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Postmenopausal syndrome refers to symptoms caused by the gradual decrease in female hormones after mid-40 years. As a target organ of estrogen, decrease in estrogen causes various changes in brain function such as a decrease in choline acetyltransferase and brain-derived neurotrophic factor, thus, postmenopausal women experience cognitive decline and more depressive symptoms than age-matched men. Radix Polygalae has been used for memory boosting and as a mood stabilizer and its components have shown neuroprotective, antidepressant, and stress relief properties. In a mouse model of estrogen depletion induced by 4-vinylcyclohexene diepoxide, Radix Polygalae was orally administered for 3 weeks. In these animals, cognitive and depression-related behaviors and molecular changes related to these behaviors were measured in the prefrontal cortex and hippocampus. Radix Polygalae improved working memory and contextual memory and despair-related behaviors in 4-vinylcyclohexene diepoxide-treated mice without increasing serum estradiol levels in this model. In relation to these behaviors, choline acetyltransferase and brain-derived neurotrophic factor in the prefrontal cortex and hippocampus and bcl-2-associated athanogene expression increased in the hippocampus. These results implicate the possible benefit of Radix Polygalae in use as a supplement of estrogen to prevent conditions such as postmenopausal depression and cognitive decline.

Purpose: The purpose of this study was to identify the influence of posttraumatic growth and health promoting behavior on quality of life (QOL) of patients with gastrointestinal cancer.Methods: The study was a cross-sectional, descriptive design. Participants were 142 patients with gastrointestinal cancer who were seen at Dongnam Institute of Radiological & Medical Sciences in Busan. Data were analyzed using descriptive statistics, t-test, one-way ANOVA, and multiple regression analysis with SPSS/WIN 23.0 program.Results: The results show that QOL had a significant correlation with posttraumatic growth (r=.24, p=.004) and health promoting behavior (r=.49, p

Background Evidence regarding the risk of cancer development after asthma diagnosis is controversial and inconclusive. Objective This study sought to determine whether asthma is associated with an increased risk for incident cancer. Methods Two independent, population-based, longitudinal cohorts were examined, and estimated hazard ratios were determined using Cox regression. One group consisted of an unmatched cohort of 475,197 participants and a propensity score–matched cohort of 75,307 participants from the National Health Insurance Service–National Sample Cohort (NHIS-NSC; claims-based data from 2003 to 2015). The other group consisted of 5,440 participants from the Ansan-Ansung cohort (interview-based data from 2001 to 2014). Results The NHIS-NSC matched cohort had 572,740 person-years of follow-up, 6,885 people with new asthma diagnoses, and 68,422 people without asthma diagnoses. Adults with asthma had a 75% greater risk of incident cancer overall. The excess risk for incident cancer was greatest during the first 2 years after asthma diagnosis, and this risk remained elevated throughout follow-up. Patients with nonatopic asthma had a greater risk of overall cancer than those with atopic asthma. A high cumulative dose of inhaled corticosteroids among asthma patients was associated with a 56% reduced risk of lung cancer, but had no effect on the risk of overall cancer. The results from the NHIS-NSC unmatched cohort and the Ansan-Ansung cohort were similar to the primary results from the NHIS-NSC matched cohort. Conclusions Asthma development was associated with an increased risk of subsequent cancer in 2 different Korean cohorts. Our findings provide an improved understanding of the pathogenesis of asthma and its relationship with carcinogenesis and suggest that clinicians should be aware of the higher risk of incident cancer among patients with asthma.

Eun Kyung Kim,1 Mi-Ae Kim,1 Jae Seung Lee,2 Sang Min Lee,3 Soyeoun Lim,4 Jisoo Park,1 Jung-Hyun Kim,1 Yeon-Mok Oh,2 Sang-Do Lee,2 Se Hee Lee,1 Ji-Hyun Lee1 On behalf of the KOLD Study Group1Department of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea; 2Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 3Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; 4Department of Radiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of KoreaCorrespondence: Ji-Hyun LeeDepartment of Pulmonology, Allergy and Critical Care Medicine, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam, 13496, Republic of KoreaTel +82-31-780-5205Fax +82-31-780-2992Email plmjhlee@cha.ac.krPurpose: Bronchiectasis (BE) is a poor prognostic factor in COPD. However, it is not clear whether the poor prognosis is a result of BE alone or accompanying chronic bronchitis symptoms. Therefore, we investigated the effect of chronic bronchitis symptoms on clinical outcomes in COPD patients with BE.Patients and Methods: We analyzed data of COPD patients from the Korean Obstructive Lung Disease (KOLD) cohort. The presence of BE was verified by chest computed tomography. Chronic bronchitis symptoms were determined using items in the symptomatic domain of the SGRQ, which is also used as an alternative definition of chronic bronchitis (CB). Patients were divided into four groups according to the presence of BE and CB symptoms: BE/CB, BE-only, CB-only, and no BE/CB. Demographic features and clinical outcomes were compared among these groups.Results: In total, 389 COPD patients were included in the analysis. BE was present in 148 (38%) patients and CB symptoms were found in 123 patients (33.2%). The patients were divided according to BE and CB symptoms, and the numbers and percentages of each group were as follows: BE/CB, 52 (13.4%); BE-only, 96 (24.7%); CB-only, 77 (19.8%); no BE/CB, 164 (42.2%). No significant differences were observed in baseline characteristics of lung function, radiological findings, and inflammatory markers among the four groups. The proportion of annual exacerbators was higher in the BE/CB and CB-only groups than the other two groups. After adjusting other parameters, the BE/CB group was significantly associated with acute exacerbation of COPD (AE-COPD) (OR = 2.110, p = 0.045).Conclusion: BE accompanying CB symptoms is associated with AE-COPD, while BE alone was not significantly associated. This finding suggests that it is more important to examine chronic bronchitis symptoms of BE to predict acute exacerbation than simply to identify BE in COPD patients.Keywords: COPD, bronchiectasis, chronic bronchitis, exacerbation

