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Validation of genetic variants associated with metabolic dysfunctionassociated fatty liver disease in an ethnic Chinese population

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World Journal of Hepatology 2020年第12期12卷 1228-1238页

作者： Guan Huei lee Wah Wah Phyo Wai Mun Loo Raymond Kwok Taufique Ahmed Asim Shabbir Jimmy So Calvin Jianyi Koh Juanda Leo Hartono Mark Muthiah Kieron Lim Poh Seng Tan Yin Mei lee Seng GeeLim Yock Young Dan Division of Gastroenterology and Hepatology Department of MedicineNational University Health SystemSingapore 119228Singapore Yong Loo Lin School of Medicine National University of SingaporeSingapore 117597Singapore Department of Medicine Khoo Teck Puat HospitalSingapore 768828Singapore Department of Surgery National University Health SystemSingapore 119228Singapore

BACKGROUND Genetic factors play an important role in the pathogenesis and development of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To study the association of single nucleotide polymorphisms(SNPs),previously identified in Western populations,with the risk of MAFLD in a Singapore Chinese population and their interactions with environmental and medical risk *** A retrospective case-control study was conducted with 72 MAFLD cases and 72 controls with no hepatic steatosis on computed tomography,magnetic resonance imaging,or controlled attenuation parameter *** were recruited from two tertiary *** alleles such as NCAN,GCKR,LYPLAL1,PNPLA3,PPP1R3B,FDFT1,COL13A1,EFCAB4B,PZP,and TM6SF2 were genotyped using the TaqMan®Predesigned SNP Genotyping *** Weight and body mass index(BMI)were 1.2-times higher in patients(70.6 kg,95%confidence interval[CI]:57.1-84.1 vs 60.8 kg,95%CI:48.5-73.1,P<0.001 and 26.9 kg,95%CI:23-40.8 vs 23.3 kg 95%CI:19-27.6,P<0.001 respectively).The prevalence of diabetes mellitus in patients was 40.3%and 20.8%in controls(P=0.011).Patients had higher mean triglycerides than controls(P<0.001).PNPLA3 GG was more likely to be associated with MAFLD(43.4%CC vs 69.7%GG,P=0.017,and 44.8%CG vs 69.7%GG,P=0.022).In multivariable analysis,hypertriglyceridemia(odds ratio[OR]:2.0495%CI:1.3-3.1,P=0.001),BMI(OR:1.295%CI:1.1-1.4,P<0.001)and PNPLA3 GG(OR:3.495%CI:1.3-9.2,P=0.014)were associated with MAFLD(area under the receiver operating characteristic curve of 0.823).CONCLUSION Among the Chinese population of Singapore,PNPLA3 homozygous GG allele is a strong predictor of MAFLD,whereas LYPLAL1,GCKR,FDFT1,COL13A1,PZP,and TM6SF2 are not significantly ***,high BMI,and PNPLA3 GG are independent predictors of MAFLD.

关键词： Single nucleotide polymorphism PNPLA3 Genotyping Metabolic dysfunction-associated fatty liver disease Non-alcoholic steatohepatitis Hypertriglyceridemia Body mass index Waist-hip ratio,Screening Hepatic steatosis

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Tip60 Tumor Suppressor Requires Its NLS Motif to Interact with Importin <i>α</i>

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CellBio 2019年第1期8卷 1-16页

作者： Eun Jeoung lee Sung Hwa Shin Sang Sun Kang CdmoGen 530 Jikji-daero Heungdeok-gu Cheongju Chungbuk Republic of Korea Department of Biology Education Chungbuk National University Chungdae-ro Seowon-gu Cheongju Chungbuk Republic of Korea

Tip60 is a specific member of MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of nuclear histone acetyltransferases (HAT). It is essential for cellular survival, differentiation, and metabolism. A putative canonical NLS motif between the chromo domain and the zinc finger of Tip60 was identified. Here we show evidence that Tip60 is associated with importin α as its substrate and transported from cytoplasm to the nucleus. Pull down assay revealed that Tip60 was physically associated with importin α both in vivo and in vitro. Confocal microscopic observation showed that Tip60 and importin α were co-localized with each other. The localization of Tip60 to the nuclear and its interaction with importin α was disrupted when its putative NLS motif for binding to importin α was mutated (219RKRK222 → 219AAAA222). However, attachment of this putative NLS motif to a cytoplasmic protein (yap 1-210 fragment) promoted its nuclear localization. Based on transient transfection, Tip60 NLS motif mutant showed a substantial reduction in self-acetylation, HAT activity, and apoptotic ability whereas wild type Tip60 did not show such reduction. Taken together, our results demonstrate that importin α transports Tip60 from the cytoplasm to the nucleus through binding to the putative NLS motif of Tip60 for its tumor suppressing function.

