Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Objective:To examine the relationship between subcortical volumes and ketamine’s antidepressant effects.Methods:Forty-five depressive patients with treatment resistance or suicide ideation were involved and received six infusions of ketamine for two weeks（0.5 mg/kg，thrice-weekly）. Depressive symptoms were assessed by Montgomery-?sberg Depression Rating Scale (MADRS) and suicide ideation was assessed by Beck Scale for Suicide Ideation-part one (SSI-Ⅰ). Subcortical volumes underwent 3.0T-weighted MRI. The Freesurfer software was used to process the T 1 images, which used a set of automated sequences to analyze subcortical volumes. Forty-five healthy controls were collected and their subcortical volumes were compared with the patients’ volumes. Linear regression analysis was used to determine the association between pre-treatment subcortical volumes and change in MADRS score as well as SSI scores after ketamine treatment (change=pre-treatment scores minus post-treatment scores). Results:In comparison to the healthy controls, depressive patients had decreased bilateral hippocampal volumes (Left:(2 993±276) mm 3vs. (2 785±263) mm 3， F=12.928， P=0.001； Right: (3 117±254) mm 3vs. (2 949±270) mm 3, F=8.217， P=0.005). Pre-treatment volumes of right thalamus were positively correlated with change in MADRS scores after six infusions in patients with treatment resistance （ B=0.009， t=3.434, P=0.002）. Conclusion:Six ketamine infusions exerted enhanced antidepressant effects in treatment-resistant depression patients with relatively larger thalamus. Volume of thalamus could be used as a biomarker of six ketamine’s antidepressants treatment outcome.

Objective:To examine the relationship between subcortical volumes and ketamine’s antidepressant effects.Methods:Forty-five depressive patients with treatment resistance or suicide ideation were involved and received six infusions of ketamine for two weeks（0.5 mg/kg，thrice-weekly）. Depressive symptoms were assessed by Montgomery-?sberg Depression Rating Scale (MADRS) and suicide ideation was assessed by Beck Scale for Suicide Ideation-part one (SSI-Ⅰ). Subcortical volumes underwent 3.0T-weighted MRI. The Freesurfer software was used to process the T 1 images, which used a set of automated sequences to analyze subcortical volumes. Forty-five healthy controls were collected and their subcortical volumes were compared with the patients’ volumes. Linear regression analysis was used to determine the association between pre-treatment subcortical volumes and change in MADRS score as well as SSI scores after ketamine treatment (change=pre-treatment scores minus post-treatment scores). Results:In comparison to the healthy controls, depressive patients had decreased bilateral hippocampal volumes (Left:(2 993±276) mm 3vs. (2 785±263) mm 3， F=12.928， P=0.001； Right: (3 117±254) mm 3vs. (2 949±270) mm 3, F=8.217， P=0.005). Pre-treatment volumes of right thalamus were positively correlated with change in MADRS scores after six infusions in patients with treatment resistance （ B=0.009， t=3.434, P=0.002）. Conclusion:Six ketamine infusions exerted enhanced antidepressant effects in treatment-resistant depression patients with relatively larger thalamus. Volume of thalamus could be used as a biomarker of six ketamine’s antidepressants treatment outcome.