Background/Aims: Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Methods: Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1’s nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. Results: DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3’UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Conclusions Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.

Objective:To analyze the clinical characteristics of hospitalized elderly patients with varying degrees of corona virus disease 2019(COVID-19), hoping to help improve the understanding and management of COVID-19.Methods:A total of 70 hospitalized COVID-19 patients with complete clinical data collected between February 7, 2020 and April 6, 2020 were enrolled.Epidemiological features, underlying conditions, clinical manifestations and treatment outcomes were analyzed.Patients were divided into the elderly group and the non-elderly group based on age and were also divide into the normal group, the severe group and the critical group based on severity.Early warning indicators of severe disease were compared and analyzed.Results:Seventy hospitalized COVID-19 patients aged from 28-92 years, with an average age of 59.2 years.Epidemiological characteristics of the patients were mainly clusters of fever within 14 days of onset, with 13(18.57%)patients with diabetes, 22(31.43%)with hypertension, 5(7.1%)with coronary heart disease and 10(14.29%)with malignant tumor.Patients with more than 2 comorbidity diseases had a poor prognosis, characterized by long hospital stays, recurrent complications and fatal complications, including acute respiratory distress syndrome(ARDS), sepsis and death.In this study, 4 patients died.Hospital stays were prolonged, peripheral blood neutrophil count increased, lymphocyte count decreased, and levels of transaminase, lactate dehydrogenase, C-reactive protein and interleukin(IL)-6 were elevated with increasing severity of COVID-19( P<0.01). Conclusions:People of all ages are susceptible to COVID-19.Clinical warning signs of exacerbation for the common type become more prominent with increasing severity of COVID-19.