Objective To explore the effects of panobinostat on the proliferation,migration and invasion of renal carcinoma cells via targeting ADP ribosylated factor-like protein 4C(ARL4C).Methods According to different treatments,human renal carinoma 786-O cells were divided into blank group(phosphate buffer treatment),experimental group(50 nmol·L-1 panobinostat treatment),empty vector group(transfection with empty vector and no treatment),overexpression group(transfection with ARL4C overexpression vector and no treatment)and combined group(transfection with ARL4C overexpression vector and 50 nmol·L-1 panobinostat treatment).The proliferation,migration and invasion of cells were detected by methyl thiazolyl tetrazolium assay and scratch assay.Cholesterol transport levels in cells were detected by enzyme-labeled assay.The mRNA and protein levels of ARL4C in cells were detected by real-time fluorescence quantitative polymerase chain reaction and Western blot.Results The indicators of cell proliferation in blank group,experimental group,empty vector group,overexpression group and combined group were(100.00±0)％,(61.08±5.82)％,(101.22±5.92)％,(121.94±6.63)％and(101.78±6.87)％;the indicators of cell migration were(44.59±2.49)％,(29.02±2.09)％,(42.75±2.42)％,(54.19±3.05)％and(41.91±2.75)％;the indicators of cell invasion were 264.50±6.52,182.70±5.83,257.80±7.91,322.40±8.27 and 266.80±8.15;the intracellular levels of cholesterol were(72.48±6.21),(36.48±3.44),(73.89±5.91),(89.21±8.89)and(73.06±6.92)mmol·L-1;the relative expression levels of ARL4C mRNA were 1.23±0.22,0.24±0.08,1.27±0.25,1.67±0.38 and 1.27±0.25;the relative expression levels of ARL4C protein were 1.06±0.03,0.17±0.04,1.03±0.05,1.37±0.18 and 1.05±0.08,respectively.Between the blank group and experimental group,the above indicators have statistically significant differences(all P＜0.05);compared with the blank group and empty vector group,the above indicators in overexpression group have statistically significant differences(all P＜0.05).Conclusion Panobinostat downregulate the intracellular levels of cholesterol by reducing the expression level of ARL4C in 786-O cells,thus inhibiting the proliferation,migration and invasion of renal carcinoma cells.

Objective To investigate the effects and mechanisms of lncRNA OIP5-AS1 on cell proliferation and apoptosis in esophageal squamous cell carcinoma(ESCC).Methods TE-1 cells were randomly divided into control(normal culture),si-NC(transfected with si-NC),si-OIP5-AS1(transfected with si-OIP5-AS1),si-OIP5-AS1+NC inhibitor(transfected with si-OIP5-AS1,NC inhibitor),si-OIP5-AS1+miR-129 inhibitor(transfected with si-OIP5-ASS1,miR-129 inhibitor),NC mimic(transfected with NC mimic),miR-129 mimic(transfected with miR-129 mimic),miR-129 mimic+Vector(transfected with miR-129 mimic,Vector),miR-129 mimic+KRAS[transfected with miR-129 mimic,Kirsten rat sarcoma virus oncogene(KRAS)]groups.The expression of OIP5-AS1 and miR-129 in each group was detected by real-time fluorescence quantitative polymerase chain reaction assay.The expression levels of KRAS,N-cadherin,Vimentin and E-cadherin in cells were detected by Western blot assay.Cell proliferation was detected by cell counting kit-8(CCK-8),and apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL)assay.Results The expression levels of OIP5-AS1 in cells of control,si-NC,si-OIP5-AS1,si-OIP5-AS1+NC inhibitor,si-OIP5-AS1+miR-129 inhibitor groups were 1.00±0.13,0.98±0.12,0.25±0.04,0.25±0.02 and 0.89±0.08;the expression levels of miR-129 were 1.00±0.15,0.97±0.07,2.06±0.17,2.04±0.11 and 1.22±0.15;72 h absorbance values(OD)were 1.16±0.12,1.11±0.09,0.58±0.03,0.58±0.05 and 0.94±0.10.The KRAS protein expression levels of NC mimic,miR-129 mimic,miR-129 mimic+Vector,and miR-129 mimic+KRAS groups were 1.08±0.07,0.41±0.06,0.40±0.06,1.03±0.10;the 72 h OD values were 1.17±0.10,0.59±0.03,0.60±0.04 and 0.90±0.05,respectively.si-NC group was compared with si-OIP5-AS1 group,si-OIP5-AS1+NC inhibitor group was compared with si-OIP5-AS1+miR-129 inhibitor group,NC mimic group was compared with miR-129 mimic group,miR-129 mimic+Vector group was compared with miR-129 mimic+KRAS group,the differences of the above indexes were statistically significant(all P＜0.05).Conclusion OIP5-AS1 can promote ESCC cell proliferation and epithelial mesenchymal transformation by regulating miR-129 targeting KRAS.

