Comparison of neurally adjusted ventilatory assist and synchronized intermittent mandatory ventilation in preterm infants after patent ductus arteriosus ligation: a retrospective study.

OBJECTIVE: This study aimed to compare the efficacy of neurally adjusted ventilatory assist (NAVA) to synchronized intermittent mandatory ventilation (SIMV) in preterm infants requiring mechanical ventilation after patent ductus arteriosus (PDA) ligation. METHODS: A retrospective analysis was conducted on intubated preterm infants who underwent PDA ligation at our hospital from July 2021 to January 2023. Infants were divided into NAVA or SIMV groups based on the ventilation mode after surgery. RESULTS: Fifty preterm infants were included. During treatment, peak inspiratory pressure (PIP) and mean airway pressure (MAP) were lower with NAVA compared to SIMV (PIP: 19.1 ± 2.9 vs. 22.4 ± 3.6 cmH2O, P < 0.001; MAP: 9.1 ± 1.8 vs. 10.9 ± 2.7 cmH2O, P = 0.002). PaO2 and PaO2/FiO2 were higher with NAVA (PaO2: 94.0 ± 11.7 vs. 84.8 ± 15.8 mmHg, P = 0.031; PaO2/FiO2: 267 [220-322] vs. 232 [186-290] mmHg, P = 0.025). Less sedation was required with NAVA (midazolam: 1.5 ± 0.5 vs. 1.1 ± 0.3 µg/kg/min, P < 0.001). CONCLUSION: Compared to SIMV, early use of NAVA post PDA ligation in preterm infants was associated with decreased PIP and MAP. Early NAVA was also associated with reduced sedation needs and improved oxygenation. However, further studies are warranted to quantify the benefits of NAVA ventilation.

Identification of autophagy-associated circRNAs in sepsis-induced cardiomyopathy of mice.

Circular RNAs (circRNAs) play a role in sepsis-related autophagy. However, the role of circRNAs in autophagy after sepsis-induced cardiomyopathy (SICM) is unknown, so we explored the circRNA expression profiles associated with autophagy in an acute sepsis mouse model. At a dose of 10 mg/kg, mice were intraperitoneally administered with lipopolysaccharides. The myocardial tissue was harvested after 6 h for microarray analysis, qRT-PCR, and western blotting. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Gene Set Enrichment Analysis were evaluated, and a competing endogenous RNA network was constructed, to evaluate the role of circRNAs related to autophagy in SICM. In total, 1,735 differently expressed circRNAs were identified in the LPS-treated group, including 990 upregulated and 745 downregulated circRNAs. The expression level of the autophagy-specific protein p62 decreased, while the ratio of LC3 II to LC3 I increased. Additionally, 309 mRNAs and 187 circRNAs were correlated with autophagy in myocardial tissue after SICM. Of these, 179 circRNAs were predicted to function as "miRNA sponges". Some distinctive circRNAs and mRNAs found by ceRNA analysis might be involved in autophagy in SICM. These findings provide insights into circRNAs and identified new research targets that may be used to further explore the pathogenesis of SICM.

Novel rapid coordination of ascorbic acid 2-phosphate and iron(III) as chromogenic substrate system based on Fe2O3 nanoparticle and application in immunoassay for the colorimetric detection of carcinoembryonic antigen.

This work for the first time reports on a simple and rapid colorimetric immunoassay with rapid coordination of ascorbic acid 2-phosphate (AAP) and iron (III) for determination of carcinoembryonic antigen (CEA, used as a model) by using Fe2O3 nanoparticle based-chromogenic substrate system. The signal was produced rapidly (1 min) from the coordination of AAP and iron (III) with color development of colorless to brown. TD-DFT calculation methods were employed to simulate the UV-Vis spectra of AAP-Fe2+ and AAP-Fe3+ complexes. Moreover, Fe2O3 nanoparticle could be dissolved with the aid of acid, thereby releasing free iron (III). Herein, a sandwich-type immunoassay was established based on Fe2O3 nanoparticle as labels. As target CEA concentration increased, the number of Fe2O3 labelled-antibodies (bound specifically) increased, resulting in loading more Fe2O3 nanoparticle on platform. The absorbance increased as the number of free iron (III), derived from Fe2O3 nanoparticle, increased. So, the absorbance of reaction solution is positively correlated with antigen concentration. Under optimal conditions, the current results showed good performance for CEA detection in the range 0.02-10.0 ng/mL with a detection limit of 11 pg/mL. Moreover, the repeatability, stability, and selectivity of the colorimetric immunoassay were also acceptable.

