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This study investigated the etiology, clinical features, and prognosis of patients diagnosed with bilateral sudden sensorineural hearing loss (BSSNHL). The clinical data of 100 patients with bilateral sudden hearing loss as a chief complaint treated at Xiangya Second Hospital of Central South University between January 2010 and August 2022, including clinical characteristics, audiometric data, and prognosis, were retrospectively analyzed. These 100 cases accounted for 8.09% (100/1235) of all patients admitted for sudden sensorineural hearing loss (SSNHL) during the same period. Of these, 71 were simultaneous cases and 29 were sequential cases of BSSNHL. Among the 200 ears analyzed in this study, 13, 36, 57, and 94 had mild, moderate, severe, and profound sensorineural hearing loss, respectively. The overall effective rate after comprehensive treatment was 32%, with significant differences in efficacy and prognosis among different degrees of hearing loss (p < 0.05). Comorbidities of hypertension (24 cases), diabetes (14 cases), and coronary heart disease (9 cases) significantly impacted therapeutic efficacy and prognosis in patients with BSSNHL (p < 0.05). Compared to unilateral SSNHL, BSSNHL exhibits distinctive characteristics.
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Introduction: Middle ear cholesteatoma is a chronic middle ear disease characterized by severe hearing loss and adjacent bone erosion, resulting in numerous complications. This study sought to identify pathways involved in N6-methyladenosine (m6A) modification of circRNA in middle ear cholesteatoma. Methods: A m6A circRNA epitranscriptomic microarray analysis was performed in middle ear cholesteatoma tissues (n = 5) and normal post-auricular skin samples (n = 5). Bioinformatics analyses subsequently explored the biological functions (Gene Ontology, GO) and signaling pathways (Kyoto Encyclopedia of Genes and Genomes, KEGG) underlying middle ear cholesteatoma pathogenesis. Methylated RNA immunoprecipitation qPCR (MeRIP-qPCR) was performed to verify the presence of circRNAs with m6A modifications in middle ear cholesteatoma and normal skin samples. Results: Microarray analysis identified 3,755 circRNAs as significantly differentially modified by m6A methylation in middle ear cholesteatoma compared with the normal post-auricular skin. Among these, 3,742 were hypermethylated (FC ≥ 2, FDR < 0.05) and 13 were hypomethylated (FC ≤ 1/2, FDR < 0.05). GO analysis terms with the highest enrichment score were localization, cytoplasm, and ATP-dependent activity for biological processes, cellular components, and molecular functions respectively. Of the eight hypermethylated circRNA pathways, RNA degradation pathway has the highest enrichment score. Peroxisome Proliferator-Activated Receptor (PPAR) signaling pathway was hypomethylated. To validate the microarray analysis, we conducted MeRIP-qPCR to assess the methylation levels of five specific m6A-modified circRNAs: hsa_circRNA_061554, hsa_circRNA_001454, hsa_circRNA_031526, hsa_circRNA_100833, and hsa_circRNA_022382. The validation was highly consistent with the findings from the microarray analysis. Conclusion: Our study firstly presents m6A modification patterns of circRNAs in middle ear cholesteatoma. This finding suggests a direction for circRNA m6A modification research in the etiology of cholesteatoma and provides potential therapeutic targets for the treatment of middle ear cholesteatoma.
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OBJECTIVES: Nipah and Hendra are deadly zoonotic diseases with pandemic potential. To date, no human vaccine or monoclonal antibody (mAb) has been licensed to prevent disease caused by these pathogens. The aim of this scoping review was to identify and describe all Phase I, II, and III clinical trials of vaccine candidates or mAbs candidates designed to prevent Nipah and Hendra in humans and to compare the characteristics of the vaccine candidates to characteristics outlined in the Target Product Profile drafted by the World Health Organisation as part of the WHO Research & Development Blueprint for Action to Prevent Epidemics. METHODS: We searched 23 clinical trial registries, the Cochrane Central Register of Clinical Trials, and grey literature up to June 2023 to identify vaccine and mAb candidates being evaluated in registered clinical trials. Vaccine candidate and trial characteristics were double-extracted for evaluation and the vaccine candidate characteristics were compared with the preferred and critical criteria of the World Health Organisation's Target Product Profile for Nipah virus vaccine. RESULTS: Three vaccine candidates (Hendra Virus Soluble Glycoprotein Vaccine [HeV-sG-V], PHV02, and mRNA-1215) and one mAb (m102.4) had a registered human clinical trial by June 2023. All trials were phase 1, dose-ranging trials taking place in the United States of America or Australia and enrolling healthy adults. Although all vaccine candidates meet the dose regimen and route of administration criteria of the Target Product Profile, other criteria such as measures of efficacy and reactogenicity will need to be evaluated in the future as evidence becomes available. CONCLUSION: Multiple vaccine candidates and one mAb candidate have reached the stage of human clinical trials and are reviewed here. Monitoring progress during evaluation of these candidates and candidates entering clinical trials in the future can help highlight many of the challenges that remain.
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Anticuerpos Monoclonales , Virus Hendra , Infecciones por Henipavirus , Virus Nipah , Vacunas Virales , Humanos , Infecciones por Henipavirus/prevención & control , Infecciones por Henipavirus/inmunología , Anticuerpos Monoclonales/uso terapéutico , Virus Hendra/inmunología , Virus Nipah/inmunología , Vacunas Virales/inmunología , Vacunas Virales/uso terapéutico , Ensayos Clínicos como Asunto , AnimalesRESUMEN
This cross-sectional study examines burn incidence rates and accessibility of American Burn Associationverified or self-designated burn centers from 2013 to 2019.