Association of Depression with Long-Term Cardiovascular Risks in Older Patients with Obstructive Sleep Apnea.

Introduction: Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease (CVD). Depression is a crucial factor among the various factors that are associated with OSA and CVD. Purpose: This study was conducted with an aim to assess the prognostic significance of depression on the MACE in older patients with OSA. Patients and Methods: 1106 older patients with OSA, without myocardial infarction (MI), history of hospitalization for unstable angina, or heart failure at baseline were enrolled and followed up prospectively. Incidence rates were expressed as cumulative incidence. Cox proportional hazards analysis was used to estimate the risk of all events. The primary outcomes were major adverse cardiovascular events (MACE). Each patient underwent polysomnography (PSG) and GDS-12 scale assessment. Those with an apnea-hypopnea index (AHI) greater than 5 were diagnosed with OSA, while those with a scale score greater than 3 were diagnosed with depression. Results: Among the 1106 older patients with OSA, depression was found in 133(12.0%) patients, 96(8.7%) patients experienced MACE during the follow-up. Depression was associated with a higher cumulative incidence of MACE in older patients with OSA. Multivariate analysis revealed that depression independently increased the risk of MACE (adjusted hazard ratio [aHR] = 2.29; 95% confidence interval [CI]: 1.34-3.90; P = 0.002). Subgroup analyses showed that male patients (aHR = 2.96; 95% CI: 1.52-5.77; P = 0.001), overweight-obese individuals (aHR = 2.98; 95% CI: 1.49-6.00; P = 0.002), and those with moderate-severe OSA (aHR = 2.82; 95% CI: 1.55-5.14; P = 0.001) and concurrent depression were at a higher risk for MACE. Conclusion: Depression is common in older patients with OSA in the absence of MI, hospitalization for unstable angina, or heart failure, and confers an independent, increased risk of MACE.

Pan-cancer analysis of Homeobox B9 as a predictor for prognosis and immunotherapy in human tumors.

BACKGROUND: Although several animal and cell studies have described the association between HOXB9 and cancers, there is no pan-cancer investigation of HOXB9. In this article, we explored the expression levels and prognosis of HOXB9 in pan-cancer. We evaluated the correlation of HOXB9 expression level with the efficacy of immunotherapy. METHODS: We conducted a survival analysis of HOXB9 in various types of cancer using publicly available databases. We also examined the relationship between HOXB9 expression levels and several factors including prognosis, immune infiltration, immune checkpoint genes, tumor mutational burden, microsatellite instability, mismatch repair, and DNA methylation. TIMER2.0 tool was conducted to explore the immune cell infiltrations related to HOXB9 in this analysis. RESULTS: It was discovered through a comprehensive analysis of multiple public datasets that HOXB9 expression was highly expressed in most tumor tissues and cancer cell lines and that distinct associations exist between HOXB9 expression and tumor patient prognosis. Besides, HOXB9 expression was closely associated with immune cell infiltration and checkpoint genes in many cancers. Further, HOXB9 was associated with immune cell infiltration, TMB, MSI, MMR, and DNA methylation. It was also confirmed that HOXB9 was highly expressed in clinical GBM tissues. Experiments further revealed that knockdown of HOXB9 expression could suppress proliferation, migration, and invasion of glioma cells. CONCLUSIONS: The results revealed that HOXB9, a robust tumor biomarker, has a significant prognostic value. HOXB9 may act as a new predictor to assess cancer prognosis and therapeutic efficacy of the immune in various cancers.

Association between Serum Cystatin C levels and long-term cardiovascular outcomes and all-cause mortality in older patients with obstructive sleep apnea.

