Objective:To investigate the anti-gout capsule ( AGC) effect on acute gouty arthritis ( AGA) rat tumor necrosis factor-α(TNF-α)level.Methods: Selected 60 SD rats,were randomly divided into normal group,model group,colchicine group(0.8 mg/kg),AGC low dose group (0.3 g/kg) and AGC high dose group (1.2 g/kg),12 rats in each group,detected each group articular cartilage,serum and synovial fluid TNF-αcontent,observed rats ankle swelling.Results: The model group 24 h,48 h gait behavior scores were(2.57±0.43)point and(2.11±0.50)point,significantly higher than other groups (P<0.05);colchicine group,AGC low dose group and AGC high dose group 24 h,48 h gait behavior score were significantly lower than that of model group (P<0.05).The model group began to swell after modeling 2 h,reached the peak at 12-24 h.The rats in the modeling 72 h each period ,the model group ankle swelling rate were significantly higher than the normal group , the difference was statistically significant ( P<0.05 ) .Colchicine group 12 h,24 h and 48 h ankle swelling rate was significantly lower than that of model group ( P<0.05 ) ,AGC high dose group 12 h,24 h,48 h and 72 h ankle swelling rate was significantly lower than that of model group ( P<0.05 ) ,AGC low dose group ankle swelling rate was lower than that of the model group only in 24 h ( P<0.05 ) .The model group articular cartilage TNF-αexpression significantly increased compared with normal group ( P<0.05 ) ,but model group and colchicine group difference were no statistically significant ( P>0.05 );AGC high dose group and low dose group articular cartilage TNF-αexpression significantly decreased than model group ( P<0.05).The model group serum and synovial fluid TNF-αcontent were significantly higher than the normal group (P<0.05);colchicine group,AGC low dose group and AGC high dose group serum and synovial fluid TNF-αcontent reduced compared with the model group (P<0.05);AGC low dose group and AGC high dose group serum TNF-αwere(0.81±0.27)ng/ml and(0.79±0.31)ng/ml,lower than the colchicines group ( P<0.05 ).Conclusion:AGC can significantly improve the joint symptoms of AGA rats ,decrease AGA rats articular cartilage tissue ,serum and synovial fluid TNF-αlevel.

Objective To study the protective effects of tBHQ on type 2 diabetic rats retina and its related mechanism.Methods Sixty SD rats were divided into normal control group (NC group),model group (diabetes mellitus,DM group) and tBHQ group.After feeding with high fat and high sugar diets for 4 weeks,the rats in model group were induced by intraperitoneal injection of STZ for the model of type 2 diabetes mellitus.1％ tBHQ were added into the high fat and high sugar feed 1 week later after successfully modeled in the tBHQ group.Fasting plasma glucose (FPG) and fasting serum insulin (FINs) were detected at 4 and 12 weeks after modeled.Immunohistochemical method and real-time fluorescent quantitative PCR (qRT-PCR) were respectively used to detect the distributions and relative expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2),heme oxygenase 1 (HO-1),B-cell lymPhoma 2 (Bcl-2) and vascular endothelial growth factor (VEGF) in retinas of the rats.Results FPG levels totally comparative differences were statistically significant between each group (F =78.531,P =0.000).The level of FPG in DM and tBHQ group were obviously higher than that in NC group,the 12 weeks was higher than 4 weeks in DM group,and the 12 weeks was lower than 4 weeks in tBHQ group (all P ＜ 0.05).Totally comparative differences in the level of FINs were statistically significant (F=22.480,P =0.000),NC group was lower than DM and tBHQ group,12 weeks was higher than 4 weeks (all P ＜ 0.05).Immunohistochemical detection showed that each factor in each group were expressed in the retina of rat,and the relative expressions of Nrf2,HO-1,Bcl-2 and VEGF protein in retina have totally statistically differences in different time points after modeled (all P ＜0.05).The expressions of each factor in DM group were more than those in the NC group.The Nrf2,HO-1 and Bcl-2 in tBHQ group were more than those in the DM group,but the VEGF was lower.At 12 weeks,the expressions of VEGF and Nrf2 in DM group were more than those at 4 weeks,but the HO-1 was lower;the Nrf2,HO-1 and Bcl-2 in tBHQ group were more than those at 4 weeks (all P ＜ 0.05).PCR tests revealed that the relative expressions of Nrf2,HO-1,Bcl-2 and VEGF mRNA in retina have totally statistically differences in different time points after modeled(all P ＜ 0.05).The expressions of each factor in DM group were more than those in the NC group.The Nrf2,HO-1 and Bcl-2 mRNA in tBHQ group were more than those in the DM group,but the VEGF mRNA was lower.At 12 weeks,VEGF mRNA in DM group and Nrf2,HO-1,Bcl-2 in tBHQ group were more than those at 4 weeks (all P ＜ 0.05).Conclusion tBHQ maybe have protection for islet function on diabetic rat,and can induce the expressions of Nrf2,HO-1,Bcl-2 in retina of diabetic rats and reduce the expression of VEGF,inhibit the oxidative stress of retinal tissue damage,reduce cell apoptosis and inhibit the proliferation of retinal blood vessels.tBHQ may protect the retina of diabetic rats through the Nrf2/HO-1/VEGF and Nrf2/Bcl-2 way.

