1.Inhibitory Action of 1,3,5-Trihydroxybenzene on UVB-Induced NADPH Oxidase 4 through AMPK and JNK Signaling Pathways
Chaemoon LIM ; Mei Jing PIAO ; Kyoung Ah KANG ; Pincha Devage Sameera Madushan FERNANDO ; Herath Mudiyanselage Udari Lakmini HERATH ; Dae Whan KIM ; Joo Mi YI ; Yung Hyun CHOI ; Jin Won HYUN
Biomolecules & Therapeutics 2024;32(4):499-507
Specific sensitivity of the skin to ultraviolet B (UVB) rays is one of the mechanisms responsible for widespread skin damage. This study tested whether 1,3,5-trihydroxybenzene (THB), a compound abundant in marine products, might inhibit UVB radiationinduced NADPH oxidase 4 (NOX4) in both human HaCaT keratinocytes and mouse dorsal skin and explore its cytoprotective mechanism. The mechanism of action was determined using western blotting, immunocytochemistry, NADP + /NADPH assay, reactive oxygen species (ROS) detection, and cell viability assay. THB attenuated UVB-induced NOX4 expression both in vitro and in vivo, and suppressed UVB-induced ROS generation via NADP + production, resulting in increased cell viability with decreased apoptosis. THB also reduced the expression of UVB-induced phosphorylated AMP-activated protein kinase (AMPK) and phosphorylated c-Jun N-terminal kinase (JNK). THB suppressed UVB-induced NOX4 expression and ROS generation by inhibiting AMPK and JNK signaling pathways, thereby inhibiting cellular damage. These results showed that THB could be developed as a UV protectant.
2.Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea
Ji Yun LEE ; Ji Hyun KWON ; Joon Young HUR ; Jun Ho YI ; Ji Hyun LEE ; Hyungwoo CHO ; Young Rok DO ; Jae-Cheol JO ; Hye Jin KANG ; Yougil KOH ; Won Sik LEE ; Sung Nam LIM ; Sang Eun YOON ; Seok Jin KIM ; Jeong-Ok LEE
Cancer Research and Treatment 2024;56(2):681-687
Purpose:
Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers.
Materials and Methods:
Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022.
Results:
The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs.
Conclusion
In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.
3.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.
4.Promising Therapeutic Effectsof Embryonic Stem Cells-Origin Mesenchymal Stem Cells in Experimental Pulmonary Fibrosis Models: Immunomodulatory and Anti-Apoptotic Mechanisms
Hanna LEE ; Ok-Yi JEONG ; Hee Jin PARK ; Sung-Lim LEE ; Eun-yeong BOK ; Mingyo KIM ; Young Sun SUH ; Yun-Hong CHEON ; Hyun-Ok KIM ; Suhee KIM ; Sung Hak CHUN ; Jung Min PARK ; Young Jin LEE ; Sang-Il LEE
Immune Network 2023;23(6):e45-
Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue diseaseILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone.Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.
5.XperCT-guided Intra-cisterna Magna Injection of Streptozotocin for Establishing an Alzheimer’s Disease Model Using the Cynomolgus Monkey (Macaca fascicularis)
Junghyung PARK ; Jinyoung WON ; Chang-Yeop JEON ; Kyung Seob LIM ; Won Seok CHOI ; Sung-hyun PARK ; Jincheol SEO ; Jiyeon CHO ; Jung Bae SEONG ; Hyeon-Gu YEO ; Keonwoo KIM ; Yu Gyeong KIM ; Minji KIM ; Kyung Sik YI ; Youngjeon LEE
Experimental Neurobiology 2022;31(6):409-418
Till date, researchers have been developing animal models of Alzheimer’s disease (AD) in various species to understand the pathological characterization and molecular mechanistic pathways associated with this condition in humans to identify potential therapeutic treatments. A widely recognized AD model that mimics the pathology of human AD involves the intracerebroventricular (ICV) injection with streptozotocin (STZ).However, ICV injection as an invasive approach has several limitations related to complicated surgical procedures. Therefore, in the present study, we created a customized stereotaxic frame using the XperCT-guided system for injecting STZ in cynomolgus monkeys, aiming to establish an AD model. The anatomical structures surrounding the cisterna magna (CM) were confirmed using CT/MRI fusion images of monkey brain with XperCT, the c-arm cone beam computed tomography. XperCT was used to determine the appropriate direction in which the needle tip should be inserted within the CM region. Cerebrospinal fluid (CSF) was collected to confirm the accurate target site when STZ was injected into the CM.Cynomolgus monkeys were administered STZ dissolved in artificial CSF once every week for 4 weeks via intracisterna magna (ICM) injection using XperCT-guided stereotactic system. The molecular mechanisms underlying the progression of STZ-induced AD pathology were analyzed two weeks after the final injection. The monkeys subjected to XperCT-based STZ injection via the ICM route showed features of AD pathology, including markedly enhanced neuronal loss, synaptic impairment, and tau phosphorylation in the hippocampus. These findings suggest a new approach for the construction of neurodegenerative disease models and development of therapeutic strategies.
