The aim of the present study was to explore the toxic effects and underlying mechanisms of nickel ions during therapeutic nickel-based alloy-treatment in congenital heart disease by investigating the metal-induced cytotoxicity to the human monocyte-derived macrophage cell line THP-1. THP-1 cells were treated with NiCl2·6H2O (25, 50, 100, 200, 400 and 800 µM) for 24, 48 and 72 h, respectively. MTT was applied to detect THP-1 cell proliferation following NiCl2 treatment. Apoptosis of THP-1 cells was quantified using flow cytometry. Illumina sequencing was used for screening the associated genes, whose mRNA expression levels were further confirmed by quantitative real-time polymerase chain reaction. High concentrations of nickel ions had a significant suppressive effect on cell proliferation at the three concentrations investigated (200, 400 and 800 µM). Treatment with nickel ions (25–400 µM) for 48 h reduced cell viability in a dose-dependent manner. The mRNA expression levels of RELB, FIGF, SPI-1, CXCL16 and CRLF2 were significantly increased following nickel treatment. The results of the present study suggested that nickel ions exert toxic effects on THP-1 cell growth, which may indicate toxicity of the nickel ion during treatment of congenital heart disease. The identification of genes modified by the toxic effects of nickel on THP-1 cells (EPOR, RELB, FIGF, SPI-1, TGF-β1, CXCL16 and CRLF2) may aid in the development of interventional measures for the treatment/prevention of nickel ion-associated toxic effects during the treatment of congenital heart disease.
Background The use of neoadjuvant immunotherapy plus chemotherapy has revolutionized the management of esophageal squamous cell carcinoma (ESCC) patients. Nevertheless, patients who would maximally benefit from these therapies have not been identified. Methods We collected postoperative specimens from 103 ESCC patients, of which 66 patients comprised a retrospective cohort and 37 comprised a prospective cohort. Patient specimens were subjected to applied multi‐omics analysis to uncover the mechanistic basis for patient responsiveness to cancer immunotherapy. The tumor microenvironment characteristics of these patient specimens was explored and identified by multiplex immunofluorescence and immunohistochemistry. Results Results demonstrated high COL19A1 expression to be a novel biomarker for successful immunotherapy ( COL19A1 high , odds ratio [95% confidence interval]: 0.31 [0.10–0.97], p = 0.044). Compared with COL19A1 low patients, COL19A1 high patients benefited more from neoadjuvant immunotherapy ( p < 0.01), obtained better major pathological remissions (63.3%, p < 0.01), with a trend toward better recurrence‐free survival ( p = 0.013), and overall survival ( p = 0.056). Moreover, analysis of an immune‐activation subtype of patients demonstrated increased B cell infiltration to be associated with favorable patient survival and a better response to neoadjuvant immunotherapy plus chemotherapy. Conclusions The findings of this study provide insight into the optimal design of individual treatments for ESCC patients.
Objective To retrospectively analyze the comprehensive treatment strategy for internal carotid artery blowout syndrome (CBS) by nasopharyngeal carcinoma (NPC). Methods Of the 311 patients of NPC with carotid artery blowout syndrome admitted at our center from April 2018 to August 2022, 288 were enrolled. Results The patients were divided into two groups: treatment group (266 cases) and control group (22 cases). After comprehensive treatment, the survival rate of the treatment group was significantly higher than that of the control group, especially within 6 months to the 1 year. Preventive intervention for CBS I type may have considerable benefits. And in the long run, this treatment strategy did not significantly increase the incidence of stroke in the treatment group. Conclusion The comprehensive treatment strategy for ICA‐CBS of patients with NPC significantly reduced the mortality of asphyxia due to epistaxis, reduced the incidence of CBS during nasal endoscopy, and finally improved survival rate.
<b><i>Background:</i></b> Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. <b><i>Summary:</i></b> We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. <b><i>Key Messages:</i></b> Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.
Background Chondrosarcoma(ChSa) is a rare malignant tumor. But it’s necessary to discuss the clinical characteristics and treatments for ChSa of paranasal sinus and the skull base. Methods The clinical characteristics of ChSa of paranasal sinus and skull base in 10 patients (6 males and 4 females) from 2001 to 2017 were analyzed. They all underwent by endoscopic surgery . The patients’ age ranged from 18 to 47 years, with a median of 35 years. Clinical symptoms: stuffy, nose bleeding, runny, headache, diplopia, eye outreach limited, blurred vision and even blindness. Surgery methods:under nasal endoscopy, after the attachment sites of the tumors to normal tissues were confirmed, the tumors were peeled off along the clear boundary between the tumors and normal tissues, and the potential residual tumor tissues on bones were cleared by a drill. Results All patients were treated with endoscopic surgery,followed up postoperatively for 24 to 108 months, with a median of 36 months. 8 of 10 patients were no recurrence,2 were alive with tumor. Conclusion ChSa of paranasal sinus and skull base can be treated by nasal endoscopic surgery with good clinical results.
Background: Squamous metaplasia (SM) is an irreversible form of airway epithelial remodeling. Hyperproliferation of basal cells was observed in squamous metaplastic epithelium of chronically inflamed airway. However, the association of such aberrant proliferation of basal cells with SM in the nasal epithelium after radiation damage remains unclear. The aim of this study was to investigate SM and accompanying levels of p63+Krt5+ (basal cell markers) cells in the nasal epithelium of patients with radiation-induced chronic rhinosinusitis (CRSr) and patients with chronic rhinosinusitis without nasal polyps (CRSsNP) compared to healthy controls.Methods: We assessed the prevalence of SM and the expression of p63+, Krt5+, p63+Krt5+, and Ki67+ cells through immunofluorescence(IF) staining of the inferior turbinate (IT) tissues from patients with CRSr (n = 36) , CRSsNP (n = 33) and controls (n = 28).Results: The prevalence of SM and the number of p63+Krt5+ cells were both significantly increased in patients with CRSr compared to patients with CRSsNP and controls. The number of Ki67+ cells were both significantly increased in patients with CRSr and CRSsNP compared to controls, but the ratio of Ki67+ cells to p63+Krt5+ cells was significantly lower in patients with CRSr compared to patients with CRSsNP. In patients with CRSr, an increased number of p63+Krt5+ basal cells was observed in SM epithelium compared to non-SM epithelium.Conclusion: SM is increased in the nasal epithelium of patients with CRSr, in which aberrant levels of p63+Krt5+ basal cells serves as an important pathologic feature in the squamous metaplastic epithelium.
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