Purpose We compared clinical characteristics of COPD patients according to symptom variability and evaluated the effect of symptom variability during the first year of enrollment on clinical outcomes of COPD. Methods We analyzed COPD patients' data from the Korean Obstructive Lung Disease (KOLD) cohort. Symptom variability was defined based on the value of standard deviation (SD) of mMRC scores obtained every 3 months during the follow-up period of the first year. Patients were divided into 2 groups: the consistent (SD of mMRC scores =0) and variable (SD of mMRC scores >0) groups. Clinical characteristics and outcomes were compared in terms of symptom variability. Results A total of 407 patients were included in the analysis. Patient age was 67.2 years and 97.8% of the subjects were male. Initial mMRC was 1.5 and the SD of mMRC scores during the first year was 0.5. There were 137 subjects (33.7%) in the consistent group and 270 (66.3%) in the variable group. The variable group showed a lower FEV1 (P=0.019) and a higher mMRC score (P=0.001). The annual incidence of acute exacerbation of COPD (AE-COPD) tended to be higher in the variable group (P=0.078) and that of severe AE-COPD was higher in the variable group than in the consistent group (P=0.002). The variable group showed a higher proportion of annual exacerbators (P=0.001) and frequent exacerbators (P=0.017). In multivariate logistic regression analysis, the variable group was significantly associated with annual exacerbators (OR =1.963, P=0.011) and frequent exacerbators (OR =2.090, P=0.055). Conclusion COPD patients with symptom variability may have higher exacerbation risk as well as lower lung function and more severe respiratory symptoms.

Although the proteasome inhibitor (PI) bortezomib (Btz) is in current clinical use as a front-line treatment for multiple myeloma, its clinical efficacy in solid tumors has not been satisfactory. Here, we show that loperamide (Lop), an antidiarrheal drug, effectively sensitizes various colon cancer cells, but not normal epithelial cells, to PI-mediated cell death. We report that combined treatment with Btz and Lop induces paraptosis-like cell death accompanied by severe endoplasmic reticulum (ER)-derived vacuolation. Furthermore, Lop potentiates Btz-mediated ER stress and ER dilation due to misfolded protein accumulation and Ca2+ imbalance, leading to CHOP upregulation and subsequent paraptosis-like cell death. Taken together, our results show for the first time that a combined regimen of PI and Lop may provide an effective and safe therapeutic strategy against solid tumors, including colon cancer, by enhancing the sensitivity to PIs and reducing the side effects of such treatment.

Purpose We aimed to determine the demographic and epidemiologic variables that are associated with no treatment in lung cancer patients. Materials and methods Patient data were collected from the Korean National Health Insurance Database. The lung cancer group included patients with an initial diagnosis of lung cancer between January 2009 and December 2014. Treated cases were defined as those that underwent surgery, radiation, or chemotherapy until death, after the diagnosis of lung cancer. Risk of no treatment was calculated by multiple logistic regression analysis. Results Among the 2148 new cases of lung cancer from 2009 to 2104, 612 (28.4%) were not treated. Risk of no treatment was higher in the following patients: patients in their 60s (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.75 to 1.84), 70s (OR, 3.64; 95% CI, 2.41 to 5.50), and >80 years old (OR, 16.55; 95% CI, 10.53 to 25.03) than those in their 50s; patients with previous myocardial infarction (OR, 2.07; 95% CI, 1.01 to 4.25) or chronic kidney disease (OR, 2.88; 95% CI, 1.57 to 5.30); and patients diagnosed at a non-referral hospital (OR, 1.40; 95% CI, 1.01 to 1.92) or primary care provider (OR, 1.81; 95% CI, 1.43 to 2.29) compared with referral hospital. Low-income patients receiving Medicaid were 1.75 times (95% CI, 1.14 to 2.68) more likely to forgo treatment than high-income patients (upper 20%). Risk was not associated with sex or the year in which the lung cancer was diagnosed. Conclusion Age predominantly determines whether patients with lung cancer undergo anti-cancer treatment.

Background & Aims Patients with or without cancers who undergo major gastrointestinal surgery suffer from malnutrition due to their catabolic status during the postoperative period. In this study, we evaluated the effect of the clinical application of protein-enhanced diet using mealworms in patients who underwent hepato-pancreato-biliary surgeries. Methods This study was designed as a prospective, two-armed, and double-blinded phase III study. The target number of enrolled patients was 216, and the patients were randomized on a 1:1 basis, either to the trial group (consuming mealworms) or to the control group (consuming grain powder). The primary endpoint was to examine the changes in body composition, including phase angle. For secondary outcomes, the activities of immune cells were evaluated using the patients’ blood samples. Results No difference in the demographic characteristics of patients was observed. The ratio of the actual protein intake to the recommended daily intake in the trial group was significantly higher than that in the control group (110.03% vs. 98.80%, p=0.023). In the data on body composition measured by InBody S-10, the ratios in body cell mass, fat free mass, muscle mass, and phase angle at the study endpoint compared to those at admission showed no statistically significant difference between the two groups. Immune cell analyses suggested that cytotoxic T cells in the trial group had higher activity than in the study group (1.192 vs. 0.974, p=0.028). Conclusions In this study, protein-enhanced diet using mealworms clinically improved the activity of immune cells. However, it did not significantly improve the patients’ nutritional status after they experienced hepato-pancreato-biliary surgeries.

