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Multi-cohort comprehensive analysis unveiling the clinical value and therapeutic effect of GNAL in glioma

Oncology Research 2024年第5期32卷 965-981页

作者： ZHEN LIU LIANGWANG YANG ZHENGXING XIE HUI YU TIANYI GU DAOMING SHI NING CAI SHENGHUA ZHUO department of neurosurgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China department of neurosurgery First Affiliated Hospital of Hainan Medical UniversityHaikou570100China department of Cardiothoracic Surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China department of General Surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China

Clinical data indicates that glioma patients have poor treatment outcomes and clinical *** role of olfactory signaling pathway-related genes(OSPRGs)in glioma has not been fully *** this study,we aimed to investigate the role and relationship between OSPRGs and *** and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts,and the target gene(G Protein Subunit Alpha L,GNAL)was *** association of GNAL expression with clinicopathological characteristics,gene mutation landscape,tumor immune microenvironment(TIME),deoxyribonucleic acid(DNA)methylation,and naris-occlusion controlled genes(NOCGs)was *** was used to evaluate GNAL level in *** analysis was conducted to evaluate the drug sensitivity,immunotherapy response,and functional enrichment of *** was an independent prognostic factor,and patients with low GNAL expression have a poor *** of GNAL was closely associated with clinicopathological characteristics,DNA methylation,and several immune-related *** infiltration analysis indicated that GNAL levels were negatively correlated with immune *** low-expression group showed efficacy with anti-PD-1 *** compounds with significantly different half-maximal inhibitory concentration(IC50)values between the GNAL high and low-expression groups were ***,its expression was associated with several immune cells,immune-related genes,and *** expression of GNAL is closely associated with clinicopathological characteristics,TIME,and the response to therapeutic interventions,highlighting its potential as a prognostic biomarker for glioma.

关键词： Glioma Olfaction GNAL Tumor immune microenvironment Immunotherapy/chemotherapy response

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Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice

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Neuroscience Bulletin 2024年第1期40卷 35-49页

作者： Shuhui Dai Yuan Feng Chuanhao Lu Hongchen Zhang Wenke Ma Wenyu Xie Xiuquan Wu Peng Luo Lei Zhang Fei Fei Zhou Fei Xia Li department of neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an 710000China National Translational Science Center for Molecular Medicine and department of Cell Biology Fourth Military Medical UniversityXi'an 710000China department of neurosurgery The Central Hospital of BaojiBaoji 721000China department of Ophthalmology Xijing HospitalFourth Military Medical UniversityXi'an 710000China

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude *** plays a critical role in ischemic brain injury,but its role in hypo-baric hypoxia(HH)remains *** we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain,and is partially responsible for HH-induced oxidative stress,neuronal loss,and brain *** autophagic agonist rapamycin only promotes the initiation of *** proteome analysis,a screen showed that protein dynamin2(DNM2)potentially regulates autophagic *** of DNM2 significantly increased the formation of autolysosomes,thus maintaining autophagic flux in combination with ***,the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH *** results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

关键词： Autophagy-Proteomics Oxidative stress Hypobaric hypoxia-Brain injury

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Succinylation modification:a potential therapeutic target in stroke

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Neural Regeneration Research 2024年第4期19卷 781-787页

作者： Jie Lian Wenwu Liu Qin Hu Xiaohua Zhang department of neurosurgery Ren Ji HospitalShanghai Jiao Tong University School of Medicine department of Diving and Hyperbaric Medicine Naval Medical CenterNaval Medical University

Stroke is a leading cause of mortality and disability *** cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain *** mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of ***,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ***,the role of succinylation modification in cell metabolism after stroke and its regulation are not well *** aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after *** also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of *** succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by *** evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic ***,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic *** between succinylation and desuccinylation has been implicated in the pathophysiology of *** agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke ***,their therapeutic efficacy in stroke patients should be validated.

关键词： mitochondria metabolism neuroprotection sirtuin 5 stroke succinylation modification

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Development and validation of an immunogenic cell death-related prognostic model, and landscape of the tumor immune microenvironment in glioblastoma

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Genes & Diseases 2024年第3期11卷 72-74页

作者： Sha Yang Mei Deng Yunbiao Xiong Bing Xiong Junwu Fu Jia Wang Jiqin Zhang Guoqiang Han Jian Liu Ying Tan Guizhou University Medical College GuiyangGuizhou 550025China department of neurosurgery Guizhou Provincial People's HospitalGuiyangGuizhou 550002China department of Anesthesiology Guizhou Provincial People's HospitalGuiyangGuizhou 550002China department of neurosurgery Chongqing Emergency Medical CenterChongqing400000China

The important role of immunogenic cell death(ICD)in many tumors is increasingly being ***,its mechanisms and potential as a biomarker and therapeutic target in glioblastoma(GBM)have not been well *** obtained GBM samples from the Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)databases,as well as the immunotherapy cohort from the IMvigor210 *** used unsupervised clustering to obtain two ICDrelated clusters,corresponding to the ICD-low and ICD-high subtypes respectively,and the tumor immune microenvironment and prognosis of the two subtypes were significantly different.

