miRNA-Mediated Suppression of a Cardioprotective Cardiokine as a Novel Mechanism Exacerbating Post-MI Remodeling by Sleep Breathing Disorders.

RATIONALE: Obstructive sleep apnea-hypopnea syndrome, a sleep breathing disorder in which chronic intermittent hypoxia (CIH) is the primary pathology, is associated with multiple cardiovascular diseases. However, whether and how CIH may affect cardiac remodeling following myocardial infarction (MI) remains unknown. OBJECTIVE: To determine whether CIH exposure at different periods of MI may exacerbate post-MI heart failure and to identify the mechanisms underlying CIH-exacerbated post-MI remodeling. METHODS AND RESULTS: Adult male mice were subjected to MI (4 weeks) with and without CIH (4 or 8 weeks). CIH before MI (CIH+MI) had no significant effect on post-MI remodeling. However, double CIH exposure (CIH+MI+CIH) or CIH only during the MI period (MI+CIH) significantly exacerbated pathological remodeling and reduced survival rate. Mechanistically, CIH activated TGF-ß (tumor growth factor-ß)/Smad (homologs of both the Drosophila protein MAD and the C. elegans protein SMA) signaling and enhanced cardiac epithelial to mesenchymal transition, markedly increasing post-MI cardiac fibrosis. Transcriptome analysis revealed that, among 15 genes significantly downregulated (MI+CIH versus MI), Ctrp9 (a novel cardioprotective cardiokine) was one of the most significantly inhibited genes. Real-time polymerase chain reaction/Western analysis confirmed that cardiomyocyte CTRP9 expression was significantly reduced in MI+CIH mice. RNA-sequencing, real-time polymerase chain reaction, and dual-luciferase reporter assays identified that microRNA-214-3p is a novel Ctrp9 targeting miRNA. Its upregulation is responsible for Ctrp9 gene suppression in MI+CIH. Finally, AAV9 (adeno-associated virus 9)-mediated cardiac-specific CTRP9 overexpression or rCTRP9 (recombinated CTRP9) administration inhibited TGF-ß/Smad and Wnt/ß-catenin pathways, attenuated interstitial fibrosis, improved cardiac function, and enhanced survival rate in MI+CIH animals. CONCLUSIONS: This study provides the first evidence that MI+CIH upregulates miR-214-3p, suppresses cardiac CTRP9 (C1q tumor necrosis factor-related protein-9) expression, and exacerbates cardiac remodeling, suggesting that CTRP9 may be a novel therapeutic target against pathological remodeling in MI patients with obstructive sleep apnea-hypopnea syndrome.

Assessment of cerebral glucose metabolism in patients with heart failure by 18F-FDG PET/CT imaging.

BACKGROUND: To evaluate the cerebral metabolism in patients with heart failure (HF). METHODS: One hundred and two HF patients were prospectively enrolled, who underwent gated 99mTc-sestamibi single photon emission computed tomography (SPECT)/CT, cardiac and cerebral 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT. Fifteen healthy volunteers served as controls. Patients were stratified by extent of hibernating myocardium (HM) and left ventricular ejection fraction (LVEF) into 4 groups where Group1: HM < 10% (n = 33); Group2: HM ≥ 10%, LVEF < 25% (n = 34); Group3: HM ≥ 10%, 25% ≤ LVEF ≤ 40% (n = 16) and Group 4: LVEF > 40% (n = 19). The standardized uptake value (SUV) in the whole brain (SUVwhole-brain) and the SUV ratios (SUVR) in 24 cognition-related brain regions were determined. SUVwhole-brain and SUVRs were compared between the 4 patient groups and the healthy controls. RESULTS: SUVwhole-brain (r = 0.245, P = 0.013) and SUVRs in frontal areas, hippocampus, and para-hippocampus (r: 0.213 to 0.308, all P < 0.05) were correlated with HM. SUVwhole-brain differed between four patient groups and the healthy volunteers (P = 0.016) and SUVwhole-brain in Group 1 was lower than that in healthy volunteers (P < 0.05). SUVRs of Group 3 in frontal areas were the highest among four patient subgroups (P < 0.05). CONCLUSIONS: Cerebral metabolism in the whole brain was reduced but maintained in cognition-related frontal areas in HF patients with HM and moderately impaired global left ventricular function.

Gustatory event-related potential alterations in olfactory dysfunction patients.

