Deep-learning-based 3D super-resolution CT radiomics model: Predict the possibility of the micropapillary/solid component of lung adenocarcinoma.

Objective: Invasive lung adenocarcinoma（ILA） with micropapillary (MPP)/solid (SOL) components has a poor prognosis. Preoperative identification is essential for decision-making for subsequent treatment. This study aims to construct and evaluate a super-resolution（SR） enhanced radiomics model designed to predict the presence of MPP/SOL components preoperatively to provide more accurate and individualized treatment planning. Methods: Between March 2018 and November 2023, patients who underwent curative intent ILA resection were included in the study. We implemented a deep transfer learning network on CT images to improve their resolution, resulting in the acquisition of preoperative super-resolution CT (SR-CT) images. Models were developed using radiomic features extracted from CT and SR-CT images. These models employed a range of classifiers, including Logistic Regression (LR), Support Vector Machines (SVM), k-Nearest Neighbors (KNN), Random Forest, Extra Trees, Extreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Multilayer Perceptron (MLP). The diagnostic performance of the models was assessed by measuring the area under the curve (AUC). Result: A total of 245 patients were recruited, of which 109 (44.5 %) were diagnosed with ILA with MPP/SOL components. In the analysis of CT images, the SVM model exhibited outstanding effectiveness, recording AUC scores of 0.864 in the training group and 0.761 in the testing group. When this SVM approach was used to develop a radiomics model with SR-CT images, it recorded AUCs of 0.904 in the training and 0.819 in the test cohorts. The calibration curves indicated a high goodness of fit, while decision curve analysis (DCA) highlighted the model's clinical utility. Conclusion: The study successfully constructed and evaluated a deep learning（DL）-enhanced SR-CT radiomics model. This model outperformed conventional CT radiomics models in predicting MPP/SOL patterns in ILA. Continued research and broader validation are necessary to fully harness and refine the clinical potential of radiomics when combined with SR reconstruction technology.

Development and validation of a risk prediction model for anxiety or depression among patients with chronic obstructive pulmonary disease between 2018 and 2020.

Anxiety and depression are important risk factors for chronic obstructive pulmonary disease (COPD). The aim of this study was to develop a prediction model to predict anxiety or depression in COPD patients. The retrospective study was conducted in COPD patients receiving stable treatment between 2018 and 2020 to develop prediction model. The variables, were readily available in clinical practice, were analysed. After data preprocessing, model training and performance evaluation were performed. Validity of the prediction model was verified in 3 comparative model training. Between 2018 and 2020, 375 eligible patients were analysed. Thirteen variables were included into the final model: gender, age, marital status, education level, long-term residence, per capita annual household income, payment method of medical expenses, direct economic costs of treating COPD in the past year, smoking, COPD progression, number of acute exacerbation of COPD in the last year, regular treatment with inhalants and family oxygen therapy. Risk score threshold in each sample in the training set was 1.414. The area under the curve value was respectively 0.763 and 0.702 in the training set and test set, which were higher than three comparative models. The simple prediction model to predict anxiety or depression in patients with COPD has been developed. Based on 13 available data in clinical indicators, the model may serve as an instrument for clinical decision-making for COPD patients who may have anxiety or depression.Key messagesThirteen variables were included into the prediction model.The AUC value was, respectively, 0.763 and 0.702 in the training set and test set, which were higher than three comparative models.The simple prediction model to predict anxiety or depression in patients with COPD has been developed.

Graph Embedding Based Novel Gene Discovery Associated With Diabetes Mellitus.

Diabetes mellitus is a group of complex metabolic disorders which has affected hundreds of millions of patients world-widely. The underlying pathogenesis of various types of diabetes is still unclear, which hinders the way of developing more efficient therapies. Although many genes have been found associated with diabetes mellitus, more novel genes are still needed to be discovered towards a complete picture of the underlying mechanism. With the development of complex molecular networks, network-based disease-gene prediction methods have been widely proposed. However, most existing methods are based on the hypothesis of guilt-by-association and often handcraft node features based on local topological structures. Advances in graph embedding techniques have enabled automatically global feature extraction from molecular networks. Inspired by the successful applications of cutting-edge graph embedding methods on complex diseases, we proposed a computational framework to investigate novel genes associated with diabetes mellitus. There are three main steps in the framework: network feature extraction based on graph embedding methods; feature denoising and regeneration using stacked autoencoder; and disease-gene prediction based on machine learning classifiers. We compared the performance by using different graph embedding methods and machine learning classifiers and designed the best workflow for predicting genes associated with diabetes mellitus. Functional enrichment analysis based on Human Phenotype Ontology (HPO), KEGG, and GO biological process and publication search further evaluated the predicted novel genes.

