| Anti-retroviral therapy(ART)can continuously inhibit the replication of human immunodeficiency virus(HIV)and restore the level of CD4+T lymphocytes,prolonging the life of HIV-infected patients and improving the quality of life.It is an effective therapy for the treatment of acquired immune deficiency syndrome(AIDS).The reconstitution of immune function is the key to the prognosis of HIV/AIDS patients,and the number of CD4+T lymphocytes is the main index to judge the reconstruction of immune function.Still,those with poor immune reconstitution or immunological nonresponder(INR)failed to achie ve the growth of CD4+T lymphocytes.The pathogenesis of INR is individually variable and the treatment is challenging.After long-term exploration,traditional Chinese medicine has recognized that INR is mainly a mixture of deficiency and excess,and the changes in symptoms and signs are mostly a process from qi deficiency to yang deficiency.The initial lesion site is in the spleen,and if it persists,it also affects the kidney.Spleen-kidney yang deficiency is the main pathological manifestation of INR patients.Traditional Chinese medicine has proven its effectiveness in treating INR by establishing the Chinese medicine diagnosis,exploring the pathogenesis and mechanism,analyzing the syndrome differentiation theory,and conducting clinical research.However,there was a lack of summaries of medication rules and clinical research on individualized treatment for patients with spleen-kidney yang deficiency.Therefore,exploring the medication rules of traditional Chinese medicine in the treatment of INR and exploring the clinical efficacy of collaborative treatment of traditional Chinese and western medicine for INR patients with spleen-kidney yang deficiency are of great practical significance for developing a systematic collaborative diagnosis and treatment plan between traditional Chinese medicine and western medicine.Based on this,this study first summarizes the current use of traditional Chinese medicine in the treatment of INR through data mining to provide ideas and directions for the treatment and clinical research of INR in traditional Chinese medicine.Second,starting from the INR patients with spleen-kidney yang deficiency,this study explores the relevant factors affecting their CD4+T lymphocytes,hoping to provide a certain foundation for the individualized diagnosis and treatment of INR.Finally,based on previous research results,this study explores the clinical efficacy of Shenling Guben formula in treating INR patients with spleen-kidney yang deficiency.1.Data miningData mining-based study on medication rules of traditional Chinese medicine to treat INRObjective:To comprehensively summarize the medication rules of traditional Chinese medicine in the treatment of INR through data mining,and systematically analyze the core medicines to provide ideas and directions for.the treatment and clinical research of INR with traditional Chinese medicine.Methods:We searched the Chinese and English literature databases(CNKI,Wanfang database,VIP database,PubMed database,Cochrane Library,etc.)about the treatment of INR with traditional Chinese medicine,screened the literature according to the inclusion and exclusion criteria,collected and entered the data of the included literature,standardized the drug name.And the analysis of frequency distribution,analysis of the meridian tropism,drug properties,and tastes,analysis of association rules,cluster analysis and factor analysis are used to comprehensively analyze the data.Results:A total of 26 related literature were included,and 54 Chinese herbs were obtained,with a total frequency of 150 times.The most frequently used Chinese medicines are Astragalus,Atractylodes,Codonopsis,Reishi,Schisandra,Poria,Licorice,Panax ginseng,Goji berries,and Semen Cuscutae.The analysis of the meridian tropism,drug nature,and tastes showed that the four qi of high-frequency drugs are mainly calm,warm,and slightly warm,the five flavors of high-frequency drugs are mainly sweet,bitter,and spicy,and the meridian tropism of high-frequency drugs is mainly lung meridian,spleen meridian,and kidney meridian.The results of association rule