Background The elevation of plasma D‐dimer levels may predict a higher risk of thrombosis and play a role in the pathological process of patients after spontaneous intracerebral hemorrhage (ICH). However, its function in predicting the prognosis of ICH has not been verified on large cases. Patients and Methods Retrospective cohort study of 1,332 consecutive patients with spontaneous ICH at an academic medical center was conducted. Functional outcome at three months after ICH was dichotomized using the modified Rankin Scale (0–2 versus 3–6). D‐dimer level in blood was analyzed within 1 hr of admission. An ICH outcome score combining D‐dimer level for evaluating poor functional outcome and mortality was tested. Results The proportion of patients with poor functional outcome and mortality at three months was significantly higher in patients with elevated D‐dimer level ( p < .001). Multivariable analysis demonstrated that elevated D‐dimer level was an independent predictor of poor functional outcome (odds ratio 1.486, 95% confidence interval 1.086–2.060, p = .014) and mortality (odds ratio 2.015, 95% confidence interval 1.186–3.423, p = .01). An increasing ICH outcome score combining D‐dimer level was associated with increased poor functional outcome and mortality. Conclusions Elevated plasma D‐dimer level after spontaneous ICH is associated with poor functional outcome and mortality. The study suggests that elevated D‐dimer level has a predictive value for outcome and mortality in patients with spontaneous ICH.

IntroductionExosomal microRNAs (miRNAs) play an essential role in near and distant intercellular communication and are potential diagnostic and prognostic biomarkers for various cancers. This study focused on evaluation of exosomal miR-2276-5p in plasma as a diagnostic and prognostic biomarker for glioma.MethodsPlasma exosomes from 124 patients with glioma and 36 non-tumor controls were collected and subjected to quantitative real-time polymerase chain reaction (qRT-PCR) analysis for the exosomal miR-2276-5p expression. Bioinformatic analyses were performed to identify a gene target, and CGGA and TCGA databases were checked for evaluation of prognostic relevance.ResultsThe exosomal miR-2276-5p in glioma patients had a significantly decreased expression, compared with non-glioma patients (p &lt; 0.01). Receiver operating characteristics (ROC) curve analyses were observed to regulate the diagnostic sensitivity and specificity of miR-2276-5p in glioma; the area under the curve (AUC) for miR-2276-5p was 0.8107. The lower expression of exosomal miR-2276-5p in patients with glioma correlated with poorer survival rates. RAB13 was identified as the target of miR-2276-5p which was high in glioma patients, especially those with higher tumor grades and correlated with poor survival.ConclusionThe circulating exosomal miR-2276-5p is significantly reduced in the plasma of glioma patients, and thus, it could be a potential biomarker for patients with glioma for diagnostic and/or prognostic purposes.

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Background Medulloblastoma (MB) is the most common intracranial malignant tumor in children. The genes and pathways involved in the pathogenesis of MB are relatively unknown. We aimed to identify potential biomarkers and small-molecule drugs for MB. Methods Gene expression profile data sets were obtained from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were identified using the Limma package in R. Functional annotation, and cell signaling pathway analysis of DEGs was carried out using DAVID and Kobas. A protein-protein interaction network was generated using STRING. Potential small-molecule drugs were identified using CMap. Result We identified 104 DEGs (29 upregulated; 75 downregulated). Gene ontology analysis showed enrichment in the mitotic cell cycle, cell cycle, spindle, and DNA binding. Cell signaling pathway analysis identified cell cycle, HIF-1 signaling pathway, and phospholipase D signaling pathway as key pathways. SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were the prominent hub genes and their expression level were verified by RT-qPCR. Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB. The five hub genes may be targets for diagnosis and treatment of MB, and the small-molecule compounds are promising drugs for effective treatment of MB. Conclusion In this study we obtained five hub genes of MB, SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were confirmed as hub genes. Meanwhile, Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB.

Tumor recurrence remains the leading cause of treatment failure following surgical resection of glioblastoma (GBM). M2-like tumor-associated macrophages (TAMs) infiltrating the tumor tissue promote tumor progression and seriously impair the efficacy of chemotherapy and immunotherapy. In addition, designing drugs capable of crossing the blood–brain barrier and eliciting the applicable organic response is an ambitious challenge. Here, we propose an injectable nanoparticle–hydrogel system that uses doxorubicin (DOX)-loaded mesoporous polydopamine (MPDA) nanoparticles encapsulated in M1 macrophage-derived nanovesicles (M1NVs) as effectors and fibrin hydrogels as in situ delivery vehicles. In vivo fluorescence imaging shows that the hydrogel system triggers photo–chemo-immunotherapy to destroy remaining tumor cells when delivered to the tumor cavity of a model of subtotal GBM resection. Concomitantly, the result of flow cytometry indicated that M1NVs comprehensively improved the immune microenvironment by reprogramming M2-like TAMs to M1-like TAMs. This hydrogel system combined with a near-infrared laser effectively promoted the continuous infiltration of T cells, restored T cell effector function, inhibited the infiltration of myeloid-derived suppressor cells and regulatory T cells, and thereby exhibited a strong antitumor immune response and significantly inhibited tumor growth. Hence, MPDA-DOX-NVs@Gel (MD-NVs@Gel) presents a unique clinical strategy for the treatment of GBM recurrence.

