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BACKGROUND & AIMS: Previous studies have reported an inconsistent relationship between overactive bladder (OAB) and the consumption of tea, coffee, and caffeine. Our study aims to determine these associations in a large and nationally representative adult sample. METHODS: This cross-sectional study included 15,379 participants from the 2005-2018 US National Health and Nutrition Examination Survey (NHANES) database. The outcome was the risk of wet OAB that was diagnosed when the OAB symptom score was ≥3 with urgent urinary incontinence and excluded other diseases affecting diagnosis. The exposures were the consumption of tea, coffee, and caffeine. Weighted logistic regression models were established to explore these associations by calculating odds ratios (OR) and 95% confidence intervals (CI), as did restricted cubic splines (RCS) used to analyze the nonlinear associations. RESULT: Of all the participants (n = 15,379), 2207 had wet OAB. Mean [SE] consumption of tea, total coffee, caffeinated coffee, decaffeinated coffee, and caffeine was 233.6 [15.7] g/day, 364.3 [15.5] g/day, 301.6 [14.9] g/day, 62.7 [7.9] g/day, 175.5 [6.6] mg/day in participants with wet OAB, respectively. In the fully adjusted model, compared to those without tea consumption, the high consumption of tea (>481 g/day) was associated with an increased risk of wet OAB (OR: 1.29; 95%CI: 1.01-1.64). Low decaffeinated coffee (0.001-177.6 g/day) had a negative association with the risk (OR: 0.66; 95%CI: 0.49-0.90). In the RCS analysis, tea consumption showed a positive linear association with the risk of wet OAB, and decaffeinated coffee showed a nonlinear relationship with the risk and had a turning point of 78 g/day in the U-shaped curve between 0 and 285 g/day. Besides, total coffee, caffeinated coffee, and caffeine consumption had no significant association with the risk. Interestingly, in the high tea consumption, participants with high total coffee consumption [>527.35 g/day, OR and 95%CI: 2.14(1.16-3.94)] and low caffeine consumption [0.1-74.0 mg/day, OR and 95%CI: 1.50(1.03-2.17)] were positively associated with the risk of wet OAB. CONCLUSION: High tea consumption was associated with the increased risk of wet OAB, especially intake together with high total coffee and low caffeine consumption, but no significant association with the single consumption of total coffee and caffeine. Low decaffeinated coffee was associated with a decreased risk of wet OAB. It is necessary to control tea intake when managing the liquid intake of wet OAB patients.
Subject(s)
Caffeine , Coffee , Nutrition Surveys , Tea , Urinary Bladder, Overactive , Humans , Coffee/adverse effects , Tea/adverse effects , Female , Male , Urinary Bladder, Overactive/epidemiology , Caffeine/adverse effects , Caffeine/administration & dosage , Cross-Sectional Studies , Adult , Middle Aged , United States/epidemiology , Aged , Risk Factors , Young AdultABSTRACT
Phenotypic transformation of vascular smooth muscle cells (VSMCs) plays a crucial role in abdominal aortic aneurysm (AAA) formation. CARMN, a highly conserved, VSMC-enriched long noncoding RNA (lncRNA), is integral in orchestrating various vascular pathologies by modulating the phenotypic dynamics of VSMCs. The influence of CARMN on AAA formation, particularly its mechanisms, remains enigmatic. Our research, employing single-cell and bulk RNA sequencing, has uncovered a significant suppression of CARMN in AAA specimens, which correlates strongly with the contractile function of VSMCs. This reduced expression of CARMN was consistent in both 7- and 14-day porcine pancreatic elastase (PPE)-induced mouse models of AAA and in human clinical cases. Functional analyses disclosed that the diminution of CARMN exacerbated PPE-precipitated AAA formation, whereas its augmentation conferred protection against such formation. Mechanistically, we found CARMN's capacity to bind with SRF, thereby amplifying its role in driving the transcription of VSMC marker genes. In addition, our findings indicate an enhancement in CAMRN transcription, facilitated by the binding of NRF2 to its promoter region. Our study indicated that CARMN plays a protective role in preventing AAA formation and restrains the phenotypic transformation of VSMC through its interaction with SRF. Additionally, we observed that the expression of CARMN is augmented by NRF2 binding to its promoter region. These findings suggest the potential of CARMN as a viable therapeutic target in the treatment of AAA.
