Epilepsy alters brain networks in patients with insular glioma.

AIMS: We intend to elucidate the alterations of cerebral networks in patients with insular glioma-related epilepsy (GRE) based on resting-state functional magnetic resonance images. METHODS: We collected 62 insular glioma patients, who were subsequently categorized into glioma-related epilepsy (GRE) and glioma with no epilepsy (GnE) groups, and recruited 16 healthy individuals matched to the patient's age and gender to form the healthy control (HC) group. Graph theoretical analysis was applied to reveal differences in sensorimotor, default mode, visual, and executive networks among different subgroups. RESULTS: No significant alterations in functional connectivity were found in either hemisphere insular glioma. Using graph theoretical analysis, differences were found in visual, sensorimotor, and default mode networks (p < 0.05). When the glioma located in the left hemisphere, the degree centrality was reduced in the GE group compared to the GnE group. When the glioma located in the right insula, the degree centrality, nodal efficiency, nodal local efficiency, and nodal clustering coefficient of the GE group were lower than those of the GnE group. CONCLUSION: The impact of insular glioma itself and GRE on the brain network is widespread. The networks altered by insular GRE differ depending on the hemisphere location. GRE reduces the nodal properties of brain networks than that in insular glioma.

Survival outcome and predictors of WHO grade 2 and 3 insular gliomas: A classification based on the tumor spread.

OBJECTIVE: The study aimed to identify if clinical features and survival outcomes of insular glioma patients are associated with our classification based on the tumor spread. METHODS: Our study included 283 consecutive patients diagnosed with histological grade 2 and 3 insular gliomas. A new classification was proposed, and tumors restricted to the paralimbic system were defined as type 1. When tumors invaded the limbic system (referred to as the hippocampus and its surrounding structures in this study) simultaneously, they were defined as type 2. Tumors with additional internal capsule involvement were defined as type 3. RESULTS: Tumors defined as type 3 had a higher age at diagnosis (p = 0.002) and a higher preoperative volume (p < 0.001). Furthermore, type 3 was more likely to be diagnosed as IDH wild type (p < 0.001), with a higher rate of Ki-67 index (p = 0.015) and a lower rate of gross total resection (p < 0.001). Type 1 had a slower tumor growth rate than type 2 (mean 3.3%/month vs. 19.8%/month; p < 0.001). Multivariate Cox regression analysis revealed the extent of resection (HR 0.259, p = 0.004), IDH status (HR 3.694, p = 0.012), and tumor spread type (HR = 1.874, p = 0.012) as independent predictors of overall survival (OS). Tumor grade (HR 2.609, p = 0.008), the extent of resection (HR 0.488, p = 0.038), IDH status (HR 2.225, p = 0.025), and tumor spread type (HR 1.531, p = 0.038) were significant in predicting progression-free survival (PFS). CONCLUSION: The current study proposes a classification of the insular glioma according to the tumor spread. It indicates that the tumors defined as type 1 have a relatively better nature and biological characteristics, and those defined as type 3 can be more aggressive and refractory. Besides its predictive value for prognosis, the classification has potential value in formulating surgical strategies for patients with insular gliomas.

Targeting the tumor microenvironment in primary central nervous system lymphoma: Implications for prognosis.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma, and there is limited research on its tumor microenvironment (TME). Nevertheless, more and more studies have evidence that TME has essential effects on tumor cell proliferation, immune escape, and drug resistance. Thus, it is critical to elucidate the role of TME in PCNSL. The understanding of the PCNSL TME is gradually unfolding, including factors that distinguish it from systemic diffuse large B-cell lymphoma (DLBCL). The TME in PCNSL exhibits both transcriptional and spatial intratumor heterogeneity. Cellular interactions between tumor cells and stroma cells reveal immune evasion signaling. The comparative analysis between PCNSL and DLBCL suggests that PCNSL is more likely to be an immunologically deficient tumor. In PCNSL, T cell exhaustion and downregulation of macrophage immune function are accompanied by suppressive microenvironmental factors such as M2 polarized macrophages, endothelin B receptor, HLA depletion, PD-L1, and TIM-3. MMP-9, Integrin-ß1, and ICAM-1/LFA-1 play crucial roles in transendothelial migration towards the CNS, while CXCL13/CXCR5, CD44, MAG, and IL-8 are essential for brain parenchymal invasion. Further, macrophages, YKL-40, CD31, CD105, PD-1/PD-L1 axis, osteopontin, galectin-3, aggregative perivascular tumor cells, and HLA deletion may contribute to poor outcomes in patients with PCNSL. This article reviews the effect of various components of TME on the progression and prognosis of PCNSL patients to identify novel therapeutic targets.