Lipopolysaccharide (LPS)-binding protein (LBP) is an acute-phase reactant that mediates innate immune responses triggered by LPS. Recent studies indicated a positive correlation of circulating LBP level with chronic low-grade inflammation, a condition present in many non-communicable diseases. We determined the association of serum LBP concentration with allergic sensitization in a general pediatric population. Serum LBP was measured in a sample of children (n = 356; mean age = 9.6 ± 0.2 years) in this population-based cross-sectional study. Skin prick tests (SPTs) were performed to assess allergic sensitization to 22 common inhalant and food allergens. One hundred and seven children (30.1%) were nonsensitized, 160 (44.9%) were monosensitized, and 89 (25.0%) were polysensitized. Children who were mono- or polysensitized had a significantly higher median serum LBP level (25.5 ng/mL, inter-quartile range [IQR] 20.3–30.7) than those who were nonsensitized (20.3 ng/mL, IQR = 14.81–25.8, P P = 0.016), with sensitization to food allergens in particular (aOR 1.080, 95% CI 1.029–1.133, P = 0.002), but not with sensitization to aeroallergens (aOR 1.010, 95% CI 0.982–1.040, P = 0.467). LBP level was not associated with allergic diseases after adjustment. We suggest the possibility of sensitization to food allergens may be related to gut-derived low-grade inflammation, and large sized longitudinal investigations are needed to elucidate the relationship.

Background Phthalates can cause respiratory and immunological disorders. However, little is known about the role of serum periostin and YKL-40 levels in mediating the effects of phthalates. We investigated the mediating role of these biomarkers in the relationship between phthalates and airway dysfunction. Methods A total of 487 children (aged 10 to 12 years-old) were examined. Four high-molecular-weight phthalate (HMWP) [Σ4 HMWP] metabolites and 3 low-molecular-weight phthalate (LMWP) [Σ3 LMWP] metabolites in urine samples were measured. Serum periostin and YKL-40 levels were measured. Airway function was measured using impulse oscillometry. A mediation model was used to quantify the mediating effects of periostin and YKL-40 on airway dysfunction. Results After adjustment for height, gender, BMI z-score, aeroallergen sensitization, secondary smoking, and vitamin D level, the level of urinary Σ3 LMWP metabolites was significantly associated with respiratory system resistance at 5 Hz (Rrs5; adjusted β: 0.020, 95% CI: 0.005 to 0.034; P = .010). The levels of urinary Σ4 HMWP and Σ3 LMWP metabolites were significantly associated with periostin level, but not with YKL-40 level. In addition, the periostin level was associated with Rrs5 (adjusted β: 0.048, 95% CI: 0.015 to 0.081; P = .005) and Rrs20-5 (adjusted β: 0.040, 95% CI: 0.011 to 0.069; P =.007). Serum periostin level had a significant effect in mediating the relationship between Σ3LMWP and Rrs5 (13.9%, 95% CI: 10.7 to 77.0; P Conclusion Exposure to LMWPs was significantly associated with airway dysfunction, and this effect was partially attributable to increased serum periostin level.

Background: Low body mass index (BMI) is an important prognostic factor in chronic obstructive pulmonary disease (COPD). However, the prognostic value of longitudinal BMI change in COPD has not been well studied. Objective: We aimed to evaluate the association between longitudinal change of BMI and prognosis of COPD in Korean COPD cohort. Methods: This study was conducted in a prospective Korean Obstructive Lung Disease (KOLD) cohort where COPD patients were recruited on an outpatient basis at 17 hospitals in South Korea. Annual BMI was measured over a period of 3 years or more. All patients were categorized into underweight (UW), normal weight (NW), and overweight (OW) groups by BMI. Clinical characteristics and outcomes including exacerbation and mortality were compared based on initial BMI grade and longitudinal change of BMI. Results: This analysis included 537 COPD patients (mean age = 67.4 ± 7.9 years, male = 97.0%, mean BMI = 23.0 ± 3.1) of KOLD cohort. The proportions of UW, NW, and OW groups were 6.9% (n = 37), 68.9% (n = 370), and 24.2% (n = 130) respectively. The UW group showed lower forced expiratory volume in 1 s (FEV1) (p < 0.001), shorter 6-minute walk distance (p < 0.001), higher modified Medical Research Council score (p = 0.002), higher St. George Respiratory Questionnaire score (p < 0.001), higher emphysema index (p < 0.001) and air-trapping index (p < 0.001), and more frequent (p < 0.001) and severe exacerbations (p = 0.003). Multivariable analyses demonstrated that decrease of BMI (hazard ratio [HR] = 0.786, p = 0.038) and the descent of BMI group (HR = 3.167, p = 0.016) at 3-year follow-up along with age, initial BMI, post-bronchodilator FEV1, and severe exacerbations were significantly associated with mortality. Conclusions: This study demonstrated that BMI decrease during follow-up was independently associated with exacerbation and higher mortality of COPD, suggesting BMI reduction in COPD should be carefully managed.

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H₁-antihistamines, even though the dose of H₁-antihistamines is increased up to 4-fold. CSU that is not controlled with H₁-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H₁-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.

Introduction Allergic rhinitis (AR) is immunologically and morphologically related to disorders in the lower airway. We investigated the relationship between the anatomy of the intranasal cavity and small airway resistance in subjects with nonallergic rhinitis (NAR). Methods We enrolled 226 children who were 7 years old and participated in the Seongnam Atopy Project 2016. We evaluated nasal patency using acoustic rhinometry to measure the volume of the nasal cavity at 0-5 cm, and measured lung function of the lower airway using an impulse oscillometry system (IOS) and spirometry. We also performed skin prick tests for 18 aero-allergens, and measured blood total eosinophil counts (TEC) and rhinitis symptom scores for the previous month using a visual analog scale (VAS, range: 0-10). Results We examined 226 children, 71 (31.7%) with AR, and 62 (27.7%) with NAR. Nasal patency in children with AR (median: 8.28 mm3 , IQR: 7.07-9.83) was lower than that of healthy children (median: 9.3 mm3 , IQR: 7.69-10.64, P = 0.011). Multivariate regression analysis showed that nasal patency was inversely associated with IOS resistance at 5 Hz after adjustment for compounding factors (B = -0.005, SE = 0.0032, P = 0.041). Analysis of NAR subjects, according to quartiles of nasal patency and quartiles of small airway resistance (Rrs5), indicated that nasal patency decreased as Rrs5 increased (linear trend: P = 0.020). Conclusion Nasal symptoms and TEC negatively correlated with nasal patency. Children with AR and NAR who had poor nasal patency had increased small airway resistance.

