Unlocking the Therapeutic Applicability of LNP-mRNA: Chemistry, Formulation, and Clinical Strategies.

Messenger RNA (mRNA) has emerged as an innovative therapeutic modality, offering promising avenues for the prevention and treatment of a variety of diseases. The tremendous success of mRNA vaccines in effectively combatting coronavirus disease 2019 (COVID-19) evidences the unlimited medical and therapeutic potential of mRNA technology. Overcoming challenges related to mRNA stability, immunogenicity, and precision targeting has been made possible by recent advancements in lipid nanoparticles (LNPs). This review summarizes state-of-the-art LNP-mRNA-based therapeutics, including their structure, material compositions, design guidelines, and screening principles. Additionally, we highlight current preclinical and clinical trends in LNP-mRNA therapeutics in a broad range of treatments in ophthalmological conditions, cancer immunotherapy, gene editing, and rare-disease medicine. Particular attention is given to the translation and evolution of LNP-mRNA vaccines into a broader spectrum of therapeutics. We explore concerns in the aspects of inadequate extrahepatic targeting efficacy, elevated doses, safety concerns, and challenges of large-scale production procedures. This discussion may offer insights and perspectives on near- and long-term clinical development prospects for LNP-mRNA therapeutics.

The diagnosis and treatment of a special rare type of Monteggia equivalent fractures in children.

Purpose: To explore the characteristics, mechanism, treatment, and prognosis of head-neck separation type of Monteggia equivalent fractures in children. Methods: Patients with this injury were reviewed retrospectively. The lesion was characterized by a fracture of the ulnar with radial neck fracture but without dislocation of the radial head. Our classification was based on the direction of displacement and angulation of fractures on radiographs, divided into the extension-valgus type and flexion-varus type. The fractures were treated with reduction and internal fixation, depending on the fracture type. The clinical results were evaluated by using radiology and the Mayo Elbow Performance Score (MEPS). Results: A total of 12 patients were followed up for an average of 40.5 months. The ulnar fractures were treated with closed reduction (CR) and K-wire fixation in one patient, elastic stable intramedullary nail (ESIN) fixation in four patients, open reduction (OR) and plate fixation in five, with no fixation in two. CR with ESIN fixation was successful in 11 patients with radial neck fractures, but one underwent OR and K-wire fixation. All fractures healed on time, with fewer complications (avascular necrosis in one patient, and bulk formation of metaphysis in another). The therapeutic efficacy was evaluated by using MEPS and was found to be excellent in 10 patients, good in one, and fair in another. Conclusions: The head-neck separation type of Monteggia equivalent fractures in children is rare. Its characteristics are different from that of Monteggia fracture. The length and anatomic structure of the ulna should be restored and stabilized first, while the radial neck fracture should be treated with CR and ESIN fixation. Satisfactory clinical results can be achieved with fewer complications.

Carbon Nanotube Fibers for Neural Recording and Stimulation.

Recordings and stimulations of neuronal electrical activity are topics of great interest in neuroscience. Many recording techniques, and even treatment of neurological disorders, can benefit from a microelectrode that is flexible, chemically inert, and electrically conducting and preferentially transfers electrons via capacitive charge injection. Commercial electrodes that currently exist and other electrodes that are being tested with the purpose of facilitating and improving the electron transport between solid materials and biological tissues still have some limitations. This paper discusses carbon nanotube (CNT)-based microelectrodes to record and stimulate neurons and compares their electron transport capabilities to noble metals such as Au and Ag. The recording ability of electrodes is tested through electroretinography on Sarcophaga bullata fly eyes by using Au and Ag wires and CNT fibers as electrodes. Stimulation is demonstrated through the implantation of Au wire and CNT fibers into the antennas of the Madagascar hissing cockroach (Gromphadorhina portentosa) to control their locomotion. Our results demonstrate that a particular property of the CNT fiber is its high rate of electron transfer, leading to an order of magnitude lower impedance compared to Au and Ag and an impressive 15.09 charge injection capacity. We also established that this carbon nanomaterial assembly performs well for in vivo electrophysiology, rendering it a promising prospect for neurophysiological applications.

Surgical results of developmental dysplasia of the hip in older children based on using three-dimensional computed tomography.

BACKGROUND: The surgical management of developmental dysplasia of the hip (DDH) in older children has been the subject of controversy. The purpose of this study was to evaluate the outcome in patients with neglected DDH who underwent individual procedures based on using three-dimensional computed tomography. METHODS: Forty-seven patients (59 hips) were treated using Pemberton osteotomy or Dega plus Pemberton osteotomy. Subtrochanteric transverse femoral shortening and derotation osteotomy were performed for all patients. The average age at the time of surgery was 10.5 y for group 1 (bilateral dislocation, 24 hips) and 11.2 y for group 2 (unilateral dislocation, 35 hips). Mean follow-up was 5.3 y for group 1 and 5.8 y for group 2. RESULTS: At the end of follow-up, 13 hips (54.2%) were rated excellent, eight hips (33.3%) were good, and three hips (12.5%) were fair in group 1. In group 2, 20 hips (57.1%) were rated excellent, 10 hips (28.6%) were good, and five hips (14.3%) were fair. There were five patients who had a limb length discrepancy of approximately 1.5 cm in group 2. Six hips in group 1 and seven hips in group 2 had osteonecrosis of varying severity. CONCLUSIONS: We believe that preoperation three-dimensional computed tomography evaluation, personalized operation plans, and experience with the surgical procedure are the main reasons for the satisfactory therapeutic effects achieved in this study in older children with DDH.