ObjectTo explore the prediction of the efficacy of bevacizumab (BEV) in treating peritumoral brain edema based on the radiomic features of T1-enhanced and T2-FLAIR MRI in patients with glioblastoma.MethodsA retrospective study was conducted on 321 glioblastoma patients who received bevacizumab treatment at The First Affiliated Hospital of Soochow University and The Second Affiliated Hospital of Soochow University from January 2020 to January 2025. The patients were randomly divided into a training set (n=224) and a validation set (n=97) at a ratio of 7:3. According to the Response Assessment in Neuro-Oncology (RANO) criteria, patients were classified into the remission group and non-remission group based on the reduction rate of peritumoral edema volume. Radiomic features were extracted from the glioma tumor and peritumoral edema regions on pretreatment baseline MRI using 3D-Slicer software. Features with significant intergroup differences were screened by univariate analysis and Lasso regression. Subsequently, three machine learning algorithms, namely logistic regression (LR), support vector machine (SVM), and random forest (RF), were used to construct radiomics prediction models. The efficacy of each model was compared using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC). The clinical practicability of the models was further evaluated by decision curve analysis.ResultsA total of 9 optimal radiomic features were finally screened out to construct the machine learning models. In the training set, the AUC values of the LR, SVM, and RF models were 0.832 (95% confidence interval [CI]: 0.690–0.973), 0.814 (95%CI: 0.730–0.897), and 0.796 (95%CI: 0.707–0.883), respectively. In the validation set, the corresponding AUC values were 0.883 (95%CI: 0.769–0.996), 0.800 (95%CI: 0.713–0.886), and 0.770 (95%CI: 0.604–0.934), respectively. For the LR model, decision curve analysis showed that the net benefit of the model was greater than 0 when the risk threshold ranged from 0.05 to 0.95.ConclusionThe LR, SVM, and RF models constructed based on MRI radiomic features all exhibit excellent predictive performance. Among them, the LR model has high clinical value and practicability with favorable net clinical benefit as confirmed by the clinical decision curve, and can be used to predict the therapeutic efficacy of bevacizumab for peritumoral brain edema in glioblastoma patients.

BACKGROUND:Glioblastoma (GBM) is a highly aggressive brain malignancy driven by glioma stem cells (GSCs). TIGAR (TP53-induced glycolysis and apoptosis regulator) is primarily known as a metabolic regulator that supports cell survival. However, its non-metabolic functions in neuro-oncology remain largely unexplored. This study aims to investigate the structural role of TIGAR in maintaining mitotic spindle integrity and its potential interplay with the ubiquitin-proteasome system in GSCs. METHODS:The clinical relevance of TIGAR expression was evaluated using GEPIA2, TCGA, CGGA, GTEx, and PDX-based analyses. TIGAR function was investigated in human GSC lines (GSC464 and GSC23) using lentiviral shRNA knockdown. Cell cycle progression and spindle morphology were analyzed with flow cytometry and immunofluorescence. Protein-protein interactions and stability were assessed via immunoprecipitation, cycloheximide chase, ubiquitination assays, NAC rescue testing, and Parkin co-depletion rescue assays. In vivo effects of TIGAR depletion were evaluated using GSC-derived orthotopic xenografts in SCID mice and an HRas-driven, p53-deficient primary glioblastoma mouse model. RESULTS:TIGAR expression is significantly upregulated in human GBM, correlating with tumor malignancy, stemness features, and poor patient prognosis. Public transcriptomic analysis showed a positive association between TIGAR expression and a GSC-related stemness signature, and double immunofluorescence staining confirmed co-localization of TIGAR with SOX2 or CD133 in two PDX models. TIGAR ablation in GSCs induced G2/M arrest and severe spindle defects, and these effects were validated in an additional GSC line. Mechanistically, TIGAR localizes to the mitotic spindle and physically interacts with βII-tubulin, protecting it from Parkin-mediated polyubiquitination and subsequent proteasomal degradation. NAC failed to rescue βII-tubulin loss after TIGAR knockdown, whereas Parkin co-depletion restored βII-tubulin levels and partially normalized the G2/M fraction. In vivo, TIGAR knockdown inhibited GSC-driven tumor growth, reduced stemness marker expression, and significantly prolonged animal survival. CONCLUSIONS:The study reveals an essential non-metabolic function of TIGAR in GBM. The TIGAR-Parkin-βII-tubulin axis serves as a critical mechanism for maintaining mitotic stability and protecting the GSC cytoskeletal network. These findings highlight TIGAR as a structural stabilizer during mitosis and a promising therapeutic target for glioblastoma, independent of p53 mutational status.

