Research On The Law Of "disease, Pulse, And Syndrome Combined Treatment" Of Cold Prescription Based On Complex Network And Time Series Analysi

The vast ancient Chinese medicine books,especially those related to cold pathogenic disease,contain valuable experience in the treatment of exogenous disease with TCM,which urgently needs to be excavated.It is an important task for us to make full use of modern information technology,deeply explore the explicit and tacit knowledge among them,improve the application value of cold pathogenic disease related ancient books and documents,and thus meet the needs of scientific research and clinical application.At present,research in the field of cold pathogenic disease based on data mining mostly focuses on the works of Zhongjing and the application of classic prescriptions,while research on other cold pathogenic disease works and other medical experts in previous dynasties is relatively rare.Taking the narrow sense of cold pathogenic disease as the research object,there are still shortcomings in the exploration and analysis of its location,pathogenesis,syndrome manifestations,treatment prescriptions and herbal medicines.The ancient Chinese medicine books have rich records of prescriptions for the treatment of cold pathogenic disease.And prescriptions are a bridge between theory and clinical practice,carrying the contents of diseases,syndromes,principles,methods,prescriptions,and medicines,which can be used as a starting point and a foothold for studying the laws of syndrome and treatment of cold pathogenic disease and its historical evolution.ObjectiveTaking the prescriptions for treating cold pathogenic disease in ancient Chinese medicine books of previous dynasties as the research object,explore the related disease names,disease location,distribution characteristics,main causes and pathogenesis,core syndrome manifestations,key treatment medication,and other contents of cold pathogenic disease in different historical periods.Provide theoretical support for clinical and scientific research of TCM,and explore new methods for organizing and utilizing ancient Chinese medicine books.MethodsLiterature researchAnalyze the understanding and evolution of the concept of typhoid fever throughout history,laying a theoretical foundation for the next step of data mining.Knowledge element indexingThe prescriptions for treating cold pathogenic disease collected in ancient Chinese medicine books from the Qin Dynasty to 1949 were proofread and organized,and then imported into the Knowledge Meta Indexing System ofAncient Chinese Medicine Books.They were deeply indexed using the "Combined Treatment of Diseases,Pulses,and Syndromes"template,extracting semantic data of various types such as disease name,disease location,pathogenesis,symptoms,pulse,tongue,and herbal medicine,forming a structured database of cold pathogenic disease prescriptions.Complex networks and time series analysisA multi-entity complex network of "Combined Treatment of Diseases,Pulses,and Syndromes" of cold pathogenic disease was constructed in chronological order based on this database.Data extraction,network construction,and calculation of complex network analysis parameters such as network global topology eigenvalue,node degree,centrality index,and edge betweenness are all implemented using self-made Python code.The sub-network similarity analysis is calculated based on the Salton cosine formula,and the Spearman correlation analysis is performed to draw a clustering heat map or network diagram.The time interval division and time series analysis are implemented using a time series similarity analysis method based on morphological similarity distance using a self-designed R language code,and a network diagram is drawn based on the Spearman correlation analysis results.ResultsDuring the Qin and Han Dynasties,cold pathogenic disease,as a disease syndrome concept,refers to a specific disease caused by injury to cold pathogenic factors.During the period from the Wei dynasty to the Tang dynasty,its concept gradually became vague and broad,often confused with Tianxing and Warm Disease.During the Song,Jin,and Yuan dynasties,the concept of cold pathogenic disease differentiated into a narrow sense and a broad sense.The narrow sense returned to the specific syndromes caused by injury to cold pathogenic factors.The broad sense was an abstract concept,which served as the general term for all exogenous diseases.During the Ming and Qing dynasties,the narrow sense of the concept of cold pathogenic disease gradually contracted,while the broad sense gradually expanded with the development of the science