Big Data Analysis On Diabetes Literature And Real-world Clinical Cases On Diabetes Treated By A Famouse Traditonal Chinese Medicine Doctor

ObjectiveFirst,the aim of this study was to assess the national contributions worldwide in the field of endocrinology and metabolism,and to analyze author's contributions from three major regions of China,inclusing Mainland China(ML),Taiwan(TW),and Hong Kong(HK)on diabetes research by bibliometric analysis on diabetes literature.Second,this study was to analyze the academic thought of Professor Xiaolin Tong for the treatment of diabetes using traditional Chinese medicine(TCM),i.e.,theory of integrated state and target,by real-world clinical cases on diabetes treated by Xiaolin Tong.We also identified state and syndrome on the different stages of diabetes,including main symptoms of syndrome,core prescription,and investigated target drugs to increased laboratory examination indexes and symptoms respectively.This study may be helpful for optimizing the theory of integrated state and target,and to provide a new idea on the treatment of diabetes using TCMMethodsBig data analysis on diabetes literature was conducted using bibliometric analysis method.Web of Science was searched for articles published in the subject categories of"endocrinology&metabolism" and articles on diabetes originated from ML,TW,and HK.The number of articles,citation,article type and articles published in high-impact journals were analyzed to assess the contribution of Chinese contribution to the field of diabetes.Big data analysis on clinical cases was performed using real-world study(RWS)methods.Patients with type 2 diabetes mellitus(T2DM)and pre-diabetes were identified by searching Xiaolin Tong's out-patient cases database.According to the data mining methods,the scale-free complex network method was applied to excavate core prescriptions to different syndromes.Mutual information method was applied for the analysis of different syndromes and symptoms.Chi-square test was performed to compare effective rate and t-test was performed to compare two means.Results1.Big data analysis on diabetes literature(1)Worldwide contribution in the field of endocrinology and metabolism:A total of 79,394 articles were published on endocrinology and metabolism from 2010 to 2014.Authors in the United States published the most articles(27.38%),followed by China(7.22%),Italy(5.70%),the United Kingdom(5.6%),and Japan(5.54%).Articles published by authors in the United States had the most citations(260,934).When normalized to population size,the ranking for the most publications was Denmark(249.95),Sweden(152.51)and the Netherlands(126.97);when normalized to GDP,the ranking was Denmark(42.1),Greece(34.13),and the Netherlands(26.78).(2)Growing trend of China's contribution to global diabetes research:A total of 9,302 articles were retrieved for three regions of China.There were 6,775 from ML,1,993 from TW,and 534 from HK,with a positive trend from 2005 to 2014.The total number of articles that were published annually increased significantly from 2005 to 2014(205 to 2,026;p=0.000),which was a 9.88-fold increase.ML published the most articles(6,775/9,302,72.83%),with TW following at 1,993/9,302(21.43%)and with HK publishing the least number of articles(534/9,302,5.74%).As of 2006,the number of articles originating from ML exceeded the numbers from TW and HK.Citations of articles published between 2005 and 2014 in ML(48,296)were highest in number compared to TW(19,265)and HK(8,492;).HK,however,had the highest mean for citations per article(15.90),which was followed by TW(9.67)and then ML(7.13;)2.Big data analysis on real-world clincal cases on diabetes treated by Xiaolin TongThe theory of integrated state and target was first reported by professor Xiaolin Tong.Based on the theroy of modern medicine and TCM for the treatment of diabetes,professor Xiaolin Tong divided the core pathogenesis of type 2 diabetes mellitus into four states,including stagnancy state,heat state,deficiency state and damage state.Moreover,he suggested to select target herbs for increased laboratory examination indexes and the improvement of symptoms.