HSPH1在肝细胞癌中的表达及临床意义

目的基于癌症基因组图谱数据库(The Cancer Genome Atlas,TCGA)、高通量基因表达数据库(Gene Expression Omnibus,GEO)及人类蛋白质图谱数据库(Human Protein Atls,HPA)等生物信息学数据库探讨热休克蛋白H1(heat shock protein H1,HSPH1)在肝细胞癌中的表达及临床意义。方法下载TCGA和GEO数据库肝细胞癌相关mRNA微阵列表达谱,比较肝细胞癌和癌旁组织的HSPH1 mRNA表达差异,并利用HPA数据库信息验证其蛋白水平的表达。分析HSPH1表达与肝细胞癌患者预后的相关性。建立ROC曲线和列线图模型,比较不同HSPH1表达组患者的生存差异。采用R软件分析HSPH1表达与肝细胞癌组织中免疫细胞浸润、免疫细胞生物标志物和免疫检查点的相关性。采用STRING数据库分析HSPH1相关蛋白质-蛋白质相互作用网络信息。并利用基因本体分析(Gene Ontology,GO)、京都基因与基因组数据库(Kyoto Encyclopedia of Genes and Genomes,KEGG)和基因集富集分析(Gene Set Enrichment Analysis,GSEA)等数据库分析HSPH1在肝细胞癌中的功能及信号通路。结果HSPH1在肝细胞癌组织中的表达水平高于癌旁组织(P=0.000),Kaplan-Meier图显示HSPH1高表达肝细胞癌患者的总体生存期(P=0.000)、疾病特异性生存期(P=0.000)和无进展间隔期(P=0.010)均较HSPH1低表达者更短,HSPH1对肝细胞癌具有较好的诊断价值(AUC=0.895,95%CI:0.862~0.928,P=0.000)。多因素Cox回归分析显示,HSPH1是肝细胞癌患者预后的预测因素(HR=2.226,95%CI:1.393~3.557,P=0.000)。时间依赖性ROC曲线图显示1年、3年和5年AUC分别为0.699、0.581、0.588。在肝细胞癌组织中,HSPH1蛋白表达水平与树突状细胞和细胞毒性细胞浸润呈负相关,与巨噬细胞、CD56高表达的NK细胞等免疫细胞浸润及免疫检查点程序性死亡受体1和细胞毒性T淋巴细胞相关蛋白4表达呈弱正相关。蛋白质-蛋白质相互作用、GO、KEGG和GSEA通路富集分析显示HSPH1与HSPA2、HSPA4、HSPA8和HSPA9等分子相互作用,并与HSPA4、HSPA8表达呈正相关,且具有调节凋亡、抗原加工和提呈、调节免疫等功能。结论HSPH1在肝细胞癌组织中高表达,是肝细胞癌潜在的诊断和预后标志物。HSPH1参与了肝细胞癌的免疫调节过程,可能成为其治疗靶点之一。

Towards development of enhanced fully-Lagrangian mesh-free computational methods for fluid-structure interaction

Simulation of incompressible fluid flow-elastic structure interactions is targeted by using fully-Lagrangian mesh-free computational methods. A projection-based fluid model（moving particle semi-implicit（MPS）） is coupled with either a Newtonian or a Hamiltonian Lagrangian structure model（MPS or HMPS） in a mathematically-physically consistent manner. The fluid model is founded on the solution of Navier-Stokes and continuity equations. The structure models are configured either in the framework of Newtonian mechanics on the basis of conservation of linear and angular momenta, or Hamiltonian mechanics on the basis of variational principle for incompressible elastodynamics. A set of enhanced schemes are incorporated for projection-based fluid model（Enhanced MPS）, thus, the developed coupled solvers for fluid structure interaction（FSI） are referred to as Enhanced MPS-MPS and Enhanced MPS-HMPS. Besides, two smoothed particle hydrodynamics（SPH）-based FSI solvers, being developed by the authors, are considered and their potential applicability and comparable performance are briefly discussed in comparison with MPS-based FSI solvers. The SPH-based FSI solvers are established through coupling of projection-based incompressible SPH（ISPH） fluid model and SPH-based Newtonian/Hamiltonian structure models, leading to Enhanced ISPH-SPH and Enhanced ISPH-HSPH. A comparative study is carried out on the performances of the FSI solvers through a set of benchmark tests, including hydrostatic water column on an elastic plate,high speed impact of an elastic aluminum beam, hydroelastic slamming of a marine panel and dam break with elastic gate.

On systematic development of FSI solvers in the context of particle methods

This paper presents a review on state-of-the-art of developments corresponding to fluid-structure interaction(FSI)solvers developed within the context of particle methods.The paper reviews and highlights the potential robustness of entirely Lagrangian meshfree FSI solvers in reproducing FSI corresponding to extreme events and portrays the future perspectives for systematic developments towards reliable engineering applications with respect to rapid advances in technology and emergence of so-called advanced materials that can result in complex and highly non-linear structural responses.Accordingly,the paper highlights the necessity for reproduction of comprehensive structural responses,including viscoelastic,elastoplastic and progressive damages/failures,by the advanced FSI solvers developed within the context of particle methods.In this regard,extensions of the structure model are suggested to be conducted in a variationally consistent framework to ensure stability,accuracy and physical reliability including thermodynamic consistency.The paper reviews basics of mathematical and numerical modelling for entirely Lagrangian meshfree hydroelastic FSI solvers and presents a brief background on extensions of such solvers towards reproducing viscoelastic structural responses.Some preliminary numerical results on structural viscoelasticity achieved by an extended Hamiltonian SPH(HSPH)model are presented.This vision paper also concisely portrays the future perspectives for systematic development of particle-based FSI solvers.