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| 1 | aunalysis of the Genome Sequence of the Medicinal Plant Salvia miltiorrhiza显示文摘 | Haibin Xu Jingyuan Song Hongmei Luo Yujun Zhang Qiushi Li Yingjie Zhu Jiang Xu Ying Li Chi Song Bo Wang Wei Sun Guoan Shen Xin Zhang Jun Qian Aijia Ji Zhichao Xu Xiang Luo Liu He Chuyuan Li Chao Sun Haixia Yah Guanghong Cui Xiwen Li Xian 'en Li Jianhe Wei Juyan Liu Yitao Wang Alice Hayward David Nelson Zemin Ning Reuben J. Peters Xiaoquan Qi Shilin Chen | 2016 | Molecular Plant2016，9，6： | 70 |
| 2 | A Novel QTL qTGW3 Encodes the GSK3/ SHAGGY-Like Kinase OsGSK5/OsSK41 that Interacts with OsARF4 to Negatively Regulate Grain Size and Weight in Rice显示文摘谷物尺寸和形状在米饭是谷物重量和产量的重要决定因素。这里,我们报导一个新主要量的特点在米饭的地点(QTL ) , qTGW3,那种控制谷物尺寸和重量。这个地点, qTGW3,编码 OsSK41 (也作为 OsGSK5 知道) , GLYCOGEN SYNTHASE KINASE 3/SHAGGY-like 家庭的一个成员。带 OsSK41 的 loss-of-function 等位基因的瑞斯 near-isogenic 线增加了谷物长度和重量。我们证明那 OsSK41 交往与并且 phosphorylates 植物生长素反应因素 4 (OsARF4 ) 。有 OsARF4 的 OsSK41 的合作表示在米饭原物增加 OsARF4 的累积。OsARF4 的功能的损失导致更大的米饭谷物。定序 RNA 分析建议 OsARF4 和 OsSK41 镇压下游的基因的一个普通集合的表示, ? 包括一些植物生长素应答的基因,在米饭谷物开发期间。在 qTGW3 的 OsSK41 的 loss-of-function 形式代表没被指向的基因编辑或 QTL 节节上升广泛地在 OsSK41 功能的米饭 breeding.?Suppression 利用了的稀罕等位基因提高米饭谷物尺寸和重量。因此,我们的学习在米饭谷物开发揭示 OsSK41 的重要角色 ?? 并且在另外的谷物庄稼在米饭并且也许为谷物产量的基因改进提供新候选人基因。 | Zejun Hu Sun-Jie Lu Mei-Jing Wang Haohua He Le Sun Hongru Wang Xue-Huan Liu Ling Jiang Jing-Liang sun Xiaoyun Xin Wei Kong Chengcai Chu Hong-Wei Xue Jinshui Yang Xiaojin Luo Jian-Xiang Liu | 2018 | Molecular Plant2018，11，5： | 47 |
| 3 | Inhibition on the production of collagen type Ⅰ, Ⅲ of activated hepatic stellate cells by antisense TIMP-1 recombinant plasmid显示文摘AIM: To investigate the inhibition effects on the productionof collagen type I, Ⅲ secreted by activated rat hepatic stellatecells (rHSCs) by antisense tissue inhibitors of metalloproteinase1 (TIMP-1) recombinant plasmid through elevating interstitialcollagenase activity.METHODS: rHSCs were extracted from normal rat liverby pronase and collagenase digestion and purified bycentrifugal elutriation, and were cultured on plastic dishesuntil they were activated to a myofibroblastic phenotypeafter 7-10 days. RT-Nest-PCR and gene recombinanttechniques were used to construct the rat antisense TIMP-1 recombinant plasmids which can express in eucaryoticcells. The recombinant plasmid and the pcDNA3 emptyplasmid were transfected in rHSCs by Effectene (QIAGEN)separately. Cells were selected after growing in DMEMcontaining 400 μg/ml G418 for 2-3 weeks. Expression ofexogenous gene was assessed by Northern blot, andexpression oflIMP-1 in rHSCs was determined by Northernblot and Western blot. We tested the interstitial collagenaseactivity with FITC-labled type I collagen as substrate.Ultimately, we quantified the type Ⅰ, Ⅲ collagen byWestern blot.RESULTS: The exogenous antisense TIMP-1 recombinantplasmid could be expressed in rHSCs well, which couldblock the expression of TIMP-1 greatly, the ratio of TIMP-1/GAPDH was 0.67, 2.41, and 2.97 separately at mRNAlevel (P<0.05); the ratio of TIMP-1/β-actin was 0.31, 0.98and 1.32 separately at protein level (P<0.05); It mightelevate active and latent interstitial collagenase activity,the collagenase activity was 0.3049, 0.1411 and 0.1196respectively. (P<0.05), which led to promotion thedegradation of type Ⅰ, Ⅲ collagen, the ratio of collagen I/β-actin was 0.63, 1.78 and 1.92 separately (P<0.05); andthe ratio of collagen Ⅲ/β-actin was 0.59, 1.81 and 1.98separately (P<0.05).CONCLUSION: These data shows that the antisense TIMP-1 recombinant plasmid has the inhibitory effects on theproduction of type Ⅰ, Ⅲ collagens secreted by activatedrHSCs in vitro. It could be a novel method to reverse hepaticfibrosis in the future. | Wen-Bin Liu Chang-Qing Yang Wei Jiang Yi-Qing Wang Jing-Sheng Guo Bo-Ming He Ji-Yao Wang Division of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai 200032, China | 2003 | World Journal of Gastroenterology2003，9，2： | 42 |
