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| 1 | 2019新型冠状病毒基因组特征和流行病学:病毒起源和受体结合的意义显示文摘研究者对来自9例新型冠状病毒肺炎住院患者的支气管肺泡灌洗液样本和培养的分离株进行了下一代测序。从这些个体中获得了严重急性呼吸综合征-冠状病毒2(severe acute respiratory syndrome-coronavirus 2,SARS-CoV-2)的完整和部分基因组序列。利用Sanger测序连接病毒重叠群以获得全长基因组,cDNA末端快速扩增确定终端区。对这些SARSCoV-2基因组和其他冠状病毒基因组进行了系统进化分析,以确定该病毒的进化史并有助于推断其可能的起源。 | 刘青(译) 刘莉(审校) Lu R Zhao X Li J Niu P Yang B Wu H Wang W Song H Huang B Zhu N Bi Y Ma X Zhan F Wang L Hu T Zhou H Hu Z Zhou W Zhao L Chen J Meng Y Wang J Lin Y Yuan J Xie Z Ma J Liu WJ Wang D Xu W Holmes EC Gao GF Wu G Chen W Shi W Tan W | 2020 | 中华高血压杂志2020，28，3： | 516 |
| 2 | Mettl3-/Mettl14-mediated mRNA N6-methyladenosine modulates murine spermatogenesis显示文摘精子发生在双 spermatogonial 干细胞(SSC ) 哪个生产 haploid 精子期间是一个区别过程。这个高度专业化的过程精确在 transcriptional, posttranscriptional,和翻译层次被控制。这里,我们报导那 N 6-methyladenosine (m 6 一) ,调整基因表示的一个 epitranscriptomic 标记,在精子发生期间起必要作用。我们现在的全面 m 6 从五个发展阶段的老鼠 spermatogenic 房间的 mRNA methylomes:无差别的 spermatogonia,类型 A 1 spermatogonia, preleptotene spermatocytes, pachytene/diplotene spermatocytes,和圆 spermatids。m 6 有 Vasa-Cre 的 RNA methyltransferase Mettl3 或 Mettl14 引起 m 6 SSC 的 A 和弄空。m 6 为 SSC 增长 / 区别被要求的抄本的一个弄空 dysregulates 翻译。在有 Stra8-GFPCre 的先进细菌房间的 Mettl3 和 Mettl14 的联合删除破坏精子形式,而有在先进细菌房间的 Mettl3 或 Mettl14 的单个删除的老鼠显示出正常精子发生。从双异种老鼠展览的 spermatids 损害了为精子形式是必要的 haploid 特定的基因的翻译。这研究加亮 mRNA m 6 在 germline 开发的修正,潜在地保证在精子发生的不同阶段协调了翻译。 | Zhen Lin Phillip J Hsu Xudong Xing Jianhuo Fang Zhike Lu Qin Zou Ke-Jia Zhang Xiao Zhang Yuchuan Zhou Teng Zhang Youcheng Zhang Wanlu Song Guifang Jia Xuerui Yang Chuan He Ming-Han Tong | 2017 | Cell Research2017，27，10： | 61 |
| 3 | 帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。 | 陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh | 2021 | 中华肿瘤防治杂志2021，28，24： | 49 |
| 4 | Nat Genet:单细胞分析解开结直肠癌细胞的神秘面纱显示文摘结合单细胞基因组学和计算机技术,一个研究团队(包括来自杰克逊实验室(JAx)单细胞生物学主任Paul Robson博士在内)鉴定出了11种结直肠癌肿瘤的癌细胞组成及邻近的非癌细胞。这对于更好的肿瘤靶向诊断和治疗很重要。”使用单细胞测序。”JAX科学家、这篇发表在Nature Genetics上的文章共同第一作者Elise Courtois说道。”我们可以根据肿瘤中的细胞组成将结直肠癌进一步分类。因为每种亚型的肿瘤病人生存率存在差别,我们的方法将为肿瘤医生提供更多的关于肿瘤预后和治疗的信息。” | Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan Shyam Prabhakar Elise T Courtois, Yuliana Tan Paul Robson Debarka Sengupta Kok Hao Chen, Jolene Jie Lin Goh Paul Jongjoon Choi Say Li Kong, Axel M Hillmer Iain Beehuat Tan Clarinda Chua Iain Beehuat Tan Lim Kiat Hon Wah Siew Tan Mark Wong Lawrence J K Wee Iain Beehuat Tan Paul Robson Paul Robson Paul Robson | 2017 | 现代生物医学进展2017，17，15： | 37 |
| 5 | Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities显示文摘Aim:To clarify the mechanism of the therapeutic action of icariin on erectlile dysfunction(ED).Methods:PDE5 was isolated from the human platelet and PDE4 form the rat liver tissue using the FPLC system (Pharmacia,Milton Keynes,UK)and the Mono Q column.The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure with [^3H]-c GMP/[^3H]-cAMP.Papaverine served as the control drug.Results:Icariin and papaverine showed dose-dependent inhibitory effects on PDE5 and PDE4 activities.The IC50 of Icariin and papaverine on PDE5 were 0.432μ mol/L and 0.680μmol/L,respectively and those on PDE4,73.50μmol/L and 3.07μmol/L,respectively.The potencies of selectivity of icariin and papaverine on PDE5(PDE4/PDE5 of IC50)were 167.67 times and 4.54 times,respectively.Conclusion:Icariin is a cGMP-specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED. | ZC Xin EK Kim CS Lin WJ Liu L Tian YM Yuan J Fu | 2003 | Asian Journal of Andrology2003，5，1： | 38 |
