Background: Thyroid-associated ophthalmopathy (TAO) involves tissue expansion and inflammation, potentially causing a hypoxic microenvironment. Hypoxia-inducible factor (HIF)-1α is crucial in fibrosis and adipogenesis, which are observed in TAO progression. We investigated the effects of hypoxia on orbital fibroblasts (OFs) in TAO, focusing on the role of HIF-1α in TAO progression. Methods: OFs were isolated from TAO and non-TAO patients (as controls). In addition to HIF-1α, adipogenic differentiation markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein (CEBP) were measured by Western blot, and phenotype changes were evaluated by Oil Red O staining under both normoxia and hypoxia. To elucidate the effect of HIF-1α inhibition, protein expression changes after HIF-1α inhibitor treatment were evaluated under normoxia and hypoxia. Results: TAO OFs exhibited significantly higher HIF-1α expression than non-TAO OFs, and the difference was more distinct under hypoxia than under normoxia. Oil Red O staining showed that adipogenic differentiation of TAO OFs was prominent under hypoxia. Hypoxic conditions increased the expression of adipogenic markers, namely PPARγ and CEBP, as well as HIF-1α in TAO OFs. Interleukin 6 levels also increased in response to hypoxia. The effect of hypoxia on adipogenesis was reduced at the protein level after HIF-1α inhibitor treatment, and this inhibitory effect was sustained even with IGF-1 stimulation in addition to hypoxia. Conclusion Hypoxia induces tissue remodeling in TAO by stimulating adipogenesis through HIF-1α activation. These data could provide insights into new treatment strategies and the mechanisms of adipose tissue remodeling in TAO.

Background: Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas. Methods: This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis. Results: In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively). Conclusions There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.

Purpose: Immune checkpoint inhibitors (ICIs) have been shown significant oncological improvements in several cancers.However, ICIs are still in their infancy in hepatocellular carcinoma (HCC). Programmed cell death-ligand 1 (PD-L1), tumorinfiltrating lymphocytes (TILs), and epithelial-mesenchymal transition (EMT) have been known as prognostic factors in HCC. Therefore, we have focused on identifying the molecular mechanisms between each marker to evaluate a predictive role. Methods: Formalin-fixed paraffin-embedded samples were obtained from 166 patients with HCC who underwent surgery. The expression of PD-L1 and TILs and EMT marker were evaluated by immunohistochemical analysis. Results: The multivariate analysis showed that TIL expression (hazard ratio [HR], 0.483; 95% confidence interval [CI], 0.269–0.866; P = 0.015) were independent prognostic factors for overall survival. The prognostic factors for disease-free survival were EMT marker expression (HR, 1.565; 95% CI, 1.019–2.403; P = 0.005). Patients with high expression of TILs had significantly better survival compared to patients with low expression (P = 0.023). Patients who were TIL+/EMT– showed a significantly better prognosis than those who were TIL–/EMT+ (P = 0.049). Conclusion This study demonstrates that PD-L1 expression of TILs is closely associated with EMT marker expression in HCC. Clinical investigations using anti–PD-1/PD-L1 inhibitors in patients with EMT-associated PD-L1 upregulation are warranted.

Objectives: . Particulate matter (PM) is a risk factor for various diseases. Recent studies have established an association between otitis media (OM) and PM exposure. To confirm this relationship, we developed a novel exposure model designed to control the concentration of PM, and we observed the effects of PM exposure on the Eustachian tube (ET) and middle ear mucosa of rats. Methods: . Forty healthy, 10-week-old, male Sprague-Dawley rats were divided into 3-day, 7-day, 14-day exposure, and control groups (each, n=10). The rats were exposed to incense smoke as the PM source for 3 hours per day. After exposure, bilateral ETs and mastoid bullae were harvested, and histopathological findings were compared using microscopy and transmission electron microscopy (TEM). The expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) in the middle ear mucosa of each group were compared using real-time reverse transcription polymerase chain reaction (RT-PCR). Results: . In the ET mucosa of the exposure group, the goblet cell count significantly increased after PM exposure (P=0.032). In the middle ear mucosa, subepithelial space thickening, increased angio-capillary tissue, and inflammatory cell infiltration were observed. Moreover, the thickness of the middle ear mucosa in the exposure groups increased compared to the control group (P<0.01). The TEM findings showed PM particles on the surface of the ET and middle ear mucosa, and RT-PCR revealed that messenger RNA (mRNA) expression of IL-1β significantly increased in the 3-day and 7-day exposure groups compared to the control group (P=0.035). VEGF expression significantly increased in the 7-day exposure group compared to the control and 3-day exposure groups (P<0.01). Conclusion . The ET and middle ear mucosa of rats showed histopathologic changes after acute exposure to PM that directly reached the ET and middle ear mucosa. Therefore, acute exposure to PM may play a role in the development of OM.

