Glioblastoma (GBM) is a notoriously lethal brain tumor, primarily owing to its inevitable resistance to temozolomide (TMZ), a frontline chemotherapy. Hypoxia-driven metabolic adaptations have been implicated in therapeutic failure; however, the role of circular RNAs remains largely underexplored. By integrating multiomics profiling with functional assays in patient-derived GBM cells, orthotopic xenografts, and clinical specimens, this study aimed to elucidate the role of hypoxia-induced hsa_circ_0000745 (circSPECC1) in mediating TMZ resistance. Mechanistic investigation included RNA pulldown, RIP, glycolysis flux analysis, and DNA damage assessment. The circSPECC1 is overexpressed in GBM and correlates with poor prognosis. Hypoxia triggers HIF-1α-mediated transcriptional upregulation of circSPECC1, which scaffolds insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) to stabilize phosphoglycerate kinase 1 (PGK1) mRNA. Importantly, circSPECC1/PGK1 axis activation enhances glycolytic flux, blunts TMZ-induced DNA damage, and confers chemoresistance. Targeting circSPECC1 disrupts PGK1-driven glycolysis, restores TMZ sensitivity, and synergizes with TMZ to extend survival in orthotopic GBM models. In conclusion, this study identifies a previously uncharacterized HIF-1α/circSPECC1/IGF2BP2/PGK1 axis that drives metabolic adaptation and TMZ resistance in GBM. Targeting this axis overcomes acquired chemoresistance, positioning circSPECC1 as both a prognostic biomarker and a therapeutic vulnerability in hypoxic GBM niches.

Fecal microbiota transplantation (FMT), aimed at rebuilding gut microbiota, has been proposed as a potential therapeutic approach to central nervous system (CNS) diseases. However, the therapeutic effects of FMT against demyelination-related white matter injury (WMI) have not yet been clarified under chronic cerebral hypoperfusion (CCH) condition. We therefore explored the potential roles and mechanisms of FMT on CCH-induced WMI, focusing on myelin integrity, axonal survival, and oligodendrogenesis. FMT restored mitochondrial electron transport chain (ETC) complex I-V activities and promoted the changes of pyruvate metabolism from lactate-generated to acetyl-CoA-generated mode, strengthening mitochondrial ATP production. Furthermore, FMT mitigated CCH-induced demyelination and axonal degeneration, effects mediated in part by oligodendrogenesis-dependent remyelination. Moreover, FMT altered CCH-induced gut microbiota composition by increasing the proportions of some bacterial groups including Verrucomicrobiae, Akkermansiaceae, Verrucomicrobiales, Verrucomicrobiota, Akkermansia, and Akkermansia_muciniphila. These gut microbiota were strongly associated with elevated fecal levels of L-tryptophan, 5-hydroxyindoleacetic acid, and N-a-acetylcitrulline, as well as with increased hippocampal concentrations of L-arginine, L-glutamine, N2-succinyl-L-ornithine, N-acetylornithine, indolepyruvate, indoleacetaldehyde, kynurenic acid, 11, 12-EET, 11, 12-DiHETrE and prostaglandin A2, which were almost involved in tryptophan and arginine related metabolism pathways. This study highlights the beneficial effects of FMT strategy in response to demyelination-mediated WMI under chronic cerebral ischemia condition.

Objective: To evaluate the effectiveness of graded nursing based on the risk early warning concept in long-term bedridden patients. Methods: The medical records of 124 long-term bedridden patients admitted to the Department of Orthopaedics at the Yongzhou Hospital of Traditional Chinese Medicine from April 2022 to March 2024 were collected retrospectively. Patients were separated into two groups: the control group which received routine nursing, and the study group which received graded nursing based on the "risk early warning" concept. Key metrics recorded included turnover frequency and time to first out-of-bed activity, Braden score, incidence of pressure injury (PI), activities of daily living (ADL), motor function, quality of life, negative emotions, complications, and patient satisfaction. Results: Low Barden score was a risk factor for PI in long-term bedridden patients (P<0.05, OR=0.040, 95% CI: 0.006-0.254). The turnover interval time and the time to first out-of-bed activity in the study group were shorter than those of the control group (all P<0.05). Compared to the control group, the Braden score, modified Barthel index score, Fugl-Meyer assessment score and quality of life scores of the study group were substantially higher (all P<0.05). The incidence of PI in the study group (4.62%) was lower than that of the control group (22.03%), and the area of PI in the study group was smaller than that of the control group (all P<0.05). Compared to the control group, the scores of self-rating anxiety scale and self-rating depression scale in the study group were substantially lower (all P<0.05). The study group had lower total incidence of complications (3.08% vs. 20.34%) and higher total satisfaction (95.38% vs. 79.66%) than the control group (all P<0.05). Conclusion: Graded nursing based on the risk early warning concept is highly effective in managing long-term bedridden patients. It reduces the occurrence of PI and complications, shortens the turnover interval time and the time to first out-of-bed activity, improves activities of daily living and motor function as well as quality of life, relieves negative emotions, and improves patient satisfaction.

