Nucleotide metabolism (NM) is a fundamental process that enables the rapid growth of tumors. Glioblastoma (GBM) primarily relies on NM for its invasion, leading to severe clinical outcomes. This study focuses on NM to identify potential biomarkers associated with GBM. Publicly available databases were used as the primary data source for this study, excluding biological tissue samples. We identified and evaluated key genes involved in NM, followed by developing and validating a prognostic model. Patients were classified into high- and low-risk groups based on this model, and the two groups were compared with respect to cellular immunity and mutation profiles. The biomarkers were confirmed using real-time reverse-transcriptase polymerase chain reaction. Our study identified UPP1, CDA, NUDT1, and ADSL as significant biomarkers associated with prognosis, all of which were upregulated in patients with GBM. The risk score and clinical factors such as age, sex, GBM stage, MGMT promoter status, and IDH mutation status were found to be independent prognostic factors. Patients with glioblastoma showed a higher overall mutation burden. Using bioinformatics, this study identifies key factors associated with NM in GBM that may influence patient prognosis. This study enhances our understanding of GBM, provides valuable insights for further research, and serves as a reference for evaluating patient outcomes.

Abstract Background: Glioblastoma (GBM) is one of the deadliest of all cancers. And nucleotide metabolism (NM) is the most critical link in malignant tumor cell replication. Therefore, we mined NM-related biomarkers to provide new direction for GBM treatment. Methods: In TCGA-GBM, differences of gene expression between tumor and normal samples were compared to obtain DEGs. And differentially expressed NM-related genes (DE-NMRGs) were screened by intersecting DEGs and NMRGs. Then, biomarkers were screened by Cox regression analysis and proportional hazards (PH) assumption to construct the prognostic model, and the prognostic model was validated by plotting ROC, survival analysis and PCA. Next, to assess the ability of the prognostic model to serve as independent prognostic factor, independent prognostic analyses were performed across numerous clinical characteristics. Finally, the regulatory mechanism of GBM by biomarkers was further explored by single-gene GSEA, immune-related analysis, gene mutation analysis and protein expression validation. Results: The NUDT1, CDA, UPP1 and ADSL were treated as the biomarkers to construct prognostic model, which indicated that the above biomarkers had good prognostic impact on GBM. The IDH mutation status, MGMT promoter status and riskScore were screened as independent prognostic factors. In TCGA-GBM samples, the expression of four biomarkers was significantly higher in GBM. Immune-related analysis showed that the cell abundance of activated memory CD4+ T cell, activated NK cell, M1 macrophage and neutrophil were significantly different between high- /low-risk groups. Tumor mutation load analysis revealed that the overall tumor mutation load was higher in the high-risk group. Conclusion: The four biomarkers were obtained by bioinformatic analysis to construct new prognostic assessment model, providing theoretical reference value to guide the treatment of GBM.

目的 测定动脉瘤性蛛网膜下腔出血(aSAH)后脑血管痉挛(CV)患者与脑血管未痉挛患者脑脊液中miRNA-3177-3p的表达情况,探讨其与CV的发病关系及临床意义.方法 将29例aSAH患者分成脑血管痉挛组(CV组)与脑血管未痉挛组(non-CV组).比较两组患者的一般临床资料;通过生物信息数据分析确定miRNA-3177-3p作为研究对象,测定两组患者脑脊液中miRNA-3177-3p实际表达情况并比较差异;预测miRNA-3177-3p下游靶基因ATP1B3,构建ATP1B3质粒,双萤光素酶报告实验验证miRNA-3177-3p与ATP1B3靶向关系;最后,ELISA法测定两组患者脑脊液中ATP1B3转录产物ATP1β3含量并比较差异.结果 CV组患者Hunt评级高于non-CV组(P＜0.05);CV组脑脊液中miRNA-3177-3p表达丰度为(0.873±0.044),与non-CV组(0.908±0.034)比较,差异有统计学意义(t=2.157,P=0.040);双萤光素酶报告实验结果显示,与miRNA-3177-3p作用后,ATP1B3-3'UTR区相较对照组活性降低15％(P＜0.05);将ATP1B3-3'UTR区进行突变,ATP1B3-3'UTR区相较突变前活性上升14％(P＜0.05);ELISA 法证实表达产物 ATP1β3 在 CV 组脑脊液中(1.776±0.013)ng/mL 高于 non-CV 组(1.722±0.016)ng/mL(t=7.778,P=0.000).结论 CV患者脑脊液中miRNA-3177-3p表达下调,ATP1B3高表达可能参与了 CV的发病过程,该机制可能在预测与治疗CV上具有一定临床意义.