| 4 | Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation显示文摘ABSTRACTHuman placenta-derived mononuclear cells (MNC) were isolated by a Percoll density gradient and cultured in mesen-chymal stem cell (MSC) maintenance medium. The homogenous layer of adherent cells exhibited a typical fibroblast-like morphology, a large expansive potential, and cell cycle characteristics including a subset of quiescent cells. In vitrodifferentiation assays showed the tripotential differentiation capacity of these cells toward adipogenic, osteogenic andchondrogenic lineages. Flow cytometry analyses and immunocytochemistry stain showed that placental MSC was ahomogeneous cell population devoid of hematopoietic cells, which uniformly expressed CD29, CD44, CD73, CD105,CD166, laminin, fibronectin and vimentin while being negative for expression of CD31, CD34, CD45 and α-smoothmuscle actin. Most importantly, immuno-phenotypic analyses demonstrated that these cells expressed class I majorhistocompatibility complex (MHC-I), but they did not express MHC-II molecules. Additionally these cells could sup-press umbilical cord blood (UCB) lymphocytes proliferation induced by cellular or nonspecific mitogenic stimuli. Thisstrongly implies that they may have potential application in allograft transplantation. Since placenta and UCB arehomogeneous, the MSC derived from human placenta can be transplanted combined with hematopoietic stem cells(HSC) from UCB to reduce the potential graft -versus-host disease (GVHD) in recipients. | Chang Dong LI Wei Yuan ZHANG He Lian LI Xiao Xia JIANG Yi ZHANG Pei Hsien TANG Ning MAO | 2005 | Cell Research2005，15，7： | 36 |
| 5 | Rhizospheric microbial communities are driven by Panax ginseng at different growth stages and biocontrol bacteria alleviates replanting mortality显示文摘The cultivation of Panax plants is hindered by replanting problems, which may be caused by plantdriven changes in the soil microbial community. Inoculation with microbial antagonists may efficiently alleviate replanting issues. Through high-throughput sequencing, this study revealed that bacterial diversity decreased,whereas fungal diversity increased, in the rhizosphere soils of adult ginseng plants at the root growth stage under different ages. Few microbial community, such as Luteolibacter, Cytophagaceae, Luteibacter, Sphingomonas,Sphingomonadaceae, and Zygomycota, were observed; the relative abundance of microorganisms, namely,Brevundimonas, Enterobacteriaceae, Pandoraea, Cantharellales, Dendryphion, Fusarium, and Chytridiomycota,increased in the soils of adult ginseng plants compared with those in the soils of 2-year-old seedlings. Bacillus subtilis 50-1, a microbial antagonist against the pathogenic Fusarium oxysporum, was isolated through a dual culture technique. These bacteria acted with a biocontrol efficacy of 67.8%. The ginseng death rate and Fusarium abundance decreased by 63.3% and 46.1%, respectively, after inoculation with B. subtilis 50-1. Data revealed that microecological degradation could result from ginseng-driven changes in rhizospheric microbial communities;these changes are associated with the different ages and developmental stages of ginseng plants. Biocontrol using microbial antagonists alleviated the replanting problem. | Linlin Dong Jiang Xu Lianjuan Zhang Ruiyang Cheng Guangfei Wei He Su Juan Yang Jun Qian Ran Xu Shilin Chen | 2018 | Acta Pharmaceutica Sinica B2018，8，2： | 27 |
| 6 | Lung transplantation in China between 2015 and 2018显示文摘Background:Lung transplantation(LT)has been demonstrated as the only effective therapy for patients with end-stage lung diseases.Increasing listed lung transplant candidates and expanding volumes of lung transplant centers across China require wellorganized programs and registry data collection based on the large population.This study aimed to summarize and analyze the data of LT development in China.Methods:We retrospectively collected and analyzed data from the China Lung Transplantation Registry(CLuTR).Key data were reported from the registry with transplant types,indications,donor and recipient characteristics,outcomes and survival.The survival<30 days,1-year and 3-year survival rates were estimated with risk factors identified.Results:CLuTR contained data from 1053 lung transplants performed through January 1st,2015 to December 31st,2018 reported by 18 registered transplant centers.The largest