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Impact of palliative therapies in metastatic esophageal cancer patients not receiving chemotherapy

World Journal of Gastrointestinal Surgery 2020年第9期12卷 377-389页

作者： Sungjin Kim Timothy P DiPeri Michelle Guan Veronica R Placencio-Hickok Haesoo Kim Jar-yee Liu Andrew Hendifar Samuel J Klempner Ryan Nipp Alexandra Gangi Miguel Burch Kevin Waters May Cho Joseph Chao Katelyn Atkins Mitchell Kamrava Richard Tuli jun Gong Biostatistics and Bioinformatics Research Center Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Surgical Oncology Department of SurgerySamuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Division of Hematology and OncologySamuel Oschin Comprehensive Cancer InstituteCedars Sinai Medical CenterLos AngelesCA 90048United States Department of Medicine Massachusetts General Hospital Cancer CenterHarvard Medical SchoolBostonMA 02114United States Department of Pathology and Laboratory Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Division of Hematology and Oncology Department of MedicineUniversity of CaliforniaDavisSacramentoCA 95817United States Department of Medical Oncology and Therapeutics Research City of Hope Comprehensive Cancer CenterDuarteCA 91010United States Department of Radiation Oncology Cedars Sinai Medical CenterLos AngelesCA 90048United States Department of Radiation Oncology Memorial Sloan Kettering Cancer CenterNew YorkNY 10065United States

BACKGROUND Palliative therapy has been associated with improved overall survival(OS)in several tumor *** all patients with metastatic esophageal cancer receive palliative chemotherapy,and the roles of other palliative therapies in these patients are *** To investigate the impact of other palliative therapies in patients with metastatic esophageal cancer not receiving *** The National Cancer Database was used to identify patients between *** with M1 disease who declined chemotherapy and had known palliative therapy status[palliative therapies were defined as surgery,radiotherapy(RT),pain management,or any combination thereof]were *** with unknown chemotherapy,RT,or nonprimary surgery status were ***-Meier estimates of OS were *** proportional hazards regression models were employed to examine factors influencing *** Among 140234 esophageal cancer cases,we identified 1493 patients who did not receive chemotherapy and had complete *** age was 70 years,most(66.3%)had a Charlson Comorbidity Index(CCI)of 0,and 37.1%were treated at an academic *** majority(72.7%)did not receive other palliative *** both univariate and multivariable analyses,there was no difference in OS between those receiving other palliative therapy(median 2.83 mo,95%CI:2.53-3.12)vs no palliative therapy(2.37 no,95%CI:2.2-2.56;multivariable P=0.290).On univariate,but not multivariable analysis,treatment at an academic center was predictive of improved OS[Hazard ratio(HR)0.90,95%CI:0.80-1.00;P=0.047].On multivariable analysis,female sex(HR 0.81,95%CI:0.71-0.92)and non-black,other race compared to white race(HR 0.72,95%CI:0.56-0.93)were associated with reduced mortality,while South geographic region relative to West region(HR 1.23,95%CI:1.04-1.46)and CCI of 1 relative to CCI of 0(HR 1.17,95%CI:1.03-1.32)were associated with increased *** histologic grade and T-stage were also as

关键词： Esophageal cancer Metastatic Palliative Chemotherapy Radiotherapy Survival

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Implementation Study of a Centralized Routing Protocol for Data Acquisition in Wireless Sensor Networks

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Wireless Sensor Network（无线传感网络） 2011年第5期

作者： Trung Hieu Pham Xue jun Li Wai yee leong Peter Han Joo Chong

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Structural Tailoring of HEV Capsid Protein for Gaining Insights into Vaccine Design

Structural Tailoring of HEV Capsid Protein for Gaining Insig...

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第四届中国结构生物学学术讨论会

作者： Shaowei Li Xuhua Tang Ying Gu Chunyan Yang jun Zhang Chow leong Hew Sivaraman J. Ningshao Xia National Institute of Diagnostics and Vaccine Development in Infectious Disease School of Life Sciences Xiamen University Department of Biological Sciences National University of Singapore