Hypoxic microenvironments are intricately linked to malignant characteristics of glioblastoma multiforme (GBM). Long non-coding ribonucleic acids (lncRNAs) have been reported to be involved in the progression of GBM and closely associated with hypoxia. Nevertheless, the differential expression profiles as well as functional roles of lncRNAs in GBM cells under hypoxic conditions remain largely obscure. We explored the expression profiles of lncRNAs in hypoxic U87 cells as well as T98G cells using sequencing analysis. The effect of differentially expressed lncRNAs (DElncRNAs) was assessed through bioinformatic analysis. Furthermore, the expression of lncRNAs significantly dysregulated in both U87 and T98G cells was further validated using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Relevant cell functional experiments were also conducted. We used predicted RNA-binding proteins (RBPs) to construct an interaction network via the interaction prediction module. U87 and T98G cells showed dysregulation of 1115 and 597 lncRNAs, respectively. Gene Ontology (GO) analysis indicated that altered lncRNA expression was associated with nucleotide-excision repair and cell metabolism in GBM cells. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed the association between dysregulated lncRNAs and the Hippo signaling pathway under hypoxia. The dysregulation of six selected lncRNAs (ENST00000371192, uc003tnq.3, ENST00000262952, ENST00000609350, ENST00000610036, and NR_046262) was validated by qRT-PCR. Investigation of lncRNA-microRNA (miRNA)-mRNA networks centered on HIF-1α demonstrated cross-talk between the six validated lncRNAs and 16 related miRNAs. Functional experiments showed the significant inhibition of GBM cell proliferation, invasion, and migration by the knockdown of uc003tnq.3 in vitro. Additionally, uc003tnq.3 was used to construct a comprehensive RBP-transcription factor (TF)-miRNA interaction network. The expression of LncRNAs was dysregulated in GBM cells under hypoxic conditions. The identified six lncRNAs might exert important effect on the development of GBM under hypoxic microenvironment.

Increasing attention has recently been focused on reducing abnormal neuroexcitability in patients with Meige’s syndrome using nerve combing surgery. However, nerve injury caused by nerve combing is of critical concern. Animal studies have shown that stem cells can repair cranial nerves; autologous adipose-derived mesenchymal stem cells have been proved to be safe and effective in clinical trials. A total of 38 patients with Meige’s syndrome were enrolled in this prospective nonrandomized controlled study and divided into a non–stem cell group (n = 30) and a stem cell group (n = 8). Patients in the non-stem cell group underwent facial and trigeminal nerve combing only; patients in the stem cell group underwent adipose-derived mesenchymal stem cell implantation after facial and trigeminal nerve combing. A blepharospasm disability index score was used to evaluate effectiveness of the surgery, and a House–Brackmann grade was used to evaluate facial nerve injury. These data were recorded before the operation and at 7 days, 3 months, and 6 months after the operation. The overall improvement percentage of blepharospasm was 93% at 6-month follow-up in the non-stem cell group. A greater number of nerve combing events during the operation led to better outcomes but increased risk of facial paralysis. Patients in the stem cell group had better facial nerve function at the 6-month follow-up (House–Brackmann grade, P = 0.003) and better blepharospasm improvement at 3 and 6 months than those in the non–stem cell group (blepharospasm disability index score, P = 0.003 and P < 0.001, respectively). Cerebrospinal fluid protein analysis showed that levels of several cytokines were significantly increased after adipose-derived mesenchymal stem cell transplantation, including interleukin-6 (P < 0.01) and interferon gamma-induced protein 10 (P < 0.0001) and the growth factors insulin-like growth factor-1 (P < 0.0001), insulin-like growth factor-binding protein-1 (P < 0.0001), growth/differentiation factor-15 (P < 0.001), and angiopoietin-like 4 (P < 0.001). Facial and trigeminal nerve combing combined with adipose-derived mesenchymal stem cell transplantation is a safe and effective remedy to improve recovery from Meige’s syndrome.