Subject(s)
Aortic Aneurysm, Abdominal , RNA, Long Noncoding , Humans , Mice , Animals , Swine , RNA, Long Noncoding/genetics , Muscle, Smooth, Vascular , NF-E2-Related Factor 2/genetics , Aortic Aneurysm, Abdominal/chemically induced , Aortic Aneurysm, Abdominal/genetics , Disease Models, AnimalABSTRACT
INTRODUCTION: Psoriasis is a chronic, inflammatory, and papulo-squamous skin disorder without a radical cure. Although previous observational analyses have discovered a relationship between medication intake and increased risk of psoriasis, they are susceptible to confounders. OBJECTIVES: We intend to ascertain if there is a causal association between specific medication intake and increased risk of psoriasis by utilizing the Mendelian randomization (MR) method. METHODS: We obtained the genome-wide association study (GWAS) data for medication intake (23 types, N = 1809) from UK Biobank samples. And we sourced the GWAS data for psoriasis from the 8th release of the FinnGen database, which included 8,075 psoriasis cases and 330,975 healthy control cases. Then a two-sample MR study was performed to determine their causal association, and inverse-variance-weighted MR (IVW-MR) was applied to calculate the effect estimates. RESULTS: The IVW-MR analysis uncovered a positive correlation between the intake of HMG CoA reductase inhibitors and the increased risk of psoriasis (odds ratio [OR] = 1.167, 95% confidence interval [CI] = 1.084-1.257). Similarly, the use of thyroid preparations (OR=1.080, 95% CI=1.026-1.138), nonsteroidal anti-inflammatory and antirheumatic products (OR=1.406, 95% CI=1.037-1.908), anilides (OR=1.379, 95% CI=1.004-1.894), antihistamines for systemic use (OR=1.341, 95% CI=1.104-1.630), and antihypertensives (OR=1.099, 95% CI=1.016-1.190) were associated with an increased risk of psoriasis. We did not find evidence from IVW-MR for other associations. CONCLUSIONS: Our study offers a causal testimony that the intake of HMG CoA reductase inhibitors, thyroid preparations, nonsteroidal anti-inflammatory and antirheumatic products, anilides, antihistamines for systemic use, and antihypertensives will potentially increase the risk of psoriasis.
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The comorbidities between gastroesophageal reflux disease (GERD) and various neurodegenerative and psychiatric disorders have been widely reported. However, the genetic correlations, causal relationships, and underlying mechanisms linking GERD to these disorders remain largely unknown. Here, we conducted a bidirectional Mendelian randomization (MR) analysis to determine the causality between GERD and 6 neurodegenerative and psychiatric disorders. Sensitivity analyses and multivariable MR were performed to test the robustness of our findings. Linkage disequilibrium score regression was used to assess the genetic correlation between these diseases as affected by heredity. Multiple bioinformatics tools combining two machine learning algorithms were applied to further investigate the potential mechanisms underlying these diseases. We found that genetically predicted GERD significantly increased the risk of Alzheimer's disease, major depressive disorder, and anxiety disorders. There might be a bidirectional relationship between GERD and insomnia. GERD has varying degrees of genetic correlations with AD, ALS, anxiety disorders, insomnia, and depressive disorder. Bioinformatics analyses revealed the hub shared genes and the common pathways between GERD and 6 neurodegenerative and psychiatric disorders. Our findings demonstrated the complex nature of the genetic architecture across these diseases and clarified their causality, highlighting that treatments for the cure or remission of GERD may serve as potential strategies for preventing and managing neurodegenerative and psychiatric disorders.
