Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to timeof-flight mass spectrometry. Correlation analyses were performed targeting the gut-microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC >0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusions Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

OBJECTIVES: We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea. METHODS: In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022. RESULTS: In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%. CONCLUSIONS The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.

Background: Disruptions of the intestinal epithelial barrier (IEB) are frequently observed in various digestive diseases, including irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). This study assessed the improvement in the IEB during the laxative activity of phlorotannin (Pt) harvested from Ecklonia cava in constipation by examining the changes in the expression of the regulatory proteins for the tight junction (TJ) and adherens junction (AJ), and inflammatory cytokines in Sprague Dawley (SD) rats with loperamide (Lm)-induced constipation after a Pt treatment. Results: The Pt treatment induced laxative activity, including the improvement of feces-related parameters, gastrointestinal transit rate, and histological structure of the mid colon in Lm-treated SD rats. In addition, significant recovery effects were detected in the histology of IEB, including the mucus layer, epithelial cells, and lamina propria in the midcolon of Lm + Pt treated SD rats. The expression levels of E-cadherin and p120-catenin for AJ and the ZO-1, occludin, and Claudin-1 genes for TJ in epithelial cells were improved remarkably after the Pt treatment, but the rate of increase was different. Furthermore, the Pt treatment increased the expression level of several inflammatory cytokines, such asTNF-α, IL-6, IL-1β, IL-13, and IL-4 in Lm + Pt treated SD rats. Conclusions These results provide the first evidence that the laxative activity of Pt in SD rats with Lm-induced constipation phenotypes involve improvements in the IEB.

Background: With the introduction of Xpert MTB/RIF assay (Xpert), its incorporation into tuberculosis (TB) diagnostic algorithm has become an important issue. The aim of this study was to evaluate the performance of the Xpert assay in comparison with a commercial polymerase chain reaction (PCR) assay. Methods: Medical records of patients having results of both Xpert and AdvanSure TB/NTM real-time PCR (AdvanSure) assays using the same bronchial washing specimens were retrospectively reviewed. Results: Of the 1,297 patients included in this study, 205 (15.8%) were diagnosed with pulmonary TB. Using mycobacterial culture as the reference method, sensitivity of the Xpert assay using smear-positive specimens was 97.5%, which was comparable to that of the AdvanSure assay (96.3%, p=0.193). However, the sensitivity of the Xpert assay using smear-negative specimens was 70.6%, which was significantly higher than that of the AdvanSure assay (52.9%, p=0.018). Usng phenotypic drug susceptibility testing as the reference method, sensitivity and specificity for detecting rifampicin resistance were 100% and 99.1%, respectively. Moreover, a median turnaround time of the Xpert assay was 1 day, which was significantly shorter than 3 days of the AdvanSure assay (p<0.001). Conclusion In comparison with the AdvanSure assay, the Xpert assay had a higher sensitivity using smear-negative specimens, a shorter turnaround time, and could reliably predict rifampin resistance. Therefore, the Xpert assay might be preferentially recommended over TB-PCR in Korean TB diagnostic algorithm.

Background: Preconditioning with inflammatory stimuli is used to improve the secretion of anti-inflammatory agents in stem cells from variant species such as mouse, human, and dog. However, there are only few studies on feline stem cells. Objectives: This study aimed to evaluate the immune regulatory capacity of feline adipose tissue-derived (fAT) mesenchymal stem cells (MSCs) pretreated with interferon-gamma (IFN-γ). Methods: To assess the interaction of lymphocytes and macrophages with IFN-γ-pretreated fAT-MSCs, mouse splenocytes and RAW 264.7 cells were cultured with the conditioned media from IFN-γ-pretreated MSCs. Results: Pretreatment with IFN-γ increased the gene expression levels of cyclooxygenase-2, indoleamine 2,3-dioxygenase, hepatocyte growth factor, and transforming growth factorbeta 1 in the MSCs. The conditioned media from IFN-γ-pretreated MSCs increased the expression levels of M2 macrophage markers and regulatory T-cell markers compared to those in the conditioned media from naive MSCs. Further, prostaglandin E 2 (PGE 2 ) inhibitor NS-398 attenuated the immunoregulatory potential of MSCs, suggesting that the increased PGE 2 levels induced by IFN-γ stimulation is a crucial factor in the immune regulatory capacity of MSCs pretreated with IFN-γ. Conclusions IFN-γ pretreatment improves the immune regulatory profile of fAT-MSCs mainly via the secretion of PGE 2 , which induces macrophage polarization and increases regulatory T-cell numbers.

: Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC. Methods : We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27). Results : The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1–77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5–27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004). Conclusion : GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.

Background: This study purposed to analyze the relationship between extinction risk regions and amenable mortality. Methods: This was a cross-sectional study based on the statistics of 2018 which was extracted from the 228 administrative districts in Korea. Cause of death statistics on each region in 2018 was used to produce the age-adjusted amenable mortality. Regional characteristics were measured by demographic factors, health behavior factors, socioeconomic factors, and medical resources factors. Multiple linear regression model was applied to test their relationship. Results: Results showed that extinction risk regions, crude divorce rates, national cancer screening rates, and independent rate of finance were significantly related to the amenable mortality. Conclusion The study demonstrated differences in health status by the extinction risks of regions. This study suggests that the use of customized community care program can provide integrated services such as housing, health care or the use of information and communications technology which can make early diagnosis.

