| Objective:Based on the rooted theoretical analysis of the ancient books related to knee osteoarthritis,the paper systematically sorted out and clarified the core disease location,etiology,pathogenesis,symptoms and signs,treatment,therapy and transmission of the disease,and mined the correlation among them to construct the disease development diagnosis and treatment system of knee osteoarthritis.At the same time,mesh meta-analysis,data mining,network pharmacology and other research methods were comprehensively used to conduct efficacy evaluation and mechanism research on the treatment of knee osteoarthritis in medical records and clinical trials,hoping to clarify the drug syndrome law of the disease,so as to provide higher quality evidence for scientific evaluation of the clinical efficacy of internal and external use of traditional Chinese medicine in the treatment of knee osteoarthritis and reveal its molecular mechanism.Finally,the aim is to explore more accurate disease characteristics and more reliable medication plan of knee osteoarthritis from multiple aspects of theoretical exposition,drug syndrome rule,molecular mechanism and efficacy evaluation.Methods:1.Rooted theoretical analysis:comprehensively search the ancient articles of knee osteoarthritis,screen and establish a database.According to the principles of preserving the original text,unifying and simplifying,the data are indexed by knowledge elements and coded at three levels,and the key disease characteristics and treatment elements of knee osteoarthritis are obtained through analysis.2.Data mining:screen the medical records of knee osteoarthritis treated by ancient and modern Chinese medicine,and input them into Excel after data standardization to establish a database.Clean,standardize and analyze the included medical records through the web platform of the ancient and modern medical record cloud platform.Through frequency statistics,association rules,cluster analysis,complex network analysis,point mutual information and other analysis methods,the clinical symptoms of knee osteoarthritis,commonly used traditional Chinese medicine and the relationship between them were explored.3.Network pharmacology:select the core traditional Chinese medicine combination for oral and external treatment of knee osteoarthritis obtained from comprehensive analysis,and preliminarily study the key components,targets and signal pathways of these two groups of traditional Chinese medicine combination on knee osteoarthritis,so as to provide a reference basis for the later study of the mechanism of traditional Chinese medicine treatment of knee osteoarthritis and other basic experimental research and clinical treatment application.4.Mesh meta-analysis:comprehensively search the randomized controlled trial literature on the treatment of knee osteoarthritis with internal and external use of traditional Chinese medicine in domestic and foreign databases and select them according to the inclusion and exclusion criteria,and then use the Review Manager 5.4.1,ADDIS 1.16.8 and Stata13.0 software to analyze the total clinical effective rate,total score of traditional Chinese medicine syndromes,VAS score,total score of WOMAC,incidence of adverse reactions and other outcome indicators,and generate a mesh relationship diagram.The probability may be arranged to analyze the treatment characteristics and advantages of internal and external use of traditional Chinese medicine compared with other commonly used western medicine.Results:1.Based on theoretical analysis,it is found that the key diseases of knee osteoarthritis are located in the muscles and bones and the Ying Wei;The etiology is mainly caused by the cold evil in the six evils,and is based on the deficiency of internal injury and qi;The pathogenesis takes the imbalance of yin and yang and the strength of positive and evil as the overall response.The key pathogenesis of the five zang organs lies in the kidney and liver.The endogenous pathogenesis of the five evils is mainly fire heat and phlegm dampness.The main manifestations of the pathogenesis of meridians are the rise and decline of qi and blood and the imbalance of movement;Clinical manifestations focus on limb symptoms,while other systemic symptoms are mainly pain;The principle of treatment is to strengthen the health and eliminate pathogenic factors,and the specific application method is to regulate the essence,qi,blood,and body fluid;The treatment is based on the flexible selection of etiology,pathogenesis,and symptoms,and the goal of meridian therapy is to promote the flow of qi and blood;The transmission of changes is influenced by the four seasons,mainly based on the theory of "five body arthralgia" and "five viscera arthralgia",from the outside to the inside,from the shallow to the deep,with symptom changes as the main manifestation.2.Based on the selected Napai standard,the data mining analysis of ancient and modern medical records found that:2.1 There were 169 medical records of KOA for oral treatment of ancient Chinese medicine,involving 549 components of traditional Chinese medicine,with a higher frequency of occurrence of angelica,licorice,achyranthes bidentata,fangfeng,ligusticum chuanxiong,and notopterygium;The "four qi" attribute of traditional Chinese medicine is the most warming medicine;The attributes of "five flavors" are pungent,sweet and bitter;It mainly belongs to the liver,spleen and kidney;The results of correlation analysis showed that white peony and angelica,licorice and white peony were the most relevant drug pairs for oral administration in ancient and modern times;Angelica sinensis and Achyranthes bidentata were clustered into five categories by cluster analysis;Similar prescriptions are classified into Fangfeng Decoction and Dabu Decoction.2.2 A total of 279 medical records were included in the modern oral treatment,involving 329 components of traditional Chinese medicine,including angelica sinensis,cinnamon twig,white peony,astragalus,achyranthes bidentata,and licorice,with a high frequency of occurrence.The "four qi" attribute of traditional Chinese medicine is the most temperate medicine,and the "five flavors" attribute is the first one,which is mainly attributed to the liver,spleen,and kidney.The association rules regard liquorice and paeonia lactiflora as the most relevant drug pair;Cinnamomum cassia and Paeonia lactiflora were clustered into five categories by cluster analysis;Similar prescriptions are classified into Dabu Decoction and Parasitic Decoction.2.3 There are 82 pieces of information about the treatment