| BackgroundAcquired Immuno-Deficiency Syndrome（AIDS）caused by Human Immuno-Deficiency Virus（HIV）,which is highly infectious and incurable,seriously influence the life and health of the people all over the world.By the end of 2020,it is reported that there are 1.045 million AIDS/HIV patients in China,with 112,000 new HIV infections that year.In the first half of 2021,there were 28,570 cases of AIDS in China,accounting for 0.84%of all infectious diseases,and 8,281 deaths,88.57%of all the infectious patients.After decades of efforts in AIDS/HIV prevention as well as treatment,China has made great efforts to stop the progress and development.At present,the accounting number of HIV/AIDS is becoming declined and the prevalence is low.But challenges remain to China’s vision of ending the epidemic.For example,the distribution of the epidemic in different provinces in China is unbalanced,the cure cannot be completely cured,the difficulty of vaccine research and development,and the social discrimination against HIV infected people.Recently,it shown that HIV infection will lead to gastrointestinal mucosal immune function destruction,intestinal microecological environment damage,resulting in the diversity of intestinal flora difference from normal.AIDS prevention and treatment of Chinese medicine research after more than 30 years of hard exploration,gradually formed in traditional Chinese and western medicine theory as the guidance,people living with HIV AIDS clinical efficacy as the core,to reduce the HIV/AIDS,centered on the morbidity and mortality as the goal,mainly for AIDS patients,rather than to simply the HIV virus,emphasis on people-oriented,overall guiding thought.We should delay the onset of HIV infection,promote immune reconstitution,alleviate adverse reactions of ART therapy,treat opportunistic infections,reduce drug resistance,improve quality of life and clean up the virus reservoir.A series of researches have been carried out.Moxibustion,as a non-invasive external use of Traditional Chinese medicine,plays a certain role in enhancing immunity,relieving clinical symptoms and improving intestinal microecological balance of patients.From the perspective of bibliometrics,this study systematically combs the research status of moxibustion in the treatment of AIDS,summarizes the characteristics of moxibustion acupoints and clinical plans,and carries out a prospective cohort clinical study to observe the effects of moxibustion on the effectiveness and safety of patients with immune function insufficiency after ART.The effects of moxibustion combined with ART therapy and ART therapy alone on the intestinal bacterial community structure of HIV/AIDS patients were compared and analyzed to provide a new strategy for improving the immune reconstruction of patients from the perspective of intervening intestinal disorders and inhibiting immune activation.Objectives1.Systematic review of relevant research literature on moxibustion in the treatment of AIDS was conducted to analyze the research status in this field,so as to provide a new diresction for clinical researches on the efficacy and safety of moxibustion in AIDS/HIV patients after ART.2.A prospective cohort study was conducted to study the effect of moxibustion on the efficacy and safety of patients with immune reconstitution insufficiency after ART.3.The effects of moxibustion+ART and ART on intestinal bacterial community structure of HIV/AIDS patients were compared and analyzed,so as to provide a new strategy for improving the immune reconstruction of patients from the perspective of intervention of intestinal disorders and inhibition of immune activation.Methods1.Bibliometric analysis of moxibustion therapy for AIDSBy searching the Chinese knowledge resource pool（CNKI）,China academic journal database（ten thousand）,Chinese science and technology periodical database（VIP）through using literature metrology analysis,through with keywords of "（AIDS or HIV or human immunodeficiency virus（HIV）or acquired immune deficiency syndrome）and（moxibustion or moxibustion or moxibustion or moxibustion）".Summarize and analyze the characteristics of literature and clinical trials that met with the inclusion/exclusion criterias.2.Effectiveness of moxibustion on efficacy and safety of patients with immune reconstitution insufficiency after ARTA prospective cohort clinical study design was used to include 200 AIDS patients with low viral load and low immunity,and they were divided into two parallel two groups（ART group&ART+moxibustion）for simultaneous clinical observation.The ART group（n=100）received