Echinochrome A (Ech A) isolated from marine organisms is a therapeutic effector for various cardiovascular diseases, but its precise mechanisms are unclear.This study identified the role and mechanisms mediating the effects of Ech A on the migration of vascular smooth muscle cells (VSMCs) induced by high-mobility group box 1 (HMGB1). Compared to the control cells, the migration of VSMCs stimulated with HMGB1 (100 ng/ml) was markedly increased, which was significantly attenuated in cells pretreated with MPIIIB10 (100 ng/ml), a neutralizing monoclonal antibody for osteopontin (OPN). In VSMCs stimulated with HMGB1, the increased expression of OPN mRNA and protein was accompanied by an increased OPN promoter activity. In reporter gene assays using OPN promoter-luciferase constructs, the promoter region 538-234 bp of the transcription start site containing the binding sites for activator protein 1 (AP-1) was shown to be responsible for the increased transcriptional activity by HMGB1. In addition, the binding activity of AP-1 was increased in HMGB1-stimulated cells, highlighting the pivotal role of AP-1 on OPN expression in HMGB1-stimulated VSMCs. An examination of the vascular effects of Ech A showed that the increased AP-1 binding/promoter activities and OPN expression induced by HMGB1 were attenuated in cells pretreated with Ech A (3 or 10 μM). Similarly, Ech A inhibited HMGB1-induced VSMC migration in a concentration-dependent manner. These findings suggest that Ech A inhibits VSMC migration by suppressing OPN expression.Hence, Ech A is suggested as a potential therapeutic strategy for vascular remodeling in the injured vasculatures.

The 5-hydroxytryptamine type3 (5-HT3 ) receptor, a ligand-gated ion channel, plays a critical role in synaptic transmission. It has been implicated in various neuropsychiatric disorders. This study aimed to elucidate the mechanism by which quetiapine, an atypical antipsychotic, could inhibit 5-HT3 receptor-mediated currents in NCB20 neuroblastoma cells. Whole-cell patch-clamp recordings were used to study effects of quetiapine on receptor ion channel kinetics and its competitive antagonism. Co-application of quetiapine shifted 5-HT concentration-response curve rightward, significantly increasing the EC50 without altering the maximal response (Emax ), suggesting a competitive inhibition. Quetiapine's IC50 varied with 5-HT concentration and treatment condition. The IC50 value of quetiapine was 0.58 μM with 3μM 5-HT and 25.23 μM with 10 μM 5-HT, indicating an inverse relationship between quetiapine efficacy and agonist concentration. Pretreatment of quetiapine significantly enhanced its inhibitory potency, reducing its IC50 from 25.23 μM to 0.20 μM.Interaction kinetics experiments revealed an IC50 of 5.17 μM for an open state of the 5-HT3 receptor, suggesting weaker affinity during receptor activation. Quetiapine also accelerated receptor deactivation and desensitization, suggesting that it could stabilize the receptor in non-conducting states. Additionally, quetiapine significantly prolonged recovery from desensitization without affecting recovery from deactivation, demonstrating its selective impact on receptor kinetics. Inhibition of the 5-HT3 receptor by quetiapine was voltage-independent, and quetiapine exhibited no usedependency, further supporting its role as a competitive antagonist. These findings provide insights into inhibitory mechanism of quetiapine on 5-HT3 receptor and suggest its potential therapeutic implications for modulating serotonergic pathways in neuropsychiatric disorders.

Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2). However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR. In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT) 3 receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells. When co-applied with 5-HT, haloperidol inhibited 5-HT3 receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (E max ) and an increase in EC 50 observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT3 receptors. Haloperidol inhibited the activation of 5-HT3 receptor, while also accelerating their deactivation and desensitization. The inhibitory effect of haloperidol showed no significant difference between pre- and co-application. Haloperidol did not alter the reversal potential of 5-HT3 receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT3 receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT3 receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT3 receptors and pharmacological actions of antipsychotics.

Background: This study evaluated adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and Korean guidelines in the prescription patterns of respiratory specialists for stable chronic obstructive pulmonary disease (COPD) management. Methods: Data were collected on medications from 2011 to 2022 using the Korea COPD Subtype Study (KOCOSS) cohort. Patients were divided into two groups: those registered before and after 2019, and we analyzed the percentage of patients meeting the recommended treatment criteria established by each guideline. Results: Among 3,477 patients, 85.6% received pharmacological therapy, and 81.6% utilized inhaled medications. Compared to patients enrolled before 2019, there was an increase in inhaler prescriptions among those registered after 2019 (79.7% vs. 86.7%), with dual bronchodilators being the predominant therapy prescribed. Of the patients receiving treatment, 56.9% adhered to the Korean 2018 guideline. Compliance with the GOLD 2019 and GOLD 2023 guidelines was observed in 31.3% and 28.0% of cases, respectively. When analyzing inhaler prescription patterns according to both subgroups and considering the Korean 2018, GOLD 2019, and GOLD 2023 guidelines concurrently, the adherence rates were as follows: (56.6%, 37.8%, 24.0%) and (57.7%, 14.0%, 38.6%). Conclusion Adherence rates were higher for the Korean guideline compared to the GOLD recommendations. Furthermore, alignment with both the Korean 2018 and GOLD 2023 guidelines increased among patients enrolled after 2019, compared to those registered earlier. These findings suggest that physicians are modifying their therapeutic strategies to align with both domestic and recent international guidelines.

