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Objective:To retrospectively analyze the bone marrow characteristics of methimazole-induced agranulocytosis and other hematologic damage, and to explore its correlation with clinical features and prognosis.Methods:The bone marrow and clinical parameters of 20 patients of Graves′ disease diagnosed with methimazole-induced agranulocytosis at the First Affiliated Hospital of Xi′an Jiaotong University from January 2000 to December 2022 were collected. The intergroup differences in bone marrow characteristics and granulocyte recovery time were analyzed. Differences in peripheral blood and bone marrow characteristics between patients with single agranulocytosis and pancytopenia were compared. Besides, literature review of the bone marrow characteristics of methimazole-induced hematologic diseases was conducted.Results:Compared to patients with bone marrow characteristics of granulocyte and precursor maturation disorders(Type Ⅱ), patients with aplastic marrow(Type Ⅰ) had significant decreases in the proportions of granulocytes in all phases( P<0.05). Patients with bone marrow characteristics of Type Ⅰ had a significant increase in the proportion of the lymphocyte system [51.00%(41.50%, 75.50%) vs 22.00%(14.00%, 35.00%), P=0.002], and got a longer to recovery time [(6.58±1.68)d vs(3.71±1.60)d, P=0.003]; Correlation analysis suggested the granulocyte to erythrocyte ratio was negatively correlated with the granulocyte recovery time( r=-0.520, P=0.023), and the proportion of the bone marrow lymphocyte was positively correlated with granulocyte recovery time( r=0.622, P=0.004). Compared to patients with single agranulocytosis, patients with pancytopenia had a markedly longer hospital stay duration [(27.14±5.27)d vs(14.15±7.36)d, P=0.001]. Literature review suggestsed that methimazole may cause various degrees of damage to blood system and bone marrow. Conclusion:Methimazole can induce a variety of hematologic damages. Analysis of bone marrow characteristics can aid in further prognosis assessment. Clinicians should be vigilant about potential hematologic adverse reactions when using methimazole and promptly diagnose and treat them to prevent serious consequences.
RESUMO
【Objective】 To investigate the effect of isoliquiritigenin on inflammatory response of vascular endothelial cells and whether the regulatory effect of isoliquiritigenin on inflammation is mediated by histone deacetylase 3 (HDAC3). 【Methods】 Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with LPS, different concentrations of isoliquiritigenin and HDAC3 specific inhibitor, respectively. Real-time PCR and Western blotting were used to detect the mRNA and protein expressions of inflammatory cytokines and HDAC3. Male C57BL/6J mice were randomly divided into vehicle group and isoliquiritigenin treatment group. The vascular inflammation model of C57BL/6J mice was established by ligation of the left carotid arteries. The mRNA expressions of inflammatory cytokines and HDAC3 in the carotid arteries of mice were detected by Real-time PCR. A molecular docking study was performed to investigate the interaction between isoliquiritigenin and HDAC3. 【Results】 Compared with the vehicle group, isoliquiritigenin reduced the mRNA expressions of inflammatory cytokines NLRP3, IL-1β, IL-18, MCP-1 and ICAM-1 and decreased the expression of HDAC3 mRNA and protein in HUVECs stimulated with LPS. In addition, isoliquiritigenin also decreased the mRNA expressions of NLRP3, IL-1β and HDAC3 in carotid arteries of ligated C57BL/6J mice. The docking of isoliquiritigenin in the active site of HDAC3 showed that isoliquiritigenin might act through HDAC3. Furthermore, HDAC3 specific inhibitor RGFP966 further promoted the inhibitory effect of isoliquiritigenin on the expression of inflammatory cytokines in vascular endothelial cells. 【Conclusion】 These results suggest that isoliquiritigenin suppresses the inflammatory response of vascular endothelial cells via HDAC3.