Abstract:Glioma is the most common primary malignant brain tumor in adults and is difficult to cure with current treatment methods. Isocitrate dehydrogenase（ IDH） mutant gliomas exhibit molecular heterogeneity. The mutated IDH gene product D-2-Hydroxyglutarate（ D-2-HG） promotes DNA hypermethylation and immune suppression thereby driving tumor growth. In recent years， IDH inhibitors such as Ivosidenib and Vorasidenib have demonstrated the ability to reduce D-2-HG levels and induce cellular differentiation in preclinical models and early-phase clinical trials. The Phase Ⅲ INDIGO trial demonstrates that Vorasidenib significantly prolongs progression-free survival in patients with non-amplified grade 2 IDH mutant gliomas， and receives FDA approval in 2024. This paper provides a detailed overview of the progress of IDH inhibitors for gliomas treatment， highlighting their role as a well-tolerated therapeutic option that offers benefits for selected patient populations. Future research combining novel drugs and combination therapies may further expand its therapeutic potential.

Abstract:Objective To explore the expression characteristics and clinical prognostic significance of tyrosine kinase binding protein（ TYROBP） gene in gliomas， providing a theoretical basis for developing targeted therapeutic strategics based on TYROBP. Methods This study conducted multidimensional analysis based on the Chinese Glioma Genome Atlas（ CGGA） and The Cancer Genome Atlas（ TCGA） databases. Firstly， a retrospective study was conducted on transcriptome sequencing data and corresponding clinical data from two independent cohorts in the CGGA database（ Dataset 1 containing 325 samples and Dataset 2 containing 693 samples） and one cohort in the TCGA database（ Dataset 3 containing 697 samples） to systematically investigate the relationship between TYROBP gene expression and patient clinical pathological characteristics. Concurrently， six surgical specimens of primary gliomas pathologically confirmed by the Department of Neurosurgery at Beijing Tiantan Hospital were collected between March and April 2025. Immunohistochemical techniques were employed to detect the expression distribution of the TYROBP in tumor tissues of different pathological types. Further research was conducted on the whole exome sequencing data of 286 glioma patients included in the CGGA database（ Dataset 4）. Based on the median TYROBP expression value（ M=148.56）， the cases were divided into TYROBP low expression group（ expression level ≤148.56， n=116） and TYROBP high expression group（ expression level＞148.56， n=115）， and the copy number variation characteristics and gene mutation spectrums were compared between the two groups. Survival analysis employed the Kaplan-Meier method to evaluate the association between TYROBP expression levels and patient overall survival， with its prognostic value validated through univariate and multivariate Cox proportional hazards models. In terms of mechanism exploration， functional enrichment analysis was performed on Dataset 1 to elucidate the biological processes involving genes co-expressed with TYROBP. The CIBERSORT algorithm was employed to quantitatively analyze the infiltration proportions of 22 immune cells within the tumor microenvironment， investigating the correlation patterns between various immune cell subpopulations and TYROBP expression. Results In Dataset 1， Dataset 2， and Dataset 3， the expression levels of the TYROBP gene increased with higher WHO grades （2-4）， with all differences being statistically significant（ F=38.379， 14.681， 76.724； all P＜0.01）. TYROBP expression levels were statistically higher in wild-type isocitrate dehydrogenase（ IDH） tumors compared to IDH-mutant tumors with 1p/19q deletion［ Dataset 1：（7.19±0.10） vs（. 5.55±0.11）（ F=54.120，P＜0.01）； Dataset 2： （7.54±0.11） vs.（ 6.54±0.10）（ F=25.151，P ＜ 0.01）， Dataset 3：（3.37±0.17） vs（ 3.07±0.17）（ F=171.19， P ＜ 0.01）］. Correlation analysis of clinical pathological characteristics revealed that TYROBP expression was statistically lower in primary tumors， low-grade tumors， and IDH-mutant cases with 1p/19q co-deletion compared to recurrent tumors， high-grade tumors， and non-IDH-mutant cases with 1p/19q co-deletion（ P ＜ 0.01）. The analysis of gene mutations and copy number changes in Dataset 1 showed that the mutation rates of E3 ubiquitin ligase 1 containing HECT and RLD domains（ HERC1）［ 4%（ 5/115）］ and thrombospondin type 1 domain containing protein 7B（ THSD7B）［ 4%（ 5/115）］ in the TYROBP high expression group were higher than those in the low expression group（ both 0%）， and the differences were statistically significant（ both