The association between obstructive sleep apnea and lung nodule, carcinoembryonic antigen.

PURPOSE: The association between obstructive sleep apnea (OSA) and cancer risks gaining more and more attention. Data on the association between OSA and lung cancer risk are limited. This study is to investigate whether a link exists between low-dose computed tomography (LDCT) scanning of the chest findings, carcinoembryonic antigen (CEA) and OSA in patients suspected of OSA. METHODS: The cross-sectional study included patients aged 18 years or older who underwent continuous nocturnal polysomnography at our sleep center between February 2019 and November 2020. All subjects underwent chest LDCT and CEA. Patients with an apnea-hypopnea index (AHI) of ≥ 15/h were classified as clinically significant OSA group, whereas patients with an AHI < 15/h were classified as control group. RESULTS: A total of 277 patients were enrolled in the study. 176 patients were categorized into the OSA group, while 101 patients were categorized into the control group. There is no relationship between any OSA-related parameter and presence of lung nodule or presence of ≥ 6 mm lung nodule in the binary logistic regression analysis. OSA group demonstrated a significant higher value of CEA than control group. Stepwise multiple linear regression analysis showed that lowest O2 saturation (ß = - 0.256, p < 0.001), smoking status (ß = 0.156, p = 0.007) and age (ß = 0.153, p = 0.008) were independent predictors of elevated CEA. CONCLUSIONS: OSA was independently related to the elevated of serum CEA level, but not with presence of pulmonary nodule or ≥ 6 mm pulmonary nodule in LDCT. Further well-designed longitudinal studies with pathology available are needed to identify the association between OSA and risk of lung cancer.

Identification of diagnostic markers related to fecal and plasma metabolism in primary Sjögren's syndrome.

BACKGROUND: Accurate diagnostic techniques for patients with primary Sjögren's syndrome (pSS) are needed. This study aimed to investigate new biomarkers related to fecal and plasma metabolism from pSS patients. METHODS: The feces and plasma of 21 pSS patients and 18 controls admitted to the Second Hospital of Shanxi Medical University were collected for analysis. Metabolites in feces and plasma were quantified using liquid chromatography-mass spectrometry. The metabolic pathway alterations caused by pSS were studied and the expression of metabolites in the intersecting pathway was analyzed in the feces and plasma of pSS patients. Metabolites that showed the same alterations in feces and plasma in pSS patients were considered as diagnostic markers and receiver operating characteristic curves were generated to analyze the sensitivity of these markers in diagnosing pSS. RESULTS: There were 114 and 92 upregulated metabolites and 54 and 125 downregulated metabolites in the feces and plasma of pSS patients, respectively. These metabolites were enriched in 8 pathways for feces and 12 pathways for plasma. Arginine biosynthesis, Linoleic acid metabolism, Tyrosine metabolism, Taurine and hypotaurine metabolism were pathways enriched by metabolites in both samples. Twelves metabolites were enriched in the above four pathways, while only 9,10-12,13-Diepoxyoctadecanoate, Tyramine, 9-OxoODE and 2-Hydroxyethanesulfonate showed the same trend. The candidate diagnostic markers were all predictive, with better diagnostic sensitivity in plasma samples. CONCLUSIONS: 9,10-12,13-Diepoxyoctadecanoate, Tyramine, 9-OxoODE, 2-Hydroxyethanesulfonate were metabolism-related diagnostic markers for pSS feces and plasma.

