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| 1 | Genetic Variation in Rhizome Lotus(Nelumbo nucifera Gaertn.ssp.nucifera) Germplasms from China Assessed by RAPD Markers显示文摘To estimate genetic variation in rhizome lotus(Nelumbo nucifera Gaertn.ssp.nucifera) germplasms in China,a total of 94 rhizome lotus germplasms collected from 18 provinces in China were assessed.The RAPD(randomly amplified polymorphic DNA) marker was employed.The selected 17 random primers detected 139 polymorphic alleles out of a total 207(67.15%).Nei's gene diversity statistics and region differentiation parameters indicated that all germplasms had a relatively high level of genetic diversity with ne = 1.3202,h = 0.1937,I = 0.2982 and the gene flow among all regions was Nm = 5.5742.The UPGMA dendrogram clustered all 94 germplasms into two clusters:One contained eight commercial cultivars and major landraces,and the other included the wild and some special landraces from five regions,and the PCA analysis exhibited the similar result.Those germplasms from southwestern and eastern China had higher genetic diversity than those from the southern,northern and central China.Predominant proportion of genetic variation(95.61%) was found significant within rather than among(4.39%) regions,as revealed by AMOVA analysis.The data analysis also revealed that the genetic diversity of rhizome lotus germplasms among different regions is positively related to their geographic distances,though it is ambiguous to find the trend from the UPGMA dendrogram and the PCA analysis.A relatively high genetic diversity and gene flow resided in the root lotus germplasms;about 96% of the variation was found within region;accessions from southwest and eastern China have higher genetic diversity than those from the southern,northern and central China. | AN Na GUO Hong-bo KE Wei-dong | 2009 | Agricultural Sciences in China2009，8，1： | 27 |
| 2 | Overexpression of p27^(KIP1)induced cell cycle arrest in G_1 phase and subsequent apoptosis in HCC-9204 cell line显示文摘AIM We have previously reported that inducibleover-expression of Bak may prolong cell cycle inG1 phase and lead to apoptosis in HCC-9204 cells.This study is to investigate whether p27KIP1playsan important role in this process.METHODS In order to elucidate the exactfunction of p27KIP1in this process,a zinc induciblep27KIP1stable transfectant and transient p27KIP1-GFP fusion transfectant were constructed.Theeffects of inducible,p27KIP1on cell growth,cellcycle arrest and apoptosis were examined in themock,control pMD vector,and pMD-KIP1transfected HCC-9204 cells.RESULTS This p27KIP1-GFP transfectant maytransiently express the fusion gene.The cellgrowth was reduced by 35% at 48 h of p27KIP1induction with zinc treatment as determined bytrypan blue exclusion assay.These differencesremained the same after 72 h of p27KIP1expression,p27KIP1caused cell cycle arrest after24 h of induction,with 40% increase in G1population.Prolonged p27KIP1expression in thiscell line induced apoptotic cell death reflected byTUNEL assay.Fourty-eight h and 72 h of p27KIP1expression showed a characteristic DNA ladder onagarose gel electrophoresis. CONCLUSION Bak may induce cell cycle arrest inG1 phase through upregulating expression ofp27KIP1and subsequently lead to apoptosis inHCC-9204 cells.The p27KIP1-GFP fusion proteincan be transiently expressed in HCC-9204 cells.The inducible p27KIP1-expressing cell line providesa model to assess p27KIP1function. | Jiang Li Xin Ke Yang Xin Xin Yu Meng Liang Ge Wen Liang Wang Jie Zhang Yun De Hou Department of Pathology,Fourth Military Medical University,Xi’an 710033,Shaanxi Province,China State Key Laboratory for Molecular Virology and Genetic Engineering,Beijing 100052,China Department of Dermatology,Beijing Hospital,Beijing 100016,China Institute of Radiation Medicine,Beijing 100085,China | 2000 | World Journal of Gastroenterology2000，6，4： | 20 |
