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| 1 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 2 | m^6A mRNA methylation sustains Treg suppressive functions显示文摘 | Jiyu Tong Guangchao Cao Ting Zhang Esen Sefik Maria Carolina Amezcua Vesely James P Broughton Shu Zhu Huabin Li Bin Li Lei Chen Howard Y Chang Bing Su Richard A Flavell Hua-Bing Li | 2018 | Cell Research2018，28，2： | 30 |
| 3 | Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine显示文摘 | Tingting Zhu Ian A Roundtree Ping Wang Xiao Wang Li Wang Chang Sun Yuan Tian Jie Li Chuan He Yanhui Xu | 2014 | Cell Research2014，24，12： | 28 |
| 4 | Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine显示文摘AIM: To investigate the reduction in hepatitis B virus(HBV) covalently closed-circular DNA(ccc DNA) with entecavir(ETV) or lamivudine(LAM). METHODS: This analysis included patients who had participated in the randomized Phase Ⅲ study ETV-022 comparing ETV vs LAM in nucleos(t)ide-naive, HBe Agpositive patients. Patients received ETV(0.5 mg daily) or LAM(100 mg daily) for a minimum of 52 wk. Patients were eligible to participate in this sub-study if they had paired biopsies at baseline and week 48 with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA. The main objective was to compare changes in hepatic HBV ccc DNA and total hepatic HBV DNA at week 48 of ETV or LAM treatment, which was a secondary endpoint of study ETV-022. Additional post hoc analyses included linear regression analyses to assess associations of baseline levels and on-treatment changes of ccc DNA with other baseline factors [sex,age, serum HBV DNA, alanine aminotransferase(ALT), Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBV genotype], or ontreatment factors(changes from baseline at week 48 in serum HBV DNA, ALT, Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBe Ag loss at week 48).RESULTS: Overall, 305 patients(ETV = 159; LAM = 146) of ETV-022 had paired baseline and week 48 liver biopsies with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA, and were included in this analysis. Baseline demographics and disease characteristics were comparable between the two arms. After 48 wk, ETV resulted in significantly greater reductions in hepatic HBV ccc DNA [-0.9 log10 copies/human genome equivalent(HGEq) vs-0.7 log10 copies/HGEq; P = 0.0033] and total hepatic DNA levels(-2.1 log10 copies/HGEq vs-1.6 log10 copies/HGEq; P < 0.0001) than LAM. Virologic, biochemical, and histologic response rates at week 48 were also greater with ETV than with LAM. Baseline HBV ccc DNA levels were positively associated with baseline levels of serum HBV DNA and total hepatic HBV DNA, and negatively associated with HBV genotype F. On-treatment changes in HBV ccc DNA levels were negatively associated with baseline levels of serum HBV DNA and baseline ALT, and were positively associated with on-treatment changes in the levels of serum HBV DNA, total hepatic HBV DNA levels, and ALT, change in Knodell necroinflammatory score, and HBe Ag loss.CONCLUSION: Forty-eight weeks of ETV resulted in greater reductions in ccc DNA and total hepatic HBV DNA than LAM, but long-term therapy may be needed for ccc DNA elimination. | Scott Bowden Stephen Locarnini Ting-Tsung Chang You-Chen Chao Kwang-Hyub Han Robert G Gish Robert A de Man Miao Yu Cyril Llamoso Hong Tang | 2015 | World Journal of Gastroenterology2015，21，15： | 11 |
