| Objective: This study explored the classical prescription in Treatise on Typhoid and Miscellaneous Diseases by Zhang Zhongjing and the time prescription for treating cancer pain of later generations,searched,collected and sorted out the clinical research literature on the treatment of cancer pain by TRADITIONAL Chinese medicine,conducted statistical analysis on the principles,methods,prescriptions and drugs included,and summarized the law of drug use.Meanwhile,the mechanism of Shentong Zhuyu Decoction in the treatment of bone metastatic cancer pain was explored based on network pharmacology,providing data support for guiding the treatment of cancer pain in clinical practice.Materials and Methods:1.In cn KI,VIP and Wanfang databases,"tumor,malignant tumor,cancer" and "cancer pain,cancer pain" were selected as keywords,and literatures published from the establishment of the database to June 2021 were searched with "jing Fang" and "time Fang" as the key words in the search results.Duplicate literatures were removed,and the final inclusion papers were determined according to the inclusion criteria of literatures.Summing up the prescription for the treatment of cancer pain.2.Keywords are "tumor,malignant tumor,cancer" and "cancer pain" respectively in CNKI,VIP and Wanfang databases.In the retrieval results,literatures published from the establishment of the database to June 2021 were retrieved with the key words of "symptoms" or "syndromes" or "TCM" or "Chinese herbal medicine" or "Traditional Chinese medicine" or "TCM" or "combination of Traditional Chinese and Western medicine" or "syndrome differentiation and treatment" or "TCM treatment".Duplicate literatures were removed,and the final inclusion papers were determined according to the inclusion criteria of literatures.Standardize the information,pathogenesis and prescriptions of the four diagnoses to unify the standards by comparing TCM Diagnostics,Practical TCM Syndrome Differentiation Manual,Syndrome Differentiation of Syndrome elements,and Differential Diagnosis of TCM Symptoms.Standardize the names of TCM by comparing Chinese Pharmacopoeia and Traditional Chinese Medicine.The collected data were input into Microsoft Excel2013,a database was established,and the data mining of the four diagnosis information,pathogenesis and prescriptions in the literature was carried out by using the methods of frequency statistics,association rules,cluster analysis and factor analysis,and the mining results were analyzed,from which the treatment experience,academic ideas and basic prescriptions were extracted.3.The databases of CNKI,VIP and Wanfang used "bone metastasis cancer,bone metastasis tumor,bone metastasis malignant tumor" and "cancer pain,cancer pain" as keywords respectively,and searched literatures published from the establishment of the database to June2021 with "Chinese herbal medicine" or "Traditional Chinese medicine" as the key words in the search results.Duplicate literatures were removed,the final included articles were determined according to the inclusion criteria of literatures,and the clinical prescription for the treatment of bone metastases was explored.4.The databases of CNKI,VIP and Wanfang used "tumor,malignant tumor,cancer" and "cancer pain and constipation" as keywords,and searched literatures published from the establishment of the database to June 2021 with "Chinese herbal medicine" or "Traditional Chinese medicine" as the key words in the search results.Duplicate literatures were removed and the final included articles were determined according to the inclusion criteria of literatures to explore the clinical prescription for the treatment of cancer pain opioid-related constipation(OIC).5.The chemical components and action targets of Shantongzhuyu Decoction were found in TCMSP,and the compound-target-disease network,drug target protein and disease target protein(PPI)were constructed.Then GO analysis and KEGG pathway enrichment analysis were performed.Results:1.Summarize eight kinds of prescriptions,including Bupleurum,rhizome,dang Categorization,rhizome,ephedra,cassia twig,Pinellia ternata,Astragalus membranaceus and Shu Di.Among them,Shiefu Blood-stasis Decoction and Bupleurum shugan Powder can be selected in the Bupleurum prescription,and Rhizoma atractylodes aconite decoction and Aconite Peony liquorice Decoction can be selected in the attached subclass prescription.Ephedra can choose