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BackgroundPatients with chronic kidney disease (CKD) are at high risk of developing heart failure and anemia, which is defined as type 4 cardiorenal-anemia syndrome (CRAS). CRAS aggravates the deterioration of both kidney and heart function, ultimately resulting in a high mortality. This study aims to examine the efficacy and safety of roxadustat in the treatment of type 4 CRAS.Methods and DesignThis study is designed as a randomized, open-label, controlled trial. A total of 68 patients diagnosed with type 4 CRAS will be randomly divided into roxadustat group and erythropoietin with a 1:1 ratio. Participants in the roxadustat group will receive roxadustat with an initial dose of 70 or 100 mg three times a week, and participants in the erythropoietin group will receive subcutaneous injection of erythropoietin for 24 weeks, to maintain a hemoglobin ranging from 100 to 120 g per liter. The primary outcome is the change in heart function, including brain natriuretic peptide (BNP), 6-min walk test (6-WT), and left ventricular ejection fraction (LVEF). Secondary outcomes to be assessed include death, cardiovascular events, hospitalization regarding heart failure, Minnesota Heart Failure Quality of life scale (MLHFQ) score, New York Heart Association (NYHA) cardiac function grade, echocardiographic parameters including left ventricular diastolic diameter and volume (LVDD and LVDV) and ventricular mass (LVM), anemia related parameters, inflammatory parameters, and safety assessments.ConclusionThe findings of this study will provide potential evidence for roxadustat in CRAS management.Trial RegistrationChinese Clinical Trial Registry, ID: ChiCTR2100050031. Registered on 16 August 2021.

Many dysregulated microRNAs (miRNAs) have been suggested to serve as oncogenes or tumor suppressors to act as diagnostic and prognostic factors for HCC patients. However, the dysregulated mechanisms of miRNAs in HCC remain largely unknown. Herein, we firstly identify 114 disordered mature miRNAs in HCC, 93 of them are caused by dysregulated transcription factors, and 10 of them are driven by the DNA methylation of their promoter regions. Secondly, we find that seven up-regulated miRNAs (miR-9-5p, miR-452-5p, miR-452-3p, miR-1180-3p, miR-4746-5p, miR-3677-3 and miR-4661-5p) can promote tumorigenesis via inhibiting multiple tumor suppressor genes participated in metabolism, which may act as oncogenes, and seven down-regulated miRNAs (miR-99-5p, miR-5589-5p, miR-5589-3p, miR-139-5p, miR-139-3p, miR-101-3p and miR-125b-5p) can suppress abnormal cell proliferation via suppressing a number of oncogenes involved in cancer-related pathways, which may serve as tumor suppressors. Thirdly, our findings reveal a mechanism that transcription factor and miRNA interplay can form various regulatory loops to synergistically control the occurrence and development of HCC. Finally, our results demonstrate that this key transcription factor FOXO1 can activate a certain number of tumor suppressor miRNAs to improve the survival of HCC patients, suggesting FOXO1 as an effective therapeutic target for HCC patients. Overall, our study not only reveals the dysregulated mechanisms of miRNAs in HCC, but provides several novel prognostic biomarkers and potential therapeutic targets for HCC patients.