Objective To study the role of sphingosine-1-phosphate(S1P)signal on the proliferation of breast cancer BT549 cells.Methods Cells were divided into control group and experimental group,experimental group were treated with 0.1,1.0,10.0 μmol·L-1 S1P receptor agonist SEW2871 for 72 h.Control group was cultured with 0.1％fetal bovine serum.Cell proliferation was detected by methyl thiazolyl tetrazolium(MTT)assay.Cell models of overexpressing S1P receptors in BT549 were divided into three groups:blank plasmid group(LUC),wild type S1P receptor overexpression group(WT),S1P receptor phosphorylation site mutation overexpression group(MUT);the proliferation ratio was detected by MTT,the number of cell clones was counted by colony formation experiment.S1P antagonist W146(10 μmol·L-1)and protein kinase(AKT)signaling inhibitor MK2206(90 nmol·L-1)were used to detect the role of S1P signaling in the proliferation of breast cancer cells.The expression of phosphorylate signal transducer and activator of transcription 3(p-STAT3),c-Myc proteins were detected by Western blot.Results The growth ratio of BT549 cells in control group and 0.1,1.0,10.0 μmol·L-1experimental groups were 1.00±0.03,1.13±0.06,1.06±0.10 and 1.07±0.03,0.1 μmol·L-1 SEW2871 promot the cell proliferation(P＜0.05).Compared between WT group,MUT group and LUC group,the growth rate and the number of clonal colonies were increased after overexpression of S1P receptor(all P＜0.05).The growth ratio of BT549 cells after treatment with W146 and MK2206 in the LUC group,WT group and MUT group were 1.25±0.12,1.31±0.03,1.43±0.14 and 0.87±0.15,0.77±0.03,0.88±0.02.Compared between MUT group,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.01).The number of cell clony formation number after treatment with W146 were 65.65±5.12,141.48±5.63 and 93.64±5.14;compared between MUT,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.05).The relative protein expression levels of p-STAT3 in LUC group,WT group and MUT group were 0.67±0.04,0.69±0.08 and 0.81±0.06,the relative protein expression levels of proto-oncogene c-Myc were 1.69±0.03,0.70±0.10 and 0.67±0.07,compared between WT group,MUT group and corresponding DMSO group,the difference was statistically significant(P＜0.05).Conclusion S1P signaling can promote proliferation in breast cancer BT549 cells,and the mechanism could be related to AKT and STAT3 signaling pathway.

