| Purpose:By searching,collecting and collating the literature on the treatment of pancreatic cancer by Jingfang and Shifang from the three self-established databases of China National Knowledge Network,Weipu Database and Wanfang Database,and collecting and collating the medical records on the treatment of pancreatic cancer from the cloud platform of ancient and modern medical records,this study studied the prescription rules of Jingfang and Shifang for the treatment of abdominal pain and jaundice symptoms of pancreatic cancer.Data mining technology was used to analyze and summarize the drug use of traditional Chinese medicine in the treatment of pancreatic cancer abdominal pain and the prevention and treatment of pancreatic cancer.Cox regression analysis was used to investigate the independent risk factors affecting the death of intermediate and advanced pancreatic cancer.The mechanism of Yinchenhao decoction in the treatment of pancreatic cancer-jaundice was investigated by network pharmacology and molecular docking methods,which provided evidence for clinical use and experimental research.Material and method:1.Search the literature related to the treatment of intermediate and advanced pancreatic cancer with traditional prescriptions and time prescriptions published from the self-built database until August 2022 from China National Knowledge Network,VIP database and Wanwang database,and search with the keyword "pancreatic cancer and traditional Chinese medicine or traditional Chinese medicine or prescriptions",and collect the medical records for the treatment of pancreatic cancer from the cloud platform of ancient and modern medical records.After strict screening and exclusion,all documents that meet the screening criteria are input into EXCEL tables to establish a literature database.To summarize and analyze the prescription rules of Jingfang and Shi Fang in treating pancreatic cancer with abdominal pain and jaundice as the main disease.2.Collect TCM prescriptions from the literature on the treatment of pancreatic cancer abdominal pain by the prescription and the prescription of the time,collect medical reports on the treatment of pancreatic cancer abdominal pain as the main disease from the cloud platform of ancient and modern medical records,establish prescription database,and use data mining technology to process the data.Excel,SPSS statistics25.0 and SPSS modeler 18.0 software were used to organize the high-frequency drugs in the prescription,analyze the commonly used pairs of drugs and Angle drugs,analyze the frequency of four qi and five flavors,and analyze the high-frequency drugs cluster.3.Literature on prevention and treatment of pancreatic cancer recurrence with traditional Chinese medicine published from the establishment of the database to August 2022 was retrieved from China National Knowledge Network,VIP database and Wanfang Database,and medical records of prevention and treatment of pancreatic cancer recurrence with traditional Chinese medicine were collected from the cloud platform of ancient and modern medical records.Extract TCM prescription from literature and medical records,establish prescription database,use data mining technology to process data,use Excel,SPSS statistics25.0,SPSS modeler 18.0 software to carry out high-frequency drug sorting of prescription drugs,analyze commonly used drug pair and Angle drugs,The frequency analysis of four qi and five tastes,and the clustering analysis of high frequency drugs.4.Death records of pancreatic cancer patients from the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 2017 to March 2022 and the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 2013 to March 2022 were collected.Basic information of patients was collected,including age,gender,smoking history,drinking history,site of disease,TCM syndrome type,admission kps score and diabetes history.The accompanying symptoms were collected whether there was cancer pain,jaundice,ascites,liver metastasis,lymph node metastasis,vascular invasion,multiple metastasis;In terms of treatment,factors such as operation,chemotherapy,radiotherapy,immunotherapy,targeted therapy,intervention time of oral Chinese medicine,and use of intravenous Chinese patent medicine were comprehensively summarized and analyzed.Data of pancreatic cancer patients was input into EXCEL to