Abstract:Abnormal formation of blood vessels is a common phenomenon in various solid tumors， particularly prominent in high-grade glioma. Multiple mechanisms have been discovered for formation of blood vessels， which promote the angiogenesis within tumor tissues and have been validated in high-grade glioma. Bevacizumab has been widely used in anti-angiogenic therapy for glioma， however， anti-angiogenic therapy still faces many problems. For example， the use of bevacizumab can improve the quality of life of patients and prolong their progression free survival. However， the overall survival of patients is not beneficial， and some patients do not show any imaging improvement after treatment. In addition， the issue of resistance to bevacizumab remains unresolved. Previous studies have suggested that the therapeutic resistance mechanisms can be mainly divided into two ways of promoting the malignant phenotype progression of tumor cells and promoting abnormal formation of blood vessels. These therapeutic resistance mechanisms may provide clues for enhancing the effectiveness of anti-angiogenic therapy and improving patient prognosis in the future.

Abstract:Objective To explore the clinicopathological features of pediatric-type diffuse low-grade glioma （DLGG） with BRAF V600E mutation. Methods From December 2021 to June 2023， 15 patients with pediatric-type DLGG who underwent surgery at the Department of Neurosurgery of Beijing Tiantan Hospital affiliated with Capital Medical University and were diagnosed with BRAF V600E mutation through postoperative pathology were selected as the study subject. Diagnosis was based on the WHO 5th edition classification of tumors of the central nervous system. The general information of the patient was analyzed， and the histopathological and molecular pathological features of the tumor were explored using hematoxylin and eosin （HE） and immunohistochemical staining， as well as next-generation sequencing. Results Among the 15 patients， 2 were ≤ 6 years old， 9 were 7 to 14 years old， and 4 were ≥ 15 years old. Six were females and 9 were males. Five cases of tumors were located above the cerebellar tentorium， and 10 cases were located below the cerebellar tentorium. Four cases had no clinical symptoms， 6 cases had clinical symptoms of headache and nausea， 3 cases had epileptic seizures， and 2 cases had visual and auditory abnormalities. The next-generation sequencing results showed that all 15 patients had BRAF V600E mutations in their tumors， and gene mutations in the IDH gene and histone H3 were excluded. The combination of next-generation sequencing and immunohistochemical staining ruled out homozygous deletion of CDKN2A/2B. Morphological analysis showed that 13 cases of tumors exhibited the morphological features of diffuse astrocytoma， while 2 cases showed oligodendrocyte astrocytoma morphology. Conclusions BRAF V600E mutation in pediatric-type DLGG is relatively rare， mainly affecting children and young adults， and often needs to be distinguished from other types of intracranial gliomas. In clinical practice， it is necessary to combine microscopic morphological features with patient clinical manifestations and molecular pathological features for comprehensive diagnosis.

Abstract:Objective To explore the expression level and function of THBS1 in glioblastoma （GBM）. Methods The data was extracted from the Cancer Genome Atlas （TCGA） and Chinese Glioma Genome Atlas （CGGA）_693、CGGA_325 and CGGA_301 datasets. Gene expression data were normalized to analyze the differential expression of THBS1 in low-grade gliomas and GBM， as well as its relationship with isocitrate dehydrogenase （IDH） mutations， 1p/19q codeletion， and survival prognosis. Based on single-cell sequencing data and spatial transcriptomic data， the distribution of THBS1 in glioma tissue was analyzed. The CellCall algorithm and MAGIC algorithm were used to explore the function of THBS1 in the cell-cell communication， THBS1 related genes and their functions. The CIBERSORTx algorithm was used to analyze the relationship between THBS1 and immune cell infiltration. Results The expression level of THBS1 in GBM tissue was higher than that in normal tissue， and the difference was statistically significant （P ＜ 0.05）. In the CGGA and TCGA datasets， the expression level of THBS1 in GBM patients was higher than that in low-grade gliomas， and the difference was statistically significant （both P ＜ 0.01）. The expression levels of THBS1 in IDH wild-type and 1p/19q non-codeletion patients were higher than those in IDH mutant and 1p/19q codeletion patients， respectively， and the differences were statistically significant （both P ＜ 0.01）. In the CGGA_693 and CGGA-325 datasets， the survival rate of patients with high expression of THBS1 gene was lower than that of patients with low expression， and the difference was statistically significant （P ＜ 0.01）. Single-cell sequencing data analysis showed that THBS1 was mainly expressed in monocyte/ macrophages of glioma tissue. Spatial transcriptome data analysis indicated that monocyte/ macrophages expressing THBS1 were spatially co-localized with astrocytes， tumor cells， neurons， oligodendrocytes， and oligodendrocyte precursor cells. The pathway activity and dependent ligand-receptor pathways of cell-cell communication between THBS1 negative and THBS1 positive monocytes/macrophages and tumor cells and neurons were different. Functional enrichment analysis showed that THBS1 related genes were involved in biological processes such as vesicle mediated transport， autophagy， and regulation of DNA-binding transcription factor activity. In the four datasets， the abundance of macrophage M0 in the high expression group of THBS1 was higher than that in the low expression group， and the difference was statistically significant （P＜ 0.05）. Conclusions THBS1 is highly expressed in GBM and is associated with poor prognosis in patients. THBS1 regulates macrophage M0 infiltration， and monocytes/macrophages expressing THBS1 may regulate the microenvironment of GBM， thereby regulating oncogenesis.

