| Part I:Meta analysis of clinical efficacy of Xuebijing injection in adjuvant treatment of severe pneumoniaResearch purposeTo evaluate the clinical effectiveness and safety of Xuebijing injection in the treatment of severe pneumonia.The research methodsChina Knowledge Network(CNKI),Wanfang Data,VIP Database(VIP),National Library of Medicine PubMed database,Dutch Medical Abstracts Embase database,Cochrane Library database and other network resources were searched by computer from the establishment of the database to the release in August 2020,to collect the randomized controlled trial(RCT)of Xuebijing injection combined with conventional Western medicine treatment(observation group)and conventional Western medicine treatment(control group)on the clinical efficacy of severe pneumonia.The literature was screened and sxtracted independently by two researchers,and the quality of the inculed literature was evaluated by Cochrane "bias risk assessment tool".RevMan 5.4 software was used for Meta analysis,and the potential bias of the included literature was evaluated by inverted funnel chart.The results of the studyA total of 22 articles were included,involving 2497 patients,including 1258 cases in the observation group and 1239 cases in the control group.The results of the risk of bias quality evaluation showed that the quality was generally low.Due to the inconsistency of the numerical expression of some indicators reported in the literature,only descriptive analysis was carried out.According to the results,compared with the control group,the total effective rate of patients in the observation group was significantly increased(OR=2.55,95%CI was 2.06 to 3.14,P<0.000 01),and the mortality rate was significantly reduced(OR=0.47,95%CI was 0.34 to 0.65,P<0.000 01),length of hospital stay(MD=-4.02,95%CI was-5.15 to-2.88,P<0.000 01)and mechanical ventilation time(MD=-3.88,95%CI was-6.15 to-1.61,P=0.000 8)were significantly shortened,oxygenation index was significantly increased(MD=51.39,95%CI was 26.45 to 76.32,P<0.000 1),white blood cell count was significantly reduced(MD=-1.90,95%CI was-2.23 to-1.57,P<0.000 01),and the observation group was better than the control group in improving the pneumonia severity index(PSI).However,there was no statistically significant difference between the two groups in pathogenic positive rate(OR=0.77,95%CI was 0.51-1.15,P=0.20).In the adverse reaction reports,only sporadic cases in the observation group showed dizziness,headache,diarrhea,chest tightness,and the difference in the incidence of adverse reactions between the two groups was not statistically significant.Funnel plot analysis of the studies included in the meta analysis of clinical total effective rate indicated that there might be potential publication bias.The research conclusionXuebijing injection has a good effect in clinical adjuvant treatment of severe pneumonia.However,due to the lack of randomized,double-blind,large-sample,multi-center RCT studies,Xuebijing injection is used in clinical adjuvant treatment The effectiveness and safety of severe pneumonia need more high-quality RCT studies to verify.Part II:The experiment of Xuebijing injection reducing inflammatory reaction and liver injury in sepsis by regulating autophagy.Research purposeSepsis is a fatal organ dysfunction caused by infection,but its pathogenesis has not been clear.In the basic research to explore the treatment of sepsis,it has been reported that there is a potential connection between autophagy of cells(Autophagy)and organ failure caused by sepsis.In China,Xuebijing injection provides new treatment ideas for improving the prognosis of patients with sepsis.But so far,there is no literature or animal experiment that combines Xuebijing injection with the improvement of autophagy levels in sepsis.Therefore,we plan to use Xuebijing injection to affect the cecal ligation and puncture model of sepsis in mice.Animal experiments of CLP(Cecal Ligation and Puncture)model hepatocyte autophagy levels are expected to discover the mechanism of action of Xuebijing injection in the treatment of sepsis.The research methodsThirty-two clean-grade male SPF-grade ICR mice aged 6-8 weeks were divided into 4 groups according to the random number table method:sham operation group,CLP group,Xuebijing group and autophagy inhibitor group.All the 4 groups received materials at 6h postoperatively.The sham operation