6.Comparison of the Optimized Intraocular Lens Constants Calculated by Automated and Manifest Refraction for Korean
Youngsub EOM ; Dong Hui LIM ; Dong Hyun KIM ; Yong-Soo BYUN ; Kyung Sun NA ; Seong-Jae KIM ; Chang Rae RHO ; So-Hyang CHUNG ; Ji Eun LEE ; Kyong Jin CHO ; Tae-Young CHUNG ; Eun Chul KIM ; Young Joo SHIN ; Sang-Mok LEE ; Yang Kyung CHO ; Kyung Chul YOON ; In-Cheon YOU ; Byung Yi KO ; Hong Kyun KIM ; Jong Suk SONG ; Do Hyung LEE
Journal of the Korean Ophthalmological Society 2022;63(9):747-753
Purpose:
To derive the optimized intraocular lens (IOL) constants from automated and manifest refraction after cataract surgery in Korean patients, and to evaluate whether there is a difference in optimized IOL constants according to the refraction method.
Methods:
This retrospective multicenter cohort study enrolled 4,103 eyes of 4,103 patients who underwent phacoemulsification and in-the-bag IOL implantation at 18 institutes. Optimized IOL constants for the SRK/T, Holladay, Hoffer Q, and Haigis formulas were calculated via autorefraction or manifest refraction of samples using the same biometry and IOL. The IOL constants derived from autorefraction and manifest refraction were compared.
Results:
Of the 4,103 eyes, the majority (62.9%) were measured with an IOLMaster 500 followed by an IOLMaster 700 (15.2%). A total of 33 types of IOLs were used, and the Tecnis ZCB00 was the most frequently used (53.0%). There was no statistically significant difference in IOL constants derived from autorefraction and manifest refraction when IOL constants were optimized with a large number of study subjects. On the other hand, optimized IOL constants derived from autorefraction were significantly smaller than those from manifest refraction when the number of subjects was small.
Conclusions
It became possible to use the IOL constants optimized from Koreans to calculate the IOL power. However, if the IOL constant is optimized using autorefraction in a small sample group, the IOL constant tends to be small, which may lead to refractive error after surgery.
7.The work and socioeconomic burden of emergency physicians in the COVID-19 pandemic: 2020 Korean Emergency Physician Survey
In Hwan YEO ; Mi Jin LEE ; Tae Jin SIM ; Hyung Min LEE ; Kwang Hyun CHO ; In Byung KIM ; Yoo Sang YOON ; Kyung Hye PARK ; Song Yi PARK ; Hong Jae KIM ; Dong Hoon KEY ; Beom Sok SEO ; Young Min JOO ; Chang Gun JEE ; Suk Jae CHOI ; Ji Hun KANG ; Woo Jin JUNG ; Dae Sung LIM ; Eu Sun LEE
Journal of the Korean Society of Emergency Medicine 2022;33(4):67-75
Objective:
This study evaluated the anxiety, work, and socioeconomic burden of emergency physicians (EP) during the coronavirus disease 2019 (COVID-19) pandemic in South Korea.
Methods:
A cross-sectional observational study was conducted using data from the 2020 Korean Emergency Physician Survey that included the following domains: hospital resources of suspected COVID-19 patients, availability of personal protective equipment, levels of home and workplace anxiety, the severity of work burnout, identification of stressors, changes in personal environments, and measures to decrease stress/anxiety.
Results:
Totally, 855 eligible participants were enrolled in the study. A statistically significant deterioration was observed in response to decreased working income or an unstable employment situation (0.46±0.88 points). The median number of patients with confirmed COVID-19 was 2.72. The risk of infection during emergency department (ED) work was found to be significantly increased (P<0.01). Of the 751 respondents (91.4%) who reported patient contact during their survey phase, 516 (62.8%) reported having taken the COVID-19 reverse transcription polymerase chain reaction test. The major factors that affected worsening of the work burden were determined to be unsuitable inter-hospital transfer arrangements for febrile patients (3.46±1.06 before vs. 1.99±1.16 after the pandemic, P<0.01) and delayed consultation for patients with fever or respiratory symptoms in the ED (3.20±1.06 before vs. 2.66±1.10 after the pandemic, P<0.01).
Conclusion
During the peak phase, the COVID-19 pandemic induced substantial workplace and socioeconomic burdens for Korean EPs. The sustained impact of the pandemic on the wellness of EPs deserves further investigation to guide targeted interventions.
8.Analysis of factors influencing emergency physician’s choice of specialty again using machine learning method
Jee Young PARK ; Hyung Min LEE ; Kwang Hyun CHO ; In Byung KIM ; Mi Jin LEE ; Yoo Sang YOON ; Kyung Hye PARK ; Song Yi PARK ; Hong Jae KIM ; Dong Hoon KEY ; Beom Sok SEO ; Young Min JOO ; Chang Gun JEE ; Suk Jae CHOI ; In Hwan YEO ; Ji Hun KANG ; Woo Jin JUNG ; Dae Sung LIM ; Eu Sun LEE
Journal of the Korean Society of Emergency Medicine 2022;33(4):57-66
Objective:
Machine learning is emerging as a new alternative in various scientific fields and is potentially a new method of interpretation. Using the Light Gradient Boosting Machine (LightGBM), we analyzed the factors that influence the rechoice of emergency medicine responders. The survey is a cross-sectional study which provides an accurate understanding of a responder's current status. However, the results may vary depending on the composition, format, and question, and the relationship between the answers may be unclear.
