Construction method for individualized traditional Chinese medicine intelligent prescription evaluation model, medicine evaluation method, processor and electronic equipment or device

Abstract

The invention relates to the field of traditional Chinese medicine, in particular to a construction method for an individualized traditional Chinese medicine intelligent prescription evaluation model, a medicine evaluation method, a processor and electronic equipment or device. The curative effect of different traditional Chinese medicine combinations on the patient is evaluated by reversing the degree of a peripheral blood mononuclear cell imbalance pathway of the patient through the traditional Chinese medicine combinations. According to the method, the traditional Chinese medicine composition is evaluated in a targeted manner or a personalized intelligent formula is prepared on the basis of the signal path enrichment condition of the peripheral blood mononuclear cells of the patient in the current disease state. According to different disease states of patients, targeted existing traditional Chinese medicine compositions are dynamically screened in real time or new effective prescriptions are intelligently designed. According to the method, a quantification method is adopted, and real-time and dynamic composition and evaluation of the traditional Chinese medicine or the composition are achieved according to the disease state of a patient.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and in particular to a method for constructing an individualized intelligent traditional Chinese medicine prescription evaluation model, a drug evaluation method, a processor, an electronic device or a device. Background Art

[0002] Traditional Chinese medicine prescriptions are mostly based on observation, auscultation, questioning, and treatment, combined with the pharmacology and properties of Chinese medicine, to combine Chinese medicines together. Such a combination of Chinese medicines is only based on thousands of years of human experience, and its scientific compatibility is difficult to explain and its efficacy is difficult to predict. Various physiological and biochemical reactions in cells are completed by a series of proteins that perform different physiological and biochemical functions. Signal pathways refer to a series of biological reaction pathways that can transmit extracellular molecular signals through the cell membrane into cells to exert their effects. Each signal pathway includes different proteins, representing a certain biological process, which is a concept higher than genes. By improving the disordered signal pathways of the body in the disease state, it is helpful to improve the disease state and achieve the purpose of treatment. Therefore, it is necessary to establish scientific, rapid and effective Chinese medicine prescription screening, evaluation and improvement methods, as well as scientific prescription guidance methods based on modern science and technology for specific diseases and TCM syndromes.

[0003] At present, Chinese medicine prescriptions are based on TCM syndrome differentiation and treatment, the pharmacology and medicinal properties of Chinese medicine, and are guided by classical prescriptions. They are empirical sciences and lack scientific guidance. The efficacy of different Chinese medicine prescriptions is difficult to quantitatively evaluate. This makes it difficult to provide personalized and targeted guidance on Chinese medicine prescriptions for specific patients and the progress and treatment of specific diseases.

[0004] Therefore, it is of great practical significance to provide a method for constructing an individualized intelligent Chinese medicine prescription evaluation model and its application, as well as an evaluation method for individualized intelligent Chinese medicine prescriptions. Summary of the invention

[0005] In view of this, this patent obtains the disordered pathways related to the disease of a single patient by real-time and dynamic collection of peripheral blood mononuclear cells (PBMC) of the patient, and obtains the transcriptome data of the patient under the disease state. Based on the relevant signal pathways, individualized precision scientific prescriptions are developed.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] In a first aspect, the present invention provides a method for constructing an individualized intelligent Chinese medicine prescription evaluation model, comprising the following steps:

[0008] Step 1: Obtain transcriptome data of peripheral blood mononuclear cells of patients;

[0009] Step 2: Obtain normal human peripheral blood mononuclear cell transcriptome data;

[0010] Step 3: Comparative analysis of the patient's peripheral blood mononuclear cell transcriptome data with the normal person's peripheral blood mononuclear cell transcriptome data; Gene Set Enrichment Analysis (GSEA) based on gene set enrichment analysis to obtain the normalized enrichment score (NES) of the specific disordered pathway in the patient's peripheral blood mononuclear cells, that is, the patient's signal pathway NES of the specific signal pathway, and the positive or negative value of NES represents the direction of the patient's signal pathway;

