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Gene editing particle system as a therapeutic approach for drug-resistant colorectal cancer

Nano Research 2020年第6期13卷 1576-1585页

作者： jee-yeon ryu You Jung Choi Eun-Jeong Won Emmanuel Hui Ho-Shik Kim Young-Seok Cho Tae-Jong Yoon Laboratory of Nanopharmacy College of PharmacyResearch Institute of Pharmaceutical Science and Technology(RIPST)Ajou UniversitySuwon16499Republic of Korea Division of Gastroenterology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul06591Republic of Korea Moogene Medi Co. Ltd.Seongnam13488Republic of Korea

The epidermal growth factor receptor(EGFR)pathway plays an important role in the progression of colorectal cancer(CRC).Anti-EGFR drugs based on antibodies have been widely used for treating CRC through inducing the cell death pathway.However,the majority of CRC patients will inevitably develop drug-resistance during anti-EGFR drug treatment,which is mainly caused by a point mutation in the KRAS oncogene.We developed a nanoliposomal(NL)particle containing the Cas9 protein and a single-guide RNA(sgRNA)complex(Cas9-RNP),for genomic editing of the KRAS mutation.The NL particle is composed of bio-compatible lipid compounds that can effectively encapsulate Cas9-RNP.By modifying the NL particle to include the appropriate antibody,it can specifically recognize EGFR expressing CRC and effectively deliver the gene-editing complexes.The conditions of NL treatment were optimized using a KRAS mutated CRC in vivo mouse model.Mice with KRAS-mutated CRC showed drug resistance against cetuximab,a therapeutic antibody drug.After treating the mice with the KRAS gene-editing NL particles,the implanted tumors showed a dramatic decrease in size.Our results demonstrated that this genomic editing complex has great potential as a therapeutic carrier system for the treatment of drug-resistant cancer caused by a point mutation.

关键词： nanoliposome clustered regularly interspaced short palindromic repeat and associated Cas9 nuclease(CRISPR/Cas9) KRAS mutation drug-resistance colorectal cancer

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Counter-balancing effects of Si on C partitioning and stacking fault energy of austenite in 10Mn quenching and partitioning steel

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Journal of Materials Science & Technology 2022年第3期98卷 248-257页

作者： Dong Hwi Kim jee-Hyun Kang Hojun Gwon Joo Hyun ryu Sung-Joon Kim Graduate Institute for Ferrous Technology Pohang University of Science and TechnologyPohang 37673Republic of Korea School of Materials Science and Engineering Institute of Materials TechnologyYeungnam UniversityGyeongsan 38541Republic of Korea POSCO Technical Research Laboratories POSCOGwangyang 57807Republic of Korea

Silicon is an essential alloying element in quenching and partitioning(Q&P)steels,because it is known to suppress carbide precipitation during partitioning step and promote carbon partitioning to stabilize austenite.When 2 wt%Si was added to 10Mn-2Al-0.2C steel,the size and fraction of the carbides formed during partitioning became smaller than in the Si-free counterpart.Moreover,the suppression of carbide formation promoted C partitioning into austenite as expected.However,austenite stability was always lower with Si under the equivalent partitioning condition because Si effectively decreased the stacking fault energy of austenite.As partitioning progressed,the both yield and tensile strengths of the Si-added steel exceeded that of the Si-free steel with the similar ductility level.This was because Si was an effective solid solution strengthener,and the austenite in the Si-added steel exhibited the appropriate stability to gradually transform into martensite throughout the deformation.The resulting strengthening effect compensated for the softening caused by martensite recovery.Consequently,strain hardening rate decreased continuously throughout deformation,which resulted in high tensile strength and ductility.