Arming Amorphous NiMoO4 on Nickel Phosphide Enables Highly Stable Alkaline Seawater Oxidation.

Seawater electrolysis holds tremendous promise for the generation of green hydrogen (H2 ). However, the system of seawater-to-H2 faces significant hurdles, primarily due to the corrosive effects of chlorine compounds, which can cause severe anodic deterioration. Here, a nickel phosphide nanosheet array with amorphous NiMoO4 layer on Ni foam (Ni2 P@NiMoO4 /NF) is reported as a highly efficient and stable electrocatalyst for oxygen evolution reaction (OER) in alkaline seawater. Such Ni2 P@NiMoO4 /NF requires overpotentials of just 343 and 370 mV to achieve industrial-level current densities of 500 and 1000 mA cm-2 , respectively, surpassing that of Ni2 P/NF (470 and 555 mV). Furthermore, it maintains consistent electrolysis for over 500 h, a significant improvement compared to that of Ni2 P/NF (120 h) and Ni(OH)2 /NF (65 h). Electrochemical in situ Raman spectroscopy, stability testing, and chloride extraction analysis reveal that is situ formed MoO4 2- /PO4 3- from Ni2 P@NiMoO4 during the OER test to the electrode surface, thus effectively repelling Cl- and hindering the formation of harmful ClO- .

Utility of contrast-enhanced MRI radiomics features combined with clinical indicators for predicting induction chemotherapy response in primary central nervous system lymphoma.

PURPOSE: To assess the utility of combining contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics features with clinical variables in predicting the response to induction chemotherapy (IC) for primary central nervous system lymphoma (PCNSL). METHODS: A total of 131 patients with PCNSL (101 in the training set and 30 in the testing set) who had undergone contrast-enhanced MRI scans were retrospectively analyzed. Pyradiomics was utilized to extract radiomics features, and the clinical variables of the patients were gathered. Radiomics prediction models were developed using different combinations of feature selection methods and machine learning models, and the best combination was ultimately chosen. We screened clinical variables associated with treatment outcomes and developed clinical prediction models. The predictive performance of radiomics model, clinical model, and combined model, which integrates the best radiomics model and clinical characteristics, was independently assessed and compared using Receiver Operating Characteristic (ROC) curves. RESULTS: In total, we extracted 1598 features. The best radiomics model we selected as the best utilized T-test and Recursive Feature Elimination (RFE) for feature selection and logistic regression for model building. Serum Interleukin 2 Receptor (IL-2R) and Eastern Cooperative Oncology Group (ECOG) Score were utilized to develop a clinical predictive model for assessing the response to induction chemotherapy. The results of the testing set revealed that the combined prediction model (radiomics and IL-2R) achieved the highest area under the ROC curve at 0.868 (0.683, 0.967), followed by the radiomics model at 0.857 (0.681, 0.957), and the clinical prediction model (IL-2R and ECOG) at 0.618 (0.413, 0.797). The combined model was significantly more accurate than the clinical model, with an AUC of 0.868 compared to 0.618 (P < 0.05). While the radiomics model had slightly better predictive power than the clinical model, this difference was not statistically significant (AUC, 0.857 vs. 0.618, P > 0.05). CONCLUSIONS: Our prediction model, which combines radiomics signatures from CE-MRI with serum IL-2R, can effectively stratify patients with PCNSL before high-dose methotrexate (HD-MTX) -based chemotherapy.

Assessing Postoperative Motor Risk in Insular Low-Grade Gliomas Patients: The Potential Role of Presurgery MRI Corticospinal Tract Shape Measures.