BackgroundGeometrical factors associated with the surrounding vasculature can affect the risk of aneurysm formation. The aim of this study was to determine the association between carotid siphon curvature and the formation and development of paraclinoid aneurysms of the internal carotid artery.MethodsDigital subtraction angiography (DSA) data from 42 patients with paraclinoid aneurysms (31 with non-aneurysmal contralateral sides) and 42 age- and gender-matched healthy controls were analyzed, retrospectively. Morphological characteristics of the carotid siphon [the posterior angle (α), anterior angle (β), and Clinoid@Ophthalmic angle (γ)] were explored via three-dimensional rotational angiography (3D RA) multiplanar reconstruction. The association between carotid siphon morphology and the formation of paraclinoid aneurysms was assessed through univariate analysis. After this, logistic regression analysis was performed to identify independent risk factors for aneurysms.ResultsSignificantly smaller α, β, and γ angles were reported in the aneurysmal carotid siphon group when compared with the non-aneurysmal contralateral healthy controls. The β angle was best for discriminating between aneurysmal and non-aneurysmal carotid siphons, with an optimal threshold of 18.25°. By adjusting for hypertension, smoking habit, hyperlipidemia, and diabetes mellitus, logistic regression analysis demonstrated an independent association between the carotid siphons angles α [odds ratio (OR) 0.953; P < 0.05], β (OR 0.690; P < 0.001), and γ (OR 0.958; P < 0.01) with the risk of paraclinoid aneurysms.ConclusionsThe present findings provide evidence for the importance of morphological carotid siphon variations and the likelihood of paraclinoid aneurysms. These practical morphological parameters specific to paraclinoid aneurysms are easy to assess and may aid in risk assessment in these patients.

This work aims to evaluate the changes in cerebrospinal fluid (CSF) hydrodynamics in patients diagnosed with communicating hydrocephalus. Besides, we establish the relationship between CSF flow dynamic parameters on the midbrain aqueduct and intracranial pressure (ICP). CSF hydrodynamics analysis was performed using Phase-Contrast Magnetic Resonance Imaging (PC-MRI) techniques on the midbrain aqueduct of 41 patients diagnosed with communicating hydrocephalus and 22 healthy volunteers. The correlation between CSF average flow in the midbrain aqueduct and intracranial pressure measured by Lumbar Puncture (LP) was assessed in patients with hydrocephalus. Pearson correlation coefficient was used to establish the correction between the average CSF flow of midbrain aqueduct and ICP. CSF dynamic parameters of the midbrain aqueduct in hydrocephalus patients, including peak positive velocity (7.348 cm/s), average velocity (0.623 cm/s), average flow (50.799 mm3/s), and regions of interest (ROI) area (9.978 mm2) were significantly higher than in the healthy controls (p < 0.05). This was after adjusting the age, gender, heart rate, systolic blood pressure, diastolic blood pressure, and body mass index. However, only the peak negative velocity of the midbrain aqueduct did not significantly differ between the groups (p = 0.209). A positive correlation was noted between the average flow (AF) of the midbrain aqueducts and ICP in hydrocephalus patients (y (AF) = 0.386× (ICP)-33.738, r = 0.787, p < 0.05). Reference data of CSF flow dynamic parameters was obtained through the PC-MRI in middle-aged healthy volunteers and communicating hydrocephalus patients. Although the sample size was constrained, this study has significant contributions. For instance, a significant correlation was noted between the average CSF flow of the aqueduct and ICP. This therefore provides a reference for clinicians to monitor ICP in patients with hydrocephalus.

A 61-year-old patient was suspected of having meningioma, and surgery was subsequently performed on the patient. It was found that the diseased tissue was closely adhered to the normal brain tissue, and extracted to determine the pathological type. Brain biopsy suggested a diagnosis of tuberculous meningitis. The patient subsequently received regular anti-tuberculosis treatment, ultimately, the myodynamia of the patient’s left limbs gradually improved, and her mental symptoms also improved. When a patient’s history, clinical manifestations, neuroimaging and other physiological changes indicate a diagnosis of intracranial infection, there is no doubt that cerebrospinal fluid examination must be performed first, and an unnecessary craniotomy should be avoided if possible. Luwei Jiang1#; Shilin Liu2#; Tao Jiang1*; Chuanbo Weng1; Mengru Gao3; Chengyu Xia4 1Department of Neurosurgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei. 2Department of Neurosurgery, The Second Affiliated Hospital of Anhui Medical University, Hefei. 3Department of Pathology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei. 4Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, PR China.

