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Impact of cytochrome P450 2D6 polymorphisms on decision-making and clinical outcomes in adjuvant hormonal therapy for breast cancer

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World Journal of clinical Oncology 2022年第8期13卷 712-724页

作者： Ern-Yu tan Lavina Bharwani Yee-Hong chia richie c t soong Sherylyn S Y Lee Juliana J c chen Patrick M Y chan Department of General Surgery Tan Tock Seng HospitalSingapore 308433Singapore Lee Kong chian School of Medicine Singapore 308232Singapore Institute of Molecular and cell Biology A*STARSingapore 138673Singapore Department of Medical Oncology Tan Tock Seng HospitalSingapore 308433Singapore cancer Science Institute of Singapore National University of SingaporeSingapore 119077Singapore

BAcKGROUND there are concerns that tamoxifen is less effective in Asian women because of the high prevalence of impaired function cytochrome P4502D6(cYP2D6)*** to evaluate how knowledge of cYP2D6 genotype impacted the choice of hormonal agent and how cYP2D6 genotype and agent were associated with clinical *** Eighty-two women were ***-eight completed cYP2D6 genotyping and were categorized into poor,intermediate(IM)and extensive or ultra metabolizer *** with poor metabolizer and IM phenotypes were recommended aromatase inhibitors as the preferred *** More than 70%of the women had an IM phenotype,32%an extensive or ultra metabolizer phenotype,and 0%had a poor metabolizer *** of genotype,more women opted for aromatase ***,80%of women completed 5 years of hormonal *** women developed recurrence,3 contralateral breast cancer,5 died,and 1 was diagnosed with a second primary ***-year recurrence-free and overall survival were slightly better in women with the extensive or ultra metabolizer phenotype compared to those with the IM phenotype,though not statistically significant[P=0.743,hazard ratio(HR):1.441,95%confidence interval(cI):0.191 to 10.17 and P=0.798,HR:1.327,95%cI:0.172 to 9.915,respectively].Women receiving aromatase inhibitors also appeared to have a better,but also nonsignificant,5-year recurrence-free and overall survival(P=0.253,HR:0.368,95%cI:0.031 to 0.258 and P=0.292,HR:0.252,95%cI:0.005 to 4.951,respectively).cONcLUSION the IM phenotype was highly prevalent but was not associated with clinical outcome.

关键词： Functional cytochrome P4502D6 polymorphisms Breast cancer Hormonal therapy

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Elevated brain temperature under severe heat exposure impairs cortical motor activity and executive function

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Journal of Sport and Health Science 2024年第2期13卷 233-244页

作者： Xiang Ren tan Mary c.Stephenson Sharifah Badriyah Alhadad Kelvin W.Z.Loh tuck Wah soong Jason K.W.Lee Ivan c.c.Low Health and Social Sciences Singapore Institute of TechnologySingapore 138683Singapore Human Potential translational Research Programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore centre for translational Magnetic Resonance Research Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117549Singapore Department of Physiology Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117593Singapore Heat Resilience and Performance centre Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117510Singapore N.1 Institute for Health National University of SingaporeSingapore 117456Singapore campus for Research Excellence and technological Enterprise(cREAtE) Singapore 138602Singapore

Background:Excessive heat exposure can lead to hyperthermia in humans,which impairs physical performance and disrupts cognitive *** heat is a known physiological stressor,it is unclear how severe heat stress affects brain physiology and ***:Eleven healthy participants were subjected to heat stress from prolonged exercise or warm water immersion until their rectal temperatures(t_(re))attained 39.5℃,inducing exertional or passive hyperthermia,*** a separate trial,blended ice was ingested before and during exercise as a cooling *** were compared to a control condition with seated rest(normothermic).Brain temperature(t_(br)),cerebral perfusion,and task-based brain activity were assessed using magnetic resonance imaging ***:t_(br)in motor cortex was found to be tightly regulated at rest(37.3℃±0.4℃(mean±SD))despite fluctuations in t_(re).With the development of hyperthermia,t_(br)increases and dovetails with the rising t_(re).Bilateral motor cortical activity was suppressed during high-intensity plantarflexion tasks,implying a reduced central motor drive in hyperthermic participants(t_(re)=38.5℃±0.1℃).Global gray matter perfusion and regional perfusion in sensorimotor cortex were reduced with passive *** function was poorer under a passive hyperthermic state,and this could relate to compromised visual processing as indicated by the reduced activation of left lateral-occipital ***,ingestion of blended ice before and during exercise alleviated the rise in both t_(re)and t_(bc)and mitigated heat-related neural ***:Severe heat exposure elevates t_(br),disrupts motor cortical activity and executive function,and this can lead to impairment of physical and cognitive performance.