category of diagnosis before transplantation was idiopathic interstitial pneumonitis.The total<30 days,1-year and 3-year survival rates in CLuTR were 81.45%,70.11%,and 61.16%with discrepancy by indications.Large proportion of recipients who were more than 60 years old required higher standard of care.Infection-related complications resulted in more death events in the early post-surgery periods.New York Heart Association grading at listing,extra-corporeal membrane oxygenation usage peri-transplantation,allograft dysfunction(primary graft dysfunction>Grade 0),renal insufficiency(estimated glomerular filtration rate<60 mL min_11.73 m^2),were independently associated with a higher risk for 3-year mortality in the entire cohort.Conclusions:Facing more end-stage of lung diseases and comorbidities,this study analyzed the outcomes and survival of LT recipients in China.Further prospectively stratified analyses with longer follow-up will be needed. | Chun-Xiao Hu Wen-Hui Ghen Jian-Xing He Ge-Ning Jiang Xiao-Shan Li Dong Wei Bo Wu Ji Zhang Chen Wang Jing-Yu Chen | 2019 | Chinese Medical Journal2019，，23： | 25 |
| 7 | 电针和经皮穴位电刺激技术在生殖医学中的应用:专家共识(英文)显示文摘本文从传统针刺治疗不孕症的选穴依据与现代电针/经皮穴位电刺激技术的相关原理着手,从最优刺激参数选择、穴位辨证、疗程与治疗次数的确定及基本原理等方面阐述了电针/经皮穴位电刺激技术在多囊卵巢综合症、取卵镇痛、卵巢储备功能降低、胚胎移植以及男性少/弱精症等生殖领域中的具体应用。首次对电针/经皮穴位电刺激技术在生殖领域优势病种中的应用进行了系统的分析和总结,在最优刺激参数选择、穴位辨证、疗程与治疗次数的确定等方面提出了一系列专家共识,并为临床实践提供了指导意见和理论依据。 | Fan QU Rong LI Wei SUN Ge LIN Rong ZHANG Jing YANG Li TIAN Guo-gang XING Hui JIANG Fei GONG Xiao-yan LIANG Yan MENG Jia-yin LIU Li-ying ZHOU Shu-yu WANG Yan WU Yi-jing HE Jia-yu YE Song-ping HAN Ji-sheng HAN | 2017 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2017，18，3： | 24 |
| 8 | The Chinese Society of Clinical Oncology(CSCO)clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma显示文摘Nasopharyngeal carcinoma(NPC)is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa.To develop these comprehensive guidelines for the diagnosis and management of NPC,the Chinese Society of Clinical Oncology(CSCO)arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write,discuss,and revise the guidelines.Based on the findings of evidencebased medicine in China and abroad,domestic experts have iteratively developed these guidelines to provide proper management of NPC.Overall,the guidelines describe the screening,clinical and pathological diagnosis,staging and risk assessment,therapies,and follow-up of NPC,which aim to improve the management of NPC. | Ling-Long Tang Yu-Pei Chen Chuan-Ben Chen Ming-Yuan Chen Nian-Yong Chen Xiao-Zhong Chen Xiao-Jing Du Wen-Feng Fang Mei Feng Jin Gao Fei Han Xia He Chao-Su Hu De-sheng Hu Guang-Yuan Hu Hao Jiang Wei Jiang Feng Jin Jin-Yi Lang Jin-Gao Li Shao-Jun Lin Xu Liu Qiu-Fang Liu Lin Ma Hai-Qiang Mai Ji-Yong Qin Liang-Fang Shen Ying Sun Pei-Guo Wang Ren-Sheng Wang Ruo-Zheng Wang Xiao-Shen Wang Ying Wang Hui Wu Yun-Fei Xia Shao-Wen Xiao Kun-Yu Yang Jun-Lin Yi Xiao-Dong Zhu Jun Ma | 2021 | Cancer Communications2021，41，11： | 22 |
| 9 | Cationic nanocarriers induce cell necrosis through impairment of Na^+/K^+-ATPase and cause subsequent inflammatory response显示文摘有积极表面费用的 Nanocarriers 以他们限制了他们的临床的应用的毒性著名。位于他们的毒性下面的机制例如煽动性的反应的正式就职,仍然保持大部分未知。在我们发现了 cationic nanocarriers 的那注射的现在的学习,包括 cationic liposomes, PEI,和 chitosan,导致了坏死的房间的快速的外观。cationic nanocarriers 导致的房间坏死依赖于他们的积极表面费用,但是不要求 RIP1 和 Mlkl。相反,细胞内部的 Na + 超载被发现伴随房间死亡。在文化媒介或有 Na +/K+-ATPase 阳离子绑定地点禁止者 ouabain 的房间的预告的处理的 Na + 的弄空,从房间坏死的保护的房间。而且,有 cationic nanocarriers 的处理在 vitro 并且在 vivo 禁止了 Na +/K+-ATPase 活动。计算模拟证明 cationic 搬运人能与 Na +/K+-ATPase 的阳离子绑定地点交往。有 ouabain 的小剂量的老鼠 pretreated 在 cationic nanocarriers 的致命的剂量的注射以后显示出改进幸存。进一步的分析建议 cationic nanocarriers 和 mitochondrial DNA 的产生的漏导致的那房间坏死能在 vivo 触发严重发炎,它被包含 TLR9 并且 MyD88 发信号的一条小径调停。一起拿,我们的结果揭示由此的新奇机制 cationic nanocarriers 通过和 mitochondrial 的随后的暴露的和 Na +/K+-ATPase, 的相互作用导致尖锐房间坏死是的联系损坏的分子的模式调停的一个关键事件煽动性的回答。我们的学习为评估 nanocarriers 的 biocompatibility 并且为药交货设计更好、更安全的有重要含意。 | Xiawei Wei Bin Shao Zhiyao He Tinghong Ye Min Luo Yaxiong Sang Xiao Liang Wei Wang Shuntao Luo Shengyong Yang Shuang Zhang Changyang Gong Maling Gou Hongxing Deng Yinglan Zhao Hanshuo Yang Senyi Deng Chengjian Zhao Li Yang Zhiyong Qian Jiong Li Xun Sun Jiahuai Han Chengyu Jiang Min Wu Zhirong Zhang | 2015 | Cell Research2015，25，2： | 21 |