Subject(s)
Depressive Disorder, Major , Gastroesophageal Reflux , Mental Disorders , Sleep Initiation and Maintenance Disorders , Humans , Depressive Disorder, Major/epidemiology , Depressive Disorder, Major/genetics , Mental Disorders/epidemiology , Mental Disorders/genetics , Anxiety Disorders/epidemiology , Anxiety Disorders/genetics , Gastroesophageal Reflux/epidemiology , Gastroesophageal Reflux/genetics , Genome-Wide Association StudyABSTRACT
BACKGROUND: Parkinson's disease (PD) is a common degenerative nervous system disease. At present, there are certain limitations in various treatment options aimed at preventing or delaying the progression of PD. Therefore, the exploration of new drugs for PD is beneficial. Mendelian randomization (MR) analysis can be used to explore the association between drugs and diseases. In this study, MR analysis was adopted to investigate the causal relationship between 23 drugs and PD. These drugs have been approved for the treatment of different diseases, such as salicylic acid and derivatives (collectively called salicylates, e.g., aspirin, used for fever and pain relief), antithrombotic agents (e.g., warfarin, aspirin, used for preventing thrombotic events). METHODS: The GWAS data for the 23 drugs were obtained from the UK Biobank (UKB) project, while the GWAS data for PD were sourced from FinnGen. Single-Nucleotide Polymorphisms (SNPs) were selected as instrumental variables (IVs). We first performed a series of quality control steps (including MR-PRESSO) to select the appropriate SNPs. Two-sample MR analysis was performed using five different methods, including inverse variance weighting (IVW) with random-effects model, weighted median, MR-Egger, simple model, and weighted model. At the same time, sensitivity analysis was carried out using the MR-Egger and Cochran's Q test to ensure the authenticity and reliability of the results. RESULTS: In MR-PRESSO, salicylates and antithrombotic agents showed statistically significant associations with PD, respectively. In the main MR analysis (IVW), there was a negative causal relationship between salicylates and PD (OR = 0.73, 95% CI = 0.54-0.98, p = .039). Similarly, there was a negative causal relationship between antithrombotic agents and PD (OR = 0.70, 95%CI = 0.52-0.96, p = .027). No statistically significant association was found between the remaining 21 drugs and PD. CONCLUSION: This MR study demonstrated that salicylates and antithrombotic agents can reduce the risk of PD, thus providing a novel avenue for future drug exploration in PD.
Subject(s)
Parkinson Disease , Humans , Parkinson Disease/drug therapy , Parkinson Disease/genetics , Fibrinolytic Agents , Mendelian Randomization Analysis , Reproducibility of Results , Aspirin/adverse effects , Salicylic Acid , Genome-Wide Association StudyABSTRACT
BACKGROUND: Chronic obstructive pulmonary disease (COPD) patients often exhibit gastrointestinal symptoms, A potential association between COPD and Colorectal Cancer (CRC) has been indicated, warranting further examination. METHODS: In this study, we collected COPD and CRC data from the National Health and Nutrition Examination Survey, genome-wide association studies, and RNA sequence for a comprehensive analysis. We used weighted logistic regression to explore the association between COPD and CRC incidence risk. Mendelian randomization analysis was performed to assess the causal relationship between COPD and CRC, and cross-phenotype meta-analysis was conducted to pinpoint crucial loci. Multivariable mendelian randomization was used to uncover mediating factors connecting the two diseases. Our results were validated using both NHANES and GEO databases. RESULTS: In our analysis of the NHANES dataset, we identified COPD as a significant contributing factor to CRC development. MR analysis revealed that COPD increased the risk of CRC onset and progression (OR: 1.16, 95% CI 1.01-1.36). Cross-phenotype meta-analysis identified four critical genes associated with both CRC and COPD. Multivariable Mendelian randomization suggested body fat percentage, omega-3, omega-6, and the omega-3 to omega-6 ratio as potential mediating factors for both diseases, a finding consistent with the NHANES dataset. Further, the interrelation between fatty acid-related modules in COPD and CRC was demonstrated via weighted gene co-expression network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment results using RNA expression data. CONCLUSIONS: This study provides novel insights into the interplay between COPD and CRC, highlighting the potential impact of COPD on the development of CRC. The identification of shared genes and mediating factors related to fatty acid metabolism deepens our understanding of the underlying mechanisms connecting these two diseases.
