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| 1 | 42,573 cases of hepatectomy in China: a multicenter retrospective investigation显示文摘Hepatectomy is currently routinely performed in most hospitals in China. China owns the largest population of liver diseases and the biggest number of liver resection cases. A nationwide multicenter retrospective investigation involving 112 hospitals was performed, and focused on liver resection for patients with hepatocellular carcinoma(HCC). 42,573 cases of hepatectomy were enrolled, and 18,275 valid cases of liver resection for HCC patients were selected for statistical analysis. The epidemiology of HCC, distribution of hepatectomy, postoperative complications and prognosis were finally analyzed. In the 18,275 HCC patients,81% had hepatitis B virus infection and 10% had hepatitis C virus infection. 38% of the HCC patients had normal Alphafetoprotein(AFP) level, and other 35% had an AFP level lower than 400 ng mL^(-1). In the study period, 97% of the hepatectomy for HCC were treated with open surgery, and 23.81% had vascular exclusion techniques. The operation time was(191.7±105.6) min,the blood loss was(546.0±562.8) m L, and blood transfusion was(543.0±1,035.2) m L. The median survival for HCC patients was 631 days, with 1-, 3-, and 5-year overall survival of 73.2%, 28.8% and 19.6%, respectively. Liver cirrhosis, multiple nodules,tumor thrombosis and high AFP level were risk factors that affect postoperative survival. | Binhao Zhang Bixiang Zhang Zhiwei Zhang Zhiyong Huang Yifa Chen Minshan Chen Ping Bie Baogang Peng Liqun Wu Zhiming Wang Bo Li Jia Fan Lunxiu Qin Ping Chen Jingfeng Liu Zhe Tang Jun Niu Xinmin Yin Deyu Li Songqing He Bin Jiang Yilei Mao Weiping Zhou Xiaoping Chen | 2018 | Science China(Life Sciences)2018，61，6： | 39 |
| 2 | Roles of Chemokine Receptor 4 (CXCR4) and Chemokine Ligand 12 (CXCL12) in Metastasis of Hepatocellular Carcinoma Cells显示文摘Chemokines are involved in human hepatocellular carcinoma (HCC) carcinogenesis. However, the exact mechanism of chemokines in HCC carcinogenesis remains unknown. Here we investigated the roles of chemokine receptor 4 (CXCR4) and chemokine ligand 12 (CXCL12) in the metastasis of HCC. We found that the expression levels of CXCR4 mRNA in HCC tissues, MHCC97 cells, and HUVEC cells were 2.52 ± 1.13, 2.34 ± 1.16 and 1.63 ± 1.26, respectively and that the CXCR4 protein levels were 1.38 ± 0.13, 1.96 ± 0.32 and 1.86 ± 0.21, respectively. In contrast, CXCR4 was not detected in normal hepatic tissues. In 78 HCC patients, we also found that the concentration of CXCL12 in cancerous ascitic fluid was 783-8,364 pg/ml and that CXCL12 mRNA level in HCC metastasis portal lymph nodes was 1.21 ± 0.87 but undetectable in normal hepatic tissues. Finally we discovered that recombinant human CXCL12 could induce MHCC97 cells and HUVEC cells to migrate with chemotactic indexes (CI) of 3.9 ± 1.1 and 4.1 ± 1.6, respectively. Cancerous ascitic fluid could also induce the migration of MHCC97 cells with a CI of 1.9 ± 0.8. Thus, our data suggest that CXCR4 and CXCL12 may play an important role in the metastasis of HCC by promoting the migration of tumor cells. | Hui Liu Zeya Pan Aijun Li Siyuan Fu Yin Lei Hangyong Sun Mengchao Wu Weiping Zhou | 2008 | Cellular & Molecular Immunology2008，5，5： | 30 |
| 3 | Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy(STRATEGY):a multicenter,randomized,controlled,non-inferiority clinical trial显示文摘Despite the current guideline's recommendation of a timely stepwise intensification therapy,the 'clinical inertia',termed as the delayed treatment intensification,commonly exists in the real world,which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy.In this clinical trial performed in 237 centers in China,5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks.The patients who did not reach the glycated hemoglobin A1c(HbA1c) goal were then further randomized into glimepiride,gliclazide,repaglinide,or acarbose group for an additional 24-week triple therapy.A mean HbAlc reduction of 0.85%was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks.Further HbAlc reductions in the 