Infectious hepatitis viral diseases are major health problems in both developing and developed countries. Hepatitis E virus（HEV） is an important cause of severe hepatitis in humans and is responsible for high rate of mortality in pregnant women. We developed a recombinant HEV vaccine based on virus-like particles（VLPs）, denoted as p239, which had been demonstrated with high efficacy against Hepatitis E and good safety profile in a large-scale, randomized, double-blind placebo-controlled phase 3 trial. At present, our HEV239 vaccine Hecolin has been licensed for use in China. To understand the functional moieties in p239, we did a series of truncations of p239 to determine the minimal structural requirements for dominant epitopes and solved the crystal structure of its minimum dimerization domain（E2s） at 2 A resolution [1]. With respect to other structures of HEV VLPs, this domain protrudes from the viral surface. Functional studies illustrated that this domain formed an intimate homodimer and that this dimerization is essential for HEV–host interactions. In addition, we also showed that the neutralizing antibody recognition site of HEV is located on the E2 s domain. Furthermore, we determined the complex crystal structure of 8C11 Fab, a neutralizing antibody, with HEV E2s（I） domain at 1.9 A resolution. The 8C11 epitopes on E2 s were identified at Asp496-Thr499, Val510-Leu514 and Asn573-Arg578. The mutagenesis and cell model assay identified Arg512 as the most crucial residue for 8C11 interaction and for the neutralization of HEV [2]. For assembly mechanism, a highly conserved 28-aa region（aa368-395） of p239 was found to be critical for particle assembly [3]. Interestingly, p239 can form particles even in 4 M urea from its homodimer precursor（as E2 forms） with a salt trigger. Three hydrophobic residues Leu372, Leu375, and Leu395 located on N-terminal of p239 were shown to play key roles in the assembly of p239 via hydrophobic interaction [4]. Thus, structural tailor

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糖尿病肾病NLRP3炎症小体活化的分子调控机制及中药的干预作用

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中国中药杂志 2020年第1期45卷 7-13页

作者：王文文韩文贝万毅刚涂玥刘不悔刘莹露吴薇 yee Hong-yun 房其军姚建南京中医药大学中西医结合鼓楼临床医学院中医科江苏南京210008 温州市中西医结合医院肾内科浙江温州325000 南京大学医学院附属鼓楼医院中医科江苏南京210008 南京中医药大学针灸推拿学院·养生康复学院中医养生学教研室江苏南京210023 南京中医药大学附属医院肾内科江苏南京210029 Division of Molecular Signaling Department of Advanced Biomedical ResearchInterdisciplinary Graduate School of Medicine and EngineeringUniversity of YamanashiYamanashi 409-3898

在糖尿病肾病(diabetic nephropathy,DN)进展的过程中,Nod样受体蛋白3(Nod-like receptor protein3,NLRP3)炎症小体活化与DN肾损伤密切相关。其特征是组分蛋白——NLRP3、凋亡相关斑点样蛋白(apoptosis-associated speck-like protien,ASC)、胱冬肽酶(caspase)-1前体表达水平和结合水平的改变以及下游的效应蛋白——caspase-1,白介素(interleukin,IL)-1β,IL-18表达水平的升高,此外,还有相关炎症介质的释放。NLRP3炎症小体活化的分子调控机制涉及多条信号通路的激活,如活性氧(reactive oxygen species,ROS)/硫氧还蛋白互作蛋白(thioredoxin-interacting protein,TXNIP)通路、核因子(nuclear factor,NF-κB)通路、核转录因子E-2相关因子-2(nuclear factor erythroid-related factor 2,Nrf2)通路、长链非编码RNA(long non-coding RNA,lncRNA)通路以及丝裂原激活蛋白激酶(mitogen-activated protein kinases,MAPKs)通路等。更为重要的是,激酶类的调节因子,如未有丝分裂曲霉相关蛋白激酶7(never in mitosis aspergillus-related kinase 7,Nek7)在上游可与NLRP3靶向结合而直接激活NLRP3炎症小体。一些中药提取物(槲皮素、姜黄素、千金藤素、胡椒碱以及红景天苷)和中药经典复方(乌梅丸)等可以通过多种途径干预NLPR3炎症小体而改善DN炎症性肾损伤。因此,基于NLRP3炎症小体活化的分子调控机制而精准揭示抗炎性中药或中药复方延缓DN进展的作用靶点是今后的发展方向之一。

关键词：糖尿病肾病 NLRP3炎症小体中药分子机制信号通路

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3-D Grid-Based Localization Technique in Mobile Sensor Networks

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Wireless Sensor Network（无线传感网络） 2010年第11期

作者： Jia Li Lei Sun Wai yee leong Peter H J Chong

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Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer:Results from 24 hospitals in China

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World Journal of Gastrointestinal Surgery 2021年第2期13卷 176-186页