Background and Aims: To investigate the association between obstructive sleep apnea (OSA) severity and baseline serum cystatin C (Cys-C) concentration and to explore the association between baseline serum Cys-C and long-term cardiovascular outcomes and mortality in older patients with OSA. Methods: Between January 2015 and October 2017, a total of 1107 consecutive eligible older patients (≥60 years) with OSA were included in this multicenter, prospective cohort study, and baseline demographics, clinical characteristics, sleep parameters, and follow-up outcomes were collected. Participants were divided into different groups based on baseline serum Cys-C levels. The primary end point was major adverse cardiovascular events (MACE) and the secondary end point was all-cause mortality. The correlation between OSA severity and baseline serum Cys-C was evaluated by Spearman correlation analysis. Multivariate Cox regression was used to analyze the association between Cys-C and the incidence of MACE and mortality. Results: Participants included 672 men and 435 women, with a median age of 66 (range, 60-96) years. At baseline, apnea-hypopnea index (AHI) (r = 0.128, p < 0.05), oxygen desaturation index (ODI) (r = 0.116, p < 0.05), and the lowest pulse oxygen saturation (LSpO2) (r = -0.097, p < 0.05) were correlated with serum Cys-C concentration. During the median follow-up period of 42 months, 97 patients (8.8%) experienced MACE and 40 patients (3.6%) experienced death. The association between serum Cys-C levels and the risk of MACE and all-cause mortality was slow rising shaped. The multivariable Cox regression analysis showed patients with a serum Cys-C concentration of ≥1.14 mg/L had higher risks of MACE (HR = 5.30, 95% CI: 2.28-12.30, p < 0.05) and all-cause mortality (HR = 9.66, 95% CI: 2.09-44.72, p < 0.05) compared with patients with serum Cys-C of ≤0.81 mg/L in older patients with OSA. The receiver-operating characteristic curve showed baseline serum Cys-C levels exhibited moderately capable of identifying patients with a long-term risk of clinical adverse events (MACE and mortality). Conclusion: OSA severity was positively correlated with serum Cys-C concentration. High levels of Cys-C were independently associated with increased risks of MACE and all-cause mortality in older patients with OSA, suggesting that lowering Cys-C levels should be considered as a therapeutic target, and monitoring serum Cys-C may be beneficial to the favorable prognosis of older patients with OSA.

Associations between abdominal obesity and the risk of stroke in Chinese older patients with obstructive sleep apnea: Is there an obesity paradox?

Background and purpose: Abdominal obesity (AO) is a well-known independent risk factor for stroke in the general population although it remains unclear in the case of the elderly, especially in Chinese older patients with obstructive sleep apnea (OSA), considering the obesity paradox. This study aimed to investigate the association between AO and stroke among Chinese older patients with OSA. Methods: Data were collected from January 2015 to October 2017, and 1,290 older patients (age 60-96 years) with OSA (apnea-hypopnea index ≥ 5 events/h on polysomnography) were consecutively enrolled from sleep centers at six hospitals, evaluated for AO defined as waist circumference (WC) using the standardized criteria for the Chinese population, and followed up prospectively for a median period of 42 months. Logistic regression and Cox regression analyses were used to determine the cross-sectional and longitudinal associations between AO and stroke risk in these participants and different groups of the severity of OSA. Results: Participants with AO had a higher prevalence of stroke at baseline. A higher incidence of stroke during a median follow-up period of 42 months in participants with AO than in participants without AO (12.4% vs. 6.8% and 8.3% vs. 2.4%, respectively; both P < 0.05) was predicted. Cross-sectional analysis revealed an association between AO and stroke (odds ratio [OR]1.96, 95% confidence interval [CI] 1.31-2.91), which was stronger among participants with moderate OSA only (OR 2.16, 95%CI 1.05-4.43). Cox regression analysis showed that, compared to participants without AO, participants with AO had a higher cumulative incidence of stroke (hazard ratio [HR] 2.16, 95% CI 1.12-4.04) during a median follow-up of 42 months, and this association was observed in patients with severe OSA only (HR 3.67, 95% CI 1.41-9.87) but not for individuals with mild OSA (HR = 1.84, 95% CI 0.43-6.23) and moderate OSA (HR = 1.98, 95% CI 0.73-6.45). Conclusion: The risk of stroke is associated with AO among Chinese older patients who have OSA, both at baseline and during follow-up, and the strength of the association varied by OSA severity. Active surveillance for early detection of AO could facilitate the implementation of stroke-preventive interventions in the Chinese older OSA population.

Prevalence and factors associated with atrial fibrillation in older patients with obstructive sleep apnea.