| 5 | Mobile Ubiquitous Service Environment显示文摘The Mobile Ubiquitous Service Environment (MUSE),established through the coordination and integration of mobile telecommunications and ubiquitous network,in the pursuit of Always Best Experience (ABE),represents the major development trend for the next generation mobile wireless network. Research on MUSE will involve the integration of the computing model system,service platform system,operating system and terminal structure system,all of which involve exploration and innovation of a new networking structure,its control and management as well as way of measuring. The change in network resources triggers the change in network computing models. To let readers have a basic understanding of MUSE,this lecture introduces it in four sections. This section focuses on the development and demand analysis of the service platform. | Zhang Ping,Ji Yang,Feng Zhiyong (Research Center for Wireless New Technology,Beijing University of Posts and Telecommunications,Beijing 100876,China) The Mobile Ubiquitous Service Environment (MUSE),established through the coordination and integration of mobile telecommunications and ubiquitous network,in the pursuit of Always Best Experience (ABE),represents the major development trend for the next generation mobile wireless network. Research on MUSE will involve the integration of the computing model system,service platform system,operating system and terminal structure system,all of which involve exploration and innovation of a new networking structure,its control and management as well as way of measuring. The change in network resources triggers the change in network computing models. To let readers have a basic understanding of MUSE,this lecture introduces it in four sections. This section focuses on the development and demand analysis of the service platform. | 2007 | ZTE Communications2007，5，2： | 10 |
| 6 | Evolution of permafrost in China during the last 20 ka显示文摘The formation and evolution of permafrost in China during the last 20 ka were reconstructed on the basis of large amount of paleo-permafrost remains and paleo-periglacial evidence, as well as paleo-glacial landforms, paleo-flora and paleofauna records. The results indicate that, during the local Last Glacial Maximum(LLGM) or local Last Permafrost Maximum(LLPMax), the extent of permafrost of China reached 5.3×106-5.4×106 km2, or thrice that of today, but permafrost shrank to only0.80×106-0.85×106 km2, or 50% that of present, during the local Holocene Megathermal Period(LHMP), or the local Last Permafrost Minimum(LLPMin). On the basis of the dating of periglacial remains and their distributive features, the extent of permafrost in China was delineated for the two periods of LLGM(LLPMax) and LHMP(LLPMin), and the evolution of permafrost in China was divided into seven periods as follows:(1) LLGM in Late Pleistocene(ca. 20000 to 13000-10800 a BP)with extensive evidence for the presence of intensive ice-wedge expansion for outlining its LLPMax extent;(2) A period of dramatically changing climate during the early Holocene(10800 to 8500-7000 a BP) when permafrost remained relatively stable but with a general trend of shrinking areal extent;(3) The LHMP in the Mid-Holocene(8500-7000 to 4000-3000 a BP)when permafrost degraded intensively and extensively, and shrank to the LLPMin;(4) Neoglaciation during the late Holocene(4000-3000 to 1000 a BP, when permafrost again expanded;(5) Medieval Warming Period(MWP) in the late Holocene(1000-500 a BP) when permafrost was in a relative decline;(6) Little Ice Age(LIA) in the late Holocene(500-100 a BP), when permafrost relatively expanded, and;(7) Recent warming(during the 20 th century), when permafrost continuously degraded and still is degrading. The paleo-climate, geography and paleopermafrost extents and other features were reconstructed for each of these seven periods. | Huijun JIN Xiaoying JIN Ruixia HE Dongliang LUO Xiaoli CHANG Shaoling WANG Sergey S MARCHENKO Sizhong YANG Chaolu YI Shijie LI Stuart A HARRIS | 2019 | Science China Earth Sciences2019，62，8： | 6 |
