ABSTRACT
OBJECTIVE: To investigate genotype-phenotype changes between rs29230 in γ-aminobutyric acid B receptor (GABBR1), rs1801278 in insulin receptor substrate-1 (IRS-1), and rs9902709 in hypocretin neuropeptide precursor (HCRT) and obstructive sleep apnea hypopnea syndrome (OSAHS) in Chinese Han individuals. MATERIALS AND METHODS: A total of 130 patients with OSAHS and 136 age- and gender-matched healthy controls were enrolled in this study. A brief description of DNA extraction and genotyping is given. Multivariate unconditional logistic regression analysis adjusted for gender and age was used to estimate the associations of single nucleotide polymorphisms (SNPs) rs29230 (GABBR1), rs1801278 (IRS-1), and rs9902709 (HCRT) with OSAHS risk. Subgroup analysis was performed to evaluate differences in these SNPs among subgroups according to gender, body mass index (BMI), and severity of disease. RESULTS: Genotype and allele frequencies of rs29230 were significantly different between cases and controls (p = 0.0205 and p = 0.0191, respectively; odds ratio = 0.493, 95% confidence interval = 0.271-0.896), especially for male patients (p = 0.0259 and p = 0.0202, respectively). Subgroup analysis according to BMI also revealed a significant allele difference for rs29230 between cases and controls in the overweight subgroup (p = 0.0333). Furthermore, allele and genotype frequencies of rs1801278 showed significant differences between cases and controls (p = 0.0488 and p = 0.0471, respectively). However, no association was observed between rs9902709 and OSAHS risk (p = 0.2762), and no differences were identified in other subgroups. CONCLUSION: In this study, there was an association between variants of rs29230 and rs1801278 and OSAHS risk in the Chinese Han population but not for rs9902709.
Subject(s)
Genetic Predisposition to Disease/genetics , Insulin Receptor Substrate Proteins/genetics , Orexins/genetics , Sleep Apnea, Obstructive/genetics , gamma-Aminobutyric Acid/genetics , Adult , Aged , Body Mass Index , Case-Control Studies , China/epidemiology , Female , Gene Frequency , Genotype , Humans , Logistic Models , Male , Middle Aged , Neuropeptides , Phenotype , Polymerase Chain Reaction , Polymorphism, Single Nucleotide/genetics , Polysomnography , Risk Factors , Sleep Apnea, Obstructive/epidemiologyABSTRACT
Background: Accurate interpretation of lung function tests requires appropriate spirometry reference values derived from large-scale population-specific epidemiological surveys. The aim of this cross-sectional study was to establish normal spirometric values for the population of healthy, nonsmoking Han Chinese adults residing in Zhejiang province, China. Methods: We measured lung function parameters such as forced expiratory volume in 1 s, forced vital capacity, peak expiratory flow, maximal midexpiratory flow, and diffusion capacity for carbon monoxide and considered age, height, and weight as independent factors that may modify these parameters. The clinical data were divided into the study arm and validation group. The study arms were used to construct predictive equations using stepwise multiple linear regression, and data from the validation group were used to assess the robustness of the equations. Results: The 3866 participants were randomized into a study arm (n = 1,949) and a validation arm (n = 1,917). Lung function parameters had a negative association with age and a positive association with height. Data from the two groups were similar. Predictive equations were constructed from the study arm, and the validation group was used to test the feasibility of the reference equations. Conclusions: The reference values we derived can be used to evaluate lung function in this cohort in both epidemiological studies and clinical practice.
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OBJECTIVE: To determine the combined efficacy of piperlongumine and gemcitabine for treatment of KRAS mutant lung cancer. METHODS: The cell growth inhibition of piperlongumine, gemcitabine, and piperlongumine plus gemcitabine was measured by Cell Counting Kit8 assay and the combination index was calculated. In addition, the combined effects of piperlongumine and gemcitabine on cell apoptosis, reactive oxygen species (ROS) contents, and microtubule-associated protein 1 light chain 3B (LC3B) expression were examined. RESULTS: Piperlongumine increased ROS contents and LC3B-II expression. Following the combined treatment with piperlongumine and 10 mM N-acetyl-L-cysteine (NAC), intracellular ROS and cell viability returned to normal levels, and the expression of LC3B-II decreased to the predose level. Gemcitabine also induced cell apoptosis, increased ROS contents, and LC3B-II expression. The combination of piperlongumine with gemcitabine exhibited a synergetic anticancer activity with the combination index <1. The combined application of gemcitabine and piperlongumine yielded synergistic effects on cell apoptosis, but failed to synergistically increase ROS levels and LC3B-II expression. CONCLUSION: Combination therapy with piperlongumine and gemcitabine is a promising treatment option for KRAS mutant lung cancer.
