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Pressure-responsive pH-triggered layer-by-layer coating of paclitaxel-eluting balloon catheters for instant high-dose drug delivery for percutaneous coronary artery intervention

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Nano Research 2024年第10期17卷 9141-9151页

作者： Jeong Yu Lee Shonit Nair Sharma Sung-Yu Hong Young-Guk Ko Yangsoo Jang Minjae Do Michael Christopher Stark Qiwen Peng Benjamin Allen Mossburg Bo Chan Seo Yuhan Lee department of Materials Science and Engineering Korea Advanced Institute of Science and TechnologyDaejeon 305-701Republic of Korea department of Anesthesiology Perioperativeand Pain MedicineCenter for Accelerated Medical Innovation&Center for NanomedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA department of Biological Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA Cardiovascular Product Evaluation Center Yonsei University College of MedicineSeoul 120-752Republic of Korea division of Cardiology Department of Internal MedicineSeverance Cardiovascular HospitalYonsei University College of MedicineSeoul 120-752Republic of Korea

Cardiovascular diseases remain the leading cause of mortality worldwide,with percutaneous coronary interventions(PCI)using drug-eluting stents(DES)as the standard treatment for coronary artery *** advancements in DES technology,challenges such as restenosis and stent thrombosis still necessitate further interventions and carry considerable risks,highlighting an urgent need for a novel therapeutic approach with lower restenosis rates and reduced reintervention *** balloons(DEBs)coated with anti-proliferative agents offer a novel method of local drug delivery for reducing restenosis by directly administering drugs to the lesion ***,efficient delivery of drugs within the brief procedural window while minimizing drug loss during maneuvering to the target site remains a ***,we developed a pressure-responsive and pH-triggered,paclitaxel(PTX)coated DEB catheter for rapid and high-dose delivery of paclitaxel to the lesion sites,overcoming the limitations of drug dispersion and inefficiencies associated with conventional *** the charge reversion of albumin around its isoelectric point,paclitaxel-loaded human serum albumin nanoparticles(PTX-HSA-NPs)and heparin were coated using a layer-by-layer deposition method at pH *** exposure to physiological pH(i.e.,7.4),the coating is rapidly released from the balloon *** with a protective shellac coating,the DEB achieved controlled release of high-dose paclitaxel to the arterial tissue in vivo(up to 400μg per gram tissue),exceeding current DEBs in the *** results suggest the pH-responsive,multi-layer coated DEB’s potential for superior procedural outcomes,addressing a critical unmet need in PCI.

关键词： drug-eluting balloon layer-by-layer coating coronary artery disease paclitaxel

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KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study

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Hepatobiliary & Pancreatic diseases International 2019年第1期18卷 62-66页

作者： Jung Hyun Jo Huapyong Kang Hee Seung Lee Moon Jae Chung Jeong Youp Park Seungmin Bang Seung Woo Park Si Young Song division of Gastroenterology Department of Internal Medicine Severance Hospital Yonsei University College of Medicine

Background: Sodium meta-arsenite(NaAsO_2, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer(BTC) resistant to gemcitabinebased chemotherapy. Methods: Forty-four patients(21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status(PS) 0–2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001(7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT. Results: After an average of 1.5 months of treatment(range: 0.5–10.0), 3 patients(6.8%) obtained progression-free status, 23 patients(52.3%) had disease progression, and 18 patients(40.9%) dropped out before evaluation. One patient(2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients(47.6%). Nine patients(20.5%) experienced grade-3 adverse events(AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation(11/44, 25%) and anemia(10/44, 22.7%). KML001 was discontinued in six patients(13.6%) due to AEs, including liver toxicity( n = 3), QTc prolongation( n = 2), and abdominal pain( n = 1). Conclusions: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.

