1.Immune Cells Are DifferentiallyAffected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice
Jung Ah KIM ; Sung-Hee KIM ; Jeong Jin KIM ; Hyuna NOH ; Su-bin LEE ; Haengdueng JEONG ; Jiseon KIM ; Donghun JEON ; Jung Seon SEO ; Dain ON ; Suhyeon YOON ; Sang Gyu LEE ; Youn Woo LEE ; Hui Jeong JANG ; In Ho PARK ; Jooyeon OH ; Sang-Hyuk SEOK ; Yu Jin LEE ; Seung-Min HONG ; Se-Hee AN ; Joon-Yong BAE ; Jung-ah CHOI ; Seo Yeon KIM ; Young Been KIM ; Ji-Yeon HWANG ; Hyo-Jung LEE ; Hong Bin KIM ; Dae Gwin JEONG ; Daesub SONG ; Manki SONG ; Man-Seong PARK ; Kang-Seuk CHOI ; Jun Won PARK ; Jun-Won YUN ; Jeon-Soo SHIN ; Ho-Young LEE ; Ho-Keun KWON ; Jun-Young SEO ; Ki Taek NAM ; Heon Yung GEE ; Je Kyung SEONG
Immune Network 2024;24(2):e7-
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.
2.Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Overview and Summary 2024
Young Joo PARK ; Eun Kyung LEE ; Young Shin SONG ; Bon Seok KOO ; Hyungju KWON ; Keunyoung KIM ; Mijin KIM ; Bo Hyun KIM ; Won Gu KIM ; Won Bae KIM ; Won Woong KIM ; Jung-Han KIM ; Hee Kyung KIM ; Hee Young NA ; Shin Je MOON ; Jung-Eun MOON ; Sohyun PARK ; Jun-Ook PARK ; Ji-In BANG ; Kyorim BACK ; Youngduk SEO ; Dong Yeob SHIN ; Su-Jin SHIN ; Hwa Young AHN ; So Won OH ; Seung Hoon WOO ; Ho-Ryun WON ; Chang Hwan RYU ; Jee Hee YOON ; Ka Hee YI ; Min Kyoung LEE ; Sang-Woo LEE ; Seung Eun LEE ; Sihoon LEE ; Young Ah LEE ; Joon-Hyop LEE ; Ji Ye LEE ; Jieun LEE ; Cho Rok LEE ; Dong-Jun LIM ; Jae-Yol LIM ; Yun Kyung JEON ; Kyong Yeun JUNG ; Ari CHONG ; Yun Jae CHUNG ; Chan Kwon JUNG ; Kwanhoon JO ; Yoon Young CHO ; A Ram HONG ; Chae Moon HONG ; Ho-Cheol KANG ; Sun Wook KIM ; Woong Youn CHUNG ; Do Joon PARK ; Dong Gyu NA ;
International Journal of Thyroidology 2024;17(1):1-20
Differentiated thyroid cancer demonstrates a wide range of clinical presentations, from very indolent cases to those with an aggressive prognosis. Therefore, diagnosing and treating each cancer appropriately based on its risk status is important. The Korean Thyroid Association (KTA) has provided and amended the clinical guidelines for thyroid cancer management since 2007. The main changes in this revised 2024 guideline include 1) individualization of surgical extent according to pathological tests and clinical findings, 2) application of active surveillance in low-risk papillary thyroid microcarcinoma, 3) indications for minimally invasive surgery, 4) adoption of World Health Organization pathological diagnostic criteria and definition of terminology in Korean, 5) update on literature evidence of recurrence risk for initial risk stratification, 6) addition of the role of molecular testing, 7) addition of definition of initial risk stratification and targeting thyroid stimulating hormone (TSH) concentrations according to ongoing risk stratification (ORS), 8) addition of treatment of perioperative hypoparathyroidism, 9) update on systemic chemotherapy, and 10) addition of treatment for pediatric patients with thyroid cancer.