Background: Solar irradiation affects sensitization to aeroallergens and the prevalence of allergic diseases. Little is known, however, about how the time and amount of solar irradiation during pregnancy affects such risks in children. We aimed to find out how solar irradiation during pregnancy affects sensitization to aero-allergens and the prevalence of allergic diseases in children. Methods: This population-based cross-sectional study involved 7301 aged 6 years and aged 12 years children. Maternal exposure to solar irradiation during pregnancy was evaluated using data from weather stations closest to each child's birthplace. Monthly average solar irradiation during the second and third trimesters was calculated with rank by quartiles. Risks of allergic sensitization and allergic disease were estimated. Results: Relative to the first (lowest) quartile, the adjusted odds ratio (aOR) for allergic sensitization in the fourth (highest) quartile was lowest within solar irradiation during pregnancy months 5–6 (aOR = 0.823, 95% CI 0.720–0.942, p

Background It is unclear as to whether sleep respiratory breathing disorder (SRBD) is a risk factor for uncontrolled asthma in children. The aim of this study was therefore to investigate whether SRBD may have an adverse effect on childhood asthma control and lung function measures. Methods This was a cross-sectional study of 220 children with well-controlled (n = 108), partly controlled (n = 92), and uncontrolled asthma (n = 20) according to the Global Initiative for Asthma guideline. SRBD was assessed using the Pediatric Sleep Questionnaire (PSQ). The association of SRBD with partly controlled/uncontrolled asthma was investigated on multivariate logistic regression analysis. Results Of 220 children with asthma, 43 (19.6%) had SRBD: well-controlled, 16.7% (18/108); partly controlled, 21.7% (20/92); and uncontrolled, 25.0% (5/20; P = 0.54). There was a significant difference in forced expiratory volume in 1 s/forced vital capacity (FEV1 /FVC; P = 0.007) and childhood asthma control test (C-ACT) score (P 0.33) had a lower C-ACT score compared with controls (PSQ ≤0.33; 19.6 ± 5.1 vs 22.0 ± 4.2, P = 0.002). PSQ score was negatively correlated with FEV1 /FVC (r = -0.16, P = 0.02). On multivariate logistic regression analysis, high PSQ score increased the odds of having partly controlled/uncontrolled asthma by 9.12 (95% CI: 1.04-79.72, P = 0.046) after adjusting for confounding factors. Conclusion SRBD is an independent risk factor for partly controlled/uncontrolled asthma and has an adverse effect on lung function measures in children. Further research is warranted to determine whether the improvement of sleep quality may also enhance level of asthma control and lung function in children.

Objective: The prevalence of local allergic rhinitis (LAR) in nonatopic children remains unknown. This study aimed to determine the prevalence, clinical characteristics, and severity of LAR in children in comparison to classical allergic rhinitis (AR) and nonallergic rhinitis (NAR). Study Design: A total of 145 children (aged 1-18 years) were enrolled and classified into 3 groups (AR, NAR, and LAR) based on a skin prick test (SPT) and a nasal provocation test (NPT) with house dust mite, i.e., Dermatophagoides pteronyssinus. NPT positivity was defined as a symptom score ≥2 standard deviations (SDs) above the healthy control score. Results: Eighty-one children had AR (55.9%), and 64 (44.1%) had symptoms of rhinitis with negative SPT; 59 NAR (40.7%) and 5 LAR (3.4%) children were identified. The κ score for agreement between the SPT and the NPT results was 0.778 (95% CI 0.726-0.830, p < 0.001). A significant correlation was observed between wheal diameter and maximum nasal symptom score provoked by D.pteronyssinus (rho = 0.589, p < 0.001). Nasal severity according to the ARIA guideline did not show any differences in the 3 groups (p = 0.693). The AR group was older than the LAR and NAR groups (AR > LAR > NAR, p = 0.003). Conclusions: Despite the evidence to support the existence of LAR in pediatric populations, we found that its prevalence was relatively low, possibly due to the high rate of agreement between SPT and NPT. Further investigations are needed to identify immunological as well as clinical implications of LAR.

PURPOSE To assess if color measurement with intraoral scanner correlates with digital colorimeter and to evaluate the possibility of application of a digital scanner for shade selection. MATERIALS AND METHODS The L*a*b* values of the five shade tabs (A1, A2, A3, A3.5, and A4) were obtained with an intraoral scanner (TRIOS Pod) and a colorimeter (ShadeEye). Both devices were calibrated according to the manufacturer's instructions before measurements. Color measurement values were compared with paired t-test, and a Pearson's correlation analysis was performed to evaluate the relationship of two methods. RESULTS The L*a*b* values of the colorimeter were significantly different from those of the digital scanner (p < 0.001). The L* and b* values of both methods were strongly correlated with each other (both p < 0.05). The device repeatability in both methods were reported to be excellent (p < 0.05). Within the limitations of this study, color measurements with digital intraoral scanners and computer-assisted image analysis were in accordance with those of the colorimeter with respect to L* and b* values; however, all the coordinates of shade tabs were significantly different between two methods. CONCLUSIONS The digital intraoral scanner may not be used as the primary method of color selection in clinical practices, considering significant differences in color parameters with colorimeter. The scanner's capability in shade selection should be further evaluated.