24-week triple therapy stage were 0.65%in glimepiride group,0.70%in gliclazide group,0.61%in repaglinide group,and 0.45%in acarbose group.The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide,but not for acarbose,compared with glimepiride,when added to metformin/sitagliptin dual therapy.The incidences of adverse events(AEs) were 29.2%in the dual therapy stage and30.3%in the triple therapy stage.Metformin/sitagliptin as baseline therapy,with the addition of a third oral antihyperglycemic agent,including glimepiride,gliclazide,repaglinide,or acarbose,was effective,safe and well-tolerated for achieving an HbAlc<7.0%goal in type 2 diabetic patients inadequately controlled with previous therapies.The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia. | Wen Xu Yiming Mu Jiajun Zhao Dalong Zhu Qiuhe Ji Zhiguang Zhou Bin Yao Anhua Mao Samuel S.Engel Bin Zhao Yan Bi Longyi Zeng Xingwu Ran Juming Lu Linong Ji Wenying Yang Weiping Jia Jianping Weng | 2017 | Science China(Life Sciences)2017，60，3： | 19 |
| 4 | An overview of the use of plastic-film mulching in China to increase crop yield and water-use efficiency显示文摘Since 1990,crop yields have stagnated in many parts of the world,posing a significant challenge to global food security[1].As such;innovative solutions are needed to increase the resource-use efficiency of cropping systems to produce more grains per unit area. | Dongbao Sun Haigang Li Enli Wang Wenqing He Weiping Hao Changrong Yan Yuzhong Li Xurong Mei Yanqing Zhang Zhanxiang Sun Zhikuan Jia Huaiping Zhou Tinglu Fan Xucheng Zhang Qin Liu Fengju Wang Chaochun Zhang Jianbo Shen Qingsuo Wang Fusuo Zhang | 2020 | National Science Review2020，7，10： | 19 |
| 5 | From concept to reality-A review to the primary test stand and its preliminary application in high energy density physics显示文摘Pulsed power technology,whereas the electrical energy stored in a relative long period is released in much shorter timescale,is an efficient method to create high energy density physics(HEDP)conditions in laboratory.Around the beginning of this century,China Academy of Engineering Physics(CAEP)began to build some experimental facilities for HEDP investigations,among which the Primary Test Stand(PTS),a multi-module pulsed power facility with a nominal current of 10 MA and a current rising time~90 ns,is an important achievement on the roadmap of the electro-magnetically driven inertial confinement fusion(ICF)researches.PTS is the first pulsed power facility beyond 10 TW in China.Therefore,all the technologies have to be demonstrated,and all the engineering issues have to be overcome.In this article,the research outline,key technologies and the preliminary HEDP experiments are reviewed.Prospects on HEDP research on PTS and pulsed power development for the next step are also discussed. | Jianjun Deng Weiping Xie Shuping Feng Meng Wang Hongtao Li Shengyi Song Minghe Xia Ji Ce An He Qing Tian Yuanchao Gu Yongchao Guan Bin Wei Xianbin Huang Xiaodong Ren Jiakun Dan Jing Li Shaotong Zhou Hongchun Cai Siqun Zhang Kunlun Wang Qiang Xu Yujuan Wang Zhaohui Zhang Guilin Wang Shuai Guo Yi He Yiwei Zhou Zhanji Zhang Libing Yang Wenkang Zou | 2016 | Matter and Radiation at Extremes2016，1，1： | 19 |
| 6 | Development of Land Surface Model BCC_AVIM2.0 and Its Preliminary Performance in LS3MIP/CMIP6显示文摘The improvements and validation of several parameterization schemes in the second version of the Beijing Climate Center Atmosphere–Vegetation Interaction Model(BCC_AVIM2.0) are introduced in this study. The main updates include a replacement of the water-only lake module by the common land model lake module(Co LM-lake) with a more realistic snow–ice–water–soil framework, a parameterization scheme for rice paddies added in the vegetation module, renewed parameterizations of snow cover fraction and snow surface albedo to accommodate the varied snow aging effect during different stages of a snow season, a revised parameterization to calculate the threshold temperature to initiate freeze(thaw) of soil water(ice) rather than being fixed at 0°C in BCC_AVIM1.0, a prognostic phenology scheme for vegetation growth instead of empirically