Development and Validation of Predicting Nomograms for Craniopharyngioma: A Retrospective, Multiple-Center, Cohort Study.

Craniopharyngiomas (CPs) are benign tumors arising from the sellar region. However, little is known about their clinical features and long-term recurrence due to low morbidity and the lack of large cohort studies. Thus, we aimed to develop nomograms to accurately predict the extent of resection and tumor recurrence using clinical parameters. A total of 545 patients diagnosed with CP between 2009 and 2019 were examined: 381 in the development cohort and 164 in the validation cohort. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were performed to establish two nomograms. Receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA) and Kaplan-Meier (KM) curves were used to evaluate their predictive performance and discriminative power, respectively, in the two cohorts. In addition, the EORTC QLQ-BN20 questionnaire was used to assess neuropsychological status in the follow-up. In the development cohort, the area under the curve (AUC) and C-index were 0.760 and 0.758, respectively, for predicting the extent of resection and 0.78 and 0.75, respectively, for predicting 3-year progression-free survival (PFS) and 5-year PFS. Additionally, the model had a predictive accuracy of 0.785. Both nomograms showed acceptable discrimination in the two cohorts. Moreover, DCA demonstrated excellent clinical benefits from the two nomograms. Finally, participants were classified into two distinct risk groups according to the risk score, and an online calculator was created for convenient clinical use. During long term follow-up, hypothyroidism (77.61%) and hypocortisolism (76.70%) were the most common endocrine dysfunction after surgery and significant deficits were observed concerning visual disorder, motor dysfunction and seizures in the recurrent groups. In particular, better quality of life was associated with gross total resection (GTR), postoperative radiation, anterior interhemispheric (AI) approach and transsphenoidal approach. To our knowledge, these are the first nomograms based on a very large cohort of patients with CP that show potential benefits for guiding treatment decisions and long-term surveillance. The current study demonstrated the online calculator serve as the practical tool for individual strategies based on the patient's baseline characteristics to achieve a better prognosis.

MiR-451 Promotes Cell Apoptosis and Inhibits Autophagy in Pediatric Acute Myeloid Leukemia by Targeting HMGB1.

MiR-451 plays a tumor suppressive role in a variety of cancers. However, the function of miR-451 in acute myeloid leukemia (AML) has not been fully understood. Herein, we focused on the effect of miR-451 in pediatric AML and its regulatory mechanism. MiR-451 and high mobility group box 1 (HMGB1) levels were tested in bone marrow of pediatric AML patients and healthy controls, and in AML cells and HS-5 cells by qRT-PCR and Western blot analysis. HL-60 and THP-1 cells were treated with miR-451 mimics, pcDNA-HMGB1, and corresponding controls. The changes in apoptosis and autophagy were evaluated in miR-451 overexpressed AML cells with MTT and flow cytometry. The interaction between miR-451 and HMGB1 was determined by dual-luciferase reporter assay, qRT-PCR, and Western blot. After cells were co-transfected with pcDNA-HMGB1 and pc-DNA-ctrl, we investigated apoptosis and autophagy in miR-451 overexpressed cells perturbed by exogenous HMGB1 through MTT, flow cytometry, and Western blot. miR-451's role in drug sensitivity was further measured. Pediatric AML bone marrow and cell lines presented low expression of miR-451 coupled with high expression of HMGB1. HMGB1 was determined to be a functional target of miR-451. MiR-451 overexpression remarkably enhanced apoptosis and reduced autophagy in both AML cell lines, which was reversed by pcDNA-HMGB1 transfection. Additionally, exogenous miR-451 significantly enhanced the sensitivity of HL-60 cells to the chemotherapy drug As2O3. MiR-451 exerted a tumor suppressive effect in enhancing cell death and reducing autophagy of AML cells by targeting HMGB1. MiR-451 might be considered a candidate target for treating pediatric AML.

