Study On Prescriptions Of Professor Mao Dewen In Treating Hepatitis B Cirrhosis Based On Data Mining Technology

Objective: Based on the clinical medical records of Professor Mao Dewen in the treatment of hepatitis B cirrhosis,using data mining technology,to analyze and summarize the prescription rules of his treatment of hepatitis B cirrhosis,in order to better inherit the clinical experience of famous doctors,in order to learn.Methods: A total of 153 outpatient cases of hepatitis B cirrhosis treated by Professor Mao Dewen were included,and the gender and age of the included cases were statistically analyzed.To evaluate liver function(ALB,AST,ALT,TBIL)and liver stiffness in patients who regularly visit the clinic and regularly take traditional Chinese medicine for 3 months and more.Hepatitis B cirrhosis was divided into compensated stage of hepatitis B cirrhosis and decompensated stage of hepatitis B cirrhosis.SPSS Modeler 18 software was used to mine the drug association rules of each drug by Aprior modeling,and the drug co-occurrence network relationship diagram,core drug pair,and keratinocyte were obtained.SPSS 26 was used to analyze each drug by systematic clustering analysis,and Pearson correlation algorithm in binary categorical variable data in systematic clustering method was used to obtain representative prescriptions of each drug.Result:(1)A total of 153 cases of hepatitis B cirrhosis and 691 visits were collected in this study.There were 100 patients with compensated hepatitis B cirrhosis and 53 patients with decompensated hepatitis B cirrhosis.Of the 691 visits,424 were for compensated hepatitis B cirrhosis and 267 were for decompensated hepatitis B cirrhosis.The majority of the patients were aged40-59 years,with a total of 81 patients,accounting for about 52.94%cumulatively.Of the 153 patients,34(22%)were female and 119(78%)were male,with a male to female ratio of 3.5:1.(2)In patients with hepatitis B cirrhosis who regularly took traditional Chinese medicine for 3 months and more,ALB was increased in 88% of patients,the restitution rate of ALT was 65%,the restitution rate of AST was66%,the restitution rate of TBIL was 47%,and LSM was decreased in 61%of patients.ALB in liver function indicators increased compared with that before treatment(P < 0.05),ALT,AST and TBIL decreased compared with those before treatment(P < 0.05),LSM also decreased compared with that before treatment(P < 0.05),and the differences had statistical significance.(3)Among the 691 encounter records,TCM diagnosis accumulation,hypochondriac pain,jaundice,bloating were included.The TCM diagnosis of compensated hepatitis B cirrhosis was jaundice,accumulation,and hypochondriac pain,with the highest frequency of accumulation,281 times,accounting for 66.27%,followed by hypochondriac pain and jaundice,with frequencies of 88 times and 55 times,accounting for 20.76% and 12.97%,respectively.The TCM diagnosis of decompensated hepatitis B cirrhosis was accumulation,hypochondriac pain,jaundice,and bloating,with the highest frequency of bloating,137 times,accounting for 51.31%,followed by jaundice,accumulation,and hypochondriac pain,with frequencies of 60 times,36 times,and 34 times,accounting for 22.47%,13.48%,and 12.73%,respectively.In the compensatory stage of hepatitis B cirrhosis,the highest frequency was liver depression and spleen deficiency syndrome,127 times,accounting for 29.95%,followed by damp-heat accumulation syndrome 119 times,accounting for 28.06%,blood stasis syndrome frequency 108 times,accounting for 25.47%,liver and kidney yin deficiency syndrome frequency40 times,accounting for 9.43%,spleen and kidney yang deficiency frequency21 times,accounting for 4.95%,water dampness stagnation syndrome frequency 9 times,accounting for 2.12%.In the decompensated stage of hepatitis B cirrhosis,the most frequent was water dampness stagnation syndrome,86 times,accounting for 32.21%,followed by liver-kidney yin deficiency syndrome,68 times,accounting for 25.47%,damp-heat accumulation syndrome,62 times,accounting for 23.22%,blood stasis syndrome,30 times,accounting for 11.24%,spleen and kidney yang deficiency syndrome,17 times,accounting for 6.37%,and liver depression and spleen deficiency syndrome,4 times,accounting for 1.50%.