Background Ring enhancement on magnetic resonance imaging (MRI) is an important characteristic of GBM. Though patients suffering from glioblastoma multiforme (GBM) with BRAF mutation (MUT BRAF) in V600E benefit from BRAF-targeted inhibitors, the relationship between ring enhancement and MUT BRAF remains elusive. The purpose of this study was to investigate the relationship between BRAF mutation status and the appearance of ring enhancement so as to guide preoperative targeted therapy for MUT BRAF GBM. Methods Patient’s population, clinical data and characteristic ring enhancement appearances on MRI were compared between GBM with MUT BRAF and GBM with WT BRAF. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the differential diagnostic significance. A nomogram was developed to predict the mutation status of BRAF. Moreover, all the variables were re-analyzed between epithelioid GBM (E-GBM) with or without MUT BRAF. Results Compared to GBM with WT BRAF, GBM with MUT BRAF had specific ring enhancement appearances with multiple rings, multiple located lobes, regular shape of ring, uniform thickness of ring and smaller diameter of ring. Area under the curve (AUC) of all the variables’ combination was 0.929. The nomogram was developed and validated. The re-analyzed results between E-GBM with or without MUT BRAF were similar to these above. AUC of the combination of quantity of ring, quantity of located lobe and shape of ring was 0.962. Conclusion The characteristic ring enhancement appearances of GBM may play an important role in predicting BRAF mutation status preoperatively, especially in E-GBM. Further study with larger cases may provide more evidences to guide the pretreatment of targeted medicine for GBM patients with MUT BRAF in future.

BackgroundThe significant difference in prognosis between IDH1 wild-type and IDH1 mutant glioblastoma multiforme (GBM) may be attributed to their metabolic discrepancies. Hence, we try to construct a prognostic signature based on glycolysis-related genes (GRGs) for IDH1-associated GBM and further investigate its relationships with immunity.MethodsDifferentially expressed GRGs between IDH1 wild-type and IDH1 mutant GBM were screened based on the TCGA database and the Molecular Signature Database (MSigDB). Consensus Cluster Plus analysis and KEGG pathway analyses were used to establish a new GRGs set. WGCNA, univariate Cox, and LASSO regression analyses were then performed to construct the prognostic signature. Then, we evaluated association of the prognostic signature with patients’ survival, clinical characteristics, tumor immunogenicity, immune infiltration, and validated one hub gene.Results956 differentially expressed genes (DEGs) between IDH1 wild-type and mutant GBM were screened out and six key prognostically related GRGs were rigorously selected to construct a prognostic signature. Further evaluation and validation showed that the signature independently predicted GBM patients’ prognosis with moderate accuracy. In addition, the prognostic signature was also significantly correlated with clinical traits (sex and MGMT promoter status), tumor immunogenicity (mRNAsi, EREG-mRNAsi and HRD-TAI), and immune infiltration (stemness index, immune cells infiltration, immune score, and gene mutation). Among six key prognostically related GRGs, CLEC5A was selected and validated to potentially play oncogenic roles in GBM.ConclusionConstruction of GRGs prognostic signature and identification of close correlation between the signature and immune landscape would suggest its potential applicability in immunotherapy of GBM in the future.