Subject(s)
Colorectal Neoplasms , Pulmonary Disease, Chronic Obstructive , Humans , Genome-Wide Association Study , Multiomics , Nutrition Surveys , Fatty Acids , Pulmonary Disease, Chronic Obstructive/genetics , Colorectal Neoplasms/geneticsABSTRACT
Bladder cancer (BLCA) is a common and difficult-to-manage disease worldwide. Most common type of BLCA is urothelial carcinoma (UC). Fibrillin 2 (FBN2) was first discovered while studying Marfan syndrome, and its encoded products are associated with elastin fibres. To date, the role of FBN2 in BLCA remains unclear. The authors first downloaded data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The patients were divided into high FBN2 expression and low FBN2 expression groups, and the survival curve, clinical characteristics, tumour microenvironment (TME), and immune cell differences were analysed between the two groups. Then, the differentially expressed genes (DEGs) were filtered, and functional enrichment for DEGs was performed. Finally, chemotherapy drug susceptibility analysis based on the high and low FBN2 groups was conducted. The authors found upregulated expression of FBN2 in BLCA and proved that FBN2 could be an independent prognostic factor for BLCA. TME analysis showed that the expression of FBN2 affects several aspects of the TME. The upregulated expression of FBN2 was associated with a high stromal score, which may lead to immunosuppression and be detrimental to immunotherapy. In addition, the authors found that NK cells resting, macrophage M0 infiltration, and other phenomena of immune cell infiltration appeared in the high expression group of FBN2. The high expression of FBN2 was related to the high sensitivity of some chemotherapy drugs. The authors systematically investigated the effects and mechanisms of FBN2 on BLCA and provided a new understanding of the role of FBN2 as a risk factor and TME influencer in BLCA.
Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Urinary Bladder Neoplasms/genetics , Fibrillin-2 , Tumor Microenvironment , Risk FactorsABSTRACT
Both mitochondrial quality control and energy metabolism are critical in maintaining the physiological function of cardiomyocytes. When damaged mitochondria fail to be repaired, cardiomyocytes initiate a process referred to as mitophagy to clear defective mitochondria, and studies have shown that PTEN-induced putative kinase 1 (PINK1) plays an important role in this process. In addition, previous studies indicated that peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) is a transcriptional coactivator that promotes mitochondrial energy metabolism, and mitofusin 2 (Mfn2) promotes mitochondrial fusion, which is beneficial for cardiomyocytes. Thus, an integration strategy involving mitochondrial biogenesis and mitophagy might contribute to improved cardiomyocyte function. We studied the function of PINK1 in mitophagy in isoproterenol (Iso)-induced cardiomyocyte injury and transverse aortic constriction (TAC)-induced myocardial hypertrophy. Adenovirus vectors were used to induce PINK1/Mfn2 protein overexpression. Cardiomyocytes treated with isoproterenol (Iso) expressed high levels of PINK1 and low levels of Mfn2, and the changes were time dependent. PINK1 overexpression promoted mitophagy, attenuated the Iso-induced reduction in MMP, and reduced ROS production and the apoptotic rate. Cardiac-specific overexpression of PINK1 improved cardiac function, attenuated pressure overload-induced cardiac hypertrophy and fibrosis, and facilitated myocardial mitophagy in TAC mice. Moreover, metformin treatment and PINK1/Mfn2 overexpression reduced mitochondrial dysfunction by inhibiting ROS generation leading to an increase in both ATP production and mitochondrial membrane potential in Iso-induced cardiomyocyte injury. Our findings indicate that a combination strategy may help ameliorate myocardial injury by improving mitochondrial quality.
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OBJECTIVE: Recent studies have found that polycyclic aromatic hydrocarbons (PAHs) exposure may increase the risk of cardiovascular disease. The present study aimed to explore the association between PAHs exposure and severe abdominal aortic calcification (AAC) in adults. METHODS: Data were collected from the 2013-2014 National Health and Nutrition Examination Survey. PAHs exposure was analyzed from urinary mono hydroxylated metabolites of PAHs. Logistic regression models and subgroup analysis were performed to explore the association of PAHs exposure with severe AAC prevalence. RESULTS: A total of 1,005 eligible individuals were recruited into the study. After adjusting for confounding factors, those with the highest quartiles of 1-hydroxynaphthalene (1-NAP: OR 2.19, 95% CI 1.03-4.68, Pfor trend < 0.001), 2-hydroxynaphthalene (2-NAP: OR 2.22, 95% CI 1.04-4.64, Pfor trend < 0.001) and 1-hydroxypyrene (1-PYR: OR 2.15, 95% CI 1.06-4.33, Pfor trend < 0.001) were associated with an increased prevalence of severe AAC in the adults compared to those who in the lowest quartile. CONCLUSION: This study found that urinary 1-NAP, 2-NAP and 1-PYR were positively associated with severe AAC prevalence in adults.