[The Value of Serum HMGB1 and sRAGE in the Diagnosis, Efficacy Monitoring and Prognosis of Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To evaluate the value of high mobility group protein B1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in the diagnosis, efficacy monitoring and prognosis of newly diagnosed multiple myeloma (MM) patients. METHODS: Fifty newly diagnosed MM patients before and after chemotherapy and 50 hematological outpatients from October 2018 to May 2020 were selected. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum HMGB1 and sRAGE levels of the patients. ROC was used to further analyze the efficacy of serum HMGB1 and sRAGE levels on the diagnosis of MM. At the same time, the serum levels of HMGB1 and sRAGE before and after chemotherapy were compared, and their values in the evaluation of curative effect of MM patients were analyzed. According to the mean values of serum HMGB1 and sRAGE, all the patients were divided into different groups, the clinical characteristics and survival status of the patients were compared. RESULTS: Before treatment the serum HMGB1 level of the patients in MM group was higher than that in control group, while sRAGE level was lower (t=11.363,6.127, P<0.001). The AUC of serum HMGB1 and sRAGE in the MM patients was 0.955 and 0.811, respectively. After 3 courses of chemotherapy, HMGB1 level of the patients in CR group was lower than before chemotherapy, while in PD group was higher, as well as sRAGE level of the patients in PR group (P<0.05). There were significant differences in R-ISS stage, HGB, CRP, ESR, CD56, CD117, D13S319 deletion between HMGB1 high expression group and HMGB1 low expression group (χ2=3.920, 6.522, 6.65, 4.16, 3.945, 6.65, 4.16, P<0.05), while there were significant differences in ISS stage, CRP and CD56 between sRAGE low expression group (28 cases) and sRAGE high expression group (22 cases) (χ2=4.565, 4.711, 5.547, P<0.05). Kaplan-Meier survival analysis showed that the patients in HMGB1 low expression group had better survival condition, for PFS Tlow>Thigh (χ2=9.470, P<0.05), and for OS Tlow>Thigh (χ2=7.808, P<0.05); there was no difference in the survival of sRAGE high expression group and low expression group, for PFS Tlow0.05), and for OS Tlow0.05). Cox analysis showed that LDH and HMGB1 were the factors affecting the prognosis of the patients, and both of them affected PFS (HR=2.771, 95% CI: 1.002-7.662, P=0.049; HR=6.022, 95% CI: 1.689-21.470, P=0.006), while HMGB1 also affected OS (HR=4.275, 95% CI: 1.183-15.451, P=0.027). CONCLUSION: The serum HMGB1 and sRAGE have certain auxiliary value for the diagnosis and curative effect monitoring of newly diagnosed MM patients, and serum HMGB1 is expected to be an auxiliary detection index for the prognosis of MM.

Long non-coding RNA MALAT1 affects intermittent hypoxia-induced endothelial injury by regulating miR-142-3p/HMGB1.

BACKGROUND: Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is strongly linked to endothelial cell functions. However, the function of MALAT1 in intermittent hypoxia (IH) associated vascular endothelial injury has not been explored yet. The current study makes great attempts to investigate the function of MALAT1 in IH-induced endothelial injury and its latent control network. METHODS: To mimic the effect of OSA, we cultured the human umbilical vein endothelial cells (HUVECs) under intermittent hypoxia. Western blot was applied to measure the expression level of associated proteins including capase-3, Bax, Bcl-2 while qRT-PCR was used in measurement of MALAT1 and miR-142-3p. Cell Counting Kit-8 (CCK-8) was carried out in assessing cell viability. Dual-luciferase reporter assay was applied to verify the relationships among high mobility group box (HMGB)1 and MALAT1, miR-142-3p. RESULTS: IH treatment significantly reduced cell viability but enhanced cell apoptosis in HUVECs. Concomitantly, MALAT1 was significantly upregulated in IH-treated HUVECs. Further experiment showed that MALAT1 knockdown augmented IH-induced injury of HUVECs. In addition, it was confirmed by dual-luciferase reporter assay that MALAT1 interacted with miR-142-3p directly. Besides, inhibition of miR-142-3p alleviated damage induced by MALAT1 knockdown in IH-treated HUVECs. Finally, miR-142-3p interacted with HMGB1 directly and inhibition of HMGB1 protein expression mediated by MALAT1 knockdown was reversed by miR-142-3p inhibitor. CONCLUSIONS: IH resulted in increased expression of MALAT1 in HUVECs. MALAT1 knockdown augmented IH-induced injury of HUVECs. MALAT1 exerted its effects on IH-treated HUVECs via miR-142-3p/HMGB1.