PURPOSE: This study sought to identify the prevalence and factors associated with atrial fibrillation (AF) in older patients with obstructive sleep apnea (OSA) in China.  METHODS: This was an explorative cross-sectional study. Between January 2015 and October 2017, we continuously recruited 1285 older patients with OSA who underwent overnight polysomnography from sleep centers of multiple hospitals. They were assessed using 12-lead ECG or 24-h dynamic ECG, and their baseline demographics, clinical characteristics, sleep parameters, and medical history were determined. Multivariate binary logistic regression analysis was used to investigate the factors related to AF in these older patients with OSA. RESULTS: The clinician classified 122 (9.5%) patients as having AF. The prevalence of AF significantly increased with age (P < 0.05) but did not significantly differ between the mild, moderate, and severe OSA groups. Additionally, the prevalence of paroxysmal AF was 7.2% among the overall study population, and it increased with OSA severity or advanced age (P < 0.05). Persistent AF was noted in 2.3% participants, and the prevalence also increased with age. The logistic regression analysis showed that age (OR = 1.054, 95%CI: 1.027-1.018, P < 0.001), history of drinking (OR = 1.752, 95%CI: 1.070-2.867, P < 0.05), chronic heart disease (OR = 1.778, 95%CI: 1.156-2.736, P < 0.01), diabetes mellitus (OR = 1.792, 95%CI: 1.183-2.713, P < 0.01), and reduced diastolic function (OR = 2.373, 95%CI = 1.298-4.337, P < 0.01) were relevant to AF among participants with OSA. CONCLUSION: The prevalence of AF is significantly common in older patients with OSA. Age, history of drinking, chronic heart disease, diabetes mellitus, and reduced diastolic function are independently related to AF in these patients.

The Impact of Non-Invasive Ventilation Combined with Montelukast on Clinical Efficiency and Pulmonary Function in Patients with Bronchial Asthma Complicated by Obstructive Sleep Apnea Hypopnea Syndrome.

PURPOSE: Our study aims to explore the impact of non-invasive ventilation (NIV) alone or combined with montelukast on clinical efficiency and pulmonary function (PF) in treating patients with bronchial asthma complicated by obstructive sleep apnea hypopnea syndrome (OSAHS). METHODS: A total of 386 patients with bronchial asthma underwent sleep monitoring. Patients were divided into 3 groups according to the different treatment methods. The changes in PF, apnea hypopnea index (AHI) score and the level of inflammatory factors in all patients before and after treatment were recorded, and the clinical effect following treatment was noted. RESULTS: Following treatment, the clinical efficiency of Group 2 was significantly better than that of both Group 1and the control group, and the therapeutic effect in Group 1 was better than in the control group (P < .05). Before treatment, vital capacity (VC), peak expiratory flow (PEF), forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) and asthma control test (ACT) scores, AHI scores, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) index were compared between the 3 groups (P > .05). In contrast, after treatment the VC, PEF, FEV1/FVC and ACT, AHI, CRP and TNF-α scores and the IL-6 index in the 3 groups were improved compared with before treatment. The indices in Groups 1 and 2 were better than in the control group, and the VC, PEF, FEV1/FVC and ACT, AHI, CRP, and TNF-α scores and IL-6 index in Group 2 reported greater beneficial effect than in Group 1. CONCLUSION: The combination of NIV and montelukast exerts a beneficial effect in treating patients with bronchial asthma complicated with OSAHS, which holds the potential of effectively improving clinical symptoms and PF, reducing ACT and AHI scores and alleviating inflammatory reactions. Hence, the combination is valid and appropriate for clinical application.

Characterization of fecal metabolome changes in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a clinical syndrome characterized by recurrent episodes of apnea or hypopnea of the upper airway, leading to increased negative intrathoracic pressure, sleep fragmentation, intermittent hypoxia during sleep, and increased risk for morbidity and mortality of affected patients. The gut microbiome plays a key role in OSA pathogenesis, and fecal metabolic profiling reflects the gut microbial functional readout and mediates host-microbiome interactions. METHODS: Herein, we conducted a cohort study to explore fecal metabolic signatures distinguishing OSA (44 patients) from healthy controls (22 healthy controls) by untargeted gas chromatography-time-of-flight mass spectroscopy. RESULTS: Significant metabolic signatures were detected in stool samples of patients with OSA: 246 metabolites of 24 ontology classes were identified, and 48 metabolites of 6 ontology classes were shifted. An enrichment of arachidonic acid, docosahexaenoic acid, and 11Z-eicosenoic acid and reduction in stearic acid, 5-hydroxyindoleacetic acid, gluconic acid, and α-hyodeoxycholic acid were observed in stool samples from patients with OSA. Fecal variance resulted in alterations in potential metabolic activities and was thereby strongly associated with host phenotypes, such as pulse blood oxygen saturation and apnea-hypopnea index. The prediction model based on feces metabolomics was established to distinguish OSA from healthy controls with high accuracy. CONCLUSIONS: This study revealed the metabolomic signatures of patients with OSA in feces, and the findings provide evidence of an association between metabolome and OSA. CITATION: Dong Y, Wang P, Lin J, et al. Characterization of fecal metabolome changes in patients with obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):575-586.