[0011] Select signaling pathways that are significantly enriched in all or part of the patient's peripheral blood mononuclear cells as the patient's dysregulated pathways;

[0012] Step 4: Build a disease cell model;

[0013] Step 5: Obtain transcriptome data of the signaling pathway effect of the cell model after the Chinese medicine to be evaluated is applied;

[0014] Obtain transcriptome data of the cell model of the Chinese medicine to be evaluated;

[0015] Obtain transcriptome data of the control group cell model;

[0016] By comparing the transcriptome data of the cell model after the Chinese medicine to be evaluated acts on the cell model with the transcriptome data of the control group cell model, GSEA is used to perform enrichment analysis of the signal pathway to obtain the NES of the Chinese medicine to be evaluated on the specific pathway, that is, the drug signal pathway NES of the specific signal pathway, and the positive or negative value of NES represents the direction of the drug signal pathway;

[0017] Step 6: Calculate the intensity of action, regulation direction and reverse regulation ratio of a single drug;

[0018] For a specific abnormal signal pathway, when the direction of the drug signal pathway of the Chinese medicine to be evaluated is opposite to that of the patient's signal pathway, it means that the Chinese medicine to be evaluated can reverse or inhibit the abnormality of this signal pathway, and is marked as a reversal pathway; when the direction of the drug signal pathway of the Chinese medicine to be evaluated is the same as that of the patient's signal pathway, it means that the Chinese medicine to be evaluated can enhance or upregulate the abnormality of this signal pathway of the patient, and is marked as an enhancement pathway;

[0019] For single Chinese medicine: for the disordered pathway set described in step 3, calculate the effect strength of single Chinese medicine (marked as drug effect enrichment score): drug effect enrichment score = the sum of drug effect enrichment scores of single medicine on all patient signal pathways; the positive or negative value of drug effect enrichment score indicates the regulation direction of single Chinese medicine on the disordered pathway set;

[0020] Calculate the pathway disorder ratio (reversal rate) of a single Chinese medicine, reversal rate = number of reversed pathways / number of disordered pathways in patients, and obtain the reverse regulation ratio;

[0021] Step 7: Calculate the effect intensity, regulation direction and reverse regulation ratio of the Chinese medicine composition;

[0022] For a specific abnormal signal pathway, the drug signal pathway NES of all single drugs in the Chinese medicine composition to be evaluated are added together to serve as the drug signal pathway NES of the Chinese medicine composition to be evaluated on the specific abnormal signal pathway;

[0023] For a specific abnormal signal pathway, when the direction of the drug signal pathway of the Chinese medicine composition to be evaluated is opposite to that of the patient's signal pathway, it means that the Chinese medicine composition to be evaluated can reverse or inhibit the abnormality of this signal pathway, which is marked as a reversal pathway, and the pharmacodynamic enrichment of the Chinese medicine composition on this pathway is divided into |NES|; when the direction of the drug signal pathway of the Chinese medicine composition to be evaluated is the same as that of the patient's signal pathway, it means that the Chinese medicine composition to be evaluated can enhance or upregulate the abnormality of this signal pathway of the patient, which is marked as an enhancement pathway, and the pharmacodynamic enrichment of the Chinese medicine composition on this pathway is divided into -|NES|;

[0024] For the Chinese medicine composition: for the disordered pathway set described in step 3, calculate the effect strength of the Chinese medicine composition (marked as the drug effect enrichment score): drug effect enrichment score = the sum of the drug effect enrichment scores of all single drugs of the Chinese medicine composition on all patient signal pathways; the positive or negative value of the drug effect enrichment score indicates the regulation direction of the Chinese medicine composition on the disordered pathway set;

[0025] The pathway disorder ratio (reversal rate) of the Chinese medicine composition was calculated, and the reversal rate = the number of reversed pathways / the number of disordered pathways in the patient, and the reverse regulation ratio was obtained.

