Bakuchicin alleviates ovalbumin-induced allergic asthma by regulating M2 macrophage polarization.

OBJECTIVE: Asthma is an airway inflammatory disease caused by activation of numerous immune cells including macrophages. Bakuchicin (BKC) is known to exhibit anti-inflammatory effects and type 2 T helper (Th2) regulation, but has not been investigated for airway inflammation. This study aimed to evaluate the effects of BKC on airway inflammation and demonstrate the mechanisms of macrophage polarization. METHODS: The anti-inflammatory effects were determined using lipopolysaccharide (LPS)-stimulated macrophages. The ovalbumin (OVA)-induced asthma mouse model was used to evaluate the effects of BKC on airway inflammation and Th2 responses. Moreover, the effect of BKC on macrophage polarization was confirmed in bone marrow-derived macrophages (BMDMs) differentiation. RESULTS: BKC suppressed nitric oxide production and expression of pro-inflammatory cytokines by inhibiting signaling pathway in LPS-stimulated macrophages. In an OVA-induced asthma model, BKC treatment alleviated histological changes and mast cell infiltration and reduced the levels of eosinophil peroxidase, ß-hexosaminidase, and immunoglobulin levels. In addition, BKC alleviated Th2 responses and M2 macrophage populations in bronchoalveolar fluid. In BMDMs, BKC suppressed IL-4-induced M2 macrophage polarization and the expression of M2 markers such as arginase-1 and Fizz-1 through inhibiting sirtuin 2 levels. CONCLUSION: BKC could be a drug candidate for the treatment of allergic asthma.

Association of early-onset diabetes, prediabetes and early glycaemic recovery with the risk of all-cause and cardiovascular mortality.

AIMS/HYPOTHESIS: The increasing incidence of diabetes among young adults is a disease burden; however, the effects of early-onset diabetes, prediabetes and glycaemic recovery on CVD or mortality remain unclear. We aimed to investigate the association of these factors with 10 year all-cause mortality, CVD mortality and CVD incidence in Korean young adults. METHODS: This large and longitudinal cohort study included data from the Korean National Health Insurance Service-National Health Information Database; 2,502,375 young adults aged 20-39 years without diabetes mellitus and CVD at baseline were included. Glycaemic status was measured twice, first in 2002-2003 and second in 2004-2005. Changes in fasting glucose levels were evaluated according to fasting glucose status: normal fasting glucose (NFG; <5.5 mmol/l), impaired fasting glucose (IFG; 5.5-6.9 mmol/l), and diabetic fasting glucose (DFG; ≥7.0 mmol/l). Primary outcomes were all-cause and CVD mortality risk. The secondary outcome was incidence of CVD, including acute myocardial infarction and stroke. All outcomes arose from the 10 year follow-up period 1 Jan 2006 to 31 December 2015. RESULTS: Individuals with NFG at baseline, who were subsequently newly diagnosed with diabetes and prediabetes (IFG), had increased all-cause mortality (HR [95% CI] 1.60 [1.44, 1.78] and 1.13 [1.09, 1.18], respectively) and CVD incidence (1.13 [1.05, 1.23] and 1.04 [1.01, 1.07], respectively). In those with DFG at baseline, early recovery to NFG and IFG was associated with decreased all-cause mortality (0.57 [0.46, 0.70] and 0.65 [0.53, 0.81], respectively) and CVD incidence (0.70 [0.60, 0.81] and 0.78 [0.66, 0.91], respectively). Among patients with IFG at baseline, early recovery to NFG was associated with decreased CVD mortality (0.74 [0.59, 0.93]). CONCLUSIONS/INTERPRETATION: Early-onset diabetes or prediabetes increased CVD risks and all-cause mortality after the 10 year follow-up. Furthermore, recovery of hyperglycaemia could reduce the subsequent 10 year risk for CVD incidence and all-cause mortality. Graphical abstract.

Breast cancer screening disparities between women with and without disabilities: A national database study in South Korea.