(4)Recipe rule of compensatory stage of hepatitis B cirrhosis : The high-frequency drugs of liver depression and spleen deficiency syndrome are Bupleurum chinense,Atractylodes macrocephala,Glycyrrhiza uralensis,Codonopsis pilosula,Pinellia ternata,Citrus sinensis,Zhishi,Hawthorn,Malt,and Huoxiang.The core drug pairs are Radix Bupleuri with Radix Paeoniae Alba,Amomum villosum with Rhizoma Atractylodis Macrocephalae,Acorus calamus with Fructus Aurantii Immaturus,Rhizoma Pinelliae with Citrus,Radix Notoginseng with Radix Salviae Miltiorrhizae Keratin drugs are Corydalis yanhusuo,Bupleurum chinense with Radix Paeoniae Alba,Cyperus rotundus,Chen Pi with Atractylodes macrocephala,Ji Nei Jin,Hawthorn with Zhishi,Zizyphus jujuba,Codonopsis pilosula with Chen Pi,Codonopsis pilosula,Zhishi with Pinellia ternate,Acorus calamus The main TCM prescriptions are Xiaoyao San,Qiweibaizhu San combined with Sini San,Chaishao Liujunzi Decoction,and Jianpi Pills.There are a total of 7therapeutic principles involved,and the frequencies from high to low are soothing the liver and regulating qi,nourishing blood and invigorating the spleen,and generating fluid in the stomach,soothing the liver and invigorating the spleen,invigorating the spleen and eliminating food,promoting blood circulation to remove blood stasis,and supplementing qi and invigorating the spleen.The high-frequency drugs of damp-heat accumulation syndrome are Zhuru,Chen Pi,Zhishi,Glycyrrhiza uralensis,Jujube,Malt,Corydalis yanhusuo,Salvia miltiorrhiza,Poria cocos,and Zizyphus jujuba.Core drug pairs are Tongcao with plantain,Scutellaria with Yinchen,Pinellia with tangerine peel and so on.Horn medicine has Magnolia officinalis,Atractylodes lancea with clam,Muxiang,Chen Pi with Zhuru,Pinellia ternata,Chen Pi with Coptis chinensis,Zhuru,Zhishi with Coptis chinensis,Scutellaria baicalensis,Yinchen with Forsythia suspensa.The main prescriptions of dampness-heat accumulation syndrome are Huanglian Wendan Decoction,Ganluxiaodan,and Pingwei Powder.There are a total of 6therapeutic principles,and the frequencies from high to low are clearing away heat and dampness,regulating qi and reducing phlegm,dissipating turbidity and detoxicating,clearing away heat and toxic substances,regulating qi and stomach,and removing dampness and nourishing the spleen.High frequency drugs in blood stasis syndrome are Salvia miltiorrhiza,Angelica sinensis,Taoren,Panax notoginseng,Corydalis yanhusuo,Bupleurum chinense,Cyperus rotundus,Astragalus membranaceus,Poria cocos,and Sophora flavescens.Core drug pairs are safflower with Cyperus rotundus,leonurus with Wulingzhi,Guizhi with Astragalus membranaceus and so on.Keratin drugs are safflower,cyperus with yanhusuo,leonurus,angelica with peach kernel,asarum,guizhi with paeony root,earthworm,cannon shell with wulingzhi,oyster,curcuma with salvia miltiorrhiza,seaweed,cyperus with bupleurum.The main prescriptions are Huaganci Decoction,Gexia Zhuyu Decoction,Huangqi Guizhi Wuwu Decoction,and Shaofu Zhuyu Decoction.There are a total of 6 therapeutic principles,and the frequencies from high to low are promoting blood circulation to remove blood stasis,softening and hardening,performing qi to relieve pain,and blood to arthralgia,benefiting temperature meridians,and warming meridians to relieve pain.