Confronted with the clinical challenges of glioma treatment, including incomplete resection and therapeutic resistance, we developed an integrative bioprinting strategy. At the core of our approach is a 3D-bioprintable, photosensitive hydrogel loaded with ruthenium-gallic acid (Ru-GA) nanoenzymes. This system is designed to seamlessly combine chemodynamic therapy (CDT) with photothermal therapy (PTT) to achieve precise and synergistic treatment of glioblastoma multiforme (GBM). Ru-GA, synthesized via Ru³⁺-gallic acid coordination, has potent peroxidase-like activity to catalyze reactive oxygen species generation from H₂O₂ in the tumor microenvironment. It also efficiently depletes glutathione to disrupt tumor redox homeostasis, and exhibits excellent near-infrared absorption and photothermal conversion efficiency. Based on GelMA and HAMA, the hydrogel is liquid at 37 °C and has the ability to be injected into tumor tissue, ensuring localized retention and sustained action of Ru-GA at tumor sites. In vitro tests verified Ru-GA kills GL261 glioma cells via CDT, and combining it with PTT further inhibits tumor cell proliferation, migration, and clonogenicity while boosting apoptosis. In 3D bioprinted tumor models, the hydrogel suppresses tumor cell aggregation and viability effectively. In vivo experiments showed intratumoral hydrogel injection plus near-infrared irradiation raises tumor temperature to 55 °C, exerting synergistic PTT/CDT effects to significantly inhibit tumor growth with excellent biosafety. Mechanistically, this therapy activates inflammatory pathways and inhibits metastasis-related signaling, offering a safe, efficient GBM treatment and laying a foundation for clinical translation of nanocatalyst-based photosensitive hydrogels.

Photothermal treatment (PTT) of glioma often requires a large number of animal models to enter the clinical stage, but the individual differences in animal models make the experimental results poor reproducibility. 3D bioprinting in vitro tumors made from hydrogels can provide efficient and accurate research models without sacrificing animals and avoiding species diversity. In this study, bioprintable and injectable TiO-loaded hydrogels were reported, which could be used for studying TiO NSs photothermal treatment of glioma. Results from the MTT kit showed that after photothermal treatment with TiO NSs, the survival rate of tumor cells in the 2D model was reduced to 35 ± 3. Rheological tests showed that the TiO-loaded hydrogels had good printability and injectability. 14 consecutive days of in vitro culture confirmed the feasibility of constructing in vitro tumors using bioinks composed of TiO-loaded hydrogels. In addition, in the photothermal therapy experiment of 3D bioprinting tumor models, the effective killing of tumor cells by TiO NSs confirmed the possibility of combining 3D bioprinted tumor models with photothermal therapy. After injecting TiO-loaded hydrogel in vivo, TiO NSs could effectively kill tumor cells by raising the temperature to 55 °C under near-infrared light irradiation for a short time. Bioprintable and injectable TiO-loaded hydrogel models are good for studying photothermal treatment of glioma, and 3D bioprinting tumor models have promising applications in photothermal therapy research for glioma.

