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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 | Enhanced mechanical properties and degradation rate of Mg-Ni-Y alloy by introducing LPSO phase for degradable fracturing ball applications显示文摘In this work,as-cast Mg-Ni-Y alloys were proposed to develop a feasible material for fracturing balls,and their mechanical performance and corrosion behavior were systematically investigated.Long period stacking order(LPSO)phase was firstly introduced to improve both the mechanical properties and degradation rate of magnesium alloys.With the increase of LPSO phase,the compressive strength was improved significantly,while the elongation of the alloys decreased owing to the relatively brittle nature of LPSO phase.Due to the higher corrosion potential of LPSO phase,the LPSO phase can accelerate the corrosion process by providing more micro-couples.However,the LPSO phase would serve as the corrosion barrier between the corrosion medium and the matrix when the contents of LPSO phase are too high in Mg92.5Ni3Y4.5 and Mg87.5Ni5Y7.5 alloys.As-cast Mg97.5Ni1Y1.5 alloy with satisfactory mechanical properties and rapid degradation rate was successfully developed,exhibiting a high degradation rate of 6675 mm/a(93℃)in 3 wt.%KCl solution and a favorable ultimate compressive strength of 410 MPa.The degradation rate of Mg97.5Ni1Y1.5 alloy is 2-5 times of the current commercial magnesium alloy fracturing materials. | Jingfeng Wang Shiqing Gao Xiuying Liu Xing Peng Kui Wang Shijie Liu Weiyan Jiang Shengfeng Guo Fusheng Pan | 2020 | Journal of Magnesium and Alloys2020，8，1： | 13 |
| 3 | CAS9 is a genome mutator by directly disrupting DNA-PK dependent DNA repair pathway显示文摘With its high efficiency for site-specific genome editing and easy manipulation,the clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR associated protein 9(CAS9)system has become the most widely used gene editing technology in biomedical research.In addition,significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases,several of which are entering clinical trials.Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA(gRNA)in human cells,promoting genomic DNA double-stranded break(DSB)damage and genomic instability.CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase(DNA-PK)complex and disrupts the interaction between KU86 and its kinase subunit,leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining(NHEJ)pathway.XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility,and dCAS9 is a CAS9 variant without nuclease activity.We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair.Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival,our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application. | Shuxiang Xu Jinchul Kim Qingshuang Tang Qu Chen Jingfeng Liu Yang Xu Xuemei Fu | 2020 | Protein & Cell2020，11，5： | 8 |
| 4 | Effect of Sn addition on the mechanical properties and bio-corrosion behavior of cytocompatible Mg-4Zn based alloys显示文摘The mechanical properties and bio-corrosion behaviors of as-extruded Mg-4Zn alloys after Sn addition were investigated,systemati-cally.A small amount of Sn addition to Mg-4Zn alloy slightly improved the mechanical properties for solid solution strengthening,and significantly controlled the bio-corrosion rates.Sn participating in the outer layer film formation as SnO/SnO_(2)resisted the bio-corrosion proceeding.Especially,Mg-4Zn-1.5Sn alloy,with a weight loss rate of 0.45 mm/y and hydrogen evolution rate of 0.099 mL/cm^(2)/day,showed cytotoxicity grade of 0 to MC3T3-E1 cells.The perfect alliance of cytocompatibility,suitable mechanical properties and low bio-corrosion rate demonstrates that this Mg-4Zn-1.5Sn alloy is a promising biodegradable magnesium alloy for orthopedic implants. | Weiyan Jiang Jingfeng Wang Weikang Zhao Qingshan Liu Dianming Jiang Shengfeng Guo | 2019 | Journal of Magnesium and Alloys2019，7，1： | 6 |
| 5 | 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://gffzz8caf4f582aa3478es9vpvw55bc60u6ooc.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 |
