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Expression and significance of sonic hedgehog signaling pathway-related components in brainstem and supratentorial astrocytomas

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Chinese Medical Journal 2011年第21期124卷 3515-3520页

作者： XIN Yu HAO Shu-yu TIAN Yong-ji ZHANG lun-ting WU Zhen WAN Hong LI Jun-hua JIANG Jian ZHANG Li-wei Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 China Beijing neurosurgical institute Capital Medical University Beijing 100050 China

Background Studies have shown that abnormal activation of the sonic hedgehog pathway is closely related to tumorigenesis in central nervous system. This study aimed to investigate the role of the sonic hedgehog signaling pathway in the occurrence of brainstem and supratentorial glioma. Methods Real-time quantitative reverse transcription polymerase chain reaction （qRT-PCR） and immunohistochemistry were used to detect the expression of sonic hedgehog-related components in 5 specimens of normal brain tissue, 10 of grade II brainstem glioma, and 10 of grade II supratentorial glioma. The significance of differences between two groups was determined using the Mann-Whitney U test or the two-sample test according to the results of normality distribution tests. Results The mRNA expression levels of sonic hedgehog-related genes were higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue. The level of protein patched homolog 1 （PTCH1） was significantly higher in brainstem astrocytomas than in supratentorial astrocytomas and normal brain tissue （P 〈0.01）. Immunohistochemistry semi-quantitative analysis was consistent with the qRT-PCR result that PTCH1 expression was increased significantly in brainstem astrocytomas at the protein level （P 〈0.05）. Conclusions Enhanced PTCH1 expression and activation of the sonic hedgehog pathway are involved in brainstem glioma. This may be related to the difference in malignant biological behavior between brainstem and hemispheric glioma and could be an ideal therapeutic target in brainstem glioma.

关键词： astrocytoma glioma brain stem Protein patched homolog 1 glioma-associated oncogene homolog 1

Auditory Rehabilitation in Rhesus Macaque Monkeys （Macaca mulatta） with Auditory Brainstem Implants

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Chinese Medical Journal 2015年第10期128卷 1363-1369页

作者： Zhen-Min Wang Zhi-Jun Yang Fu Zhao Bo Wang Xing-Chao Wang Pei-Ran Qu Pi-Nan Liu Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 China Department of Neural Reconstruction Beijing Neurosurgical Institute Beijing 100050 China

Background：The auditory brainstem implants （ABIs） have been used to treat deafness for patients with neurofibromatosis Type 2 and nontumor patients.The lack of an appropriate animal model has limited the study of improving hearing rehabilitation by the device.This study aimed to establish an animal model of ABI in adult rhesus macaque monkey （Macaca mulatta）.Methods：Six adult rhesus macaque monkeys （M.mulatta） were included.Under general anesthesia,a multichannel ABI was implanted into the lateral recess of the fourth ventricle through the modified suboccipital-retrosigmoid （RS） approach.The electrical auditory brainstem response （EABR） waves were tested to ensure the optimal implant site.After the operation,the EABR and computed tomography （CT） were used to test and verify the effectiveness via electrophysiology and anatomy,respectively.The subjects underwent behavioral observation for 6 months,and the postoperative EABR was tested every two weeks from the 1st month after implant surgery.Result：The implant surgery lasted an average of 5.2 h,and no monkey died or sacrificed.The averaged latencies of peaks Ⅰ,Ⅱ and Ⅳ were 1.27,2.34 and 3.98 ms,respectively in the ABR.One-peak EABR wave was elicited in the operation,and one-or two-peak waves were elicited during the postoperative period.The EABR wave latencies appeared to be constant under different stimulus intensities;however,the amplitudes increased as the stimulus increased within a certain scope.Conclusions：It is feasible and safe to implant ABIs in rhesus macaque monkeys （M.mulatta） through a modified suboccipital RS approach,and EABR and CT are valid tools for animal model establishment.In addition,this model should be an appropriate animal model for the electrophysiological and behavioral study of rhesus macaque monkey with ABI.