Glioblastoma (GBM) is one of the most treatment-resistant brain malignancies. Dysregulation of Wnt/β-catenin signaling might be implicated in tumorigenesis of GBM. In this study, spatial transcriptomic analysis revealed elevated expression of Wnt target genes within tumor regions compared with peritumoral tissues. Overexpression of porcupine (PORCN), an O-acyltransferase for Wnt secretion, correlated with poor prognosis of GBM patients. Treatment with Wnt-C59, a PORCN inhibitor, inhibited Wnt signaling, hindered GBM cell proliferation and invasion, and inhibited GBM stem cells' self-renewal properties in a dose-dependent manner. Moreover, using β-catenin knockout and knockdown cells, FOXM1 was identified as a downstream transcription target of Wnt/β-catenin signaling. Wnt-C59 inhibited the expression of FOXM1 in GBM cells. Furthermore, Wnt-C59 demonstrated the ability to impede tumor formation and enhance the overall survival of mice bearing GBM in a preclinical model. Notably, the combined treatment of Wnt-C59 with temozolomide further enhanced therapeutic outcomes, leading to a significant extension of overall survival in GBM-bearing mice. Mechanistically, Wnt-C59 significantly down-regulated the expression of oncogenic targets associated with Wnt/β-catenin signaling (FOXM1, cyclin D, and C-Myc) both in vitro and in orthotopic GBM models. Our findings reveal that targeting Wnt/β-catenin signaling via PORCN inhibition, especially in combination with temozolomide, offers a promising therapeutic strategy for treating GBM.

Mesenchymal glioblastoma (GBM) is highly resistant to radio-and chemotherapy and correlates with worse survival outcomes in GBM patients; however, the underlying mechanism determining the mesenchymal phenotype remains largely unclear. Herein, it is revealed that FBXO7, a substrate-recognition component of the SCF complex implicated in the pathogenesis of Parkinson's disease, confers mesenchymal properties and chemoresistance in GBM by controlling Rbfox2-mediated alternative splicing. Specifically, FBXO7 ubiquitinates Rbfox2 Lys249 through K63-linked ubiquitin chains upon arginine dimethylation at Arg341 and Arg441 by PRMT5, leading to Rbfox2 stabilization. FBXO7 controls Rbfox2-mediated splicing of mesenchymal genes, including FoxM1, Mta1, and Postn. FBXO7-induced exon Va inclusion of FoxM1 promotes FoxM1 phosphorylation by MEK1 and nuclear translocation, thereby upregulates CD44, CD9, and ID1 levels, resulting in GBM stem cell self-renewal and mesenchymal transformation. Moreover, FBXO7 is stabilized by temozolomide, and FBXO7 depletion sensitizes tumor xenografts in mice to chemotherapy. The findings demonstrate that the FBXO7-Rbfox2 axis-mediated splicing contributes to mesenchymal transformation and tumorigenesis, and targeting FBXO7 represents a potential strategy for GBM treatment.

Cerebral cavernous malformations (CCMs) are common vascular anomaly diseases in the central nervous system associated with seizures, cerebral microbleeds, or asymptomatic mostly. CCMs can be classified as sporadic or familial, with familial cerebral cavernous malformations (fCCMs) being the autosomal dominant manner with incomplete penetrance. Germline mutations of KRIT1, CCM2, and PDCD10 are associated with the pathogenesis of fCCMs. Till now, little is known about the fCCMs mutation spectrum in the Han Chinese population. In this study, we enrolled a large, aggregated family, 11/26 of the family members were diagnosed with CCMs by pathological or neuroradiological examination, with a high percentage (5/9) of focal spinal cord involvement. Genomic DNA sequencing verified a novel duplication mutation (c.1119dupT, p.L374Sfs*9) in exon 9 of the Krev interaction trapped 1 (KRIT1) gene. The mutation causes a frameshift and is predicted to generate a truncated KRIT1/CCM1 protein of 381 amino acids. All our findings confirm that c.1119dupT mutation of KRIT1 is associated with fCCMs, which enriched the CCM genes’ mutational spectrum in the Chinese population and will be beneficial for deep insight into the pathogenesis of Chinese fCCMs. Additionally, with a retrospective study, we analyzed the molecular genetic features of Chinese fCCMs, most of the Chinese fCCMs variants are in the KRIT1 gene, and all these variants result in the functional deletion or insufficiency of the C-terminal FERM domain of the KRIT1 protein.

