| BackgroundDiabetic nephropathy(DN)is one of the common chronic microvascular complications of diabetes,and one of the main causes of the prevalence of end-stage renal disease and the death of diabetes mellitus(DM)patients worldwide.According to the 10th version of the map published by the international Diabetes federation(IDF)in 2021,the number of diabetic patients will continue to increase globally.However,China currently holds the highest number of diabetic patients in the world,with one in every eight adults diabetic.Up to 116 million.The increase in the number of diabetic patients is bound to lead to an increase in the number of diabetic nephropathy.According to statistics,from 2009 to 2013,the number of type 2 diabetic patients with nephropathy was as high as 40%,which brought serious economic burden to the society and ordinary families.The course of diabetic nephropathy is long.In terms of treatment,due to the unknown pathogenesis,there is a lack of effective treatment means.Western medicine focuses on basic treatment such as blood sugar,blood pressure and blood fat control in the early stage of treatment,and alternative treatment(kidney dialysis,kidney transplantation,etc.)is needed when the disease develops to the later stage.In recent years,it has been found that inflammation plays an important role in the progression of DN,and related inflammatory factors have also become potential biomarkers for the diagnosis and evaluation of DN.As this inflammation is extremely mild,it is called "micro-inflammation".Anti-inflammatory therapy has become a new idea and method for the treatment of diabetic nephropathy.Traditional Chinese medicine has certain potential in immune regulation,anti-inflammatory,improvement of clinical symptoms,delay of disease course and other aspects,and has attracted a lot of attention in the treatment of DN in recent years.Compared with conventional treatment,TCM or integrated Chinese and western therapy has significant effects on reducing urinary protein,protecting renal function and improving inflammation,which is worth our in-depth exploration,discovery and sorting out.ObjectiveThis study aims to analyze Chinese literature on the improvement of DN microinflammation by traditional Chinese medicine through bibliometrics,so as to understand the current research status and hot spots in this field,explore the future development trend,and evaluate the efficacy and safety of traditional Chinese medicine in the treatment of DN microinflammation by systematic evaluation,in order to provide objective evidence for scientific researchers and clinical medical personnel.MethodsThe study was conducted in two parts.The first part is the bibliometric analysis of literatures on the improvement of DN microinflammatory state by traditional Chinese medicine.Specific Methods:Data source:The research on the treatment of microinflammation in diabetic nephropathy by traditional Chinese medicine was retrieved from China National Knowledge Network(CNKI).The retrieval time was from the establishment of the database to December 2022.There was no restriction on the type of literature and publication.Literature metrology was used to analyze the annual publication of literatures related to the improvement of DN microinflammation by traditional Chinese medicine,the distribution of literature journals,and the funding.Citespace 6.1.R2 was used for co-occurrence analysis of authors and institutions,cluster analysis and breakout analysis of keywords.The second part systematically evaluated the efficacy and safety of traditional Chinese medicine in improving the microinflammatory state of DN through meta analysis.Specific methods:Literature retrieval database:Chinese database:CNKI,Wanfang,VIP,China Biomedical Literature Database(CBM),etc.Foreign language databases:PubMed,Cochrane library,Embase,Web of Science,etc.Search time:The database will be available until December 2022.Type of study design:A randomized controlled clinical trial(RCTS)of traditional Chinese medicine for the treatment of microinflammatory states in diabetic nephropathy,regardless of whether blind and random-assigned hiding methods were described in detail.Subjects:Patients in stage DNIII and above who met the diagnosis criteria of diabetic nephropathy and Mogensen,and did not receive clinical dialysis treatment.Intervention measures:The control group was treated with routine basic DN therapy.On the basis of the control group,the experimental group was given oral treatment of traditional Chinese medicine(including Chinese patent medicine,Chinese herbal extract,Chinese herbal compound,etc.),and the intervention cycle was not less than 8 weeks.Outcome indicators:(1)Main outcome indicators:hypersensitive C-reactive protein(hs-CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α);(2)Secondary outcome indicators:serum creatinine(Scr),urea nitrogen(BUN),urinary albumin excretion rate(UAER),24-hour urinary protein quantification(UTP),fasting blood glucose(FBG),2 hours postmeal blood glucose(2hPG),glycohemoglobin(HbA1c),adverse reactions.The literature is retrieved according to the search strategy,and the literature data is screened:(1)Import the selected bibliographies into the software Endnote,and use the software to eliminate duplicates.