关键词： Animal Model Auditory Brain Stem Implants Aural Rehabilitation Feasibility Studies Macaca mulatta

An Experimental Study on the Optimal Timing for the Repair of Incomplete Facial Paralysis by Hypoglossal-facial‘Side'-to-side Neurorrhaphy in Rats

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Biomedical and Environmental Sciences 2018年第6期31卷 413-424页

作者： WANG Bin Bin ZHANG Shao Dong FENG Jie LI Jun Hua LIU Song LI De Zhi WAN Hong Beijing neurosurgical institute Capital Medical UniversityBeijing 100050China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China

Objective To investigate the optimal timing for the repair of persistent incomplete facial paralysis by hypoglossal-facial ‘side＇-to-side neurorrhaphy in rats. Methods A total of 30 adult rats with crushed and bulldog-clamped facial nerve injury were randomly divided into 5 groups（n = 6 each） that were subjected to injury without nerve repair or with immediate repair, 2-week-delayed repair, 4-week-delayed repair, or 8-week-delayed repair. Three months later, the effects of repair in each rat were evaluated by facial symmetry assessment, electrophysiological examination, retrograde labeling, and axon regeneration measurement. Results At 3 months after injury, the alpha angle significantly increased in the group of rats with 4-week-delayed repair compared with the other four groups. Upon stimulation of the facial nerve or Pre degenerated nerve, the muscle action potentials MAPs were recorded in the whisker pad muscle, and the MAP amplitude and area under the curve in the 4-week-delayed repair group were significantly augmented at 3 months post-injury. Similarly, the number of retrograde-labeled motor neurons in the facial and hypoglossal nuclei was quantified to be significantly greater in the 4-week-delayed repair group than in the other groups, and a large number of regenerated axons was also observed. Conclusion The results of this study demonstrated that hemi HN-FN neurorrhaphy performed 4 weeks after facial nerve injury was most effective in terms of the functional recovery of axonal regeneration and activation of facial muscles.

关键词： Facial paralysis Hypoglossal-facial nerve anastomosis Nerve autograft Optimal time

Early intervention improves clinical responses to seasonal allergic rhinitis by stimulation in sphenopalatine ganglion(Xinwu acupoint)

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中医杂志:英文版 2023年第4期43卷 787-794页

作者： GUO Yuhao HUANG Liangran ZHANG Lei YANG Wei HUANG Lixia LIU Wei FAN Yuyan Department of Traditional Chinese Medicine Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China Beijing neurosurgical institute Beijing 100050China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China Department of Radiology Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China Department of Traditional Chinese Medicine Beijing Tongren HospitalBeijing 100005China

OBJECTIVE:To examine the efficacy of early intervention(4 weeks before pollen dispersal)with sphenopalatine ganglion(Xinwu acupoint)stimulation in patients with allergies after the onset of seasonal allergic rhinitis(SAR).METHODS:This is a prospective,randomized and unblinded half-open study.Forty-one SAR volunteers were randomly assigned to either the sphenopalatine ganglion(SPG)acupuncture plus supplementary acupuncture(SPG group)or the sham-SPG acupuncture plus supplementary acupuncture(SA group)stimulation 4 weeks before the onset of allergy season.The changes of the total nasal symptom score(TNSS)and the Rhinoconjunctivitis Quality of Life Questionnaire(RQLQ)scores were measured on the first week in the onset of allergy season.RESULTS:Four patients dropped out due to local hematoma and pain in the SPG and SA groups.The remaining 37 patients continued through to the end of the trial.After early intervention 4 weeks before the onset of allergy season,the sneezing,nasal congestion and itchiness scores in the first week of onset time were significantly lower in the SPG group than in the SA group patients(P<0.001).The RQLQ score obtained at the onset of symptoms indicated that symptoms were more significantly ameliorated in the SPG group than in the SA group(P<0.001).CONCLUSIONS:The results of this study confirmed that early intervention by sphenopalatine ganglion(Xinwu acupoint)stimulation can effectively improve the symptoms and the quality of SAR patients'daily lives.

