Excessive advanced glycation end products (AGEs) can lead to cardiovascular diseases such as myocardial fibrosis (MF). Although studies have found that AGEs induce cuproptosis, and cuproptosis promotes fibrosis, it has not been confirmed whether AGEs promote MF through cuproptosis. AGEs increased intracellular copper levels, promoted the expression of solute carrier family 31 member 1 (SLC31A1), and downregulated the expression of ferredoxin 1 (FDX1), lipoic acid synthetase (LIAS), lipoylated (Lip)-dihydrolipoamide S-succinyltransferase (DLST), and Lip-dihydrolipoamide S-acetyltransferase (DLAT) in cardiac fibroblasts (CFs). All of these key cuproptosis regulatory gene expression abnormalities indicate that cuproptosis is induced. AGEs also decreased adenosine triphosphate content and inhibited the activities of mitochondrial complexes I and III, but these regulatory effects were significantly weakened after SLC31A1 downregulation. Meanwhile, AGEs significantly promoted the expression of alpha smooth muscle actin, collagen I, collagen III, and transforming growth factor-β1, while SLC31A1 siRNA or copper chelator ammonium tetrathiomolybdate (TTM) blocked these promoting effects. Similarly, CuCl₂ also induced fibrosis gene expression, while SLC31A1 overexpression (SLC31A1-O) further enhanced these effects, but TTM reduced CF activation induced by CuCl₂ plus SLC31A1-O. In addition, AGEs significantly promoted cell migration and enhanced the expression and secretion of matrix metalloproteinase (MMP)-2 and MMP-9, while SLC31A1 siRNA or TTM weakened these effects. SLC31A1-O plus copper treatment also had similar effects to AGEs, and these effects could also be blocked by TTM. Therefore, AGEs enhance copper transport by promoting SLC31A1 expression, which leads to intracellular copper overload and then induces cuproptosis, and finally promotes CF activation and migration.

Test the hypothesis that conservative fluid management with active deresuscitation would not adversely affect tissue perfusion or kidney injury and would be associated with reduced vascular injury compared with usual care.

Secondary analysis of the Role of Active Deresuscitation After Resuscitation-2 (RADAR-2) trial.

ICUs.

Critically ill patients enrolled in the RADAR-2 trial.

Conservative fluid management with active deresuscitation vs. usual care.

Measures of tissue hypoperfusion (whole blood lactate), acute kidney injury (AKIRisk score and urinary cystatin-C), and vascular injury (plasma hyaluronan, syndecan-1, and angiopoietin-2) were compared between groups. For each analyte, change from baseline was compared between groups and the median inter-group difference at each timepoint was estimated with bootstrapped CIs. Exploratory logistic regression examined associations between plasma biomarker levels (including N-terminal pro-B-type natriuretic peptide [NT-proBNP]), 28-day mortality, and treatment allocation. Whole blood lactate levels were similar between groups at all timepoints. Using change from baseline comparisons, no statistically detectable between-group differences were observed in AKIRisk scores or urinary cystatin-C levels. Plasma vascular injury biomarkers showed no statistically detectable between-group differences at any timepoint. High baseline hyaluronan (adjusted odds ratio [aOR], 5.75; 95% CI, 1.94-17.02; p = 0.002), syndecan-1 (aOR, 8.82; 95% CI, 2.67-29.15; p < 0.001), and NT-proBNP greater than 2500 pg/mL (aOR, 21.48; 95% CI, 3.57-129.41; p < 0.001) were independently associated with increased 28-day mortality. There was no evidence of differential treatment response based on these biomarker levels.

Conservative fluid management and active deresuscitation were not associated with worsening tissue perfusion or acute kidney injury. A reduction in vascular injury markers was not observed. Given the modest sample size and resultant imprecision, clinically important effects cannot be excluded.

The global nursing shortage underscores the critical need to retain experienced clinicians. The postpartum return to clinical practice represents a vulnerable transition period that can significantly impact nurse retention, yet the nuanced lived experiences of nurses during this reintegration are not well synthesized.

To systematically review and synthesize qualitative evidence on the clinical work experiences of nurses returning to work after childbirth.

A systematic review and meta-synthesis.

A systematic search was conducted in PubMed, Cochrane Library, CINAHL, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Database, Weipu Database and China Biomedical Literature Database (CBM) to identify qualitative studies published between December 1990 and December 2025 that focused on the clinical work experiences of nurses returning to work postpartum. This systematic review follows the meta-synthesis method guided by ENTREQ and PRISMA and uses the Critical Appraisal Skills Programme (CASP) to assess the quality of included studies. Qualitative findings from the primary studies were integrated and analyzed using thematic synthesis.

A total of 19 studies were included, with 76 main findings extracted, summarized into 9 subthemes, and organized into 3 main themes: The Multi-Faceted Challenges of Reintegrating into Professional Practice, Enduring Multidimensional Physical and Psychological Strain, and Relying on a Multilayered Support Ecosystem for Successful Transition.

The return to clinical work postpartum is a period of multidimensional strain and identity negotiation. Retention is contingent upon a coherent support ecosystem. Moving beyond broad work-family conflict narratives, this review offers a targeted evidence base supporting essential structural enablers-such as flexible work policies, protected lactation facilities, and tailored reintegration pathways-alongside culturally competent interpersonal support, to promote sustainable reintegration and preserve an experienced nursing workforce.