BACKGROUND: Insular low-grade gliomas (LGGs) are surgically challenging due to their proximity to critical structures like the corticospinal tract (CST). PURPOSE: This study aims to determine if preoperative CST shape metrics correlate with postoperative motor complications in insular LGG patients. STUDY TYPE: Retrospective. POPULATION: 42 patients (mean age 40.26 ± 10.21 years, 25 male) with insular LGGs. FIELD STRENGTH/SEQUENCE: Imaging was performed using 3.0 Tesla MRI, incorporating T1-weighted magnetization-prepared rapid gradient-echo, T2-weighted space dark-fluid with spin echo (SE), and diffusional kurtosis imaging (DKI) with gradient echo sequences, all integrated with echo planar imaging. ASSESSMENT: Shape metrics of the CST, including span, irregularity, radius, and irregularity of end regions (RER and IER, respectively), were compared between the affected and healthy hemispheres. Total end region radius (TRER) was determined as the sum of RER 1 and RER 2. The relationships between shape metrics and postoperative short-term (4 weeks) and long-term (>8 weeks) motor disturbances assessing by British Medical Research Council grading system, was analyzed using multivariable regression models. STATISTICAL TESTING: Paired t-tests compared CST metrics between hemispheres. Logistic regression identified associations between these metrics and motor disturbances. The models were developed using all available data and there was no independent validation dataset. Significance was set at P < 0.05. RESULTS: Short-term motor disturbance risk was significantly related to TRER (OR = 199.57). Long-term risk significantly correlated with IER 1 (OR = 59.84), confirmed as a significant marker with an AUC of 0.78. Furthermore, the CST on the affected side significantly had the greater irregularity, larger TRER and RER 1, and smaller span compared to the healthy side. DATA CONCLUSION: Preoperative evaluation of TRER and IER 1 metrics in the CST may serve as a tool for assessing the risk of postoperative motor complications in insular LGG patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Exploring MGMT methylation-driven structural connectivity changes in insular gliomas: a tractography and graph theoretical analysis.

OBJECTIVES: This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. METHODS: We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. RESULTS: The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. CONCLUSION: Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.

Amorphous Co-Mo-P film on nickel foam: a superior bifunctional electrocatalyst for alkaline seawater splitting.

Seawater splitting is a compelling avenue to produce abundant hydrogen, which requires high-performance and cost-effective catalysts. Constructing bimetallic transition metal phosphides is a feasible strategy to meet the challenge. Here, an amorphous Co-Mo-P film supported on nickel foam (Co-Mo-P/NF) electrode is developed with bifunctional properties for both the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline seawater. Corresponding results indicate that the introduction of Mo can improve the active sites and regulate the intrinsic activity. Such a Co-Mo-P/NF behaves with prominent electrocatalytic activity towards both HER and OER, demanding low overpotentials of 193 and 352 mV at 100 mA cm‒2in alkaline seawater, respectively. Furthermore, the assembled electrolyzer demands a pronounced overall seawater splitting activity with a low cell voltage of 1.76 V to deliver 100 mA cm-2presenting excellent durability without obvious attenuation after 24 h continuous stability test. This work expands the horizon to develop transition metal-phosphorus electrocatalysts with robust and efficient activity for overall seawater splitting.

A preliminary study on corticospinal tract morphology in incidental and symptomatic insular low-grade glioma: implications for post-surgical motor outcomes.

OBJECTIVE: Our study aimed to investigate the shape and diffusion properties of the corticospinal tract (CST) in patients with insular incidental and symptomatic low-grade gliomas (LGGs), especially those in the incidental group, and evaluate their association with post-surgical motor function. METHODS: We performed automatic fiber tracking on 41 LGG patients, comparing macroscopic shape and microscopic diffusion properties of CST between ipsilateral and contralateral tracts in both incidental and symptomatic groups. A correlation analysis was conducted between properties of CST and post-operative motor strength grades. RESULTS: In the incidental group, no significant differences in mean diffusion properties were found between bilateral CST. While decreased anisotropy of the CST around the superior limiting sulcus and increased axial diffusivity of the CST near the midbrain level were noted, there was no significant correlation between pre-operative diffusion metrics and post-operative motor strength. In comparison, we found significant correlations between the elongation of the affected CST in the preoperative scans and post-operative motor strength in short-term and long-term follow ups (p = 1.810 × 10-4 and p = 9.560 × 10-4, respectively). CONCLUSIONS: We found a significant correlation between CST shape measures and post-operative motor function outcomes in patients with incidental insular LGGs. CST morphology shows promise as a potential prognostic factor for identifying functional deficits in this patient population.