BACKGROUND: Health disparities among individuals with disabilities remain underrecognized. The objective of the current study was to investigate: 1) whether disparities exist in breast cancer screening rates among women with disabilities compared with women without disabilities; 2) whether breast cancer screening rates vary according to the type and severity of disabilities; and 3) trends in breast cancer screening disparities according to disability status over time. METHODS: Using national administrative databases concerning disability status and national cancer screening programs in Korea, age-standardized participation rates were calculated according to the type and severity of disabilities. RESULTS: The age-standardized rate for breast cancer screening in individuals with disabilities increased from 30.2% in 2006 to 53.7% in 2015 (change of +23.5%), whereas that among those without a disability increased from 29.3% to 60.1% (change of +30.8%). In general, disability was associated with slightly lower breast cancer screening rates (adjusted odds ratio [aOR], 0.824; 95% CI, 0.820-0.828). However, screening rates were especially low in women with severe disabilities (aOR, 0.465; 95% CI, 0.461-0.469) and among women with autism (aOR, 0.235; 95% CI, 0.143-0.388), renal failure (aOR, 0.342; 95% CI, 0.337-0.348), brain injury (aOR, 0.349; 95% CI, 0.346-0.352), intellectual disabilities (aOR, 0.403; 95% CI, 0.397-0.410), mental disorders (aOR, 0.494; 95% CI, 0.488-0.501), or ostomies (aOR, 0.529; 95% CI, 0.512-0.546). CONCLUSIONS: Even without a cost barrier, significant disparities were found in breast cancer screening participation, especially in women with severe disabilities and brain-related and/or mental disabilities. Policy efforts, such as ensuring the accessibility of information and equipment, transportation support, and access to a usual source of care, should be made to decrease this disparity.

Income differences in screening, incidence, postoperative complications, and mortality of thyroid cancer in South Korea: a national population-based time trend study.

BACKGROUND: The incidence of thyroid cancer (TC) has increased rapidly over the past few decades in Korea. This study investigated whether the TC epidemic has been driven by overdiagnosis. METHODS: We calculated the TC screening rate from mid-2008 through mid-2014, and the incidence, postoperative complication, and mortality rates of TC between 2006 and 2015, using data from the Korea Community Health Survey, the National Health Insurance Database, and the cause-of-death data of Statistics Korea. Trends in age-standardized rates of all indicators were examined, along with income gaps therein. Analyses were conducted for lung cancer and stroke as negative control outcomes. RESULTS: The incidence rate of TC increased from 46.6 per 100,000 to 115.0 per 100,000 between 2006 and 2012, and then decreased to 63.5 per 100,000 in 2015. Despite these remarkable changes in incidence, mortality did not fluctuate during the same period. High income was associated with high rates of screening, incidence, and postoperative complications, while low income showed an association with a high mortality rate. Analyses using negative control outcomes showed that high income was associated with low rates of both incidence and mortality, which contrasted with the patterns of TC. The recent decreases in TC incidence and postoperative complications, which reflect societal concerns about the overdiagnosis of TC, were more pronounced in high-income individuals than in low-income individuals. CONCLUSIONS: The time trends in income gaps in screening, incidence, postoperative complications, and mortality of TC, as well as negative control outcomes, provided corroborating evidence of TC overdiagnosis in Korea.

AGK2 ameliorates mast cell-mediated allergic airway inflammation and fibrosis by inhibiting FcεRI/TGF-ß signaling pathway.

Asthma is characterized by airway hyperresponsiveness and allergic inflammation, detrimentally affecting the patients' quality of life. The development of new drugs for the treatment of asthma is warranted to alleviate these issues. Recent studies have demonstrated that sirtuin2 (SIRT2) aggravates asthmatic inflammation by up-regulation of T-helper type 2 responses and macrophage polarization. However, effects of SIRT2 on mast cell activation remain obscure. In this study, we investigated the effects of AGK2, an inhibitor for SIRT2, on mast cell-mediated allergic airway inflammation. Pre-treatment with AGK2 inhibited degranulation of mast cells by suppressing the FcεRI signaling pathway and intracellular calcium influx. The expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-4, IL-5, IL-6, and IL-8, was inhibited via regulation of transcription factors such as NF-κB and NRF2. These effects of AGK2 were verified in passive cutaneous anaphylaxis and acute lung injury animal models. AGK2 attenuated Evans blue pigmentation by inhibiting mast cell activation and lung barrier dysfunction by inhibiting inflammatory responses in these animal models. In the ovalbumin (OVA)-induced allergic airway inflammation murine model, AGK2 alleviated allergic asthma symptoms such as lung histological changes (immune cell and mast cell infiltration, collagen deposition, and α-smooth muscle actin expression) and serum immunoglobulins (Ig) levels (IgE, OVA-specific IgE, IgG1, and IgG2a). Moreover, AGK2 reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-4, IL-5, and IL-6) and inflammatory mediators (myeloperoxidase, eosinophil peroxidase, and tumor growth factor-α) in the bronchoalveolar lavage fluid and lung tissues. In addition, the anti-fibrotic effects of AGK2 were verified using lung epithelial cells and TGF-ß/Smad reporter stable cells. In conclusion, our findings suggest that SIRT2 plays a role in mast cell-mediated airway inflammatory disease. Therefore, AGK2 is a good potential candidate for treating allergic asthma and lung inflammation.