| 6 | Experiment and simulation on the pyrite removal from the recirculating load of pulverizer with a dilute phase gas-solid fluidized bed显示文摘In order to reduce the energy consumption and subsequent air pollution of coal-fired power station, based on the analysis to size and density distribution of particles from the recirculating load of the classifier of pulverizer, the separation experiment on sampling material from power plant with a dilute phase fluidized bed to remove pyrite and other minerals and numerical simulation on the separation process were done. The results show that the minimum fluidization velocity is 1.62 cm/s. Pyrite and other minerals in the material are separated. Ash of the upper and bottom layer material account for 33.34% and 73.42% respectively and sulfur content occupy 1.12% and 8.96% respectively. Scanning electron microscopy and spectroscopy tests show that sulfur in the bottom material exist in the form of pyrite. Numerical simulation on the flow field form of the dilute phase separation bed with gas-solid two phase and particle motion verifies the experimental results. | Wang Shuai He Yaqun He Jingfeng Ge Linhan Liu Qing | 2013 | International Journal of Mining Science and Technology2013，23，2： | 6 |
| 7 | Development of integrated two-stage thermoelectric generators for large temperature difference显示文摘Multi-stage thermoelectric(TE) modules can withstand a large temperature difference and can be used to obtain a high conversion efficiency. In this study, two-stage PbTe/Bi2Te3 TE modules were developed with an enhanced efficiency through a comprehensive study of device structure design, module fabrication, and performance evaluation. PbTe-based AgPbmSbTem+2(abbreviated as LAST) is a typically high ZT material, while the corresponding TE module was rarely reported so far. How to utilize LAST to fabricate high efficiency TE modules therefore remains a central problem. Finite element simulation indicates that the temperature stability of the two-stage module for LAST is better than that of two-segmented module. Compared to Cu,Ni, and Ni-Fe alloys, Co-Fe alloy is an effective metallization layer for PbTe due to its low contact resistance and thin diffusion layer. By sintering a slice of Cu on TE legs, pure tinfoil can be used as a common welding method for mid-temperature TE modules. A maximum efficiency(ηmax) of 9.5% was achieved in the range of 303 to 923 K in an optimized PbTe/Bi2Te3 based two-stage module, which was almost twice that of a commercial TE module. | PEI Jun LI LiangLiang LIU DaWei ZHANG BoPing XIAO Yu LI JingFeng | 2019 | Science China(Technological Sciences)2019，62，9： | 6 |
| 8 | MHC polymorphism and disease-resistance to Edwardsiella tarda in six turbot(Scophthalmus maximus) families显示文摘This study examined genetic variation in the major histocompatibility complex(MHC) Class II B gene in turbot(Scophthalmus maximus) by virulent bacterial pathogen challenge.One hundred fry from each of six families were infected with Edwardsiella tarda by intraperitoneal injection.Family mortality ranged from 28.0% to 83.3%.Complete exon 2 and intron 1 sequences of MHC Class II B genes were amplified from five survivor and five non-survivor individuals per family using the clone-sequence method.Thirty-seven sequences from 60 individuals revealed 37 different alleles,25 of which were unique to this study.The 25 unique alleles belonged to 16 major allele types.Nine alleles were used to examine the association between alleles and resistance/susceptibility to disease.Five alleles were present in an individual,suggesting a minimum of three loci or copies of the turbot MHC Class II B gene.The rate of non-synonymous substitution(d N) was 2.30 and 1.58 times higher than synonymous substitution(d S) in the peptide-binding regions(PBR) and non-PBR in whole families,respectively,which suggested balancing selection on exon 2 of the MHC Class II B gene in turbot.One allele,Scma-DBB1*02,was significantly more prevalent in survivor stock than in non-survivor stock(P=0.001).Therefore,this allele might be associated with resistance to bacteria.A second allele,Scma-DBB1*10,was significantly more prevalent in non-survivor stock(P=0.021),and is likely associated with susceptibility to bacteria. | DU Min CHEN SongLin LIU YanHong NIU BaoZhen YANG JingFeng ZHANG Bo | 2012 | Chinese Science Bulletin2012，57，25： | 5 |