Impact of obstructive sleep apnea complicated with type 2 diabetes on long-term cardiovascular risks and all-cause mortality in elderly patients.

BACKGROUND: The prognostic significance of obstructive sleep apnea (OSA) in elderly patients with type 2 diabetes is unclear. The aim of this study was to determine the risk of cardiovascular disease (CVD) and mortality in elderly patients with OSA complicated with type 2 diabetes compared to patients with OSA without type 2 diabetes. METHODS: From January 2015 to October 2017, 1113 eligible elderly patients with OSA, no history of cardiovascular, ≥60 years of age, and complete follow-up records were enrolled in this consecutive multicentre prospective cohort study. All patients had completed polysomnography (PSG) examinations. An apnoea-hypopnoea index of ≥5 events per hour recorded by polysomnography was defined as the diagnostic criterion for OSA. We collected baseline demographics, clinical characteristics, sleep parameters and follow-up outcomes. The primary aim of this study was to identify the risk of incident major adverse cardiovascular events (MACE). Secondary outcomes were all-cause mortality, components of MACE and a composite of all events. Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate whether type 2 diabetes was associated with incident events. RESULTS: A total of 266 (23.9%) patients had OSA complicated with type 2 diabetes. MACE occurred in 97 patients during the median 42-month follow-up. Kaplan-Meier survival curves indicated a significant relationship between type 2 diabetes and MACE (log-rank P = 0.003). Multivariable Cox regression analysis showed that type 2 diabetes increased the risk of MACE (HR = 1.64, 95% CI:1.08-2.47, P = 0.019), hospitalisation for unstable angina (HR = 2.11, 95% CI:1.23-3.64, P = 0.007) and a composite of all events in elderly patients with OSA (HR = 1.70, 95% CI:1.17-2.49, P = 0.007). However, there were no significant differences in the incidence of cardiovascular death, all-cause mortality, MI and hospitalisation for heart failure between patients with and without diabetes (P > 0.05). The subgroup analysis demonstrated that females (AHR = 2.46, 95% CI:1.17-5.19, P = 0.018), ≥ 70 years (AHR = 1.95, 95% CI:1.08-3.52, P = 0.027), overweight and obese (AHR = 2.04, 95% CI:1.29-3.33, P = 0.002) with mild OSA (AHR = 2.42, 95% CI: 1.03-5.71, P = 0.044) were at a higher risk for MACE by diabetes. CONCLUSION: OSA and type 2 diabetes are interrelated and synergistic with MACE, hospitalisation for unstable angina and a composite of all events development. Overweight and obese females, ≥ 70 years with mild OSA combined with type 2 diabetes presented a significantly high MACE risk.

The Adverse Effects of TiO2 Photocatalycity on Paraloid B72 Hybrid Stone Relics Protective Coating Aging Behaviors under UV Irradiation.

The incorporation of photocatalytic nanomaterials into polymer coatings is used to protect stone relics from weathering. However, the photocatalytic nanomaterials might generate excess free radicals to degrade the polymer matrix. In this work, a certain amount of TiO2 nanoparticles were dispersed into Paraloid B72 and applied onto sandstone relics to explore the adverse effects of TiO2 nanoparticles on Paraloid B72 under ultraviolet (UV) irradiation. To fulfill this goal, the effects of TiO2 on pore formation and the structure of Paraloid B72 was studied by scanning electron microscopy (SEM). Moreover, the surface chemical composition, pore structure, surface roughness and surface wettability were explored via Fourier transform infrared (FTIR) spectroscopy, SEM, optical profilometer and water contact angle measurement under UV irradiation. Results showed that the incorporation of TiO2 nanoparticles prohibited the generation of pores in Paraloid B72 and there were no pores formed when the content of TiO2 exceeded 0.8 wt%. The water contact angle of origin Paraloid B72 and TiO2/Paraloid B72 decreased with the prolonging UV irradiation. Moreover, TiO2 nanoparticles were extracted from the matrix and the pores cannot be detected with the prolonging UV irradiation time under a higher content of TiO2. These research findings might promote the understanding of using photocatalytic nanomaterials in developing stone relics' protective coating.

