Dynamic Efficacy Of BajhenTang With Addition And Subtraction In The Treatment Of AIDS And Mechanism

Background:AIDS(Acquired Immune Deficiency Syndrome)is an infectious disease that poses a serious threat to human health.A large number of clinical practices have proven that TCM treatment of AIDS can promote the re-establishment of immune function,delay the onset of disease,reduce opportunistic infections and improve the quality of survival of patients.Clinical studies over the past 30 years have provided a large amount of evidence-based evidence to clarify the etiology and pathogenesis of AIDS in TCM,evaluate the efficacy of TCM intervention protocols,and optimize TCM intervention protocols for AIDS complications,etc.However,there is a lack of evidence related to the long-term intervention effects and mechanisms of TCM treatment of AIDS.To this end,this study evaluates the dynamic efficacy of Bajhen Tang in the treatment of AIDS with the addition and subtraction of symptoms through a dynamic Markov model and a network pharmacology approach,based on retrospective cases from a pilot project on the treatment of AIDS with Chinese medicine,to explore the pathways of action of Bajhen Tang in the treatment of AIDS and to supplement the evidence-based evidence on the dynamic efficacy of Bajhen Tang in the treatment of AIDS.Objective:This study was conducted to investigate the dynamic efficacy and mechanism of Bazhen Tang plus and minus in the treatment of AIDS patients.Based on a retrospective cohort study,the trend of efficacy indicators over time during the treatment period of 0-60 months was analysed to clarify the dynamic efficacy of Bazhen Tang plus and minus in the treatment of AIDS patients with Qi and Blood deficiency.Subsequently,based on Markov model,the dynamic characteristics of symptoms and signs and intervention protocols of effective treatment cases were analysed over time to clarify the dynamic efficacy relationship.Finally,based on the network pharmacology approach,the core components,core targets and core pathways of the effective treatment regimen were analysed to identify the dynamic efficacy mechanism.Based on a large amount of longitudinal data on the treatment of AIDS with TCM,this study introduces a Markov model with a time parameter t to explore the dynamic efficacy and mechanism of the stepwise progression of TCM plus or minus treatment,providing real-world evidence-based and methodological ideas for the evaluation of the long-term efficacy of TCM in the treatment of AIDS.Material:(1)Subjects:The cases in this study were obtained from cases of AIDS patients in the pilot project of Chinese medicine treatment of AIDS from August 2004 to December 2010.(2)Inclusion and exclusion criteria:Inclusion criteria:cases in which the patients’ evidence was diagnosed as Qi and Blood deficiency and liver-depression,Qi stagnation and fire,and the intervention protocol was Bazhen Tang Plus and Danjuania Punyao San Plus,and cases that were consistently treated with Bazhen Tang Plus and Danjuania Punyao San Plus for two or more times;cases in which the patients’ demographic information,diagnostic information,clinical manifestations and medication information were relatively complete(some missing information was allowed);cases in which the patients’Karofsky score,symptom-sign score and The patient’s Karofsky score,symptom score and peripheral blood CD4+T-lymphocyte count are relatively complete(some missing information is allowed).Exclusion criteria:Cases in which the patient is not taking Chinese medicine at the start of treatment;cases in which the patient’s diagnostic information and medication information are missing or recorded only once;cases in which the patient’s clinical manifestations of symptoms and signs are recorded only once.(3)Relevant criteria.Primary efficacy index evaluation criteria:Effective:(1)patient’s CD4+T lymphocyte count increased by at least 30%or increased by 50/mm3 and remained stable;(2)no change in patient’s CD4+T lymphocyte count;ineffective:patient’s CD4+T lymphocyte count decreased by 30%or 50/mm3.Secondary efficacy index symptom and sign score evaluation criteria:Effective:patients’ clinical symptoms and signs have improved significantly and the total score has decreased by one-third or more;Stable:patients’ clinical symptoms and signs have improved insignificantly and the total score has decreased by less than one-third;Ineffective:patients’ clinical symptoms and signs have not improved or have further deteriorated and the total score has increased.The secondary efficacy index,Karofsky score,was evaluated as follows:effective:the increase of Karofsky score was more than 10 points;stable:the increase or decrease of Karofsky score was less than 10 points;ineffective:the decrease of Karofsky score was more than 10 points.(4)Statistical methods:SPSS 25.0 software was used for statistical analysis.The measurement data were described by Description,and the count data were described by frequency and composition ratio.The data before and after matching between the two groups conformed to normal distribution by t-test,and the measurement data that did not conform to normal distribution were tested by wilcoxon rank sum test,and the difference was considered statistically significant at P<0.05.Missing values were treated by interpolation using the last count value interpolation method.The age,gender and diagnostic stage of the two groups were matched 1:1 by Propensity Score Matching(PSM)with a Match Tolerance of 0.02 to adjust the baseline data to ensure that the new data set formed was balanced and comparable between the two groups.