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Purpose: Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response. Materials and Methods: To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins. Results: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways. Conclusions: These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC.

Asthma: Antioxidant-boosting protein improves stem cell treatment A cellular protein that promotes a key antioxidant will be a crucial component in stem cell therapies for allergic asthma. Stem cells derived from umbilical cords have been proposed as treatments for incurable allergic asthma, due to their ability to combat inflammation and regenerate damaged cells. Now, Dong-Myung Shin at University of Ulsan College of Medicine in Seoul, South Korea, and co-workers have shown that the activating transcription factor 2 (ATF2) acts to maintain healthy levels of the antioxidant glutathione, which is essential for the effectiveness of stem cell therapy. Specifically, ATF2 interplays with a specific nuclear protein to activate genes involved in glutathione synthesis. The researchers showed that the ability of MSC treatments to reduce airway inflammation in asthmatic mouse models was greatly reduced by silencing ATF2, and enhanced by its over-expression.

Abstract Molecular programs involved in embryogenesis are frequently upregulated in oncogenic dedifferentiation and metastasis. However, their precise roles and regulatory mechanisms remain elusive. Here, we showed that CDK1 phosphorylation of TFCP2L1, a pluripotency‐associated transcription factor, orchestrated pluripotency and cell‐cycling in embryonic stem cells (ESCs) and was aberrantly activated in aggressive bladder cancers (BCs). In murine ESCs, the protein interactome and transcription targets of Tfcp2l1 indicated its involvement in cell cycle regulation. Tfcp2l1 was phosphorylated at Thr177 by Cdk1, which affected ESC cell cycle progression, pluripotency, and differentiation. The CDK1‐TFCP2L1 pathway was activated in human BC cells, stimulating their proliferation, self‐renewal, and invasion. Lack of TFCP2L1 phosphorylation impaired the tumorigenic potency of BC cells in a xenograft model. In patients with BC, high co‐expression of TFCP2L1 and CDK1 was associated with unfavorable clinical characteristics including tumor grade, lymphovascular and muscularis propria invasion, and distant metastasis and was an independent prognostic factor for cancer‐specific survival. These findings demonstrate the molecular and clinical significance of CDK1‐mediated TFCP2L1 phosphorylation in stem cell pluripotency and in the tumorigenic stemness features associated with BC progression.

Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.

The purpose of this study was to reduce the amount of stem cells used in treating preclinical interstitial cystitis (IC model) by investigating the synergistic effects of multipotent mesenchymal stem cells (M-MSCs; human embryonic stem cell-derived) and N-acetylcysteine (NAC). Eight-week-old female Sprague-Dawley rats were divided into seven groups, i.e., sham (n = 10), lipopolysaccharide/protamine sulfate (LPS/PS; n = 10), LPS/PS + NAC (n = 10), LPS/PS with 25K MSC (n = 10), LPS/PS with 50K MSC (n = 10) LPS/PS + 25K MSC + NAC (n = 10), and LPS/PS + 50K MSC + NAC (n = 10). To induce the IC rat model, protamine sulfate (10 mg, 45 min) and LPS (750 μg, 30 min) were instilled once a week for five consecutive weeks via a transurethral PE-50 catheter. Phosphate-buffered saline (PBS) was used in the sham group. One week after the final instillation, M-MSCs with two suboptimal dosages (i.e., 2.5 or 5.0 × 104 cells) were directly transplanted into the outer-layer of the bladder. Simultaneously, 200 mg/kg of NAC or PBS was intraperitoneally injected daily for five days. The therapeutic outcome was evaluated one week after M-MSC or PBS injection by awake cystometry and histological analysis. Functionally, LPS/PS insult led to irregular micturition, decreased intercontraction intervals, and decreased micturition volume. Both monotherapy and combination therapy significantly increased contraction intervals, increased urination volume, and reduced the residual volume, thereby improving the urination parameters compared to those of the LPS group. In particular, a combination of NAC dramatically reduced the amount of M-MSCs used for significant restoration in histological damage, including inflammation and apoptosis. Both M-MSCs and NAC-based therapy had a beneficial effect on improving voiding dysfunction, regenerating denudated urothelium, and relieving tissue inflammation in the LPS-induced IC/BPS rat model. The combination of M-MSC and NAC was superior to MSC or NAC monotherapy, with therapeutic efficacy that was comparable to that of previously optimized cell dosage (1000K) without compromised therapeutic efficacy.