The phenomenon that longstanding impaired olfactory function is associated with the decreased gustatory function was described in present studies, which was seems attributed to mutual chemosensory interactions. And the interaction between olfaction and gustation still needs more research to figure out. The objective of the study was to investigate how the taste was influenced by olfactory impairment in the central pathway. We tested 33 subjects with normal (n = 19) or impaired (n = 14) olfactory function for their gustatory event-related potentials (gERPs). Validated tests were used for olfactory and gustatory testing (Sniffin' Sticks, gERPs, and three-drop test). This study reported an objective gustatory function decline in olfactory dysfunction participants. However, it also reported the increased gustatory event-related potentials of olfactory dysfunction participants, especially at the frontal electrode (FZ) and electrode 16 (E16), and the reduced latency of P2 peak of them at electrode 21 (E21), while no obvious difference was observed at the centro-parietal electrode (PZ). Inferior insula might be the main response area for the increase in gERPs, and this increase averaged amplitude of the P2 component may attribute to compensation of the secondary gustatory response that occurred in the gustatory processing of olfactory-impaired patients.

Effects of obstructive sleep apnea hypopnea syndrome on postoperative complications in patients who undergo off-pump coronary artery bypass grafting.

PURPOSE: To investigate the prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) in patients undergoing off-pump coronary artery bypass grafting (OPCABG) and analyze the effects of OSAHS on the incidence of post-OPCABG complications, length of stay in intensive care unit (ICU) and hospitalization, and hospital expense. MATERIALS AND METHODS: This prospective study included patients undergoing OPCABG at Beijing An Zhen hospital from January 2018 to December 2018. OSAHS was diagnosed by using a portable sleep monitor before surgery. RESULTS: Among 74 patients, the prevalence of OSAHS and moderate to severe OSAHS (apnea hypopnea index (AHI) ≥ 15) was 70% and 53%, respectively. Compared with the no to mild OSAHS group (AHI < 15), the moderate to severe OSAHS group presented a lower ejection fraction (P = 0.013). Between these two groups, the incidence of post-OPCABG complications; the duration of intubation, ICU stay, and hospitalization; and the hospital expense did not differ. Notably, the ejection fraction was significantly negatively correlated with the duration of ICU stay and hospital expense. CONCLUSIONS: Patients undergoing OPCABG with severe OSAHS are likely to exhibit a low ejection fraction and poor heart function, which may require a longer ICU stay and incur higher hospital expenses.

Predictive significance of the questionnaire of olfactory disorders-negative statements for olfactory loss in patients with chronic rhinosinusitis.

OBJECTIVES: The questionnaire of olfactory disorder-negative statements (QOD-NS) is a valid and reliable instrument for assessing the olfactory-specific quality of life. This study aimed to explore the association between the QOD-NS and objective olfactory metrics (including objective olfactory cleft assessment) and then evaluate the predictive significance of the QOD-NS for olfactory loss in Chinese patients with chronic rhinosinusitis (CRS). METHODS: A total of 70 patients with CRS were enrolled in the study. Olfaction was assessed with Sniffin' Sticks. The olfactory cleft was assessed by the sinus CT scan and nasal endoscopy (the Lund-Mackay olfactory cleft scale, LM-OC and olfactory cleft endoscopy scale, OCES). The QOD-NS and its short version were utilized to assess the patient-reported olfaction. The predictors associated with olfactory loss were analyzed by the logistic regression analysis. The optimal cutoff points of the predictors were determined by the receiver-operating characteristic curves and the Youden index. RESULTS: The TDI score in patients with CRS significantly correlated with the QOD-NS (r = - 0.755, P < 0.001), OCES (r = - 0.520, P < 0.001), LM-OC (r = - 0.615, P < 0.001). After adjusting for patient demographics and comorbidities, QOD-NS was significantly associated with olfactory dysfunction [odds ratio (OR) = 1.243; P = 0.001] and anosmia in patients with CRS (OR = 1.838; P = 0.006). Furthermore, the QOD-NS significantly correlated with the LM-OC (r = 0.610, P < 0.001), and the OCES (r = 0.464, P < 0.001) in patients with CRS. The QOD-NS had the highest predictive value for olfactory dysfunction (optimal cutoff = 10.5; Youden index = 0.635; area under the curve = 0.861) and anosmia (optimal cutoff = 20.5; Youden index = 0.790; area under the curve = 0.928) in patients with CRS. CONCLUSION: The QOD-NS showed high validity and correlated well with objective olfactory metrics and olfactory cleft assessment in patients with CRS. The QOD-NS was a reliable predictor for olfactory dysfunction and anosmia in patients with CRS, which may aid in the fast screening of olfactory loss in the clinic.