establish a database.SPSS statistics25.0 and SPSS PRO were used for data processing and analysis.Univariate analysis was performed by Kaplan-Meier method and survival curves of the two groups were compared by Log-rank method.Cox proportional risk regression model was used to analyze the death of patients with pancreatic cancer by multiple factors,and the independent factors affecting the death of patients were determined comprehensively.5.Chemical components of Yinchenao decoction and related targets of pancreatic cancerjaundice disease were obtained through TCM System Pharmacology database(TCMSP)and Gene database(Genecard),and the Venn diagram of drug-pancreatic cancer-jaundice disease was drawn to determine their common targets.Cytoscape 3.8.2 software was used to establish the visual relationship diagram of active components of Yinchenhao Decoction,pancreatic cancer and jaundice disease.At the same time,the STRING database is used to construct the PPI network.GO and KEGG were enriched for related targets using R x64 4.0.5 software,so as to further understand the possible mechanism of action and the corresponding pathway of Yinchenhao decoction in the treatment of pancreatic cancer and jaundice.Molecular docking technology was used to analyze the binding ability of key targets of active components in Yinchenhao Decoction by SYBYL2.0 software.Results:1.A total of 58 literatures on the treatment of intermediate-advanced pancreatic cancer with meridian prescription and temporal prescription were included,40 of which were mainly abdominal pain,including 15 literatures involving meridian prescription(including 6 with combined prescription),14 literatures involving temporal prescription and 11 self-designed prescriptions,involving 489 cases.The results showed that the symptoms of abdominal pain improved obviously.The effective rate of the treatment group was 52.63% ～ 100%,and that of the control group was 35.0% ～ 80%.The earliest onset time of pain was 2 days.In 5 literatures,pancreatic cancer abdominal pain was treated with prolonged survival,and in 4 literatures,pancreatic cancer abdominal pain was treated with CT without enlargement or disappearance,without abnormalities.The KPS score and TCM symptom score of the treatment group were higher than those of the control group.In the literature,the prescription for pancreatic cancer abdominal pain can be obtained after the removal of prescription,including small bupleurum decoction,large bupleurum decoction,Sini powder,Wumei Wan,Banxia Xiexin decoction,small depression chest decoction,Guizhi Jiagui soup,poria coia Guizhi Licorice and date soup,and the time prescription includes Sijunzi decoction,Liujunzi decoction,bupleurum Shugan powder,Zuojin Wan,Xuefu Zhuyu decoction,and lifting powder.There were 18 literatures on the treatment of icterus as the main symptom of advanced pancreatic cancer with meridian prescription and temporal prescription,including12 literatures on meridian prescription,2 literatures on combination of meridian prescription and temporal prescription,and 4 literatures on self-designed prescription.A total of 339 cases were involved.The results showed that the jaundice disappeared or was alleviated.The effective rate of the treatment group was 40%-90.9%,and that of the control group was 20%-82.4%.In the literature,there were Yinchenhao Decoction,Yinchen Wuling Powder,Xiaobupleurum decoction,Dabupleurum decoction,Shifang Bupleurum Shugan Powder,Yinchen Jiangfu Decoction,Huanglian Jiedu Decoction,Sijunzi Decoction and Liujunzi decoction for the treatment of pancreatic cancer jaundice.2.In the literature on the treatment of pancreatic cancer abdominal pain by Jingfang and Shi Fang,the high-frequency drugs were mainly deficiency tonifying drugs,heat-clearing drugs and blood-activating drugs,and the core drugs were atractylodes atractylodes,poria cocos,Hedyshyotis vulgaris,paeoniae paeoniae and bupleurum bupleurum.Drug properties to bitter,xin,sweet drug mainly,four characteristics to warm most.The core drug pairs obtained by association analysis were white Rhizoma atractylodes and Tangerine peel,Hedyotis alba and corydalis corydalis,hedyotis alba and schistodes alba.The core horn drugs were poria codonopsis and Rhizoma atractylodes,Rhizoma atractylodes and Rhizoma atractylodes,Rhizoma corydalis and chinaberry seed and