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Prognostic significance of the neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with stage Ⅲ and Ⅳcolorectal cancer

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World Journal of Gastroenterology 2017年第3期23卷 505-515页

作者： Jae Hyun kim Jun Yeop Lee hae koo kim Jin Wook Lee Sung Gyu Jung Kyoungwon Jung Sung Eun kim Won Moon Moo In Park Seun Ja Park Division of Gastroenterology Department of Internal MedicineKosin University College of MedicineBusan 602-702South Korea

AIM To evaluate the prognostic value of the neutrophil-tolymphocyte ratio(NLR) and platelet-to-lymphocyte ratio(PLR) in patients with colorectal cancer(CRC).METHODS Between April 1996 and December 2010, medical records from a total of 1868 patients with CRC were retrospectively reviewed. The values of simple inflammatory markers including NLR and PLR in predicting the long-term outcomes of these patients were evaluated using Kaplan-Meier curves and Cox regression models.RESULTS The median follow-up duration was 46 mo(interquartile range, 22-73). The estimation of NLR and PLR was based on the time of diagnosis. In multivariate Cox regression analysis, high NLR (≥ 3.0) and high PLR(≥ 160) were independent risk factors predicting poor long-term outcomes in patients with stage Ⅲ and Ⅳ CRC. However, high NLR and high PLR were not prognostic factors in patients with stage Ⅰ and Ⅱ CRC.CONCLUSION In this study, we identified that high NLR (≥ 3.0) and high PLR (≥ 160) are useful prognostic factors to predict long-term outcomes in patients with stage Ⅲ and Ⅳ CRC.

关键词： Colorectal cancer Neutrophil Lymphocyte Platelet Prognosis

Nanozyme‑Engineered Hydrogels for Anti‑Inflammation and Skin Regeneration

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Nano-Micro Letters 2024年第6期16卷 127-179页

作者： Amal George Kurian Rajendra K.Singh Varsha Sagar Jung‑Hwan Lee hae‑Won kim Institute of Tissue Regeneration Engineering(ITREN) Dankook UniversityCheonan 31116Republic of Korea Department of Nanobiomedical Science&BK21 NBM Global Research Center for Regenerative Medicine Dankook UniversityCheonan 31116Republic of Korea Department of Biomaterials Science School of DentistryDankook UniversityCheonan 31116Republic of Korea UCL Eastman‑Korea Dental Medicine Innovation Centre Dankook UniversityCheonan 31116Republic of Korea Cell and Matter Institute Dankook UniversityCheonan 31116Republic of Korea Mechanobiology Dental Medicine Research Center Dankook UniversityCheonan 31116Republic of Korea

Inflammatory skin disorders can cause chronic scarring and functional impairments,posing a significant burden on patients and the healthcare system.Conventional therapies,such as corticosteroids and nonsteroidal anti-inflammatory drugs,are limited in efficacy and associated with adverse effects.Recently,nanozyme(NZ)-based hydrogels have shown great promise in addressing these challenges.NZ-based hydrogels possess unique therapeutic abilities by combining the therapeutic benefits of redox nanomaterials with enzymatic activity and the water-retaining capacity of hydrogels.The multifaceted therapeutic effects of these hydrogels include scavenging reactive oxygen species and other inflammatory mediators modulating immune responses toward a pro-regenerative environment and enhancing regenerative potential by triggering cell migration and differentiation.This review highlights the current state of the art in NZ-engineered hydrogels(NZ@hydrogels)for anti-inflammatory and skin regeneration applications.It also discusses the underlying chemo-mechano-biological mechanisms behind their effectiveness.Additionally,the challenges and future directions in this ground,particularly their clinical translation,are addressed.The insights provided in this review can aid in the design and engineering of novel NZ-based hydrogels,offering new possibilities for targeted and personalized skin-care therapies.

