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PD-1 blockade-unresponsive human tumor-infiltrating CD8^(+)T cells are marked by loss of CD28 expression and rescued by IL-15

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Cellular & Molecular Immunology 2021年第2期18卷 385-397页

作者： Kyung Hwan Kim Hong Kwan Kim Hyung-Don Kim Chang Gon Kim Hoyoung Lee Ji Won Han Seong Jin Choi Seongju jeong minwoo Jeon Hyunglae Kim Jiae Koh Bo mi Ku Su-Hyung Park Myung-Ju Ahn Eui-Cheol Shin Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and TechnologyDaejeonRepublic of Korea Department of Thoracic and Cardiovascular Surgery Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea Biomedical Science and Engineering Interdisciplinary Program Korea Advanced Institute of Science and TechnologyDaejeonRepublic of Korea Research Institute for Future Medicine Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea Department of Radiation Oncology Yonsei Cancer CenterYonsei University College of MedicineSeoulRepublic of Korea Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea

Blockade of programmed death-1(PD-1)reinvigorates exhausted CD8^(+)T cells,resulting in tumor regression in cancer ***,reinvigoration of exhausted CD8^(+)T cells following PD-1 blockade was shown to be CD28-dependent in mouse ***,we examined the role of CD28 in anti-PD-1 antibody-induced human T cell reinvigoration using tumor-infiltrating CD8^(+)T cells(CD8^(+)TILs)obtained from non-small-cell lung cancer ***-cell analysis demonstrated a distinct expression pattern of CD28 between mouse and human CD8^(+)***,we found that human CD28^(+)CD8^(+)but not CD28^(–)CD8^(+)TILs responded to PD-1 blockade irrespective of B7/CD28 blockade,indicating that CD28 costimulation in human CD8^(+)TILs is dispensable for PD-1 blockade-induced reinvigoration and that loss of CD28 expression serves as a marker of anti-PD-1 antibody-unresponsive CD8^(+)*** and phenotypically,PD-1 blockade-unresponsive human CD28^(–)PD-1^(+)CD8^(+)TILs exhibited characteristics of terminally exhausted CD8^(+)T cells with low TCF1 ***,CD28^(–)PD-1^(+)CD8^(+)TILs had preserved machinery to respond to IL-15,and IL-15 treatment enhanced the proliferation of CD28^(–)PD-1^(+)CD8^(+)TILs as well as CD28^(+)PD-1^(+)CD8^(+)*** together,these results show that loss of CD28 expression is a marker of PD-1 blockade-unresponsive human CD8^(+)TILs with a TCF1–signature and provide mechanistic insights into combining IL-15 with anti-PD-1 antibodies.

关键词： anti-PD-1 T cells TCF1 CD28 IL-15

Efficacy of early treatment with infliximab in pediatric Crohn’s disease

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World Journal of Gastroenterology 2010年第14期16卷 1776-1781页

作者： Jong Seung Lee Jee Hyun Lee Ji Hyuk Lee Hye Jin Lee mi Jin Kim Hae jeong Lee Yon Ho Choe Department of Pediatrics College of Medicine Chung-Ang University Yongsan Hospital Yongsan Seoul 140-757 South Korea Department of Pediatrics Samsung Medical Center Sungkyunkwan University School of Medicine Gangnam Seoul 135-710 South Korea

AIM: To investigate the effectiveness of early infliximab use for induction and maintenance therapy in pediatric Crohn’s disease. METHODS: We performed a retrospective chart review of 36 patients with Crohn’s disease. Ten patients (group A) were treated with mesalamine after induction therapy with oral prednisolone, and 13 patients (group B) were treated with azathioprine after induction therapy with oral prednisolone. Thirteen patients (group C) received infliximab and azathioprine for induction and maintenance therapy for the first year, and were treated with azathioprine after 1 year. All patients were followed for at least 24 mo. Efficacy was determined by the relapse rate using the pediatric Crohn’s disease activity index score in each group at 12 and 24 mo. RESULTS: At the 1 year follow-up, the relapse ratee, mi Jin Kim, Hae jeong Lee, Yon Ho Choe (23.1%, 3 of 13 patients) in group C was lower than that (61.5%, 8 of 13 patients) in group B (P = 0.047). At the 2 years follow-up, the relapse rate (38.5%, 5 of 13 patients) in group C was lower than that (76.9%, 10 of 13 patients) in group B (P = 0.047). Adverse events in group C were fewer than in groups A and B. CONCLUSION: Early induction with infliximab at diagnosis, known as "top-down" therapy, was effective for reducing the relapse rate compared to conventional therapies for at least 2 years.