| 6 | Molecular and cellular characterization during chondrogenic differentiation of adipose tissue-derived stromal cells in vitro and cartilage formation in vivo显示文摘 | Lin Y Luo E Chen X Liu L Qiao J Yan Z Li Z Tang W Zheng X Tian W | 2006 | 中国生物学文摘2006，20，5： | 31 |
| 7 | 血管周围脂肪组织中的Bmal1通过血管紧张素原转录调控管理静息期血压显示文摘血管周围脂肪组织(perivascular adipose tissue,PVAT)围绕血管,构成了在生理条件下保持血管张力所需的脉管系统的独特的功能整体层。然而,关于PVAT与血压调节之间的关系的资料很少,包括其对昼夜血压变化的潜在作用。 | Chang L Xiong W Zhao X Fan Y Guo Y Garcia-Barrio M Zhang J Jiang Z Lin JD Chen YE 刘青 叶鹏 | 2018 | 中华高血压杂志2018，26，2： | 23 |
| 8 | 亚太地区胃食管反流病的处理共识:更新版显示文摘背景与目的:自从2004年亚太地区胃食管反流病(GERD)共识发表以来,更多关于GERD流行病学和处理的文献资料相继出现。有必要对这些资料进行循证综述,对共识作出更新。方法:由多学科专家组应用德尔菲(Delphi)法制定共识条文,提呈相关资料,并对证据质量、推荐力度和共识水平进行分级。结果:亚洲GERD发生率日益增加。其危险因素包括老年、男性、种族、家族史、社会经济地位高、体重指数增加和吸烟。对于有典型症状而无报警症状的患者,对质子泵抑制剂(PPI)试验有症状应答具有诊断意义。如PPI试验失败,停止治疗后pH监测结果阴性可排除GERD。窄带成像、胶囊内镜检查和无线pH监测的作用尚未明确。亚洲诊断策略的制定须考虑到并存的胃癌和消化性溃疡。减轻体质量和抬高床头可改善反流症状。PPIs是最有效的内科治疗手段。对于非糜烂性反流病(NERD)患者,按需治疗较为适宜。有慢性咳嗽、喉炎和典型GERD症状的患者在排除非GERD病因后,应予PPI每天两次治疗。如有经验丰富的外科医师,GERD患者可行胃底折叠术。除临床试验外,GERD不应采用内镜治疗。结论:新的诊断方法和内镜治疗的作用有待进一步研究阐明。亚洲GERD诊断策略的制定须考虑到并存的胃癌和消化性溃疡。PPIs仍为治疗的基石。 | Kwong Ming Fock Nicholas J Talley Ronnie Fass Khean Lee Goh Peter Katelaris Richard Hunt Michio Hongo Tiing Leong Ang Gerald Holtmann Sanjay Nandurkar San Ren Lin Benjamin CY Wong Francis KL Chan Abdul Aziz Rani Young-Tae Bak Jose Sollano Khek Yu Ho Sathoporn Manatsathit 钱本余 | 2008 | 胃肠病学2008，13，7： | 21 |
| 9 | Multilineage differentiation of adipose-derived stromal cells from GFP transgenic mice显示文摘 | Lin Y Chen X Yan Z Liu L Tang W Zheng X Li Z Qiao J Li S Tian W | 2006 | 中国生物学文摘2006，20，5： | 16 |
| 10 | Tumor size as a prognostic factor in patients with advanced gastric cancer in the lower third of the stomach显示文摘AIM: To explore the impact of tumor size on outcomes in patients with advanced gastric cancer in the lower third of the stomach. METHODS: We retrospectively analyzed the clinical records of 430 patients with advanced gastric cancer in the lower third of the stomach who underwent distal subtotal gastrectomy and D2 lymphadenectomy in our hospital from January 1998 to June 2004. Receiver-operating characteristic (ROC) curve analysis was used to determine the appropriate cutoff value for tumor size, which was measured as maximum tumor diameter. Based on this cutoff value, patients were divided into two groups: those with large-sized tumors (LSTs) and those with small-sized tumors (SSTs). The correlations between other clinicopathologic factors and tumor size were investigated, and the 5-year overall survival (OS) rate was compared between the two groups. Potential