Exploratory Study of Relationship Between Obstructive Sleep Apnea Syndrome and Growth Hormones and Inflammatory Factors in Children.

Purpose: In children, obstructive sleep apnea (OSA) is associated with growth hormone level abnormalities and chronic systemic inflammation. This study was performed to investigate the relationship of the degree of OSA with insulin-like growth factor 1 (IGF-1) and inflammatory cytokines in pediatric OSA and the inter-relationship between inflammatory cytokines and growth hormones. Methods: Children with OSA and controls without OSA participated in the study. Information included polysomnography followed by measurement of IGF-1 and inflammatory marker levels. In total, 226 patients aged 2 to 12 years were divided into 4 groups: non-OSA, n = 57 (25.2%); mild OSA, n = 116 (51.3%); moderate OSA, n = 23 (10.2%); and severe OSA, n = 30 (13.3%). Results: Body height was not significantly different among the 4 groups. However, the minimum oxygen saturation and IGF-1 significantly differed among the different OSA groups (P = .0001 and P = .036, respectively). IGF-1 was significantly higher in the non-OSA group (P < .05) and mild OSA group (P < .01) than in the severe OSA group. As the severity of OSA increased, the interleukin-5 level significantly increased, which caused a difference between mild OSA and moderate OSA (P < .05) and between mild OSA and severe OSA (P < .001). In the univariate quantile regression analysis of IGF-1, there was a negative relationship between IGF-1 and IL-5 (P < .001). IGF-1 was positively correlated with age, height, and minimum oxygen saturation. Furthermore, there was a negative correlation between the IGF-1 level and the severity of OSA. Quantile regression analysis on the multivariable analysis of the IGF-1 association showed that height, sex, and severity of OSA played important roles in affecting IGF-1 levels. Conclusion: High IL-5 levels may lead to the low secretion of growth hormone level (IGF-1) in children, thus affecting growth and development.

Electrochemically-driven actuators: from materials to mechanisms and from performance to applications.

Soft actuators, pivotal for converting external energy into mechanical motion, have become increasingly vital in a wide range of applications, from the subtle engineering of soft robotics to the demanding environments of aerospace exploration. Among these, electrochemically-driven actuators (EC actuators), are particularly distinguished by their operation through ion diffusion or intercalation-induced volume changes. These actuators feature notable advantages, including precise deformation control under electrical stimuli, freedom from Carnot efficiency limitations, and the ability to maintain their actuated state with minimal energy use, akin to the latching state in skeletal muscles. This review extensively examines EC actuators, emphasizing their classification based on diverse material types, driving mechanisms, actuator configurations, and potential applications. It aims to illuminate the complicated driving mechanisms of different categories, uncover their underlying connections, and reveal the interdependencies among materials, mechanisms, and performances. We conduct an in-depth analysis of both conventional and emerging EC actuator materials, casting a forward-looking lens on their trajectories and pinpointing areas ready for innovation and performance enhancement strategies. We also navigate through the challenges and opportunities within the field, including optimizing current materials, exploring new materials, and scaling up production processes. Overall, this review aims to provide a scientifically robust narrative that captures the current state of EC actuators and sets a trajectory for future innovation in this rapidly advancing field.

Multiscale architecture design of 3D printed biodegradable Zn-based porous scaffolds for immunomodulatory osteogenesis.

Reconciling the dilemma between rapid degradation and overdose toxicity is challenging in biodegradable materials when shifting from bulk to porous materials. Here, we achieve significant bone ingrowth into Zn-based porous scaffolds with 90% porosity via osteoinmunomodulation. At microscale, an alloy incorporating 0.8 wt% Li is employed to create a eutectoid lamellar structure featuring the LiZn4 and Zn phases. This microstructure optimally balances high strength with immunomodulation effects. At mesoscale, surface pattern with nanoscale roughness facilitates filopodia formation and macrophage spreading. At macroscale, the isotropic minimal surface G unit exhibits a proper degradation rate with more uniform feature compared to the anisotropic BCC unit. In vivo, the G scaffold demonstrates a heightened efficiency in promoting macrophage polarization toward an anti-inflammatory phenotype, subsequently leading to significantly elevated osteogenic markers, increased collagen deposition, and enhanced new bone formation. In vitro, transcriptomic analysis reveals the activation of JAK/STAT pathways in macrophages via up regulating the expression of Il-4, Il-10, subsequently promoting osteogenesis.