Abstract:Objective To explore the histopathological and molecular pathological features of isocitrate dehydrogenase （IDH） wild-type glioblastoma （GBM）. Methods From September 2021 to August 2023， 74 GBM patients with surgery at the Department of Neurosurgery， Affiliated Hospital of Hebei University were selected as the study subject. Hematoxylin-eosin staining was used to observe the pathological characteristics of tissues. Immunohistochemical staining and next-generation sequencing were used to analyze molecular pathological features. Kaplan-Meier method was used to plot survival analysis curves to analyze the relationship between patient survival and IDH1 mutations. Results Among 74 cases of GBM， males accounted for 60.81% （45/74）， and the age was （55.23±4.58） years old. Fifty-eight cases of tumors were located in the frontal lobe and 16 cases were located in the temporal lobe. The histological results of hematoxylin-eosin staining showed that 82.43% （61/74） of tumor tissues showed typical palisade necrosis， vascular proliferation， and significant tumor atypia， consistent with the typical GBM tissue morphological characteristics. The morphology of other tumor tissues matched the morphological characteristics of grade 2 or 3 astrocytoma. Immunohistochemical staining showed that all tumors were negative for IDH1 R132H staining， while Ki-67 staining showed an average positive rate of 38%. Results of the next-generation sequencing molecular pathology showed that all tissues were negative for IDH1/2， with positive amplification of epidermal growth factor receptor （EGFR） accounting for 74.32% （55/74） and telomerase reverse transcriptase （TERT） promoter region mutations accounting for 59.46% （44/74）.The proportion of pure deletion of cyclin dependent kinase inhibitor 2A/B （CDKN2A/B） was 33.78% （25/74）. The high expression level of methylation in the promoter region of O6-methylguanine-DNA methyltransferase （MGMT） accounted for 47.30% （35/74）. Conclusions GBM exhibits molecular features of IDH wild-type， with some cases accompanied by EGFR amplification， TERT promoter region mutations， CDKN2A/B homozygous deletion， and MGMT promoter region hypermethylation.

Abstract:Objective To investigate the clinicopathological and molecular pathological features of diffuse hemispheric glioma （DHG）. Methods A total of 27 DHG patients who underwent surgical resection or stereotactic biopsy at the Neurosurgery Department of Beijing Tiantan Hospital Affiliated to Capital Medical University from January 2021 to May 2023 were selected as the study subjects. Clinical data of the patients were collected and followed up. Hematoxylin eosin staining and immunohistochemical staining were used to detect the characteristic protein expression in tumor cells. The next generation sequencing and pyrosequencing methods were used to detect the molecular pathology characteristics of tumors. Results The median age of onset for 27 DHG patients was 22.5 years old； 59.3% （16/27） were males； 24 cases of tumors mainly located in unilateral frontal， parietal， and temporal lobes， with only 3 cases located in bilateral cerebral hemispheres. The histopathological results showed that 5 out of 27 tumors had the morphology of astrocytoma， 17 had the morphology of glioblastoma， 1 had glioblastoma with ganglion like differentiation， and 4 had the morphology of primitive neuroectodermal tumors. The immunohistochemical staining results showed that all 27 cases of tumor glial fibrillary acidic protein staining were diffuse positive， and transcription factor 2 protein expression in oligodendrocytes was negative， α- the expression of X-chromosome related genes in thalassemia/mental retardation syndrome was missing， and p53 protein was expressed with missense or nonsense mutations. Isocitrate dehydrogenase 1 R132H， isocitrate dehydrogenase 2 R172K， H3K27M， and BRAF V600E proteins were all negative. 24 cases of tumor cell nuclei expressed H3.3G34R protein to varying degrees， and 3 cases of tumors diffusely expressed H3.3G34V protein. The Ki67 proliferation index varied from 3%-80%. The molecular pathological results showed that all tumors had H3F3A gene H3.3 G34 （35） mutations， 23 cases with ATRX deletion， and 27 cases with TP53 mutations. Follow up for 2-24 months， of which 5 cases died 10-24 months after diagnosis， with a median progression free survival of 6.5 months and a median total survival of 11 months. 5 cases were lost to follow-up. Conclusions DHG has a high degree of malignancy， and despite the addition of radiotherapy or chemotherapy for total or near total resection lesions， patients still quickly relapse， progress， or die. Therefore， immunohistochemical and molecular pathological testing of DHG is necessary， which is more conducive to active treatment and prognostic evaluation of DHG patients.

