Limited data exist regarding the real-world practices and clinical outcomes in patients with ischemic heart failure with reduced left ventricular ejection fractions (LVEFs). Using nationwide registry data from South Korea, we aimed to investigate long-term outcomes and clinical practices, especially implantable cardioverter defibrillators (ICDs) implantation, in patients with reduced LVEFs at least 40 days after acute myocardial infarction (AMI). Of 13,056 patients with AMI between 2011 and 2015, we analyzed 350 (median age, 66 years [interquartile range, 56-75]) who had LVEFs <40% on follow-up transthoracic echocardiogram 40 days after the index event. The primary outcome was cardiac-cause mortality at 3 years. Secondary outcomes comprised major cardiovascular events as well as outcomes defined by the use of ICDs, cardiac resynchronization therapy defibrillators (CRT-Ds), and electrophysiology studies. Among 350 patients, 39 (11.1%) died from cardiac causes during 3 years of follow-up. Eleven (3.1%) were hospitalized for ventricular tachycardia. The rate of ICD or CRT-D implantation up to 3 years was 5.7% (20/350). Cox time-to-event analysis revealed older age, LVEF <30%, diabetes mellitus, and previous MI or revascularization as positively associated with cardiac death, whereas the use of statins and body weight <67 kg were negatively associated. This nationwide Korean registry demonstrated that only 5.7% of patients who had reduced LVEFs after 40 days of AMI underwent ICD implantations over 3 years. Considering the high mortality, concerted efforts are needed to improve clinical outcomes for patients who may have been candidates for ICD implantation.
The interstitial cells of Cajal (ICC) generate spontaneous pacemaker activities responsible for producing slow waves in the gut smooth muscles. Prostaglandin E2 (PGE2) is one of the most important prostanoids in the gut, playing a crucial role in multiple physiological and pathological processes. Because information regarding the effects of PGE2 on colonic ICC is limited, we investigated the effects of PGE2 and its underlying signaling pathways in murine colonic ICC. Whole-cell patch-clamp recordings and reverse transcription polymerase chain reaction (RT-PCR) analyses were performed to evaluate the effects of PGE2 on mouse colonic ICC. PGE2 had a dual effect on pacemaker potential in the current-clamp mode. RT-PCR data suggested the expression of EP3 and EP4 receptors in colonic ICC. Low PGE2 concentrations induced membrane depolarization and generation of pacemaker activities. And this effect is mimicked by sulprostone (an EP3 agonist). The low PGE2 concentration-induced effect was inhibited by anoctamin-1 (ANO1) or a T-type Ca2+ channel blocker. Conversely, high PGE2 concentrations induced membrane hyperpolarization and blocked pacemaker potential generation. However, this inhibitory effect was blocked by an ATP-sensitive potassium (KATP) channel blocker but not by other K+ channel blockers. Low concentrations of PGE2 activated EP3 receptors, leading to excitation of pacemaker activity through regulation of ANO1 and T-type Ca2+ channels in colonic ICC. In contrast, higher concentrations of PGE2 activated EP4 receptors and opened ATP-sensitive K+ channels, resulting in inhibition of pacemaker activity in colonic ICC.
Inflammatory biomarkers reflecting acute immune responses may aid prognostic stratification in patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (COPD). The eosinophil-neutrophil ratio (ENR) integrates two key inflammatory cell populations; however, its prognostic value in the acute exacerbation of COPD has not been fully established. We conducted a retrospective cohort study of patients hospitalized for acute exacerbation of COPD between 2016 and 2021. ENR was calculated using peripheral blood eosinophil and neutrophil counts obtained at hospital admission. Patients were categorized into quartiles based on ENR, and outcomes were compared between the lowest quartile (Q1) and the upper three quartiles (Q2-Q4). The primary outcome was in-hospital mortality, and secondary outcomes included all-cause mortality within one year. A total of 435 patients were included (Q1, n=109; Q2-Q4, n=326). The cohort was predominantly male, with a mean age of 74 years. Mean ENR values were significantly lower in Q1 than in Q2-Q4 (0.0002 vs. 0.0471, p<0.001). In-hospital mortality was significantly higher in the Q1 group compared with the Q2-Q4 group (5.5% vs. 1.2%, p=0.019). In multivariable logistic regression analyses, low ENR remained independently associated with an increased in-hospital (adjusted odds ratio, 9.05; 95% confidence interval, 2.19-37.39; p=0.002). ENR was not associated with long-term survival. A low ENR at hospital admission is an independent predictor of in-hospital mortality in patients hospitalized with acute exacerbation of COPD, reflecting heightened acute-phase disease severity.