目的 探讨重症动脉瘤性蛛网膜下腔出血(SaSAH)患者的预后及影响预后改善的危险因素.方法 回顾性分析2016年1月至2020年12月苏州大学附属第二医院神经外科重症监护病房收治的SaSAH患者的临床资料.评估出院及术后6个月时的改良Rankin量表评分(mRS),并比较其差异.采用单因素分析和多因素logistic回归分析探讨影响SaSAH患者出院后预后改善(术后6个月的mRS较出院时降低≥1分)的危险因素.纳入独立危险因素构建联合预测模型,绘制受试者工作特征(ROC)曲线并计算曲线下面积(AUC),以评估联合预测模型对SaSAH患者出院后6个月预后改善的预测价值.结果 研究共纳入154例患者.术后6个月,53.2％(82/154)的SaSAH患者预后良好(mRS≤3分),51.9％(80/154)预后有改善;出院时的mRS高于术后6个月的mRS[分别为(3.75±0.97)分和(3.13±1.57)分,配对t=7.86,P＜0.001].经多因素logistic回归分析发现,年龄＞65 岁(OR=15.74,95％CI:5.46～45.39,P＜0.001)、术前为高级别动脉瘤(OR=5.96,95％CI:1.93～18.39,P=0.002)、术前存在脑疝(OR=15.26,95％CI:2.72～85.46,P=0.002)以及术后发生脑梗死(OR=2.90,95％CI:1.13～7.45,P=0.027)是影响SaSAH患者术后6个月预后改善的独立危险因素.ROC曲线分析结果显示,联合预测模型预测SaSAH患者预后改善的AUC值为0.86(95％CI:0.80～0.92,P＜0.001).结论 年龄＞65岁、高级别动脉瘤、术前存在脑疝以及术后发生脑梗死不利于SaSAH患者术后6个月的预后改善.联合预测模型能够有效预测SaSAH患者的预后改善情况.

Background:Brain metastases (BMs) are the most common central nervous system (CNS) malignant tumors, with rapid disease progression and extremely poor prognosis. The heterogeneity between primary lung cancers and BMs leads to the divergent efficacy of the adjuvant therapy response to primary tumors and BMs. However, the extent of heterogeneity between primary lung cancers and BMs, and the evolutionary process remains little known.Methods:To deeply insight into the extent of inter-tumor heterogeneity at a single-patient level and the process of these evolutions, we retrospectively analyzed a total of 26 tumor samples from 10 patients with matched primary lung cancers and BMs. One patient underwent four times brain metastatic lesion surgery with diverse locations and one operation for the primary lesion. The genomic and immune heterogeneity between primary lung cancers and BMs were evaluated by utilizing whole-exome sequencing (WESeq) and immunohistochemical analysis.Results:In addition to inheriting genomic phenotype and molecular phenotype from the primary lung cancers, massive unique genomic phenotype and molecular phenotype were also observed in BMs, which revealed unimaginable complexity of tumor evolution and extensive heterogeneity among lesions at a single-patient level. By analysis of a multi-metastases case (Case 3) of cancer cells' subclonal composition, we found similar multiple subclonal clusters in the four spatial and temporal isolated brain metastatic focus, with the characteristics of polyclonal dissemination. Our study also verified that the expression level of immune checkpoints-related molecule Programmed Death-Ligand 1 (PD-L1) (P = 0.0002) and the density of tumor-infiltrating lymphocytes (TILs) (P = 0.0248) in BMs were significantly lower than that in paired primary lung cancers. Additionally, tumor microvascular density (MVD) also differed between primary tumors and paired BMs, indicating that temporal and spatial diversity profoundly contributes to the evolution of BMs heterogeneity.Conclusion:Our study revealed the significance of temporal and spatial factors to the evolution of tumor heterogeneity by multi-dimensional analysis of matched primary lung cancers and BMs, which also provided novel insight for formulating individualized treatment strategies for BMs.