(1)Analysis of basic characteristics:A total of 4561 outpatients(19857 diagnosed times)with T2DM or prediabetes treated by Xiaolin Tong from 2000 to 2015 were included.Among them,2399 cases were male patients,and 2162 cases were female patients.(2)Distribution Characteristics of four states:The number of patients with heat state is the most,followed by deficiency state,damage state and stagnancy state.In stagnancy state,the largest proportion is combinated state,that is stagnancy state,heat state,and deficiency state.Heat state exist in the whole process of disease progression,even in the damage state.Deficiency state is much more common in late stage of the disease and tend to appear with heat state or damage state together.Damage state was the complication of diabetes and often intermingled with each other kinds of states,in which heat state and deficiency state appear most commonly.(3)Stagnancy state:The common syndrome of stagnancy state are liver qi stagnation syndrome,spleen and stomach stagnation syndrome,and phlegm stagnation syndrome.The main symptoms of stagnancy state are fat and greasy yellow tongue coating thickness.Core prescriptions for liver qi stagnation syndrome are Radix Bupleuri,Fructus Aurantii Immaturus,Radix Paeoniae Alba,Rhizoma Zingiberis Recens,Rhizoma Coptidis,Radix Curcumae and Rhizoma Pinelliae Preparata.Core prescriptions for spleen and stomach stagnation syndrome are Fructus Aurantii Immaturus,Cortex Magnoliae Officinalis,Radix et Rhizoma Rhei,Rhizoma Anemarrhenae,Rhizoma Coptidis,and Herba Artemisiae Scopariae.Core prescriptions for phlegm stagnation syndrome are Rhizoma Pinelliae,Poria,and Cortex Magnoliae Officinalis.(4)Heat state:The top four syndrome of heat state are gastrointestinal damp heat syndrome,phlegm heat stasis syndrome,stagnated heat in liver and stomach syndrome,and gastrointestinal excess heat syndrome.Main symptoms of gastrointestinal damp heat syndrome are dry stool,thick yellow tongue coating rot greasy,and core prescriptions are Radix Puerariae,Radix Scutellariae,Rhizoma Coptidis,and Rhizoma Zingiberis.Main symptoms of phlegm heat stasis syndrome are red tongue,thick yellow tongue coating rot greasy,pulse slide,frowsty bosom etc.,and the core prescriptions are Rhizoma Coptidis,Rhizoma Pinelliae Preparata,and Semen Trichosanthis.Main symptoms of stagnated heat in liver and stomach syndrome are upset,irritability,mouth pain,dry stool,and core prescriptions are Radix Bupleuri,Rhizoma Coptidis,and Radix Scutellariae.Main symptoms of gastrointestinal excess heat syndrom are dry mouth,dry stool,red tongue,yellow and greasy fur,and core prescriptions are Rhizoma Coptidis,Radix et Rhizoma Rhei,Rhizoma Anemarrhenae,Radix Paeoniae Rubra,and Rhizoma Zingiberis Recens.(5)Deficiency state:The top three syndromes are spleen deficiency and heat in the stomach syndrome,deficiency of spleen and stomach stagnation syndrome,yin deficiency and heat syndrome.The main symptoms of spleen deficiency and heat in the stomach syndrome are fatigue,dry mouth,afraid of the cold,dizziness,sweating,dry stool,white tongue coating,greasy tongue,red tongue,weak pulse,etc,and the core prescritions are Rhizoma Coptidis,and Rhizoma Zingiberis,Radix Scutellariae,and Radix Panacis Quinquefolii.The main symptoms of deficiency of spleen and stomach stagnation syndrome are bloating,fatigue,dry mouth,anorexia,dry stool,acid regurgitation,tongue has scalloped,greasy,and bitter taste,and core prescriptions are Rhizoma Coptidis,Rhizoma Pinelliae Preparata,Rhizoma Zingiberis Recens,Radix Scutellariae,Radix Glycyrrhizae,Radix Codonopsis,and Rhizoma Atractylodis Macrocephalae.The main symptoms yin deficiency and heat syndrome are sweating,fatigue,dry mouth,poor sleep,dreams,red tongue,tongue dry,and the core prescriptions are Cortex Phellodendri,Rhizoma Anemarrhenae,Radix Rehmanniae Recens,Concha Ostreae,and Os Draconis.