Machine learning unveils immune-related signature in multicenter glioma studies.

In glioma molecular subtyping, existing biomarkers are limited, prompting the development of new ones. We present a multicenter study-derived consensus immune-related and prognostic gene signature (CIPS) using an optimal risk score model and 101 algorithms. CIPS, an independent risk factor, showed stable and powerful predictive performance for overall and progression-free survival, surpassing traditional clinical variables. The risk score correlated significantly with the immune microenvironment, indicating potential sensitivity to immunotherapy. High-risk groups exhibited distinct chemotherapy drug sensitivity. Seven signature genes, including IGFBP2 and TNFRSF12A, were validated by qRT-PCR, with higher expression in tumors and prognostic relevance. TNFRSF12A, upregulated in GBM, demonstrated inhibitory effects on glioma cell proliferation, migration, and invasion. CIPS emerges as a robust tool for enhancing individual glioma patient outcomes, while IGFBP2 and TNFRSF12A pose as promising tumor markers and therapeutic targets.

Pan-cancer analysis revealed prognosis value and immunological relevance of RAMPs.

Whether receptor activity-modifying proteins (RAMPs) play a key role in human cancer prognosis and immunity remains unknown. We used data from the public databases, The Cancer Genome Atlas, Therapeutically Applicable Research to Generate Effective Treatments, and the Genotype-Tissue Expression project. We utilized bioinformatics methods, R software, and a variety of online databases to analyze RAMPs. In general, RAMPs were significantly and differentially expressed in multiple tumors, and RAMP expression was closely associated with prognosis, immune checkpoints, RNA-editing genes, tumor mutational burden, microsatellite instability, ploidy, and stemness indices. In addition, the expression of RAMPs is strongly correlated with tumor-infiltrating lymphocytes in human cancers. Moreover, the RAMP co-expression network is largely involved in many immune-related biological processes. Quantitative reverse transcription polymerase chain reaction and Western blot proved that RAMP3 was highly expressed in glioma, and RAMP3 promoted tumor proliferation and migration. RAMPs exhibit potential as prognostic and immune-related biomarkers in human cancers. Moreover, RAMPs can be potentially developed as therapeutic targets or used to enhance the efficacy of immunotherapy.

Mast cell activation mediates blood-brain barrier impairment and cognitive dysfunction in septic mice in a histamine-dependent pathway.

Introduction: Sepsis-associated encephalopathy (SAE) is a diffuse cerebral dysfunction resulting from a systemic inflammatory response to infection; however, its pathophysiology remains unclear. Sepsis-induced neuroinflammation and blood-brain barrier (BBB) disruption are crucial factors in brain function disturbance in SAE. Mast cells (MCs) activation plays an important role in several neuroinflammation models; however, its role in SAE has not been comprehensively investigated. Methods: We first established a SAE model by cecal ligation puncture (CLP) surgery and checked the activation of MCs. MCs activation was checked using immumohistochemical staining and Toluidine Blue staining. We administrated cromolyn (10mg/ml), a MC stabilizer, to rescue the septic mice. Brain cytokines levels were measured using biochemical assays. BBB disruption was assessed by measuring levels of key tight-junction (TJ) proteins. Cognitive function of mice was analyzed by Y maze and open field test. Transwell cultures of brain microvascular endothelial cells (BMVECs) co-cultured with MCs were used to assess the interaction of BMVECs and MCs. Results: Results showed that MCs were overactivated in the hippocampus of CLP-induced SAE mice. Cromolyn intracerebroventricular (i.c.v) injection substantially inhibited the MCs activation and neuroinflammation responses, ameliorated BBB impairment, improved the survival rate and alleviated cognitive dysfunction in septic mice. In vitro experiments, we revealed that MCs activation increased the sensitivity of BMVECs against to lipopolysaccharide (LPS) challenge. Furthermore, we found that the histamine/histamine 1 receptor (H1R) mediated the interaction between MCs and BMVECs, and amplifies the LPS-induced inflammatory responses in BMVECs by modulating the TLR2/4-MAPK signaling pathway. Conclusions: MCs activation could mediate BBB impairment and cognitive dysfunction in septic mice in a histamine-dependent pathway.

Electrocorticography-guided surgical treatment of solitary supratentorial cavernous malformations with secondary epilepsy.