3.Association of Soy Foods With Gastric Cancer Considering Helicobacter pylori:A Multi-Center Case-Control Study
Su Youn NAM ; Seong Woo JEON ; Joong Goo KWON ; Yun Jin CHUNG ; Yong Hwan KWON ; Si Hyung LEE ; Ju Yup LEE ; Chang Hun YANG ; Junwoo JO
Journal of Gastric Cancer 2024;24(4):436-450
Purpose:
This study aims to explore the relationship between soy food consumption and gastric cancer (GC) risk, accounting for Helicobacter pylori infection status.
Materials and Methods:
We analyzed data from patients with GC and healthy individuals prospectively enrolled by 6 hospitals between 2016 and 2018. Dietary intake was evaluated using questionnaires that categorized seven dietary habits and 19 food groups. Multivariate logistic regression models were applied to examine associations. Model I adjusted for various epidemiological factors, while Model II included further adjustments for H. pylori infection.Primary exposures examined were consumption frequencies of nonfermented, unsalted soy foods (soybean/tofu) and fermented, salty soy foods (soybean paste stew).
Results:
A total of 5,535 participants were included, with 1,629 diagnosed with GC. In Model I, the frequency of soybean/tofu consumption was inversely related to GC risk; adjusted odd ratios (aORs) were 0.62 (95% confidence interval [CI], 0.48–0.8), 0.38 (95% CI, 0.3–0.49), 0.42 (95% CI, 0.33–0.53), and 0.33 (95% CI, 0.27–0.42) for 1 time/week, 2 times/week, 3 times/week, and ≥4 times/week. Consumption of 2 servings/week of soybean paste stew showed the lowest GC association, forming a V-shaped curve. Both low (aOR, 4.03; 95% CI, 3.09–5.26) and high serving frequencies of soybean paste stew (aOR, 2.23; 95% CI, 1.76–2.82) were associated with GC. The association between soy foods and GC in Model II was similar to that in Model I. The soy food-GC associations were consistent across sexes in Model I.Nonetheless, the positive correlation between frequent consumption of soybean paste stew (≥5 times/week) and GC was more pronounced in women (aOR, 7.58; 95% CI, 3.20–17.99) compared to men (aOR, 3.03; 95% CI, 1.61–5.88) in Model II. Subgroup analyses by H. pylori status and salty diet revealed a consistent inverse relationship between soybean/tofu and GC risk. In contrast, soybean paste stew showed a V-shaped relationship in H. pylori-positive or salty diet groups and no significant association in the H. pylori-negative group.
Conclusions
Soybean/tofu intake is consistently associated with a decreased risk of GC.However, the relationship between soybean paste stew consumption and GC risk varies, depending on H. pylori infection status and dietary salt intake.
4.Clinical Features of Mpox Patients in Korea: A Multicenter Retrospective Study
So Yun LIM ; Hyeon Jae JO ; Su-Yeon LEE ; Miyoung AHN ; Yeonjae KIM ; Jaehyun JEON ; Eu Suk KIM ; BumSik CHIN ; Jae-Phil CHOI ; Nam Joong KIM
Journal of Korean Medical Science 2024;39(4):e19-
Background:
Mpox is a viral illness with a characteristic skin rash caused by the monkeypox virus. In 2022, Mpox spread throughout the world, and an epidemic through domestic transmission started in South Korea in early 2023. This study aimed to summarize the clinical features of Mpox patients in South Korea.
Methods:
This is a multicenter retrospective study conducted at four hospitals in South Korea. All adult patients diagnosed with Mpox who were admitted to the study hospitals between June 1, 2022 and May 26, 2023 and were discharged by June 30, 2023 were reviewed.
Results:
Sixty patients were included, accounting for 65.9% of Mpox cases reported in South Korea during the study period. Median age was 32 years and 97% (58/60) of patients were male. In total, 85% (51/60) of patients reported their sexual orientation as homosexual or bisexual. The most common route of transmission was sexual or close contact (55/60). Every patient had a skin rash and 88% (53/60) had constitutional symptoms. In total, 42% (25/60) of patients had human immunodeficiency virus and 25% (15/60) had concomitant sexually transmitted infections. Severe manifestations of Mpox were identified in only two patients.