[0026] In some specific embodiments of the present invention, the method for obtaining the transcriptome data of peripheral blood mononuclear cells of patients in step 1 is: real-time and dynamic collection of peripheral blood mononuclear cells of patients, extraction of total RNA of peripheral blood mononuclear cells, construction of transcriptome sequencing library, and high-throughput sequencing;

[0027] The method for obtaining normal human peripheral blood mononuclear cell transcriptome data described in step 2 is: collecting peripheral blood mononuclear cells from normal healthy people, extracting total RNA of peripheral blood mononuclear cells, constructing a transcriptome sequencing library, and performing high-throughput sequencing.

[0028] In some specific embodiments of the present invention, the method for obtaining the transcriptome data after the single drug or Chinese medicine composition to be evaluated acts on the cell model in step 5 is: taking the extract of the single drug or Chinese medicine composition to be evaluated to treat the disease cell model, extracting total RNA, constructing a transcriptome sequencing library, and performing high-throughput sequencing;

[0029] The method for obtaining the transcriptome data of the control group cell model in step 5 is: taking the solvent of the extract of the Chinese medicine to be evaluated as the control group to treat the disease cell model, extracting total RNA, constructing a transcriptome sequencing library, and performing high-throughput sequencing.

[0030] In some specific embodiments of the present invention, in steps 6-7, for a specific abnormal signal pathway, when the drug signal pathway NES of the single drug or Chinese medicine composition to be evaluated is in opposite directions to the patient's signal pathway NES, that is, the direction of the drug signal pathway is opposite to that of the patient's signal pathway, it indicates that the single drug or Chinese medicine composition to be evaluated can reverse or inhibit the abnormality of this signal pathway in the patient; when the drug signal pathway NES of the Chinese medicine to be evaluated is in the same direction as the patient's signal pathway NES, that is, the direction of the drug signal pathway is the same as that of the patient's signal pathway, it indicates that the single drug or Chinese medicine composition can enhance or up-regulate the abnormality of this signal pathway in the patient.

[0031] In some specific embodiments of the present invention, in steps 6-7, the proportion (reversal rate) of pathway disorders of the single drug or Chinese medicine combination to be evaluated, reversal rate = number of reversed pathways / number of disordered pathways in the patient*100%.

[0032] In some specific embodiments of the present invention, in steps 6-7, the proportion (reversal rate) of pathway disorders of the single drug or Chinese medicine combination to be evaluated, reversal rate = number of reversed pathways / number of disordered pathways in the patient*100%.

[0033] In some specific embodiments of the present invention, the standardized enrichment score of the Chinese medicine composition is the sum of the standardized enrichment scores of the single Chinese medicines to be evaluated on the disordered pathway.

[0034] For single Chinese medicine: for the disordered pathway set described in step 3, calculate the effect strength of the single Chinese medicine (marked as the drug effect enrichment score): drug effect enrichment score = the sum of the drug effect enrichment scores of the single medicine on all pathways; the positive or negative value of the drug effect enrichment score indicates the regulation direction of the single Chinese medicine on the disordered pathway set;

[0035] For the Chinese medicine composition: for the disordered pathway set described in step 3, calculate the effect strength of the Chinese medicine composition (marked as the drug effect enrichment score): drug effect enrichment score = the sum of the drug effect enrichment scores of all single drugs in the Chinese medicine composition on all pathways; the positive or negative value of the drug effect enrichment score indicates the regulation direction of the Chinese medicine composition on the disordered pathway set;

[0036] In some specific embodiments of the present invention, the disease suffered by the patient includes but is not limited to cancer, acute disease or chronic disease;

[0037] Preferably, the cancer includes but is not limited to lung cancer;

[0038] Preferably, the acute disease includes but is not limited to infectious diseases; more preferably, the acute disease includes novel coronavirus infection;

[0039] Preferably, the chronic disease includes but is not limited to chronic obstructive pulmonary disease;

[0040] Preferably, the disease involves the nervous system, digestive system, circulatory system, respiratory system, urogenital system, skeletal muscle system, blood system, endocrine system, skin or appendages;

[0041] Preferably, the disease includes but is not limited to metabolic diseases or rheumatic diseases.