Improved Electrochemical Alkaline Seawater Oxidation over Cobalt Carbonate Hydroxide Nanowire Array by Iron Doping.

Constructing efficient and low-cost oxygen evolution reaction (OER) catalysts operating in seawater is essential for green hydrogen production but remains a great challenge. In this study, we report an iron doped cobalt carbonate hydroxide nanowire array on nickel foam (Fe-CoCH/NF) as a high-efficiency OER electrocatalyst. In alkaline seawater, such Fe-CoCH/NF demands an overpotential of 387 mV to drive 500 mA cm-2, superior to that of CoCH/NF (597 mV). Moreover, it achieves excellent electrochemical and structural stability in alkaline seawater.

Challenges in the management of primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is a rare extranodal non-Hodgkin lymphoma. Stereotactic biopsy remains the gold standard for the pathological diagnosis of PCNSL. However, certain new auxiliary diagnostic methods are considered to have good application prospects; these include cytokine and tumor circulating DNA, among others. Although new drugs such as immunomodulators, immune checkpoint inhibitors, chimeric antigen receptor T-cells, and Bruton tyrosine kinase inhibitors have brought hope owing to their improved efficacy, the high recurrence rate and subsequent high mortality remain barriers to long-term survival. Increasing emphasis is therefore being placed on consolidation treatments. Consolidation treatment strategies include whole brain radiotherapy, autologous hematopoietic stem cell transplantation, and non-myeloablative chemotherapy. As studies directly comparing the effectiveness and safety of different consolidation treatment schemes are lacking, the optimal consolidation strategy remains uncertain. This article will review the diagnosis and treatment of PCNSL, focusing on the progress in research pertaining to consolidation therapy.

Improved Alkaline Seawater Splitting of NiS Nanosheets by Iron Doping.

Seawater electrolysis driven by renewable electricity is deemed a promising and sustainable strategy for green hydrogen production, but it is still formidably challenging. Here, we report an iron-doped NiS nanosheet array on Ni foam (Fe-NiS/NF) as a high-performance and stable seawater splitting electrocatalyst. Such Fe-NiS/NF catalyst needs overpotentials of only 420 and 270 mV at 1000 mA cm-2 for the oxygen evolution reaction and hydrogen evolution reaction in alkaline seawater, respectively. Furthermore, its two-electrode electrolyzer needs a cell voltage of 1.88 V for 1000 mA cm-2 with 50 h of long-term electrochemical durability in alkaline seawater. Additionally, in situ electrochemical Raman and infrared spectroscopy were employed to detect the reconstitution process of NiOOH and the generation of oxygen intermediates under reaction conditions.

Highly efficient activation of peroxymonosulfate by biomass juncus derived carbon decorated with cobalt nanoparticles for the degradation of ofloxacin.

The cobalt nanoparticles decorated biomass Juncus derived carbon (Co@JDC) was prepared by facile calcination strategy and applied to activate peroxymonosulfate (PMS) for eliminating ofloxacin (OFX) in the water environment. The results of catalytic experiments show that 97% of OFX degradation efficiency and 70.4% of chemical oxygen demand removal rate are obtained within 24 min at 0.1 g L-1 Co@JDC, 0.2 g L-1 PMS, 20 mg L-1 OFX (100 mL), and pH = 7, which indicates that Co@JDC/PMS system exhibits excellent performance. Meanwhile, the experimental results of affect factor show that Co@JDC/PMS system can operate in a wider pH range (3-9) and Cl-1, NO3-1, and SO42- have an ignorable effect on OFX degradation. The radical identification experiments confirm that SO4˙-, ·OH, O2˙-, and 1O2 are involved in the process of PMS activation, especially SO4˙- and 1O2 are the main contributors. Furthermore, a possible PMS activation mechanism by Co@JDC was proposed and the degradation pathways of OFX were deduced. Finally, the stable catalytic activity, negligible leaching of Co2+, and the outstanding degradation efficiency for other antibiotics prove that Co@JDC possesses good stability and universality.