| 9 | An improved neural network model for prediction of mechanical properties of magnesium alloys显示文摘An improved neural network model was developed for prediction of mechanical properties in the de-sign and development of new types of magnesium alloys by refining the types of input variables and using a more reasonable algorithm. The results showed that the improved model apparently decreased the prediction errors, and raised the accuracy of the prediction results. Better preprocessing parame-ters were found to be [0.15, 0.90] for the tensile strength, [0.1, 0.9] for the yield strength, and [0.15, 0.90] for the elongation. When the above parameters were used, the relativity for predicition of strength was bigger than 0.95. By using improved ANN analysis, more reasonable process parameters and compo- sition could be obtained in some magnesium alloys without addition of strontoum. | TANG AiTao LIU Bin PAN FuSheng ZHANG Jing PENG Jian WANG JingFeng | 2009 | Science China(Technological Sciences)2009，52，1： | 5 |
| 10 | Strain hardening of as-extruded Mg-xZn(x=1, 2, 3 and 4 wt%) alloys显示文摘The influence of Zn on the strain hardening of as-extruded Mg-x Zn(x = 1, 2, 3 and 4 wt%) magnesium alloys was investigated using uniaxial tensile tests at 10^(-3)s^(-1) at room temperature. The strain hardening rate,the strain hardening exponent and the hardening capacity were obtained from true plastic stress-strain curves. There were almost no second phases in the as-extruded Mg-Zn magnesium alloys. Average grain sizes of the four as-extruded alloys were about 17.8 μm. With increasing Zn content from 1 to 4 wt%, the strain hardening rate increased from 2850 MPa to 6810 MPa at(б-б_(0.2)) = 60 MPa, the strain hardening exponent n increased from 0.160 to 0.203, and the hardening capacity, Hc increased from 1.17 to 2.34.The difference in strain hardening response of these Mg-Zn alloys might be mainly caused by weaker basal texture and more solute atoms in the α-Mg matrix with higher Zn content. | Chaoyue Zhao Xianhua Chen Fusheng Pan Jingfeng Wang Shangyu Gao Teng Tu Chunquan Liu Jiahao Yao Andrej Atrens | 2019 | Journal of Materials Science & Technology2019，35，1： | 4 |
| 11 | Effect of Ni on the microstructure, mechanical properties and corrosion behavior of MgGd_1Ni_(x) alloys for fracturing ball applications显示文摘The effects of Ni addition on the mechanical properties, corrosion behaviors, and corrosion mechanism of Mg Gd_1 Ni_(x) alloys have been investigated by compressive tests, weight loss, hydrogen evolution, and scanning electron microscopy. The results show that the constitution of the second phase is large dependence on Ni/Gd molar ratios, which can transform from LPSO(long-period stacking ordered)+Mg_5 Gd,LPSO to eutectic phase. In addition, with increasing Ni/Gd molar ratios, the content of second phase increases gradually, while the LPSO phase shows a parabola relationship. Furthermore, the formation of Nicontaining LPSO phase not only can improve the strength but also accelerate the degradation of Mg alloys owing to the galvanic corrosion. The optimal properties with ultimate compressive strength, degradation rate are 340 MPa, 2066 mm/y for Mg Gd1 Ni0.75, respectively, which can meet the engineering application standard of fracturing ball and can be used as candidate materials for fracturing ball. | Kai Ma Shijie Liu Chaoneng Dai Xiuying Liu Jie Ren Yuanlang Pan Yinhong Peng Chen Su Jingfeng Wang Fusheng Pan | 2021 | Journal of Materials Science & Technology2021，，32： | 4 |
| 12 | Chinese expert consensus on conversion therapy for hepatocellular carcinoma(2021 edition)显示文摘Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma(HCC)have resulted in improved response rates.This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection,a‘conversion therapy’strategy.However,conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed.Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice.Evidence review:Many research centers in China have accumulated significant experience implementing HCC conversion therapy.Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC;however,there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields.In order to summarize and learn from past experience and review current challenges,the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma(2021 Edition)was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice.Sixteen consensus statements on the implementation of conversion therapy for HCC were developed.The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC. | Hui-Chuan Sun Jian Zhou Zheng Wang Xiufeng Liu Qing Xie Weidong Jia Ming Zhao Xinyu Bi Gong Li Xueli Bai Yuan Ji Li Xu Xiao-Dong Zhu Dousheng Bai Yajin Chen Yongjun Chen Chaoliu Dai Rongping Guo Wenzhi Guo Chunyi Hao Tao Huang Zhiyong Huang Deyu Li Gang Li Tao Li Xiangcheng Li Guangming Li Xiao Liang Jingfeng Liu Fubao Liu Shichun Lu Zheng Lu Weifu Lv Yilei Mao Guoliang Shao Yinghong Shi Tianqiang Song Guang Tan Yunqiang Tang Kaishan Tao Chidan Wan Guangyi Wang Lu Wang Shunxiang Wang Tianfu Wen Baocai Xing Bangde Xiang Sheng Yan Dinghua Yang Guowen Yin Tao Yin Zhenyu Yin Zhengping Yu Bixiang Zhang Jialin Zhang Shuijun Zhang Ti Zhang Yamin Zhang Yubao Zhang Aibin Zhang Haitao Zhao Ledu Zhou Wu Zhang Zhenyu Zhu Shukui Qin Feng Shen Xiujun Cai Gaojun Teng Jianqiang Cai Minshan Chen Qiang Li Lianxin Liu Weilin Wang Tingbo Liang Jiahong Dong Xiaoping Chen Xuehao Wang Shusen Zheng Jia Fan 无 | 2022 | Hepatobiliary Surgery and Nutrition2022，11，2： | 4 |
| 13 | Functions of p53 in pluripotent stem cells显示文摘Pluripotent stem cells(PSCs)are capable of unlimited self-renewal in culture and differentiation into all functional cell types in the body,and thus hold great promise for regenerative medicine.To achieve their clinical potential,it is critical for PSCs to maintain genomic stability during the extended proliferation.The critical tumor suppressor p53 is required to maintain genomic stability of mammalian cells.In response to DNA damage or oncogenic stress,p53 plays multiple roles in maintaining genomic stability of somatic cells by inducing cell cycle arrest,apoptosis,and senescence to prevent the passage of genetic mutations to the daughter cells.p53 is also required to maintain the genomic stability of PSCs.However,in response to the genotoxic stresses,a primary role of p53 in PSCs is to induce the differentiation of PSCs and inhibit pluripotency,providing mechanisms to maintain the genomic stability of the self-renewing PSCs.In addition,the roles of p53 in cellular metabolism might also contribute to genomic stability of PSCs by limiting oxidative stress.In summary,the elucidation of the roles of p53 in PSCs will be a prerequisite for developing safe PSC-based cell therapy. | Xuemei Fu Shouhai Wu Bo Li Yang Xu Jingfeng Liu | 2020 | Protein & Cell2020，11，1： | 4 |
| 14 | Pluripotent Stem Cell-derived Strategies to Treat Acute Liver Failure: Current Status and Future Directions显示文摘Liver disease has long been a heavy health and economic burden worldwide.Once the disease is out of control and progresses to end-stage or acute organ failure,orthotopic liver transplantation(OLT)is the only therapeutic alternative,and it requires appropriate donors and aggressive administration of immunosuppressive drugs.Therefore,hepatocyte transplantation(HT)and bioartificial livers(BALs)have been proposed as effective treatments for acute liver failure(ALF)in clinics.Although human primary hepatocytes(PHs)are an ideal cell source to support these methods,the large demand and superior viability of PH is needed,which restrains its wide usage.Thus,a finding alternative to meet the quantity and quality of hepatocytes is urgent.In this context,human pluripotent stem cells(PSC),which have unlimited proliferative and differential potential,derived hepatocytes are a promising renewable cell source.Recent studies of the differentiation of PSC into hepatocytes has provided evidence that supports their clinical application.In this review,we discuss the recent status and future directions of the potential use of PSC-derived hepatocytes in treating ALF.We also discuss opportunities and challenges of how to promote such strategies in the common applications in clinical treatments. | Jingfeng Liu Zhiming Yuan Qingwen Wang | 2022 | Journal of Clinical and Translational Hepatology2022，10，4： | 4 |
| 15 | Numerical Simulation of Solidification Microstructure and Effects of Phase-field Parameters on Grain Growth Morphologies显示文摘By a simple phase field model, a series of numerical simulations of solidification microstructure was performed to show a rich variety of dendritic patterns. At the same time, the relation between the morphology of grain growth and some parameters including the strength of anisotropy, dimensionless latent heat and the size of initial solid zone was studied. It is for the first time that patterns of grain growth were associated with the size of initial solid zone, which is an interesting issue. The possible reason for this may be that variation in the size of initial solid zone may bring about fluctuation of the interface energy, making the interface unstable. | Jingfeng LIU+, Ruixiang LIU and Liliang CHEN Research Studio of Solidification Simulation, College of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074, China | 2005 | Journal of Materials Science & Technology2005，21，6： | 4 |
