enrolled at two centers;their ictal epileptiform discharge onsets were determined using electrode contacts in the hippocampus during stereo-EEG.The three patients underwent anterior temporal lobectomies and remained seizure-free at 1-5 years after surgery.Postoperative pathological examinations confirmed hippocampal sclerosis in all three patients.Furthermore,postoperative intelligence quotient improvement was evident in one patient,while the quality of life was improved in two patients at 12 months after surgery.

关键词： Anterior temporal lobectomy Hippocampal sclerosis Temporal lobe epilepsy Tuberous sclerosis complex

Long-term outcomes and prognosis factors of vagus nerve stimulation in patients with refractory epilepsy

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Acta Epileptologica 2022年第3期5卷 201-207页

作者： Cuiping Xu Hua Lin Jiwen Xu Xiaohua Zhang Guiliang Hao Qiang Qiang Liu Chengyun Ding Shan Wang Quanjun Zhao Xiaojun Bai Kui Chen Duanyu Ni Yongjie Li Tao Yu Yuping Wang department of functional neurosurgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China department of functional neurosurgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China department of Epilepsy First Affiliated HospitalGeneral Hospital of People’s Liberation ArmyBeijing 100048China department of neurosurgery The 306th Hospital of PLABeijing 100101China department of Neurology Beijing Friendship HospitalBeijing 100050China

Background:Vagus nerve stimulation(VNS)is an effective treatment for patients with refractory epilepsy,yet with varied predictive factors and heterogeneous long-term outcomes.Adjustment of VNS parameters is critical for obtaining favorable efficacy.In this study,we aimed to investigate the long-term outcomes and the possible predictive factors of VNS in patients with refractory epilepsy.Methods:Eighty-six patients(59 males and 27 females)who underwent VNS implantation for treatment of refractory epilepsy between May 2016 and May 2017 at five Epilepsy Centers were enrolled.The clinical data,including sex,age at epilepsy onset,VNS implantation,epilepsy duration,seizure type,MRI findings,history of neurosurgical operations,and responder rate(responders were those with≥50%seizure reduction),were analyzed.Results:Four-year follow-up data were available for 76 patients(53 males and 23 females).The mean current intensity at the last follow-up was 1.8±0.3 mA(range:0.75–2.5 mA).The mean seizure reduction was 36.2%at 6 months,38.5%at 1 year,69.4%at 3 years,and 56.7%at 4 years.A favorable outcome of≥50%reduction in seizure frequency occurred in 40.0%of the patients at 6 months,55.9%at 1 year with 4 patients being seizure-free,63.2%at 3 years with 5 patients being seizure-free,and 68.4%at 4 years with 5 patients being seizure-free.Earlier onset age(P<0.001)and shorter duration(P=0.042)were associated with favorable prognosis.Compared with generalized tonicclonic seizures,tonic seizures had a favorable outcome(P=0.026).Twenty-three patients underwent neurosurgical operations before VNS implantation,and the responder rate was 60.9%at the last follow-up.Conclusions:VNS is an adjunctive and effective treatment for patients with refractory epilepsy who are not good candidates for surgical resection or have failed to respond to surgical treatment.The stimulation efficacy increases over time after implantation,and earlier exposure to VNS improves the prognosis.

关键词： Refractory epilepsy Vagus nerve stimulation Generalized seizures Long-term efficacy

Pipeline Embolization Device for intracranial aneurysms presenting with mass effect:a large Chinese cohort

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Stroke & Vascular Neurology 2024年第1期9卷 50-58页

