Feasibility of a Percutaneous and Non-Fluoroscopic Procedure for Transcatheter Mitral Valve Edge-to-Edge Repair

Background: Transcatheter edge-to-edge repair (TEER) of the mitral valve has emerged as an alternative treatment for mitral regurgitation (MR). However, the high radiation exposure during the process has been associated with multiple adverse effects for medical staff. In this study, we assessed the feasibility and safety of TEER performed solely under the echocardiographic (echo) guidance. Methods: Between April 2021 to August 2021, we retrospectively collected characteristics of 23 patients with MR who underwent TEER under echocardiographic guidance exclusively. Follow-up evaluations were performed at 1- , 3-months and 1-year post procedure. Results: All 23 patients (mean age, 66.1 ± 12.1 years; 65.2% males) successfully underwent echo-guided TEER, with 22 patients under transesophageal echo (TEE) guidance and 1 patient under transthoracic echo (TTE) guidance for severe esophageal stenosis. Of the patients, 60.9% received 1 implant and 39.1% received 2 implants. The median total procedural time was 130 (interquartile range, IQR: 90–150) min and the device procedure time was 73 (IQR: 58–100) min. The median length of stay was 6 (IQR: 5–9) days. At 3-months follow-up, 63.6% of patients had an MR ≤1+ and 90.9% had an MR ≤2+ (p < 0.001 vs. baseline). Improvement in functional status was observed, with 40.9% of patients classified as New York Heart Association (NYHA) functional class I and 45.5% as NYHA functional class II (p < 0.001 compared to baseline) at 3-months. At 1-year follow-up, 90.4% maintained MR reduction with MR ≤2+ (p < 0.001 vs. baseline). Single leaflet device attachment (SLDA) occurred in one patient (4.3%) 1-week post procedure. Conclusions: This retrospective, single-center, and pilot study demonstrates the feasibility, safety, and low complication rates of TEER guided solely by echocardiography. Our findings support the systematic use of echocardiography as the sole guidance modality for TEER, highlighting its potential as an alternative to fluoroscopy-guided procedures. Further multicenter and comparative studies are warranted to confirm these results and provide a more comprehensive evaluation of this approach

Supramolecular Polymer‐Nanomedicine Hydrogel Loaded with Tumor Associated Macrophage‐Reprogramming polyTLR7/8a Nanoregulator for Enhanced Anti‐Angiogenesis Therapy of Orthotopic Hepatocellular Carcinoma

Abstract Anti‐angiogenic therapies targeting inhibition of vascular endothelial growth factor (VEGF) pathway show clinical benefit in hypervascular hepatocellular carcinoma (HCC) tumors. However, HCC expresses massive pro‐angiogenic factors in the tumor microenvironment (TME) in response to anti‐angiogenic therapy, recruiting tumor‐associated macrophages (TAMs), leading to revascularization and tumor progression. To regulate cell types in TME and promote the therapeutic efficiency of anti‐angiogenic therapy, a supramolecular hydrogel drug delivery system (PLDX‐PMI) co‐assembled by anti‐angiogenic nanomedicines (PCN‐Len nanoparticles (NPs)) and oxidized dextran (DX), and loaded with TAMs‐reprogramming polyTLR7/8a nanoregulators (p(Man‐IMDQ) NRs) is developed for orthotopic liver cancer therapy. PCN‐Len NPs target tyrosine kinases of vascular endothelial cells and blocked VEGFR signaling pathway. p(Man‐IMDQ) NRs repolarize pro‐angiogenic M2‐type TAMs into anti‐angiogenic M1‐type TAMs via mannose‐binding receptors, reducing the secretion of VEGF, which further compromised the migration and proliferation of vascular endothelial cells. On highly malignant orthotopic liver cancer Hepa1‐6 model, it is found that a single administration of the hydrogel formulation significantly decreases tumor microvessel density, promotes tumor vascular network maturation, and reduces M2‐subtype TAMs, thereby effectively inhibiting tumor progression. Collectively, findings in this work highlight the great significance of TAMs reprogramming in enhancing anti‐angiogenesis treatment for orthotopic HCC, and provides an advanced hydrogel delivery system‐based synergistic approach for tumor therapy

Extracellular Matrix/Glycopeptide Hybrid Hydrogel as an Immunomodulatory Niche for Endogenous Cardiac Repair after Myocardial Infarction

Abstract The treatment of myocardial infarction (MI) remains a substantial challenge due to excessive inflammation, massive cell death, and restricted regenerative potential, leading to maladaptive healing process and eventually heart failure. Current strategies of regulating inflammation or improving cardiac tissue regeneration have limited success. Herein, a hybrid hydrogel coassembled by acellular cardiac extracellular matrix (ECM) and immunomodulatory glycopeptide is developed for endogenous tissue regeneration after MI. The hydrogel constructs a niche recapitulating the architecture of native ECM for attracting host cell homing, controlling macrophage differentiation via glycopeptide unit, and promoting endotheliocyte proliferation by enhancing the macrophage‐endotheliocyte crosstalk, which coordinate the innate healing mechanism for cardiac tissue regeneration. In a rodent MI model, the hybrid hydrogel successfully orchestrates a proreparative response indicated by enhanced M2 macrophage polarization, increased angiogenesis, and improved cardiomyocyte survival, which alleviates infarct size, improves wall thicknesses, and enhances cardiac contractility. Furthermore, the safety and effectiveness of the hydrogel are demonstrated in a porcine MI model, wherein proteomics verifies the regulation of immune response, proangiogenesis, and accelerated healing process. Collectively, the injectable composite hydrogel serving as an immunomodulatory niche for promoting cell homing and proliferation, inflammation modulation, tissue remodeling, and function restoration provides an effective strategy for endogenous cardiac repair

Autocrine/paracrine human growth hormone-stimulated microRNA 96-182-183 cluster promotes epithelial-mesenchymal transition and invasion in breast cancer

10.1074/jbc.M115.653261Journal of Biological Chemistry2902213812-1382