Abstract:Gliomas are the most common primary malignant tumors in the intracranial region， among which glioblastoma （GBM）， as the most aggressive primary brain tumor， is characterized by high heterogeneity and an abnormally rapid proliferation capacity. Due to the presence of the blood-brain barrier （BBB）， traditional treatments such as surgery， radiotherapy， and chemotherapy have limited efficacy in treating GBM. In recent years， immunotherapy has emerged as a cutting-edge strategy in cancer treatment， showing tremendous potential. However， the immunosuppressive microenvironment of GBM and its complex immune evasion mechanisms present significant challenges to the application of immunotherapy. Therefore， in-depth research into the characteristics of the GBM microenvironment and its interactions with tumor cells has become critical for improving therapeutic outcomes.This review focuses on the major cellular components of the GBM microenvironment， including tumor cells， immune cells， and their interactions， as well as the roles of key cytokines in tumor progression. Furthermore， it explores novel immunotherapeutic strategies， such as chimeric antigen receptor T cell （CAR-T） therapy， immune checkpoint inhibitors， and other immunomodulatory approaches， analyzing their challenges and potential advantages in clinical applications. Additionally， it highlights new research directions and therapeutic concepts targeting non-tumor cellular components in the microenvironment， such as the regulation of tumor-associated macrophages （TAMs） and T cells. A comprehensive understanding of the complexity and dynamic changes within the GBM immune microenvironment will facilitate the identification of more effective therapeutic targets， driving the development of personalized treatments and significantly improving patient survival and quality of life. Future research should focus on the synergistic interactions among different cell types within the microenvironment and their regulatory mechanisms to develop more precise and efficient therapeutic strategies.

Abstract:Glioma is the most common primary intracranial malignant tumor. Due to the strong genetic variation and significant individual differences among patients， as well as the difficulty in generating new mutations and antigens during the progression of glioblastoma， the research progress of targeted therapy has encountered more obstacles compared to other tumors. Immunotherapy and tumor-treating fields （TTF） are new concepts in cancer treatment， and their phased breakthroughs have greatly inspired the field of glioma research. This article provides an overview of the new discoveries and advances in the treatment of gliomas in recent years， to provide reference for future clinical treatment of gliomas.

Abstract:Objective To investigate the effects of accelerated repetitive transcranial magnetic stimulation （arTMS） based on resting-state functional magnetic resonance imaging （rs-fMRI） in patients with melancholic depressive disorder and to characterize the functional brain imaging changes. Methods Forty patients who visited the Second People's Hospital of Guizhou Province from August 2021 to November 2023 and were diagnosed with melancholic depressive disorder were selected for the study. The patients were randomly divided into study group and pseudo-stimulation group using the random number table method， with 20 cases in each group. Conventional medication was given to both groups， where patients in study group were given arTMS for five consecutive days， and pseudo-stimulation was given to pseudo-stimulation group. Patients in both groups received one 24-item Hamilton Depression Scale （HAMD-24） assessment and rs-fMRI scan before treatment and on the day of the end of treatment. The changes of HAMD-24 scores and regional homogeneity （ReHo） values and functional connectivity （FC） values before and after treatment were analyzed in both groups， and the correlation between rs-fMRI indexes and HAMD-24 score reduction rate was further calculated using Pearson correlation. Results Thirty-six patients were finally included， 19 in study group and 17 in pseudo-stimulation group. Before treatment， the difference in HAMD-24 scores between the two groups was not statistically significant （P ＞ 0.05）. After treatment， the HAMD-24 scores of patients in both groups were lower than those before treatment， and the HAMD-24 scores of patients in study group were lower than those in pseudo-stimulation group， and the differences were statistically significant （all P ＜ 0.05）. There was no statistically significant difference in the ReHo values of brain regions before and after treatment in pseudo-stimulation group （P ＞ 0.05）. After five days of arTMS， the ReHo value of the right fusiform gyrus of the patients in study group was statistically reduced （t=-4.723， P ＜ 0.05）， and the FC value of the right fusiform gyrus with the right middle temporal gyrus and the right angular gyrus was statistically reduced （P ＜ 0.05）. Correlation analysis showed that the pre-treatment FC values of the right middle temporal gyrus and the right fusiform gyrus were negatively correlated with the HAMD-24 score reduction rate in study group patients， and the difference was statistically significant （r=-0.50， P＜ 0.05）. Conclusions arTMS improves depressive symptoms in patients with melancholic depressive disorder. arTMS treatment may affect patients' right fusiform gyrus function， and the pre-treatment FC values of the right fusiform gyrus and the right middle temporal gyrus can be used as a predictor of efficacy of arTMS in the treatment of melancholic depressive disorder.

