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.
目的:调查分析医护在线医学教育现状,为医学继续教育模式探讨对策建议.方法:采用定性定量结合的问卷调查法随机对医护进行问卷调查.问卷主要由三部分14个问题组成,采用单选、多选及梯度评价等多种方式.结果:137名医护完成了有效调查问卷;疫情导致在线教育所占比例较传统线下教育明显增加(P<0.01);最常选用的直播软件平台主要是zoom(59.12%)、腾讯会议(15.33%)、skype(7.30%)等;在线上课程评价中,对教师质量和教学内容的满意度比较高,参与度表现的最差.结论:COVID-19的流行导致在线教育所占比例明显提升,弥补了线下教育的缺失,但在线教学存在不足.因此,在线医学继续教育需要进一步改进.
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.
A 45-year-old man was admitted with severe headache and left-sided weakness, which worsened over 1 week. Brain imaging revealed a small lesion close to the sagittal sinus in the right frontal lobe with severe perilesional edema and showed enhancement on both CT and MRI obtained with contrast. Serological findings were positive for toluidine red unheated serum test (TRUST) positivity and Treponema pallidum particle agglutination assay. The patient was first suspected of having a malignant brain tumor and subsequently received emergency craniotomy. Brain biopsy suggested a diagnosis of syphilitic cerebral gumma; meanwhile the postoperative CSF TRUST titer was positive, and the patient's improvement with high-dose intravenous aqueous crystalline penicillin further supported this etiology. Finally, the lesion on the right frontal lobe had disappeared during the follow-up imaging examination and the myodynamia of the left limbs gradually improved. The authors recommend that diagnostic penicillin treatment should be first implemented. When a patient's history, clinical manifestations, syphilis serology, CSF examination, and other physiological changes indicate a diagnosis of syphilitic cerebral gumma, there is no doubt that surgery should be performed in patients with acute intracranial hypertension, but unnecessary craniotomy should be avoided as far as possible.
OBJECTIVETo explore the functions of temporal parietal junction (TPJ) as parts of attention networks in the pathogenesis of online game addiction using resting-state functional magnetic resonance imaging (fMRI).METHODSA total of 17 online game addicts (OGA) were recruited as OGA group and 17 healthy controls during the same period were recruited as CON group. The neuropsychological tests were performed for all of them to compare the inter-group differences in the results of Internet Addiction Test (IAT) and attention functions. All fMRI data were preprocessed after resting-state fMRI scanning. Then left and right TPJ were selected as regions of interest (ROIs) to calculate the linear correlation between TPJ and entire brain to compare the inter-group differences.RESULTSObvious differences existed between OGA group (71 ± 5 scores) and CON group (19 ± 7 scores) in the IAT results and attention function (P < 0.05). Compared with the controls, right TPJ in online game addicts showed decreased functional connectivity with bilateral ventromedial prefrontal cortex (VMPFC), bilateral hippocampal gyrus and bilateral amygdaloid nucleus, but increased functional connectivity with right cuneus.However, left TPJ demonstrated decreased functional connectivity with bilateral superior frontal gyrus and bilateral middle frontal gyrus, but increased functional connectivity with bilateral cuneus (P < 0.05).CONCLUSIONAltered functional connectivity of TPJ reflected its dysfunction in online game addicts.It suggests that TPJ is an important component of attention networks participating in the generation of online game addiction.
Online game addiction (OGA) has attracted greater attention as a serious public mental health issue. However, there are only a few brain magnetic resonance imaging studies on brain structure about OGA. In the current study, we used voxel-based morphometry (VBM) analysis and tract-based spatial statistics (TBSS) to investigate the microstructural changes in OGA and assessed the relationship between these morphology changes and the Young's Internet Addiction Scale (YIAS) scores within the OGA group. Compared with healthy subjects, OGA individuals showed significant gray matter atrophy in the right orbitofrontal cortex, bilateral insula, and right supplementary motor area. According to TBSS analysis, OGA subjects had significantly reduced FA in the right genu of corpus callosum, bilateral frontal lobe white matter, and right external capsule. Gray matter volumes (GMV) of the right orbitofrontal cortex, bilateral insula and FA values of the right external capsule were significantly positively correlated with the YIAS scores in the OGA subjects. Our findings suggested that microstructure abnormalities of gray and white matter were present in OGA subjects. This finding may provide more insights into the understanding of the underlying neural mechanisms of OGA.