关键词： Tip60 Importin α Nuclear Localization Sequence Protein-Protein Interaction HAT Activity Cell Survival

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Endoscopic transnasal canaliculorhinostomy for refractory common canalicular obstruction with an unidentifiable lacrimal sac

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International Journal of Ophthalmology(English edition) 2020年第8期13卷 1238-1243页

作者： Zhao-Qi Pan Jian-Ju Liu Xian-Ke Jia Jason Kian Seng lee Yun-Hai Tu Jie-Liang Shi Bo Yu En-De Wu Wen-Can Wu The Mini-invasive Orbital&Oculoplastic Surgery Center Eye Hospital of Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Department of Ophthalmology the First Affiliated Hospital of Harbin Medical UniversityHarbin150000Heilongjiang ProvinceChina Department of Ophthalmology the People’s Hospital of PingyangWenzhou 325400Zhejiang ProvinceChina Ophthalmology and Visual Sciences Department Khoo Teck Puat Hospital999002Singapore

AIM:To describe the role of endoscopic transnasal canaliculorhinostomy(ETC)in refractory common canalicular obstruction(CCO)associated with an absent or unidentifiable lacrimal ***:The records of patients with refractory CCO who underwent ETC at the Eye Hospital of Wenzhou Medical University from October 2007 to December 2016 were retrospectively ***:Fifty-six patients(56 eyes)with refractory CCO were recruited into the *** patients were excluded due to the presence of a residual lacrimal sac or failure to complete the follow-up *** anatomic and functional success rates were both 85.4%(41/48)at a mean follow-up of 18.6 *** cases failed as a result of ostial synechia and two failed because of ostial obstruction by *** complications included mild nasal bleeding in 5 cases,dried nasal feeling in 8 cases,and olfactory dysfunction in 4 ***:Although being surgically challenging,ETC has comparable findings to its external approach counterpart or conjunctivodacryocystorhinostomy(CDCR)with Jones *** it may prove to be a novel alternate surgical technique for patients with refractory CCO without identifiable lacrimal sac.

关键词： refractory common canalicular obstruction endoscopic transnasal canaliculorhinostomy lacrimal reconstructive surgery

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Delivering a high-quality colonoscopy service fit for the 21st century

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Artificial Intelligence in Gastrointestinal Endoscopy 2024年第3期5卷 1-8页

作者： Brian Wing Kin Ip Daniel Jin Keat lee Kok Yang Tan Department of General Surgery Khoo Teck Puat HospitalSingapore 768828Singapore Department of Surgery Khoo Teck Puat HospitalSingapore 768828Singapore

Colorectal cancer(CRC)is the third most prevalent cancer *** is a concerning increase in its incidence among younger *** remains the gold standard for CRC *** the introduction of population-based bowel screening and increased public awareness,there has been a significant rise in referrals for *** providers worldwide will need to strategically evaluate how to allocate resources to adequately train the next generation of colonoscopists who will need to provide accurate endoscopic assessment and treatment for premalignant polyps and early *** review outlines the current workload challenges faced by colonoscopists whilst exploring emerging technologies such as artificial intelligence for adenoma ***,advanced endoscopic surgical techniques like endoscopic submucosal dissection are discussed.

关键词： Colonoscopy Colorectal cancer Bowel screening Polyps Adenoma

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Epidemiological characteristics of Asian children with inflammatory bowel disease at diagnosis: Insights from an Asian-Pacific multicentre registry network

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World Journal of Gastroenterology 2022年第17期28卷 1830-1844页

作者： James Guoxian Huang Yoko Kin Yoke Wong Kee Seang Chew Pornthep Tanpowpong Karen Sophia Calixto Mercado Almida Reodica Shaman Rajindrajith Kai-Chi Chang Yen-Hsuan Ni Suporn Treepongkaruna Way-Seah lee Marion Margaret Aw Khoo teck Puat-National University Children’s Medical Institute National University Health SystemSingapore 119228Singapore Department of Pediatrics Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119228Singapore Epidemiology Singapore Clinical Research InstituteSingapore 138669Singapore Department of Paediatrics Faculty of MedicineUniversity MalayaKuala Lumpur 50603Malaysia Department of Pediatrics Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand Department of Pediatrics Makati Medical CentreManila 1229Philippines Department of Pediatrics The Medical CityManila 0900Philippines Department of Pediatrics Faculty of MedicineUniversity of ColomboColombo 00800Sri Lanka Department of Pediatrics National Taiwan University HospitalTaipei 100229Taiwan

