The Study Of Analysis Of Influence Factor Of TCM Deficiency Syndrome In Septic Shock And Yiqi Fumai Injection Intervention

ObjectiveTo summary the distribution of TCM Syndromes of septic shock by retrospective analysis of literature;To explore the factors affecting the changes of acute deficiency syndrome in traditional Chinese medicine in septic shock by clinical investigation;Meta analysis of the clinical efficacy of Yiqi Fumai Injection in the treatment of septic shock;To discussion the protective effect and mechanism of Yiqi Fumai Injection on animal model of septic shock.Methods1.Retrospective analysis of literature:The literatures on TCM Syndromes of septic shock from the self built databases of CNKI,Wanfang China academic journal database,VIP Information Chinese journal service platform,China biomedical literature database(CBM),local PubMed retrieval system and EMBASE to Septmber 1,2022 were searched.Standardize the names of syndrome types in the literature included in the study,according to《TCM internal medicine》《TCM diagnostics》《TCM clinical diagnosis and treatment terminology syndrome part》and relevant TCM syndrome diagnosis standards for septic shock formulated by the severe Medicine Association of the Chinese Medical Association and the professional committee of emergency medicine of the Chinese society of integrated traditional Chinese and Western medicine》.SPSS 21.0 statistical softwarewas used to analyze the frequency of TCM syndromes,to concluded that deficiency syndrome was the main TCM syndrome of septic shock.2.Clinical research:Cross sectional survey was used to analyze the factors affecting acute deficiency syndrome of traditional Chinese medicine.76 patients with septic shock were included in Guangdong Hospital of traditional Chinese medicine,Foshan Hospital of traditional Chinese medicine and Shenzhen Hospital of Beijing University of traditional Chinese medicine.The patient’s TCM symptoms,Apache Ⅱ score,SOFA score,mean arterial pressure(MAP),oxygenation index,CRP,neutrophil ratio,Interleukin-6(IL6),procalcitonin and the number of T lymphocyte subsets were collected.To Analysis of factors affecting acute asthenia syndrome in septic shock.3.Meta analysis:We searched China Knowledge Network(CNKI),Wanfang China academic journal database,VIP Information Chinese journal service platform,China biomedical literature database(CBM),PubMed,Cochrane Library,EMBASE self built database to September 1,2022 for the randomized controlled trial(RCT)of Yiqi Fumai Injection in the treatment of septic shock.Two researchers carried out literature data extraction and quality evaluation,used Cochrane’s official manual for literature quality evaluation,made a bias risk assessment map with Revman version 5.4 software,and used the meta package in R language for paired meta-analysis.4.Animal experiment:The mouse model of early septic shock was prepared by intraperitoneal injection of lipopolysaccharide(LPS).The animals were randomly divided into three groups with 10 animals in each group:control group(NC),septic shock model group(SS)and Yiqi Fumai intervention group(YQFM).The intervention group animals were injected with Yiqi Fumai Injection before two hours of injecting lipopoly saccharide(LPS).The dose of Yiqi Fumai Injection was 0.338g/kg·d.SS group mice were intraperitoneally injected with the same amount of 0.9%normal saline according to their body weight.The changes of mental state,activity,food intake and urine volume of mice were observed.The exercise tolerance and blood pressure of mice were measured.The blood routine,lactic acid,superoxide dismutase(SOD)and serum inflammatory factors(Creactive protein,tumor necrosis factor-α,Interleukin-6)of mice were analyzed by biochemical analysis.The T lymphocyte subsets and the level of reactive oxygen species(ROS)in peripheral blood of mice were analyzed by flow cytometry.The cardiac function of mice was