(5)Sample size estimation:This study is a retrospective cohort study design,Bazhen Tang plus or minus for the treatment group for,the control group for Danjuana Prosperity San plus or minus,the CD4+T lymphocyte count of the study subjects as the main efficacy index,according to the review of literature,the difference between the treatment group and the control group is 10,the standard deviation is 5,set bilateral α=0.05 that is unilateral is 0.025,the degree of certainty that is 1-β is 0.9.The superiority threshold was 5,and the sample size ratio of the test group to the control group was 1:1;the sample size of the test group was 22 cases and the sample size of the control group was 22 cases,calculated using R language with reference to the method of Chow et al.Taking into account the 10%of missed visits and refusals,a minimum of 25 cases in the treatment group and 25 cases in the control group were required,giving a total sample size of 50 cases.(6)Study content and grouping methodAccording to the principle of treatment to support the righteousness and dispel the evil,195 patients who met the inclusion and exclusion criteria were treated with Bazhen Tang for Qi and Blood deficiency as the treatment group,and 261 patients treated with Danjian Yi Yao San for liver depression,Qi stagnation and fire as the control group.Patients were matched 1:1 using propensity score matching and 360 pairs were successfully matched,180 cases each in the treatment and control groups.The study included patient demographic information,basic sign information,infection route status,and clinical typing.Method:Firstly,according to the treatment principle of Chinese medicine in treating AIDS to support the righteousness and dispel the evil,the demographic data,medication information and diagnostic information of 180 patients with Qi and Blood deficiency in Chinese medicine for AIDS were collected,and the efficacy indexes such as CD4+T lymphocyte count,symptom and sign score,Karofsky score and peripheral blood CD4+T lymphocyte count were recorded in detail for 60 consecutive months in the enrolled AIDS patients.A retrospective cohort of the Bazhen Tang treatment group and the Danjian Yiyao San control group was designed to evaluate the effectiveness of Bazhen Tang in treating AIDS patients with Qi and Blood deficiency and Danjian Yiyao San in treating AIDS patients with liver depression,Qi stagnation and fire in the long-term improvement of CD4+T lymphocytes.Then,we longitudinally observed the above patients with Qi and Blood deficiency in the treatment of AIDS with Bazhen Tang plus and minus,and clarified the characteristics of symptoms and changes in intervention protocols corresponding to Bazhen Tang plus and minus,and established Markov models to evaluate the long-term efficacy of Bazhen Tang plus and minus treatment.Finally,a network pharmacology approach was applied to establish the drug-component-target-disease networks of the Bazhen Tang,Bazhen Tang+Chai Hu Dredging Liver San and Bazhen Tang+Tonifying Zhong Yi Qi Tang intervention regimens,and to explore the pathways and mechanisms of action of Bazhen Tang.Results:A retrospective cohort study was conducted to evaluate the effectiveness of Bazhen Tang and Danjian Yiyao San in treating patients with AIDS Qi and Blood deficiency syndrome in improving CD4+T lymphocytes in the long term.The results showed that as the disease progressed during the latent,onset,acute and recovery phases of AIDS,the TCM pathology was characterized by a mixture of deficiency and actuality,with deficiency being the main cause,and the deficiency evidence continued throughout the course of the disease.After 60 months of treatment,Bazhen Tang,which is the main treatment for Qi and Blood deficiency,was superior to Danjian Yiyao San,which is the main treatment for eliminating evil,in improving the CD4+T lymphocyte count in patients with AIDS.The difference in the total symptom and sign score between the two groups before and after treatment(-4.51 ±7.34 in the treatment group,3.04±5.92 in the control group,P=0.321)and the difference in the Karofsky score between the two groups before and after treatment(9.69±20.67 in the treatment group,3.92±17.85 in the control group,P<0.01).The results showed that the evolution of symptoms in the population of patients with AIDS Qi and Blood deficiency was as follows:Qi and Blood deficiency→Qi and Blood deficiency,Qi deficiency mainly→Qi deficiency,corresponding to the evolution of symptoms:weakness,shortness of breath(chest tightness),dullness,abdominal distension,joint pain,itchy skin,etc.Among them,weakness and shortness of breath(chest tightness)are the most frequent symptoms in the whole treatment population,and the characteristics of the population show an increasingly pronounced state of Qi deficiency.The corresponding treatment protocols are:Bazhen Tang,Chai Hu Dredging Liver Dispersion and Tonifying Zhong Yi Qi Tang.The common active ingredients,targets and signalling pathways of Bazhen Tang,Bazhen Tang+Chai Hu Dredging Liver San and Bazhen Tang+Tonifying Zhong Yi Qi Tang,which are effective in treating AIDS,were analysed by network pharmacology methods,and it was found that the main active ingredients are quercetin,kaempferol,lignan,methoxyisoflavone,isorhamnetin and naringenin,which may affect the immune regulation process by regulating the expression of cellular inflammatory factors and participating in the activation of immune cells.It is also closely related to TNF,IL6,AKT1,TP53,VEGFA,STAT3,HSP90AA1,MAPK3,MAPK1 and other targets involved in the human cytomegalovirus infection signalling pathway,Kaposi’s sarcoma-associated herpesvirus infection signalling pathway and phosphatidylinositol 3-kinase-protein kinase pathway.