Conclusion
Mpox patients in South Korea were mainly young adult males and were infected through sexual contact. The clinical outcomes were favorable.
5.Caregiver Burden of Patients With Huntington’s Disease in South Korea
Chan Young LEE ; Chaewon SHIN ; Yun Su HWANG ; Eungseok OH ; Manho KIM ; Hyun Sook KIM ; Sun Ju CHUNG ; Young Hee SUNG ; Won Tae YOON ; Jin Whan CHO ; Jae-Hyeok LEE ; Han-Joon KIM ; Hee Jin CHANG ; Beomseok JEON ; Kyung Ah WOO ; Seong-Beom KOH ; Kyum-Yil KWON ; Jangsup MOON ; Young Eun KIM ; Jee-Young LEE
Journal of Movement Disorders 2024;17(1):30-37
Objective:
This is the first prospective cohort study of Huntington’s disease (HD) in Korea. This study aimed to investigate the caregiver burden in relation to the characteristics of patients and caregivers.
Methods:
From August 2020 to February 2022, we enrolled patients with HD from 13 university hospitals in Korea. We used the 12-item Zarit Burden Interview (ZBI-12) to evaluate the caregiver burden. We evaluated the clinical associations of the ZBI-12 scores by linear regression analysis and investigated the differences between the low- and high-burden groups.
Results:
Sixty-five patients with HD and 45 caregivers were enrolled in this cohort study. The average age at onset of motor symptoms was 49.3 ± 12.3 years, with an average cytosine-adenine-guanine (CAG)n of 42.9 ± 4.0 (38–65). The median ZBI-12 score among our caregivers was 17.6 ± 14.2. A higher caregiver burden was associated with a more severe Shoulson–Fahn stage (p = 0.038) of the patients. A higher ZBI-12 score was also associated with lower independence scale (B = -0.154, p = 0.006) and functional capacity (B = -1.082, p = 0.002) scores of patients. The caregiving duration was longer in the high- than in the low-burden group. Caregivers’ demographics, blood relation, and marital and social status did not affect the burden significantly.
Conclusion
HD patients’ neurological status exerts an enormous impact on the caregiver burden regardless of the demographic or social status of the caregiver. This study emphasizes the need to establish an optimal support system for families dealing with HD in Korea. A future longitudinal analysis could help us understand how disease progression aggravates the caregiver burden throughout the entire disease course.
6.Antenatal Magnesium Sulfate Is Not Associated With Improved Long-Term Neurodevelopment and Growth in Very Low Birth Weight Infants
Ga Won JEON ; So Yoon AHN ; Su Min KIM ; Misun YANG ; Se In SUNG ; Ji-Hee SUNG ; Soo-young OH ; Cheong-Rae ROH ; Suk-Joo CHOI ; Yun Sil CHANG
Journal of Korean Medical Science 2023;38(44):e350-
Background:
Though antenatal magnesium sulfate (MgSO4 ) is widely used for fetal neuroprotection, suspicions about the long-term neuroprotection of antenatal MgSO4 have been raised.
Methods:
We investigated short- and long-term outcomes of antenatal MgSO4 use for 468 infants weighing < 1,500 g with a gestational age of 24–31 weeks.
Results:
Short-term morbidities and the risk of developmental delay, hearing loss, and cerebral palsy at a corrected age of 18–24 months and 3 years of age did not decrease in the MgSO4 group (infants who were exposed to MgSO4 for any purpose) or neuroprotection group (infants who were exposed to MgSO4 for fetal neuroprotection) compared with the control group (infants who were not exposed to MgSO4 ). The z-scores of weight, height, and head circumference did not increase in the MgSO4 group or neuroprotection group compared with the control group.
Conclusion
Antenatal MgSO4 including MgSO4 for neuroprotection did not have beneficial effects on long-term neurodevelopmental and growth outcomes.