(2)Two researchers independently screened the literature according to the inclusion and exclusion criteria,conducted preliminary screening by reading the title and abstract,excluded the literature irrelevant to this study(including research object,intervention measures,intervention period,etc.),read the full text of the literature that met the criteria,and excluded the literature irrelevant to this study(including research type,intervention measures,outcome indicators,etc.).In case of uncertainty or disagreement,a third party shall arbitrate the final inclusion of the document.(3)Two researchers will independently extract data and cross-examine.In case of uncertainty or disagreement,the third party will arbitrate the result.Literature quality evaluation:(1)Score the literature by referring to JADAD scale.(2)Cochrane bias risk assessment table was used to evaluate the quality of the included literatures from random method,allocation hiding,blind method,loss of follow-up and publication bias,and the risk bias assessment table was drawn.Literature data analysis:Software RevMan5.4 was used for data statistical analysis.ResultsPart I:285 literatures were included in this study.From the annual number of published papers,the number of published papers was relatively small from 2005 to 2013,but then increased steadily.Although there was a decrease in 2020,the research on the prevention and treatment of diabetes and nephropathy by traditional Chinese medicine is on the rise,and the number of published papers is expected to continue to increase in the future.According to the knowledge graph analysis of researchers and research institutions,Yang Lixia and Xiang Shaowei published the most papers,followed by Wan Yigang,Hua Chuan,Liu Jing,Yu Borui,Liu Tonghua and Liu Ying.Meanwhile,the cooperation among the teams was also very close.From the perspective of fund distribution,the National Natural Science Foundation projects have the largest number of funded literatures,indicating that the improvement of DN microinflammation by traditional Chinese medicine has received national attention and support.According to the keyword co-occurrence map,keyword clustering map and keyword frequency statistical analysis,the clustering results were Q=0.6776>0.3,S=0.8953>0.5,indicating a significant clustering structure,reasonable results and credibility.It can be seen from the results that the current research directions in the field of improving DN microinflammation by traditional Chinese medicine mainly include:1)Related drug research:such as TCM monomer and its extract;2)Laboratory indicators,such as selection of inflammatory factors,IL-6,etc.;3)Research methods:Mainly experimental mechanism and literature review;4)Study on the rules of TCM syndromes:The dialectical theory of TCM is used to treat DN micro-inflammation,such as the theory of toxic damage to kidney collaterals.Currently,hot research syndromes include the syndrome of Qi and Yin deficiency,the syndrome of blood stasis,and the syndrome of dampness-heat.Emergent words can reflect the research hotspot in this field to some extent.As can be seen from the keyword emergence,the research contents lay equal emphasis on clinical observation and animal experiments.The clinical research population is concentrated in the elderly population,and the deficiency of Qi and Yin has been the research hotspot in the past two years,corresponding to the syndrome distribution in the elderly DN population.Part II:27 literatures were included in this study,all of which were journal papers published between 2014 and 2022.A total of 2,764 subjects were included in this study,including 1384 subjects in the experimental group and 1380 subjects in the control group.The 27 literature studies conducted statistical analysis on gender,age and other baseline data before treatment,showing no statistical significance,indicating that the studies were comparable.Meta-analysis showed that the effect of total response rate:the total response rate of the experimental group in the treatment of diabetic nephropathy was higher than that of the control group(OR=3.87,95%CI[3.09,4.85],P<0.00001).Eighteen studies reported the results of hs-CRP in the experimental group and the control group.The diamond was in favor of the experimental group,indicating that the experimental group was better than the control group in improving hs-CRP(95%CI[-2.14,-1.68],Z=16.24,P<0.00001).Fourteen studies reported the results of IL-6 in both experimental and control groups,and the diamond shape was in favor of the experimental