Colorectal cancer (CRC) is a leading cause of cancer-related deaths. Long non-coding RNAs are emerging as key regulators in cancer by modulating functions of microRNAs thereby affecting expression of genes involved in the pathogenesis of cancers. Since the CTHRC1 gene (Collagen Triple-Helix-Repeat Containing-1) encodes an extracellular matrix protein involved in collagen regulation and cell migration, this study investigated the role of LINC01748 in CRC and its interaction with the Let-7b-5p/CTHRC1 axis. RNA sequencing data from The Cancer Genome Atlas database was analyzed to identify differentially expressed lncRNAs, miRNAs, and mRNAs in CRC. Interactions between LINC01748, miRNAs, and mRNAs were predicted, a protein-protein interaction network was constructed, and functional enrichment analysis was performed to reveal the biological activity of target genes. Additionally, the expression of LINC01748, Let-7b-5p, and CTHRC1 in CRC tissues and adjacent non-cancerous tissues were determined using RT-qPCR and western blotting. Collagen density was also evaluated by histopathological examination. 107 differentially expressed lncRNAs, 313 miRNAs, and 1,479 mRNAs were identified in CRC samples. Bioinformatics analysis indicated that LINC01748 may function as a competing endogenous-RNA for Let-7b-5p, regulating CTHRC1 expression. RT-qPCR confirmed upregulation of LINC01748 and CTHRC1 and downregulation of Let-7b-5p in CRC. Significant positive correlation of LINC01748 with CTHRC1, and a negative correlation with Let-7b-5p were detected. Gene Ontology and KEGG pathway analysis suggested the involvement of LINC01748/Let-7b-5p/CTHRC1 axis in ECM organization and collagen content. This study revealed the role of LINC01748 in the Let-7b-5p/CTHRC1 axis, highlighting its clinical significance in CRC.
Oral anticoagulants are widely used to prevent and treat thromboembolic disorders, but inappropriate use can increase adverse effects and reduce therapeutic efficacy. This study evaluated the utilization patterns, dosing appropriateness, and adverse effects of oral anticoagulants in a tertiary hospital in Iran. A retrospective cross-sectional study was conducted at Razi Educational Hospital, Birjand University of Medical Sciences, from April 2020 to September 2022. Data were collected from medical records and pharmacy databases for patients aged ≥18 years who received warfarin, rivaroxaban, or apixaban. Dosing appropriateness was assessed using 2021 European Heart Rhythm Association (EHRA) and UpToDate guidelines, while adverse effects were classified according to 2020 American College of Cardiology (ACC) criteria. Among 1,027 patients (mean age 64±16.4 years; 52.3% male), rivaroxaban was the most prescribed anticoagulant (43.5%), followed by warfarin (33.2%) and apixaban (23.3%). Warfarin was primarily used for valvular heart disease, whereas DOACs were mainly prescribed for non-valvular atrial fibrillation and venous thromboembolism. Adverse effects occurred in 12.1% of patients, mostly minor bleeding, with warfarin accounting for the majority. Guideline-based dosing was achieved in 61.9% of apixaban and 58.6% of rivaroxaban users; 46.9% of warfarin patients reached therapeutic INR (2-3). Correct renal dose adjustments were applied in 40.5% of apixaban and 33% of rivaroxaban users. Guideline adherence for oral anticoagulant dosing was suboptimal. Improved prescriber education, enhanced drug utilization evaluation, and routine renal monitoring may enhance patient safety and optimize anticoagulation outcomes.
