Independent relationship between sleep apnea-specific hypoxic burden and glucolipid metabolism disorder: a cross-sectional study.

OBJECTIVES: Obstructive sleep apnea (OSA) is associated with abnormal glucose and lipid metabolism. However, whether there is an independent association between Sleep Apnea-Specific Hypoxic Burden (SASHB) and glycolipid metabolism disorders in patients with OSA is unknown. METHODS: We enrolled 2,173 participants with suspected OSA from January 2019 to July 2023 in this study. Polysomnographic variables, biochemical indicators, and physical measurements were collected from each participant. Multiple linear regression analyses were used to evaluate independent associations between SASHB, AHI, CT90 and glucose as well as lipid profile. Furthermore, logistic regressions were used to determine the odds ratios (ORs) for abnormal glucose and lipid metabolism across various SASHB, AHI, CT90 quartiles. RESULTS: The SASHB was independently associated with fasting blood glucose (FBG) (ß = 0.058, P = 0.016), fasting insulin (FIN) (ß = 0.073, P < 0.001), homeostasis model assessment of insulin resistance (HOMA-IR) (ß = 0.058, P = 0.011), total cholesterol (TC) (ß = 0.100, P < 0.001), total triglycerides (TG) (ß = 0.063, P = 0.011), low-density lipoprotein cholesterol (LDL-C) (ß = 0.075, P = 0.003), apolipoprotein A-I (apoA-I) (ß = 0.051, P = 0.049), apolipoprotein B (apoB) (ß = 0.136, P < 0.001), apolipoprotein E (apoE) (ß = 0.088, P < 0.001) after adjustments for confounding factors. Furthermore, the ORs for hyperinsulinemia across the higher SASHB quartiles were 1.527, 1.545, and 2.024 respectively, compared with the lowest quartile (P < 0.001 for a linear trend); the ORs for hyper-total cholesterolemia across the higher SASHB quartiles were 1.762, 1.998, and 2.708, compared with the lowest quartile (P < 0.001 for a linear trend) and the ORs for hyper-LDL cholesterolemia across the higher SASHB quartiles were 1.663, 1.695, and 2.316, compared with the lowest quartile (P < 0.001 for a linear trend). Notably, the ORs for hyper-triglyceridemia{1.471, 1.773, 2.099} and abnormal HOMA-IR{1.510, 1.492, 1.937} maintained a consistent trend across the SASHB quartiles. CONCLUSIONS: We found SASHB was independently associated with hyperinsulinemia, abnormal HOMA-IR, hyper-total cholesterolemia, hyper-triglyceridemia and hyper-LDL cholesterolemia in Chinese Han population. Further prospective studies are needed to confirm that SASHB can be used as a predictor of abnormal glycolipid metabolism disorders in patients with OSA. TRIAL REGISTRATION: ChiCTR1900025714 { http://www.chictr.org.cn/ }; Prospectively registered on 6 September 2019; China.

T266M variants of ANGPTL4 improve lipid metabolism by modifying their binding affinity to acetyl-CoA carboxylase in obstructive sleep apnea.

BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) is recognized as a crucial regulator in lipid metabolism. Acetyl-CoA carboxylases (ACACAs) play a role in the ß-oxidation of fatty acids. Yet, the functions of ANGPTL4 and ACACA in dyslipidemia of obstructive sleep apnea (OSA) remain unclear. METHODS: This study included 125 male OSA subjects from the Shanghai Sleep Health Study (SSHS) who were matched for age, body mass index (BMI), and lipid profile. Serum ANGPTL4 levels were measured via ELISA. The ANGPTL4 T266M variants of 4455 subjects along with their anthropometric, fasting biochemical, and standard polysomnographic parameters were collected. Linear regression was used to analyze the associations between quantitative traits and ANGPTL4 T266M. Molecular docking and molecular dynamic simulation were employed to compare the effects of the wild-type ANGPTL4 and its T266M mutation on ACACA. RESULTS: Serum ANGPTL4 levels significantly decreased with increasing OSA severity (non-OSA: 59.6 ± 17.4 ng/mL, mild OSA: 50.0 ± 17.5 ng/mL, moderate OSA: 46.3 ± 15.5 ng/mL, severe OSA: 19.9 ± 14.3 ng/mL, respectively, p = 6.02 × 10-16). No associations were found between T266M and clinical characteristics. Molecular docking indicated that mutant ANGTPL4 T266M had stronger binding affinity for the ACACA protein, compared with wild-type ANGPTL4. In terms of protein secondary structure, mutant ANGTPL4 T266M demonstrated greater stability than wild-type ANGPTL4. CONCLUSIONS: Serum ANGTPL4 levels were significantly decreased in OSA patients, particularly among individuals with severe OSA. Although functional ANGTPL4 T266M variants were not associated with lipid levels in OSA, ANGTPL4 T266M could enhance binding affinity for the ACACA protein, potentially regulating lipid metabolism.

[An analysis of clinical efficacy of microvascular decompression for 21 inpatients suffering from primary hemifacial spasm].

Objective:To assess the effectiveness of microvascular decompression（MVD） in treating inpatients suffering from primary hemifacial spasm（HFS）. Methods:A total of 21 inpatients with HFS underwent MVD. The clinical effect was follow up evaluated according to the clinical symptoms until post operative 6 months. Results:The effective rate of MVD for 1 day, 14 days, 1 month, 3 months and 6 months post-operation was 95.2%, 100%, 100%, 100% and 100%, respectively.one patient had transient tinnitus and the symptom disappeared within 6 days postoperatively.one patient developed postoperative incomplete facial paralysis（HB grade IV facial nerve function, grade Ⅱ） and recovered 6 days after surgery; There was no cerebrospinal fluid leakage, intracranial infection, death or disability occurred during follow-up. Conclusion:Microvascular decompression is a safe and effective method for the treatment of primary hemifacial spasm, which is worthy of clinical promotion.

The role of ATP in sleep-wake regulation: In adenosine-dependent and -independent manner.

ATP plays a crucial role as an energy currency in the body's various physiological functions, including the regulation of the sleep-wake cycle. Evidence from genetics and pharmacology demonstrates a strong association between ATP metabolism and sleep. With the advent of new technologies such as optogenetics, genetically encoded biosensors, and novel ATP detection methods, the dynamic changes in ATP levels between different sleep states have been further uncovered. The classic mechanism for regulating sleep by ATP involves its conversion to adenosine, which increases sleep pressure when accumulated extracellularly. However, emerging evidence suggests that ATP can directly bind to P2 receptors and influence sleep-wake regulation through both adenosine-dependent and independent pathways. The outcome depends on the brain region where ATP acts and the expression type of P2 receptors. This review summarizes the experimental evidence on the relationship between ATP levels and changes in sleep states and outlines the mechanisms by which ATP is involved in regulating the sleep-wake cycle through both adenosine-dependent and independent pathways. Hopefully, this review will provide a comprehensive understanding of the current research basis and progress in this field and promote further investigations into the specific mechanisms of ATP in regulating sleep.

Global burden of head and neck cancers from 1990 to 2019.

Head and neck cancer (HNC) exerts a significant healthcare burden worldwide. Insufficient data impedes a comprehensive understanding of its global impact. Through analysis of the 2019 Global Burden of Disease (GBD) database, our secondary investigation unveiled a surging global incidence of HNC, yet a decline in associated mortality and disability-adjusted life years (DALYs) owing to enhanced prognosis. Particularly noteworthy is the higher incidence of escalation among females compared to males. Effective resource allocation, meticulous control of risk factors, and tailored interventions are imperative to curtail mortality rates among young individuals afflicted with HNC in underprivileged regions, as well as in elderly individuals grappling with thyroid cancer.

Association between multiple sleep dimensions in obstructive sleep apnea and the early sign of atherosclerosis.

