Research On Drug Use Rules And Drug Action Mechanism In Ancient Atrophy Syndrome And Modern Amyotrophic Lateral Sclerosis Literature

ObjectiveAmyotrophic lateral sclerosis(ALS)is one of the common neurodegenerative diseases,which causes degeneration of upper and lower motor neurons of the central nervous system.Usually manifested as muscle weakness,paralysis,and eventually death due to respiratory failure.Traditional Chinese medicine has been inherited for thousands of years,and has profound cultural background and treatment experience.Although there is no TCM disease name for ALS,it is found that the clinical symptoms of such patients are very similar to the "failure syndrome" of TCM.In order to improve the current situation of difficult treatment of ALS,this study comprehensively collected the literature of ancient dysfunction syndrome and the literature of modern ALS,relying on the traditional Chinese medicine inheritance calculation platform(V3.0)using frequency analysis and association rules The method analyzed the drug rule of ALS.Compare the top 10 drugs in the ancient and modern literatures,find out the overlapping drugs as the core drug combination for the treatment of ALS,and then analyze the high-frequency drug pairs used in the treatment through the association rules,and make the clinical addition and subtraction during the treatment.Out of guidance.And through network pharmacology,the core drug combination was studied to provide a theoretical basis for the clinical treatment of ALS.MethodsData mining:In terms of screening of ancient documents,the search terms are set as dysfunction,wilt,dysfunction,dysfunction,dysfunction,etc.In the "Chinese Medical Code 5.0",the prescriptions of traditional Chinese medicine for the treatment of "dysfunction syndrome" are selected;the selection of modern literature is searched by setting The words are" ALS " and "Motor Neuron Disease" in Chinese and English.The search terms for intervention measures are:Chinese Medicine,Chinese Medicine,Chinese Herbal Medicine,Drugs or Chinese Herbal,in Wanfang,HowNet,Weipu,Pubmed and other databases Search all relevant literature prescriptions and medicines from the establishment of the database to December 1,2020.Use Excel file software to establish a database to standardize and extract research data,focus on extracting prescription information and import it into the traditional Chinese medicine inheritance calculation platform(V3.0),using frequency analysis and Apriori association rules based data mining methods to separately count the frequency of drug use,Medicinal properties,meridian,four qi and five flavors and drug equivalence information,and compare the top 10 drugs in ancient and modern literature to find out overlapping drugs as the core drug combination for the treatment of ALS.Set different degrees of support and confidence to obtain high-frequency drug pairs used in ancient and modern literature.Network pharmacology:Based on the Traditional Chinese Medicine System Pharmacology Analysis Platform(TCMSP),the chemical components and potential targets of the core drug combination in the data mining results were screened,and the drug compound-protein-target relationship diagram was constructed through Cytoscape 3.7.2.Through DisGeNet,TTD,GeneCards and OMIM multiple database databases,the disease targets of ALS were screened.Use Excel software to screen and obtain the target intersection genes of core drugs and diseases,and then use online drawing tools to create a Venn diagram for visual display,and enter the obtained common targets into the String database to run to obtain the PPI network(protein interaction network model),and export it As a result,Cytoscape 3.7.2 software was used for parameter calculation and analysis to determine the core target.The core target is imported into the metascape platform,and the gene ontology(GO)biological process analysis and the Kyoto Encyclopedia of Gene and Genome(KEGG)pathway analysis are performed,and the visual analysis is performed through the WeChat platform.ResultsThe ancient literature on this subject contains a total of 376 prescriptions,of which there are many documents from Ming and Qing dynasties.311 medicines,the total frequency of use is 4239 times.Among them,there are 35 kinds of drugs with a frequency of>30 times,with a total frequency of 61.71%.The top ten drugs used are Dihuang,Codonopsis,Poria,Angelica,Aconite,Achyranthes,Cinnamon,Licorice,Atractylodes,Astragalus.The drugs are divided into 21 categories,and the frequency of use is>10 times,the frequency is as high as 90.98%,and they are respectively tonic,warming,clearing heat,promoting blood circulation and removing blood stasis,diuresis and dampness,regulating qi,relieving surface,and dispelling rheumatism.Category,astringent category,and dehumidification category.The medicinal properties from high to low are warm,calm,cold,hot,and cold.The most commonly used drugs are mostly warm drugs,accounting for up to 44%.The medicinal tastes from high to low are sweet,bitter,pungent,sour,and salty.The proportions of sweet,bitter,and pungent are the top three,38%,26%,and 24%respectively.The first three meridians of the medicine are the spleen meridian,kidney meridian and liver meridian.There were 118 pairs of drug combination use frequency?38,and the top three drug combinations were "Dangshen,Poria","Dangshen,Angelica" and "Rehmannia,Poria".Among them,72 pairs of core combinations of two-flavored traditional Chinese medicine,40 pairs of core combination of three-flavored traditional Chinese medicine,and 6 pairs of core combination of four-flavored traditional Chinese medicine.In the case of "support rate of 38(10%)and confidence rate of 0.8",22 association rule combinations are obtained through analysis.A total of 31 pairs of drug combinations with a frequency of>56 times were obtained,including 25 pairs of core combinations of two-flavored Chinese medicine and 6 pairs of core combinations of three-flavored traditional Chinese medicine.In the case of setting "support as 56(15%)and confidence as 0.8",5 associations will be combined after the analysis is obtained.There are 61 modern documents,62 prescriptions,involving 149 kinds of drugs,and the total frequency of use is 824 times.Among them,there are 23 kinds of drugs with a frequency of?10 times,and the total frequency of use is 55.83%.The top ten drugs used are:Astragalus,Codonopsis,Rehmannia,Atractylodes,Poria,Eucommia,Licorice,Angelica,Tangerine Peel,White Peony.The drugs are divided into 18 categories,among which the frequency of use is?20 times,the frequency is as high as 92.45%,and they are respectively tonic,promoting blood circulation and removing blood stasis,relieving surface,diuresis and dampness,calming liver and wind,eliminating rheumatism,and clearing heat Class,Qi-regulating class,Wenli class,Astringent class,Digestive class.The medicinal properties from high to low are warm,calm,cold,cold,and hot.The most commonly used drugs are mostly warm drugs,accounting for up to 47%.The medicinal flavors from high to low are sweet,bitter,pungent,sour,and salty.The proportions of sweet,bitter,and pungent are the top three,respectively,43%,24%,and 21%.The first three meridians of the medicine are the spleen meridian,liver meridian and lung meridian.When the frequency of drug combination use is?12,63 pairs of combinations are obtained,and the top three drug combinations are "Astragalus,Codonopsis","Astragalus,Atractylodes" and "Dangshen,Atractylodes".Among them,there are 34 pairs of two-flavored Chinese medicine,25 pairs of three-flavored traditional Chinese medicine,and 4 pairs of four-flavored traditional Chinese medicine.In the case of "support of 12(20%)and confidence of 0.8",55 association rule combinations are obtained by analysis.A total of 21 pairs of drug combinations were used when the frequency of use was?18 times,including 15 pairs of core combinations of two-flavored Chinese medicine and 6 pairs of core combinations of three-flavored traditional Chinese medicine.Under the condition of setting "support as 18(30%)and confidence as 0.8",19 association rule combinations are obtained by analysis.Screening of core drug combinations(Astragalus,Codonopsis,Poria,Atractylodes,Rehmannia glutinosa and Angelica)yielded 52 chemical components and 277 potential targets.14594 disease targets were obtained,and there were 264 intersection genes between drugs and diseases,of which CXCL8 was the core target,followed by ADRA2A,ADRA2C,CXCL2 and so on.GO gene annotation function analysis yielded 49 entries(P<0.01),20 cell composition entries,9 molecular function entries,and 20 biological process entries.Through the KEGG enrichment pathway,the core drug combination for the treatment of ALS was obtained.A total of 20 enrichment pathways were obtained for the target pathways(P<0.01).ConclusionsTraditional Chinese medicine has rich experience in the treatment of dysfunction syndrome,and with the in-depth study of ALS in modern Chinese medicine,it can provide more effective methods for clinical diagnosis and treatment.This study analyzed the medication rules of traditional Chinese medicine for the treatment of ALS and related dysfunction syndromes through data mining.The core drug combination is mainly Astragalus,Codonopsis,Poria,Atractylodes,Rehmannia glutinosa,and Angelica.It looks like Bazhen Decoction.They all focus on invigorating qi and blood,strengthening the body and consolidating the foundation.At the same time,according to the different focus of the disease,the treatment should be based on the overall treatment,and the drug can be increased or the dose can be increased according to the different symptoms.If you see the lack of qi and water,you can reuse "Poria Atractylodes",and those with yin deficiency and blood stasis.Re-use "Rehmannia-Angelica","Cinnamon-Aconite" can be reused for patients with yang deficiency and cold coagulation.For the performance of ALS accompanied by muscle movement,high-frequency drugs such as windproof,stiff silkworm,whole scorpion,etc.Silkworms are supplemented with anti-wind medicine.And combined the research results with the clinical experience of the tutor,and put forward the rational use of the method of invigorating the kidney,filling the essence,opening the brain orifice,and detoxifying the marrow,providing medication guidance for flexibly coping with the diversified clinical symptoms of ALS.Finally,the use of network pharmacology to study the mechanism of the core drug combination in the treatment of ALS,and discovered the characteristics of the multi-level,multi-target,and multi-channel treatment of ALS with traditional Chinese medicine,which is the characteristics of ALS.Provide theoretical basis for clinical treatment of disease.