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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

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Prevalence of nonalcoholic fatty liver disease in pediatrics and adolescents:a systematic review and meta-analysis

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World Journal of Pediatrics 2024年第6期20卷 569-580页

作者： Eun Joo Lee Miyoung Choi Sang Bong ahn Jeong-ju Yoo Seong Hee Kang Yuri Cho Do Seon Song Hong Koh Dae Won Jeon Hye Won Lee Department of Pediatrics Yonsei University College of MedicineSeoulKorea Clinical Evidence Research National Evidence-Based Healthcare Collaborating Agency(NECA)SeoulKorea Department of Internal Medicine Nowon Eulji Medical CenterEulji University College of MedicineSeoulKorea Department of Internal Medicine Soonchunhyang University Bucheon HospitalBucheonKorea Department of Internal Medicine Sangkye Paek HospitalInje University College of MedicineSeoulKorea Center for Liver and Pancreatobiliary Cancer National Cancer CenterGoyangKorea Department of Internal Medicine College of MedicineSt.Vincent's HospitalThe Catholic University of KoreaSuwonKorea Department of Internal Medicine Hanyang University College of MedicineSeoulKorea Department of Internal Medicine Yonsei University College of MedicineSeoulKorea

Background As childhood obesity escalates worldwide,the prevalence of nonalcoholic fatty liver disease(NAFLD)in pediatric and adolescent populations is also ***,systematic studies and meta-analyses evaluating the prevalence of pediatric NAFLD remain *** The MEDLINE,Korean Medical Database(KMBASE),Embase,Global Health,and Cochrane Library databases were searched from January 1997 to April *** terms included NAFLD or steatosis;nonalcoholic or steatohepatitis;child(ren),adolescent,or teenager;and prevalence,incidence,or epidemiology.A random-effects meta-analysis model was used to estimate the prevalence of pediatric *** A total of 2116 publications were found,of which 62 were included in the *** them,27 reported the prevalence in the general population and 39 in the obese *** worldwide pooled prevalence of pediatric NAFLD was 13%[95%confidence interval(CI)9-18%]in the general population and 47%(95%CI 41%–53%)in the obese *** 16 studies in the general population and 18 in the obese population,NAFLD prevalence varied by *** the general population,the prevalence of NAFLD was 15%(95%CI 8%–23%)in males and 10%(95%CI 6%–15%)in *** the obese population,it was 54%(95%CI 46%–61%)in males and 39%(95%CI 30%–49%)in *** The global prevalence of pediatric NAFLD is rising in both the general and obese *** the increasing rates of childhood obesity,epidemiological studies on the prevalence and incidence of NAFLD are needed.

关键词： Meta-analysis Nonalcoholic fatty liver disease Pediatric Prevalence

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Transparent high-performance piezoceramics through pressureless sintering

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Journal of Advanced Ceramics 2024年第5期13卷 561-567页

作者： Hye-Lim Yu Woo-Seok Kang ju-Hyeon Lee Temesgen Tadeyos Zate Young-Jin Lee Bo-Kun Koo Dong-Jin Shin Min-Soo Kim Soon-Jong Jeong Young Ghyu ahn Wook Jo Department of Material Science and Engineering Ulsan National Institute of Science and TechnologyUlsan 44919Republic of Korea Energy Conversion Research Center Korea Electrotechnology Research InstituteChangwon 51543Republic of Korea MLCC Development Team Component Biz.UnitSamsung Electro-Mechanics Co.Ltd.Suwon 16674Republic of Korea

