Association between visceral adipose tissue and asthma based on the NHANES and Mendelian randomization study.

BACKGROUND: Obesity is a crucial risk factor for asthma. Observational studies have examined the association between abdominal obesity and asthma symptoms. This study aimed to investigate the causal relationship between visceral adipose tissue (VAT) and asthma and its potential as an independent indicator. METHODS: This study utilized data from the National Health and Nutrition Examination Survey spanning 2011-8. Multivariable logistic regression and stratified variable selection were employed to identify associations between asthma and VAT. Moreover, a two-sample Mendelian randomization analysis, using 221 genetic variants as instrumental variables, was conducted to assess this relationship further. RESULTS: Our findings indicated that individuals with higher VAT levels were more likely to develop asthma. Visceral obesity remained a significant risk factor for asthma after adjusting for demographic characteristics. Genetic predictions suggest a positive association between VAT and an elevated risk of asthma (odds ratio [OR] = 1.393, 95% confidence interval [CI]: 1.266-1.534, and P = 1.43E-11). No significant polymorphisms were detected using the Mendelian randomization-Egger intercept test. CONCLUSIONS: This study presents potential evidence supporting the causal role of VAT in asthma development. Furthermore, the findings from the Mendelian randomization analysis further reinforce the relationship between VAT and asthma risk.

Integrated Multi-omics Analyses Identify CDCA5 as a Novel Biomarker Associated with Alternative Splicing, Tumor Microenvironment, and Cell Proliferation in Colon Cancer Via Pan-cancer Analysis.

Background: CDCA5 has been reported as a gene involved in the cell cycle, however current research provides little details. Our goal was to figure out its functions and probable mechanisms in pan-cancer. Methods: Pan-cancer bulk sequencing data and web-based analysis tools were applied to analyze CDCA5's correlations with the gene expression, clinical prognosis, genetic alterations, promoter methylation, alternative splicing, immune checkpoints, tumor microenvironment and enrichment. Real­time PCR, cell clone formation assay, CCK-8 assay, cell proliferation assay, migration assay, invasion assay and apoptosis assay were used to evaluate the effect of CDCA5 silencing on colon cancer cell lines. Results: CDCA5 is highly expressed in most tumors, which has been linked to a poor prognosis. Immune checkpoints analysis revealed that CDCA5 was associated with the immune gene CD276 in various tumors. Single-cell analysis showed that CDCA5 correlated with proliferating T cell infiltration in COAD. Enrichment analysis demonstrated that CDCA5 may modify cell cycle genes to influence p53 signaling. The examination of DLD1 cells revealed that CDCA5 increased the proliferation and blocked cell apoptosis. Conclusion: This study contributes to the knowledge of the role of CDCA5 in carcinogenesis, highlighting the prognostic potential and carcinogenic involvement of CDCA5 in pan-cancer.

The causal relationship between osteoarthritis and bladder cancer: A Mendelian randomization study.

OBJECTIVE: The causal association between osteoarthritis (OA) and bladder cancer remains unclear. This Mendelian randomization (MR) study was carried out to assess the potential causal effects of any OA, knee OA and hip OA, and bladder cancer. METHOD: Genome-wide association study (GWAS) summary data for OA and bladder cancer were obtained in GWAS CATALOG, UK Biobank, and FinnGen Consortium. Inverse-variance weighted (IVW) approach was primarily conducted to evaluate the causal relationships between OA and bladder cancer, and MR-Egger intercept and Cochran's Q test were mainly used to estimate heterogeneity and pleiotropy. MR-PRESSO was used to test the presence of horizontal outliers. Leave-one-out analysis was utilized to ensure the reliability of the results. RESULTS: A higher genetic predisposition to any OA has a causal association with bladder cancer risk, while neither knee OA nor hip OA is causally linked to bladder cancer. MR-Egger intercept analysis exhibited that any OA and knee OA had no pleiotropic effect on the risk of bladder cancer, and Cochran's Q test showed that any OA, knee OA and hip OA had no heterogeneity on bladder cancer risk. Neither MR PRESSO analysis nor leave-one-out analysis revealed any outlier SNPs. CONCLUSIONS: This MR study exhibited a positive cause-and-effect relationship between any type of OA and bladder cancer risk, but not between site-specific OA, knee OA and hip OA, and bladder cancer. Attention should be paid to the screening and prevention of bladder cancer in OA patients at any site.