prognostic factors were evaluated by univariate KaplanMeier survival analysis and multivariate Cox's propor-tional hazard model analysis. The 5-year OS rates in the two groups were compared according to pT stage and pN stage. RESULTS: The 5-year OS rate in the 430 patients with advanced gastric cancer in the lower third of the stomach was 53.7%. The mean ± SD tumor size was 4.9 ± 1.9 cm, and the median tumor size was 5.0 cm. ROC analysis indicated that the sensitivity and specificity results for the appropriate tumor size cutoff value of 4.8 cm were 80.0% and 68.2%, respectively (AUC=0.795, 95%CI: 0.751-0.839, P=0.000). Using this cutoff value, 222 patients (51.6%) had LSTs (tumor size ≥ 4.8 cm) and 208 (48.4%) had SSTs (tumor size<4.8 cm). Tumor size was significantly correlated with histological type (P=0.039), Borrmann type (P=0.000), depth of tumor invasion (P=0.000), lymph node metastasis (P=0.000), tumor-nodes metastasis stage (P=0.000), mean number of metastatic lymph nodes (P=0.000) and metastatic lymph node ratio (P=0.000). Patients with LSTs had a significantly lower 5-year OS rate than those with SSTs (37.1% vs 63.3%, P=0.000). Univariate analysis showed that depth of tumor invasion (c 2=69.581, P=0.000), lymph node metastasis (c 2=138.815, P=0.000), tumor size (c 2=78.184, P=0.000) and metastatic lymph node ratio (c 2=139.034, P=0.000) were significantly associated with 5-year OS rate. Multivariate analysis revealed that depth of tumor invasion (P=0.000), lymph node metastasis (P=0.019) and tumor size (P=0.000) were independent prognostic factors. Gastric cancers were divided into 12 subgroups: pT2N0; pT2N1; pT2N2; pT2N3; pT3N0; pT3N1; pT3N2; pT3N3; pT4aN0; pT4aN1; pT4aN2; and pT4aN3. In patients with pT2-3N3 stage tumors and patients with pT4a stage tumors, 5-year OS rates were significantly lower for LSTs than for SSTs (P<0.05 each), but there were no significant differences in the 5-year OS rates in LST and SST patients with pT23N0-2 stage tumors (P > 0.05). CONCLUSION: Using a tumor size cutoff value of 4.8cm, tumor size is a prognostic factor in patients with pN3 stage or pT4a stage advanced gastric cancer located in the lower third of the stomach. | Hong-Mei Wang, Chang-Ming Huang, Chao-Hui Zheng, Ping Li, Jian-Wei Xie, Jia-Bin Wang, Jian-Xian Lin, Jun Lu, Department of Gastric Surgery, Affiliated Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China Author contributions: Wang HM and Huang CM conceived of the study, analyzed the data, and drafted the manuscript Zheng CH, Li P and Xie JW helped revise the manuscript critically for important intellectual content Wang JB, Lin JX and Lu J helped collect data and design the study and all authors read and approved the final manuscript. | 2012 | World Journal of Gastroenterology2012，18，38： | 15 |