analysis showed that Astragalus,Atracty lodes,Codonopsis were the core drugs with the highest frequency of use,and Astragalus had a high degree of association with Atractylodes,Codonopsis,Poria,Panax ginseng,Goji berries.After clustering analysis of the highfrequency drugs,three latent core formula groups were obtained:C1:Panax ginseng,Poria,Atractylodes,Licorice;C2:Goji berries,Fructus Ligustri Lucidi,Schisandra;C3:Codonopsis,Reishi,Astragalus.After factor analysis,four common factors were extracted:F1:Atractylodes,Poria,Licorice;F2:Codonopsis,Reishi,Schisandra;F3:Astragalus,Goji berries,Fructus Ligustri Lucidi;F4:Panax ginseng,Schisandra.Conclusion:The treatment of INR with traditional Chinese medicine is primarily composed of sweet,neutral,spicy,and warm medicines,the treatment is mainly composed of warming the kidney and strengthening the spleen,supplemented by invigorating the lung and replenishing the qi.Because of the continuous damage to the body caused by the epidemic virus,the treatment is supplemented by clearing heat,which conforms to the etiology,pathogenesis,and development law of INR.In particular,the PoriaAtractylodes pair and Sijunzi decoction,which are the medicine pairs and formulas for strengthening the spleen and the vital qi,the Goji berries-Semen Cuscutae and Wuzi Yanzong pill,which are the medicine pairs and formulas for warming the kidney and reinforcing the yang,and the Schisandra and Astragalus,which are the medicines for tonifying the lung and benefiting the qi,are the important components of the medicine.It is expected that further exploration can be carried out to provide a basis for clinical studies and new drug research for traditional Chinese medicine of INR based on the results of this study.2.Clinical Study2.1 Analysis of the influence factors of CD4+T lymphocytes in INR with spleenkidney yang deficiencyObjective:To explore the related factors that may affect the recovery of CD4+T lymphocytes in INR with spleen-kidney yang deficiency.Methods:According to the inclusion and exclusion criteria,the INR patients with spleenkidney yang deficiency were screened.The CD4+T lymphocytes,CD8+T lymphocytes,CD8+CD38+T lymphocytes,CD4+Ki67+/CD4+,CD8+Ki67+/CD8+and other related immunological indexes were detected,and the basic data of the patients were recorded.The correlation analysis between CD4+T lymphocyte count and other immunological indexes and basic data was analyzed.With the CD4+T lymphocyte count stratification(≥ 200 cells/μL or<200 cells/μL)as the dependent variable,and other immunological indexes and basic data as the independent variable,the relevant factors that may affect the CD4+T lymphocyte count of INR patients with spleen-kidney yang deficiency were screened.Results:The CD4+T lymphocyte count in INR patients with spleen-kidney yang deficiency was negatively correlated with CD8+CD38+T lymphocyte count,CD4+Ki67+/CD4+and CD8+Ki67+/CD8+(P<0.05),and positively correlated with CD4+T lymphocyte count before ART,CD8+T lymphocyte count,ART treatment time and course of disease(P<0.05).At the same time,the expression of Ki67 in CD4+T and CD8+T lymphocytes was positively correlated with CD8+TCD38+T lymphocytes.Multivariate Logistic regression analysis showed that the CD4+T lymphocyte count before ART(OR=1.004,95%CI=1-1.007,P=0.041),CD8+T lymphocytes(OR=1.002,95%CI=1.0011.003,P<0.001)and CD4+Ki67+/CD4+level(OR=0.93,95%CI=0.7-0.898,P<0.001)levels were the influencing factors of CD4+T lymphocyte count in INR patients with spleen-kidney yang deficiency.Conclusion:CD4+T lymphocytes in INR patients with spleen-kidney yang deficiency are correlated with multiple factors.CD4+T lymphocyte count before ART,CD8+T lymphocyte count,and CD4+Ki67+/CD4+level may be independent factors that affect CD4+T lymphocyte count in INR patients with spleen-kidney yang deficiency.2.2 Clinical Study on INR Patients with Spleen-Kidney Yang Deficiency treated by Shenling Guben FormulaObjective:To explore the clinical efficacy of Shenling Guben Formula in the treatment of INR patients with spleen-kidney yang deficiency by clinical research,and to explore the therapeutic advantages of integrated traditional Chinese and western medicine on