Postgraduate medical journal
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Adverse drug reactions pose a significant threat to patient safety and public health and often become apparent only after widespread clinical use. Mendelian randomization (MR) analysis is a valuable tool that can be used to infer causality by using genetic variants as instrumental variables, which can predict the occurrence of adverse drug reactions before they occur. Compared with traditional observational studies, MR Analysis can reduce the potential bias of confounding factors. This article reviews the principles of MR Analysis and its application in the prediction of adverse drug reactions, the challenges and future directions, and summarizes how to harness the power of this innovative epidemiological method to put us at the forefront of improving drug safety assessment and personalized medicine.
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Epoxyeicosatrienoic acids (EETs) are closely associated with lipoprotein metabolism, and changes in lipid profiles potentially affect their levels and functions. Given the alterations in lipid metabolism after cholecystectomy, this study aimed to investigate the levels of four EET regioisomers (free and esterified) and lipid profiles in patients with cholelithiasis after laparoscopic cholecystectomy (LC) and explore correlations between these parameters. ⋯ In this study, we observed significant changes in lipid profile 6 months after LC. While HDL, low-density lipoprotein, and EET levels showed a decreasing trend post-surgery, this change was not statistically significant. This trend and their significant correlations may indicate a complex relationship between HDL and EET metabolism. In addition, the negative correlation between EET levels and BMI changes highlights the need for further research to elucidate the metabolic impact and weight regulation of EETs after LC.
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The formation of gallstones is a multifactorial process involving lifestyle habits, lipid metabolism disorders, and genetic factors. This study aims to explore the association between 19 types of dietary fatty acids and gallstone disease using large-scale population data, assess the correlation between dietary fatty acids and serum fatty acids, and investigate the causal relationship between plasma lipids and gallstone disease from a genetic perspective. ⋯ Our study identifies a significant association between ARA intake and reduced gallstone risk, underscoring its potential in gallstone prevention. The weak correlation between dietary and serum fatty acids suggests complex physiological regulation mechanisms. Mendelian randomization analysis establishes a protective causal link between specific plasma lipids containing ARA and gallstone disease, highlighting the genetic underpinnings of gallstone formation. This research provides a foundation for dietary interventions and underscores the importance of genetic factors in lipid metabolism for future gallstone research and clinical management. Key message What is already known on this topic? Gallstone formation is a multifactorial process, and PUFAs may have a preventive effect, but the specific relationships between dietary fatty acids, serum fatty acids, plasma lipids, and gallstone disease are not well-established. What this study adds? This study finds a significant association between eicosatetraenoic acid (20:4) intake and reduced gallstone risk, and establishes a protective causal link between plasma lipids containing arachidonic acid (20:4) and gallstone disease through Mendelian randomization analysis. How this study might affect research, practice, or policy? The results highlight the potential of dietary interventions targeting eicosatetraenoic acid (20:4) for gallstone prevention and underscore the importance of genetic factors in lipid metabolism for gallstone research and clinical management.
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Endoscopic submucosal dissection (ESD) is currently one of the most curative treatments for early esophageal cancer. We conducted a retrospective case analysis to identify the characteristics of early esophageal cancer that indicate esophageal stenosis prevention measures. Our aim was to provide a reference for clinical decision-making. ⋯ It is necessary to take measures to prevent esophageal stenosis after ESD for early esophageal cancer lesions with a circumferential ratio of 75%-99%.
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Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment; however, the emergence of ICI-associated myocarditis (ICI-MC) presents a severe and potentially fatal complication with poorly understood pathophysiological mechanisms. This study aimed to identify crucial immune-related genes in ICI-MC and uncover potential therapeutic targets using bioinformatics. ⋯ KG7, GZMH, and KLRB1 were identified as pivotal immune-related genes in ICI-MC. Biological enrichments included pathways involved in cell lysis, the CD8+ T-cell receptor pathway, natural killer cell-mediated cytotoxicity, RAGE signaling, and proinflammatory responses. The ceRNA network illuminated the role of critical molecules and underscored the importance of avoiding drugs such as acetohydroxamic acid in ICI treatment. Key message What is already known on this topic Myocarditis is recognized as a serious ICI-associated toxicity, seemingly infrequent yet often fulminant and lethal. The underlying mechanisms of ICI-associated myocarditis remain not fully understood. Although the significance of T cells and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is evident, the inciting antigens, the reasons for their recognition, and the mechanisms causing cardiac cell injury are not well characterized. An improved understanding of ICI-associated myocarditis will provide insights into the equilibrium between the immune and cardiovascular systems. What this study adds Our study further validates the significance of T cells and CTLA-4 in ICI-associated myocarditis. More importantly, we identified three genes-NKG7, GZMH, and KLRB1-essential for the development of ICI-MC and proposed ceRNA networks involving these three key genes. How this study might affect research, practice or policy The newly discovered key genes and their intricate molecular interactions offer a comprehensive perspective on the mechanisms underlying ICI-MC. Furthermore, our findings advise caution regarding the use of drugs like acetohydroxamic acid during ICI treatment. As our understanding of these regulatory networks deepens, our study provides valuable insights that could inform future therapeutic strategies for ICI-MC.