(5)Rule of syndrome differentiation and treatment of decompensated hepatitis B cirrhosis:High frequency drugs in water dampness stagnation syndrome are Dazhu bark,Alisma orientalis,Plantago asiatica,Fangji,Astragalus membranaceus,Atractylodes macrocephala,malt,licorice,Panax notoginseng,and Zhishi.The core medicine pair has storage with plantain,Alisma with Dazhu skin,Astragalus with Atractylodes macrocephala,Achyranthes bidentata and so on.Keratin medicine has storage,talc with rhubarb,Morus alba,Dazhu peel with ginger peel,Morus alba,Poria cocos peel with Dazhu peel,Poria cocos,Achyranthes bidentata with yam,cardamom,Zhuru with Huoxiang,leonurus,platycodon with Dazhu peel.The main prescriptions were Fangji Huangqi Decoction combined with Wuling Powder,Bazheng Powder,and Wupi Yinhe Weiling Decoction.There are a total of five therapeutic principles involved,and the frequencies from high to low are water subsidence,warming yang and dissipating qi,clearing away heat and purging fire,promoting qi and water,and stomach dampness.The high-frequency drugs for liver-kidney yin deficiency syndrome are Gorgon fruit,Cornus officinalis,Astragalus membranaceus,Bai Zi Ren,Yam,Atractylodes macrocephala,Citrus sinensis,Ophiopogon japonicus,Scrophularia sinensis,and Citrus aurantium.Core medicine pairs are Achyranthes bidentata with Cornus officinalis,Yam with Gorgon fruit,Asparagus with Ophiopogon japonicus,Artemisia annua with turtle and so on.Keratin drugs are Artemisia annua,turtle with Yinchaihu,chrysanthemum,neem with wolfberry,angelica,hemp kernel with astragalus,Rehmannia glutinosa,Achyranthes bidentata with cornus officinalis,Achyranthes bidentata,yam with gorgon fruit,Radix Ginseng,Radix Ophiopogonis with neem.The main prescriptions are Huishen Shaping Decoction,Yiguan Decoction,and Artemisia annua Biejia Decoction.There are 4 treatment principles,from high to low frequency is to nourish the liver and kidney,invigorate the spleen and nourish yin,nourish yin and soothe the the liver,nourish yin and diathermy.The high-frequency drugs in the damp-heat accumulation syndrome are Artemisia capillaris,Coptis chinensis,Zhuru,Poria cocos,Zhishi,Citrus sinensis,Pinellia ternata,Jujube,Malt,and Glycyrrhiza uralensis.The core drugs are Huoxiang with talc,Qu Mai with gardenia,Chen Pi with Zhishi,hawthorn with six Shen Qu and so on.Keratins are plantain,storage with Qumai,Pinellia ternata,Coptis chinensis with Zhishi,Forsythia suspensa,Scutellaria baicalensis with Yinchen,Huoxiang,Yinchen with talc,Alisma orientalis,Akebia with Poria cocos,Chen Pi,Zhuru with Pinellia ternata.The main prescriptions are Huanglian Wendan Decoction,Ganluxiaodan Siling Powder,and Yinchenhao Decoction Bazheng Powder.There are a total of 6therapeutic principles,and the frequencies from high to low are clearing away heat and dampness,regulating qi and reducing phlegm,clearing away heat and water,clearing away heat and toxic substances,removing dampness and yellowing,and clearing away heat and purging fire.(6)Representative prescriptions of compensated stage of hepatitis B cirrhosis: Liver depression and spleen deficiency syndrome was obtained by cluster analysis to obtain two representative prescriptions,one corner drug and two drug pairs.Among them,prescription 1 consisted of Radix Bupleuri,Rhizoma Pinelliae,Radix Glycyrrhizae,Radix Paeoniae Alba,Radix Salviae Miltiorrhizae,Poria cocos,and Radix Notoginseng.Prescription 2 consisted of Acorus calamus,Mint,Zhishi,Hawthorn,Codonopsis pilosula,and Amomum villosum.Formulation 3 consisted of malt,astragalus,and zizyphus seed.The two medicinal pairs are Radix Pseudostellariae and Radix Atractylodis Macrocephalae,Pericarpium Citri Reticulatae and Rhizoma Atractylodis Macrocephalae.Four representative prescriptions,two herbs,were obtained by cluster analysis for dampness-heat accumulation syndrome.Prescription 1 consisted of Scutellaria baicalensis,Akebia,Talc,Forsythia suspensa,Huoxiang,Mint,Acorus calamus,and Artemisia capillaris.Prescription 2 consisted of Prunella vulgaris,Pseudostellaria heterophylla,Atractylodes lancea,Salvia miltiorrhiza,and Zizyphus jujuba.Formulation 3 consisted of Corydalis yanhusuo,Atractylodes lanceolata,Panax notoginseng,and Radix Angelicae Dahuricae.Prescription 4 consists of Zhishi,Zhuru,Huanglian,Dazao,Poria cocos,Pinellia ternata,Malt,Glycyrrhiza uralensis,and Citrus sinensis.The two herbs are Astragalus membranaceus and Coix seed.Two representative prescriptions and one drug pair were obtained by cluster analysis for blood stasis blocking complex syndrome.Prescription 1consisted of Angelica sinensis,Semen Persicae,Wulingzhi,Cannon Shanjia,Eupolyphaga sinensis,Rhizoma Atractylodis Macrocephalae,Radix Salviae Miltiorrhizae,Poria cocos,Radix Bupleuri,and Rhizoma Corydalis.Prescription 2 consisted of Rhizoma Polygonati,Phyllanthus urinaria,Radix Sophorae Flavescentis,Radix Notoginseng,Rhizoma Curcumae,Seaweed,Biejia,Oyster,Laminaria japonica,and Rhizoma Cyperi.The drug pair consists of Astragalus membranaceus and Cinnamomum cassia.