χ2=4.117，both P＜0.05）. In Dataset 1， Dataset 2， and Dataset 3， the overall survival（ OS） of the TYROBP high expression group was shorter than that of the low expression group， with statistically significant differences （all P ＜ 0.05）. Multivariate Cox regression analysis showed that glioblastoma（ GBM）［ HR=2.218， 95%CI （1.438，3.422）， P＜0.001）， 1p/19q co-deletion［ HR=0.279， 95%CI（ 0.163，0.481），P＜0.01］， and TYROBP overexpression［ HR=1.582，95%CI（ 1.155， 2.168），P＜ 0.01］ were independent risk factors of the prognosis of glioma patients， and the differences were statistically significant. Functional enrichment analysis indicated that TYROBP participated in tumor microenvironment remodeling by regulating leukocyte-mediated immune responses and immunomodulatory processes. Correlation analysis revealed that this gene was positively correlated with the degree of M2 macrophage infiltration（ r=0.42， P＜0.001） and negatively correlated with the degree of initial CD4+ T cell infiltration（ r=-0.45，P ＜ 0.001）， with statistically significant differences. The expression of TYROBP was closely related to multiple key genes in leukocyte-mediated immunity. C1QA （r=0.924） and C1QC （r=0.904） were significantly positively correlated with TYROBP expression， and significantly negatively correlated with PIK3CB （r=-0.407） and PIK3R1 （r=-0.405）， with statistically significant differences（ all P ＜ 0.05）. Conclusions This study confirms that the expression pattern of TYROBP exhibits significant tumor type specificity. Its expression levels are not only closely associated with patient prognosis but also play a crucial role in regulating the tumor immune microenvironment. These findings provide a theoretical basis for developing targeted therapeutic strategies based on TYROBP.

Abstract:Objective To explore the expression characteristics， clinical correlations， and potential biological functions of the ATPase Na+/K+ transporting subunit alpha 2（ ATP1A2） gene in glioma， and thoroughly analyze its biological role in the pathological progression of glioma. Methods mRNA sequencing data from the Chinese Glioma Genome Atlas（ CGGA）（ n=325） and The Cancer Genome Atlas（ TCGA）（ n=675） glioma cohorts were retrospectively analyzed to assess ATP1A2 expression levels. Based on the X-tile platform and the surv_ cutpoint function in the R language's survminer package， the cutoff value most significantly associated with survival was selected（ CGGA： 6.446 1， TCGA： 12.660 23）. The group with ATP1A2 expression levels above the most significant cutoff value was classified as the ATP1A2 high-expression group， while the group with levels below the cutoff was classified as the ATP1A2 low-expression group. Kaplan-Meier curve， log-rank test， and Cox proportional hazard model were employed to evaluate the relationship between ATP1A2 expression and overall survival in patients. The functions of genes co-expressed with ATP1A2 were explored through Gene Ontology（ GO） annotation and Kyoto Encyclopedia of Genes and Genomes（ KEGG） pathway enrichment analysis. Results The comparison of clinical and pathological characteristics between CGGA and TCGA cohorts revealed statistically significant differences between the two cohorts in primary WHO grading， isocitrate dehydrogenase（ IDH） mutation status， and 1p/19q co-deletion（ all P ＜ 0.05）. mRNA sequencing data from two cohorts showed statistically significant differences in ATP1A2 expression levels in WHO grade 2 to 4 glioma tissues（ F=28.67， 48.26； both P ＜ 0.01）， with a decreasing trend observed as tumor grade increased. Further analysis revealed that in both the CGGA and TCGA databases， ATP1A2 expression was statistically higher in IDH-mutant gliomas compared to IDH wild-type gliomas（ both P ＜ 0.01）. No statistical differences in ATP1A2 expression were observed across different O6-methylguanine-DNA methyltransferase（ MGMT） promoter methylation states（ all P＞ 0.05）. Analysis of CGGA and GSE131928 single-cell data indicated that ATP1A2 was primarily expressed in tumor cells. Patients with low ATP1A2 expression exhibited significantly short overall survival in both the CGGA and TCGA cohorts， with statistically significant differences（ CGGA： ATP1A2 high-expression group 6.411 years， ATP1A2 low-expression group 1.203 years， χ2=41.05， P＜0.01； TCGA： ATP1A2 high-expression group 4.233 years， ATP1A2 low-expression group 1.467 years， χ2=28.81， P＜0.01）. Univariate［ HR=0.721， 95%CI（ 0.654， 0.794）］ and multivariate Cox［ HR=0.793， 95%CI（ 0.716， 0.879）］ analysis demonstrated that ATP1A2 expression was an independent risk factor for glioma， with statistically significant differences （P ＜ 0.01）. GO enrichment analysis