[0042] In a second aspect, the present invention also provides an evaluation method for individualized intelligent Chinese medicine prescriptions, based on the evaluation model constructed by the construction method, the Chinese medicine to be tested that reverses the disordered pathway is selected to obtain a Chinese medicine composition.

[0043] In a third aspect, the present invention further provides a processor, wherein the processor is used to run a program, and the program executes the construction method or the evaluation method when running.

[0044] In a fourth aspect, the present invention further provides an electronic device or apparatus, the electronic device comprising: a memory and the processor;

[0045] Wherein, one or more computer programs are stored in the memory, and the one or more computer programs include instructions; when the instructions are executed by the processor, the electronic device executes the construction method or the evaluation method;

[0046] The device includes one or more components, and the one or more components implement the construction method or the evaluation method.

[0047] In a fifth aspect, the present invention also provides a Chinese medicine composition for treating lung cancer, comprising the following components in parts by weight:

[0048]

[0049]

[0050] In some specific embodiments of the present invention, the Chinese medicine composition includes 9g of Rhizoma Cyrthospermi, 15g of Polygonum cuspidatum, 10g of Perilla leaf, 30g of Astragalus, 12g of Ophiopogon japonicus, 12g of Ganoderma lucidum, 9g of donkey-hide gelatin, 6g of Licorice, 15g of White Peony Root, 10g of Bupleurum Root, 12g of Albizzia Julibrissin, 10g of Charred Areca Nut, 9g of Ginger, 6g of Schisandra chinensis, 10g of Lotus Leaf, 10g of Schizonepeta Spike, 10g of Bombyx Batryticatus, 10g of Angelica dahurica, 10g of Eucommia ulmoides, and 10g of Polygala tenuifolia.

[0051] The beneficial effects of the present invention include but are not limited to:

[0052] (1) This patent provides a method for dynamically screening effective Chinese medicine or Chinese medicine combination and designing new effective prescriptions in real time based on peripheral blood mononuclear cell transcriptome data for different disease states of patients. This method overcomes the shortcomings of the traditional prescription based on observation, auscultation, questioning and palpation, and syndrome differentiation and treatment, which is difficult to scientifically explain the compatibility and predict the efficacy. It is a method for screening and evaluating Chinese medicine and Chinese medicine prescriptions dynamically and in real time for the patient himself.

[0053] (2) This patent provides the evaluation of traditional Chinese medicine and traditional Chinese medicine combination and the combination of traditional Chinese medicine formula based on multiple cell models and from different angles of the disease, making the evaluation and formula more comprehensive and systematic.

[0054] (3) Traditional Chinese medicine and Chinese medicine compositions for reversing specific abnormal signaling pathways in patients with lung cancer.

[0055] (4) This patent also provides a spectrum of abnormal signal pathways related to lung cancer patients, which is used to evaluate and scientifically formulate prescriptions for lung cancer patients.

[0056] (5) This patent provides Chinese medicine and Chinese medicine composition for reversing specific abnormal signal pathways in lung cancer patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0057] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art are briefly introduced below.

[0058] Figure 1 Shows changes in the pathways of disordered signals after treatment of patients;

[0059] Figure 2 Show the inhibitory effect of the prescription on tumor cells A549. DETAILED DESCRIPTION

[0060] The present invention discloses a method for constructing an individualized intelligent Chinese medicine prescription evaluation model, a drug evaluation method, a processor, an electronic device or a device. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters for implementation. It is particularly important to point out that all similar substitutions and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The methods and applications of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0061] The traditional prescription based on observation, auscultation, questioning and palpation, and syndrome differentiation and treatment is difficult to explain scientifically and predict the efficacy. Therefore, it is necessary to establish a scientific, rapid and effective Chinese medicine prescription screening, evaluation and improvement method, as well as a scientific prescription guidance method based on modern science and technology for specific diseases and TCM syndromes.

