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H3K27M-mutant diffuse midline glioma (DMG) is a type of high-grade glial tumor, which occurs in the midline structure and develops mostly in children. Extraneural metastases (ENM) are exceedingly rare in patients with H3K27M-mutant DMG. A 9-year-old male patient presented with a headache, nausea and vomiting. Following magnetic resonance imaging and immunohistochemical molecular testing examination, the patient was diagnosed with H3K27M-mutant DMG and received chemoradiotherapy plus five cycles of chemotherapy with temozolomide intermittently as an adjuvant therapy. The treatment resulted in a slight reduction of the tumor volume. However, 2 months later, the patient was admitted to hospital with complaints of drooping of the mouth, and waist and back pain. Magnetic resonance imaging and positron-emission tomography-computed tomography revealed an unusual presentation with multiple vertebral metastases and craniospinal leptomeningeal dissemination. Following discussion between the members of a multidisciplinary medical team, the patient underwent one cycle of chemotherapy with cyclophosphamide, vincristine and cisplatin. However, the condition did not improve and the patient died 4 weeks after the diagnosis of ENM. The mechanisms underlying the development of these rare metastases remain unclear. The present case report provides insights into the clinical characteristics and potential metastasis mechanisms of this aggressive disease and may help to elucidate new pathways for the management of ENM.
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Objective: This study aims to provide an updated overview of the relationship between carbon monoxide poisoning (COP) and cardiovascular disease. Methods: A systematic literature search was conducted in PubMed, Embase, Cochrane, and Web of Science databases up to September 2023. The association between COP patients and cardiovascular adverse events was examined and summarized. The outcomes included arrhythmia, coronary heart disease, heart failure, myocardial infarction, major adverse cardiovascular events (MACE), carboxyhaemoglobin percent (COHB%), Pondus Hydrogenii (PH) electrocardiography (ECG) parameters. Results: Eight eligible articles, involving a total of 251,971 patients, were included for evidence synthesis. The analysis revealed a heightened incidence of MACE in patients with COP. Additionally, COP exhibited an impact on specific ECG parameters. The incidence of MACE after COP was found to be similar in Korean and Chinese populations, and there was no significant effect of gender or underlying diseases on MACE incidence following COP. The incidence of MACE after COP did not differ significantly in individuals aged 50 years and older. Conclusions: Considering the observed heterogeneity and potential biases in the selected studies, emergency physicians should be aware of the increased likelihood of cardiovascular events in patients diagnosed with COP.
RESUMO
Objective: The purpose of the study is to explore the mechanism of NRAGE enhancing radioresistance of esophageal squamous cell carcinoma (ESCC) in 2D and 3D levels. Methods: Stably NRAGE-overexpressed ESCC cells and 3D-printing models for ESCC cells were established. Then, cellular malignancy indexes, such as cell morphology, proliferation, radioresistance, motility, apoptosis, cell cycle, and proteins of the Wnt/ß-catenin pathway, were compared between radioresistant and its parental cells in 2D and 3D levels. Additionally, 44 paraffin ESCC specimens with radical radiotherapy were selected to examine NRAGE and ß-catenin protein expression and analyze the clinical correlation. Results: Experiments in 2D culture showed that morphology of the Eca109/NRAGE cells was more irregular, elongated spindle-shaped and disappeared polarity. It obtained faster growth ability, stronger resistance to irradiation, enhanced motility, reduced apoptosis ratio and cell cycle rearrangement. Moreover, Western blot results showed ß-catenin, p-Gsk-3ß and CyclinD1 expressions were induced, while p-ß-catenin and Gsk-3ß expressions decreased in Eca109/NRAGE cells. Experiments in the 3D-printing model showed Eca109/NRAGE cell-laden 3D scaffolds had the advantage on growth and spheroiding according to the brightfield observation, scanning electron microscopy and Ki-67 IHC staining, and higher expression at the ß-catenin protein. Clinical analysis showed that NRAGE expression was higher in tumor tissues than in control tissues of ESCC patients from the Public DataBase. Compared with radiotherapy effective group, both NRAGE total and nuclear and ß-catenin nuclear expressions were significantly upregulated from ESCC specimens in invalid group. Further analysis showed a positive and linear correlation between NRAGE nuclear and ß-catenin nuclear expressions. Additionally, results from univariate and multivariate analyses revealed NRAGE nuclear expression could serve as a risk factor for ESCC patients receiving radical radiotherapy. Conclusion: ESCC cells with NRAGE nuclear accumulation demonstrated greater radioresistance, which may be related to the activation of the Wnt/ß-catenin signaling pathway. It indicated that NRAGE nuclear expression was a potential biomarker for monitoring radiotherapeutic response.