detected by ultrasound.Results1.Retrospective analysis of literature:①There are 7 TCM syndromes with a frequency of more than 3%,in order from more to less,which are sudden Collapse of Yang-Qi,Deficiency of Qi and Yin,Heat toxin syndrome,Exhaustion of yin and removal of Yang,Qi depredation,Yin depletion,and fu-organ pattern with heat;②Further analysis of syndromes with frequency>3%,the main TCM syndrome was deficiency syndrome,accounting for 78%,and sthenia syndrome accounts for 22%;sudden Collapse of Yang-Qi and Deficiency of Qi and Yin are the main types of deficiency syndrome,and heat toxin syndrome is the main type of sthenia syndrome.2.Clinical research:①Compared with the non deficiency syndrome group,the MAP level and the proportion of CD3+CD4+ T lymphocytes in the deficiency syndrome group were lower[(62.27±10.05)mmHgvs(80.6 1 ± 19.60)mmHg;(29.71 ± 10.86)%vs(36.69±11.31)%,P<0.05],and the TCM syndrome score was higher[(16.13±4.06)score vs(10.88±2.55)score,P<0.05];②Spearman correlation analysis showed that TCM syndrome score was positively correlated with APACHE Ⅱ score(r was 0.522,P<0.05);TCM syndrome score was negatively correlated with map,oxygenation index and CD3+CD4+T lymphocytes(r were-0.630,-0.451 and-0.383,respectively,P<0.05).③Multiple linear regression analysis was used to analyze the factors affecting TCM syndrome score.It was concluded that MAP and APACHE Ⅱ score maybe predictors of the changes of TCM syndrome score(P<0.05).④Binary logistic regression analysis showed that MAP and the proportion of CD3+CD4+T lymphocytes were the factors affecting the changes of acute deficiency syndrome(P<0.05).3.Meta analysis:①Yiqi Fumai Injection can effectively reduce the 28 day mortality of patients with septic shock[RR=0.31,95%CI(0.12,0.80)],improve the total effective rate of patients[RR=1.33,95%CI(1.18,1.51)];②Yiqi Fumai Injection decreased the levels of blood lactic acid[SMD=-0.51,95%CI(-0.81,-0.21)]and heart rate[SMD=-1.66,95%CI(1.95,-1.37)],and increased ScvO2[SMD=0.45,95%CI(0.22,0.68)],urine volume[SMD=4.70,95%CI(4.21,5.19)],CVP[SMD=0.49,95%CI(0.26,0.72)]and map in patients with septic shock[SMD=0.87,95%CI(0.63,1.10)].4.Animal experiment:①Compared with the model group,the exercise tolerance[(187.33± 13.01)s vs(244.00±28.58)s,P<0.05],MAP[(72.66±4.93)mmHgvs(60.00±1.00)mmHg,P<0.05],the proportion of CD4+CD44+T lymphocytes[(0.09410.013)%vs(0.024±0.006)%,P<0.05]were increasedin the treatment group after treatment;②Compared with the model group,the activity of SOD increased[(1.37±0.26)mmol/L vs(0.57±0.76)mmol/L,P<0.05]and the level of ROS in lymphocytes decreased[(2.73±0.45)mmol/L vs(4.36±0.49)mmol/L,P<0.05]in the treatment group.③Compared with the model group,the level of CRP decreased[(1 165.7±289.9)ng/ml vs(1588.2±272.2)ng/ml,P<0.05]、the level of TNF-α decreased[(15.3±4.6)ng/ml vs(34.3±15.9)ng/ml,P<0.05]and the level of IL6 decreased[(349.2±176.4)ng/mlvs(421.2±521.6)ng/ml,P<0.05]。Conclusion1.Deficiency syndrome is the main TCM syndrome of septic shock,and deficiency of Qi and Yin is one of the main types of deficiency syndrome of septic shock.2.MAP and the proportion of CD3+CD4+T lymphocytes are maybe the factors affecting the changes of acute deficiency Syndrome in septic shock.3.Meta analysis show that Yiqi Fumai Injection can reduce the mortality of patients with septic shock and improve the clinical efficacy.The mechanism may be related to increasing blood pressure,improving hypoperfusion and improving oxygenation.4.Animal experiments is preliminaryverified that Yiqi Fumai Injection can increase the blood pressure in septic shock,and found that it can increase the number of T lymphocyte subsets,SOD activity and reduce intracellular ROS,serum inflammatory factors(CRP,TNF-α,IL6)in mice.The protective mechanism of Yiqi Fumai injection against septic shock may be related to the imbalance of antioxidant stress and inhibition of inflammatory response.