A Dose-Dependent Spatiotemporal Response of Angiogenesis Elicited by Zn Biodegradation during the Initial Stage of Bone Regeneration.

Zinc (Zn) plays a crucial role in bone metabolism and imbues biodegradable Zn-based materials with the ability to promote bone regeneration in bone trauma. However, the impact of Zn biodegradation on bone repair, particularly its influence on angiogenesis, remains unexplored. This study reveals that Zn biodegradation induces a consistent dose-dependent spatiotemporal response in angiogenesis,both in vivo and in vitro. In a critical bone defect model, an increase in Zn release intensity from day 3 to 10 post-surgery is observed. By day 10, the CD31-positive area around the Zn implant significantly surpasses that of the Ti implant, indicating enhanced angiogenesis. Furthermore,angiogenesis exhibits a distance-dependent pattern closely mirroring the distribution of Zn signals from the implant. In vitro experiments demonstrate that Zn extraction fosters the proliferation and migration of human umbilical vein endothelial cells and upregulates the key genes associated with tube formation, such as HIF-1α and VEGF-A, peaking at a concentration of 22.5 µM. Additionally, Zn concentrations within the range of 11.25-45 µM promote the polarization of M0-type macrophages toward the M2-type, while inhibiting polarization toward the M1-type. These findings provide essential insights into the biological effects of Zn on bone repair, shedding light on its potential applications.

Psoralen synergies with zinc implants to promote bone repair by regulating ZIP4 in rats with bone defect.

BACKGROUND: The regulation of dose-dependent biological effects induced by biodegradation is a challenge for the production of biodegradable bone-substitute materials, especially biodegradable zinc (Zn) -based materials. Cytotoxicity caused by excess local Zn ions (Zn2+) from degradation is one of the factors limiting the wide application of Zn implants. Given that previous studies have revealed that delayed degradation of Zn materials by surface modification does not reduce cytotoxicity; in the present study, we explore whether preventing the entry of excess Zn2+ into cells may can reduce local Zn toxicity by applying Psoralen (PRL) to Zn implants and assessing its ability to regulate intracellular Zn2+ concentrations. METHODS: The effects of different concentrations of Zn2+ on cellular activity and cytotoxicity were investigated; briefly, we identified natural compounds that regulate Zn transporters, thereby regulating the concentrations of intracellular Zn2+, and applied them to Zn materials. Of these materials, PRL, a natural, tricyclic, coumarin-like aromatic compound that promotes the proliferation and differentiation of osteoblasts and enhances osteogenic activity, was loaded onto the surface of a Zn material using peptides and chitosan (CS), and the surface characteristics, electrochemical properties, and activity of the modified Zn material were evaluated. In addition, the ability of Zn + CS/pPRL implants to promote bone formation and accelerate large-scale bone defect repairs was assessed both in vitro and in vivo. RESULTS: We determined that 180 µM Zn2+ significantly induced pre-osteoblast cytotoxicity, and a 23-fold increase in Zrt- and Irt-like protein 4 (ZIP4) expression. We also found that PRL dynamically regulates the expression of ZIP4 in response to Zn2+ concentration. To address the problem of cytotoxicity caused by excessive Zn2+ in local Zn implants, PRL was loaded onto the surface of Zn implants in vivo using peptides and CS, which dynamically regulated ZIP4 levels, maintained the balance of intracellular Zn2+ concentrations, and enhanced the osteogenic activity of Zn implants. CONCLUSIONS: This study reveals the importance of Zn2+ concentration when using Zn materials to promote bone formation and introduces a natural active ingredient, PRL, that can regulate intracellular Zn2+ levels, and thus may be clinically applicable to Zn implants for the treatment of critical bone defects.

The advantages of domestic ear molding system in molding bilateral neonatal congenital auricular deformities.