Background: Preconditioning with inflammatory stimuli is used to improve the secretion of anti-inflammatory agents in stem cells from variant species such as mouse, human, and dog. However, there are only few studies on feline stem cells. Objectives: This study aimed to evaluate the immune regulatory capacity of feline adipose tissue-derived (fAT) mesenchymal stem cells (MSCs) pretreated with interferon-gamma (IFN-γ). Methods: To assess the interaction of lymphocytes and macrophages with IFN-γ-pretreated fAT-MSCs, mouse splenocytes and RAW 264.7 cells were cultured with the conditioned media from IFN-γ-pretreated MSCs. Results: Pretreatment with IFN-γ increased the gene expression levels of cyclooxygenase-2, indoleamine 2,3-dioxygenase, hepatocyte growth factor, and transforming growth factorbeta 1 in the MSCs. The conditioned media from IFN-γ-pretreated MSCs increased the expression levels of M2 macrophage markers and regulatory T-cell markers compared to those in the conditioned media from naive MSCs. Further, prostaglandin E 2 (PGE 2 ) inhibitor NS-398 attenuated the immunoregulatory potential of MSCs, suggesting that the increased PGE 2 levels induced by IFN-γ stimulation is a crucial factor in the immune regulatory capacity of MSCs pretreated with IFN-γ. Conclusions IFN-γ pretreatment improves the immune regulatory profile of fAT-MSCs mainly via the secretion of PGE 2 , which induces macrophage polarization and increases regulatory T-cell numbers.

BACKGROUND/OBJECTIVES: In this study, we investigated the beneficial effects of skate cartilage extracts containing chondroitin sulfate (SCS) on hyperlipidemia-induced inflammation and oxidative stress in high cholesterol diet (HCD)-fed mice in comparison with the effects of shark cartilage-derived chondroitin sulfate (CS).MATERIALS/METHODS: Low-density lipoprotein receptor knockout (LDLR-KO) mice were fed HCD with an oral administration of CS (50 and 100 mg/kg BW/day), SCS (100 and 200 mg/kg BW/day), or water, respectively, for ten weeks. RESULTS: The administration of CS or SCS reduced the levels of serum triglyceride (TG), total cholesterol (TC), and LDL cholesterol and elevated the levels of high-density lipoprotein cholesterol, compared with those of the control group (P < 0.05). Furthermore, CS or SCS significantly attenuated inflammation by reducing the serum levels of interleukin (IL)-1β and hepatic protein expression levels of nuclear factor kappa B, inducible nitric oxide synthase, cyclooxygenase-2, and IL-1beta (P < 0.05). In particular, the serum level of tumor necrosis factor-alpha was reduced only in the 100 mg/kg BW/day of SCS-fed group, whereas the IL-6 level was reduced in the 100 and 200 mg/kg BW/day of SCS-fed groups (P < 0.05). In addition, lipid peroxidation and nitric oxide production were attenuated in the livers of the CS and SCS groups mediated by the upregulation of hepatic proteins of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase (P < 0.05). CONCLUSIONS These results suggest that the biological effects of SCS, similar to those of CS, are attributed to improved lipid profiles as well as suppressed inflammation and oxidative stress induced by the intake of HCD.

BACKGROUND: Recent evidences indicate that early rapid renal function decline is closely associated with the development and progression of diabetic kidney disease. We have investigated the association between carotid atherosclerosis and rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function.METHODS: In a prospective, multicenter cohort, a total of 967 patients with type 2 diabetes mellitus and preserved renal function were followed for 6 years with serial estimated glomerular filtration rate (eGFR) measurements. Common carotid intima-media thickness (CIMT) and presence of carotid plaque were assessed at baseline. Rapid renal function decline was defined as an eGFR decline >3.3% per year.RESULTS: Over a median follow-up of 6 years, 158 participants (16.3%) developed rapid renal function decline. While there was no difference in CIMT, the presence of carotid plaque in rapid decliners was significantly higher than in non-decliners (23.2% vs. 12.2%, P<0.001). In multivariable logistic regression analysis, presence of carotid plaque was an independent predictor of rapid renal function decline (odds ratio, 2.33; 95% confidence interval, 1.48 to 3.68; P<0.0001) after adjustment for established risk factors. The model including the carotid plaque had better performance for discrimination of rapid renal function decline than the model without carotid plaque (area under the receiver operating characteristic curve 0.772 vs. 0.744, P=0.016).CONCLUSION: Close monitoring of renal function and early intensive management may be beneficial in patients with type 2 diabetes mellitus and carotid plaques.
Carotid Artery Diseases ; Carotid Intima-Media Thickness ; Carotid Stenosis ; Cohort Studies ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Discrimination (Psychology) ; Follow-Up Studies ; Glomerular Filtration Rate ; Humans ; Logistic Models ; Prospective Studies ; Risk Factors ; ROC Curve