• BMB Reports
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• 제56권5호
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• pp.314-319
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• 2023

Sepsis is a life-threatening multi-organ dysfunction with high mortality caused by the body's improper response to microbial infection. No new effective therapy has emerged that can adequately treat patients with sepsis. We previously demonstrated that interferon-β (IFN-β) protects against sepsis via sirtuin 1-(SIRT1)-mediated immunosuppression. Another study also reported its significant protective effect against acute respiratory distress syndrome, a complication of severe sepsis, in human patients. However, the IFN-β effect cannot solely be explained by SIRT1-mediated immunosuppression, since sepsis induces immunosuppression in patients. Here, we show that IFN-β, in combination with nicotinamide riboside (NR), alleviates sepsis by blocking endothelial damage via SIRT1 activation. IFN-β plus NR protected against cecal ligation puncture-(CLP)-induced sepsis in wild-type mice, but not in endothelial cell-specific Sirt1 knockout (EC-Sirt1 KO) mice. IFN-β upregulated SIRT1 protein expression in endothelial cells in a protein synthesis-independent manner. IFN-β plus NR reduced the CLP-induced increase in in vivo endothelial permeability in wild-type, but not EC-Sirt1 KO mice. IFN-β plus NR suppressed lipopolysaccharide-induced up-regulation of heparinase 1, but the effect was abolished by Sirt1 knockdown in endothelial cells. Our results suggest that IFN-β plus NR protects against endothelial damage during sepsis via activation of the SIRT1/heparinase 1 pathway.

• Journal of Digestive Cancer Research
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• 제4권1호
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• pp.1-9
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• 2016

The abundance of multi-drug resistance ATPase binding cassette and deranged self-renewal pathways shown in cancer stem cells (CSCs) played a crucial role in tumorigenesis, tumor resistance, tumor recurrence, and tumor metastasis. Therefore, elucidation of CSCs biology can improve diagnosis, enable targeted treatment, and guide the follow up of GI cancer patients. In order to achieve chemoquiescence, seizing cancer through complete ablation of CSCs, CSCs are rational targets for the design of interventions that will enhance responsiveness to traditional therapeutic strategies and contribute in the prevention of local recurrence as well as metastasis. However, current cancer treatment strategies fail to either detect or differentiate the CSCs from their non-tumorigenic progenies mostly due to the absence of specific biomarkers and potent agents to kill CSCs. Recent advances in knowledge of CSCs enable to produce several candidates to ablate CSCs in gastrointestinal (GI) cancers, especially cancers originated from inflammation-driven mutagenesis such as Barrett's esophagus (BE), Helicobacter pylori-associated gastric cancer, and colitis-associated cancer (CAC). Our research teams elucidated through revisiting old drugs that proton pump inhibitor (PPI) and potassium competitive acid blocker (p-CAB) beyond authentic acid suppression, chloroquine for autophage inhibition, sonic hedgehog (SHH) inhibitors, and Wnt/β-catenin/NOTCH inhibitor can ablate CSCs specifically and efficiently. Furthermore, nanoformulations of these molecules could provide an additional advantage for more selective targeting of the pathways existing in CSCs just like current molecular targeted therapeutics and sustained action, while normal stem cells intact. In this review article, the novel approach specifically to ablate CSCs existing in GI cancers will be introduced with the introduction of explored mode of action.