Subject(s)
Polycyclic Aromatic Hydrocarbons , Humans , Adult , Polycyclic Aromatic Hydrocarbons/adverse effects , Polycyclic Aromatic Hydrocarbons/metabolism , Nutrition Surveys , Naphthalenesulfonates , BiomarkersABSTRACT
Bipolar disorder (BD) is a common chronic mental disorder usually characterized by manic, hypomanic and depressive episodes. Patients diagnosed with BD have cognitive impairments in both the mood attack and remission stages, that is impairment of attention, memory and executive function. Up till the present moment, the causative mechanisms of cognitive impairment in BD patients remain poorly understood. Several studies have demonstrated that cognitive impairment in patients with bipolar disorder is not associated with a single factor, but with gene polymorphism, brain structural and functional variables, inflammatory and metabolic factors. Herein, we reviewed and summarized the recent reports on cognitive impairment mechanisms in patients with BD. To prevent or alleviate cognitive damage at an early stage, we propose that future research should focus on investigating the pathological mechanism of specific cognitive dimension damage as well as the pathological mechanism network between the damage of each dimension. It is crucial to recognize mechanisms of cognitive impairment for improving the symptoms and prognosis of BD patients, restoring their social function and integration.
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Objective: Heart failure with mildly reduced ejection fraction (HFmrEF) has been recently recognized as a unique phenotype of heart failure (HF) in current practical guideline. However, risk stratification models for mortality and HF re-hospitalization are still lacking. This study aimed to develop and validate a novel machine learning (ML)-derived model to predict the risk of mortality and re-hospitalization for HFmrEF patients. Methods: We assessed the risks of mortality and HF re-hospitalization in HFmrEF (45-49%) patients enrolled in the TOPCAT trial. Eight ML-based models were constructed, including 72 candidate variables. The Harrell concordance index (C-index) and DeLong test were used to assess discrimination and the improvement in discrimination between models, respectively. Calibration of the HF risk prediction model was plotted to obtain bias-corrected estimates of predicted versus observed values. Results: Least absolute shrinkage and selection operator (LASSO) Cox regression was the best-performing model for 1- and 6-year mortality, with a highest C-indices at 0.83 (95% CI: 0.68-0.94) over a maximum of 6 years of follow-up and 0.77 (95% CI: 0.64-0.89) for the 1-year follow-up. The random forest (RF) showed the best discrimination for HF re-hospitalization, scoring 0.80 (95% CI: 0.66-0.94) and 0.85 (95% CI: 0.71-0.99) at the 6- and 1-year follow-ups, respectively. For risk assessment analysis, Kansas City Cardiomyopathy Questionnaire (KCCQ) subscale scores were the most important predictor of readmission outcome in the HFmrEF patients. Conclusion: ML-based models outperformed traditional models at predicting mortality and re-hospitalization in patients with HFmrEF. The results of the risk assessment showed that KCCQ score should be paid increasing attention to in the management of HFmrEF patients.
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Abdominal aortic aneurysm (AAA) refers to local abnormal expansion of the abdominal aorta and mostly occurs in elderly men. MicroRNA (miRNA) is single-stranded RNA consisting of 18-25 nucleotides. It plays a key role in posttranscriptional gene expression and in the regulation of human functions and disease development. miRNA exerts its function mainly through the binding of complementary base pairs to the 3' regulatory region of mRNA transcripts. Therefore, miRNA-related single-nucleotide polymorphisms (miRSNPs) can affect miRNA expression and processing kinetics. miRSNPs can be classified based on their location: miRSNPs within miRNA-producing genes and miRSNPs within miRNA target genes. Increasing evidence indicates that miRSNPs play an important role in the pathogenic kinetics of cardiovascular diseases. The aim of this study was to identify potential miRNAs and integrate them into a miRSNP-based disease-related pathway network, the results of which are of great significance to the interpretation of the potential mechanisms and functions of miRSNPs in the pathogenesis of diseases.