[0062] It is difficult to provide personalized and targeted guidance on the formulation of traditional Chinese medicine for specific patients and the progress and treatment of specific diseases. This patent obtains transcriptome data of patients in disease states by real-time and dynamic collection of peripheral blood mononuclear cells of patients, and obtains disordered pathways related to the disease. Based on the relevant signal pathways, scientific formulation is carried out.

[0063] This patent provides a method for formulating and evaluating prescriptions based on the patient's real-time, dynamically changing signal pathways.

[0064] This patent obtains the disease-related disorder pathways of a single patient by real-time and dynamic collection of peripheral blood mononuclear cells of patients to obtain transcriptome data under the disease state. Based on the relevant signal pathways, individualized precision scientific prescriptions are developed.

[0065] The main steps include:

[0066] (1) Real-time and dynamic collection of peripheral blood mononuclear cells from patients, extraction of total RNA from peripheral blood mononuclear cells, construction of transcriptome sequencing library, and high-throughput sequencing to obtain transcriptional data of peripheral blood mononuclear cells from patients. One or more biological replicates can be constructed for each patient at the same time.

[0067] (2) Peripheral blood mononuclear cells were collected from normal healthy people, and total RNA of peripheral blood mononuclear cells was extracted. Transcriptome sequencing library was constructed and high-throughput sequencing was performed to obtain transcriptome data of normal human peripheral blood mononuclear cells.

[0068] (3) Through comparative analysis of the transcriptome data of peripheral blood mononuclear cells of patients and normal people, the gene set enrichment analysis method (GSEA) was used to perform signal pathway enrichment analysis to obtain the normalized enrichment score (NES) of the specific dysregulated pathway in the peripheral blood mononuclear cells of patients, that is, the patient signal pathway NES of the specific signal pathway. The positive and negative values ​​of NES represent the direction of the patient's signal pathway.

[0069] All or part of the significantly enriched signaling pathways can be selected as patient-specific disease-related dysregulated pathways.

[0070] (4) Treating disease cell models with Chinese medicine extracts to obtain transcriptome data of cell models after Chinese medicine treatment, and based on the solvent control treatment group, obtaining differential gene expression profiles of specific cell models treated with Chinese medicine extracts, and obtaining a list of differentially regulated genes that are significantly upregulated or downregulated;

[0071] (5) GSEA is used to perform enrichment analysis of the signal pathway to obtain the NES of the Chinese medicine to be tested on the disordered pathway, that is, the drug signal pathway NES of the specific signal pathway, and the positive and negative of the NES represent the direction of the drug signal pathway. The signal pathway can be a gene pathway included in the KEGG (Kyoto Encyclopedia of Genes and Genomes) Kyoto Gene and Genome Encyclopedia Database, Reactome Signal Pathway Database (https: / / reactome.org / ), DAVID Database, Gene Ontology (GeneOntology), Wikipathways, Biocarta Database, or a custom disease-related signal pathway.

[0072] For a specific abnormal signal pathway, when the direction of the drug signal pathway of the Chinese medicine to be evaluated is opposite to the direction of the patient's signal pathway, it means that the Chinese medicine to be evaluated can reverse or inhibit the abnormality of this signal pathway, and is marked as a reversal pathway; when the direction of the drug signal pathway of the Chinese medicine to be evaluated is the same as the direction of the patient's signal pathway, it means that the Chinese medicine to be evaluated can enhance or upregulate the abnormality of this signal pathway of the patient, and is marked as an enhancement pathway.

[0073] (6) Calculate the intensity of action, regulation direction and reverse regulation ratio of a single drug. For a specific abnormal signal pathway, when the direction of the drug signal pathway of the Chinese medicine to be evaluated is opposite to that of the patient's signal pathway, it means that the Chinese medicine to be evaluated can reverse or inhibit the abnormality of this signal pathway, and is marked as a reversal pathway; when the direction of the drug signal pathway of the Chinese medicine to be evaluated is the same as that of the patient's signal pathway, it means that the Chinese medicine to be evaluated can enhance or upregulate the abnormality of this signal pathway of the patient, and is marked as an enhancement pathway.