| 3 | Precise nanomedicine for intelligent therapy of cancer显示文摘Precise nanomedicine has been extensively explored for efficient cancer imaging and targeted cancer therapy, as evidenced by a few breakthroughs in their preclinical and clinical explorations. Here, we demonstrate the recent advances of intelligent cancer nanomedicine, and discuss the comprehensive understanding of their structure-function relationship for smart and efficient cancer nanomedicine including various imaging and therapeutic applications, as well as nanotoxicity. In particular, a few emerging strategies that have advanced cancer nanomedicine are also highlighted as the emerging focus such as tumor imprisonment, supramolecular chemotherapy, and DNA nanorobot. The challenge and outlook of some scientific and engineering issues are also discussed in future development. We wish to highlight these new progress of precise nanomedicine with the ultimate goal to inspire more successful explorations of intelligent nanoparticles for future clinical translations. | Huabing Chen Zhanjun Gu Hongwei An Chunying Chen Jie Chen Ran Cui Siqin Chen Weihai Chen Xuesi Chen Xiaoyuan Chen Zhuo Chen Baoquan Ding Qian Dong Qin Fan Ting Fu Dayong Hou Qiao Jiang Hengte Ke Xiqun Jiang Gang Liu Suping Li Tianyu Li Zhuang Liu Guangjun Nie Muhammad Ovais Daiwen Pang Nasha Qiu Youqing Shen Huayu Tian Chao Wang Hao Wang Ziqi Wang Huaping Xu Jiang-Fei Xu Xiangliang Yang Shuang Zhu Xianchuang Zheng Xianzheng Zhang Yanbing Zhao Weihong Tan Xi Zhang Yuliang Zhao | 2018 | Science China Chemistry2018，61，12： | 19 |
| 4 | ZmMs30 Encoding a Novel GDSL Lipase Is Essential for Male Fertility and Valuable for Hybrid Breeding in Maize显示文摘Genic male sterility (GMS) is very useful for hybrid vigor utilization and hybrid seed production. Although a large number of GMS genes have been identified in plants, little is known about the roles of GDSL lipase members in anther and pollen development. Here, we report a maize GMS gene, ZmMs30, which encodes a novel type of GDSL lipase with diverged catalytic residues. Enzyme kinetics and activity assays show that ZmMs30 has lipase activity and prefers to substrates with a short carbon chain. ZmMs30 is specifically expressed in maize anthers during stages 7-9. Loss of ZmMs30 function resulted in defective anther cuticle, irregular foot layer of pollen exine, and complete male sterility. Cytological and lipidomics analyses demonstrate that ZmMs30 is crucial for the aliphatic metabolic pathway required for pollen exine formation and anther cuticle development. Furthermore, we found that male sterility caused by loss of ZmMs30 function was stable in various inbred lines with different genetic background, and that it didn't show any negative effect on maize heterosis and production, suggesting that ZmMs30 is valuable for crossbreeding and hybrid seed production. We then developed a new multi-control sterility system using ZmMs30 and its mutant line, and demonstrated it is feasible for generating desirable GMS lines and valu. able for hybrid maize seed production. Taken together, our study sheds new light on the mechanisms of anther and pollen development, and provides a valuable male-sterility system for hybrid breeding maize. | Xueli An Zhenying Dong Youhui Tian Ke Xie Suowei Wu Taotao Zhu Danfeng Zhang Van Zhou Canfang Niu Biao Ma Quancan Hou Jianxi Bao Simiao Zhang Ziwen Li Yanbo Wang Tingwei Yan Xiaojing Sun Yuwen Zhang Jinping Li Xiangyuan Wan | 2019 | Molecular Plant2019，12，3： | 15 |