Background The CKLF-like MARVEL transmembrane domain-containing 3 (CMTM3) is differentially expressed in a variety of tumors and closely related to tumor occurrence and progression. The expression of CMTM3 was significantly elevated in glioma compared with normal brain tissue, to explore the potential function of CMTM3 in the prognosis and immune infiltration of glioma has certain clinical significance. Methods The tumor data in this study were derived from the sequencing data of various tumors in The Cancer Genome Atlas (TCGA) database. Low-grade glioma (LGG) data in the TCGA database include sequencing and clinical data. Clinical data mainly include survival time, survival outcome, age, WHO classification and other information. Sequencing data for normal tissues were obtained from the Genotype Tissue Expression (GTEx) database. Statistical analyses were mainly performed using bioinformatics tools and the corresponding R software (version 3.6.3). The Mann-Whitney U test (Wilcoxon rank sum test) was used to compare the expression differences between the tumor group and the normal group. Survival analysis was conducted using log-rank test to compare whether the overall survival (OS) time was statistically different between the CMTM3 high and low expression groups. The Tumor Immunity Estimation Resource (TIMER) database was used for immune infiltration analysis. Results The results showed that the expression of CMTM3 in World Health Organization (WHO) II and WHO III gliomas was significantly higher than that of normal tissues (P<0.05). Glioma with high CMTM3 expression showed a lower overall survival (OS) (P<0.05). Gene enrichment analysis showed that CMTM3 was significantly enriched in 4 pathways (FDR <0.25, P<0.05). A high correlation was detected between CMTM3 and a variety of immune cells. CMTM3 is highly correlated with macrophages (r=0.536, P=1.31e-36), dendritic cells (r=0.546, P=2.85e-38), CD4+ T cells (r=0.517, P=6.17e-34). Conclusions The CMTM3 gene can be used as a potential prognostic marker for WHO grade II and WHO grade III glioma, is related to the immune infiltration in glioma microenvironment, and may became a new immunotherapy target.

Background To analyze the key prognostic genes and potential traditional Chinese medicine targets in glioblastoma (GBM) by bioinformatics and network pharmacology. Methods GBM datasets were obtained from the Gene Expression Omnibus (GEO) database to clarify the differentially-expressed genes (DEGs) in the carcinoma and paracancerous tissues. The molecular functions (MF) and signaling pathways of enriched DEGs were analyzed by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The STRING database and Cytoscape software were used to construct the protein-protein interaction (PPI) network and screen hub genes to focus on genes with greater clinical significance. The transcription expression and prognosis of hub genes were analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database. The important compounds and target molecules were obtained via the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) database. We identified the active ingredients by setting the property values of pharmacokinetic attribute values. We constructed the network of “Chinese medicine ingredients-DEGs target” and screened out the target genes and active ingredients with high correlation scores. Finally, molecular docking verification was carried out using AutoDock Tools and PyMOL. Results We obtained 271 DEGs, including 212 up-regulated genes and 59 down-regulated genes and screened ten hub genes. GO and KEGG analyses suggested that the hub genes were mainly involved in the following biological processes: the cell cycle, cell division, and cell adhesion, as well as extracellular matrix adhesion-related pathways, the p53 signaling pathways, and cadherin binding involved in cell-cell adhesion. We established the interaction network between the components and DEGs to screen out the traditional Chinese medicine active component (luteolin) and target genes (BIRC5 and CCNB1) for the treatment of GBM. The molecular docking results showed that the bindings of protein receptors, BIRC5 and CCNB1, with the compound ligand, luteolin, were stable and formed by hydrogen bonding interaction. Conclusions In this study, we determined that luteolin potentially inhibits glioblastoma proliferation and migration through key target genes, BIRC5 and CCNB1, via bioinformatics and network pharmacology analysis, and affects the prognosis of GBM patients, providing new ideas for clinical targeted therapy and new drug development.

The majority of oligodendrogliomas exhibit an intrinsic tendency to develop into malignant high-grade tumors. Angiogenesis is a major factor contributing to the malignant transformation of oligodendroglioma, and its molecular regulatory mechanism needs further study. We provide a case report of an oligodendroglioma patient with two recurrences whose disease progressed from WHO grade II to grade III. We showed that the expression of insulin gene enhancer protein (ISL2) and its angiogenic ability were positively correlated with the progression of oligodendroglioma. In Low-grade glioma (LGG) patients, including oligodendroglioma patients, overexpression of ISL2 was correlated with poor prognosis, and this correlation was not affected by gender or isocitrate dehydrogenase 1(IDH1) mutation status. ISL2 expression and ISL2-mediated angiogenic pathway activity are ideal biomarkers for the malignant transformation of oligodendroglioma. Anti-ISL2 therapy is also a potential treatment option for malignantly transformed oligodendroglioma.

