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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 patients.Recently,reinvigoration of exhausted CD8^(+)T cells following PD-1 blockade was shown to be CD28-dependent in mouse models.Herein,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 patients.Single-cell analysis demonstrated a distinct expression pattern of CD28 between mouse and human CD8^(+)TILs.Furthermore,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^(+)TILs.Transcriptionally and phenotypically,PD-1 blockade-unresponsive human CD28^(–)PD-1^(+)CD8^(+)TILs exhibited characteristics of terminally exhausted CD8^(+)T cells with low TCF1 expression.Notably,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^(+)TILs.Taken 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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Trends in colorectal cancer incidence according to an increase in the number of colonoscopy cases in Korea

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 51-60页

作者： Ga Hee kim Yeong Chan Lee Tae Jun kim Sung Noh Hong Dong Kyung chang Young-Ho kim Dong-Hoon Yang chang Mo Moon Kyunga kim Hyun Gun kim Eun-Ran kim Division of Gastroenterology Department of Internal MedicineAsan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505South Korea Department of Digital Health Samsung Advanced Institute for Health Science and TechnologySungkyunkwan University School of MedicineSeoul 06351South Korea Division of Gastroenterology Department of Internal MedicineSamsung Medical CenterSungkyunkwan University School of MedicineSeoul 06351South Korea Division of Gastroenterology Department of Internal MedicineEwha Womans UniversitySeoul 07985South Korea Biomedical Statistics Center Samsung Medical CenterSeoul 06351South Korea Division of Gastroenterology Department of Internal MedicineSoonchunhyang University College of MedicineSeoul 04401South Korea

BACKGROUND The incidence of colorectal cancer(CRC)and preinvasive CRC(e.g.,early colon cancer and advanced adenoma)is gradually increasing in several countries.AIM To evaluate the trend in incidence of CRC and preinvasive CRC according to the increase in the number of colonoscopies performed in Korea.METHODS This retrospective cohort study enrolled Korean patients from 2002 to 2020 to evaluate the incidence of CRC and preinvasive CRC,and assess the numbers of diagnostic colonoscopies and colonoscopic polypectomies.Colonoscopy-related complications by age group were also determined.RESULTS The incidence of CRC showed a rapid increase,then decreased after 2012 in the 50-75 year-age group.During the study period,the rate of incidence of preinvasive CRC increased at a similar level in patients under 50 and 50-75 years of age.Since 2009,the increase has been rapid,showing a pattern similar to the increase in colonoscopies.The rate of colonoscopic polypectomy in patients aged under 50 was similar to the rate in patients over 75 years of age after 2007.The rate of complications after colonoscopy and related deaths within 3 mo was high for those over 75 years of age.CONCLUSION The diagnosis of preinvasive CRC increased with the increase in the number of colonoscopies performed.As the risk of colonoscopy-related hospitalization and death is high in the elderly,if early lesions at risk of developing CRC are diagnosed and treated under or at the age of 75,colonoscopy-related complications can be reduced for those aged 76 years or over.

关键词： Colorectal cancer Preinvasive colorectal cancer Colorectal polypectomy Colonoscopy

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Roles of host proteases in the entry of SARS-CoV-2

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Animal Diseases 2024年第1期4卷 27-39页

作者： Alexandria Zabiegalal Yunjeong kim Kyeong-Ok chang Department of Diagnostic Medicine and Pathobiology College of Veterinary MedicineKansas State University1800 Denison Avenue ManhattanKS 66506USA

The spike protein(S)of SARS-CoV-2 is responsible for viral attachment and entry,thus a major factor for host suscep-tibility,tissue tropism,virulence and pathogenicity.The S is divided with S1 and S2 region,and the S1 contains the receptor-binding domain(RBD),while the S2 contains the hydrophobic fusion domain for the entry into the host cell.Numerous host proteases have been implicated in the activation of SARS-CoV-2 S through various c leavage sites.In this article,we review host proteases including furin,trypsin,transmembrane protease serine 2(TMPRSS2)and cathepsins in the activation of SARS-CoV-2 S.Many betacoronaviruses including SARS-CoV-2 have polybasic residues at the S1/S2 site which is subjected to the cleavage by furin.The S1/S2 cleavage facilitates more assessable RBD to the receptor ACE2,and the binding triggers further conformational changes and exposure of the S2'site to proteases such as type Il transmembrane serine proteases(TTPRs)including TMPRSS2.In the presence of TMPRSS2 on the target cells,SARS-CoV-2 can utilize a direct entry route by fusion of the viral envelope to the cellular membrane.In the absence of TMPRSS2,SARS-CoV-2 enter target cells via endosomes where multiple cathepsins cleave the S for the successful entry.Additional host proteases involved in the cleavage of the S were discussed.This article also includes roles of 3C-like protease inhibitors which have inhibitory activity against cathepsin L in the entry of SARS-CoV-2,and discussed the dual roles of such inhibitors in virus replication.