ObjectiveTraumatic subdural effusion (TSE) is a common complication of traumatic brain injury (TBI). This study aimed to determine the risk factors associated with subdural effusion and to propose a nomogram to predict the risk of TSE in patients with mild TBI.MethodsWe retrospectively analyzed 120 patients with mild TBI between January 2015 and December 2020 at the Third People's Hospital of Hefei. The risk factors of TSE were selected using univariate and multivariable logistic regression analysis. A nomogram was developed to predict the incidence of TSE. Receiver operating characteristics and calibration plots were used to evaluate the discrimination and fitting performance.ResultsOf the 120 patients, 32 developed subdural effusion after mild TBI. Univariate analysis showed that gender, age, history of hypertension, traumatic subarachnoid hemorrhage, subdural hematoma, basilar skull fracture, and cerebral contusion were varied significantly between groups (p < 0.05). Logistic multivariate regression analysis showed that the gender, age, history of hypertension, and basilar skull fracture were independent risk factors for TSE. Based on these results, a nomogram model was developed. The C-index of the nomogram was 0.78 (95% CI: 0.70–0.87). The nomogram had an area under the receiver operating characteristic curve of 0.78 (95% CI: 0.70–0.87). The calibration plot demonstrated the goodness of fit between the nomogram predictions and actual observations.ConclusionGender, age, history of hypertension, and basilar skull fracture can be used in a nomogram to predict subdural effusion after mild TBI.

The hypoxia microenvironment is highly associated with GBM’s malignant phenotypes. CircRNAs were reported involved in GBM’s biological characteristics and regulated by HIF-1α. However, the differential expression profile and role of circRNAs in GBM cells under hypoxia are still unclear. The expression profiles of circRNAs in LN229 and T98G under hypoxia were explored via circRNA sequencing analysis. Those circRNAs significantly dysregulated both in LN229 and T98G and could be found in circBase were selected and validated by qRT-PCR, RNase R digestion reaction, and Sanger sequencing. Normal cell line and fresh GBM tissues were also used for qRT-PCR validation. The roles of differentially expressed circRNAs were evaluated by bioinformatics analyses. There were 672 dysregulated circRNAs in LN229 and 698 dysregulated circRNAs in T98G. GO analysis indicated that the alteration of circRNA expression related to GBM cell’s biogenesis and metabolism. KEGG analysis demonstrated that TGF-β signaling pathway, HIF-1 signaling pathway, and metabolism-related signaling pathway were closely associated with differentially expressed circRNAs under hypoxia. These results were confirmed by GSEA analysis. The 6 selected and dysregulated circRNAs both in LN229 and T98G including hsa_circ_0000745, hsa_circ_0020093, hsa_circ_0020094, hsa_circ_0000943, hsa_circ_0004874, and hsa_circ_0002359 were validated by qRT-PCR. Inhibition of hsa_circ_0000745 inhibited GBM cell’s proliferation, migration, and invasion. HIF-1α centered circRNA-miRNA-mRNA networks analysis showed that the 6 validated circRNAs could cross-talk with 11 related miRNAs. The circRNA expressions are dysregulated in GBM cell under hypoxia. The 6 validated circRNAs could participate in GBM’s development and progression when hypoxia occurs. They might be the candidates for prognostic markers and adjuvant therapeutics of GBM in the future.

OBJECTIVE:CTNNB1-targeted inhibitor is demonstrated to be an effective neoadjuvant therapy in adamantinomatous craniopharyngioma (ACP) patients and cystic degeneration is a canonical sign of pediatric ACP. This study aimed to investigate the relationship between the cystic performances and CTNNB1 mutation (CTNNB1 MUT) status so as to analyze the possible diagnostic criteria of CTNNB1 MUT in pediatric cystic ACP (PCACP).METHODS:Patient's population, clinical characteristics, tissue samples and MRI data were collected and summarized in PCACP patients. The results were compared between CTNNB1 MUT and CTNNB1 wild-type (WT) groups according to the Sanger sequencing. MRI features of the cyst were also recorded. The receiving operating characteristic (ROC) curve analysis was applied to evaluate the differential diagnostic value.RESULTS:19 of the 61 patients manifested CTNNB1 MUT PCACP and 42 patients were CTNNB1 WT PCACP. Multiple cysts, irregular shape of cyst, hypo-intense interior signal of cyst on non-contrast T1W1, compression with optic chiasm and pituitary stalk and enhancement signal of cystic wall have been demonstrated in CTNNB1 MUT PCACP patients on MRI. Only the Area under the curve (AUC) values of quantity of cyst, shape of cyst and interior signal of cyst on non-contrast T1W1 were over 0.7. For criteria based on the combination of the 6 characteristic features, the AUC value was 0.928.CONCLUSION:Preoperative MRI may provide an effective value in predicting PCACP patients with CTNNB1 MUT and offer potential evidence for preoperative management with molecular targeted agents.