INTRODUCTION Rhinitis and obstructive sleep apnea syndrome (OSAS) are different diseases, but have some similar risk factors. OBJECTIVE The aims of this study were to compare the risk factors and clinical biomarkers for rhinitis and OSAS in children. METHODS We examined 3917 children (age 4-13 years) who were enrolled in a cross-sectional study conducted in Seongnam, Korea. Their parents completed the Pediatric Sleep Questionnaire (PSQ) for evaluation of OSAS and the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire for evaluation of rhinitis. Clinical biomarkers, including total eosinophil count and neutrophil-lymphocyte ratio (NLR), were measured in a subset of these children. RESULTS OSAS and rhinitis had prevalences of 4.0% and 43.5%, respectively. Body mass index (P < 0.001) and prematurity (P = 0.016) were significantly associated with OSAS, but not with rhinitis. Higher parental education and income increased the risk for rhinitis, but decreased the risk for OSAS. Having more siblings and birth by Cesarean delivery decreased the risk for rhinitis, but living in a new household increased the risk for rhinitis. A short distance of the residence to a main road during pregnancy significantly increased the risk of OSAS. Males, increased exposure to mould, and firstborns had increased risk of OSAS and rhinitis. The NLR was higher in OSAS patients than in those with allergic rhinitis (P = 0.001). CONCLUSION OSAS and rhinitis shared some risk factors, whereas other factors had inverse association with the two disorders. These results imply that different strategies might be used for prevention of rhinitis and OSAS.

Pneumonia severity index (PSI) is an important scoring system that can assess the severity of community acquired pneumonia and determine admission status. However, there is a lack of research on whether this scoring system can be applied to viral community acquired pneumonia. The purpose of this study was to evaluate the usefulness of PSI in viral community acquired pneumonia. This retrospective cohort study included 1,434 adult patients (aged ≥18 years) who were admitted to the emergency department of a university hospital during 2013-2015 because of community-acquired pneumonia. Viral infections were diagnosed by multiplex PCR. Patients diagnosed with non-viral community-acquired pneumonia were included in the control group (N = 1,173). The main outcome was 30-day all-cause mortality. multivariate Cox regression analyses were performed to calculate the risk of death. Respiratory viruses were detected in 261 (18.2%) patients with community-acquired pneumonia. Two types of respiratory viruses were detected in 7 cases. Of the 254 cases detected with only one virus, 62 were influenza A, 18 were influenza B, 65 were rhinovirus, 35 were respiratory syncytial virus, 25 were metapneumovirus, 20 were parainfluenza, 17 were coronavirus, 7 were bocavirus, and 5 were adenovirus. Mortality was not significantly different between patients with respiratory virus and those without respiratory virus; the 30-day all-cause mortality rates were 20.3% and 22.4%, respectively (P = 0.45). Mortality rate increased with an increasing PSI score with or without respiratory viral infection. Pulmonary severity index was significantly associated with mortality adjusted for respiratory virus detection (hazard ratio = 1.024, 95% confidence interval = 1.020-1.028). Pneumonia severity index score is an important factor for assessing the prognosis of patients with community-acquired pneumonia, regardless of respiratory virus detection.

In the era of novel coronavirus epidemics, vaccines against coronavirus disease 2019 (COVID-19) have been recognized as the most effective public health interventions to control the pandemic. An adverse event following immunization (AEFI) is defined as any untoward occurrence following immunization, and the majority of AEFIs are caused by protective immune responses stimulated by vaccines. Most of the reported AEFIs are not serious, and many are not immunologically mediated or even reproducible on re-exposure. However, uncommon severe allergic adverse reactions, such as anaphylaxis or other allergic reactions, can occur after vaccinations. Confirmed allergic reactions to vaccines may be caused by residual non-human protein, preservatives, or stabilizers in the vaccine formulation (also known as excipients). There are 2 main potential allergenic/immunogenic excipients in COVID-19 vaccines, polyethylene glycol (PEG) and polysorbate 80. PEG, also known as macrogol, is an ingredient in various laxatives and injectable formulations, such as depot steroids. Polysorbate 80 is present in various medical products, creams, ointments, lotions, and medication tablets. Contraindications to the administration of COVID-19 vaccines include a previous history of severe allergic reactions to the first dose of COVID-19 vaccine or proven hypersensitivity to a vaccine component, such as PEG or polysorbate 80. Anaphylaxis or other allergic reactions following immunization can cause fear and loss of confidence in the safety of vaccines among the public. A better understanding of these events is thought to help alleviate concerns about the current COVID-19 vaccines and provide reassurance to the general population by analyzing the exact incidence of anaphylaxis and potential risk factors. COVID-19 vaccine-associated anaphylaxis could be prevented and managed by risk stratification based on our local and global experience.

Background Soluble inflammatory mediators are known to exacerbate sepsis-induced acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) has been suggested to play a part in immunomodulation by cytokine removal. However, the effect of continuous venovenous hemodiafiltration (CVVHDF) dose on inflammatory cytokine removal and its influence on patient outcomes are not yet clear. Study Design Prospective, randomized, controlled, open-label trial. Setting & Participants Septic patients with AKI receiving CVVHDF for AKI. Intervention Conventional (40mL/kg/h) and high (80mL/kg/h) doses of CVVHDF for the duration of CRRT. Outcomes Patient and kidney survival at 28 and 90 days, circulating cytokine levels. Results 212 patients were randomly assigned into 2 groups. Mean age was 62.1 years, and 138 (65.1%) were men. Mean intervention durations were 5.4 and 6.2 days for the conventional- and high-dose groups, respectively. There were no differences in 28-day mortality (HR, 1.02; 95% CI, 0.73-1.43; P =0.9) or 28-day kidney survival (HR, 0.96; 95% CI, 0.48-1.93; P =0.9) between groups. High-dose CVVHDF, but not the conventional dose, significantly reduced interleukin 6 (IL-6), IL-8, IL-1b, and IL-10 levels. There were no differences in the development of electrolyte disturbances between the conventional- and high-dose groups. Limitations Small sample size. Only the predilution CVVHDF method was used and initiation criteria were not controlled. Conclusions High CVVHDF dose did not improve patient outcomes despite its significant influence on inflammatory cytokine removal. CRRT-induced immunomodulation may not be sufficient to influence clinical end points.