Association of Metabolic Syndrome With Long-Term Cardiovascular Risks and All-Cause Mortality in Elderly Patients With Obstructive Sleep Apnea.

BACKGROUND: Evidence suggests that an increased risk of major adverse cardiac events (MACE) and all-cause mortality is associated with obstructive sleep apnea (OSA), particularly in the elderly. Metabolic syndrome (MetS) increases cardiovascular risk in the general population; however, less is known about its influence in patients with OSA. We aimed to assess whether MetS affected the risk of MACE and all-cause mortality in elderly patients with OSA. METHODS: From January 2015 to October 2017, 1,157 patients with OSA, aged ≥60 years, no myocardial infarction (MI), and hospitalization for unstable angina or heart failure were enrolled at baseline and were followed up prospectively. OSA is defined as an apnea-hypopnea index of ≥5 events per hour, as recorded by polysomnography. Patients were classified on the basis of the presence of MetS, according to the definition of the National Cholesterol Education Program (NCEP). Incidence rates were expressed as cumulative incidence. Cox proportional hazards analysis was used to estimate the risk of all events. The primary outcomes were MACE, which included cardiovascular death, MI, and hospitalization for unstable angina or heart failure. Secondary outcomes were all-cause mortality, components of MACE, and a composite of all events. RESULTS: MetS was present in 703 out of 1,157 (60.8%) elderly patients with OSA. During the median follow-up of 42 months, 119 (10.3%) patients experienced MACE. MetS conferred a cumulative incidence of MACE in elderly patients with OSA (log-rank, P < 0.001). In addition, there was a trend for MACE incidence risk to gradually increase in individuals with ≥3 MetS components (P = 0.045). Multivariate analysis showed that MetS was associated with an incidence risk for MACE [adjusted hazard ratio (aHR), 1.86; 95% confidence interval (CI), 1.17-2.96; P = 0.009], a composite of all events (aHR, 1.54; 95% CI, 1.03-2.32; P = 0.036), and hospitalization for unstable angina (aHR, 2.01; 95% CI, 1.04-3.90; P = 0.039). No significant differences in the risk of all-cause mortality and other components of MACE between patients with and without MetS (P > 0.05). Subgroup analysis demonstrated that males (aHR, 2.23; 95% CI, 1.28-3.91, P = 0.05), individuals aged <70 years (aHR, 2.36; 95% CI, 1.27-4.39, P = 0.006), overweight and obese individuals (aHR, 2.32; 95% CI, 1.34-4.01, P = 0.003), and those with moderate-severe OSA (aHR, 1.81;95% CI: 1.05-3.12, P = 0.032) and concomitant MetS were at a higher risk for MACE. CONCLUSION: MetS is common in elderly patients with OSA in the absence of MI, hospitalization for unstable angina or heart failure. Further, it confers an independent, increased risk of MACE, a composite of all events, and hospitalization for unstable angina. Overweight and obese males, aged <70 years with moderate-severe OSA combined with MetS presented a significantly higher MACE risk.

Association Cystatin C and Risk of Stroke in Elderly Patients With Obstructive Sleep Apnea: A Prospective Cohort Study.

Background: Few prospective cohort studies have assessed the relationship between Cystatin C (Cys-C) and risk of stroke in elderly patients with obstructive sleep apnea (OSA). The study sought to examine the association between baseline serum Cys-C and long-term risk of stroke among elderly OSA patients. Methods: A total of 932 patients with OSA, no history of stroke, ≥60 years of age, and complete serum Cys-C records were included in this study. All patients had completed polysomnography (PSG). OSA was defined as an apnea-hypopnea index (AHI) of ≥5 events per hour. Participants were categorized into four groups according to baseline serum Cys-C concentration, split into quartiles. Multivariate Cox regression were used to evaluate the association between Cys-C and the incidence of new-onset stroke. Results: Stroke occurred in 61 patients during the median 42-month follow-up period. The cumulative incidence rate of stroke was 6.5%, which included 54 patients with ischemic stroke and 7 patients with hemorrhagic stroke. The cumulative incidence of stroke was higher among patients with baseline serum Cys-C concentration of ≥1.15 mg/L when compared with other groups (P Log-rank < 0.001). After adjusting for potential confounding factors in the Cox regression model, patients with a serum Cys-C concentration of ≥1.15 mg/L had a 2.16-fold higher risk of developing stroke compared with patients with serum Cys-C ≤ 0.81 mg/L (HR, 2.16, 95%CI, 1.09-6.60; P = 0.017). Additionally, there was a higher risk in those of age ≥70 years (HR, 3.23, 95%CI, 1.05-9.24; P = 0.010). The receiver-operating characteristic curves showed that the capability of Cys-C to identify elderly patients with OSA who had a long-time risk of stroke was moderate (AUC = 0.731, 95% CI: 0.683-0.779, P = 0.001). Conclusion: Increased Cys-C concentration was identified as a risk factor in the incidence of stroke in elderly patients with OSA, independent of gender, BMI, hypertension and other risk factors. Additionally, it conferred a higher risk in patients of age ≥70 years.

