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A novel IRAK4/PIM1 inhibitor ameliorates rheumatoid arthritis and lymphoid malignancy by blocking the TLR/MYD88-mediated NF-κB pathway

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Acta Pharmaceutica Sinica B 2023年第3期13卷 1093-1109页

作者： Sae-Bom yoon Hyowon Hong Hee-Jong Lim Ji Hye Choi yoon Pyo Choi Seong wook Seo Hyuk woo Lee Chong Hak Chae woo-Kyu Park Hyun young Kim Daeyoung Jeong Tran Quang De Chang-Seon Myung Heeyeong Cho Therapeutics&Biotechnology Division Korea Research Institute of Chemical TechnologyYuseong-guDaejeon 34114Republic of Korea Department of Pharmacology Chungnam National University College of PharmacyYuseong-guDaejeon 34134Republic of Korea Future Medicine Co. Ltd.Rm616 LH-Business Growth CenterSeongnamGyeonggido 13449Republic of Korea Department of Chemistry College of Natural SciencesCan Tho UniversityCan Tho city 9000Viet Nam

Interleukin-1 receptor-associated kinase 4(IRAK4)is a pivotal enzyme in the Toll-like receptor(TLR)/MYD88 dependent signaling pathway,which is highly activated in rheumatoid arthritis tissues and activated B cell-like diffuse large B-cell lymphoma(ABC-DLBCL).Inflammatory responses followed by IRAK4 activation promote B-cell proliferation and aggressiveness of ***,proviral integration site for Moloney murine leukemia virus 1(PIM1)functions as an anti-apoptotic kinase in propagation of ABC-DLBCL with ibrutinib *** developed a dual IRAK4/PIM1 inhibitor KIC-0101 that potently suppresses the NF-κB pathway and proinflammatory cytokine induction in vitro and in *** rheumatoid arthritis mouse models,treatment with KIC-0101 significantly ameliorated cartilage damage and ***-0101 inhibited the nuclear translocation of NF-κB and activation of JAK/STAT pathway in *** addition,KIC-0101 exhibited an anti-tumor effect on ibrutinib-resistant cells by synergistic dual suppression of TLR/MYD88-mediated NF-κB pathway and PIM1 *** results suggest that KIC-0101 is a promising drug candidate for autoimmune diseases and ibrutinib-resistant B-cell lymphomas.

关键词： Drug discovery IRAK4 PIM1 NF-κB pathway Rheumatoid arthritis ABC-DLBCL Ibrutinib resistance Dual inhibitor

Gastric choriocarcinoma admixed with an α-fetoprotein-producing adenocarcinoma and separated adenocarcinoma

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World Journal of Gastroenterology 2009年第40期15卷 5106-5108页

作者： Bang wool Eom So-Youn Jung Hongman yoon Myeong-Cherl Kook Keun Won Ryu Jun Ho Lee young-woo Kim Center for Gastric Cancer National Cancer Center

We report a case of gastric choriocarcinoma admixed with an α-fetoprotein (AFP)-producing adeno-carcinoma. A 70-year-old man was hospitalized for gastric cancer that was detected during screening by esophagogastroduodenoscopy (EGD). Initial laboratory data showed the increased serum level of AFP and EGD revealed a 5-cm ulcerofungating mass in the greater curvature of the gastric antrum. The patient underwent radical subtotal gastrectomywith D2 lymph node dissection and Billroth gastrojejunostomy. Histopathological evaluation confirmed double primary gastric cancer: gastric choriocarcinoma admixed with an AFP-producing adenocarcinoma and separated adenocarcinoma. At 2 wk postoperatively, his human chorionic gonadotropin and AFP levels had reduced and six cycles of adjuvant chemotherapy were initiated. No recurrence or distant metastasis was observed at 4 years postoperatively.

关键词： α-fetoproteins Adenocarcinoma Choriocarcinoma Stomach neoplasms

Photodynamic therapy prolongs metal stent patency in patients with unresectable hilar cholangiocarcinoma

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World Journal of Gastroenterology 2012年第39期18卷 5589-5594页

作者： Tae yoon Lee young Koog Cheon Chan Sup Shim young Deok Cho Digestive Disease Center Department of Internal MedicineKonkuk University Medical CenterKonkuk University School of MedicineSeoul 143-729South Korea Institute for Digestive Research and Digestive Disease Center Soonchunhyang University College of MedicineSeoul 140-743South Korea

AIM:To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS:This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Fortyeight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS:The PDT and control patients were comparable with respect to age, gender, health status, pretreatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION:Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.