关键词： Nanozymes Hydrogels ROS scavenging Anti-inflammation Skin regeneration

Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites

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Cancer Communications 2024年第1期44卷 47-75页

作者： Ji Eon kim So-Young Park Chulhwan Kwak Yoonji Lee Dae-Geun Song Jae Woo Jung haesong Lee Eun-Ae Shin Yangie Pinanga Kyung-hee Pyo Eun hae Lee Wonsik kim Soyeon kim Chang-Duck Jun Jeanho Yun Sun Choi Hyun-Woo Rhee Kwang-Hyeon Liu Jung Weon Lee Department of Pharmacy College of PharmacySeoul National UniversitySeoulRepublic of Korea Research Institute of Pharmaceutical Sciences College of PharmacySeoul National UniversitySeoulRepublic of Korea BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit College of Pharmacy and Research Institute of Pharmaceutical SciencesKyungpook National UniversityDaeguRepublic of Korea Department of Chemistry Seoul National UniversitySeoulRepublic of Korea College of Pharmacy Chung-Ang UniversitySeoulRepublic of Korea Natural Product Informatics Research Center Korea Institute of Science and Technology(KIST)Gangneung-siGangwon-doRepublic of Korea School of Life Sciences Gwangju Institute of Science and Technology(GIST)GwangjuRepublic of Korea Department of Biochemistry College of MedicineDong-A UniversityBusanRepublic of Korea Global AI Drug Discovery Center College of Pharmacy and Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoulRepublic of Korea Interdisciplinary Program in Genetic Engineering Seoul National UniversitySeoulRepublic of Korea

Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic contexts.It is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of metabolisms.Methods:Here,we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites(MLCSs),using in vitro cells and in vivo animal systems,via approaches by immunofluorescence,proximity labelling based proteomics analysis,organelle reconstitution etc.Results:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal TM4SF5.Proximity labeling showed molecular clustering of phospho-dynamic-related protein I(DRP1)and certain mitophagy receptors at TM4SF5-enriched MLCSs,leading to mitochondrial fis-sion and autophagy.TM4SF5 bound NPC intracellular cholesterol transporter 1(NPC1)and free cholesterol,and mediated export of lysosomal cholesterol to mitochondria,leading to impaired oxidative phosphorylation but intact tri-carboxylic acid(TCA)cycle andβ-oxidation.In mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver malignancy.Conclusions:Our findings suggested that TM4SF5-enriched MLCSs regu-late glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming,presumably while hepatocellular carcinogenesis,recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial repro-gramming to support biomolecule synthesis in addition to glycolytic energetics.

关键词： cholesterol fluorescent imaging glucose catabolism hepatocellular carcinogenesis mem-brane contact sites mitochondria function mitophagy oxidative phosphorylation protein-protein interaction tetraspanin

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 applications.There has been a consistent demand for transparent piezoelectric materials for optoelectrical applications.Therefore,despite the inherent tradeoff between the transparency and the piezoelectricity,numerous strategies have been explored to develop the transparent piezoelectric materials.Nonetheless,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 applicability.Therefore,we introduce a novel piezoelectric material that ensures transparency through co-doping and pressureless sintering of polycrystalline ceramics.In 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)ceramics.By 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/N.This 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

Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

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Journal of Animal Science and Biotechnology 2024年第1期15卷 456-462页

作者： Gyeong-Min Gim Kyeong-Hyeon Eom Dong-Hyeok Kwon Dae-Jin Jung Dae-Hyun kim Jun-koo Yi Jae-Jung Ha Ji-Hyun Lee Seong-Beom Lee Woo-Jae Son Soo-Young Yum Won-Wu Lee Goo Jang Laboratory of Theriogenology and Biotechnology Department of Veterinary Clinical ScienceCollege of Veterinary Medicine and the Research Institute of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea LARTBio Co. Ltd.SeoulRepublic of Korea Gyeongsangbukdo Livestock Research Institute YeongjuRepublic of Korea Comparative Medicine Disease Research Center Seoul National UniversitySeoulRepublic of Korea

Background Genome editing has been considered as powerful tool in agricultural fields.However,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising cost.Furthermore,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in cattle.In this point of view,electroporation in embryos has been risen as an alternative.Results First,editing efficiency of our electroporation methods were tested for embryos.Presence of mutation on embryo was confirmed by T7E1 assay.With first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,respectively.In case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for BLG.Afterwards,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep sequencing.Thirteen recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double KO.Ten surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both genes.Conclusions These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively applied.Finally,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