Income-related inequality in quality-adjusted life expectancy in Korea at the national and district levels.

BACKGROUND: The aim of this study was to measure differences in quality-adjusted life expectancy (QALE) by income in Korea at the national and district levels. METHODS: Mortality rates and EuroQol-5D (EQ-5D) scores were obtained from the National Health Information Database of the National Health Insurance Service and the Korea Community Health Survey, respectively. QALE and differences in QALE among income quintiles were calculated using combined 2008-2014 data for 245 districts in Korea. Correlation analyses were conducted to investigate the associations of neighborhood characteristics with QALE and income gaps therein. RESULTS: QALE showed a graded pattern of inequality according to income, and increased over time for all levels of income and in both sexes, except for low-income quintiles among women, resulting in a widened inequality in QALE among women. In all 245 districts, pro-rich inequalities in QALE were found in both men and women. Districts with higher QALE and smaller income gaps in QALE were concentrated in metropolitan areas, while districts with lower QALE and larger income gaps in QALE were found in rural areas. QALE and differences in QALE by income showed relatively close correlations with socioeconomic characteristics, but relatively weak correlations with health behaviors, except for smoking and indicators related to medical resources. CONCLUSIONS: This study provides evidence of income-based inequalities in health measured by QALE in all subnational areas in Korea. Furthermore, QALE and differences in QALE by income were closely associated with neighborhood-level socioeconomic characteristics.

Provider factors influencing prescriptions of recommended antihypertensive medications among patients with diabetes and hypertension
.

OBJECTIVE: Managing hypertension to prevent complications in patients with diabetes requires appropriate pharmacotherapy. This study aimed to analyze healthcare provider factors influencing prescriptions of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) as the first-line therapy in managing hypertension among patients with diabetes in primary care. MATERIALS: This study used National Health Insurance Claims Data in Korea. METHODS: We calculated the prescription rate of angiotensin-converting enzyme inhibitors (ACE inhibitors) or ARBs by dividing the number of patients prescribed an ACE inhibitor or an ARB by the number of patients with diabetes prescribed hypoglycemic agents and antihypertensive agents. We performed a logistic regression to investigate the factors influencing the prescription rate of ACE inhibitors or ARBs. RESULTS: The mean prescription rate of ACE inhibitors or ARBs was 69.8%. The prescription rate of ACE inhibitors or ARBs decreased with increasing physician and patient age. The rate was higher for male patients than for females. The rate was higher in institutions with a greater number of physicians and among internists than among general practitioners, surgery-related and internal medicine-related specialists. The rate was significantly influenced by the mean monthly number of patients with hypertension per medical institution, the number of physicians per medical institution, and the physician's age and specialty. CONCLUSION: The age and specialty of the prescribing physician influenced the use of ACE inhibitors or ARBs in patients with diabetes and hypertension in primary care. Efforts are needed to promote information exchange among physicians and the appropriate prescriptions of antihypertensive agents in patients with diabetes and hypertension in primary care.

Use of the National Health Information Database for Estimating Town-Level Mortality in Korea: Comparison with the National Administrative Data, 2014-2017.

BACKGROUND: This study addressed town-level mortality rates using the National Health Information Database (NHID) of the National Health Insurance Service in Korea in comparison with those derived from the National Administrative Data (NAD) of the Ministry of Interior and Safety. METHODS: We employed the NHID and NAD between 2014 and 2017. We compared the numbers of population and deaths at the national level between these two data sets. We also compared the distribution of the town-level numbers of population and deaths of the two data sets. Correlation analyses were performed to investigate the relation between the NHID and NAD in the town-level numbers of population and deaths, crude mortality rate, and standardized mortality ratio (SMR). RESULTS: The numbers of population and deaths in the NHID were almost identical to those in the NAD, regardless of gender. The distribution of the town-level numbers of population and deaths was also similar between the two data sets during the entire study period. Throughout the study period, the Pearson correlation coefficients between the two databases for the town-level numbers of population and deaths and the crude mortality rate were 0.996 or over. The correlation coefficients for the SMR ranged from 0.937 to 0.972. CONCLUSION: Town-level mortality showed significant correlation and concordance between the NHID and NAD. This result highlights the possibility of producing future analyses of town-level health-related indicators in Korea, including the mortality rate, using the NHID.