(7)Representative prescriptions for decompensated hepatitis B cirrhosis:Four representative prescriptions and one corner drug were obtained by cluster analysis for water dampness stagnation syndrome.Prescription 1consisted of Polyporus umbellatus,Poria cocos,Alisma orientalis,Fangji,Astragalus membranaceus,and Atractylodes macrocephala Koidz.Prescription 2 consisted of Huoxiang,Yinchen,Zhishi,and Poria cocos.Prescription 3 consisted of malt,notoginseng,plantain,Akebia,and Zhuru.Prescription 4 consisted of Glycyrrhiza uralensis,Citrus sinensis,Platycodon grandiflorum,and Cinnamomum cassia.Keratin consists of Achyranthes bidentata,Yam,and Dazhu skin.Three representative prescriptions were obtained by cluster analysis for liver-kidney yin deficiency syndrome.Prescription 1 consists of Cornus officinalis,Gorgon fruit,Cypress seed kernel,Scrophularia sinensis,Yam,Gentian,and Rhodiola rosea.Prescription 2 consisted of Rehmannia glutinosa,Poria cocos,Atractylodes macrocephala,and Ophiopogon japonicus.Prescription 3 consisted of Citrus sinensis,Corydalis yanhusuo,Citrus aurantium,Hemp seed,Astragalus membranaceus,Lycium barbarum,Angelica sinensis,and Rehmannia glutinosa.Dampness-heat accumulation syndrome obtained two representative prescriptions and one drug pair by cluster analysis.Prescription 1 consisted of Pinellia ternata,Coptis chinensis,Glycyrrhiza uralensis,Jujube,Poria cocos,Malt,Zhishi,Citrus sinensis,Salvia miltiorrhiza,Coix seed,Acorus calamus,and Atractylodes macrocephala.Prescription 2 consisted of Gardenia jasminoides,Dazhu peel,Rheum officinale,Alisma orientalis,Poria cocos,Talc,Akebia,and Artemisia capillaris.The medicinal pair consists of Zhuru and Panax notoginseng.Conclusion:(1)The age of onset of hepatitis B cirrhosis is mainly between 40 and 59 years,with the majority of males.(2)In patients with hepatitis B cirrhosis who regularly took traditional Chinese medicine for 3 months and more,ALB was increased in 88% of patients,the restitution rate of ALT was 65%,the restitution rate of AST was66%,the restitution rate of TBIL was 47%,and LSM was decreased in 61%of patients.(3)Professor Mao Dewen’s core drugs for the treatment of liver depression and spleen deficiency syndrome in the compensatory stage of hepatitis B cirrhosis are Radix Bupleuri with Radix Paeoniae Alba,Amomum villosum with cloth skin,Codonopsis pilosula with Rhizoma Atractylodis Macrocephalae,etc.;keratins are Rhizoma Corydalis,Radix Bupleuri with Radix Paeoniae Alba,Rhizoma Cyperi,Fructus Chen with Rhizoma Atractylodis Macrocephalae,Ji Nei Jin,Fructus Crataegi with Fructus Aurantii The core drug pairs of damp-heat accumulation syndrome are Tongcao with Plantago asiatica,Scutellaria baicalensis with Yinchen,Pinellia ternata with Chen Peel,etc.;horn drugs are Magnolia officinalis,Atractylodes lancea with Chen Peel,Muxiang,Chen Peel with Zhuru,Pinellia ternata,Chen Peel with Coptis chinensis,Zhuru,Zhishi with Coptis chinensis,Scutellaria baicalensis,Yinchen with Forsythia suspensa The core drugs of blood stasis blocking syndrome are safflower with Cyperus rotundus,leonurus with Wulingzhi,Guizhi with Astragalus membranaceus and so on.Keratin drugs are safflower,cyperus with yanhusuo,leonurus,angelica with peach kernel,asarum,guizhi with paeony root,earthworm,cannon shell with wulingzhi,oyster,curcuma with salvia miltiorrhiza,seaweed,cyperus with bupleurum.The core drugs of water dampness stagnation syndrome in decompensated stage of hepatitis B cirrhosis are