revealed that genes positively correlated with ATP1A2 in the TCGA and CGGA databases were primarily involved in biological processes such as acidic amino acid transport， L-glutamate transmembrane transport， and amino acid transport. KEGG pathway enrichment analysis indicated that genes positively correlated with ATP1A2 in the CGGA database were associated with GABAergic synapses and neuroactive ligand signaling. Genes positively correlated with ATP1A2 in the TCGA database were associated with the metabolism of alanine， aspartate， and glutamate， as well as the reabsorption of bicarbonate in the proximal tubule. Conclusions This study confirms that ATP1A2 is an independent prognostic biomarker for glioma， with its low expression indicating poor patient prognosis. This discovery not only provides a novel molecular tool for assessing the prognosis of gliomas， but also identifies potential targets within associated biological pathways for developing new therapeutic strategies targeting ion metabolism and neurotransmitter homeostasis within the tumor microenvironment.

Abstract:The initiation and progression of brain tumors are jointly regulated by multiple factors. In recent years， skull bone marrow— a crucial immunoregulatory microenvironment— has been increasingly recognized for its key regulatory role in brain tumors. Skull bone marrow not only directly participates in tumor immune evasion processes but also profoundly influences the remodeling of the tumor microenvironment and the efficacy of immunotherapy by regulating the recruitment and function of immune cells. However， the specific mechanisms by which skull bone marrow regulates the immune microenvironment of brain tumors remain largely unexplored. In-depth investigation into the role of skull bone marrow in brain tumors not only aids in understanding the dynamic changes within the tumor immune microenvironment but also provides new theoretical foundations for developing precise and effective immunotherapy strategies. This paper reviews the role of skull bone marrow in the immune microenvironment of brain tumors， focusing on its key functions in tumor immune evasion， immune microenvironment remodeling， and immunotherapy， while also exploring its potential for future clinical translation based on the latest research advances.

Abstract:low-grade developmental and epilepsy-associated brain tumors（ LEAT） are the second most common cause of focal epilepsy in adolescents. These tumors present primarily with epileptic seizures and carry a favorable prognosis. Common types include ganglioglioma（ GG） and dysembryoplastic neuroepithelial tumor （DNT）. The 2021 fifth edition of the WHO Classification of Tumors of the Central Nervous System（ CNS WHO 5th） has introduced molecular typing， which aids in the diagnosis and classification of LEAT. LEAT molecular types include tumors predominantly driven by BRAF V600E mutation， fibroblast growth factor receptor 1（ FGFR1） mutation， and MYB alterations. Surgical treatment is the primary method for this condition. Most patients experience relief from epileptic symptoms after surgery. However， for patients with persistent seizures， longterm use of antiepileptic drugs is recommended. At present， the impact of LEAT molecular typing on treatment and prognosis requires further investigation. This paper provides a review of LEAT based on CNS WHO 5th， aiming to provide reference for the diagnosis and treatment of LEAT

Abstract:The hypothalamus is a vital neuroendocrine center in the human body， playing a crucial regulatory role in the autonomic nervous system and endocrine system. Surgery for tumors in the hypothalamic region remains one of the most challenging neurosurgical procedures to date. Surgical damage to the hypothalamus often leads to hypopituitarism， water-electrolyte imbalances， hypothalamic obesity， thermoregulatory disorder， abnormal sleep rhythms， and emotional disturbances. Autonomic nervous system dysfunction plays a significant role in the pathogenesis of the aforementioned complications. Heart rate variability， urinary catecholamine metabolites， and microneurography are currently the most commonly used methods for assessing autonomic nervous system activity. Currently， evidence indicates that patients with hypothalamic injury exhibit autonomic nervous dysfunction， but there is no consensus on the specific type of dysfunction. Modulation of autonomic nervous system activity holds promise as a novel therapeutic target for patients with hypothalamic injury， and accurate assessment of autonomic nervous function represents a crucial step in developing treatment plans for these patients.