Sphingosine-1-phosphate receptor 3 is implicated in BBB injury via the CCL2-CCR2 axis following acute intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a catastrophic cerebrovascular disease with high morbidity and mortality. Evidence demonstrated that sphingosine-1-phosphate receptor (S1PR) plays a vital role in inflammatory damage via the upregulation of CCL2 expression. However, whether S1PR3 is involved in blood-brain barrier (BBB) breakdown via CCL2 activation after ICH has not been described. METHODS: We investigated the expression profiles of all S1PRs using high-throughput RNA-seq analysis and RT-PCR. The potential role of S1PR3 and interaction between S1PR3 and CCL2 were evaluated via Western blotting, immunofluorescence, and flow cytometry. BBB disruption was examined via magnetic resonance imaging, transmission electron microscopy, and Evans blue extravasation. Microglial activation, proliferation, and polarization were assessed via histopathological analysis. The expression levels of CCL2, p-p38 MAPK, ICAM-1, and ZO-1 were examined in vitro and in vivo. RESULTS: The present results showed that the levels of S1PR3 and its ligand, sphingosine 1-phosphate (S1P), were dramatically increased following ICH, which regulated the expression of CCL2 and p38MAPK. Moreover, reductions in brain edema volume, amelioration of BBB integrity, and improvements in behavioral deficits were achieved after the administration of CAY10444, an S1PR3 antagonist, to rats. Remarkably increased CCL2, p-p38MAPK, and ICAM-1 expression and decreased ZO-1 expression were observed in cocultured human astrocytes (HAs) and hCMEC/D3 cells after S1P stimulation. However, the expression levels of CCL2, p-p38 MAPK, and ICAM-1 were decreased and ZO-1 expression was increased after S1PR3 inhibition. In addition, microglial proliferation and M1 polarization were attenuated after CAY10444 administration. CONCLUSION: To the best of our knowledge, this is the first demonstration of the neuroprotective role of S1PR3 modulation in maintaining BBB integrity by inhibiting the S1PR3-CCL2 axis after ICH, providing a novel treatment for ICH by targeting S1PR3.

Identification and Characterization of TF-lncRNA Regulatory Networks Involved in the Tumorigenesis and Development of Adamantinomatous Craniopharyngioma.

Craniopharyngiomas (CPs) are rare tumors arising from the sellar region. Although the best outcome for patients with one subtype, adamantinomatous craniopharyngioma (ACP), is obtained by gross total resection, little is known about the roles of long noncoding RNAs (lncRNAs) and transcription factors (TFs) in ACP tumorigenesis. In total, 12 human ACP and 5 control samples were subjected to transcriptome-level sequencing. We built an integrated algorithm for identifying lncRNAs and TFs regulating the CP-related pathway. Furthermore, ChIP-Seq datasets with binding domain information were used to further verify and identify TF-lncRNA correlations. RT-PCR and immunohistochemistry staining were performed to validate the potential targets. Five pathways associated with ACP were identified and defined by an extensive literature search. Based on the specific pathways and the whole gene expression profile, 266 ACP-related lncRNAs and 39 TFs were identified by our integrating algorithm. Comprehensive analysis of the ChIP-Seq datasets revealed that 29 TFs were targeted by 12000 lncRNAs in a wide range of tissues, including 161 ACP-related lncRNAs that were identified by the computational method. These 29 TFs and 161 lncRNAs, constituting 1004 TF-lncRNA pairs, were shown to potentially regulate different ACP-related pathways. A total of 232 TF-lncRNA networks were consequently established based on differential gene expression. Validation by RT-PCR and immunohistochemistry staining revealed positive expression of the ACP-related TFs E2F2 and KLF5 in ACP. Moreover, the expression of the lncRNA RP11-360P21.2 was shown to be upregulated in ACP tissues. In this study, we introduced an integrated algorithm for identifying lncRNAs and TFs regulating the ACP-related pathway. This is the first comprehensive study to systematically investigate the potential TF and lncRNA regulatory network in ACP. The resulting data serve as a valuable resource for understanding the mechanisms underlying ACP-related lncRNAs and TFs.

Chemokine CCL2 contributes to BBB disruption via the p38 MAPK signaling pathway following acute intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) remains a devastating type of stroke that lacks an effective treatment. Recent evidence has demonstrated that CCL2 is involved in the blood-brain barrier (BBB) disruption and propagermanium (PG) as a CCL2 receptor inhibitor is neuroprotective in ischemic stroke. However, whether PG therapy exert effective role in acute ICH still unclear. In this study, our goal was to investigate the potential role of CCL2 and the effects of PG in ICH. Differentially expressed RNAs including CCL2 were detected in human ICH. CCL2 and the activation of p-p38 MAPK and AQP4 expression were analyzed in rats after ICH. Brain water content and BBB integrity as well as neurological function were also examined after PG administration. In addition, the mechanism by which CCL2-mediated BBB injury was further investigated by cell coculture. Our findings showed that PG could effectively reduce brain edema and improve neurobehavioral functions. p-p38 MAPK and AQP4 expression were significantly inhibited by PG in vivo and in vitro. To the best of our knowledge, this is the first demonstration of PG in neuroprotecting the BBB integrity by inhibition of CCL2-CCR2-p38 MAPK pathway following ICH, targeting CCL2 could be developed as a novel treatment for hemorrhagic stroke.

A novel neuroimaging assessment of predictive risk factors associated with intraoperative massive hemorrhage in intracranial solid hemangioblastoma.

