Efficacy of Oral Appliance for Mild, Moderate, and Severe Obstructive Sleep Apnea: A Meta-analysis.

OBJECTIVE: Oral appliances (OA) are the recommended first-line option for mild-to-moderate obstructive sleep apnea (OSA)-hypopnea. However, there is a lack of evidence to compare the effectiveness of OA in different severities of OSA. The purpose of this study was to investigate the therapeutic effects of preferred OA (tongue retention devices [TRD] and mandibular advancement device [MAD]) in different severities of OSA. DATA SOURCES: PubMed/MEDLINE, The Cochrane Library, and Web of Science. REVIEW METHODS: Concentrating on the efficacy of OA, 2 authors searched 3 databases up to November 10, 2022, independently and systematically, following the requirements and steps of the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. RESULTS: Ultimately, 42 studies with 2265 patients met the criteria for inclusion in OA. Overall, the apnea-hypopnea index improved by 48% (5.6), 67% (14.92), and 62% (32.1) in mild, moderate, and severe OSA, respectively. Subgroup analysis showed a significant difference between MAD and TRD efficacy in mild OSA (58% vs 21%). However, no significant difference was seen between MAD and TRD efficacy in moderate (67% vs 66%) and severe OSA (66% vs 51%). There was no significant difference across groups in the Epworth Sleepiness Scale, oxygen desaturation index (ODI), and lowest oxygen saturation (LSAT). CONCLUSION: Overall, both TRD and MAD are effective treatments for moderate and severe OSA. MAD is efficacious in mild OSA, while TRD requires further validation. Furthermore, mild-moderate and severe OSA received similar improvements in sleepiness, ODI, and LSAT. This study complements the evidence for the efficacy of OA.

Association between overnight repetitive respiratory events and the accumulation of genioglossus fatigue in male patients with severe obstructive sleep apnea.

PURPOSE: To evaluate the correlation between median frequency (MF) as a measure of genioglossus (GG) fatigue and overnight repetitive respiratory events in male patients with severe obstructive sleep apnea (OSA). METHODS: GG electromyography (EMG) data were collected synchronously with polysomnography (PSG). Overnight respiratory events were divided based on whether they occurred during the first or second halves of the total number of overnight respiratory events, and differences in MF in the respiratory phase were compared in the same segments. Events were then sampled in pairs to compare MF. The correlation between MF and the order of respiratory events, as well as interindividual differences, were analyzed. RESULTS: Twenty-two male patients were enrolled in this study and 2210 respiratory events were recorded. Before and during respiratory events, MF decreased significantly in the second half, especially during the inspiratory phase (segments 1-4: P = 0.014, P < 0.001, P < 0.001, P < 0.001, respectively). This trend was observed in non-rapid eye movement sleep and lateral position, but not in rapid eye movement sleep or the supine position, and remained after pairing for duration, stage, and position. MF correlated negatively with the order of respiratory events during the inspiratory phase. The trend of decrease in MF only existed in patients with apnea-hypopnea index > 30 events/h. CONCLUSION: Overnight repetitive respiratory events were associated with increased GG fatigue, influenced by sleep stage and body position in male patients with severe OSA. GG fatigue depends on the order and frequency of respiratory events.

Associations Between Sleep Spindle Metrics, Age, Education and Executive Function in Young Adult and Middle-Aged Patients with Obstructive Sleep Apnea.