随着新型毒品的泛滥,甲基苯丙胺滥用及成瘾已成为严重的公共卫生问题和社会问题。既往对于药物成瘾神经机制的研究主要集中于鸦片、吗啡、海洛因等传统毒品,而甲基苯丙胺等新型毒品的研究则相对缺乏。本文回顾近年来甲基苯丙胺成瘾的研究进展,从神经生物学和功能性神经影像学角度对甲基苯丙胺成瘾的神经机制进行了综述。
Objective To analyze the brain areas having functional connectivity with nucleus accumbens in internet game addicts with resting- state functional magnetic resonance imaging (fMRI),and to find out the role of nucleus accumbens dysfunction in the pathogenesis of internet game addiction.Methods Seventeen participants with internet game addiction(IGA),and seventeen healthy controls took part in this study.First,all subjects took 60 minutes for playing their favorite online games and then stopped immediately to assess degree of wishing to play of online games based on psychological measurement; MR imaging was performed on a Philips Intera 3.0T MR imaging scanner,after that,the left and right nucleus accumbens were selected as regions of interest (ROIs) separately,and the linear correlation between the nucleus accumbens and the entire brain was calculated to find out the functional connectivity of the nucleus accunbens during the resting state ; Finally,a two - sample t test was performed to explore the functional connectivity difference between the internet game addicts and controls.Correlation analysis was performed to assess the relationship between the voxels value of the brain regions and degree of wishing to play online games within the IGA gourp.Results Compared with the controls,the score of the degree of wishing to play online games were higher in the internet game addicts ( P < 0.05 ). During the resting state,the functional connectivity between the nucleus accumbens and the anterior cingulate cortex,the midbrain,the hippocampal gyrus in the internet game addiction group were increased,the functional connectivity between the nucleus accumbens and the prefrontal cortex,the temporal lobe,the occipital lobe were decreased(P < 0.05 ).The voxels value of the prefrontal cortex,the anterior cingulate cortex,the midbrain and the hippocampal gyrus in the game addiction group showed a positive correlation with the degree of wishing to play online games ( r =0.70,0.76,0.65,0.79,P < 0.05 ). Conclusion The nucleus accumbens dysfunction indicated that the nucleus accumbens was an important component of.reward system in the brainof internet game addicts and may be involved in the forming and maintaining of the intemet game addiction.
Objective To explore the changes of functional connectivity of anterior cingulate cortex (ACC) in online game addicts during the resting state,and to analyze the function of ACC in the pathogenesis of online game addiction from a perspective of resting-state functional connectivity.Methods Seventeen online game addicts treated in our hospital from March 2011 to October 2011 were recruited as addiction group and 17 healthy controls at the same period were recruited as HC group.The baseline characteristics of all 34 subjects were investigated and compared between the addiction group and the HC group.All fMRI data were preprocessed after a resting-state fMRI scan,and then,the left and right anterior cingulate cortexes were selected as regions of interest (ROIs) to calculate the linear correlation between the ACC and the entire brain to compare the differences between the online game addicts and normal controls.Results Obvious differences between the addiction group and HC group were noted in hours and days of online game using and degree of thirst to play online games (P<0.05);within the functional connectivity of ACC during the resting state,in contrast to the controls,the online game addicts showed increased connectivity with posterior cingulate,medium cingulate,midbrain,nucleus accumbens and supplementary motor area,but reduced connectivity with prefrontal cortex,temporal lobe and occipital lobe (P<0.05).Conclusion Altered functional connectivity of the ACC reflects the dysfunction in ACC of online game addicts,which may be linked to the forming and maintaining of the online game addiction.
OBJECTIVE:To explore the possible brain mechanism of online game addiction (OGA) in terms of brain morphology through voxel-based morphometric (VBM) analysis.METHODS:Seventeen subjects with OGA and 17 age- and gender-matched healthy controls (HC group) were recruited from Department of Psychology at our hospital during February-December 2011. The internet addiction scale (IAS) was used to measure the degree of OGA tendency. Magnetic resonance imaging (MRI) scans were performed to acquire 3-dimensional T1-weighted images. And FSL 4.1 software was employed to confirm regional gray matter volume changes. For the regions where OGA subjects showed significantly different gray matter volumes from the controls, the gray matter volumes of these areas were extracted, averaged and regressed against the scores of IAS.RESULTS:The OGA group had lower gray matter volume in left orbitofrontal cortex (OFC), left medial prefrontal cortex (mPFC), bilateral insula (INS), left posterior cingulate cortex (PCC) and left supplementary motor area (SMA). Gray matter volumes of left OFC and bilateral INS showed a negative correlation with the scores of IAS (r = -0.65, r = -0.78, P < 0.05).CONCLUSION:Gray matter volume changes are present in online game addicts and they may be correlated with the occurrence and maintenance of OGA.