关键词： Steels Q&P steel Silicon Austenite stability Tensile deformation Stacking fault energy Medium Mn steel

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Psychological predictors of bipolarity in panic disorder

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World Journal of Psychiatry 2021年第6期11卷 242-252页

作者： Da Hye Oh Doo-Heum Park Seung-Ho ryu jee Hyun Ha Hong Jun Jeon Department of Psychiatry Konkuk University Medical CenterSeoul 05030South Korea Department of Psychiatry Konkuk University School of MedicineSeoul 05029South Korea

BACKGROUND Panic disorders frequently occur with affective disorders,particularly bipolar disorder.Patients with panic disorder and bipolar disorder are more likely to present with severe symptoms,such as high rates of suicidal behavior,poor symptomatic and functional recovery,and poor drug responses.AIM To investigate the psychological characteristics of panic disorder patients related to bipolarity.METHODS A total of 254 patients(136 men and 118 women,mean age=33.48±3.2 years)who were diagnosed with panic disorder were included in the study.Panic disorder with bipolarity(BP+)was defined as a score of≥7 on the Korean version of the Mood Disorder Questionnaire(K-MDQ),and a score lower than 7 was considered as a panic disorder without bipolarity(BP-).Self-report questionnaires were analyzed to examine their association with bipolarity.Psychological tests used in the study were the Mood Disorder Questionnaire(MDQ),Panic Disorder Severity Scale,Beck Depression Inventory,State-Trait Anxiety Inventory(STAI),Temperament and Character Inventory(TCI),and Minnesota Multiphasic Personality Inventory(MMPI).Statistical analyses were performed to evaluate the correlation between bipolarity of panic disorder patients and various psychological test results indicative of psychological characteristics.RESULTS Patients with a K-MDQ score of 7 or more were considered to have a history of manic or hypomanic episodes(BP+group,n=128),while patients with K-MDQ scores below 7 were defined as those without bipolarity(BP-group,n=126).The BP+group were more likely to be unmarried(single 56.2%vs 44.4%,P=0.008)and younger(30.78±0.59 vs 37.11±3.21,P<0.001).Additionally,the BP+group had significantly higher scores on psychological assessment scales,such as the hypochondriasis,psychopathic deviate,masculinity-femininity,psychasthenia,schizophrenia,and hypomania(Ma)in MMPI,and novelty seeking,harm avoidance and self-transcendence in TCI,and STAI(state and trait)compared to the BP-group.In logistic regression analysis,depression in MMPI,selfdirec

关键词： Panic disorder Bipolar disorder Bipolarity Anxiety Minnesota Multiphasic Personality Inventory Temperament and Character Inventory

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Exploring ideal operative time for best outcomes in gastric cancer surgery:A multi-institutional study based on KLASS-07 database

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Chinese Journal of Cancer Research 2023年第6期35卷 660-674页

作者： Shin-Hoo Park Ye-Rim Shin Hoon Hur Chang Min Lee Jae Seok Min Seung Wan ryu Hyun Dong Chae Oh Jeong Chang-In Choi Kyo-Young Song Ho Goon Kim Ye Seob jee Kwang Hee Kim Jeong Goo Kim Kyung Sook Yang Hua Huang Sungsoo Park Division of Foregut Surgery Korea University College of MedicineSeoul 02841Republic of Korea Division of Foregut Surgery Korea University Anam HospitalSeoul 02841Republic of Korea Department of Surgery Ajou University School of MedicineSuwon 16499Republic of Korea Division of Foregut Surgery Korea University Ansan HospitalAnsan 15355Republic of Korea Department of Surgery Dongnam Institute of Radiological and Medical SciencesCancer CenterBusan 46033Republic of Korea Department of Surgery Keimyung University Dongsan Medical CenterDaegu 41931Republic of Korea Department of Surgery Catholic University of Daegu School of MedicineDaegu 42472Republic of Korea Department of Surgery Chonnam National University Medical SchoolHwasun 58128Republic of Korea Department of Surgery Pusan National University HospitalPusan 49241Republic of Korea Department of Surgery Catholic University of Seoul St Mary’s HospitalSeoul 06591Republic of Korea Department of Surgery Chonnam National University Medical SchoolGwangju 61469Republic of Korea Department of Surgery Dankook University College of MedicineCheonan 31116Republic of Korea Department of Surgery Busan Paik HospitalInje UniversityBusan 14905Republic of Korea Department of Surgery Daejeon St.Mary’s HospitalCollege of Medicinethe Catholic University of KoreaDaejeon 34943Republic of Korea Department of Biostatistics Korea University College of MedicineSeoul 02841Republic of Korea Department of Gastric Cancer and Soft Tissue Sarcoma Fudan University Shanghai Cancer CenterShanghai 200433China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200433China