Abstract:Objective To analyze the characteristics and significance of cell communication in the microenvironment of isocitrate dehydrogenase （IDH） mutation gliomas. Methods Seurat and clusterProfiler were used to analyze cell types， proportions， and functions in IDH mutation glioma tissues. CellphoneDB was used to analyze cell-cell communication characteristics and screen ligand-receptor （LR） pairs with significant differences. Univariate Cox regression was used to analyze the association between LR pairs expression and overall survival in IDH mutation glioma patients. Patients were classified into different subtypes using consistent clustering based on LR pairs expression and prognostic information. Log-rank， Gene Set Enrichment Analysis （GSEA）， ESTIMATE， and CIBERSORT were used to compare the survival differences， functional differences， and immune characteristics of patients with different subtypes. Based on the correlation of LR pairs expression and least absolute shrinkage and selection operator （LASSO） analysis， a risk prediction model was constructed to analyze the association between risk scores， patient subtypes and pathological indicators. Kaplan-Meier survival curve， Log-rank test and Cox regression model were used to evaluate the relationship between risk score and survival of IDH mutation glioma patients. Results A total of 27 154 cells were obtained， annotated and divided into six cell types. In the IDH mutation patients of CGGA693 and CGGA325 datasets， there were 140 and 131 LR pairs， respectively， that were associated with patient prognosis （P＜ 0.05）， and patients were divided into two molecular subtypes with significant differences in prognosis （P ＜ 0.05）， and the differences were statistically significant. Compared with subtype 1 with good prognosis， subtype 2 had a higher proportion of glioma patients with grade Ⅳ and 1p/19q co deletion （P＜ 0.05）. Hallmark enrichment analysis showed that subtype 2 was associated with MYC target genes， DNA repair， and oxidative phosphorylation. KEGG pathway enrichment analysis showed that subtype 2 was mainly associated with ribosomes， oxidative phosphorylation， Parkinson's disease， Huntington's disease， and Alzheimer's disease. Compared with subtype 1， subtype 2 had lower tumor purity and higher degree of immune infiltration. There were 14 LR pairs with expression correlation coefficients greater than 0.5 between ligands and receptors. A risk scoring model consisting of DLL4-NOTCH3， CXCL12-CR4， COPA-SORT1， PLAU-PLAUR， and EPHB2-EFNB1 was constructed using LASSO regression. LR pair risk score was higher in subtype 2 （P＜ 0.05）， which increased with pathological grade （P＜ 0.05）， and LR pair risk score was higher in the 1p/19q co deletion group （P＜ 0.05）， and the differences were statistically significant. In patients with IDH mutation， IDH mutation， and 1p/19q non deficient gliomas， the high-risk group had a shorter survival period compared to the low-risk group with a statistical difference （P ＜ 0.000 1）. Univariate and multivariate Cox regression analysis showed that WHO pathological grade （grade Ⅲ all P＜0.05； grade Ⅳ all P＜0.001）， 1p/19q status （all P＜0.05）， and risk score （all P＜0.001） were statistically significant factors affecting the overall survival of patients with IDH mutation gliomas. Conclusions LR pairs can serve as a predictive factor for molecular subtypes and prognosis in patients with IDH mutation gliomas