Development of an apparatus and procedure for evaluating the efficiency of nasal irrigation.

BACKGROUND: Although different methods of nasal irrigation have been utilized, irrigation efficiency in nasal cavities has not been well assessed. The objective of this study was to develop an apparatus and procedure for evaluating the irrigation efficiency and to explore the optimal head position during irrigation. METHODS: Casts of the left sinonasal cavity from a healthy volunteer were made from high-resolution-computed tomography data using 3D printing with composite materials. An adjustable apparatus that allowed cast fixation at the different head positions was built. The yogurt was used to simulate mucus. The cast with 5 ml yogurt filled around the superior, middle, and inferior turbinate was fixed in six head positions including head tilt 10°, 45°, and 60° forward with or without leaning 30° to the right. The cast was irrigated with 120 ml, 175 ml, and 240 ml dyed water and was video recorded. The irrigation efficiency was calculated based on the weight difference of the cast before and after the irrigation. RESULTS: Most residual yogurt was located around the superior meatus after the irrigation under different volumes and head positions. The irrigation efficiency of the rinse bottle or the pulsatile device was volume dependent, with the highest irrigation efficiency under 240 ml water. When the left sinonasal cavity was irrigated, the head position of tilt 45° forward with leaning 30° to the right was the optimal head position for these two devices when compared to other positions. The pulsatile device with 240 ml water performed better than the rinse bottle with 240 ml water regarding the irrigation efficiency under the optimal head position (0.8700 ± 0.0138 vs 0.7536 ± 0.0099, p = 0.003). CONCLUSIONS: The developed apparatus provided a potential method for evaluating the irrigation efficiency. The head position of tilt 45° forward with leaning 30° was suitable for patients to perform the nasal irrigation.

Nocturnal nasal congestion is associated with uncontrolled blood pressure in patients with hypertension comorbid obstructive sleep apnea.

OBJECTIVE: To determine the independent role of nasal obstruction on blood pressure (BP) control in patients with hypertension comorbid obstructive sleep apnea (OSA). SUBJECTS AND METHODS: This cross-sectional study comprised of 326 newly diagnosed OSA comorbid hypertension patients from March 2018 to December 2021. Sixty-six patients have controlled hypertension, two hundred and nine with uncontrolled hypertension and fifty-one with resistant hypertension. Information on demographic characteristics, sleep data, hypertension status was collected. Multivariate logistic regression models were used to determine the odds ratios (OR). RESULTS: Patients with nocturnal nasal congestion had more difficult to control blood pressure, with more numbers of antihypertensive drugs. They tended to have more severe OSA, lower nocturnal oxygen saturation and more severe sleepiness. Univariate analysis showed that nocturnal nasal congestion and Nasal Obstruction Symptom Evaluation (NOSE) Scale scores were associated with uncontrolled BP. After adjusting for age, sex, smoking, alcohol use, OSA severity and CT90, multivariate logistic analysis models showed that nocturnal nasal congestion was independently associated with uncontrolled hypertension (OR = 2.09, p = 0.023). When analyzed more severe resistant hypertension, nocturnal nasal congestion showed a higher association (OR = 2.96, p = 0.014). CONCLUSION: This cross-sectional study demonstrated that the nocturnal nasal congestion was independently associated with uncontrolled BP. The use of nasal decongestants or nasal surgery may be a potential therapeutic target for resistant hypertension in the future.

The association between glucocorticoid receptor (NR3C1) gene polymorphism and difficult-to-treat rhinosinusitis.

BACKGROUND: Difficult-to-treat rhinosinusitis (DTRS) seriously affects the quality of work and life of patients, and the cause is still unclear. We aimed to explore the association between the glucocorticoid receptor (NR3C1) gene polymorphisms and DTRS. METHODS: A nested case-control study was conducted. The exons of NR3C1 gene were sequenced by an ABI 9700 DNA analyzer in 30 DTRS patients and 70 matched chronic rhinosinusitis (CRS) patient with good outcome (non-DTRS). The genotypic and allele frequencies were calculated and linkage disequilibrium was analyzed. RESULTS: The three SNPs showed a significant difference between the DTRS and non-DTRS groups. In allelic model analysis, we found that the allele "C" of rs6196, the allele "A" of rs258751, and the allele "T" of rs6194 were associated with increased the risk of DTRS (all p < 0.05). In addition, the haplotype CAT of the 3 SNPs was detected to be significantly associated with DTRS risk (p = 0.001), while the haplotype TGC was associated with the decreased risk of DTRS (p = 0.008). CONCLUSION: NR3C1 gene polymorphisms are significantly associated with the DTRS.