| 7 | Mi R-122 in hepatitis B virus and hepatitis C virus dual infection显示文摘Hepatitis B virus(HBV) and hepatitis C virus(HCV) infections are the most common causes of chronic liver diseases and hepatocelluar carcinomas. Over the past few years, the liver-enriched micro RNA-122(mi R-122) has been shown to differentially regulate viral replication of HBV and HCV. It is notable that thelevel of mi R-122 is positively and negatively regulated by HCV and HBV, respectively. Consistent with the welldocumented phenomenon that mi R-122 promotes HCV accumulation, inhibition of mi R-122 has been shown as an effective therapy for the treatment of HCV infection in both chimpanzees and humans. On the other hand, mi R-122 is also known to block HBV replication, and HBV has recently been shown to inhibit mi R-122 expression; such a reciprocal inhibition between mi R-122 and HBV suggests an intriguing possibility that mi R-122 replacement may represent a potential therapy for treatment of HBV infection. As HBV and HCV have shared transmission routes, dual infection is not an uncommon scenario, which is associated with more advanced liver disease than either HBV or HCV mono-infection. Thus, there is a clear need to further understand the interaction between HBV and HCV and to delineate the role of mi R-122 in HBV/HCV dual infection in order to devise effective therapy. This review summarizes the current understanding of HBV/HCV dual infection, focusing on the pathobiological role and therapeutic potential of mi R-122. | Kyoungsub Song Chang Han Srikanta Dash Luis A Balart Tong Wu | 2015 | World Journal of Hepatology2015，7，3： | 6 |
| 8 | Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density显示文摘 | W.S Simonet D.L Lacey C.R Dunstan M Kelley M.-S Chang R Lüthy H.Q Nguyen S Wooden L Bennett T Boone G Shimamoto M DeRose R Elliott A Colombero H.-L Tan G Trail J Sullivan E Davy N Bucay L Renshaw-Gegg T.M Hughes D Hill W Pattison P Campbell S Sander G Van | 1997 | Cell1997，，2： | 6 |
| 9 | Age and menopausal status are important factors influencing the serum human epididymis secretory protein 4 level:a prospective cross-sectional study in healthy Chinese people显示文摘Background::Human epididymis secretory protein 4(HE4)is a new ovarian cancer biomarker.The factors influencing HE4 levels are not clear,and the reference data in China are limited.Here,we aim to evaluate the effects of menopause and age on HE4 levels and to provide a possible reference value for HE4 in healthy Chinese people.Methods::A total of 2493 healthy females aged 40 years or older were recruited from March 2013 to March 2017 with the cooperation of four medical institutions across Beijing,China.The serum levels of HE4 and cancer antigen 125(CA125)were measured by enzyme-linked immunosorbent assay.The Wilcoxon rank-sum test of variance and a stratified analysis were used to analyze the relationships among age,menopausal status,and levels of HE4 or CA125.Confidence intervals(5%-95%)were determined for reference ranges in different populations.Results::There was a statistically significant difference in median HE4 levels between the post-menopausal(n=2168)and premenopausal groups(n=325)(36.46 vs.24.04 pmol/L,Z=-14.41,P<0.001).HE4 increased significantly with age in the post-menopausal groups(H=408.18,P<0.001)but not in the pre-menopausal subjects(Z=-0.43,P=0.67).The upper 95th percentile of HE4 levels were 44.63 pmol/L for pre-menopausal women,78.17 pmol/L for post-menopausal women,and 73.3 pmol/L for all women.In the post-menopausal population,the HE4 reference ranges were 13.15 to 47.31,14.31 to 58.04,17.06 to 73.51,24.50 to 115.25,and 35.71 to 212.37 pmol/L for different age groups from forty divided by decade.The CA125 level was affected mainly by menopausal status and not age.Conclusions::Menopausal status and age were both important factors influencing the level of HE4,and age affected HE4 levels mainly in post-menopausal women.The HE4 level was higher in the post-menopausal population than in the pre-menopausal population and increased with age. | Hong-Yan Cheng Lin Zeng Xue Ye Rui-Qiong M a Zhi-Jian Tang Hong-Ling Chu Yi-M ing Zhao Li-Rong Zhu Yu-Nong Gao Xiao-Hong Chang Heng Cui | 2020 | Chinese Medical Journal2020，，11： | 6 |