conventional ART treatment for 48 weeks,and the treatment group（n=100）received ART+moxibustion treatment,3 times a week（once every other day）,10 courses of treatment on a weekly basis,2 weeks apart,4 courses in total,a total of 48 weeks.Plasma CD4+、CD8+、CD45RA+、CD45RO+、CD4+CD28+、CD8+CD38+、CD4+CD38+、CD4+ki67+/CD4+、CD8+ki67+/CD8+、mitochondrial membrane potential,relevant clinical symptom score and safety indicators were detected at different time points in 2 groups.3.Effectiveness of moxibustion on intestinal microflora diversity of AIDS patientsUsing 16S rRNA high-throughput sequencing technology,the differences in intestinal bacterial community structure between the ART group and the moxibustion group（both from Study 2）were compared and analyzed,providing a new strategy for improving the immune reconstitution of patients from the perspective of intervening intestinal disorders and inhibiting immune activation.Results1.Bibliometric analysis of moxibustion therapy for AIDS1.1 Literature characteristics analysis:Literature publication time analysis,moxibustion treatment of AIDS related literature was first published in 1989;Before 2005,the publication of relevant literatures in this field was at a low level,and showed a rapid upward trend since 2006.The number of published papers in 2006,2011 and 2017 was up to 17,and showed a downward trend until 2020.The included literatures were published in 104 journals,including 36（14.2%）in Chinese core journals and 83（32.8%）in Chinese source journals of science and Technology statistics.Acupuncture and Moxiation and Liaoning Journal of Traditional Chinese Medicine is the first one of the largest number publications.According to the analysis of the distribution of published regions and the bibliometric analysis of the first author’s unit address,the top 10 provinces and cities（countries）published a total of 174 papers,accounting for 68.8%of the total number of literatures,among which the top three published papers were Henan province（36.2%）,Beijing（17.2%）and Guangxi province（14.4%）.1.2 Keywords:Content analysis Keywords co-occurrence graph analysis,according to a frequency of 5 or more keywords can be divided into AIDS disease（HIV,infections,immune function,diarrhea,patients）,treatment related（moxibustion,traditional Chinese medicine,acupuncture,traditional Chinese medicine,Chinese medicine treatment,intervention,ginger moxibustion）and the scientific research of AIDS related（curative effect observation,research status,control,review,research progress,etc.）;Keyword cluster analysis,literature research from small to large scale of acupuncture and moxibustion therapy（#0）respectively,moxibustion（#1）,HIV/AIDS（#2）,（#3）,Chinese medicine treatment of HIV（#4）,diarrhea（#5）,（#6）resear ch progress and deficiency of vital qi（#7）,according to the label content can be divided into AIDS disease characteristics and the Chinese medicine treatment,acupuncture and moxibustion,etc.);According to research trend analysis,the key words of "immune function","acupuncture","Traditional Chinese medicine" and"diarrhea" emerged from 1998 to 2013,and the key words of "moxibustion" and"ginger moxibustion" emerged from 2014 to 2021.Based on the results of clustering,the time chart shows that cluster#0（acupuncture therapy）,cluster#1（moxibustion）,and cluster#2（AIDS）represent the fields of research from 1989,1978,1978 to the present.2.Effectiveness of moxibustion on efficacy and safety of immune reconstitution insufficiency patients after ARTIn this study,188 cases that met the inclusion/exclusion criteria were observed,including88 cases in the ART group and100 cases in the moxibustion group.2.1 Baseline:88 participants（71 males;17 females,mean age 45.16±11.32 years）were enrolled in ART alone group.There were 100 participants（male 77 cases,female 23 cases,mean age 47.78±10.57 years）in moxibustion with no significant difference.CD4+T lymphocyte counts were 183.60±66.31 and 202.80±61.64 in the ART group and the moxibustion group,and CD8+T lymphocyte number were 709.15±325.60 and 696.43±420.36,respectively.No significant difference was seen between the ART group and moxibustion group（P=0.07,P=0.28）.2.2 Comparisons of effectiveness in the ART group and moxibustion group at different time points:① Comparisons of CD4+T cell number between the ART group and moxibustion group:at 24 and 36 weeks’ treatment,the CD4+T lymphocyte count in the moxibustion group was obviously higher than that in the ART group（P=0.01;P=0.00）.