| 5 | Chinese herbal medicine reduces mortality in patients with severe and critical coronavirus disease 2019: a retrospective cohort study显示文摘This study aimed to evaluate the efficacy of Chinese herbal medicine(CHM)in patients with severe/critical coronavirus disease 2019(COVID-19).In this retrospective study,data were collected from 662 patients with severe/critical COVID-19 who were admitted to a designated hospital to treat patients with severe COVID-19 in Wuhan before March 20,2020.All patients were divided into an exposed group(CHM users)and a control group(non-users).After propensity score matching in a 1:1 ratio,156 CHM users were matched by propensity score to 156 non-users.No significant differences in seven baseline clinical variables were found between the two groups of patients.All-cause mortality was reported in 13 CHM users who died and 36 non-users who died.After multivariate adjustment,the mortality risk of CHM users was reduced by 82.2%(odds ratio 0.178,95%CI 0.076–0.418;P<0.001)compared with the non-users.Secondly,age(odds ratio 1.053,95%CI 1.023–1.084;P<0.001)and the proportion of severe/critical patients(odds ratio 0.063,95%CI 0.028–0.143;P<0.001)were the risk factors of mortality.These results show that the use of CHM may reduce the mortality of patients with severe/critical COVID-19. | Guohua Chen Wen Su Jiayao Yang Dan Luo Ping Xia Wen Jia Xiuyang Li Chuan Wang Suping Lang Qingbin Meng Ying Zhang Yuhe Ke An Fan Shuo Yang Yujiao Zheng Xuepeng Fan Jie Qiao Fengmei Lian Li Wei Xiaolin Tong | 2020 | Frontiers of Medicine2020，14，6： | 10 |
| 6 | Normal Structure and Function of Endothecium Chloroplasts Maintained by ZmMs33-Mediated Lipid Biosynthesis in Tapetal Cells Are Critical for Anther Development in Maize显示文摘Genic male sterility(GMS)is critical for heterosis utilization and hybrid seed production.Although GMS mutants and genes have been studied extensively in plants,it has remained unclear whether chloroplast-associated photosynthetic and metabolic activities are involved in the regulation of anther development.In this study,we characterized the function of ZmMs33/ZmGPAT6,which encodes a member of the glycerol-3-phosphate acyltransferase(GPAT)family that catalyzes the first step of the glycerolipid synthetic pathway.We found that normal structure and function of endothecium(En)chloroplasts maintained by ZmMs33-mediated lipid biosynthesis in tapetal cells are crucial for maize anther development.ZmMs33 is expressed mainly in the tapetum at early anther developmental stages and critical for cell proliferation and expansion at late stages.Chloroplasts in En cells of wild-type anthers function as starch storage sites before stage 10 but as photosynthetic factories since stage 10 to enable starch metabolism and carbohydrate supply.Loss of ZmMs33 function inhibits the biosynthesis of glycolipids and phospholipids,which are major components of En chloroplast membranes,and disrupts the development and function of En chloroplasts,resulting in the formation of abnormal En chloroplasts containing numerous starch granules.Further analyses reveal that starch synthesis during the day and starch degradation at night are greatly suppressed in the mutant anthers,leading to carbon starvation and low energy status,as evidenced by low trehalose-6-phosphate content and a reduced ATP/AMP ratio.The energy sensor and inducer of autophagy,SnRK1,was activated to induce early and excessive autophagy,premature PCD,and metabolic reprogramming in tapetal cells,finally arresting the elongation and development of mutant anthers.Taken together,our results not only show that ZmMs33 is required for normal structure and function of En chloroplasts but also reveal that starch metabolism and photosynthetic activities of En chloroplasts at different developmental stages are essential for normal anther development.These findings provide novel insights for understanding how lipid biosynthesis in the tapetum,the structure and function of En chloroplasts,and energy and substance metabolism are coordinated to maintain maize anther development. | Taotao Zhu Ziwen Li Xueli An Yan Long Xiaofeng Xue Ke Xie Biao Ma Danfeng Zhang Yijian Guan Canfang Niu Zhenying Dong Quancan Hou Lina Zhao Suowei Wu Jinping Li Weiwei Jin Xiangyuan Wan | 2020 | Molecular Plant2020，13，11： | 9 |
