Medicine
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Gut microbiota has been recognized as an extrahepatic manifestation of gastro-esophageal reflux disease (GERD) in observational studies. However, the directionality and causality of the association and whether cytokines act as a mediator remain unclear. We aim to estimate the casual relationship between gut microbiota, inflammatory cytokines and GERD using a 2-sample Mendelian randomization method. ⋯ We identified causal effects between 6 bacterial traits, 5 inflammatory cytokines, and GERD. Notably, we furnished causal evidence linking TRAIL levels to a substantial proportion of the risk attributed to genus Family XIII UCG001 and genus Senegalimassilia, thereby mediating the risk of GERD. These findings offer novel avenues for therapeutic interventions targeting individuals with GERD.
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Previous investigations through observation have found that matrix metalloproteinase-3 (MMP-3) has benefits for ankylosing spondylitis (AS) but it is uncertain whether there is a true positive causal connection. Our goal was to demonstrate the relationship between AS and MMP-3. We executed Mendelian randomization (MR) research utilizing genome-wide association studies genetic data (n = 21,758) for MMP-3 publicly available from IEU Open and genome-wide association studies data for AS (n = 297,932) from FinnGen Biobank. ⋯ The IVW method demonstrated that MMP-3 had a causal effect on AS (odds ratio, 0.9047 [95% confidence interval, 0.8080-1.0129]; P = .0823). Certainly, other MR techniques were in accordance with the tendency of the IVW method (P < .05), and sensitivity testing verified the reliability of this MR result. This MR study substantiates the causal role of MMP-3 in the development of AS, offering valuable insights into the disease mechanism and potential therapeutic targets.
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The role of circulating immune cells in coronary atherosclerosis remains unclear. This study aimed to assess the causal effects of various immune cells on coronary atherosclerosis using Mendelian randomization (MR). Circulating immune cell datasets were obtained from genome-wide association studies, and coronary atherosclerosis datasets were obtained from FinnGen. ⋯ Cochran Q showed no heterogeneity (P ≥ .05), and the sensitivity analysis indicated that the results were robust. The MR analysis revealed various markers and immune cell subsets, including effector memory DN (CD4-CD8-) %DN, CD4 on CD39+ CD4+, C-X3-C motif chemokine receptor on CD14+ CD16- monocytes, C-C chemokine receptor 7 on naive CD4+, and IgD- CD38- %lymphocytes, associated with increased genetic susceptibility to coronary atherosclerosis. This provides a genetic explanation for the role of specific immune cells in inducing and exacerbating coronary artery disease and offers new ideas for the exploration of immune markers and immune-targeted drugs.
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Observational Study
Neoadjuvant chemoradiation therapy application in radical esophagectomy surgery: Safety and feasibility: A descriptive study in Vietnam.
Esophageal cancer (EC) ranks as the 7th most prevalent form of cancer and the 6th leading cause of cancer-related mortality globally. Neoadjuvant therapy, encompassing neoadjuvant chemotherapy or chemoradiotherapy, has shown promise in reducing the staging of EC and mitigating the risk of early systemic spread. This study seeks to assess the safety and viability of implementing neoadjuvant chemoradiotherapy (nCRT) in conjunction with radical esophagectomy surgery for Vietnamese patients diagnosed with locally advanced EC. ⋯ R0 resection was achieved in 29 (96.7%) patients, with 43.4% attaining pathological complete response and 56.7% demonstrating tumor complete response. The study's outcomes emphasize the safety and feasibility of employing esophagectomy subsequent to nCRT in Vietnamese patients, as evidenced by the absence of mortality, low complication rates, and favorable surgical results. It also suggests the potential advantages of utilizing a lower daily Gy dose for enhanced safety and considering squamous cell carcinoma as a specific criterion for nCRT.
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Acute myocardial infarction (AMI), a critical cardiovascular condition, is often associated with serious health risks. Recent studies suggest a link between copper-induced apoptosis and immune cell infiltration. Specifically, abnormal accumulation of copper ions can lead to intracellular oxidative stress and apoptosis, while also affecting immune cell function and infiltration. ⋯ A comprehensive examination of immune infiltration in AMI samples revealed significant differences in the levels of 11 types of immune cells, with GZMA displaying the highest correlation with activated mast cells and CD8 + T cells. We observed markedly lower expression levels of GZMA, GIMAP6, and TRAF3IP3 in the AMI group compared to controls. This study identified 5 cuproptosis-related biomarkers (GZMA, GIMAP7, GIMAP5, GIMAP6, and TRAF3IP3) associated with AMI, laying a theoretical foundation for the treatment of AMI.