② Comparisons of immune reconstructive effective response between the two groups:Although there was no obviously significant statistical difference of the immune reconstructive effective rate between the ART group and moxibustion group in different treatment periods（P>0.05,respectively）,at 48 weeks of treatment,the immune reconstructive effective rate of moxibustion group（40（41.67%））was higher than that in the ART group（23（34.33%））.③ Comparisons of secondary efficacy indicators between the ART group and moxibustion group:at 24 and 48 weeks’ treatment,the CD8+T cell number and CD45RO+count in moxibustion were significantly as higher as that in ART group（P=0.01;P=0.03;P=0.00;P=0.00）,and the number of mitochondrial membrane potential/CD4+ and mitochondrial membrane potential/CD8+ in the moxibustion group and the ART group obviously declined（P<0.05,respectively）;After 48 weeks’ treatment,the CD45RA+level in moxibustion group was significantly higher than that in the ART group（P=0.00）.After 24 weeks’ treatment,the CD4+CD25+and CD4+ki67+/CD4+level in moxibustion group were significanty lower than that in ART group（P<0.05;P=0.00）.④ Comparisons of clinical symptom and sign scores and effectiveness at different time points between the ART group and moxibustion group:at the 4 weeks’ treatment,the total symptom and sign scores in moxibustion group was obviously lower than that in the ART group（P<0.01）;Compared with the ART group,after 4 weeks of moxibustion,the symptoms of fatigue,tenderness of waist and knee and lymphadenopathy were significantly relieved（P<0.01;P=0.01;P=0.03）,at 12 weeks,the symptoms of cough and stupor were significantly relieved（P=0.01;P=0.04）,at 48 weeks,symptoms of nerdiness,anorexia and soreness and weakness on waist and knee were significantly relieved（P<0.05;P<0.05;P=0.04）;Although at the 24th and 36th weeks of treatment,the efficacy of symptom and sign score was relatively high in the ART group（P=0.00;P=0.03）,but from the overall trend analysis,the effectiveness of clinical symptoms and signs integral showed an overall increasing trend in the moxibustion group,while the effectiveness reached the highest in the ART group at the 36th week of treatment,but gradually decreased at the 48th week.⑤ Comparisons of immune reconstruction-related evaluation indexes between the ART group and moxibustion group at different time points:After 48 weeks’ treatment,the total scores of the ART group and moxibustion groups showed an overall downward trend,and the scores reached the lowest at 48 weeks.At the 4th,12th and 48th week of treatment,the total scores of immune reconstruction-related evaluation indexes in the moxibustion group was much more lower than that in the ART group,significantly（P=0.03;P=0.01;P=0.00）;After 48 weeks’ treatment,the each scores of 9 immune reconstruction-related evaluation symptoms of cold,fever,sore throat,diarrhea,infectious rash,non-infectious rash,herpes virus infection,combined with other head infection and oral mucosal ulcer were improved in 2 groups.Compared with the ART group,the symptoms of sore throat and non-infectious rash were significantly relieved after 4 weeks of moxibustion（all P<0.05）.After 12 weeks of moxibustion,the symptoms of non-infectious rash and oral mucosal ulcer were significantly relieved（all P<0.05）.After 24 weeks of moxibustion,the symptoms of sore throat were relieved significantly（P<0.05）.After 36 weeks of moxibustion,the symptoms of sore throat,herpes virus infection and oral mucosal ulcer were significantly relieved（P<0.05,respectively）.At 48 weeks of moxibustion,the cold and fever symptoms were significantly relieved（P<0.05,respectively）,but no significant differences were shown at other time points（P>0.05）.2.3 Analysis of safety indicators:After 12 weeks’ treatment,the number of patients with abnormal aspartate aminotransferase and creatinine values after moxibustion treatment decreased significantly compared with the ART group（P=0.04;P=0.03）;At 24 weeks of treatment,the number of patients with abnormal alanine aminotransferase,aspartate aminotransferase,urea nitrogen and creatinine values with clinical significance was significantly lower than that in ART group（P=0.03;P=0.02;P=0.01;P=0.01）;After 36 weeks’ treatment,the number of patients with abnormal aspartate aminotransferase,urea nitrogen and creatinine values with clinical significance decreased significantly compared with ART group（P=0.01;P=0.01;P=0.04）.After 48 days of treatment,no significant differences were shown in liver and kidney function among the above groups（all P>0.05）.3.Effectiveness of moxibustion on intestinal microflora diversity in AIDS patients3.1 Differences in fecal and