LncRNA XR_596701 protects H9c2 cells against intermittent hypoxia-induced injury through regulation of the miR-344b-5p/FAIM3 axis.

Long noncoding RNAs (lncRNAs) participate in various biological processes and cardiovascular diseases. Recently, a novel lncRNA XR_596701 was found to be differentially expressed in obstructive sleep apnea (OSA)-induced myocardial tissue compared to normal myocardial tissues. However, the pathological effect and regulatory mechanism of XR_596701 in intermittent hypoxia (IH)-mediated cardiomyocytes damage have not been studied. The subcellular localization of XR_596701 was determined by fluorescence in situ hybridization (FISH). Gene expressions of XR_596701 and miR-344b-5p were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in IH-induced H9c2 cells. Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) staining assay. Cell apoptosis was detected by Hoechst 33342/PI staining and immunofluorescence (IF). Apoptotic protein of H9c2 cells was measured by western blot. The direct interaction between XR_596701 and miR-344b-5p as well as miR-344b-5p and Fas apoptotic inhibitory molecule 3 (FAIM3) were examined using dual-luciferase reporter assay. The significance of XR_596701 and miR-344b-5p on cell proliferation and apoptosis was evaluated by using gain-of-function and loss-of-function approaches. XR_596701 was upregulated, while miR-344b-5p downregulated in IH-induced H9c2 cells. Functionally, suppression of XR_596701 and overexpression of miR-344b-5p inhibited cell proliferation and promoted cell apoptosis in H9c2 cells. The roles of XR_596701 were achieved by sponging miR-344b-5p. And the function of miR-344b-5p was reversed by targeting FAIM3. Additionally, FAIM3 mediated IH-induced H9c2 cells damage by XR_596701. XR_596701 was serve as a novel lncRNA that indicated protective roles on proliferation and apoptosis of IH-induced H9c2 cells through the miR-344b-5p/FAIM3 axis.

Obstructive sleep apnea and the risk of mortality in patients with lung cancer: a meta-analysis.

PURPOSE: Prior reports have examined the relationship between obstructive sleep apnea (OSA) and the mortality rate of lung cancer. However, the findings remain controversial. The present meta-analysis was performed to assess the relationship between OSA and increased risk of mortality in patients with lung cancer. METHODS: PubMed, Web of Science, and Embase were systematically searched for the correlative studies. Data were analyzed and pooled to evaluate odds ratios (ORs) of lung cancer mortality related to OSA. RESULTS: From 249 identified studies, 3 met inclusion criteria and were analyzed, including 67 patients with lung cancer and comorbid OSA and 45 patients with lung cancer and no OSA. The meta-analysis indicated that OSA was not significantly correlated with mortality rate in lung cancer (OR = 2.005, 95% CI = 0.703 to 5.715, z = 1.30, p = 0.193). There was no significant publication bias according to Begg's tests (p = 0.296) and Egger's tests (p = 0.097). CONCLUSION: This meta-analysis suggests that OSA is not significantly correlated with the mortality rate in lung cancer.

Association between obstructive sleep apnea and non-alcoholic fatty liver disease in pediatric patients: a meta-analysis.

BACKGROUND: Some studies have reported a relationship between obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in pediatric population. However, this issue remains controversial. OBJECTIVES: The purpose of the present study was to investigate the association between OSA and NAFLD in pediatric population. METHODS: We systematically searched PubMed, Web of Science, Embase for eligible studies. The data involving markers of NAFLD including alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatic inflammation, hepatic fibrosis of both OSA group and control group were extracted. Pooled standardised mean difference (SMD) and weighted mean difference (WMD) were appropriately calculated through a fixed or random-effect model. RESULTS: Nine cross-sectional studies with 1133 children and adolescents were included. OSA was significantly associated with ALT, AST, and NAFLD fibrosis stage, but not NAFLD inflammation grade. Subgroup analysis indicated that both mild OSA and severe OSA were significantly associated with elevated ALT and AST. Furthermore, in the studies with all main confounding factors (age, gender, and BMI) matched, OSA group had higher ALT and AST levels than control group. CONCLUSIONS: This meta-analysis suggested that OSA was associated with NAFLD evidenced by elevated liver enzymes and progressive hepatic fibrosis in pediatric population. Screening and monitoring of NAFLD in pediatric patients with obesity-related OSA are necessary.