Purpose: This study aimed to investigate the association between sleep spindle metrics and executive function in individuals with obstructive sleep apnea (OSA). Furthermore, we examined the association of age and education on executive function. Patients and Methods: A total of 230 (40.90 ± 8.83 years, F/M = 45/185) participants were enrolled. Overnight electroencephalogram (C3-M2) recording detected sleep spindles by a novel U-Net-type neural network that integrates temporal information with time-frequency images. Sleep spindle metrics, including frequency (Hz), overall density (events/min), fast density (events/min), slow density (events/min), duration (sec) and amplitude (µV), were measured. Executive function was assessed using standardized neuropsychological tests. Associations between sleep spindle metrics, executive function, and demographic factors were analyzed using multivariate linear regression. Results: In fully adjusted linear regression models, higher overall sleep spindle density (TMT-A, B=-1.279, p=0.009; TMT-B, B=-1.813, p=0.008), fast sleep spindle density (TMT-A, B=-1.542, p=0.048; TMT-B, B=-2.187, p=0.036) and slow sleep spindle density (TMT-A, B=-1.731, p=0.037; TMT-B, B=-2.449, p=0.034) were associated with better executive function. And the sleep spindle duration both during N2 sleep time (TMT-A, B=-13.932, p=0.027; TMT-B, B=-19.001, p=0.034) and N3 sleep time (TMT-B, B=-29.916, p=0.009; Stroop-incongruous, B=-21.303, p=0.035) was independently associated with better executive function in this population. Additionally, age and education were found to be highly associated with executive function. Conclusion: Specific sleep spindle metrics, higher overall density, fast density and slow density during N2 sleep time, and longer duration during N2 and N3 sleep time, are independent and sensitive indicators of better executive function in young adult and middle-aged patients with OSA. Further research is needed to explore the underlying mechanisms and clinical implications of these findings.

Adipose-derived mesenchymal stem cells (MSCs) are a superior cell source for bone tissue engineering.

Effective bone regeneration through tissue engineering requires a combination of osteogenic progenitors, osteoinductive biofactors and biocompatible scaffold materials. Mesenchymal stem cells (MSCs) represent the most promising seed cells for bone tissue engineering. As multipotent stem cells that can self-renew and differentiate into multiple lineages including bone and fat, MSCs can be isolated from numerous tissues and exhibit varied differentiation potential. To identify an optimal progenitor cell source for bone tissue engineering, we analyzed the proliferative activity and osteogenic potential of four commonly-used mouse MSC sources, including immortalized mouse embryonic fibroblasts (iMEF), immortalized mouse bone marrow stromal stem cells (imBMSC), immortalized mouse calvarial mesenchymal progenitors (iCAL), and immortalized mouse adipose-derived mesenchymal stem cells (iMAD). We found that iMAD exhibited highest osteogenic and adipogenic capabilities upon BMP9 stimulation in vitro, whereas iMAD and iCAL exhibited highest osteogenic capability in BMP9-induced ectopic osteogenesis and critical-sized calvarial defect repair. Transcriptomic analysis revealed that, while each MSC line regulated a distinct set of target genes upon BMP9 stimulation, all MSC lines underwent osteogenic differentiation by regulating osteogenesis-related signaling including Wnt, TGF-ß, PI3K/AKT, MAPK, Hippo and JAK-STAT pathways. Collectively, our results demonstrate that adipose-derived MSCs represent optimal progenitor sources for cell-based bone tissue engineering.

[Effect of mouth breathing on upper airway structure in patients with obstructive sleep apnea].