Piezoelectricity offers an electromechanical coupling that is widely utilized in transducer *** has been a consistent demand for transparent piezoelectric materials for optoelectrical ***,despite the inherent tradeoff between the transparency and the piezoelectricity,numerous strategies have been explored to develop the transparent piezoelectric ***,the most transparent piezoelectric materials developed to date is either a single crystal or materials that achieve transparency via hot-press sintering,limiting its industrial ***,we introduce a novel piezoelectric material that ensures transparency through co-doping and pressureless sintering of polycrystalline *** this study,we employed a compositional optimization approach to enhance the synergistic effect between the transparency and the piezoelectric properties of 0.71Pb(Mg_(1/3)Nb_(2/3))O_(3)–0.29PbTiO_(3)(PMN–0.29PT)*** utilizing the tape casting process for mass production and large-area manufacturing,our Pb_(0.913)La_(0.0145)Sm_(0.0145)(Mg_(1/3)Nb_(2/3))_(0.71)Ti_(0.29)O_(3)(TP2.9)ceramics exhibited over 60%transparency and large piezoelectric coefficient(d33)of 1104 pC/*** material holds considerable promise for a wide range of industrial applications in both the optical and electronic domains.

关键词： piezoelectric ceramics transparency pressureless sintering co-doping tape casting

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Weekly docetaxel and gemcitabine in previously treated metastatic esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2015年第14期21卷 4268-4274页

作者： Min-Young Lee Ki Sun jung Hae Su Kim Ji Yun Lee Sung Hee Lim Moonjin Kim Hyun Ae jung Sung Min Kim Jong Mu Sun myung-ju ahn Jeeyun Lee Se Hoon Park Seong Yoon Yi In Gyu Hwang Sang-Cheol Lee Hee Kyung ahn Do Hyoung Lim Soon Il Lee Keon Woo Park Division of Hematology-Oncology Department of MedicineSamsung Medical CenterSungkyunkwan University School of Medicine Division of Hematology-Oncology Department of Internal MedicineInje University Ilsan-Paik Hospital Division of Hematology-Oncology Department of Internal MedicineChung-Ang University Hospital Division of Hematology-Oncology Department of Internal MedicineSoonchunhyang University Hospital Division of Hematology-Oncology Department of Internal MedicineGachon University Gil Hospital Division of Hematology-Oncology Department of Internal MedicineDankook University College of Medicine

AIM: To assess the efficacy and safety of weekly docetaxel plus a fixed-dose rate(FDR) of gemcitabine in metastatic esophageal squamous cell carcinoma(SCC).METHODS: A multi-center, open-label, prospective phase Ⅱ study was ***-three esophageal SCC patients with documented progression after fluoropyrimidine/platinum-based first-line chemotherapy were enrolled and treated with docetaxel 35 mg/m2 and gemcitabine 1000 mg/m2 iv at a FDR(10 mg/m2 per minute) on days 1 and *** was repeatedevery twenty-one days until disease progression, unacceptable toxicity, or consent *** primary endpoint was response rate(RR), and secondary endpoints were safety, progression-free survival(PFS) and overall survival(OS).RESULTS: Combination of weekly docetaxel and FDR gemcitabine was well tolerated: the most common treatment-related adverse events were anemia(97%), fatigue(64%) and neutropenia(55%).One patient with multiple lung and lymph node metastases died of respiratory failure after receiving four cycles of chemotherapy, and the possibility of drug-induced pneumonitis could not be completely *** control(objective response plus stable disease) in the ITT population was achieved in 88% of patients, and the overall RR was 30%(95%CI: 15%-46%).The median PFS and OS were 4.0(95%CI: 3.4-4.6) and 8.8 mo(95%CI: 7.8-9.8 mo), ***: A combination of weekly docetaxel and FDR gemcitabine showed promising antitumor activity and tolerability in previously treated, metastatic esophageal SCC.

关键词： Clinical trial Phase Ⅱ Chemotherapy Carcinoma,Esop

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Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice

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Journal of Integrative Medicine 2024年第5期22卷 600-613页

