• Journal of Life Science
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• v.32 no.4
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• pp.271-278
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• 2022

The detailed mechanism by which cancer upregulated gene 2 (CUG2) overexpression induces cancer stem cell-like phenotypes is not fully understood. The downregulation of FBXW7 E3 ligase, a tumor suppressor known for its proteolytic regulation of oncogenic proteins such as cyclin E, c-Myc, Notch, and Yap1, has been frequently reported in several types of tumor tissues, including those in the large intestine, cervix, and stomach. Therefore, we investigated whether FBXW7 is involved in CUG2-induced oncogenesis. In this study, the decreased expression of FBXW7 was examined in human lung adenocarcinoma A549 (A549-CUG2) and human bronchial BEAS-2B cells (BEAS-CUG2) overexpressing CUG2 and compared with control cells stably expressing an empty vector (A549-Vec or BEAS-Vec). Treatment with MG132 (a proteosome inhibitor) prevented the degradation of FBXW7 and Yap1 proteins, which are substrates of the FBXW7 E3 ligase. To address the role of Fbxw7 in the development of cancer stem cell (CSC) phenotypes, we suppressed Fbxw7 protein levels using its siRNA. We observed that decreased levels of FBXW7 enhanced cell migration, invasion, and spheroid size and number in A549-Vec and BEAS-Vec cells. The enforced expression of FBXW7 produced the opposite results in A549-CUG2 and BEAS-CUG2 cells. Furthermore, the downregulation of FBXW7 elevated the activities of EGFR, Akt, and ERK1/2 and upregulated β-catenin, Yap1, and NEK2, while the enforced expression of FBXW7 generated the opposite results. We thus propose that FBXW7 downregulation induced by CUG2 confers CSC-like phenotypes through the upregulation of both the EGFR-ERK1/2 and β-catenin-Yap1-NEK2 signaling pathways.

• Molecules and Cells
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• v.45 no.12
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• pp.896-910
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• 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and potentially fatal virus. So far, most comprehensive analyses encompassing clinical and transcriptional manifestation have concentrated on the lungs. Here, we confirmed evident signs of viral infection in the lungs and spleen of SARS-CoV-2-infected K18-hACE2 mice, which replicate the phenotype and infection symptoms in hospitalized humans. Seven days post viral detection in organs, infected mice showed decreased vital signs, leading to death. Bronchopneumonia due to infiltration of leukocytes in the lungs and reduction in the spleen lymphocyte region were observed. Transcriptome profiling implicated the meticulous regulation of distress and recovery from cytokine-mediated immunity by distinct immune cell types in a time-dependent manner. In lungs, the chemokine-driven response to viral invasion was highly elevated at 2 days post infection (dpi). In late infection, diseased lungs, post the innate immune process, showed recovery signs. The spleen established an even more immediate line of defense than the lungs, and the cytokine expression profile dropped at 7 dpi. At 5 dpi, spleen samples diverged into two distinct groups with different transcriptome profile and pathophysiology. Inhibition of consecutive host cell viral entry and massive immunoglobulin production and proteolysis inhibition seemed that one group endeavored to survive, while the other group struggled with developmental regeneration against consistent viral intrusion through the replication cycle. Our results may contribute to improved understanding of the longitudinal response to viral infection and development of potential therapeutics for hospitalized patients affected by SARS-CoV-2.

• Journal of Life Science
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• v.33 no.2
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• pp.158-168
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• 2023

Natural products have been used to mitigate the effects of cancer and infectious diseases, as they feature diverse bioactivities, such as antioxidant, antibacterial, anti-inflammatory, and immunomodulatory effects. Here, we chose 10 natural products that are well-known as pulmonary enhancers and investigated their bactericidal effects on Streptococcus pneumoniae. In the disk diffusion assay, the growth of S. pneumoniae was significantly regulated by G. fructus treatment regardless of extraction method used. We first adopted spraying as a novel delivery method for G. fructus. Interestingly, mice exposed to G. fructus three times a day for 2 weeks were resistant to S. pneumoniae intranasal infection (shown both through body weight loss and survival rates compared to the control group). Moreover, we confirmed that exposure to G. fructus regulated the colonization of the bacteria despite the sustained inflammation in the lung after exposure to S. pneumoniae, indicating that migrated inflammatory immune cells may involve a host defense mechanism against pulmonary infectious diseases. While a similar number of granulocytes (CD11b⁺Ly6C⁺Ly6G⁺), neutrophils (CD11b⁺Ly6C^intLy6G⁺), and monocytes (CD11b⁺Ly6C^intLy6G^-) were found between groups, a significantly increased number of alveolar macrophages (CD11b⁺CD11c^hiF4/80⁺) was detected in BAL fluids of mice pre-exposed to G. fructus at 5 days after S. pneumonia infection. Taken together, our data suggest that this usage of G. fructus can induce protective immunity against bacterial infection, indicating that facial spray may be helpful in enhancing the defense mechanism against pulmonary inflammation and in evaluating the efficacy of natural products as immune enhancers against respiratory diseases.

