Research of the molecular mechanism of Hai Honghua medicinal liquor in the treatment of fracture based on network pharmacology combined with molecular docking

Background:Hai Honghua medicinal liquor(HHML),a famous hospital formula composed of 19 traditional Chinese medicines,has been successfully applied in treating soft tissue injury,fresh closed fracture,limb dysfunction after fracture healing,shoulder,neck and leg pain,knee joint pain and other clinical multiple diseases for 30 years in clinical.However,research on the material basis of HHML for the treatment of fracture healing-related disorders is still in a gap.Therefore,it is particularly important to explore the active ingredients,core targets and potential pharmacological mechanisms of HHML to promote fracture healing.Methods:We screened the core active components of each traditional Chinese medicine in formula and its action targets through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine database.The fracture related targets were retrieved from several different public databases,including GeneCards,Online Mendelian Inheritance in Man,DisGeNET and Therapeutic Target Database.Bioinformatics analysis to obtain key bioactive components,underlying targets and signaling pathways,containing the Venn diagram of the intersection with components and diseases gene targets,protein–protein interaction,as well as the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analysis,and finally molecular docking.Results:A total of 249 bioactive ingredients of HHML and 325 HHML-fracture-related targets were screened.The network analysis revealed that quercetin,luteolin,kaempferol,Licochalcone A,naringenin and 8-Isopentenyl-kaempferol may be potential candidate agents.Multiple targets are involved including TP53,MAPK3,STAT3,AKT1,MAPK1,HSP90AA1,ESR1 and PIK3CA may be closely linked targets.PI3K-AKT signaling pathway may play a significant role of HHML in treatment of fracture.What’s more,molecular docking suggested that 8-isopentenyl kaempferol,glycyrrhiza chalcone A,and naringenin bound to AKT1,PIK3CA,and ESR1,respectively,exhibiting lower energy and more stable characteristics.Conclusions:The findings indicate the potential active ingredients,target proteins and molecular mechanisms of HHML for the treatment of fractures to provide the exact idea for the next research on the mechanism of action of HHML formula for fracture treatment.

Numerical study of the splashing wave induced by a seaplane using mesh-based and particle-based methods

In recent years,forest fires and maritime accidents have occurred frequently,which have had a bad impact on human production and life.Thus,the development of seaplanes is an increasingly urgent demand.It is important to study the taxiing process of seaplanes for the development of seaplanes,which is a strong nonlinear fluid-structure interaction problem.In this paper,the smoothed particle hydrodynamics(SPH)method based on the Lagrangian framework is utilized to simulate the taxiing process of seaplanes,and the SPH results are compared with those of the finite volume method(FVM)based on the Eulerian method.The results show that the SPH method can not only give the same accuracy as the FVM but also have a strong ability to capture the splashing waves in the taxiing process,which is quite meaningful for the subsequent study of the effect of a splash on other parts of the seaplane.

Isolation and culture of human primary osteoblasts:Comparing the effects of differences in method details on osteoblast characteristics

Osteoblasts are essential in the maintenance of human bone homeostasis.1 The abnormal formation and impaired differentiation ability of osteoblasts are pivotal factors leading to bone-related diseases,suggesting that an indepth study of osteoblasts can provide novel treatment strategies for these diseases.2 Human primary osteoblasts are precious experimental models in bone-related research.3 However,the isolation and culture of human primary osteoblasts still have some difficulties and limitations.Here,we refined a method to isolate and culture human primary osteoblasts by taking cancellous bone through a bone tissue sampler and pre-digesting it with pancreatin,which makes the process easier,cheaper,and more efficient.Furthermore,we compared the effects of the subtle changes in isolation and culture methods on the phenotype of human primary osteoblasts and examined the differences in morphology,proliferation,and differentiation between micro-explants cultured osteoblasts(MECOBs)and explants cultured osteoblasts(EC-OBs).

基于δ+-SPH模型的三维鱼自主游动问题研究

仿生推进研究对水下潜器的水动力性能和续航能力提升具有重要意义.为此,本文采用光滑粒子流体动力学(Smoothed Particle Hydrodynamics,SPH)方法研究了三维鱼自主游动的流固耦合(fluid-structure interaction,FSI)问题.为提高SPH模型的计算精度和效率,文中采用了δ+-SPH模型并结合了张力不稳定控制技术(tensile instability control,TIC)和自适应粒子细化(adaptive particle refinement,APR)算法等.计算结果部分,为了验证SPH结果的精度和稳定性,首先采用三维球体绕流基准算例进行验证,随后将三维鱼游动速度与文献结果进行对比.通过比较二维和三维鱼自主推进的结果发现,两者预报的游动速度和涡量场均存在较大差异,凸显了三维研究的必要性.此外,本文对三维鱼尾流的涡结构进行了可视化,并展开详细讨论.结果表明,本文所建立的三维δ+-SPH模型为研究真实鱼类的仿生水动力性能提供了一种新的可靠手段.