作者： Mijung Yeom Sora ahn Dae-Hyun Hahm Sun-Young Jang Se Hoon Jang Su-Yang Park Jae-Hwan Jang Jihan Park ju-Young Oh In-Seon Lee Kyuseok Kim Soon-Kyeong Kwon Hi-Joon Park Acupuncture and Meridian Science Research Center College of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea Department of Physiology School of MedicineKyung Hee UniversitySeoul 02447Republic of Korea BioNanocomposite Research Center Kyung Hee UniversitySeoul 02447Republic of Korea Department of Science in Korean Medicine College of Korean MedicineGraduate SchoolKyung Hee UniversitySeoul 02447Republic of Korea College of Korean Medicine Kyung Hee UniversitySeoul 02447Republic of Korea Department of Ophthalmology Otorhinolaryngology and Dermatology of Korean MedicineCollege of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea Division of Applied Life Science(BK21) Gyeongsang National UniversityJinju 52828Republic of Korea Department of Anatomy&Information Sciences College of Korean MedicineKyung Hee UniversitySeoul 02447Republic of Korea

Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut *** has been proven to be effective in reducing AD symptoms without serious adverse events,but its underlying mechanism is not completely *** purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut *** AD-like skin lesions were induced by applying MC903 topically to the cheek of the *** was done at the Gok-Ji(LI11)***-like symptoms were assessed by lesion scores,scratching behavior,and histopathological changes;intestinal barrier function was measured by fecal output,serum lipopolysaccharide levels,histopathological changes,and mRNA expression of markers involved in intestinal permeability and *** microbiota was profiled using 16S rRNA gene sequencing from fecal *** Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening,and also significantly altered gut microbiota structure as revealed byβ-diversity indices and analysis of *** beneficial effects were eliminated by antibiotic depletion of gut microbiota,but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated ***,AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability,atrophy of the mucosal structure(reduced villus height and crypt depth),decreased expression of tight junctions and mucus synthesis genes,and increased expression of inflammatory mediators in the *** attenuated these abnormalities,which was gut *** Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier,providing new perspective for non-pharmacological strategies for

关键词： Atopic dermatitis Acupuncture Gut microbiota Intestinal barrier function

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Invariant submanifolds for systems of vector fields of constant rank

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Science China Mathematics 2016年第7期59卷 1417-1426页

作者： ahn Heung ju HAN Chong Kyu School of Undergraduate Study Daegu Gyeongbuk Institute of Sceince and Technology Department of Mathematics College of Natural SciencesSeoul National University

Given a system of vector fields on a smooth manifold that spans a plane field of constant rank, we present a systematic method and an algorithm to find submanifolds that are invariant under the flows of the vector fields. We present examples of partition into invariant submanifolds, which further gives partition into orbits. We use the method of generalized Frobenius theorem by means of exterior differential systems.

关键词： control system vector fields reachability orbits invariant submanifolds

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Minimal circumscribed Hermitian ellipsoid of Hartogs domains and an application to an extremal problem

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Science China Mathematics 2009年第8期52卷 1699-1716页

作者： ahn Heung-ju PARK Jong-do Department of Mathematical Sciences Seoul National University School of Mathematics Korea Institute for Advanced Study Hoegiro 87 Dongdaemun-gu Seoul 130-722 Korea

In this paper we construct circumscribed Hermitian ellipsoids of Hartogs domains of least volume and as an application, we obtain the Carathéodory extremal mappings between the Hartogs domains and the unit ball, and ... 详细信息

关键词： Hartogs domain minimal circumscribed Hermitian ellipsoid extremal problem 32H02 32F45

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Postpartum hemophagocytic lymphohistiocytosis:A case report

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世界临床病例杂志 2023年第26期11卷 6183-6188页

作者： ju Ho An jung Hwan ahn Department of Emergency Medicine Ajou University School of MedicineSuwon 16499Gyeonggi-doSouth Korea

BACKGROUND Postpartum hemophagocytic lymphohistiocytosis(HLH)is a rare disease with unclear *** is a secondary HLH diagnosed using the pediatric diagnostic criteria;however,the clinical diagnosis of postpartum HLH remains ***,HLH may remain undiagnosed,leading to poor patient ***,improvements in the accuracy of postpartum HLH diagnoses and treatments are *** SUMMARY We report the case of a 40-year-old female with postpartum *** patient attended the postpartum care center for 3 wk after giving birth and underwent needle aspiration due to thyroid gland enlargement 11 d before an emergency department visit precipitated by fever and abdominal *** no abnormal emergency room findings were noted,the patient was discharged with a prescription for broad-spectrum *** days later,she returned to the emergency room in a hemodynamically unstable state and was admitted to the intensive care unit with suspected sepsis or hematologic *** patient was treated,without effect,for sepsis using broad-spectrum antibiotics,and for suspected hematologic disease with steroid ***,she died due to rapidly worsening *** Rapid recognition and appropriate treatment of postpartum HLH are needed to improve the prognosis.