Objective:While a rushed operation can omit essential procedures,prolonged operative time results in higher morbidity.Nevertheless,the optimal operative time range remains uncertain.This study aimed to estimate the ideal operative time range and evaluate its applicability in laparoscopic cancer surgery.Methods:A prospectively collected multicenter database of 397 patients who underwent laparoscopic distal gastrectomy were retrospectively reviewed.The ideal operative time range was statistically calculated by separately analyzing the operative time of uneventful surgeries.Finally,intraoperative and postoperative outcomes were compared among the shorter,ideal,and longer operative time groups.Results:The statistically calculated ideal operative time was 135.4-165.4 min.The longer operative time(LOT)group had a lower rate of uneventful,perfect surgery than the ideal or shorter operative time(IOT/SOT)group(2.8%vs.8.8%and 2.2%vs.13.4%,all P<0.05).Longer operative time increased bleeding,postoperative morbidities,and delayed diet and discharge(all P<0.05).Particularly,an uneventful,perfect surgery could not be achieved when the operative time exceeded 240 min.Regardless of ideal time range,SOT group achieved the highest percentage of uneventful surgery(13.4%),which was possible by surgeon's ability to retrieve a higher number of lymph nodes and perform≥150 gastrectomies annually.Conclusions:Operative time longer than the ideal time range(especially≥240 min)should be avoided.If the essential operative procedure were faithfully conducted without compromising oncological safety,an operative time shorter than the ideal range leaded to a better prognosis.Efforts to minimize operative time should be attempted with sufficient surgical experience.

关键词： Operative time laparoscopic surgery gastric cancer gastrectomy morbidity

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Effect of tellurium on the microstructure and mechanical properties of Fe-14Cr oxide-dispersion-strengthened steels produced by additive manufacturing

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Journal of Materials Science & Technology 2021年第36期95卷 114-126页

作者： Barton Mensah Arkhurst jee Hwan Bae Min Young Na Hye Jung Chang Hyun Gil Kim Il Hyun Kim Ho Jin ryu Jeoung Han Kim School of Materials Science and Engineering University of New South Wales SydneyNSW 2052Australia Advanced Analysis Center Korea Institute of Science and Technology SeoulSeongbuk-guRepublic of Korea LWR Fuel Technology Division Korea Atomic Energy Research InstituteDaejeonYuseong-guRepublic of Korea Department of Nuclear and Quantum Engineering KAISTDaejeonYuseong-guRepublic of Korea Department of Materials Science&Engineering Hanbat National UniversityRepublic of Korea

Conventionally,Te has primarily been used to improve the machinability of steel and its alloys.In this work,Te was used to refine the grains of an oxide-dispersion-strengthened(ODS)steel produced by additive manufacturing(AM)with fixed processing parameters.Addition of Te to the raw powder produced an ODS steel with a fine-grained microstructure,in contrast to the ODS steel manufactured without Te.Moreover,the addition of Te resulted in superior yield strength and ultimate tensile strength,which was attributed to the combined effects of grain refinement and the finer nanoparticles(NPs)composed of Terich composite NPs and Cr-rich NPs.For the first time,the AM technique was used to obtain grain and nanoparticle sizes of~3.4μm and 6 nm,respectively,from the Te-added ODS steel.