• Pediatric Infection and Vaccine
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• 제31권1호
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• pp.140-146
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• 2024

소아 다기관 염증 증후군(multisystem inflammatory syndrome in children, MIS-C)은 코로나바이러스감염증-19 (코로나 19; coronavirus disease 2019, COVID-19)의 드문 합병증으로 심장, 폐, 신장, 소화관 및 신경계를 포함한 다기관 손상을 일으킨다. 코로나19 팬데믹 이후 MIS-C 사례가 증가함에 따라 MIS-C에 대한 적절한 치료의 중요성이 강조되고 있다. anakinra, infliximab, 스테로이드와 같은 면역 조절제는 MIS-C에 대한 intravenous immunoglobulin (IVIG)의 1차 치료에 대한 추가 요법으로 고려되지만 cytomegalovirus (CMV), Epstein-Barr 바이러스 및 결핵과 같은 2차 감염을 유발할 소지가 있다. 저자들 MIS-C로 IVIG, steroid 및 infliximab을 투여한 환자에서 동반된 CMV 감염으로 인하여 약 한달간 지속되는 발열이 발생한 3세 남아의 증례 1례를 처음으로 보고하였다.

• 대한통합의학회지
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• 제12권1호
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• pp.109-124
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• 2024

Purpose : The purpose of this study was to examine the effects of a virtual reality-based complex cognitive training program for depression, cognitive function, and digital divide reduction in the elderly who have not been diagnosed with dementia or MCI. Methods : We enrolled 16 participants who were over 65 years old and not been diagnosed with dementia or MCI. We randomly divided into three groups (A, B, C). Participants underwent an 8-week virtual reality-based complex cognitive training program (60 minutes each session, twice per week). At a baseline, all participants completed questionnaires on general features, depression and cognitive function. After four weeks, all participants completed questionnaires on depression and cognitive function. After the end of the last program, participants conducted questionnaires on depression, cognitive function, and usability evaluation. Results : At the 8-week follow-up, 16 participants completed the program. Compared to the baseline, the average score of cognitive function was increased (from 26.5 to 28.5), although it was not statistically significant (p<.061). There were no significant differences between baseline and post-training evaluations on depression scores. The average score of usability evaluation was 75.56, which corresponds to good. Conclusion : Even though the results showed no statistically significant findings in cognitive function and depression after the virtual reality-based complex cognitive training intervention, this pilot study proposed the possibility of utilizing the virtual reality program as a tool that provides active learning opportunities for the elderly and helps improve their cognitive function through multi-sensory components. Also, the findings of this study suggested a positive reevaluation of the elderly's digital access capabilities while reducing the digital divide. A virtual reality-based complex cognitive training program improved the social network of the elderly. We expect that it will expand in size and help with their social participation of the elderly.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제50권4호
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• pp.216-221
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• 2024

Objectives: This study aimed to develop and validate a model to predict the need for intensive care unit (ICU) admission in patients with dental infections using an automated machine learning (ML) program called H2O-AutoML. Materials and Methods: Two models were created using only the information available at the initial examination. Model 1 was parameterized with only clinical symptoms and blood tests, excluding contrast-enhanced multi-detector computed tomography (MDCT) images available at the initial visit, whereas model 2 was created with the addition of the MDCT information to the model 1 parameters. Although model 2 was expected to be superior to model 1, we wanted to independently determine this conclusion. A total of 210 patients who visited the Department of Oral and Maxillofacial Surgery at the Dankook University Dental Hospital from March 2013 to August 2023 was included in this study. The patients' demographic characteristics (sex, age, and place of residence), systemic factors (hypertension, diabetes mellitus [DM], kidney disease, liver disease, heart disease, anticoagulation therapy, and osteoporosis), local factors (smoking status, site of infection, postoperative wound infection, dysphagia, odynophagia, and trismus), and factors known from initial blood tests were obtained from their medical charts and retrospectively reviewed. Results: The generalized linear model algorithm provided the best diagnostic accuracy, with an area under the receiver operating characteristic values of 0.8289 in model 1 and 0.8415 in model 2. In both models, the C-reactive protein level was the most important variable, followed by DM. Conclusion: This study provides unprecedented data on the use of ML for successful prediction of ICU admission based on initial examination results. These findings will considerably contribute to the development of the field of dentistry, especially oral and maxillofacial surgery.

