Third Affiliated Hospital of Southern Medical University

To describe and compare the reporting patterns and signal strengths of male sexual dysfunction associated with six commonly prescribed SSRIs in the FDA Adverse Event Reporting System. Adverse event data for six representative SSRIs, fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, and escitalopram, were retrieved from the FAERS database, spanning from the first quarter of 2004 to the first quarter of 2025. Disproportionality analysis was conducted using both the reporting odds ratio (ROR) and proportional reporting ratio (PRR) to identify potential signals of adverse drug events associated with these medications. We analyzed 6,631,746 adverse drug event reports associated with SSRIs and detected significant disproportionality signals indicative of male sexual dysfunction in patients with depression. Across all SSRIs, erectile dysfunction was the most commonly reported adverse event [fluoxetine (ROR: 4.97, 95%CI: 4.25-5.82), paroxetine (ROR: 3.99, 95%CI: 3.53-4.5), sertraline (ROR: 6.11, 95%CI: 5.53-6.75), fluvoxamine (ROR: 1.08, 95%CI: 0.35-3.36), citalopram (ROR: 7.7, 95%CI: 6.81-8.69), and escitalopram (ROR: 7.93, 95%CI: 6.99-8.99)], followed by sexual dysfunction [fluoxetine (ROR: 11.94, 95%CI: 10.01-14.23), paroxetine (ROR: 11.39, 95%CI: 10.05-12.91), sertraline (ROR: 13.34, 95%CI: 11.86-15.01), fluvoxamine (ROR: 9.64, 95%CI: 5.01-18.56), citalopram (ROR: 15.09, 95%CI: 12.98-17.54), and escitalopram (ROR: 16.42, 95%CI: 14.11-19.12)]. This FAERS analysis detected significant disproportionality signals for male sexual dysfunction across SSRIs. Signal variation reflects reporting differences, not comparative risk, due to database limitations. These findings highlight the need for clinical vigilance and further investigation.

Adipose tissue hypertrophy, the local infiltration of immune cells, the increased production of proinflammatory cytokines, the whitening of brown adipose tissue, local hypoxia and angiogenesis disorders occur in obese individuals, which in turn lead to adipose tissue inflammation and promote the occurrence and development of metabolic diseases such as type 2 diabetes (T2DM), atherosclerosis and metabolic dysfunction-associated steatotic liver disease (MASLD). In recent years, N6-methyladenine (m6A), the most representative epigenetic modification, has been shown to be significantly altered in individuals with obesity and to participate in the regulation of various metabolic diseases. In the present review, the links between m6A modification and obesity-related metabolic diseases, such as MASLD and T2DM, from the perspective of adipose tissue inflammation are examined. Additionally, the challenges and prospects associated with targeting m6A in adipose tissue inflammation and metabolic diseases are discussed to provide new ideas for the treatment of these conditions.

Non-melanoma skin cancer (NMSC) is the most common cancer type globally, with a significantly higher incidence than other types of skin cancer. However, detailed analyses of the global burden of disease and changing trends in NMSC remain scarce. We extracted data from the Global Burden of Disease (GBD) 2021 to assess the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) associated with NMSC at the global, regional, and country levels. Linear regression models were used to analyze temporal trends in the global burden of disease from 1990 to 2021. Additionally, frontier analyses were conducted to determine the minimum achievable incidence, prevalence, morbidity, mortality, and DALYs. In 2021, NMSC caused 56,913 deaths and resulted in a reduction of 1,212,872 DALYs globally. The age-standardized prevalence of NMSC increased from 18.42 (95% UI, 15.26-22.12) cases per 100,000 people in 1990 to 32.51 (95% UI, 28.22-37.54) cases per 100,000 people in 2021. The burden of disease increases with age. The prevalence is consistently higher in men than in women. Prevalence rates were highest in high SDI regions such as the United States, Northern Europe, and North America. Conversely, mortality rates were highest in low SDI regions, including Latin America and the Caribbean. Furthermore, countries with higher Human Development Index (HDI) scores exhibited lower age-standardized mortality rates and DALYs for NMSC. The global burden of NMSC is increasing. Effective prevention strategies and public health policies are urgently needed to reduce this burden and improve overall health outcomes.

Abstract BACKGROUND Abdominal aortic aneurysm (AAA) is a life-threatening condition with >80% mortality upon rupture and no effective pharmacotherapy available. Despite epidemiological evidence linking metformin use to reduced AAA progression, its mechanism remains elusive. Notably, peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, encoded by Ppargc1a ) is downregulated in human AAA, yet its functional role in metformin’s protection is unknown. METHODS We employed porcine pancreatic elastase (PPE)-induced murine AAA, VSMC-specific Ppargc1a knockout ( Ppargc1a VSMC-KO ), primary VSMC senescence models, and pharmacological inhibition (Compound C for AMPK; Ex-527 for SIRT1) to define the AMPK–SIRT1–PGC-1α axis. RESULTS Metformin significantly inhibited AAA expansion, suppressed VSMC senescence (p53/p21↓, SA-β-gal↓), and preserved contractile phenotype (SMTN↑, IL-6/TNF-α↓). Crucially, all benefits were abrogated in Ppargc1a VSMC-KO mice, which exhibited accelerated aneurysm growth, mitochondrial fragmentation, ATP depletion, and ROS accumulation. Mechanistically, metformin activated AMPK/SIRT1 to upregulate PGC-1α; AMPK or SIRT1 inhibition blocked this cascade and reversed protection. CONCLUSION Metformin restrains AAA by restoring VSMC mitochondrial homeostasis via the AMPK/SIRT1→PGC-1α axis, positioning PGC-1α as a non-redundant, cell-autonomous guardian against vascular degeneration. These findings provide a mechanistic foundation for repurposing metformin and developing PGC-1α-targeted therapies in AAA.