作者： Tai Ren Yong-Sheng Li Xue-Yi Dang Yang Li Zi-Yu Shao Run-Fa Bao Yi-jun Shu Xu-An Wang Wen-Guang Wu Xiang-Song Wu Mao-Lan Li Hong Cao Kun-Hua Wang Hong-Yu Cai Chong Jin Hui-Han Jin Bo Yang Xiao-Qing Jiang Jian-Feng Gu Yun-Fu Cui Zai-Yang Zhang Chun-Fu Zhu Bei Sun Chao-Liu Dai Lin-Hui Zheng Jing-Yu Cao Zhe-Wei Fei Chang-jun Liu Bing Li jun Liu Ye-Ben Qian Yi Wang Ya-Wei Hua Xi Zhang Chang Liu Wan-yee Lau Ying-Bin Liu Department of General Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Shanghai Key Laboratory of Biliary Tract Disease Research Shanghai 200092China Department of Biliary-Pancreatic Surgery Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China State Key Laboratory for Oncogenes and Related Genes Shanghai 200127China Department of General Surgery Shanxi Provincial Cancer HospitalTaiyuan 030013Shanxi ProvinceChina Department of GI Surgery China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of Gastrointestinal and Hernia Surgery The First Affiliated Hospital of Kunming Medical UniversityKunming 650031Yunnan ProvinceChina Department of Hepatobiliary Surgery Nantong Tumor HospitalNantong 226361Jiangsu ProvinceChina Department of General Surgery Taizhou Municipal HospitalTaizhou 318000Jiangsu ProvinceChina Department of Hepatobiliary Surgery Wuxi Second People's HospitalWuxi 214002Jiangsu ProvinceChina Department of General Surgery The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325015Zhejiang ProvinceChina Department of Biliary Tract Surgery Second Military Medical UniversitySecondary Military Medical UniversityShanghai 200438China Department of General Surgery Changshu No.1 People’s Hospital Affiliated to Soochow UniversityChangshu 215500Jiangsu ProvinceChina Department of Hepatopancreatobiliary Surgery Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086Heilongjiang ProvinceChina Department of General Surgery Shaoxing Second HospitalShaoxing 312000Zhejiang ProvinceChina Department of HPB Surgery Changzhou No.2 People’s HospitalChangzhou 213003Jiangsu ProvinceChina Department of Pancreatic and Biliary Surgery The First Affiliated Hospital of Harbin Medical UniversityHarbin 150009Heilongjiang ProvinceChina Department of Hepatobiliary Surgery Shengjing Hospital of China Medical UniversityShenyang 1

BACKGROUND Whether regional lymphadenectomy(RL)should be routinely performed in patients with T1b gallbladder cancer(GBC)remains a subject of *** To investigate whether RL can improve the prognosis of patients with T1b *** We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in *** logrank test and Cox proportional hazards model were used to compare the overall survival(OS)of patients who underwent cholecystectomy(Ch)+RL and those who underwent Ch *** investigate whether combined hepatectomy(Hep)improved OS in T1b patients,we studied patients who underwent Ch+RL to compare the OS of patients who underwent combined Hep and patients who did *** Of the 121 patients(aged 61.9±10.1 years),77(63.6%)underwent Ch+RL,and 44(36.4%)underwent Ch ***(9.1%)patients in the Ch+RL group had lymph node *** 5-year OS rate was significantly higher in the Ch+RL group than in the Ch group(76.3%vs 56.8%,P=0.036).Multivariate analysis showed that Ch+RL was significantly associated with improved OS(hazard ratio:0.51;95%confidence interval:0.26-0.99).Among the 77 patients who underwent Ch+RL,no survival improvement was found in patients who underwent combined Hep(5-year OS rate:79.5%for combined Hep and 76.1%for no Hep;P=0.50).CONCLUSION T1b GBC patients who underwent Ch+RL had a better prognosis than those who underwent ***+Ch showed no improvement in prognosis in T1b GBC *** recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines,RL was only performed in 63.6%of T1b GBC *** Ch+RL should be advised in T1b GBC.