OBJECTIVE: To evaluate the efficacy of electrocorticographic (ECoG) monitoring and the application of different surgical approaches in the surgical treatment of solitary supretentorial cavernous malformations with secondary epilepsy. METHODS: This study enrolled a consecutive series of 36 patients with solitary supratentorial cavernous malformations and secondary epilepsy who underwent surgery with intraoperative ECoG monitoring in the Department of Neurosurgery between January 2004 and January 2008. The patients were composed of 15 males and 21 females, aged between 8 and 52 years (mean age 27.3±2.8 years) at the time of surgery. Epilepsy history, the type of epilepsy at the presentation, lesion location, the incidence of residual epileptiform discharges, and postoperative outcomes were evaluated. RESULTS: Histopathological examination indicated cavernous malformations and hippocampal sclerosis in 36 and 5 cases, respectively. Neuronal degeneration, glial cell proliferation, and neurofibrillary tangles were found in all the resected cerebral tissues of extended lesionectomy of residual epileptic foci. Lesionectomy, anterior temporal lobectomy, anterior temporal lobectomy plus cortical thermocoagulation, extended lesionectomy, extended lesionectomy plus cortical thermocoagulation were performed in 4, 4, 1, 14, and 13 cases, respectively. Residual epileptiform discharges were captured in 9 out of the 14 patients who had additional cortical thermocoagulation. According to Engle class for postoperative outcomes, 27 cases were class I (75.00%), 5 were class II (13.89%), 2 were class III (5.56%), and 2 were class IV (5.56%), thus the total effective rate (class I+class II) was 88.89%. Neither of epilepsy history, the type of epilepsy, and the location of cavernous malformation was significantly related to outcomes (P>0.05). A significant relationship was found between the incidence of residual epileptiform discharges and outcomes (P=0.041). CONCLUSIONS: Intraoperative ECoG monitoring, the application of different surgical approaches, and the resection of residual epileptic foci could produce good result in the surgical treatment of supratentorial cavernous malformation with secondary epilepsy. Postoperative residual epileptiform discharges could be a useful predictor for evaluating the outcomes.

[Treatment of lesions in mesencephalic aqueduct and around it by neuroendoscope].

OBJECTIVE: To explore the surgical efficacy of lesions in mesencephalic aqueduct and around it with neuroendoscope. METHODS: A total of 14 cases with lesion underwent neuroendoscope. Endoscopic third ventriculostomy (ETV), excision or biopsy and mesencephalic aqueduct plasty were performed. RESULTS: There were primary obstruction (n = 4), glioma (n = 4), intraventricular cysticercosis (n = 2), pineal cell tumor (n = 1), lymphoma (n = 1), brain abscess (n = 1) and germinoma (n = 1). Postoperative cranial computed tomography (CT) and/or magnetic resonance imaging (MRI) showed narrowed ventricle. The outcomes were symptomatic improvement (n = 5), no change (n = 5), worsening (n = 4) and mortality (n = 0). CONCLUSION: ETV, lesion biopsy or partial lesion resection and aqueductal plasty are efficacious for the patients with lesions in mesencephalic aqueduct and around it.

Individual surgical treatment of intracranial arachnoid cyst in pediatric patients.