Subject(s)
Aortic Aneurysm, Abdominal , MicroRNAs , Aged , Humans , Male , Aortic Aneurysm, Abdominal/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , Polymorphism, Single Nucleotide/genetics , RNA, Messenger/geneticsABSTRACT
Objective: This study aimed to assess the association between triglyceride-glucose (TyG) index/homeostasis model assessment-insulin resistance (HOMA-IR) within young adults and congestive heart failure (CHF), and to explore whether TyG index can replace HOMA-IR as a surrogate marker for IR in predicting the risk of CHF. Methods: A total of 4,992 participants between the ages of 18 and 30 years were enrolled from the Coronary Artery Risk Development in Young Adults (CARDIA) investigation [from 1985 to 1986 (year 0)]. A Cox proportional hazard regression analysis was conducted for assessing correlations between baseline TyG index/HOMA-IR and CHF events, together with the receiver operating characteristic (ROC) curve employed for scrutinizing TyG index/HOMA-IR and the risk of CHF. Results: During the 31-year follow-up period, 64 (1.3%) of the 4,992 participants developed CHF. In multivariable Cox proportional hazards models, adjusted for confounding factors for CHF, an increased risk of CHF was associated with a per-unit increase in the TyG index [hazard ratio (HR) 2.8; 95% confidence interval (CI), 1.7-4.7] and HOMA-IR (HR 1.2; 95% CI, 1.1-1.3). A Kaplan-Meier curve analysis showed that participants in the TyG index and HOMA-IR index Q4 group had a higher risk of CHF than those in the Q1 group. The area under curve (AUC) for the TyG index and HOMA-IR consisted of 0.67 (95% CI, 0.6-0.742) and 0.675 (95% CI, 0.604-0.746), respectively. There were no significant differences between the TyG index and HOMA-IR for AUC (p = 0.986). Conclusion: The higher TyG index and HOMA-IR are independent risk factors for CHF. The TyG index can replace HOMA-IR in young adulthood as a surrogate marker for IR to predict the risk of CHF.
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Objective: To explore the association between dietary fiber and heart failure (HF). Methods: Data were collected from the 2009-2018 National Health and Nutrition Examination Survey. Dietary fiber intake data were obtained from two 24-h dietary recall interviews. Logistic regression and restricted cubic spline models were used to explore the association of dietary intakes of total, cereal, fruit, and vegetable fiber with HF prevalence. Results: A total of 21869 adults were included in this study. After adjusting for multiple confounding factors, the odds ratios (OR) and 95% confidence intervals (CI) for HF was 0.49 (0.28 to 0.87, P for trend = 0.016) for the highest tertile versus lowest tertile of total fiber intake. Similar results were observed for cereal but not fruit and vegetable fiber intake. Dose-response analysis indicated that dietary intake of total and cereal fiber were inversely associated with HF in a linear manner. Conclusion: Intakes of total and cereal fiber were inversely associated with HF in adults.
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Wilms tumor (WT) is a common pediatric renal cancer, with a poor prognosis and high-risk recurrence in some patients. The inflammatory microenvironment is gradually gaining attention in WT. In this study, novel inflammation-related signatures and prognostic model were explored and integrated using bioinformatics analysis. The mRNA profile of pediatric patients with WT and inflammation-related genes (IRGs) were acquired from Therapeutically Available Research to Generate Effective Treatments (TARGET) and Gene Set Enrichment Analysis (GSEA) databases, respectively. Then, a novel prognostic model founded on 7-IRGs signature (BICC1, CSPP1, KRT8, MYCN, NELFA, NXN, and RNF113A) was established by the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression to stratify pediatric patients with WT into high- and low-risk groups successfully. And a stable performance of the prognostic risk model was verified in predicting overall survival (OS) by receiver-operating characteristic (ROC) curves, Kaplan-Meier (KM) curves, and independent prognostic analysis (p < 0.05). In addition, a novel nomogram integrating risk scores with good robustness was developed and validated by C-index, ROC, and calibration plots. The potential function and pathway were explored via Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and GSEA, with mainly inflammation and immune-related biological processes. The higher-risk scores, the lower immune infiltration, as shown in the single-sample GSEA (ssGSEA) and tumor microenvironment (TME) analysis. The drug sensitivity analysis showed that regulating 7-IRGs signature has a significant correlation with the chemotherapy drugs of WT patients. In summary, this study defined a prognostic risk model and nomogram based on 7-IRGs signature, which may provide novel insights into clinical prognosis and inflammatory study in WT patients. Besides, enhancing immune infiltration based on inflammatory response and regulating 7-IRGs signature are beneficial to ameliorating the efficacy in WT patients.