Objective To investigate the role of miR-27a-3p in sevoflurane-induced neurocognitive dysfunction.Methods Bioinformatics prediction and validation:Predicted the target genes of miR-27a-3p using bioinformatics databases,and verified the interaction between miR-27a-3p and target genes using dual-luciferase reporter gene assay and Western blot.Cell experiments:Cells were divided into two groups,the miR-27a-3p interference control(Sevo+NC)group was transfected with miR-27a-3p interference control plasmid,and the miR-27a-3p interference treatment(Sevo+anti-miR-27a-3p)group was transfected with miR-27a-3p interference plasmid.Before transfection,the plasmids were treated with 4％sevoflurane for 6 h.Western blot was used to detect the protein expression levels of tau and phosphorylaed tau(p-tau)in SY5Y cells of each group.Animal experiments:Mice were randomly divided into control group(no treatment),sevoflurane group(treated with 4％sevoflurane only),miR-27a-3p interference control group(Sevo+NC,injected with miR-27a-3p interference control plasmid after 4％sevoflurane treatment)and miR-27a-3p interference treatment group(Sevo+anti-miR-27-3p,injected with miR-27a-3p interference plasmid after 4％sevoflurane treatment).The neurocognitive abilities of mice were tested using the water maze experiment,and the level of tau phosphorylation in the hippocampal tissue of mice was detected by immunofluorescence.Results Bioinformatics prediction and validation:Bioinformatics prediction suggested that presenilin 1(PSEN1)might be a target gene of miR-27 a-3p.Dual-luciferase reporter gene assay and Western blot showed that miR-27 a-3p interacted with PSEN1.Cell experiments:The levels of p-tau in Sevo+NC group and Sevo+anti-miR27-3p group were 0.69±0.08 and 0.21±0.05,respectively.Animal experiments:The escape latency times of the control group,sevoflurane group,Sevo+NC group and Sevo+anti-miR-27-3p group were(27.54±3.67),(52.38±6.12),(55.16±5.79)and(38.46±4.78)s,respectively;the results of the novel object exploration index were 0.78±0.11,0.31±0.07,0.33±0.06,and 0.57±0.08,respectively.Immunofluorescence detection showed a significant decrease in p-tau levels in the hippocampal tissue of mice(P＜0.05).Conclusion miR-27 a-3p regulates the p-tau protein by targeting the PSEN1 gene,and interfering with miR-27 a-3p can alleviate sevoflurane-induced neurocognitive dysfunction in mice.

Objective To study the effect of ligustilide regulating stimulator of interferon genes(STING)/Tank-binding kinase 1(TBK1)/nuclear factor-κB(NF-κB)signaling on lung tissue damage in mouse model of lipopolysaccharide(LPS)-induced acute lung injury.Methods Mice were divided into control group,model group(LPS lung injury mouse model),experimental-L group(LPS lung injury mouse model,20 mg·kg-1 ligustilide treatment),experimental-M group(LPS lung injury mouse model,60 mg·kg-1 ligustilide treatment),experimental-H group(LPS lung injury mouse model,100 mg·kg-1 ligustilide treatment),DMXAA group(LPS lung injury mouse model,100 mg·kg-1 ligustilide,STING signal agonist DMXAA treatment),Western blot was used to detect the STING,p-TBK1,TBK1,p-p65,p65 protein expression,bicinchoninic acid(BCA)method was used to detect total protein in bronchoalveolar lavage fluid,Swiss Giemsa staining was used to count the number of inflammatory cells in bronchoalveolar lavage fluid,the content of tumor necrosis factor-alpha(TNF-α)was detected by enzyme-linked immunosorbent assay(ELISA),and the content of malondialdehyde(MDA)in lung tissue was detected by thiobarbituric acid method.Results The relative expression levels of STING protein in the control,model,experimental-L,experimental-M,experimental-H groups,and DMXAA group were 0.13±0.03,0.46±0.02,0.36±0.04,0.27±0.02,0.20±0.03 and 0.38±0.04,p-TBK1/TBK1 protein ratios were 0.15±0.02,0.56±0.02,0.43±0.01,0.31±0.01,0.20±0.02 and 0.30±0.02,p-p65/p65 protein ratios were 0.24±0.01,0.66±0.03,0.41±0.02,0.32±0.04,0.22±0.02 and 0.42±0.03,the total protein contents in bronchoalveolar lavage fluid were(173.79±15.44),(304.21±19.29),(243.59±17.60),(212.51±18.24),(187.11±11.59)and(241.69±30.12)μg·mL-1;the number of macrophages were(0.11±0.02)×108,(0.94±0.09)×108,(0.72±0.08)×108,(0.57±0.04)×108,(0.41±0.04)×108 and(0.71±0.08)×108 cell·mL-1.The difference of the above indicators between model group and control group were all statistically significant(all P＜0.05);the difference between experimental-L,experimental-M,experimental-H groups and model group were all statistically significant(all P＜0.05);there were statistically significant difference between DMXAA group and experimental-H group(all P＜0.05).Conclusion Ligustolide inhibits STING/TBK1/NF-κB signaling to alleviate lung tissue damage in a mouse model of LPS-induced acute lung injury.