Circulating lymphocyte subpopulations in patients with systemic lupus erythematosus and their correlation with disease activity.

The aim of the present study was to evaluate the overall alterations of peripheral blood lymphocyte subsets in patients with systemic lupus erythematosus (SLE). A total of 120 patients diagnosed with SLE and 64 health donors were enrolled. The lymphocyte subsets were detected using flow cytometry. Then the changes of lymphocyte subsets in patients and their correlation with disease activity were investigated. Compared with healthy controls, the counts of lymphocytes, T cells, B cells and NK cells in SLE patients were significantly decreased. Further analysis of T cells subpopulations revealed that the decrease in T cells counts in SLE patients was mainly attributed to a sharp decrease in CD4 + T cells counts. Meanwhile, there was a positive correlation between CD4 + T cells counts and serum complement 3 levels, and patients with lower CD4 + T cells counts had higher SLEDAI score. The counts of CD8 + T cells were comparable between SLE patients and controls, while the proportion of CD8 + T cells and cytotoxic T cells (CD8 + CD28 +) was prominently higher in SLE patients. Besides, the expression of HLA-DR on the surface of T and NK cells was significantly upregulated in SLE patients. Circulating lymphocyte subsets of SLE patients were seriously dysregulated, characterized by a decrease in CD4 + T cells and NK cells, as well as an increase in the proportion of activated T and NK cells. Reduction in CD4 + T cells in SLE patients was highly consistent with disease activity, indicating the crucial role of CD4 + T cells in the onset and progression of SLE.

Clinical significance of circulating neutrophils and lymphocyte subsets in newly diagnosed patients with diffuse large B-cell lymphoma.

Lymphocytes play crucial roles in tumor surveillance in diffuse large B-cell lymphoma (DLBCL). Neutrophil-to-lymphocyte ratio (NLR), a biomarker for systematic inflammation, has been confirmed to be a prognostic factor for many malignant diseases. Herein, we conducted a systemic in-depth study of circulating neutrophils and lymphocyte subsets in DLBCL patients and their dynamics along with chemoimmunotherapy. A total of 61 patients with DLBCL were enrolled. Detection of lymphocyte subsets by flow cytometry was conducted at diagnosis and after 2/4/6/8 cycles' treatment of R-CHOP. Clinical significance, including incidence of infection, curative effect and disease-free survival (DFS), was analyzed based on the patients' clinical data and the quantity of lymphocyte subsets. The absolute numbers of neutrophils in stage III-IV DLBCL patients were obviously increased (p = 0.012), while the absolute numbers of lymphocytes were decreased (p = 0.025). Consequently, DLBCL patients had significantly higher NLR than healthy controls (p < 0.001). Further analysis of lymphocyte subsets showed a significantly reduced CD4 + T cells in DLBCL patients (p = 0.001). Patients with a lower lymphocyte counts (< 1.26*10E9/L) were more susceptible to infection (p < 0.001). NK cells were much higher in patients achieving complete remission than those of non-complete remission (p = 0.032). Higher neutrophils and NLR were closely associated with poorer DFS (p = 0.001 and p = 0.045, respectively). Circulating cells in DLBCL patients were dysregulated, featured with increased neutrophils and reduced lymphocytes. Higher NK cells before treatment predicted better therapeutic outcome. Higher neutrophils and NLR can be regarded as inferior prognostic predictors for DLBCL patients at diagnosis.

Peripheral blood lymphocyte subsets of newly diagnosed DLBCL patients and their dynamic changes with rituximab based immunochemotherapy.

The purpose of this study was to explore lymphocyte subsets of newly diagnosed DLBCL patients, and dynamics along with treatment of R-CHOP. A total of 40 DLBCL patients were enrolled. ALC of grade III-IV DLBCL patients was significantly lower than that of health controls (1.33*10E9/L vs 1.89*10E9/L, p = 0.003), mostly attributing to decreased CD4+ cells (p = 0.012). And serum LDH level of patients was negatively correlated with ALC (p = 0.033). ALC progressively decreased along with treatment, so as to CD3+, CD4+ and CD19+ cells, while proportion of CD4+ and CD8+ cells increased significantly after two cycles' treatment (p < 0.05). CR of ALC low (<1.18*10E9/L) group was lower than that of ALC high group (37.5% vs 73.3%), though not statistically significant (p = 0.179).