Abstract:Objective To explore the clinical pathological and molecular genetic characteristics of polymorphous low-grade neuroepithelial tumor of the young （PLNTY）. Methods A total of 16 patients with PLNTY were recruited as research subjects， who underwent surgical treatment at Beijing Tiantan Hospital affiliated to Capital Medical University from May 2021 to May 2023. The clinical and imaging data were collected. Hematoxylin eosin staining， immunohistochemistry staining， and gene sequencing were used to detect morphological and molecular genetic changes in tumor tissue. Patients were followed up on symptom improvement， the presence of radiotherapy and chemotherapy， and tumor recurrence through telephone and imaging follow-up. Results The median age of onset was 24 years in the 16 cases of PLNTY， and the male-to-female ratio was 1∶1. Five cases （5/16） presented with acute onset （onset time ＜ 3 months）. The clinical symptoms are mainly characterized by varying degrees of epileptic seizures. Eight cases （8/16） were located in the temporal lobe， and 5 cases （5/16） were located in the parietal occipital lobe. Enhanced magnetic resonance imaging scan showed no significant enhancement in 11 cases （11/16）， mild heterogeneous enhancement in 3 cases （3/16）， and significant heterogeneous enhancement in 2 cases （2/16）. Fourteen patients （14/16） showed improvement in postoperative epilepsy symptoms， with 1 case experiencing recurrence. The histopathological results showed that the tumor showed invasive growth， located in the cortex and subcortical white matter， with pleomorphic and oligodendrocyte like cell morphology and branching small blood vessels. Twelve cases （12/16） were accompanied by calcification. One case of recurrent resected specimen showed malignant transformation， characterized by increased local cell density， visible nuclear mitotic figures， neovascularization， and palisading necrosis. The immunohistochemical staining results of 16 cases of tumors showed diffuse positive expression of glial fibrillary acidic protein （GFAP）， oligodendrocyte transcription factor 2 （Olig2）， and CD34， while synaptophysin was negatively expressed. Among them， 14 cases （14/16） had a Ki67 proliferation index ≤ 4%， and the Ki67 proliferation index of malignant transformation cases was 20%. Second-generation sequencing results of 7 cases showed that BRAF or FGFR molecular mutations were predominant， with three cases （3/7） showing methylation of the O6-methylguanine-DNA methyltransferase promoter （MGMT）； FGFR3：：TACC3 fusion with TERT promoter mutation was detected in 1 primary and recurrent case， and chromosome 10 deletion and CDK4 and MDM2 amplification were observed in the recurrent cases. Conclusions PLNTY is common in adolescents and is a long-term epilepsy related tumor， commonly found in the temporal and parietal occipital lobes. The tumor shows invasive growth， with visible pleomorphic and oligodendrocyte cell components. CD34 is diffusely positive， and molecular changes are mainly BRAF or FGFR variants. The prognosis is mostly favorable with significant improvement in postoperative seizure symptoms. Individual cases may experience malignant transformation after recurrence， and molecular genetic results show FGFR3：： TACC3 fusion with TERT promoter mutation. It is important for clinicians to thoroughly assess clinical， pathological characteristics and molecular genetic alterations of PLNTY and be vigilant.