关键词： Additive manufacturing Directed energy deposition Oxide-dispersion-strengthened steel Nanoparticle Tellurium

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Uhwang Chungsim Won Decreases Blood Oxygen Level-Dependent fMRI Signal Response to A Motor Stimulation Task

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Chinese Journal of Integrative Medicine 2015年第7期21卷 493-499页

作者： Woo-Sang Jung Jong-Man ryu Young-jee Kim Seong-Uk Park Geon-Ho Jahng Jung-Mi Park Sang-Kwan Moon Chang-Nam Ko Ki-Ho Cho Department of Cardiovascular&Neurologic Diseases(Stroke Center) College of Oriental MedicineKyung Hee University Department of Radiology College of MedicineKyung Hee University

Objectives： TO evaluate the effect of Uhwang Chungsim Won [UC, Niuhuang Qingxin Pill （牛黄清心丸] on the blood oxygen level-dependent （BOLD） functional magnetic resonance imaging （fMRI） signal response to a motor stimulation task using a hand grasping paradigm. Methods： Ten healthy right-handed male volunteers were recruited. Their BOLD fMRI signal characteristics during hand grasping were determined before and 1 h after consuming UC. Results： With the administration of UC, BOLD responses to the right hand motor task showed a decrease in both hemispheres including the right cerebellar culmen, right and left medial frontal gyrus, right parahippocampal gyrus, right and left sublobar insula, right and left posterior cingulate, left precuneus, and right precentral gyrus. Decreased BOLD responses to the left hand motor task were shown in the right lingual gyrus, right cerebellar culmen, left superior temporal gyrus, right and left middle frontal gyrus, and right precentral gyrus after UC administration. Increased BOLD responses to the left hand motor task were shown in the left and right posterior cingulate, while there was no increased response to the right hand motor task after UC administration. Conclusions： UC administration significantly decreased fMRI BOLD signal responses to hand grasping in most of the brain areas including the primary motor cortex, but it is not clear whether these decreased responses were caused by a decrease in neuronal activities or by an increase in cerebral blood flow due to the cerebral vasodilatory effects of UC. Further studies using positron emission tomography or single photon emission computed tomography are needed to fully elucidate these findings.

关键词： Uhwang Chungsim Won Niuhuang Qingxin Pfll pharmacological fMRI cerebral blood flow

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Comparative effectiveness of combined antiplatelet treatments in acute minor ischaemic stroke

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Stroke & Vascular Neurology 2022年第1期7卷 13-21页

作者： Shina Kim Joon-Tae Kim Ji Sung Lee Beom Joon Kim Jong-Moo Park Kyusik Kang Soo Joo Lee Jae Guk Kim Jae-Kwan Cha Dae-Hyun Kim Tai Hwan Park Sang-Soon Park Kyung Bok Lee Jun Lee Keun-Sik Hong Yong-Jin Cho Hong-Kyun Park Byung-Chul Lee Kyung-Ho Yu Mi Sun Oh Dong-Eog Kim Wi-Sun ryu Jay Chol Choi jee-Hyun Kwon Wook-Joo Kim Dong-Ick Shin Sung-Il Sohn Jeong-Ho Hong Man-Seok Park Kang-Ho Choi Ki-Hyun Cho Juneyoung Lee Hee-Joon Bae Department of Neurology Chonnam National University HospitalChonnam National University Medical SchoolGwangjuKorea Clinical Research Center Asan Institute for Life SciencesAsan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea Department of Neurology Cerebrovascular CenterSeoul National University Bundang HospitalSeongnamKorea Department of Neurology Uijeongbu Eulji Medical CenterEulji University School of MedicineUijeongbu-siKorea Department of Neurology Nowon Eulji Medical CenterEulji UniversitySeoulKorea Department of Neurology Eulji University HospitalEulji UniversityDaejeonKorea Department of Neurology Dong-a UniversityBusanKorea Department of Neurology Seoul Medical CenterSeoulKorea Department of Neurology Soonchunhyang University HospitalSeoulKorea Department of Neurology Yeungnam University HospitalDaeguKorea Department of Neurology Inje University Ilsan Paik HospitalInje University College of MedicineGoyangKorea Department of Neurology Hallym University Sacred Heart HospitalAnyangKorea Department of Neurology Dongguk University Ilsan HospitalGoyangKorea Department of Neurology Jeju National University HospitalJeju National University School of MedicineJejuKorea Department of Neurology University of Ulsan College of MedicineUlsanKorea Department of Neurology Chungbuk National University HospitalCheongjuKorea Department of Neurology Keimyung University Dongsan Medical CenterDaeguKorea Department of Biostatistics Korea University College of MedicineSeoulKorea