BACKGROUND AND AIM: Intracranial arachnoid cysts (IAC) are benign congenital cystic lesions filled with cerebrospinal fluid (CSF). This study evaluated microsurgical craniotomy and endoscopy in the surgical treatment of IAC. MATERIALS AND METHODS: Eight-one consecutive pediatric patients with IAC were surgically treated between January 2004 and January 2011. The surgical procedures included microsurgical craniotomy and endoscopy. Symptoms at presentation, location of IAC, surgical treatment options, and effectiveness were evaluated. RESULTS: There were 43 males and 38 females and the mean age was 8.7 years (range between 1 month and 14 years) at the time of surgery. The cyst location was supratentorial in 72 patients and infratentorial in 9 patients, arachnoid cyst were identified. Follow-up period ranged between 2 and 8 years. Of the 49 patients with headache 83.67% of patients had cure and 10.2% had significant improvement. Of the eight patients with hydrocephalus and gait disturbances, six (75%) had complete total relief of symptoms and two (25%) patients had significant improvement. Four of the six patients with cognitive decline and weakness showed improvement. Of the 18 patients with epilepsy seizure freedom was: Engle class I grade I in 14 (77.78%) patients; class II in 2 (11.11%) patients; and class III in 2 (11.11%) patients. Follow-up studies from 2 to 8 years showed that headache was cured in 41 of the 49 cases (83.67%), significantly improved in 5 cases (10.20%), and showed no variation in 3 cases (6.12%). Hydrocephalus and gait disturbances were controlled in six of the eight cases (75.00%) and significantly improved in two cases (25.00%). Cognitive decline and weakness were obviously improved in four of the six cases (66.67%) and exhibited no variation in two cases (33.33%). According to the Engle standard, the following results were obtained from 18 patients with epilepsy: Grade I in 14 cases (77.78%); grade II in 2 cases (11.11%); and grade III in 2 cases (11.11%). Eleven cases with local or general enlarged skull exhibited no further progression. On follow-up computed tomography (CT) scan, there was variable alleviation of mass effect in all the 81 patients. Cystic size was significantly reduced in 65 patients with supratentorial arachnoid cysts and in 9 patients with infratentorial archnoid cysts. Twenty-one patients who had decreased skull thickness, had no further progression. Four patients who had cranioplasty had good outcome. CONCLUSION: The endoscopic approach was highly effective for most cases of IAC, particularly for cysts in the suprasellar and quadrigeminal regions as well as in the posterior fossa. Microsurgical craniotomy was recommended for IAC in the extracerebral convexity and intracerebrum. Local skull cranioplasty is needed for patients, or patients with preoperative diagnosis showed signs of cystic tumor and cyst-related epilepsy.

Surgical treatment of intracranial arachnoid cyst in adult patients.

BACKGROUND: Intracranial arachnoid cyst (IAC) is a benign cystic lesion filled with cerebrospinal fluid (CSF). Different surgical treatments were evaluated to determine the most effective technique among several. MATERIALS AND METHODS: A consecutive series of 68 adult patients (43 males, mean age 30.3 years, range 18-42 years) with IAC were surgically treated between January 2004 and January 2011. The cysts were supratentorial in location in 53 and infratentorial in 15 patients. Symptoms at presentation, location of the IAC, surgical treatment modalities, and postoperative complications were evaluated. RESULTS: Of the 51 patients with headache, 44 (86.27%) patients had complete relief of the headache, five (9.80%) patients had significant improvement, and two (3.92%) had no worthwhile change. Three of the four patients with hydrocephalus and gait disturbances had relief of the symptoms and one patient had significant improvement. Of the five patients with cognitive decline and weakness, three (60.00%) patients showed improvement, and two (40.00%) patients had no significant change. Five (62.50%) of the eight patients with epilepsy had seizure remission, two (25.00%) patients had non-disabling seizures, and one had no change. Follow-up computed tomography (CT) scans showed variable change in the mass effect of IAC in 68 patients; cystic size was significantly reduced in 51 patients, no significant change in two patients of supratentorial arachnoid cysts. Cystic size was reduced in seven patients, but no significant change was observed in eight patients of infratentorial cysts. Three patients with enlarged head circumference had no further increase in the head circumference. CONCLUSION: Adult patients with IAC symptoms should be treated efficiently. Surgical treatment is associated with significant improvement in the symptoms and signs.

[Surgical treatment of neuroendoscopy with supported channel for hypertensive intraventricular hemorrhage].

OBJECTIVE: To evaluate the value and efficacy of surgical treatment with neuroendoscopy with supported channel for hypertensive intraventricular hemorrhage (HIVH). METHODS: The clinical data of 32 patients with hypertensive intraventricular hemorrhage were retrospectively analyzed. And they underwent neuroendoscopy with supported channel. RESULTS: Computed tomography scans at Day 1 postoperation revealed that the evacuation of intraventricular hematoma was 85.4% in all patients. The Glasgow coma score (GCS) at Week 1 postoperation was significantly higher than that at preoperation. The postoperative outcomes were intracranial infection (n = 1), mortality (n = 1) and secondary hemorrhage (n = 3). All patients were followed up for 3 months. According to Glasgow outcome scale (GOS), there were excellent recovery (n = 17), moderate disability (n = 7), severe disability (n = 5) and vegetative survival (n = 3). CONCLUSION: The surgical treatment of neuroendoscopy with supported channel for HIVH offers great advantages with a low rate of complications and favorable outcomes.