Cervical cancer remains a significant public health concern, with persistent high-risk human papillomavirus (HPV) infections being a major contributing factor. This retrospective study investigates the correlation between multiple HPV infections and cervical cytology abnormalities in patients tested at a single hospital in Seoul, South Korea. A total of 6,869 HPV genotyping tests conducted between January 2017 and December 2023 were analyzed, with 1,396 cases testing positive for HPV. High-risk HPV (HRHPV) types were detected in 59.0% of HPV-positive cases, with HPV 53 being the most prevalent genotype. The frequency of squamous intraepithelial abnormalities (SIA) increased with the number of concurrent HPV infections. Among single infections, 24.2% had SIA, compared to 38.4% for two genotypes, 43.9% for three, and 70.0% for four. HRHPV-positive cases had a significantly higher prevalence of high-grade lesions (ASC-H and HSIL) compared to non-HRHPV and HPV-negative cases. However, no significant difference in cytological outcomes was observed among different co-infection groups. These findings suggest that multiple HPV infections may associated with increased cytological abnormalities, particularly in HRHPV-positive cases. Regional variations in HPV genotype prevalence highlight the need for tailored vaccination and screening strategies. While this study provides valuable epidemiological insights, its retrospective nature and lack of long-term follow-up warrant further research.
This study aimed to estimate the recurrence rate of pelvic organ prolapse (POP) following traditional total vaginal hysterectomy (TVH) with anteroposterior (AP) colporrhaphy using the Pelvic Organ Prolapse-Quantification (POP-Q) system, to evaluate the utility of these classical surgical approaches, and to identify risk factors associated with recurrence after pelvic organ prolapse surgery. In this retrospective cohort study, data were collected from 158 patients who underwent TVH with AP colporrhaphy for POP at Chonnam National University Hospital between January 2015 and April 2020 and had follow-up data exceeding 6 months. Data regarding age, body mass index, menopausal status, prolapse severity, surgical method, and POP-Q stage during outpatient post-operative tracking were collected. All 158 patients underwent TVH. Of these, 147 (93.0%) underwent TVH with AP colporrhaphy; two (1.3%) underwent hysterectomy with anterior colporrhaphy, and nine (5.7%) underwent hysterectomy with posterior colporrhaphy. Before the initial surgery, 16 (10.1%), 113 (71.5%), and 29 (18.3%) patients had stages II, III, and IV disease, respectively. The anterior compartment was the most commonly affected (74.1%), followed by the apical (19.6%) and the posterior (6.3%) compartments. Recurrence was observed in 13 patients (8.2%). Parity, menopausal status, and stage of POP did not significantly influence disease recurrence. Traditional TVH with AP colporrhaphy is associated with a relatively low recurrence rate and, thus, remains a valuable surgical treatment option for POP.
The pathogenesis of endotoxin-induced acute lung injury is fundamentally driven by dysregulated innate immune responses, where macrophage-mediated cytokine surges and subsequent signaling cascades trigger neutrophil infiltration and tissue damage. This study investigated whether curcumin modulates inflammatory signaling pathways and attenuates lung injury in experimental endotoxemia. Using endotoxin-stimulated murine macrophages and a mouse model of intratracheal lipopolysaccharide challenge, inflammatory cytokine production, mitogen-activated protein kinase activation, pulmonary edema, neutrophil accumulation, histopathologic injury, and short-term survival were assessed. Curcumin suppressed endotoxin-induced tumor necrosis factor-α production and selectively inhibited ERK1/2 and JNK phosphorylation without affecting p38 signaling in macrophages. In vivo, curcumin reduced pulmonary cytokine levels, neutrophil infiltration, lung edema, and histologic injury, and was associated with improved survival following severe endotoxin exposure. These findings indicate that curcumin attenuates acute lung injury by selectively modulating intracellular inflammatory signaling pathways, supporting the concept that targeted inhibition of specific kinase cascades may mitigate inflammatory lung damage without broad immune suppression.