关键词： SARS-CoV-2 Spike protein(S) Host proteases Cleavage site Virus entry

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Immediate secondary rhinoplasty using a folded dermofat graft for resolving complications related to silicone implants: A case report

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World Journal of Clinical Cases 2024年第14期12卷 2426-2430页

作者： Hoon kim Jong Hyup kim In chang Koh Soo Yeon Lim Department of Plastic and Reconstructive Surgery Konyang University HospitalUniversity of Konyang College of MedicineMyunggok Medical Research InstituteDaejeon 35365South Korea

BACKGROUND Various surgical techniques have been developed to enhance the nose shapes of Asian patients.Silicone implant augmentation rhinoplasty is widely used because it is relatively easy to perform and often yields satisfactory outcomes.However,this technique may lead to complications,including ischemia,necrosis,and over-augmentation.The most appropriate management of these complications,including infection,is immediate implant removal and revision surgery once the accompanying inflammation has healed.Occasionally,the patient may experience distress from nasal deformities during the intervention period.CASE SUMMARY Herein,we describe the case of a patient who underwent a secondary dorsal augmentation,with a folded dermofat graft harvested from the inguinal area and simultaneous implant removal,successfully preventing dimpling of the nasal deformity.CONCLUSION This surgical method can effectively manage implant-related complications following augmentation rhinoplasty using a silicone implant and provide satis-factory patient outcomes.

关键词： Complications Nose deformities Acquired Rhinoplasty Dermofat Surgery Plastic Case report

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High mobility group box 1 in the central nervous system:regeneration hidden beneath inflammation

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Neural Regeneration Research 2025年第1期20卷 107-115页

作者： Hanki kim Bum Jun kim Seungyon Koh Hyo Jin Cho Xuelian Jin Byung gon kim Jun Young Choi Department of Brain Science Ajou University School of MedicineSuwonSouth Korea Department of Biomedical Sciences Ajou University Graduate School of MedicineSuwonSouth Korea Department of Neurology Ajou University School of MedicineSuwonSouth Korea Department of Geriatrics The Affiliated Suqian First People’s Hospital of Nanjing Medical UniversitySuqianJiangsu ProvinceChina

High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.

关键词： central nervous system damage-associated molecular pattern ethyl pyruvate glycyrhizzin high mobility group box 1 inflammation neural stem cells neurodevelopment oligodendrocyte progenitor cells redox status regeneration

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Endoscopic ultrasound-guided tissue sampling induced pancreatic duct leak resolved by the placement of a pancreatic stent:A case report

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World Journal of Clinical Cases 2024年第9期12卷 1677-1684页

作者： Ki-Hyun kim chang Hwan Park Eunae Cho Yohan Lee Department of Internal Medicine Chonnam National University HospitalGwangju 61469South Korea Department of Gastroenterology Chonnam National University HospitalGwangju 61469South Korea

BACKGROUND Pancreatic ductal leaks complicated by endoscopic ultrasonography-guided tissue sampling(EUS-TS)can manifest as acute pancreatitis.CASE SUMMARY A 63-year-old man presented with persistent abdominal pain and weight loss.Diagnosis:Laboratory findings revealed elevated carbohydrate antigen 19-9(5920 U/mL)and carcinoembryonic antigen(23.7 ng/mL)levels.Magnetic resonance imaging of the pancreas revealed an approximately 3 cm ill-defined space-occupying lesion in the inferior aspect of the head,with severe encasement of the superior mesenteric artery.Pancreatic ductal adenocarcinoma was confirmed after pathological examination of specimens obtained by EUS-TS using the fanning method.Interventions and outcomes:The following day,the patient experienced severe abdominal pain with high amylase(265 U/L)and lipase(1173 U/L)levels.Computed tomography of the abdomen revealed edematous wall thickening of the second portion of the duodenum with adjacent fluid collections and a suspicious leak from either the distal common bile duct or the main pancreatic duct in the head.Endoscopic retrograde cholangiopancreatography revealed dye leakage in the head of the main pancreatic duct.Therefore,a 5F 7 cm linear plastic stent was deployed into the pancreatic duct to divert the pancreatic juice.The patient’s abdominal pain improved immediately after pancreatic stent insertion,and amylase and lipase levels normalized within a week.Neoadjuvant chemotherapy was then initiated.CONCLUSION Using the fanning method in EUS-TS can inadvertently cause damage to the pancreatic duct and may lead to clinically significant pancreatitis.Placing a pancreatic stent may immediately resolve acute pancreatitis and shorten the waiting time for curative therapy.When using the fanning method during EUSTS,ductal structures should be excluded to prevent pancreatic ductal leakage.

