ObjectiveTo investigate the functional role and underlying molecular mechanisms of fumarylacetoacetate hydrolase （FAH） in the progression of glioblastoma （GBM）. MethodsDifferential expression analysis was performed on the TCGA-GBM， GSE4290， and GSE116520 datasets. Weighted gene co-expression network analysis （WGCNA） was used to identify key modules， and Cox regression and risk modeling were used to screen prognostic genes. Immune infiltration analysis of prognostic genes was carried out by using single-cell RNA sequencing panels. The clinical expression signature of FAH in GBM was analyzed in the TCGA and HPA databases. The functional role of FAH was validated by in vitro and in vivo experiments， and pathway analysis was performed to explore the underlying mechanisms. ResultsA total of 152 overlapping genes were identified across the three GBM datasets （P<0.05）. WGCNA revealed that the turquoise module was most strongly associated with tumor purity， stromal score， immune score， and ESTIMATE score （P<0.001）. Compared with normal tissues， three prognostic genes （CTSD， FAH， and THBD） were upregulated in GBM and correlated with immune infiltration （P<0.05）. FAH mRNA and protein levels were elevated in GBM tissues relative to normal tissues， and its expression was significantly associated with age stratification and TP53 mutation （P<0.05）. CCK-8 assay results showed that， compared with the shNC group， the proliferative activity of GBM cells in the shFAH group was reduced （P<0.001）. Transwell migration and invasion assays demonstrated that， relative to the shNC group， the numbers of migrated and invaded cells in the shFAH group decreased （P<0.05）. Western blot analysis revealed that the protein expression levels of PI3K， p-AKT， and p-mTOR in the shFAH group decreased compared with those in the shNC group （P<0.05）. In vivo subcutaneous xenograft experiments further confirmed that tumor volume and weight significantly decreased in the shFAH group compared with the shNC group （P<0.001）. ConclusionFAH promotes GBM progression by activating the PI3K/AKT/mTOR signaling pathway and may serve as a potential therapeutic target for GBM.

Objective:To study the abnormal suppressive capacity of regulatory T cells ( Tregs) to effector cells,Th17 cells and Th9 cells in patients with mild to moderate asthma attack.Methods: Recruited asthmatic patients (n=30) and healthy control (n=30),collected peripheral venous blood from healthy control and asthmatic patients in mild to moderate attack stage respectively,and then isolated CD4+CD25+CD127-/low Tregs and CD4+CD25-T effect cells with immunomagnetic beads method ( purity was above 90%).The effect cells were cultured with PHA stimulation with or without Tregs.Measured the proliferation (3H-Thymidine), expression of RORC and PU.1 ( RT-PCR) genes,production of IL-17 and IL-9 ( LUMNEX) in effect cells with or without Tregs inter-vention.Analyzed the abnormality of Th17 and Th9 cells and the supressive capacity of Tregs on Th17 and Th9 cells in patients with asthma attack,comparing with control group.Results:Tregs of asthmatic patients could suppress the proliferation of effector cells,but less effectively than healthy control (P=0.03).In asthmatic patients,RORC expression and IL-17 production increased (P<0.05), and the suppressive capacity of Tregs to RORC expression decreased, when compared with healthy group ( P<0.05 ) .In asthmatic patients,IL-9 production of effector cells increased significantly (P<0.05),but PU.1 expression was higher than healthy group only with intervention of Tregs ( P=0.04 ) .And the suppressive capacity of Tregs to the expression of PU.1 and production of IL-9 in patients with asthma attack did not decrease (P>0.05).Conclusion:The suppressive capacity and amount of Tregs decreased,but the specific gene expression and cytokines production of Th17 cells and Th9 cells were upregulated in patients with mild to moderate asthma attack.This deficiency for the suppressive capacity of Tregs to Th17 but not Th9 cells may indicate some pathogenesis of asthma devel-opment.

Objective To investigate the gene expressions of IL-1 and TNF-? in bronchoalveolar lavage fluid(BALF) and lung tissues in mice with pulmonary fibrosis(PF) at various periods and to study the effects of cytokines on pulmonary fibrosis.Methods Forty male mice were randomly divided into two groups:experimental group(n=30) and control group(n=10),and poured respectively by bleomycin solutions and saline and killed on the 3rd,7th,14th,28th and 56th day.RT-PCR method was used to analyse the mRNA expressions of IL-1 and TNF-?.Results ① The expressions of IL-1 mRNA and TNF-? mRNA in BALF in experimental group were higher than those in control group(P

Objective Objective To study the effect of Mycobacterium tuberculosis (Mtb) on IFN-? signaling pathway in macrophages. Methods Humans and mice macrophages were isolated and infected by Mtb, condition medium were collected after a few days culture; Macrophage surface expression of Fc?RI (human) or MHC II (mouse) was measured by flow cytometry to explore the effect of condition medium on macrophage response to IFN-?. Results Surface expression of Fc?RI in human macrophages cultured in condition medium was significantly decreased compared to those without condition medium (p