作者： Yang Zhao Junlin Lu Hongqi Zhang Tianxiao LI Donglei Song Sheng Guan Aisha Maimaitili Yunyan Wang Wenfeng Feng Yang Wang Jieqing Wan Guohua Mao Huaizhang Shi Xinjian Yang Jianmin Liu Yuanli Zhao department of neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of neurosurgery Peking University International HospitalBeijingChina department of neurosurgery West China HospitalSichuan UniversityChengduSichuanChina department of neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina department of Interventional Neuroradiology Zhengzhou University People's HospitalZhengzhouHenanChina department of neurosurgery Shanghai Donglei Brain HospitalShanghaiChina department of Interventional Neuroradiology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina department of neurosurgery The First Affiliated Hospital of Xinjiang Medical UniversityUrumqiXinjiangChina department of neurosurgery Qilu Hospital of Shandong University QingdaoJinanShandongChina department of neurosurgery Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongChina department of neurosurgery The First Affiliated Hospital of Nanchang UniversityNanchangJiangxiChina department of neurosurgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina department of neurosurgery The Second Affiliated Hospital of Nanchang UniversityNanchangJiangxiChina department of neurosurgery The First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina department of neurosurgery Changhai HospitalNaval Medical UniversityShanghaiChina

Background Unruptured intracranial aneurysm treatment aims to reduce the risk of aneurysm rupture and bleeding,relieves symptoms and improve the quality of life for patients.This study aimed to assess the safety and efficacy of Pipeline Embolization Device(PED,Covidien/Medtronic,Irvine,CA)treatment for intracranial aneurysms presenting with mass effect in real-world settings.Methods We selected patients from the PED in China Post-Market Multi-Center Registry Study with mass effect presentation.The study endpoints included postoperative mass effect deterioration and mass effect relief at follow-up(3–36 months).We conducted multivariate analysis to identify factors associated with mass effect relief.Subgroup analyses by aneurysm location,size and form were also performed.Results This study included 218 patients with a mean age of 54.3±11.8 years and a female predominance of 74.0%(162/218).The postoperative mass effect deterioration rate was 9.6%(21/218).During a median follow-up period of 8.4 months,the mass effect relief rate was 71.6%(156/218).Notably,immediate aneurysm occlusion following treatment was significantly associated with mass effect relief(OR 0.392,95%CI,0.170 to 0.907,p=0.029).Subgroup analysis demonstrated that adjunctive coiling contributed to mass effect relief in cavernous aneurysms,while dense embolism impeded symptom relief in aneurysms<10mm and saccular aneurysms.Conclusions Our data confirmed the efficacy of PED in relieving mass effect.The findings of this study provide support for endovascular treatment to alleviate mass effect in unruptured intracranial aneurysms.Trial registration number NCT03831672.

关键词： aneurysm intracranial Irvine

Resection of a dysembryoplastic neuroepithelial tumor in the precentral gyrus

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World Journal of Pediatrics 2015年第3期11卷 281-283页

作者： Hai Xue Olafur Sveinsson Yong-Jie Li Beijing Institute of functional neurosurgery Department of Functional NeurosurgeryXuanwu HospitalCapital Medical UniversityBeijingChina department of Neurology Karolinska University HospitalStockholmSweden

Background:Dysembryoplastic neuroepithelial tumors(DNTs)are common causes of intractable epilepsy in pediatric epilepsy patients.The effect of surgical intervention is often limited when the tumor is located in the precentral gyrus.Furthermore,complete surgical resection is often not performed in order to avoid permanent neurological deficits.Methods:Here,we present a pediatric patient with intractable epilepsy caused by a simple DNT located in the precentral gyrus.Intracranial electrodes were implanted and used in combination with magnetic resonance imaging,video-electroencephalography and electrical cortical stimulation to assess neurological function,and where the epileptogenic zone was located.Results:The results of intracranial electrode monitoring suggested that the epileptogenic zone was located in the tumor area and that cortical function had been reorganized.We completely resected the tumor based on these findings.The patient has been seizure free after the surgery and has not had any neurological deficits.Conclusions:Simple form DNTs in the precentral gyrus can be completely resected with careful preoperative assessment of cortical function.Cortical reorganization could partly explain the functional preservation after surgery.