ERp29 downregulation enhances lung adenocarcinoma cell chemosensitivity to gemcitabine by upregulating HSP27 phosphorylation.

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.

Oxidative stress does not contribute to the release of proinflammatory cytokines through activating the Nod-like receptor protein 3 inflammasome in patients with obstructive sleep apnoea.

PURPOSE: The study was conducted to test the hypothesis that oxidative stress leads to the release of proinflammatory cytokines by activating the Nod-like receptor protein (NLRP)3 inflammasome in patients with obstructive sleep apnoea (OSA). METHODS: The study recruited 247 participants who were divided into cases and healthy control groups. OSA patients were subdivided into four subgroups according to sex, blood pressure, body mass index (BMI), and severity of disease. No significant differences were found between cases and controls with respect to age or sex. Peripheral blood samples were collected for analysis after examination, and the serum concentrations of oxidative stress (8-isoprostane), inflammation (interleukin (IL)-18, IL-1ß, IL-6, tumour necrosis factor (TNF)-α), and NLRP3 inflammasome components (NLRP3, caspase-1, and ASC) were detected by enzyme-linked immunosorbent assay. RESULTS: The serum concentrations of both oxidative stress and proinflammatory factors were higher in OSA patients than healthy controls. Subgroup analysis also revealed significant differences according to the apnoea-hypopnea index and BMI. Additionally, correlations were identified between 8-isoprostane and proinflammatory factors (IL-1ß, IL-18, and TNF-α). Multiple regression analysis suggested that sleep parameters and BMI affected inflammation. However, no differences were observed in the serum level of NLRP3 inflammasome components between patients and controls. Furthermore, stratified analysis revealed no additional differences. CONCLUSIONS: The current study suggests that oxidative stress leads to inflammation by mechanisms other than activation of the NLRP3 inflammasome in OSA patients. Furthermore, both sleep apnoea and BMI influenced the serum concentration of inflammatory mediators.

Regulatory effects of the long non­coding RNA RP11­543N12.1 and microRNA­324­3p axis on the neuronal apoptosis induced by the inflammatory reactions of microglia.

The present study aimed to examine how the long non­coding RNA (lncRNA) RP11­543N12.1 interacted with microRNA (miR)­324­3p to modify microglials (MIs)­induced neuroblastoma cell apoptosis, which may pose benefits to the treatment of Alzhemier's disease (AD). The cell model of AD was established by treating SH­SY5Y cells with amyloid ß (Aß)25­35, and MI were acquired using primary cell culture technology. The lncRNAs that were differentially expressed between SH­SY5Y and control cells were screened through a microarray assay and confirmed via polymerase chain reaction. In addition, overexpression of RP11­543N12.1 and miR­324­3p was established by transfection of SH­SY5Y cells with pcDNA3.1(+)­RP11­543N12.1 and miR­324­3p mimics, respectively, while downregulation of RP11­543N12.1 and miR­324­3p was achieved by transfection with RP11­543N12.1­small interfering RNA (siRNA) and miR­324­3p inhibitor, respectively. The interaction between RP11­543N12.1 and miR­324­3p was confirmed with a dual­luciferase reporter gene assay. The results revealed that the expression levels of total and phosphorylated tau in SH­SY5Y cells were significantly elevated following Aß25­35 treatment (P<0.05), and RP11­543N12.1 was found to be differentially expressed between the control and Aß25­35­treated cells (P<0.05). Furthermore, the targeted association of RP11­543N12.1 and miR­324­3p was predicted based on miRDB4.0 and PITA databases, and then validated via the dual­luciferase reporter gene assay. SH­SY5Y cells transfected with siRNA or inhibitor, and treated with Aß25­35 displayed cellular survival and apoptosis that were similar to the normal levels (P<0.05). Finally, co­culture of MI and SH­SY5Y cells transfected with RP11­543N12.1­siRNA/miR­324­3p inhibitor significantly enhanced cell apoptosis (P<0.05). In conclusion, RP11­543N12.1 targeted miR­324­3p to suppress proliferation and promote apoptosis in the AD cell model, suggesting that RP11­543N12.1 and miR­324­3p may be potential biomarkers and therapeutic targets for AD.