Yang and soup;Cassia branch kind can choose peony liquorice soup,pinellia kind can choose xiangsha six gentleman soup,Astragalus kind can choose buyang also five soup,cooked ground kind can choose Liuwei dihuang pill,when classified in the party can choose body pain by blood stasis soup,diaphragm by blood stasis soup for the treatment of cancer pain.2.Overall results of the literature,a total of 3872 literatures were collected,including 81 literatures related to symptoms,tongue and pulse(including 94 symptoms,76 tongue and 80pulse),165 literatures related to pathogenesis and pathologic features(including 178 pathogenesis and pathologic features),and 279 literatures related to cancer pain were included according to literature inclusion criteria.There were 123 references involving disease sites(including 134 disease sites),and 184 references involving cancer pain(including 197prescriptions).(1)Four-diagnosis information: In all the cancer pain literature,The main clinical symptoms were fatigue(48.94%),tingling(32.98%),dull(31.91%),pain with specific location(31.91%),soreness of waist and knee(27.66%),severe pain at night(26.60%),emaciation(23.40%),refusal to press(21.28%),dry mouth and pharynx(21.28%),joints Pain(1915%);Petechiae,petechiae(42.11%)purplish dark(32.89%),light(25.00%),wide open tongue pulse(17.11%),red(17.11%),little moss(14.47%),fat(14.47%),white moss(13.16%),pale white moss(13.16%),thin white moss(10.53%);Fine(57.50%),chord(47.50%),sink(41.25%),astringent(37.50%),and number(21.25%).(2)Pathogenesis: Of all the cancer pain literature,The main pathogenesis frequency from high to low was qi stagnation and blood stasis(29.70%),obstruction of blood flow(18.18%),deficiency of kidney essence(15.15%),interaction of phlegm and blood stasis(14.55%),qi deficiency and blood stasis(7.88%),internal deficiency of positive qi(7.27%),obstruction of channels and collectorals(6.67%),invasion of evil poison(6.67%),deficiency of Yang qi(6).67%).The main disease of renal(41.46%),liver(30.89%),spleen(18.70%),meridian(15.45%),lung(13.01%).The main pathological factors were blood stasis(54.55%),qi stagnation(35.76%),blood stasis(21.82%),qi deficiency(21.21%),phlegm(21.21%),poison(15.15%),sperm deficiency(15.15%),Yang deficiency(13.33%),Yin deficiency(12.12%),positive deficiency(7.27%).(3)Prescription medication: Of all the cancer pain literature,Drugs in frequency in the top 10 list is yanhusuo(48.22%),licorice root(41.12%),angelica(39.59%),astragalus membranaceus(35.53%),radix paeoniae alba(30.96%),atractylodes(30.46%),radix bupleuri(28.93%)and rhizoma chuanxiong(28.93%),poria cocos(28.93%),the codonopsis pilosula(27.92%).The core drugs are peach kernel-safflower,Rhizoma corydalis-Aconitum,Rhizoma curcuma-three rims,Fructus aurantii-Radix platycodon,myrrh-frankincense,Wuling zhi-Puhuang,Bupleurum-Poncirus aurantii,Rhizoma corydalis-Chinadian seed,Atractylodes rhizoma-Codonopsis,Centipede-scorpion,Poria cotylodes rhizoma-Rhizoma corydalis-Rhizoma corydalis.Common drug combinations are: peach kernel,safflower,angelica;Angelica,radix paeoniae,Bupleurum;Angelica,peony root,licorice;Atractylodes macrocephala,Poria cocos and Astragalus membranaceus;Atractylodes macrocephala,Tangerine peel,Codonopsis pilosula;Tangerine peel,pinellia ternata,licorice;Myrrh,frankincense,corydalis;Angelica,safflower,peach kernel,chuanxiong;Angelica,radix paeoniae,Ligusticum chuanxiong and Rhizoma corydalis;Safflower,peony root,peach kernel,Bupleurum,chuanxiong;Angelica,safflower,red peony root,peach kernel,rhizoma corydalis,etc.,the compatibility of these core drugs can include the meridian prescription and the time prescription,including Xuefu Blood-stasis Soup,Peony and liquorice soup,peach red Siwu soup,Dixixia blood-stasis Soup,Chaihu shugan Powder,xiangsha Liujunzi Soup.3.Overall results of literature on bone metastasis cancer pain: A total of 434 literatures were collected,and 95 literatures related to bone metastasis cancer pain(including 95 prescriptions)were finally included after eliminating duplicate literatures and combining with literature inclusion criteria.Of all the bone metastatic cancer pain literature,The top 10 drugs in frequency were rehmannia glutinosa(47.37%),Psoraleae psoraleae(44.21%),Rhizoma corydalis(44.21%),Scorpion(36.84%),glycyrrhiza glycyrrhiza(34.74%),Angelica(33.68%),Astragalus membranaceus(32.63%),centipede(28.42%),rhizoma corydalis(27.37%),achyrantha