关键词： cortical reorganization dysembryoplastic neuroepithelial tumor epilepsy precentral gyrus surgery

Excitatory Crossmodal Input to a Widespread Population of Primary Sensory Cortical Neurons

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Neuroscience Bulletin 2022年第10期38卷 1139-1152页

作者： Yuan-Jie Xiao Lidan Wang Yu-Zhang Liu Jiayu Chen Haoyu Zhang Yan Gao Hua He Zheng Zhao Zhiru Wang Institute and Key Laboratory of Brain functional Genomics of the Chinese Ministry of Education Shanghai Key Laboratory of Brain Functional GenomicsSchool of Life SciencesEast China Normal UniversityShanghai200062China department of neurosurgery Third Affiliated Hospital of the Navy Military Medical UniversityShanghai200438China department of Neuroscience University of PittsburghPittsburgh15260USA

Crossmodal information processing in sensory cortices has been reported in sparsely distributed neurons under normal conditions and can undergo experience-or activity-induced plasticity.Given the potential role in brain function as indicated by previous reports,crossmodal connectivity in the sensory cortex needs to be further explored.Using perforated whole-cell recording in anesthetized adult rats,we found that almost all neurons recorded in the primary somatosensory,auditory,and visual cortices exhibited significant membrane-potential responses to crossmodal stimulation,as recorded when brain activity states were pharmacologically down-regulated in light anesthesia.These crossmodal cortical responses were excitatory and subthreshold,and further seemed to be relayed primarily by the sensory thalamus,but not the sensory cortex,of the stimulated modality.Our experiments indicate a sensory cortical presence of widespread excitatory crossmodal inputs,which might play roles in brain functions involving crossmodal information processing or plasticity.

关键词： Crossmodal input Crossmodal response Crossmodal plasticity Sensory cortex Crossmodal task Sensory loss GABAergic transmission

Clinical features, treatment strategies and outcomes of craniocervical junction arteriovenous fistulas: a cohort study of 193 patients

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Stroke & Vascular Neurology 2024年第1期9卷 18-29页

作者： Yongjie Ma Zihao Song Yinqing Wang Jiachen Wang Chuan He Guilin Li Peng Zhang Tao Hong Liyong Sun Peng Hu Ming Ye Hongqi Zhang department of neurosurgery Xuanwu Hospital Capital Medical University

Background Craniocervical junction(CCJ)arteriovenous fistulas(AVFs)are rare.The current treatment strategies for AVFs with different angioarchitecture need to be clarified.The present study aimed to analyse the correlation between angioarchitecture and clinical characteristics,share our experience in treating this disease and identify risk factors associated with subarachnoid haemorrhage(SAH)and poor outcomes.Methods A total of 198 consecutive patients with CCJ AVFs from our neurosurgical centre were retrospectively reviewed.The patients were grouped according to their clinical manifestations,and their baseline clinical characteristics,angioarchitecture,treatment strategies and outcomes were summarised.Results The patients’median age was 56 years(IQR 47–62 years).The majority of patients were men with 166(83.8%)patients.The most common clinical manifestation was SAH(52.0%),followed by venous hypertensive myelopathy(VHM)(45.5%).The most common CCJ AVFs type was dural AVF,with 132(63.5%)fistulas.The most frequent fistula location was C-1(68.7%)and dural branch of vertebral artery(70.2%)was the most involved arterial feeders for fistulas.The most common direction of venous drainage was descending intradural drainage(40.9%),followed by ascending intradural drainage(36.5%).Microsurgery was the most common treatment strategy applied for 151(76.3%)patients,15(7.6%)patients were treated with interventional embolisation only,and 27(13.6%)received both interventional embolisation and microsurgical treatment.The learning curve for microsurgery only was analysed by cumulative summation method,and the turning point was the 70th case,and blood loss in post-group was lower than that in pre-group(p=0.034).At the last follow-up,there were 155(78.3%)patients with favourable outcomes(modified Rankin Scale(mRS)<3).Age≥56(OR 2.038,95%CI 1.039 to 3.998,p=0.038),VHM as the clinical manifestation(OR 4.102,95%CI 2.108 to 7.982,p<0.001)and pretreatment mRS≥3(OR 3.127,95%CI 1.617 to 6.047,p<0.001)were significantly associated with poor out