Olfactory dysfunction is associated with cognitive impairment in patients with obstructive sleep apnea: a cross-sectional study.

PURPOSE: Obstructive sleep apnea (OSA) increases the risk for olfactory dysfunction. However, the relationship between olfactory function and cognition in OSA patients is unclear. The present study aimed to investigate the relationship between cognition and olfactory dysfunction (OD) in patients with OSA. METHOD: This was a cross-sectional study in which 74 patients with OSA and 22 controls were recruited. All subjects completed polysomnography, Sniffin' Sticks, and -neurocognitive assessments. According to results of Sniffin' Sticks, OSA patients were divided into two groups: OSA with OD (53 cases) and OSA without OD (21 cases). Neurocognitive function was assessed by Montreal Cognitive Assessment (MoCA), Memory and Executive Screening (MES), and Shape Trail Test (STT). Cognition was compared between OSA with and without OD. Correlation between olfactory parameters and respiratory sleep parameters and neurocognitive assessments was analyzed. RESULTS: Compared with OSA without OD, OSA with OD showed significantly decreased neurocognitive scores of MoCA (29-27 vs 27-23, p < 0.01), MES-5R (45-40.1 vs 43-33.5, p < 0.01) and increased consuming time of STT-B (91.66 vs 121.63, p < 0.01). A positive correlation was found between the scores of MoCA and MES-5R and all olfactory parameters. In addition, a negative correlation was present between the time consumed for STT-B and odor thresholds (r = - 0.344, p < 0.01), odor identification (r = - 0.335, p < 0.01), and threshold-discrimination-identification scores (r = - 0.448, p < 0.01). CONCLUSION: Olfactory function is associated cognitive function in patients with OSA and may provide a new direction for early treatment interventions in OSA patients at risk for cognitive impairment.

Clinical significance of the cognition-related pathogenic proteins in plasma neuronal-derived exosomes among normal cognitive adults over 45 years old with olfactory dysfunction.

OBJECTIVES: Exosomal Phospho-Tau-181(P-T181-tau), Total tau (T-tau), and amyloid-ß peptide 42 (Aß42) have been proved the capacity for the amnestic mild cognitive impairment (MCI) and the diagnosis of Alzheimer's disease (AD). This study aimed to explore the cognitive function and the levels of P-T181-tau, T-tau, and Aß42 in neuronal-derived exosomes (NDEs) extracted from plasma in normal cognitive adults over 45 years old with olfactory dysfunction. METHODS: A cross-sectional survey of 29 participants aged over 45 was conducted. Plasma exosomes were isolated, precipitated, and enriched by immuno-absorption with anti- L1 cell adhesion molecule (L1CAM) antibody. NDEs were characterized by CD81, and extracted NDE protein (P-T181-tau, T-tau, and Aß42) biomarkers were quantified by enzyme-linked immunosorbent assay (ELISAs). Olfactory performance was assessed by Sniffin' Sticks and cognitive performance was assessed by Montreal Cognitive Assessment (MoCA). RESULTS: There was no significant difference between adults with olfactory dysfunction and without olfactory dysfunction regarding the cognitive function as measured by MoCA and all the participants showed normal cognition. Adults with olfactory dysfunction showed a higher concentration of P-T181-tau in plasma NDEs than did adults without olfactory dysfunction (P = 0.034). Both the levels of P-T181-tau (r = - 0.553, P = 0.003) and T-tau (r = - 0.417, P = 0.034) negatively correlated with the odor identification scores. In addition, the level of T-tau negatively correlated with MoCA scores (r = - 0.597, P = 0.002). The levels of P-T181-tau (r = - 0.464, P = 0.022) and T-tau (r = - 0.438, P = 0.032) negatively correlated with the delayed recall scores. CONCLUSIONS: This study demonstrated that cognition-related pathogenic proteins including P-T181-tau in plasma NDEs were significantly increased in adults over 45 years old with olfactory dysfunction before the occurrence of cognitive impairment. The impaired odor identification and the delayed recall function were highly associated with the increased levels of P-T181-tau and T-tau in plasma NDEs.