BACKGROUND There remains a dearth of Asian epidemiological literature for paediatric inflammatory bowel disease(PIBD).AIM To describe the presenting features of PIBD from 7 Asia-Pacific pediatric gastroenterology centers via a central standardised electronic data *** Clinical,endoscopic and radiologic data at diagnosis from the registry were extracted between 1^(st) January 1995 to 31^(st) December *** phenotypic characteristics were classified as per the Paris classification *** There was a distinct rise in new PIBD cases:Nearly half(48.6%)of the cohort was diagnosed in the most recent 5 years(2015-2019).The ratio of Crohn’s disease(CD):Ulcerative colitis(UC):IBDUnclassified was 55.9%:38.3%:5.8%.The mean age was 9.07 years with a high proportion of very early onset IBD(VEO-IBD)(29.3%)and EO-IBD(52.7%).An over-representation of the Indian/South Asian ethnic group was observed which accounted for 37.0% of the overall Singapore/Malaysia subcohort(6.8%-9.0%Indians in census).Indian/South Asian CD patients were also most likely to present with symptomatic perianal disease(P=0.003).CD patients presented with significantly more constitutional symptoms(fever,anorexia,malaise/fatigue and muscle-wasting)than UC and higher inflammatory indices(higher C-reactive protein and lower albumin levels).CONCLUSION We observed a high incidence of VEO-IBD and an over-representation of the Indian *** Asian CD patients were more likely to have symptomatic perianal disease.

关键词： Asia Inflammatory bowel disease Paediatrics Crohn’s disease Ulcerative colitis Registry

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Wikicliki: 在智能手机时代下的储存习惯

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当代美术家 2021年第3期 78-81页

作者：叶淑惠沙布尔·侯赛因·穆斯塔法不详

美术馆能否激发讨论,让艺术家探讨收藏的意义?对此,新加坡美术馆从艺术家不断变化的创作和呈现方式中汲取灵感,推出展览“Wikicliki:在智能手机时代下的储存习惯”,以探索如今当代艺术收藏所需的关键策略。“Wikicliki”展出了6位艺术... 详细信息

美术馆能否激发讨论,让艺术家探讨收藏的意义?对此,新加坡美术馆从艺术家不断变化的创作和呈现方式中汲取灵感,推出展览“Wikicliki:在智能手机时代下的储存习惯”,以探索如今当代艺术收藏所需的关键策略。“Wikicliki”展出了6位艺术家的作品,他们通过各自的工作模式为新加坡当代艺术家面临的一系列问题提供了独特的见解。此次展览将呈现6组艺术家与策展员的合作成果——分别为张奕满(Heman Chong)与叶淑惠(Selene yap)、蔡财德(Chua Chye teck)与郑嘉韵(Cheng Jia Yun)、陈美美(Debbie Ding)与沙布尔·侯赛因·穆斯塔法(Shabbir Hussain Mustafa)、巴尼·海卡尔(Bani Haykal)与Chanon Kenji Praepipatmongkol、王良吟(Amanda Heng)与丁彦惠(Teng Yen Hui)及林育荣(Charles Lim Yi Yong)与郑伟汉(Kenneth Tay)。《当代美术家》采访策展人叶淑惠和沙布尔·侯赛因·穆斯塔法,就展览主题和策划等话题展开了讨论。

关键词：收藏数码时代

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MUC4阴性的硬化性上皮样纤维肉瘤亚型可检出伴高频性yap1和KMT2A基因重排

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临床与实验病理学杂志 2020年第8期36卷 915-915页

作者： Kao Y C lee J C Zhang L 王婷(摘译) 余英豪(审校) 不详福建省泉州市中医院病理科泉州362000 中国人民解放军联勤保障部队第900医院病理科福州350025

硬化性上皮样纤维肉瘤是一种侵袭性软组织肉瘤,其组织学特征为在致密硬化的胶原间质内散在上皮样细胞,免疫组化标志物MUC4常阳性,通常存在包括EWSR1在内的基因融合。由于与低度恶性纤维黏液样肉瘤在组织形态和遗传学特征方面有一些重叠... 详细信息

硬化性上皮样纤维肉瘤是一种侵袭性软组织肉瘤,其组织学特征为在致密硬化的胶原间质内散在上皮样细胞,免疫组化标志物MUC4常阳性,通常存在包括EWSR1在内的基因融合。由于与低度恶性纤维黏液样肉瘤在组织形态和遗传学特征方面有一些重叠,推测两者发病机制可能存在关联。实验显示有一小部分硬化性上皮样纤维肉瘤免疫组化MUC4阴性,且缺乏典型EWSR1/FUS基因重排。作者最初发现3例为MUC4阴性及EWSR1/FUS基因重排阴性的硬化性上皮样纤维肉瘤,经靶向RNA测序检测发现存在yap1-KMT2A融合。

关键词：硬化性上皮样纤维肉瘤 MUC4 软组织肉瘤上皮样细胞基因重排组织学特征基因融合遗传学特征

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