BACKGROUND: There are different types of ear molding devices on the market. However, due to high cost, the wide application of the ear molding is hindered, especially for children with bilateral congenital auricular deformities (CAD). This study is designed to correct the bilateral CAD with the flexible use of Chinese domestic ear molding system. METHODS: Newborns diagnosed with bilateral CAD were recruited in our hospital from September 2020 to October 2021. For each subject, one ear wore a set of domestic ear molding system, while the contralateral ear used only matching Retractor and Antihelix Former. Medical charts were reviewed to collect data on the types of CAD, the incidence of complications, the initiation and duration of treatment, as well as the satisfaction after treatment. Treatment outcomes were graded into three levels: excellent, good, and poor, according to the improvement of auricular morphology evaluated by both doctors and parents, respectively. RESULTS: A total of 16 infants (32 ears) were treated with the Chinese domestic ear molding system, which contains 4 cases with Stahl's ear (8 ears), 5 cases with Helical rim deformity (10 ears), 3 cases with Cup ear (6 ears), 4 cases with Lop ear (8 ears). All infants accomplished the correction completely. Both parents and doctors were satisfied with the outcomes. No obvious complication was observed. CONCLUSIONS: Ear molding is an effective nonsurgical treatment for CAD. Molding with Retractor and Antihelix Former is simple and effective. Domestic ear molding system can be flexibly used in correcting bilateral CAD. With this approach, infants with bilateral CAD will benefit more in the near future.

miR-146a-5p targets Sirt1 to regulate bone mass.

MicroRNAs (miRNAs) have been proven to serve as key post-transcriptional regulators, affecting diverse biological processes including osteogenic differentiation and bone formation. Recently, it has been reported that miR-146a-5p affects the activity of both osteoblasts and osteoclasts. However, the target genes of miR-146a-5p in these procedures remain unknown. Here we identify miR-146a-5p as a critical suppressor of osteoblastogenesis and bone formation. We found that miR-146a-5p knockout mice exhibit elevated bone formation and enhanced bone mass in vivo. Consistently, we also found that miR-146a-5p inhibited the osteoblast differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. Importantly, we further demonstrated that miR-146a-5p directly targeted Sirt1 to inhibit osteoblast activity. Additionally, we showed that the expression of miR-146a-5p gradually increased in femurs with age not only in female mice but also in female patients, and miR-146a-5p deletion protected female mice from age-induced bone loss. These data suggested that miR-146a-5p has a crucial role in suppressing the bone formation and that inhibition of miR-146a-5p may be a strategy for ameliorating osteoporosis.

[Effects of hyoid position on surgical treatment outcome for patients with obstructive sleep apnea hypopnea syndrome].

OBJECTIVE: To evaluate the predictive value of the position of the hyoid in surgical outcomes of velopharyngeal surgery for obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: The polysomnography, CT, and anthropometry data were retrospectively reviewed from patients who underwent revised uvulopalatopharyngoplasty with uvula preservation (H-UPPP) simply or the combination of H-UPPP and transpalatal advance pharyngoplasty (TAP) for OSAHS from July 2008 to December 2011. OSAHS was diagnosed by polysomnography (PSG) in 128 patients who underwent H-UPPP or H-UPPP with TAP surgery for their sleep disorder. After surgical treatment, the patients were evaluated by PSG. RESULTS: The 128 patients included were all male, the mean age of these patients was (39.6±8.5) years, ranged from 19 to 66 years. Seventy-seven patients were successfully treated and 51 did not respond to surgical treatment. The overall apnea hypopnea index (AHI) improved from (58.2±22.4) times/h preoperatively to (20.6±18.1) times/h postoperatively (t=14.9, P<0.001). The vertical distance from inferior margin of hyoid to the inferior mandibular margin (D-HM) was the only parameter that had a significant difference between responders [(14.6±7.7)mm] and non-responders [(19.4±8.0)mm] (t=3.452, P=0.001). D-HM, AHI and the lowest blood oxygen saturation were significant predictors of surgical outcomes (P<0.05). There was a significant correlation between the D-HM and the postoperative AHI (r=0.284, P=0.001). The D-HM of ≥23 mm could predict the postoperative AHI of >10 times/h a specificity of 95.2%. CONCLUSION: The D-HM is a negative predictor of surgical outcomes, patients with a D-HM of ≥23 mm are inappropriate candidates for velopharyngeal surgery.

The combination of anatomy and physiology in predicting the outcomes of velopharyngeal surgery.

