Discovery Of Evidence And Treatment Patterns Of Diabetes Mellitus Related Proprietary Chinese Medicine Based On Partial Order Structure Analysis

ObjectiveBased on the research background of Chinese medicine in Guangzhou University of Traditional Chinese Medicine and the clinical experience of the Endocrinology Team of the First Affiliated Hospital in the treatment of DM,this thesis relies on the knowledge discovery and visualization method of partial-order structural analysis theory,which has been proven for its usability and effectiveness,to visualize and correlate the relevant diabetic prescriptions from an application point of view,such as the combination,usage,dosage and precautions.The aim is to comprehensively discover the pattern of DM Chinese patent medicines so as to provide reference for clinicians to make appropriate,safe and feasible decisions on Chinese patent medicines for specific clinical situations.This can then improve the overall diagnosis and treatment of DM and its complications with Chinese patent medicines for the benefit of public health.MethodsFirstly,data related to DM-related proprietary Chinese medicines were collected.The source of proprietary Chinese medicines is mainly from proprietary Chinese medicines with official drug production lot numbers in the database approved by the China Food and Drug Administration and with clear functional main treatment of DM or elimination of thirst in the drug instructions.It is further supplemented with data from the single disease Chinese Medicine treatment protocols of the National Administration of Traditional Chinese Medicine,“Chinese Medicine Prevention and Treatment Guide for Diabetes”,“Chinese Medicine Prevention and Treatment Standards for Diabetes(Draft)”,“Clinical Evidencebased Practice Guidelines for Chinese Medicine in Diabetes(2016 Edition)","Series on the Clinical Rational Use of Proprietary Chinese Medicines for Common Diseases(Endocrinology)",and "Clinical Application Guidelines for Proprietary Chinese Medicines"and other recommended DM-related proprietary Chinese medicine varieties as supplements.Then,by sorting the data of diabetic proprietary Chinese medicines,using Syndrome Types,common symptoms and physical presentations,function and main treatment,prescriptions and combinations,dosage and usage,precautions,etc.,the data structure is studied by using database tools,and the preliminary knowledge base is constructed on this basis to realise the preliminary digitisation,standardisation and structure of DM proprietary Chinese medicine metadata.This lays the foundation for knowledge,graph construction,knowledge discovery and application.Furthermore,the preliminary organised and standardised knowledge of diabetic proprietary Chinese medicines is transformed to build a formal context for expressing DM proprietary Chinese medicines knowledge.In order to obtain the most concise data representation and ensure the comprehensiveness of the data,a hierarchical optimisation method and attribute simplification method of the formal context of DM proprietary Chinese Medicines are studied,as well as a multi-level,multi-scale and multirelationship visualisation method of DM proprietary Chinese Medicines knowledge graph.Finally,using pre-diabetes,DM and its complications as the outline,the Syndrome Type as the objective,and common symptoms and physical presentations as the basis,the data is supplemented improved,forming various data groups– the treatment and efficacy group,the formula combination group,the dosage and usage group,and the precautions group.They are studied in detail for specific diseases,evidence types,symptoms,and evidence-syndrome combinations,respectively,in order to comprehensively reveal the basic laws of the group structure and sub-group structure.In the combined use of DM Chinese patent medicines,drug interactions,and superposition effects,“18 Incompatible Herbs” and “19 Herbs of Mutual Antagonism” are also considered,with the possibility of discovering previously hidden knowledge.ResultsFirstly,a database of DM-related proprietary Chinese medicines was created.After collection,the data was processed and quality control was performed,constructing a knowledge database of proprietary Chinese medicines for DM.It integrated and differentiated the related proprietary Chinese medicines,which included 175 proprietary Chinese medicines,11 western