关键词： Beta-lactoglobulin Cattle CRISPR-Cas9 Electroporation Knockout MSTN PRNP

Distinctive clinical features of spontaneous pneumoperitoneum in neonates: A retrospective analysis

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World Journal of Clinical Cases 2022年第23期10卷 8124-8132页

作者： Soo-Hong kim Yong-Hoon Cho hae-Young kim Department of Surgery Pusan National University Yangsan HospitalPusan National University School of MedicineYangsan 50612South Korea Research Institute for Convergence of Biomedical Science and Technology Pusan National University Yangsan HospitalYangsan 50612South Korea

BACKGROUND Spontaneous pneumoperitoneum(SP) without gastrointestinal perforation rarely occurs in neonates, with most SP cases being idiopathic. Although SP usually follows a benign clinical course with favorable prognosis, it can become lifethreatening in certain situations. In these cases, urgent surgical intervention may be required. Therefore, it may be difficult to decide when or how to perform prompt interventions.AIM To demonstrate the distinct clinical features of SP to guide appropriate management by comparing characteristics between SP and typical pneumoperitoneum secondary to gastrointestinal perforation.METHODS We retrospectively reviewed electronic medical records and identified 37 neonates with radiological evidence of pneumoperitoneum who were treated at our institution. Clinical variables were compared between neonates with SP without gastrointestinal perforation(Group A) and those with pneumoperitoneum secondary to gastrointestinal perforation(Group B). Clinical variables between groups were compared using Student’s t-test and the chi-square test. The risk factors related to mortality were examined using multi-logistic regression analysis.RESULTS Group A comprised 35.1%(13/37) of the patients. The frequency of persistent pulmonary hypertension(53.8%) and pneumothorax(46.2%) before the development of pneumoperitoneum was significantly higher in group A than in group B(P =0.004). Platelet count and partial pressure of arterial oxygen(PaO) were significantly lower in group A(P = 0.015 and 0.025, respectively). Overall mortality was significantly higher in group A than in group B(76.9% vs 16.7%, P = 0.001). Only preterm infants were significantly associated with high mortality(P = 0.041;odds ratio = 18.0). Accompaniment with persistent pulmonary hypertension and pneumothorax were also significantly high(P = 0.004) in group A, but these were not strongly associated with high mortality.CONCLUSION This study identified a higher mortality rate in patients with SP than that described in previous reports.

关键词： Spontaneous pneumoperitoneum Thrombocytopenia Persistent pulmonary hypertension Pneumothorax Preterm

Materials and extracellular matrix rigidity highlighted in tissue damages and diseases:Implication for biomaterials design and therapeutic targets

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Bioactive Materials 2023年第2期20卷 381-403页

作者： Jae Hee Park Seung Bin Jo Jung-Hwan Lee hae-Hyoung Lee Jonathan CKnowles hae-Won kim Institute of Tissue Regeneration Engineering(ITREN) Dankook UniversityCheonan31116Republic of Korea Department of Nanobiomedical Science and BK21 NBM Global Research Center for Regenerative Medicine Dankook UniversityCheonan31116Republic of Korea Department of Biomaterials Science College of DentistryDankook UniversityCheonan31116Republic of Korea Cell&Matter Institute Dankook UniversityCheonan31116Republic of Korea Mechanobiology Dental Medicine Research Center Dankook UniversityCheonan31116Republic of Korea UCL Eastman-Korea Dental Medicine Innovation Centre Dankook UniversityCheonan31116Republic of Korea Division of Biomaterials and Tissue Engineering UCL Eastman Dental InstituteUniversity College LondonRoyal Free HospitalRowland Hill StreetLondonNW32PFUnited Kingdom