storage with plantain,Alisma orientalis with Dazhu peel,Astragalus membranaceus with Atractylodes macrocephala,Achyranthes bidentata with Achyranthes bidentata,etc.The core drug pairs of liver-kidney yin deficiency syndrome are Achyranthes bidentata with Cornus officinalis,Yam with Gorgon fruit,Asparagus officinalis with Ophiopogon japonicus,Artemisia annua with turtle and so on.Keratin drugs are Artemisia annua,turtle with Yinchaihu,chrysanthemum,neem with wolfberry,angelica,hemp kernel with astragalus,Rehmannia glutinosa,Achyranthes bidentata with cornus officinalis,Achyranthes bidentata,yam with gorgon fruit,Radix Ginseng,Radix Ophiopogonis with neem.The core drugs of damp-heat accumulation syndrome are Huoxiang with talc,Qu Mai with gardenia,Chen Pi with Zhishi,hawthorn with six Shen Qu and so on.Keratins are plantain,storage with Qumai,Pinellia ternata,Coptis chinensis with Zhishi,Forsythia suspensa,Scutellaria baicalensis with Yinchen,Huoxiang,Yinchen with talc,Alisma orientalis,Akebia with Poria cocos,Chen Pi,Zhuru with Pinellia ternata.Professor Mao Devon applied different treatments according to different methods.The treatment of liver depression and spleen deficiency syndrome in compensatory stage of hepatitis B cirrhosis is mainly to soothe the liver and regulate qi,nourish blood and invigorate the spleen,and the treatment of damp-heat accumulation syndrome is mainly to clear away heat and dampness,regulate qi and remove phlegm,and the treatment of blood stasis blocking collateral syndrome is mainly to promote blood circulation and remove blood stasis,and dissipate soft and firm mass.The treatment of water dampness stagnation syndrome in decompensated stage of hepatitis B cirrhosis is mainly to benefit water and detumescence,warm yang and dissipate qi,the treatment of liver-kidney yin deficiency syndrome is mainly to nourish liver and kidney,invigorate spleen and nourish yin,and the treatment of damp-heat accumulation syndrome is mainly to clear away heat and dampness,regulate qi and remove phlegm,and clear away heat and water.(4)The representative prescriptions of liver depression and spleen deficiency syndrome in compensated stage of hepatitis B cirrhosis are the similar prescriptions of Chaishao Liujunzi Decoction and Jianpi Pills,respectively.The representative prescriptions of damp-heat accumulation syndrome were the prescriptions of Ganluxiaodan and Huanglian Wendan Decoction,respectively;the other two prescriptions were composed of Prunella vulgaris,Pseudostellaria heterophylla,Atractylodes lancea,Salvia miltiorrhiza,and Zizyphus jujuba and Corydalis yanhusuo,Muxiang,Panax notoginseng,and Radix Angelicae dahuricae.The representative prescriptions of blood stasis blocking collateral syndrome are the prescriptions of Gexia Zhuyu Decoction and Huagan Jianfang.The representative prescriptions of water dampness stagnation syndrome in decompensated hepatitis B cirrhosis were those of Fangji Huangqi Decoction combined with Wuling Powder and those of Bazheng Powder;the other two prescriptions were composed of Huoxiang,Yinchen,Zhishi,and Poria cocos and licorice,clam,platycodon grandiflorum,and Guizhi,respectively.The representative prescriptions of liver-kidney yin deficiency syndrome are Huishen Zhengsheng Decoction and Yiguan Decoction,respectively,and the other prescription consists of Rehmannia glutinosa,Poria cocos,Atractylodes macrocephala,and Ophiopogon japonicus.The representative prescriptions of dampness-heat accumulation syndrome are those of Huanglian Wendan Decoction and Yinchenhao Decoction combined with Bazheng Powder.In this study,the syndrome of dampness-heat accumulation in TCM accounted for the majority in both compensated and decompensated hepatitis B cirrhosis,which was consistent with the etiology and etiology of hepatitis B cirrhosis.Because Guangxi is located in subtropical coastal areas,with many rainwater,high environmental humidity and easy to gather the evil of damp-heat,the syndrome of damp-heat accumulation is common.