Nurse managers should proactively establish supportive structural policies, including flexible scheduling and dedicated lactation facilities, to support the successful reintegration of postpartum nurses. Developing tailored return-to-work orientation pathways and fostering a supportive, empathetic ward culture are critical managerial strategies to mitigate transition-related stress, enhance job satisfaction, and retain experienced clinical staff amidst the global nursing shortage.

Cardiovascular diseases are the leading cause of death in Chile and worldwide, representing a major public health challenge that demands urgent preventive and therapeutic strategies. In atrial fibrillation, anticoagulation is essential, and in Chile acenocoumarol rather than warfarin, used in most countries, is the standard agent. Its dosing shows substantial interindividual variability due to CYP2C9 and VKORC1 polymorphisms. We developed a cohort-based Markov model to compare standard care, genotype-guided dosing, and genotype-guided dosing adjusted for population-level adherence in 123 Chilean patients with atrial fibrillation and 123 matched simulated individuals. Outcomes were measured as quality-adjusted life years (QALYs) and direct medical costs, with cost-effectiveness assessed at a willingness-to-pay (WTP) threshold of US$17,093, estimated using the international approach of approximating the country's GDP per capita rather than a Chilean policy-based value. Genotype-guided dosing achieved the highest effectiveness (2938.34 QALYs) with an incremental cost-effectiveness ratio of US$436.86/QALY versus standard care, remaining cost-effective in sensitivity analyses up to test prices far exceeding the current US$190. The adherence-adjusted strategy was weakly dominated. These results strongly support implementing pharmacogenetic testing for acenocoumarol dosing to optimize anticoagulation safety, efficacy, and cost-effectiveness in Chile.

Fibrosis, a critical global health challenge, is primarily characterized by pathological scar formation due to an imbalance in tissue injury repair mechanisms, ultimately leading to progressive organ dysfunction. Notably, the Yes-associated protein (YAP), a central effector molecule in the Hippo signaling pathway, serves as a pivotal molecular regulator across fibrotic processes in multiple organs. Aberrant YAP activation is a hallmark of fibrosis in multiple organs, including the liver, kidney, heart, and lung, where it drives pro-fibrotic gene expression. Although basic research has highlighted YAP's essential role in fibrotic diseases, translating these insights into clinical applications remains complex. The current repertoire of targeted therapeutic options for fibrosis is restricted, further complicated by variations in tissue-specific responses to YAP modulation. This highlights the urgent need for a thorough analysis of the YAP regulatory network. In this review, we analyze the YAP protein interaction network to clarify the dynamic regulation of its nuclear-cytoplasmic trafficking. Furthermore, we explore the distinct signaling characteristics of YAP during organ fibrosis, summarize recent developments in anti-fibrotic strategies targeting YAP, and assess the translational potential of intervening in YAP and its upstream and downstream pathways for effective anti-fibrotic therapy.

Enteroviruses (EVs) cause a wide range of pediatric illnesses. In Taiwan, changes in serotype distribution and COVID-19-related public health measures may have influenced recent EV trends. We retrospectively reviewed EV-positive pediatric inpatients (< 18 years) at National Taiwan University Hospital from 2015 to 2023. Cases were identified via PCR or viral culture. Among 678 cases, incidence declined markedly during the COVID-19 period but rebounded after public health restrictions were relaxed, with seasonal peaks in June persisting. Echovirus 11 emerged as the predominant serotype among neonatal cases (23.1%) and severe cases (9.5%), whereas EV-A71 was mainly associated with hand-foot-mouth disease. Severe cases were significantly younger (median 0.8 vs. 1.5 years, p = 0.002) and more likely to have underlying conditions, including congenital syndromes and cardiovascular diseases. The only mortality occurred in a neonate with echovirus 11 infection. Viral or bacterial co-detections were not associated with severity. Echovirus 11 has replaced EV-A71 as a leading cause of severe and neonatal EV infections in Taiwan. Younger age and underlying conditions were significant risk factors for severe disease. Ongoing surveillance and vaccine development should prioritize currently circulating virulent serotypes and high-risk pediatric populations.

Family members of critically ill or severely injured patients experience considerable distress, which may negatively affect mental health and family functioning. Family-focused interventions are therefore needed and form an essential part of intensive care.

This article defines evidence-informed family interventions and engagement practices, highlights their complexity, identifies implementation challenges, and describes approaches to establishing state-of-the-art family care that reaches families in reliable ways.

Theoretical framing and narrative overview of the current state of knowledge on the implementation of complex family interventions in adult intensive care units.

Family interventions engage patients and close others in care activities and address their cognitive, affective, and behavioral needs. They are often delivered in combinations and are therefore classified as complex health interventions. Despite the evidence base being incomplete in some areas, a consensus has emerged on best practices for involving, informing, communicating with, and supporting families. The integration of these evidence-informed practices is influenced by factors at the individual, team, and organizational levels, which often act as barriers. Thus, systematic, theory-guided, and empirically grounded implementation process is crucial.

The integration of evidence-informed recommendations for working with families in intensive care units requires a communal effort. Implementation science offers systematic, theory-driven models to support the sustainable integration of context-specific family-focused interventions in intensive care units.