Subject(s)
Gene Expression Profiling , Wilms Tumor , Biomarkers, Tumor/genetics , Child , Female , Gene Expression Regulation, Neoplastic , Humans , Inflammation/genetics , Kaplan-Meier Estimate , Male , Tumor Microenvironment/genetics , Wilms Tumor/geneticsABSTRACT
CONTEXT: Diabetes has a bidirectional association with nonalcoholic fatty liver disease (NAFLD) and increases the risk of cirrhosis and related complications. OBJECTIVE: To investigate the association between visit-to-visit fasting glucose (FG) variability in early adulthood and NAFLD in middle age. METHODS: This prospective cohort study included 2467 Black and White adults aged 18 to 30 years at baseline (1985-1986) who were followed over 25 years in the Coronary Artery Risk Development in Young Adults Study. FG variability measures included coefficient of variation about the mean FG (CV-FG), the SD of FG (SD-FG), and the average real variability of FG (ARV-FG) across 25 years (year 0, 7, 10, 15, 20, and 25 examinations). NAFLD was defined as liver attenuationâ ≤â 40 Hounsfield units on computed tomography scan at year 25 examination after excluding other causes of hepatic steatosis. RESULTS: Of the 2467 participants, 241 (9.8%) had NAFLD at year 25. In multivariate analysis, the odds ratio for NAFLD was 2.80 (95% CI, 1.69-4.64; P trendâ <â 0.001) for the fourth quartile vs first quartile of CV-FG after adjusting for confounding variables, including mean FG. Similar results were observed for SD-FG and ARV-FG. CONCLUSION: Greater visit-to-visit FG variability in early adulthood was associated with higher risk of NAFLD in middle age independent of mean FG level. FG variability may help identify individuals at high risk for NAFLD.
Subject(s)
Fasting , Non-alcoholic Fatty Liver Disease , Adult , Blood Glucose/analysis , Glucose , Humans , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Prospective Studies , Risk Factors , Young AdultABSTRACT
AIMS: This study sought to investigate the association between blood pressure (BP) trajectories from early to middle adulthood and echocardiographic indices of structure and function in middle age. METHODS AND RESULTS: This prospective cohort study included 4717 black and white adults aged 18-30 years at baseline (1985-86) who were followed over 30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Trajectories of systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) from the Year 0 examination to Year 30 examination were identified using latent mixture modelling. Echocardiographic indices of myocardial structure, systolic function, and diastolic function were assessed at the Year 30 examination. Five distinct SBP trajectory groups were identified: low-stable [1110 participants (23.5%)], moderate-stable [2188 (46.4%)], high-stable [850 (18.0%)], moderate-increasing [416 (8.8%)], and high-increasing [153 (3.2%)]. After adjustment for clinical variables, a significant decreasing trend was observed from the high-increasing and moderate-increasing groups through to the low-stable group for left ventricular (LV) mass index [mean (SE): high-increasing, 112.3 (3.4); moderate-increasing, 99.3 (2.6); high-stable, 88.9 (2.5); moderate-stable, 86.1 (2.3); low-stable, 82.1 (2.4), P trend < 0.01], as well as LV end-diastolic dimension, left atrial volume index, and E/e', while an increasing trend was apparent for LV longitudinal strain, E/A ratio, and average e' velocities. Results were generally consistent for trajectories of DBP and PP. CONCLUSIONS: Higher BP trajectories from early to middle adulthood were associated with worse indices of myocardial modelling and LV systolic and diastolic function at middle age.
Subject(s)
Echocardiography , Hypertension , Adolescent , Adult , Blood Pressure/physiology , Humans , Hypertension/complications , Middle Aged , Prospective Studies , Systole , Young AdultABSTRACT
BACKGROUND: Elevated blood pressure (BP) is a risk factor for cognitive impairment. OBJECTIVE: We aim to explore the association between the duration of hypertension in early adulthood, with cognitive function in midlife. Furthermore, we investigate whether this asssociation is altered among participants with controlled BP. METHODS: This prospective study included 2,718 adults aged 18-30 years without hypertension at baseline who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Duration of hypertension was calculated based on repeat measurements of BP performed at 2, 5, 7, 10, 15, 20, and 25 years after baseline. Cognitive function was assessed at Year-25 using the Rey Auditory Verbal Learning Test (RAVLT), Digit Symbol Substitution Test (DSST), and Stroop test. RESULTS: After multivariable adjustment, a longer hypertension duration was associated with worse verbal memory (RAVLT, p trendâ=â0.002) but not with processing speed (DSST, p trendâ=â0.112) and executive function (Stroop test, p trendâ=â0.975). Among subgroups of participants with controlled (BPâ<â140/90âmmHg) and uncontrolled (SBP≥140âmmHg or DBP≥90âmmHg) BP at the time of cognitive assessment (i.e., Year-25 BP), longer duration of hypertension was associated with worse verbal memory. Similar results were observed in subgroups with controlled and uncontrolled average BP prior to cognitive assessment. CONCLUSION: Longer duration of hypertension during early adulthood is associated with worse verbal memory in midlife regardless of current or long-term BP control status. The potential risk of hypertension associated cognitive decline should not be overlooked in individuals with a long duration of hypertension, even if BP levels are controlled.