prescribed dates for leaf onset/fall, and a renewed scheme to depict solar radiation transfer through the vegetation canopy. The above updates have been implemented in BCC_AVIM2.0 to serve as the land component of the BCC Climate System Model(BCC_CSM). Preliminary results of BCC_AVIM in the ongoing Land Surface, Snow, and Soil Moisture Model Intercomparison Project(LS3 MIP) of the Coupled Model Intercomparison Project Phase 6(CMIP6) show that the overall performance of BCC_AVIM2.0 is better than that of BCC_AVIM1.0 in the simulation of surface energy budgets at the seasonal timescale. Comparing the simulations of annual global land average before and after the updates in BCC_AVIM2.0 reveals that the bias of net surface radiation is reduced from-12.0 to-11.7 W m-2 and the root mean square error(RMSE) is reduced from 20.6 to 19.0 W m-2;the bias and RMSE of latent heat flux are reduced from 2.3 to-0.1 W m-2 and from 15.4 to14.3 W m-2, respectively;the bias of sensible heat flux is increased from 2.5 to 5.1 W m-2 but the RMSE is reduced from 18.4 to 17.0 W m-2. | Weiping LI Yanwu ZHANG Xueli SHI Wenyan ZHOU Anning HUANG Mingquan MU Bo QIU Jinjun JI | 2019 | Journal of Meteorological Research2019，33，5： | 14 |
| 7 | Application of next-generation sequencing technology to precision medicine in cancer: joint consensus of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology显示文摘Next-generation sequencing(NGS) technology is capable of sequencing millions or billions of DNA molecules simultaneously.Therefore, it represents a promising tool for the analysis of molecular targets for the initial diagnosis of disease, monitoring of disease progression, and identifying the mechanism of drug resistance. On behalf of the Tumor Biomarker Committee of the Chinese Society of Clinical Oncology(CSCO) and the China Actionable Genome Consortium(CAGC), the present expert group hereby proposes advisory guidelines on clinical applications of NGS technology for the analysis of cancer driver genes for precision cancer therapy. This group comprises an assembly of laboratory cancer geneticists, clinical oncologists, bioinformaticians,pathologists, and other professionals. After multiple rounds of discussions and revisions, the expert group has reached a preliminary consensus on the need of NGS in clinical diagnosis, its regulation, and compliance standards in clinical sample collection. Moreover, it has prepared NGS criteria, the sequencing standard operation procedure(SOP), data analysis, report, and NGS platform certification and validation. | Xuchao Zhang Zhiyong Liang Shengyue Wang Shun Lu Yong Song Ying Cheng Jianming Ying Weiping Liu Yingyong Hou Yangqiu Li Yi Liu Jun Hou Xiufeng Liu Jianyong Shao Yanhong Tai Zheng Wang Li Fu Hui Li Xiaojun Zhou Hua Bai Mengzhao Wang You Lu Jinji Yang Wenzhao Zhong Qing Zhou Xuening Yang Jie Wang Cheng Huang Xiaoqing Liu Xiaoyan Zhou Shirong Zhang Hongxia Tian Yu Chen Ruibao Ren Ning Liao Chunyan Wu Zhongzheng Zhu Hongming Pan Yanhong Gu Liwei Wang Yunpeng Liu Suzhan Zhang Tianshu Liu Gong Chen Zhimin Shao Binghe Xu Qingyuan Zhang Ruihua Xu Lin Shen Yilong Wu | 2019 | Cancer Biology & Medicine2019，16，1： | 14 |
| 8 | Risk Assessment of Heavy Metal Pollution in Sediments of the Fenghe River by the Fuzzy Synthetic Evaluation Model and Multivariate Statistical Methods显示文摘Concentrations of heavy metals in 74 sediment samples from the Fenghe River, which originates from the north of the Qinling Mountains and flows through Xi'an, Shaanxi Province, China, were characterized by employing geographic information system(GIS)mapping, fuzzy synthetic assessment, and multivariate statistical analysis to determine the enrichment characteristics of heavy metals as well as their potential risks of pollution to sediments. Al, Cd, and Co were the major pollutants, with a high enrichment factor(EF) value. Heavy metal concentrations from samples near the paper plant were maintained at a high level. Significant enrichment of Al, Ba, Cr, Ni, Pb, and Co was found in the midstream and downstream, while high concentration of Cu occurred in the headwater stream. Based on the cluster and principal