Abstract BackgroundAs Korea rapidly transforms into a super-aged society, research indicates that digital literacy among older adults enhances their life satisfaction. Digital literacy refers to the ability to efficiently use digital technologies, encompassing access, competency, and utilization. It reflects the capacity to navigate and benefit from digital environments effectively. Furthermore, social capital positively influences the quality of life, and digital literacy facilitates social capital formation. However, since most studies have only focused on the direct relationship between digital literacy and life satisfaction, research on the mediating role of social capital remains limited. ObjectiveTo analyze the effect of digital literacy on the life satisfaction of older adults in South Korea and to verify whether social capital acts as a mediating factor in this process. MethodsThis descriptive cross-sectional study used data from the 2023 Report on the Digital Divide—an annual survey conducted by the Korean Ministry of Science and Information and Communications Technology. The study targeted individuals aged 65 years or older. Descriptive statistics, the Pearson correlation analyses, and the 3-step multiple regression analysis proposed by Baron and Kenny were performed. The bootstrap method was employed, and all analyses were conducted using R, version 4.4.1. ResultsThe study included 869 participants. Digital literacy had a significant positive effect on their life satisfaction (βPβPβPβPβPβP ConclusionsThis study analyzed the association between digital literacy, social capital, and life satisfaction among older adults in Korea. We identified that social capital mediates the association between digital literacy and life satisfaction among older adults. These findings indicate that tailored digital literacy programs and support policies that promote social capital formation could help bridge the digital divide and foster social inclusion. These measures would enable older adults to access essential services, reduce social isolation, and enhance health and well-being, ultimately improving the overall quality of life.

Abstract Polygenic risk score (PRS) is useful for capturing an individual’s genetic susceptibility. However, previous studies have not fully exploited the potential of the risk factor PRS (RFPRS) for disease prediction. We explored the potential of integrating disease-related RFPRSs with disease PRS to enhance disease prediction performance. We constructed 112 RFPRSs and analyzed the association of RFPRSs with diseases to identify disease-related RFPRSs in 700 diseases, using the UK Biobank dataset. We uncovered 6157 statistically significant associations between 247 diseases and 109 RFPRSs. We estimated the disease PRSs of 70 diseases that exhibited statistically significant heritability, to generate RFDiseasemetaPRS—a combined PRS integrating RFPRSs and disease PRS—and compare the prediction performance metrics between RFDiseasemetaPRS and disease PRS. RFDiseasemetaPRS showed better performance for Nagelkerke’s pseudo-R 2, odds ratio (OR) per 1 SD, net reclassification improvement (NRI) values and difference of R 2 considered by variance of R 2 in 31 out of 70 diseases. Additionally, we assessed risk classification between two models by examining OR between the top 10% and remaining 90% individuals for the 31 diseases; RFDiseasemetaPRS exhibited better R 2, NRI and OR than disease PRS. These findings highlight the importance of utilizing RFDiseasemetaPRS, which can provide personalized healthcare and tailored prevention strategies.

Abstract Several studies have utilized a lipid nanoparticle delivery system to enhance the effectiveness of mRNA therapeutics and vaccines. However, these nanoparticles are recognized as foreign materials by the body and stimulate innate immunity, which in turn impacts adaptive immunity. Therefore, it is crucial to understand the specific type of innate immune response triggered by lipid nanoparticles. This article provides an overview of the immunological response in the body, explores how lipid nanoparticles activate the innate immune system, and examines the adverse effects and immunogenicity-related development pathways associated with these nanoparticles. Finally, we highlight and explore strategies for regulating the immunogenicity of lipid nanoparticles.