Methods:
This study evaluated the modified 2020 Korean Emergency Physician Survey raw data. We applied the preferred model for random relationship check, random forest, support vector machine, and LightGBM models. The stacking ensemble model was used for the final decision process.
Results:
‘It is fun working in an emergency room’was the most selected response factor for re-choice, followed by ‘interesting major’. The physical burden of age and lack of identity had a negative impact, whereas burnout and emotional stress factors had a lesser effect. Anxiety caused by the coronavirus disease 2019 (COVID-19) is thought to have a significant impact on this decision making.
Conclusion
Establishing the identity of emergency medicine and being faithful to its fundamental mission is a way to increase the rate of re-choice. Decreasing the burden of workload modified according to age is recommended to establish career longevity. The method of machine learning presents us with a new possibility of checking the relevance of survey results quickly and easily.
9.The workload of emergency physician using Korean Emergency Physician Survey
Yoo Sang YOON ; DongWoo SON ; Ji Hun KANG ; Kwang Hyun CHO ; In Byung KIM ; Mi Jin LEE ; Hyung Min LEE ; Kyung Hye PARK ; Song Yi PARK ; Hong Jae KIM ; Dong Hoon KEY ; Beom Sok SEO ; Young Min JOO ; Chang Gun JEE ; Suk Jae CHOI ; In Hwan YEO ; Woo Jin JUNG ; Dae Sung LIM ; Eu Sun LEE
Journal of the Korean Society of Emergency Medicine 2022;33(4):49-56
Objective:
It has been reported that emergency physicians experience high levels of depression and psychological burnout due to night shifts and tend to consider early retirement. This study intended to check working hours and intensity, individual health, satisfaction, and overall welfare, given the increase in the numbers of emergency physicians.
Methods:
The study used the results of the ‘2020 Korean Emergency Physician Survey (KEPS)’ conducted from January 15 to February 26, 2021, which targeted 2,138 emergency physicians registered with the Korean Society of Emergency Medicine. The survey was conducted online through the web and mobile application.
Results:
One thousand three hundred seven out of the 2,167 emergency physicians (60.3%) registered at the society responded. The average age of the respondents was 42.6 years, and there were 1,148 male emergency physicians and 158 female emergency physicians. The average professional experience was 8.2 years, with 325 professors, 122 commissioned doctors, 648 public servants of which 90 had military service, and 45 medical practitioners.
Conclusion
In conclusion, the number of working hours of emergency physicians showed a decreasing trend compared to 2010 and 2015. However, emergency physicians often expected early retirement. This suggests that, while the absolute working hours are decreasing, the actual working intensity has not decreased. For the proper development of the emergency medical system, it is necessary to establish a stable working environment for emergency physicians. A systematic study is needed on the working hours and work intensity of emergency physicians.
10.Analysis of work, life, and occupation perception of emergency physician by generations
Jun Se PARK ; Beom Sok SEO ; Kwang Hyun CHO ; In Byung KIM ; Mi Jin LEE ; Yoo Sang YOON ; Kyung Hye PARK ; Song Yi PARK ; Hong Jae KIM ; Dong Hoon KEY ; Hyung Min LEE ; Young Min JOO ; Chang Gun JEE ; Suk Jae CHOI ; In Hwan YEO ; Ji Hun KANG ; Woo Jin JUNG ; Dae Sung LIM ; Eu Sun LEE
Journal of the Korean Society of Emergency Medicine 2022;33(4):38-48
Objective:
As the history of emergency medicine grows longer, emergency medicine specialists are observed to comprise various age groups. There have been no prior studies on the generation shift analysis of emergency medicine specialists. Our study is designed to identify the characteristics of each generation and predict the generation shift in emergency medicine physicians.
Methods:
The analysis was based on the results of the 2020 survey of emergency medicine specialists. The study was conducted on 1,307 respondents and finally, the responses of 967 people were analyzed after excluding 199 who were not in charge of emergency room treatments and 141 who gave incomplete responses. The respondents were divided into four groups based on the following generations: first generation (1996-1999), second generation (2000-2008), third generation (2009-2014), and fourth generation (2015-2020), classified by the year in which they acquired their emergency medicine board license. The intergenerational difference analysis was done using the Kruskall-Wallis test.
Results:
The first generation was characterized by a high proportion of university hospital professors, large non-clinical activity hours, a few night shifts, higher social contributions, low satisfaction with the training and education environment, and a high retirement age compared to the later generations. In the second generation, the characteristics of the first, third, and fourth generations were generally mixed. The third and fourth generations showed similar characteristics overall, though there were differences in some categories.
Conclusion
There were significant differences by generation in the working environments, motivation for application, and retirement age. This is the first study that quantifies generational differences. Considering these trends, a discussion about the work environment needs to be initiated.

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