Impact of chronic intermittent hypoxia on the long non-coding RNA and mRNA expression profiles in myocardial infarction.

Chronic intermittent hypoxia (CIH) is the primary feature of obstructive sleep apnoea (OSA), a crucial risk factor for cardiovascular diseases. Long non-coding RNAs (lncRNAs) in myocardial infarction (MI) pathogenesis have drawn considerable attention. However, whether CIH participates in the modulation of lncRNA profiles during MI is yet unclear. To investigate the influence of CIH on MI, cardiac damage was assessed by histology and echocardiography, and lncRNA and mRNA integrated microarrays were screened. MI mouse model showed myocardial hypertrophy, aggravated inflammation and fibrosis, and compromised left ventricle function under CIH. Compared with normoxia, 644 lncRNAs and 1084 differentially expressed mRNAs were identified following CIH for 4 weeks, whereas 1482 lncRNAs and 990 mRNAs were altered at 8 weeks. Strikingly, reoxygenation after CIH markedly affected 1759 lncRNAs and 778 mRNAs. Of these, 11 lncRNAs modulated by CIH were restored after reoxygenation and were validated by qPCR. The GO terms and KEGG pathways of genes varied significantly by CIH. lncRNA-mRNA correlation further showed that lncRNAs, NONMMUT032513 and NONMMUT074571 were positively correlated with ZEB1 and negatively correlated with Cmbl. The current results demonstrated a causal correlation between CIH and lncRNA alternations during MI, suggesting that lncRNAs might be responsible for MI aggravation under CIH.

Extracellular vesicle microRNA cargoes from intermittent hypoxia-exposed cardiomyocytes and their effect on endothelium.

Intermittent hypoxia (IH), a main characteristic of obstructive sleep apnea (OSA) syndrome, is an independent risk factor of cardiovascular complications. However, the mechanism has not been fully elucidated. Growing evidence has revealed alterations of extracellular vesicle (EV) contents, mostly miRNAs, playing a pathogenic role in cardiovascular complications. In current study, we attempt to compare the disparity of myocardial EV miRNA components after IH or normoxia treatment and determine whether EVs from IH-treated cardiomyocytes could affect endothelial function. 63 differentially expressed miRNAs were identified in EVs from IH-exposed cardiomyocytes by miRNA chip assay. Among them, 16 miRNAs with homologous sequence in mouse and human were verified by qPCR assay and 11 miRNAs were proved with the same tendency as miRNA chip assay. KEGG predicted that the function of differentially expressed miRNA was enriched to Akt signaling pathway. Notably, EVs from IH-exposed cardiomyocytes dramatically impaired endothelial-dependent relaxation and inhibited Akt/eNOS expression in endothelial cells. This study provides the first evidence that IH significantly alters myocardial EV miRNA composition and reveals a novel role of myocardial EVs in endothelial function under IH status, which will help to understand the OSA- or IH-related endothelial dysfunction from a new scope.

Assessment of cardiac tumors by 18F-FDG PET/CT imaging: Histological correlation and clinical outcomes.

BACKGROUND: To evaluate the diagnostic value of 18F-FDG PET/CT in distinguishing benign versus malignant cardiac tumors as well as to assess its prognostic value. METHODS: We analyzed 38 patients with cardiac tumors who underwent 18F-FDG PET/CT and followed for median 8.5 ± 12.5 months. SUVmax and TBRmax (maximum tumor-to-background ratio) by receiver-operating characteristic (ROC) curve analysis were used to obtain threshold for the diagnosis of malignancy as defined by histology (n = 38). Survival was assessed and correlated with the dignity of the lesions and PET parameters. RESULTS: Optimal cut-off values indicating malignancy were as follows: SUVmax = 3.44, with 100% sensitivity and 92.9% specificity, and TBRmax = 1.55, with 95.8% sensitivity and 92.9% specificity. A significant difference of 18F-FDG uptake was observed between primary benign (n = 14, SUVmax = 2.35 ± 1.31, TBRmax = 1.05 ± 0.50) compared to primary malignant cardiac tumors (n = 11, SUVmax = 8.90 ± 4.23, TBRmax = 3.82 ± 1.44) as well as cardiac metastases and lymphoma (n = 13, SUVmax = 14.37 ± 8.05, TBRmax = 6.19 ±  3.38) (all P < .001). Survival rate was significantly lower in patients with malignant as compared to benign cardiac tumors (P < .05). Regression analysis revealed that the lesion dignity determined by the cut-off value of SUVmax was an independent predictor for death in patients with cardiac tumors (P < .05). CONCLUSION: 18F-FDG uptake in cardiac tumors can differentiate between benign and malignant cardiac tumors and predicts survival.