关键词： Biliary tract neoplasms Cholangiocarcinoma Gallbladder neoplasms KML001 Sodium meta-arsenite

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Incidence, prevalence and risk of stroke in patients with Takayasu arteritis: a nationwide population-based study in South Korea

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Stroke & Vascular Neurology 2022年第2期7卷 149-157页

作者： Sung Soo Ahn Minkyung Han Yong-Beom Park Inkyung Jung Sang-Won Lee department of internal medicine Yongin Severance HospitalYonsei University College of MedicineYonginSouth Korea Biostatistics Collaboration Unit Department of Biomedical Systems InformaticsYonsei University College of MedicineSeoulSouth Korea division of Rheumatology Department of Internal MedicineYonsei University College of MedicineSeoulSouth Korea Institute for Immunology and Immunological diseases Yonsei University College of MedicineSeoulSouth Korea division of Biostatistics Department of Biomedical Systems InformaticsYonsei University College of MedicineSeoulSouth Korea

Background Takayasu arteritis(TAK)is a disease associated with increased risk of cardiovascular *** aimed to evaluate the incidence,prevalence and risk of stroke in patients with *** Data from 1065 patients were obtained from a national database(2010–2018).The annual incidence and prevalence per 100000 persons were estimated using the registration population in the midst of every year,and the standardised incidence ratio(SIR)of stroke was compared with the general population based on the data from the 2006 national report for cardiovascular and cerebrovascular ***-adjusted incidence rate ratio(IRR)of stroke based on the time interval after diagnosis was also calculated.A time-dependent Cox regression was conducted to investigate predictive factors of *** The overall incidence rate of TAK ranged between 0.2 and 0.3/100000 person-years annually;the prevalence of TAK gradually increased,reaching 3.25/100000 person-years in ***-three(6.9%)patients experienced stroke during follow-up,and the risk of developing stroke was higher than the general population(overall SIR 7.39,95%CI 5.79 to 9.29;men:SIR 5.70,95%CI 2.84 to 10.20;women:SIR 7.06,95%CI 5.41 to 9.05).Most stroke events(90.9%)were cerebral infarction for men,whereas the proportion of cerebral infarction was lower(62.9%)in *** half of stroke events occurred within 6 months after diagnosis,and stroke was more common within 6 months of diagnosis compared with after 3 years in women(IRR 13.46,95%CI 6.86 to 26.40).In Cox regression analysis,age was the sole predictor of stroke(adjusted HR 1.02,95%CI 1.00 to 1.04,p=0.043).Conclusions The annual incidence of TAK was similar to the previous studies from Asia,and the risk of stroke increased in *** patterns of subtype and incidence of stroke were found according to sex,although age was the only predictor.

关键词： prevalence patients diagnosis

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Characterization of CD8＋CD57＋ T cells in patients wit acute myocardial infarction

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Cellular & Molecular Immunology 2015年第4期12卷 466-473页

作者： Hee Tae Yu Jong-Chan Youn Jino Lee Seunghyun Park Ho-Seok Chi Jungsul Lee Chulhee Choi Sungha Park Donghoon Choi Jong-Won Ha Eui-Cheol Shin Laboratory of Immunology and infectious diseases Graduate School of Medical Science and Engineering KAIST Daejeon Republic of Korea Cardiology division Severance Cardiovascular Hospital Yonsei University College of Medicine Seoul Republic of Korea department of Bio and Brain Engineering KAIST Daejeon Republic of Korea ' ' The first two authors contributed equally to this article

Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction （MI）. We studied the immunological characteristics and clinical impact of CD8＋CD57＋ T cells in acute MI patients. The frequency of CD57＋ cells among CD8＋ T cells was examined in peripheral blood sampled the morning after acute MI events. Interestingly, the frequency of CD57＋ cells in the CD8＋ T-cell population correlated with cardiovascular mortality 6 months after acute MI. The immunological characteristics of CD8＋CD57＋ T cells were elucidated by surface immunophenotyping, intracellular cytokine staining and flow cytometry. Immunophenotyping revealed that the CD8＋CD57＋ T cells were activated, senescent T cells with pro-inflammatory and tissue homing properties. Because a high frequency of CD8＋CD57＋ T cells is associated with short-term cardiovascular mortality in acute MI patients, this specific subset of CD8＋ T cells might contribute to acute coronary events via their pro-inflammatory and high cytotoxic capacities. Identification of a pathogenic CD8＋ T-cell subset expressing CD57 may offer opportunities for the evaluation and management of acute MI.