Background No study has thoroughly compared the effectiveness of combined antiplatelet treatments(other than clopidogrel–aspirin)versus clopidogrel–aspirin or aspirin alone for early secondary prevention in acute ischaemic stroke.Methods We identified patients with acute,minor,non-cardiogenic ischaemic stroke treated with aspirin alone,clopidogrel–aspirin or other combination treatment.Propensity scores considering the inverse probability of treatment weighting were used to adjust for baseline imbalances.The primary outcome was the composite of all strokes(ischaemic or haemorrhagic),myocardial infarction and all-cause mortality at 3 months.Results Among 12234 patients(male:61.9%;age:65.5±13 years)who met the eligibility criteria,aspirin,clopidogrel–aspirin and other combination treatments were administered in 52.2%,42.9%and 4.9%of patients,respectively.In the crude analysis,the primary outcome event at 3 months occurred in 14.5%of the other combination group,14.4%of the aspirin group and 13.0%of the clopidogrel–aspirin group.In the weighted Cox proportional hazards analysis,the 3-month primary outcome event occurred less frequently in the clopidogrel–aspirin group than in the other combination group(weighted HR:0.82(0.59–1.13)),while no association was found between the aspirin group(weighted HR:1.04(0.76–1.44))or other combination group and the 3-month primary outcome.Conclusion Other combined antiplatelet treatment,compared with aspirin alone or clopidogrel–aspirin,was not associated with reduced risks of primary composite vascular events or recurrent stroke during the first 3 months after stroke.Therefore,the results suggest that other combination treatments,particularly the cilostazol-based combination,may not be effective alternatives for clopidogrel–aspirin to prevent early vascular events in patients with acute minor stroke.Further exploration in clinical trials will be needed.

关键词： prevention treatment alone

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A Study on Water Repellent Effectiveness of Natural Oil-Applied Soil as a Building Material

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Open Journal of Civil Engineering 2015年第1期5卷 139-148页

作者： Jong-Kook Lee jee-Eun Lee Seong-Cheol Park Hee-Dong Cho Hye-Woong Yoo Young-Sang Kim Seong-Ryong ryu Woo-Suk Kim Dong-Joon Ahn School of Architecture Kumoh National Institute of Technology Gumi Republic of Korea

This study was performed to investigate the water repellent effectiveness of natural oil-applied soil when it is used as a building material. Natural oil types such as olive oil, bean oil, perilla oil and linseed oil, which are being used for producing water repellent timber, are selected for the experiments. It is expected that perilla oil and in seed oil, which are drying oil types will have better water repellent effectiveness than the other types. For the evaluation of water repellence of natural oil-applied soil, a contact angle test was performed. A contact angle of water drop on various surface conditions were tested, and large differences were seen between the natural oil-applied soil and untreated soil. As a result, it is showed that all natural oil types have water repellent effectiveness. However, linseed oil, which is a drying oil type, shows an outstanding water repellent effectiveness value, while perila oil, which is also a drying oil type, shows the lowest value. Additionally, results show that there is no link between water repellent effectiveness and the number of applications of natural oil. Nevertheless, existing commercial water repellents show better performance than natural oil, and it is anticipated that the results of this study will provide essential information for further research to enhance the water repellent effectiveness of soil as a building material.

关键词： Natural Oil Water Repellent Soil as a Building Material Contact Angle Iodine Value

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