关键词： Endoscopic ultrasound-guided tissue sampling Pancreatitis Pancreatic duct leak Pancreatic stent Case report

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Experience of primary intestinal lymphangiectasia in adults: Twelve case series from a tertiary referral hospital

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World Journal of Clinical Cases 2024年第4期12卷 746-757页

作者： Ji Eun Na Ji Eun kim Sujin Park Eun Ran kim Sung Noh Hong Young-Ho kim Dong Kyung chang Department of Internal Medicine Inje University Haeundae Paik HospitalBusan 48108South Korea Department of Medicine Samsung Medical CenterSeoul 06351South Korea Department of Pathology Samsung Medical CenterSeoul 06351South Korea

BACKGROUND While primary intestinal lymphangiectasia(PIL)is considered a rare condition,there have been several reported cases in adults.Nevertheless,the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients.AIM To enhance understanding by investigating clinical presentation,diagnosis,treatment,complications,and prognoses in adult PIL cases.METHODS We enrolled adult patients diagnosed with PIL between March 2016 and September 2021.The primary outcome involved examining the diagnosis and treatment process of these patients.The secondary outcomes included identifying complications(infections,thromboembolism)and assessing prognoses(frequency of hospitalization and mortality)during the follow-up period.RESULTS Among the 12 included patients,peripheral edema(100%)and diarrhea(75%)were the main presenting complaints.Laboratory tests showed that all the pati-ents exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia.Radiologically,the predominant findings were edema of the small intestine(67%)and ascites(58%).The typical endoscopic finding with a snowflake appearance was observed in 75%of patients.Among the 12 patients,two responded positive-ly to octreotide and sirolimus,and eight who could undergo maintenance therapy discontinued subsequently.Complications due to PIL led to infection in half of the patients,thromboembolism in three patients,and one death.CONCLUSION PIL can be diagnosed in adults across various age groups,with different severity and treatment responses among patients,leading to diverse complications and prognoses.Consequently,tailored treatments will be necessary.We anticipate that our findings will contribute to the management of PIL,an etiology of protein-losing enteropathy.

关键词： Primary intestinal lymphangiectasia in adults Protein-losing enteropathy Diagnosis Treatment Prognosis

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Porocarcinoma in a palm reconstructed with a full thickness skin graft: A case report

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World Journal of Clinical Cases 2024年第3期12卷 665-670页

作者： Seok Beom Lim Kun Young Kwon Hoon kim Soo Yeon Lim In chang Koh Department of Plastic and Reconstructive Surgery Konyang University Medical CenterKonyang University of College of MedicineDaejeon 35365South Korea Department of Pathology Konyang University Medical CenterKonyang University of College of MedicineDaejeon 35365South Korea

BACKGROUND Porocarcinoma is a rare type of skin cancer that originates from sweat gland tumors.It is an aggressive malignant skin cancer that is difficult to diagnose clinically owing to its rarity and similarity to squamous cell carcinoma(SCC).CASE SUMMARY This case involved a 92-year-old woman,a farmer by profession,presented with an exophytic and verrucous mass on her left palm that had formed 2 years prior and caused chronic pain and frequent bleeding.Initially,the patient was diagnosed with SCC using a punch biopsy;however,a repeat biopsy with addi-tional immunohistochemical tests was performed for porocarcinoma.Ultimately,the patient was diagnosed with porocarcinoma and reconstruction was planned using a full-thickness skin graft.After treatment,the range of motion of the palm was preserved,and the aesthetic outcome was favorable.At 6 mo of follow-up,the patient was satisfied with the outcome.CONCLUSION Porocarcinoma is commonly misdiagnosed as SCC;therefore,clinicians should consider porocarcinomas when evaluating mass-like lesions on the hands.