关键词： Brain functional activity cognition Heat stress Hyperthermia Motor function

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Process tolerant and Power Efficient SRAM cell for Internet of things Applications

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computers, Materials & continua 2022年第8期72卷 3425-3446页

作者： t.G.Sargunam Lim Way soong c.M.R.Prabhu Ajay Kumar Singh Faculty of Engineering and technology Multimedia UniversityMelaka75450Malaysia School of Engineering and computing Manipal International UniversityNilai71800Malaysia Electronics and communication Engineering Department NIIT UniversityNeemarana301705India

the use of Internet of things(Iot)applications become dominant in many *** on-chip data processing and computations are also increasing *** battery enabled and low leakage memory system at subthreshold regime is a critical requirement for these Iot *** cache memory designed on Static Random-Access Memory(SRAM)cell with features such as low power,high speed,and process tolerance are highly important for the Iot memory ***,a process tolerant SRAM cell with low power,improved delay and better stability is presented in this research *** proposed cell comprises 11 transistors designed with symmetric approach for write operations and single ended circuit for read operations that exhibits an average dynamic power saving of 43.55%and 47.75%for write and 35.59%and 36.56%for read operations compared to 6 t and 8 t SRAM *** cell shows an improved write delay of 26.46%and 37.16%over 6 t and 8t and read delay is lowered by 50.64%and 72.90%against 6 t and 10 t *** symmetric design used in core latch to improve the write noise margin(WNM)by 17.78%and 6.67%whereas the single ended separate read circuit improves the Read Static Noise Margin(RSNM)by 1.88x and 0.33x compared to 6 t and 8t *** read power delay product and write power delay product are lower by 1.94x,1.39x and 0.17x,2.02x than 6 t and 8 t cells *** lower variability from 5000 samples validates the robustness of the proposed *** simulations are carried out in cadence virtuoso simulator tool with Generic Process Design Kit(GPDK)45 nm technology file in this work.

关键词： SRAM cell low power process efficient read stability write ability static noise margin PVt variation internet of things

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IL-33 induces immunosuppressive neutrophils via a type 2 innate lymphoid cell/IL-13/StAt6 axis and protects the liver against injury in LcMV infection-induced viral hepatitis

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cellular & Molecular Immunology 2019年第2期16卷 126-137页

作者： Yuejin Liang Panpan Yi Denley Ming Kee Yuan Zuliang Jie Zakari Kwota Lynn soong Yingzi cong Jiaren Sun Department of Microbiology and Immunology University of Texas Medical BranchGalvestonTX 77555-1070USA Department of Infectious Diseases Key Laboratory of Viral Hepatitis of HunanXiangya HospitalCentral South UniversityChangsha 410008China Pathology and Institute for Human Infections and Immunity University of Texas Medical BranchGalvestonTX 77555-1070USA

Viral hepatitis is still a public health problem affecting several million people around the *** are polymorphonuclear cells that have a critical role in antibacterial ***,the role of neutrophils in viral infection is not fully *** using a mouse model of lymphocytic choriomeningitis virus infection-induced viral hepatitis,we observed increased neutrophil recruitment in the liver accompanied by enhanced cD8+t-cell *** neutrophils expressed high levels of immunomodulatory cytokines,such as c-X-c chemokine ligand 2,arginase-1,inducible nitric oxide synthase and interleukin(IL)-10,demonstrating immunosuppressive *** of neutrophils in vivo by a neutralizing antibody resulted in the exacerbation of liver injury and the promotion of t-cell responses at the immune contraction ***-33 significantly induced neutrophil recruitment in the liver and attenuated liver injury by limiting effector t-cell ***,we found that IL-33 promoted the expression of arginase-1 in neutrophils through the type 2 innate lymphoid cell(ILc2)-derived ***,IL-13 increased the inhibitory effect of neutrophils on cD8+t-cell proliferation in vitro,partially through ***,we found that IL-13 induced arginase-1 expression,depending on signal transducer and activator of transcription factor 6(StAt6)***,IL-33 induced immunosuppressive neutrophils via an ILc2/IL-13/StAt6 ***,our findings shed new light on the mechanisms associated with IL-33-triggered neutrophils in the liver and suggest potential targets for therapeutic investigation in viral hepatitis.