关键词： patients treatment hypertensive

Intranasal administration of stem cell-derived exosomes for central nervous system diseases

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Neural Regeneration Research 2024年第6期19卷 1249-1255页

作者： Shuho Gotoh Masahito Kawabori Miki Fujimura department of neurosurgery Hokkaido University Graduate School of Medicine

Exosomes, lipid bilayer-enclosed small cellular vesicles, are actively secreted by various cells and play crucial roles in intercellular communication. These nanosized vesicles transport internalized proteins, mRNA, miRNA, and other bioactive molecules. Recent findings have provided compelling evidence that exosomes derived from stem cells hold great promise as a therapeutic modality for central nervous system disorders. These exosomes exhibit multifaceted properties including antiapoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Furthermore, exosomes offer several advantages over stem cell therapy, such as high preservation capacity, low immunogenicity, the ability to traverse the blood-brain barrier, and the potential for drug encapsulation. Consequently, researchers have turned their attention to exosomes as a novel therapeutic avenue. Nonetheless, akin to the limitations of stem cell treatment, the limited accumulation of exosomes in the injured brain poses a challenge to their clinical application. To overcome this hurdle, intranasal administration has emerged as a non-invasive and efficacious route for delivering drugs to the central nervous system. By exploiting the olfactory and trigeminal nerve axons, this approach enables the direct transport of therapeutics to the brain while bypassing the blood-brain barrier. Notably, exosomes, owing to their small size, can readily access the nerve pathways using this method. As a result, intranasal administration has gained increasing recognition as an optimal therapeutic strategy for exosomebased treatments. In this comprehensive review, we aim to provide an overview of both basic and clinical research studies investigating the intranasal administration of exosomes for the treatment of central nervous system diseases. Furthermore, we elucidate the underlying therapeutic mechanisms and offer insights into the prospect of this approach.

关键词： central nervous system disease exosome extracellular vesicle intranasal administration stem cell

Theta Oscillations Support Prefrontal-hippocampal Interactions in Sequential Working Memory

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Neuroscience Bulletin 2024年第2期40卷 147-156页

作者： Minghong Su Kejia Hu Wei Liu Yunhao Wu Tao Wang Chunyan Cao Bomin Sun Shikun Zhan Zheng Ye Institute of Psychology Chinese Academy of SciencesBeijing 100101China department of Psychology University of Chinese Academy of SciencesBeijing 100049China department of neurosurgery Center for Functional NeurosurgeryRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of Neuroscience Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China

The prefrontal cortex and hippocampus may support sequential working memory beyond episodic memory and spatial navigation.This stereoelectroencephalography(SEEG)study investigated how the dorsolateral prefrontal cortex(DLPFC)interacts with the hippocampus in the online processing of sequential information.Twenty patients with epilepsy(eight women,age 27.6±8.2 years)completed a line ordering task with SEEG recordings over the DLPFC and the hippocampus.Participants showed longer thinking times and more recall errors when asked to arrange random lines clockwise(random trials)than to maintain ordered lines(ordered trials)before recalling the orientation of a particular line.First,the ordering-related increase in thinking time and recall error was associated with a transient theta power increase in the hippocampus and a sustained theta power increase in the DLPFC(3–10 Hz).In particular,the hippocampal theta power increase correlated with the memory precision of line orientation.Second,theta phase coherences between the DLPFC and hippocampus were enhanced for ordering,especially for more precisely memorized lines.Third,the theta band DLPFC→hippocampus influence was selectively enhanced for ordering,especially for more precisely memorized lines.This study suggests that theta oscillations may support DLPFC-hippocampal interactions in the online processing of sequential information.

关键词： Sequential working memory Hippocampus Dorsolateral prefrontal cortex Theta oscillations Stereoelectroencephalography(SEEG) Phase coherence Granger causality