| 10 | Research on Benefit Distribution Mechanism of Farmers’ Specialized Cooperative Economic Organization显示文摘On the basis of conducting survey in Jiaonan City,the thesis analyzes benefit distribution mechanism of farmers’ specialized cooperative economic organizations:firstly,the benefit correlation is mainly the contract correlation;secondly,the profit distribution is mainly the dividend;thirdly,patronage refund has many connotations;fourthly,the public accumulation has not yet been quantified to individual;fifthly,the government support capital is ill-defined.Based on these,the measures are put forward in order to improve benefit distribution pattern of farmers’ specialized cooperative economic organizations:firstly,reform structure of property rights and realize farmers’ ownership;secondly,change mode of decision-making,and realize farmers’ control;thirdly,increase turnover rebate and realize farmers’ benefiting;fourthly,quantify public accumulation and government support fund. | SUN Hao-jie1,WANG Zheng-bing2,WANG Yun-hui3 1.School of Economics and Management,Chang’ an University,Xi’an 710064,China 2.College of Economics and Management,Northwest A & F University,Yangling 712100,China 3.Publicity Office of Party Committee,Xi’an Branch of the People’ Bank of China,Xi’an 710064,China | 2011 | Asian Agricultural Research2011，3，4： | 5 |
| 11 | Plecanatide-mediated activation of guanylate cyclase-C suppresses inflammation-induced colorectal carcinogenesis in Apc+/Min-FCCC mice显示文摘AIM To evaluate the effect of orally administered plecanatide on colorectal dysplasia in Apc^(+/Min-FCCC) mice with dextran sodium sulfate(DSS)-induced inflammation. METHODS Inflammation driven colorectal carcinogenesis was induced in Apc^(+/Min-FCCC) mice by administering DSS in their drinking water. Mice were fed a diet supplemented with plecanatide(0-20 ppm) and its effect on the multiplicity of histopathologically confirmed polypoid,flat and indeterminate dysplasia was evaluated. Plecanatide-mediated activation of guanylate cyclase-C(GC-C) signaling was assessed in colon tissues by measuring cyclic guanosine monophosphate(cG MP) by ELISA, protein kinase G-II and vasodilator stimulated phosphoprotein by immunoblotting. Ki-67, c-myc and cyclin D1 were used as markers of proliferation. Cellular levels and localization of b-catenin in colon tissues were assessed by immunoblotting and immunohistochemistry, respectively. Uroguanylin(UG) and GC-C transcript levels were measured by quantitative reverse transcription polymerase chain reaction(RT-PCR). A mouse cytokine array panel was used to detect cytokines in the supernatant of colon explant cultures. RESULTS Oral treatment of Apc^(+/Min-FCCC) mice with plecanatide produced a statistically significant reduction in the formation of inflammation-driven polypoid, flat and indeterminate dysplasias. This anti-carcinogenic activity of plecanatide was accompanied by activation of cG MP/GC-C signaling mediated inhibition of Wnt/b-catenin signaling and reduced proliferation. Plecanatide also decreased secretion of pro-inflammatory cytokines(IL-6, IL-1 TNF), chemokines(MIP-1, IP-10) and growth factors(GCSF and GMCSF) from colon explants derived from mice with acute DSS-induced inflammation. The effect of plecanatidemediated inhibition of inflammation/dysplasia on endogenous expression of UG and GC-C transcripts was measured in intestinal tissues. Although GC-C expression was not altered appreciably, a statistically significant increase in the level of UG transcripts was detected in the proximal small intestine and colon, potentially due to a reduction in intestinal inflammation and/or neoplasia. Taken together, these results suggest that reductions in endogenous UG, accompanied by dysregulation in GC-C signaling, may be an early event in inflammation-promoted colorectal neoplasia; an event that can potentially be ameliorated by prophylactic intervention with plecanatide.CONCLUSION This study provides the first evidence that orally administered plecanatide reduces the multiplicity of inflammation-driven colonic dysplasia in mice, demonstrating the utility for developing GC-C agonists as chemopreventive agents. | Wen-Chi L Chang Shet Masih Anusha Thadi Viren Patwa Apoorva Joshi Harry S Cooper Vaseem A Palejwala Margie L Clapper Kunwar Shailubhai | 2017 | World Journal of Gastrointestinal Pharmacology and Therapeutics2017，8，1： | 5 |