关键词： IL-33 ILc2 neutrophils viral infection liver

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MMP-2和tIMP-2基因多态性与胃癌发病风险的研究

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现代预防医学 2014年第1期41卷 130-133页

作者：陈凤杨淑娟田智温圆圆谢瑶潘雄飞 Marie Loh 黄荷兰慧温莹赵志梅 richie soong 杨春霞四川大学华西公共卫生学院 (华西第四医院) 重庆市巴南区第二人民医院杭州市疾病预防控制中心 cancer Science Institute of Singapore National University of Singapore

目的探讨西南汉族人群中基质金属蛋白酶-2（matrix metallopmteinase-2,MMP-2）和金属蛋白酶组织抑制剂-2（tissue inhibitor of metalloproteinase-2,tIMP-2）基因启动子区域单核苷酸多态性与胃癌发病风险的关系。方法在美国Sequenom M... 详细信息

目的探讨西南汉族人群中基质金属蛋白酶-2（matrix metallopmteinase-2,MMP-2）和金属蛋白酶组织抑制剂-2（tissue inhibitor of metalloproteinase-2,tIMP-2）基因启动子区域单核苷酸多态性与胃癌发病风险的关系。方法在美国Sequenom MassARRAY系统上利用基质辅助激光解吸电离飞行时间质谱法（MALDI-tOF MS）针对308对胃癌病例和对照分析MMP-2-1306c/t和tIMP-2-418G/c基因多态特征。同时利用自行设计的问卷收集研究对象的人口学特征和日常生活习惯。结果 MMP-2-1306c/t的cc、ct和tt基因型在病例组和对照组中的频率分别为:79.5%、19.8%、0.6%和79.8%、19.2%、1%;tIMP-2-418G/c的GG、Gc和cc基因型在病例组和对照组中的频率分别为:71.4%、26.6%、2.0%和70.5%、27.8%、1.7%;MMP-2-1306c/t（P=0.936和0.984）和tIMP-2-418G/c（P=0.817和0.898）的基因型和等位基因频率分布在胃癌组与对照组间均无统计学差异（P>0.05）。同时未发现基因-基因联合作用（OR=1.004;95%cI:0.460;.191）和基因-环境之间的交互作用。结论本研究未发现MMP-2-1306c/t和tIMP-2-418G/c多态性与胃癌发病风险有关,且两单核苷酸多态之间无基因-基因联合作用,也未发现基因与环境的交互作用。

关键词：胃癌 MMP-2 tIMP-2 单核苷酸多态性

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飞秒激光辅助后部板层角膜移植术:眼库保存眼手术方法的初步研究

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世界核心医学期刊文摘（眼科学分册） 2005年第5期1卷 50-51页

作者： soong H.K. Mian S. Abbasi O. Juhasz t. 张鹏

to perfect the technique of femtosecond laser-assisted cutting of the lamella r corneal disc in posterior lamellar keratoplasty. Experimental study. the femto second laser was used to make the posterior corneal lamellar interface and treph ine (side) cut in 20 eye bank globes and 9 eye bank corneoscleral buttons. Laser parameters were energy 7.4±0.1 μJ (lamellar cut) and 8.7±0.1 μJ (trephinati on cut), spot size2.4 μm, firingrate 15kHz,and trephination diameter 6.0 to 8.0 mm. the thicknesses of the excised corneal discs were measured with a digital m icrometer and compared with values calculated from the laser treatment parameter s and the preoperative ultrasound pachymetric readings. the cut surfaces were ex amined by light microscopy and scanning electron microscopy. In globes, the corn eal disc was removed from the eye after laser treatment through a blade incision in the peripheral cornea. In corneoscleral buttons, the posterior disc was peel ed off the cornea with forceps after laser treatment on an artificial anterior c hamber device. In simulated transplantation, the excised corneal disc was placed into the posterior stromal bed in 7 globes. the femtosecond laser was successful in making posterior lame llar and trephination cuts in cornea. the cut surfaces were of very good quality with straight, orthogonal edges, albeit with a mild stucco texture of the lamel lar stromal surfaces. In 3 globes, the lamellar surface showed shallow concentri c ridges. the measured thickness of the excised discs was 55±61 μm thicker tha n the preoperatively predicted values. these preliminary studies show that the f emtosecond laser can make nonmechanical cuts for poste-rior lamellar keratoplas ty with relative ease and reliability, thus facilitating the most technically di fficult step in this surgery.

