Recent advances in microneedles-mediated transdermal delivery of protein and peptide drugs

Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity. However, the inherent properties of these drugs, such as large molecular weight, poor stability, and conformational flexibility, make them difficult to be formulated and delivered. Injection is the primary route for clinical administration of protein and peptide drugs, which usually leads to poor patient's compliance. As a portable, minimally invasive device, microneedles (MNs) can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation. In this review, we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs. Emphasis was given to the latest development in representative MNs design and fabrication. We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery, especially in the field of infectious disease, diabetes, cancer, and other disease therapy. Finally, the current status of clinical translation and a perspective on future development are also provided.

Mid-term clinical outcome analysis of aortic valve repair for rheumatic aortic valve disease / 中华胸心血管外科杂志

Objective:To evaluate the mid-term outcomes of patients with rheumatic heart disease who underwent aortic valve repair surgery in a prospective cohort.Methods:From January 2016 to December 2020, a total of 54 patients with rheumatic heart disease underwent aortic valve repair surgery in Beijing Anzhen Hospital, with an average age of (50.61±13.29) years, including 29 females (53.7%). There were 31 patients (57.4%) had pure aortic insufficiency, 2 patients (3.7%) had pure aortic stenosis and 21 patients (38.9%) had mixed lesion. During the same period, 43 patients (80.0%) underwent mitral valve surgery, 36 patients (66.7%) underwent tricuspid valve surgery, and 20 patients (37.0%) underwent atrial fibrillation radiofrequency ablation.The follow-up period was from 1 month to 61 months (median follow-up was 25 months). Paired rank-sum test was used to compare the differences in continuous variables among subjects, and Kaplan- Meier method was used to analyze the clinical outcomes during the follow-up period. Results:Proportion of moderate and severe aortic regurgitation Preoperatively was higher than that of discharge data, aortic valve orifice maximum velocity and left ventricular end-diastolic diameter were significantly lower than discharge data (all P<0.05). The 5-year survival rate was (96.1±2.7)% (2 patients died). The 5-year freedom from reoperation after aortic valve repair was (89.5±4.5)%(5 patients underwent redo surgery). The 5-year freedom from valvular-related complications was (91.3±4.2)%(3 patients suffered from complications). Conclusion:Aortic valve repair surgery for rheumatic aortic valve disease is feasible and has excellent early and mid-term results, it can be a reliable treatment option.

Tailored core‒shell dual metal-organic frameworks as a versatile nanomotor for effective synergistic antitumor therapy

Malignant tumor has become an urgent threat to global public healthcare. Because of the heterogeneity of tumor, single therapy presents great limitations while synergistic therapy is arousing much attention, which shows desperate need of intelligent carrier for co-delivery. A core‒shell dual metal-organic frameworks (MOFs) system was delicately designed in this study, which not only possessed the unique properties of both materials, but also provided two individual specific functional zones for co-drug delivery. Photosensitizer indocyanine green (ICG) and chemotherapeutic agent doxorubicin (DOX) were stepwisely encapsulated into the nanopores of MIL-88 core and ZIF-8 shell to construct a synergistic photothermal/photodynamic/chemotherapy nanoplatform. Except for efficient drug delivery, the MIL-88 could be functioned as a nanomotor to convert the excessive hydrogen peroxide at tumor microenvironment into adequate oxygen for photodynamic therapy. The DOX release from MIL-88-ICG@ZIF-8-DOX nanoparticles was triggered at tumor acidic microenvironment and further accelerated by near-infrared (NIR) light irradiation. The

A homogenous nanoporous pulmonary drug delivery system based on metal-organic frameworks with fine aerosolization performance and good compatibility

Pulmonary drug delivery has attracted increasing attention in biomedicine, and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs. However, the existing methods for preparing porous particles using porogens have several drawbacks, such as the inhomogeneous and uncontrollable pores, drug leakage, and high risk of fragmentation. In this study, a series of cyclodextrin-based metal-organic framework (CD-MOF) particles containing homogenous nanopores were delicately engineered without porogens. Compared with commercial inhalation carrier, CD-MOF showed excellent aerosolization performance because of the homogenous nanoporous structure. The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments, including cytotoxicity assay, hemolysis ratio test, lung function evaluation,

Surgical repair strategy for rheumatic mitral valvular disease / 中华胸心血管外科杂志

Rheumatic mitral valve disease is one of the main causes of mitral valve disease in China,as one of the ideal surgical methods for rheumatic mitral valve disease,mitral valve repair is more complicated than replacement of mitral valve.Although the surgical strategy of mitral valve repair is similar to that of degenerative changes,rheumatic lesions and ischemic mitral valve diseases and our team experience,the degree,characteristics and location of mitral valve rheumatic lesions are significantly different from that of degenerative and ischemic lesions,so the choice of repair strategy is also different.Combined with the characteristics of rheumatic mitral valve diseases,the surgical repair strategies of rheumatic mitral valve diseases are reviewed.