Clinical features and risk factors in patients with asthma complicated with obstructive sleep apnea-hypopnea syndrome: a hospital-based study.

PURPOSE: The current study was conducted to explore the clinical features and risk factors of patients with asthma complicated by obstructive sleep apnea-hypopnea syndrome (OSAHS). METHODS: Patients with asthma who underwent polysomnography in our hospital from August 2017 to December 2019 were enrolled in the study. Data on demographics, pulmonary function testing, polysomnography, blood gases, mean pulmonary artery pressure, and vascular endothelial growth factor (VEGF) were compared between the two groups. RESULTS: Of 238 patients with asthma, 93 who also had OSAHS formed the observation group and were subclassified into mild (n = 33), moderate (n = 41), and severe (n = 19) categories, while 145 patients with asthma alone were assigned to the control group. No significant differences were found in sex, age, course of disease, or pulmonary function between the two groups (P > 0.05), while the observation group showed more frequent allergic rhinitis and had greater BMI, neck circumference, mean pulmonary artery pressure (mPAP), and VEGF than those in the control group (P < 0.001). The peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and FEV1/FVC in the mild group and the moderate group were higher than those in the severe group (P < 0.001). The durations of AHI and SaO2 < 90% in the mild group and the moderate group were shorter than that in the severe group, and the lowest level of SaO2 in the mild group and the moderate group was higher than that in the severe group (P <  0.05). The mPAP and VEGF of the mild and moderate groups were lower than those of severe group (P < 0.001), with mild group lower than moderate group (P < 0.001). CONCLUSION: Significant differences in allergic rhinitis, BMI, neck circumference, AHI, SaO2, mPAP, and VEGF were observed in patients with asthma complicated by OSAHS. These parameters are risk factors associated with asthma complicated by OSAHS.

Risk factors and fraction of exhaled nitric oxide in obstructive sleep apnea in adults.

OBJECTIVE: This study aimed to evaluate the relationship between obstructive sleep apnea (OSA) and the fraction of exhaled nitric oxide (FENO), and to assess the effect of risk factors of airway inflammation on OSA. METHODS: Medical records of patients in the Respiratory Sleep Center at Chao-Yang Hospital in Beijing between January 2015 and June 2017 were analyzed. All patients were diagnosed with OSA. Data of the medical history, clinical examinations, FENO, and upper airway computed tomographic findings were collected. Logistic regression was used to evaluate risk factors of OSA. RESULTS: A total of 181 patients were admitted to the Respiratory Sleep Center during the study and 170 had a diagnosis of OSA and were included in the study. Single factor analysis showed that male sex, age, body mass index, smoking index, alcohol consumption, FENO, soft palate thickness, soft palate length, the narrowest transverse diameter of the upper airway, tonsil size, and nasal sinusitis were risk factors for sleep-disordered breathing and disease severity. CONCLUSIONS: Male sex, age, body mass index, FENO, the narrowest transverse diameter of the upper airway, and normal tonsil size are associated with OSA and disease severity. The severity of OSA is associated with FENO levels.

Circular RNA circHIPK3 modulates the proliferation of airway smooth muscle cells by miR-326/STIM1 axis.