Objective:To compare the clinical efficacy and safety of surgeries via frontal keyhole approach assisted by neuro-endoscope and via temporal keyhole approach assisted by microscope in cerebral basal ganglia hemorrhage. Methods:One hundred and five patients with basal ganglia cerebral hemorrhage admitted to our hospital from January 2017 to January 2020 were chosen in our study; 51 patients underwent surgeries via frontal keyhole approach assisted by neuro-endoscope (neuro-endoscopy group) and 54 patients underwent surgeries via temporal keyhole approach assisted by microscope (microscopy group). The clinical data of these patients were retrospectively analyzed; and the differences of hematoma clearance rate, intraoperative blood loss, duration of surgery, length of hospital stays, Glasgow Coma Scale (GCS) scores one week after surgery, incidence of postoperative complications, and activity of daily living (ADL) scores 6 months after surgery were compared between the 2 groups. Results:There were no significant differences in hematoma clearance rate and length of hospital stays between the 2 groups ( P>0.05). As compared with the microscopy group, the neuro-endoscopy group had significantly lower intraoperative blood loss, significantly shorter duration of surgery, and statistically higher GCS scores one week after surgery ( P<0.05). There were no significant differences in incidence of postoperative complications and ADL scores 6 months after surgery between 2 groups ( P>0.05). Conclusion:Both surgeries via frontal keyhole approach assisted by neuro-endoscope and via temporal keyhole approach assisted by microscope can effectively clear the intracranial hematoma in patients with cerebral hemorrhage in the basal ganglia and protect neurological function; however, surgeries via frontal keyhole approach assisted by neuro-endoscope has advantages of shorter duration of surgery and lower intraoperative blood loss, and earlier neurological function recovery.

Background: Glioma is the most common and aggressive primary brain tumor in adults. Proteasome 26S subunit, non-ATPase 12 (PSMD12), an important subunit in the 26S proteasome, is known to be involved in the growth and apoptosis of breast cancer cells. However, its exact function and underlying molecular mechanisms in glioma remain unknown. Methods: PSMD12 expression was detected in glioma tissue specimens by immunohistochemistry (IHC) and TCGA database. Overexpression and down-regulation of PSMD12 and Nrf2 were induced in glioma cell lines, and CCK-8 and Transwell assays were used to detect cell proliferation and invasion evaluation, respectively. Xenograft model was used to observe the effect of knockdown of PSMD12 on tumor growth. Immunohistochemical assays and TCGA database were conducted to reveal the relationships between PSMD12 expression and Nrf2. Finally, Western blot and related biological function experiments were used to explore the mechanism of PSMD12 regulating the glioma progression and Nrf2. Results: We revealed that PSMD12 is upregulated in glioma, especially in high-grade glioma, by analyzing bioinformatics data and clinical specimens. PSMD12 upregulation was associated with poor prognosis in glioma patients. Knockdown of PSMD12 inhibited the growth of glioma cells in vitro and in vivo and decreased their invasion ability, whereas PSMD12 overexpression had the opposite effect. Mechanistic analysis revealed that PSMD12 increased the expression of nuclear factor E2-related factor 2 (Nrf2), which functions as a tumor promoter in the development of glioma. Similar to PSMD12, Nrf2, which exhibited a strong positive correlation with PSMD12, was abnormally elevated in glioma tissues and contributed to worse overall survival (OS). Nrf2 overexpression reversed the inhibitory effects induced by PSMD12 knockdown. Finally, PSMD12 enhanced the proliferation and invasion of glioma cells via Akt signaling-mediated Nrf2 expression. Conclusions: These results suggest that PSMD12 is considered to be a crucial regulator of the development and progression of glioma and may serve as a potential biomarker or therapeutic target for the treatment of glioma.