group only performed laparotomy without cecal ligation and perforation;the CLP group received cecal ligation and perforation;the Xuebijing group received 6ml/kg intraperitoneal injection of Xuebijing injection+cecal ligation and perforation 2 hours before the operation;autophagy In the inhibitor group,6ml/kg intraperitoneal injection of Xuebijing injection 2h before operation+15mg/kg intraperitoneal injection of autophagy inhibitor 3-methyladenine(3-MA)+cecal ligation and perforation 1h before operation.The mice in the 4 groups were dissected 6 hours after the operation to obtain liver tissue,and blood was collected by cardiac puncture and blood samples were collected.Then the specimens were stained by immunohistochemistry to observe the number of microtubule-associated protein light chain 3(LC3 protein)in liver tissue;Western Blot was used to detect the ratio of LC3-Ⅱ/LC3-Ⅰ;enzyme-linked immunosorbent method(ELISA)detection of tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)index changes;HE staining to observe the pathological condition of liver tissue;biochemical method to detect liver function alanine aminotransferase(ALT)and aspartate aminotransferase(AST).Use SPSS 26.0 software for statistical analysis.Measurement data are shown as mean ± standard deviation(x ± s).For data with normal distribution and uniform variance,two independent sample T test is used for comparison between two groups;data that does not conform to normal distribution or uneven variance is used Nonparametric statistical rank sum test.P<0.05 considered the difference to be statistically significant.The results of the study1.CLP model construction resultsThe liver damage and inflammatory factor levels in the CLP group were significantly higher than those in the sham operation group,and the difference between the groups was statistically significant(P<0.05).The results of HE staining of liver tissue also showed that the hepatocytes of the CLP group had a significant inflammatory response,and after the mice were taken from the abdomen,it was found that the color of the cecal ligation was black and necrotic,and the abdominal cavity was foul,which can indicate that the experimental sepsis mice were successfully modeled..2.Results of application of Xuebijing injectionComparison of ALT between CLP group and Xuebijing group,CLP group mean ±standard deviation(572.267 ± 159.496)U/L,Xuebijing group mean ± standard deviation(376.810 ± 53.258)U/L,p=0.019<0.05,The difference is statistically significant;CLP and Xuebijing group compared AST,CLP group mean±standard deviation(348.165±99.484)U/L,Xuebijing group mean ± standard deviation(229.092±38.161)U/L,p=0.023<0.05,the difference is statistically significant.Comparing IL-6 between CLP group and Xuebijing group,CLP group mean±standard deviation(339.793±79.313)pg/ml,Xuebijing group mean ± standard deviation(194.192 ± 72.895)pg/ml,p=0.035<0.05,the difference is statistically significant.CLP and Xuebijing group compared TNF-α,the data of this group is too small for statistical analysis.The comparison of HE staining between CLP and Xuebijing group was observed in liver tissue.After the application of Xuebijing,the structure of liver cells was clear,and the damaged liver cells were improved compared with CLP group.The ratio of autophagy-related protein LC3Ⅱ/LC3Ⅰ in liver tissue was detected by Western Blot.The Xuebijing group compared with the CLP group,p<0.05,the difference was statistically significant.The result of immunohistochemical staining showed that the area value of Xuebijing group was 44.833±9.362.Compared with CLP group,p=0.048<0.05,the difference was statistically significant.3.Results of application of autophagy inhibitorsThe ratio of autophagy-related protein LC3Ⅱ/LC3Ⅰ in liver tissue was detected by Western Blot.The mean ± standard deviation(2.305±1.356)of the inhibitor group was compared with the mean ± standard deviation(6.441 ±1.209)of Xuebijing group,p<0.05,The difference was statistically significant.Comparing liver function,inflammatory reaction indicators and immunohistochemical staining results,there was no statistically significant difference between the inhibitor group and the Xuebijing group.The research conclusionXuebijing injection reduces the inflammatory response and liver damage of sepsis by increasing the autophagy level of hepatocytes in septic mice. |
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