Incidence of ischemic complications and technical nuances of arteries preservation for insular gliomas resection.

Introduction: Insular gliomas have complex anatomy and microvascular supply that make resection difficult. Furthermore, resection of insular glioma is associated with a significant risk of postoperative ischemic complications. Thus, this study aimed to assess the incidence of ischemic complications related to insular glioma resection, determine its risk factors, and describe a single surgeon's experience of artery-preserving tumor resection. Methods: We enrolled 75 consecutive patients with insular gliomas who underwent transcortical tumor resection. Preoperative and postoperative demographic, clinical, radiological [including diffusion-weighted imaging (DWI)], intraoperative neurophysiological data, and functional outcomes were analyzed. Motor evoked potentials (MEPs) and radiological characteristics like the relationship between the proximal segment of the lateral lenticulostriate arteries (LLSAs) and the tumor, the flat inner edge sign (the inner edge of the insular glioma is well-defined) or obscure inner edge sign, the distance between the lesion and posterior limb of the internal capsule and the invasion of the superior limiting sulcus by the tumor were analyzed. Strategies such as "residual triangle," "basal ganglia outline reappearance," and "sculpting" technique were used to preserve the LLSAs and the main branches of M2 for maximal tumor resection according to the Berger-Sinai classification. Results: Postoperative DWI showed acute ischemia in 44 patients (58.7%). Moreover, nine patients (12%) had developed new motor deficits, as determined by the treating neurosurgeons. The flat inner edge sign [odds ratio (OR), 0.144; 95% confidence interval (CI), 0.024-0.876) and MEPs (>50%) (OR, 18.182; 95% CI, 3.311-100.00) were significantly associated with postoperative core ischemia, which affected the posterior limb of the internal capsule or corona radiata. Conclusions: Insular glioma resection was associated with a high incidence of ischemia, as detected by DWI, as well as new motor deficits that were determined by the treating neurosurgeons. Insular glioma patients with obscure inner edge signs and intraoperative MEPs decline >50% had a higher risk of developing core ischemia. With our strategies, maximal safe resection of insular gliomas may be achieved.

In vitro and in vivo anticancer activity of Lycorine in prostate cancer by inhibiting NF-κB signaling pathway.

NF-κB transcription factors critically regulate the expression of genes which are involved in important cellular processes, including cellular proliferation and apoptosis. Abnormal activation of the NF-κB signaling pathway has been implicated in a variety of human cancers. Hyper-activation of the NF-κB signaling pathway has been found to lead to tumor survival, anti-apoptosis and invasion in the development of prostate cancer. In the present work, we identified Lycorine as a potent NF-κB inhibitor using a NF-κB activity dependent luciferase reporter in PC3 and DU145 prostate cancer cells. With this reporter gene assay, we found that Lycorine significantly suppressed the constitutive NF-κB activity as well as the NF-κB activity induced by TNF-α, LPS, PMA and IL-1ß. Western blotting analysis of the NF-κB signaling pathway further showed that Lycorine inhibited IκB-α (inhibitor of κB) phosphorylation, IκB-α degradation, and p65 phosphorylation. Consistent with this, the subsequent nuclear translocation of p65 was blocked by Lycorine as evidenced in the immunofluorescence assay and western blotting. Furthermore, we observed that cell cycle was arrested at G2/M in Lycorine treated cells using FACS analysis. Western blotting analysis indicated that Lycorine increased the expression of Cyclin D1 but decreased the expression of p21. In addition, FACS analysis showed that Lycorine induced apoptosis in DU145 and PC3 cells. Western blotting analysis revealed that Lycorine decreased the expression of anti-apoptosis genes myc, survivin and Bcl-2 while increased cleavage of PARP. Finally, we observed a significant anticancer effect of Lycorine in a RM-1 prostate cancer xenograft mouse model. In agreement with its in vitro anticancer effect, Lycorine inhibited p65 phosphorylation, IKK-ß phosphorylation and the expression of Ki-67, while increased the cleavage of Caspase 3 in tumor tissue. Taken together, our data demonstrated the in vitro and in vivo anti-prostate cancer activity of Lycorine by inhibiting the NF-κB signaling pathway, and highlighted it as a lead compound for further development into an effective anticancer drug.