关键词： acute myocardial infarction CD8+CD57+ T cells immunosenescence

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T cell epitopes in SARS-CoV-2 proteins are substantially conserved in the Omicron variant

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Cellular & Molecular Immunology 2022年第3期19卷 447-448页

作者： Seong Jin Choi Dong-Uk Kim Ji Yun Noh Sangwoo Kim Su-Hyung Park Hye Won Jeong Eui-Cheol Shin division of infectious Disease Department of Internal MedicineSeoul National University HospitalSeoulRepublic of Korea Graduate School of Medical Science and Engineering Korea Advanced Institute of Science and Technology(KAIST)DaejeonRepublic of Korea division of infectious diseases Department of Internal MedicineKorea University College of MedicineSeoulRepublic of Korea department of Biomedical Systems Informatics Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineSeoulRepublic of Korea department of internal medicine Chungbuk National University College of MedicineCheongjuRepublic of Korea The Center for Viral Immunology Korea Virus Research InstituteInstitute for Basic Science(IBS)DaejeonRepublic of Korea

In November 2021,the Omicron variant(B.1.1.529)emerged and was designated a variant of concern(VOC)by the World Health ***,Omicron was reported to extensively escape neutralizing antibodies elicited by COVID-19 vaccination or natural infection[1,2,3].However,whether Omicron evades the T cell immunity elicited by COVID-19 vaccination or natural infection remains to be *** address this issue,we analyzed the amino acid sequences of T cell epitopes identified from the original SARS-CoV-2 strain(Wuhan-Hu-1)in the Omicron variant(hCoV-19/South Africa/CERI-KRISP-K032284/2021).

关键词： neutral conserved elucidated

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Risk factors for tuberculosis after gastrectomy in gastric cancer

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World Journal of Gastroenterology 2016年第8期22卷 2585-2591页

作者： Won Jai Jung Young Mok Park Joo Han Song Kyung Soo Chung Song Yee Kim Eun Young Kim Ji Ye Jung Moo Suk Park Young Sam Kim Se Kyu Kim Joon Chang Sung Hoon Noh Ji Yeong An Young Ae Kang division of Respiratory and Critical Care medicine Department of Internal Medicine Korea University College of Medicine division of Pulmonology Department of Internal Medicine Severance Hospital Institute of Chest Diseases Yonsei University College of Medicine department of Surgery Yonsei University College of Medicine

AIM: To examine incidence of tuberculosis(TB) in gastrectomy patients and investigate the risk factors for developing TB after gastrectomy in patients with gastric ***: A retrospective cohort study of gastrectomy patients with gastric cancer was performed at a university-affiliated hospital in Seoul, South Korea between January 2007 and December 2009. We reviewed patient medical records and collected data associated with the risk of TB, surgery, and gastric cancer. Standardized incidence ratios(SIRs) of TB were calculated to compare the incidence of TB in gastrectomy patients with that in the general Korean population, and risk factors for TB after gastrectomies were ***: Among the 1776 gastrectomy patients, 0.9%(16/1776) developed post-gastrectomy TB, with an incidence of 223.7 cases per 100000 patients per year. The overall incidence of TB in gastrectomy patients, adjusted by sex and age, was significantly higher thanthat in the general population(SIR = 2.22, 95%CI: 1.27-3.60). Previous TB infection [odds ratio(OR) = 7.1, P < 0.001], lower body mass index(BMI)(kg/m2; OR = 1.21, P = 0.043) and gastrectomy extent(total gastrectomy vs subtotal gastrectomy)(OR = 3.48, P = 0.017) were significant risk factors for TB after gastrectomy in a multivariate ***: TB incidence after gastrectomy is higher than that in the general population. Previous TB infection, lower BMI, and total gastrectomy are risk factors for TB after gastrectomy in patients with gastric cancer.

关键词： Tuberculosis Gastrectomy Body mass index Risk factor Gastric cancer

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Novel Influenza A（H1N1）Infection Rate of Exposed Person Without Respiratory Protector in hospital

Novel Influenza A（H1N1）Infection Rate of Exposed Person Wi...

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中国医院协会第十七届全国医院感染管理学术年会暨第九届东...