| 11 | Surveillance-response systems: the key to elimination of tropical diseases显示文摘Tropical diseases remain a major cause of morbidity and mortality in developing countries.Although combined health efforts brought about significant improvements over the past 20 years,communities in resource-constrained settings lack the means of strengthening their environment in directions that would provide less favourable conditions for pathogens.Still,the impact of infectious diseases is declining worldwide along with progress made regarding responses to basic health problems and improving health services delivery to the most vulnerable populations.The London Declaration on Neglected Tropical Diseases(NTDs),initiated by the World Health Organization’s NTD roadmap,set out the path towards control and eventual elimination of several tropical diseases by 2020,providing an impetus for local and regional disease elimination programmes.Tropical diseases are often patchy and erratic,and there are differing priorities in resources-limited and endemic countries at various levels of their public health systems.In order to identify and prioritize strategic research on elimination of tropical diseases,the‘First Forum on Surveillance-Response System Leading to Tropical Diseases Elimination’was convened in Shanghai in June 2012.Current strategies and the NTD roadmap were reviewed,followed by discussions on how to identify and critically examine prevailing challenges and opportunities,including inter-sectoral collaboration and approaches for elimination of several infectious,tropical diseases.A priority research agenda within a‘One Health-One World’frame of global health was developed,including(i)the establishment of a platform for resource-sharing and effective surveillance-response systems for Asia Pacific and Africa with an initial focus on elimination of lymphatic filariasis,malaria and schistosomiasis;(ii)development of new strategies,tools and approaches,such as improved diagnostics and antimalarial therapies;(iii)rigorous validation of surveillance-response systems;and(iv)designing pilot studies to transfer Chinese experiences of successful surveillance-response systems to endemic countries with limited resources. | Ernest Tambo Lin Ai Xia Zhou Jun-Hu Chen Wei Hu Robert Bergquist Jia-Gang Guo Jürg Utzinger Marcel Tanner Xiao-Nong Zhou | 2014 | Infectious Diseases of Poverty2014，3，1： | 14 |
| 12 | Design of TRIP Steel With High Welding and Galvanizing Performance in Light of Thermodynamics and Kinetics显示文摘A new type of transformation induced plasticity (TRIP) steel with not only high strength and high ductility but also superior welding and galvanizing properties was designed and developed recently. Low carbon and low silicon content were preliminarily selected with the aim of meeting the requirements of superior quality in both welding and galvanizing. Phosphorus was chosen as one of the alloying elements, because it could reduce carbon activity in cementite and increase the stability of austenite. In addition, the possibility of phosphorus segregating at grain boundary was also discussed by thermodynamics as well as kinetics. Phase diagram was estimated at high temperature and the composition of the steel was then selected in the hyperperitectic range to avoid