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: The aim of this study was to examine whether a combined exercise (EX), including aerobic, resistance, and inspiratory muscle training, reduces fatigue and dyspnea, improves physical fitness, and if increased physical fitness after exercise is associated with attenuating symptoms in young adults with mild long coronavirus disease (COVID) symptoms. Methods: Twenty-eight young adults (aged 23±4 years) with long COVID were randomly assigned to either the EX group (n=14), which underwent aerobic, resistance, and inspiratory muscle training three times per week for 8 weeks, or the control (CON) group (n=14). Symptoms of dyspnea and fatigue were assessed using self-report questionnaires.Cardiorespiratory fitness was directly measured during cardiopulmonary exercise testing, while muscle strength was measured by isokinetic muscle testing. These variables were measured before and after the exercise intervention. Results: Compared to the CON group, the EX group showed improvements in symptoms of fatigue and dyspnea, maximal oxygen consumption (VO2peak ), and peak torque, with significant interaction effects observed (p＜ 0.05). The EX group exhibited a mean difference of 2.9 mL/kg/min in VO2peak (95% confidence interval [CI], 1.8−4.0) and 13.0 Nm (95% CI, 6.1−19.8) in peak torque compared to the CON group (p＜0.05). Improvements in VO2peak were negatively associated with attenuations in both fatigue and dyspnea after the exercise intervention (p＜0.05). Conclusion These findings indicate that EX training can effectively alleviate symptoms and improve physical fitness in young adults with mild long COVID. Structured exercise training may serve as an effective intervention to improve the health of those with long COVID.

Purpose: Identifying and managing risk factors for lower urinary tract symptoms (LUTS) is crucial because it impacts the quality of life of elderly individuals. Lifestyle factors, including physical activity (PA), and their relationship with LUTS have not been well studied. This objective of this study was to investigate the association between PA and LUTS. Materials and Methods: A total of 7,296 men were included in this cross-sectional study. PA was quantified in metabolic equivalent (MET)-hours per week, and LUTS severity was assessed using the international prostate symptom score. Logistic regression was used to analyze the association between PA and LUTS, including voiding and storage symptoms. Results: The average age of the participants was 57.8 years, and the prevalence of LUTS was 41.3%. After adjusting for potential confounders, PA was inversely associated with the prevalence and severity of moderate-to-severe LUTS, showing a dose-response pattern (all p for trend <0.01). Compared to the minimal activity group, which engaged in <5 MET-hours per week of PA, the odds ratios for moderate to severe LUTS were 0.83 (95% confidence interval [CI]: 0.72–0.97) for men engaging in 15–30 MET-hours per week, 0.82 (95% CI: 0.71–0.95) for 30–60 MET-hours per week, and 0.72 (95% CI: 0.62–0.84) for ≥60 MET-hours per week. The possible protective effect of PA was still observed in the additional analysis for voiding and storage symptoms showing the same dose-response pattern (all p for trend <0.01). Conclusions A higher PA level was associated with a lower prevalence and severity of total, voiding, and storage LUTS in a dose-dependent manner in Korean men.

BACKGROUND: Osteoporosis, characterized by decreased bone mineral density due to an imbalance between osteoblast and osteoclast activity, poses significant challenges in bone healing, particularly in postmenopausal women. Current treatments, such as bisphosphonates, are effective but associated with adverse effects like medication-related osteonecrosis of the jaw, necessitating safer alternatives. METHODS: This study investigated the use of L-serine-incorporated gelatin sponges for bone regeneration in calvarial defects in an ovariectomized rat model of osteoporosis. Thirty rats were divided into three groups: a control group, a group treated with a gelatin sponge containing an amino acid mixture, and a group treated with a gelatin sponge containing L-serine. Bone regeneration was assessed using micro-computed tomography (micro-CT) and histological analyses. RESULTS: The L-serine group showed a significant increase in bone volume (BV) and bone area compared to the control and amino acid groups. The bone volume to total volume (BV/TV) ratio was also significantly higher in the L-serine group.Immunohistochemical analysis demonstrated that L-serine treatment suppressed the expression of cathepsin K, a marker of osteoclast activity, while increasing serine racemase activity. CONCLUSION These findings suggest that L-serine-incorporated gelatin sponges not only enhance bone formation but also inhibit osteoclast-mediated bone resorption, providing a promising and safer alternative to current therapies for osteoporosis-related bone defects. Further research is needed to explore its clinical applications in human patients.