Purpose This study intended to introduce new approaches to identify the intellectual structure of supply chain management(SCM) researches, which combines author co-citation analysis(ACA) and social network analysis(SNA). Design/methodology/approach We searched RISS(www.riss.kr) and NDSL(www.ndsl.or.kr) database and collected 292 academic papers on supply chain management between 2001 and 2011. Among 9,637 references of these papers, we analyzed 1,848 references that were published by domestic authors. We produced a correlation matrix of 32 author co-citation matrix and conducted multi-variate statistical analysis such as factor analysis. We also performed social network analysis to identify the main researchers in SCM. Findings We found four main sub-areas of supply chain management research: SCM adoption factors, logistics, SCM performance, and SCM structure. We could present the authors who played important roles within the network by using SNA indicators. The finding of this research also suggests more collaborations among domestic researchers are required to overcome the low co-citation rates among domestic authors.

Background: Although the prevalence of anaphylaxis is increasing worldwide, the large-scale studies in Asia evaluating anaphylaxis in all age groups are limited. We aimed to collect more precise and standardized data on anaphylaxis in Korea using the first multicenter web-based registry. Methods: Twenty-two departments from 16 hospitals participated from November 2016 to December 2018. A web-based case report form, designed by allergy specialists, was used to collect anaphylaxis data. Results: Within the 2-year period, 558 anaphylaxis cases were registered. The age of registered patients ranged from 2 months to 84 years, and 60% were aged

Severe asthma (SA) presents in about 3%-5% of adult asthmatics and is responsible for over 60% of asthma-related medical expenses, posing a heavy socioeconomic burden. However, to date, a precise definition of or clear diagnostic criteria for SA have not been established, and therefore, it has been challenging for clinicians to diagnose and treat this disease. Currently, novel biologics targeting several molecules, such as immunoglobulin E, interleukin (IL)5, and IL4/IL13, have emerged, and many new drugs are under development. These have brought a paradigm shift in understanding the mechanism of SA and have also provided new treatment options. However, we need to agree on a precise definition of and its diagnostic criteria for SA. Additionally, it is necessary to explain the diagnostic criteria and to summarize current standard and additional treatment options. This review is an experts' opinion on SA from the Korean Academy of Asthma, Allergy, and Clinical Immunology, the Working Group on Severe Asthma, and aims to provide a definition of and diagnostic criteria for SA, and propose future direction for SA diagnosis and management in Korea.

Purpose Anaphylaxis is an immediate allergic reaction characterized by potentially life-threatening, severe, systemic manifestations. While studies have evaluated links between serious illness and posttraumatic stress disorder (PTSD), few have investigated PTSD after anaphylaxis in adults. We sought to investigate the psychosocial burden of recent anaphylaxis in Korean adults. Methods A total of 203 (mean age of 44 years, 120 females) patients with anaphylaxis were recruited from 15 university hospitals in Korea. Questionnaires, including the Impact of Event Scale-Revised-Korean version (IES-R-K), the Korean version of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Beck Depression Inventory (K-BDI), were administered. Demographic characteristics, causes and clinical features of anaphylaxis, and serum inflammatory markers, including tryptase, platelet-activating factor, interleukin-6, tumor necrosis factor-α, and C-reactive protein, were evaluated. Results PTSD (IES-R-K ≥ 25) was noted in 84 (41.4%) patients with anaphylaxis. Of them, 56.0% had severe PTSD (IES-R-K ≥ 40). Additionally, 23.2% and 28.1% of the patients had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17), respectively. IES-R-K was significantly correlated with both K-BAI (r = 0.609, P < 0.0001) and K-BDI (r = 0.550, P < 0.0001). Among the inflammatory mediators, tryptase levels were lower in patients exhibiting PTSD; meanwhile, platelet-activating factor levels were lower in patients exhibiting anxiety and depression while recovering from anaphylaxis. In multivariate analysis, K-BAI and K-BDI were identified as major predictive variables of PTSD in patients with anaphylaxis. Conclusions In patients with anaphylaxis, we found a remarkably high prevalence of PTSD and associated psychological distresses, including anxiety and depression. Physicians ought to be aware of the potential for psychological distress in anaphylactic patients and to consider psychological evaluation.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

PURPOSE: Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergy in pollinosis patients caused by raw fruits and vegetables and is the most common food allergy in adults. However, there has been no nationwide study on PFAS in Korea. In this study, we investigated the prevalence and clinical characteristics of PFAS in Korea. METHODS: Twenty-two investigators participated in this study, in which patients with allergic rhinoconjunctivitis and/or bronchial asthma with pollen allergy were enrolled. The questionnaires included demographic characteristics, a list of fruits and vegetables, and clinical manifestations of food allergy. Pollen allergy was diagnosed by skin prick test and/or measurement of the serum level of specific IgE. RESULTS: A total of 648 pollinosis patients were enrolled. The prevalence of PFAS was 41.7% (n = 270). PFAS patients exhibited cutaneous (43.0%), respiratory (20.0%), cardiovascular (3.7%) or neurologic symptoms (4.8%) in addition to oropharyngeal symptoms. Anaphylaxis was noted in 8.9% of the PFAS patients. Seventy types of foods were linked to PFAS; e.g., peach (48.5%), apple (46.7%), kiwi (30.4%), peanut (17.4%), plum (16.3%), chestnut (14.8%), pineapple (13.7%), walnut (14.1%), Korean melon (12.6%), tomato (11.9%), melon (11.5%) and apricot (10.7%). Korean foods such as taro/taro stem (8.9%), ginseong (8.2%), perilla leaf (4.4%), bellflower root (4.4%), crown daisy (3.0%), deodeok (3.3%), kudzu root (3.0%) and lotus root (2.6%) were also linked to PFAS. CONCLUSIONS: This was the first nationwide study of PFAS in Korea. The prevalence of PFAS was 41.7%, and 8.9% of the PFAS patients had anaphylaxis. These results will provide clinically useful information to physicians.