CD4+T lymphocytes,immune reconstitution efficiency,and T lymphocyte subsets.Methods:A multicenter,randomized,double-blind,placebo-controlled clinical trial was conducted.A total of 121 INR patients with spleen-kidney yang deficiency were enrolled according to the inclusion and exclusion criteria,with a treatment group receiving Shenling Guben Formula plus ART and a control group receiving a simulated Shenling Guben Formula plus ART,for a treatment course of 48 weeks.Comparisons were made between the two groups regarding CD4+T lymphocyte count,immune reconstitution efficiency,CD4+/CD8+,CD8+T lymphocyte count,CD45RA+T lymphocyte count,CD45RO+T lymphocyte count,CD4+CD38+T lymphocyte count,CD8+CD38+T lymphocyte count,CD4+Ki67+/CD4+,CD8+Ki67+/CD8+,and safety.Results:There were 121 patients in total,with 65 patients in the treatment group and 56 patients in the control group.(1)Among the main efficacy indicators,at 24 weeks of treatment,there was no significant difference in the CD4+T lymphocyte count,CD4+/CD8+ratio,and immune reconstitution efficiency between the treatment group and the control group(P>0.05),and the CD4+T lymphocyte count in the treatment group and the control group was significantly higher than that before treatment(P<0.05).At 48 weeks of treatment,the CD4+T lymphocyte count in the treatment group was significantly higher than that in the control group(P<0.05),and the CD4+T lymphocyte count in the treatment and control groups was significantly higher than that before treatment(P<0.05).(2)Among the secondary efficacy indicators,at 24 weeks of treatment,the CD45RO+T lymphocyte count in the treatment group was significantly higher than that in the control group(P<0.05),the CD8+T lymphocyte count,CD45RA+T lymphocyte count,and CD45RO+T lymphocyte count in the treatment group were significantly higher than before treatmen(P<0.05),while the CD4+Ki67+/CD4+levels and CD8+Ki67+/CD8+levels in the treatment group and control group were significantly lower than that before treatment(P<0.05).At 48 weeks of treatment,the CD8+Ki67+/CD8+ levels in the treatment group were significantly lower than that in the control group(P<0.05),the CD45RA+T lymphocyte count and CD45RO+T lymphocyte count in the treatment group and the control group were significantly higher than that before treatment(P<0.05),while the CD4+Ki67+/CD4+ levels and CD8+Ki67+/CD8+ levels in the treatment group and control group were significantly lower than that before treatment(P<0.05).(3)Subgroup analysis showed that in the subgroup with CD4+T lymphocyte count ≥200 cells/μL in baseline,at 24 weeks of treatment,the CD4+/CD8+ratio in the control group was significantly higher than that before treatment(P<0.05);at 48 weeks of treatment,the CD4+T lymphocyte count in the treatment group and control group was significantly higher than that before treatment(P<0.05).In the subgroup with CD4+T lymphocyte count<200 cells/μL in baseline,The CD4+T lymphocyte count and immune reconstitution efficiency rate in the treatment group were significantly higher than those in the control group(P<0.05),the CD4+/CD8+ratio in the treatment group was significantly higher than that before treatment(P<0.05),and the CD4+T lymphocyte count in the treatment group and control group was significantly higher than that before treatment(P<0.05).(4)Safety indicators showed no statistically significant difference in blood routine abnormalities rate,urine routine abnormalities rate,liver and kidney function abnormalities rate between the two groups after 24 weeks and 48 weeks of treatment(P>0.05).Conclusion:The combination of Shenling Guben Formula and ART has a certain effect on promoting the growth of CD4+T lymphocyte count in INR patients with spleen-kidney yang deficiency.It is more effective in populations with CD4+T lymphocyte count lower than 200 cells/μL and helps to inhibit immune activation-mediated cell proliferation.Combined with the impact of Shenling Guben Formula on T lymphocyte subgroups,we speculated that Shenling Guben Formula may improve the immune function of INR patients by improving thymus function and promoting immune responsiveness. |
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