关键词： rhinitis allergic seasonal acupuncture sphenopalatine Xinwu acupoint early intervention

Antitumor activity of F90, an epidermal growth factor receptor tyrosine kinase inhibitor, on glioblastoma cell line SHG-44

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Chinese Medical Journal 2008年第17期121卷 1702-1706页

作者： LIU Fang-jun GUI Song-bai LI Chu-zhong SUN Ze-lin ZHANG Ya-zhuo Beijing neurosurgical institute Capital Medical University Beijing 100050 China Department of Neurosurgery Beijing Tiantan Hospital Capital Medical University Beijing 100050 China

Background Over-expression of epidermal growth factor receptor （EGFR） is thought to be related to cell proliferation, invasion, metastasis, resistance to chemoradiotherapy and poor prognosis of various human cancers. Forty percent to fifty percent of glioblastoma multiforme （GBM） possess deregulated EGFR, which may contribute to the aggressive and refractory course of GBM. Therefore, blockade of EGFR signal transduction may be a promising treatment strategy for GBM. Methods MTT assay, cell growth curve assay and tumor xenograft model were used to evaluate the antitumor activity of F90 against SHG-44 in vitro and in vivo. Western blot assay was applied to evaluate the expression of p-EGFR, p-ERK1, p-JNK, p-P38, Bcl2 and P53 proteins. Results F90 inhibited the cell proliferation in a dose-dependent manner in vitro. The growth of SHG-44 tumor xenografts was suppressed by F90 at a high dose level （100 mg.kg^-1·d^-1）. Phosphorylation of EGFR and activated downstream signaling proteins, such as ERK1, JNK and P38, were found to be depressed after incubation with F90 for 48 hours in vitro. Down-regulated Bcl2 protein and up-regulated P53 protein were also observed. Conclusions The results demonstrate that F90 is effective in inhibiting the proliferation of SHG-44 cells in vitro and tumor growth in vivo, suggesting that F90 may be a new therapeutic option for treatment of GBM.

关键词： glioblastoma epidermal growth factor receptor Iressa

CT perfusion imaging and CT subtraction angiography in the diagnosis of ischemic cerebrovascular disease within 24 hours

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Chinese Medical Journal 2003年第3期116卷 49-53页

作者：管小亭于学英刘翔龙洁戴建平 Department of Neurology Beijing Tiantan Hospital Capital University of Medical Sciences Beijing 100050 China Department of Neuroradiology Beijing Neurosurgical Institute Beijing 100050 China

Objective To evaluate the value of the clinical use of CT perfusion imaging (CTPI) and CT subtraction angiography (CTSA) for diagnosing acute ischemic cerebrovascular disease (AICVD). Methods Twenty-four patients with AICVD onset within 24 hours were examined with regular CT, CTPI, and CTSA. Some cases received CTPI, magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), digital subtraction angiography (DSA) or single photon emission computer tomography (SPECT) during follow-up examinations.Results Of the 24 cases, 11 had negative results from regular CT scans 3-6 hours after onset of stroke in 6 cases, 6-12 hours in 3 cases, and 12-24 hours in 2 cases. Ten of these cases were then confirmed by CTPI as having ischemic lesions, 2 with middle cerebral artery occlusion (MCAO), and 1 case with transient ischemic attack (TIA) with CTPI negative. Of the 24 cases, 13 had positive results from regular CT, 9 were diagnosed with ischemic lesions larger by using CTPI than regular CT, 1 case had MCAO and 1 had internal carotid artery occlusion (ICAO). There were 4 cases with ischemic lesions observed with regular CT having nearly the same range as that of lacunar infarctions using CTPI. Another 4 cases had more than 2 lesion areas. The peak time (PT), mean transit time (MTT) and relative flow (RF) of 24 cases were markedly different. The sides of ischemic lesions compared to each other and the core of the lesion compared to peripheral zones were also altered significantly (P<0.01).Conclusions Combined CTPI with CTSA can detect acute ischemic lesions at early and hyper-early stages and could distinguish between TIA, lacunar infarction and a larger area of infarction. Using semiquantitative blood perfusion analysis status, CTPI with CTSA could define position, area and range of the ischemic lesion and penumbra. These scans can also analyze the brain blood perfusion status. It is important to early diagnose the occlusion of the entire division of the internal carotid artery or middle cerebral artery and it is m

关键词： computerized tomography diagnosis cerebral ischemia

Personalized assessment and training of neurosurgical skills in virtual reality:An interpretable machine learning approach

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虚拟现实与智能硬件（中英文） 2024年第1期6卷 17-29页