| 10 | Blocking the recruitment of naive CD4+ T cells reverses immunosuppression in breast cancer显示文摘渗入肿瘤的 Tregs 的起源,肿瘤免疫力的抑制的批评调停人,是不清楚的。这里,,我们证明在人的乳癌的渗入肿瘤的天真的 CD4 + T 房间和 Tregs 有重叠 TCR 全部剧目几乎别与传播 Tregs 重叠,建议 intratumoral Tregs 主要在 situ 而非从招募的 Tregs 从天真的 T 房间发展。而且,许多天真的 CD4 + T 房间和 Tregs 密切被相关,两个显示的穷人为乳癌病人的预后。天真的 CD4 + T 房间与许多生产 CCL18 巨噬细胞成比例遵守肿瘤片。而且,采纳地转移的人的天真的 CD4 + T 房间以一种 CCL18 依赖的方式渗入人的乳癌 orthotopic 异种皮移植。在在人性化的鼠标的人的乳癌异种皮移植,由将 PITPNM3 的表达式击倒堵住天真的 CD4 + T 房间的招募进肿瘤, CCL18 受体,显著地减少 intratumoral Tregs 并且禁止肿瘤前进。这些调查结果建议那个乳房渗入肿瘤的 Tregs 从在 situ 区分进 Tregs 的传播天真的 CD4 + T 房间的趋化性产生。由防碍 CCL18 的 PITPNM3 识别禁止天真的 CD4 + T 房间招募进肿瘤可以是为 anticancer 免疫疗法的吸引人的策略。 | Shicheng Su Jianyou Liao Jiang Liu Di Huang Chonghua He Fei Chen LinBing Yang Wei Wu Jianing Chen Ling Lin Yunjie Zeng Nengtai Ouyang Xiuying Cui Herui Yao Fengxi Su Jian-dong Huang Judy Lieberman Qiang Liu Erwei Song | 2017 | Cell Research2017，27，4： | 19 |
| 11 | Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis显示文摘Background:Critical patients with the coronavirus disease 2019(COVID-19),even those whose nucleic acid test results had turned negative and those receiving maximal medical support,have been noted to progress to irreversible fatal respiratory failure.Lung transplantation(LT)as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.Methods:From February 10 to March 10,2020,three male patients were urgently assessed and listed for transplantation.After conducting a full ethical review and after obtaining assent from the family of the patients,we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.Results:Two of the three recipients survived post-LT and started participating in a rehabilitation program.Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved.The pathological results of the explanted lungs were concordant with the critical clinical manifestation,and provided insight towards better understanding of the disease.Government health affair systems,virology detection tools,and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.Conclusions:LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis.If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT,LT provided the final option for these patients to avoid certain death,with proper protection of transplant surgeons and medical staffs.By ensuring instant seamless care for both patients and medical teams,the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained. | Jing-Yu Chen Kun Qiao Feng Liu Bo Wu Xin Xu Guo-Qing Jiao Rong-Guo Lu Hui-Xing Li Jin Zhao Jian Huang Yi Yang Xiao-Jie Lu Jia-Shu Li Shu-Yun Jiang Da-Peng Wang Chun-Xiao Hu Gui-Long Wang Dong-Xiao Huang Guo-Hui Jiao Dong Wei Shu-Gao Ye Jian-An Huang Li Zhou Xiao-Qin Zhang Jian-Xing He | 2020 | Chinese Medical Journal2020，，12： | 19 |
| 12 | Wnt5a participates in hepatic stellate cell activation observed by gene expression profile and functional assays显示文摘AIM:To identify differentially expressed genes in quiescent and activated hepatic stellate cells(HSCs)and explore their functions.METHODS:HSCs were isolated from the normal Sprague Dawley rats by in suit perfusion of collagenase and pronase and density Nycodenz gradient centrifugation.Total RNA and mRNA of quiescent HSCs,and cultureactivated HSCs were extracted,quantified and reversely transcripted into cDNA.The global gene expression profile was analyzed by microarray with Affymetrix rat genechip.Differentially expressed genes were annotated with Gene Ontology(GO)and analyzed with Kyoto encyclopedia of genes and genomes(KEGG)pathway using the Database for Annotation,Visualization and Integrated Discovery.Microarray data were validated by quantitative real-time polymerase chain reaction(qRTPCR).The function of Wnt5a on human HSCs line LX-2 was assessed with lentivirus-mediated Wnt5a RNAi.The expression of Wnt5a in fibrotic liver of a carbon tetrachloride(CCl4)-induced fibrosis rat model was also analyzed with Western blotting.RESULTS:Of the 28 700 genes represented on this chip,2566 genes displayed at least a 2-fold increase or decrease in expression at a P<0.01 level with a false discovery rate.Of these,1396 genes were upregulated,while 