component analyses, sediment metals mainly came from the paper plants, agronomic practices, natural sources, and tourism, with a contribution of 51.59%, 23.01%, 14.21%, and 9.88%, respectively. Sediment pollution assessment explored using fuzzy theory based on the entropy method and toxicity coefficient showed that 26, 32, and 11 sites fell into Class III(slightly polluted), Class IV(moderately polluted), and Class V(heavily polluted), respectively, and their scores of membership degree in the polluted level were on the rise, suggesting a relatively high degree of sediment metal pollution in the study area. Closely related to the excessive industrial and agricultural applications, metal pollution in sediment is necessary to be addressed in the Fenghe River. | YANG Yang ZHOU Zhengchao BAI Yanying CAI Yimin CHEN Weiping | 2016 | Pedosphere2016，26，3： | 12 |
| 9 | Anomaly Detection of Industrial Control Systems Based on Transfer Learning显示文摘Industrial Control Systems(ICSs)are the lifeline of a country.Therefore,the anomaly detection of ICS traffic is an important endeavor.This paper proposes a model based on a deep residual Convolution Neural Network(CNN)to prevent gradient explosion or gradient disappearance and guarantee accuracy.The developed methodology addresses two limitations:most traditional machine learning methods can only detect known network attacks and deep learning algorithms require a long time to train.The utilization of transfer learning under the modification of the existing residual CNN structure guarantees the detection of unknown attacks.One-dimensional ICS flow data are converted into two-dimensional grayscale images to take full advantage of the features of CNN.Results show that the proposed method achieves a high score and solves the time problem associated with deep learning model training.The model can give reliable predictions for unknown or differently distributed abnormal data through short-term training.Thus,the proposed model ensures the safety of ICSs and verifies the feasibility of transfer learning for ICS anomaly detection. | Weiping Wang Zhaorong Wang Zhanfan Zhou Haixia Deng Weiliang Zhao Chunyang Wang Yongzhen Guo | 2021 | Tsinghua Science and Technology2021，26，6： | 11 |
| 10 | Laser-Assisted Reduction of Highly Conductive Circuits Based on Copper Nitrate for Flexible Printed Sensors显示文摘Stretchable electronic sensing devices are defining the path toward wearable electronics. High-performance flexible strain sensors attached on clothing or human skin are required for potential applications in the entertainment,health monitoring, and medical care sectors. In this work,conducting copper electrodes were fabricated onpolydimethylsiloxane as sensitive stretchable microsensors by integrating laser direct writing and transfer printing approaches. The copper electrode was reduced from copper salt using laser writing rather than the general approach of printing with pre-synthesized copper or copper oxide nanoparticles. An electrical resistivity of 96 l X cm was achieved on 40-lm-thick Cu electrodes on flexible substrates. The motion sensing functionality successfully demonstrated a high sensitivity and mechanical robustness.This in situ fabrication method leads to a path toward electronic devices on flexible substrates. | Shi Bai Shigang Zhang Weiping Zhou Delong Ma Ying Ma Pooran Joshi Anming Hu | 2017 | Nano-Micro Letters2017，9，4： | 10 |
| 11 | Effect of the span of Australian GPS coordinate time series in establishing an optimal noise model显示文摘并列时间系列的跨度影响一个最佳的噪音模型的决心。我们分析了在澳大利亚的板上从 1998.0 为 10 个连续全球放系统(GPS ) 地点记录到 mid-2009 估计最好的噪音模型并且此后获得速度的真无常的位置数据,采用最大的可能性的评价(MLE ) 方法。MLE 被采用以四个方法分析数据。在开始的二分析,噪音被假定是闪烁噪音的联合,为未加工的时间系列并且空间地的白噪音过滤了时间系列。在期末考试二分析,光谱索引和振幅同时在未加工的时间加白噪音模型为幂定律噪音被估计系列和空间地过滤的时间系列。我们断定在澳大利亚的 GPS 时间系列的噪音模型能是描述为闪烁噪音和白噪音的联合的最好。时间跨度超过 9.5 年的在 0.2 公里 / 年下面的速度无常秋天。在未加工、空间地过滤的时间系列之间的噪音振幅和最大的可能性的评价价值的比较建议移开普通模式的错误的传统的空间过滤可能不对这个区域的未加工的时间系列适用。 | JIANG WeiPing ZHOU XiaoHui | 2015 | Science China Earth Sciences2015，58，4： | 9 |