• The Journal of Korean Medicine
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• v.44 no.1
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• pp.65-75
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• 2023

Objectives: Objectives: In this study, we define a medical service type that combines Western medicine, Korean medicine, and complementary and alternative medicine (CAM) as an integrated medical service. This study, as part of tertiary hospital-based integrated medical service model and clinical field application, aims to collect status and opinions on integrated medical service for medical staff in the field. Methods: This is a survey study, and was conducted on doctors from Kyung Hee University Hospital and Korean medicine doctors from Kyung Hee University Korean Medicine Hospital. Respondents were recruited on a first-come, first-served basis until the number of respondents reached 120. The investigation was conducted for a total of 16 days from October 4, 2021 to October 19, 2021 by e-mail. Results: Recognition of integrated medical services was confirmed to be 45.8%, and 49.2% responded positively to the necessity of it. As a group of diseases that require the establishment of integrated medical services in the future, 'disorders of musculoskeletal systems and connective tissues' was the highest. The most expected advantages of providing integrated medical services were 'increased satisfaction of patients and guardians' and 'increased treatment effects.' Conclusions: In this study, we investigated the perception of doctors and Korean medicine doctors on integrated medical services that combine Western medicine, Korean medicine, and CAM. It has been confirmed that medical staff generally have a positive perception of integrated medical services, and if the scientific basis for the effect of integrated medical services is supported, the rate of positive perception is expected to increase.

• Journal of Intelligence and Information Systems
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• v.28 no.1
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• pp.329-352
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• 2022

It is reported that particulate matter(PM) penetrates the lungs and blood vessels and causes various heart diseases and respiratory diseases such as lung cancer. The subway is a means of transportation used by an average of 10 million people a day, and although it is important to create a clean and comfortable environment, the level of particulate matter pollution is shown to be high. It is because the subways run through an underground tunnel and the particulate matter trapped in the tunnel moves to the underground station due to the train wind. The Ministry of Environment and the Seoul Metropolitan Government are making various efforts to reduce PM concentration by establishing measures to improve air quality at underground stations. The smart air quality management system is a system that manages air quality in advance by collecting air quality data, analyzing and predicting the PM concentration. The prediction model of the PM concentration is an important component of this system. Various studies on time series data prediction are being conducted, but in relation to the PM prediction in subway stations, it is limited to statistical or recurrent neural network-based deep learning model researches. Therefore, in this study, we propose four transformer-based models including spatiotemporal transformers. As a result of performing PM concentration prediction experiments in the waiting rooms of subway stations in Seoul, it was confirmed that the performance of the transformer-based models was superior to that of the existing ARIMA, LSTM, and Seq2Seq models. Among the transformer-based models, the performance of the spatiotemporal transformers was the best. The smart air quality management system operated through data-based prediction becomes more effective and energy efficient as the accuracy of PM prediction improves. The results of this study are expected to contribute to the efficient operation of the smart air quality management system.

• Journal of the Korean Orthopaedic Association
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• v.54 no.2
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• pp.164-171
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• 2019

Purpose: A dedifferentiated chondrosarcoma is a rare lethal tumor characterized by a low grade chondrosarcoma juxtaposed with a high grade dedifferentiated sarcoma, such as osteosarcoma, fibrosarcoma. The aim of our study was to document the clinical manifestation and oncologic outcomes of a dedifferentiated chondrosarcoma. Materials and Methods: This study identified 11 patients who were diagnosed and treated for dedifferentiated chondrosarcoma between January 2007 and December 2016. The identified cohort was then reviewed regarding age, sex, symptom onset, tumor location, magnetic resonance imagings (MRIs), surgical margin, and pathologic diagnosis. The time to local recurrence and/or metastasis, follow-up duration, and the patients' final status were analyzed. Results: The patients were comprised of 7 males and 4 females with a mean age of 54 years (range, 33-80 years). The location of the tumor was in the femur in 6 cases, pelvis in 4 cases, and metatarsal in 1 case. The average tumor diameter was 12.7 cm (range, 6.0-26.1 cm). At the time of diagnosis, 2 patients showed pathologic fracture; 1 patient was Enecking stage IIA, 9 patients were stage IIB, and 1 patient was stage III. Eight patients were classified as a primary dedifferentiated chondrosarcoma and 3 patients were secondary. One of the primary lesions was misinterpreted initially as a low grade chondroid lesion by MRI and underwent curettage. Local recurrence occurred in 8 cases and distant metastasis occurred in 10 cases with a mean duration of 8 months (range, 2-23 months) and 7 months (range, 1-32 months), respectively. The three-year overall survival of patients with dedifferentiated chondrosarcoma was 18%, and 10 patients died due to disease progression. Conclusion: Dedifferentiated chondrosarcoma developed lung metastases in the early period of the clinical courses and the prognosis was dismal.