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.

Purpose: Recently, microRNA (miRNA) has been evaluated to provide a new diagnostic and therapeutic modality hepatocellular carcinoma (HCC) and other tumors. They are small non-coding RNA molecules that function as transcriptional and post-transcriptional regulators of gene expression by silencing target genes. The aim of this study was to evaluate the clinical significance of microRNA-18a, 221 (miR-18a, miR-221) expression in HCC formalin-fixed paraffin-embedded (FFPE) tissue. Methods: miR-18a and miR-221 expressions were assessed by reverse transcription and real-time quantitative reverse transcription polymerase chain reaction in 50 pairs of FFPE HCC and the adjacent noncancerous liver tissues. And we evaluated the expression level in HCC tissues as compared with their adjacent noncancerous counterparts. And the relationship between miR-18a, miR-221 level and clinicopathological data and survival rates were analyzed. Results: miR-221 and miR-18a were overexpressed in HCC tissue as compared with their adjacent noncancerous liver tissue (P<0.001). miR221 expression was found to be correlated with larger tumor size (P=0.048). miR-18a expression was correlated with modified Union for International Cancer Control stage (P=0.05). The overall survival (P=0.02) of HCC patients with high miR-221 expression was significantly poorer compared to those patients with low expression. Multivariate analyses demonstrated that miR-221 may be a poor prognostic factor of HCC patients. Conclusion High expression of miR-221 in FFPE tissues could provide significance for prognosis of HCC patients. Although, miR-18a expression was significantly upregulated in HCC tissues, they are not correlated with prognosis. Further large prospective studies are needed to determine their clinical significance.

Purpose: With changing fungal epidemiology and azole resistance in Aspergillus species, identifying fungal species and susceptibility patterns is crucial to the management of aspergillosis and mucormycosis. The objectives of this study were to evaluate performance of panfungal polymerase chain reaction (PCR) assays on formalin-fixed paraffin embedded (FFPE) samples in the identification of fungal species and in the detection of azole-resistance mutations in the Aspergillus fumigatus cyp51A gene at a South Korean hospital. Materials and Methods: A total of 75 FFPE specimens with a histopathological diagnosis of aspergillosis or mucormycosis were identified during the 10-year study period (2006–2015). After deparaffinization and DNA extraction, panfungal PCR assays were conducted on FFPE samples for fungal species identification. The identified fungal species were compared with histopathological diagnosis. On samples identified as A. fumigatus, sequencing to identify frequent mutations in the cyp51A gene [tandem repeat 46 (TR46), L98H, and M220 alterations] that confer azole resistance was performed. Results: Specific fungal DNA was identified in 31 (41.3%) FFPE samples, and of these, 16 samples of specific fungal DNA were in accord with a histopathological diagnosis of aspergillosis or mucormycosis; 15 samples had discordant histopathology and PCR results. No azole-mediating cyp51A gene mutation was noted among nine cases of aspergillosis. Moreover, no cyp51A mutations were identified among three cases with history of prior azole use. Conclusion Panfungal PCR assay with FFPE samples may provide additional information of use to fungal species identification. No azole-resistance mediating mutations in the A. fumigatus cyp51A gene were identified among FFPE samples during study period.