of KOA with ancient Chinese medicine for external use,involving 264 traditional Chinese medicine,of which myrrh,aconite,frankincense,angelica dahurica,angelica sinensis,ginger and cinnamon appear more frequently,and the "four qi" of traditional Chinese medicine is mostly warm;"Five flavors"belong to pungent flavor;Most of them belong to the liver and spleen;The association rules regard frankincense and myrrh as the most relevant drug pair;Angelica dahurica was clustered into five categories by cluster analysis;Similar prescriptions are classified as medicines for dispelling wind and dispersing cold.2.4 A total of 75 medical records were included in the treatment of KOA with modern external Chinese medicine,involving 191 traditional Chinese medicine,with the highest frequency of Achyranthes bidentata,Aconitum chuanwu,Safflower,Strelitzia tenuifolia,and Osmanthus peruviana;The "four qi" attribute of Chinese medicine is the most temperate medicine,and the "five flavors" attribute is led by the sweet taste.The meridians are mainly the liver,spleen,kidney and heart;The association rules regard Aconitum monkshood and Aconitum monkshood as the most relevant drug pair;Achyranthes bidentata was clustered into five categories by cluster analysis;Similar prescriptions are classified into the formula for relaxing tendons and activating blood circulation and the decoction for dispersing blood stasis and activating blood circulation.2.5 In the comprehensive analysis of ancient and modern symptoms,knee pain,poor flexion and extension,joint swelling and difficult walking were listed as the core symptoms of the disease.The clinical manifestations of ancient medical records revolve around the local sensation around the knee joint,with the main symptoms of pain;The clinical manifestations of modern medical records focus on joint function and concurrent diseases.2.6 Based on Chi-square and point mutual informatics analysis,Radix angelica,Radix glycyrrhiza and Radix ranthosa were the core oral drugs for the treatment of KOA.The core drugs for topical treatment of KOA are sinj injia and Turbia.3.The network pharmacological analysis showed that:3.1 the main components of the core Chinese medicine combination "Angelica sinensis licorice achyranthes bidentata" for oral administration of the disease were quercetin,kaempferol,skullcap,7-methoxy-2-methylisoflavone,etc;Key target genes include TNF,IL6,AKT1 and IL-1β、VEGFA,TP53 and JUN;The main signal pathways involved in regulation are AGE-RAGE signaling pathway,cancer signaling pathway and IL-17 signaling pathway in diabetes complications.3.2 The main components of the core traditional Chinese medicine for external use of this disease that play a role in "Streptomyces tenuifolia" are quercetin,kaempferol βSitosterol,anthocyanin and stigmasterol;Key target genes include TNF,IL6,AKT1 and IL-β、VEGFA,TP53 and MMP9;The signaling pathways involved in regulation include cancer pathway,lipid and atherosclerosis pathway and AGE-RAGE signaling pathway in diabetes complications.4.Based on reticular meta-analysis,the clinical evaluation of the treatment of knee osteoarthritis by oral and external use of traditional Chinese medicine combined with three commonly used western drugs was included in 77 randomized controlled trials,involving 6567 patients.The results of the analysis of the main outcome indicators showed that the treatment of KOA with external use of traditional Chinese medicine+internal use of traditional Chinese medicine+glucosamine therapy had the highest clinical effectiveness;Celecoxib combined with oral administration of traditional Chinese medicine is the best treatment to improve the score of traditional Chinese medicine syndromes in KOA patients;External use of Chinese medicine and internal use of Chinese medicine have better effect on improving VAS score of KOA patients;External use of traditional Chinese medicine+internal administration of traditional Chinese medicine is the most likely to be the best treatment to improve the total WOMAC score;The combination of external use of traditional Chinese medicine and internal administration of traditional Chinese medicine may be the treatment measure with the least adverse reactions in the treatment of KOA.Conclusion:1.The disease location of knee osteoarthritis is divided into tangible and intangible,and affected by internal and external causes,it is classified into the whole,five viscera,endogenous five evils,multiple pathogenesis of meridians,multiple symptoms and signs that extend from the limbs,and transmission with symptom changes as the main manifestation.Based on the etiology,pathogenesis,symptoms,signs,and transmission of the disease,its treatment principles and therapies have developed a guideline that focuses on strengthening the body and eliminating pathogenic factors,and aims at promoting the flow of qi and blood.Influenced by many aspects such as the origin of disease,theoretical development,and school characteristics,its theoretical cognition and clinical application have gradually been enriched and improved.2.Through multi-dimensional data mining,it is clear that the ancient medical records of knee osteoarthritis highlight exogenous diseases,the clinical manifestations are mainly pain,and the drugs are mainly based on the efficacy of dispelling wind and dispersing cold;However,modern medical records focus on the deficiency of liver and kidney,clinical manifestations focus more on joint function and concurrent diseases,and medication focuses on strengthening kidney and spleen and other tonifying functions.3.The core traditional Chinese medicine for oral and external use obtained in this study has a preventive and therapeutic effect on KOA.In multiple signal pathways such as cancer pathway and AGE-RAGE signal pathway in diabetes complications,quercetin,kaempferol and other active ingredients are used to act on genes such as TNF,IL6,AKT1,IL1B,VEGFA,TP53,etc.by inhibiting the secretion of inflammatory factors by cells,repairing chondrocytes Inhibition of apoptosis and other functions can prevent and treat the occurrence and development of KOA.4.Internal or external use of traditional Chinese medicine can improve clinical efficacy,improve TCM syndrome score,VAS score,WOMAC total score,WOMAC pain score,Lysholm score and Lequesne score,and reduce serum IL-1 content and TNF-α The content and reduction of adverse reactions are better than western medicine alone in the treatment of knee osteoarthritis,which may be the best method to treat KOA at present. |
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