intestinal microbiota composition between the ART group and the moxibustion group:PCA score plot results analyzed that the distribution and situation of the ART group and the moxibustion group was similar at the time of enrollment,indicating similar baseline fecal and intestinal microbiota composition.After 48 weeks’ treatment,the distribution locations and phase limits of patients in the ART group and the moxibustion group were obviously different,and compared with ART group,the points represented by the moxibustion group after treatment and before treatment were far apart,that is,the composition of microbes in the moxibustion group was significantly different after treatment compared with that before treatment.3.2 Differences of intestinal flora in ART group before and after 48 weeks’treatment:After 48 weeks’ ART treatment,in phyla level,nihilic bacteria,firmicutes,firmicutes,nitrocellulosa were significantly increased,while enterobacteria,floating mycobacteria,cyanobacteria,Bacteroidetes,proteobacteria were significantly decreased.At the class level,the orders of pleniformia,erysipelomycetes,clostridium,and δ proteobacteria were significantly increased,while the orders of fillobacter,α-proteobacteria,Bacteroidetes,y-proteobacteria,and actinomycetes were significantly decreased.At the family level,spinstolomonas,Clostridium,Prevosiaceae,succinvibrio,clostridium decreased significantly,while erysipelaceae,Bacteroideaceae,Tanneraceae,Lactobacillus,bifidobacteria,enterobacteriaceae increased significantly.At the genus level,clostridium,Prevotella-9 and Prevotella2 were significantly increased,while streptococcus,Spironella,Microbacteriae,succinovibrio and bifidobacteria were significantly decreased.Statistically significant differences were shown in the above microflora（P<0.05）.3.3 Differences of intestinal microbiota in the moxibustion group before and after treatment:After 48 weeks of moxibustion treatment,firmicutes,Enterobacteria,Proteobacteria and actinobacteria significantly increased,while spirochetes,cyanobacteria,nitrocellulospira,Blastomonas and Bacteroides significantly decreased.At class level,clostridium,γ proteobacteria and actinomycetes increased significantly,while Bacteroidetes,δ proteobacteria,bacillus,α-proteobacteria and erysipelomycetes decreased significantly.At the family level,succinvibrio,digestistreptococcus,Prevosiaceae,Clostridium and Burkholderaceae were significantly decreased,while salvia,Enterobacteriaceae,Clostridium,bifidobacteriaceae and Lactobacillus were significantly increased.At the genus level,the Spironella,Clostridium,Prevotella and succinovibrio were significantly increased.However,dordolella,Microbacter,rare micrococcus,bifidobacteria,Escherichia coli shigella decreased obviously.Statistically significant differences were shown in the above microflora（P<0.05）.3.4 Differences of intestinal microbiota between the ART group and the moxibustion group after treatment:At the level of phylum after 48 weeks of treatment,enterobacteria,Proteobacteria and Clostridium were dominant in the ART group（P<0.05）,while bacterobacteria,Firmicutes,Bacteroidetes and actinobacteria were dominant in the moxibustion group（P<0.05）.At class level,fusobacteria,Bacteroidetes,Fusobacteria and clostridium were dominant in ART group（P<0.05）,while blastomonas,α-proteobacteria,δ proteobacteria,erysipelomycetes,actinomycetes and Clostridium were dominant in Moxibustion group（P<0.05）.At the family level,clostridium,Prevosiaceae and Burkholderaceae were predominant in ART group（P<0.05）,while enterobacteriaceae,Bacteroideaceae,trichospiraceae,bifidobacteriaceae and succinvibrio were predominant in moxibustion group（P<0.05）.At the genus level,Paracetobacter,prevotella,Prevotella-9and Prevotella-2 were dominant in ART group（P<0.05）,while bifidobacteria,succinovibrio,Microbacteriae and Escherichia coli shigella were dominant in moxibustion group（P<0.05）.Conclusions1.Moxibustion treatment of AIDS started earlier,but there is a low high-quality clinical evidence-based evidence2.Moxibustion can improve the Count of CD4+and CD8+T lymphocytes in Patients with AIDS immune insufficiency,delay the apoptosis process of CD4+ and CD8+T lymphocytes,quickly and continuously relieve the symptoms of cough,fatigue,stupor,loss of appetite,soreness of waist and knee,and lymph node enlargement,and has better liver and kidney function protection.3.Moxibustion can improve the intestinal microbial composition of AIDS patients,which is significantly different from ART therapy in improving the dominant bacteria. |
PDF Full Text Request