Objective To investigate the molecular mechanism of tetramethylpyrazine(TMP)in the treatment of acute myocardial infarction(AMI).Methods SD rats were randomly divided into sham group(only threading without ligation),AMI(ligation of left anterior descending coronary artery),AMI+TMP(20 mg·kg-1 TMP),AMI+TMP+miR-155-5p(20 mg·kg-1 TMP+miR-155-5p 200 μL),AMI+TMP+miR-155-5p+ACTA1 group(20 mg·kg-1 TMP+miR-155-5p and ACTA1 200 μL).The cardiac function of rats was detected by ultrasound.The expression of cardiac troponin Ⅰ(cTn Ⅰ)was detected by immunohistochemistry.Creatine kinase MB(CK-MB)was detected by enzyme-linked immunosorbent assay(ELISA).Terminal deoxynucleotidyl transferase-mediated nick end labeling(Tunel)assay was used to detect the apoptosis rate of cardiomyocytes.The levels of miR-155-5p and ACTA1 mRNA were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results The expression levels of cTn Ⅰ in sham group,AMI,AMI+TMP,AMI+TMP+miR-155-5p,AMI+TMP+miR-155-5p+ACTA1 group were 1.04±0.21,13.63±1.92,7.88±2.23,11.96±3.02,8.34±1.88;the expression levels of miR-155-5p were 1.03±0.21,3.67±0.56,1.85±0.43,3.12±0.66,1.92±0.64,respectively;CK-MB levels were(37.03±7.98),(163.39±20.04),(77.63±15.77),(147.98±11.30),(80.56±10.39)U·L-1,respectively;the above indexes were compared between AMI+TMP group and AMI group,AMI+TMP+miR-155-5p group and AMI+TMP group,AMI+TMP+miR-155-5p+ACTA1 group and AMI+TMP+miR-155-5p group,and the differences were statistically significant(all P＜0.05).Conclusion TMP may inhibit apoptosis,reduce inflammation and myocardial fibrosis through miR-155-5p/ACTA1 molecular axis,and improve myocardial injury in AMI.

Objective To investigate the preventive effects of puerarin apioside on a non-alcoholic fatty liver disease(NAFLD)mouse model and its influence on hepatic lipid metabolism.Methods Thirty-two male C57BL/6J mice were randomly divided into the normal group,model group and experimental-L,-H groups,with 8 mice in each group.The normal group was given regular maintenance feed;the other 3 groups were fed to construct NAFLD model.Experimental-L,-H groups were given 5 and 10 mg·kg-1 puerarin apioside by gavage.Normal and model groups were treated with an equal amount of dimethylsulfoxide by gavage.Four groups were administered once a day for 8 weeks.Changes in mouse body weight were measured.Serum levels of glutamic-pyruvic transaminase(GPT)and glutamic-oxaloacetic transaminase(GOT)and the levels of total cholesterol(TC)and triglycerides(TG)in hepatic tissue were determined by kit.Western blot was used to evaluate the expression levels of acetyl-coenzyme A carboxylase 1(ACC1)and phosphorylated 5'-adenosine monophosphate-activated protein kinase(p-AMPK).Results The body weights of mice in the normal,model and experimental-L,-H groups were(32.69±1.37),(45.51±3.29),(41.18±3.22)and(38.28±2.62)g;serum GPT levels were(36.53±6.44),(134.56±39.91),(121.54±43.38)and(75.92±25.98)U·L-1;serum GOT levels were(60.81±8.74),(188.51±39.70),(156.02±41.67)and(126.79±16.49)U·L-1;hepatic TC levels were(2.17±0.24),(6.46±1.22),(5.86±0.66)and(3.62±0.45)mmol·L-1;hepatic TG levels were(0.57±0.09),(1.39±0.27),(1.28±0.34)and(0.73±0.19)mmol·L-1;the relative expression levels of ACC1 protein were 1.01±0.04,2.00±0.02,1.47±0.08 and 1.20±0.09;the relative expression levels of p-AMPK protein were 1.03±0.09,0.33±0.02,0.66±0.04 and 0.95±0.08,respectively.The differences between the model group and the normal and experimental-H groups were statistically significant for all the above indicators(all P＜0.05).Conclusion Puerarin apioside can improve the hepatic lipid metabolism in NAFLD mice by regulating the AMPK signaling pathway.

