This study examined the inhibitory effects of pluviatolide, a lignan derived from Podophyllum hexandrum, on mast cell activation and IgE-mediated type I hypersensitivity, focusing on FcεRI-dependent and calcium-mediated pathways. Using bone marrowderived mast cells (BMMCs) and rat basophilic leukemia (RBL)-2H3 cells, we found that pluviatolide significantly decreased β-hexosaminidase release and suppressed the expression and secretion of TNF-α and IL-6 in a concentration-dependent manner, without causing cytotoxicity. While we initially hypothesized that it would selectively modulate antigen-specific FcεRI signaling, pluviatolide also inhibited degranulation induced by calcium ionophore and thapsigargin, indicating its effects extend to receptorindependent, Ca2+-dependent activation mechanisms. Immunoblot analyses revealed decreased phosphorylation of proximal kinases (Lyn, Syk), adaptor proteins (LAT, PLCγ1), MAPKs (ERK1/2, JNK, p38), and NF-κB p65. In a passive cutaneous anaphylaxis (PCA) mouse model, oral administration of pluviatolide significantly reduced Evans blue extravasation and mast cell degranulation in ear tissues. These findings demonstrate that pluviatolide suppresses both early and late-phase mast cell responses through multi-nodal inhibition of activation pathways, highlighting its potential as a therapeutic candidate for both IgE-mediated and non-IgE-mediated allergic disorders.

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells.Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. Methods: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. Results: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7(19–88) years and mean BMI was 22.5 (16.9–34.1) kg/m2 . The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475–3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367–0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385–2.469). Conclusion Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Background: Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells.Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. Methods: Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. Results: In our study, 3,798 eligible patients were included. Mean age of patients was 42.7(19–88) years and mean BMI was 22.5 (16.9–34.1) kg/m2 . The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475–3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367–0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385–2.469). Conclusion Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

Objective: To analyze the differences in characteristics and outcomes between public bath (PB)- related and non-PB-related out-of-hospital cardiac arrest (OHCA) patients in South Korea. Methods: We performed a retrospective observational analysis of collected data from the Smart Advanced Cardiac Life Support (SALS) registry between September 2015 and December 2018. We included adult OHCA patients (aged >18 years) with presumed OHCA of non-traumatic etiology who were attended by dispatched emergency medical services. SALS is a field advanced life support with smartphone-based direct medical direction. The primary outcome was the survival to discharge rate measured at the time of discharge. Results: Of 38,995 cardiac arrest patients enrolled in the SALS registry, 11,889 were included in the final analysis. In total, 263 OHCAs occurred in PBs. Male sex and bystander cardiopulmonary resuscitation proportions appeared to be higher among PB patients than among non-PB patients. Percentages for shockable rhythm, witnessed rate, and number of underlying disease were lower in the PB group than in the non-PB group. Prehospital return of spontaneous circulation (11.4% vs. 19.5%, P=0.001), survival to discharge (2.3% vs. 9.9%, P<0.001), and favorable neurologic outcome (1.9% vs. 5.8%, P=0.007) in PB patients were significantly poorer than those in non-PB patients. Conclusion Patient characteristics and emergency medical services factors differed between PB and non-PB patients. All outcomes of PB-related OHCA were poorer than those of non-PB-related OHCA. Further treatment strategies should be developed to improve the outcomes of PBrelated cardiac arrest.