Rhizoma atractylodes.High-frequency drug cluster analysis was divided into four categories.The first category was atractyloides,poria cocos,tangerine peel,malt,Radix japonica,hawthorn and radix pseudostellariae.The second category for August,Coix seed,white flower hyoglossia,Schistoderma,Yu Jin;The third category was Rhizoma curcuma,Astragalus,Angelica sinensis,Coptis Rhizoma,dried ginger,codonopsis codonopsis and Paeony.The fourth species were rhizoma corydalis,Chinadrach seed,Radix paeoniae,bupleurum,Scutellaria,rhubarb,Fructus aurantii and salviorrhiza.3.After searching,714 literatures reported the studies on the treatment of postoperative recurrence of pancreatic cancer with traditional Chinese medicine,and 50 literatures were finally included for analysis based on the nanol standard.In the prevention and treatment of pancreatic cancer recurrence after operation,sweet and warm drugs were mainly used,and deficiency and heat clearing drugs were the main drugs.The use times of poria were the most,accounting for 62% of the whole prescription.The second was atractylodes,accounting for50% of the total prescriptions.According to the correlation analysis,the commonly used drugs were poria cocos and Atractylodes,poria cocos and codonopsis cocos,bupleurum bupleurum and Fructus aurantii,poria cocos and Fructus aurantii,poria cocos and atractylodes.The commonly used drugs for horn were atractylodes cocos and radix astragalus and atractylodes,poria cocos and atractylodes pinellia and atractylodes.Cluster analysis can be divided into 9 categories,among which the drug composition of more than 5 flavors for the first category: Shanci mushroom,hydoglossia officinalis,Schistoderma semilaria,Rhizoma coix,augusto,Coix seed,the second category: yam,Dendrobium dendrobium,Coptis chinensis,Shenqu,Radix amariae,Radix pseudostellariae,the third category: poria cocos,atractylodes,codonopsis codonopsis,Hawthorn,Astragalus,Curcuma curcuma,malt,the fourth category: Rhubarb,Fructus aurantii,Bupleurum,pinellia pinellia,Scutellaria scutellaria,Centipede.4.In this study,73 patients died of pancreatic cancer.In this study,the overall median survival time(m OS)of pancreatic cancer patients was 4 months,and the cumulative survival rates at 6 months,1 year and 2 years were 32.9%,11% and 2.7%,respectively.Univariate analysis showed that smoking history,admission KPS score,cancer pain,liver metastasis,surgery,chemotherapy and duration of TCM intervention were important factors affecting the death of pancreatic cancer.However,gender,age,drinking history,site of disease,previous history of diabetes,jaundice,ascites,lymph node metastasis,vascular invasion,multiple metastasis,radiotherapy,immunotherapy,TCM syndromes and TCM injection were not factors affecting the death of pancreatic cancer.By COX regression model analysis,cancer pain was found to be an independent prognostic risk factor for pancreatic cancer.Surgical treatment,chemotherapy treatment and Chinese medicine intervention time are independent protective factors for pancreatic cancer prognosis.5.A total of 40 active ingredients of Yinchenhao decoction could be retrieved through TCMSP database,all of which were in line with oral bioavailability(OB)≥30% and druglike drug(DL)≥0.18.The 40 active ingredients are divided into: There were 11 active ingredients in the drugs of Artemisia,13 active ingredients in the drugs of gardenia and 14 active ingredients in the drugs of rhubarb.quercetin was the common active ingredient of Artemisia and gardenia,and beta-sitosterol was the common active ingredient of Artemisia,gardenia and rhubarb.A total of 181 intersections were found between active components of Yinchenhao Decoction and targets related to pancreatic cancer and jaundice.The key target proteins of Yinchenhao decoction in the treatment of pancreatic cancer and jaundice are AKT1,TP53,VEGFA,IL6,etc.Through GO functional enrichment analysis,these genes were mainly involved in cell proliferation regulation,negative regulation of apoptosis,oxidative stress response,inflammatory response,signal transduction pathway,lipid metabolism and other biological processes.According to statistics,the total number reached2601,including 2303 biological processes(BP),2303 cell composition(CC)and 216 molecular functions(MF).After enrichment analysis of KEGG pathway,173 pathways were