STUDY OBJECTIVES: We investigated the associations between multiple sleep dimensions in obstructive sleep apnea (OSA) and carotid intima-media thickness (CIMT), an early sign of atherosclerosis, in subjects from the Shanghai Sleep Health Study (SSHS). METHODS: We performed secondary analysis of SSHS in a group of subjects performed the ultrasound evaluation from 2018 to 2022. Multiple sleep dimensions were measured using standard polysomnography. CIMT was measured from ultrasound images as an early sign of atherosclerosis. Multivariable-adjusted linear regression and logistic regression analyses were performed to detect associations between sleep traits in OSA and CIMT. RESULTS: CIMT was found to increase with increasing severity of OSA (P < 0.001). When adjusted for conventional risk factors, microarousal index (MAI) and hypoxic burden (HB) were positively correlated with CIMT while slow wave sleep (SWS) and mean apnea-hypopnea event duration (MAHD) showed negative correlation with CIMT (all P < 0.01). In binary logistic regression analysis, participants with high MAI, less SWS, higher HB and shorter MAHD showed a higher prevalence of thick CIMT with no evidence of interaction by age, sex, or body mass index (P-interaction > 0.05). CONCLUSIONS: Subjects with more severe sleep fragmentation, more severe hypoxemia and increased arousability were more likely to have increased CIMT after adjusting for potential confounders. It is important to evaluate novel indices of sleep fragmentation, hypoxemia and arousability in OSA for early detection and prevention of cardiovascular disease, including stroke. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry; URL: http://www.chictr.org.cn/showproj.aspx?proj=43057; No. ChiCTR1900025714.

Differences in Physiological Endotypes Between Nonpositional and Positional OSA: Results From the Shanghai Sleep Health Study Cohort.

BACKGROUND: Positional OSA (POSA) is a recognized subtype of OSA that exhibits distinct endotypic characteristics when compared with nonpositional OSA (NPOSA). The basis for the disparity in endotypes between these subtypes remains poorly understood. RESEARCH QUESTION: (1) Do individuals with NPOSA and POSA have different underlying OSA endotypes? (2) Which endotypic characteristics are critical in determining NPOSA and POSA severity?. STUDY DESIGN AND METHODS: Within the Shanghai Sleep Health Study cohort, individuals with OSA were recruited and classified as having POSA or NPOSA. Endotypes were calculated using polysomnography. RESULTS: Endotype analysis was conducted in 1,036 individuals with OSA. Compared with individuals with NPOSA, those with POSA had lower loop gain in all sleep stages and all sleep positions (LGAll) (0.55; 95% CI, 0.46-0.66 vs 0.68, 95% CI, 0.52-0.90; P < .001), lower arousal threshold in all sleep stages and all sleep positions (138.67; 95% CI, 118.94-180.87 %Veupnea vs 189.00; 95% CI, 129.71-257.76 %Veupnea; P < .001), higher pharyngeal collapsibility in all sleep stages and all sleep positions (VpassiveAll) (91.85; 95% CI, 83.13-95.15 %Veupnea vs 76.38; 95% CI, 23.77-92.08 %Veupnea; P < .001), and higher muscle compensation in all sleep stages and all sleep positions (6.50; 95% CI, -6.77 to 16.39 %Veupnea vs 3.65; 95% CI, -10.47 to 12.14 %Veupnea; P = .003). Logistic regression analyses indicated that higher VpassiveAll was associated with increased odds of POSA vs NPOSA. In NPOSA, fully adjusted linear regression analyses indicated that VpassiveAll (ß = -0.55; 95% CI, -0.68 to -0.42; P < .001) and LGAll (ß = 0.19; 95% CI, 0.08-0.30; P < .001) were significant independent predictors of the apnea hypopnea index, with VpassiveAll being the most critical factor. In contrast, in POSA, collapsibility appeared to be less influential (ß = -0.09; 95% CI, -0.21 to 0.03; P = .138). Nonanatomic endotypic characteristics (LGAll: ß = 0.29; 95% CI, 0.18-0.41; P < .001; arousal threshold in all sleep stages and all sleep positions: ß = 0.15; 95% CI, 0.01-0.28; P = .031; muscle compensation in all sleep stages and all sleep positions: ß = -0.21; 95% CI, -0.29 to -0.12; P < .001) were significant in determining the severity of POSA, with loop gain being the most crucial factor. INTERPRETATION: This study highlights the differences in endotypes between NPOSA and POSA. In Chinese individuals, anatomic factors were more significant in determining the severity of NPOSA, whereas nonanatomic traits were more likely to determine the severity of POSA. Future research should focus on developing personalized management strategies for individuals with NPOSA and POSA based on their endotypes. TRIAL REGISTRATION: Chinese Clinical Trial Registry; No.: ChiCTR1900025714; URL: https://www.chictr.org.cn/indexEN.html.

