RAGE is a potential biomarker implicated in immune infiltrates and cellular senescence in lung adenocarcinoma.

BACKGROUND: Receptor for Advanced Glycation End-products (RAGE) is an oncogene abnormally expressed in various cancers. However, the clinical value of RAGE and the biological role of RAGE in lung cancer have not been fully investigated. METHODS: We compared the RAGE expression using several public databases. The relationship between RAGE expression and clinicopathological variables was assessed. The R software package was used to carry out enrichment analyses of RAGE co-expression and gene set enrichment analysis (GSEA). Additionally, we used the TIMER database to assess the association between immune infiltration and RAGE expression. The correlation between RAGE expression and senescence biomarkers in lung adenocarcinoma was analyzed using the TCGA database. RESULTS: Our findings indicated that the expression of RAGE was downregulated in lung adenocarcinoma, and down-regulation of RAGE was related to poor overall survival and disease-free survival. Functional enrichment analysis indicated that RAGE co-expression genes were mainly associated with neutrophil activation involved in immune response, neutrophil degranulation, and regulation of leukocyte-mediated immunity. Correlation analysis revealed that RAGE expression was closely related to the purity of the tumor and immune infiltration. GSEA indicated that the RAGE-related differential genes were mainly enriched in senescence-related pathways. Besides, the RAGE expression was significantly associated with senescence-related genes. CONCLUSION: Down-regulation of RAGE expression was associated with poor prognosis, as well as defective immune infiltration and cellular senescence in lung adenocarcinoma.

Construction and validation of a prognostic signature based on anoikis-related lncRNAs in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is characterized by a high death rate and a poor prospect for survival. Anoikis, which is a kind of programmed cell apoptosis, is an important factor in the advancement of tumors. Nonetheless, the function of anoikis-related lncRNAs (ARLRs) in LUAD is still not well understood. The TCGA database was queried for genomic and clinical information. A prognostic signature for ARLRs was established via the use of coexpression analysis and Cox regression. Validation of the model's accuracy was conducted utilizing K-M curves and receiver operating characteristic (ROC) curves, and the signature was utilized to develop a nomogram. LncRNAs were implicated in the progression of tumors, as determined by functional enrichment analysis. There was an improvement in prognosis, increased immune cell infiltration, and higher immune scores among the low-risk patients. Additionally, we found that the two groups had varied anticancer drug sensitivities, which could help guide treatment. The impact of one ARLR, AC026355.2, on migration and invasion was validated by in vitro experiments in LUAD cells. Herein, a new lncRNA signature associated with anoikis was identified and estimated, potentially serving as a prognostic indicator for LUAD patients.

Clinical Features and Contributing Factors of Excessive Daytime Sleepiness in Chinese Obstructive Sleep Apnea Patients: The Role of Comorbid Symptoms and Polysomnographic Variables.

Background: The occurrence and severity of excessive daytime sleepiness (EDS) vary considerably among obstructive sleep apnea (OSA) patients. This study was designed to investigate the characteristics of EDS and identify its contributing factors in OSA patients. Methods: This was a cross-sectional study from a tertiary medical center in China. A total of 874 consecutive patients with newly diagnosed OSA were included. Subjective daytime sleepiness was assessed with the Epworth Sleepiness Scale (ESS). The subjects were assigned to the non-EDS group (582 patients), mild to moderate EDS group (227 patients), and severe EDS group (65 patients) according to the ESS scores. The clinical features and polysomnographic parameters were acquired and analyzed to identify the differences between groups and the determinants of EDS. Results: The age of patients with severe EDS (49.5 ± 11.3) was slightly greater than that of patients with mild to moderate EDS (44.5 ± 10.2) (p < 0.05) and non-EDS patients (45.2 ± 12.0) (p < 0.05). Body mass index (BMI) was highest in the severe EDS group (29.1 ± 3.6 kg/m2) (p < 0.0001), intermediate in the mild to moderate EDS group (27.9 ± 3.3 kg/m2), and lower in the non-EDS group (26.8 ± 3.3 kg/m2). Logistic regression analysis showed waist circumference, memory loss, work/commute disturbances, and sleep efficiency were independently associated with mild to moderate EDS, and the microarousal index, apnea-hypopnea index (AHI), and saturation impair time below 90% were independent contributing factors of mild to moderate EDS. Meanwhile, age, neck circumference, gasping/choking, memory loss, work/commute disturbances, and sleep latency were independently associated with severe EDS, and the AHI and mean SpO2 were independent contributing factors of severe EDS. Conclusions: OSA patients with various severities of EDS are more obese and have more comorbid symptoms compared to patients without EDS. Sleep fragmentation, respiratory events, and nocturnal hypoxia may be predictors of EDS. Comprehensive consideration of demographic, clinical, and polysomnographic factors is required when evaluating OSA patients.