[0074] For single Chinese medicine: for the disordered pathway set described in step 3, calculate the effect strength of the single Chinese medicine (marked as the drug effect enrichment score): drug effect enrichment score = the sum of the drug effect enrichment scores of the single medicine on all pathways; the positive or negative value of the drug effect enrichment score indicates the regulation direction of the single Chinese medicine on the disordered pathway set;

[0075] The pathway disorder ratio (reversal rate) of a single Chinese medicine was calculated, and the reversal rate = the number of reversed pathways / the number of disordered pathways in the patient, to obtain the reverse regulation ratio.

[0076] (7) Calculate the effect intensity, regulation direction and reverse regulation ratio of the Chinese medicine composition. For a specific abnormal signal pathway, the drug signal pathway NES of all single drugs in the Chinese medicine composition are added together to obtain the drug signal pathway NES of the Chinese medicine composition on the specific abnormal signal pathway.

[0077] For a specific abnormal signal pathway, when the direction of the drug signal pathway of the Chinese medicine composition to be evaluated is opposite to the direction of the patient's signal pathway, it means that the Chinese medicine composition to be evaluated can reverse or inhibit the abnormality of this signal pathway, and is marked as a reversal pathway; when the direction of the drug signal pathway of the Chinese medicine composition to be evaluated is the same as the direction of the patient's signal pathway, it means that the Chinese medicine composition to be evaluated can enhance or upregulate the abnormality of this signal pathway of the patient, and is marked as an enhancement pathway.

[0078] For the Chinese medicine composition: for the disordered pathway set described in step 3, calculate the effect strength of the Chinese medicine composition (marked as the drug effect enrichment score): drug effect enrichment score = the sum of the drug effect enrichment scores of all single drugs in the Chinese medicine composition on all pathways; the positive or negative value of the drug effect enrichment score indicates the regulation direction of the Chinese medicine composition on the disordered pathway set;

[0079] The pathway disorder ratio (reversal rate) of the Chinese medicine composition was calculated, and the reversal rate = the number of reversed pathways / the number of disordered pathways in the patient, and the reverse regulation ratio was obtained.

[0080] (8) The Chinese medicine to be tested that can reverse the disordered pathway can be arbitrarily selected to obtain a Chinese medicine composition.

[0081] The gene set enrichment analysis uses GSEA to perform enrichment analysis of signal pathways to obtain the disorder of each Chinese medicine in each pathway. In some specific embodiments of the present invention, the disease can be cancer (such as lung cancer), acute disease (such as infectious disease, new coronavirus infection), or chronic disease (such as chronic obstructive pulmonary disease); the disease can involve the nervous system, digestive system (, circulatory system, respiratory system, urogenital system, skeletal muscle system, blood system, endocrine system, skin and appendages, metabolic disease, rheumatic disease.

[0082] The efficacy of different Chinese medicine combinations on patients is evaluated by the degree to which the Chinese medicine combination reverses the disordered pathways of the patient's peripheral blood mononuclear cells. The present invention specifically evaluates Chinese medicine compositions or conducts personalized prescriptions based on the enrichment of signal pathways in peripheral blood mononuclear cells of the patient's current disease state. This method dynamically screens targeted existing Chinese medicine compositions or intelligently designs new effective prescriptions for different disease states of patients in real time. The present invention adopts a quantitative method to achieve real-time and dynamic prescription and evaluation of Chinese medicine or compositions for the patient's disease state.

[0083] This patent obtains transcriptome data of patients in disease state by real-time and dynamic collection of peripheral blood mononuclear cells of patients, and compares with peripheral blood mononuclear cell transcriptome data of normal healthy people to obtain standardized enrichment scores of disease-related disordered pathways and related pathways. Based on the related signal pathways, prescription evaluation and scientific prescription formulation are carried out.