Obesity is a systemic vascular disease characterized by the convergence of metabolic excess and adipose dysfunction, leading to endothelial injury and plasticity. Beyond hemodynamic stress, chronic nutritional and inflammatory stimuli trigger oxidative and pro-thromboinflammatory pathways, reduce nitric oxide bioavailability, and promote endothelial-to-mesenchymal transition (EndMT). This process contributes to fibrotic remodeling, plaque vulnerability, arterial stiffening, and microvascular rarefaction. Non-coding RNAs (ncRNAs)-microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)-play pivotal roles as regulators within the vascular wall and across tissues via extracellular vesicles (EVs) derived from adipose tissue and perivascular fat. We synthesize evidence demonstrating that ncRNAs integrate TGF-β/Smad, NF-κB, HIF-1α, and Wnt/β-catenin signaling pathways with the endothelial metabolic state, including the epigenetic regulation of EndMT linked to fatty acid oxidation. Single-cell and lineage-tracing studies identify nascent EndMT subpopulations in obese tissues, while in vitro models reveal cytokine and lipotoxic triggers that shift ncRNA networks, stabilizing mesenchymal programs. Translationally, circulating and EV-associated ncRNAs mirror adiposity, dyslipidemia, insulin resistance, and endothelial dysfunction, improving with weight loss. This underscores their potential as dynamic biomarkers for patient stratification, particularly when integrated with vascular imaging and functional assays. Furthermore, we discuss therapeutic strategies such as miRNA antagomirs, lncRNA gapmers, and circRNA inhibitors, addressing the critical challenge of endothelium-targeted delivery through approaches like ligand-directed nanoparticles, endothelial-tropic liposomes, and engineered EVs. This review positions obesity-associated vascular disease as an ncRNA-driven network disorder and outlines pathways toward precision diagnostics and RNA-based interventions.
To compare optic nerve head (ONH) and peripapillary structural OCT parameters between eyes with and without visual field (VF) defects one year after an episode of acute primary angle closure (APAC) in a cohort treated uniformly treated with early clear-lens extraction. Forty-seven eyes of 47 patients with a history of APAC episode who underwent early clear-lens extraction at Chonnam National University Hospital were retrospectively reviewed. Spectral-domain optical coherence tomography (SD-OCT) performed one year after the episode was used to assess Bruch's membrane opening-minimum rim width (BMO-MRW), retinal nerve fiber layer (RNFL) thickness, lamina cribrosa (LC) thickness and depth, and parapapillary atrophy (PPA) subdivided into PPA+BM and PPA-BM. Patients were classified according to the presence or absence of VF defects. At one year, 23 eyes (48.9%) had variable degrees of visual field (VF) defects. Compared with eyes with normal VF, the VF-defect group showed significantly thinner global BMO-MRW (p<0.001) and peripapillary RNFL (p<0.001), reduced LC thickness (p<0.001), shallower LC depth (p=0.028), and a wider PPA+BM (p<0.001). APAC patients who underwent early lens extraction may develop residual VF defect despite normalization of IOP. These defects were associated with structural damage in the rim, RNFL, LC, and PPA+BM as detected by SD-OCT. Comprehensive OCT analysis may help identify patients at risk of long-term functional sequelae after APAC.
The COVID-19 pandemic has adversely affected the mental health of the global population. This study aimed to assess the acute and persistent symptoms of depression, as well as factors related to their manifestation, through a longitudinal study design. A total of 1,492 community-dwelling adults from an online public panel across three regions were evaluated at baseline, with 908 adults (60.9%) followed up after six months. Depression symptoms were evaluated using Patient Health Questionnaire-9 (PHQ-9). Participants also completed self-administered questionnaires on sociodemographic information, psychosocial experiences related to COVID-19, the UCLA Loneliness Scale, and the Korean version of the Gratitude Questionnaire (K-GQ-6).The prevalence of acute and persistent depression symptoms was 8.4% and 12.0%, respectively. Multivariate logistic regression analysis identified changes in predictors of depression over time, with younger age and self-isolation experience found to be associated with acute depression. Factors such as underlying mental illness, eating and sleeping disturbances, loneliness, and COVID-19-related stress emerged as significant risk factors for persistent depression. A disposition toward gratitude was identified as a protective factor for persistent depressive symptoms. These findings suggest that during any long-term pandemic crisis such as COVID-19, timely support and attention are essential for vulnerable populations, including young people and individuals with mental health conditions, to prevent depression. Specifically, promoting daily routines such as regular eating and sleeping patterns, and managing COVID-19-related stress may be critical in preventing persistent depression. Additionally, psychological support that reduces loneliness and fosters gratitude may help mitigate depression risk.