关键词： Efficacy Infliximab Pediatric Crohn’s disease Relapse rate Top-down treatment

Anticancer effects of oligomeric proanthocyanidins on human colorectal cancer cell line, SNU-C4

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World Journal of Gastroenterology 2005年第30期11卷 4674-4678页

作者： Youn-Jung Kim Hae-jeong Park Seo-Hyun Yoon mi-Ja Kim Kang-Hyun Leem Joo-Ho Chung Hye-Kyung Kim Department of Dental Hygiene Department of Pharmacology Department of Obesity Management College of Oriental Medicine Department of Food and Biotechnology

AIM: Oligomeric proanthocyanidins (OPC), natural polyphenolic compounds found in plants, are known to have antioxidant and anti-cancer effects. We investigated whether the anti-cancer effects of the OPC are induced by apoptosis on human colorectal cancer cell line, ***: Colorectal cancer cell line, SNU-C4 was cultured in RPmi 1640 medium supplemented with 10% fetal bovine serum. The cytotoxic effect of OPC was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylt-etrazolium bromide (MTT) assay. To find out the apoptotic cell death, 4, 6-diamidino-2-phenylindole (DAPI) staining,terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, reverse transcriptionpolymerase chain reaction (RT-PCR), and caspase-3 enzyme assay were ***: In this study, cytotoxic effect of OPC on SNUC4 cells appeared in a dose-dependent manner. OPC treatment (100 μg/mL) revealed typical morphological apoptotic features. Additionally OPC treatment (100 μg/mL)increased level of BAX and CASPASE-3, and decreased level of BCL-2 mRNA expression. Caspase-3 enzyme activity was also significantly increased by treatment of OPC (100 μg/mL) compared with ***: These data indicate that OPC caused cell death by apoptosis through caspase pathways on human colorectal cancer cell line, SNU-C4.

关键词： Oligomeric pranthocyanidins Apoptosis Anticancer effects Colorectal cancer

Long-term clinical outcome between beta-blocker with ACEI or ARB in patients with NSTEmi who underwent PCI with drug-eluting stents

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Journal of Geriatric Cardiology 2019年第3期16卷 280-290页

作者： Yong Hoon Kim Ae-Young Her Eun-Seok Shin Myung Ho jeong Division of Cardiology Department of Internal MedicineKangwon National University School of MedicineChuncheonSouth Korea Division of Cardiology Department of Internal MedicineUlsan Medical CenterUlsan HospitalUlsanSouth Korea Chonnam National University Hospital GwangjuSouth Korea

Background Because limited comparative data are available,we decided to compare 2-year major clinical outcomes between beta-blockers (BB) with angiotensin converting enzyme inhibitors (ACEI) and BB with angiotensin receptor blockers (ARB) therapy in patients with non-ST-segment elevation myocardial infarction (NSTEmi) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).Methods A total 11,288 NSTEmi patients who underwent PCI with DES were enrolled and they were divided into two groups,the BB with ACEI group (n = 7600) and the BB with ARB group (n = 3688).The major clinical endpoint was the occurrence of major adverse cardiac events (MACE) defined as all-cause death,recurrent myocardial infarction (re-mi),total revascularization [target lesion revascularization (TLR),target vessel revascularization (TVR),non-TVR] rate during the 2-year follow-up *** After propensity score-matched (PSM) analysis,two PSM groups (3317 pairs,n = 6634,C-statistic = 0.695) were *** the cumulative incidences of all-cause death,cardiac death,TLR,and non-TVR were similar between the two groups,MACE (HR = 0.832,95% CI: 0.704?0.982,P = 0.030),total revascularization rate (HR = 0.767,95% CI: 0.598?0.984,P = 0.037),and TVR rate (HR = 0.646,95% CI: 0.470?0.888,P = 0.007) were significantly lower in the BB with ACEI group after *** In this study,we suggest that the combination of BB with ACEI may be beneficial for reducing the cumulative incidences of MACE,total revascularization rate,and TVR rather than the BB with ARB after PCI with DES in NSTEmi patients.