| 12 | GENETIC PROGRAMMING TO PREDICT SKI-JUMP BUCKET SPILLWAY SCOUR显示文摘Researchers in the past had noticed that application of Artificial Neural Networks (ANN) in place of conventional statistics on the basis of data mining techniques predicts more accurate results in hydraulic predictions. Mostly these works pertained to applications of ANN. Recently, another tool of soft computing, namely, Genetic Programming (GP) has caught the attention of researchers in civil engineering computing. This article examines the usefulness of the GP based approach to predict the relative scour depth downstream of a common type of ski-jump bucket spillway. Actual field measurements were used to develop the GP model. The GP based estimations were found to be equally and more accurate than the ANN based ones, especially, when the underlying cause-effect relationship became more uncertain to model. | AZAMATHULLA H. MD GHANI A. AB ZAKARIA N. A LAI S. H CHANG C. K LEOW C. S ABUHASAN Z | 2008 | Journal of Hydrodynamics2008，20，4： | 4 |
| 13 | HETEROPHYLLIN-A AND B,TWO CYCLOPEPTIDES,FROM THE ROOTS OF PSEUDOSTELLARIA HETEROPHYLLA显示文摘Two cyclopeptides,heterophyllin A and B,have been isolated from the rootsof Pseudostellaria heterophylla.Their structures were elucidated by chemical,spectroscopic,and enzymatic methods. | Ning Hua TAN Shou Xun ZHAO a Department of Phytochemistry,China Pharmaceutical University,Nanjing,210009 Jun ZHOU Hong Jie ZHANG De Zu WANG Chang Xiang CHEN Xiao Zhu LIU b Laboratory of Phytochemistry,Kunming Institute of Botany,Academia Sinica,Kunming,650204 | 1992 | Chinese Chemical Letters1992，3，8： | 4 |
| 14 | A 10-miRNA risk score-based prediction model for pathological complete response to neoadjuvant chemotherapy in hormone receptor-positive breast cancer显示文摘Patients with hormone receptor(HR)-positive tumors breast cancer usually experience a relatively low pathological complete response(p CR)to neoadjuvant chemotherapy(NAC).Here,we derived a 10-micro RNA risk score(10-mi RNA RS)-based model with better performance in the prediction of p CR and validated its relation with the disease-free survival(DFS)in 755 HRpositive breast cancer patients(273,265,and 217 in the training,internal,and external validation sets,respectively).This model,presented as a nomogram,included four parameters:the 10-mi RNA RS found in our previous study,progesterone receptor(PR),human epidermal growth factor receptor 2(HER2)status,and volume transfer constant(K).Favorable calibration and discrimination of 10-mi RNA RS-based model with areas under the curve(AUC)of 0.865,0.811,and 0.804 were shown in the training,internal,and external validation sets,respectively.Patients who have higher nomogram score(>92.2)with NAC treatment would have longer DFS(hazard ratio=0.57;95%CI:0.39–0.83;P=0.004).In summary,our data showed the 10-mi RNA RS-based model could precisely identify more patients who can attain p CR to NAC,which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HRpositive breast cancer. | Chang Gong Ziliang Cheng Yaping Yang Jun Shen Yingying Zhu Li Ling Wanyi Lin Zhigang Yu Zhihua Li Weige Tan Chushan Zheng Wenbo Zheng Jiajie Zhong Xiang Zhang Yunjie Zeng Qiang Liu RStephanie Huang Andrzej LKomorowski Eddy SYang François Bertucci Francesco Ricci Armando Orlandi Gianluca Franceschini Kazuaki Takabe Suzanne Klimberg Naohiro Ishii Angela Toss Mona PTan Mathew A Cherian Erwei Song | 2022 | Science China(Life Sciences)2022，65，11： | 3 |
| 15 | Antagonism of miR-33 in mice promotes reverse cholesterol transport and regression of atherosclerosis显示文摘 | Rayner Katey J Sheedy Frederick J Esau Christine C Hussain Farah N Temel Ryan E Parathath Saj van Gils Janine M Rayner Alistair J Chang Aaron N Suarez Yajaira Fernandez-Hernando Carlos Fisher Edward A Moore Kathryn J | 2011 | Journal of Clinical Investigation2011，，7： | 2 |
