Purpose: Autophagy plays essential roles in the development of COPD. We aim to identify and validate the potential autophagy-related genes of COPD through bioinformatics analysis and experiment validation. Methods: The mRNA expression profile dataset GSE38974 was obtained from GEO database. The potential differentially expressed autophagy-related genes of COPD were screened by R software. Then, protein–protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed autophagy-related genes. Finally, RNA expression of top five differentially expressed autophagy-related genes was validated in blood samples from COPD patients and healthy controls by qRT-PCR. Results: A total of 40 differentially expressed autophagy-related genes (14 up-regulated genes and 26 down-regulated genes) were identified between 23 COPD patients and 9 healthy controls. The PPI results demonstrated that these autophagy-related genes interacted with each other. The GO and KEGG enrichment analysis of differentially expressed autophagy-related genes indicated several enriched terms related to autophagy and mitophagy. The results of qRT-PCR showed that the expression levels of HIF1A, CDKN1A, BAG3, ERBB2 and ATG16L1 in COPD patients and healthy controls were consistent with the bioinformatics analysis results from mRNA microarray. Conclusion: We identified 40 potential autophagy-related genes of COPD through bioinformatics analysis. HIF1A, CDKN1A, BAG3, ERBB2 and ATG16L1 may affect the development of COPD by regulating autophagy. These results may expand our understanding of COPD and might be useful in the treatment of COPD.

Cigarette smoke (CS)-caused ferroptosis was involved in the pathogenesis of COPD, but the role of ferroptosis in lung epithelial injury and inflammation is not clear. Rats were treated with CS or CUR and BEAS-2B cells were exposed to CS extract (CSE), ferrostatin-1 (Fer-1), deferoxamine (DFO), or CUR to detect reactive oxygen species (ROS) accumulation, lipid peroxidation, iron overload, and ferroptosis-related protein, which were the characteristic changes of ferroptosis. Compared with the control group, CSE-treated BEAS-2B cells had more cell death, higher cytotoxicity, and lower cell viability. The infiltration of inflammatory cell around the bronchi in the CS group of rats was more than that in the normal group. Meanwhile, CSE/CS elevated the levels of interleukin-6 and tumor necrosis factor-α in BEAS-2B cells and bronchoalveolar lavage fluid of rats. Besides, accumulative ROS and depleted glutathione was observed in vitro. In BEAS-2B cells and lung tissues of rats, CSE/CS increased malondialdehyde and iron; down-regulated solute carrier family 7, glutathione peroxidase 4, and ferritin heavy chain levels; and up-regulated transferrin receptor level. These changes were rescued by pretreatment of Fer-1 or DFO in vitro, and mitigated by CUR in vitro and in vivo. Collectively, this study reveals that ferroptosis was involved in lung epithelial cell injury and inflammation induced by CS, and CUR may alleviate CS-induced injury, inflammation, and ferroptosis of lung epithelial cell.

Purpose: The diagnosis and severity of obstructive sleep apnea (OSA) are commonly based on the apnea hypopnea index (AHI). However, patients with similar severity AHIs may show widely varying comorbidities and risks for cardiovascular disease, which may be associated with different severities of nocturnal hypoxia. The percentage of cumulative time with oxygen saturation below 90% in total sleep time (T90) is receiving increasing attention in OSA research because it describes the duration and degree of hypoxia during the whole sleep. This study aimed to explore the distribution of T90 in OSA patients with similar severity and to evaluate the relationship between T90 and hypertension. Patients and Methods: A total of 775 patients with OSA were enrolled in this study, all participants were divided into groups according to the T90 value: light hypoxia (T90≤ 5%), mild hypoxia (T90 accounted for 5– 10%), moderate hypoxia (T90 accounted for 10– 25%), and severe hypoxia (T90> 25%). Multivariate logistic regression analysis was performed to assess the association between T90 and hypertension. Results: Of the patients with mild OSA, 94.33% had light hypoxia, and 88.64% of moderate OSA patients had light hypoxia. The proportions of light, mild, moderate, and severe hypoxia among patients with severe OSA were 28.60%, 17.69%, 21.40%, and 32.31%, respectively. After adjustment for potential confounders, the risk of hypertension in patients with severe OSA increased according to the severity categories of T90. The odds ratio for T90 accounting for 10– 25% relative to T90≤ 5% was 2.544 (95%confidence interval, 1.254– 5.164; P=0.010) and as high as 2.692 (95%confidence interval, 1.403– 5.166; P=0.003) in patients with T90> 25%. Conclusion: OSA patients with similar degree of AHI may have different T90 values, especially in severe OSA. A higher T90 was independently associated with the risk of hypertension after adjustment for traditional risk factors in patients with severe OSA. Our findings highlight the potential role for T90 in predicting hypertension in patients severe OSA.