关键词： Angiotensin converting enzyme inhibitor Angiotensin receptor blocker Beta-blocker Myocardial infarction

Association of chronic viral hepatitis B with insulin resistance

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World Journal of Gastroenterology 2012年第42期18卷 6120-6126页

作者： jeong Gyu Lee sangyeoup Lee Yun Jin Kim Byung Mann Cho Joo Sung Park Hyung Hoi Kim JaeHun Cheong Dong Wook jeong Yu Hyun Lee Young Hye Cho mi Jin Bae Eun Jung Choi Department of Family Medicine Pusan National University School of MedicineBeomeo-ri Mulgeum-eupYangsan 626-770South Korea Department of Family Medicine Medical Research InstitutePusan National University HospitalBusan 602-739South Korea Medical Education Unit Pusan National University School of MedicineBeomeo-ri Mulgeum-eupYangsan 626-770South Korea Family Medicine Clinic Yangsan Pusan National University HospitalBeomeo-ri Mulgeum-eupYangsan 626-770South Korea Department of Preventive Medicine and Occupational Medicine Pusan National University School of MedicineBeomeo-ri Mulgeum-eupYangsan 626-770South Korea Department of Family Medicine Dong-A University Medical CenterBusan 602-715South Korea Department of Laboratory Medicine Biomedical Informatics UnitPusan National University School of MedicineBeomeo-ri Mulgeum-eupYangsan 626-770South Korea Department of Molecular Biology College of Natural SciencesPusan National UniversityBusan 602-739South Korea

AIM:To investigate the relationship between chronic viral hepatitis B(CVHB) and insulin resistance(IR) in Korean ***:A total of 7880 adults(3851 men,4029 women) who underwent a comprehensive medical examination were enrolled in this *** diagnosed with either diabetes mellitus,or any other disorder that could influence their insulin sensitivity,were ***,metabolic risk factors,hepatitis B surface antigen,hepatitis B surface antibody,hepatitis B core antibody,fasting plasma glucose and insulin were measured for all *** model assessment(HOMA),quantitative insulin check index(QUICKI),and Mf fm index were used for determining insulin *** participant was categorized into a negative,recovery,or CVHB *** compare variables between groups,a t-test and/or one-way analysis of variance were *** correlation coefficients were computed to present the association between insulin resistance and other *** logistic regression analysis was used to assess the independent association between CVHB and ***:The mean age of men and women were 48.9 and 48.6 years,*** in the CVHB group had significantly higher waist circumference [(86.0 ± 7.7 cm vs 87.3 ± 7.8 cm,P = 0.004 in men),(78.3 ± 8.6 cm vs 80.5 ± 8.5 cm,P mi)(r = 0.378,P < 0.001),waist circumference(r =0.356,P < 0.001),percent body fat(r = 0.296,P < 0.001),systolic blood pressure(r = 0.202,P < 0.001),total cholesterol(r = 0.134,P < 0.00

关键词： Hepatitis B Insulin resistance Diabetes mellitus type 2 Metabolic syndrome

Assessing the impact of meteorological factors on malaria patients in demilitarized zones in Republic of Korea

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Infectious Diseases of Poverty 2016年第1期5卷 180-191页

作者： Se-min Hwang Seok-Joon Yoon Yoo-mi Jung Geun-Yong Kwon Soo-Nam Jo Eun-jeong Jang Myoung-Ok Kwon Korea Human Resource Development Institute for Health&Welfare OsongRepublic of Korea Department of Preventive Medicine College of MedicineKorea UniversitySeoulRepublic of Korea Department of Preventive Medicine Armed Forces Medical CommandSeongnamRepublic of Korea Department of Health Policy and Hospital Management Graduate School of Public HealthKorea University73 Inchon-ro.Seongbuk-GuSeoul 136-705Republic of Korea Korea Armed Forces Nursing Academy 90 Jaun-roYuseong-guDaejeon 305-153Republic of Korea Korean Centers for Disease Control and Prevention OsongRepublic of Korea