Background: Computed tomography (CT) scans are utilized to assess emphysema, a prominent phenotype of chronic obstructive pulmonary disease (COPD). Variability in CT protocols and equipment across hospitals can impact accuracy. This study aims to implement kernel conversion across different CT settings and evaluate changes in the correlation between the emphysema index pre- and post-kernel conversion, along with clinical measures in COPD patients. Methods: Data were extracted from the Korea COPD Subgroup Study database, which included CT scan images from 484 COPD patients. These images underwent kernel conversion. Emphysema extent was quantified using the percentage of low-attenuation areas (%LAA-950) determined by a deep learning-based program. The correlation between %LAA-950 and clinical parameters, including lung function tests, the modified Medical Research Council (mMRC), 6-minute walking distance (6MWD), COPD assessment test (CAT), and the St. George’s Respiratory Questionnaire for COPD (SGRQ-c), was analyzed. Subsequently, these values were compared across various CT settings. Results: A total of 484 participants were included. Kernel conversion significantly reduced the variance in %LAA-950 values (before vs. after: 12.6±11.0 vs. 8.8±11.9). Post-kernel conversion, %LAA-950 demonstrated moderate correlations with forced expiratory volume in 1 second (r=–0.41), residual volume/total lung capacity (r=0.42), mMRC (r=0.25), CAT score (r=0.12), SGRQ-c (r=0.21), and 6MWD (r=0.15), all of which were improved compared to the unconverted dataset (all p<0.01). Conclusion CT images processed through kernel conversion enhance the correlation between the extent of emphysema and clinical parameters in COPD.

Connective tissue disease (CTD), comprising a range of autoimmune disorders, is often accompanied by lung involvement, which can lead to life-threatening complications. The primary types of CTDs that manifest as interstitial lung disease (ILD) include rheumatoid arthritis, systemic sclerosis, Sjögren’s syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematosus. CTD-ILD presents a significant challenge in clinical diagnosis and management due to its heterogeneous nature and variable prognosis. Early diagnosis through clinical, serological, and radiographic assessments is crucial for distinguishing CTD-ILD from idiopathic forms and for implementing appropriate therapeutic strategies. Hence, we have reviewed the multiple clinical manifestations and diagnostic approaches for each type of CTD-ILD, acknowledging the diversity and complexity of the disease. The importance of a multidisciplinary approach in optimizing the management of CTD-ILD is emphasized by recent therapeutic advancements, which include immunosuppressive agents, antifibrotic therapies, and newer biological agents targeting specific pathways involved in the pathogenesis. Therapeutic strategies should be customized according to the type of CTD, the extent of lung involvement, and the presence of extrapulmonary manifestations. Additionally, we aimed to provide clinical guidance, including therapeutic recommendations, for the effective management of CTD-ILD, based on patient, intervention, comparison, outcome (PICO) analysis.

Background: Malnutrition exacerbates the prognosis of numerous diseases; however, its specific impact on severe coronavirus disease 2019 (COVID-19) outcomes remains insufficiently explored. Methods: This multicenter study in Korea evaluated the nutritional status of 1,088 adults with severe COVID-19 using the Geriatric Nutritional Risk Index (GNRI) based on serum albumin levels and body weight. The patients were categorized into two groups: GNRI >98 (no-risk) and GNRI ≤98 (risk). Propensity score matching, adjusted for demographic and clinical variables, was conducted. Results: Of the 1,088 patients, 642 (59%) were classified as at risk of malnutrition. Propensity score matching revealed significant disparities in hospital (34.3% vs. 19.4%, p<0.001) and intensive care unit (ICU) mortality (31.5% vs. 18.9%, p<0.001) between the groups. The risk group was associated with a higher hospital mortality rate in the multivariate Cox regression analyses following propensity score adjustment (hazard ratio [HR], 1.64; p=0.001). Among the 670 elderly patients, 450 were at risk of malnutrition. Furthermore, the risk group demonstrated significantly higher hospital (52.1% vs. 29.5%, p<0.001) and ICU mortality rates (47.2% vs. 29.1%, p<0.001). The risk group was significantly associated with increased hospital mortality rates in the multivariate analyses following propensity score adjustment (HR, 1.66; p=0.001). Conclusion Malnutrition, as indicated by a low GNRI, was associated with increased mortality in patients with severe COVID-19. This effect was also observed in the elderly population. These findings underscore the critical importance of nutritional assessment and effective interventions for patients with severe COVID-19.