Abstract:Objective To explore the expression level and clinical significance of claudin 7 （CLDN7） in glioblastoma （GBM） tissues. Methods The gene expression data related to GBM and normal brain tissues were obtained from The Cancer Genome Atlas （TCGA） and Genotype-Tissue Expression （GTEx） databases， respectively， and the correlation between CLDN7 and clinical data was analyzed by comparing the differences in CLDN7 gene expression within the two groups with the help of R software. The prognosis of CLDN7 in patients with human GBM was assessed using Kaplan-Meier survival analysis， receiver operating characteristic （ROC） curve analysis， and nomogram. STRING database was used to evaluate the interacting genes and signaling pathways of CLDN7. Results A total of 689 normal samples and 1 157 GBM samples were collected. The expression of CLDN7 in GBM tissue was higher than that in normal brain tissue ［1.029 （0.642，1.546）］ vs. ［0.475 （0.275， 0.740）］， and the difference was statistically significant （Z=-20.004， P＜ 0.001）. The expression level of CLDN7 in patients aged ＞ 60 years， with high WHO pathological grade and 1p/19q non co-deletion was higher than that in patients aged ≤ 60 years， with low WHO pathological grade and 1p/19q co-deletion， and the difference was statistically significant （Z=-20.683，154.210，-2.699， all P ＜ 0.001）. Survival analysis showed that CLDN7 high expression group had a shorter survival period compared to the low expression group， and the difference was statistically significant （P ＜ 0.001）. ROC curve showed that the area under the curve for diagnosing glioblastoma patients with CLDN7 was 0.776. Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis revealed that proteins associated with CLDN7 were mainly involved in signaling pathways such as tight junctions， adhesion links， cell adhesion molecules， and leukocyte transendothelial migration. Conclusions CLDN7 is highly expressed in GBM tissues and may be an indicator of diagnosis of GBM and poor prognosis.

Abstract:Objective To explore the expression characteristics of laminin subunit alpha-2 （LAMA2） in gliomas and the biological processes it may be involved in， so as to tap its clinical significance. Methods Clinical information and RNAseq data of glioma patients in the Chinese Glioma Genome Atlas （CGGA） RNAseq database were extracted. Cases with missing data information were excluded and then standardized， and clinical and sequencing data were matched to extract the expression characteristics of LAMA2. The glioma data of validation group was selected from The Cancer Genome Atlas （TCGA） mRNA sequencing database， the REMBRANDT microarry database， and the GSE16011 microarry database. KaplanMeier survival curves， Cox univariate and multivariate regression analyses were used to evaluate the value of LAMA2 in the overall survival and prognosis of glioma patients. Gene enrichment analysis was performed in two datasets， CGGA and TCGA， and intersections were taken to obtain the functions of LAMA2-related genes. Results Between different grades of gliomas in CGGA325， TCGA and REMBRANDT microarry databases， the expression of LAMA2 was the lowest in grade Ⅱ gliomas and the highest in grade Ⅳ gliomas，and the differences were all statistically significant （all P ＜ 0.05）. In the subtype analysis data of brain gliomas， the expression level of LAMA2 in highly malignant classical and mesenchymal glioma groups was higher than that of less malignant preneuronal and neuronal types， and the differences were all statistically significant （all P ＜ 0.01）. In CGGA325， CGGA693， GSE16011 and TCGA databases， the expression level of LAMA2 in IDH wild-type gliomas was higher than that in IDH mutant gliomas， and the difference was statistically significant （P ＜ 0.01）. Kaplan-Meier survival analysis in both full-grade gliomas and low-grade gliomas in the CGGA325 database showed that the overall survival of patients in high-expression group of the LAMA2 gene was worse than that of low-expression group， and the difference was statistically significant （all P ＜ 0.05）. Multivariate Cox regression analysis showed that age， pathological grade， 1p19q co-deletion， and LAMA2 expression were independent influencing factors of survival in patients with primary glioma， and the differences were all statistically significant （all P ＜ 0.05）. DEG enrichment analysis showed that LAMA2 was associated with biological processes such as extracellular matrix organization， external encapsulated structural organization， extracellular structural organization， collagen fiber organization， vascular development， vascular morphogenesis， and angiogenesis in glioma cells. Conclusions The expression of LAMA2 is positively correlated with the malignancy degree of gliomas， which can be used as a prognostic indicator and potential therapeutic target for patients with primary gliomas.

Abstract:DNA in the human body is constantly damaged by endogenous or exogenous stimuli， such as base pairing errors， abnormal modifications， and even single stranded and double stranded DNA breaks. Most of DNA damages can be compensated or repaired by human cells through various DNA damage repair methods. However， some DNA damage exceeds the compensatory and repair capacity of human cells， which will lead to abnormal life activities of human cells， resulting in various diseases and cancerous tumor cells. Gliomas are the most common primary malignant brain tumors in adults. A full understanding of the forms of DNA damage and a full appreciation of the DNA damage repair pathways is very helpful in adequately preventing as well as treating human gliomas. This review describes the research progress， treatment resistance， and potential new directions for the treatment of glioma in terms of different DNA damage repair pathways， in order to provide a reference for the treatment of glioma.