Abstract Background More than 200 asthma-associated genetic variants have been identified in genome-wide association studies (GWASs). Expression quantitative trait loci (eQTL) data resources can help identify causal genes of the GWAS signals, but it can be difficult to find an eQTL that reflects the disease state because most eQTL data are obtained from normal healthy subjects. Methods We performed a blood eQTL analysis using transcriptomic and genotypic data from 433 Korean asthma patients. To identify asthma-related genes, we carried out colocalization, Summary-based Mendelian Randomization (SMR) analysis, and Transcriptome-Wide Association Study (TWAS) using the results of asthma GWASs and eQTL data. In addition, we compared the results of disease eQTL data and asthma-related genes with two normal blood eQTL data from Genotype-Tissue Expression (GTEx) project and a Japanese study. Results We identified 340,274 cis-eQTL and 2,875 eGenes from asthmatic eQTL analysis. We compared the disease eQTL results with GTEx and a Japanese study and found that 64.1% of the 2,875 eGenes overlapped with the GTEx eGenes and 39.0% with the Japanese eGenes. Following the integrated analysis of the asthmatic eQTL data with asthma GWASs, using colocalization and SMR methods, we identified 15 asthma-related genes specific to the Korean asthmatic eQTL data. Conclusions We provided Korean asthmatic cis-eQTL data and identified asthma-related genes by integrating them with GWAS data. In addition, we suggested these asthma-related genes as therapeutic targets for asthma. We envisage that our findings will contribute to understanding the etiological mechanisms of asthma and provide novel therapeutic targets.

Abstract Polycystic ovary syndrome (PCOS) is a highly complex reproductive metabolic disorder and women with PCOS have high prevalence of non-alcoholic fatty liver disease (NAFLD). Despite both hyperandrogenism and insulin resistance are common pathophysiologies in NAFLD and PCOS, this association is still controversial. Therefore, the aim of this study is to evaluate the relationship between hyperandrogenism and NAFLD in females diagnosed with PCOS. We recruited 667 women diagnosed with PCOS and 289 women with regular menstrual cycles as control. The PCOS diagnosis was made using National Institute of Child Health and Human Disease criteria. Total and free testosterone levels (TT and TF, respectively), and free androgen index (FAI) were used as measures of hyperandrogenism. Fatty liver index and liver fat score (FLI and LFS, respectively), and hepatic steatosis index (HSI) were used to assess NAFLD. The prevalence of NAFLD in PCOS women evaluated by LFS, FLI, and HIS were 19.9, 10.3, and 32.2%, respectively. In the control group, the incidence was 2.1, 0.7, and 4.2%, respectively. Both FT and FAI levels showed significant association with increased NAFLD-related indices, after adjusting for insulin resistance and other factors (LFS (OR 3.18 (95% CI 1.53–6.63) in FT; 1.12 (1.04–1.22) in FAI), FLI (OR 2.68 (95% CI 1.43–5.03) in FT; 1.13 (1.06–1.20) in FAI), and HSI (OR 3.29 (95% CI 2.08–5.21) in FT; 1.5 (1.09–1.21) in FAI). TT did not exhibit association with any NAFLD index. In women with PCOS, significantly higher rate of NAFLD was observed compared to the control women. The FT and FAI were independently associated with NAFLD in women with PCOS. The findings suggest the possibility of hyperandrogenism contributing to the progression and/or development of NAFLD in PCOS.

Objective Previous animal studies have shown the anti-obesity effect of kimchi-derived probiotic lactic acid bacteria. However, only a few epidemiological studies have investigated the association between kimchi consumption and obesity. Therefore, we aim to assess this relationship in Korean adults.Design Cross-sectional study.Setting The Health Examinees study was conducted from 2004 to 2013.Participants This study analysed 115 726 participants aged 40–69 years enrolled in the Health Examinees study in Korea.Primary and secondary outcome measures Obesity was defined as body mass index ≥25 kg/m2, and abdominal obesity was defined as waist circumference ≥90 cm in men and ≥85 cm in women. Kimchi consumption was assessed by the validated food frequency questionnaire.Results In men, total kimchi consumption of 1–3 servings/day was related to a lower prevalence of obesity (OR: 0.875 in 1–2 servings/day and OR: 0.893 in 2–3 servings/day) compared with total kimchi consumption of