[0084] (1) This patent provides a method for obtaining the patient's disease signal pathway in real time through the patient's peripheral blood mononuclear cells, which can display the patient's abnormal signal pathway in real time.

[0085] (2) This patent provides a method for dynamically designing and evaluating new effective prescriptions in real time for different disease states of individual patients based on the transcriptome data of peripheral blood mononuclear cells of patients. This method overcomes the shortcomings of the traditional prescription method that relies on observation, auscultation, questioning, and palpation, and syndrome differentiation and treatment, which is difficult to scientifically explain the compatibility and predict the efficacy of the medicine.

[0086] (3) The signal pathway can be a gene pathway included in the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome signal pathway database (https: / / reactome.org / ), DAVID database, Gene Ontology, Wikipathways, and biocarta database, or it can be a custom disease-related signal pathway.

[0087] (4) Traditional Chinese medicine and Chinese medicine compositions for reversing abnormal signaling pathways specific to lung cancer patients.

[0088] (5) This patent also provides a spectrum of abnormal signal pathways related to lung cancer patients, which is used to evaluate and scientifically formulate prescriptions for lung cancer patients.

[0089] (6) This patent provides Chinese medicine and Chinese medicine composition for reversing abnormal signal pathways specific to lung cancer patients.

[0090] (7) This patent provides a Chinese medicine formula for treating lung cancer, characterized in that the formula is composed of Rhizoma Cynomorii, Polygonum cuspidatum, Perilla leaf, Astragalus, Ophiopogon japonicus, Ganoderma lucidum, donkey-hide gelatin, Licorice, White Peony Root, Bupleurum Root, Albizzia Julibrissin Bark, Scorched Areca Nut, Ginger, Schisandra chinensis, Lotus Leaf, Nepeta Tenuifolia Spike, Bombyx Batryticatus, Angelica dahurica, Eucommia ulmoides, and Polygala tenuifolia.

[0091] In the method for constructing an individualized intelligent Chinese medicine prescription evaluation model, the drug evaluation method, the processor, the electronic device or the apparatus provided by the present invention, the raw materials, reagents and components used can all be purchased from the market.

[0092] The present invention will be further described below in conjunction with embodiments:

[0093] Example 1: Real-time and dynamic acquisition of disordered pathways in peripheral blood mononuclear cells of patients

[0094] 1. Total RNA extraction from peripheral blood mononuclear cells of patients or normal subjects

[0095] 1) Pipette lymphocyte separation solution into a centrifuge tube for later use. Invert the blood sample to mix well, and then slowly add it to the upper layer of lymphocyte separation solution. Centrifuge at 25℃±5℃, 400×g for 20min to separate the peripheral blood mononuclear cells. Gently collect the peripheral blood mononuclear cell layer in the middle of the lymphocyte separation solution, place it in a centrifuge tube, and then add PBS to wash the cells once.

[0096] 2) Add TRIZOL cell lysis buffer, mix well by pipetting until there is no obvious precipitation, and transfer the lysate to a new centrifuge tube. Let stand at 25℃±5℃ for 5 minutes to ensure sufficient lysis. Add 0.2mL chloroform to 1mL of peripheral blood mononuclear cell lysis buffer, mix well, and let stand at 25℃±5℃ for 3 minutes. Centrifuge at 12000rpm at 4℃ for 15 minutes.

[0097] 3) Pipette the supernatant into another new centrifuge tube, add 0.5 mL of isopropanol, mix well, place at -20°C for 30 min, and centrifuge at 12,000 rpm for 15 min at 4°C.

[0098] 4) Discard the supernatant carefully, add 1 mL of 75% ethanol, and wash once. Dry naturally in a clean bench for 20 minutes. Add UltraPure Distilled Water (DNase / RNase Free) to dissolve RNA until the precipitate disappears completely.