Subject(s)
Apoptosis/drug effects , Deoxycytidine/analogs & derivatives , Dioxolanes/pharmacology , Lung Neoplasms/genetics , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , A549 Cells , Antimetabolites, Antineoplastic/pharmacology , Cell Proliferation/drug effects , Cell Survival/drug effects , Deoxycytidine/pharmacology , Drug Synergism , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Microtubule-Associated Proteins/metabolism , Proto-Oncogene Proteins p21(ras)/metabolism , Reactive Oxygen Species/metabolism , GemcitabineABSTRACT
BACKGROUND: Pentraxin 3 is an acute inflammatory protein of the long pentraxin subfamily. A meta-analysis was performed to assess diagnostic accuracy of pentraxin 3 for respiratory tract infections. METHODS: We identify studies examining diagnostic value of pentraxin 3 for respiratory tract infections by searching Pubmed, Web of Knowledge, and Cochrane Library. The sensitivity, specificity, negative likelihood ratio (LR), positive LR, and diagnostic odds ratio were pooled. The area under the summary receiver operator characteristic (SROC) curve and Q point value (Q*) were calculated. RESULTS: A total of 8 studies with 961 individuals were eligible for this meta-analysis. The pooled sensitivity of pentraxin 3 in diagnosis of respiratory tract infections was 0.78, the pooled specificity was 0.73, the area under the SROC curve was 0.84, and the Q* was 0.77. The area under the SROC curve of serum and bronchoalveolar lavage fluid (BALF) pentraxin 3 was 0.85 and 0.89, respectively. Meta-regression analysis revealed that cutoff value was the source of heterogeneity among the included studies. The Deek funnel plot test suggested no evidence of publication bias. Subgroup analyses showed that the area under the SROC curve of pentraxin 3 in diagnosis of ventilator-associated pneumonia (VAP) was 0.89. CONCLUSION: Pentraxin 3 has a moderate accuracy for diagnosing respiratory tract infections and VAP. The overall diagnostic value of BALF level of pentraxin 3 is superior to its serum concentration.
Subject(s)
C-Reactive Protein/analysis , Respiratory Tract Infections/blood , Respiratory Tract Infections/diagnosis , Serum Amyloid P-Component/analysis , Biomarkers , Bronchoalveolar Lavage Fluid/chemistry , Humans , Odds Ratio , Pneumonia, Ventilator-Associated/blood , Pneumonia, Ventilator-Associated/diagnosis , Predictive Value of Tests , ROC CurveABSTRACT
BACKGROUND: To validate the accuracy of ultra-wideband (UWB) wireless radar for the screening diagnosis of sleep apnea. METHODS: One hundred and seventy-six qualified participants were successfully recruited. Apnea-hypopnea index (AHI) results from polysomnography (PSG) were reviewed by physicians, while the radar device automatically calculated AHI values with an embedded chip. All results were statistically analyzed. RESULTS: A UWB radar-based AHI algorithm was successfully developed according to respiratory movement and body motion signals. Of all 176 participants, 63 exhibited normal results (AHI <5/hr) and the remaining 113 were diagnosed with obstructive sleep apnea. Significant correlation was detected between radar AHI and PSG AHI (Intraclass correlation coefficient 0.98, P<0.001). Receiver operating characteristic curve (ROC) analysis revealed high sensitivity and specificity. High concordance in participants with varying gender, age, BMI, and PSG AHI was reached. CONCLUSIONS: The UWB radar may be a portable, convenient, and reliable device for obstructive sleep apnea screening.
ABSTRACT
The aim of the current study was to assess the underlying mechanism of endoplasmic reticulum protein 29 (ERp29) in lung adenocarcinoma chemosensitivity to gemcitabine. Western blot analysis was performed to detect ERp29 expression following lung adenocarcinoma cell treatment with gemcitabine. The effects of gemcitabine in combination with ERp29 siRNA on cell apoptosis, cell cycle and heat shock protein 27 (HSP27) expression were assessed. The results demonstrated that ERp29 expression was increased on exposure to gemcitabine. The apoptotic rate of lung adenocarcinoma cells were also increased following gemcitabine treatment and the combined application of gemcitabine and ERp29 siRNA synergistically increased apoptotic rates further. It was also revealed that gemcitabine and ERp29 siRNA synergistically increased the ratio of phosphorylated to total HSP27 protein. In addition, downregulation of HSP27 significantly reduced lung adenocarcinoma chemosensitivity to gemcitabine. These data indicate that ERp29 affects lung adenocarcinoma cell chemosensitivity to gemcitabine by regulating phosphorylated HSP27. ERp29 is a novel target, which may be used to enhance the therapeutic effect of lung adenocarcinoma treatment with gemcitabine.
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PURPOSE: This study aimed to test the hypothesis that erectile dysfunction (ED) is common in men with obstructive sleep apnea (OSA). We also assessed the efficacy of continuous positive airway pressure (CPAP) treatment for ED and sex hormone levels in patients with severe OSA and ED. METHODS: A total of 153 OSA patients and 60 healthy controls were enrolled in this study. The International Index of Erectile Dysfunction-5 (IIEF-5) score was obtained, and blood samples were collected for analysis of sex hormones after polysomnography. The IIEF-5 score, sex hormone levels, and polysomnographic parameters were re-evaluated in 32 patients with severe OSA and ED after 1 month of CPAP treatment. RESULTS: The present study showed that the prevalence of ED was 47.1% in all cases and only 13.3% in controls, and a lower sex hormone levels was presented in OSA patients. OSA patients with ED had greater severity of disease, and lower serum levels of follicle stimulating hormone (FSH) and testosterone than OSA patients without ED (p < 0.05). After CPAP therapy, there was a significant increase in the IIEF-5 score, and serum levels of FSH, luteinizing hormone, and testosterone, were elevated compared with baseline levels (p < 0.05). Multivariate regression analysis indicated the serum level of testosterone had impact on the ED. CONCLUSIONS: OSA patients had lower sex hormone levels and a higher occurrence of ED than controls, and serum level of testosterone had effect on ED. CPAP treatment ameliorated the symptoms of ED and elevated serum levels of FSH, luteinizing hormone, and testosterone.