• 보건의료생명과학 논문지
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• 제11권2호
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• pp.449-455
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• 2023

본 연구는 중년 성인의 대사증후군 유무에 따른 운동 관련요인의 차이를 분석하고자 하였다. 국민건강영양조사 제7기(2016-2018) 원시자료 중 중년 성인 5,421명 중 응답이 불충분한 903명을 제외한 4,518명을 최종 분석대상자로 선정하였다. 연구결과 여성, 교육수준이 낮을수록, 주관적 건강상태가 낮을수록, 신체활동은 적을수록 대사증후군과 매우 유의한 관련성이 있었다. 본 연구결과로부터 중년 성인의 대사증후군 예방 및 관리를 위해서는 적극적인 신체활동이 필요하다고 판단되며, 향후 더 다양한 요인분석과 다면적인 연구가 필요하다고 사료된다.

• 한국의학물리학회지:의학물리
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• 제22권2호
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• pp.99-105
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• 2011

본 연구에서는 미국의학물리학회(AAPM)에서 제안된 세기조절방사선치료(IMRT)의 commissioning 및 정도관리를 위해 제안된 일련의 시험을 통해 본원의 세기조절방사선치료의 정확도를 평가하고 정도관리 절차를 수립하고자 하였다. TG119에 제시된 5가지 세기조절방사선치료의 표적체적: multi-target, 두경부, 전립선, 및 두 가지의 C-shape (easy&hard)을 대상으로 CT 스캔된 팬텀을 이용하여 치료계획시스템에서 IMRT 치료계획을 수행하였다. 얻어진 치료계획을 dynamic sliding window 전달방식으로 팬텀에 조사하였다. 절대 선량은 표적 및 위험장기 부위에 이온 전리함(CC13, IBA)을 이용하여 측정하고, 2차원 상대 선량분포는 EBT2 필름을 사용하여 측정하였다. 측정된 값들은 해당하는 치료계획시스템 계산값과 비교하여 오차의 평균 및 표준편차를 구하였다. 이를 바탕으로 TG119에 제시된 신뢰구간을 계산하여 제시된 값과 비교하였다. 이온 전리함을 이용한 측정 결과에서 표적 및 위험장기에 대한 계산값과 측정값 사이의 평균오차는 각각 $1.2{\pm}1.1%$과 $1.2{\pm}0.7%$이었고, 95% 신뢰구간은 각각 3.4%와 2.6%으로 TG119에서 제시하고 있는 4.5%와 4.7% 이내에 있었다. 필름을 이용한 측정 결과에서는 허용기준 3%/3 mm를 통과하는 감마인덱스는 평균$ 97.7{\pm}0.8%$로 95% 신뢰구간은 3.9%로 TG119에서 제시하고 있는 7.0% 이내에 있었다. 따라서 TG119에서 제시된 일련의 표준화된 시험을 통해 본원의 세기조절방사선치료의 commissioning 및 정도관리를 평가할 수 있었다. 이온 전리함을 이용한 절대 선량에 대한 action level은 표적과 위험장기에서 각각 ${\pm}4%$와 ${\pm}3%$로, EBT2 필름을 이용한 2차원 상대선량분포는 허용기준 3%/3 mm 기준으로 감마인덱스 1이하를 통과하는 비율이 96%로 정할 수 있었다. 이를 통해 TG119에서 제시된 일련의 표준화된 시험을 통해 각 기관의 IMRT 정확도 평가에 대한 객관적인 지표로 이용될 수 있을 것으로 기대된다.

