Research On The Mechanism Of DHLX In Preventing The Early Recurrence Of Calculus After PTCSL And Regulating Bile Duct Inflammation

Objective: The postoperative recurrence rate of hepatolithiasis is high.Biliary tract infection is currently recognized as an independent risk factor leading to the formation of stones.Controlling inflammation by regulating inflammatory signal pathways can improve the bile duct environment and reduce the postoperative recurrence rate of hepatolithiasis.In this study,DHLX intervention was performed on patients with hepatolithiasis after PTCSL to analyze the clinical efficacy,prognosis and safety of patients,and to evaluate the clinical effect of DHLX in preventing early recurrence of hepatolithiasis and regulating inflammation after PTCSL.To improve the bile duct environment as the starting point,combined with experimental research to explore the mechanism of DHLX to improve the inflammatory response of bile duct cells to prevent hepatolithiasis.Methods:(1)Clinical study: 80 patients diagnosed with intrahepatic bile duct stones and treated with PTCSL were randomly divided into DHLX group(experimental group)and control group with 40 cases each.Patients in the control group received conventional treatment after PTCSL treatment;patients in the experimental group received oral DHLX treatment on the basis of conventional treatment for three months of continuous medication.Before and after treatment,the syndrome scores were used to observe the improvement of the syndromes;before and after the medication,the inflammation indicators and liver function indicators were monitored to understand the postoperative recovery and follow-up for the recurrence of hepatolithiasis,and finally evaluate the clinical efficacy of the drug.(2)Experimental study: The SD rat bile duct epithelial cells were divided into 9groups: group 1(normal control group),group 2(LPS model group),group 3(LPS + traditional Chinese medicine group),group 4(LPS)+PDTC group),group 5(LPS+SB203580),group 6(LPS+PDTC+SB203580 group),group 7(LPS+PDTC+Chinese medicine group),group 8(LPS+SB203580+Chinese medicine group),9 In the group(LPS+PDTC+SB203580 group+Chinese medicine group),the interaction between TAK1 and ASK1 in the cells of each group was detected by immunoprecipitation technology,and the distribution and co-localization of TAK1 and ASK1 in the cells were observed by laser confocal microscope.Results:(1)Clinical study:(1)In this study,77 patients were actually enrolled(38 cases in the control group and 39 cases in the test group).There was no statistically significant difference between the two groups of patients in gender,age,body mass index(BMI),course of disease,classification and other general data before medication,and the difference was not statistically significant(P>0.05),and they were comparable.(2)Comparison of the syndrome scores of the two groups of patients before treatment,and the difference between the groups was not statistically significant(P>0.05);after treatment,the syndrome scores of the two groups of patients were compared,and the syndrome scores of the test group were lower than those of the control group.Statistically significant(P<0.001).Comparison within the group: The syndrome scores of the two groups of patients before and after treatment were compared,and the syndrome scores after treatment were lower than before treatment,and the difference was statistically significant(P<0.001).(3)Comparing the effective rates of the two groups,the total effective rate of the experimental group was 100%;the total effective rate of the control group was 81.6%,and the effective rate of the experimental group was higher than that of the control group.The difference was statistically significant(P<0.05).(4)Comparison of the indicators of inflammation(WBC,CRP)and liver function(TBIL,DB,ALP,GGT)between the two groups after treatment,the difference was statistically significant;time comparison: the two groups of patients were treated for WBC,CRP,TBIL at various time periods Compared with,DB,ALP and GGT,the time effect was statistically significant;the difference between time and group interaction was statistically significant(P<0.001).(5)Comparison of the recurrence of stones in the two groups of patients 1 year after the treatment,the control group had 3 patients with recurrence of stones within 1 year,and the test group had no recurrence patients,the difference was not statistically significant(P>0.05).(6)In the experimental group,there were 3 patients with diarrhea,0 patients with rash,0 patients with fatigue,and no other serious adverse reactions.(2)Experimental study:(1)The immunoprecipitation technique test showed that compared with the first group,the interaction between TAK1 and ASK1 was not significantly different in the second,fourth,fifth,and sixth groups(P>0.05);compared with the first group Compared with groups 3,7,8,and 9,the interaction between TAK1 and ASK1 was enhanced,and the difference was significant(P <0.05);the third and ninth groups were extremely significant(P <0.01).(2)It can be seen under a confocal microscope,the blank group(group 1)has intact nuclei(blue)and clearly visible envelopes.ASK1 protein is labeled with green fluorescence,and TAK1 protein is labeled with red fluorescence,which is expressed in the cytoplasm;after modeling,TAK1 The protein increases.After the signal pathway blocker is blocked,the TAK1 protein is mainly expressed in the nucleus(see groups 4,5,and 6),and the green fluorescence labeled with ASK1 protein in the cytoplasm is reduced;after administration,the TAK1 protein is distributed in the cytoplasm and The ASK1 protein interacts,and the fluorescence shows yellow light with overlapping red and green fluorescence(see groups 7,8,9).Conclusion:(1)DHLX has a good effect in improving patients’ syndromes,adjusting serum inflammation indicators and improving liver function.(2)DHLX has a certain effect on preventing the early recurrence of stones after PTCSL.(3)DHLX is safe for patients without serious adverse reactions.(4)DHLX may promote the mutual antagonism of TAK1 and ASK1 to down-regulate the NF-κB signaling pathway,at the same time weaken the communication between the NF-κB and MAPK signaling pathways.This may be one of the mechanisms by which DHLX reduces the inflammatory response of bile duct cells.