| 16 | Microstructure and mechanical properties of large-scale Mg-Gd-Y-Zn-Mn alloys prepared through semi-continuous casting显示文摘Large-scale Mg-8Gd-4Y-1Zn-Mn(wt.%)alloy ingot with a diameter of 315 mm and a length of 2410 mm was prepared through semi-continuous casting.Chemical composition,microstructure and mechanical properties at different locations of the samples with as-cast,T4 and T6 heat-treated states,respectively,were investigated.No obvious macro segregation has been detected in the high-quality alloy ingot.The main eutectic structures at all different locations are composed ofα-Mg,Mg3RE-type,Mg5RE-type and LPSO phases.At the edge of ingot,the unusual casting twins including 10-12 extension twins and 10-11 compression twins were observed due to the intensive internal stress.In T4 heat-treated alloy,the micro segregation was eliminated.The remained phases wereα-Mg and LPSO phase.Combined with the remarkable age-hardening response,T6 samples exhibits improved mechanical properties at ambient temperature,which derives from the dense prismaticβ'precipitates and profuse basalγ'precipitates. | Kui Wang Jingfeng Wang Xiaoxu Dou Yuanding Huang Norbert Hort Sarkis Gavras Shijie Liu Yanwu Cai Jinxing Wang Fusheng Pan | 2020 | Journal of Materials Science & Technology2020，52，17： | 4 |
| 17 | High-temperature Electric Properties of Polycrystalline La-doped CaMnO_3 Ceramics显示文摘Polycrystalline La-doped CaMnO3 ceramics have been prepared by a solid-state sintering method.Analysis of microstructure and phase composition indicates that the addition of La can prohibit the further growth of grain,and no impurity phase appears.The results revealed that the La doping can lead to a large change of the activation energy(from 0.22 to 0.02 eV),and thus result in a marked increase in electric conductivity of 2-4 orders of magnitude.The power factor can reach about 1.5×10-4 W·m-1·K-2 in a wide temperature range,which potentially make them attractive for n-type high-temperature thermoelectric materials. | Jinle Lan Yuanhua Lin Ao Mei Cewen Nan Yong Liu Boping Zhang Jingfeng Li | 2009 | Journal of Materials Science & Technology2009，25，4： | 3 |
| 18 | Development of a novel RNAi therapy:Engineered miR-31 exosomes promoted the healing of diabetic wounds显示文摘Rationale:Chronic wounds associated with diabetes exact a heavy burden on individuals and society and do not have a specific treatment.Exosome therapy is an extension of stem cell therapy,and RNA interference(RNAi)-based therapy is a type of advanced precision therapy.Based on the discovery of chronic wound-related genes in diabetes,we combined exosome therapy and RNAi therapy through an engineering approach for the treatment of diabetic chronic wounds.Methods:We combined exosome therapy and RNAi therapy to establish a precision therapy for diabetes-associated wounds via an engineered exosome approach.Results:First,chronic diabetic wounds express low levels of miR-31-5p compared with nondiabetic wounds,and an miR-31-5p mimic was shown to be effective in promoting the proliferation and migration of three wound-related cell types in vitro.Second,bioinformatics analysis,luciferase reporter assays and western blotting suggested that miR-31-5p promoted angiogenesis,fibrogenesis and reepithelization by inhibiting factor-inhibiting HIF-1(HIF1AN,also named FIH)and epithelial membrane protein-1(EMP-1).Third,engineered miR-31 exosomes were generated as a miR-31-5p RNAi therapeutic agent.In vivo,the engineered miR-31 exosomes promoted diabetic wound healing by enhancing angiogenesis,fibrogenesis and reepithelization.Conclusion:Engineered miR-31 exosomes are an ideal disease pathophysiology-initiated RNAi therapeutic agent for diabetic wounds. | Jinghuan Huang Muyu Yu Wenjing Yin Bo Liang Ang Li Jingfeng Li Xiaolin Li Shichang Zhao Fang Liu | 2021 | Bioactive Materials2021，6，9： | 3 |