The natural product pectolinarigenin exerts anti-inflammatory activity and anti-tumor effects, and exhibits different biological functions, particularly in autophagy and cell cycle regulation. However, the antineoplastic effect of pectolinarigenin on glioblastoma (GBM) remains unclear. In the present study, we found that pectolinarigenin inhibits glioblastoma proliferation, increases autophagic flux, and induces cell cycle arrest by inhibiting ribonucleotide reductase subunit M2 (RRM2), which can be reversed by RRM2 overexpression plasmid. Additionally, pectolinarigenin promoted RRM2 protein degradation via autolysosome-dependent pathway by increasing autophagic flow. RRM2 knockdown promoted the degradation of CDK1 protein through autolysosome-dependent pathway by increasing autophagic flow, thereby inhibiting the proliferation of glioblastoma by inducing G2/M phase cell cycle arrest. Clinical data analysis revealed that RRM2 expression in glioma patients was inversely correlated with the overall survival. Collectively, pectolinarigenin promoted the degradation of CDK1 protein dependent on autolysosomal pathway through increasing autophagic flux by inhibiting RRM2, thereby inhibiting the proliferation of glioblastoma cells by inducing G2/M phase cell cycle arrest, and RRM2 may be a potential therapeutic target and a prognosis and predictive biomarker in GBM patients.

Background: Since the mutation of isocitrate dehydrogenase 1 was confirmed to be different in the tumor microenvironment of multiple cancer types, several researchers have included it in the study of tumor-infiltrating immune cells. Interferon-stimulated exonuclease gene 20 (ISG20) plays a role in the modulation of immunity and inflammation, and its abnormally high expression is conducive for the progression of tumor malignancy. However, whether ISG20 is associated with isocitrate dehydrogenase 1 mutation during tumorigenesis and cancer progression remains unknown to date. Methods: TIMER2.0, ONCOMINE, GEPIA2, TCGA and CGGA were applied to assess the clinical significance of ISG20 and its correlation with tumor-infiltrating immune cells in glioma. cBioPortal and MethSurv databases were used to observe the genetic and DNA methylation changes of ISG20, respectively. Visualization of data was mostly achieved by R language. Quantitative real-time PCR (qRT-PCR) and Immunohistochemistry (IHC) was performed to evaluate the mRNA and protein expression.Results: ISG20 expression was significantly different in most cancers. However, when we combined ISG20 with isocitrate dehydrogenase 1 mutation, we found significant differences only in glioblastoma (GBM). The clinical values of ISG20 in glioblastoma showed that the ISG20 overexpression was strongly associated with a worse overall survival (OS). Additionally, ISG20 was altered in 9% of samples of patients with GBM, and ISG20 expression was negatively correlated with its DNA methylation level. More importantly, ISG20 expression was associated with macrophage alternatively activated (M2) polarization in glioblastoma. Conclusions: ISG20 overexpression is conducive to malignant phenotype but adverse to OS, suggesting that ISG20 is a potential therapeutic target and prognosis and predictive biomarker in patients with GBM.

The utility of noncontrast computed tomography markers in the prognosis of spontaneous intracerebral hemorrhage has been studied. This study aimed to investigate the predictive value of the computed tomography (CT) irregularity shape for poor functional outcomes in patients with spontaneous intracerebral hemorrhage. We retrospectively reviewed all 782 patients with intracranial hemorrhage in our stroke emergency center from January 2018 to September 2019. Laboratory examination and CT examination were performed within 24 h of admission. After three months, the patient's functional outcome was assessed using the modified Rankin Scale. Multinomial logistic regression analyses were applied to identify independent predictors of functional outcome in patients with intracerebral hemorrhage. Out of the 627 patients included in this study, those with irregular shapes on CT imaging had a higher proportion of poor outcomes and mortality 90 days after discharge (P < 0.001). Irregular shapes were found to be significant independent predictors of poor outcome and mortality on multiple logistic regression analysis. In addition, the increase in plasma D-dimer was associated with the occurrence of irregular shapes (P = 0.0387). Patients with irregular shapes showed worse functional outcomes after intracerebral hemorrhage. The elevated expression level of plasma D-dimers may be directly related to the formation of irregular shapes.