Int J Med Sci
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Aminoglycosides and cisplatin drugs are extensively utilized for their high efficacy in treating various conditions in the clinic, however, their ototoxic side effects warrant significant attention. These drugs could penetrate the inner ear via specific channels or transporters, which not only affect the survival of hair cells but also induce the overproduction of reactive oxygen species. Currently, scientific research mainly addresses this issue through the downstream intervention of reactive oxygen species. ⋯ It is, therefore, imperative to investigate the regulatory role of the MET channel in the up-taking of ototoxic drugs, serving as a pivotal point for the development of preventative and therapeutic approaches. This review aims to highlight the mechanism of inhibition of ototoxic substances absorption by auditory hair cells, explore how to develop novel ear protection methods by targeting these channels and transporters, and provide a new perspective and strategy for addressing drug-induced ototoxicity. The approach to protecting hair cells by targeting these channels and transporters not only broadens our understanding of the underlying mechanisms of ototoxicity, but could also spur further research and progress in the field of auditory protection.
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Persistent methamphetamine use causes many toxic effects in various organs, including the brain, heart, liver, kidney and eyes. The extent of its toxicity depends on numerous pharmacological factors, including route of administration, dose, genetic polymorphism related to drug metabolism and polysubstance abuse. ⋯ This review revisits the pharmacological profiles of methamphetamine and its effects on the brain, heart, liver, eyes, kidneys and endothelium. Understanding the mechanisms of methamphetamine toxicity is essential in developing treatment strategies to reverse or attenuate the progress of methamphetamine-associated organ damage.
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Background: Gastric cancer (GC) remains a significant global health challenge. This study aimed to comprehensively analyze GC epidemiology and risk factors to inform prevention and intervention strategies. Methods: We analyzed the Global Burden of Disease Study 2021 data, conducted 16 different machine learning (ML) models of NHANES data, performed Mendelian randomization (MR) studies on disease phenotypes, dietary preferences, microbiome, blood-based markers, and integrated differential gene expression and expression quantitative trait loci (eQTL) data from multiple cohorts to identify factors associated with GC risk. ⋯ Integrated genomic analysis identified 10 genes significantly associated with GC risk, with strong evidence for colocalization in genes such as CCR6 and PILRB. Conclusions: This systematic analysis reveals complex global trends in GC burden and identifies novel clinical, disease phenotypes, dietary preferences, microbial, blood-based, and genetic risk factors. These findings provide potential targets for improved risk stratification, prevention, and intervention strategies to reduce the global burden of GC.
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Introduction: Diabetes mellitus (DM) is associated with worse surgical outcomes, and is a risk factor for bladder cancer and subsequent oncological outcomes. This study evaluated outcomes robot-assisted radical cystectomy (RARC) compared to open radical cystectomy (ORC) in patients with DM. Materials and Methods: Data of adults ≥ 18 years old with DM who underwent radical cystectomy were extracted from the United States National Inpatient Sample database 2005-2018. ⋯ Of patients < 70 years old, RARC was significantly associated with decreased odds for urinary complications (aOR = 0.59, 95% CI: 0.41, 0.84) and wound and device-related complications (aOR = 0.55, 95% CI: 0.32, 0.94) compared to ORC. In patients with a Charlson Comorbidity Index score of 0-1, RARC was associated with a lower risk of urinary complications (aOR = 0.74, 95% CI: 0.56, 0.98) and wound and device-related complications (aOR = 0.63, 95% CI: 0.43, 0.93) compared to ORC. Conclusions: In patients with DM and bladder cancer, RARC appears to be associated with better short-term outcomes in terms of reduced risks of prolonged LOS, unfavorable discharge, urinary complications, and wound and device-related complications compared to ORC.
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Purpose: The aim of this study is to utilize two-sample Mendelian randomization (MR) to investigate the potential causal relationship among psoriasis, iridocyclitis, and non-alcoholic fatty liver disease (NAFLD), and to explore any potential mediation effects. Methods: Pooled data were derived from the public genome-wide association study (GWAS) in NAFLD (finn-b-NAFLD), iridocyclitis (finn-b-H7_IRIDOCYCLITIS) and psoriasis (finn-b-L12_PSORI_VULG). Univariable MR (UVMR) analysis was implemented to explore the causal relationship among psoriasis, iridocyclitis, and NAFLD, and inverse variance weighting (IVW) was used as the primary analytical method. ⋯ The LOO analysis demonstrated that the instrumental variables were appropriately chosen, suggesting the reliability of the MR results. Ultimately, MVMR and mediation analysis revealed iridocyclitis affected the development of NAFLD, 20.81% of which was caused by the pathway of iridocyclitis induced psoriasis leading to NAFLD. Conclusion: This study highlighted that iridocyclitis was significantly associated with an increased risk of NAFLD and that psoriasis was involved in the mechanism by which iridocyclitis triggered NAFLD, which might offer potential preventive strategies for NAFLD.