Background Apoptosis is a primary clinical pathological mechanism of diabetic retinopathy (DR).Oxidative stress and high glucose can activate cell apoptosis pathway and thus leads to cellular damage.It is confirmed that tert-butyl hydroquinone (tBHQ) plays an antioxidation effect,however,whether it has a protective role on retinal cells in DR is still unelucidated.Objective This study was to investigate the effect of tBHQ on vascular endothelial growth factor (VEGF) and bcl-2 expressions in retina of type 2 diabetic rats and its possible mechanism via nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signal pathway.Methods Fifty clean healthy male SD rats were included in this experimental study.Ten rats were fed with normal diet as the normal control group,and other rats were fed with high fatty and high sugar food for 4 weeks.After 12 hours of fasting,streptozotoin (STZ) (30 mg/kg) was intraperitoneally injected to induce the type 2 diabetic models.The model rats were randomly divided into the diabetic control group and tBHQ group and 1％ tBHQ was added into the high fatty and sugar food 1 week after modeling in the tBHQ group.Fasting plasma glucose (FPG) level,blood total cholesterol (TC) level,blood triglyceride (TG) level,high density lipoprotein-cholesterol (HDL-C),low density lipoproteincholesterol (LDL-C) and fasting serum insulin (FINs) were detected 4 and 12 weeks after modeling,respectively,and radio immunoassay was used to detect the FIN levels of the rats.The relative expression of VEGF and bcl-2 in retinas of the rats were assayed by immunohistochemistry and fluorescence real-time quantitative PCR (qRT-PCR).The use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State and Technology Commission.Results Type 2 diabetic models were successfully established in 35 rats with successful rate 92.1％.The FIN levels were significantly different among different groups and time points (Fgroup =22.480,P =0.000;Ftime =7.636,P =0.008).The FPG,TC,TG and LDL-C levels were significantly different among the groups (FPG:Fgroup =78.531,P =0.000;TC:Fgroup =28.049,P =0.000;TG:Fgroup =13.108,P =0.000;LDL-C:Fgroup =6.804,P＜0.05).Immunohistochemistry showed that VEGF and bcl-2 were mainly expressed in retinal ganglion cell layer,inner plexiform layer and outer plexiform layer.The expressions of VEGF and bcl-2 proteins were significantly different among different groups (VEGF:Fgroup =11.805,P =0.000;bcl-2:Fgroup =22.943,P =0.000);the expression level of bcl-2 protein was higher in 12 weeks after modeling than that in 4 weeks after modeling in the tBHQ group (P＜0.05).The expressions of VEGF and Bcl-2 mRNA in rat retinas were significantly different among different groups and time points (VEGF:Fgroup =79.220,P =0.000;Ftimo =6.090,P＜0.05;Bcl-2:Fgroup =105.000,P=0.000;Ftime =13.170,P=0.001).Four and eight weeks after modeling,the expressions of VEGF and Bcl-2 mRNA in the diabetic control group and tBHQ group were significantly higher than that in the normal control group,and the expressions of Bcl-2 mRNA in the tBHQ group were significantly higher than that in the model control group (all at P＜0.05);the expression of Bcl-2 mRNA was higher at 12 weeks after modeling than that at 4 weeks in the tBHQ group (P＜0.05).Conclusions tBHQ produces anti-oxidative-damage and anti-apoptosis effects on retinal cells by up-regulating VEGF expression and down-regulating bcl-2 expression in DR rats.In addition,tBHQ may have effects on lowering high blood sugar,regulating insulin and blood lipid levels.

