Objective:To compare the effectiveness and safety profile of tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF), especially the effects on lipid metabolism in the treatment of chronic hepatitis B.Methods:A retrospective study was conducted on the virological response rate, biochemical response rate, renal function indicators, and lipid metabolism status of 159 cases with chronic hepatitis B (72 cases with TMF and 87 cases with TAF) after 48 weeks of antiviral treatment. The effects of the two drugs on lipid metabolism were further explored through cell and animal experiments.Results:There were no statistically significant differences in baseline age, gender ratio, treatment-na?ve and treatment-experienced proportions, hepatitis B virus (HBV) DNA and aminotransferase levels, renal function indicators, and serum lipid levels between the two groups. The levels of HBV DNA and transaminase were significantly reduced after 48 weeks of treatment in both groups. However, there were no statistically significant differences in virological response (84.2% vs. 75.8%, χ2=0.733, P=0.392) and biochemical response rate (86.1% vs. 85.1%, χ2=0.035, P=0.851) between the two groups. There was no significant change in the renal function index levels before and after treatment between the two groups of patients. Triglyceride [TG, 1.30 (0.93, 1.81) mmol/L vs. 1.30 (0.82, 1.84) mmol/L, Z=-0.196, P=0.844], total cholesterol [TC, 4.53 (3.91, 5.15) mmol/L vs. 4.55 (3.88, 5.24) mmol/L, Z=-1.131, P=0.258], high-density lipoprotein [HDL-C, 1.04 (0.90, 1.3) mmol/L vs. 1.08 (0.94, 1.30) mmol/L, Z=-0.811, P=0.417], low-density lipoprotein [LDL-C, 2.68 (2.04, 3.29) mmol/L vs. 2.57 (1.99, 3.49) mmol/L, Z=-1.716, P=0.086] and the ratio of total cholesterol to high-density lipoprotein [TC/HDL-C, 4.52 (3.10, 5.23) vs. 4.30 (3.27, 5.01), Z=-0.410, P=0.682] had not statistically significant differences in the TMF group before and after treatment. TG [1.24(0.95, 1.98) mmol/L vs. 1.42(1.09, 2.21) mmol/L, Z=-2.895, P=0.004], TC [4.44(3.74, 5.26) mmol/L vs. 4.68(4.07), 5.46) mmol/L, Z=-2.825, P=0.005], low-density lipoprotein (LDL-C) [2.74 (2.05, 3.58) mmol/L vs. 2.87 (2.34, 3.50) mmol/L, Z=-2.419, P=0.016] , and TC/HDL-C [3.89(3.13, 4.82) vs. 4.39(3.70, 5.40), Z=-4.478, P<0.001] levels were increased after TAF treatment, while HDL-C levels were decreased [1.19 (0.98, 1.35) mmol/L vs. 1.04 (0.90, 1.33) mmol/L, Z=-3.070, P=0.002]. The absolute values comparison changes had no statistically significant differences in TG [-0.04(-0.37, 0.46) mmol/L and 0.18 (-0.14, 0.46) mmol/L, Z=-1.853, P=0.064], TC [0.06(-0.38, 0.63) mmol/L vs. 0.23(-0.21, 0.65) mmol/L, Z=-1.010, P=0.312] and LDL-C level [-0.19(-0.33, 0.18) mmol/L vs. 0.18 (-0.13, 0.58) mmol/L, Z=-0.523, P=0.601] before and after treatment between the two groups of patients. The TMF group had higher HDL-C [0.06 (-0.16, 1.84) mmol/L vs. -0.12 (-0.26,0.04) mmol/L, Z=-2.890, P=0.004], but lower TC/HDL-C [-0.04(-0.67, 0.44) vs. 0.40(-0.14, 1.33), Z=-3.959, P<0.001] than the TAF group. HepG2 cells were interfered with 10 μg/ml TMF and TAF for 72 hours, respectively. Microscopic examination revealed that in the TMF group [12 196 (10 740, 14 345) vs. 4 029 (3 086, 5 425) cells, Z=-4.815, P<0.001] and TAF group [12 484 (11 176, 15 824) vs. 4 029 (3 086, 5 425), Z=-4.815, P<0.001], the number of intracellular lipid droplets was higher than that in the control group after Oil Red O staining, but the difference between the two groups was not statistically significant. Ten-week-old C57/BL6J male mice were given 3.8 mg/kg TMF or TAF by continuous gavage for 12 weeks. The liver tissue was stained with Oil Red O. The number of lipid droplets was higher in the liver tissue of mice in the TAF group than that of the control group [30 647 (28 050, 34 821) and 27 614 (25 214, 29 176), Z=-2.529, P=0.011], while the difference between the TMF group and control group was not statistically significant. The serum TG levels were higher in the TAF group mice [1.17 (1.11, 1.19) μmol/L vs. 1.06 (1.04, 1.09) μmol/L, Z=-2.060, P=0.039], TC [2.58 (2.55, 2.80) μmol/L L vs. 2.33 (2.18, 2.54) μmol/L, Z=-2.084, P=0.037] than those of the control group after drug administration, while HDL-C levels were lower than those of the control group [1.14 (1.13, 1.16) μmol/L vs. 1.29 (1.28, 1.32) μmol/L, Z=-2.313, P=0.021] and TMF group [1.14 (1.13, 1.16) μmol/L vs. 1.30 (1.28, 1.38) μmol/L, Z=-2.795, P=0.005]. However, there was no statistically significant difference in TG, TC, and HDL-C levels between the TMF and the control group. Conclusion:Both TMF and TAF can effectively inhibit HBV replication and promote liver function recovery, with no significant impact on renal function. However, TAF may generate an adverse effect on lipid metabolism in the body, while TMF has no obvious effect.