1170 genes were downregulated in culture-activated HSCs.These differentially expressed transcripts were grouped into 545 GO based on biological process GO terms.The most enriched GO terms included response to wounding,wound healing,regulation of cell growth,vasculature development and actin cytoskeleton organization.KEGG pathway analysis revealed that Wnt5a signaling pathway participated in the activation of HSCs.Wnt5a was significantly increased in cultureactivated HSCs as compared with quiescent HSCs.qRTPCR validated the microarray data.Lentivirus-mediated suppression of Wnt5a expression in activated LX-2 resulted in significantly impaired proliferation,downregulated expressions of typeⅠcollagen and transforming growth factor-β1.Wnt5a was upregulated in the fibrotic liver of a CCl4-induced fibrosis rat model.CONCLUSION:Wnt5a is involved in the activation of HSCs,and it may serve as a novel therapeutic target in the treatment of liver fibrosis. | Wu-Jun Xiong Li-Juan Hu Yi-Cheng Jian Li-Jing Wang Ming Jiang Wei Li Yi He | 2012 | World Journal of Gastroenterology2012，18，15： | 17 |
| 13 | A phase Ⅱ study of paclitaxel and nedaplatin as front-line chemotherapy in Chinese patients with metastatic esophageal squamous cell carcinoma显示文摘AIM:To evaluate the efficacy and safety of paclitaxelnedaplatin combination as a front-line regimen in Chinese patients with metastatic esophageal squamous cell carcinoma(ESCC).METHODS:A two-center,open-label,single-arm phaseⅡstudy was designed.Thirty-nine patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events.Patients received 175mg/m2of paclitaxel over a 3 h infusion on 1 d,followed by nedaplatin 80 mg/m2in a 1 h infusion on 2 d every3 wk until the documented disease progression,unac-ceptable toxicity or patient’s refusal.RESULTS:Of the 36 patients assessable for efficacy,there were 2 patients(5.1%)with complete response and 16 patients(41.0%)with partial response,giving an overall response rate of 46.1%.The median progression-free survival and median overall survival for all patients were 7.1 mo(95%CI:4.6-9.7)and 12.4 mo(95%CI:9.5-15.3),respectively.Toxicities were moderate and manageable.Grade 3/4 toxicities included neutropenia(15.4%),nausea(10.3%),anemia(7.7%),thrombocytopenia(5.1%),vomiting(5.1%)and neutropenia fever(2.6%).CONCLUSION:The combination of paclitaxel and nedaplatin is active and well tolerated as a first-line therapy for patients with metastatic ESCC. | Yi-Fu He Chu-Shu Ji Bing Hu Ping-Sheng Fan Chang-Lu Hu Feng-Shou Jiang Jian Chen Lei Zhu Yi-Wei Yao Wei Wang | 2013 | World Journal of Gastroenterology2013，19，35： | 16 |
| 14 | Small molecule inhibitors reveal allosteric regulation of USP14 via steric blockade显示文摘The ubiquitin system is important for drug discovery,and the discovery of selective small-molecule inhibitors of deubiquitinating enzymes (DUBs) remains an active yet extremely challenging task. With a few exceptions,previously developed inhibitors have been found to bind the evolutionarily conserved catalytic centers of DUBs,resulting in poor selectivity. The small molecule IU1 was the first-ever specific inhibitor identified and exhibited surprisingly excellent selectivity for USP14 over other DUBs. However,the molecular mechanism for this selectivity was elusive. Herein,we report the high-resolution co-crystal structures of the catalytic domain of USP14 bound to IU1 and three IU1 derivatives. All the structures of these complexes indicate that IU1 and its analogs bind to a previously unknown steric binding site in USP14,thus blocking the access of the C-terminus of ubiquitin to the active site of USP14 and abrogating USP14 activity. Importantly,this steric site in USP14 is very unique,as suggested by structural alignments of USP14 with several known DUB X-ray structures. These results,in conjunction with biochemical characterization,Indicate a coherent steric blockade mechanism for U5P14 inhibition by compounds of the IU series. In light of the recent report of steric blockade of USP7 by FT671,this work suggests a potential generally applicable allosteric mechanism for the regulation of DUBs via steric blockade,as showcased by our discovery of IU1-248 which is 10-fold more potent than IU1. | Yiwei Wang Yuxuan Jiang Shan Ding Jiawang Li Ningjing Song Yujing Ren Danning Hong Cai Wu Bin Li Feng Wang Wei He Jiawei Wang Ziqing Mei | 2018 | Cell Research2018，28，12： | 15 |