• Pediatric Infection and Vaccine
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• v.31 no.1
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• pp.37-45
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• 2024

Purpose: This study aimed to examine the clinical features and determinants of macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMP) and to assess the differences in the time to fever resolution between doxycycline (DXC), tosufloxacin (TFX) and corticosteroid (CST) as second-line treatment. Methods: We retrospectively analyzed the medical records of patients under the age of 18 who were admitted to Nowon Eulji University Hospital between July 2018 and February 2020, diagnosed with mycoplasma pneumonia. Macrolide resistance was confirmed by detecting point mutations in the 23S rRNA gene. MUMP was clinically defined by persistent fever (≥38.0℃) lasting for 72 hours or more after the initiation of macrolide treatment. In cases of MUMP, patients were treated with an addition of CST, or the initial macrolide was replaced either DXC or TFX. Results: Out of 157 cases of mycoplasma pneumonia, 83 cases (52.9%) did not respond to macrolides. Patients with MUMP exhibited significantly higher C-reactive protein (CRP) levels (3.2±3.0 vs. 2.4±2.2 mg/dL, P=0.047), more frequent lobar/segmental infiltrations or pleural effusions (56.6% vs. 27.0%, P<0.001; 6.0% vs. 0.0%, P=0.032), and a higher prevalence of 23S rRNA gene mutations (96.4% vs. 64.6%, P<0.001) when compared to those with macrolide-susceptible M. pneumoniae pneumonia. In terms of second-line treatment, 15 patients (18.1%) responded to CST, 30 (36.1%) to DXC, and 38 (45.8%) to TFX. The time to defervescence (TTD) after initiation second-line treatment was significantly shorter in the CST group compared to the DXC (10.3±12.7 vs. 19.4±17.2 hours, P=0.003) and TFX groups (10.3±12.7 vs. 25.0±20.1 hours, P=0.043), with no significant difference observed between the DXC and TFX groups (19.4±17.2 vs. 25.0±20.1 hours, P=0.262). Conclusions: High CRP levels, the presence of positive 23S rRNA gene mutation, lobar or segmental lung infiltration, and pleural effusion observed in chest X-ray findings were significant factors associated with macrolide unresponsiveness. In this study, CST demonstrated a shorter TTD compared to DXC or TFX. Further, larger-scale prospective studies are needed to determine the optimal second-line treatment for MUMP.

• Pediatric Infection and Vaccine
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• v.30 no.3
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• pp.111-120
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• 2023

Purpose: Human rhinovirus (HRV) infections can result in lower respiratory tract infections (LRTIs). We aimed to investigate the characteristics of severe HRV LRTI in young children. Methods: Medical records were reviewed retrospectively in patients who were hospitalized for HRV LRTIs from 2016 to 2020 at the Samsung Medical Center in Seoul, Korea. Patients aged 90 days or older and younger than 5 years were included. Patients with co-infections with other respiratory pathogens were excluded. Severe HRV LRTI was defined as the following: the need for high-flow oxygenation, mechanical ventilation, or intensive care unit admission. Results: A total of 115 cases were identified. The median age was 17 months (range, 3-56 months) and the median hospital days were 4 days (range, 2-31 days). Of the 115 cases, 18 patients (15.7%) developed severe HRV LRTI. The median age was younger in the severe group compared to the non-severe group (9.5 months vs. 19.0 months, P=0.001). Of 18 patients with severe HRV LRTI, 11 (61.1%) had underlying diseases - chronic lung diseases accounted for the largest proportion (63.6%). Six patients (33.3%) required mechanical ventilation. Of note, 7 previously healthy children were diagnosed with severe HRV LRTI. Of those 7 children, 4 of them were diagnosed with asthma later. When the 115 cases were divided into previously healthy (n=60) and underlying disease (n=55) groups, severe courses of HRV LRTI were observed in 11.7% and 20.0% of children, respectively (P=0.219). Conclusions: HRV can cause severe LRTI even in previously healthy children as well as in children with comorbidities.