Objective To explore the improvement effect of leonurine(LEO)on primary nephrotic syndrome(PNS)rats by regulating Ras homolog gene family member A(RhoA)/Rho associated coiled-coil containing protein kinase(ROCK)signaling pathway.Methods Rat glomerular mesangial cells HBZY-1 were cultured and randomly grouped into control group,proliferation group(100 ng·mL-1 LPS),low concentration experimental group(100 ng·mL-1 LPS+5 μmol·L-1 LEO),high concentration experimental group[100 ng·mL-1 lipopolysaccharide(LPS)+10 μmol·L-1LEO],and combined treatment group(100 ng·mL-1LPS+10 μmol·L-1 LEO+10 nmol·L-1 RhoA activator U46619).Cell counting kit-8 assay was applied to detect cell proliferation activity;flow cytometry was applied to detect apoptosis.Sixty SPF Wistar rats were randomly grouped into normal group,model group,low-dose experimental group(10 mg·kg-1 LEO),high-dose experimental group(20 mg·kg-1 LEO),and combination group(20 mg·kg-1 LEO+10 mmol·L-1 U46619),with 12 rats in each group.Except the normal group,the other groups were injected with adriamycin hydrochloride via tail vein to establish PNS rat model;coomassie brilliant blue method was applied to detect 24-hour urinary protein content in rats.Enzyme linked immunosorbent assay was used to detect the levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin(IL)-4 in renal tissue.Western blot was used to detect RhoA and Rock1 protein expression in rat kidney.Results In the cell experiment,the proliferation activities(optical density value)of HBZY-1 cells in control group and hyperplasia group was 0.32±0.03 and 0.70±0.07;the apoptosis rate were(9.23±1.04)％and(1.64±0.22)％,with statistical significance(all P＜0.05).In animal experiments,24 h urinary protein content of normal group,model group,low-dose experimental group,high-dose experimental group and combination group were(21.45±2.28),(127.38±14.70),(120.85±13.34),(43.15±6.68)and(96.20±10.63)mg;TNF-α levels were(0.27±0.05),(1.58±0.16),(1.56±0.16),(0.44±0.05)and(1.03±0.10)ng·mL-1;IL-4 levels were(0.17±0.02),(1.24±0.12),(1.20±0.12),(0.29±0.03)and(0.87±0.09)ng·mL-1;RhoA protein expression levels were 0.27±0.03,0.78±0.08,0.76±0.07,0.34±0.03 and 0.72±0.07;the expression levels of ROCK1 protein were 0.22±0.02,0.85±0.09,0.83±0.08,0.41±0.04 and 0.75±0.08.The differences of above indexes were statistically significant between the high-dose experimental group and the combination group(all P＜0.05).Conclusion LEO may improve PNS in rats by down-regulating RhoA/ROCK signaling pathway.

Objective To observe the effects of traditional Chinese medicine compound Platycodon grandiflorum Bai powder on the growth of subcutaneously implanted tumor and the expression of B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax),cysteinyl aspartate specific proteinase(caspase)-3 and caspase-9 in subcutaneously implanted tumor of Lewis lung cancer mice.Methods The model of transplanted tumor of Lewis lung cancer in mice was established.Seventy SPF male C57BL/6 mice were randomly divided into blank group,model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combined group.Blank group and model group were given 0.9％NaCl 0.2 mL by gavage;control group was given 0.9％NaCl by gavage and 25 mg·kg-1cisplatin intraperitoneally;high,medium,low dose experimental groups were given 193,96,48 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,respectively;combined group was given 96 mg·kg-1·d-1 Platycodon grandiflorum Bai powder 0.2 mL by gavage,and 25 mg·kg-1 cisplatin intraperitoneally,once every other day.The myelogenous suppressor cells(MDSCs)of mouse bone marrow were detected by flow cytometry,and the expressions of Bel-2,Bax,caspase-3 and caspase-9 in tumor cells were detected by immunofluorescence.Results The percentage of MDSCs in bone marrow of mice in blank group,model group,low dose experimental,medium,high dose experimental group,control group and combination group were(32.50±2.76)％,(63.13±3.14)％,(48.43±2.23)％,(42.53±1.28)％,(32.93±3.56)％,(51.30±4.25)％and(19.90±6.21)％,respectively.The fluorescence intensities of Bax in model group,low dose experimental group,medium dose experimental group,high dose experimental group,control group and combination group were 10.42±0.68,12.40±1.23,15.14±0.65,22.95±1.76,27.18±1.62 and 31.61±1.28;Bel-2 were 36.85±0.80,33.92±4.20,28.88±1.01,20.04±2.21,15.69±2.36 and 6.05±0.73;caspase-3 were 5.28±0.44,7.63±0.55,9.66±0.85,14.73±1.18,17.95±1.29 and 22.92±1.95;caspase-9 were 9.48±0.90,11.57±0.72,13.45±0.93,15.73±1.44,19.20±0.96 and 23.21±1.51.There were significant differences between medium,high dose experimental groups and model group(all P＜0.05),and there were significant differences between combined group and control group(all P＜0.05).Conclusion Platycodon grandiflorum Bai powder can up-regulating the expression of Bax,caspase-3 and caspase-9,down-regulating the expression of Bel-2,inhibiting MDSCs,promoting tumor cell apoptosis and inhibiting tumor growth.