Comparison of healing of acute total tympanic membrane perforation between rats with and without excision of the mallear handle.

Objective: We compared the histological changes and hearing restoration during the healing of acute total tympanic membrane (TM) perforations between Sprague-Dawley (SD) rats with and without excision of the mallear handle. Materials and methods: Bilateral, acute, and total TM perforations were created in 36 male SD rats. The mallear handle was preserved in the left ear (handle-preserved ear [HPE]) and excised from the right ear (handle-excised ear [HEE]). Endoscopical examination, auditory brainstem response (ABR) thresholds, histopathological, and scanning electron microscope (SEM) analysis were performed. Results: Endoscopic photographs showed that all perforations in the 18 SD rats were closed. The mean closure times were 6.83 ± 0.85 and 8.50 ± 0.71 days in the HPE and HEE groups, respectively (p < .001). SEM images showed radial arrangement of fiber bundles in a single direction in HPEs, although normal arrangement was not achieved. In contrast, HEEs showed disorganized arrangement. At 1 month after perforation closure, the ABR thresholds at high frequencies were significantly higher in the HEE group than in the HPE group (p = .029 and p = .017 for 16 and 32 kHz, respectively). Additionally, the changes in ABR threshold were significantly different at high frequencies (p = .011 and p = .017 for 16 and 32 kHz, respectively) before and 1 month after perforation closure between the HPE and HEE groups, although the differences were not statistically significant at the remaining frequencies. Conclusion: Although the malleus handle may not affect the closure of total perforation in SD rats, it contributes to accelerate the perforation closure by possible guide the migration of proliferative epithelial cell on the upper halves of the annulus. Additionally, resection of the malleus handle impairs high frequency hearing recovery following spontaneous closure of the TM.

The use of the sleep apnea-specific hypoxic burden to predict obstructive sleep apnea hypopnea syndrome: Evidence from a large cross-sectional study.

OBJECTIVES: Obstructive sleep apnea hypopnea syndrome (OSA) is an independent risk factor for neurocognitive and behavioral problems and cardiovascular and metabolic morbidities, ultimately increasing mortality. However, OSA diagnosis is time-consuming, labor-intensive, and expensive. We evaluated the predictive utility of the sleep apnea-specific hypoxic burden (SASHB) in terms of OSA and the severity thereof in Han Chinese individuals. METHODS: From January 2019 to July 2022, subjects with suspected OSA were recruited in the sleep center of the Shanghai Sixth People's Hospital during sleep evaluation via standard polysomnography. Basic anthropometric measurements and polysomnographic indicators were collected; SASHB was calculated based on the SpO2 trends of apnea or hypopnea events. Models predictive of OSA were established via logistic regression in the experimental group and verified in an independent group by drawing receiver operating characteristic (ROC) curves. RESULTS: A total of 2303 subjects with suspected OSA (1200 in the experimental group and 1103 in the validation group) were included. SASHB was positively correlated with the apnea-hyponea index (AHI) in all subjects (r = 0.823, P < 0.001). SASHB distinguished OSA from non-OSA subjects in both the experimental group {area under the curve (AUC) 0.948 [0.934∼0.962]} and the validation group (AUC 0.931 [0.913∼0.949]). SASHB predicted OSA severity well, better than did the neck, waist, or hip circumference; the lowest or mean oxygen saturation; and the Epworth sleepiness scale score. CONCLUSION: SASHB predicted OSA both accurately and efficiently in a Chinese Han population. Further studies are warranted to verify our findings in community samples.