Background:The trend of military patients becoming infected with vivax malaria reemerged in the Republic of Korea(ROK)in *** common explanation has been that infective Anopheles mosquitoes from the Democratic People’s Republic of Korea have invaded Republic of Korea’s demilitarized zone(DMZ).The aim of this study was to verify the relationship between meteorological factors and the number of malaria patients in the military in this ***:The authors estimated the effects of meteorological factors on vivax malaria patients from the military based on the monthly number of malaria cases between 2006 and ***,precipitation,snow depth,wind velocity,relative humidity,duration of sunshine,and cloud cover were selected as the meteorological factors to be studied.A systematic pattern in the spatial distribution of malaria cases was assessed using the Moran’s *** causality tests and cross-correlation coefficients were used to evaluate the relationship between meteorological factors and malaria patients in the ***:Spatial analysis revealed significant clusters of malaria patients in the military in Republic of Korea in 2011(Moran’s I=0.136,p-value=0.026).In the six years investigated,the number of malaria patients in the military in Paju decreased,but the number of malaria patients in the military in Hwacheon and Chuncheon *** average,maximum and minimum temperatures;wind velocity;and relative humidity were found to be predicting factors of malaria in patients in the military in *** contrast,wind velocity alone was not able to predict malaria in Hwacheon and Chuncheon,however,precipitation and cloud cover were able to predict malaria in Hwacheon and ***:This study demonstrated that the number of malaria patients in the military is correlated with meteorological *** variation in occurrence of malaria cases was principally attributed to differences in meteorological factors by regions of

关键词： Malaria Plasmodium vivax Meteorological factors

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Breast Imaging Experiences at Academic Medical Centers during COVID-19: Restructuring, Reopening, and Preparing for Possible Resurgence

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Open Journal of Radiology 2020年第3期10卷 115-126页

作者： Stefanie Woodard Brian Stahl Elizabeth Allen Kernesha Weatherly Angela Choe Tiffany L. Chan Chelsea Pyle jeong mi Park The University of Alabama at Birmingham Birmingham AL USA School of Medicine The University of Alabama at Birmingham Birmingham AL USA Penn State Health milton S. Hershey Medical Center Hershey PA USA Ronald Reagan UCLA Medical Center Los Angeles CA USA Oregon Health & Science University Portland OR USA

Severe acute respiratory syndrome coronavirus 2 has thoroughly reshaped the medical landscape. Much has been written and discussed of the adaptations required by this pandemic, particularly in the realm of elective medical care. While some areas of the country have, in recent weeks, seen a plateau or even a decrease in coronavirus 2019 case-burden, others remain face-to-face with significant ongoing morbidity and mortality. Furthermore, given eased restrictions across numerous states and municipalities, a widespread resurgence of the disease is not precluded. To that end, we have attempted to summarize experiences and best practices in the handling of breast imaging against the backdrop of the novel coronavirus, and we consider future directions.

关键词： Breast Coronavirus 2019 Scheduling Resurgence Planning Reopening

Functional magnetic resonance imaging of cerebellar activation and lateralization during verbal and visuospatial tasks

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Neural Regeneration Research 2010年第3期5卷 226-231页

作者： mi-Hyun Choi Su-jeong Lee Jae-Woong Yang Jin-Seung Choi Hyung-Sik Kim jeong-Han Yi Gye-Rae Tack Soon-Cheol Chung Byung-Chan min Se-Jin Park Jong-Rak Park Jae-Hoon Jun Department of Biomedical Engineering Research Institute of Biomedical Engineering College of Biomedical & Health Science Konkuk University Department of Industrial & Management Engineering Hanbat National University Division of Technology Services National Center for Standard Reference Data Korea Research Institute of Standards and Science Department of Photonic Engineering Chosun University