| 7 | Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference显示文摘Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics. | Shujuan Yan Ruyi Zhang Ke Wu Jing Cui Shifeng Huang Xiaojuan Ji Liping An Chengfu Yuan Cheng Gong Linghuan Zhang Wei Liu Yixiao Feng Bo Zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Bo Liu Rex C.Haydon Michael J.Lee Russell R.Reid Jennifer Moriatis Wolf Qiong Shi Hue H.Luu Tong-Chuan He Yaguang Weng | 2018 | Genes & Diseases2018，5，2： | 8 |
| 8 | The relationship between acoustic radiation modes and structural modes and its applications显示文摘然而,两个声学的放射模式和结构的模式在忍受结构的声音的地里起一个重要作用很少工作都没为在这些二种模式之间的固有的关系被做。这份报纸集中于在放射模式和结构的模式和它的物理机制之间的关系。首先,为联系放射模式的一个管理方程和结构的模式基于模式的特征被给。用二种模式的对称或反对称的性质,然后,相应关系被介绍。然后,数字例子被给证实理论调查,和它被看了那为在低频率颤动的一块简单地支持的矩形的面板,第一个放射模式是主导的相应于(奇怪,奇怪) 结构的模式;下列放射模式是分别地主导的相应于(甚至,奇怪) ,(奇怪,甚至) ,并且(甚至,弄平) 结构的模式。最后,如此的关系被用于活跃声学的结构的控制并且为活跃控制策略和第二等的力量的安排的设计提供直接帮助。 | LI Shuang CHEN Ke'an | 2007 | Chinese Journal of Acoustics2007，26，2： | 7 |
| 9 | Thermal Expansion of Al Matrix Composites Reinforced with Hybrid Micro-/nano-sized Al_2O_3 Particles显示文摘The thermal expansion behavior of aluminum matrix composites reinforced with hybrid(nanometer and micrometer) Al_2O_3 particles was measured between 100 and 600℃ and compared to theoretical models.The results revealed that the nanoparticle concentration had significant effect on the thermal expansion behavior of the composites.For the composites with lower nanoparticle concentration,their coefficient of thermal expansion(CTE) is determined by a stress relaxation process.While for the composites with higher nanoparticle concentration,their CTE is determined by a percolation process. | Zhibo Lei Ke Zhao Yiguang Wang Linan An | 2014 | Journal of Materials Science & Technology2014，30，1： | 6 |
| 10 | Blood hibernation: a novel strategy to inhibit systemic inflammation and coagulation induced by cardiopulmonary bypass显示文摘背景发炎和凝结亲密地是二大多数的 cross-linked 防卫机制,如果并非所有有机体到损害。在期间心肺绕过(CPB ) ,这二过程被激活并且通过几条普通小径与对方一起交往,它可以导致随后的机关机能障碍。在现在的学习,我们假设了氮的氧化物,前列腺素 E1 (PGE1 ) ,和到全身的发行量的 aprotinin 的增加,在此把冬眠叫作血,将稀释 CPB 导致的发炎和凝结。三十条成年杂种狗同等地被划分成五个组,的方法 anesthetized 并且放了在低体温的 CPB (32 C ) 上。每个组分别地接受了下列处理:(1 ) 40 ppm 的吸入氮的氧化物;(2 ) 20 ng 的静脉内的注入 ????? ??? ???? ￣ ???????? 倠 ???‵?? | ZHOU Jing WU Xiao-dong LIN Ke Raphael C. Lui AN Qi TAO Kai-yu DU Lei LIU Jin | 2010 | Chinese Medical Journal2010，，13： | 5 |
| 11 | Stability and water control of nitrogen foam in bulk phase and porous media显示文摘Foam is widely used in the petroleum industry thanks to its unique properties and performance. Its application to water control in oil wells has received more and more attention. The stability of nitrogen foam was investigated in pressurized equipment and sand pack. The result indicated that with increasing pressure (0-2 MPa) the stability of foam in the pressurized equipment increased linearly. Increased nitrogen injection pressure caused better dispersion of nitrogen-foaming solution in porous media. The initial residual resistance factor to gas was an exponential function of injection pressure, but the residual resistance factor (to gas and liquid) decreased exponentially with time. The half- life of foam in porous media (expressed in residual resistance factor) was much longer than that in bulk phase (expressed in foam height). Pore model analysis indicated that good dispersion in porous media and the presence of thick liquid fi lm during dispersion were the main reasons for high stability. Field test indicated that effective residence of foam in the formation not only resulted in much better heat insulation, but also improved steam stimulation by enhancing steam heating. | Zhao Renbao Hou Yongli Ke Wenqi Yue Xiang'an | 2009 | Petroleum Science2009，6，2： | 5 |