AIMS: Emerging findings demonstrate the critical roles of noncoding RNA (ncRNA) in asthma development. Nevertheless, the biological roles of circular RNA (circRNA) in airway remodeling are still elusive. Here, the present research focuses on the regulation of circRNA circHIPK3 in airway smooth muscle cells (ASMCs) proliferation and migration. MATERIALS AND METHODS: The sequence of circRNA was detected using Sanger sequencing. Cellular phenotypes were detected using CCK-8 assay, transwell and flow cytometer assay. The potential binding of miRNA and downstream and upstream targets was detected using dual-luciferase reporter assay. KEY FINDINGS: Results showed that circHIPK3 was significantly upregulated in platelet-derived growth factor (PDGF) induced ASMCs. Functional analysis using CCK-8, transwell migration assays and flow cytometry analysis showed that circHIPK3 knockdown repressed proliferation, migration and up-regulated the apoptosis in ASMCs. Mechanistic assays showed that circHIPK3 sponged miR-326 in the cytoplasm, thereby targeting stromal interaction molecule 1 (STIM1) to regulate ASMCs' proliferation, migration and apoptosis. SIGNIFICANCE: Collectively, the data elucidates that circHIPK3 functions as a regulator in the airway remodeling during the asthma development through miR-326/STIM1 axis, providing a novel insight for the therapeutic target.

Long noncoding RNA TUG1 promotes airway smooth muscle cells proliferation and migration via sponging miR-590-5p/FGF1 in asthma.

The proliferation and migration of airway smooth muscle cells (ASMCs) plays an important role in asthma. Recently, the function of long noncoding RNA (lncRNA) in the ASMCs has been realized. This study tries to investigate the role of lncRNA TUG1 for the ASMCs and focus on the deepgoing mechanism in the proliferation and migration. In the asthma rat model, TUG1 expression level was increased comparing with control. In the cellular assay with gain and loss of functions, lncRNA TUG1 promoted the ASMCs proliferation and migration, and reduces apoptosis. In the mechanical investigation, results unveiled that miR-590-5p acted as the target of TUG1, while FGF1 was targeted by miR-590-5p. Overall, this study reveals the vital regulation of TUG1/miR-590-5p/FGF1 axis for the proliferation and migration of ASMCs.

Effect of cigarette smoke extract on the role of protein kinase C in the proliferation of passively sensitized human airway smooth muscle cells.

To investigate the effect of cigarette smoke extract (CSE) on the role of protein kinase C (PKC) in the proliferation of passively sensitized human airway smooth muscle cells (HASMCs). After synchronization of cultured HASMCs, they were divided into a group A and Group B. The group A was treated with normal human serum and served as controls and the group B was treated with the serum of asthma patients. The group A was further divided into group of A1, A2 and A3 and the group B was sub-divided into the group of B1, B2, B3, B4 and B5. No other agents were added to the group A1 and B1. The cells of group A2 and B2 were stimulated with 5% CSE for 24 h. HASMCs from group A3 and B3 were treated with PKC agonist PMA (10 nmol/L) and CSE (5%) for 24 h. PKC inhibitor Ro-31-8220 (5 micromol/L) was added to the HASMCs of group B4 for 24 h. The cells from group B5 were stimulated with Ro-31-8220 (5 micromol/L) and CSE (5 %) for 24 h. The proliferation of HASMCs isolated from group A and B was examined by cell cycle analysis, MTT colorimetric assay and 3H-TdR incorporation test. The expression of PKC-a in each group was observed by Western blotting and RT-PCR, respectively. The results showed that the percentage of S phase, absorbance (A) value, the rate of 3H-TdR incorporation, the ratios of A value of PKC-alpha mRNA and the A value of PKC-alpha protein in HASMCs from group B1, B2 and B3 were significantly increased compared to those of group A1, A2 and A3 correspondingly and respectively (P< 0.01). The proliferation of HASMCs of group A2 and B2 stimulated with CSE and group A3 and B3 stimulated with CSE and PMA were also significantly enhanced when group A1, A2 and A3 and group B1, B2 and B3 compared to each other (P<0.05, P<0.01, respectively). The percentage of S phase, absorbency (A) value, 3H-TdR incorporation rate, the ratios of A value of PKC-alpha mRNA and the A value of PKC-alpha protein in HASMCs from group B4 treated with Ro-31-8220 and group B5 treated with CSE and Ro-31-8220 were significantly decreased as compared to those of group B1 and B2 correspondingly and respectively (P<0.05, P<0.01). It was concluded that CSE can enhance the passively sensitized HASMC proliferation and the expression of PKC alpha. PKC and its alpha subtype may contribute to this process. Our results suggest cigarette may play an important role in ASMCs proliferation of asthma through PKC signal pathway.