Non-Myeloablative Chemotherapy as Consolidation Strategy After High-Dose Methotrexate-Based Chemoimmunotherapy in Patients With Primary CNS Lymphoma: A Retrospective Single Center Study in China.

Primary central nervous system lymphoma (PCNSL) remains a disease with poor outcome and high recurrence rate. We retrospectively analyzed the clinical data of 243 immunocompetent patients with PCNSL in Beijing Tiantan Hospital. The median age of PCNSL patients was 57 years (range 10-95 years). For induction therapy, 94.7% of patients received high-dose methotrexate (HD-MTX) containing regimens, and 59.3% received rituximab, which increased over time. The overall response rate was 72.8%, with 58.8% achieving complete response. With a median follow-up of 27.0 months (95% confidence interval 23.6-30.4), the median progression-free survival (PFS) time was 14.0 months (95% CI 9.45-18.55), and the 2-year PFS rate was 33.2%. The median overall survival (OS) was not reached (NR), with an estimated overall survival rate at 4 years of 61.6%. Among 95 patients who completed sequential consolidation chemotherapy with either pemetrexed or etoposide plus cytarabine, the median PFS was 28 months (95% CI 17.11-38.89), and the estimated overall survival at 4 years was 78.7%. In conclusion, HD-MTX based induction chemotherapy with non-myeloablative sequential consolidation chemotherapy is an alternative feasible treatment option.

The PI3K/AKT/mTOR signaling pathway is aberrantly activated in primary central nervous system lymphoma and correlated with a poor prognosis.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a specific subtype of non-Hodgkin lymphoma that is highly invasive and confined to the central nervous system (CNS). The vast majority of PCNSLs are diffuse large B-cell lymphomas (DLBCLs). PCNSL is a highly heterogeneous disease, and its pathogenesis has not yet been fully elucidated. Further studies are needed to guide individualized therapy and improve the prognosis. METHODS: In this study, we detected 1) the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 by immunohistochemistry (IHC) and Western blotting, 2) the mRNA expression by real-time qPCR and 3) the deletion of PTEN gene by immunofluorescence in situ hybridization (FISH) in order to investigate the activation status of the PI3K/AKT/mTOR signaling pathway in PCNSL. Samples of reactive hyperplasia lymphnods were used as the control group. The correlations between the clinical characteristics and prognosis of PCNSL patients and the expression of p-AKT, p-mTOR, p-S6 and p-4E-BP1 and the deletion of PTEN were assessed. RESULTS: The IHC results showed that the positive expression rates of p-AKT, p-mTOR, p-S6 and p-4E-BP1 in PCNSL were significantly higher in the PCNSL group than in the control group (P < 0.05). The relative mRNA expression level of MTOR in PCNSL samples was significantly increased (P = 0.013). Correlation analysis revealed that the expression of p-mTOR was correlated with that of p-AKT, p-S6, p-4E-BP1. PTEN deletion was found in 18.9% of PCNSL samples and was correlated with the expression of p-AKT (P = 0.031). Correlation analysis revealed that the PCNSL relapse rate in the p-mTOR-positive group was 64.5%, significantly higher than that in the negative group (P = 0.001). Kaplan-Meier survival analysis showed inferior progression-free survival (PFS) in the p-mTOR- and p-S6-positive groups (P = 0.002 and 0.009, respectively), and PTEN deletion tended to be related to shorter overall survival (OS) (P = 0.072). Cox regression analysis revealed p-mTOR expression as an independent prognostic factor for a shorter PFS (hazard ratio (HR) =7.849, P = 0.046). CONCLUSIONS: Our results suggest that the PI3K/AKT/mTOR signaling pathway is aberrantly activated in PCNSL and associated with a poor prognosis, which might indicate new therapeutic targets and prognostic factors.

Reduced sensitivity to delayed time and delayed reward of the post-operative insular glioma patients in delay discounting.