Objective:To investigate the efficacy of Silybinin meglumine on hepatic fibrosis rats and possible mecha -nisms.Methods:The liver fibrosis rats were randomly divided into 4 groups,the model group,Silybinin meglumine 120 mg/kg group, Silybinin meglumine dose group 60 mg/kg and Silybinin meglumine low dose group 30 mg/kg,and the control group.All groups had been treated for 4 groups.Results:No deaths rat.Compared with the control group ,the reduced body weight ,less dynamic,dark hair, decreased liver and spleen indexes ,increased ALT,AST,TBIL,TG,TC and LDLC,and the decreased ALB, and the increased LXRαand SREBP1c had been observed in the model group (P<0.05).Compared with the model group ,better activity and body weight ,the in-creased liver and spleen indexs decreased ALT ,AST,TBIL,TG,TC and LDLC,and the increased ALB , and the decreased LXRαand SREBP1c had been observed in the Silybinin meglumine groups (P<0.05),in a way of dose-depended.Conclusion: The Silibinin meglumine can treat liver fibrosis ,by improving liver function,lowing lipid and decreaseing LXRαand SREBP1c expression in liver tis-sue.But the mechanism of two proteins reduced remains for further investigation .

Lung cancer is one of the most common cancers worldwide, and its mortality rate remains high. In addition to conventional surgery, radiotherapy, and chemotherapy, immunotherapy methods have been developed and used in recent years for the treatment of non-small cell lung cancer (NSCLC). However, only a small number of patients with NSCLC can benefit from immunotherapy strategies, and some patients even have hyperprogression after receiving immunotherapy. Therefore, precision immunotherapy requires effective biomarkers to guide it. In this paper, tissue samples, blood samples, intestinal microbiota, and other biomarkers are reviewed according to different sample sources. Blood samples, including TCR immune repertoire, Tregs cells, cytokines, lactate dehydrogenase, and other markers, are summarized and analyzed to provide reference for clinicians' diagnosis and treatment decisions.

OBJECTIVE: To explore the correlation between altered levels of neurotransmitters in the frontal lobe and hippocampus and behavioral abnormalities in a Clock variant mice modeling bipolar disorder manic disorder. METHODS: Open field test and Elevated plus-maze test were carried out on the Clock mutant and wild-type control groups. The frontal lobe and hippocampus of Clock mutant mice and controls were dissected, and neurotransmitters in tissue extracts were analyzed by high-performance liquid chromatography and mass spectrometry. The concentration of neurotransmitters and behavioral indicators were assessed by t test and Pearson correlation analysis using SPSS 22.0. RESULTS: The Clock mutant mice showed a significant increase in activity, albeit with no difference in the level of anxiety from the wild-type controls, which suggested that the Clock mutant mice can be used as a model for manic attack of bipolar disorder. Altered neurotransmitter levels were detected in the frontal and hippocampal regions, including elevated histamine in the left hippocampus, reduced histamine in the right hippocampus, reduced gamma-aminobutyric acid (GABA) in bilateral hippocampus, elevated dihydroxyphenylalanine (DOPA) in the left frontal lobe and reduced DOPA in the right hippocampus, and decreased glutamine in bilateral frontal lobes. The reduced glutamine in the left frontal lobe and GABA in the right hippocampus correlated with the increased activity of Clock mutant mice. CONCLUSION Clock mutant mice showed abnormal behavior with increased activity. Reduced glutamine in the left frontal lobe and GABA in the right hippocampus were correlated with increased activity.