| 19 | Improving in vitro and in vivo corrosion resistance and biocompatibility of Mg-1Zn-1Sn alloys by microalloying with Sr显示文摘Magnesium(Mg)and its alloys have attracted attention as potential biodegradable materials in orthopedics due to their mechanical and physical properties,which are compatible with those of human bone.However,the effect of the mismatch between the rapid material degradation and fracture healing caused by the adverse effect of hydrogen(H2),which is generated during degradation,on surrounding bone tissue has severely restricted the application of Mg and its alloys.Thus,the development of new Mg alloys to achieve ideal degradation rates,H2 evolution and mechanical properties is necessary.Herein,a novel Mg-1Zn-1Sn-xSr(x=0,0.2,0.4,and 0.6 wt%)quaternary alloy was developed,and the microstructure,mechanical properties,corrosion behavior and biocompatibility in vitro/vivo were investigated.The results demonstrated that a minor amount of strontium(Sr)(0.2 wt%)enhanced the corrosion resistance and mechanical properties of Mg-1Zn-1Sn alloy through grain refinement and second phase strengthening.Simultaneously,due to the high hydrogen overpotential of tin(Sn),the H2 release of the alloys was significantly reduced.Furthermore,Sr-containing Mg-1Zn-1Sn-based alloys significantly enhanced the viability,adhesion and spreading of MC3T3-E1 cells in vitro due to their unique biological activity and the ability to spontaneously form a network structure layer with micro/nanotopography.A low corrosion rate and improved biocompatibility were also maintained in a rat subcutaneous implantation model.However,excessive Sr(>0.2 wt%)led to a microgalvanic reaction and accelerated corrosion and H2 evolution.Considering the corrosion resistance,H2 evolution,mechanical properties and biocompatibility in vitro and in vivo,Mg-1Zn-1Sn-0.2Sr alloy has tremendous potential for clinical applications. | Yafeng Wen Qingshan Liu Jingfeng Wang Qiming Yang Weikang Zhao Bo Qiao Yuling Li Dianming Jiang | 2021 | Bioactive Materials2021，6，12： | 3 |
| 20 | Profiling of hepatocellular carcinoma neoantigens reveals immune microenvironment and clonal evolution related patterns显示文摘Objective: Neoantigens derived from tumor-specific genomic alterations have demonstrated great potential for immunotherapeutic interventions in cancers. However, the comprehensive profile of hepatocellular carcinoma(HCC) neoantigens and their complex interplay with immune microenvironment and tumor evolution have not been fully addressed.Methods: Here we integrated whole exome sequencing data, transcriptome sequencing data and clinical information of 72 primary HCC patients to characterize the HCC neoantigen profile, and systematically explored its interactions with tumor clonal evolution, driver mutations and immune microenvironments.Results: We observed that higher somatic mutation/neoantigen load was associated with better clinical outcomes and HCC patients could be further divided into two subgroups with distinct prognosis based on their neoantigen expression patterns. HCC subgroup with neoantigen expression probability high(NEP-H) showed more aggressive pathologic features including increased incidence of tumor thrombus(P=0.038), higher recurrence rate(P=0.029),more inclined to lack tumor capsule(P=0.026) and with more microsatellite instability sites(P=0.006). In addition,NEP-H subgroup was also characterized by higher chance to be involved in tumor clonal evolution [odds ratio(OR)=46.7, P<0.001]. Gene set enrichment analysis revealed that upregulation of MYC and its targets could suppress immune responses, leading to elevated neoantigen expression proportion in tumor cells. Furthermore, we discovered an immune escape mechanism that tumors could become more inconspicuous by evolving subclones with less immunogenicity. We observed that smaller clonal mutation clusters with higher immunogenicity in tumor were more likely to involve in clonal evolution. Based on identified neoantigen profiles, we also discovered series of neoantigenic hotspot genes, which could serve as potential actionable targets in future.Conclusions: Our results revealed the landscape of HCC neoantigens and discovered two clinically relevant subgroups with distinct neoantigen expression patterns, suggesting the neoantigen expression should be fully considered in future immunotherapeutic interventions. | Zhenli Li Geng Chen Zhixiong Cai Xiuqing Dong Lei He Liman Qiu Yongyi Zeng Xiaolong Liu Jingfeng Liu | 2021 | Chinese Journal of Cancer Research2021，33，3： | 3 |
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