| 15 | Effects of Qishen Yiqi Dripping Pills(芪参益气滴丸) in Reducing Myocardial Injury and Preserving Microvascular Function in Patients Undergoing Elective Percutaneous Coronary Intervention:A Pilot Randomized Study显示文摘Objectives:To evaluate the effect of treatment with Qishen Yiqi Dripping Pills(芪参益气滴丸,QSYQ) on myocardial injury and myocardial microvascular function in patients undergoing elective percutaneous coronary intervention(PCI).Methods:Eighty patients undergoing elective PCI were randomly assigned to QSYQ and control groups.The QSYQ group received QSYQ at a dosage of 0.5 g 3 times daily(3–7 days before PCI and then daily for 1 month) and regular medication,which comprised of aspirin,clopidogrel,statin,β-blocker,and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker in the absence of contradiction.The control group received only the regular medication.The index of microcirculatory resistance(IMR) was measured at maximal hyperemia after PCI.The fractional flow reserve was measured before and after the procedure.Troponin Ⅰ levels were obtained at baseline and 20–24 h after the procedure.Results:Pre-PCI troponin Ⅰ levels between the two groups were similar(0.028±0.05 vs.0.022±0.04 ng/m L,P=0.55).However,postPCI troponin Ⅰ levels in the QSYQ group were significantly lower than that in the control group(0.11±0.02 vs.0.16±0.09 ng/m L,P<0.01).IMR values were significantly lower in the QSYQ group as compared to the control group(16.5±6.1 vs.31.2±16.0,P<0.01).Multivariate analysis identified QSYQ treatment as the only independent protective factor against IMR >32(odds ratio=0.29,95% confidence interval:0.11–0.74,P=0.01).Conclusion:The present study demonstrated the benefit of QSYQ in reducing myocardial injury and preserving microvascular function during elective PCI. | HE Gui-xin XIE Jun JIANG Hao TAN Wei XU Biao | 2018 | Chinese Journal of Integrative Medicine2018，24，3： | 15 |
| 16 | Large-scale analysis of small RNAs derived from traditional Chinese herbs in human tissues显示文摘Plant-derived microRNAs have recently been reported to function in human blood and tissues. Controversy was immediately raised due to possible contamination and the lack of large sample sizes. Here, we report thousands of unique small RNAs derived from traditional Chinese medicine(TCM) herbs found in human blood cells and mouse lung tissues using a large-scale analysis.We extracted small RNAs from decoctions of 10 TCM plants(Ban Zhi Lian, Chai Hu, Chuan Xin Lian, Di Ding Zi Jin, Huang Qin, Jin Yin Hua, Lian Qiao, Pu Gong Ying, Xia Ku Cao, and Yu Xing Cao) and obtained millions of RNA sequences from each herb. We also obtained RNA-Seq data from the blood cells of humans who consumed herbal decoctions and from the lung tissues of mice administered RNAs from herbal decoctions via oral gavage. We identified thousands of unique small RNA sequences in human blood cells and mouse lung tissues. Some of these identified small RNAs from Chuan Xin Lian and Hong Jing Tian could be mapped to the genomes of the herbs, confirming their TCM plant origin. Small RNAs derived from herbs regulate mammalian gene expression in a sequence-specific manner, and thus are a superior novel class of herbal drug components that hold great potential as oral gene-targeted therapeutics, highlighting the important role of herbgenomics in their development. | Fengming Huang Jianchao Du Zhu Liang Zhichao Xu Jiantao Xu Yan Zhao Yexuan Lin Song Mei Quan He Jindong Zhu Qiang Liu Yanxu Zhang Yuhao Qin Wei Sun Jingyuan Song Shilin Chen Chengyu Jiang | 2019 | Science China(Life Sciences)2019，62，3： | 14 |