作者： Oh Mee Kweon Dongsuk Lee Eun Suk Park Chang Oh Kim Sang Hun Han June Myung Kim Ki Hwan Kim Ju Hyun Lee Eun Jin Ha Kyungwon Lee department of Infection Control yonsei university college of medicine SeoulKorea severance hospital division of infectious diseases department of internal medicine yonsei university college of medicine SeoulKorea department of Pediatrics yonsei university college of medicine SeoulKorea department of Laboratory medicine Yonsei University College of MedicineSeoulKorea

＜正＞Background Novel influenza A（H1N1） is transmitted by air or ***,we should wear the respiratory protector to prevent infection spread during contact with infected or suspected *** purpose of this study is to investigate the infection status of the exposed persons who made a contact without a respiratory protector in the

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Comparison of clinical outcomes between culprit vessel only and multivessel percutaneous coronary intervention for ST-segment elevation myocardial infarction patients with multivessel coronary diseases

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Journal of Geriatric Cardiology 2015年第3期12卷 208-217页

作者： Kwang Sun Ryu Hyun Woo Park Soo Ho Park Ho Sun Shon Keun Ho Ryu Dong Gyu Lee Mohamed EA Bashir Ju Hee Lee Sang Min Kim Sang Yeub Lee Jang Whan Bae Kyung Kuk Hwang Dong Woon Kim Myeong Chan Cho Young Keun Ahn Myung Ho Jeong Chong Jin Kim Jong Seon Park Young Jo Kim Yang Soo Jang Hyo Soo Kim Ki Bae Seung Database and Bioinformatics Laboratory School of Electrical and Computer Engineering Chungbuk National University Cheongju Chungbuk South Korea Human Genome Center Institute of Medical Science University of Tokyo Minatoku Tokyo Japan Faculty of Computer Science and Information Technology University of Meddcal Sciences and Technology Khartoum Sudan Regional Curdiovcascular Disease Center Chungbuk National University Ho spital Cheonglu Chungbuk South Korea division of Cardiology Department of Internal Medicine College of Medicine Chungbuk National University Cheongju Chungbuk South Korea department of Cardiology Chonnam National University Hospital Donggu Gwangju South Korea department of internal medicine Kyunghee University Gangdong Hospital Seoul South Korea department of internal medicine Yeungnam University Hospital Medical Center Daegu South Korea division of Cardiology Yonsei University Severance Hospital Seoul South Korea Cardiovascular Center and department of internal medicine Seoul National University Hospital Seoul South Korea department of Cardiovascular medicine Catholic University St. Mary's Hospital Seoul South Korea

Background The clinical significance of complete revascularization for ST segment elevation myocardial infarction （STEMI） pa- tients during admission is still debatable. Methods A total of 1406 STEMI patients from the Korean Myocardial Infarction Registry with multivessel diseases without cardiogenic shock who underwent primary percutaneous coronary intervention （PPCI） were analyzed. We used propensity score matching （PSM） to control differences of baseline characteristics between culprit only intervention （CP） and multivessel percutaneous coronary interventions （MP）, and between double vessel disease （DVD） and triple vessel disease （TVD）. The major adverse cardiac event （MACE） was analyzed for one year after discharge. Results TVD patients showed higher incidence of MACE （14.2% vs. 8.6%, P = 0.01）, any cause of revascularization （10.6% vs. 5.9%, P - 0.01）, and repeated PCI （9.5% vs. 5.7%, P = 0.02）, as compared to DVD patients during one year after discharge. MP reduced MACE effectively （7.3% vs. 13.8%, P = 0.03）, as compared to CP for one year, but all cause of death （1.6% vs. 3.2%, P= 0.38）, Ml （0.4% vs. 0.8%, P = 1.00）, and any cause ofrevascularization （5.3% vs. 9.7%, P = 0.09） were comparable in the two treatment groups. Conclusions STEMI patients with TVD showed higher rate of MACE, as compared to DVD MP performed during PPCI or ad hoc during admission for STEMI patients without cardiogenic shock showed lower rate of MACE in this large scaled database. Therefore, MP could be considered as an effective treatment option for STEMI patients without cardiogenic shock.