关键词： Bile duct cancer Palliative endoscopic stent-ing Photodynamic therapy Outcome

Performance evaluations on inner vs. outer decomposition first parallel join algorithms for two nested loop joins

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Journal of Central South University 2014年第10期21卷 3873-3882页

作者： Seo-young NOH Heejun yoon Il-Yeon YEO yoon-su JEONG Hyungwoo PARK National Institute of Supercomputing and Networking Korea Institute of Science and Technology Information Department of Information Communication Engineering Mokwon University

Two popular traditional join algorithms and their parallel versions are introduced. When designing join algorithms in serial computing environment, decomposing inner relation is considered as the right direction to save disk I/Os. However, two different decomposition algorithms are compared, such as inner vs. outer decomposition first algorithms for tuple-based and block-based nested loop joins, showing that the proposed approach is 20% better than general approach. Also lemmas are proved, when we have to use the outer decomposition first parallel join algorithms.

关键词： parallel join performance inner decomposition outer decomposition

Recent updates and current issues of sentinel node navigation surgery for early gastric cancer

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Chinese Journal of Cancer Research 2021年第2期33卷 142-149页

作者： Sung Gon Kim Bang wool Eom Hong Man yoon Chan Gyoo Kim Myeong-Cherl Kook young-woo Kim Keun Won Ryu Center for Gastric Cancer Research Institute&HospitalNational Cancer CenterGoyang-si 410-769Republic of Korea

With the increase in the incidence of early gastric cancer(EGC),several endoscopic and laparoscopic approaches,such as endoscopic submucosal dissection and function-preserving gastrectomy,have been accepted as standard *** node navigation surgery(SNNS)is an ideal surgical option for preservation of most parts of the stomach and consequent maintenance of normal gastric function to improve quality of life in patients with *** many previous studies and clinical trials have demonstrated the safety and feasibility of the sentinel node concept in gastric cancer,the clinical application of SNNS is *** issues regarding technical standardization and oncological safety need to be *** several studies to resolve these problems are being actively performed,and SNNS might be an important surgical option in the treatment of gastric cancer in the future.

关键词： Sentinel node navigation surgery function-preserving surgery early gastric cancer SENORITA

Factors associated with metastasis in superior mesenteric vein lymph node in subtotal gastrectomy for gastric cancer:Retrospective case control study

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Chinese Journal of Cancer Research 2020年第1期32卷 43-50页

作者： Won Ho Han Jungnam Joo Bang wool Eom Keun Won Ryu young-woo Kim Myeong-cherl Kook Hong Man yoon Center for Gastric Cancer Research Institute&HospitalNational Cancer CenterGoyang-si 410-769Republic of Korea Division of Cancer Epidemiology and Prevention National Cancer CenterGoyang-si 410-769Republic of Korea

Objective: The revised Japanese treatment guideline for gastric cancer recommends dissection of the superior mesenteric vein lymph node(No. 14v LN) if there is metastasis in infrapyloric lymph node(No. 6 LN). However,it is still controversial whether LN dissection is necessary. The aim of this study was to investigate the factors associated with metastasis in No. 14v ***: Patients who underwent D2 lymphadenectomy between 2003 and 2010 were included. We excluded patients who underwent total gastrectomy, had multiple lesions, or had missing data about the status of metastasis in the LNs that were included in D2 lymphadenectomy. Clinicopathologic characteristics and the metastasis in regional LNs were compared between patients with No. 14v LN metastasis(14v+) and those without(14v-).Results: Five hundred sixty patients were included in this study. Univariate analysis showed that old age, larger tumor size, tumor location, differentiation, lymphatic invasion, venous invasion, perineural invasion, T classification, and N classification were related to metastasis in No. 14v LN. Multivariate analysis showed differentiation(P=0.027) and N classification(P<0.001) were independent related factors. Metastasis in infrapyloric lymph node(No. 6 LN) and proxiaml splenic lymph node(No. 11p LN) was independently associated with metastasis in No. 14v ***: Differentiation and N classification were independent factors associated with No. 14v LN metastasis, and No. 6 and No. 11p LN metastasis were independent risk factors for No. 14v LN metastasis.

关键词： Gastric cancer gastrectomy lymphadenectomy superior mesenteric vein risk factor

Investigation of Domain Wall Velocity to External Fields for High-Quality Waveguide-Type Periodically Poled LiNbO_(3) Fabrication

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Journal of Rare Earths 2006年第Z1期24卷 131-135页

作者： Soo woo Kwon woo Seok Yang H M Lee woo Kyung Kim Hang Yong Lee Dae Ho yoon Yo Seung Song Department of Materials Engineering Hankuk Aviation UniversityGoyang 412-791Korea Nano Bio-Photonics Team Korea Electronics Technology InstituteBundang 463-816Korea Department of Advanced Material Engineering Sungkyunkwan UniversitySuwon 440-746Korea

The Ti-doped waveguide-type periodically poled LiNbO_(3)(PPLN)were fabricated and the dependence of domain wall velocity on an external field applied for domain inversion was *** whole polarization reversal process was computer-controlled to regulate domain wall expansion at a feedback time shorter than 5μ*** coercive voltage and several values of excess voltage were applied on 500μm-thick wafers serially connected to a 1-MOhm external resistor which had an effect of the poling current reduction,*** deceleration of domain wall *** domain wall velocity is sensitive to the poling voltage,precisely speaking,to the excess *** domain wall velocities were 28.70,16.02 and 5.75μm·s^(-1)under poling field of 23.5,22.0 and 21.0 kV·mm^(-1),***,average duty cycle of PPLN is about 49.93%.