Melatonin attenuates chronic intermittent hypoxia-induced intestinal barrier dysfunction in mice.

BACKGROUND AND PURPOSE: Chronic intermittent hypoxia (CIH) triggers subclinical intestinal barrier disruption prior to systemic low-grade inflammation. Increasing evidence suggests therapeutic effects of melatonin on systemic inflammation and gut microbiota remodelling. However, whether and how melatonin alleviates CIH-induced intestinal barrier dysfunction remains unclear. EXPERIMENTAL APPROACH: C57BL/6 J mice and Caco-2 cell line were treated. We evaluated gut barrier function spectrophotometrically using fluorescein isothiocyanate (FITC)-labelled dextran. Immunohistochemical and immunofluorescent staining were used to detect morphological changes in the mechanical barrier. Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) revealed the expression of tight junctions, signal transducer and activator of transcription 3 (STAT3) levels. 16 S rRNA analysis of the colonic contents microflora. Flow cytometry was used to detect cytokines and Th17 cells with and without melatonin supplementation. KEY RESULTS: We found that CIH could induce colonic mucosal injury, including reduction in the number of goblet cells and decrease the expression of intestinal tight junction proteins. CIH could decrease the abundance of the beneficial genera Clostridium, Akkermansia, and Bacteroides, while increasing the abundance of the pathogenic genera Desulfovibrio and Bifidobacterium. Finally, CIH facilitated Th17 differentiation via the phosphorylation of signal transducer and activator of transcription 3 (STAT3) in vitro and elevated the circulating pro-inflammatory cytokine in vivo. Melatonin supplementation ameliorated CIH-induced intestinal mucosal injury, gut microbiota dysbiosis, enteric Th17 polarization, and systemic low-grade inflammation reactions mentioned-above. CONCLUSION AND IMPLICATIONS: Melatonin attenuated CIH-induced intestinal barrier dysfunction by regulating gut flora dysbiosis, mucosal epithelium integrity, and Th17 polarization via STAT3 signalling.

Measuring endogenous levels of unconjugated bilirubin released from isolated murine brain tissue during oxygen-glucose deprivation.

Quantitative assessment of endogenously synthesized and released bilirubin from brain tissue remains a challenge. Here, we present a sensitive and reproducible experimental paradigm to quantify, in real time, unconjugated bilirubin (UCB) from isolated murine brain tissue during oxygen-glucose deprivation (OGD). We describe steps for perfusion, brain dissection, brain slice preparation and incubation, glucose depletion, and OGD processing. We then detail procedures for standard calibration plotting and sample UCB measurement. For complete details on the use and execution of this protocol, please refer to Liu et al.1.

Redistribution of the astrocyte phenotypes in the medial vestibular nuclei after unilateral labyrinthectomy.

Astrocytes are highly heterogeneous and involved in different aspects of fundamental functions in the central nervous system (CNS). However, whether and how this heterogeneous population of cells reacts to the pathophysiological challenge is not well understood. To investigate the response status of astrocytes in the medial vestibular nucleus (MVN) after vestibular loss, we examined the subtypes of astrocytes in MVN using single-cell sequencing technology in a unilateral labyrinthectomy mouse model. We discovered four subtypes of astrocytes in the MVN with each displaying unique gene expression profiles. After unilateral labyrinthectomy, the proportion of the astrocytic subtypes and their transcriptional features on the ipsilateral side of the MVN differ significantly from those on the contralateral side. With new markers to detect and classify the subtypes of astrocytes in the MVN, our findings implicate potential roles of the adaptive changes of astrocyte subtypes in the early vestibular compensation following peripheral vestibular damage to reverse behavioral deficits.