| 12 | Chronic intermittent hypoxia accelerates liver fibrosis in rats with combined hypoxia and nonalcoholic steatohepatitis via angiogenesis rather than endoplasmic reticulum stress显示文摘In the present study,we aimed to investigate the role of endoplasmic reticulum stress(ERS)and its related inflammation and angiogenesis in liver fibrosis in a rat model of combined hypoxia and nonalcoholic steatohepatitis(NASH)and to confirm whether the intervention of hypoxia-inducible factor 1α(HIF1α)can improve fibrosis.Liver histological changes and biochemical indices,HIF1α,inflammatory factors,ERS-related parameters(GRP78,CHOP,caspase-3,and caspase-12),and angiogenesis indices(VEGFA,VEGFR2,and CD34)were evaluated.Compared with the control rats,the liver tissue of rats with hypoxia and NASH had obvious NASH characteristics and hepatic fibrosis was significantly aggravated,including bridging fibrosis in some rats.The mRNA expression levels of HIF1α,VEGFA,and VEGFR2 and total immunohistochemical staining scores of VEGFR2 and CD34 were significantly increased.In addition,HIF1α silencing significantly decreased HIF1α,biochemical indices(ALT,AST,and TG),inflammatory factors(TNFα,IL6,and IL1β),and angiogenesis indices(CD34 and VEGFR2),consequently,improved the hepatic fibrosis score in the rat model of combined hypoxia and NASH.Taken together,chronic intermittent hypoxia accelerates liver fibrosis in rats with combined hypoxia and NASH via angiogenesis rather than ERS and HIF1α intervention can improve liver fibrosis,angiogenesis,inflammatory factors,and biochemical indices.Therefore,HIF1α is a key regulatory factor of liver fibrosis in rats with combined hypoxia and NASH. | Wei Wu Weiping Li Jiaojiao Wei Chunsheng Wang Yunliang Yao Weihua Zhu Weimei He Weimei Zhou Jiang Liu | 2019 | Acta Biochimica et Biophysica Sinica2019，51，2： | 8 |
| 13 | BRIF and CARIF progress显示文摘China Institute of Atomic Energy (CIAE) is currently constructing Beijing rare ion beam facility (BRIF) and is proposing China advanced rare ion beam facility (CARIF). This paper is aiming at introducing the progress of BRIF project and the con ceptual design CARIF. The ISOL type facility BRIF under construction is composed of a 100 MeV 300 ?A proton cyclotron, an ISOL with mass resolution of 20000, and a super-conducting LINAC of 2 MeV/q, and will be commissioned in 2013. CARIF facility proposed is planned to use both ISOL and PF techniques. It is based on a China advanced research reactor CARR that was critical, with ISOL separation of fission fragment, post acceleration to 150 MeV/u, and fragmentation of neu tron-rich fission fragment beam like 132Sn. Such unique combination will allow CARIF to deliver beam intensity better than the best world facilities by more than one order of magnitude. | LIU WeiPing, LI ZhiHong, BAI XiXiang, WANG YouBao, GUO Bing, PENG ChaoHua, YANG Yi, SU Jun, CUI BaoQun, ZHOU ShuHua, ZHU ShengYun, XIA HaiHong, GUAN XiaLing, ZENG Sheng, ZHANG HuanQiao, CHEN YongShou, TANG HongQing, HUANG Li & FENG BeiYuan China Institute of Atomic Energy, P. O. Box 275(1), Beijing 102413, China | 2011 | Science China(Physics,Mechanics & Astronomy)2011，54，S1： | 8 |
| 14 | Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis显示文摘Berberine has been shown to reduce acute liver injury although the underlying mechanism is not fully understood. Because of the anatomic connection, the liver is constantly exposed to gut-derived bacterial products and metabolites. In this study, we showed that berberine has beneficial effects on both hepatotoxicity and intestinal damage in a rat model of chronic or acute liver injury. Microbiota transplantation from the rats with chronic hepatotoxicity could aggravate acute hepatotoxicity in mice treated with diethylnitrosamine(DEN). In rat models with gut homeostasis disruption induced by penicillin or dextran sulfate sodium(DSS), their fecal microbiota could also cause an enhanced hepatotoxicity of recipient mice. When treated with berberine,the DSS-induced enteric dysbacteriosis could be mitigated and their fecal bacteria were able to reduce acute hepatotoxicity in recipient mice. This study indicates that berberine could improve intestinal dysbacteriosis, which reduces the hepatotoxicity caused by pathological or pharmacological intervention. Fecal microbiota transplantation might be a useful method to directly explore homeostatic alteration in gut microbiota. | Chenjie Qin Huilu Zhang Linghao Zhao Min Zeng Weijian Huang Gongbo Fu Weiping Zhou Hongyang Wang Hexin Yan | 2018 | Science China(Life Sciences)2018，61，12： | 8 |