of Warm Diseases.Since the Song Dynasty,doctors have attached great importance to the differential diagnosis of cold pathogenic disease and warm diseases.Although doctors after the Song Dynasty widely recognized cold pathogenic disease in a broad sense as a general term,when discussing clinical syndrome differentiation and treatment,they still focused on the narrow and specific cold pathogenic disease.After dual processing of knowledge element indexing and terminology standardization,a structured database of cold pathogenic disease prescriptions with accurate content and a diagnosis and treatment logic of "Combined Treatment of Diseases,Pulses,and Syndromes"has been formed.There are a total of 2990 prescriptions for treating cold pathogenic disease,involving 245 ancient Chinese medicine books,including 92 disease names,38 disease locations,6 disease nature,65 disease mechanisms,171 symptoms,27 pulse manifestations,17 tongue manifestations,590 herbal medicines,and 6 mistreatment.The complex network has a total of 1012 nodes,70785 edges,a clustering coefficient of 0.756,and an average path length of 1.884,presenting a "small world" nature.The scale and shape of the network are constantly changing at different time periods.The number of prescriptions for treating cold pathogenic disease significantly increased during the Song Dynasty,with more diverse disease names.The number of disease locations,pathogenesis,symptoms,pulse patterns,and traditional Chinese medicine also increased,and the network scale rapidly expanded,indicating that the Song Dynasty was an important turning point in the academic development of typhoid fever.The analysis of sub-network similarity also indicates that networks before and after the Song Dynasty were clustered together,respectively.The similarity of sub-networks in the Song Dynasty and later periods are higher.The better the clustering effect is in the later period,the more stable the centrality ranking of various types of nodes is.At the later stage,their clustering effect is better,and the centrality ranking of each type of nodes are more stable.The above results show that the understanding of TCM and the treatment of cold pathogenic disease continued to develop in the Song,Jin and Yuan Dynasties,and gradually matured and improved in the Ming and Qing Dynasties.The results of complex network and time series analysis indicate that the frequency and centrality of disease name nodes such as pediatric cold pathogenic disease,female cold pathogenic disease,gestational cold pathogenic disease,yin syndrome cold pathogenic disease,and winter month cold pathogenic disease is relatively high.The centrality of pediatric cold pathogenic disease,female cold pathogenic disease,and gestational cold pathogenic disease increased from the Sui and Tang dynasties,and stabilized during the Ming and Qing dynasties.The centrality of Tianxing and Shixing was relatively high during the Wei,Jin,Sui,and Tang dynasties,but significantly decreased after the Song Dynasty.The disease names related to seasons such as winter cold pathogenic disease and summer cold pathogenic disease were raised during the Ming and Qing dynasties.The main location of cold pathogenic disease is in the stomach,heart,spleen,chest,lungs,etc.Headache,fever,body pain,sweating,floating pulse and so on usually indicate that the disease is located in the exterior.Irritability,thirst,vomiting,palpitations under the heart,deep pulse,slow and intermittent pulse and so on usually indicate that the disease is located in the interior.The causes of anorexia,vomiting and diarrhea are mainly due to the dysfunction of spleen and stomach.Symptoms such as panic,vexation,and trance often indicate that the lesion is in the heart.Symptoms such as chest discomfort,chest pain,asthma,cough,expectoration,and spontaneous sweating suggest that the disease is located in the lung or chest.The frequency,centrality,and sub-network scale of the heat syndrome is higher than those of the cold syndrome,while the frequency and centrality of the deficiency syndrome are higher than those of the excess syndrome.The heat syndrome of cold pathogenic disease is more than the cold syndrome,and the deficiency syndrome is more than the excess syndrome.When the disease is cold syndrome,it often appears vomiting,diarrhea,abdominal pain,limbs frosty,pale complexion,deep pulse,weak pulse,thready pulse,etc.The disease is mostly in the spleen,stomach,middle Jiao,kidney,commonly used dried ginger,aconite,asarum and other herbal medicines.When the disease is heat syndrome,it often appears fever,irritability,delirium,constipation,thirst,rapid pulse,flood