| 12 | 3D printing of Mg-substituted wollastonite reinforcing diopside porous bioceramics with enhanced mechanical and biological performances显示文摘Mechanical strength and its long-term stability of bioceramic scaffolds is still a problem to treat the osteonecrosis of the femoral head.Considering the long-term stability of diopside(DIO)ceramic but poor mechanical strength,we developed the DIO-based porous bioceramic composites via dilute magnesium substituted wollastonite reinforcing and three-dimensional(3D)printing.The experimental results showed that the secondary phase(i.e.10%magnesium substituting calcium silicate;CSM10)could readily improve the sintering property of the bioceramic composites(DIO/CSM10-x,x=0-30)with increasing the CSM10 content from 0%to 30%,and the presence of the CSM10 also improved the biomimetic apatite mineralization ability in the pore struts of the scaffolds.Furthermore,the flexible strength(12.5 -30 MPa)and compressive strength(14-37 MPa)of the 3D printed porous bioceramics remarkably increased with increasing CSM10 content,and the compressive strength of DIO/CSM10-30 showed a limited decay(from 37 MPa to 29 MPa)in the Tris buffer solution for a long time stage(8 weeks).These findings suggest that the new CSM10-reinforced diopside porous constructs possess excellent mechanical properties and can potentially be used to the clinic,especially for the treatment of osteonecrosis of the femoral head work as a bioceramic rod. | Dongshuang He Chen Zhuang Sanzhong Xu Xiurong Ke Xianyan Yang Lei Zhang Guojing Yang Xiaoyi Chen Xiaozhou Mou An Liu Zhongru Gou | 2016 | Bioactive Materials2016，1，1： | 5 |
| 13 | Evaluation of NR2B peptide as subunit vaccines against experimental neuropathic pain显示文摘背景 NR2B 包含 N-methyl-D-aspartate (NMDA ) 受体在神经病的疼痛的容易和维护起一个重要作用。在中央神经系统(CNS ) 的 NR2B 子单元的分离分发可以支持在这个地点有选择地行动的代理人的减少的副作用。因此,我们调查了指向 NMDA 受体的 NR2B 子单元的体液的自体免疫的回答减轻的假设象外部 injury.Methods 老鼠生产的行为一样的疼痛在二星期的间隔与 NR2B 锁眼恋栈者 Hemocyanin (NR2B-KLH ) 皮下地被使免疫三次。在 sera 和脑髓的液体的 NR2B 特定的 IgG titres 被间接 ELISA 决定。在第三免疫以后的七天,臀部的神经(胫骨、普通的小腿侧的神经) 的 3 个终端分支中的 2 个紧被绑扎。行为的测试在外科以后在每隔一天被执行,直到在外科以后的 7 天。腰部的针的绳索(L4-6 ) 在在结扎以后的白天 7 上被移开。在腰部的针的绳索的 NR2B 蛋白质的表示在第二种痘以后用西方的 blotting.Results 被决定,在 sera 的 NR2B 特定的 IgG 被检测是在九只老鼠中的六个的 0.5 g/ml。在第三种痘以后,所有使免疫的老鼠有 2.2 g/ml。在 sera 的 NR2B 特定的 IgG 的 Titres 达到顶点 42 天张贴起始的免疫并且坚持了超过 70 天。没有 NR2B 特定的 IgG 从 PBS 或 KLH group.The 在 sera 被检测行为在 NR2B 组的阀值比在在结扎以后的白天 7 上的 PBS 和 KLH 组的那些显著地高。在在 NR2B 组的 CSF 的 NR2B 特定的 IgG 不能在在针的解剖前的白天 1 上被检测;但是能在在外科以后的白天 7 上被检测。在组 NR2B 的 NR2B 蛋白质的表示比在在 surgery.Conclusion 以后的白天 7 上的 PBS 和 KLH 组 NR2B 肽能对神经病的疼痛被用作一支疫苗的显著地低,它能在腰部的针的绳索与 NR2B 蛋白质的减小被联系。 | WANG Gong-ruing TIAN Yu-ke CHEN Jian-ping TIAN Xu-bi GAO Feng YANG Hui AN Ke MA Guo-ping | 2007 | Chinese Medical Journal2007，，8： | 5 |
| 14 | Diagnosis of Early Esophageal Cancer Based on TCM Tongue Inspection显示文摘Esophageal cancer is a common malignant carcinoma that occurs in the digestive tract and leads to around three million deaths worldwide.Patients commonly present with symptoms,such as dysphagia,cough,hoarseness,and pain in the esophagus.According to researches,smoking,alcohol consumption,exposure to radiation,contaminated food,chronic throat irritation,consumption of extremely hot beverages,genetic mutation,and dystrophia are influential factors in the development of esophageal carcinoma[1]. | SONG An Yi LOU Yan Ni YANG Qian Xi LI Dong Fang SONG Guo Hui HUANG Lai Qiang YUAN Ke Hong JIA Li Qun | 2020 | Biomedical and Environmental Sciences2020，33，9： | 5 |