problems, which might occur in sheet steel continuous casting. Phase diagram in the inter-critical temperature was estimated for the steel to obtain the starting temperature of fast cooling. For understanding the minimum rate of fast cooling, pearlite growth kinetics was calculated with self-developed diffusion coefficients of elements in grain boundary. Overaging temperature was determined through the calculation of T0 temperature by both equilibrium and para-equilibrium assumptions, which was different from the current determination, which is only based on an equilibrium estimation. | LI Lin DE COOMAN B C LIU Ren-dong VLEUGELS j ZHANG Mei SHI Wen | 2007 | Journal of Iron and Steel Research(International)2007，14，6： | 13 |
| 13 | Encapsulating peritoneal sclerosis显示文摘Encapsulating peritoneal sclerosis(EPS) is a debilitating condition characterized by a fibrocollagenous membrane encasing the small intestine, resulting in recurrent small bowel obstructions. EPS is most commonly associated with long-term peritoneal dialysis, though medications, peritoneal infection, and systemic inflammatory disorders have been implicated. Many cases remain idiopathic. Diagnosis is often delayed given the rarity of the disorder combined with non-specific symptoms and laboratory findings. Although cross-sectional imaging with computed tomography of the abdomen can be suggestive of the disorder, many patients undergo exploratory laparotomy for diagnosis. Mortality approaches 50% one year after diagnosis. Treatment for EPS involves treating the underlying condition or eliminating possible inciting agents(i.e. peritoneal dialysis, medications, infections) and nutritional support, frequently with total parenteral nutrition. EPSspecific treatment depends on the disease stage. In the inflammatory stage, corticosteroids are the treatment of choice, while in the fibrotic stage, tamoxifen may be beneficial. In practice, distinguishing between stages may be difficult and both may be used. Surgical intervention, consisting of peritonectomy and enterolysis, is timeconsuming and high-risk and is reserved for situations in which conservative medical therapy fails in institutions with surgical expertise in this area. Herein we review the available literature of the etiology, pathogenesis, diagnosis, and treatment of this rare, but potentially devastating disease. | Christopher J Danford Steven C Lin Martin P Smith Jacqueline L Wolf | 2018 | World Journal of Gastroenterology2018，24，28： | 13 |
| 14 | A functional C-terminal TRAF3-binding site in MAVS participates in positive and negative regulation of the IFN antiviral response显示文摘病毒的 RNA 的识别由 cytosolic 传感器 retinoic 组织酸可诱导的基因 --(RIG-I ) 我导致表明与类型的产生达到顶点的串联的激活我干扰素(IFN ) 抗病毒的反应。对病毒的病原体的抗病毒、煽动性的回答的发作要求表明改编者, kinases 和 transcriptional 蛋白质到 mitochondrial 的调整空间与时间的招募抗病毒的发信号蛋白质(MAVS ) 。我们以前示威了 serine/threonine kinase IKKε被招募到 MAVS 后面的仙台或小囊的口炎病毒(VSV ) 感染的 C 终端区域,在 Lys500 由 MAVS 的连接 Lys63 的 polyubiquitination 调停了,导致下游的 IFN 发信号的抑制(Paz 等,摩尔房间 Biol, 2009 ) 。在这研究,我们证明 MAVS 的 C 终点在 MAVS 的 aa450-468 区域怀有一个新奇 TRAF3 有约束力的地点。