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.

Purpose: To compare the perioperative and postoperative outcomes between traditional trans-vesical robot-assisted simple prostatectomy (TV-RASP) and the newly introduced urethral-sparing (US) RASP. Materials and Methods: We retrospectively reviewed 42 patients who underwent TV-RASP (n=22) or US-RASP (n=20) performed by two experienced surgeons at two tertiary centers. Perioperative outcomes including operation time, estimated blood loss, length of hospital stay, and catheterization time were assessed. Postoperative outcomes were evaluated using the International Prostate Symptom Score (IPSS), quality of life (QoL), uroflowmetry parameters, Male Sexual Health Questionnaire-Ejaculation Dysfunction-Short Form (MSHQ-EjD-SF) scores, and maintenance of anterograde ejaculation. Results: This study analyzed 22 and 20 patients who underwent TV-RASP and US-RASP, respectively. Except for the TV-RASP group being older (70.0 years) than the US-RASP group (64.5 years) (p=0.028), no differences among other baseline characteristics existed. Perioperative outcomes indicated that hospital stay and catheterization time were significantly shorter in the US-RASP group than in the TV-RASP group (p<0.001). At postoperative month 1, the median IPSS and QoL scores were significantly better in the US-RASP group than in the TV-RASP group (p=0.001 and p=0.002, respectively). However, at months 6 and 12, no significant differences were noted in IPSS, QoL, maximum flow rate, and postvoid residual urine between the two groups. Sexually active patients in the US-RASP group maintained postoperative MSHQ-EjD functional and bother scores, whereas the TV-RASP group experienced a decline. Notably, 75.0% of patients in the US-RASP group preserved antegrade ejaculation, compared to only 20.0% in the TV-RASP group (p<0.001). Conclusions US-RASP is not inferior to TV-RASP in terms of functional outcomes. In addition, US-RASP yielded more rapid symptom improvements and preserved antegrade ejaculation than TV-RASP. However, larger prospective studies are required to confirm these findings and to further investigate the long-term efficacy and safety of US-RASP.

Background: Respiratory infections play a major role in acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study assessed the prevalence of bacterial and viral pathogens and their clinical impact on patients with AECOPD. Methods: This retrospective study included 1,186 patients diagnosed with AECOPD at 28 hospitals in South Korea between 2015 and 2018. We evaluated the identification rates of pathogens, basic patient characteristics, clinical features, and the factors associated with infections by potentially drug-resistant (PDR) pathogens using various microbiological tests. Results: Bacteria, viruses, and both were detected in 262 (22.1%), 265 (22.5%), and 129 (10.9%) of patients, respectively. The most common pathogens included Pseudomonas aeruginosa (17.8%), Mycoplasma pneumoniae (11.2%), Streptococcus pneumoniae (9.0%), influenza A virus (19.0%), rhinovirus (15.8%), and respiratory syncytial virus (6.4%). Notably, a history of pulmonary tuberculosis (odds ratio [OR], 1.66; p=0.046), bronchiectasis (OR, 1.99; p=0.032), and the use of a triple inhaler regimen within the past 6 months (OR, 2.04; p=0.005) were identified as significant factors associated with infection by PDR pathogens. Moreover, patients infected with PDR pathogens exhibited extended hospital stays (15.9 days vs. 12.4 days, p=0.018) and higher intensive care unit admission rates (15.9% vs. 9.5%, p=0.030). Conclusion This study demonstrates that a variety of pathogens are involved in episodes of AECOPD. Nevertheless, additional research is required to confirm their role in the onset and progression of AECOPD.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Purpose: Smoking may have a protective role in developing ulcerative colitis (UC) but have the opposite effect on Crohn’s disease (CD). This study aimed to determine the risk of developing inflammatory bowel disease (IBD) according to smoking status and onset age of smoking. Materials and Methods: We collected data on the smoking experiences of participants aged 20–39 years who underwent biannual examinations provided by the Korean National Health Screening Program from 2009 to 2012. IBD diagnosis was identified using the National Health Insurance Service. The risk of IBD according to smoking status and onset age of smoking was analyzed after adjusting for major clinical variables. Results: During a median 10.59-year follow-up, the risk of UC in ex-smokers was significantly higher than that in non-smokers, and the earlier ex-smokers started smoking, the higher risk of UC [ex-smokers whose onset age of smoking was <20 years, adjusted hazard ratio (aHR) 1.928, 95% confidence interval (CI)=1.649–2.255; 20–24 years, aHR 1.728, 95% CI=1.541–1.939; 25–29 years, aHR 1.676, 95% CI=1.489–1.887; ≥30 years, aHR 1.226, 95% CI=1.010–1.486]. The risk of UC was significantly lower in current smokers whose onset age of smoking was 25–29 years than in non-smokers (aHR 0.825, 95% CI=0.709–0.959). The risk of CD did not differ according to smoking status and onset age of smoking. Conclusion Ex-smokers who started smoking at a young age have a high risk of UC, even after adjusting for the smoking amount.