Patient factors that affect trust in physicians: a cross-sectional study.

BACKGROUND: While trust in physicians has been rigorously investigated regarding its concept, measurement, and factors, the studies have mainly focused on the attributes of the physicians. This approach can lead to a limited understanding of trust in physicians as trust is based on the relationship, an interaction of both parties: patients and physicians. This study aimed to investigate the factors for trust in physicians among the Koreans by focusing on patients' traits which are related to their subjective perceptions. METHODS: A web-based survey was conducted between August and September 2016 among 1000 Korean adults aged 18 to 59 years. Survey participants were selected by a proportionate quota sampling based on age, sex and place of residence. The t-test and analysis of variance (ANOVA) were performed to examine the difference in trust in physicians among the different groups in each variable of patient characteristics. An ordinal logistic regression model was employed to examine the association between trust in physicians and patient attributes. RESULTS: Negative health-related traits, such as stress and low self-rated health, were likely to lower trust in physicians, and women were less likely to trust physicians. The negative attitudes toward the current health care system were strongly associated with low trust in physicians. Meanwhile, recent experience of hospitalization or outpatient visit was positively associated with trust in physicians, and experience of not being able to use health facilities showed no significant association. These results suggest that trust in physicians is more likely to be lowered by negative perception than by the objective conditions or experience. CONCLUSION: In investigating the factors for trust in physicians, the patients' predispositions, which make them less likely to trust physicians, should be considered. The attributes of the patients in Korea, which could negatively affect trust in physicians, need to be investigated in consideration of the recent changes in patient-physician relationships and the medical environment in Korea.

Comparison of District-level Smoking Prevalence and Their Income Gaps from Two National Databases: the National Health Screening Database and the Community Health Survey in Korea, 2009-2014.

BACKGROUND: We compared age-standardized prevalence of cigarette smoking and their income gaps at the district-level in Korea using the National Health Screening Database (NHSD) and the Community Health Survey (CHS). METHODS: Between 2009 and 2014, 39,049,485 subjects participating in the NHSD and 989,292 participants in the CHS were analyzed. The age-standardized prevalence of smoking and their interquintile income differences were calculated for 245 districts of Korea. We examined between-period correlations for the age-standardized smoking prevalence at the district-level and investigated the district-level differences in smoking prevalence and income gaps between the two databases. RESULTS: The between-period correlation coefficients of smoking prevalence for both genders were 0.92-0.97 in NHSD and 0.58-0.69 in CHS, respectively. When using NHSD, we found significant income gaps in all districts for men and 244 districts for women. However, when CHS was analyzed, only 167 and 173 districts for men and women, respectively, showed significant income gaps. While correlation coefficients of district-level smoking prevalence from two databases were 0.87 for men and 0.85 for women, a relatively weak correlation between income gaps from the two databases was found. CONCLUSION: Based on two databases, income gaps in smoking prevalence were evident for nearly all districts of Korea. Because of the large sample size for each district, NHSD may provide stable district-level smoking prevalence and its income gap and thus should be considered as a valuable data source for monitoring district-level smoking prevalence and its socioeconomic inequality.

Prevalence of Overweight and Income Gaps in 245 Districts of Korea: Comparison Using the National Health Screening Database and the Community Health Survey, 2009-2014.

BACKGROUND: We compared age-standardized overweight prevalence and their income gaps at the level of district in Korea using the National Health Screening Database (NHSD) and the Community Health Survey (CHS). METHODS: We analyzed 39,093,653 subjects in the NHSD and 926,580 individuals in the CHS between 2009 and 2014. For the comparison of body mass index (BMI) distributions, data from 26,100 subjects in the Korea National Health and Nutrition Examination Survey (KNHANES) were also analyzed. We calculated the age-standardized overweight prevalence and its interquintile income gap at the district level. We examined the magnitudes of the between-period correlation for age-standardized overweight prevalence. The differences in overweight prevalence and its income gap between the NHSD and the CHS were also investigated. RESULTS: The age-adjusted mean BMI from the CHS was lower than those from the NHSD and the KNHANES. The magnitudes of the between-period correlation for overweight prevalence were greater in the NHSD compared to the CHS. We found that the district-level overweight prevalence in the NHSD were higher in all districts of Korea than in the CHS. The correlation coefficients for income gaps in overweight prevalence between the two databases were relatively low. In addition, when using the NHSD, the district-level income inequalities in overweight were clearer especially among women than the inequalities using the CHS. CONCLUSION: The relatively large sample size for each district and measured anthropometric data in the NHSD are more likely to contribute to valid and reliable measurement of overweight inequality at the district level in Korea.