Objective:To compare the changes of morphology of pharynx in patients with obstructive sleep apnea hypopnea syndrome （OSAHS） and healthy individuals during oral or nasal breathing, and explore the relevant influencing factors. Methods:Twenty-nine adult patients with OSAHS and 20 non-snoring controls underwent MRI to obtain upper airway structural measurements while the subjects were awake and during mouth breathing with a nasal clip.The following were analyzed. ①The changes of upper airway structure of oral and nasal respiration in non-snoring control/OSAHS patients were observed; ②The differences and influencing factors of upper airway structure changes between OSAHS patients and controls were compared during breathing. Results:The control group consisted of 15 males and 5 females, with an apnea-hypopnea index （AHI）<5 events/h, while the OSAHS group comprised 26 males and 3 females with an AHI of 40.4±23.1 events/h and the mean lowest arterial oxygen saturation （LSaO2） was 79.5% ±10.0%. In the both groups, the vertical distance between the mandible and the posterior pharyngeal wall decreased （P<0.05）; The long axis of tongue body decreased （P<0.05）, and the contact area between tongue and palate decreased. There was no significant change in the total volume of the retropalatine（RP） and retroglossal（RG） airway in the control group （P>0.05）. However, the minimum cross-sectional area and volume of the RP airway in OSAHS decreased （P<0.001）. The lateral diameters of uvula plane in OSAHS decreased during mouth breathing, which was contrary to the trend in the control group （P=0.017）. The AHI of patients was positively correlated with the reduction of the volume of the RP airway during oral breathing （P=0.001）; The reduction of the distance between the mandible and the posterior pharyngeal wall was positively correlated with the length of the airway （P<0.001）. Conclusion:Mouth breathing leads to the shortening of the long axis of the tongue, the reduction of the contact area between the soft palate and the tongue, vertical distance between the mandible and the posterior pharyngeal wall, and the cross-sectional area of the epiglottis plane. These changes vary between OSAHS patients and controls. During mouth breathing, the diameters, areas and volumes of the RP area decreased, and were more significant in severe cases.

Analysis of nasal resistance regulation mechanism during postural changes in patients with obstructive sleep apnea by measuring heart rate variability.

STUDY OBJECTIVES: Changes in nasal resistance (NR) during postural changes are influenced by venous filling pressure and autonomic nervous system mediation, and heart rate variability (HRV) can reflect changes in the autonomic nervous system. This study aimed to explore the regulatory mechanisms of NR in patients with obstructive sleep apnea (OSA) during postural changes. METHODS: Healthy controls (apnea-hypopnea index < 5 events/h) and patients with OSA were recruited. NR and electrocardiogram data were collected in sitting, supine, left-lateral, and right-lateral postures. HRV parameters were obtained by analyzing the electrocardiogram data from each posture. Subgroups were divided according to sitting-supine NR changes, and HRV parameters were compared between different postures and groups/subgroups. RESULTS: In total, 34 healthy controls and 39 patients with OSA (mean apnea-hypopnea index 34.34 ± 22.44 events/h) were recruited. During sitting-supine postural changes, the NR increased in the control group but did not change significantly in the OSA group. None of the autonomic nervous system-related HRV parameters changed significantly. After the groups were divided into NR-elevated and NR-unchanged subgroups, sympathetic activity-related HRV parameters were higher in the NR-unchanged subgroup but only statistically significant in the OSA group. When comparing the left and right postures, there was no significant change in NR; however, the OSA group had lower parasympathetic activity-related HRV parameters when in the right posture. CONCLUSIONS: During postural changes from the sitting to supine positions, the total NR increases, and this increment is smaller in patients with OSA. This is likely due to overregulation of sympathetic activity, which may occur in patients with OSA. CITATION: Shi Y, Lou H, Wang H, et al. Analysis of nasal resistance regulation mechanism during postural changes in obstructive sleep apnea patients by measuring heart rate variability. J Clin Sleep Med. 2023;19(4):643-650.

Evaluation of obstructive sleep apnea: an analysis based on aberrant genes.

BACKGROUND: Obstructive sleep apnea (OSA) is an upstream disorder that frequently causes multisystem disorders. Much research has revealed the pathogenesis of OSA, but there is still a lack of research on the complications caused by OSA. METHODS: The mRNA expression and methylation dataset based on peripheral blood mononuclear cells (PBMCs) were downloaded from the Gene Expression Omnibus (GEO) database. All differential expressed genes (DEGs) were ranked using the Robust Rank Aggregation (RRA) algorithm. A weighted gene co-expression network analysis (WGCNA) was constructed. Subsequently, we used immune infiltration, enrichment analysis, and least absolute shrinkage and selection operator (LASSO) regression analysis for apnea and hypopnea index (AHI) and hypertension and excessive daytime sleepiness (EDS) and constructed diagnostic model using random forest algorithm. RESULTS: In the present study, we identified 318 DEGs in PBMCs involved in pathogenesis or continuous positive airway pressure (CPAP) therapy. Pathway enrichment identified DEGs associated with protein regulation and metabolism. Notably, through intra group analysis, we found that the immune disorder was more significant for OSA in males, non-daytime sleepy, or non-hypertensive OSA. The area under the ROC curve of model for EDS prediction is 0.889 and 0.852 for hypertension. Notably, we found that the diagnostic model had a high linear predictive value for AHI. CONCLUSIONS: Our results indicate that PBMCs are a significant component of alterations in OSA and are expected to explain the mechanism of multisystem diseases caused by OSA. The present study provides new insights for symptom evaluation, classification and treatment of OSA from the molecular level.