关键词： immune Cancer prognosis

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Placenta-derived mesenchymal stem cells attenuate secondary brain injury after controlled cortical impact in rats by inhibiting matrix metalloproteinases

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BIOCELL 2024年第1期48卷 149-162页

作者： PING YANG YUANXIANG LAN ZHONG ZENG YAN WANG HECHUN XIA department of neurosurgery School of Clinical MedicineNingxia Medical UniversityYinchuanChina Key Laboratory of Ningxia Stem Cell and Regenerative Medicine General Hospital of Ningxia Medical UniversityYinchuanChina department of neurosurgery Xi’an International Medical Center HospitalXi’anChina

Background:As a form of biological therapy,placenta-derived mesenchymal stem cells(PDMSCs)exhibit considerable promise in addressing the complex pathological processes of traumaticbrain injury(TBI)due to their multi-target and multi-pathway mode of ***&Methods:This study investigates the protective mechanisms and benefits of PDMSCs in mitigating the effects of controlled cortical impact(CCI)in rats and glutamate-induced oxidative stress injury in HT22 cells in *** primary objective is to provide evidence supporting the clinical application of ***:In the in vivo arm of our investigation,we observed a swift elevation of matrix metalloproteinase-9(MMP-9)in the proximal cortex of injured brain tissues after ***,distinguished by their heightened expression of metalloproteinase tissue inhibitors-1 and-2(TIMP-1 and TIMP-2):were intravenously administered via the caudal *** intervention yielded significant reductions in the permeability of the blood-brain barrier(BBB):the extent of brain edema,the levels of inflammatory cytokines IL-1βand TNF-αin damaged brain tissue,and the activation status of microglia in CCI-afflicted *** the realm of in vitro experiments,PDMSC-conditioned media demonstrated substantial reductions in mortality rates and cleaved caspase-3 levels in glutamate-induced HT22 cells compared with conventional ***,this advantage was negated upon the introduction of neutralizing antibodies targeting TIMP-1 and ***:Collectively,our findings underscore the potential of PDMSCs in alleviating oxidative stress injury and secondary brain injury in the pathological process of TBI.

关键词： Traumatic brain injury Mesenchymal stem cells Oxidative stress Matrix metalloproteinases

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Transcriptomic analysis identifies the neuropeptide cortistatin (CORT) as an inhibitor of temozolomide (TMZ) resistance by suppressing the NF-kB-MGMT signaling axis in human glioma

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Genes & Diseases 2024年第3期11卷 385-399页

作者： Zongze He Bo Peng Qi Wang Jie Tian Ping Liu Jie Feng Yiwei Liao Longyi Chen Ping Jia Jian Tang department of neurosurgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China department of Rehabilitation Medicine Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China department of neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Glioma is a common tumor originating in the brain that has a high mortality ***(TMZ)is the first-line treatment for high-grade ***,a large pro-portion of gliomas are resistant to TMZ,posing a great challenge to their *** the study,the specific functions and mechanism(s)by which cortistatin(CORT)regulates TMZ resis-tance and glioma progression were *** decreased expression of CoRT was detected in glioma tissues,and highly expressed CORT was associated with a better survival rate in pa-tients with *** overexpression notably decreased the capacity of glioma cells to pro-liferate and migrate in vitro and to form tumors in *** overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT,p21,and Puma ***,CORT overexpression reduced the resistance of gliomas to TMZ in *** expression Was negatively correlated with MGMT expression in both glioma tissues and cells,and it was found that CORT inhibited NF-kB pathway activation in glioma cells,thereby inhibiting MGMT *** conclusion,CORT regulates glioma cell growth,migration,apoptosis,and TMZ resistance by weakening the activity of NF-kB/p65 and thereby regulating MGMT *** CORT/NF-kB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to *** data also suggest that CORT regulates the viability and metastatic potential of glioma cells,independent of its effects on TMZ resistance,providing evidence of novel therapeutic targets for glioma that should be evaluated infurther studies.

关键词： Cortistatin Glioma MGMT NF-kB pathway Temozolomide

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Gabapentinoids for the treatment of stroke

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Neural Regeneration Research 2024年第7期19卷 1509-1516页

作者： Ying Zhang Chenyu Zhang Xiaoli Yi Qi Wang Tiejun Zhang Yuwen Li department of Pharmacy West China HospitalSichuan UniversityChengduSichuan ProvinceChina department of neurosurgery West China HospitalSichuan UniversityChengduSichuan ProvinceChina

Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure *** research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium *** this review,we briefly elaborate on the medicinal history and ligand-binding sites of *** systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro *** review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related *** preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in ***,gabapentinoids have both opportunities and challenges in the treatment of stroke.