Application of High-Frequency Oscillation Ventilation Combined With Volume Guarantee in Preterm Infants With Acute Hypoxic Respiratory Failure After Patent Ductus Arteriosus Ligation.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of high-frequency oscillation ventilation combined with volume guarantee (HFOV-VG) in preterm infants with acute hypoxemic respiratory failure (AHRF) after patent ductus arteriosus ligation. METHODS: We retrospectively analyzed the clinical data of 41 preterm infants, who were ventilated for AHRF after patent ductus arteriosus ligation between January 2020 and January 2022. HFOV alone was used in 20 of the 41 infants, whereas HFOV-VG was used in the other 21 infants. RESULTS: There was no statistically significant difference in the demographic information and baseline characteristics of preterm infants included in the study. The average frequency tidal volume (VThf) of the HFOV-VG group was lower than that of the HFOV group (2.6 ± 0.6 mL versus 1.9 ± 0.3 mL, P < .001). In addition, the incidence of hypocapnia and hypercapnia in infants supported with HFOV-VG was significantly lower (15 versus 8, P < .001; 12 versus 5, P < .001). Furthermore, the duration of invasive ventilation in the HFOV-VG group also was lower than in the HFOV group (3.7 ± 1.2 days versus 2.1 ± 1.0 days, P < .01). CONCLUSION: Compared with HFOV alone, HFOV-VG decreases VThf levels and reduces the incidence of hypercapnia and hypocapnia in preterm infants with acute hypoxic respiratory failure after patent ductus arteriosus ligation.

Injectable cellulose-based hydrogels as nucleus pulposus replacements: Assessment of in vitro structural stability, ex vivo herniation risk, and in vivo biocompatibility.

Current treatments for intervertebral disc degeneration and herniation are palliative only and cannot restore disc structure and function. Nucleus pulposus (NP) replacements are a promising strategy for restoring disc biomechanics and height loss. Cellulose-based hydrogel systems offer potential for NP replacement since they are stable, non-toxic, may be tuned to match NP material properties, and are conducive to cell or drug delivery. A crosslinked, carboxymethylcellulose-methylcellulose dual-polymer hydrogel was recently formulated as an injectable NP replacement that gelled in situ and restored disc height and compressive biomechanical properties. The objective of this study was to investigate the translational potential of this hydrogel system by examining the long-term structural stability in vitro, the herniation risk and fatigue bending endurance in a bovine motion segment model, and the in vivo biocompatibility in a rat subcutaneous pouch model. Results showed that the hydrogels maintained their structural integrity over a 12-week period. AF injury significantly increased herniation risk and reduced fatigue bending endurance in bovine motion segments. Samples repaired with cellulosic hydrogels demonstrated restored height and exhibited herniation risk and fatigue endurance comparable to samples that underwent the current standard treatment of nucleotomy. Lastly, injected hydrogels elicited a minimal foreign body response as determined by analysis of fibrous capsule development and macrophage presence over 12 weeks. Overall, this injectable cellulosic hydrogel system is a promising candidate as an NP substitute. Further assessment and optimization of this cellulosic hydrogel system in an in vivo intradiscal injury model may lead to an improved clinical solution for disc degeneration and herniation.

Composite biomaterial repair strategy to restore biomechanical function and reduce herniation risk in an ex vivo large animal model of intervertebral disc herniation with varying injury severity.