7.Effects of sevoflurane on metalloproteinase and natural killer group 2, member D (NKG2D) ligand expression and natural killer cell-mediated cytotoxicity in breast cancer: an in vitro study
Hyae Jin KIM ; Soeun JEON ; Hyeon Jeong LEE ; Jaeho BAE ; Hyun-Su RI ; Jeong-Min HONG ; Sung In PAEK ; Seul Ki KWON ; Jae-Rin KIM ; Seungbin PARK ; Eun-Jung YUN
Korean Journal of Anesthesiology 2023;76(6):627-639
Background:
We investigated the effects of sevoflurane exposure on the expression of matrix metalloproteinase (MMP), expression and ablation of natural killer group 2, member D (NKG2D) ligands (UL16-binding proteins 1–3 and major histocompatibility complex class I chain-related molecules A/B), and natural killer (NK) cell-mediated cytotoxicity in breast cancer cells.
Methods:
Three human breast cancer cell lines (MCF-7, MDA-MB-453, and HCC-70) were incubated with 0 (control), 600 (S6), or 1200 μM (S12) sevoflurane for 4 h. The gene expression of NKG2D ligands and their protein expression on cancer cell surfaces were measured using multiplex polymerase chain reaction (PCR) and flow cytometry, respectively. Protein expression of MMP-1 and -2 and the concentration of soluble NKG2D ligands were analyzed using western blotting and enzyme-linked immunosorbent assays, respectively.
Results:
Sevoflurane downregulated the mRNA and protein expression of the NKG2D ligand in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells but did not affect the expression of MMP-1 or -2 or the concentration of soluble NKG2D ligands in the MCF-7, MDA-MB-453, and HCC-70 cells. Sevoflurane attenuated NK cell-mediated cancer cell lysis in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells (P = 0.040, P = 0.040, and P = 0.040, respectively).
Conclusions
Our results demonstrate that sevoflurane exposure attenuates NK cell-mediated cytotoxicity in breast cancer cells in a dose-dependent manner. This could be attributed to a sevoflurane-induced decrease in the transcription of NKG2D ligands rather than sevoflurane-induced changes in MMP expression and their proteolytic activity.
8.Generative Adversarial Network-Based Image Conversion Among Different Computed Tomography Protocols and Vendors: Effects on Accuracy and Variability in Quantifying Regional Disease Patterns of Interstitial Lung Disease
Hye Jeon HWANG ; Hyunjong KIM ; Joon Beom SEO ; Jong Chul YE ; Gyutaek OH ; Sang Min LEE ; Ryoungwoo JANG ; Jihye YUN ; Namkug KIM ; Hee Jun PARK ; Ho Yun LEE ; Soon Ho YOON ; Kyung Eun SHIN ; Jae Wook LEE ; Woocheol KWON ; Joo Sung SUN ; Seulgi YOU ; Myung Hee CHUNG ; Bo Mi GIL ; Jae-Kwang LIM ; Youkyung LEE ; Su Jin HONG ; Yo Won CHOI
Korean Journal of Radiology 2023;24(8):807-820
Objective:
To assess whether computed tomography (CT) conversion across different scan parameters and manufacturers using a routable generative adversarial network (RouteGAN) can improve the accuracy and variability in quantifying interstitial lung disease (ILD) using a deep learning-based automated software.
Materials and Methods:
This study included patients with ILD who underwent thin-section CT. Unmatched CT images obtained using scanners from four manufacturers (vendors A-D), standard- or low-radiation doses, and sharp or medium kernels were classified into groups 1–7 according to acquisition conditions. CT images in groups 2–7 were converted into the target CT sty le (Group 1: vendor A, standard dose, and sharp kernel) using a RouteGAN. ILD was quantified on original and converted CT images using a deep learning-based software (Aview, Coreline Soft). The accuracy of quantification was analyzed using the dice similarity coefficient (DSC) and pixel-wise overlap accuracy metrics against manual quantification by a radiologist. Five radiologists evaluated quantification accuracy using a 10-point visual scoring system.