BACKGROUND: Glycolysis is an important metabolic manner in glioblastoma multiforme (GBM)'s rapid growth. It has been reported that glutamate-oxaloacetate transaminase 1 (GOT1) is low-expressed in GBM and patients with high-expressed GOT1 have better prognosis. However, the effect and mechanism of GOT1 on glycolysis and malignant phenotypes of GBM cells are still unclear. METHODS: The expression differences of GOT1 between GBM parenchyma and adjacent tissues were detected. The prognosis and clinical data with different levels of GOT1 were also analyzed. The glucose consumption, production of lactate and pyruvate were measured after GOT1 was knocked down or overexpressed. The effects of GOT1 on GBM cell's malignant phenotypes were analyzed by Western blot, CCK-8 assay, and flow cytometry. The relationship between GOT1 and pyruvate carboxylase (PC) was examined by immunoprecipitation and immunofluorescence. RESULTS: GOT1 was expressed little in GBM, and patients with highly expressed GOT1 had longer survival periods. Overexpressed GOT1 inhibited the glycolysis and malignant phenotypes of GBM cells. 2-DG treatment could partially reverse the enhancement of malignant phenotypes caused by knockdown of GOT1. The expression of GOT1 was positively correlated with PC. The inhibitory effect of GOT1 on glycolysis could be partially reversed by PC's knockdown.-BACKGROUND: Glycolysis is an important metabolic manner in glioblastoma multiforme (GBM)'s rapid growth. It has been reported that glutamate-oxaloacetate transaminase 1 (GOT1) is low-expressed in GBM and patients with high-expressed GOT1 have better prognosis. However, the effect and mechanism of GOT1 on glycolysis and malignant phenotypes of GBM cells are still unclear. -METHODS: The expression differences of GOT1 between GBM parenchyma and adjacent tissues were detected. The prognosis and clinical data with different levels of GOT1 were also analyzed. The glucose consumption, production of lactate and pyruvate were measured after GOT1 was knocked down or overexpressed. The effects of GOT1 on GBM cell's malignant phenotypes were analyzed by Western blot, CCK-8 assay, and flow cytometry. The relationship between GOT1 and pyruvate carboxylase (PC) was examined by immunoprecipitation and immunofluorescence. -RESULTS: GOT1 was expressed little in GBM, and patients with highly expressed GOT1 had longer survival periods. Overexpressed GOT1 inhibited the glycolysis and malignant phenotypes of GBM cells. 2-DG treatment could partially reverse the enhancement of malignant phenotypes caused by knockdown of GOT1. The expression of GOT1 was positively correlated with PC. The inhibitory effect of GOT1 on glycolysis could be partially reversed by PC's knockdown. CONCLUSIONS: GOT1 could impair glycolysis by interacting with PC and further inhibit the malignant phenotypes of GBM cells.

Objective: The aim of this study was to explore the possible pathogenesis of primary hemifacial spasm (HFS) according to the performances of preoperative high-resolution magnetic resonance (MR) sequence and investigate the correlations between the neuroimaging parameters and the prognosis of microvascular decompression (MVD). Methods: 106 patients with HFS and 121 age-matched and gender-matched healthy controls (HCs) were included in this study. Electronic medical records and neuroimaging data were collected. The facial-nerve angle, cross-sectional area of CPA cistern and length of the cistern segment of the facial nerve were measured on affected side and unaffected as well as healthy individuals. The receiver operating characteristic curve was used for assessing the predictive performances. Results: 100 patients achieved complete relief postoperatively. 13 of the 100 complete relief patients developed a relapse in the follow-up. The preoperative facial-pontine angle and cross-sectional area of the CPA cistern on the affected side was significantly smaller than the unaffected side and HC. The facial-pontine angle and the cross-sectional area of the CPA cistern was significantly smaller in recurrent group than the non-recurrent group. The AUC value of both facial-pontine angle and cross-sectional area of the CPA cistern were over 0.7. Conclusion: Small facial-nerve angle and cross-sectional area of CPA cistern may be regarded as the possible pathogenesis of primary HFS. The measurement of facial-nerve angle and cross-sectional area of CPA cistern preoperatively might be used to predict the surgical effect of MVD.