Impact of upper airway configuration on CPAP titration assessed by CT during Müller's maneuver in OSA patients.

PURPOSE: Continuous positive airway pressure (CPAP) is the current gold-standard treatment for moderate to severe obstructive sleep apnea (OSA), and upper airway anatomy plays an increasingly important role in evaluating the efficacy of CPAP therapy. The aim of this observational study was to investigate the influence of upper airway anatomy on CPAP titration in OSA patients assessed by computed tomography (CT) during Müller's maneuver. METHODS: Consecutive patients under investigation for OSA by undergoing polysomnography and CT scan of the upper airway while awake were enrolled. Successful full-night manual titration was performed to determine the optimal CPAP pressure level for OSA patients in supine position using a nasal mask. RESULTS: A total of 157 subjects (134 males and 23 females) were included. Both apnea-hypopnea index (AHI) and LaSO2 significantly correlated with CPAP titration level, upper airway length (UAL), distance from mandibular plane to hyoid bone (MPH), and neck circumference (all p < 0.05). There were significant positive correlations between CPAP titration level and UAL (r = 0.348, p = 0.000) and MPH (r = 0.313, p = 0.002). Stepwise multiple linear regression analyses were performed to evaluate the independent predictors of AHI, LaSO2, and CPAP titration level. CPAP titration level was identified as an independent explanatory variable for AHI and LaSO2 after adjustment for confounders. Multiple linear regression analyses also indicated that body mass index (BMI) and UAL were independently associated with CPAP titration level (all p < 0.05). CONCLUSIONS: Upper airway abnormalities combined with anthropometric parameters play important roles in CPAP titration for OSA patients, providing additional insight into the factors influencing OSA treatment strategies. UAL and BMI should be taken into consideration when choosing CPAP titration level to improve CPAP compliance.

The role of ferroptosis in chronic intermittent hypoxia-induced liver injury in rats.

PURPOSE: Obstructive sleep apnea (OSA) has been related to an increased risk of liver injury. Ferroptosis is a form of programmed cell death implicated in multiple physiological and pathological processes. This study aimed to explore the role of ferroptosis in chronic intermittent hypoxia (CIH)-induced liver injury as well as to uncover the underlying mechanisms using a CIH rat model. METHODS: Fourteen male Sprague-Dawley rats were randomly allocated to either the normal control (NC) (n = 7) or the CIH group (n = 7). Rats were exposed to intermittent hypoxia for 8 weeks in CIH group. Liver function, histological changes, and markers of oxidative stress were evaluated. The protein levels of hypoxia-inducible factor-1α, nuclear factor E2-related factor 2 (Nrf2), Acyl-CoA synthetase long-chain family member 4 (ACSL4), and glutathione peroxidase 4 (GPX4) in liver were examined by Western blot analysis. RESULTS: CIH treatment caused significant increase of serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde (MDA). Liver MDA was significantly higher in CIH group than that in NC group. Histology showed that CIH treatment induced discernible swelled, disordered hepatocytes, necrosis, and infiltrated inflammatory cells. CIH treatment significantly reduced the expression of GPX4, while markedly up-regulated expression of ACSL4, indicating elevation in hepatic ferroptosis. In addition, the protein expression of Nrf2 in CIH group was significantly lower than that in NC group. CONCLUSIONS: Ferroptosis played a crucial role in CIH-induced liver injury. The hepatic ferroptosis in CIH rat model might be mediated by the dysregulation of Nrf2. This highlights a potential therapeutic target for the treatment of OSA-related liver injury.