| 15 | Combined effects of p53 and MDM2 polymorphisms on susceptibility and surgical prognosis in hepatitis B virus-related hepatocellular carcinoma显示文摘The p53 signaling pathway works as a potent barrier to tumor progression.Two single nucleotide polymor-phisms(SNPs)in the gene loci of p53 pathway,p53 codon 72 Arg72Pro and MDM2 SNP309(T>G),have been shown to cause perturbation of p53 function,but the effect of the two SNPs on the risk of hepatocellular carcinoma(HCC)remains inconsistent.This study in-vestigated the influence of combined p53 Arg72Pro and MDM2 SNP309 on the risk of developing HCC in pa-tients with chronic hepatitis B virus infection,and evaluated the significance of the two combined SNPs on patient prognosis.In total,350 HCC patients,230 non-HCC patients,and 96 healthy controls were geno-typed for the p53 Arg72Pro and MDM2 SNP309.The combined p53 Pro/Pro and MDM2 G/G genotype was significantly associated with HCC risk(P=0.047).Mul-tivariate analysis indicated that combined p53 Pro/Pro and MDM2 G/G genotype was an independent factor affecting recurrence and survival(P<0.05).Patients with combined p53 Pro/Pro and MDM2 G/G genotypes had a poorer prognosis than other genotypes,P<0.01 for both disease-free survival(DFS)and overall survival(OS).DFS and OS rates also differed significantly be-tween Barcelona Clinic Liver Cancer(BCLC)stage A patients with combined p53 Pro/Pro and MDM2 G/G and other genotypes(P<0.05).Thus,the combined p53 Pro/Pro and MDM2 G/G genotype is associated with increased risk of developing HCC and is an independ-ent adverse prognostic indicator in early stage HCC. | Yun Yang Tian Xia Ning Li Jin Zhang Yuan Yang Wenming Cong Qiang Deng Ke Lan Weiping Zhou | 2013 | Protein & Cell2013，4，1： | 8 |
| 16 | Whole-exome sequencing identifies a novel INS mutation causative of maturity-onset diabetes of the young 10显示文摘 | Jing Yan Feng Jiang Rong Zhang Tongfu Xu Zhou Zhou Wei Ren Danfeng Peng Yong Liu Cheng Hu Weiping Jia | 2017 | Journal of Molecular Cell Biology2017，9，5： | 7 |
| 17 | Heat shock protein 90 promotes RNA helicase DDX5 accumulation and exacerbates hepatocellular carcinoma by inhibiting autophagy显示文摘Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor prognosis.RNA helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell growth.Heat shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival.Methods:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,respectively.The interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal microscopy.The autophagy signal was detected by Western blot.The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines.Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor.Results:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway.The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling pathway.The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model.High levels of HSP90 and DDX5 protein were associated with poor prognoses.Conclusions:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation.DDX5 and HSP90 are therefore potential therapeutic targets for HCC. | Ting Zhang Xinrui Yang Wanping Xu Jing Wang Dawei Wu Zhixian Hong Shengxian Yuan Zhen Zeng Xiaodong Jia Shanshan Lu Rifaat Safadi Sen Han Zhihong Yang Leonard M.Neckers Suthat Liangpunsakul Weiping Zhou Yinying Lu | 2021 | Cancer Biology & Medicine2021，18，3： | 7 |