Previous studies have shown that the insula is closely related to addiction, and the structure's role in delay discounting can be measured by a specific task, but the specific role of the insula has been less studied. In this study, we first conducted a lesion study in which we recruited healthy controls (n = 30) and patients with unilateral insula injury (n = 16) to complete a behavioral delay discounting task. Then we conducted a functional magnetic resonance imaging (fMRI) study, and a separate group healthy volunteers (n = 51) completed a delay discounting task during the fMRI scan. The lesion study showed a significant difference between the two groups in the delay discounting task, which revealed that insula injury was associated with impaired decision making. The fMRI study revealed choice-sensitive insula activation that was modulated by delayed time and delayed reward, indicating an important role of the insula in delay discounting. Overall, our results provide evidence for a role of the insular lobe in delay discounting and suggests that this structure may be considered an important factor in the future treatment and diagnosis of addiction disorders.

Development and performance evaluation of TaqMan real-time fluorescence quantitative methylation specific PCR for detecting methylation level of PER2.

BACKGROUND: PER2 gene methylation is closely related to the occurrence and progress of some cancers, but there is no method to quantitatively detect PER2 methylation in conventional laboratories. So, we established a TaqMan real-time fluorescence quantitative methylation specific PCR (TaqMan real-time FQ-MSP) assay and use it for quantitative detection of PER2 methylation in leukemia patients. METHODS: According to the PER2 sequence searched by GenBank, a CpG sequence enrichment region of the PER2 gene promoter was selected, and the methylated and unmethylated target sequences were designed according to the law of bisulfite conversion of DNA to construct PER2 methylation positive and negative reference materials. Specific primers and probe were designed. The reference materials were continuously diluted into gradient samples by tenfold ratio to evaluate the analytical sensitivity, specificity, accuracy and reproducibility of the method, and the analytical sensitivity of TaqMan real-time FQ-MSP assay was compared with that of the conventional MSP assay. At the same time, the new-established TaqMan real-time FQ-MSP assay and the conventional MSP assay were used to detect the PER2 methylation level of 81 patients with leukemia, and the samples with inconsistent detection results of the two assays were sent to pyromethylation sequencing to evaluate the clinical detection performance. RESULTS: The minimum detection limit of TaqMan real-time FQ-MSP assay for detecting PER2 methylation level established in this study was 6 copies/uL, and the coefficient of variation(CV) of intra-assay and inter-assay was less than 3%. Compared with the conventional MSP assay, it has higher analytical sensitivity. For the samples with inconsistent detection results, the results of pyrosequencing and TaqMan real-time FQ-MSP assay are consistent. CONCLUSION: TaqMan real-time FQ-MSP assay of PER2 methylation established in this study has high detection performance and can be used for the detection of clinical samples.

Contralesional Structural Plasticity in Different Molecular Pathologic Subtypes of Insular Glioma.

Neuroplasticity may preserve neurologic function in insular glioma, thereby improving prognosis following resection. However, the anatomic and molecular bases of this phenomenon are not known. To address this gap in knowledge, the present study investigated contralesional compensation in different molecular pathologic subtypes of insular glioma by high-resolution three-dimensional T1-weighted structural magnetic resonance imaging. A total of 52 patients with insular glioma were examined. We compared the gray matter volume (GMV) of the contralesional insula according to histological grade [low-grade glioma (LGG) and high-grade glioma (HGG)] and molecular pathology status [isocitrate dehydrogenase (IDH) mutation, telomerase reverse-transcriptase (TERT) promoter mutation, and 1p19q codeletion] by voxel-based morphometry (VBM). A cluster of 320 voxels in contralesional insula with higher GMV was observed in glioma with IDH mutation as compared to IDH wild-type tumors by region of interest-based VBM analysis (family-wise error-corrected at p < 0.05). The GMV of the entire contralesional insula was also larger in insular glioma patients with IDH mutation than in patients with wild-type IDH. However, there was no association between histological grade, TERT promoter mutation, or 1p19q codeletion and GMV in the contralesional insula. Thus, IDH mutation is associated with greater structural compensation in insular glioma. These findings may be useful for predicting neurocognitive and functional outcomes in patients undergoing resection surgery.