Association of Blood Pressure Classification in Korean Young Adults According to the 2017 American College of Cardiology/American Heart Association Guidelines With Subsequent Cardiovascular Disease Events.

Importance: Among young adults, the association of the 2017 American College of Cardiology/American Heart Association (ACC/AHA) High Blood Pressure Clinical Practice Guidelines with risk of cardiovascular disease (CVD) later in life is uncertain. Objective: To determine the association of blood pressure categories before age 40 years with risk of CVD later in life. Design, Setting, and Participants: This population-based cohort study from the Korean National Health Insurance Service consisted of 2 488 101 adults aged 20 through 39 years with blood pressure measurements taken twice from 2002 through 2005. Starting from January 1, 2006, participants were followed up until the date of CVD diagnosis, death, or December 31, 2015. Exposures: Participants were categorized by blood pressure readings: normal (systolic, <120 mm Hg; diastolic, <80 mm Hg), elevated (sytolic, 120-129 mm Hg; diastolic, <80 mm Hg), stage 1 hypertension (systolic, 130-139 mm Hg; diastolic, 80-89 mm Hg), and stage 2 hypertension (systolic, ≥140 mm Hg; diastolic, ≥90 mm Hg). Main Outcomes and Measures: The primary outcome was CVD defined as 2 or more days of hospitalization due to CVD or death due to CVD. The secondary outcomes were coronary heart disease (CHD) and stroke. Results: The study population consisted of 2 488 101 participants (median age, 31 years [interquartile range, 27-36 years], 789 870 women [31.7%]). A total of 44 813 CVD events were observed during a median follow-up duration of 10 years. Men with baseline stage 1 hypertension compared with those with normal blood pressure had higher risk of CVD (incidence, 215 vs 164 per 100 000 person-years; difference, 51 per 100 000 person-years [95% CI, 48-55]; adjusted hazard ratio [HR], 1.25 [95% CI, 1.21-1.28]), CHD (incidence, 134 vs 103 per 100 000 person-years; difference, 31 per 100 000 person-years [95% CI, 28-33]; adjusted HR, 1.23 [95% CI, 1.19-1.27]), and stroke (incidence, 90 vs 67 per 100 000 person-years; difference, 23 per 100 000 person-years [95% CI, 21-26]; adjusted HR, 1.30 [95% CI, 1.25-1.36]). Women with baseline stage 1 hypertension compared with those with normal blood pressure had increased risk of CVD (incidence, 131 vs 91 per 100 000 person-years; difference, 40 per 100 000 person-years [95% CI, 35-45]; adjusted HR, 1.27 [95% CI, 1.21-1.34]), CHD (incidence, 56 vs 42 per 100 000 person-years; difference, 14 per 100 000 person-years [95% CI, 11-18]; adjusted HR, 1.16 [95% CI, 1.08-1.25]), and stroke (incidence, 79 vs 51 per 100 000 person-years; difference, 28 per 100 000 person-years [95% CI, 24-32]; adjusted HR [1.37, 95% CI, 1.29-1.46]). Results for state 2 hypertension were consistent. Conclusions and Relevance: Among Korean young adults, stage 1 and stage 2 hypertension, compared with normal blood pressure, were associated with increased risk of subsequent cardiovascular disease events. Young adults with hypertension, defined by the 2017 ACC/AHA criteria, may be at increased risk of cardiovascular disease.

Geographic Variation in Morbidity and Mortality of Cerebrovascular Diseases in Korea during 2011-2015.