关键词： cortical spreading depolarization gabapentinoid intracerebral hemorrhage pain after stroke stroke subarachnoid hemorrhage

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Factors that influence the results of indirect decompression employing oblique lumbar interbody fusion

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World Journal of Orthopedics 2024年第8期15卷 734-743页

作者： Andrey E Bokov Svetlana Y Kalinina Mingiyan I Khaltyrov Alexandr P Saifullin Anatoliy A Bulkin department of neurosurgery Institute of Traumatology and OrthopedicsPrivolzhsky Research Medical UniversityNizhny Novgorod603005Russia department of Traumatology Orthopedics and NeurosurgeryPrivolzhsky Research Medical UniversityNizhny Novgorod603005Russia

BACKGROUND Indirect decompression is one of the potential benefits of anterior reconstruction in patients with spinal *** the other hand,the reported rate of revision surgery after indirect decompression highlights the necessity of working out prediction models for the radiographic results of indirect decompression with assessing their clinical *** To assess factors that influence radiographic and clinical results of the indirect decompression in patients with stenosis of the lumbar *** This study is a single-center cross-sectional evaluation of 80 consecutive patients(17 males and 63 females)with lumbar spinal stenosis combined with the instability of the lumbar spinal *** underwent single level or bisegmental spinal instrumentation employing oblique lumbar interbody fusion(OLIF)with percutaneous pedicle screw *** results of the indirect decompression were assessed using computerized tomography,while MacNab scale was used to assess clinical *** After indirect decompression employing anterior reconstruction using OLIF,the statistically significant increase in the disc space height,vertebral canal square,right and left lateral canal depth were detected(Р<0.0001).The median(M)relative vertebral canal square increase came toМ=24.5%with 25%-75%quartile border(16.3%;33.3%)if indirect decompression was achieved by restoration of the segment *** patients with the reduction of the upper vertebrae slip,the median of the relative increase in vertebral canal square accounted for 49.5%with 25%-75%quartile border(2.35;99.75).Six out of 80 patients(7.5%)presented with unsatisfactory results because of residual nerve root *** critical values for lateral recess depth and vertebral canal square that were associated with indirect decompression failure were 3 mm and 80 mm2 *** Indirect decompression employing anterior reconstruction is achieved by the increase in disc height al

关键词： Indirect decompression Anterior reconstruction Central lumbar spinal stenosis Degenerative spondylolisthesis Lateral recess stenosis Spinal instability Oblique lateral interbody fusion

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Consensus of Chinese experts on glioma multidisciplinary team management(2nd edition)

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Chinese Medical Journal 2024年第11期137卷 1267-1270页

作者： Jinsong Wu Zhirui Zhou Zanyi Wu Zhiwei Tang Ming Li Siyuan Yin Xufei Luo Ling Wang Yaolong Chen Guoguang Zhao Tao Jiang Ying Mao The National Glioma MDT Alliance of National Center for Neurological Diseases department of neurosurgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China department of Radiation Oncology Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China department of neurosurgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China neurosurgery department The First Affiliated Hospital of Kunming Medical UniversityKunmingYunnan 650032China department of neurosurgery Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan 463599China State Key Laboratory of Pharmaceutical Biotechnology Institute for Brain SciencesAdvanced Institute for Life SciencesSchool of Life SciencesNanjing UniversityNanjingJiangsu 210023China Evidence-Based Medicine Center School of Basic Medical SciencesLanzhou UniversityLanzhouGansu 730000China School of Public Health Lanzhou UniversityLanzhouGansu 730000China department of neurosurgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China department of neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China 不详

To increase the consistency of glioma multidisciplinary team(MDT)management across different regions and hospitals at varying levels,we have updated the Expert Consensus on MDT of Glioma in China based on the currently available *** version has revised and updated the process-management rules and quality-control standards for a glioma MDT,providing reference and guidance for relevant clinical disciplines and *** members of the Consensus Expert Group,abstract,background,and prospects can be seen in supplementaryle,http://***/CM9/B999.

关键词： glioma MDT Expert

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Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization

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Neural Regeneration Research 2024年第10期19卷 2259-2269页

作者： Zeyan Liang Zhelun Yang Haishu Xie Jian Rao Xiongjie Xu Yike Lin Chunhua Wang Chunmei Chen department of neurosurgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina Fujian Neurosurgical Institute FuzhouFujian ProvinceChina

Spinal cord injury is a disabling condition with limited treatment *** studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord ***,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic *** thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord *** or HSEVs were isolated from bone marrow MSC supernatants by density gradient *** administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord *** regulate macrophage polarization towards the M2 phenotype in vivo and in *** RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase *** mi R-146a-5p expression in HSEVs partially attenuated macrophage *** data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage *** study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.

关键词： bone marrow mesenchymal stem cells hypoxia preconditioning interleukin-1 receptor-associated kinase 1 macrophages mesenchymal stem cells small extracellular vesicles spinal cord injury

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