Objective To prepare a verteporfin-loaded poly(lactic-co-glycolic acid)nanoparticle(PLGA-VP NPs)and to verify its inhibitory effect on hepatocellular carcinoma cell line Hepa 1-6 and its in vivo safety.Methods PLGA-VP NPs were prepared by emulsion evaporation method,and the particle size and potential of PLGA-VP NPs were detected by dynamic light scattering(DLS).Mouse hepatocellular carcinoma cell line Hepa 1-6 was cultured in vitro and divided into control group(without any treatment),PLGA NPs group(adding PLGA NPs)and PLGA-VP NPs group(adding PLGA-VP NPs).The cell proliferation was detected by the Alamar Blue;the uptake of PLGA-VP NPs and apoptosis rate of cells were detected by flow cytometry;the expression levels of programmed death-ligand 1(PD-L1)protein,B-cell lymphoma-2(Bcl-2)protein and Bcl-2 associated X protein(Bax)were detected by Western blotting.C57 mice were divided into control group(phosphate buffered saline 100 μL)and PLGA-VP NPs group(tail vein injection of 2 μg·μL-1 PLGA-VP NPs 100 μL).The main organs of mice were observed by hematoxylin-eosin(HE)staining.Results The particle size of PLGA-VP NPs was about(124.00±1.80)nm,and the potential was about(-38.00±1.40)mV.When the concentrations of PLGA-VP NPs were 0,0.5,1,2,2.5,3,4,5 mg·mL-1,the cell survival rates were(100.00±2.02)％,(87.33±3.74)％,(55.86±9.71)％,(30.32±6.30)％,(26.03±2.60)％,(23.81±2.09)％,(23.63±1.29)％and(19.75±3.32)％;the half maximal inhibitory concentration of PLGA-VP NPs on Hepa 1-6 was 0.87 mg·mL-1.The uptake rates of Hepa 1-6 to PLGA-VP NPs at 0,2,4,8,12 and 24 h were 0,(3.27±0.10)％,(7.32±1.36)％,(27.03±1.11)％,(44.97±1.43)％and(68.37±0.94)％,respectively.The apoptosis rates of the control group,the PLGA NPs group and the PLGA-VP NPs group were(9.26±1.42)％,(11.08±1.16)％and(27.27±1.12)％;the relative expression levels of PD-L1 protein were 1.00±0.01,1.00±0.08 and 0.21±0.06;the relative expression levels of Bcl-2 protein were 1.20±0.02,0.43±0.01 and 0.54±0.07;the relative expression levels of Bax protein were 0.35±0.02,1.09±0.07 and 1.30±0.06,respectively.The above indexes show statistically significant differences in between the PLGA-VP NPs group and the control group,PLGA NPs group(all P＜0.05).After HE staining,comparing to the normal group,there was no obvious abnormality in the main organs of the mice in the PLGA-VP NPs group.Conclusions PLGA-VP NPs were successfully synthesized,and the nanoparticles have inhibitory effects on Hepa 1-6 hepatocellular carcinoma cells,can reduce the expression of PD-L1 protein,and have good in vivo safety.