一个一致交往 TRAF 主题(提姆) , 455-PEENEY-460,在这以内,地点为 TRAF3 绑定和 IFN 抗病毒的反应基因的激活被要求,而 TIM 的变化消除 TRAF3 绑定和下游的 IFN 反应。有表示 MAVS 的一个变异提姆的版本的构造的 MAVS −/− 老鼠胚胎成纤维细胞的宪法没能恢复抗病毒的反应或块 VSV 复制,而野类型的 MAVS 重新组成 VSV 复制的抗病毒的抑制。而且, IKKε 的招募;到在经由 Lys500 的 MAVS 的一个邻近的 C 终端地点(aa 468-540 ) , ubiquitination 减少了 TRAF3 绑定和蛋白质稳定性,因此贡献 IKKε调停 IFN 反应关机。这研究证明 MAVS 怀有功能的 C 终端参予 IFN 抗病毒的反应的积极、否定的规定的 TRAF3 有约束力的地点。 | Suzanne Paz Myriam Vilasco Steven J Werden Meztli Arguello Deshanthe Joseph-Pillai Tiejun Zhao Thi Lien-Anh Nguyen Qiang Sun Eliane F Meurs Rongtuan Lin John Hiscott | 2011 | Cell Research2011，21，6： | 12 |
| 15 | 曹雪涛院士科研团队论文荣膺中国百篇最具影响国际学术论文--长链非编码RNA1nc-DC通过STAT3调控人DC的分化和功能显示文摘树突状细胞(DC)是免疫系统中重要的抗原提呈细胞,其成熟和功能状态决定着免疫应答的走向和强度。哺乳动物基因组能够转录产生大量的长链非编码RNA(long noncoding RNA,IncRNA),其在免疫系统中的功能还知之甚少。
曹雪涛院十科研团队王品副教授课题组采用了转录组芯片二代测序高通量筛选方法、RNA-pulldown、ChIP-seq等技术展开了对IncRNA在DC分化和功能中作用的研究,发现并鉴定了特异性高表达于DC的1ncRNA,命名为1nc-DC,其可通过抑制STAT3去磷酸化,从而促进DC分化和功能。该研究成果发表于Science杂志[2014,344(6181):310-313],并于2015年12月被评为“中国百篇最具影响国际学术论文”。 | wang p xue y han y lin l wu c xu s jiang z xu j liu q cao x | 2016 | 中国肿瘤生物治疗杂志2016，23，1： | 10 |
| 16 | Advances in immuno-oncology biomarkers for gastroesophageal cancer:programmed death ligand 1,microsatellite instability,and beyond显示文摘Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer. | Emily M Lin Jun Gong Samuel J Klempner Joseph Chao | 2018 | World Journal of Gastroenterology2018，24，25： | 10 |
| 17 | Serial imaging of human embryonic stem-cell engraftment and teratoma formation in live mouse models显示文摘表示为基于 radiopharmaceutical 的成像为生物体之发光成像或 HSV1 thymidine kinase (HSV1-TK ) 编码任何一个萤火虫酶(fLuc ) 的记者 transgene 的 lentiviral 向量的二种新类型被构造监视人的胚胎的干细胞(hESC ) 在在移植以后的活老鼠的嫁接和增长。任何一个 transgene 的组成的表示没在文化改变 hESCs 的性质。我们下次在 SCID 鼠标监视了 teratomas 的形成到测试(1 ) 是否修改基因的 hESCs 维持他们的发展 pluripotency,并且(2 ) 是否支撑了记者基因表示,允许 noninvasive,在一个活鼠标模型的 hESC 衍生物的整个身体的成像。我们在接种以后从修改基因的房间以及野类型的 hESCs 2-4 月的两种类型观察了 teratoma 形成。用一个光成像系统,从 fLuc-transduced hESCs 的生物体之发光容易在在摸得出的肿瘤能被检测以前,长忍受 teratomas 的老鼠被检测。开发一个 noninvasive 成像方法对诊所更容易地可译,我们也利用了 HSV1-TK 和它的特定的底层, 1-(2 鈥 ? deoxy-2 鈥 ?fluoro- 尾 - D-arabinofuranosyl )-5-[125I]iodouracil ([125I ] FIAU ) ,记者 / 探查对。在全身的管理以后,[125I ] FIAU 是仅仅由编码 transgene 的 HSV1-TK 酶的 phosphorylated 并且在 transduced 以内保留(并且移植) 房间,由单个光子的排放允许敏感、量的成像计算了断层摄影术。象这些那样的 Noninvasive 成像方法可以使我们能在实时接受者以内重复地监视移植人的干细胞的存在和分发在上一通过记者基因的表达式长期。 | Martin G Pomper Holly Hammond Xiaobing Yu Zhaohui Ye Catherine A Foss Doris D Lin James J Fox Linzhao Cheng | 2009 | Cell Research2009，19，3： | 9 |
| 18 | 桑叶多糖对早期断奶仔猪生长性能、腹泻、血液指标和肠道菌群的影响显示文摘研究旨在探讨日粮补充桑叶多糖(MLPs)对早期断奶仔猪生长性能、腹泻、血液生化指标和肠道菌群的影响。共选取(28±2)日龄、体重为(9.18±0.46)kg的'杜洛克×长白×约克夏'杂交断奶仔猪150头,随机分成5个处理组,每组6个重复,每个重复5头猪。饮食处理如下:对照组(CT):基础日粮(BD);低剂量桑叶多糖组(LT):0.3 g·kg-1MLPs+BD;中剂量桑叶多糖组(MT):0.6 g·kg-1MLPs+BD;高剂量桑叶多糖组(HT):0.9 g·kg-1MLPs+BD;抗生素处理组(AT):0.15 g·kg-1金霉素+BD。分别在第0、10、21天的早晨,每头猪空腹测量体重并记录采食量,这些数据用来计算平均日增重(ADG)、平均日采食量(ADFI)和料重比(F/G)。每天两次(上午和下午)对每头仔猪的腹泻状况进行检查并记录。在试验结束时,收集血液样本用于生化分析,并收集盲肠、结肠和直肠内容物进行识别和量化相关的肠道菌群。研究结果表明,MLPs处理组间的日增重、平均日采食量和料重比无显著差异(P>0.05),但低剂量组(LT)、中剂量组(MT)、高剂量组(HT)的平均日采食量高于对照组(CT)和抗生素组(AT)。