FKBP5 genetic variants are associated with respiratory- and sleep-related parameters in Chinese patients with obstructive sleep apnea.

Introduction: Obstructive sleep apnea (OSA) has been associated with psychiatric disorders, especially depression and posttraumatic stress disorder (PTSD). FKBP5 genetic variants have been previously reported to confer the risk of depression and PTSD. This study aimed to investigate the association of single nucleotide polymorphisms (SNPs) in the FKBP5 gene with OSA and OSA-related quantitative traits. Methods: Four SNPs within the FKBP5 gene (rs1360780, rs3800373, rs9296158, rs9470080) were genotyped in 5773 participants with anthropometric and polysomnography data. Linear regression and logistic regression analyses were performed to evaluate the relationship between FKBP5 SNPs and OSA-related traits. Binary logistic regression was used to assess the effect of SNPs on OSA susceptibility. Interacting genes of SNPs were assessed based on the 3DSNP database, and expression quantitative trait loci (eQTL) analysis for SNPs was adopted to examine the correlation of SNPs with gene expression. Gene expression analyses in human brains were performed with the aid of Brain Atlas. Results: In moderate-to-severe OSA patients, all four SNPs were positively associated with AHIREM, and rs9296158 showed the strongest association (ß = 1.724, p = 0.001). Further stratified analyses showed that in men with moderate OSA, rs1360780, rs3800373 and rs9470080 were positively associated with wake time (p = 0.0267, p = 0.0254 and p = 0.0043, respectively). Rs1360780 and rs3800373 were 28 and 29.4%more likely to rate a higher ordered MAI category (OR (95% CI) = 1.280 (1.042 - 1.575), p = 0.019; OR (95% CI) = 1.294 (1.052 - 1.592), p = 0.015, respectively). Rs9296158 and rs9470080 increased the risk of low sleep efficiency by 25.7 and 28.1% (OR (95% CI) = 1.257 (1.003 - 1.575), p = 0.047; OR (95% CI) = 1.281 (1.026-1.6), p = 0.029, respectively). Integrated analysis of eQTL and gene expression patterns revealed that four SNPs may exert their effects by regulating FKBP5, TULP1, and ARMC12. Conclusion: Single nucleotide polymorphisms in the FKBP5 gene were associated with sleep respiratory events in moderate-to-severe OSA patients during REM sleep and associated with sleep architecture variables in men with moderate OSA. FKBP5 variants may be a potential predisposing factor for sleep disorders, especially in REM sleep.

Adenoid lymphocyte heterogeneity in pediatric adenoid hypertrophy and obstructive sleep apnea.

Introduction: Adenoid hypertrophy is the main cause of obstructive sleep apnea in children. Previous studies have suggested that pathogenic infections and local immune system disorders in the adenoids are associated with adenoid hypertrophy. The abnormalities in the number and function of various lymphocyte subsets in the adenoids may play a role in this association. However, changes in the proportion of lymphocyte subsets in hypertrophic adenoids remain unclear. Methods: To identify patterns of lymphocyte subsets in hypertrophic adenoids, we used multicolor flow cytometry to analyze the lymphocyte subset composition in two groups of children: the mild to moderate hypertrophy group (n = 10) and the severe hypertrophy group (n = 5). Results: A significant increase in naïve lymphocytes and a decrease in effector lymphocytes were found in severe hypertrophic adenoids. Discussion: This finding suggests that abnormal lymphocyte differentiation or migration may contribute to the development of adenoid hypertrophy. Our study provides valuable insights and clues into the immunological mechanism underlying adenoid hypertrophy.

Surface Functional Modification by Ti3 C2 Tx MXene on PLLA Nanofibers for Optimizing Neural Stem Cell Engineering.