• 동의생리병리학회지
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• 제17권1호
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• pp.1-24
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• 2003

This study was done to compile 104 experimental theses which are related to the antitumor and immuno-activating therapies between February 1990 through February 2002. Master's and doctoral theses were dassified by schools, degrees, materials, effects, experimental methods of antitumor and immunoactivity, and results. The following results were obtained from this study : 1. Classifying the theses by the school, 34.6% were presented by Daejeon University, 29.8% by Kyung-hee University and 11.5% by Won-kwang University. Of all theses, 51.0% were aimed for the doctoral degree and 43.3% were for the master's degree. All of three universities have their own cancer centers. 2. Classifying the theses by herb materials, complex prescription accounted for 60.3%, single herb accounted for 24.8% and herbal acupuncture accounted for 14.2%. Considering the key principles of the traditional medicine, complex prescription was much more thoroughly studied than single herb prescription. The results showed that the complex prescription had both antitumor activity and immuno-activating activity, which might reflects on multi-activation mechanisms by complex components. 3. Classifying the theses by the efficacy of herbs examined, in single herb, invigorating spleen and supplementing was 35.5%, expelling toxin and cooling was 29.0%, activating blood flow and removing blood stasis was 12.9%. In herbal acupuncture, invigorating spleen and supplementing was 52.9%, expelling toxin and cooling was 29.4%. In complex prescription, pathogen-free status was 41.9%, strengthening healthy qi to eliminate pathogen was 35.5%, strengthening healthy qi was 22.6%. It is presumed that the antitumor and immunoactivating therapy based on syndrome differentiation is the best way to develop oriental oncology. 4. Classifying the theses by antitumor experiments, cytotoxic effect was 48.1 %, survival time was 48.1 % and change of tumor size was 42.3%. Survival rate was not necessarily correlated with cytotoxicity. These data reflect the characteristic, wholistic nature of the oriental medicine which is based on BRM (biological response modifier). 5. Classifying the theses by immunoactivating experiments, hemolysin titer was 51.0%, hemagglutinin titer was 46.2% and NK cell's activity was 44.2%. In the future studies, an effort to elucidate specific molecular and cellular mechanisms of cytokine production in the body would be crucial. 6. Classifying the theses according to the data in terms of antitumor activity, 50% was evaluated good, 24.0% was excellent, and 15.5% have no effect. In an evaluation of immuno-activating activity, 35.9% was excellent and 18.0% showed a little effect. The index point, as described here, may helps to use experimental data for clinical trials. Changes in index points by varying dosage implicate the importance of oriental medical theory for prescription. 7. In 167 materials, IIP (immunoactivating index point, mean : 3.12±0.07) was significantly higher than AIP(antitumor index point, mean : 2.83±0.07). These data demonstrate that the effect of herb medicine on tumor activity depends more on immunoactivating activity than antitumor activity. This further implies that the development of herbal antitumor drugs must be preceded by the mechanistic understanding of immunoactivating effect. 8. After medline-searching tumor and herb-related articles from NCBI web site, we conclude that most of the studies are primarily focused on biomolecular mechanisms and/or pathways. Henceforth, we need to define the biomolecular mechanisms and/or pathways affected by herbs or complicated prescriptions. 9. Therefore, the most important point of oriental medical oncology is to conned between experimental results and clinical trials. For the public application of herbal therapy to cancer, it is critical to present the data to mass media. 10. To develop the relationship of experimental results and clinical trials, university's cancer clinic must have a long-range plan related to the university laboratories and, at the same time, a regular consortium for this relationship is imperative. 11. After all these efforts, a new type herbal medicine for cancer therapy which is to take care of the long-term administering and safety problem must be developed. Then, it would be expected that anti-tumor herbal acupuncture can improve clinical symptoms and quality of life (QOL) for cancer patients. 12. Finally, oriental medical cancer center must be constructed in NCC (National Cancer Center) or government agency for the development of oriental medical oncology which has international competitive power.