Introduction: Severe obesity is often present with non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA). Emerging researches suggest OSA plays an important role in NAFLD development and progression while the relationship between OSA and NAFLD is still conflicting. The interaction of OSA and NAFLD should be further evaluated as obesity surges. The purpose of this study was to assess the prevalence of OSA and NAFLD in patients with obesity undergoing bariatric surgery and evaluate the association between OSA and severity of NAFLD. Methods: 141 patients with severe obesity undergoing preoperative polysomnography and intraoperative liver biopsy during bariatric surgery were investigated. Clinical, anthropometric variables, liver enzymes, fasting blood glucose, fasting serum insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. The severity of NAFLD was assessed by degree of steatosis, ballooning, intralobular inflammation, and NAFLD activity score. The diagnosis and severity assessment of OSA was based on an apnea/hypopnea index (AHI). Results: OSA was diagnosed in 127 (90.07%), NAFLD in 124 (87.94%), and non-alcoholic steatohepatitis in 72 (51.06%) patients. There was a statistical difference in BMI, waist circumstance, neck circumstance, high-density lipoprotein cholesterol, fasting insulin, and HOMA-IR among the three groups divided by the severity of AHI. In addition, the distribution of hepatic steatosis grades among the three groups was statistically different (p = 0.025). AHI was significantly associated with HOMA-IR and hepatic steatosis when assessing the association between OSA parameters and liver histology in NAFLD (p < 0.05). Patients with steatosis of grades 1–3 had significantly elevated aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, triglycerides, fasting insulin, fasting glucose, HOMA-IR, and AHI compared with the patients with steatosis of grade 0. In a multivariable logistic analysis, the positive association between AHI and hepatic steatosis attenuated after adjusting for HOMA-IR. Conclusion: Prevalence of OSA and NAFLD was high in patients with obesity eligible for bariatric procedures. HOMA-IR, but not AHI, was an independent risk factor for hepatic steatosis in this population.

Background: Hypothyroidism could cause obstructive sleep apnea (OSA), however, the specific association of them remained unclear. This cross-sectional study aimed to determine the prevalence of hypothyroidism among patients with OSA, and the characteristics and predictors of hypothyroidism associated with OSA.Methods: A total of 573 patients with OSA were included in the study. Serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) were measured in all participants. Univariate and binary logistic regression analysis were performed to assess the association of OSA with hypothyroidism while controlling for potential confounders. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the OSA effect in the distinction between euthyroid and hypothyroidism.Results: The prevalence of hypothyroidism was 6.75%、5.12%、10.38% in the total, men, and women cohort, respectively, and the prevalence rate in women OSA patients was significantly higher than that in men OSA patients (P=0.018). The men OSA patients with hypothyroidism had a higher Epworth sleepiness scale (ESS) than women OSA patients with hypothyroidism (P=0.022). Additionally, the ESS was significantly higher in men OSA patients with hypothyroidism than those with euthyroid (P=0.042), while women OSA patients had no such difference (P=0.822). In men patients with OSA, ROC curve analyses revealed that the risk of hypothyroidism increased in accordance with increasing ESS after adjustment for potential confounders, and the optimal cutoff value was 10 score. Higher ESS category was significantly associated with a higher risk of prevalent hypothyroidism in men patients with OSA [odds ratio (OR) = 4.898 for ESS≥10 relative to ESS &lt;10, 95% confidence interval (CI) 1.628-14.731, P = 0.005].Conclusions: The prevalence of hypothyroidism in OSA patients was relatively higher, especially in women OSA patients. ESS was significantly and positively associated with hypothyroidism in men patients with OSA, suggesting that ESS may have a potential role in identification and diagnosis of men OSA patients complicated with hypothyroidism.