Optimizing cell substrates by surface modification of neural stem cells (NSCs), for efficient and oriented neurogenesis, represents a promising strategy for treating neurological diseases. However, developing substrates with the advanced surface functionality, conductivity, and biocompatibility required for practical application is still challenging. Here, Ti3 C2 Tx MXene is introduced as a coating nanomaterial for aligned poly(l-lactide) (PLLA) nanofibers (M-ANF) to enhance NSC neurogenesis and simultaneously tailor the cell growth direction. Ti3 C2 Tx MXene treatment provides a superior conductivity substrate with a surface rich in functional groups, hydrophilicity, and roughness, which can provide biochemical and physical cues to support NSC adhesion and proliferation. Moreover, Ti3 C2 Tx MXene coating significantly promotes NSC differentiation into both neurons and astrocytes. Interestingly, Ti3 C2 Tx MXene acts synergistically with the alignment of nanofibers to promote the growth of neurites, indicating enhanced maturation of these neurons. RNA sequencing analysis further reveals the molecular mechanism by which Ti3 C2 Tx MXene modulates the fate of NSCs. Notably, surface modification by Ti3 C2 Tx MXene mitigates the in vivo foreign body response to implanted PLLA nanofibers. This study confirms that Ti3 C2 Tx MXene provides multiple advantages for decorating the aligned PLLA nanofibers to cooperatively improve neural regeneration.

Anthropometric Determinants of Autonomic Control in Obstructive Sleep Apnea: A Large-Scale Study.

OBJECTIVE: Autonomic dysfunction is an independent risk factor for cardiovascular disease (CVD). Both obesity and obstructive sleep apnea (OSA) are associated with heart rate variability (HRV) (a hall marker of sympathetic arousal) and increased risk of CVD. This study aims to investigate whether anthropometric parameters could predict reduced HRV in adult OSA during wakefulness. STUDY DESIGN: Cross-sectional study. SETTING: Sleep center of Shanghai Jiao Tong University Affiliated Sixth Hospital from 2012 to 2017. METHODS: Total of 2134 subjects (503 non-OSA and 1631 OSA) were included. Anthropometric parameters were recorded. HRV was recorded during a 5-minute wakefulness period and analyzed by using time-domain method and frequency-domain method. Multiple step-wise linear regressions were performed to determine significant predictors of HRV with and without adjustments. Multiplicative interactions between gender, OSA, and obesity on HRV were also determined and evaluated. RESULTS: Waist circumference (WC) was significant negative determinant of root mean square of successive NN intervals (ß = -.116, p < .001) and high-frequency power (ß = -.155, p < .001). Age was the strongest determining factor of HRV. Significant multiplicative interactions between obesity and OSA on HRV, gender, and obesity on cardiovascular parameters were observed. CONCLUSION: Anthropometric parameters could predict reduced HRV during wakefulness in patients with OSA, especially WC was the strongest influenceable factor. Obesity and OSA had significant multiplicative interaction on HRV. Gender and obesity had significant multiplicative interaction on cardiovascular parameters. Early intervention for obesity, especially centripetal obesity, may improve reduction of autonomic function and risk of CVD.

Integrative Analysis and Experimental Validation of Competing Endogenous RNAs in Obstructive Sleep Apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent yet underdiagnosed. This study aimed to develop a predictive signature, as well as investigate competing endogenous RNAs (ceRNAs) and their potential functions in OSA. METHODS: The GSE135917, GSE38792, and GSE75097 datasets were collected from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. Weighted gene correlation network analysis (WGCNA) and differential expression analysis were used to identify OSA-specific mRNAs. Machine learning methods were applied to establish a prediction signature for OSA. Furthermore, several online tools were used to establish the lncRNA-mediated ceRNAs in OSA. The hub ceRNAs were screened using the cytoHubba and validated by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Correlations between ceRNAs and the immune microenvironment of OSA were also investigated. RESULTS: Two gene co-expression modules closely related to OSA and 30 OSA-specific mRNAs were obtained. They were significantly enriched in the antigen presentation and lipoprotein metabolic process categories. A signature that consisted of five mRNAs was established, which showed a good diagnostic performance in both independent datasets. A total of twelve lncRNA-mediated ceRNA regulatory pathways in OSA were proposed and validated, including three mRNAs, five miRNAs, and three lncRNAs. Of note, we found that upregulation of lncRNAs in ceRNAs could lead to activation of the nuclear factor kappa B (NF-κB) pathway. In addition, mRNAs in the ceRNAs were closely correlated to the increased infiltration level of effector memory of CD4 T cells and CD56bright natural killer cells in OSA. CONCLUSIONS: In conclusion, our research opens new possibilities for diagnosis of OSA. The newly discovered lncRNA-mediated ceRNA networks and their links to inflammation and immunity may provide potential research spots for future studies.

