Rapid reduction in plaque inflammation by sonodynamic therapy inpatients with symptomatic femoropopliteal peripheral artery disease:A randomized controlled trial.

BACKGROUND: Inflammation is actively involved in the clinical manifestation of peripheral artery disease (PAD). Sonodynamic therapy (SDT), a novel non-invasive, plaque-based, macrophage-targeted anti-inflammatory regimen for atherosclerosis has the potential to improve walking performance by reducing plaque inflammation. METHODS: This phase-2, randomized, sham-controlled, double-blind clinical trial enrolled 32 participants with symptomatic femoropopliteal PAD. The primary outcome was the 30-day change in the target-to-background ratio (TBR) within the most diseased segment (MDS) of the femoropopliteal artery assessed through positron emission tomography/computed tomography (PET/CT). The secondary outcomes were changes in walking performance, limb perfusion, lesional morphology and quality of life measurements. RESULTS: The mean age was 64.7 years and 63% were male. Thirty-one completed follow-up. SDT significantly decreased the MDS TBR by 0.53 (95% CI, -0.70 to -0.36, P < 0.001) compared with control. Furthermore, SDT increased peak walking time by 118.6 s (95% CI, 74.3 to 163.0, P < 0.001), increased ankle-brachial index by 0.11 (95% CI, 0.07 to 0.14, P < 0.001), decreased lesional diameter and area stenosis by 7.2% (95% CI, -8.6 to -4.5, P < 0.001) and 9.6% (95% CI, -24.5 to -5.3, P = 0.005), respectively, and increased the walking speed score of the Walking Impairment Questionnaire by 16.1 (95% CI, 2.6 to 29.5, P = 0.021) and the physical functioning score of the 36-item Short-Form Health Survey by 10.0 (95% CI, 5.0 to 20.0, P = 0.003) compared with control. These improvements were maintained in the SDT group up to 6-month. CONCLUSIONS: SDT rapidly reduced plaque inflammation and improved walking performance among patients with symptomatic PAD. TRIAL REGISTRATION: Clinical Trials NCT03457662.

Identification of miR-194-5p as a potential biomarker for postmenopausal osteoporosis.

The incidence of osteoporosis is high in postmenopausal women due to altered estrogen levels and continuous calcium loss that occurs with aging. Recent studies have shown that microRNAs (miRNAs) are involved in the development of osteoporosis. These miRNAs may be used as potential biomarkers to identify women at a high risk for developing the disease. In this study, whole blood samples were collected from 48 postmenopausal Chinese women with osteopenia or osteoporosis and pooled into six groups according to individual T-scores. A miRNA microarray analysis was performed on pooled blood samples to identify potential miRNA biomarkers for postmenopausal osteoporosis. Five miRNAs (miR-130b-3p, -151a-3p, -151b, -194-5p, and -590-5p) were identified in the microarray analysis. These dysregulated miRNAs were subjected to a pathway analysis investigating whether they were involved in regulating osteoporosis-related pathways. Among them, only miR-194-5p was enriched in multiple osteoporosis-related pathways. Enhanced miR-194-5p expression in women with osteoporosis was confirmed by quantitative reverse transcription-polymerase chain reaction analysis. For external validation, a significant correlation between the expression of miR-194-5p and T-scores was found in an independent patient collection comprised of 24 postmenopausal women with normal bone mineral density, 30 postmenopausal women with osteopenia, and 32 postmenopausal women with osteoporosis (p < 0.05). Taken together, the present findings suggest that miR-194-5p may be a viable miRNA biomarker for postmenopausal osteoporosis.