Background: s/Aims: Radiofrequency ablation (RFA) is widely employed for managing recurrent hepatocellular carcinoma (HCC) following transarterial chemoembolization (TACE). However, local tumor progression (LTP) after treatment remains a significant challenge. This study evaluates the efficacy of saline-perfused bipolar RFA using twin internally cooled-perfusion (TICP) electrodes in managing recurrent HCC post-TACE. Methods: Between September 2017 and January 2019, 100 patients with 105 nodules (mean diameter, 1.6±0.5 cm) were prospectively enrolled. Bipolar RFA with TICP electrodes was performed under ultrasound-computed tomography/magnetic resonance fusion guidance. The primary outcome was the 2-year cumulative incidence of LTP. Results: The technical success and technique efficacy rates were 100% and 97%, respectively. During a median follow-up period of 34.0 months (range, 3-41), the estimated LTP rates were 13.3% at 1 year and 17.7% at 2 years. Progression-free survival rates were 37.8% and 27.7% at 1 year and 2 years, respectively. Conclusions Saline-perfused bipolar RFA using TICP electrodes demonstrates promising results for recurrent HCC after TACE, achieving high technical success and effective local tumor control rates.

Purpose: Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain. Materials and Methods: We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021. Results: Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding. Conclusion Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.

Objective: Several miRNAs have been identified as differentially expressed in patients with poor ovarian response (POR) compared to those with normal responses. This study aims to assess the potential of serum miR-329-3p as a biomarker for diagnosing POR. Methods: We conducted a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to confirm the target genes of miR-329-3p. KGN cells were transfected with both miR-329-3p mimic and inhibitor to assess the differential expression of these target genes. In accordance with the Bologna criteria, we enrolled 16 control patients and 16 patients with POR. We collected patient samples, including serum from day 2 and the human chorionic gonadotropin (hCG) day, as well as granulosa and cumulus cells, to validate the expression of miR-329-3p using quantitative real-time polymerase chain reaction. Results: KEGG pathway analysis revealed that miR-329-3p targeted adenylyl cyclase 9 (ADCY9) and protein kinase A subunit beta (PRKACB), both of which are involved in ovarian steroidogenesis. In KGN cells treated with a miR-329-3p mimic, ADCY9 and PRKACB expression levels were significantly reduced (p<0.05). Elevated levels of miR-329-3p suppressed aromatase expression and 17β-estradiol production by modulating ADCY9 and PRKACB in KGN cells. These effects were also observed in POR patients. Follicle-stimulating hormone receptor (FSHR) expression was diminished in the granulosa cells of POR patients. On day 2, on hCG day, and in granulosa cells, miR-329-3p exhibited high expression levels in the serum of POR patients. Conclusion miR-329-3p exhibited increased expression in granulosa cells and in the sera of POR patients. Consequently, we propose that miR-329-3p may be a potential biomarker for the diagnosis of POR.