| 16 | 饲料中添加发酵豆粕对岩鱼生长性能、身体组成、抗氧化酶活性和抗病性能的影响显示文摘试验研究用发酵豆粕鱼料(FSM)代替常规鱼料(FM)对幼鱼期和生长期岩鱼(又名许氏鲆鲉)生长性能、身体组成、抗氧化酶活性和抗病能力的影响。FSM含量分别为0、8%、16%、24%和32%的等氮(51%)和等热量(MJ·kg^(-1))鱼料代替FM蛋白质含量约0、10%、20%、30%和40%的鱼料(分别为FSM0组、FSM8组、FSM16组、FSM24组和FSM32组)。每组鱼料分别饲喂3组幼生期岩鱼(1.2±0.04 g;EXPⅠ组)和3组生长期岩鱼(148.2±2.9 g;EXPⅡ组),2次·d^(-1),共8周。与FSM0组、FSM8组和FSM16组相比,饲喂FSM32组幼生期岩鱼的体增重(WG)显著降低。FSM16组、FSM24组和FSM32组的饲料效率(FE)和岩鱼蛋白质功效比值(PER)显著低于FSM0组和FSM8组。FSM24组的日采食量(DFI)显著低于FSM0组和FSM8组。但生长期岩鱼的生长性能和饲料利用率未表现出显著改变。FSM32组幼生期岩鱼的内脏指数(VSI)显著低于其他各组。FSM替代FM量达到40%,对幼生期和生长期岩鱼的整个身体和肌肉指标、氨基酸组成均无显著影响。与对照组相比,鱼料中含有FSM的生长期岩鱼的血清抗氧化酶活性显著提高。腹腔注射迟钝爱德华菌后存活的幼生期岩鱼不受饲料变化的影响。试验结果表明,FSM是一种成功的FM替代品,幼生期岩鱼鱼料中替代量可达10%,生长期岩鱼料中替代量达40%时,对其生长性能仍无不良影响。 | Sang M L Hamid M A Kyung H Chang | 2016 | 饲料博览2016，0，7： | 2 |
| 17 | Disruption of crosstalk between LX-2 and liver cancer stem-like cells from MHCC97H cells by DFOG via inhibiting FOXM1显示文摘Hepatic stellate cell(HSC)line LX-2 is activated by liver cancer stem-like cells(LCSLCs)and produces various cytokines that make up most of the hepatocellular carcinoma(HCC)microenvironment.The new genistein derivative,7-difluoromethoxyl-5,4-dirboctylgenistein(DFOG),shows anticancer effects in multiple malignancies by controlling forkhead box M1(FOXM1).In this study,we aimed to assess whether DFOG disrupts the crosstalk between human HSC LX-2 cells and LCSLCs.Distinct gen erations of MHCC97H-derived spheres were obtained with the sec ond generation considered as LCSLCs which displayed enhanced self-renewal ability and elevated expression levels of CD133,CD44,and EpCAM proteins,as well as tumorigenicity,as revealed by colony formation assay in vitro and tumorigenicity assay in vivo.LX-2 and MHCC97H cells were co-cultured with/without DFOG(1,5,and 10 pM,respectively)using the transwell system.FOXM1 overexpression and/or knockdown were employed for mechanistic investigations.Our results suggested that Co-CM promoted LX-2 cell transformation into liver cancer-associated HSCs.Meanwhile,FOXM1 was up-regulated and the level of hepatocyte growth factor(HGF)was in creased in LX-2 cells and in the super nata nt after Co-CM stimulati on.Sphere and colony formation abilities in MHCC97H cells,and protein levels of CD133r CD44,and EpCAM,were also markedly elevated.DFOG dose-dependently inhibited the above effects,similar to FOXM1 knockdown in LX-2 cells.FOXM1 overexpression reversed the inhibitory effects of DFOG or FOXM1 knockdown or both on LX-2 cell activation and LCSLC feature induction in MHCC97H cells by LCSLC/LX-2 co-culture.This study demonstrated that DFOG disrupts the crosstalk between HSCs and LCSLCs to suppress LCSLC features via dowrrregulating FOXM1 expression and reducing HGF secretion in HSCs. | A Chen Chang Xu Yimin Luo Lihua Liu Kun Song Guangqi Deng Mengjie Yang Jianguo Cao Liming Yuan Xiang Li | 2019 | Acta Biochimica et Biophysica Sinica2019，51，12： | 2 |
| 18 | Application of artificial intelligence-driven endoscopic screening and diagnosis of gastric cancer显示文摘The landscape of gastrointestinal endoscopy continues to evolve as new technologies and techniques become available.The advent of image-enhanced and magnifying endoscopies has highlighted the step toward perfecting endoscopic screening and diagnosis of gastric lesions.Simultaneously,with the development of convolutional neural network,artificial intelligence(AI)has made unprecedented breakthroughs in medical imaging,including the ongoing trials of computer-aided detection of colorectal polyps and gastrointestinal bleeding.In the past demi-decade,applications of AI systems in gastric cancer have also emerged.With AI’s efficient computational power and learning capacities,endoscopists can improve their diagnostic accuracies and avoid the missing or mischaracterization of gastric neoplastic changes.So