关键词： Gallbladder cancer Lymphadenectomy Hepatectomy Staging Prognosis Surgery

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Cytogenetic and molecular aberrations of multiple myeloma patients： a single-center study in Singapore

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Chinese Medical Journal 2013年第10期126卷 1872-1877页

作者： LIM Alvin Soon Tiong LIM Tse Hui SEE Karen Hsu Shien NG Yit jun TAN Yu Min CHO0 Natasha Swee Lian LIM Sherry Xin Er yee Yenny LAU Lai Ching TIEN Sim Leng Kumar Sathish TAN Daryl Chen Lung Cytogenetics Laboratory Department of Pathology SingaporeGeneral Hospital Singapore School of Biological Sciences Nanyang Technological UniversitySingapore Temasek Applied Science School Temasek Polytechnic Singapore Department of Haematology Singapore General HospitalSingapore

Background Much is known about the cytogenetic lesions that characterize multiple myeloma （MM） patients from the USA, Europe, and East Asia. However, little has been published about the disease among Southeast Asians. The aim of this study was to determine the chromosomal abnormalities of MM patients in our Singapore population. Methods Forty-five newly-diagnosed, morphologically confirmed patients comprising 18 males and 27 females, aged 46-84 years （median 65 years） were investigated by karyotyping and fluorescence in situ hybridization （FISH）. FISH employing standard panel probes and lp36/lq21 and 6q21/15q22 probes was performed on diagnostic bone marrow samples. Results Thirty-four cases （75.6%） had karyotypic abnormalities. Including FISH, a total detection rate of 91.1% was at- tained. Numerical and complex structural aberrations were common to both hyperdiploid and non-hyperdiploid patients. Numerical gains of several recurring chromosomes were frequent among hyperdiploid patients while structural rear- rangements of several chromosomes including 8q24.1 and 14q32 characterized non-hyperdiploid patients. With FISH, immunoglobulin heavy chain （IGH） gene rearrangements, especially fibroblast growth factor receptor 3 （FGFR3）/IGH and RB1 deletion/monosomy 13 were the most common abnormalities （43.4%）. Amplification lq21 was 10 times more frequent （42.5%） than del（1p36） and del（6q21）. Conclusions We have successfully reported the comprehensive cytogenetic profiling of a cohort of newly-diagnosed myeloma patients in our population. This study indicates that the genetic and cytogenetic abnormalities, and their frequencies, in our study group are generally similar to other populations.

关键词： amp(l q21), del(13q) fluorescence in situ hybridization, immunoglobulin heavy chain, Southeast Asia

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非编码RNA调控自噬的分子机制及中药的干预作用

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中国中药杂志 2019年第21期44卷 4545-4551页

作者：涂玥万毅刚顾一煌刘不悔刘莹露王文文房其军 yee Hong-yun 吴薇万子玥南京中医药大学针灸推拿学院·养生康复学院中医养生学教研室江苏南京210023 Section of Comparative Medicine Yale University School of MedicineNew Haven06511 南京大学医学院附属鼓楼医院中医科江苏南京210008 南京中医药大学附属医院肾内科江苏南京210029 南京中医药大学中西医结合鼓楼临床医学院中医科江苏南京210008 Department of Social Work Meiji Gakuin UniversityTokyo108-8636

在哺乳动物细胞内,以长链非编码RNA(long non-coding RNA,lncRNA)和微小RNA(microRNA,miRNA)为代表的非编码RNA在调控自噬的上游发挥着重要作用。lncRNA和miRNA参与了自噬过程的各个阶段,包括起始、囊泡成核、自噬体成熟以及自噬体融合... 详细信息

在哺乳动物细胞内,以长链非编码RNA(long non-coding RNA,lncRNA)和微小RNA(microRNA,miRNA)为代表的非编码RNA在调控自噬的上游发挥着重要作用。lncRNA和miRNA参与了自噬过程的各个阶段,包括起始、囊泡成核、自噬体成熟以及自噬体融合等。具有双向调控自噬作用的非编码RNA包括母系表达基因3(maternally expressed gene 3,MEG3),H19和miRNA-21(miR-21);具有抑制自噬作用的非编码RNA包括生长阻滞特异转录本5(growth arrest-specific transcript 5,GAS5),miRNA-34a(miR-34a)和miRNA-30a(miR-30a);具有促进自噬作用的非编码RNA包括转移相关的肺腺癌转录本1(metastasis associated lung adenocarcinoma transcript 1,MALAT1),miRNA-152(miR-152)和miRNA-24(miR-24)。非编码RNA调控自噬的作用具有条件性、多样性和复杂性的特点。近年来,国内外学者相继发现,白蔹素、丹酚酸B、丹皮酚等单味中药提取物和加味八珍方可以在体内外干预非编码RNA而调控自噬。最新的研究表明,植物源性短链非编码RNA(small non-coding RNA,sncRNA)作为中药的有效成分之一可以直接进入循环血液和内脏而跨界调控人类基因表达。此外,大黄酸、金丝桃苷以及虫草菌丝均能在体内外通过调控自噬相关信号通路而干预肾小管上皮细胞自噬,减轻肾脏损伤和肾脏衰老,其部分药理机制可能与miR-34a通路介导有关。总之,针对肿瘤、免疫性疾病、代谢性疾病以及神经退行性疾病等临床常见疾病而揭示非编码RNA(lncRNA和miRNA)调控自噬的分子机制,这是建立精准治疗策略和阐明中药药理作用的必由之路。

