Annals of translational medicine最新文献

Obesity is a global health concern, affecting nearly half of the world's population and significantly increasing cardiovascular disease (CVD) risk. Among various cardiac impacts, left atrial (LA) dysfunction is a notable complication, especially given its association with atrial fibrillation (AF), heart failure with preserved ejection fraction (HFpEF), and diastolic dysfunction. This comprehensive review synthesizes findings from studies across age groups, from children to adults, evaluating obesity-induced alterations in LA structure and function. Using advanced diagnostic tools like speckle tracking echocardiography, we examine the impact of obesity on LA function, the potential reversibility of LA dysfunction, and implications for CVD progression. Studies show that elevated body mass index (BMI) correlates with LA enlargement, increased stiffness, and impaired reservoir and conduit strain, with specific changes observed across different cardiovascular conditions. In children, obesity-related insulin resistance is associated with increased LA stiffness, marking early indicators of metabolic and cardiac dysfunction. In adults, higher BMI independently reduces LA strain, compromising function and raising the likelihood of AF recurrence post-cardioversion or percutaneous interventions. Additionally, clinical manifestations such as exercise intolerance in obese HFpEF patients highlight LA stiffness as a predictor of poorer quality of life and reduced physical capacity. Importantly, weight loss interventions, including bariatric surgery, show promise in reversing LA dysfunction, suggesting a potential for reducing obesity-related cardiac risks. Our review underscores the value of incorporating LA strain metrics in routine cardiac assessments to identify subclinical changes early and guide preventive strategies in obese patients. Further research into therapeutic approaches targeting LA function is essential for reducing HFpEF incidence and improving cardiovascular outcomes in obesity.

Background: Bladder cancer (BLCA) is a prevalent and life-threatening condition that significantly impacts patients' quality of life while imposing substantial financial costs on healthcare systems. Advancing our knowledge of the mechanisms underlying tumor development is crucial for improving treatment outcomes. Emerging studies emphasize the critical role of the RNA modification 6-methyladenine (m⁶A) and its associated proteins, methyltransferase-like 3 (METTL3), Vir-like m⁶A methyltransferase associated (VIRMA) (writers), Alkb homolog 5 (ALKBH5) and fat mass and obesity associated protein (FTO) (erasers), in maintaining m⁶A homeostasis. Dysregulation of these enzymes leads to aberrant m⁶A methylation, a hallmark of various cancers, including BLCA. Furthermore, m⁶A modifications influence cisplatin sensitivity, a key drug in muscle-invasive bladder cancer (MIBC) treatment. With this background, we investigated the combined effects of ALKBH5 and FTO knock-down in bladder tumor cell lines.

Methods: We first investigated the expression of METTL3, VIRMA, ALKBH5 and FTO in BLCA tissues and human bladder tumor cell lines from urinary cancer cells by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Simultaneous knock-down of the expression of the erasers was then performed to explore their consequences in bladder cells. We then conducted cisplatin and mitomycin (MMC) treatment in knock-down cells to decipher the effect of their reduction. The cell viability was evaluated with cell counting kit-8 (CCK-8) assay after the two treatment regimes.

Results: Lower expression of ALKBH5 and FTO was identified in BLCA tissue and bladder tumor cell lines. Notably, this trend was consistent across both low-grade and high-grade tissue samples. Furthermore, lower expression levels of ALKBH5 and FTO were observed in tumor cell lines derived from both men and women compared to the non-tumorigenic SV-HUC1 cell line. In contrast, both tissue and cell line data revealed an increased expression tendency of the m⁶A writers METTL3 and VIRMA. Additionally, knock-down of the two m⁶A erasers was found to enhance tolerance to cisplatin and MMC treatment, resulting in increased resistance to cell death.

Conclusions: Our findings reveal that ALKBH5 and FTO are down-regulated in BLCA and their knock-down confers resistance to cisplatin and MMC in vitro. This suggests that m⁶A erasers play a critical role in modulating chemotherapy sensitivity, potentially serving as biomarkers or therapeutic targets for enhancing treatment efficacy in BLCA.

Background and objective: Climate change and global warming pose increasing threats to human health. These could have significant impact on healthcare systems, especially emergency services. In this narrative review, we aim to examine how climate change affects emergency attendances and operations, and to suggest strategies to reduce environmental impact through sustainability efforts.