BACKGROUND: A solid hemangioblastoma (SH) is a benign and highly vascularized tumor. Microsurgical treatment of SH is still challenging due to excessive intraoperative bleeding. METHODS: Sixty-six consecutive patients with SH were retrospectively analyzed. The volume of intraoperative blood loss (IBL) and the features detected by magnetic resonance imaging (MRI) were evaluated by a neurosurgeon and multiple neuroradiologists. RESULTS: Four striking MRI features-peritumoral edema, the flow-void effect, large draining veins, and a visible feeding artery-were related to excessive IBL. Regarding the weighted values of these risk factors, the flow-void effect was the factor most significantly correlated with IBL (P<0.01, R=0.418). The feeding artery also contributed substantially to excessive IBL (P<0.05, R=0.412). The next most influential factor was the presence of large draining veins (P<0.05, R=0.350), followed by peritumoral edema (P<0.05, R=0.308). The four major risk factors-the flow-void effect, feeding arteries, large draining veins, and peritumoral edema-were assigned point values of 3, 3, 2, and 1, respectively, for a maximum total score of 9 points. A higher total score indicates that a higher volume of bleeding is more likely to occur during surgery. CONCLUSIONS: This study reports the potential neuroimaging-based risk factors leading to abundant IBL in SH by neuroimaging assessment. The study proposes a novel scoring system to predict IBL, potentially decreasing the risk involved in the surgical treatment of SH.

Risk factors associated with postoperative recurrence in atypical intracranial meningioma: analysis of 263 cases at a single neurosurgical centre.

OBJECTIVE: Atypical meningioma (AM) has a high rate of local recurrence after surgery, and the role of adjuvant radiotherapy in AM remains controversial. We analysed progression-free survival (PFS) and identified the factors associated with postoperative recurrence in AM patients. METHODS: Data were obtained from 263 AM patients who underwent surgery at our institution between October 2009 and September 2018. Analyses included factors such as the extent of surgical resection, MIB-1 labelling index, brain invasion and therapy modality. Univariate and multivariate analyses were used to assess recurrence-related prognostic factors. RESULT: The median follow-up duration was 41 months, and the median PFS was 28 months. Gross total resection (GTR) was achieved in 213 (81.0%) patients, and 86 (32.7%) patients received postoperative radiation therapy (RT). During follow-up, there were 61 (23.2%) tumour recurrences. In a Cox multivariate analysis, MIB-1 labelling index (hazard ratio = 2.637; p < 0.001), secondary tumour (hazard ratio = 3.541; p < 0.001), tumour size (hazard ratio = 1.818; p = 0.032) and extent of resection (hazard ratio = 2.861; p < 0.001) were independent significant predictors of tumour recurrence. RT was associated with reduced tumour recurrence in subtotal resection (STR) (p = 0.023) but not GTR (p = 0.923). An analysis of 6 meningioma patients who underwent more than 3 operations suggested that the recurrence time became shorter and the MIB-1 labelling index increased as the number of recurrences increased. CONCLUSIONS: MIB-1 labelling index, secondary tumour, tumour size and extent of resection were powerful predictors of recurrence in AM patients. Postoperative RT did not decrease the risk of recurrence in GTR patients.

Multiple Distinctive Demyelinating Lesions Caused by Eosinophilic Granulomatosis With Polyangiitis: Case Report and Literature Review.

Eosinophilic granulomatosis with polyangiitis (EGPA) is an extremely rare rheumatic immune disease characterized by vasculitis of small- and medium-sized blood vessels. Central nervous system (CNS) involvement frequently consists of cerebrovascular disease; a manifestation with multiple demyelinating lesions has never been reported in detail. This report describes a 38-year-old man, who presented with progressive memory deterioration and underwent microsurgery; EGPA was subsequently confirmed. Unique clinical and radiological features as well as immunohistological outcomes and DNA sequencing revealed a potential disease-associated human leukocyte antigen (HLA) type, and single-nucleotide polymorphisms (SNPs) are described for this uncommon case. Although EGPA rarely involves the CNS, this differential diagnosis should be considered when patients present with a history of nasosinusitis, elevated eosinophil percentage, clinical pulmonitis, and neurological manifestations. Microsurgery is necessary for precise diagnosis and effective treatment.

Automatic lung fields segmentation in CT scans using morphological operation and anatomical information.

Segmenting lung fields from CT (Computed Tomography) scans is an important task for the analysis, diagnosis and treatment of pulmonary diseases. Although many segmentation methods have been presented, some new automatic segmentation methods for the lung fields are still proposed for the CT scans. This paper proposes a novel segmentation method for lung fields by using morphological closing operations and thresholding for normal lungs in CT scans. Additionally, under the guidance of anatomic information, the lung fields could be well segmented with lobar fissure, thin junction between the left/right lung fields, indentation of the blood vessels and bronchi-walls. This experiment is performed by employing the thoracic CT scans datasets, and it is proved to be an effective method.