Objective To explore the efficacy of vagus nerve stimulation (VNS) for the treatment of drug resistant epilepsy.Methods The clinical data of 110 patients with drug resistant epilepsy who underwent VNS at Department of Neurosurgery,Provincial Hospital Affiliated to Anhui Medical University (the First Affiliated Hospital of University of Science and Technology of China) from February 2014 to March 2018 were analyzed retrospectively.The frequency and severity of seizures were followed up by outpatient review,and the efficacy was analyzed according to the McHugh seizure outcome classifications.Results The results of McHugh grade of 110 patients were as follows:grade ⅠA in 10 cases,grade ⅠB in 6,grade ⅡA in 25,grade ⅡB in 7,grade ⅢA in 30,grade ⅢB in 8,grade Ⅳ in 1 and grade Ⅴ in 20,and 3 patients were lost to follow-up.There was significant difference in seizure frequency between preoperative and postoperative conditions (P ＜0.001).None of the factors including the patient's age,sex,type of seizure and course of disease would be associated with the difference above (all P ＞ 0.05).In terms of seizure types,there were significant difference in the distribution of the McHugh classifications between patients with seizures of unclassified onset,focal onset and generalized onset (all P ＜0.05).The frequency of seizures decreased gradually with prolonged VNS stimulation time(P ＜ 0.05).Conclusions VNS could significantly reduce the frequency of seizure.VNS has a better effect on seizures with focal onset and generalized onset,while it has a poor effect on seizure types that cannot be classified.With the increase of stimulation time,the therapeutic effect of VNS is graduallv improved.However,the age,sex or duration of disease is not related to the effect of VNS.

BACKGROUND AND PURPOSE:Epilepsy is one of the most common diseases of the nervous system. Approximately one-third of epilepsy cases are drug-resistant, among which generalized-onset seizures are very common. The present study aimed to analyze abnormalities of the thalamocortical fiber pathways in each hemisphere of the brains of patients with drug-resistant generalized epilepsy.MATERIALS AND METHODS:The thalamocortical structural pathways were identified by diffusion tensor imaging (DTI) in 15 patients with drug-resistant generalized epilepsy and 16 gender/age-matched controls. The thalami of both groups were parcellated into subregions according to the local thalamocortical connectivity pattern. DTI measures of thalamocortical connections were compared between the two groups.RESULTS:Probabilistic tractography analyses showed that fractional anisotropy of thalamocortical pathways in patients with epilepsy decreased significantly, and the radial diffusivity of the left thalamus pathways with homolateral motor and parietal-occipital cortical regions in the drug-resistant epilepsy group increased significantly. In addition to the right thalamus pathway and prefrontal cortical region, fractional anisotropy of all other pathways was inversely correlated with disease duration.CONCLUSION:The results provide evidence indicating widespread bilateral abnormalities in the thalamocortical pathways in epilepsy patients and imply that the degree of abnormality in the pathway increases with the disease duration.

Objective To explore the changes of the structure connection of the default mode network (DMN) in brains of patients with refractory epilepsy using DTI , and discuss their significance.Methods DTI and T1 data of 13 patients with refractory epilepsy admitted from outpatient department of Affiliated Provincial Hospital of Anhui Medical University from December 2017 to April 2018 (epilepsy group) and 14 healthy people recruited at the same time ( healthy control group ) were obtained.Probabilistic fiber tracing technique was used to obtain the fractional anisotropy (FA) values and radial diffusivity (RD) values of the DMN brain-fiber bundles, and the DMN structure network was constructed.The structural connection differences of DMN were compared between epilepsy group and healthy control group.Results Compared with healthy control group , FA values of DMN fiber bundles were significantly decreased, and RD values were significantly increased in epilepsy group (all P＜0.05).Conclusions The DMN structural network of patients with refractory epilepsy has a marked decline in nerve fiber integration and connectivity, and their myelin is damaged.This may be an important cause of dysfunction in DMN function in patients, and ultimately in environmental monitoring , memory extraction, social cognition, self-control and other ability obstacles.