并且,LT、MT和HT组的料重比低于CT和AT组。与CT和AT组相比,LT、MT和HT组仔猪的腹泻发病率也显著降低(P<0.05)。生化分析表明,MLPs各处理组仔猪的血糖(GLU)水平均显著低于CT或AT组(P<0.05)。MT和HT组血液尿素氮(BUN)水平与CT和AT组存在显著差异(P<0.05),HT组T3水平显著高于CT和AT组(P<0.05)。虽然MLPs各处理组的T4水平与AT组并没有显著差异(P>0.05),但MT组的胰岛素样生长因子Ⅰ(IGF-Ⅰ)和生长激素(GH)水平较CT或AT组均显著升高(P<0.05)。LT、MT和HT 3组在抑制肠道大肠杆菌生长和促进肠道乳酸杆菌和双歧杆菌生长的整体效果上均优于CT和AT组。值得注意的是,与CT和AT组相比,HT组(0.9 g·kg-1MLPs)对抑制肠道大肠杆菌以及促进肠道有益菌群具有更显著效果(P<0.05)。结果表明,日粮添加桑叶多糖可以改善早期断奶仔猪肠道菌群的生态环境,降低腹泻率,提高整体生长性能。 | Zhao X J Lin L Luo Q L Ye M Q Luo G Q Kuang Z S | 2015 | 饲料博览2015，0，7： | 7 |
| 19 | 乳腺癌发生模型MCF10各细胞系中APC基因启动子区甲基化及mRNA表达检测显示文摘目的探讨乳腺癌发生模型MCF10中抑癌基因APC启动子区甲基化状态及其对mRNA表达的影响。方法应用甲基化特异性聚合酶链反应(MSP)及双亚硫酸钠基因测序技术检测MCF10模型的乳腺增生细胞系MCF10A、癌前细胞系MCF10AT、导管内癌细胞系MCF10DC IS.com、浸润癌细胞系MCF10CA1 a、MCF10CA1d、MCF10CA1h及经典乳腺癌细胞系MCF-7和正常乳腺组织中APC基因启动子1A甲基化状态,然后用逆转录聚合酶链反应(RT-PCR)和实时PCR技术检测上述样品的mRNA表达水平。结果在MCF10模型的增生细胞系、癌前细胞系、导管内癌细胞系、浸润癌细胞系中,APC基因启动子1A处于低甲基化状态;与正常乳腺组织相比,各细胞系APC基因mRNA表达无明显减少,MCF10AT、MCF10CA1d、MCF10CA1h、MCF10DC IS.com的mRNA表达分别减少0.27、0.96、1.78、2.70、2.03倍,MCF10A和MCF-7分别增加0.02和0.33倍)。结论MCF10模型中乳腺癌的发生发展过程与APC基因启动子区异常甲基化无关。 | 杨举伦 David Klinkebiel Michael J Boland Lin Tang Judith K Christman | 2006 | 中华病理学杂志2006，35，1： | 7 |
| 20 | Utilizing gastric cancer organoids to assess tumor biology and personalize medicine显示文摘While the incidence and mortality of gastric cancer (GC) have declined due to public health programs, it remains the third deadliest cancer worldwide. For patients with early disease, innovative endoscopic and complex surgical techniques have improved survival. However, for patients with advanced disease, there are limited treatment options and survival remains poor. Therefore, there is an urgent need for more effective therapies. Since novel therapies require extensive preclinical testing prior to human trials, it is important to identify methods to expedite this process. Traditional cancer models are restricted by the inability to accurately recapitulate the primary human tumor, exorbitant costs, and the requirement for extended periods of development time. An emerging in vitro model to study human disease is the patient-derived organoid, which is a three-dimensional system created from fresh surgical or biopsy tissues of a patient’s gastric tumor. Organoids are cultured in plastic wells and suspended in a gelatinous matrix, providing a substrate for extension and growth in all dimensions. They are rapid-growing and highly representative of the molecular landscape, histology, and morphology of the various subtypes of GC. Organoids uniquely model tumor initiation and growth, including steps taken by normal stomach cells to transform into invasive, intestinal-type tumor cells. Additionally, they provide ample material for biobanking and screening novel therapies. Lastly, organoids are a promising model for personalized therapy and warrant further investigation in drug sensitivity studies for GC patients. | Miranda Lin Mei Gao Michael J Cavnar Joseph Kim | 2019 | World Journal of Gastrointestinal Oncology2019，11，7： | 7 |
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