BACKGROUND: Previous studies have examined the association between alcohol consumption and metabolic syndrome (MetS) in adults, but studies in the elderly are lacking. We examined the relationship between high-risk alcohol consumption and MetS in elderly Korean men using the Alcohol Use Disorders Identification Test (AUDIT) questionnaire from the 2010–2012 Korean National Health and Nutrition Examination Survey. METHODS: Among 25,534 subjects, 2,807 were men >60 years of age; after exclusions, we included 2,088 men in the final analysis. We categorized the study participants into three groups according to AUDIT score: low risk (0–7), intermediate risk (8–14), and high risk (≥15 points). RESULTS: Among the study population, 17.0% of the men were high-risk drinkers, who had the highest mean waist circumference, systolic and diastolic blood pressure (BP), fasting plasma glucose (FPG), and triglyceride (TG) levels. The overall prevalence of MetS was 41.9% in the elderly men, and it was significantly higher in the group with high (48.3%) versus low (31.9%) AUDIT scores. The prevalence of MetS components (elevated BP, high FPG, high TG, and low high-density lipoprotein cholesterol) was associated with a high AUDIT score. The odds ratios (95% confidence interval) of the high-risk group for MetS, elevated BP, and high TG were 1.40 (1.03–1.89), 1.82 (1.28–2.60), and 1.77 (1.30–2.41) after adjustment for confounding variables. CONCLUSION: AUDIT score was correlated with most MetS components in elderly Korean men.
Adult ; Aged* ; Alcohol Drinking ; Blood Glucose ; Blood Pressure ; Confounding Factors (Epidemiology) ; Cross-Sectional Studies ; Drinking* ; Fasting ; Humans ; Lipoproteins ; Male ; Nutrition Surveys* ; Odds Ratio ; Prevalence ; Triglycerides ; Waist Circumference

Tumor necrosis factor-inducible gene 6 protein (TSG-6) has recently been shown to protect the liver from acute damage. However, the mechanism underlying the effect of TSG-6 on the liver remains unclear. Autophagy is a catabolic process that targets cell components to lysosomes for degradation, and its functions are reported to be dysregulated in liver diseases. Here we investigate whether TSG-6 promotes liver regeneration by inducing autophagic clearance in damaged livers. Mice fed a methionine choline-deficient diet supplemented with 0.1% ethionine (MCDE) for 2 weeks were injected with TSG-6 (the M+TSG-6 group) or saline (the M+V group) and fed with MCDE for 2 additional weeks. Histomorphological evidence of injury and increased levels of liver enzymes were evident in MCDE-treated mice, whereas these symptoms were ameliorated in the M+TSG-6 group. Livers from this group contained less active caspase-3 and more Ki67-positive hepatocytic cells than the M+V group. The autophagy markers ATG3, ATG7, LC3-II, LAMP2A and RAB7 were elevated in the M+TSG-6 group compared with those in the M+V group. Immunostaining for LC3 and RAB7 and electron microscopy analysis showed the accumulation of autophagy structures in the M+TSG-6 group. TSG-6 also blocked both tunicamycin- and palmitate-induced apoptosis of hepatocytes and increased their viability by inducing autophagy formation in these cells. An autophagy inhibitor suppressed TSG-6-mediated autophagy in the injured hepatocytes and livers of MCDE-treated mice. These results therefore demonstrate that TSG-6 protects hepatocytes from damage by enhancing autophagy influx and contributes to liver regeneration, suggesting that TSG-6 has therapeutic potential for the treatment of liver diseases.
Animals ; Apoptosis ; Autophagy* ; Caspase 3 ; Cellular Structures ; Diet ; Ethionine ; Hepatocytes ; Liver Diseases ; Liver Regeneration ; Liver* ; Lysosomes ; Methionine ; Mice* ; Microscopy, Electron ; Necrosis*

PURPOSE: The purpose of this study is to compare birth outcomes based on maternal ethnicity in Korea. METHODS: Using the birth data of Statistics Korea from 2010 to 2015, this study selected data from infants with a Vietnamese mother and Korean father (Vietnamese/Korean group), and a Chinese mother and Korean father (Chinese/Korean group), to compare them with that of a Korean mother and Korean father (Korean/Korean group). The newborn infants' birth outcomes and parental characteristics were investigated, and trends in annual changes were compared. In addition, this study investigated whether the mother's ethnicity affected the mean birth weight. RESULTS: Gestational age and birth weight were highest in the Chinese/Korean group, and were slightly lower in the Korean/Korean and Vietnamese/Korean group, in that order. The highest rate of preterm birth before 37 weeks and low birth weight rate were observed in the Vietnamese/Korean group; 4.62% and 4.26%, respectively. From 2010 to 2015, the mean gestational age decreased in all the three groups, and the preterm birth rate increased at gestational ages less than 37 weeks. However, the birth weight decreased only in the Korean/Korean group, but increased in the Chinese/Korean and Vietnamese/Korean groups. In addition, we found that factors such as parents' educational levels, percentage of hospital births, and appropriate maternal age improved in the Vietnamese/Korean group. CONCLUSION: This study confirms that the mean birth weight and low birth weight rate are affected by maternal ethnicity in Korea. Therefore, careful research and active national support policies are needed.
Asian Continental Ancestry Group* ; Birth Weight ; Continental Population Groups ; Cultural Diversity ; Emigrants and Immigrants ; Fathers ; Gestational Age ; Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Korea* ; Maternal Age ; Mothers ; Parents ; Parturition* ; Premature Birth