Yanming Chen Second A liated Hospital of Soochow University Xiaoxiao Dai Second A liated Hospital of Soochow University Ji Wang Second A liated Hospital of Soochow University Chuming Tao Second A liated Hospital of Soochow University Ye Wang Second A liated Hospital of Soochow University Qing Zhu Second A liated Hospital of Soochow University Liqun Yuan Second A liated Hospital of Soochow University Zhongyong Wang Second A liated Hospital of Soochow University Minfeng Sheng Second A liated Hospital of Soochow University Tan Zhang Second A liated Hospital of Soochow University Shenggang Li Second A liated Hospital of Soochow University Yongsheng Zhang Second A liated Hospital of Soochow University Jun Dong Second A liated Hospital of Soochow University Qing Lan Second A liated Hospital of Soochow University Jizong Zhao (  zhaojizong@bjtth.org ) Second A liated Hospital of Soochow University https://orcid.org/0000-0001-9194-0580

Due to the extremely intrinsic heterogeneity among glioma patients, the outcomes of these patients are tremendously different. Therefore, the exploitation of novel biomarker classification of glioma is vitally important for deep insight into the essence and predicting the prognosis of glioma. We aim to analyze the correlation between TP73 mRNA expression, DNA methylated alteration and the prognosis of WHO grade II/III glioma, utilizing bioinformatics to evaluate its significance as a risk-factor in predicting the prognosis of these glioma patients. The analysis found that TP73 expression was positively correlated with the grade of glioma, and showed a strong correlation with glioma molecular classification, which revealed significantly higher TP73 expression in IDH-wildtype than in IDH-mutant subtype of WHO grade II/III glioma. Cox regression analysis indicated that high expression of TP73 shared an independent high-risk factor impacting the prognosis of WHO grade II/III glioma. We discovered 8 DNA promoter methylation sites with prognostic significance, which were negatively associated with TP73 expression, and positively associated with beneficial overall survival (OS) and progression-free survival (PFS). Integrating with four independent glioma datasets, subsequent Meta-analysis verified that low expression of TP73 was closely related to favorable OS, especially in IDH-mutant subtype. Moreover, we found that 1p/19qCodel /TP73low subgroup shared the most favorable OS, 1p/19qNon-codel /TP73high subgroup suffered the worst OS. Meanwhile, the enrichment analysis of TP73-related differential mRNAs demonstrated that TP73 aberration in WHO grade II/III glioma might be closely related to cell cycle and P53 signaling pathways. Finally, TP73 expression of 53 glioma specimens was measured by qRT-PCR, which was consistent with the previous analytical result, and TP73 high-expression subgroup suffered worse PFS than TP73 low-expression subgroup. In summary, our funding supports that TP73 gene can perform as a reliable biomarker to evaluate the survival outcome of patients diagnosed with WHO grade II/III glioma.

目的 分析神经外科临床教学中PBL教学法的应用价值.方法 将80名医学生学员分为两组,每组40例.对照组接受常规教学,观察组接受PBL教学,分析结果.结果 和对照组相比,观察组无论是在理论考试成绩、临床实践成绩、临床教学效果、各项能力提升、自我评价以及教学满意度方面得分明显更高,P<0.05.结论 PBL教学法有着开放性的特征,运用此教学法对学生们开展教学,有助于培养学生学习知识的主观能动性.此法重视理论和实践相结合教学效果,另外也能够培养学生的学习知识思维能力水平.

Oligodendroglioma is an important type of lower-grade glioma (LGG), which is a slowly progressing brain tumor. Many LGGs eventually transform into a more aggressive or malignant type. Enhanced angiogenesis is a characteristic of malignantly transformed oligodendroglioma (m-oligodendroglioma). However, the pathogenesis and signaling pathways associated with angiogenesis and proliferation in m-oligodendroglioma are not well understood. In this study, we identified that Insulin Gene Enhancer Protein (ISL2) and its angiogenic capacity were inversely related to survival according to LGG patient data from an online database, and this was further confirmed with pathological LGG patient samples, including malignantly transformed samples, by detecting the expression of ISL2, the angiogenic markers vascular endothelial growth factor (VEGFA) and CD31 and the proliferation marker Ki-67. We then established novel oligodendroglioma patient tumor-derived orthotopic xenograft mouse models and cell lines to verify the role of ISL2 in regulating angiogenesis to promote oligodendroglioma growth and malignant transformation. Furthermore, ISL2 regulated ANGPT2 transcription by binding to the ANGPT2 promoter. Then, ANGPT2, a downstream gene, activated angiogenesis through VEGFA to promote oligodendroglioma malignant transformation. Finally, combining AAV-ISL2-shRNA with temozolomide suppressed oligodendroglioma progression more effectively than either monotherapy in vivo and in vitro. Thus, hypoxia-induced ISL2 regulated ANGPT2, which subsequently induced angiogenesis to promote oligodendroglioma growth and malignant transformation. Malignancy was accompanied by worsened hypoxia inside the tumor mass, creating a positive feedback loop. In conclusion, this study suggests that ISL2 is a biomarker for oligodendroglioma progression and that anti-ISL2 therapy may offer a potential clinical strategy for treating m-oligodendroglioma.