Subject(s)
Aging/physiology , Blood Pressure/physiology , Cognition/physiology , Cognitive Dysfunction/epidemiology , Hypertension/epidemiology , Adult , Executive Function , Female , Humans , Longitudinal Studies , Male , Memory/physiology , Middle Aged , Prospective Studies , Risk Factors , Stroop Test , Young AdultABSTRACT
Background: Despite that nutritional deficiency existed in congestive heart failure (CHF), there is a large amount of CHF patients suffering from obesity. This study aimed to identify the differences for increased BMI or obesity in CHF patients. Methods: This cross-sectional study included adults from the National Health and Nutrition Examination Survey 2007-2016. Differences were compared between CHF participants vs. non-CHF participants, and BMI ≥ 30 kg/m2 vs. BMI < 30 kg/m2 CHF participants. Results: CHF participants were with higher BMI, lower energy and macronutrient intake, lower physical activity level and longer rest time, and lower hematocrit and hemoglobin level (all P < 0.05) than non-CHF participants. The prevalence of BMI ≥ 30 kg/m2 in participants with CHF was 53.48%. There was no significant difference observed in energy and macronutrient intake between CHF participants with BMI ≥ 30 kg/m2 or <30 kg/m2. The water intake (P = 0.032), sedentary time (P = 0.002), and hematocrit (P = 0.028) were significantly different between CHF with BMI ≥ 30 kg/m2 and with <30 kg/m2. Conclusion: Compared with non-CHF participants, CHF participants exhibited higher BMI with lower energy and macronutrient intake, lower physical activity level, longer rest time, and hemodilution with lower hematocrit and hemoglobin level. Among CHF participants with BMI ≥ 30 kg/m2, higher sedentary time and hematocrit were observed.
ABSTRACT
Heart failure (HF) is not uncommon among patients with hematologic malignancies (HM) undergoing hematopoietic stem cell transplantation (HSCT) and is associated with an increased mortality. Among HSCT patients without signs or symptoms of HF, groups with elevated and normal N-terminal probrain natriuretic peptide (NT-proBNP) levels have been poorly characterized in previous literature. Herein, we reviewed consecutive admissions for HM undergoing HSCT (n = 301). Based on NT-proBNP levels and clinical signs or symptoms of HF at follow-up (one month after HSCT), patients were grouped into ENPH (elevated NT-proBNP > 125 pg/mL, presence of HF symptoms or signs), ENAH (elevated NT-proBNP > 125 pg/mL, absence of HF symptoms or signs), and NN (normal NT-proBNP < 125 pg/mL). ENPH, ENAH, and NN were observed in 22.9%, 54.5%, and 22.6% of patients, respectively. ENPH patients had a significantly higher baseline NT-proBNP level, followed by the ENAH and NN groups, respectively (P < 0.001). Frequencies of HLA partially matched related donors, stem cell source (bone marrow+peripheral blood), and utilization of graft-versus-host disease prophylaxis regimens (ciclosporin+methotrexate+antithymocyte globulin±mycophenolate mofetil) were also the highest in the ENPH group, followed by ENAH and NN groups, respectively (all P < 0.05). Uric acid and hemoglobin levels, transplant type, and cyclophosphamide-based conditioning regimens utilized were similar between the ENAH and ENPH groups. We found that ENPH and ENAH are commonly observed in HM hospitalized for HSCT. Serum NT-proBNP levels may allow for earlier identification of HSCT patients at high risk of developing cardiac dysfunction.