Abstract:Objective To explore the clinical efficacy of Xuesaitong combined with Argatroban in acute cerebral infarction. Methods From March 2020 to December 2021， 124 patients with acute cerebral infarction admitted to the Sixth People's Hospital of Hengshui were selected for subjects. Randomized numerical method was used to divide the patients into combined group （62 cases） and control group （62 cases）. Control group was given conventional treatment and Argatroban， and combined group was treated with Xuesaitong in addition to control group. National Institute of Health Stroke Scale （NIHSS） scores， cerebral circulation dynamics indices， soluble tumor necrosis factor-like weak inducer of apoptosis （sTWEAK） levels， overall efficiency， and adverse effect were compared between the two groups of patients before treatment and after 14 days of treatment. Results After 14 days of treatment， the overall efficiency of 90.32% （56/62） in combined group was higher than the overall efficiency of 70.97% （44/62） in control group， and the difference was statistically significant （χ2 =7.440， P＜ 0.05）. There was no statistically significant difference in NIHSS scores， minimum blood flow velocity （Vmin）， minimum blood flow （Qmin）， cerebrovascular resistance （R）， and sTWEAK levels between the two groups before treatment （all P＞ 0.05）. After treatment， NIHSS scores ［（4.21±1.02） vs. （6.98±1.21）］， R ［（1 802.50）±188.64） vs. （1 925.41±199.86） Pa·s/ml］， and sTWEAK levels ［（78.21±10.42） vs. （125.98±13.25）］ in combined group were lower than those in control group， and the levels of Vmin ［（10.51±1.73） vs. （9.25±1.64） cm/s］， and levels of Qmin ［（4.75±0.98） vs （4.26±0.95） ml/s］ were higher than those of control group， and the difference between the two groups before and after treatment was also statistically significant （all P＜ 0.05）. The difference in the total incidence of adverse reactions between the two groups was not statistically significant （P＞ 0.05）. Conclusions The efficacy of Xuesaitong combined with Argatroban for acute cerebral infarction is good， which can improve the patients' cerebral blood circulation status as well as the recovery of neurological function.

Abstract:Objective To explore the current status of violent aggressive behavior among Alzheimer's disease （AD） patients with behavioral and psychological symptoms of dementia （BPSD）， and analyze its related factors. Methods The general data of 126 patients who met the diagnostic criteria for AD and BPSD during their first-time hospitalization at the Chongqing Changshou District Mental Health Hospital from March 2023 to March 2024 were retrospectively analyzed. Patients' aggressive behavior， neuropsychiatric symptoms， and degree of dementia were evaluated using the Modified Overt Aggression Scale （MOAS）， Neuropsychiatric Inventory-Questionnaire （NPI-Q）， and Hasegama's Dementia Scale （HDS）. Patients were divided into violent aggressive group （MOAS weighted total score≥4， n=72） and non-violent aggressive behavior group （MOAS weighted total score＜4，n=54） based on MOAS weighted total score， and the differences in general data， clinical data， NPI-Q score， and HDS score between the two groups were compared. Binary Logistic regression was used to analyze the risk factors of violent aggressive behavior. Results Univariate analysis showed that there were statistically significant differences in gender， disease duration， smoking history， history of violent behavior， and NPI-Q score between violent aggressive group and non-violent aggressive behavior group （all P ＜ 0.05）. Binary Logistic regression analysis showed that gender ［OR=0.281， 95%CI：0.083-0.945， P=0.040］， disease duration ［OR=0.490， 95%CI：0.351-0.683，P ＜ 0.001］， history of violent behavior ［OR=15.280， 95%CI：3.029-77.081，P=0.001］， and total NPI-Q score ［OR=1.138， 95%CI：1.034-1.253， P=0.008］ were influencing factors of violent aggressive behavior in AD patients with BPSD， and the difference was statistically significant. Conclusions The incidence of violent aggressive behavior is high in first-time hospitalized AD patients with BPSD， and male gender， short disease duration， history of violent behavior， and high NPI-Q score are risk factors.

Abstract:In view of the increasing severity of psychosomatic problems， it is urgent to train high-quality psychiatry professionals. Virtual standardized patient （VSP）， computer programs that simulate real clinical diagnostic and therapeutic processes， have been used with remarkable success as a new method of medical education and training. This paper sorts out the application of VSP in the teaching of mental disorder diagnosis， empathic communication training， psychopharmacology teaching， and motivational interviewing teaching， aiming to provide ideas and reference for exploring new psychiatry teaching methods.