Clinical significance of calcium-binding protein S100A8 and S100A9 expression in non-small cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate the correlation between calcium-binding protein S100A8 and S100A9 expression in non-small cell lung cancer (NSCLC) and patients' clinical features. METHODS: Fifty-two NSCLC patients who underwent surgery at Zhejiang Hospital from February 2014 to January 2016 were included in this study. Calcium-binding protein S100A8 and S100A9 expression patterns in cancer and para-cancer tissues were examined by immunohistochemistry assay. The correlation between calcium-binding protein S100A8 and S100A9 expression patterns and NSCLC patients' clinical characteristics, including age, gender, tumor node metastasis stage, and pathology type, were evaluated. RESULTS: S100A8 and S100A9 were generally expressed on the cytoplasm and nucleus of NSCLC cells, mainly located in the cytoplasm, stained with brown particles, and distributed evenly. The positive expression rates of S100A8 and S100A9 in cancer tissues were 71.2% and 76.9%, respectively, which were significantly higher than in para-cancer tissues at 11.5% and 19.2%, respectively, with statistical significance (P < 0.05). S100A8 and S100A9 positive expression was associated with tumor differentiation degree (P < 0.05) but were not correlated with age, gender, smoking history, tumor diameter, pathology type, tumor node metastasis stage, or pleural effusion (Pall > 0.05). CONCLUSION: S100A8 and S100A9 positive expression in cancer tissues was significantly higher than in para-cancer tissues and was correlated with tumor differentiation, which may be a potential marker for poor prognosis.

Efficacy of nasal continuous positive airway pressure on patients with OSA with erectile dysfunction and low sex hormone levels.

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.

Association between Single Nucleotide Polymorphisms in Gamma-Aminobutyric Acid B Receptor, Insulin Receptor Substrate-1, and Hypocretin Neuropeptide Precursor Genes and Susceptibility to Obstructive Sleep Apnea Hypopnea Syndrome in a Chinese Han Population.

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.

Single Nucleotide Polymorphisms in Adiponectin Gene Are Not Directly Associated with Increased Risk of Obstructive Sleep Apnea Syndrome in a Chinese Han Population.

PURPOSE: This study aims to test the possible correlation between single nucleotide polymorphisms (SNPs) in the adiponectin gene and increased risk of obstructive sleep apnea syndrome (OSAS) in a Chinese Han population. MATERIALS AND METHODS: A total of 266 subjects were enrolled into the study to detect 9 SNPs in the adiponectin gene. Multivariate unconditional logistic regression analysis, adjusted for gender and age, was used to estimate the associations of these SNPs with OSAS risk. RESULTS: No evidence of a direct association was observed between these SNPs and the risk of OSAS in the Chinese Han population. However, the stratified analysis also revealed a remarkable genotype difference for SNP rs6773957 between cases and controls in the overweight subgroup (p < 0.05). In addition, the allele or genotype distributions of rs12495941, rs182052, and rs16861205 had significant differences with regard to the severity of OSAS (p < 0.05). No differences were identified in the other subgroups. CONCLUSION: The current research demonstrated that the SNPs in the adiponectin gene did not represent susceptibility loci for OSAS in Chinese Han individuals overall. However, variants of rs6773957 have an association with OSAS in overweight individuals. In addition, polymorphisms of rs12495941, rs182052, and rs16861205 are associated with the severity of OSAS.

Interleukin-16 polymorphism is associated with an increased risk of ischemic stroke.

Clinical and experimental data have demonstrated that inflammation plays fundamental roles in the pathogenesis of ischemic stroke. Interleukin-16 (IL-16) is identified as a proinflammatory cytokine that is a key element in the ischemic cascade after cerebral ischemia. We aimed to examine the relationship between the IL-16 polymorphisms and the risk of ischemic stroke in a Chinese population. A total of 198 patients with ischemic stroke and 236 controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing method. We found that the rs11556218TG genotype and G allele of IL-16 were associated with significantly increased risks of ischemic stroke (TG versus TT, adjusted OR = 1.88; 95% CI, 1.15-3.07; G versus T, adjusted OR = 1.54; 95% CI, 1.05-2.27, resp.). However, there were no significant differences in the genotype and allele frequencies of IL-16 rs4778889 T/C and rs4072111 C/T polymorphisms between the two groups, even after stratification analyses by age, gender, and the presence or absence of hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia. These findings indicate that the IL-16 polymorphism may be related to the etiology of ischemic stroke in the Chinese population.