BACKGROUND: Prescription of inappropriate medicine to elderly patients is a major public health care concern. The Beers criteria have been commonly employed as a screening tool to identify the use of potentially inappropriate medications (PIMs). The present study investigated the prevalence of PIM use according to the Beers criteria as well as factors related to PIM use. METHODS: Data obtained from a retrospective survey included 25,810 outpatients aged ≥65 years from a university medical center in Seoul, Korea. PIMs were defined using the Beers criteria. Factors associated with PIM use were evaluated using multiple regression analysis. RESULTS: Of all participants, 7,132 (27.6%) were prescribed at least one PIM. The most commonly prescribed PIMs were alprazolam (11.2%), clonazepam (10.8%), zolpidem (8.7%), quetiapine (8.4%), and hydroxyzine (5.4%). In multivariate logistic regression analysis, having five or more prescription medicines (odds ratio [OR], 11.32; 95% confidence interval [CI], 9.38 to 13.66) and five or more prescribing doctors (OR, 4.40; 95% CI, 3.59 to 5.39) were strongly associated with PIM. In a likelihood ratio test for trend, an increasing number of medications and prescribing doctors were both significantly associated with PIM. CONCLUSION: At a university medical center, the number of medications and the number of prescribing doctors was associated with PIM in older outpatients.
Academic Medical Centers ; Aged ; Alprazolam ; Beer* ; Clonazepam ; Humans ; Hydroxyzine ; Korea ; Logistic Models ; Mass Screening ; Outpatients* ; Potentially Inappropriate Medication List* ; Prescriptions ; Prevalence* ; Public Health ; Quetiapine Fumarate ; Retrospective Studies ; Risk Factors* ; Seoul

BACKGROUND: Prescription of inappropriate medicine to elderly patients is a major public health care concern. The Beers criteria have been commonly employed as a screening tool to identify the use of potentially inappropriate medications (PIMs). The present study investigated the prevalence of PIM use according to the Beers criteria as well as factors related to PIM use. METHODS: Data obtained from a retrospective survey included 25,810 outpatients aged ≥65 years from a university medical center in Seoul, Korea. PIMs were defined using the Beers criteria. Factors associated with PIM use were evaluated using multiple regression analysis. RESULTS: Of all participants, 7,132 (27.6%) were prescribed at least one PIM. The most commonly prescribed PIMs were alprazolam (11.2%), clonazepam (10.8%), zolpidem (8.7%), quetiapine (8.4%), and hydroxyzine (5.4%). In multivariate logistic regression analysis, having five or more prescription medicines (odds ratio [OR], 11.32; 95% confidence interval [CI], 9.38 to 13.66) and five or more prescribing doctors (OR, 4.40; 95% CI, 3.59 to 5.39) were strongly associated with PIM. In a likelihood ratio test for trend, an increasing number of medications and prescribing doctors were both significantly associated with PIM. CONCLUSION: At a university medical center, the number of medications and the number of prescribing doctors was associated with PIM in older outpatients.
Academic Medical Centers ; Aged ; Alprazolam ; Beer* ; Clonazepam ; Humans ; Hydroxyzine ; Korea ; Logistic Models ; Mass Screening ; Outpatients* ; Potentially Inappropriate Medication List* ; Prescriptions ; Prevalence* ; Public Health ; Quetiapine Fumarate ; Retrospective Studies ; Risk Factors* ; Seoul