Application value of two-dimensional shear wave elastography and serological models in the staging of liver fibrosis in patients with chronic hepatitis B / 临床肝胆病杂志

ObjectiveTo investigate the value of two-dimensional shear wave elastography （2D-SWE） or serological models used alone or in combination in determining the stage of liver fibrosis in patients with chronic hepatitis B. MethodsA retrospective analysis was performed for the clinical data of 327 patients with chronic hepatitis B who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from August 2020 to August 2022 and underwent 2D-SWE and liver histopathological examination， including sex， age， serological markers， and 2D-SWE results. According to the degree of liver fibrosis， they were divided into S0-S1， S≥2， S≥3， and S=4 groups， and the serological models were calculated based on serological markers. A Spearman correlation analysis was used to investigate the correlation of 2D-SWE and serological models with liver fibrosis stage； the receiver operating characteristic curve was plotted with the results of liver histopathology as the standard to compare the efficiency of each parameter used alone or in combination in determining the stage of liver fibrosis； the Delong test was used to investigate the difference between different methods. ResultsLiver stiffness measurement measured by 2D-SWE was strongly correlated with the stage of liver fibrosis （r=0.741， P<0.001）， and as for the serological model， six markers （APRI， FIB-4， GPR， GP， RPR， and S index）， other than AAR， were positively correlated with the stage of liver fibrosis （all P<0.001）. 2D-SWE had an area under the ROC curve （AUC） of 0.878， 0.932， and 0.942， respectively， in the diagnosis of S≥2， S≥3， and S=4 liver fibrosis （all P<0.001）， with an optimal cut-off value of 6.9 kPa， 7.9 kPa， and 9.4 kPa， respectively. Among the serological models， APRI had the largest AUC of 0.788 and 0.875， respectively， in the diagnosis of S≥2 and S=4 liver fibrosis， and S index had the largest AUC of 0.846 in the diagnosis of S≥3 liver fibrosis. In the diagnosis of S≥2， S≥3， and S=4 liver fibrosis， 2D-SWE combined with APRI increased the AUC values to 0.887， 0.938， and 0.950， respectively， and 2D-SWE combined with S index increased the AUC values to 0.879， 0.935， and 0.941， respectively， while there were no significant differences between 2D-SWE and the above combinations （P>0.05）. Conclusion2D-SWE has a better diagnostic efficacy than the above seven serological models in determining liver fibrosis stage. The serological models have a certain diagnostic value， among which APRI and S index have a relatively high diagnostic value. There is no significant difference between 2D-SWE and 2D-SWE combined with serological models， and such combinations cannot significantly improve diagnostic efficiency. Therefore， further studies are needed to explore new combinations of diagnostic methods.

Activation of liver X receptors induced pancreatic β cell cycle arrest by up-regulating the expression of p27 protein / 临床检验杂志

Objective To investigate the effects of liver X receptor (LXR) agonist on the proliferation of mouse pancreatic β cell line MIN6 cells.Methods The viability,changes of cell cycle,mRNA levels of S phase kinase associated protein 2 (Skp2) and p27,and protein levels of Skp2 and p27 in MIN6 cells treated with LXR agonist T0901317 were determined by the CCK-8 method,flow cytometry,real-time RT-PCR and western blot,respectively.Results The viability of MIN6 cells treated with 1 μmol/L,5 μmol/L and 10 μnol/L of T0901317 were (98.54 ±0.94)％,(87.03 ±0.93)％ and (75.57 ± 1.85)％ of the controls,respectively,and there was significant difference among them (F =301.90,P ＜ 0.01).The percentages of G1 phase cells in the MIN6 cells treated with 0 μmol/L,1 μmol/L,5 μmol/L and 10 μmol/L of T0901317 were (35.93 ±2.25)％,(38.45 ±0.91)％,(45.46±1.34)％ and (53.28 ± 1.14) ％,respectively,and there was significant difference among them (F =80.83,P ＜ 0.01).Similarly,the percentages of S phase cells in the MIN6 cells treated with 0 μmol/L,1 μmol/L,5 μmol/L and 10 μmoi/L of T0901317 were (52.87 ± 1.19) ％,(48.65 ± 0.85) ％,(36.31 ± 1.37) ％ and (31.45 ± 1.22) ％,respectively,and there was also significant difference among them (F =221.30,P ＜ 0.01).The protein levels of p27 in the MIN6 cells treated with 10 μmol/L of T0901317 (2.84 ± 0.14) were significantly higher than that in the controls (2.28 ± 0.10) (t =4.54,P ＜ 0.05),while there was no significant difference in the mRNA levels of p27 between them (t =0.28,P ＞ 0.05).However,10 μmol/L of T0901317 significantly decreased mRNA (0.52 ± 0.02,t =29.22,P ＜ 0.01) and protein levels (0.98 ± 0.12 vs 1.89 ± 0.01,t =10.98,P ＜ 0.01) of Skp2 in MIN6 cells.Based on the control siRNA transfection group as a reference (100％),the cell survival rates of the p27 siRNA transfection group,10 μmol/L of T0901317 treatment group and the intervention group (p27 siRNA transfection + T0901317 treatment) were (100.97 ± 1.08) ％,(75.03 ± 1.83) ％ and (86.67 ± 2.45) ％,respectively.There was no significant difference between the control siRNA and p27 siR-NA transfection groups (t =1.542,P ＞ 0.05).Compared with the control siRNA transfection group,the cell survival rates of the T0901317 treatment group decreased (t =23.58,P ＜ 0.01).There was also significant difference in the cell survival rates between the T0901317 treatment group and the intervention group (t =7.77,P ＜ 0.01).Conclusion The activation of LXR may induce pancreatic β cell cycle arrest by up-regulating the expression of p27 and down-regulating the expression of Skp2.