(6)Damage state:The damage state include renal collaterals damage,limb collaterals damage,eye collaterals damage,heart collaterals damage,brain collaterals damage,and stomach collaterals damage,etc.The main symptoms of kidney collaterals damage are swollen limbs,numbness,cold,night urination,dry stool,scalloped tongue,red tongue,yellow and greasy tongue,and core prescriptions are Hirudo powder,Rhizoma Coptidis,Radix Astragali seu Hedysari,Radix Salviae Miltiorrhizae,Rhizoma Zingiberis Recens,and Radix et Rhizoma Rhei.The main symptoms of limb collaterals damage are the limb numbness,cold,limbs pain,weakness,scalloped tongue,red tongue,weak pulse,etc,and the core prescriptions are Ramulus Cinnamomi,Caulis Spatholobi,Radix Astragali seu Hedysari,Radix Paeoniae Alba,Radix Aconiti Preparata,Radix Aconiti Kusnezoffii Preparata,Radix Glycyrrhizae,Radix Glycyrrhizae,Rhizoma Zingiberis Recens,and Rhizoma Anemarrhenae.The main symptoms of eye collaterals damage are as fuzzy,fatigue,dry mouth,insomnia,dry stool,leg pain,red tongue,dizziness,urine with the foam,and the core prescriptions are Rhizoma Coptidis,Radix Astragali seu Hedysari,Hirudo powder,Rhizoma Zingiberis Recens,Radix et Rhizoma Rhei,Radix Notoginseng,Radix Salviae Miltiorrhizae,Caulis Spatholobi,and Ramulus Cinnamomi.(7)Target herbs including medication target to increased laboratory examination indexes and symptoms.Target herbs for glycosylated hemoglobin(HbA1c)are Radix Puerariae,Rhizoma Coptidis.Target herbs for triglyceride(TG)are Rhizoma Coptidis,Radix Notoginseng.Target herbs for cholesterol(CHO)are Rhizoma Coptidis,Rhizoma Anemarrhenae,Rhizoma Pinelliae Preparata,and Radix Trichosanthis.Target herbs for low density lipoprotein(LDL)are Radix Trichosanthis,Rhizoma Zingiberis Recens.Target herb for blood uric acid is Radix Clematidis.Target herbs for dry mouth are Rhizoma Coptidis,Rhizoma Anemarrhenae,Radix Scutellariae,Radix Trichosanthis,Radix Paeoniae Rubra,and Radix Panacis Quinquefolii.Target herbs for numbness are Caulis Spatholobi,Radix Astragali seu Hedysari,Ramulus Cinnamomi,and Hirudo powder.Target herbs for cold intolerance are Radix Astragali seu Hedysari,Ramulus Cinnamomi,Caulis Spatholobi,and Radix Aconiti Lateralis Preparata,etc.Target herbs for blurred vision are Radix Notoginseng,Hirudo powder,Radix Puerariae,etc.Target herbs for sweat are Cortex Phellodendri,Concha Ostreae,and Os Draconis,etc.Target herbs for dry stool are Radix et Rhizoma Rhei,Rhizoma Coptidis,etc.Conclusion1.The big data analysis on diabetes literature demostrated that although Chinese authors' contributions in the field of endocrine and metabolic research rank the second worldwide,the overall quality of articles from China is relatively low.There has been a significant increase in the number of articles published on diabetes research from China during the past decades,especially Mainland.Since 2006,the number of published articles associated with diabetes in ML surpassed HK and TW,but HK had the highest quality.2.The big data analysis on real-world clincal cases suggested that big data analysis can be used to analyze basic characteristics of Xiaolin Tong's theory of integrated state and target for the treatment of T2DM,excavate various syndromes to different states,dialectical points,core prescriptions for each syndrome,and target herbs.Therefore,this study may be helpful for optimizing the theory of integrated state and target in treating T2DM using TCM.