Objective:To compare the effectiveness and safety profile of tenofovir amibufenamide (TMF) and tenofovir alafenamide (TAF), especially the effects on lipid metabolism in the treatment of chronic hepatitis B.Methods:A retrospective study was conducted on the virological response rate, biochemical response rate, renal function indicators, and lipid metabolism status of 159 cases with chronic hepatitis B (72 cases with TMF and 87 cases with TAF) after 48 weeks of antiviral treatment. The effects of the two drugs on lipid metabolism were further explored through cell and animal experiments.Results:There were no statistically significant differences in baseline age, gender ratio, treatment-na?ve and treatment-experienced proportions, hepatitis B virus (HBV) DNA and aminotransferase levels, renal function indicators, and serum lipid levels between the two groups. The levels of HBV DNA and transaminase were significantly reduced after 48 weeks of treatment in both groups. However, there were no statistically significant differences in virological response (84.2% vs. 75.8%, χ2=0.733, P=0.392) and biochemical response rate (86.1% vs. 85.1%, χ2=0.035, P=0.851) between the two groups. There was no significant change in the renal function index levels before and after treatment between the two groups of patients. Triglyceride [TG, 1.30 (0.93, 1.81) mmol/L vs. 1.30 (0.82, 1.84) mmol/L, Z=-0.196, P=0.844], total cholesterol [TC, 4.53 (3.91, 5.15) mmol/L vs. 4.55 (3.88, 5.24) mmol/L, Z=-1.131, P=0.258], high-density lipoprotein [HDL-C, 1.04 (0.90, 1.3) mmol/L vs. 1.08 (0.94, 1.30) mmol/L, Z=-0.811, P=0.417], low-density lipoprotein [LDL-C, 2.68 (2.04, 3.29) mmol/L vs. 2.57 (1.99, 3.49) mmol/L, Z=-1.716, P=0.086] and the ratio of total cholesterol to high-density lipoprotein [TC/HDL-C, 4.52 (3.10, 5.23) vs. 4.30 (3.27, 5.01), Z=-0.410, P=0.682] had not statistically significant differences in the TMF group before and after treatment. TG [1.24(0.95, 1.98) mmol/L vs. 1.42(1.09, 2.21) mmol/L, Z=-2.895, P=0.004], TC [4.44(3.74, 5.26) mmol/L vs. 4.68(4.07), 5.46) mmol/L, Z=-2.825, P=0.005], low-density lipoprotein (LDL-C) [2.74 (2.05, 3.58) mmol/L vs. 2.87 (2.34, 3.50) mmol/L, Z=-2.419, P=0.016] , and TC/HDL-C [3.89(3.13, 4.82) vs. 4.39(3.70, 5.40), Z=-4.478, P<0.001] levels were increased after TAF treatment, while HDL-C levels were decreased [1.19 (0.98, 1.35) mmol/L vs. 1.04 (0.90, 1.33) mmol/L, Z=-3.070, P=0.002]. The absolute values comparison changes had no statistically significant differences in TG [-0.04(-0.37, 0.46) mmol/L and 0.18 (-0.14, 0.46) mmol/L, Z=-1.853, P=0.064], TC [0.06(-0.38, 0.63) mmol/L vs. 0.23(-0.21, 0.65) mmol/L, Z=-1.010, P=0.312] and LDL-C level [-0.19(-0.33, 0.18) mmol/L vs. 0.18 (-0.13, 0.58) mmol/L, Z=-0.523, P=0.601] before and after treatment between the two groups of patients. The TMF group had higher HDL-C [0.06 (-0.16, 1.84) mmol/L vs. -0.12 (-0.26,0.04) mmol/L, Z=-2.890, P=0.004], but lower TC/HDL-C [-0.04(-0.67, 0.44) vs. 0.40(-0.14, 1.33), Z=-3.959, P<0.001] than the TAF group. HepG2 cells were interfered with 10 μg/ml TMF and TAF for 72 hours, respectively. Microscopic examination revealed that in the TMF group [12 196 (10 740, 14 345) vs. 4 029 (3 086, 5 425) cells, Z=-4.815, P<0.001] and TAF group [12 484 (11 176, 15 824) vs. 4 029 (3 086, 5 425), Z=-4.815, P<0.001], the number of intracellular lipid droplets was higher than that in the control group after Oil Red O staining, but the difference between the two groups was not statistically significant. Ten-week-old C57/BL6J male mice were given 3.8 mg/kg TMF or TAF by continuous gavage for 12 weeks. The liver tissue was stained with Oil Red O. The number of lipid droplets was higher in the liver tissue of mice in the TAF group than that of the control group [30 647 (28 050, 34 821) and 27 614 (25 214, 29 176), Z=-2.529, P=0.011], while the difference between the TMF group and control group was not statistically significant. The serum TG levels were higher in the TAF group mice [1.17 (1.11, 1.19) μmol/L vs. 1.06 (1.04, 1.09) μmol/L, Z=-2.060, P=0.039], TC [2.58 (2.55, 2.80) μmol/L L vs. 2.33 (2.18, 2.54) μmol/L, Z=-2.084, P=0.037] than those of the control group after drug administration, while HDL-C levels were lower than those of the control group [1.14 (1.13, 1.16) μmol/L vs. 1.29 (1.28, 1.32) μmol/L, Z=-2.313, P=0.021] and TMF group [1.14 (1.13, 1.16) μmol/L vs. 1.30 (1.28, 1.38) μmol/L, Z=-2.795, P=0.005]. However, there was no statistically significant difference in TG, TC, and HDL-C levels between the TMF and the control group. Conclusion:Both TMF and TAF can effectively inhibit HBV replication and promote liver function recovery, with no significant impact on renal function. However, TAF may generate an adverse effect on lipid metabolism in the body, while TMF has no obvious effect.

Objective To investigate the effect of ischemia reperfusion (I/R) injury on apoptosis of pancreatic cells in rats with acute pancreatitis(AP). Methods Fifty four SD rats were randomized into 3 groups: pancreatitis group ( n =24), I/R injury group ( n =24) and control group ( n =6). The animal model of AP was induced by retrograde injection of 3% sodium taurocholate into biliopancreatic duct in rats. Pancreatic I/R was caused by blocking the inferior splenic artery and removing the clamp after AP induction. At 1 h, 3 h, 6 h and 12 h, groups of rats were sacrificed. A terminal deoxynucleotidyl transferase mediated dUTP biotion nick end labeling (TUNEL) was used to detect pancreatic apoptosis, and histological changes of the pancreas were observed. Results Pancreatic hemorrhage, necrosis were respectively observed in the pancreatitis rats at 6 h and the I/R injury rats at 1 h. Histological changes of the pancreatitis rats at 1 h and 3 h were only congestion and edema. Apoptoic acinar cells increased after AP induction, the peak respectively appeared at 6 h in the pancreatitis rats and at 3 h in the I/R injury rats. Compared with the pancreatitis rats, apoptosis index (AI) of the I/R injury rats was significantly higher at 1 h and 3 h ( P

Objective To investigate the effect of tuftsin and its inhibitor on pancreas microcirculation in acute pancreatitis(AP). Methods Sprague Dawley (SD) rats were randomly divided into five groups. Murine AP model was produced by retrograde injection of 4% sodium taurocholate into pancreatic duct, tuftsin or its inhibitor was injected at a dosage of 75 ?g/kg. At the time of 0,3, 6, 12 h, pancreas was harvested for pathology of microthrombus. esults Microthrombus in control group was not different with that in tuftsin group; At the time of 3、6 and 12 h microthrombus in other 3 groups significantly increased than control group and tuftsin group; With time, microthrombus in AP group、AP+ tuftsin group and AP+inhibitor group increased steadily and statistically significant; Tuftsin inhibitor significantly decreased microthrombus at the time of 6、12 h.Conclusions In acute pancreatitis tuftsin deteriorated pancreas microcirculation, which could be partially reversed by the administration of tuftsin inhibitor.

Objective To evaluate the relationship between hypertriglyceridemia and acute pancreatitis.Methods Data was analyzed from 41 patients with acute pancreatits from Apr.1998 to Oct.2000 in our hospital.Of the 13 patients(GroupⅠ) with plasma TG level being higher than 11.3 mmol/L, 8 accompanied with gallstone(61.5%)and 5 without gallstone(38.5%)of the 28 patients (GroupⅡ) with plasma TG level being lower than 11.3 mmol/L,19 accompanied with gallstone(47.3%)and 9 without gallstone(52.7%)RANSON score,morbidity of complications and the level of ALT and AST were compared between two groaps.The correlation between TG and RANSON score was analysed.Results There were significant difference between the two groups on RANSON score,morbidity of complications and level of ALT and AST(P0.05).Conclusion There is an close relationship between hypertriglyceridemia and acute pancreatitis,the high level of plasma TG plags a key a role in acute pancreatitis,patients with acute pancreatitis with hypertriglyceridemia are more likely to have higher morbidity of complications and liver function aggravating.