BACKGROUND: Little is known about within-country variation in morbidity and mortality of cerebrovascular diseases (CVDs). Geographic differences in CVD morbidity and mortality have yet to be properly examined. This study examined geographic variation in morbidity and mortality of CVD, neighborhood factors for CVD morbidity and mortality, and the association between CVD morbidity and mortality across the 245 local districts in Korea during 2011-2015. METHODS: District-level health care utilization and mortality data were obtained to estimate age-standardized CVD morbidity and mortality. The bivariate Pearson correlation was used to examine the linear relationship between district-level CVD morbidity and mortality Z-scores. Simple linear regression and multivariate analyses were conducted to investigate the associations of area characteristics with CVD morbidity, mortality, and discrepancies between morbidity and mortality. RESULTS: Substantial variation was found in CVD morbidity and mortality across the country, with 1074.9 excess CVD inpatients and 73.8 excess CVD deaths per 100,000 between the districts with the lowest and highest CVD morbidity and mortality, respectively. Higher rates of CVD admissions and deaths were clustered in the noncapital regions. A moderate geographic correlation between CVD morbidity and mortality was found (Pearson correlation coefficient = .62 for both genders). Neighborhood level indicators for socioeconomic disadvantages, undersupply of health care resources, and unhealthy behaviors were positively associated with CVD morbidity and mortality and the relative standing of CVD mortality vis-à-vis morbidity. CONCLUSIONS: Policy actions targeting life-course socioeconomic conditions, equitable distribution of health care resources, and behavioral risk factors may help reduce geographic differences in CVD morbidity and mortality in Korea.

2-Hydroxy-3-methoxybenzoic acid attenuates mast cell-mediated allergic reaction in mice via modulation of the FcεRI signaling pathway.

Mast cells are important effector cells in immunoglobulin (Ig) E-mediated allergic reactions such as asthma, atopic dermatitis and rhinitis. Vanillic acid, a natural product, has shown anti-oxidant and anti-inflammatory activities. In the present study, we investigated the anti-allergic inflammatory effects of ortho-vanillic acid (2-hydroxy-3-methoxybenzoic acid, o-VA) that was a derivative of vanillic acid isolated from Amomum xanthioides. In mouse anaphylaxis models, oral administration of o-VA (2, 10, 50 mg/kg) dose-dependently attenuated ovalbumin-induced active systemic anaphylaxis and IgE-mediated cutaneous allergic reactions such as hypothermia, histamine release, IgE production and vasodilation; administration of o-VA also suppressed the mast cell degranulator compound 48/80-induced anaphylaxis. In cultured mast cell line RBL-2H3 and isolated rat peritoneal mast cells in vitro, pretreatment with o-VA (1-100 µmol/L) dose-dependently inhibited DNP-HSA-induced degranulation of mast cells by decreasing the intracellular free calcium level, and suppressed the expression of pro-inflammatory cytokines TNF-α and IL-4. Pretreatment of RBL-2H3 cells with o-VA suppressed DNP-HSA-induced phosphorylation of Lyn, Syk, Akt, and the nuclear translocation of nuclear factor-κB. In conclusion, o-VA suppresses the mast cell-mediated allergic inflammatory response by blocking the signaling pathways downstream of high affinity IgE receptor (FcεRI) on the surface of mast cells.

Using the National Health Information Database of the National Health Insurance Service in Korea for Monitoring Mortality and Life Expectancy at National and Local Levels.

This study explores whether the National Health Information Database (NHID) can be used to monitor health status of entire population in Korea. We calculated the crude mortality rate and life expectancy (LE) at birth across the national, provincial, and municipal levels using the NHID eligibility database from 2004 to 2015, and compared the results with the corresponding values obtained from the Korean Statistical Information Service (KOSIS) of Statistics Korea. The study results showed that the ratio of crude mortality rate between the two data was 0.99. The absolute difference between the LE of the two data was not more than 0.5 years, and did not exceed 0.3 years in gender specific results. The concordance correlation coefficients (CCC) between the crude mortality rates from NHID and the rates from KOSIS ranged 0.997-0.999 among the municipalities. For LE, the CCC between the NHID and KOSIS across the municipalities were 0.990 in 2004-2009 and 0.985 in 2010-2015 among men, and 0.952 in 2004-2009 and 0.914 in 2010-2015 among women, respectively. Overall, the NHID was a good source for monitoring mortality and LE across national, provincial, and municipal levels with the population representativeness of entire Korean population. The results of this study indicate that NHID may well contribute to the national health promotion policy as a part of the health and health equity monitoring system.

1,2,4,5-Tetramethoxybenzene Suppresses House Dust Mite-Induced Allergic Inflammation in BALB/c Mice.