far,several AI systems that incorporated both traditional and novel endoscopy technologies have been developed for various purposes,with most systems achieving an accuracy of more than 80%.However,their feasibility,effectiveness,and safety in clinical practice remain to be seen as there have been no clinical trials yet.Nonetheless,AI-assisted endoscopies shed light on more accurate and sensitive ways for early detection,treatment guidance and prognosis prediction of gastric lesions.This review summarizes the current status of various AI applications in gastric cancer and pinpoints directions for future research and clinical practice implementation from a clinical perspective. | Yu-Jer Hsiao Yuan-Chih Wen Wei-Yi Lai Yi-Ying Lin Yi-Ping Yang Yueh Chien Aliaksandr A Yarmishyn De-Kuang Hwang Tai-Chi Lin Yun-Chia Chang Ting-Yi Lin Kao-Jung Chang Shih-Hwa Chiou Ying-Chun Jheng | 2021 | World Journal of Gastroenterology2021，27，22： | 2 |
| 19 | ^(99m)TC-Methylene diphosphonate uptake at injury site correlates with osteoblast differentiation and mineralization during bone healing in mice显示文摘99m Tc-Methylene diphosphonate(99m Tc-MDP) is widely used in clinical settings to detect bone abnormalities.However, the mechanism of99 m Tc-MDP uptake in bone is not well elucidated. In this study, we utilized a mouse tibia injury model, single-photon emission computed tomography(gamma scintigraphy or SPECT),ex vivo micro-computed tomography, and histology to monitor99 m Tc-MDP uptake in injury sites during skeletal healing. In an ex vivo culture system, calvarial cells were differentiated into osteoblasts with osteogenic medium, pulsed with99 m Tc-MDP at different time points, and quantitated for99 m Tc-MDP uptake with a gamma counter. We demonstrated that99 m Tc-MDP uptake in the injury sites corresponded to osteoblast generation in those sites throughout the healing process. The99 m Tc-MDP uptake within the injury sites peaked on day 7 post-injury, while the injury sites were occupied by mature osteoblasts also starting from day 7.99 m Tc-MDP uptake started to decrease 14 days post-surgery, when we observed the highest level of bony tissue in the injury sites. We also found that99 m Tc-MDP uptake was associated with osteoblast maturation and mineralization in vitro. This study provides direct and biological evidence for99 m Tc-MDP uptake in osteoblasts during bone healing in vivo and in vitro. | Zhendong A Zhong Anderson Peck Shihong Li Jeff Van Oss John Snider Casey J Droscha Tingtung A Chang Bart O Williams | 2015 | Bone Research2015，3，2： | 2 |
| 20 | Personalising pancreas cancer treatment:When tissue is the issue显示文摘The treatment of advanced pancreatic cancer has not moved much beyond single agent gemcitabine until recently when protocols such as FOLFIRINOX(fluorouracil,leucovorin,irinotecan and oxaliplatin)and nab-paclitaxelgemcitabine have demonstrated some improved outcomes.Advances in technology especially in massively parallel genome sequencing has progressed our understanding of the biology of pancreatic cancer especially the candidate signalling pathways that are involved in tumourogenesis and disease course.This has allowed identification of potentially actionable mutations that may be targeted by new biological agents.The heterogeneity of pancreatic cancer makes tumour tissue collection important with the aim of being able to personalise therapies for the individual as opposed to a one size fits all approach to treatment of the condition.This paper reviews the developments in this area of translational research and the ongoing clinical studies that will attempt to move this into the everyday oncology practice. | Katrin M Sjoquist Venessa T Chin Lorraine A Chantrill Chelsie O'Connor Chris Hemmings David K Chang Angela Chou Marina Pajic Amber L Johns Adnan M Nagrial Andrew V Biankin Desmond Yip | 2014 | World Journal of Gastroenterology2014，20，24： | 2 |
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