Abstract:Objective To explore the expression and clinical significance of phosphoglucomutase 2 （PGM2） in glioma. Methods Clinical data and mRNA sequencing data of glioma patients were collected from the Chinese Glioma Genome Atlas （CGGA） database and the Cancer Genome Atlas （TCGA） database. After matching the sequencing data with clinical data， the gene expression of PGM2 was extracted， and cases with missing clinical data were excluded. According to the cut-off value obtained from the receiver operating characteristic （ROC） curve， the cases were divided into PGM2 high expression group and PGM2 low expression group. The predictive value of PGM2 expression on the overall survival rate of glioma patients was evaluated using area under the ROC curve （AUC） and Kaplan Meier survival curve. Univariate analysis was used to explore the clinical and pathological factors affecting the expression level of PGM2 in gliomas. Univariate and multivariate Cox regression were used to analyze the relationship between prognosis in glioma patients and clinical and pathological factors related to glioma， as well as PGM2 expression. Gene Ontology （GO） enrichment analysis and KEGG pathway analysis were performed by screening co-expressed genes to explore the involvement of PGM2 in biological processes and related signaling pathways regulation. CIBERSORT algorithm was used to analyze the relationship between PGM2 expression in gliomas and immune cell infiltration. Results A total of 273 cases were left after the deletion of missing values from the CGGA-325 and 560 cases were left after the deletion of missing values from the TCGA. ROC curve analysis of PGM2 expression predicting the overall survival rate of glioma patients showed that the AUC in the CGGA-325 database was 0.705 ［95%CI （0.640， 0.769）］， with a cut-off value of 10.1， and the AUC in the TCGA database was 0.739 ［95%CI （0.699， 0.778）］， with a cut-off value of 8.9. According to the cut off value， the cases were divided into PGM2 high expression group and PGM2 low expression group. Kaplan Meier survival analysis showed that the overall survival rate of patients in PGM2 high expression group decreased compared to those in PGM2 low expression group， and the difference was statistically significant （P ＜ 0.001）. In the CGGA-325 and TCGA databases， there were statistically significant differences in glioma grade， IDH type， and 1p/19q deletion between PGM2 low expression group and PGM2 high expression group （both P ＜ 0.05）. Multivariate Cox regression analysis showed that the common independent prognostic factors in the CGGA-325 and TCGA databases were glioma grade and co-deletion of 1P/19q， and the expression of PGM2 was an independent prognostic factor in the CGGA-325 database， and the difference was statistically significant （all P ＜ 0.05）. GO enrichment analysis and KEGG pathway analysis showed that PGM2 expression was associated with endoplasmic reticulum protein transportation， Toll-like receptor signaling pathway， and I-κB kinase/NF-κB signal pathway. CIBERSORT analysis showed that the initial CD4+ T cells， activated memory CD4+ T cells， regulatory T cells， monocytes， macrophages （M0， M1， M2）， and neutrophils in PGM2 low expression group and PGM2 high expression group were compared in terms of immune infiltration degree， and the differences were statistically significant （all P ＜ 0.05）. Conclusions High expression of PGM2 is associated with a poorer prognosis in glioma and may serve as a prognostic indicator for glioma patients and is expected to become a potential therapeutic target for glioma in the future.

Abstract:Objective To explore the clinical efficacy of Modified Suanzaoren Decoction for chronic insomnia disorder （CID） patients and the neuroimaging mechanism of resting-state functional magnetic resonance imaging （rs-fMRI）. Methods From October 2020 to January 2022， 39 CID patients with yin-deficiency and fire-hyperactivity were selected from the Clinic of Inner Mongolia Autonomous Region Mental Health Center， Community Clinic and WeChat Official Account as research objects. Patients were given a 4-week treatment with Modified Suanzaoren Decoction. The scores of the Insomnia Severity Index （ISI）， Pittsburgh Sleep Quality Index （PSQI）， Hamilton Anxiety Scale （HAMA）， 24-item Hamilton Depression Scale （HAMD-24）， Repeatable Battery for Assessment of Neuropsychological Status （RBANS）， as well as polysomnography and rs-fMRI were compared before and after treatment in patients. Pearson correlation was used to analyze the correlation between testing time series mean and PSQI， ISI， HAMA， and HAMD-24 reduction rates. Results Twenty-seven patients with CID were finally included and after treatment with Modified Suanzaoren Decoction， the total PSQI score ［（9.85±3.48） vs （12.82±2.92）］， ISI score ［（9.44±5.66） vs （17.30±5.45）］， HAMA score ［（6.67±3.89） vs （11.19±4.71）］， and HAMD-24 score ［（6.70±4.48） vs （11.52±6.44）］ of the patients were all lower than before treatment， and the differences were statistically significant （all P ＜ 0.05）. The total score of RBANS （98.72±9.30） was higher than before treatment （88.92±8.59）， and the difference was statistically significant （P ＜ 0.05）. There was no statistically significant difference in the results of polysomnography after treatment compared to before treatment （P＞ 0.05）. The functional connections of the hippocampus， thalamus， posterior cingulate gyrus， and orbital frontal gyrus changed， and the differences were statistically significant （all P＜0.05）. The decrease in functional connection between the left posterior cingulate gyrus and the left frontal gyrus was positively correlated with the reduction rate of HAMD-24 （r=0.422， P=0.028）， while the decrease in functional connection between the left orbital frontal gyrus and the left anterior cingulate gyrus and the paracingulate gyrus was negatively correlated with the reduction rate of HAMD-24 （r=-0.399， P=0.039）， and the differences were statistically significant. Conclusions After treatment with Modified Suanzaoren Decoction， the insomnia symptoms and emotions of CID patients improve significantly. The mechanism is related to the regulation of abnormal functional activities in areas such as the hippocampus， thalamus， posterior cingulate gyrus， and orbital frontal gyrus.

