According to the working principle of vertical ultrasonic vial washing machine, receiving respective force of small water droplets on the inside wall of vials and the minimum air velocity of blowing off water droplets can be obtained based on the analysis of water-droplet-related parameters. The inside wall model of 7 mL vial created by GAMBIT was divided into fine grids. Then the Realizable k-epsilon Two Equation Turbulence Model was adopted and the flow field of vial by FLUENT software was simulated when air was flushing inside the wall. In that case, the optimal position, inner diameter and the corresponding minimum air velocity of needle can be acquired to meet the needs of vial washing machine applied to 7 mL vial.
Equipment Design ; Models, Theoretical ; Needles ; Software

Objective To explore the molecular mechanism of Xiaojin Pills in the treatment of breast cancer using an integrated network pharmacology and experimental verification.Methods The chemical components and potential targets of Xiaojin Pills were obtained from TCMSP,TCM-ID,ETCM and SwissTargetPrediction databases.Breast cancer related targets were collected from GeneCards,OMIM and KEGG databases.The overlapped targets were imported into STRING database to analysis a protein-protein interaction(PPI).The key targets of PPI networks were screened based on node topology parameter values through Cytoscape 3.8.0.DAVID database was used to analyze the GO and KEGG pathway enrichment to build drug-chemical components-key targets-signaling pathway network.The breast cancer cell lines MDA-MB-231 and SK-BR-3 were used to study the effects of Xiaojin Pills extract on cell apoptosis,migration and invasion,and to verify the key pathway obtained by enrichment analysis.Results Totally 181 chemical components in Xiaojin Pills were obtained,including quercetin,myricetin,pinocembrin and β-sitosterol.615 potential targets were identified for the anti-breast cancer effects of Xiaojin Pills.After overlapping,170 key targets against breast cancer were identified based on the topological analysis,which included SRC,ERK1/2,AKT1,EGFR,etc.KEGG analysis enriched pathways including pathways in cancer,MAPK signaling pathway,endocrine resistance,PI3K-AKT signaling pathway,EGFR tyrosine kinase inhibitor resistance,apoptosis,and HIF-1 signaling pathway,which may play important roles in the therapeutic effects of Xiaojin Pills against breast cancer.GO enrichment was involved in protein phosphorylation,inflammatory response,negative regulation of apoptosis,and positive regulation of ERK1 and ERK2 cascades.Cell experiments showed that Xiaojin Pills further induced mitochondria-dependent apoptosis by inhibiting the activation of MAPK and PI3K-AKT pathways.At the same time,the expressions of ZO-1 and β-catenin increased,and the epithelial-mesenchymal transformation process was reversed to inhibit the metastasis of breast cancer cells.Conclusion The key targets and signaling pathways of Xiaojin Pills in the treatment of breast cancer are studied through network pharmacology combined with in vitro experiments,which provided a basis for further study of its pharmacodynamic material basis,mechanism of action and clinical application.

ObjectiveTo investigate the therapeutic effect of Ganmai Dazao Tang on breast cancer-related depression and explore the mechanism of the decoction in regulating immune inflammation and neurotransmitters via the mitogen-activated protein kinase （MAPK）/nuclear factor-κB （NF-κB） pathway. MethodBALB/c mice were randomized into control， model， fluoxetine （5 mg·kg^-1·d^-1）， and low- and high-dose （crude drug 20 and 40 g·kg^-1， respectively） Ganmai Dazao Tang groups （n=10）. The mouse model of 4T1 orthotopic transplantation-induced breast cancer-related depression-like behavior was established. The depression-like behavior of mice was assessed by the tail suspension test and the forced swimming test. RT-qPCR was employed to determine the mRNA levels of interleukin （IL）-17A， forkhead box P3 （FoxP3），IL-1β， IL-6， and tumor necrosis factor-α （TNF-α） in the cerebral cortex. Flow cytometry was employed to measure the proportions of immune cell subsets in the spleen and thymus. HPLC-MS/MS was employed to measure neurotransmitter levels in the cerebral cortex. Western blotting was employed to detect the activation of the MAPK/NF-κB pathway. ResultCompared with the model group， administration of Ganmai Dazao Tang at a dose of 40 g crude drug·kg^-1 continuously for 4 weeks shortened the immobility time of modeled mice in the tail suspension and forced swimming tests （P<0.05）， down-regulated the mRNA levels of IL-1β， IL-17A， and TNF-α （P<0.05）， increased the proportions of T cells， CD4⁺ T cells， B cells， helper T 17 （Th17） cells， and regulatory T （Treg） cells， and reduced the proportion of CD8⁺ T cells （P<0.05）. Furthermore， it lowered the levels of 5-hydroxyindoleacetic acid （5-HIAA） and kynurenine （Kyn）， decreased the kynurenine/tryptophan （Kyn/Trp） ratio （P<0.05）， increased the content of 5-hydroxytryptamine （5-HT）， and down-regulated the protein levels of phosphorylated extracellular signal-regulated kinase （p-ERK）， phosphorylated p38 MAPK， and phosphorylated nuclear factor-κB p65 （P<0.05）. ConclusionGanmai Dazao Tang can down-regulate the expression of inflammatory cytokines such as IL-1β， IL-17A， and TNF-α， restore 5-HT metabolism and Kyn/Trp balance， increase the 5-HT content， and reduce the activation of p38 MAPK， ERK， and the MAPK-mediated NF-κB signaling pathway to reduce neuroinflammation in the treatment of cancer-related depression.