medical diseases,53 syndrome types,145 symptoms,31 physical presentations,126 treatments and efficacies,309 types of Chinese herbs,83 dosage and usage methods,64 contraindications,70 kinds of adverse reactions and 60 types of pharmacological toxicology.The visualisation and knowledge discovery of the groups related to diseases,symptoms and conditions,treatment and efficacy,prescriptions and combinations,dosages and usages,precautions and sub-groups under their parent groups were then established respectively.Using “disease as the outline”,the structure chart of the western medical disease group of proprietary Chinese Medicine for DM is mainly based on treatment.At pre-diabetes,proprietary Chinese medicine such as Shen Qi Jiang Tang granules,Tang Mai Kang capsules,Jin Qi Jiang Tang tablets(capsules or granules),Jiang Tang pills,Yang Yin Jiang Tang tablets,Tian Qi Jiang Tang capsules can be used as reference.In the complications involved in western medical diseases such as diabetic nephropathy,proprietary Chinese medicines like Yu Quan pills(capsules,granules,or powder),Qi Zhi Jiang Tang capsules(or tablets),Qi Yao Xiao Ke capsules can be used.For diabetic peripheral neuropathy,Jin Li Da granules,Tong Mai Jiang Tang capsules,Xiao Ke Tong Mai oral liquid can be used.For diabetic retinopathy,Qi Ming granules is the main choice.For DM combined with erectile dysfunction,Qi Wei Xiao Ke capsules are chosen.Using “syndrome as the outline”,Yin deficiency is the main syndrome and it can be accompanied by Qi deficiency and blood stasis,kidney deficiency with internal heat,dryness with intense fire,and internal fire and liver exuberance.Using “symptoms as the outline”,the "symptom-based" DM herbal medicine group shows that 93 herbal medicines are mainly used for the treatment of fatigue and mouth dryness.To emphasise the typical clinical symptoms,the group was separately structured for symptoms such as weakness,dry mouth,excessive drinking,easy hunger and excessive eating,shortness of breath,polyuria,and emaciation,etc.For example,in the sub-group chart,the medication pattern when weakness-dry mouth is the main symptom is found to be different in the fourth group set.If the patient presents with symptoms of weakness-polydypsia – proneness to hunger and excessive consumption of food,Xiao Ke Ling tablets,Gan Lu Xiao Ke capsules,Xiao Ke pills,Jiang Tang capsules,Tang Niao Le capsules(or tablets),Jiang Tang Tong Mai capsules,and Jiang Tang Ning capsules can be selected as the first choice for medication.If the symptoms of mouth dryness-polydypsia-proneness to hunger and excessive consumption of food,Yu Quan pills(capsules,granules,or powder),Xiao Ke Kang granules,and Yi Jin Jiang Tang capsules can be selected as the first choice for medication.Typical clinical symptoms are polydipsia,polyphagia,polyuria and emaciation.In the chart for common symptoms subgroups,the following proprietary Chinese medicines can be used as reference – Xiao Ke Ling tablets,Xiao Ke Ping tablets,Jin Li Da granules,Tang Niao Ling tablets,Qi Zhi Jiang Tang capsules(or tablets),Shen Qi Jiang Tang granules(capsules or tablets),Jiang Tang capsules,Jiang Tang Shu capsules,Xiao Tang Ling tablets(or capsules),Jiang Tang Jia tablets.In the chart for the group of DM-related proprietary Chinese medicines and their application for common signs and symptoms,thready pulse is predominantly observed,consistent with the pathogenesis of Yin deficiency syndrome.Thready pulse is a sign of deficiency and strain,with Deficiency of Yin and blood being the main syndrome.In general,a thready and rapid pulse is present for Yin deficiency,while a thready and weak pulse is present for blood deficiency,mostly observed in anaemic cases,later-stage febrile diseases,chronic wasting disease,etc.In the chart of DM proprietary Chinese medicine treatment and efficacy group,it can be observed that there are 79 proprietary Chinese medicines with the nourishment of Qi as the main medicinal efficacy.It is often combined other efficacies,such as the replenishment of Yin and generating body fluids,promoting blood circulation and removing blood stasis,nourishing Yin and tonifying the kidneys,clearing heat and strengthening spleen.In the group of herbs composition for proprietary Chinese medicine formulae,the most commonly used herbs are Radix Astragali(Huang Qi),Radix Trichosanthis(Tian Hua Fen)and Radix