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: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Background and Objectives: The aim of this study was to confirm the effect of intralesional triamcinolone acetonide injections (TRIAM) to treat granulomatous tissue surrounding the tracheostomy stoma.Subjects and Method We reviewed and documented the medical charts of 20 patients who were administered with TRIAM to treat granulomatous tissue surrounding the tracheostomy stoma from January 2018 to June 2019 were. The surface area of the granulomatous tissue was measured using Image J. The differences between the area of the granulomatous tissue after conventional treatment and after TRIAM on the same patient were compared. Results: A total of 20 patients consisting of 12 males and 8 females were included, with the patients’ average age being 60.0±14.3 years. The initial surface area of granulation tissue was 1.266±0.449 cm2, and 1.243±0.432 cm2 after conventional treatment, showing no statistically significant difference in the tissue area (p=0.143). The pre-injection surface area of granulation tissue was 1.243±0.432 cm2, and the area on the 7th day after the third injection was 0.477±0.217 cm2, showing a significant difference (p<0.001). Conclusion Compared to the conventional treatment, the surface area of granulomatous tissue surrounding the tracheostomy stoma significantly decreased after being treating with TRIAM. This finding suggests the effectiveness of TRIAM as a treatment of granulomatous tissue surrounding the tracheostomy stoma without complications such as bleeding.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Objective: To assess the performance of novel qualitative diagnostic criteria using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to identify the pathologic complete response (pCR) of primary tumors in esophageal cancer after neoadjuvant chemoradiation (nCRT). Materials and Methods: Patients who underwent nCRT, subsequent MRI, positron emission tomography/computed tomography (PET/CT), endoscopy, or esophagectomy for esophageal cancer between October 2021 and October 2023 were retrospectively analyzed. The DCE-MRI response of primary tumors was interpreted using five grades by thoracic radiologists as follows: G1 (compatible with CR), G2 (probable CR), G3 (probable partial response [PR]), G4 (compatible with PR), and G5 (stable or progressive disease). The performances of MRI, PET/CT, endoscopy, and their combinations in diagnosing pCR in primary tumors were calculated. Results: A total of 52 patients (male:female, 46:6; age, 61.2 ± 8.0 years) were included. Surgical specimens revealed pCR (ypT0) in 34 patients. G1 as the MRI criterion for pCR of primary tumors yielded a positive predictive value (PPV), specificity of 100% (18/18), and low sensitivity (23.5% [8/34]). Combining G1 and G2 as the MRI criteria increased the sensitivity to 73.5% (25/34), with a specificity of 88.9% (16/18), accuracy of 78.8% (41/52), and PPV of 92.6% (25/27). Adding the DCEMRI results (G1-2) significantly improved accuracy for both PET/CT (from 65.4% [34/52] to 80.8% [42/52], P = 0.03) and endoscopy (from 55.8% [29/52] to 76.9% [40/52], P = 0.005), with increase in sensitivity (from 55.9% [19/34] to 82.4% [28/34] for PET/CT-based evaluation [P = 0.008] and from 47.1% [16/34] to 82.4% [28/34] for endoscopy-based evaluation [P = 0.001]). Conclusion DCE-MRI-based grading shows high diagnostic performance for identifying pCR in primary tumors, particularly in terms of PPV and specificity, and enhances response evaluation when combined with PET/CT and endoscopy.