Detection of aortic prosthetic graft infection with 18F-FDG PET/CT imaging, concordance with consensus MAGIC graft infection criteria.

OBJECTIVES: The aim of this study was to investigate the diagnostic yield of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for detecting thoracic aortic graft infection (AGI) in comparison to expert consensus MAGIC criteria. METHODS: Patients suspected clinically of having thoracic-AGI were prospectively recruited. Consensus MAGIC criteria for AGI were compared to findings on FDG PET imaging. MAGIC criteria were verified against clinical/surgical, radiological, and microbiological/laboratory predefined major and minor parameters. FDG images were interpreted using a semiquantitative visual grading score (VGS, abnormal ≥ 3), focal uptake and quantitative maximum standard FDG uptake value (SUVmax, abnormal ≥ 7.3), and target-to-background FDG ratio (TBRmax, abnormal ≥ 4.2). RESULTS: Of 35 patients suspected of having thoracic-AGI, MAGIC diagnostic criteria were positive for AGI in 25 patients (71%) and negative in 10 (29%). FDG PET imaging was abnormal in 27 patients (77%). Abnormal and normal FDG imaging findings were concordant with MAGIC criteria in 31 patients (88.6%). In 4 patients, FDG imaging results were discordant with MAGIC criteria. By ROC analysis, optimal FDG cut-off values for detecting AGI by MAGIC were ≥ 3 for VGS, ≥ 7.3 for SUVmax and ≥ 4.2 for TBRmax, with concordance with MAGIC criteria in 88.6%, 85.7%, and 88.6% of patients, respectively. Two or more FDG imaging parameters (VGS, focal uptake, SUVmax, and TBRmax) yielded highest diagnostic concordance of 91.4%. VGS inverse odds ratio for AGI was 7.14. In 4 of 6 selective patients who had repeat FDG PET imaging during antibiotic treatment, quantitative FDG imaging values improved over time with associated improvement of laboratory markers of inflammation. CONCLUSIONS: FDG PET/CT imaging, using (semi-)quantitative imaging parameters, showed high concordance with expert consensus MAGIC criteria for AGI. These data suggest a potential complementary role of quantitative FDG/CT imaging, not only to detect AGI, but also to monitor response to antibiotic treatment.

Extracellular Vesicles Derived from Intermittent Hypoxia-Treated Red Blood Cells Impair Endothelial Function Through Regulating eNOS Phosphorylation and ET-1 Expression.

PURPOSE: Intermittent hypoxia (IH), a main characteristic of obstructive sleep apnea (OSA) syndrome, has been known as a dominant cause of OSA-related endothelial dysfunction and hypertension. However, the underlying mechanism still remains unclear. Extracellular vesicles (EVs), small vesicles secreted by various cells, can be absorbed by endothelial cells and then influence vascular function. The aim of this research is to clarify whether and how EVs shedding from red blood cells (RBCs) are involved in IH-induced endothelial dysfunction. METHODS: EVs were extracted by ultracentrifugation. After the identification of property and purity, EVs from IH-exposed RBCs (IH REVs) and normoxia-exposed RBCs (NOR REVs) or from OSA and non-OSA patient RBCs were utilized to treat C57BL/6 mouse aortas or human umbilical vein endothelial cells (HUVECs) for mechanistic exploration. RESULTS: Functional results demonstrated that REVs from OSA patients dramatically impaired endothelium-dependent relaxations (EDRs). Similarly, in vivo and ex vivo studies showed that IH REVs caused significant endothelial dysfunction compared to control group. Further results presented that IH REVs blocked endothelial nitric oxide synthase (eNOS) phosphorylation through inhibiting PI3K/Akt pathway and enhanced endothelin-1 (ET-1) expression through activating Erk1/2 pathway in endothelial cells. Meanwhile, endothelial dysfunction caused by IH REVs was reversed by Akt activator SC79 as well as Erk kinase inhibitor PD98059, suggesting that PI3K/Akt/eNOS and Erk1/2/ET-1 pathways were implicated in IH REV-induced impaired EDRs. CONCLUSIONS: This study reveals a novel role of REVs in endothelial dysfunction under IH and dissects the relevant mechanism involved in this process, which will help to establish a comprehensive understanding of OSA or IH-related endothelial dysfunction from a new scope.