Influence of postural changes on nasal resistance in patients with obstructive sleep apnea.

OBJECTIVE: Increased nasal resistance (NR) can augment upper airway collapse in patients with obstructive sleep apnea (OSA). Posture change can lead to altered nasal resistance. Our study aimed to investigate the influence of posture changes on NR in patients with OSA. METHODS: Healthy controls without subjective nasal obstruction (apnea-hypopnea index (AHI) < 5 events/h), patients with OSA and subjective nasal obstruction, and patients with OSA and no subjective nasal obstruction were recruited. NR was measured by active anterior rhinomanometry in sitting, supine, left-lateral, and right-lateral postural positions. Total NR and postural change-related NR increments were calculated and compared among groups. RESULTS: In total, 26 healthy controls and 72 patients with OSA (mean AHI 39.7 ± 24.8 events/h) were recruited. Of patients with OSA, 38/72 (53%) had subjective nasal obstruction. Compared with controls, patients with OSA and no subjective nasal obstruction had lower total NR (inspiration, p = 0.037; expiration, p = 0.020) in the supine postural position. There was no difference in sitting, left-lateral, and right-lateral total NR among groups. Total NR was higher in lateral compared to sitting posture in both patients with OSA and in controls. The NR increment for sitting to supine postural change was significantly lower in patients with OSA (inspiration, p = 0.003; expiration, p = 0.005) compared with controls. The change in NR showed no statistically significant difference among groups in supine-left or supine-right postural change. CONCLUSION: Patients with OSA had lower supine total NR and lower total NR increment in the sitting to supine postural change, which may be related to a different posture-related NR regulatory mechanism. This study provides a new exploratory direction for the compensatory mechanism of the upper airway to collapse during sleep.

[Graduate training mode of acupuncture-moxibustion and tuina based on "three crosses and two integrations": a preliminary study].

In view of the core tasks and weak links in the training of medical graduate in the new era, based on the characteristics and development needs of the discipline, a new "three crosses and two integrations" graduate training mode of acupuncture-moxibustion and tuina is proposed, with "equal emphasis on inheritance and innovation, theory and practice" as the core, with "curriculum cross" as the basis, with "academic cross" as the connotation, and with "discipline cross" as the pathway. This new training mode focuses on the comprehensive cultivation of graduates' comprehensive abilities, aiming to achieve the training goal of "strong inheritance ability, excellent innovation ability, good practical ability and broad international perspective".

One-pot controlled synthesis of sea-urchin shaped Bi2S3/CdS hierarchical heterostructures with excellent visible light photocatalytic activity.

In this study, sea-urchin shaped Bi2S3/CdS hierarchical heterostructures are successfully synthesized via a convenient one-pot growth rate controlled route. The product is mainly composed of Bi2S3 nanorods and CdS nanoparticles grown on their surfaces. The formation mechanism was proposed based on the evolution of morphology as a function of solvothermal time, which involves fast formation of the initial sea-urchin shaped Bi2S3 nanoflowers, followed by the gradual growth of numerous CdS nanoparticles on Bi2S3 nanoflowers. The effects of CdS in the composites on their microstructures, optical absorption properties, and photocatalytic activity were investigated comparatively. Due to the synergetic effects between hierarchical Bi2S3 nanoflowers and CdS nanoparticles, the obtained Bi2S3/CdS hierarchical heterostructures exhibit superior catalytic activity over the independent components. Furthermore, the obtained Bi2S3/CdS hierarchical heterostructure composite shows a strong structure-induced enhancement of the photocatalytic performance for the photodegradation of rhodamine B.

