Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

Objective To analyze the core functional component groups(CFCG)in Yinchenhao Decoction(YCHD)and their possible pathways for treating hepatic fibrosis based on network pharmacology.Methods PPI data were extracted from DisGeNET,Genecards,CMGRN and PTHGRN to construct a weighted network using Cytoscape 3.9.1.The data of the chemical components in YCHD were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential active components and targets were selected using PreADMET Web server and SwissTargetPrediction.A fusion model was constructed to obtain the functional effect space and evaluate the effective proteins to identify the CFCG followed by GO and KEGG pathway enrichment analyses for all the targets.In cultured human hepatic stellate cells(LX-2 cells),the cytotoxicity of different compounds in YCHD was tested using CCK-8 assay;the effects of these compounds on collagen α1(Col1a1)mRNA expression and the pathways in 20 ng/mL TGF-β1-stimulated cells were analyzed using RT-qPCR and Western blotting.Results A total of 1005 pathogenic genes,226 potential active components and 1529 potential targets in YCHD and 52 potential targets of CFCG were obtained.Benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid were selected for CCK-8 verification,and they all showed minimal cytotoxicity below the concentration of 200 μmol/L.Clorius,polydatin,lauric acid and ferulic acid all effectively inhibited TGF-β1-induced LX-2 cell activation.At the concentration of 200 μmol/L,all these 4 components inhibited PI3K,p-PI3K,AKT,p-AKT,ERK,p-ERK,P38 MAPK and p-P38 MAPK expressions in TGF-β1-induced LX-2 cells.Conclusion The therapeutic effect of YCHD on hepatic fibrosis is probably mediated by its core functional components including benzyl acetate,vanillic acid,clorius,polydatin,lauric acid and ferulic acid,which inhibit the PI3K-AKT and MAPK pathways in hepatic stellate cells.

Objective To analyze the serum differential metabolites and metabolic pathways of patients with refractory gout of spleen deficiency and damp-heat type by metabolomics based on 1 H-NMR.Methods A total of 40 patients with refractory gout acute attack of spleen deficiency and damp-heat type were selected as gout group,and 20 healthy subjects were selected as healthy group.Erythrocyte sedimentation rate and serum C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),serum adiponectin and creatinine levels were used as observation indicators.Serum metabolomics analysis was performed using 1 H-NMR method.The obtained data were subjected to principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)to determine the corresponding metabolites and analyze the potential metabolic pathways of the differential metabolites.Results Compared with the healthy group,the erythrocyte sedimentation rate,serum CRP,IL-6,TNF-α and other inflammatory indicators and cell chemokine levels in the gout group were significantly increased(P＜0.01);the serum adiponectin level was significantly decreased(P＜0.01),and the serum creatinine level was significantly increased(P＜0.01).There were significant differences in the content of serum metabolites between the healthy group and the gout group.A total of 44 differential metabolites were obtained,involving 12 potential metabolic pathways such as aminoacyl tRNA biosynthesis,valine,leucine and isoleucine biosynthesis,alanine,aspartic acid and glutamic acid metabolism,glycolysis/gluconeogenesis,ketone synthesis and degradation,citric acid cycle(TCA cycle),glutathione metabolism,glyceride metabolism.Conclusion Acute attacks of refractory gout with spleen deficiency and damp-heat type may be associated with disorders of mitochondrial energy metabolism,leading to abnormalities in glucose metabolism,lipid metabolism,and amino acid metabolism.

Auto-inhibited Ca²⁺-ATPase (ACA) is one of the Ca²⁺-ATPase subfamilies that plays an important role in maintaining Ca²⁺ concentration balance in plant cells. To explore the function and gene expression pattern of the RcACA gene family in castor, bioinformatics analysis was used to identify the members of the RcACA gene family in castor. The basic physical and chemical properties, subcellular location, protein secondary and tertiary structure, conserved domain, conserved motif, gene structure, chromosome location and collinear relationship, as well as the evolutionary characteristics and promoter cis-acting elements were predicted and analyzed. The expression pattern of the RcACA gene under abiotic stress was analyzed by expression (fragments per kilobase of exon model per million mapped fragments, FPKM) in castor transcriptome data. The results showed that 8 RcACA gene family members were identified in castor, acidic proteins located in the plasma membrane. In the secondary structure of all proteins, the α-helix and random coil is more; the RcACA genes were clustered into three categories, and the design of the genes in the same category was similar to the conserved motif. Both of them had four typical domains, RcACA3-RcACA8 had a Ca²⁺-ATPase N-terminal autoinhibitory domain. The RcACA gene is mostly located on the long arm of the chromosome and has 2 pairs of collinear relationships. There are more light response elements but fewer hormone-induced elements located upstream of the RcACA coding region. Interspecific clustering showed that the evolution of ACA genes among species was conservative. Tissue expression pattern analysis showed that RcACA genes showed apparent tissue expression specificity, and most of the genes showed the highest expression level in male flowers. Expression analysis under abiotic stress showed that RcACA2-RcACA8 were up-regulated under high salt and drought stress, and RcACA1 was up-regulated at 0-24 h under low-temperature stress, indicating that RcACA genes positively responded to abiotic stresses. The above results provide a theoretical basis for exploring the role of the RcACA gene in castor growth, development and stress response.
Genome, Plant ; Stress, Physiological/genetics* ; Transcriptome ; Promoter Regions, Genetic ; Phylogeny ; Plant Proteins/metabolism* ; Gene Expression Regulation, Plant

Objective: To evaluate the potential dose influence to organs at risk (OARs) and targets of adaptive radiotherapy (ART) for non-small cell lung cancer (NSCLC). Methods:Twice positional CT images of 12 patients with locally advanced NSCLC were captured during radio-(n=3) or radio-chemotherapy (n=9) for ART simulation. The twice positional scanningplan was fused using MIM software. The variation of irradiation doses for the lung, heart, and spinal cord was evaluated, and the prescription doses for the targets were escalated. Results:Adaptive radiation enabled dose reduction by an average of 3.53%for lung V20 and by 2.55%for V30. The mean dose for the lung decreased by 2.11 Gy. The dose was reduced by an average of 4.17%for heart V30 and by 3.37%for V40. Meanwhile, the maximum dose for the spinal cord was reduced by 3.52 Gy on average. Lung sparing with ART enabled an iso-mean lung dose escalation of the Planning gross tumor target volume dose, which improved by an average of 1.25 Gy. Conclusion:The adap-tation of radiotherapy for continuous tumor shrinkage during the treatment course for NSCLC reduces doses to OARs, enables signifi-cant dose escalation, and has the potential to increase local control.