关键词： periodically poled lithium niobate coerciv field duty cycle domain wall velocity quasi phase matching

Severe thrombocytopenia before liver transplantation is associated with delayed recovery of thrombocytopenia regardless of donor type

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World Journal of Gastroenterology 2008年第37期14卷 5723-5729页

作者： Jae Hyuck Chang Jong young Choi Hyun young woo Jung Hyun Kwon Chan Ran You Si Hyun Bae Seung Kew yoon Myung-Gyu Choi In-Sik Chung Dong Goo Kim Department of Internal Medicine College of Medicine the Catholic University of Korea505 Banpo-Dong Seocho-Gu Seoul 137-040 Korea Department of Surgery College of Medicine the Catholic University of Korea505 Banpo-Dong Seocho-Gu Seoul 137-040 Korea

AIM： To compare the recovery of thrombocytopenia and splenomegaly during long-term follow-up after liver transplantation in patients receiving a living donor transplant or a cadaveric donor transplant. METHODS： This was a retrospective cohort study of 216 consecutive liver transplant patients who survived for 〉 6 mo after transplantation; 169 received a liver transplant from a living donor and 47 from a cadaveric donor. The platelet counts or spleen volumes were examined before transplant, i, 6, and 12 mo after transplant, and then annually until 5 years after transplant. RESULTS： The mean follow-up period was 49 mo （range, 21-66）. Platelet counts increased continuously for 5 years after orthotopic liver transplant. The restoration of platelet counts after transplant was significantly slower in patients with severe pretransplant thrombocytopenia （〈 50000/μL） until 4 years after transplant （P = 0.005）. Donor type did not significantlyaffect the recovery of platelet count and spleen volume in either patient group. In multivariate analysis, pretransplant severe thrombocytopenia （〈 50000/μL） was an independent factor associated with sustained thrombocytopenia （P 〈 0.001, odds ratio 6.314; confidence interval, 2.828-14.095）. Thrombocytopenia reappeared after transplant in seven patients with portal flow disturbance near the anastomosis site. CONCLUSION： Our study suggests that severe thrombocytopenia before transplant is closely associated with delayed recovery of platelet count after transplant and donor type did not affect the recovery of thrombocytopenia. The reappearance of thrombocytopenia after transplant should be considered a possible indicator of flow disturbance in the portal vein.

关键词： Liver transplantation Thrombocytopenia Splenomegaly Hypersplenism

Current Usage of Terminologies Related to Acupotomy: A Literature Research and Standardization Suggestion

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Chinese Journal of Integrative Medicine 2019年第2期25卷 147-150页

作者： Sang-Hoon yoon yoon-Sik Kim Hee-Guen Jo Chan-young Kwon Chung-Yeon Medical Institute Department of Clinical Korean Medicine Graduate SchoolKyung Hee University Yanggu Public Health Center

Objective: To investigate the current usage of terminologies related to acupotomy through systematic search and analyze the pros and cons of each for proposing a standard terminology. Methods: Seven medical journal databases were searched including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Oriental Medicine Advanced Searching Integrated System, KoreaMed, and Korean studies Information Service System using 10 candidate terminologies as searching terms. All studies published from their inception to July 26, 2017 were collected. Articles were included if the title stated one of the 10 candidate terminologies consistent with the definition of acupotomy. Priorly established frequency and consistency of each candidate terminology from medical databases were calculated and evaluated. Moreover, the pros and cons of each were analyzed to propose a standard terminology. Results: A total of 112 studies in English databases, 1,129 studies in Chinese database, and 44 studies in Korean databases were included. The most frequently used terminologies were needle knife(35.71%), acupotomy(48.54%) and acupotomy(90.90%) in English, Chinese and Korean database, respectively. Overall, acupotomy and needle knife were the most frequently used. Others like acupotomology, needle scalpel, miniscalpel acupuncture and miniscalpel needle were used within 10% of the total searched literature. Acupotome, stiletto needle, sword like needle, and Xiaozhendao were rarely used. Acupotomy had the advantages of high frequency and consistency but lacked representativeness. Needle knife also showed a high frequency, but the consistency was poor. Though miniscalpel acupuncture and miniscule needle were used less frequently, they had advantages of inclusiveness and clarity. Conclusions: A debate for standardization of the terminology is necessary. This preliminary research can provide a basic outline for the standardization consensus process, and

关键词： acupuncture Chinese medicine acupotomy terminology