PURPOSE:To compare the different levels of inflammatory markers, hormone markers, and radiological appearances between PCACP with and without calcification so as to explore the relationships between these markers and calcification.METHODS:The inflammatory markers, hormone markers, and radiological appearances were compared not only between PCACP with and without calcification, but also among its different forms of calcification. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic significance of all markers between these groups.RESULTS:It was showed that the white blood cell (WBC) count, neutrophil count, monocyte count, prognostic nutritional index (PNI), prolactin (PRL), and T1WI signal of cysts were higher in PCACP with calcification than in PCACP without calcification. The neutrophil count was significantly higher in PCACP with eggshell calcification than in other groups. The PCACP with mixed calcification had the highest PRL level in all kinds of PCACP with calcification. Only the area under curve (AUC) values of neutrophil count and PRL level were greater than 0.8.CONCLUSION:It is found that inflammation and hormone are related to PCACP's calcification. High neutrophil count and PRL level may indicate possible calcification tendency in PCACP. Improved intracystic therapies based on these results may help to inhibit the formation of calcification in PCACP in future.

To compare the different levels of preoperative inflammatory markers in peripheral blood samples between craniopharyngioma (CP) and other sellar region tumors so as to explore their differential diagnostic value. The level of white blood cell (WBC), neutrophil, lymphocyte, monocyte, platelet, albumin, neutrophil lymphocyte ratio (NLR), derived NLR (dNLR), platelet lymphocyte ratio (PLR), monocyte lymphocyte ratio (MLR) and prognostic nutritional index (PNI) were compared between the CP and other sellar region tumors. A receiver operating characteristics (ROC) curve analysis was performed to evaluate the diagnostic significance of the peripheral blood inflammatory markers and their paired combinations for CP including its pathological types. Patients with CP had higher levels of pre-operative WBC, lymphocyte and PNI. The papillary craniopharyngioma (PCP) group had higher neutrophil count and NLR than the adamantinomatous craniopharyngioma (ACP) and healthy control groups whereas the ACP group had higher platelet count and PNI than the PCP and healthy control groups. There were not any significant differences in preoperative inflammatory markers between the primary and recurrent CP groups. The AUC values of WBC, neutrophil, NLR + PLR and dNLR + PLR in PCP were all higher than 0.7. Inflammation seems to be closely correlated with CP’s development. The preoperative inflammatory markers including WBC, neutrophil, NLR + PLR and dNLR + PLR may differentially diagnose PCP, pituitary tumor (PT) and Rathke cleft cyst (RCC). In addition, some statistical results in this study indirectly proved previous experimental conclusions and strictly matched CP’s biological features.