• Journal of the Korean Society of Radiology
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• v.84 no.5
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• pp.1123-1133
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• 2023

Purpose Our study aimed to evaluate the association between automated quantified body composition on CT and pulmonary function or quantitative lung features in patients with chronic obstructive pulmonary disease (COPD). Materials and Methods A total of 290 patients with COPD were enrolled in this study. The volume of muscle and subcutaneous fat, area of muscle and subcutaneous fat at T12, and bone attenuation at T12 were obtained from chest CT using a deep learning-based body segmentation algorithm. Parametric response mapping-derived emphysema (PRM^emph), PRM-derived functional small airway disease (PRM^fSAD), and airway wall thickness (AWT)-Pi10 were quantitatively assessed. The association between body composition and outcomes was evaluated using Pearson's correlation analysis. Results The volume and area of muscle and subcutaneous fat were negatively associated with PRM^emph and PRM^fSAD (p < 0.05). Bone density at T12 was negatively associated with PRM^emph (r = -0.1828, p = 0.002). The volume and area of subcutaneous fat and bone density at T12 were positively correlated with AWT-Pi10 (r = 0.1287, p = 0.030; r = 0.1668, p = 0.005; r = 0.1279, p = 0.031). However, muscle volume was negatively correlated with the AWT-Pi10 (r = -0.1966, p = 0.001). Muscle volume was significantly associated with pulmonary function (p < 0.001). Conclusion Body composition, automatically assessed using chest CT, is associated with the phenotype and severity of COPD.

• Journal of Hospice and Palliative Care
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• v.1 no.1
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• pp.47-55
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• 1998

Background : It is almost important therapy modality to control pain for the terminal cancer patients for the last 24 hours because those terminally illed patient deserved to have pain free and peaceful time before death. Physician who is deal with terminal cancer patients for their last 24 hours does not need to worry about drug addiction or other untoward side reactions of pain medications. The purpose of this study was to evaluate if terminally illed cancer patient was given pain medication properly and sufficiently and if there was any different behavior to control pain of terminal cancer patients between medical physicians and surgeons in terms of type, amount and administration route and frequency. Methods : A retrospective chart audit of analgesic type, amount and administration route was performed on the medical recorders of 160 hospitalized terminal cancer patients who had died in the Korea University Medical Center Anam Hospital during the period of July 1, 1994 to June 30, 1995. Patients were classified into 103 patients were cared for by medical physicians and 57 patients were cared for by surgeons. After then, we analysed the difference of pain control pattern between them. Different types and amount of analgesics were converted to a common standard, an oral morphine equivalents(OME) relative to 1mg of oral morphine. Results : 1) The total number of patients was 160, male 102 cases(63.8%), and the female was 58 cases(36.2%) respectively. 2) The mean age was 56.4(${\pm}14.62$) years old and mean admission period was 27.8 days(${\pm}34.85$). 3) The frequent cancer site was stomach 42 cases(26.315), lung and liver 29 cases(18.1%) each, pancreas 10 cases(6.2%) in order 4) 125 out of 160 subjects (78.13%) complained pain, and 66 out of 103(64.08%) and 31 out of 57(54.39%) were treated with analgesics to relieve pain. 50 out of 97(51.55%) were able to continue on oral medication. 5) 86 cases(53.75%) were well oriented 24 hours prior to death. 6) The frequent analgesics for regular basis were long acting form of oral morphine 34 cases(Medical phsicians 24, Surgeons 10), intravenous morphine 26 cases(Medical physicians 20, Surgeons 6) in order, and the most common p.r.n.(pro re nata) analgesics used was intravenous morphine. 7) The mean amount of analgesics on regular basis was 115.41 OME by medical physicians and 52.7 OME by surseons(P<0.05). The mean amount of p.r.n. analgesics was significantly larger in patients are for by surgeons(66.64 OME) than medical physicians 23.49 OME(P<0.01). 8) The mean frequency of administrated number of p.r.n. analgesics was 0.62 times/day on medical part and 1.88 times/day on surgical part (P<0.001). Conclusion : Of the 97 patients with advanced cancer, 51.55% were able to take oral medications in the last day of life. The parenteral analgesics were more frequently used in the patients cared for by surgeons than medical physicians. Over the half of terminal cancer patients were well oriented in the last day of life. Doctor's knowledge and attitude towards pain is very important to mange the pain, effectively.