Hierarchical core-shell carbon nanofiber@ZnIn2S4 composites for enhanced hydrogen evolution performance.

Improvement of hydrogen evolution ability is an urgent task for developing advanced catalysts. As one of the promising visible-light photocatalysts, ZnIn2S4 suffers from the ultrafast recombination of photoinduced charges, which limits its practical application for efficient solar water splitting. Herein, we reported a two-step method to prepare hierarchical core-shell carbon nanofiber@ZnIn2S4 composites. One-dimensional carbon nanofibers were first prepared by electrospinning and carbonization in N2. The subsequent solvothermal process led to the in situ growth of ZnIn2S4 nanosheets on the carbon nanofibers to fabricate hierarchical structure composites. The hierarchical core-shell configuration structure can help to form an intimate contact between the ZnIn2S4 nanosheet shell and the carbon nanofiber backbone compared with the equivalent physical mixture and can facilitate the interfacial charge transfer driven by the excitation of ZnIn2S4 under visible-light irradiation. Meanwhile, the ultrathin ZnIn2S4 nanosheets were uniformly grown on the surface of the carbon nanofibers, which can avoid agglomeration of ZnIn2S4. These synergistic effects made this unique hierarchical structure composite exhibit a significantly higher visible-light photocatalytic activity toward hydrogen evolution reaction compared with pure ZnIn2S4 or a physical mixture of ZnIn2S4 and carbon nanofibers in the absence of noble metal cocatalysts.

Growth rate controlled synthesis of hierarchical Bi2S3/In2S3 core/shell microspheres with enhanced photocatalytic activity.

Core/shell heterostructure composite has great potential applications in photocatalytic field because the introduction of core can remarkably improve charge transport and enhance the electron-hole separation. Herein, hierarchical Bi2S3/In2S3 core/shell structured microspheres were prepared via a simple one-pot hydrothermal process based on different growth rate of the two kinds of sulphides. The results showed that, the as-prepared hierarchical Bi2S3/In2S3 core/shell heterostructure exhibits significant visible light photocatalytic activity for degradation of 2, 4-dichlorophenol. The introduction of Bi2S3 core can not only improve charge transport and enhance the electron-hole separation, but also broaden the visible light response. The hierarchical porous folwer-like shell of In2S3 could increase the specific surface area and remarkably enhanced the chemical stability of Bi2S3 against oxidation.

Synthesis of hierarchical TiO2 nanoflower with anatase-rutile heterojunction as Ag support for efficient visible-light photocatalytic activity.

Hierarchical flower-like TiO2 with an anatase-rutile heterojunction was prepared by a hydrothermal process in the presence of titanium trichloride and poly(sodium-p-styrenesulfonate) (PSS). The morphology evolution process and formation mechanism of the as-obtained products were investigated in detail. It was found that morphology and crystalline phase can be easily adjusted by changing the reaction time or solution system. On the basis of this hierarchical nanoflower structure, a visible light sensitive Ag/hierarchical flower-like TiO2 plasmonic photocatalyst was fabricated. The obtained composite exhibited significantly visible-light photocatalytic activity, which could be attributed to the existence of a large number of uniformly distributed Ag-TiO2 effective nanojunctions, enhanced visible light-harvesting and improved charge separation due to the migration across the anatase-rutile interface.

In situ controlled growth of ZnIn2S4 nanosheets on reduced graphene oxide for enhanced photocatalytic hydrogen production performance.

A reduced graphene oxide (RGO)-ZnIn(2)S(4) nanosheet composite was successfully synthesized via an in situ controlled growth process. The as-obtained RGO-ZnIn(2)S(4) composite showed excellent visible light H(2) production activity in the absence of noble metal cocatalysts.