| 17 | Clinical presentations of gastric small gastrointestinal stromal tumors mimics functional dyspepsia symptoms显示文摘AIM: To explore whether clinical presentations of gastric small gastrointestinal tumors(GISTs) mimics gastrointestinal dyspepsia symptoms.METHODS: The endosonographic data of 167 patients who underwent endoscopic submucosal dissection at the Tianjin Medical University General Hospital, China between 2009 and 2011 were analyzed. GISTs and leiomyomas had a similar intragastric distribution and similar locations within the gastric wall. Therefore, patients with GISTs were chosen as the study group and those with leiomyomas were chosen as the control group. Dyspepsia symptom questionnaires were used to investigate and compare the gastrointestinal symptoms of patients with GISTs and those with gastric leiomyomas before and after endoscopic submucosal dissection(ESD). The questionnaires evaluated symptoms such as epigastric pain, heartburn, regurgitation, epigastric discomfort, nausea and vomiting, abdominal bloating, and eructation. Symptoms were assessed using a four-point scoring scale.RESULTS: GISTs were the most common gastric submucosal lesion(67 cases, 40.12%), followed by leiomyomas(38 cases, 22.75%). Both groups were similar in terms of gender distribution(P = 0.49), intragastric location(P = 0.525), and originating layer within the gastric wall(P = 0.449), but leiomyomas were more commonly found in the proximal fundus(P < 0.05). Overall, 94.2% of the patients with small GISTs and 93.5% of those with gastric leiomyomas experienced some dyspepsia; however, total symptom scores were significantly lower in the GIST group than in the leiomyoma group(1.34 ± 1.27 vs 2.20 ± 1.70, P < 0.05). Each component of the symptom score demonstrated a statistically significant improvement in the GIST patients after ESD(P < 0.05), including epigastric pain(0.80 ± 0.90 vs 0.13 ± 0.46), heartburn(0.63 ± 1.08 vs 0.13 ± 0.41), regurgitation(0.55 ± 0.87 vs 0.22 ± 0.57), epigastric discomfort(0.70 ± 0.98 vs 0.32 ± 0.47), nausea and vomiting(0.27 ± 0.62 vs 0.05 ± 0.21), abdominal bloating(0.70 ± 0.90 vs 0.27 ± 0.49), and eructation(0.36 ± 0.61 vs 0.21 ± 0.46). For leiomyoma patients, symptoms such as heartburn, nausea, vomiting, and eructation improved after treatment; however, these improvements were not statistically significant(P > 0.05). Thus, the pathophysiology of dyspepsia symptoms may be different between the two groups. CONCLUSION: Symptoms of gastric small GISTs may mimic those of functional dyspepsia. An alternative diagnosis should be considered in patients with functional dyspepsia and treatment failure. | Qing-Xiang Yu Zhan-Kun He Jiang Wang Chao Sun Wei Zhao Bang-Mao Wang | 2014 | World Journal of Gastroenterology2014，20，33： | 14 |
| 18 | Insight-HXMT observations of the first binary neutron star merger GW170817显示文摘Finding the electromagnetic(EM) counterpart of binary compact star merger, especially the binary neutron star(BNS) merger,is critically important for gravitational wave(GW) astronomy, cosmology and fundamental physics. On Aug. 17, 2017,Advanced LIGO and Fermi/GBM independently triggered the first BNS merger, GW170817, and its high energy EM counterpart,GRB 170817 A, respectively, resulting in a global observation campaign covering gamma-ray, X-ray, UV, optical, IR, radio as well as neutrinos. The High Energy X-ray telescope(HE) onboard Insight-HXMT(Hard X-ray Modulation Telescope) is the unique high-energy gamma-ray telescope that monitored the entire GW localization area and especially the optical counterpart(SSS17 a/AT2017 gfo) with very large collection area(~1000 cm^2) and microsecond time resolution in 0.2-5 MeV. In addition,Insight-HXMT quickly implemented a Target of Opportunity(ToO) observation to scan the GW localization area for potential X-ray emission from the GW source. Although Insight-HXMT did not detect any significant high energy(0.2-5 MeV) radiation from GW170817, its observation helped to confirm the unexpected weak and soft nature of GRB 170817 A. Meanwhile,Insight-HXMT/HE provides one of the most stringent constraints(~10^(-7) to 10^(-6) erg/cm^2/s) for both GRB170817 A and any other possible precursor or extended emissions in 0.2-5 MeV, which help us to better understand the properties of EM radiation from this BNS merger. Therefore the observation of Insight-HXMT constitutes an important chapter in the full context of multi-wavelength and multi-messenger observation of this historical GW event. | TiPei Li ShaoLin Xiong ShuangNan Zhang FangJun Lu