ABSTRACT
Objective:To explore the association of miRNA-146a (miR-146a), miRNA-196a2 (miR-196a2), and miRNA-499 (miR-499) single nucleotide polymorphisms with genetic susceptibility in hepatocellular carcinoma.Methods:A case-control study was designed. A total of 175 patients (hepatocellular carcinoma group) in Affiliated Hospital of Yangzhou University from April 2015 to March 2019 and 302 healthy people undergoing physical examination during the same period (the control group) were selected. The genotype distribution of miR-146a, miR-196a2 and miR-499 in the peripheral blood of the two groups were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Logistic regression model was used to analyze the association of 3 genotypes of miRNA, genotypes of hepatitis virus infectors with genetic susceptibility in hepatocellular carcinoma. The relationship between miR-146a gene polymorphism and demography factor as well as the clinical characteristics was also analyzed by using Spearman correlation analysis.Results:In hepatocellular carcinoma group, miR-146a single nucleotide polymorphism of CC, CG, GG site genotypes had 52 (29.7%) cases, 86 (49.1%) cases, 37 (21.1%) cases, respectively; in the control group, the corresponding genotypes had 137 (45.4%) cases, 135 (44.7%) cases and 30 (9.9%) cases, respectively, and the difference in genotype distribution of both groups was statistically significant ( χ2 = 17.23, P < 0.05). There were no statistical differences in genotype distribution of miR-196a2 and miR-499 ( χ2 = 0.51, P = 0.776; χ2 = 0.05, P = 0.976). Single factor logistic regression analysis showed that in the co-dominant model of miR-146a genotype, genotypes of CG ( OR = 1.96, 95% CI 1.13-3.41, P = 0.017) and GG ( OR = 3.30, 95% CI 1.85-5.89, P<0.01) had elevated risk of hepatocellular carcinoma compared with CC genotype. In the dominant model, the risk of hepatocellular carcinoma in CG+GG genotypes was increased compared with that in CC genotype ( OR=1.97, 95% CI 1.33-2.93, P = 0.001); in the recessive model, the risk of hepatocellular carcinoma in GG genotype was increased compared with that in CG+ GG genotype ( OR=2.43, 95% CI 1.44-4.11, P = 0.001). Single factor logistic regression analysis showed that there was no significant difference in the risk of hepatocellular carcinoma in the co-dominant, dominant and recessive models between miR-196a2 and miR-499 genotypes (all P > 0.05). For hepatocellular carcinoma patients with positive hepatitis B virus (HBV), CG genotype had a 2.02-fold (95% CI 1.06-5.07) risk of hepatocellular carcinoma compared with CC genotype, and GG genotype had a 3.12-fold (95% CI 1.66-10.07) risk of hepatocellular carcinoma compared with CC genotype; CG+GG genotype had a 1.91-fold (95% CI 1.85-3.38) compared with CC genotype, GG genotype had a 1.54-fold (95% CI 1.15-6.08) compared with CG+GG genotype. The increasing risk of hepatocellular carcinoma by miR-146a gene polymorphisms was not found in hepatocellular carcinoma patients with hepatitis C virus (HCV) infection or without HBV and HCV infection. Spearman correlation analysis showed that miR-146a gene polymorphisms was not related with age, gender, smoking, drinking, family history of cancer, alanine transaminase and aspartate aminotransferase (all P>0.05). Conclusions:GG and CG genotypes of miR-146a increase the risk of genetic susceptibility in hepatocellular carcinoma, especially for patients with HBV infection. miR-196a2 and miR-499 single nucleotide polymorphisms don't increase the risk of hepatocellular carcinoma.
ABSTRACT
Objective To explore the protective effect of astilbin in hepatic ischemia-reperfusion injury (HIRI).Methods SD rats were divided into Sham group (control group),HIRI group (ischemia-reperfusion group),astilbe (low dose group,middle dose group,high dose group),and estabilished the model of rat HIRI.After liver were reperfused with blood (in 4 h,8 h,16 h),collecting the specimens of blood and liver tissues.Detection of serum alanine aminotransferase (ALT),aspertate aminotransferase (AST);Then observed the changes of liver cell microstructure;Western blot analysised the expression of HMGB1,TLR4,NF-kB,TNF-α in liver tissue.Results The serum ALT levels of Sham group in 4 h,8 h,16 h were (58.11 ±4.81) U/L,(57.12 ± 5.33) U/L,(57.63 ±4.54) U/L,the serum ALT levels of HIRI group in 4 h,8 h,16 h were (540.38 ± 21.41) U/L,(831.21 ± 20.11) U/L,(191.95 ± 15.35) U/L.Compared with Sham group,the serum ALT levels of HIRI group were significantly increased(P ＜ 0.01).Compared with HIRI group,The serum ALT levels of three dose groups in 4 h,8 h,16 h were significantly declined,including high dose group lower the most obvious (The serum ALT levels of high dose group in 4 h,8 h,16 h were (223.75 ± 10.53) U/L,(412.14 ±23.59) U/L,(205.25 ± 15.48) U/L (P ＜0.01).The results of light microscope indicated that drug groups significantly reduce the liver cell damage.The results of Western blot displayed that High dose group of HMGB1,TLR4 protein expression in 4 h,8 h,16 h drop significantly than HIRI group(P ＜0.05).High dose group of NFkB,TNF-α protein expression in postoperative 8 h,16 h decrease significantly than HIRI group (P ＜ 0.05),but in postoperative 8 h,there was no statistically significant difference compared with group HIRI (P＞0.05).Conclusion Astilbe pretreatment can reduce HIRI and its mechanism may be associated with downregulating the axis of HMGB1/TLR4/NF-kB/TNF-α,proceed to the next inhibiting the inflammatory response.
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This paper discusses the problems, clinical application and limitations of argon-helium cryosurgical scalpel and liquid nitrogen cryosurgical scalpel. The feasibility of self-absorption liquid-CO2 cryosurgical scalpel is analyzed. The result shows that self-absorption liquid-CO2 cryosurgical scalpel can be applied to cryosurgery.