Objective To investigate changes in the betweenness in brain network and the functional connectivity between brain regions with abnormal betweenness among patients with refractory epilepsy based on graph theory.Methods Resting-state functional magnetic resonance imaging (RS-fMRI) was performed in patients with refractory epilepsy and healthy controls.The acquired RS-fMRI data were preprocessed with the Network Analysis module (Gretna) to calculate the betweenness value of each brain region.Statistical analysis was performed to detect the brain regions with differential betweenness values.The REST software was used to calculate the functional connectivity value between each pair of brain regions (regions of interest).Statistical analysis was performed to detect the differential functional connectivity.Results In the patients with refractory epilepsy,the betweenness value increased in the right triangular part of the inferior frontal gyrus and the right olfactory cortex and decreased in the right dorsolateral superior frontal gyrus,the left orbital part of the superior frontal gyrus,the left anterior cingulate gyms,the right superior temporal gyrus,and the right inferior temporal gyrus,as compared with the healthy controls.The functional connectivity between the triangular part of the inferior frontal gyrus and the superior temporal gyrus was lower in the patients with refractory epilepsy than in the healthy controls.Conclusions There are changes in the betweenness in brain network and the functional connectivity between brain regions with abnormal betweenness among patients with refractory epilepsy,which affects the information communication between brain regions and may cause cognitive impairment in epilepsy patients.

Objective Transient brain function inhibition is a common symptom after mild brain injury,but some patients show persistent post-concussional syndrome (PCS).The aims of this study are to assess functional and causal connectivity of attention and default mode network using resting-state functional MR imaging (fMRI) to investigate the abnormal connectivity and its significance in PCS patients.Methods Resting-state fMRI data were collected from 23 PCS patients with attention disorders,admitted to our hospital from November 2015 to October 2016 and 21 age-,gender,and education-matched healthy controls recruited at the same period.The fMRI data were analyzed by group independent component analysis (ICA) toolbox to attention networks and default mode network (DMN).The components of the selected networks were compared in PCS and healthy controls to explore the changes of functional connectivity (FC).Granger causality analysis (GCA) was performed by taking the above significant brain areas as regions of interest (ROIs) to calculate bivariate coefficient of each pair of ROIs.Comparisons were performed to find the significant different causal connectivity of the two groups.Results In attention networks,the FC value of left frontal eye field (FEF),bilateral intraparietal sulcus (IPS),bilateral ventral prefrontal cortex (vPFC) and bilateral temporo-parietal junction (TPJ) was decreased.In DMN,the FC value of bilateral medial prefrontal cortex (mPFC) was reduced and bilateral precuneus (PCUN) was enhanced.Correlating GCA value,it was increased significantly from left FEF to left PCUN and IPS,while it was reduced from left PCUN and IPS to left FEF;and it was decreased from left IPS to left vPFC and increased from left TPJ to left PCUN.Conclusion The attention networks are restrained in resting state,which may influence the attention function in PCS patients;and the causal connection is altered in the above ROIs,and these changes may be related to inhibition of activation of default network to compensate for the loss of attention function by antagonistic effects in PCS patients.

Purpose: Epilepsy is considered a disorder of neural networks. Patients diagnosed with refractory epilepsy frequently experience attention impairments. Seizure activity in epilepsy may disturb brain networks and damage the brain function of attention. The aims of this study were to assess functional and causal connectivities of the attention networks and default mode network using resting-state functional magnetic resonance imaging (fMRI). Method: Resting-state fMRI data were gathered from 19 patients with refractory epilepsy (mixed localization and aetiologies) and 21 healthy people. The fMRI data were analyzed by group independent component analysis (ICA) fMRI toolbox to extract dorsal attention network (DAN), ventral attention network (VAN), and default mode network (DMN). The components of the selected networks were compared between patients and healthy controls to explore the change in functional connectivity (K). Granger causality analysis was performed by taking the aforementioned significant brain areas as regions of interest (ROls) to calculate autoregression coeffidents of each pair of RON. Comparisons were done to find the significantly different causal connectivity when FC was changed between patients and healthy controls. Results: In DAN, the FC values of the bilateral frontal eye field (FEF) and left intraparietal sulcus (IPS) were decreased. In VAN, the FC values of the double-side ventral prefrontal cortex (vPFC) and the temporoparietal junction (TPJ) were reduced. As for DMN, the FC values of the bilateral medial prefrontal cortices (mPFC) were decreased whereas those for the bilateral precuneus (PCUN) were increased. Granger causal connectivity values were correlated: causal influence was decreased significantly from the left IPS (in DAN) to the double side of the vPFC but remained the same for the right FEF (in DAN) to the right TPJ. The value was decreased from the left PCUN (in DMN) to the right TPJ and FEF, and the causal flow from the right PCUN to the right TPJ and bilateral vPFC was also significantly inhibited (p <0.05). Conclusion: Frequent seizures in patients with refractory epilepsy may damage the cortex and disturb DAN, VAN, and DMN, leading to functional and causal connectivity alteration. In addition, epileptic activity may disrupt network interactions and further influence information communication. (C) 2018 Elsevier Inc. All rights reserved.