The effects of high-sensitivity C-reactive protein on the clinical outcomes in obstructive sleep apnea patients undergoing off-pump coronary artery bypass grafting.

PURPOSE: To investigate the relationship between obstructive sleep apnea (OSA) severity and high-sensitivity C-reactive protein (Hs-CRP), and their respective impact on the clinical outcomes in patients undergoing off-pump cardiac artery bypass grafting (OPCABG). METHODS: We enrolled consecutive eligible patients listed for elective OPCABG who underwent cardiorespiratory polygraphy before surgery between January 2019 and December 2019 in this prospective observational single-center study. Baseline, intraoperative, and postoperative clinical data were compared between absent-mild and moderate-severe OSA groups. Regression analysis investigated the relationship between Hs-CRP level and severity of OSA, and further assessed the factors influencing postoperative atrial fibrillation, duration of hospitalization, and hospital cost. RESULTS: Patients with moderate-severe OSA accounted for 42.3% (52/123) of the cohort. Partial pressure of carbon dioxide (PCO2), Hs-CRP, apnea hypopnea index (AHI), mean apnea time, maximum apnea time, and oxygen desaturation index ODI ≥ 3% were significantly higher in the moderate-severe OSA group than in the absent-mild OSA group. Left ventricle ejection fraction (LVEF), lowest arterial oxygen saturation (SaO2), and mean SaO2 were significantly lower in the moderate-severe OSA group. Moderate-severe OSA was associated with elevated Hs-CRP level (OR = 2.356, 95% CI 1.101-5.041, P = 0.027). Hs-CRP was an independent risk factor for post-CABG atrial fibrillation (POAF) (OR = 1.212, P = 0.01). Hs-CRP level independently correlated with duration of hospitalization (B = 0.456, P = 0.001) and hospital cost (B = 1.111, P = 0.044). CONCLUSION: Hs-CRP level was closely related to OSA severity and have potential utility in predicting POAF, duration of hospitalization, and hospital costs in patients undergoing OPCABG.

Low arousal threshold is associated with unfavorable shift of PAP compliance over time in patients with OSA.

PURPOSE: To determine the predictive factors of initial and long-term adherence to positive airway pressure (PAP) therapy and factors leading to an unfavorable shift of PAP compliance. METHODS: This follow-up study was comprised of newly diagnosed patients with obstructive sleep apnea (OSA) amenable to PAP therapy from January 2017 to April 2019. Information on basic demographics, comorbidities, and sleep-related symptoms were collected. PAP adherence data were collected at the end of the first week and the third month. RESULTS: Of 166 patients enrolled, data from 142 (86%) were in the final analysis. Overall PAP usage was worse at 3 months declining from the first week. After adjusting for age and gender, multinomial logistic regression analysis showed that a small number of sleep-related symptoms (OR, 0.69; 95% CI, 0.52-0.91) and low arousal threshold (ArTH) (OR, 4.44; 95% CI, 1.52-12.98) were associated with higher odds of noncompliance. Low ArTH (OR, 2.87; 95% CI, 1.09-7.57) and lower body mass index (BMI) (OR, 0.88; 95% CI, 0.78-0.99) increased the risk of compliance-to-noncompliance shift. Sixty-two patients with polysomnography were analyzed separately. After adjustment for age and gender, poor sleep efficiency (OR, 0.80; 95% CI, 0.68-0.94) was associated with higher odds of consistent noncompliance. Low ArTH (OR, 15.36; 95% CI, 1.44-164.24) increased the risk of compliance-to-noncompliance shift in this subgroup. CONCLUSIONS: Lower BMI and low ArTH were associated with an unfavorable shift of PAP compliance over time in patients with OSA, which was different from the predictors of consistent PAP noncompliance of patients with OSA.

Subclinical left ventricular systolic dysfunction detected in obstructive sleep apnea with automated function imaging and its association with nocturnal hypoxia.