OBJECTIVE Glioma is the most common form of brain tumor and has high lethality. The authors of this study aimed to elucidate the efficiency of preoperative inflammatory markers, including neutrophil/lymphocyte ratio (NLR), derived NLR (dNLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and prognostic nutritional index (PNI), and their paired combinations as tools for the preoperative diagnosis of glioma, with particular interest in its most aggressive form, glioblastoma (GBM). METHODS The medical records of patients newly diagnosed with glioma, acoustic neuroma, meningioma, or nonlesional epilepsy at 3 hospitals between January 2011 and February 2016 were collected and retrospectively analyzed. The values of NLR, dNLR, PLR, LMR, and PNI were compared among patients suffering from glioma, acoustic neuroma, meningioma, and nonlesional epilepsy and healthy controls by using nonparametric tests. Correlations between NLR, dNLR, PLR, LMR, PNI, and tumor grade were analyzed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic significance of NLR, dNLR, PLR, LMR, PNI, and their paired combinations for glioma, particularly GBM. RESULTS A total of 750 patients with glioma (Grade I, 81 patients; Grade II, 208 patients; Grade III, 169 patients; Grade IV [ GBM], 292 patients), 44 with acoustic neuroma, 271 with meningioma, 102 with nonlesional epilepsy, and 682 healthy controls were included in this study. Compared with healthy controls and patients with acoustic neuroma, meningioma, or nonlesional epilepsy, the patients with glioma had higher values of preoperative NLR and dNLR as well as lower values of LMR and PNI, whereas PLR was higher in glioma patients than in healthy controls and patients with nonlesional epilepsy. Subgroup analysis revealed a positive correlation between NLR, dNLR, PLR, and tumor grade but a negative correlation between LMR, PNI, and tumor grade in glioma. For glioma diagnosis, the area under the curve (AUC) obtained from the ROC curve was 0.722 (0.697-0.747) for NLR, 0.696 (0.670-0.722) for dNLR, 0.576 (0.549-0.604) for PLR, 0.760 (0.738-0.783) for LMR, and 0.672 (0.646-0.698) for PNI. The best diagnostic performance was obtained with the combination of NLR+LMR and dNLR+LMR, with AUCs of 0.777 and 0.778, respectively. Additionally, NLR (AUC 0.860, 95% CI 0.832-0.887), dNLR (0.840, 0.810-0.869), PLR (0.678, 0.641-0.715), LMR (0.837, 0.811-0.863), and PNI (0.740, 0.706-0.773) had significant predictive value for GBM compared with healthy controls and other disease groups. As compared with the Grade I-III glioma patients, the GBM patients had an AUC of 0.811 (95% CI 0.778-0.844) for NLR, 0.797 (0.763-0.832) for dNLR, 0.662 (0.622-0.702) for PLR, 0.743 (0.707-0.779) for LMR, and 0.661(0.622-0.701) for PNI. For the paired combinations, NLR+LMR demonstrated the highest accuracy. CONCLUSIONS The NLR+LMR combination was revealed as a noninvasive biomarker with relatively high sensitivity and specificity for glioma diagnosis, the differential diagnosis of glioma from acoustic neuroma and meningioma, GBM diagnosis, and the differential diagnosis of GBM from low-grade glioma.

Craniopharyngiomas (CPs) are usually benign, non-metastasizing embryonic malformations originating from the sellar area. They are, however, locally invasive and generate adherent interfaces with the surrounding brain parenchyma. Previous studies have shown the tumor microenvironment is characterized by a local abundance of adenosine triphosphate (ATP), infiltration of leukocytes and elevated levels of pro-inflammatory cytokines that are thought to be responsible, at least in part, for the local invasion. Here, we examine whether ATP, via the P2X7R, participates in the regulation of cytokine expression in CPs. The expression of P2X7R and pro-inflammatory cytokines were measured at the RNA and protein levels both in tumor samples and in primary cultured tumor cells. Furthermore, cytokine modulation was measured after manipulating P2X7R in cultured tumor cells by siRNA-mediated knockdown, as well as pharmacologically by using selective agonists and antagonists. The following results were observed. A number of cytokines, in particular IL-6, IL-8 and MCP-1, were elevated in patient plasma, tumor tissue and cultured tumor cells. P2X7R was expressed in tumor tissue as well as in cultured tumor cells. RNA expression as measured in 48 resected tumors was positively correlated with the RNA levels of IL-6, IL-8 and MCP-1 in tumors. Furthermore, knockdown of P2X7R in primary tumor cultures reduced, and stimulation of P2XR7 by a specific agonist enhanced the expression of these cytokines. This latter stimulation involved a Ca2+-dependent mechanism and could be counteracted by the addition of an antagonist. In conclusion, the results suggest that P2X7R may promote IL-6, IL-8 and MCP-1 production and secretion and contribute to the invasion and adhesion of CPs to the surrounding tissue.

Periostin (POSTN) is an extracellular matrix protein (ECM) critical for epithelial–mesenchymal transitions (EMT) in several kinds of tumor cells. Previous studies have indicated that EMT exists in craniopharyngioma (CP), and expression of POSTN is a significant factor in the prognosis of CP. However, it has never been explored whether POSTN exists in CP, or how it activates CP's EMT. The expression of POSTN was examined in adamantinomatous craniopharyngioma (ACP) primary cells and tissues by immunohistochemistry, PCR and Western blot, respectively. The effects and mechanisms of POSTN on ACP cells' EMT were also analyzed. It was found that POSTN expression increased in ACP-associated fibroblasts. Overexpressed POSTN significantly elevated the EMT of ACP cells by regulating the expression of associated genes. More importantly, our further study revealed that the upregulated POSTN activated Akt signaling pathway to regulate the EMT. This study showed that POSTN is responsible for the EMT of ACP cells, and POSTN might be a potential molecular therapeutic target for ACP treatment in future.

