| Object iveTo observe the clinical efficacy of Shentao Ruangan Formula in patients with hepatitis B-related hepatocellular carcinoma(HBV-HCC)and to explore the effect of this prescription on the whole-genome DNA methylation status of HBV-HCC patients.MethodAccording to the relevant standards,42 patients were enrolled from the outpatient and inpatient departments of the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,and the patients were diagnosed as primary liver cancer with chronic hepatitis B virus infection.They were randomly divided into treatment group and control group,each group 21 people.The treatment group was treated with Shentao Ruangan Formula combined with entecavir maleate,and the control group was treated with entecavir maleate alone.The trial treatment was 30 days.AFP,CA19-9,HBV-DNA load,ALT,NLR,PLR,and TCM syndrome scores were measured and analyzed before treatment and after 30 days of treatment.In addition,3 patients in the treatment group were randomly selected to take one tube of blood before and after taking the drug for whole-genome DNA methylation status detection.ResultThere were no significant differences in the age,gender,cirrhosis,hepatitis B type,BCLC stage,child-pugh grade,and TACE history between the two groups(all P>0.05),which was comparable.The results of the comparative analysis are as follows:1.The TCM syndrome scores of the treatment group were improved compared with those before treatment.The difference was statistically significant P=0.010(P<0.05).The mean scores of symptom scores before and after treatment were(29.52±3.66)VS(25.67±6.92)points respectively.After 30 days in the control group,the scores of symptoms were not significantly P=0.809(P>0.05).The mean scores of symptoms before and after treatment were(30.24±3.48)VS(29.90±6.56).2.After treatment for 30 days,AFP and CA19-9 were higher than before(all P<0.05).The mean values before and after treatment with AFP in the treatment group were(500.1(17.14,22861))ng/ml VS(642.4(27,26052))ng/ml,P=0.008.The mean values before and after treatment with AFP in the control group were(155(27.6,11010))ng/ml VS(845(49.6,5802))ng/ml,P=0.008.The mean values of treatment group CA19-9 before and after treatment were(27.38(11.51,49.23))U/ml VS(29.8(15.5,48.5))U/ml,P=0.035;the mean values of control group CA19-9 before and after treatment were respectively(24.93(17.97,45.98))U/ml VS(35.2(22.8,119.6))U/ml,P=0.004.The disease progressed in the middle and late stage liver cancer patients.Although the treatment group showed a steady upward trend compared with the control group,the treatment plans of the two groups did not have obvious control effects on the tumor indicators.3.In terms of HBV-DNA load,the mean values of the treatment group before and after treatment were(3.42(2.3 1,4.26))Log10IU/ml VS(2.40(2.00,3.29))Log10IU/ml,and the HBV-DNA load decreased significantly after 30 days,statistical significance P=0.001(P<0.05).The mean value of the control group before and after treatment was(2.61(2.00,4.15))Log10IU/ml VS(2.45(2.00,3.25))Log10IU/ml.There was no significant difference after 30 days P=0.589(P>0.05).Therefore,it is believed that Shentao Ruangan Formula combined with entecavir may have certain advantages in inhibiting the virus.In terms of ALT level,there was no significant difference between the two groups(all P>0.05),the intra-group comparison was P=0.509 and P=0.247,respectively.The comparison between groups was P=0.162 and P=0.232,respectively.However,the mean values of ALT levels before and after treatment in the treatment group were(31(26,38))U/L VS(30(23,75))U/L,and the mean values of ALT levels before and after the control group were(39(29,80))U/L VS(41(31,78))U/L,indicating that the ALT levels were generally good and the changes were not significant before and after treatment.4.The NLR levels in the treatment group and the control group changed significantly after 30 days.The comparison of NLR levels before and after treatment was P=0.491(P>0.05),P=0.008(P<0.05).The mean NLR of the treatment group before and after treatment was(3.43±1.28)VS(2.58±0.85),which was significantly lower than the previous P=0.004(P<0.05).The mean NLR of the control group before and after treatment was(3.08±1.90)VS(3.92±1.98),significantly higher than the previous P=0.005(P<0.05).The mean PLR before and after treatment in the treatment group were(120(82.0,250))VS(107(75.3,167.8)),P=0.063(P>0.05),while the mean PLR before and after treatment in the control group were(126(68.7,261.5))VS(137(87.5,210.5)),P=0.986(P>0.05),PLR levels remained stable before and after treatment(P>0.05),P=0.910,P=0.339,respectively.The above results indicate that Shentao Ruangan Formula may have a certain effect on controlling inflammation indicators.5.(1)Three patients were randomly selected from the treatment group.One tube of whole blood samples were collected before and after treatment.After sequencing,each sample produced 127.876 Gb of filtered clean bases.The Unique Mapped Rate of all samples was above 85%.The bisulfite conversion rate is as high as 99.5%or more.The methylation site of the CG type of the sample accounted for more than 96%of the total methylation site type.The proportion of 9 bases in the upstream and downstream of the methylation site was uniform and there was no obvious bias.(2)From the chromosomes,it was shown that the density of DNA methylation before and after treatment changed greatly on the whole chromosome,and the density distribution of mCG/CG was the largest.(3)Three patients had high levels of methylation in the CpG-dense region of the whole genome.(4)Through GO enrichment analysis of differentially methylated genes,it is mainly enriched in biofeedback regulation,cell development and transformation,cell signaling,plasma membrane-associated cellular components,and molecular binding functions.6.In terms of safety,in the treatment group,except for one patient,the number of stools increased,and two patients had mild nausea,there were no serious adverse reactions and deaths such as gastrointestinal bleeding and hepatic encephalopathy in the two groups during the treatment.ConclusionShentao Ruangan Formula has certain effects on improving clinical symptoms,inhibiting viral activity and controlling inflammation in patients with HBV-HCC,and may have certain influence on DNA methylation level in patients with HBV-HCC. |
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