Study on the mechanism of SND in the treatment of anxiety disorders based on network pharmacology, molecular docking and experiment validation

Background:Sini decoction(SND)is a classic traditional Chinese medicine(TCM)formulation that can be used to treat anxiety-related disorders,but the active substance and underlying molecular mechanism of its anxiolytic effects are unknown.In this study,network pharmacology,molecular docking research and experimental verification methods were used to preliminarily explore the bioactive compounds and potential target mechanisms of SND anxiolytic.Methods:The active components and corresponding targets of SND were collected by TCMSP.GeneCards,OMIM,PharmGkb,TTD and Drugbank were used to search for the targets of anxiety disorders.The core target of SND in the treatment of anxiety was screened by PPI.R language was used to analyze the intersection targets of SND in the treatment of anxiety disorders by GO and KEGG enrichment analysis.AutoDock Vina was used for molecular docking,and Discovery Studio was used for visual conformation analysis after docking.The anti-anxiety effect and molecular mechanism of SND were studied by in vivo experiment.Results:Based on network pharmacological analysis,we obtained 112 active ingredients and 350 effective targets related to anxiety from SND.In PPI analysis,26 targets such as STAT3,MAPK3,MAPK1,MAPK14,SRC,HSP90AA1,TP53 and PIK3CA were identified as core targets.GO and KEGG analysis showed that the anxiolytic mechanism of SND may be related to the neuroactive ligand-receptor interaction pathway and inflammatory pathway.Molecular docking showed that quercetin,naringenin,licochalcone A had high affinity with JAK2,MAPK14 and MAPK3.Animal experiments have shown that SND reverses the upregulation of GluN2B(NMDAR)and GluA1(AMPAR)proteins,and SND improves anxiety disorders by regulating glutamate transmitter levels,which may be related to neuroactive ligand-receptor interaction pathways,particularly glutamate receptors.Conclusion:This study shows that SND can improve FS-induced behavioral changes in mice and can modulate hippocampal synapse-associated protein defects,partially reversing glutamate receptor expression through the neuroactive ligand-receptor interaction pathway,and further improved anxiety disorders.At the same time,combined with network pharmacology and molecular docking,the key components,core targets and related pathways of SND are discussed,which shows that the active components of SND play an effective role in anxiety through multi-targets and multi-pathways,which provides a reference for the material basis and mechanism of SND.

Equivalent protection factor of bi-layer ceramic metal structures

With increasing ballistic threat levels,there is ever more demand on developing ceramic armor designs with improved performance.This paper presents finite element simulations that investigate the performance of silicon carbide ceramic with steel 4340 backing material and titanium alloy,graphite as buffer layers when subjected to normal and oblique impacts by a tungsten alloy long rod projectile(LRP).Depth of penetration from experimental measurements is compared with simulations to confirm the validity of constitutive,failure model parameters.Titanium alloy cover plate and graphite interface weak layer laterally spread the impact shock away from the SiC tile and reduces the amplification of the stress accumulation at the front surface of the SiC tile.The dwelling time increases before it penetrates into ceramic armor.Further,using AUTODYN®numerical simulations detailed parametric study is carried out to identify the minimum areal density armor for a given ballistic limit velocity.The equivalent protection factor for the bi-layer armor is a simple function of the cosine of the angle of impact.

Systemic analysis of pre-hospital trauma emergency treatment in Zhengzhou

Objective: To analyze the data of pre-hospital emergency treatment in zhengzhou from 2007 to 2016, and evaluate the current situation of pre-hospital trauma emergency treatment, in order to provide a scientific basis for effective use of first aid resources and enhance success rate of trauma emergency treatment. Methods: Retrospective analysis was conducted based on pre-hospital emergency resources of Zhengzhou Emergency Medical Rescue Center from 2007 to 2016. Results: The total number of pre-hospital emergency treatment cases was 9305687 from 2007 to 2016 in Zhengzhou, of which 418882 were trauma cases. The top five causes of injury were traffic accident injury, cutting injury, beating injury, crushing injury and falling injury. The top five emergency treatments used were oxygen, hemostasis, dressing and fixation, fluid supplementation, analgesics and sputum aspiration. According to different directions of diagnosis, the pre-hospital emergency patients were divided into four groups:emergency treatment group, emergency observation group, admission to general ward group and admission to ICU group. There was no statistical difference in the ages among the four groups (P>0.05). There were significantly statistical differences in gender composition among the four groups, with more males than females (P<0.01). Significant statistical differences also showed in CRAMS scores among the four groups (P<0.01). Before and after the training of primary trauma care, there was no significant difference in the constituent ratio of the trauma (P>0.05), but the mortality of the trauma, the average arrival time, and the mean treatment time were significantly different (P<0.01). Conclusions: The number of pre-hospital emergency trauma patients increased year by year, but the constituent ratio changed little. CRAMS score is important for the patients triage. Through the training of primary trauma care, the constituent ratio of death was reduced, and the average treatment time was shortened.