| 15 | Metabolism Study on Tobacco-specific N-Nitrosamines in Rabbit by Solid-phase Extraction and Liquid Chromatography-electrospray Ionization-mass Spectrometry Method显示文摘Metabolism of four tobacco-specific N-nitrosamines (TSNAs), N′-nitrosonornicotine (NNN), N′-nitrosoanatabine (NAT), N′-nitrosoanabasine (NAB) and 4-(methyl nitrosamino)-1- (3-pyridyl)-1-butanone (NNK) was studied by solid-phase extraction (SPE) and liquid chromato- graphy-electrospray ionization-mass spectrometry (LC-ESI-MS). SPE and LC-ESI-MS method was evaluated to be rapid, simple, sensitive and selective for analysis of TSNAs in rabbit serum. The doses of TSNAs administrated were 4.666 μgkg and 11.665 μgkg according to different levels in cigarettes. Metabolic curves of four TSNAs and 4-(methyl nitrosamino)-1-(3-pyridyl)- 1-butanone (NNAL), the metabolite of NNK, were obtained. | Jian Xun ZHANG Chen Chen LI Zheng CHEN Zhi Hua RAO Da Wei WEN Ke An LI Hu Wei LIU | 2005 | Chinese Chemical Letters2005，16，12： | 5 |
| 16 | Analysis of 72 patients with colorectal high-grade neuroendocrine neoplasms from three Chinese hospitals显示文摘BACKGROUND Colorectal high-grade neuroendocrine neoplasms(HGNENs)are rare and constitute less than 1%of all colorectal malignancies.Based on their morphological differentiation and proliferation identity,these neoplasms present heterogeneous clinicopathologic features.Opinions regarding treatment strategies for and improvement of the clinical outcomes of these patients remain controversial.AIM To delineate the clinicopathologic features of and explore the prognostic factors for this rare malignancy.METHODS This observational study reviewed the data of 72 consecutive patients with colorectal HGNENs from three Chinese hospitals between 2000 and 2019.The clinicopathologic characteristics and follow-up data were carefully collected from their medical records,outpatient reexaminations,and telephone interviews.A survival analysis was conducted to evaluate their outcomes and to identify the prognostic factors for this disease.RESULTS According to the latest recommendations for the classification and nomenclature of colorectal HGNENs,61(84.7%)patients in our cohort had poorly differentiated neoplasms,which were categorized as high-grade neuroendocrine carcinomas(HGNECs),and the remaining 11(15.3%)patients had well differentiated neoplasms,which were categorized as high-grade neuroendocrine tumors(HGNETs).Most of the neoplasms(63.9%)were located at the rectum.More than half of the patients(51.4%)presented with distant metastasis at the date of diagnosis.All patients were followed for a median duration of 15.5 mo.In the entire cohort,the median survival time was 31 mo,and the 3-year and 5-year survival rates were 44.3%and 36.3%,respectively.Both the univariate and multivariate analyses demonstrated that increasing age,HGNEC type,and distant metastasis were risk factors for poor clinical outcomes.CONCLUSION Colorectal HGNENs are rare and aggressive malignancies with poor clinical outcomes.However,patients with younger age,good morphological differentiation,and without metastatic disease can have a relatively favorable prognosis. | Zhi-Jie Wang Ke An Rui Li Wei Shen Man-Dula Bao Jin-Hua Tao Jia-Nan Chen Shi-Wen Mei Hai-Yu Shen Yun-Bin Ma Fu-Qiang Zhao Fang-Ze Wei Qian Liu | 2019 | World Journal of Gastroenterology2019，25，34： | 5 |