OBJECTIVES: The purpose of this study was to identify and compare the difference and related factors with general characteristic and health behaviors, a experience of diagnosis and treatment of chronic diseases between rural and urban among elderly in Korea. METHODS: We used the data of Community Health Survey 2017 which were collected by the Korean Center for Disease Control and Prevention. The study population comprised 67,835 elderly peopled aged 65 years or older who participated in the survey. The chi-square test, univariate and multivariate logistic regression analysis were used to analyze data. RESULTS: We identified many significant difference of health behaviors, an experience of diagnosis and treatment with chronic diseases between rural and urban. Compared to urban elderly, the odds ratios (ORs) (95% confidence interval) of rural elderly were 1.136 (1.092–1.183) for diagnosis of diabetes, 1.278 (1.278–1.386) for diagnosis of dyslipidemia, 0.940 (0.904–0.977) for diagnosis of arthritis, 0.785(0.736–0.837) for treatment of arthritis, 1.159 (1.116–1.203) for diagnosis of cataracts, and 1.285(1.200–1.375) for treatment of cataracts. In the experience of diagnosis and treatment of chronic diseases, various variables were derived as contributing factors for each disease. Especially, there were statistically significant difference in the experience of diabetes diagnosis, arthritis diagnosis, cataract diagnosis and dyslipidemia except for hypertension diagnosis (p<0.01) between urban and rural elderly. There were statistically significant differences in the experience of treatment for arthritis and cataract (p<0.01), but there was no significant difference in the experience of treatment for hypertension, diabetes, dyslipidemia between urban and rural elderly. CONCLUSION Therefore, it would be necessary to implement a strategic health management project for diseases that showed significant experience of chronic diseases with diagnosis and treatment, reflecting the related factors of the elderly chronic diseases among the urban and rural areas.

PURPOSE: Recently, the neutrophil-to-lymphocyte ratio (NLR), an inflammatory response marker, has been reported to be associated with the prognosis in patients with various type of cancer. However, there have been no studies until now that have explored the prognostic role of combined detection of NLR and CEA in patients with synchronous liver-limited colorectal metastases (sCRLM). METHODS: Eighty-three patients who histologically diagnosed as sCRLM were selected. Their laboratory and clinical data were collected retrospectively. Using receiver operating characteristic curve analysis, the cutoff value of NLR was calculated based on which patients were assigned to a high NLR (more than 1.94) group and low NLR (less than 1.94) group. A cutoff value of 100 ng/mL for serum CEA level was used in light of the previous literature. RESULTS: CEA level and Poorly differentiated histology of colon cancer was significantly correlated with high NLR (P = 0.005 and P = 0.048, respectively). The multivariate analysis identified the high NLR as independent prognostic factors for OS and DFS in all patients (P = 0.010 and P = 0.006, respectively). Patients with both low levels of NLR and CEA had a significantly longer OS and DFS (P = 0.026 and P = 0.009, respectively). CONCLUSION: In conclusion, elevated preoperative NLR is strongly correlated with both survival and recurrence in patients who have been diagnosed with resectable sCRLM. The combination of NLR and CEA level could be a more powerful prognostic marker than NLR alone.
Colonic Neoplasms ; Colorectal Neoplasms ; Humans ; Liver ; Multivariate Analysis ; Neoplasm Metastasis ; Neutrophils ; Prognosis ; Recurrence ; Retrospective Studies ; ROC Curve

BACKGROUND: Antepartum, intrapartum, and postpartum preventive measures with antiretroviral drugs, appropriate delivery methods, and discouraging breastfeeding significantly decrease the risk of mother-to-child transmission of human immunodeficiency virus (HIV) infection. Herein, we investigated the pregnancy outcomes in HIV-infected Korean women. METHODS: We retrospectively reviewed medical records of childbearing-age HIV-infected women between January 2005 and June 2017 at four tertiary care hospitals in Korea. RESULTS: Among a total of 95 HIV infected women of child-bearing age with 587.61 years of follow-up duration, 15 HIV-infected women experienced 21 pregnancies and delivered 16 infants. The pregnancy rate was 3.57 per 100 patient-years. Among the 21 pregnancies, five ended with an induced abortion, and 16 with childbirth including two preterm deliveries at 24 and 35 weeks of gestation, respectively. The two preterm infants had low birth weight and one of them died 10 days after delivery due to respiratory failure. Among the 14 full-term infants, one infant was small for gestational age. There were no HIV-infected infants. CONCLUSION: The pregnancy rate of HIV-infected women in Korea is lower than that of the general population. Although several adverse pregnancy outcomes were observed, mother-to-child transmission of HIV infection was successfully prevented with effective preventive measures.
Abortion, Induced ; Breast Feeding ; Female ; Follow-Up Studies ; Gestational Age ; HIV ; HIV Infections ; Humans ; Infant ; Infant, Low Birth Weight ; Infant, Newborn ; Infant, Premature ; Korea* ; Medical Records ; Parturition ; Postpartum Period ; Pregnancy Outcome ; Pregnancy Rate* ; Pregnancy* ; Respiratory Insufficiency ; Retrospective Studies ; Tertiary Healthcare