pulse,etc.The disease is mostly located in the heart,lungs,stomach,and interior.Medicines such as scutellaria baicalensis,rhubarb,gardenia,and anemarrhena are commonly used.The syndrome differentiation of six meridians of cold pathogenic disease has been valued since the Song Dynasty.Taiyang syndrome often causes headache,fever,aversion to cold,floating pulse and tense pulse,and is commonly treated with herbal medicines such as ephedra,cinnamon twig,saposhnikovia divaricata,and notopterygium root.Yangming syndrome often causes headache,thirst,delirium,constipation,rapid pulse,and bounding pulse,and is commonly treated with herbal medicines such as pueraria lobata,scutellaria baicalensis,gypsum,and anemarrhena asphodeloides.Shaoyang syndrome often causes cold and heat exchange,vomiting,hypochondriasis,bitter mouth,taut pulse and rapid pulse,and is commonly treated with herbal medicines such as bupleurum chinense,scutellaria baicalensis,pinellia ternata,and ginseng.Taiyin syndrome often causes abdominal pain,vomiting,diarrhea,abdominal distension,deep pulse,and thready pulse,and is commonly treated with herbal medicines such as dried ginger,atractylodes macrocephala,tuckahoe,and ginseng.Shaoyin syndrome often causes abdominal pain,diarrhea,vomiting,limbs frosty,deep pulse and weak pulse,and is commonly treated with herbal medicines such as dried ginger,aconite,ginseng,and white peony.Jueyin syndrome often causes abdominal pain,diarrhea,limbs frosty,vomiting,weak pulse and deep pulse,and is commonly treated with herbal medicines such as aconite,dried ginger,angelica,cinnamon,and evodia rutaecarpa.The most common pulse manifestations of cold pathogenic disease include floating pulse,deep pulse,rapid pulse,thready pulse,weak pulse,etc.During the Wei,Jin,Sui,and Tang dynasties,the centrality of the floating pulse was higher than that of the deep pulse;During the Song,Jin,and Yuan dynasties,the centrality of deep pulse was the highest;From the Ming and Qing dynasties to the Republic of China,the centrality of the floating pulse and deep pulse was basically equal and stable at a high level.Pediatric cold pathogenic disease commonly occurs in floating pulse,rapid pulse,and bounding pulse.Female,pregnant women,and postpartum cold pathogenic disease commonly have rapid pulse,deep pulse,taut pulse,etc.Winter cold pathogenic disease commonly occurs in floating pulse,tense pulse,and weak pulse.After mistakenly treating cold pathogenic disease,it is common to have rapid pulse,deep pulse,weak pulse,etc.The core herbal medicines for treating typhoid fever include licorice,ginseng,tuckahoe,scutellaria baicalensis,atractylodes macrocephala,cinnamon,ephedra,bupleurum chinense,etc.The choice of exterior-releasing herbal medicines has changed throughout history.The centrality of ephedra,cinnamomum cassia remains high at an early stage.After the Jin and Yuan dynasties,the centrality of saposhnikovia divaricata,notopterygium root,and bupleurum chinense gradually increased,surpassing that of cinnamomum cassia and ephedra,becoming the most core exterior-releasing herbal medicines.The selection of exterior-releasing herbal medicines and the application of herbal medicines with cold or warm properties are related to changes in climate,disease spectrum,and the rise of warm disease science.This study also discovered some combinations of closely related differentiation and treatment factors,such as effluvium-malaria,heart-macula,chest-phlegm,phlegm-cough,blood deficiency-abdominal pain,yang toxin-baicalin,diarrhea-aconite,madness-schisandra,kudzu root-gardenia,akebia-ginger,etc.SignificanceThis project innovatively adopts a complex network and time series analysis method.The results are mostly consistent with the academic ideas of TCM theory and typhoid fever contained in the medical texts of the past generations,and some new knowledge that has not been discussed or not paid attention to in the literature of the past generations has been discovered.This method is an important practice for studying complex and dynamic problems in the field of Chinese medicine,and is applicable to the study of internal patterns and trends of diseases,etc.This study explored and analyzed the characteristics of the disease,pulse,syndrome,and treatment of cold pathogenic disease and its developmental lineage,and explores the collective experience and wisdom of successive generations of physicians in understanding and treating cold pathogenic disease during the academic development of TCM.Hope that provide inspiration for the excavation and utilization of ancient Chinese medicine books and treat exogenous diseases with TCM.