关键词： Culprit only intervention Multivessel intervention Multivessel coronary disease Myocardial infarction Primary percutaneous coronary intervention

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Anti-C4d chimeric antigen receptor regulatory T cells suppressed allograft rejection in ABO-incompatible heart transplantation

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Genes & diseases 2022年第1期9卷 1-4页

作者： Sun-Kyung Lee Jerome Han Honglin Piao Nara Shin Joon Young Jang Ji-Jing Yan Hyori Kim Junho Chung Jaeseok Yang Biomedical Research Institute Seoul National University HospitalSeoul 03080Republic of Korea department of medicine Graduate SchoolSeoul National University College of MedicineSeoul 03080Republic of Korea department of Biochemistry and Molecular Biology Seoul National University College of MedicineSeoul 03080Republic of Korea department of Biomedical Science Seoul National University College of MedicineSeoul 03080Republic of Korea Cancer Research Institute Seoul National University College of MedicineSeoul 03080Republic of Korea division of Nephrology Department of Internal MedicineYonsei University College of MedicineSeoul 03722Republic of Korea Convergence medicine Research Center Asan Medical CenterSeoul 05505Republic of Korea

ABO blood group-incompatible(ABOi)transplantation has been developed to overcome the serious problem of donor organ ***,antibody-mediated rejection(ABMR)remains as the main limitation to successful ABOi *** of desensitization treatment improved the outcomes of ABOi transplantation by suppressing ABMR;however,this strong,nonspecific immunosuppression also increases infectious ***,chimeric antigen receptor regulatory T cells(CAR Tregs)were developed to improve the antigen specificity,viability,and suppressive activity of Tregs.C4d deposition is a marker of ABMR and is also found in most ABOi allograft *** on these findings,we developed anti-C4d CAR Tregs to suppress ABMR in ABOi allografts.

关键词： C4d ABO allograft

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Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine

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World Journal of Gastroenterology 2015年第15期21卷 4644-4651页

作者： Scott Bowden Stephen Locarnini Ting-Tsung Chang You-Chen Chao Kwang-Hyub Han Robert G Gish Robert A de Man Miao Yu Cyril Llamoso Hong Tang Victorian infectious diseases Reference Laboratory division of Gastroenterology Department of Internal Medicine National Cheng Kung University Hospital division of Gastroenterology Department of Internal Medicine Tri-Service General Hospital National Defense Medical Center division of Gastroenterology Department of Internal Medicine Severance Hospital of Yonsei University Consultants LLC San Diego St Joseph’s hospital and Medical Center Phoenix Hepatitis B Foundation Doylestown department of Gastroenterology and Hepatology Room H375 Erasmus Medical Center Bristol-Myers Squibb Research and Development 5 Research Pkwy Wallingford Center Bristol-Myers Squibb Research and Development Princeton

AIM: To investigate the reduction in hepatitis B virus(HBV) covalently closed-circular DNA(ccc DNA) with entecavir(ETV) or lamivudine(LAM). METHODS: This analysis included patients who had participated in the randomized Phase Ⅲ study ETV-022 comparing ETV vs LAM in nucleos(t)ide-naive, HBe Agpositive patients. Patients received ETV(0.5 mg daily) or LAM(100 mg daily) for a minimum of 52 wk. Patients were eligible to participate in this sub-study if they had paired biopsies at baseline and week 48 with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA. The main objective was to compare changes in hepatic HBV ccc DNA and total hepatic HBV DNA at week 48 of ETV or LAM treatment, which was a secondary endpoint of study ETV-022. Additional post hoc analyses included linear regression analyses to assess associations of baseline levels and on-treatment changes of ccc DNA with other baseline factors [sex,age, serum HBV DNA, alanine aminotransferase(ALT), Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBV genotype], or ontreatment factors(changes from baseline at week 48 in serum HBV DNA, ALT, Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBe Ag loss at week 48).RESULTS: Overall, 305 patients(ETV = 159; LAM = 146) of ETV-022 had paired baseline and week 48 liver biopsies with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA, and were included in this analysis. Baseline demographics and disease characteristics were comparable between the two arms. After 48 wk, ETV resulted in significantly greater reductions in hepatic HBV ccc DNA [-0.9 log10 copies/human genome equivalent(HGEq) vs-0.7 log10 copies/HGEq; P = 0.0033] and total hepatic DNA levels(-2.1 log10 copies/HGEq vs-1.6 log10 copies/HGEq; P < 0.0001) than LAM. Virologic, biochemical, and histologic response rates at week 48 were also greater with ETV than with LAM. Baseline HBV ccc DNA levels were positivel

关键词： Hepatitis B virus Nucleos(t)ide analogtherapy Intrahepatic hepatitis B virus DNA Antiviralsuppression Virologic cure

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