Objective To investigate the clinical factors influencing prognosis of glioblastoma multiforme (GBM).Methods This study included 198 patients with newly diagnosed primary glioblastoma treated from January 2008 to January 2013 treated at our hospital.Kaplan-Meier method was used to analyze the 11 factors related to prognosis,with Cox multivariate regression analysis.Results Following a univariate regression analysis,with no epilepsy before operation,good preoperative Karnofsky performance status,location of tumor,extent of resection,postoperative Concurrent chemoradiotherapy and postoperative intracranial infection associated with better overall survival rates (P ＜ 0.05).Multivariate Cox regression analysis found that extent of resection,location of tumor,KPS,postoperative concurrent chemoradiotherapy and postoperative intracranial infection were independent prognostic factors for the survival (P ＜ 0.05).Conclusion Extent of resection,location of tumor,postoperative KPS,concurrent chemoradiotherapy were independent prognostic factors influencing the survival.It is likely that the patients with intracranial infection postoperatively have more prolonged survival because infection can stimulate immune response to tumor.

Objective Using new method to culture the craniopharyngioma cells in order to provide the foundation of clinical and basic researches on cell level. Methods Using new method to culture, purify and pass two pathological patterns of craniopharyngioma cells. The cells were identified by morphology under microscope, immunohistochemistry and proliferation assay. Results The craniopharyngioma cells cultured by the new method were seen around the tumor piece with better state and greater numbers than the cells cultured by the traditional method. These two kinds of cells were determined to be the craniopharyngioma cells. The proliferation assay showed that the cells were still proliferating and dividing in vitro. Conclusions Using new method which was simple and cheap to culture the craniopharyngioma cells could harvest better cells in state and greater in numbers. Though this method could not solve all the problems about cell culture of craniopharyngioma, it could still provide the foundation of clinical and basic researches about tumor biological characteristics on the cell level by establishment of a stable cell line.

Background A subgroup of meningioma demonstrates clinical aggressive behavior. We set out to determine if the radiological parameters can predict histopathological aggressive meningioma, and propose a classification to predict survival and aggressive meningioma behavior. Methods A retrospective review of medical records was conducted for patients who underwent surgical resection of their convexity meningioma. WHO-2007 grading was used for histopathological diagnosis. Preoperative radiologic parameters were analyzed, each parameter was scored 0 or 1. Signal intensity on diffusion weighted MRI (DWI) (hyperintensity=1), heterogeneity on T1-weighted gadolinium enhanced MRI (heterogeneity=1), disruption of arachnoid at brain-tumor interface=1and peritumoral edema (PTE) on T2-weighted MRI (presence of PTE=1) and tumor shape (irregular shape=1). Multivariate logistic regression analyses were conducted to determine association of radiological parameters to histopathological grading. Kaplan-Meier and Cox regression models were used to determine the association of scoring system to overall survival and progression free survival (PFS). Reliability of the classification was tested using Kappa co-efficient analysis. Results Hyperintensity on DWI, disruption of arachnoid at brain-tumor interface, PTE, heterogenicitiy on T1-weighted enhanced MRI and irregular tumor shape were independent predictors of non-grade I meningioma. Mean follow-up period was 94.6 months (range, 12-117 months). Median survival and PFS in groups-I, II and III was 114.1±1.2 and 115.7± 0.8, 88± 3.3 and 58.5±3.9, 43.2± 5.1 and 18.2±1.7 months respectively. In cox regression analysis model, age (P<0.0001, OR–1.039, CI-1.017-0.062), WHO non-grade-I meningioma (P=0.017, OR–3.014, CI-1.217-7.465), radiological classification groups II (P=0.002, OR–6.194, CI–1.956-19.610) and III (P<0.0001, OR–21.658, CI–5.701-82.273) were independent predictors of unfavorable survival outcomes. Conclusions Preoperative radiological classification can be used as a supplement to the histopathological grading. Group-I meningiomas demonstrate benign radiological, histopathological and clinical features; group-III demonstrates aggressive features. Group-II meningiomas demonstrate intermediate features; the need for more aggressive follow-up and/or treatment should be further investigated.