Background Respiratory syncytial virus (RSV) infection constitutes a substantial disease burden in the general population. However, the risk of death for RSV infection has been rarely evaluated with confounders or comorbidities adjusted. We aimed to evaluate whether RSV infection is associated with higher mortality than seasonal influenza after adjusting for confounders and comorbidities and the effect of oseltamivir on the mortality in patients with influenza infection. Methods A retrospective cohort study was conducted on adult (≥18 years) patients admitted to the emergency department and ward of a university teaching hospital for suspected viral infection during 2013–2015 (N = 3743). RSV infection was diagnosed by multiplex PCR (N = 87). Adults hospitalized for seasonal influenza during the study period were enrolled as a comparison group (n = 312). The main outcome was 20-day all-cause mortality.We used Cox proportional hazard regression analyses to calculate the relative risk of death. Results Adult patients were less likely to be diagnosed with RSV than with influenza (2.3 vs 8.3%, respectively), were older and more likely to be diagnosed with pneumonia, chronic obstructive pulmonary disease, hypoxemia, and bacterial co-infection. In patients with RSV infection, the 20-day all-cause mortality was higher than that for influenza, (18.4 vs 6.7%, respectively). RSV infection showed significantly higher risk of death compared to the seasonal influenza group, with hazard ratio, 2.32 (95% CI, 1.17–4.58). Oseltamivir had no significant effect on mortality in patients with influenza. Conclusions RSV infection was significantly associated with a higher risk of death than seasonal influenza, adjusted for potential confounders and comorbidities.

Purpose: The objective of the present study was to evaluate the effects of occupational exposure to low dose organic solvents on the prevalence of cardiovascular risk factors. Methods: Study design was retrospective cohort study subjected on 191 exposures and 118 controls working in a petrochemical manufacture company. The eight indicators related to CVD risk were followed up for five years from 2008 to 2012. The risk level was compared during the follow up years and subject’s characteristics, and the change of risk level were analyzed with repeated measures ANOVA and multiple logistic regression analysis. Results: At the start year 2008, the rate over cutoff value (ROCV) of BS (p

Background: The presence of bronchiectasis in patients with COPD is considered to be associated with severe airflow obstruction, frequent exacerbation and a higher degree of functional impairment. So, we evaluated the incidence of bronchiectasis on high-resolution computed tomography scan (HRCT) in a longitudinal cohort of COPD patients and its clinical characteristics and prognostic value. Methods: We analyzed 479 COPD patients enrolled in the Korean Obstructive Lung Disease (KOLD) cohort. Patients were divided into two groups based on the presence of bronchiectasis on HRCT. The severity of bronchiectasis was evaluated using the modified Bhalla score. Severe bronchiectasis was defined as modified Bhalla score ≥ 5.5. Results: Bronchiectasis was present in 187 (39.0%) patients. No differences were found between the groups for lung function, dyspnea, exacerbation, and mortality. However, COPD patients with severe bronchiectasis were older with lower BMI, lower serum albumin level, lower FEV1, lower diffusing capacity, higher MMRC and SGRQ score, higher emphysema index, and lower muscle mass. A multivariate Cox regression analysis revealed that age (p Conclusions: Our data support that severe bronchiectasis, not the presence of bronchiectasis was associated with severe airflow obstruction, higher emphysema index, nutritional and functional impairment. Severe bronchiectasis may be considered as a significant prognostic factor in patients with COPD.

Background Serum periostin might be a biomarker of the pathogenesis of T helper 2–type allergic diseases. The aim of this study is to investigate the relationship between serum periostin levels and the severity and chronicity of atopic dermatitis (AD) in children. Methods This population-based study examined 4,076 children from aged 4 to 13 years between June 2015 and July 2015. Of the 4,076 children, 196 including 137 with a history of AD in the AD group and 59 without allergic diseases history in the healthy control (HC) group were included for the final analysis. Results Serum periostin levels were higher in the AD group than in the HC group (P < 0.001) and were found to be positively associated with SCORAD score (Spearman's rho [r] = 0.24, P = 0.001). Children with AD onset time < 2 years had significantly higher periostin levels (P = 0.030) compared to those with AD onset time ≥ 2 years. The total eosinophil (P = 0.189) and IgE levels (P = 0.140) were comparable between children with AD onset time < 2 years and those with AD onset time ≥ 2 years. After adjustment for age, gender, and parental allergic history, serum periostin level (OR 1.03, 95% CI 1.00 - 1.06, P = 0.046) contributed to the development of AD in children with AD onset time < 2 years. Conclusion Serum periostin level may play a role in the severity and chronicity of AD in children. This article is protected by copyright. All rights reserved.

Objective.To investigate the repeatability and safety of measuring impulse oscillation system (IOS) parameters and the point of wheezing during bronchoprovocation testing of preschool children.Methods.Two sets of methacholine challenge were conducted in 36 asthma children. The test was discontinued if there was a significant change in reactance (Xrs5) and resistance (Rrs5) at 5 Hz (Condition 1) or respiratory distress due to airway obstruction (Condition 2). The repeatability of PC80_Xrs5, PC30_Rrs5, and wheezing (PCw) was assessed. The changes inZ-scores and SD-indexes from prebaseline (before testing) to postbaseline (after bronchodilator) were determined.Results.For PC30_Rrs5, PC80_Xrs5, and PCw for subjects, PC80_Xrs5 showed the highest repeatability. Fifteen of 70 tests met Condition2. The changes from pre- and postbaseline values varied significantly for Rrs5 and Xrs5. Excluding subjects withZ-scores higher than 2SD, we were able to detect 97.1% of bronchial hyperresponsiveness during methacholine challenge based on the change in Rrs5 or Xrs5. A change in IOS parameters was associated with wheezing at all frequencies.Conclusion. Xrs5 and Rrs5 have repeatability comparable with FEV1, and Xrs5 is more reliable than Rrs5. Clinicians can safely perform a challenge test by measuring the changes in Rrs5, Xrs5, andZ-scores from the prebaseline values.

Purpose Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. Methods A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. Results Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. Conclusions Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two.