Roflumilast, a phosphodiesterase 4 (PDE4) inhibitor, reduces neutrophilic airway inflammation and exacerbations in chronic obstructive pulmonary disease (COPD). However, the effect of coexisting bronchiectasis on its efficacy remains unclear. This study evaluates the long-term impact of roflumilast use in this population. A retrospective cohort study was conducted using data from 2,181 COPD patients. Of them, 180 had bronchiectasis confirmed on CT, with 162 not using roflumilast and 18 receiving it. Baseline data, including demographics, symptom scores, pulmonary function, and biomarkers, were collected. Patients were followed for one year to assess exacerbations and mortality, and survivors were monitored for up to three years for symptom and pulmonary function changes. Multivariate logistic regression was performed to determine predictors of exacerbations. Moderate and severe exacerbations occurred more frequently in the roflumilast group, but mortality did not differ between groups. Roflumilast users showed significant improvements in post-bronchodilator forced expiratory volume in one second (FEV1) (p=0.028), as well as in the ratio of forced expiratory volume in one second to the forced vital capacity (FEV1/FVC) ratio (p=0.015) compared to no roflumilast group. In multivariate analysis, roflumilast use was independently associated with a higher exacerbation risk (p=0.004, OR=14.643, 95% CI: 2.36-90.848). While roflumilast improved pulmonary function and symptoms in COPD patients with bronchiectasis, it was also linked to a higher risk of exacerbations. These findings suggest caution in its use for this population, and further randomized controlled trials are needed to assess its safety and efficacy.
Nonalcoholic fatty liver disease (NAFLD) refers to a comprehensive range of conditions, encompassing simple steatosis to advancing nonalcoholic steatohepatitis (NASH), hepatic fibrosis, and cirrhosis. While both aerobic exercise and resistance training (RT) have been shown to provide advantages for patients with NAFLD, there is still a need to investigate and delve into the potential effectiveness of exercise mode. The purpose of this study is to investigate the effect of exercise mode in NAFLD-induced rats. Twenty-one male Wistar rats were divided into three groups: 1) normal control, 2) NAFLD, and 3) NAFLD+combined training (CT). The intervention groups received HFFD for 15 weeks to induce NAFLD. After determination of NAFLD, CT was done for 8 weeks. Aspartate transaminase (AST) and triglyceride (TG) were significantly reduced in the NAFLD+CT compare to NAFLD.While there was no significant difference in the Low-density lipoprotein (LDL), AST, and alkaline phosphatase (ALP) in the NAFLD+CT. CT can lead to a reduction in liver fat content, improved liver function, and lowered levels of TG and cholesterol that causes improvement of NAFLD. Therefore, they can be used to reduce the complications of NAFLD. Although more studies are needed to confirm the results.
Subclinical cerebral infarction might be developed even adequate oral anticoagulation after direct current cardioversion (DCCV) in patients with atrial fibrillation (AF). Although apixaban is preferred to prevent thromboembolism and minimize bleeding risk in patients with AF, clinical outcomes after DCCV have not been known well. This study aimed to compare the occurrence of subclinical infarction between apixaban and warfarin in patients with AF after DCCV. A total of 60 patients diagnosed with non-valvular AF were randomized to receive either Apixaban or warfarin. At least 3-week anticoagulation was warranted before DCCV. Brain magnetic resonance image (MRI) was checked 3 days later after DCCV. All of the patients were followed upto 1-month. The primary end-point was the occurrence of subclinical infarction, while secondary end-point included death, stroke, and hospitalization due to heart failure. Safety end-point focused on major bleeding. Micro-embolic infarction causing subclinical infarction were not observed in the warfarin group, while 1 patient (4.3%) in the apixaban group, without statistical difference. Stroke and hospitalization were not developed at both groups. Brain MRI revealed micro-bleeding in 1 patient (4.3%) in the apixaban group, while there was no major or micro-bleeding in the warfarin group. The incidence of micro-embolic events causing subclinical infarction following DCCV was comparable between apixaban and warfarin. Clinical outcomes after DCCV were comparable between the 2 groups. These findings suggest that both apixban and warfarin exhibit similar safety and efficacy profiles during DCCV.