group,indicating that the experimental group was superior to the control group in improving IL-6 in diabetic nephropathy(MD=-5.02,95%CI[-6.51,-3.52],P<0.00001).Fifteen studies reported TNF-α,and the experimental group was better than the control group in improving TNF-α in diabetic nephropathy(MD=-6.67,95%CI[-8.2,-5.15],P<0.00001).Nine studies reported UAER,and the results showed that the diamond shape was located on the side favorable to the experimental group,which was superior to the control group in improving UAER in diabetic nephropathy(SMD=-1.91,95%CI[-2.57,-1.26],P<0.00001).Eight studies reported 24h urinary protein quantification,and the results showed that the diamond shape was in favor of the experimental group,and the experimental group was better than the control group in improving 24h urinary protein quantification in diabetic nephropathy(MD=-0.42,95%CI[-0.59,-0.26],P<0.00001).Fifteen studies reported BUN,and the results showed that the diamond shape was in favor of the experimental group,indicating that the experimental group was better than the control group in improving the BUN of diabetic nephropathy(MD=-1.70,95%CI[-2.19,-1.21],P<0.00001).Eighteen studies reported SCRS,and the results showed that the diamond shape was in favor of the experimental group,indicating that the experimental group was better than the control group in improving the Scr of diabetic nephropathy(MD=-14.79,95%CI[-21.57,-8.00],P<0.0001).Five studies described blood glucose 2 hours after a meal,indicating that the experimental group was better than the control group in improving blood glucose 2 hours after a meal(MD=-0.50,95%CI[-0.88,-0.12],P=0.01).Twelve studies reported FBG,and the results showed that the diamond shape was in favor of the experimental group,indicating that the experimental group was better than the control group in improving FBG of diabetic nephropathy(MD=-0.73,95%CI[-1.09,-1.38],P<0.0001 the difference was statistically significant).A total of 9 studies described HBA1c,and the results showed that the diamond shape was in favor of the experimental group,indicating that the experimental group was better than the control group in improving HbA1c(MD=-0.68,95%CI[-1.08,-0.28],Z=0.3,35,P=0.0008).Among the 27 studies included,9 studies were described for safety evaluation,among which 4 studies showed no adverse reactions in both the experimental group and the control group,and 5 studies described adverse reactions.The results of these 5 studies showed that the rhombus intersected with the invalid line,RR=0.80,95%CI[0.46,1.39],Z=0.79,P=0.43,indicating that there was no significant difference in the incidence of adverse reactions between the experimental group and the control group,and the safety of TCM treatment was good.The 24 studies that reported the total response rate were evaluated for publication bias,the low degree of symmetry between the two sides of the null line suggests the existence of publication bias.Conclusion1.Research in the field of traditional Chinese medicine prevention and treatment of diabetic nephropathy in China is on the rise,and it is expected that the number of published papers will continue to increase in the future.Currently,the overall quality of published journals is high,and the level of literature fund projects is high.2.The main research institutions on the improvement of diabetic microinflammation by traditional Chinese medicine are mainly in the University of Traditional Chinese Medicine and its affiliated hospitals,and the geographical distribution is mainly in North China,Northeast China and South China.There is close cooperation within the teams,but the cooperation between the teams needs to be strengthened.3.At present,TCM syndrome research,elderly population research,inflammatory factors and other aspects are the focus of the research on the improvement of DN microinflammation state by TCM.The research trends in this field are single medicine and its extract,clinical study and experimental mechanism study.4.Traditional Chinese medicine combined treatment can improve the levels of inflammatory factors,such as IL-6,TNF-α and hs-CRP,better than simple Western medicine treatment,and can relieve the micro-inflammatory state of DN.5.Chinese medicine combined therapy is better than Western medicine alone in improving renal function such as UAER and 24h urinary protein.6.Chinese medicine combined treatment was generally superior to Western medicine alone in reducing FBG,2hPG and glycosylated hemoglobin,but in DN34 and DN4 stages,the improvement of FBG in the experimental group was similar to that in the control group,considering that the improvement of DN microinflammation by Chinese medicine may be independent of hypoglycemia.7.The safety of traditional Chinese medicine in the treatment of DN microinflammation is similar to that of Western medicine,with good safety. |
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