BACKGROUND: Atopic dermatitis (AD) is the most common allergic inflammatory skin disease. The activation of innate immunity by house dust mite (Dermatophagoides farinae extract, DFE) allergen plays an important role in the pathogenesis of AD. We previously showed the inhibitory effect of an extract of Amomum xanthioides on allergic diseases, and isolated 1,2,4,5-tetramethoxybenzene (TMB) as a major active component. In this study, we investigated whether TMB relieves DFE-induced allergic inflammation symptoms. METHODS: We established a DFE-induced allergic inflammation model in BALB/c mice by repeated skin exposure to DFE. To define the underlying mechanisms of action, we used a tumor necrosis factor-α and interferon-x03B3;-activated human keratinocytes (HaCaT cell line) and mouse keratinocytes (3PC cell line) cell line model. RESULTS: Oral administration of TMB suppressed allergic inflammation symptoms, such as histopathological analysis and ear thickness, in addition to serum IgE, DFE-specific IgE and IgG2a levels. TMB decreased the serum histamine levels and tissue infiltration of inflammatory cells, including mast cells and eosinophils. TMB also inhibited CD4+IFN-x03B3;+, CD4+IL-4+, and CD4+IL-17A+ lymphocyte expansion in the draining lymph nodes and expression of the Th2 cytokines in the ear tissue. TMB significantly inhibited the expression of cytokines and chemokines by the downregulation of the mitogen-activated protein kinases and nuclear factor of activated cytoplasmic T cells in HaCaT cells. CONCLUSIONS: TMB improved DFE-induced allergic inflammation by suppressing the production of proinflammatory cytokines and chemokines. Our results suggest that TMB might be a potential therapeutic agent for AD.

Factors associated with the specialty choice of Korean medical students: a cross-sectional survey.

BACKGROUND: An imbalance of physician supply by medical specialty has been observed in most countries. In Korea, there is a greater tendency to avoid surgical specialties and specialty choices in nonclinical medicine, such as the basic science of medicine. In this study, we identified factors affecting the specialty choice of physicians in order to provide a basis for policies to address this problem. METHODS: We used the results of a 2013 nationwide survey of 12 709 medical students (82.7 % responded) to analyze the data of 9499 students after excluding missing data. Descriptive analyses of all students' specialty choice were performed. Logistic regression was performed by selecting gender, age, grade level, type of medical school, hometown, and the location of the medical school as the independent variables. Medical specialty was the dependent variable. The dependent variable, or specialty of medicine, was categorized into three groups: nonclinical/clinical medicine, surgical-medical specialty, and controllable lifestyle specialty. RESULTS: The order of preferred medical specialties was internal medicine, psychiatry, and pediatrics; for surgical specialties, the order was orthopedic surgery, general surgery, and ophthalmology. Medical specialties were most favored by women and students in the third (men) and second (women) year of the medical program, whereas surgical specialties were most preferred by men and students in the first year of the program. Students in the third year mostly favored nonclinical medicine. Medical college students had a stronger preference for nonclinical medicine (odds ratio [OR] 1.625, 95 % confidence interval [CI] 1.139-2.318) than graduate medical school students. Surgical specialties were more favored by men (OR 2.537, 95 % CI 2.296-2.804) than by women. However, they were favored less by medical college students (OR 0.885, 95 % CI 0.790-0.991) than by graduate medical school students and by medical students in metropolitan areas (OR 0.892, 95 % CI 0.806-0.988) than by medical students in nonmetropolitan areas. A controllable lifestyle specialty was less favored by men (OR 0.802, 95 % CI 0.730-0.881) than by women. CONCLUSIONS: Based on these results, we can evaluate the effectiveness of the government's educational policies for solving the imbalance of physician supply and provide empirical evidence to understand and solve this problem.

Hispidulin Alleviates Mast Cell-Mediated Allergic Airway Inflammation through FcεR1 and Nrf2/HO-1 Signaling Pathway.