Abstract mRNA‐based protein replacement therapy has received much attention as a novel intervention in clinical disease treatment. Lipid nanoparticles (LNPs) are widely used for their therapeutic potential to efficiently deliver mRNA. However, clinical translation has been hampered by the immunogenicity of LNPs that may aggravate underlying disease states. Here, we report a novel ionizable LNP with enhanced potency and safety. The piperazine‐based biodegradable ionizable lipid (244cis) was developed for LNP formulation and its level of protein expression and immunogenicity in the target tissue was evaluated. It was found that 244cis LNP enabled substantial expression of the target protein (human erythropoietin), while it minimally induced the secretion of monocyte chemoattractant protein 1 (MCP‐1) as compared to other conventional LNPs. Selective lung targeting of 244cis LNP was further investigated in tdTomato transgenic mice with bleomycin‐induced pulmonary fibrosis (PF). The repeated administration of 244cis LNP with Cre recombinase mRNA achieved complete transfection of lung endothelial cells (~80%) and over 40% transfection of Sca‐1‐positive fibroblasts. It was shown that 244cis LNP allows the repeated dose of mRNA without the loss of activity due to its low immunogenicity. Our results demonstrate that 244cis LNP has great potential for the treatment of chronic diseases in the lungs with improved potency and safety.

The purpose of this study was to reduce the amount of stem cells used in treating preclinical interstitial cystitis (IC model) by investigating the synergistic effects of multipotent mesenchymal stem cells (M-MSCs; human embryonic stem cell-derived) and N-acetylcysteine (NAC). Eight-week-old female Sprague-Dawley rats were divided into seven groups, i.e., sham (n = 10), lipopolysaccharide/protamine sulfate (LPS/PS; n = 10), LPS/PS + NAC (n = 10), LPS/PS with 25K MSC (n = 10), LPS/PS with 50K MSC (n = 10) LPS/PS + 25K MSC + NAC (n = 10), and LPS/PS + 50K MSC + NAC (n = 10). To induce the IC rat model, protamine sulfate (10 mg, 45 min) and LPS (750 μg, 30 min) were instilled once a week for five consecutive weeks via a transurethral PE-50 catheter. Phosphate-buffered saline (PBS) was used in the sham group. One week after the final instillation, M-MSCs with two suboptimal dosages (i.e., 2.5 or 5.0 × 104 cells) were directly transplanted into the outer-layer of the bladder. Simultaneously, 200 mg/kg of NAC or PBS was intraperitoneally injected daily for five days. The therapeutic outcome was evaluated one week after M-MSC or PBS injection by awake cystometry and histological analysis. Functionally, LPS/PS insult led to irregular micturition, decreased intercontraction intervals, and decreased micturition volume. Both monotherapy and combination therapy significantly increased contraction intervals, increased urination volume, and reduced the residual volume, thereby improving the urination parameters compared to those of the LPS group. In particular, a combination of NAC dramatically reduced the amount of M-MSCs used for significant restoration in histological damage, including inflammation and apoptosis. Both M-MSCs and NAC-based therapy had a beneficial effect on improving voiding dysfunction, regenerating denudated urothelium, and relieving tissue inflammation in the LPS-induced IC/BPS rat model. The combination of M-MSC and NAC was superior to MSC or NAC monotherapy, with therapeutic efficacy that was comparable to that of previously optimized cell dosage (1000K) without compromised therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The polygenic risk score (PRS) could be used to stratify individuals with high risk of diseases and predict complex trait of individual in a population. Previous studies developed a PRS-based prediction model using linear regression and evaluated the predictive performance of the model using the R2 value. One of the key assumptions of linear regression is that the variance of the residual should be constant at each level of the predictor variables, called homoscedasticity. However, some studies show that PRS models exhibit heteroscedasticity between PRS and traits. This study analyzes whether heteroscedasticity exists in PRS models of diverse disease-related traits and, if any, it affects the accuracy of PRS-based prediction in 354,761 Europeans from the UK Biobank. We constructed PRSs for 15 quantitative traits using LDpred2 and estimated the existence of heteroscedasticity between PRSs and 15 traits using three different tests of the Breusch-Pagan (BP) test, score test, and F test. Thirteen out of fifteen traits show significant heteroscedasticity. Further replication using new PRSs from the PGS catalog and independent samples (N = 23,620) from the UK Biobank confirmed the heteroscedasticity in ten traits. As a result, ten out of fifteen quantitative traits show statistically significant heteroscedasticity between the PRS and each trait. There was a greater variance of residuals as PRS increased, and the prediction accuracy at each level of PRS tended to decrease as the variance of residuals increased. In conclusion, heteroscedasticity was frequently observed in the PRS-based prediction models of quantitative traits, and the accuracy of the predictive model may differ according to PRS values. Therefore, prediction models using the PRS should be constructed by considering heteroscedasticity.