LiMing Song XueLei Cao Zhi Chang Gang Chen Li Chen TianXiang Chen Yong Chen YiBao Chen YuPeng Chen Wei Cui WeiWei Cui JingKang Deng YongWei Dong YuanYuan Du MinXue Fu GuanHua Gao He Gao Min Gao MingYu Ge YuDong Gu Ju Guan ChengCheng Guo DaWei Han Wei Hu Yue Huang Jia Huo ShuMei Jia LuHua Jiang WeiChun Jiang Jing Jin YongJie Jin Bing Li ChengKui Li Gang Li MaoShun Li Wei Li Xian Li XiaoBo Li XuFang Li YanGuo Li ZiJian Li ZhengWei Li XiaoHua Liang JinYuan Liao CongZhan Liu GuoQing Liu HongWei Liu ShaoZhen Liu XiaoJing Liu Yuan Liu YiNong Liu Bo Lu XueFeng Lu Tao Luo Xiang Ma Bin Meng Yi Nang JianYin Nie Ge OU JinLu Qu Na Sai Liang Sun Yin Tan Lian Tao WenHui Tao YouLi Tuo GuoFeng Wang HuanYu Wang Juan Wang WenShuai Wang YuSa Wang XiangYang Wen BoBing WU Mei Wu GuangCheng Xiao He Xu YuPeng Xu LinLi Yan JiaWei Yang Sheng Yang YanJi Yang AiMei Zhang ChunLei Zhang ChengMo Zhang Fan Zhang HongMei Zhang Juan Zhang Qiang Zhang Shu Zhang Tong Zhang Wei Zhang WanChang Zhang WenZhao Zhang Yi Zhang Yue Zhang YiFei Zhang YongJie Zhang Zhao Zhang ZiLiang Zhang HaiSheng Zhao JianLing Zhao XiaoFan Zhao ShiJie Zheng Yue Zhu YuXuan Zhu ChangLin Zou | 2018 | Science China(Physics,Mechanics & Astronomy)2018，61，3： | 12 |
| 19 | Alterations of DNA damage response pathway:Biomarker and therapeutic strategy for cancer immunotherapy显示文摘Genomic instability remains an enabling feature of cancer and promotes malignant transformation.Alterations of DNA damage response(DDR)pathways allow genomic instability,generate neoantigens,upregulate the expression of programmed death ligand 1(PD-L1)and interact with signaling such as cyclic GMPe AMP synthase-stimulator of interferon genes(cGASe STING)signaling.Here,we review the basic knowledge of DDR pathways,mechanisms of genomic instability induced by DDR alterations,impacts of DDR alterations on immune system,and the potential applications of DDR alterations as biomarkers and therapeutic targets in cancer immunotherapy. | Minlin Jiang Keyi Jia Lei Wang Wei Li Bin Chen Yu Liu Hao Wang Sha Zhao Yayi He Caicun Zhou | 2021 | Acta Pharmaceutica Sinica B2021，11，10： | 12 |
| 20 | PD-L1 is a direct target of cancer-FOXP3 in pancreatic ductal adenocarcinoma(PDAC),and combined immunotherapy with antibodies against PD-L1 and CCL5 is effective in the treatment of PDAC显示文摘High expression of PD-L1 marks the poor prognosis of pancreatic ductal adenocarcinomas(PDAC).However,the regulatory mechanism of PD-L1 remains elusive.We recently reported that cancer Forkhead box protein 3(Cancer-FOXP3 or C-FOXP3)promoted immune evasion of PDAC by recruiting Treg cells into PDAC via upregulation of CCL5.In this study,we confirmed that PD-L1 was overexpressed in PDAC samples from two independent cohorts of patients with radical resection.Moreover,C-FOXP3 was colocalized and correlated with the expression of PD-L1 in tumor cells at the mRNA and protein levels,and this finding was confirmed by the The Cancer Genome Atlas(TCGA)database.Chromatin immunoprecipitation(ChIP)revealed that C-FOXP3 directly bound to the promoter region of PD-L1 in pancreatic cancer cells.Furthermore,overexpression of C-FOXP3 activated the luciferase reporter gene under the control of the PD-L1 promoter.However,mutation of the binding motif-a completely reversed the luciferase activity.In addition,C-FOXP3-induced upregulation of PD-L1 effectively inhibited the activity of CD8+T cells.Based on our recent finding that the CCL-5 antibody achieved a better response to PDAC models with high C-FOXP3 levels,we further demonstrated that the PD-L1 antibody strengthened the antitumor effect of CCL-5 blockade in xenograft and orthotopic mouse models with high C-FOXP3 levels.In conclusion,C-FOXP3 directly activates PD-L1 and represents a core transcription factor that mediates the immune escape of PDAC.Combined blockade of PD-L1 and CCL-5 may provide an effective therapy for patients with PDAC that have high C-FOXP3 levels. | Xiuchao Wang Xin Li Xunbin Wei Haiping Jiang Chungen Lan Shengyu Yang Han Wang Yanhui Yang Caijuan Tian Zanmei Xu Jiangyan Zhang Jihui Hao He Ren | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 11 |
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