Rehmanniae(Di Huang),and the next most commonly used herbs are Fructus Schisandrae(Wu Wei Zi),Radix Ophiopogonis(Mai Dong)and Rhizoma Dioscoreae(Shan Yao).Using Radix Astragali(Huang Qi)as an example,formulas with common pairs of drugs include: 1.Radix Astragali(Huang Qi)and Rhizoma Dioscoreae(Shan Yao): Radix Astragali(Huang Qi)is effective in treating wasting-thirst disorder,while Rhizoma Dioscoreae(Shan Yao)emphasises on the nourishing spleen Yin.Combining these two herbs,one Yang and one Yin,Yin and Yang are in harmony,resulting in the strengthening of the spleen and stomach,promoting transportation and transformation,restraining spleen essence,preventing leakage,and eliminating sugar in urine.2.Radix Astragali(Huang Qi)and Radix Trichosanthis(Tian Hua Fen): Radix Astragali(Huang Qi)nourishes Qi and raises Yang,Radix Trichosanthis(Tian Hua Fen)clears heat and purges fire,generates body fluids and quenches thirst.This pair of herbs can be used to elevate hypoglycemia,reducing the activity of hyperglycemia.In the chart for the group for the dosage and usage of DM-related Chinese medicine structure chart,oral consumption is the main administration of medication.The usage is three times a day,according to the severity of the patient’s condition,in line with the theories of “stopping after the disease is treated”and “the efficacy determines the dosage of medication”.In the chart for the group of contraindications for the use of proprietary Chinese medicines for DM,fever and hyperthermia are the main symptoms.There are 11 proprietary Chinese medicines that should not be taken in cases of fever or hyperthermia.Due to low immunity of patients,it is easy to contract external pathogens or suffer from internal injury induced by catching a cold on in a state of fever,resulting in bacteria taking advantage of deficiency and infecting the body,causing blood sugar to increase and aggravate the disease.In the chart for the group of precautions and adverse drug reaction for DM proprietary Chinese medicines,nausea is predominantly observed,suggesting that consuming the medicines will elicit a nausea reaction.For example: Mu Dan granules cannot be used casually,and menstruation periods or persons with allergic constitutions must be considered as it can easily cause adverse drug reactions.In the chart for the group of pharmacological and toxicological group of DM proprietary Chinese medicines,hypoglycemia is predominantly observed.Due to the diverse composition of proprietary Chinese medicines,each medicine has unique medicinal components,which are mutually matched to make the medicines effective in treating the disease.In addition to lowering blood sugar,proprietary Chinese medicines can also improve insulin resistance,and at the same time protect the kidney and enhance the immunity of the body in order to prevent and delay the development and spread of the disease.ConclusionThis thesis completes the standardised expression and knowledge database construction of the concepts related to DM-related proprietary Chinese medicines.With pre-diabetes,DM and its complications as the outline,Traditional Chinese Medicine syndromes as the objective,and common clinical symptoms as the basis,the thesis reveals the structure pattern of "disease-syndrome-symptoms-formulas-medicine-dosage-contraindication" and its clustering sub-groups structure.Through this review and analysis,insufficiencies in the current DM-related proprietary Chinese medicines are found,such as when using “disease as the outline”,it mainly focuses on DM,with a lack of varieties for pre-diabetes and complications.In using “syndrome as the outline”,the main focus is on deficiency of Qi and Yin,with an emphasis on blood stasis.However,there are not enough varieties for Yang deficiency.In using “symptoms as the outline”,emphasis is placed on "Three Excess and One Loss" and fatigue and shortness of breath,with few mentions on the improvement of disease complications.This study will not only lay the knowledge foundation for subsequent construction of the artificial intelligent recommendation models of DM-related proprietary Chinese medicines,but it will also help to improve the diagnosis and treatment of DM and its complications through the use of proprietary Chinese medicines and provide a reference direction for the future selection and development of DM-related proprietary Chinese medicines.