Objective To observe the effects of Jianpi Qutan Huayu Prescription on oxidative stress and inflammatory response in mini-pigs with atherosclerosis(AS);To explore its mechanism based on the NOX5-ERK1/2 signaling pathway.Methods Twelve Bama mini-pigs were randomly divided into control group,model group,and Jianpi Qutan Huayu Prescription low-and high-dosage groups,with 3 pigs in each group.A high-fat diet was used to feed for 24 weeks to construct an AS model,and the treatment group was also supplemented with Jianpi Qutan Huayu Prescription in the feed.The general condition of mini-pigs(body length,abdominal circumference,body mass,food intake,and fecal water content)was measured at week 0,16,and 24 of administration,HE staining was used to observe the morphology of aortic tissue,while oil red O staining was used to observe lipid deposition in aortic and myocardial tissue,transmission electron microscopy was used to observe the ultrastructure of aortic tissue,and a fully automated biochemical analyzer was used to detect serum contents of TC,HDL-C,and LDL-C.ELISA was used to detect the contents of serum reactive oxygen species(ROS),interleukin(IL)-6,IL-10,tumor necrosis factor(TNF)-α,hypersensitivity-C-reactive protein(hs-CRP),vascular cell adhesion molecule-1(VCAM-1),and intercellular adhesion molecule-1(ICAM-1).Western blot was used to detect the expressions of NADPH oxidase 5(NOX5),extracellular signal regulated kinase 1/2(ERK1/2),p-ERK1/2,VCAM-1,and proliferating cell nuclear antigen(PCNA)proteins.Results Compared with the control group,the abdominal circumference,body mass,and food intake of mini-pigs in the model group increased at 16 and 24 weeks(P<0.01),there was significant thickening of the inner membrane of aorta,destruction of endothelial cells,lipid deposition,edema of smooth muscle cells,and significant swelling of mitochondria,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,VCAM-1,and ICAM-1 increased,while the content of HDL-C decreased(P<0.01);the expressions of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue increased(P<0.01).Compared with the model group,Jianpi Qutan Huayu Prescription low-and high-dosage groups showed a decrease in abdominal circumference,body mass,and food intake at 16 and 24 weeks(P<0.05,P<0.01),the plaque area and lipid deposition were reduced,and the damage to endothelial cells was alleviated,serum TC,LDL-C contents and the contents of ROS,IL-6,IL-10,TNF-α,hs-CRP,ICAM-1,and VCAM-1 decreased,and the content of HDL-C increased(P<0.01,P<0.05);the expressiond of NOX5,p-ERK1/2,VCAM-1,and PCNA proteins in aortic tissue decreased(P<0.01,P<0.05).Conclusion Jianpi Qutan Huayu Prescription can effectively alleviate AS in mini-pigs,and its mechanism may be related to inhibiting the activation of the NOX5-ERK1/2 signaling pathway and alleviating oxidative stress-induced inflammatory response.

Genome-wide association studies(GWAS)have identified thousands of genomic loci asso-ciated with complex diseases and traits,including cancer.The vast majority of common trait-associated variants identified via GWAS fall in non-coding regions of the genome,posing a chal-lenge in elucidating the causal variants,genes,and mechanisms involved.Expression quantitative trait locus(eQTL)and other molecular QTL studies have been valuable resources in identifying can-didate causal genes from GWAS loci through statistical colocalization methods.While QTL colo-calization is becoming a standard analysis in post-GWAS investigation,an easy web tool for users to perform formal colocalization analyses with either user-provided or public GWAS and eQTL datasets has been lacking.Here,we present ezQTL,a web-based bioinformatic application to interactively visualize and analyze genetic association data such as GWAS loci and molecular QTLs under different linkage disequilibrium(LD)patterns(1000 Genomes Project,UK Biobank,or user-provided data).This application allows users to perform data quality control for variants matched between different datasets,LD visualization,and two-trait colocalization analyses using two state-of-the-art methodologies(eCAVIAR and HyPrColoc),including batch processing.

The emergence of next-generation sequencing (NGS) technologies has significantly improved sequencing throughput and reduced costs.However,the short read length,duplicate reads and massive volume of data make the data processing much more difficult and complicated than the first-generation sequencing technology.Although there are some software packages developed to assess the data quality,those packages either are not easily available to users or require bioinformatics skills and computer resources.Moreover,almost all the quality assessment software currently available didn't taken into account the sequencing errors when dealing with the duplicate assessment in NGS data.Here,we present a new user-friendly quality assessment software package called BIGpre,which works for both Illumina and 454 platforms.BIGpre contains all the functions of other quality assessment software,such as the correlation between forward and reverse reads,read GC-content distribution,and base Ns quality.More importantly,BIGpre incorporates associated programs to detect and remove duplicate reads after taking sequencing errors into account and trimming low quality reads from raw data as well.BIGpre is primarily written in Peal and integrates graphical capability from the statstics package R.This package produces both tabular and graphical summaries of data quality for sequencing datasets from Illumina and 454 platforms.Processing hundreds of millions reads within minutes,this package provides immediate diagnostic information for user to manipulate sequencing data for downstream analyses. BIGpre is freely available at http://bigpre.sourceforge.net/.