Back pain commonly arises from intervertebral disc (IVD) damage including annulus fibrosus (AF) defects and nucleus pulposus (NP) loss. Poor IVD healing motivates developing tissue engineering repair strategies. This study evaluated a composite injectable IVD biomaterial repair strategy using carboxymethylcellulose-methylcellulose (CMC-MC) and genipin-crosslinked fibrin (FibGen) that mimic NP and AF properties, respectively. Bovine ex vivo caudal IVDs were evaluated in cyclic compression-tension, torsion, and compression-to-failure tests to determine IVD biomechanical properties, height loss, and herniation risk following experimentally-induced severe herniation injury and discectomy (4 mm biopsy defect with 20% NP removed). FibGen with and without CMC-MC had failure strength similar to discectomy injury suggesting no increased risk compared to surgical procedures, yet no biomaterials improved axial or torsional biomechanical properties suggesting they were incapable of adequately restoring AF tension. FibGen had the largest failure strength and was further evaluated in additional discectomy injury models with varying AF defect types (2 mm biopsy, 4 mm cruciate, 4 mm biopsy) and NP removal volume (0%, 20%). All simulated discectomy defects significantly compromised failure strength and biomechanical properties. The 0% NP removal group had mean values of axial biomechanical properties closer to intact levels than defects with 20% NP removed but they were not statistically different and 0% NP removal also decreased failure strength. FibGen with and without CMC-MC failed at super-physiological stress levels above simulated discectomy suggesting repair with these tissue engineered biomaterials may perform better than discectomy alone, although restored biomechanical function may require additional healing with the potential application of these biomaterials as sealants and cell/drug delivery carriers.

Cell-Seeded Adhesive Biomaterial for Repair of Annulus Fibrosus Defects in Intervertebral Discs.

Defects in the annulus fibrosus (AF) of intervertebral discs allow nucleus pulposus tissue to herniate causing painful disability. Microdiscectomy procedures remove herniated tissue fragments, but unrepaired defects remain allowing reherniation or progressive degeneration. Cell therapies show promise to enhance repair, but methods are undeveloped and carriers are required to prevent cell leakage. To address this challenge, this study developed and evaluated genipin-crosslinked fibrin (FibGen) as an adhesive cell carrier optimized for AF repair that can deliver cells, match AF material properties, and have low risk of extrusion during loading. Part 1 determined that feasibility of bovine AF cells encapsulated in high concentration FibGen (F140G6: 140 mg/mL fibrinogen; 6 mg/mL genipin) for 7 weeks could maintain high viability, but had little proliferation or matrix deposition. Part 2 screened tissue mechanics and in situ failure testing of nine FibGen formulations (fibrin: 35-140 mg/mL; genipin: 1-6 mg/mL). F140G6 formulation matched AF shear and compressive properties and significantly improved failure strength in situ. Formulations with reduced genipin also exhibited satisfactory material properties and failure behaviors warranting further biological screening. Part 3 screened AF cells encapsulated in four FibGen formulations for 1 week and found that reduced genipin concentrations increased cell viability and glycosaminoglycan production. F70G1 (70 mg/mL fibrinogen; 1 mg/mL genipin) demonstrated balanced biological and biomechanical performance warranting further testing. We conclude that FibGen has potential to serve as an adhesive cell carrier to repair AF defects with formulations that can be tuned to enhance biomechanical and biological performance; future studies are required to develop strategies to enhance matrix production.

Lower crosslinking density enhances functional nucleus pulposus-like matrix elaboration by human mesenchymal stem cells in carboxymethylcellulose hydrogels.

Engineered constructs represent a promising treatment for replacement of nucleus pulposus (NP) tissue. Recently, photocrosslinked hydrogels comprised of methacrylated carboxymethylcellulose (CMC) were shown to support chondrogenic differentiation of encapsulated human mesenchymal stem cells (hMSCs) and promote accumulation of NP-like extracellular matrix (ECM). The objective of this study was to investigate the influence of CMC crosslinking density, by varying macromer concentration and modification (i.e., methacrylation) percentage, on NP-like differentiation of encapsulated hMSCs. Constructs of lower macromer concentration (2%, w/v) exhibited significantly greater collagen II accumulation, more homogeneous distribution of ECM macromolecules, and a temporal increase in mechanical properties compared to hydrogels of higher macromer concentration (4%, w/v). Constructs of higher modification percentage (25%) gave rise to significantly elevated collagen II content and the formation of cell clusters within the matrix relative to samples of lower modification percentage (10% and 15%). These differences in functional ECM accumulation and distribution are likely attributed to the distinct crosslinked network structures of the various hydrogel formulations. Overall, CMC constructs of lower macromer concentration and modification percentage were most promising as scaffolds for NP tissue engineering based on functional ECM assembly. Optimization of such hydrogel fabrication parameters may lead to the development of clinically relevant tissue-engineered NP replacements.