| Part ?:A Single-center Randomized Controlled Study on Early anti-inflammation Treatment of Acute PancreatitisObjective:This study is a single-center,randomized,single-blind,parallel-controlled clinical trial,which aims to explore the efficacy of indomethacin suppositories in the early treatment of AP patients.Methods:AP hospitalized patients were continuously included who were treated in our hospital from June 1,2018 to March 30,2 021,and the AP onset time was within 48 hours of admission.The clinical efficacy of standard treatment and standard treatment combined with indomethacin suppository was compared.Results:1.A total of 133 AP patients were included in the analysis.There was no significant difference in the baseline data of the indomethacin group(n=59)and the standard treatment group(n=74),and the indicators were in good agreement.2.Comparing the clinical symptoms and test indicators in the course of the two groups of patients,on the fourth day of hospitalization(d4),the body temperature of the indomethacin group was significantly lower than that of the standard treatment group(36.93±0.76 vs 37.32±0.81,P=0.034).On the 7th day of hospitalization(d7),the number of white blood cells in the indomethacin group was significantly lower than that of the standard treatment group(9.15±4.92 vs 11.42±5.54,P=0.042),with lower ratio of neutrophils(69.56±12.4 vs 75.08±11.37,P=0.029).Standard deviation of red blood cell distribution width was also significantly lower than that of the standard treatment group(40.3±2.98 vs 42.24±4.22,P=0.018).3.Comparing the prognosis of the two groups of patients,the length of stay in the indomethacin group,the rate of admission to the ICU,the length of stay in the ICU,and the rate of infectious necrosis were lower than those in the standard treatment group,but the difference was not statistically significant.4.Comparing the rates of organ failure in the two groups of patients after admission to the hospital,the rates of renal failure,respiratory failure,shock,and multiple organ failure in the indomethacin group were lower than those in the standard treatment group,and no significant difference was reached.5.Comparing the newly-appearing organ failure of the two groups of patients,the rate of renal failure in the indomethacin group was higher than that of the standard treatment group,and the rates of respiratory failure,shock,and multiple organ failure were lower than that of the standard treatment group,but the difference was not statistically significant.6.Drug safety analysis showed that the creatinine level of the indomethacin group on the 7th day of hospitalization was not higher than that of the control group,and the rate of gastrointestinal bleeding during the course of the disease was not higher than that of the control group.Conclusions:The application of indomethacin in the early onset of AP has certain benefits,and there are no obvious drug-related adverse reactions.In the future,the sample size needs to be expanded for further research.Part ?:The Role of CD177+Neutrophil Subsets in Taurocholate-induced Acute Pancreatitis Mice ModelObjective:Compare the differences between CD 177-/-mice and WT mice in the acute pancreatitis(AP)model induced by 5%taurocholic acid,so as to explore the role of CD177+neutrophils in acute pancreatitis.Methods:Wild-type(WT)mice were divided into sham operation group(Sham)and AP group,n=10 mice in each group,n=5 mice were randomly selected for transcriptome sequencing,and the comparison between Sham group and AP group Differentially expressed genes.CD 177-/-mice were divided into sham operation group(Sham)and AP group,and compared with 4 groups of WT mice Sham group and AP group.The AP modeling method was retrograde injection of 5%taurocholic acid into the pancreaticobiliary duct of mice,and peripheral blood,pancreas,lung and colon tissues were collected 24 hours after modeling.Peripheral blood was isolated from serum to detect pancreatin levels;pancreas and lungs were subjected to pathological sections and H&E staining to evaluate organ damage;immunohistochemical staining was used to observe the expression levels of MPO and CD177 in the tissue;mRNA was extracted from lung tissue for transcriptome sequencing(RNA-seq).MRNA was extracted from lung and colon tissues for qRT-PCR to compare gene transcription levels.Results:1.The RNA-seq results showed that compared with the sham operation(NC)group,the AP group had 1737 differential genes significantly up-regulated,and 1585 differential genes significantly down-regulated.The expression of CD 177 gene in the lung tissue of the AP group was up-regulated by 1.61 times.GO functional analysis found that the differentially expressed genes in lung tissues of Sham group and AP group were mainly enriched in the pathways of leukocyte activation,migration,differentiation,cytokine secretion,and lymphocyte differentiation.Protein interaction network predicts proteins that interact with CD 177 in mouse species,such as formyl peptide receptors(FPR2,FPR3),integrin aL(ITGAL),integrin ?M(ITGAM),integrin ?2(ITGB2)etc..2.The area of pancreatic necrosis and the degree of destruction of acinar structure in the AP group of CD 177-/-mice were significantly more severe than that in the AP group of WT mice,and the total pathological score increased significantly.The serum amylase level of CD177-/-AP group was higher than that of WT AP group,but it did not reach significance.Most of the MPO-positive cells in the pancreatic stroma and necrotic tissue of the AP group of WT mice were also CD 177-positive,but the MPO-positive cells in the CD177-/-AP group were almost not CD 177-positive.3.There was no significant difference in the degree of lung tissue pathological damage between the AP group of WT mice and the AP group of CD177-/-mice.The level of NF-?B mRNA in the lung tissue of the CD177-/-mouse AP group was significantly higher than that of the WT mouse AP group.4.CD 177-/-mouse AP group compared with WT mouse AP group,the intestinal mucosal-associated protein Occludin mRNA and E-cadherin mRNA levels decreased,but did not reach statistical differences.Conclusions:The differentially expressed genes in the lungs of the Sham group and the AP group of WT mice were mainly enriched in the pathways of leukocyte activation,migration,differentiation,cytokine secretion,and lymphocyte differentiation.The lack of CD 1 77+neutrophils leads to aggravation of AP pancreatic pathological damage,and aggravation of AP mid-intestinal mucosal barrier function damage.Lack of CD 177+neutrophils leads to increased levels of NF-?B mRNA in the lungs. |
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