作者： Fei LI Zhibao QIN Kai QIAN Shaojun LIANG Chengli LI Yonghang TAI Yunnan Key Laboratory of Opto-electronic Information Technology Yunnan Normal UniversityKunming 650500China Department of Thoracic Surgery Institute of The First People’s Hospital of Yunnan ProvinceKunming 650500China Faculty of Life and Biotechnology Kunming University of Science and TechnologyKunming 650031China

Background Virtual reality technology has been widely used in surgical simulators,providing new opportunities for assessing and training surgical skills.Machine learning algorithms are commonly used to analyze and evaluate the performance of participants.However,their interpretability limits the personalization of the training for individual participants.Methods Seventy-nine participants were recruited and divided into three groups based on their skill level in intracranial tumor resection.Data on the use of surgical tools were collected using a surgical simulator.Feature selection was performed using the Minimum Redundancy Maximum Relevance and SVM-RFE algorithms to obtain the final metrics for training the machine learning model.Five machine learning algorithms were trained to predict the skill level,and the support vector machine performed the best,with an accuracy of 92.41%and Area Under Curve value of 0.98253.The machine learning model was interpreted using Shapley values to identify the important factors contributing to the skill level of each participant.Results This study demonstrates the effectiveness of machine learning in differentiating the evaluation and training of virtual reality neurosurgical performances.The use of Shapley values enables targeted training by identifying deficiencies in individual skills.Conclusions This study provides insights into the use of machine learning for personalized training in virtual reality neurosurgery.The interpretability of the machine learning models enables the development of individualized training programs.In addition,this study highlighted the potential of explanatory models in training external skills.

关键词： Machine learning Neurosurgery Shapley values Virtual reality Human-robot interaction

The Oncogenesis of Glial Cells in Diffuse Gliomas and Clinical Opportunities

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Neuroscience Bulletin 2023年第3期39卷 393-408页

作者： Qiyuan Zhuang Hui Yang Ying Mao Department of Neurosurgery Huashan HospitalFudan UniversityShanghai 200040China National Center for Neurological Disorders Huashan HospitalFudan UniversityShanghai 200040China Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration Huashan HospitalFudan UniversityShanghai 200040China institute for Translational Brain Research Fudan UniversityShanghai 200032China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Institute for Translational Brain ResearchInstitutes of Brain ScienceFudan UniversityShanghai 200032China neurosurgical institute of Fudan University Shanghai 200032China

Glioma is the most common and lethal intrinsic primary tumor of the brain.Its controversial origins may contribute to its heterogeneity,creating challenges and difficulties in the development of therapies.Among the components constituting tumors,glioma stem cells are highly plastic subpopulations that are thought to be the site of tumor initiation.Neural stem cells/progenitor cells and oligodendrocyte progenitor cells are possible lineage groups populating the bulk of the tumor,in which gene mutations related to cell-cycle or metabolic enzymes dramatically affect this transformation.Novel approaches have revealed the tumor-promoting properties of distinct tumor cell states,glial,neural,and immune cell populations in the tumor microenvironment.Communication between tumor cells and other normal cells manipulate tumor progression and influence sensitivity to therapy.Here,we discuss the heterogeneity and relevant functions of tumor cell state,microglia,monocyte-derived macrophages,and neurons in glioma,highlighting their bilateral effects on tumors.Finally,we describe potential therapeutic approaches and targets beyond standard treatments.

关键词： Glioma origin Stem/progenitor cell Oncometabolite Immune heterogeneity Neuron-tumor interaction

Advances in the adjuvant chemotherapy of glioblastoma multiforme： opportunities and challenges for the neurosurgeons in China

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Chinese Medical Journal 2009年第11期122卷 1243-1244页

作者： LI Shou-wei JIANG Tao Department of Neurosurgery Beijing Tiantan Hospital Affiliated to Capital Medical University Beijing Neurosurgical Institute Beijing 100050 China

Glioblastoma multiforme （GBM） is the most common primary malignant brain tumor in adults, which accounts for approximately 50% of all gliomas. Its prognosis is particularly disappointing with a median life expectancy less than a year even when the patients are treated with the most aggressive regimens. Over the past 10 years, a number of trials have tried to establish whether adjuvant chemotherapy, as well as molecularly targeted therapy, provides GBM patients with clinically meaningful benefits.

关键词： TEMOZOLOMIDE MGMT TRIAL