| 17 | Dihydroartemisinin suppresses renal fibrosis in mice by inhibiting DNA-methyltransferase 1 and increasing Klotho显示文摘Renal fibrosis is an unavoidable end result of all forms of progressive chronic kidney diseases(CKD).Discovery of efficacious drugs against renal fibrosis is in crucial need.In a preliminary study we found that a derivative of artemisinin,dihydroartemisinin(DHA),exerted strong renoprotection,and reversed renal fibrosis in adenine-induced CKD mouse model.In this study we investigated the anti-fibrotic mechanisms of DHA,particularly its specific target in renal cells.Renal fibrosis was induced in mice by unilateral ureteral obstruction(UUO)or oral administration of adenine(80 mg·kg^(-1)),the mice received DHA(30 mg·kg^(-1)·d^(-1),i.g.)for 14 or 21 days,respectively.We showed that DHA administration markedly attenuated the inflammation and fibrotic responses in the kidneys and significantly improved the renal function in both the renal fibrosis mouse models.In adenine-treated mice,DHA was more effective than 5-azacytidine against renal fibrosis.The anti-fibrotic effects of DHA were also observed in TGF-β1-treated HK-2 cells.In order to determine the target protein of DHA,we conducted pull-down technology coupled with shotgun proteomics using a small-molecule probe based on the structure of DHA(biotin-DHA).As a results,DNA methyltransferase 1(DNMT1)was identified as the anti-fibrotic target of DHA in 3 different types of renal cell lines(HK-2,HEK293 and 3T3).We demonstrated that DHA directly bound to Asn 1529 and Thr 1528 of DNMT1 with a Kd value of 8.18μM.In primary mouse renal tubular cells,we showed that DHA(10μM)promoted DNMT1 degradation via the ubiquitin–proteasome pathway.DHA-reduced DNMT1 expression effectively reversed Klotho promoter hypermethylation,which led to the reversal of Klotho protein loss in the kidney of UUO mice.This subsequently resulted in inhibition of the Wnt/β-catenin and TGF-β/Smad signaling pathways and consequently conferred renoprotection in the animals.Knockdown of Klotho abolished the renoprotective effect of DHA in UUO mice.Our study reveals a novel pharmacological activity for DHA,i.e.,renoprotection.DHA exhibits this effect by targeting DNMT1 to reverse Klotho repression.This study provides an evidence for the possible clinical application of DHA in the treatment of renal fibrosis. | Wei Zhou Min-min Chen Hui-ling Liu Zi-lin Si Wen-hui Wu Hong Jiang Lin-xiao Wang Nosratola D.Vaziri Xiao-fei An Ke Su Cheng Chen Ning-hua Tan Zhi-hao Zhang | 2022 | Acta Pharmacologica Sinica2022，43，10： | 4 |
| 18 | Microseismic monitoring and numerical simulation on the stability of high-steep rock slopes in hydropower engineering显示文摘For high-steep slopes in hydropower engineering, damage can be induced or accumulated due to a series of human or natural activities, including excavation, dam construction, earthquake, rainstorm, rapid rise or drop of water level in the service lifetime of slopes. According to the concept that the progressive damage(microseismicity) of rock slope is the essence of the precursor of slope instability, a microseismic monitoring system for high-steep rock slopes is established. Positioning accuracy of the monitoring system is tested by fixed-position blasting method. Based on waveform and cluster analyses of microseismic events recorded during test, the tempo-spatial distribution of microseismic events is analyzed.The deformation zone in the deep rock masses induced by the microseismic events is preliminarily delimited. Based on the physical information measured by in situ microseismic monitoring, an evaluation method for the dynamic stability of rock slopes is proposed and preliminarily implemented by combining microseismic monitoring and numerical modeling. Based on the rock mass damage model obtained by