bidentata(25.26%).Core drug pairs include: Nourishing Yin and tonifying kidney,ripe rehmannia glutinosa-Yam,ripe rehmannia glutinosa-Cornus officinalis,etc.Kidney tonifying and Yang strengthening psoraleae-bone broken butch,deer antler-white mustard seed;Dispelling wind and dampness and collaterals,gentiana gentiana,Gentiana gentiana,Peach seed gentiana gentiana;Promoting blood stasis and relieving pain safflower-peach kernel,Angelica-Chuanxiong,Angelica-safflower,Niugenus-Wuling Lipid,Angelica-Wuling lipid,etc.Invigorate qi,invigorate blood and relieve pain,such as Achyranthes bidentata and Peach kernel,etc.Scorpion-centipede,scorpion-earthworm,etc.;Spleen-invigorating qi class astragalus-Codonopsis pilosula.The most commonly used combinations of three herbs and four herbs were peach kernel,safflower,ligusticum chuanxiong,Angelica sinensis,licorice,Gentiana macrophylla,Rhizome Officinalis,Wuling fat and ripe ground.4.Overall results of cancer pain opioid-related constipation(OIC)literature,a total of 468 literatures were collected,and duplicate literatures were excluded.According to the literature inclusion criteria,78 OIC literatures(including 78 prescriptions)were included.The top 10 drugs in frequency were Aurantii Trifoliata(43.59%),Rehmanniae rehmanniae(42.31%),Radix scrophulariae(42.31%),Magnolia officinalis(38.46%),Hemp seed(38.46%),Radix Danggui(35.90%),Astragalus membranaceus(35.90%),Radix Maiopogonis(33.33%)and Atractylodes macrocephala(29.49%).OIC core drugs are rhubarb-mirabilite,rhubarb-Magnolia officinalis,Rhubarb-Immaturus aurantii,Immaturus aurantii-Magnolia officinalis and other components of large chengqi soup;Radix scrophulariae-Radix ophiopogonis,Radix rehmanniae-Radix scrophulariae soup components;Rhubarb-hemp seed,hemp seed-paeony,rhubarb-bitter almond,Magnolia officinalis-bitter almond and other components of pockseed pills;Areca-black medicine,rhubarb-areca,rhubarb-woody components of the six mill soup.OIC was treated with rhubarb,Magnolia officinalis,Immaturus aurantii,Mirabilite,radix scrophulariae,Radix ophiopogonis,rehmannia glutinosa,hemp seed,bitter almond and hemp seed with high frequency of combination.5.The active ingredients of Shentongzhuyu Decoction were searched by TCMSP and obtained 7 chuanxiong,2 Angelica,22 safflower,45 myrrh,20 achyranthes bidentata,92 licorice,15 Qianhuo,2 Gentiana macrophylla,27 peach kernel and 18 Rhizome.The repeated active ingredients were deleted and 127 were reserved.There were 6499 targets for bone metastasis cancer pain,and shentong Zhuyu Decoction and bone metastasis cancer pain had111 target proteins.A total of 111 nodes and 2408 edges,including 1 disease node and 10 drug nodes,were obtained in the compound target-disease network of Shentong Zhuyu Decoction for the treatment of bone metastatic cancer pain.By screening,The core active ingredients are Glycyrol,isorhamnetin,Inermine,Medicarpin,formononetin,Euchrenone and Sitostero Alcohol),hederagenin(osthole).A total of 129 GO items were obtained by GO bioenrichment analysis,and the main biological functions involved were protein linkage,gene transfer,etc.KEGG pathway enrichment analysis revealed a total of 132 pathways.They include PI3K-Akt signaling pathway,MAPK signaling pathway,age-rage signaling pathway in diabetic complications,TUMOR necrosis factor signaling pathway,IL-17 signaling pathway,p53 signaling pathway,NF-?B signaling pathway,Toll-like receptor signaling pathway,T cell receptor signaling pathway,etc.Conclusion:1.In the clinical treatment of cancer pain,prescription drugs can be selected according to the patient's constitution or the occurrence of boxy syndrome.Pain and see the liver depression and qi stagnation syndrome radix bupleuri optional class,and see Yang haemorrheological nature card can be used with subclasses,and see the gangrene of cold phlegm grinds to ephedra optional class,and see the disorder of blood deficiency,liver and spleen syndrome can choose guizhi class party,see and taste with the pinellia optional class,qi deficiency and see the astragalus optional class,and see the kidney Yin deficiency syndrome can choose cultivated land class party,Also see blood stasis syndrome can choose to be classified.And then according to the specific clinical manifestations of patients to choose the specific prescriptions in the class of prescriptions for treatment.Bupleurum can choose xuefu Zhuyu Decoction,Bupleurum shugan