Abstract:Objective To explore the incidence and risk factors of delirium in mechanically ventilated adult patients through meta-analysis， so as to provide a reference for early clinical prevention of delirium. Methods Cross-sectional studies， cohort studies， and case-control studies on the incidence and risk factors of delirium in mechanically ventilated patients were retrieved from The Cochrane Library， PubMed， Embase， Web of Science， China National Knowledge Infrastructure， WanFang Data， VIP and China Biomedical Literature Database. The search period was from database establishment to August 13， 2023. After evaluating the included studies， a meta-analysis of incidence and risk factors was conducted using Stata 17.0. Results A total of 25 studies were included， including 5 936 mechanically ventilated patients. The incidence of delirium in mechanically ventilated patients was 0.42［ 95%CI（ 0.34， 0.50）］. Meta-analysis revealed that risk factors for delirium included advanced age［ OR=1.15， 95%CI（ 1.07， 1.24）］， high Acute Physiology and Chronic Health EvaluationⅡ（ APACHE Ⅱ） scores［ OR=1.40， 95%CI（ 1.24， 1.58）］， prolonged mechanical ventilation ［OR=1.30， 95%CI（ 1.16， 1.45）］， use of sedatives［ OR=1.88， 95%CI（ 1.07， 3.29）］， hypoxemia［ OR=4.09， 95%CI（ 1.77， 9.45）］， prolonged length of ICU stay［ OR=1.18， 95%CI（ 1.04， 1.35）］， sleep deprivation ［OR=12.38， 95%CI（ 4.61， 33.22）］， pain［ OR=2.02， 95%CI（ 1.85， 2.21）］， physical restraints［ OR=2.79， 95%CI（ 1.57， 4.98）］， history of drinking［ OR=2.42， 95%CI（ 1.45， 4.05）］， and history of hypertension ［OR=1.78， 95%CI（ 1.44， 2.20）］. Conclusions The incidence of delirium is relatively high among mechanically ventilated patients. Advanced age， high APACHE II score， prolonged mechanical ventilation， use of sedatives， hypoxemia， prolonged length of ICU stay， sleep deprivation， pain， physical restraints， history of drinking， and hypertension are risk factors for delirium in mechanically ventilated patients. Early prevention， identification， and implementation of effective preventive measures should be based on the patient's condition and risk factors to reduce the incidence of delirium in mechanically ventilated patients.

Abstract:Objective To investigate the interaction effects of hyperactive behaviors in children with autism spectrum disorder（ ASD） and parental self-esteem on parental depressive disorder， along with subgroup differences， so as to provide theoretical support for developing targeted psychological intervention strategies for parents of children with ASD. Methods Parents of all children with ASD who met the inclusion and exclusion criteria and attended outpatient visits at the Fourth People's Hospital of Wuhu from November 2023 to February 2025 were consecutively enrolled. Concurrently， convenience sampling was used to sequentially recruit 273 parents of children with ASD who were diagnosed at the Fourth People's Hospital of Wuhu or had a diagnosis documentation from a Class Ⅲ Grade A psychiatric hospital and voluntarily participated in the study. General Information Questionnaire， Self-Rating Depression Scale（ SDS）， Rosenberg Self-Esteem Scale （RSES）， and Swanson， Nolan and Pelham， Version IV（ SNAP- Ⅳ） were used to assess demographic data， children's hyperactive behaviors， parental depressive symptoms， and self-esteem levels， respectively. The χ2 test was performed using SPSS 26.0. Stratified binary Logistic regression analysis was conducted to examine the independent effects， interaction effects， and subgroup differences between hyperactive behaviors in children with ASD and parental self-esteem on parental depressive symptoms. Results Among 273 parents of children with ASD， 167（61.2%，167/273） exhibited depressive symptoms. Univariate analysis revealed statistically significant differences in the incidence of depressive symptoms among parents of children with ASD across various factors， including parental self-esteem levels， questionnaire respondents， monthly household income， child's school type， educational attainment， and children's hyperactive behavior（ all P ＜ 0.05）. Regression analysis showed that both children's hyperactive behavior and parental low self-esteem increased the risk of parental depressive disorder， and the