关键词：自噬长链非编码RNA 微小RNA 中药分子机制

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CNT toughened aluminium and CFRP interface for strong adhesive bonding

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纳米材料科学 2022年第3期

作者： gang han bo tan fei cheng binhua wang yee-kwong leong xiaozhi hu

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雷公藤甲素抑制NLRP3炎症小体活化改善高糖诱导的足细胞上皮-间充质转分化

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中国中药杂志 2019年第24期44卷 5457-5464页

作者：吴薇刘不悔万毅刚孙伟刘莹露王文文房其军涂玥 yee Hong-yun 袁灿灿万子玥南京大学医学院附属鼓楼医院中医科江苏南京210008 南京中医药大学中西医结合鼓楼临床医学院中医科江苏南京210008 南京中医药大学附属医院肾内科江苏南京210029 南京中医药大学针灸推拿学院·养生康复学院中医养生学教研室江苏南京210023 Department of Social Work Meiji Gakuin UniversityTokyo108-8636

基于糖尿病肾病(diabetic kidney disease,DKD)肾组织Nod样受体蛋白3(Nod-like receptor protein 3 inflammasome,NLRP3)炎症小体活化的调控机制而探讨雷公藤有效成分——雷公藤甲素(triptolide,TP)在体外改善高糖(high glucose,HG)诱导足细胞上皮-间充质转分化(epithelial-mesenchymal transition,EMT)的作用。将体外培养的小鼠永生化足细胞分为正常(the normal,N)组、HG组、低剂量TP(the low dose of TP,L-TP)组、高剂量TP(the high dose of TP,H-TP)组以及甘露醇(the mannitol,MNT)组。分别进行不同的干预,即N组加入5 mmol·L^-1D-葡萄糖(D-glucose,DG),HG组加入30 mmol·L^-1HG,L-TP组加入30 mmol·L^-1HG+5μg·L^-1TP,H-TP组加入30 mmol·L^-1HG+10μg·L^-1TP,MNT组加入5 mmol·L^-1DG+24.5mmol·L^-1MNT。在干预后的不同时间点(24,48,72 h),首先,观察HG或TP对足细胞增殖活性的影响;其次,检测足细胞上皮细胞标志性分子nephrin和ZO-1、间充质细胞标志性分子Ⅰ型胶原(collagenⅠ)和纤维连接蛋白(fibronectin,FN)的蛋白表达水平;最后,检测足细胞NLRP3炎症小体活化关键信号分子NLRP3,凋亡相关斑点样蛋白(apoptosis-associated speck-like protien,ASC)以及下游效应蛋白caspase-1、白介素(interleutin,IL)-1β、IL-18的蛋白表达水平。结果表明,对于体外培养的足细胞,HG能引起nephrin,ZO-1蛋白表达水平下调,collagenⅠ,FN蛋白表达水平上调,诱导其发生EMT;还能引起NLRP3,ASC以及caspase-1,IL-1β,IL-18蛋白表达水平上调,诱导其NLRP3炎症小体活化。此外,L-TP或H-TP与HG联合干预足细胞能恢复nephrin,ZO-1蛋白表达水平,抑制collagenⅠ,FN蛋白表达水平,改善EMT;还能下调NLRP3,ASC蛋白表达水平,抑制NLRP3炎症小体活化,并减少其下游效应分子caspase-1,IL-1β,IL-18蛋白表达水平。总之,HG在体外能激活NLRP3炎症小体而诱导足细胞EMT;TP在适当的剂量范围内能抑制NLRP3炎症小体活性而改善足细胞EMT,这可能是TP保护DKD足细胞炎症性损伤的关键分子机制之一。

关键词：糖尿病肾病雷公藤甲素足细胞 NLRP3炎症小体活化上皮-间充质转分化

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