powder;Atractylodes aconite decoction and Aconite Peony and Liquorice Decoction can be used in the prescription.Ephedra can choose Yang and soup;Cassia branch can choose peony liquorice soup;Pinellia can choose xiangsha six gentleman soup;Astragalus can choose buyang also five soup;Ripe ground kind can choose liuwei rehmanniao pills;When classified in the side can choose body pain by blood stasis soup,diaphragm by blood stasis soup.2.Based on the comprehensive analysis of the literature on cancer pain including the information of four diagnoses,pathogenesis and prescription medication,it was found that the etiology of cancer pain was complex,with positive deficiency usually as the cause of the disease,and phlegm,blood stasis and poison as the standard of the disease.The common pathogenesis was the empirical "not general pain" and the "not glorious pain" of deficiency syndrome.In the early stage,the disease is mainly characterized by deficiency and reality,in the middle stage,the deficiency and reality are mixed,and in the late stage,the deficiency syndrome is mainly.The syndrome types mainly include liver and kidney Yin deficiency syndrome,Yang Ming syndrome,qi deficiency syndrome,blood stasis syndrome,Yang deficiency cold coagulation syndrome,Qi deficiency syndrome,blood deficiency syndrome,liver stagnation and qi stagnation syndrome.The lesion site is uncertain,often involving the viscera to the lung,spleen,liver,kidney and other four organs and meridians,early lung,spleen,liver,liver,late involved in the kidney;The main pathological factors were blood stasis,qi stagnation,phlegm obstruction,cold coagulation,cancer toxicity,qi deficiency,blood deficiency,Yang deficiency and Yin deficiency.In view of "not general pain",the treatment is based on qi and blood,and the method of regulating qi,promoting blood circulation and removing stasis is commonly used,as well as regulating liver and regulating qi,promoting blood circulation and removing stasis,clearing heat and detoxifying,invigorating spleen and changing dampness and dispersing cold and expectorating phlegm to remove evil;According to the different degrees of deficiency loss,there are "nourishing qi","nourishing blood","nourishing Yin","warming Yang".The first is nourishing qi,nourishing spleen and kidney,and nourishing liver and kidney.The general treatment is nothing more than "fuzheng" and "removing evil".Through the analysis of comprehensive drug use rules,the commonly used meridian and time prescriptions are summarized as Chaihu Shugan Powder,Xuefu Stasis Decoction,Taohong Siwu Decoction,Dixixia Stasis Decoction,Peony and liquorice Decoction,xiangsha Liujunzi Decoction,etc.3.The pain of bone metastasis cancer is mainly caused by blood stasis or individual with rheumatism,and pain caused by meridian obstruction.Peach Red Siwu Decoction and Body pain Zhuyu Decoction are often used to promote blood circulation,remove stasis,dispel wind and dehumidify to achieve the purpose of xuanbi and pain relief.Summarized the shu Di type and when categorizing the prescription,bone metastasis cancer pain combined with kidney Yin deficiency syndrome can be used for shu Di type,combined with blood stasis syndrome can be used for when categorizing the prescription,shu Di type can be used for Liuwei Dihuang pill,when categorizing can be used for body pain zhuyu decoction.4.OIC patients with Yang Ming Fu can be used under the big chengqi decoction hot constipation,hot stomach for the spleen about constipation,sesame seed pills can be used to moisten the intestine heat purging,qi purging,constipation can be added liquid soup water row,moisten the intestines.5.Based on network pharmacology,it was concluded that the main active ingredients in Shentong Zhuyu Decoction for preventing and treating bone metastasis cancer pain were glycyrrhizin,isorhamnetin,indolamine,medipteranthin,formononetin,parvone,sitosterol,osthole,etc.Mainly involved in protein linkage and gene transfer and other biological functions.KEGG pathway enrichment analysis revealed a total of 132 pathways.They include PI3K-Akt signaling pathway,MAPK signaling pathway,age-rage signaling pathway in diabetic complications,TUMOR necrosis factor signaling pathway,IL-17 signaling pathway,p53 signaling pathway,NF-?B signaling pathway,Toll-like receptor signaling pathway,T cell receptor signaling pathway,etc. |
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