Rigidity(or stiffness)of materials and extracellular matrix has proven to be one of the most significant extracellular physicochemical cues that can control diverse cell behaviors,such as contractility,motility,and spreading,and the resultant pathophysiological phenomena.Many 2D materials engineered with tunable rigidity have enabled researchers to elucidate the roles of matrix biophysical cues in diverse cellular events,including migration,lineage specification,and mechanical memory.Moreover,the recent findings accumulated under 3D environments with viscoelastic and remodeling properties pointed to the importance of dynamically changing rigidity in cell fate control,tissue repair,and disease progression.Thus,here we aim to highlight the works related with material/matrix-rigidity-mediated cell and tissue behaviors,with a brief outlook into the studies on the effects of material/matrix rigidity on cell behaviors in 2D systems,further discussion of the events and considerations in tissue-mimicking 3D conditions,and then examination of the in vivo findings that concern material/matrix rigidity.The current discussion will help understand the material/matrix-rigidity-mediated biological phenomena and further leverage the concepts to find therapeutic targets and to design implantable materials for the treatment of damaged and diseased tissues.

关键词： Matrix rigidity Biophysical cue Cell and tissue engineering 3D biomaterials conditions Therapeutic targets

Radiation therapy for extrahepatic bile duct cancer: Current evidences and future perspectives

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World Journal of Clinical Cases 2019年第11期7卷 1242-1252页

作者： Taeryool koo hae Jin Park Kyubo kim Department of Radiation Oncology Hallym University Sacred Heart Hospital Anyang 14068 South Korea Department of Radiation Oncology Hanyang University College of Medicine Seoul 04763 South Korea Department of Radiation Oncology Ewha Womans University College of Medicine Seoul 07985 South Korea

Extrahepatic bile duct cancer (EBDC) is a rare malignancy that involves neoplastic changes extending from both hepatic ducts to the common bile duct. The treatment of choice is surgical resection, but the predominant pattern of initial treatment failure is locoregional recurrence. Accordingly, adjuvant radiotherapy has been administered after surgical resection based on these rationales. At this time, there is minimal evidence supporting adjuvant radiotherapy, because there have been no phase III trials evaluating its benefit. Relatively small retrospective studies have tried to compare outcomes associated with EBDC treated with or without radiotherapy. We aimed to review studies investigating adjuvant radiotherapy for resected EBDC. Because less than onethird of EBDC cases are amenable to curative resection at diagnosis, other locoregional treatment modalities need to be considered, including radiotherapy. The next aim of this review was to summarize reports of definitive radiotherapy for unresectable EBDC. Patients with advanced EBDC often experience biliary obstruction, which can lead to jaundice and progress to death. Biliary stent insertion is an important palliative procedure, but stents are prone to occlusion after subsequent ingrowth of the EBDC. Radiotherapy can be effective for maintaining the patency of inserted stents. We also reviewed the benefit of palliative radiotherapy combined with the biliary stent insertion. Lastly, we discuss the existing gaps in the evidence supporting radiotherapy in the management of EBDC.

关键词： Extrahepatic bile duct cancer Patterns of failure Adjuvant radiotherapy Definitive radiotherapy Palliative radiotherapy Biliary stent

Uncontrolled high blood pressure under total intravenous anesthesia with propofol and remifentanil:A case report

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World Journal of Clinical Cases 2022年第26期10卷 9411-9416页

作者： Min Jung Jang Jee Hee kim hae Jeong Jeong Anesthesiology and Pain Medicine National Cancer CenterGoyang 10408South Korea

BACKGROUND Although propofol generally reduces blood pressure,rarely,it causes hypertension.However,the mechanism by which propofol increases blood pressure has not been established,and so far,there are only a few reported cases.CASE SUMMARY A 46-year-old woman,diagnosed with thyroid cancer,was administered general anesthesia with propofol and remifentanil for a thyroid lobectomy.An increase in the concentrations of intravenous anesthetics further increased her blood pressure.The blood pressure remained stable when anesthesia was maintained with sevoflurane and remifentanil after the interruption of propofol administration.CONCLUSION We concluded that propofol administration was the cause of increased blood pressure.

关键词： Anesthesia Intravenous Hypertension Propofol Remifentanil Tachycardia Case report