back analysis of microseismic information, the rock mass elements within the microseismic damage zone are automatically searched by finite element program. Then the stiffness and strength reductions are performed on these damaged elements accordingly. Attempts are made to establish the correlation between microseismic event, strength deterioration and slope dynamic instability, so as to quantitatively evaluate the dynamic stability of slope. The case studies about two practical slopes indicate that the proposed method can reflect the factor of safety of rock slope more objectively. Numerical analysis can help to understand the characteristics and modes of the monitored microseismic events in rock slopes. Microseismic monitoring data and simulation results can be used to mutually modify the sensitive rock parameters and calibrate the model. Combination of microseismic monitoring and numerical simulation provides a more objective basis for the numerical model and parameters and a solid mechanical foundation for the microseismic monitoring. | Chun’an Tang Lianchong Li Nuwen Xu Ke Ma | 2015 | Journal of Rock Mechanics and Geotechnical Engineering2015，7，5： | 4 |
| 19 | Ionic Liquid-salt Aqueous Two-phase System, a Novel System for theExtraction of Abused Drugs显示文摘A 1-butyl-3-methylimidazolium chloride-salt aqueous two-phase system was studied on extraction of abused drugs. The effects of sorts of salts, temperature, concentration of salt and drugs on system were investigated systematically. A satisfactory extraction efficiency of 93% was obtained for papaverine while that of morphine was 65%. The extraction mechanism was primarily discussed. | She Hong LI Chi Yang HE Hu Wei LIU Ke An LI Feng LIU | 2005 | Chinese Chemical Letters2005，16，8： | 4 |
| 20 | The development of a sensitive fluorescent protein-based transcript reporter for high throughput screening of negative modulators of lncRNAs显示文摘While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs),which are critical components of epigenetic regulation.lncRNAs are emerging as critical regulators of gene expression and genomic stability.However,it remains largely unknown about how lncRNAs are regulated.Here,we develop a highly sensitive and dynamic reporter that allows us to identify and/or monitor negative modulators of lncRNA transcript levels in a high throughput fashion.Specifically,we engineer a fluorescent fusion protein by fusing three copies of the PEST destruction domain of mouse ornithine decarboxylase(MODC)to the C-terminal end of the codon-optimized bilirubin-inducible fluorescent protein,designated as dBiFP,and show that the dBiFP protein is highly destabilized,compared with the commonly-used eGFP protein.We further demonstrate that the dBiFP signal is effectively down-regulated when the dBiFP and mouse lncRNA H19 chimeric transcript is silenced by mouse H19-specific siRNAs.Therefore,our results strongly suggest that the dBiFP fusion protein may serve as a sensitive and dynamic transcript reporter to monitor the inhibition of lncRNAs by microRNAs,synthetic regulatory RNA molecules,RNA binding proteins,and/or small molecule inhibitors so that novel and efficacious inhibitors targeting the epigenetic circuit can be discovered to treat human diseases such as cancer and other chronic disorders. | Zongyue Zeng Bo Huang Shifeng Huang Ruyi Zhang Shujuan Yan Xinyi Yu Yi Shu Chen Zhao Jiayan Lei Wenwen Zhang Chao Yang Ke Wu Ying Wu Liping An Xiaojuan Ji Cheng Gong Chengfu Yuan Linghuan Zhang Wei Liu Yixiao Feng Bo Zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Rex C.Haydon Hue H.Luu Lan Zhou Russell R.Reid Tong-Chuan He Xingye Wu | 2018 | Genes & Diseases2018，5，1： | 4 |
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