Background: Vascular smooth muscle cells (VSMC) switch to macrophage‐like cells after cholesterol loading, and this change may play an important role in atherogenesis. Muscleblind‐like splicing regulator 1 (MBNL1) is a well‐known splicing factor that has been implicated in many cellular processes. However, the role of MBNL1 in VSMC macrophage‐like transdifferentiation is largely unknown. In this study, we aim to characterize the role of MBNL1‐induced gene splicing during atherogenesis.Methods: The expression of MBNL1 and Abelson interactor 1 (Abi1) splice variants (Abi1‐e10 and Abi1‐Δe10) was compared between artery tissues from healthy donors and atherosclerosis patients. Regulatory mechanisms of MBNL1‐induced Abi1 gene splicing were studied, and the signal pathways mediated by Abi1 splice variants were investigated in VSMC.Results: Loss of MBNL1 was found in the macrophage‐like VSMC (VSMC‐M) in artery wall from atherosclerosis patients. In vitro and in vivo evidence confirmed that Abi1 is one of the MBNL1 target genes. Loss of MBNL1 significantly induces the Abi1‐Δe10 isoform expression. Compared to the known actin organization activities of the Abi1 gene, we discovered a novel action of Abi1‐Δe10, whereby Abi1‐Δe10 activates Rac1 independent of upstream stimulation and triggers the Rac1‐NOX1‐ROS pathway, which results in increased expression of transcription factor Kruppel‐like factor 4 (KLF4). While Abi1‐Δe10 inhibits contractile VSMC biomarkers expression and cell contraction, it stimulates VSMC proliferation, migration and macrophage‐like transdifferentiation.Conclusion: Loss‐of‐function of MBNL1 activates VSMC‐M transdifferentiation to promote atherogenesis through regulating Abi1 RNA splicing.

Objective: This study was conducted to retrospectively analyze the clinical characteristics of CTD-ILD patients to provide strategies for clinical management. Methods: This study collected and analyzed the clinical data and relevant examination results of 161 patients diagnosed with CTD-ILD between 01 January 2018 and 01 January 2021. Results: A total of 161 CTD-ILD patients, 74.53% were females and 25.47% were males, 32.92% were elderly and 67.08% were non-elderly. The main clinical symptoms of CTD-ILD patients were cough (44.72%), decreased activity tolerance (40.37%). RA-ILD was the most common one in the non-elderly and the elderly CTD-ILD patients (48.15% and 50.94%, respectively). Compared with non-elderly, elderly patients with CTD-ILD had a longer duration of CTD (p=0.04). However, fatigue (p=0.005), activity tolerance (p=0.029), the incidence of pulmonary diffusion dysfunction (p=0.047), and systemic immunoinflammatory index (SII, p=0.014) (platelet × NLR) were all decreased. The standard deviation of red blood cell distribution width (RDW) (p=0.024) and immunoglobulin (IgA) (p=0.033) was significantly increased. The smoking index was significantly higher in men than in women with CTD-ILD (p=0.000), but symptoms of reduced activity tolerance were less pronounced than in women (p< 0.05). Elderly CTD-ILD patients (p=0.003) and women from non-elderly patients were prone to lower hemoglobin (p=0.000). Among the elderly, the lymphocyte ratio was more significantly elevated in female CTD-ILD patients than in males (p=0.018). In contrast, neutrophil to lymphocyte ratio (NLR) and SII were lower in female (p=0.038) than in male CTD-ILD patients (p=0.043). Conclusion: CTD-ILD mainly affects non-elderly and women. Age may not be involved with decreased activity tolerance and increased lung function impairment in CTD-ILD patients. However, the elderly patients with CTD-ILD, especially the elderly female patients with low inflammation levels and high immune disorders, have a poor prognosis.

Purpose: This study investigated the 1-year clinical outcomes of directional atherectomy combined with drug-coated balloon (DA + DCB) in femoropopliteal artery disease (FPAD) from real-world experience. Materials and Methods: A retrospective study was conducted of patients treated between July 2016 and June 2019 using DA + DCB for FPAD. Patients’ demographics, comorbidities, clinical characteristics and outcomes, and angiography and duplex ultrasound findings were analyzed. The 6-month and 1-year primary patency, primary assisted patency, secondary patency, and freedom from clinically-driven target lesion revascularization (CD-TLR) were evaluated. Univariate and multivariate analyses were performed to identify risk factors of primary patency loss or CD-TLR. Results: Seventy-nine consecutive patients (83 lesions, mean age 70.9 years, 52 men) were included. Twenty-seven limbs had lifestyle-limiting claudication and 56 limbs had critical limb ischemia. There were 73 and 10 limbs with de novo lesion and in-stent restenosis, respectively. The mean lesion length of all the patients was 22.1 cm. The mean length of chronic total occlusions (CTOs) was 8.3 cm. Severe calcification was found in 32.5% cases. The 1-year primary patency rate was 80.8% and freedom from CD-TLR was 92.2%. The bailout stenting rate was 2.4%. Patients with CTO >10 cm had significantly lower 1-year primary patency rate and freedom from CD-TLR than did patients with CTO ≤10 cm. Total length of CTO (stratified as ≤5 cm, 5–10 cm, >10 cm) was identified as an independent risk factor of 1-year primary patency loss and CD-TLR. Conclusion: DA + DCB appears to be a safe and effective endovascular therapy to treat FPAD in real-world clinical practice, with a promising 1-year patency rate with a low rate of bailout stenting.