Results:
Three hundred and fifty CT slices from 150 patients (mean age: 67.6 ± 10.7 years; 56 females) were included. The overlap accuracies for quantifying total abnormalities in groups 2–7 improved after CT conversion (original vs. converted: 0.63vs. 0.68 for DSC, 0.66 vs. 0.70 for pixel-wise recall, and 0.68 vs. 0.73 for pixel-wise precision; P < 0.002 for all). The DSCs of fibrosis score, honeycombing, and reticulation significantly increased after CT conversion (0.32 vs. 0.64, 0.19 vs. 0.47, and 0.23 vs. 0.54, P < 0.002 for all), whereas those of ground-glass opacity, consolidation, and emphysema did not change significantly or decreased slightly. The radiologists’ scores were significantly higher (P < 0.001) and less variable on converted CT.
Conclusion
CT conversion using a RouteGAN can improve the accuracy and variability of CT images obtained using different scan parameters and manufacturers in deep learning-based quantification of ILD.
9.Current Status of Low-Density Lipoprotein Cholesterol Target Achievement in Patients with Type 2 Diabetes Mellitus in Korea Compared with Recent Guidelines
Soo Jin YUN ; In-Kyung JEONG ; Jin-Hye CHA ; Juneyoung LEE ; Ho Chan CHO ; Sung Hee CHOI ; SungWan CHUN ; Hyun Jeong JEON ; Ho-Cheol KANG ; Sang Soo KIM ; Seung-Hyun KO ; Gwanpyo KOH ; Su Kyoung KWON ; Jae Hyuk LEE ; Min Kyong MOON ; Junghyun NOH ; Cheol-Young PARK ; Sungrae KIM
Diabetes & Metabolism Journal 2022;46(3):464-475
Background:
We evaluated the achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with type 2 diabetes mellitus (T2DM) according to up-to-date Korean Diabetes Association (KDA), European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS), and American Diabetes Association (ADA) guidelines.
Methods:
This retrospective cohort study collected electronic medical record data from patients with T2DM (≥20 years) managed by endocrinologists from 15 hospitals in Korea (January to December 2019). Patients were categorized according to guidelines to assess LDL-C target achievement. KDA (2019): Very High-I (atherosclerotic cardiovascular disease [ASCVD]) <70 mg/dL; Very High-II (target organ damage [TOD], or cardiovascular risk factors [CVRFs]) <70 mg/dL; high (others) <100 mg/dL. ESC/EAS (2019): Very High-I (ASCVD): <55 mg/dL; Very High-II (TOD or ≥3-CVRF) <55 mg/dL; high (diabetes ≥10 years without TOD plus any CVRF) <70 mg/dL; moderate (diabetes <10 years without CVRF) <100 mg/dL. ADA (2019): Very High-I (ASCVD); Very High-II (age ≥40+ TOD, or any CVRF), for high intensity statin or statin combined with ezetimibe.
Results:
Among 2,000 T2DM patients (mean age 62.6 years; male 55.9%; mean glycosylated hemoglobin 7.2%) ASCVD prevalence was 24.7%. Of 1,455 (72.8%) patients treated with statins, 73.9% received monotherapy. According to KDA guidelines, LDL-C target achievement rates were 55.2% in Very High-I and 34.9% in Very High-II patients. With ESC/EAS guidelines, target attainment rates were 26.6% in Very High-I, 15.7% in Very High-II, and 25.9% in high risk patients. Based on ADA guidelines, most patients (78.9%) were very-high risk; however, only 15.5% received high-intensity statin or combination therapy.
Conclusion
According to current dyslipidemia management guidelines, LDL-C goal achievement remains suboptimal in Korean patients with T2DM.
10.Botulinum Toxin A Ameliorates Neuroinflammation in the MPTP and 6-OHDA-Induced Parkinson’s Disease Models
Hyeon Joo HAM ; In Jun YEO ; Seong Hee JEON ; Jun Hyung LIM ; Sung Sik YOO ; Dong Ju SON ; Sung-Su JANG ; Haksup LEE ; Seung-Jin SHIN ; Sang Bae HAN ; Jae Suk YUN ; Jin Tae HONG
Biomolecules & Therapeutics 2022;30(1):90-97
Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson’s disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

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