Background: Lung ultrasound (LUS) has proven valuable in the initial assessment of coronavirus disease 2019 (COVID-19), but its role in detecting pulmonary fibrosis following intensive care remains unclear. This study aims to assess the presence of pulmonary sequelae and fibrosis-like changes using LUS in survivors of severe COVID-19 pneumonia one month after discharge. Methods: We prospectively enrolled patients with severe COVID-19 who required mechanical ventilation in the intensive care unit (ICU) and conducted LUS assessments from admission to the outpatient visit after discharge. We tracked changes in key LUS findings and applied our proprietary LUS scoring system. To evaluate LUS accuracy, we correlated measured LUS values with computed tomography scores. Results: We evaluated B-line presence, pleural thickness, and consolidation in 14 eligible patients. The LUS scores exhibited minimal changes, with values of 19.1, 19.2, and 17.5 at admission, discharge, and the outpatient visit, respectively. Notably, the number of B-lines decreased significantly, from 1.92 at admission to 0.56 at the outpatient visit (p<0.05), while pleural thickness increased significantly, from 2.05 at admission to 2.48 at the outpatient visit (p≤0.05). Conclusion This study demonstrates that LUS can track changes in lung abnormalities in severe COVID-19 patients from ICU admission through to outpatient follow-up. While pleural thickening and B-line patterns showed significant changes, no correlation was found between LUS and high-resolution computed tomography fibrosis scores. These findings suggest that LUS may serve as a supplementary tool for assessing pulmonary recovery in severe COVID-19 cases.

Background: The development of frailty at hospital discharge affects the clinical outcomes in severe coronavirus disease 2019 (COVID-19) survivors who had no frailty before hospitalization. We aimed to describe the prevalence of new frailty using the clinical frailty scale (CFS) and evaluate its associated factors in patients with severe COVID-19 without pre-existing frailty before hospitalization. Methods: We performed a secondary analysis of clinical data from a nationwide retrospective cohort collected from 22 hospitals between January 1, 2020 and August 31, 2021. The patients were at least 19 years old and survived until discharge after admission to the intensive care unit (ICU) because of severe COVID-19. Development of new frailty was defined as a CFS score ≥5 at hospital discharge. Results: Among 669 severe COVID-19 survivors without pre-existing frailty admitted to the ICU, the mean age was 65.2±12.8 years, 62.5% were male, and 50.2% received mechanical ventilation (MV). The mean CFS score at admission was 2.4±0.9, and new frailty developed in 27.8% (186/483). In multivariate analysis, older age, cardiovascular disease, CFS score of 3–4 before hospitalization, increased C-reactive protein level, longer duration of corticosteroid treatment, and use of MV and extracorporeal membrane oxygenation were identified as factors associated with new-onset frailty. Conclusion Our study suggests that new frailty is not uncommon and is associated with diverse factors in survivors of severe COVID-19 without pre-existing frailty.

Background: This study aimed to identify the clinical characteristics of multidrug-resistant/ rifampicin-resistant tuberculosis (MDR/RR-TB) in the Republic of Korea. Methods: Data of notified people with tuberculosis between July 2018 and December 2021 were retrieved from the Korea Tuberculosis Cohort database. MDR/RR-TB was further categorized according to isoniazid susceptibility as follows: multidrug-resistant tuberculosis (MDR-TB), rifampicin-monoresistant tuberculosis (RMR-TB), and RR-TB if susceptibility to isoniazid was unknown. Multivariable logistic regression analysis was conducted to identify the factors associated with MDR/RR-TB. Results: Between 2018 and 2021, the proportion of MDR/RR-TB cases among all TB cases and TB cases with known drug susceptibility test results was 2.1% (502/24,447). The proportions of MDR/RR-TB and MDR-TB cases among TB cases with known drug susceptibility test results were 3.3% (502/15,071) and 1.9% (292/15,071), respectively. Among all cases of rifampicin resistance, 31.7% (159/502) were RMR-TB and 10.2% (51/502) were RR-TB. Multivariable logistic regression analyses revealed that younger age, foreigners, and prior tuberculosis history were significantly associated with MDR/ RR-TB. Conclusion Rapid identification of rifampicin resistance targeting the high-risk populations, such as younger generations, foreign-born individuals, and previously treated patients are necessary for patient-centered care.