Toward nanotechnology-enabled application of bilirubin in the treatment and diagnosis of various civilization diseases.

Bilirubin, an open chain tetrapyrrole, has powerful antioxidant, anti-inflammatory, immuno-suppressive, metabolic-modulating and anti-proliferative activities. Bilirubin is a natural molecule that is produced and metabolized within the human body, making it highly biocompatible and well suited for clinical use. However, the use of bilirubin has been hampered by its poor water solubility and instability. With advanced construction strategies, bilirubin-derived nanoparticles (BRNPs) have not only overcome the disadvantages of bilirubin but also enhanced its therapeutic effects by targeting damaged tissues, passing through physiological barriers, and ensuring controlled sustained release. We review the mechanisms underlying the biological activities of bilirubin, BRNP preparation strategies and BRNP applications in various disease models. Based on their superior performance, BRNPs require further exploration of their efficacy, biodistribution and long-term biosafety in nonhuman primate models that recapitulate human disease to promote their clinical translation.

Effects of obstructive sleep apnea during rapid eye movement sleep on cardiac autonomic dysfunction: Results from the Shanghai sleep health study cohort.

In our large-scale study, the correlation between obstructive sleep apnea (OSA) related to rapid eye movement (REM) sleep and cardiac autonomic dysfunction was assessed by standard polysomnography (PSG). Cardiac autonomic dysfunction was evaluated by the measurement of heart rate variability (HRV). The cardiovascular disease (CVD) risk was determined using the cross-sectional prevalence of CVD and its overall 10 year risk according to the Framingham risk score (FRS). 4152 individuals were included in the study. A higher apnea-hypopnea index during REM sleep (AHIREM ) was correlated with increased CVD risk. The adjusted odds ratios (95% CIs) for CVD prevalence and its high 10 year risk in participants having severe OSA during REM sleep (AHIREM ≥30 events/h) were 1.452 (1.012-2.084) and 1.904 (1.470-2.466) in the demographic adjusted model and 1.175 (0.810-1.704) and 1.716 (1.213-2.427) in the multivariate adjusted model, respectively, compared with the group with a AHIREM of <5 events/h. Fully adjusted multivariate linear regression models showed the independent association between AHIREM and a more elevated ratio of low-frequency and high-frequency (LF/HF) and LF in normalised units [LF (n.u.)] (P = 0.042, P = 0.027 in all participants and P = 0.033, P = 0.029 in participants with AHI during non-REM sleep <5 events/h, respectively). Mediation analysis demonstrated that OSA during REM sleep and CVD risk was significantly mediated by LF/HF and LF (n.u.). OSA during REM sleep may be a marker behind CVD risk because it promotes cardiac autonomic dysfunction.

Effects of bilirubin on the development and electrical activity of neural circuits.

In the past several decades, bilirubin has attracted great attention for central nervous system (CNS) toxicity in some pathological conditions with severely elevated bilirubin levels. CNS function relies on the structural and functional integrity of neural circuits, which are large and complex electrochemical networks. Neural circuits develop from the proliferation and differentiation of neural stem cells, followed by dendritic and axonal arborization, myelination, and synapse formation. The circuits are immature, but robustly developing, during the neonatal period. It is at the same time that physiological or pathological jaundice occurs. The present review comprehensively discusses the effects of bilirubin on the development and electrical activity of neural circuits to provide a systematic understanding of the underlying mechanisms of bilirubin-induced acute neurotoxicity and chronic neurodevelopmental disorders.