Recent studies recommend periostin as a systemic biomarker of eosinophilic airway inflammation to predict responses to novel treatments that targets eosinophilic TH2-driven inflammation in asthmatic patients.To investigate the clinical implications of serum periostin levels in patients with aspirin-exacerbated respiratory disease (AERD) based on its overlapping TH2-mediated pathogenesis with the eosinophilic asthma.Serum periostin levels were measured by human periostin enzyme-linked immunosorbent assay (ELISA) in serum samples from 277 adults with asthma. Serum periostin levels were compared between patients with AERD and aspirin tolerant asthma (ATA) with other asthma phenotypes, such as severe or nonsevere asthma and eosinophilic or noneosinophilic asthma. The association of serum periostin levels with clinical parameters (including disease severity and comorbid condition) was analyzed.Serum periostin levels were significantly higher in patients with AERD vs ATA, patients with severe asthma vs nonsevere asthma, and patients with eosinophilic asthma vs noneosinophilic asthma (P=.005, P=.02, and P=.001, respectively). Multivariate regression analysis revealed serum periostin levels as a significant parameter to predict AERD phenotype (P=.006) together with severe asthma phenotype (P=.04). In addition, serum periostin levels correlated with blood eosinophil counts (Spearman ñ = 0.244, P.001) and sputum eosinophil counts (Spearman ñ = 0.261, P0.001). Higher serum periostin levels were noted in comorbid AERD patients with more severe chronic rhinosinusitis (Lund-Mackay stages 3 and 4) than those with less severe chronic rhinosinusitis (Lund-Mackay stages 1 and 2) (P = .03).Serum periostin levels are significantly elevated in AERD patients and associated with AERD phenotype and disease severity.

Allergen-specific immunotherapy (SIT) reduces allergen specific IgE (sIgE) levels and achieves clinical and immunological tolerance by modulating innate and adaptive immunological responses. Increased temperature and CO2 concentrations caused by climate changes contribute to an increase of pollen count and allergenicity that influences clinical SIT outcomes. In this study, we investigated the changes of IgE binding components to tree and weed pollens in pollinosis patients who showed a paradoxical increase of serum sIgE level during pollen-SIT. We enrolled nine patients who showed an increasing pattern of serum sIgE level to alder, birch, ragweed and mugwort pollens by enzyme-linked immunosorbant assay. IgE immunoblot analysis confirmed the intensification or new generation of major IgE binding components that could be induced by climate change. The findings suggest that the regular monitoring of sIgE levels and symptom changes is required to improve the clinical outcomes of SIT in patients undergoing SIT for tree and weed pollens. Graphical Abstract

Tissue transglutaminase (tTG) is a post-translational modifying enzyme located in airway epithelial cells. A potential contribution of serum specific IgG (sIgG) to tTG in airway inflammation of toluene diisocyanate (TDI)-induced occupational asthma (OA) has been suggested.To prepare a TDI-tTG conjugate and detect serum specific antibodies in sera of patients with TDI-OA to understand this mechanism.Ninety-nine patients with TDI-OA, 76 asymptomatic exposed controls, 208 patients with non-OA, and 74 unexposed controls were enrolled for this study. The TDI-tTG conjugate was prepared and confirmed by a native gel. Serum sIgG and/or sIgE antibodies to tTG, TDI-tTG, TDI conjugated to human serum albumin, cytokeratin 19, and serum cytokine levels, such as interleukin-8, transforming growth factor-β1, and tissue inhibitor of metalloproteinase-1, were measured by enzyme-linked immunosorbent assay. The level of interleukin-8 produced from airway epithelial cells (A549) treated with tTG was evaluated to investigate the inflammatory effect of tTG and TDI-tTG.In the TDI-OA group, the prevalence of serum sIgG to TDI-tTG (17.2%) was higher than that of sIgG to tTG (11.1%), which were significantly higher than those of the 3 control groups (P.05 for all groups). TDI-exposed subjects with high levels of serum sIgG to TDI-tTG had a high prevalence of sIgG to cytokeratin 19 and higher serum levels of transforming growth factor-β1 and tissue inhibitor of metalloproteinase-1. The tTG and TDI-tTG dose-dependently increased interleukin-8 production from A549 cells.These findings suggest that TDI exposure in the workplace binds to tTG to form a conjugate that can induce serum sIgG antibody production, airway inflammation, and airway remodeling in patients with TDI-OA.

Ultrasonic welding is faster, environmental friendly, and more efficient than conventional welding. Ultrasonic welding stack, the key part in ultrasonic welding equipment, is composed of transducer, booster, and horn. In the case of ultrasonic welding, wear in the welding tips or breakage of horn occurs because ultrasonic vibration of tips is transmitted directly to the welding material. If grinding of the tips is repeated several times, the mass of horn is reduced and the frequency characteristic is changed. So, there is a limit to refurbishment. In additions, as materials of horn are relatively expensive, some cost problems could be occurred for replacing horns. This study, in order to reduce the manufacturing cost of horn, devised a tip-replaceable ultrasonic horn so that its tip can be easily replaced whenever it is worn. For the designed shape, natural frequency and vibration mode are analyzed using FEA. Through the FEA, the optimal tip-replaceable horn with resonance frequency of 40 kHz is proposed.

The aim of this study was to discover small-molecule anticoagulants from Scolopendra subspinipes mutilans (SSM). A new acylated polyamine (1) and a new sulfated quinoline alkaloid (2) were isolated from SSM. Treatment with the new alkaloids 1, 2, and indole acetic acid 4 prolonged the activated partial thromboplastin time and prothrombin time and inhibited the activity and production of thrombin and activated factor X. Furthermore, compounds 1, 2, and 4 inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In accordance with these potential in vitro antiplatelet activities, compounds 1, 2, and 4 showed enhanced antithrombotic effects in an in vivo pulmonary embolism and arterial thrombosis model. Compounds 1, 2, and 4 also elicited anticoagulant effects in mice. Collectively, this study may serve as the groundwork for commercializing SSM or compounds 1, 2, and 4 as functional food components for the prevention and treatment of pathogenic conditions and serve as new scaffolds for the development of anticoagulants.