risk of depressive disorder among mothers of these children was 2.288 times higher than that among fathers， with a statistically significant difference（ P ＜ 0.01）. Subgroup analysis revealed that in the male pediatric subgroup， hyperactive behavior significantly increased the risk of parental depressive disorder by 4.831 times， with a statistically significant difference（ P ＜ 0.01）. Interaction effect analysis showed a statistically significant positive additive interaction effect between children's hyperactive behavior and parental low self-esteem on parental depressive symptoms. The relative excess risk of interaction （RERI）， attributable proportion（ AP）， and synergy index（ S） were 6.751［ 95%CI（ 0.365，27.922）］， 0.561 ［95%CI（ 0.041， 0.830）］， and 2.578［ 95%CI（ 1.039， 7.763）］， respectively. Conclusions Mothers of children with ASD exhibit significant depressive disorder， and hyperactive behaviors in male children further exacerbate parental depressive disorder. Hyperactive behaviors of children and parental self-esteem show a significant additive interaction effect on parental depressive disorder.

Abstract:Objective To explore the relationship between laboratory tests， infarct site， respiratory events， sleep quality， neurological function of obstructive sleep apnea（ OSA） primarily characterized by rapid eye movement（ REM） and clinical prognosis of acute cerebral infarction. Methods This study was a retrospective cohort study. From September 2023 to September 2024， 270 patients with acute cerebral infarction and underwent polysomnography（ PSG） in the Department of Neurology of the Affiliated Hospital of Yangzhou University were selected as study subjects. Patients' general information， blood routine， magnetic resonance imaging（ MRI） Epworth Sleepiness Scale（ ESS）， Pittsburgh Sleep Quality Index（ PSQI）， the National Institutes of Health Stroke Scale（ NIHSS）， Barthel Index（ BI） Rating Scale， Modified Rankin Sca（l mRs）， objective sleep data obtained from PSG， and prognostic indicators obtained from follow-up were collected. Linear regression was applied to analyze the relationship between rapid eye movement apnea hypopnea index（ REM-AHI） and clinical data， and binary Logistic regression was applied to analyze the factors influencing the REM-OSA in patients with acute cerebral infarction. Results A total of 270 patients in the entire acute cerebral infarction cohort received overnight PSG. A total of 229（ 84.8%） patients with acute cerebral infarction were diagnosed with OSA， including 37（ 16.2%） in REM-OSA group and 192（ 83.8%） in NREM-OSA group. Leukocyte and neutrophil counts were higher in REM-OSA group than those in NREM-OSA group， and the differences were statistically significant（ both P＜0.05）. The percentage of patients in REM-OSA group with acute cerebral infarction sites in the basal ganglia was higher than that in NREM-OSA group， and the difference was statistically significant （P＜ 0.05）. The ESS score was lower in EEM-OSA group than that in NREM-OSA group， the PSQI scores for time to sleep and sleep efficiency dimensions were higher in REM-OSA group than those in NREM-OSA group， and the differences were statistically significant（ all P ＜ 0.05）. The N2 duration， number of NREM apneas， NREM-AHI， AHI， oxygen desaturation index（ ODI）， arousal index， and respiratory event-related arousal index in REM-OSA group were lower than those in NREM-OSA group， and the REM-AHI in REM-OSA group was higher than that in NREM-OSA group， which were statistically significant differences（ all P＜0.05）. Binomial Logistic regression showed that mRS scores was an influencing factor of REM-OSA in acute cerebral infarction， and the difference was statistically significant（ P ＜ 0.05）. Linear regression analysis showed that body mass index and leukocytes were the influencing factors of REM-AHI in patients with acute cerebral infarction， and the difference was statistically significant（ both P＜0.05）. Conclusions Compared with NREM-OSA， patients with acute cerebral infarction complicated by REM-OSA exhibit high inflammatory markers， a great tendency for infarction to involve the basal ganglia， prominent respiratory events during REM， and poor sleep quality and neurological functional outcomes.