关键词：板层角膜移植术飞秒激光板层角膜植片巩膜片角膜板层盘状角巩膜角膜基质环切光斑直径

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东沙珊瑚共附生真菌ZH-IV-2的活性成分研究

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中国海洋药物 2018年第5期37卷 21-28页

作者：郑玉冰汤华宋克义周雅岚毛俊琴张文福建中医药大学药学院福建福州350122 中国人民解放军第二军医大学药学院上海200433 台湾国立中山大学台湾高雄80824 上海浦东新区人民医院上海201200

目的研究软珊瑚Sarcophyton sp.共附生真菌ZH-IV-2中的活性成分。方法采用正相硅胶柱色谱、反相ODS柱色谱、凝胶Sephadex LH-20柱色谱以及高效液相色谱(HPLc)等分离手段对真菌ZH-IV-2的乙酸乙酯提取物分离纯化;并通过理化性质、波谱学... 详细信息

目的研究软珊瑚Sarcophyton sp.共附生真菌ZH-IV-2中的活性成分。方法采用正相硅胶柱色谱、反相ODS柱色谱、凝胶Sephadex LH-20柱色谱以及高效液相色谱(HPLc)等分离手段对真菌ZH-IV-2的乙酸乙酯提取物分离纯化;并通过理化性质、波谱学数据等信息结构并文献报道数据鉴定化合物结构;采用羧基荧光素琥珀酰亚胺酯(cFSE)流式细胞法和酒石酸抗性酸磷酸酶(tRAP)染色法体外评价化合物对原代淋巴细胞的免疫调节活性及对髓系巨噬细胞的破骨细胞分化活性。结果分离得到7个已知化合物,结构分别鉴定为:aspergillusidone B(1)及c(2),emeguisin A(3),unguinol(4),diorcinol(5),6-butyl-3-methyl-(3R,3aR,6S,6aS)-perhydrofuro[3,4-b]furan-2,4-dione(6),unguisin A(7)。在体外活性测试中,化合物3在0.5和1μmol/L时对淋巴细胞增殖有明显的促进作用,化合物6在0.5和1μmol/L时对破骨细胞生成有明显的促进作用,结果均具有显著性差异。结论报道化合物4的13 c-NMR核磁数据,并对化合物7核磁数据归属进行校正。首次对化合物3的免疫调节活性及化合物6的破骨前体细胞分化活性进行报道,具有进一步研究价值。

关键词：珊瑚共附生真菌真菌ZH-IV-2 缩酚酸环醚环肽

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comparative transcriptomics of central Asian Vitis vinifera accessions reveals distinct defense strategies against powdery mildew

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Horticulture Research 2015年第1期2卷 143-153页

作者： Katherine c H Amrine Barbara Blanco-Ulate Summaira Riaz Dániel Pap Laura Jones Rosa Figueroa-Balderas M Andrew Walker Dario cantu Department of Viticulture and Enology University of CaliforniaDavisDavis95616CAUSA Department of Genetics and Plant Breeding Corvinus University of BudapestVillányiút 29-341118BudapestHungary

Grape powdery mildew(PM),caused by the biotrophic ascomycete Erysiphe necator,is a devastating fungal disease that affects most Vitis vinifera *** have previously identified a panel of *** accessions from central Asia with partial resistance to PM that possess a Ren1-like local *** this study,we show that in addition to the typical Ren1-associated late post-penetration resistance,these accessions display a range of different levels of disease development suggesting that alternative alleles or additional genes contribute to determining the outcome of the interaction with the *** identify potential Ren1-dependent transcriptional responses and functions associated with the different levels of resistance,we sequenced and analyzed the transcriptomes of these central Asian accessions at two time points of PM *** were compared to identify constitutive differences and PM-inducible responses that may underlie their disease resistant *** to *** in all resistant accessions were characterized by an early up-regulation of 13 genes,most encoding putative defense functions,and a late down-regulation of 32 genes,enriched in transcriptional regulators and protein *** Ren1-dependent responses included a hotspot of co-regulated genes on chromosome *** also identified 81 genes whose expression levels and dynamics correlated with the phenotypic differences between the most resistant accessions‘Karadzhandahal’,DVIt3351.27,and O34-16 and the other *** study provides a first exploration of the functions associated with varying levels of partial resistance to PM in *** accessions that can be exploited as sources of genetic resistance in grape breeding programs.

关键词： breeding mildew cultivar

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