Methods: We performed literature search of published studies on healthcare environmental sustainability and climate change in PubMed, Embase, Google Scholar and Scopus databases using the following search terms: ("climate change" OR "global warming" OR "heatwave" OR "heat wave" OR "greenhouse effect") AND ("emergency department" OR "emergency medicine" OR "emergency, hospital services"), ("sustainability in healthcare" OR "environmental footprint" OR "carbon footprint" OR "carbon emission" OR "greenhouse gas" OR "energy us*" OR "waste") AND ("health care system" OR "health system" OR "health care" OR "healthcare" OR "health sector"). Study team members conducted independent searches of articles and any discrepancy between two members was resolved by a third independent co-investigator.

Key content and findings: Climate change increases incidences of both communicable and non-communicable diseases through heat-related illnesses, respiratory and infectious diseases, and physical injuries from natural disasters, leading to higher demand on emergency services. Structural damage and physical injuries from natural disasters also negatively impact healthcare resources. Vulnerable populations like the very young and elderly are extremely susceptible. Ironically, the healthcare sector contributes significantly to greenhouse gas emissions and waste production. There are challenges faced by both patients and healthcare providers in adopting sustainability in healthcare. We proposed the SCRAP strategy (Stewardship of resources, Carbon footprint reduction, Research, Advocacy for change, and Policies and education) to attain sustainable healthcare: (I) stewardship of resources; (II) carbon footprint reduction; (III) research; (IV) advocacy for change; and (V) policies and education.

Conclusions: As the frontline of most healthcare systems, emergency departments bear the brunt of resultant increased attendances. Urgent actions by the emergency medicine fraternity are needed to understand and tackle the causes and consequences of climate change in tandem with environmental sustainability efforts to mitigate these issues.

[This corrects the article DOI: 10.21037/atm-21-3390.].

Background: Diseases of the human cornea often necessitate corneal transplantation. However, donor corneas are not always readily available, leaving many patients waiting for donated corneas. Porcine corneas are a promising alternative to human donor corneas due to their close anatomical and physiological similarities. In this study, we produced GGTA1/CMAH/β4GalNT2 knockout pigs [triple knockout (TKO)] to minimize immune rejection. We investigated the efficacy and safety of a novel corneal decellularization process using sodium cocoyl glutamate (SCG) and supernuclease (SN).

Methods: We harvested cornea stromal grafts from 2-month-old TKO pigs, decellularized them using SCG and SN. The optical transparency, DNA content, collagen content, glycosaminoglycan content, and tensile strength of the decellularized corneas were measured. The in vivo safety and efficacy of the decellularized corneas were evaluated by transplanting them into the stromal pockets of rabbit corneas. Comparisons between wild type (WT) and TKO corneas, both decellularized and non-decellularized, were performed over a 4-week period post-transplantation.

Results: Compared to a previous method using sodium N-lauroyl glutamate (SLG), the method using 0.5% SCG and SN more effectively removed DNA from the corneal stroma without significantly changing tensile strength, transparency, collagen, or glycosaminoglycan content. When decellularized corneas were implanted into corneal stromal pockets of rabbits, at 4 weeks post-surgery, decellularized corneas from WT pigs showed significant corneal neovascularization and opacity. In contrast, those from TKO pigs with 0.5% SCG plus SN decellularization maintained good transparency with minimal vascularization.

Conclusions: Corneas from TKO pigs could be successfully decellularized using 0.5% SCG plus SN method, showing promising results after transplanting them into rabbit corneas.

[This retracts the article DOI: 10.21037/atm-20-8027.].

Distant metastasis marks a critical transition in prostate cancer, separating potentially curable from canonically incurable disease. Oligometastatic disease, defined as limited metastases (e.g., less than 3, 5, or 10), can encompass different clinical scenarios, including oligorecurrent disease (characterized by a limited number of metastatic lesions that recur after initial definitive treatment), and has emerged as an intermediate or transitional state. While intensified systemic therapies are increasingly applied to metastatic cases, many patients prefer to delay starting castrating therapies. Metastasis-directed therapy (MDT) is a safe and effective alternative to systemic therapy in a subset of patients with well-defined oligometastatic disease. Recent advances in imaging technologies and emerging treatment paradigms pose clinical challenges for patient risk stratification and optimal treatment selection. Here, we explore two key developments in the field: the influence of advanced imaging on clinical decision-making and the growing role of radiotherapy (RT) in oligometastatic disease management. We explore the landscape of novel biomarkers to estimate micrometastatic disease burden, which eludes imaging, using the concept of "liquid tumor burden" (LTB) measured by blood-based markers like circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and tumor-derived extracellular vesicles (tdEVs). Promising data suggest that LTB assessment may refine patient selection for MDT and systemic treatment. These findings suggest potential for a combined approach of MDT and systemic therapy in oligometastatic prostate cancer (omPC).

[This corrects the article DOI: 10.21037/atm-21-2947.].