| 18 | Development of a machine learning model to predict early recurrence for hepatocellular carcinoma after curative resection显示文摘Background:Early recurrence is common for hepatocellular carcinoma(HCC)after surgical resection,being the leading cause of death.Traditionally,the COX proportional hazard(CPH)models based on linearity assumption have been used to predict early recurrence,but predictive performance is limited.Machine learning models offer a novel methodology and have several advantages over CPH models.Hence,the purpose of this study was to compare random survival forests(RSF)model with CPH models in prediction of early recurrence for HCC patients after curative resection.Methods:A total of 4,758 patients undergoing curative resection from two medical centers were included.Fifteen features including age,gender,etiology,platelet count,albumin,total bilirubin,AFP,tumor size,tumor number,microvascular invasion,macrovascular invasion,Edmondson-Steiner grade,tumor capsular,satellite nodules and liver cirrhosis were used to construct the RSF model in training cohort.Discrimination,calibration,clinical usefulness and overall performance were assessed and compared with other models.Results:Five hundred survival trees were used to generate the RFS model.The five highest Variable Importance(VIMP)were tumor size,macrovascular invasion,microvascular invasion,tumor number and AFP.In training,internal and external validation cohort,the C-index of RSF model were 0.725[standard errors(SE)=0.005],0.762(SE=0.011)and 0.747(SE=0.016),respectively;the Gönen&Heller’s K of RSF model were 0.684(SE=0.005),0.711(SE=0.008)and 0.697(SE=0.014),respectively;the time-dependent AUC(2 years)of RSF model were 0.818(SE=0.008),0.823(SE=0.014)and 0.785(SE=0.025),respectively.The RSF model outperformed early recurrence after surgery for liver tumor(ERASL)model,Korean model,American Joint Committee on Cancer tumor-node-metastasis(AJCC TNM)stage,Barcelona Clinic Liver Cancer(BCLC)stage and Chinese stage.The RSF model is capable of stratifying patients into three different risk groups(low-risk,intermediate-risk,high-risk groups)in the training and two validation cohorts(all P<0.0001).A web-based prediction tool was built to facilitate clinical application(http://gffzz8caf4f582aa3478esx60popf9w50c69f6.ffgz.tsg.suse.edu.cn/surgery_predict/).Conclusions:The RSF model is a reliable tool to predict early recurrence for patients with HCC after curative resection because it exhibited superior performance compared with other models.This novel model will be helpful to guide postoperative follow-up and adjuvant therapy. | Jianxing Zeng Jinhua Zeng Kongying Lin Haitao Lin Qionglan Wu Pengfei Guo Weiping Zhou Jingfeng Liu | 2022 | Hepatobiliary Surgery and Nutrition2022，11，2： | 6 |
| 19 | Highly efficient base editing in human tripronuclear zygotes显示文摘 | Changyang Zhou Meiling Zhang Yu Wei Yidi Sun Yun Sun Hong Pan Ning Yao Wanxia Zhong Yixue Li Weiping Li3 Hui Yang Zi-jiang Chen | 2017 | Protein & Cell2017，8，10： | 6 |
| 20 | Upregulated KPNA2 promotes hepatocellular carcinoma progression and indicates prognostic significance across human cancer types显示文摘Hepatocellular carcinoma(HCC)is one of the most aggressive cancers worldwide.Identification of the molecular mechanisms underlying the development and progression of HCC is particularly important.Here,we demonstrated the expression pattern,clinical significance,and function of Karyopherin α2(KPNA2)in HCC.The expression of KPNA2 was upregulated in tumor tissue and negatively associated with the survival time,and a significant correlation between KPNA2 expression and aggressive clinical characteristics was established.Both in vitro and in vivo experiments demonstrated that knockdown of KPNA2 reduced migration and proliferation capacities of HCC cells,while over-expression of KPNA2 increased these malignant characteristics.The analysis of the Cancer Genome Atlas cohorts also reveals that high-KPNA2 expression is associated with poor outcome in multiple cancer types.In addition,gene sets enrichment analysis exhibited cell cycle and DNA replication as the top altered pathways in the high-KPNA2 expression group in HCC and other two cancer types.Overall,this study identified KPNA2 as a potential diagnostic and prognostic biomarker in HCC and other neoplasms,probably by regulating cell cycle and DNA replication. | Xinggang Guo Zhiheng Wang Jianing Zhang Qingguo Xu Guojun Hou Yuan Yang Chuanpeng Dong Gang Liu Chenhua Liang Lei Liu Weiping Zhou Hui Liu | 2019 | Acta Biochimica et Biophysica Sinica2019，51，3： | 6 |
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