Abstract:Objective To investigate the neuroprotective effect of verbascoside （VB） on the brain of Parkinson's disease （PD） model mice and its possible mechanism. Methods A total of 75 C57/BL mice （SPF grade， healthy male， 24-26 g） were randomly divided into blank control group， model group （MPTP group）， and experimental group （low dose group： MPTP+30 mg/kg VB； medium dose group： MPTP+60 mg/kg VB； high dose group： MPTP+120 mg/kg VB）， with 15 mice in each group. After the establishment of the model， the movement ability of mice in different groups was detected by rod climbing and hanging experiments； dopaminergic neurons were detected by ultramicroelectron microscopy； the number of tyrosine hydroxylase （TH） positive cells was detected by immunohistochemical staining； the expression of tyrosine hydroxylase （TH）， α-synuclein （α-syn），nuclear factor erythroid 2-related factor 2 （Nrf2）， heme oxygenase-1 （HO-1）， glutathione peroxidase 4 （GPX4） signaling pathway related proteins was detected by Western blotting； glutathione， total iron ion， superoxide dismutase （SOD）， and malondialdehyde in brain tissue was detected by enzyme-linked immunosorbent assay. Results The time of rod climbing experiment of mice in model group was significantly longer than that of blank control group， the time of rod climbing experiment of mice in experimental group was significantly shorter than that of model group， with statistical significance （P＜ 0.05）； the score of hanging experiment of mice in model group was lower than that of blank control group， the score of hanging experiment of mice in experimental group was higher than that of model group， with statistical significance （P ＜ 0.05）. The degeneration and necrosis of dopaminergic neurons in substantia nigra of the midbrain of mice in the model group （MPTP group） were more obvious than those in the experimental group under electron microscope； immunohistochemical staining experiment showed that the number of TH positive cells in the model group was much lower than that in the blank control group， the number of TH positive cells in the experimental group was much higher than that in the model group， with statistical significance （P＜ 0.05）. Western blotting experiment showed that the expression of TH， Nrf2， HO-1， and GPX4 in the model group was lower than that in the blank control group， the expression of TH， Nrf2， HO-1， and GPX4 in the experimental group was higher than that in the model group， with statistical significance （P ＜ 0.05）； the expression of α-syn in the model group was higher than that in the blank control group， the expression of α-syn in the experimental group was lower than that in the model group， with statistical significance （P＜0.05）. The results of ELISA showed that the expression of glutathione and SOD in the model group was significantly lower than that in the blank control group， the expression of glutathione and SOD in the experimental group was significantly higher than that in the model group， with statistical significance （P＜ 0.05）； the expression of malondialdehyde and total iron ions in the model group was significantly lower than that in the blank control group， the expression of malondialdehyde and total iron ions in the experimental group was significantly lower than that in the model group， with statistical significance （P ＜ 0.05）. Conclusions Verminoside may play a protective role by inhibiting iron death of dopaminergic neurons in the substantia nigra of Parkinson's disease model mice

Abstract:Schizophrenia is a serious mental disorder with high disability rate and heavy disease burden. Vocational rehabilitation can effectively improve the social function level of patients and improve the prognosis of patients. It is one of the important focus points of mental rehabilitation. This paper introduces the methods and current situation of vocational rehabilitation research in China and abroad， and looks forward to the future of vocational rehabilitation research in China.

Abstract:Attention deficit and hyperactivity disorder （ADHD） is a highly prevalent neurodevelopmental disorder in children， with a global prevalence rate of 5.29%. The correlation between the onset of ADHD and neuroinflammatory response is gradually being confirmed. Abnormal active neuroinflammatory responses are commonly present in patients with ADHD. This paper reviews the potential mechanisms of neuroinflammatory response in the pathogenesis of ADHD， with a focus on the association among changes in inflammatory factor levels， abnormal activation of glial cells， and changes in blood-brain barrier permeability with ADHD， so as to provide reference for the diagnosis and treatment of ADHD.