BACKGROUND: Early detection of left ventricular (LV) dysfunction is crucial in obstructive sleep apnea (OSA) due to its close relationship with cardiovascular diseases. Global longitudinal strain (GLS) derived from automated function imaging (AFI) can precisely assess global longitudinal function. The aim of this study was to determine if LV GLS was reduced in patients with OSA and a normal LV ejection fraction (LVEF) and to assess any associated determinants. METHODS: Polysomnography (PSG) and echocardiography were done in consecutive patients with suspected OSA and normal LVEF in this prospective study. Patients were divided into two groups according to apnea-hypopnea index (AHI) (Group 1, normal or mild OSA: AHI < 15/h; Group 2, moderate-to-severe OSA: AHI ≥ 15/h). Clinical, PSG, and echocardiographic parameters were compared between the two groups and the associated factors were investigated. RESULTS: Of 425 consecutive patients, 244 were analyzed after exclusions. Patients in Group 2 had significantly worse GLS than those in Group 1 (p < 0.001). The prevalence of GLS reduction (defined as < - 19.7%) was 25% and 76%, respectively (χ2 = 34.19, p < 0.001). Nocturnal lowest pulse oxygen saturation (SpO2), AHI, body mass index (BMI), and gender were associated with GLS reduction (all p < 0.05). Further multivariate analysis showed that the lowest SpO2 (OR: 2.15), gender (OR: 2.45), and BMI (OR: 2.66) remained independent (all p < 0.05), and the lowest SpO2 was the most powerful determinant (χ2 = 33.0, p < 0.001) in forward regression analysis. The intra- and inter-operator variability for AFI and coefficient of repeatability was low even in those with relatively poor images. CONCLUSIONS: In patients with normal LVEF, more severe OSA was associated with a worse GLS. The major determinants were lowest nocturnal SpO2, gender, and obesity, but not AHI. GLS can be rapidly and reliably assessed using AFI.

Serum exosomes mediate delivery of arginase 1 as a novel mechanism for endothelial dysfunction in diabetes.

Exosomes, abundant in blood, deliver various molecules to recipient cells. Endothelial cells are directly exposed to circulating substances. However, how endothelial cells respond to serum exosomes (SExos) and the implications in diabetes-associated vasculopathy have never been explored. In the present study, we showed that SExos from diabetic db/db mice (db/db SExos) were taken up by aortic endothelial cells, which severely impaired endothelial function in nondiabetic db/m+ mice. The exosomal proteins, rather than RNAs, mostly account for db/db SExos-induced endothelial dysfunction. Comparative proteomics analysis showed significant increase of arginase 1 in db/db SExos. Silence or overexpression of arginase 1 confirmed its essential role in db/db SExos-induced endothelial dysfunction. This study is a demonstration that SExos deliver arginase 1 protein to endothelial cells, representing a cellular mechanism during development of diabetic endothelial dysfunction. The results expand the scope of blood-borne substances that monitor vascular homeostasis.

Prognostic value of olfactory evoked potentials in patients with post-infectious olfactory dysfunction.

PURPOSE: Prognostic assessment of patients with post-infectious olfactory dysfunction (PIOD) poses a challenge for clinicians. While there have been some studies on the prognostic factors of PIOD focusing on demographic factors, the aim of this study was to investigate whether event-related potentials (ERPs) could be used as a new predictor of olfactory recovery in PIOD. METHODS: This was a retrospective study involving patients who underwent olfactory examinations using Sniffin' Sticks test before treatment and after 1 year of follow-up. The responder group was defined by an increase of threshold-discrimination-identification (TDI) score of ≥ 6 points. All patients underwent ERP examination and the amplitude and latency of each wave of ERPs were recorded before treatment. RESULTS: A total of 61 patients (age 47.50 ± 11.04 years, 27 males) were analyzed. The presence of olfactory ERPs (oERPs) was greater in the responder group than in the non-responder group (P = 0.007), while that of trigeminal ERPs (tERPs) did not differ between the two groups (P = 0.346). Logistic-regression analyses showed that factors associated with improvement of subjective olfactory function were duration (OR, 1.604; 95% CI, 1.062-2.423; P = 0.025), initial threshold (odds ratio [OR], 0.043; 95% confidence interval [CI], 0.004-0.439; P = 0.008), and latency of N1 in oERPs (OR, 1.007; 95% CI, 1.001-1.013; P = 0.021). CONCLUSION: Our study shows that duration of OD, initial threshold, and latency of N1 in oERPs were associated with olfactory improvement in PIOD patients, which may provide guidance for clinicians.