OBJECTIVES/HYPOTHESIS: To explore whether the variables resulting from anatomical and physiological examinations can be combined to predict the outcomes of velopharyngeal surgery for obstructive sleep apnea (OSA). STUDY DESIGN: Prospective design with a retrospective review. METHODS: A total of 119 patients with OSA received velopharyngeal surgery, including revised uvulopalatopharyngoplasty with uvula preservation and transpalatal advancement pharyngoplasty. The preoperative examinations of these patients, including polysomnography (PSG), physical examination, and three-dimensional computer tomography (3-D CT), were obtained for analysis. RESULTS: The overall success rate was 62.2%. Three factors were found to be predictive in treatment outcomes (P<0.05). These were tonsil size, the percentage of time with oxygen saturation below 90% (CT90), and the vertical distance between the lower edge of the mandible and the lower edge of the hyoid (MH). After changing CT90 and MH into level variables, another regression analysis was performed and the result suggested that all three level variables could be included. A scoring system was then created based on these three variables and their odds ratio values. The total scores of all patients were calculated by the following equation: Total score=2.7 tonsil size (score)+2.2 CT90 (score)+1.6 MH (score). The differences in success rates among patients with total scores of <14, 14 to 17, 17 to 22, and ≥22 were all significant (P<0.05). CONCLUSION: The anatomy of the pharynx and the physiology of OSA are both important in deciding outcomes of velopharyngeal surgery. Variables that could represent these two aspects can be combined to better guide patient selections. LEVEL OF EVIDENCE: 4.

[Upper airway changes in obstructive sleep apnea suffers after H-uvulopalatopharyngoplasty and H-uvulopalatopharyngoplasty combined with transpalatal advancement pharyngoplasty].

OBJECTIVE: To compare the different postoperative changes of the pharynx in obstructive sleep apnea hypopnea syndrome (OSAHS) patients treated with H-uvulopalatopharyngoplasty (H-UPPP) combined with transpalatal advancement pharyngoplasty (PA) surgery or H-UPPP alone. METHODS: The upper airway in 43 patients with OSAHS were scanned during the end of normal respiration before and after treatment. There were 17 patients undergoing H-UPPP alone, 26 patients undergoing H-UPPP combined with PA, with PSG before and after treatment. To compare the efficacy of H-UPPP with PA surgery or H-UPPP alone, upper airway characteristics were measured following each procedure in 43 patients using a quantitative 3-D CT. The 3-D CT measurement were made in lateral and anterior-posterior diameters, cross-section areas and volumes of retropalatal and retroglossal region. The changes in the structure of OSAHS patients treated with H-UPPP combined with PA surgery and H-UPPP alone were compared preoperatively and postoperatively, and the correction features that were presented in AHI and structural changes were analysed. RESULTS: The difference between H-UPPP combined with PA (n = 26) and H-UPPP (n = 17) in the changes in apnea hypopnea index (AHI) were (67.5 ± 18.9, 38.7 ± 42.0, t = 2.84, P < 0.05), hard palate lengths were (4.50 ± 3.72) mm and (0.06 ± 0.22) mm (t = 5.55, P < 0.01); anteroposterior diameters of the hard palate level were (3.5 ± 4.3) mm and (-1.7 ± 4.4) mm (t = 3.90, P < 0.01); the minimum anteroposterior diameters of retropalatal were (1.2 ± 2.2) mm and (-1.2 ± 2.3) mm (t = -3.49, P < 0.01); the minimum lateral diameters of retroglossal area were (4.9 ± 9.6) mm and (13.1 ± 9.1) mm (t = 2.80, P < 0.01) preoperatively and postoperatively. The changes in the hard palate lengths were positively correlated to the change in AHI (r = 0.407, P < 0.01), also the change in anteroposterior diameter of the hard palate level (r = 0.351, P < 0.05), the minimum anteroposterior diameter of retropalatal area (r = 0.381, P < 0.01), and the minimum cross-section area of retropalatal (r = 0.312, P < 0.05). CONCLUSIONS: H-UPPP combined with PA offers benefit over H-UPPP alone in OSAHS patients, which may be achieved by increased retropalatal airway size. Both the anteroposterior dimensions and the cross-area size are related with the efficacy of surgery.