BackgroundCardiovascular disease is the leading cause of morbidity and mortality in postmenopausal women. Early menarche may be associated with an increased risk of metabolic diseases such as diabetes and cardiovascular disease. This study aimed to investigate the effect of menarche age and the risk of diabetes and metabolic syndrome in Korean postmenopausal women.MethodsWe analyzed 4,933 postmenopausal women (mean age: 64.7 years) using the Korean National Health and Nutritional Examination Survey 2016-2018. Subjects were divided into three groups according to menarche age (early menarche: ≤ 12 years (n = 451), reference: 13-16 years (n = 3,421), and late menarche: ≥ 17 years (n = 1,061)). Logistic regression analysis was used to estimate the odds ratio (OR) for diabetes and metabolic syndrome.ResultsWomen with an early menarche age were younger, more educated, and had higher income than the other groups (p-value < 0.001). There were no differences in body mass index, blood pressure, fasting glucose, HbA1c, and cholesterol levels among the three groups. After adjusting for potential confounding factors, early menarche age was significantly associated with the risk of diabetes (OR 1.435, 95% confidence interval (CI): 1.069-1.928). The prevalence of metabolic syndrome in all subjects was 41.1%. After adjusting for potential confounding factors, the OR of metabolic syndrome in the early menarche group was 1.213 (95% CI: 0.971-1.515).ConclusionThe risk of diabetes was 1.43 times higher in postmenopausal Korean women with early menarche. Although the risk of metabolic syndrome was not statistically significant, it showed a tendency to increase in the early menarche group. Our results suggest that age at menarche may be helpful in diabetes risk stratification and early interventions for postmenopausal women.

Drug–drug interactions (DDI) occur because of the unexpected pharmacological effects of drug pairs. Although drug efficacy can be improved by taking two or more drugs in the short term, this may cause inevitable side effects. Currently, multiple drugs are prescribed based on the experience or knowledge of the clinician, and there is no standard database that can be referred to as safe co-prescriptions. Thus, accurately identifying DDI is critical for patient safety and treatment modalities. Many computational methods have been developed to predict DDIs based on chemical structures or biological features, such as target genes or functional mechanisms. However, some features are only available for certain drugs, and their pathological mechanisms cannot be fully employed to predict DDIs by considering the direct overlap of target genes. In this study, we propose a novel deep learning model to predict DDIs by utilizing chemical structure similarity and protein–protein interaction (PPI) information among drug-binding proteins, such as carriers, transporters, enzymes, and targets (CTET) proteins. We applied the random walk with restart (RWR) algorithm to propagate drug CTET proteins across a PPI network derived from the STRING database, which will lead to the successful incorporation of the hidden biological mechanisms between CTET proteins and disease-associated genes. We confirmed that the RWR propagation of CTET proteins helps predict DDIs by utilizing indirectly co-regulated biological mechanisms. Our method identified the known DDIs between clinically proven epilepsy drugs. Our results demonstrated the effectiveness of PRID in predicting DDIs in known drug combinations as well as unknown drug pairs. PRID could be helpful in identifying novel DDIs and associated pharmacological mechanisms to cause the DDIs.