关键词： Eccrine porocarcinoma Hand defects Reconstructive surgery Sweat gland tumor Skin graft Case report

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Absence of enhancement in a lesion does not preclude primary central nervous system T-cell lymphoma:A case report

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World Journal of Clinical Cases 2024年第2期12卷 374-382页

作者： Chan-Seop kim Chi-Hoon Choi Kyung Sik Yi Yook kim Jisun Lee chang Gok Woo Young Hun Jeon Department of Radiology Chungbuk National University HospitalChungbuk National University College of MedicineCheongju-si 28644Chungcheongbuk-doSouth Korea Department of Pathology Chungbuk National University HospitalChungbuk National University College of MedicineCheongju-si 28644Chungcheongbuk-doSouth Korea Department of Radiology Seoul National University HosptialSeoul 03080South Korea

BACKGROUND Primary central nervous system lymphoma(PCNSL)is a non-Hodgkin lymphoma that originates in the central nervous system(CNS)and is exclusively limited to the CNS.Although most PCNSLs are diffuse large B-cell lymphomas,primary CNS T-cell lymphomas(PCNSTLs)are rare.PCNSTLs typically demonstrate some degree of enhancement on contrast-enhanced magnetic resonance imaging(MRI).To the best of our knowledge,non-enhancing PCNSTL has not been reported previously.CASE SUMMARY A 69-year-old male presented to the neurology department with complaints of mild cognitive impairment and gradual onset of left lower leg weakness over a span of two weeks.Initial MRI showed asymmetric T2-hyperintense lesions within the brain.No enhancement was observed on the contrast-enhanced T1 image.The initial diagnosis was neuro-Behçet’s disease.Despite high-dose steroid therapy,no alterations in the lesions were identified on initial MRI.The patient’s symptoms deteriorated further.An MRI performed one month after the initial scan revealed an increased lesion extent.Subsequently,brain biopsy confirmed the diagnosis of PCNSTL.The patient underwent definitive combined chemoradiotherapy.However,the patient developed bacteremia and died of septic shock approximately three months after diagnosis.CONCLUSION The absence of enhancement in the lesion did not rule out PCNSTL.A biopsy approach is advisable for pathological confirmation.

关键词： Central nervous system neoplasms Non-Hodgkin Lymphoma T-cell Lymphoma Primary central nervous system lymphoma Primary central nervous system T-cell lymphoma Case report

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Oxygen vacancy engineering for tuning the catalytic activity of LaCoO_(3) perovskite

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Journal of Rare Earths 2024年第3期42卷 506-514,I0003页

作者： Jeong Hyun Cho Minjae kim Inchan Yang Kyung Tae Park chang Houn Rhee Hai Woong Park Ji Chul Jung Department of Chemical Engineering Myongji UniversityYongin 17058Republic of Korea Institute of Advanced Composite Materials Korea Institute of Science and TechnologyWanju-gunJeollabuk-do 55324Republic of Korea Iron&Steel Process Engineering Research Group POSCOPohang 37859Republic of Korea Hydrogen Research Center Research Institute of Industrial Science&Technology(RIST)Pohang 37673Republic of Korea

Herein, we attempted to engineer oxygen vacancies on the surface of LaCoO_(3) perovskite through simple post-treatments(acid or reductive thermal treatments). Acid treatment induces oxygen vacancies through the selective etching of the La cations, whereas thermal treatment in a reducing atmosphere generates oxygen vacancies by directly removing lattice oxygen. The characterization results confirm that the number of surface oxygen vacancies, which are crucial in various catalytic oxidation reactions,considerably increases in the LaCoO_(3) catalysts treated with acid or reducing gas. Acid treatment enriches the oxygen vacancies while maintaining the structure of the LaCoO_(3) catalysts, which can not be achieved through reductive thermal treatment. Therefore, the acid treatment is considered a promising technique for oxygen vacancy engineering of perovskite catalysts for tuning their catalytic activities. Furthermore,the catalytic activities of the posttreated LaCoO_(3) catalysts for CO oxidation were evaluated and are noted to be considerably better than those of the pristine LaCoO_(3) catalyst due to their abundant oxygen vacancies. Consequently, we conclude that the oxygen vacancies of perovskite catalysts can be effectively engineered via two simple methods and play a significant role in CO oxidation.

关键词： LaCoO_(3)perovskite Acid treatment Reductive thermal treatment Oxygen vacancy CO oxidation Rare earths

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