• Tuberculosis and Respiratory Diseases
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• 제67권2호
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• pp.88-94
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• 2009

Background: From November 2006, The national health insurance system in the Republic of Korea began to cover prescribed long-term oxygen therapy (LTOT) in patients with chronic respiratory insufficiency. This study examined the current status of LTOT after national health insurance coverage. Methods: Between November 1, 2006 and June 30, 2008, the medical records of patients who were prescribed LTOT by chest physicians were reviewed. The data was collected from 13 university hospitals. Results: 197 patients (131 male and 66 female) were prescribed LTOT. The mean age was 64.3${\pm}$13.0 years. The most common underlying disease was chronic obstructive pulmonary disease (n=103, 52.3%). Chest physicians prescribed LTOT using arterial blood gas analysis or a pulse oxymeter (74.6%), symptoms (14%), or a pulmonary function test (11.2%). The mean oxygen flow rate was 1.56${\pm}$0.68 L/min at rest, 2.08${\pm}$0.91 L/min during exercise or 1.51${\pm}$0.75 L/min during sleep. Most patients (98.3%) used oxygen concentrators. Only 19% of patients used ambulatory oxygen supplies. The oxygen saturation before and after LTOT was 83.18${\pm}$10.48% and 91.64${\pm}$7.1%, respectively. After LTOT, dyspnea improved in 81.2% of patients. The mean duration of LTOT was 16.85${\pm}$6.71 hours/day. The rental cost for the oxygen concentrator and related electricity charges were 48,414${\pm}$15,618 won/month and 40,352${\pm}$36,815 won/month, respectively. Approximately 75% of patients had a regular visit by the company. 5.8% of patients had personal pulse oxymetry. 54.9% of patients had their oxygen saturation checked on each visit hospital. 8% of patients were current smokers. The most common complaint with LTOT was the limitation of daily activity (53%). The most common complaint with oxygen concentrators was noise (41%). Conclusion: The patients showed good compliance with LTOT. However, only a few patients used an ambulatory oxygen device or had their oxygen saturation measured.

• 한국의학물리학회지:의학물리
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• 제26권1호
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• pp.42-51
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• 2015

양성자 치료 시 양성자 빔을 사용하여 정밀한 치료를 수행하고 환자의 안전을 제고하기 위해서는 인체 내 양성자 빔의 선량 분포를 확인하는 것이 중요하다. 이를 위해 본 연구팀은 이전 연구에서 1차원 배열형 검출기를 종형으로 배치하여 빔 진행방향으로 이동시켜가면서 2차원적인 즉발감마선 분포를 측정하여 양성자 선량 분포와 유사한 분포를 갖는 것을 확인하였다. 본 연구에서는 이를 바탕으로 즉발감마선 이차원분포를 실시간으로 측정하기 위해 이차원 평행다공형 집속 장치, 이차원 배열의 NaI(Tl) 섬광체와 MA-PMT로 이루어진 즉발감마선 이차원분포 측정 장치를 개발하였다. 개발한 즉 발감마선 이차원분포 측정 장치의 성능을 평가한 결과 $^{22}Na$ 감마선원의 에너지 분해능은 $10.9%{\pm}0.23p%$ (0.511 MeV)와 $6.4%{\pm}0.24p%$ (1.275 MeV)로 평가되었으며, $^{137}Cs$은 $9.8%{\pm}0.18p%$ (0.662 MeV)로 평가되었다. 고에너지 Am-Be 선원의 double escape 피크인 3.416 MeV의 에너지 분해능은 $11.4%{\pm}3.6p%$로 평가되었다. 본 측정 장치를 이용하여 45 MeV 양성자 빔을 PMMA에 조사하여 발생한 즉발감마선 이차원분포를 측정한 결과 0.5 nA의 세기의 양성자 빔에서 $9{\times}10^9$ 양성자 조사 시 양성자 선량 분포와 유사한 즉발감마선 이차원분포를 측정할 수 있음을 확인하였다. 추가로 측정한 즉발감마선 이차원분포의 프로파일 분포를 이용하여 양성자 빔의 비정을 평가해 본 결과 $17.0{\pm}0.4mm$로 평가되었고, 실제 비정인 17.4 mm과 굉장히 밀접한 관련이 있음을 확인하였다.