Background The guanine nucleotide-binding protein, alpha stimulating (GNAS) gene has been associated with growth hormone (GH)-secreting pituitary adenoma. We investigated the prevalence of GNAS mutations in Korean patients with acromegaly and assessed whether mutation status correlated with biochemical or clinical characteristics. Methods We studied 126 patients with acromegaly who underwent surgery between 2005 and 2014 at Severance Hospital. We performed GNAS gene analysis and evaluated age, sex, hormone levels, postoperative biochemical remission, and immunohistochemical staining results of the tumor. Results GNAS mutations were present in 75 patients (59.5%). Patients with and without GNAS mutations showed similar age distribution and Knosp classification. The proportion of female patients was 76.5% and 48.0% in the GNAS-negative and GNAS-mutation groups, respectively (P=0.006). In immunohistochemical staining, the GNAS-mutation group showed higher GH expression in pituitary tumor tissues than the mutation-negative group (98.7% vs. 92.2%, P=0.015). Patients with GNAS mutations had higher preoperative insulin-like growth factor-1 levels (791.3 ng/mL vs. 697.0 ng/mL, P=0.045) and lower immediate postoperative basal (0.9 ng/mL vs. 1.0 ng/mL, P=0.191) and nadir GH levels (0.3 ng/mL vs. 0.6 ng/mL, P=0.012) in oral glucose tolerance tests. Finally, the GNAS-mutation group showed significantly higher surgical remission rates than the mutation-negative group, both at 1 week and 6 months after surgical resection (70.7% vs. 54.9%, P=0.011; 85.3% vs. 82.4%, P=0.007, respectively). Conclusion GNAS mutations in GH-secreting pituitary tumors are associated with higher preoperative insulin-like growth factor-1 levels and surgical remission rates and lower immediate postoperative nadir GH levels. Thus, GNAS mutation status can predict surgical responsiveness in patients with acromegaly.

OBJECTIVES Metabolic syndrome (MetS) is closely associated with dietary intake; however, few studies have investigated whether the consumption of fruits and vegetables and multivitamin use affect MetS in the Korean population. This study aimed to examine these effects in Korean adults. METHODS This was a cross-sectional study of 89,548 participants aged between 40 years and 69 years selected from the baseline data of the Health Examinees study conducted in Korea. Fresh vegetable and fruit consumption was assessed using a validated 106-item food frequency questionnaire. MetS and its components were defined using the National Cholesterol Education Program, Adult Treatment Panel III criteria. Multivariate logistic regression analyses were conducted to identify associations of fresh vegetable, fruit, and fresh vegetable+fruit consumption and multivitamin use with the prevalence of MetS. RESULTS Female in the highest quartile of fresh vegetable, fruit, and fresh vegetable + fruit consumption exhibited a lower prevalence of MetS than those in the lowest quartile. An inverse association with the prevalence of MetS was observed among male with only fresh vegetable consumption. The interaction between the 3 categories and multivitamin intake on the prevalence of MetS was not significant (all pinteraction>0.05), regardless of sex. CONCLUSIONS Multivitamin use and consumption of fresh vegetables and fruits had no significant synergistic effects. Although fresh vegetable and fruit consumption showed an inverse association with the prevalence of MetS, this relationship was not altered by multivitamin use.

BackgroundAnti-spasmodic agents are commonly injected during esophagogastroduodenoscopy (EGD) to improve visualization of the gastric mucosa by inhibiting gastrointestinal (GI) peristalsis. The availability of oral anti-spasmodic agents would increase convenience. In this study, we evaluated the effectiveness of oral phloroglucinol (Flospan®) as a premedication for unsedated EGD.MethodsA prospective, double-blinded, placebo-controlled, randomized controlled trial was conducted in a tertiary hospital. Individuals scheduled to undergo unsedated EGD were randomly assigned to receive either oral phloroglucinol or matching placebo 15 min before EGD. The primary outcome was the rate of complete gastric peristalsis suppression. Outcomes were assessed by independent investigators according to the classification of gastric peristalsis and ease of intragastric observation at the beginning (Period A) and end (Period B) of EGD.ResultsOverall, 71 phloroglucinol-treated and 71 placebo-treated participants (n = 142 total) were included. The phloroglucinol group showed significantly higher proportions of participants with complete gastric peristalsis suppression than the placebo group (22.5% vs. 9.9%, P = 0.040). The ease of intragastric observation was significantly better in the phloroglucinol group than in the placebo group at Periods A (P < 0.001) and B (P = 0.005). Patients in both groups had comparable adverse events and showed willingness to take the premedication at their next examination.ConclusionsOral phloroglucinol significantly suppressed gastrointestinal peristalsis during unsedated EGD compared with placebo (Clinical trial registration number: NCT03342118).