The effect of helium-oxygen-assisted mechanical ventilation on chronic obstructive pulmonary disease exacerbation: A systemic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often accompanied by acute exacerbations. Patients of COPD exacerbation suffering from respiratory failure often need the support of mechanical ventilation. Helium-oxygen can be used to reduce airway resistance during mechanical ventilation. The aim of this study is to evaluate the effect of helium-oxygen-assisted mechanical ventilation on COPD exacerbation through a meta-analysis. METHODS: A comprehensive literature search through databases of Pub Med (1966∼2016), Ovid MEDLINE (1965∼2016), Cochrane EBM (1991∼2016), EMBASE (1974∼2016) and Ovid MEDLINE was performed to identify associated studies. Randomized clinical trials met our inclusion criteria that focus on helium-oxygen-assisted mechanical ventilation on COPD exacerbation were included. The quality of the papers was evaluated after inclusion and information was extracted for meta-analysis. RESULTS: Six articles and 392 patients were included in total. Meta-analysis revealed that helium-oxygen-assisted mechanical ventilation reduced Borg dyspnea scale and increased arterial PH compared with air-oxygen. No statistically significant difference was observed between helium-oxygen and air-oxygen as regards to WOB, PaCO2 , OI, tracheal intubation rates and mortality within hospital. CONCLUSIONS: Our study suggests helium-oxygen-assisted mechanical ventilation can help to reduce Borg dyspnea scale. In terms of the tiny change of PH, its clinical benefit is negligible. There is no conclusive evidence indicating the beneficial effect of helium-oxygen-assisted mechanical ventilation on clinical outcomes or prognosis of COPD exacerbation.

Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways.

Obstructive sleep apnea (OSA) associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH) triggered tissue damage. Receptor for advanced glycation end product (RAGE) and its ligand high mobility group box 1 (HMGB1) are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE), the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1) normal air (NA), (2) CIH, (3) CIH+sRAGE, and (4) NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6), apoptotic (Bcl-2/Bax), and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK) signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.

Clinical assessment and polysomnographic study of sleep apnea in a Chinese population of snorers.

BACKGROUND AND OBJECTIVES: While an increasing number of people who snore are seeking medical consultations, the clinical characteristics of snorers are rarely reported. The aim of this study is to characterize the clinical and polysomnographic features in a population of snorers. METHODS: A total of 490 subjects were examined retrospectively. The clinical history, Epworth Sleepiness Scale (ESS) scores, physical examination, and full-night polysomnography (PSG) data were obtained for all the subjects. The correlations between the neck circumference, waist circumference, ESS scores, body mass index (BMI), and apnea-hypopnea index (AHI) of obstructive sleep apnea (OSA) patients were explored. The gender and age differences in OSA patients were analyzed. RESULTS: OSA was diagnosed in 84.7% of the sample, with 21.2% of the patients having a mild form, 15.4% having a moderate form, and 63.4% having a severe form of OSA. The ESS scores, neck circumference, waist circumference, and BMI were positively correlated with AHI in OSA patients. The ESS scores and BMI were negatively correlated with nadir oxygen saturation (SaO2). A greater number of men than women exhibited moderate to severe forms of the disease. OSA affects the work of males more commonly compared with females. Nocturia was a more common complaint in elderly OSA patients. Heart diseases coexisted more frequently with OSA in elderly patients. CONCLUSIONS: In a population of snorers, OSA is the most common condition identified. The ESS scores and BMI were well correlated with the severity of the disease. Men had a more severe form of OSA than women. Nocturia frequently occurred in elderly OSA patients, as did the coexistence of heart disease.