found to have influence on the target.The biological signaling pathways involved in the study include IL-17,PI3K-Akt,TNF and MAPK,etc.,which play an important role in biological functions.The key genes in the core target were selected for molecular docking with the first10 active components with high degree values,among which 8 active components were successfully docking with the target.Conclusion:1.Through the analysis and induction of the included literature,the main prescriptions for the treatment of pancreatic cancer abdominal pain include bupleurum,pinellia,cassia,Coptis,Junzi and other prescriptions.The main prescription for the treatment of jaundice of middle and late pancreatic cancer are rhubarb prescription,bupleurum prescription,coptis prescription and junzi prescription.2.According to the analysis of medication rules of TCM dispensing prescription,the highfrequency drugs,the antithesis drugs and the Angle drugs used by Jingfang and Shi Fang in the treatment of abdominal pain of middle and advanced pancreatic cancer are mainly deficiency tonifying drugs,heat clearing drugs and blood circulation and blood stasis removing drugs.The medicinal properties are mainly bitter drugs,and the four qi drugs are warm drugs most frequently used.Cluster analysis can be divided into four categories: the first type of drugs based on Sijunzi Decoction,the second type of anti-cancer drugs for clearing heat and antidosing,the third type of drugs for promoting blood circulation and removing blood stasis and replenishing qi and nourishing blood,and the fourth type of drugs based on Dacaihu decoction.In the middle and late stage of pancreatic cancer,the deficiency of healthy qi and the local condition are the pathogenesis.3.Poria tuckaia was the most frequently used high-frequency drugs in the prevention and treatment of postoperative pancreatic cancer recurrence,while the high-frequency drugs,antipyretic drugs and horn drugs were mainly deficiency tonifying drugs,heat clearing drugs and digestion drugs.Among the five flavors,Gan was the most frequently used drug,and the four qi was the most frequently used drug.In cluster analysis,there are four categories of traditional Chinese medicine consisting of more than 5 flavors.The first category is mainly composed of commonly used anti-tumor traditional Chinese medicine combined with heatclearing and detoxifying drugs to prevent and cure postoperative cancer recurrence and metastasis.The second category of tonifying drugs with clearing heat and drying dampness,dampness and qi,used to treat pancreatic cancer after the operation of physical weakness,loss of healthy qi;The third category is Sijunzi decoction plus or less medication,tonifying drugs with Xiaoshi and spleen drugs,preventing and controlling the spleen and stomach caused by tonifying drugs,Xiaoshi and spleen,care for the spleen and stomach.The fourth category of big bupleurum decoction plus or minus medication,for clearing heat and purging fire,anticancer and detoxification.4.The death of patients with pancreatic cancer is jointly affected by smoking history,admission KPS score,cancer pain,liver metastasis,surgery,chemotherapy and duration of intervention of traditional Chinese medicine.Cancer pain is an independent risk factor for prognosis of pancreatic cancer,and patients with cancer pain have a higher risk of death than those without cancer pain.In the treatment of pancreatic cancer,surgery and chemotherapy can reduce the risk of death of patients,and the risk of death can be reduced when the duration of TCM intervention is more than 4 months.5.Through the network pharmacology and molecular docking study,it was found that the active ingredients in Yinchenhao decoction could combine well with the core target.The core targets of Heyin Chenhao decoction are AKT1,TP53,VEGFA,etc.IL-17 signaling pathway,PI3K-Akt signaling pathway and TNF signaling pathway are the key action pathways of Yinchenao Decoction in the treatment of pancreatic cancer-jaundice,and the active components are quercetin,kaempferol,β-sitosterol,etc.In this study,the composition,target and mechanism of Yinchenhao decoction in the treatment of pancreatic cancer-jaundice were preliminarily discussed,which provided theoretical basis for future experimental research. |
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