Objective To explore the improved method of precisely locating related bony structures in intradural anterior transpetrosal approach.Methods On the 10 dry skulls,the highest point of arcuate eminence (A),the petrous apex (P),the most lateral point of groove for the greater petrosal nerve (B),foramen spinosum (C),foramen ovale (D),trigeminal impression (E) and t foramen lacerum (F) were marked.Using point A as reference point and the line AP as the baseline,the distances of AB,AC,AD,AE and AF and the angles of / BAP,/ CAP,/ DAP,/ EAP and / FAP were measured.Samples were analyzed by mean and standard deviation,and the data on both sides were compared by t test.Results 1.AB:(11.61±2.31) mm (left),10.44±2.31 mm (right),t=1.084;AC:(23.14± 3.07) mm (left),(21.08 ± 2.67) mm (right),t=1.596;AD:(24.95± 2.82) mm (left),(24.38±3.44) mm (right),t=0.408;AE:(18.98± 3.11) mm (left),(19.21± 3.09) mm (right),t=-0.164;AF:(29.68±2.62) mm (left),(29.25±2.77) mm (right),t=0.725.2.∠BAP:(49.15 ± 12.10) ° (left),(52.78 ± 14.27) ° (right),t =-0.624;∠CAP:(43.98 ±6.95) ° (left),(48.73 ±8.02)° (right),t=-1.418;∠DAP:(38.68 ±4.81)° (left),(41.48 ±3.14)° (right),t=-1.543;∠EAP:(21.93 ±5.29)° (left),(25.94 ±6.43)° (right),t=-1.523;∠∠FAP:(15.96±2.78)° (left),(17.20 ±3.44)° (right),t=-0.882.There were no significant differences between the left and right sides (P ＞ 0.05).Confusion Using point A and P as referent indexes,the bony structures which represent the corresponding nerves and blood vessels can be precisely lo cated for grinding Kawase triangle via intradural anterior transpetrosal approach.

ObjectiveTo explore the application of conceive-design-implement-operate (CDIP) teaching modein the training for neurosurgical specialist nurses' core competence. MethodsA total of 76 trainees of neurosurgery specialist nurses in the Second Affiliated Hospital of Soochow University from October 2014 to August 2018 were selected as the research objects. The goal and content of core competence training were formulated by CDIO teaching mode, and the training program was designed and implemented. The results of core competence, general self-efficacy, theoretical assessment and nursing practice assessment before and after training were compared. ResultsThe total score of general self-efficacy of trainees after training was (29.54±5.02), higher than that before training (27.43±4.73), with statistical difference (P＜0.01); the core competencies of trainees after training included critical thinking and scientific research (CR), clinical care (CC), leadership (LD), interpersonal relationship (IR), law and ethics (LE), professional development (PD) and teaching consultation (TC) were (31.29±5.52), (29.11±4.73), (32.08±5.35), (25.78±4.97), (25.72±5.10), (20.13±3.25), (22.37±4.42) respectively, higher than those before training[ (27.33±6.08),(26.93±5.84), (29.32±6.51),(23.13±5.38),(22.92±5.75),(18.87±4.33),(20.72±5.19)]with statistical significance (P＜0.05). The scores of theoretical and nursing practice assessment of trainees after training were (91.96±3.58), (95.17±2.34) respectively, higher than those before training [(78.87±4.96), (83.21±3.98)] with statistical difference (P＜0.01). ConclusionsThe application of CDIO teaching model in the training of neurosurgical specialist nurses can improve students' core competence and general self-efficacy,and provide useful reference for the training of neurosurgical specialist nurses' core competence.