BACKGROUND： Previous studies have analyzed cerebral activation and lateralization of cognitive functions, as well as cerebellar function with reference to high-level cognitive processing. However, there has been very little research on systematization and diversification. In particular, there are no reports on cerebellar lateralization, although reliable results have been reported on cerebral lateralization. OBJECTIVE： This study analyzed cerebellar activation and lateralization in relation to verbal and visuospatial tasks using functional magnetic resonance imaging （fMRI）. DESIGN, TIME AND SETTING： A block design for fMRI observation was performed at the fMRI Laboratory, Brain Science Research Center, Korea Advanced Institute of Science and Technology from May 2006 to September 2008. PARTICIPANTS： Sixteen healthy, male, college students, aged （23.3 ± 0.5） years, and 16 healthy, male, college students, aged （21.5 ± 2.3） years, participated in the study, respectively. METHODS： Verbal and visuospatial tasks were presented while functional brain images were acquired using a 3T fMRI system. Verbal analogy testing required the subject to select the word with the same relationship as one of the given words. Verbal antonym testing required the subject to select the word with a different meaning among four words. Visuospatial tasks involved selecting a shape that corresponded to a given figure with four examples, as well as selecting a development figure of a diagram. MAIN OUTCOME MEASURES： Changes in cerebellar activation and lateralization between two cognition tasks. RESULTS： Bilateral hemisphere Iobules VI and IX, right hemisphere Iobule VIII, bilateral hemisphere Iobules Crus I, and vermis Iobule IV, V, and Vl were closely related to verbal tasks in comparison to visuospatial tasks. Conversely, bilateral hemisphere Iobules IV and V, as well as the right hemisphere Iobule VI, were closely related to visuospatial tasks compared to verbal tasks. There was no great differe

关键词： cerebellum lateralization functional magnetic resonance imaging verbal and visuospatial tasks neuroimaging neural regeneration

Differential diagnosis of left-sided abdominal pain:Primary epiploic appendagitis vs colonic diverticulitis

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World Journal of Gastroenterology 2013年第40期19卷 6842-6848页

作者： jeong Ah Hwang Sun Moon Kim Hyun Jung Song Yu mi Lee Kyung min Moon Chang Gi Moon Hoon Sup Koo Kyung Ho Song Yong Seok Kim Tae Hee Lee Kyu Chan Huh Young Woo Choi Young Woo Kang Woo Suk Chung Division of Gastroenterology and Hepatology Department of Internal MedicineKonyang University College of MedicineDaejeon 302-718South Korea Department of Diagnostic Radiology Konyang University College of MedicineDaejeon 302-718South Korea

AIM:To investigate the clinical characteristics of left primary epiploic appendagitis and to compare them with those of left colonic ***:We retrospectively reviewed the clinical records and radiologic images of the patients who presented with left-sided acute abdominal pain and had computer tomography(CT) performed at the time of presentation showing radiological signs of left primary epiploic appendagitis(PEA) or left acute colonic diverticulitis(ACD) between January 2001 and December 2011. A total of 53 consecutive patients were enrolled and evaluated. We also compared the clinical characteristics,laboratory findings,treatments,and clinical results of left PEA with those of left ***:Twenty-eight patients and twenty-five patients were diagnosed with symptomatic left PEA and ACD,respectively. The patients with left PEA had focal abdominal tenderness on the left lower quadrant(82.1%). On CT examination,most(89.3%) of the patients with left PEA were found to have an oval fatty mass with a hyperattenuated ring sign. In cases of left ACD,the patients presented with a more diffuse abdominal tenderness throughout the left side(52.0%vs 14.3%; P = 0.003). The patients with left ACD had fever and rebound tenderness more often than those with left PEA(40.0% vs 7.1%,P = 0.004; 52.0% vs14.3%,P = 0.003,respectively). Laboratory abnormalities such as leukocytosis were also more frequently observed in left ACD(52.0% vs 15.4%,P = 0.006).CONCLUSION:If patients have left-sided localized abdominal pain without associated symptoms or laboratory abnormalities,clinicians should suspect the diagnosis of PEA and consider a CT scan.

关键词： Acute abdomen Differential diagnosis Appendix epiploica Colonic diverticulitis Multidetector computed tomography