Allergic asthma is a type 2 immune-response-mediated chronic respiratory disease. Mast cell activation influences the pathogenesis and exacerbation of allergic asthma. Therefore, the development of mast cell-targeting pharmacotherapy is important for managing allergic airway inflammation. We investigated the efficacy of hispidulin (HPD), natural flavone, in a mast-cell-mediated ovalbumin (OVA)-induced allergic airway inflammation model. HPD alleviated symptoms of allergic asthma and decreased the levels of immunoglobulin (Ig) E, type 2 inflammation, immune cell infiltration, and mast cell activation in the lung. Furthermore, in vivo analysis confirmed the efficacy of HPD through the evaluation of IgE-mediated allergic responses in a mast cell line. HPD treatment inhibited mast cell degranulation through inhibition of the FcεR1 signaling pathway and suppressed the expression of inflammatory cytokines (TNF-α, IL-4, IL-6, and IL-13) through suppression of the NF-κB signaling pathway. The antioxidant effects of HPD in activated mast cells were identified through modulation of antioxidant enzymes and the Nrf2/HO-1 signaling pathway. In conclusion, HPD may be a potential therapeutic candidate for allergic airway inflammation of asthma and acts by suppressing mast cell activation and oxidative stress.

National trend in the prevalence and mortality of COPD in South Korea from 2008 to 2017.

BACKGROUND: Existing studies on chronic obstructive pulmonary disease (COPD) in Korea lack full population coverage, relying on small sample sizes. Therefore, this study aims to investigate the prevalence and mortality of COPD in the entire Korean population. METHODS: This serial cross-sectional study used national databases, linking the National Health Information Database (2008-2017) with Causes of Death Statistics. Identification of individuals with COPD used diagnostic codes (International Classification of Diseases-10: J41-J44) or a history of COPD-related hospitalisation, focusing on adults aged 40 and above. Prevalence and mortality rates, calculated for 2008-2017, encompassed both crude and age-standardised and sex-standardised measures. A multivariate Poisson regression model estimated the association between COPD and all-cause and cause-specific mortality, presenting incidence rate ratios (IRRs) and 95% CIs, using data from the year 2017. RESULTS: Age-adjusted COPD prevalence exhibited a notable increase from 2008 (7.9%) to 2017 (16.7%) in both sexes. The prevalences of diabetes mellitus, hypertension, dyslipidaemia, ischaemic heart disease, cancer, osteoporosis and tuberculosis were higher in the COPD group than in the group without COPD (p for all <0.001). The incidence of stroke and myocardial infarction (p for all <0.001) and overall mortality were higher in the COPD group (adjusted IRR 1.23, 95% CI 1.22 to 1.24, p<0.001). In particular, incidence rate and risk of mortality due to lung cancer were higher than that of those without COPD compared with other cancer types (adjusted IRR 2.51, 95% CI 2.42 to 2.60, p<0.001). It was significantly higher the incidence rate and risk of mortality among group with COPD than those without COPD in lower respiratory disease (adjusted IRR 16.62, 95% CI 15.07 to 18.33, p<0.001), asthma (adjusted IRR 6.41, 95% CI 5.47 to 7.51, p<0.001) and bronchiectasis (adjusted IRR 11.77, 95% CI 7.59 to 18.26, p<0.001), respectively. DISCUSSION: Our study showed that the prevalence of COPD is gradually increasing from 9.2% in 2009 to 16.7% in 2018. Furthermore, in overall (all-cause) mortality, it was significantly higher in group with COPD than in group without COPD. The mortality rate of group with COPD was much higher than the overall mortality rate but is gradually decreasing.

Ferulic Acid Derivatives Ameliorate Intestine Barrier Destruction by Alleviating Inflammatory Responses in Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), a chronic disorder affecting the colon and rectum, involves the overproduction of pro-inflammatory cytokines causing damage to tight junctions (TJ) in the intestinal epithelial cells and chronic inflammation. The current mainstay of treatment, sulfasalazine, often causes adverse effects, thereby necessitating the exploration of alternative herbal medicines with fewer side effects. Portulaca oleracea L. (P. oleracea), a traditional medicinal herb, contains feruloyl amide compounds. We synthesized new compounds by conjugating ferulic acid (FA) with (±)-octopamine. Our study focused on novel FA derivatives that demonstrate protective effects against the intestinal epithelial barrier and inflammatory responses. In lipopolysaccharide-induced cells, C1 and C1a inhibited the production of inflammatory mediators. In Caco-2 cells, these compounds maintained the TJ protein expression, thereby demonstrating their protective effects on the epithelial barrier. In a mouse model of dextran sulfate sodium-induced IBD, a treatment with these compounds ameliorated features including a body weight reduction, colon shortening, an increased disease activity index, and histopathological changes. Furthermore, C1a demonstrated greater efficacy than C1 at the same concentration. These findings suggest that the novel FA derivative (C1a) effectively alleviates clinical signs and inflammatory mediators in IBD, making these compounds potential candidates as natural medicines for the treatment of IBD.