关键词： Bone marrow Pregnancy Lymphohistiocytosis Infection Steroids Case report

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Treatment of syringomyelia using uncultured umbilical cord mesenchymal stem cells: A case report and review of literature

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World Journal of Stem Cells 2022年第4期14卷 303-309页

作者： Hyunjun ahn Sang Yeon Lee Won-ju jung Kye-Ho Lee Stem Cell Treatment and Research Institute(STRI) bio Beauty and Health Company(bBHC)Seoul 04420South Korea Stem Cell Treatment 97.7 Beauty and Health ClinicSeoul 04420South Korea

BACKGROUND Syringomyelia is a disease caused by the formation of a cavity inside the spinal cord and is accompanied by such symptoms as pain,paresthesia,and urination and defecation disorders,and in severe cases causes various ***,there are only surgical methods for the treatment of syringomyelia,but these methods carry the possibility of failure,recurrence,and side *** SUMMARY The patient was a 59-year-old woman who suffered from pain due to *** treatment,the patient received transplant of uncultured umbilical cord-derived mesenchymal stem *** intended,the patient's pain was relieved after ***,an additional benefit was found in that the size of the cavity also *** 2 years from the last treatment,the patient's cavity had almost completely disappeared and her syringomyelia was deemed *** Using uncultured umbilical cord-derived mesenchymal stem cells may be a new treatment alternative for syringomyelia.

关键词： Syringomyelia Umbilical cord mesenchymal stem cells Cell therapy Allogenic stem cells Chiari malformations Case report

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Alopecia treatment using minimally manipulated human umbilical cord-derived mesenchymal stem cells:Three case reports and review of literature

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World Journal of Clinical Cases 2021年第15期9卷 3741-3751页

作者： Hyunjun ahn Sang Yeon Lee Won ju jung Kye-Ho Lee bio Beauty&Health Company(bBHC)-Stem Cell Treatment&Research Institute(STRI) Seoul 04420South Korea Department of Functional Genomics University of Science and Technology KRIBB SchoolDeajeon 34113South Korea 97.7 Beauty&Health(B&H)Clinics Seoul 04420South Korea

BACKGROUND Alopecia areata(AA)is a common autoimmune disease characterized by hair *** appears in extensive forms,such as progressive and diffusing hair loss(diffuse AA),a total loss of scalp hair(alopecia totalis),and complete loss of hair over the entire body(alopecia universalis).Recently,mesenchymal stem cells(MSCs)have been identified as a therapeutic alternative for autoimmune *** this reason,preclinical and case studies of AA and related diseases using MSCs have been *** SUMMARY Case 1:A 55-year-old woman suffered from AA in two areas of the *** was given 15 rounds of minimally manipulated umbilical cord-MSCs(MM-UC-MSCs)over 6 *** AA gradually improved 3 mo after the first *** patient was cured,and AA did not *** 2:A 30-year-old woman,with history of local steroid hormone injections,suffered from AA in one area on the *** was given two rounds of MM-UC-MSCs over 1 *** AA immediately improved after the first *** patient was cured,and AA did not *** 3:A 20-year-old woman,who was diagnosed with alopecia universalis at the age of 12,was given 14 rounds of MM-UC-MSCs over 12 *** hair began to grow about 3 mo after the first *** patient was cured,and alopecia universalis did not *** MM-UC-MSC transplantation potentially treats patients who suffer from AA and related diseases.

关键词： Alopecia areata Umbilical cord-derived mesenchymal stem cells Allogenic Cell therapy Minimal manipulation Case report

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