[0099] 2. Construction of RNA transcriptome library of peripheral blood mononuclear cells from patients or normal subjects

[0100] 1) Mix 4uL RNA sample, 0.7uL 10×PCR Buffer II (without MgCl2), 0.25uL 25mM Mgcl2, 0.3uL 10% NP40, 0.25uL 0.1M DTT, 0.2uL SUPERase-In (20U / μL), 0.2uL RNase inhibitor (40U / μL), 0.25uL 0.5μM UP1 Primer and 0.15uL dNTP mix (2.5mM each), react at 70℃ for 90s, and quickly place on ice;

[0101] 2) Add 0.6uL of M-MLV (200U / uL), 0.2uL of RNase inhibitor (40U / uL) and 0.2uL of Nuclease-free water to the above reaction. Mix by hand, centrifuge at 2500g for 30S and place on ice. React at 42℃ for 60min; inactivate at 70℃ for 15min; centrifuge at 7500g for 30S at 4℃ and quickly place on ice for 1min.

[0102] 3) Add 1.0uL of ExoSAP-IT to the First strand cDNA product from the previous step; after manual flicking to mix, centrifuge at 2500g for 30S and place on ice. React at 37℃ for 30min; inactivate at 80℃ for 15min; centrifuge at 7500g for 30S at 4℃ and quickly place on ice for 1min;

[0103] 4) Add 0.8uL of 10×PCR buffer II (without Mgcl2), 0.5uL of 25MmMgcl2, 0.25uL of 100MmdATP, 5.55uL of Nuclease-free water, 0.5uL of Terminaltransferase (15U / uL) and 0.4uL of Ambio TMRNaseH (10U / uL) to the reaction solution in the previous step. After manual flicking to mix, centrifuge at 2500g for 30s and place on ice. Then react at 37℃ for 15min; inactivate the reaction at 70℃ for 10min; centrifuge at 7500g for 30S at 4℃ and quickly place on ice for 1min.

[0104] 5) Add 1.5uL of UP2 Primer (25μM) and 17.5uL of KAPA HiFiHot Start Ready Mix (2×), mix by hand, centrifuge at 2500g for 30s, and place on ice. React at 95℃ for 3min, 50℃ for 2min, and 72℃ for 10min; quickly place on ice for 1min, centrifuge at 7500g for 30s at 4℃, and quickly place on ice for 1min;

[0105] 6) After the above reaction is completed, put it on ice immediately, add 2.0μL of UP1 primer (25μM) to the tube, mix well and continue PCR reaction. The PCR program is 95℃ reaction for 3min, 12 cycles: 95℃ heating for 30s, 67℃ annealing for 1min, 72℃ extension for 6min, and finally keep at 4℃. After the reaction is completed, centrifuge at 2000rpm for 1min at 4℃ and quickly put it on ice for 1min. Freeze at -80℃ or purify with magnetic beads.

[0106] 7) The above products were constructed using the Tn5 library construction method and sequenced.

[0107] 3. Patient disorder pathway acquisition

[0108] By comparing the transcriptome data of peripheral blood mononuclear cells of patients with those of normal people, the gene expression change fold analysis was performed, and the expression change fold of genes was obtained by using the DEseq2 method. Gene set enrichment analysis (GSEA) was used to perform enrichment analysis of signal pathways to obtain disease state signal pathways. At the same time, the standardized enrichment scores of the disordered pathways and related pathways related to the patient's disease were obtained. NES is positive, indicating that the gene set of the Chinese medicine is enriched at the top of the gene (high expression value), and NES is negative, indicating that the gene set is enriched at the bottom of the gene (low expression value). All or part of the significantly enriched signal pathways can be selected as patient-specific disease-related disordered pathways.

[0109] This example is for a lung cancer patient with systemic metastasis and shortness of breath, activity disorder, anemia, poor appetite, bone metastasis cancer pain, insomnia, venous thrombosis, and occult blood. The patient's first peripheral blood mononuclear cell transcriptome data screened the KEGG-listed dysregulated pathways; after the patient was treated, the patient's peripheral blood mononuclear cells were extracted again, and the transcriptome data were sequenced, and the pathway changes were analyzed for the first dysregulated pathway.

[0110] Example 2: Transcriptome data and signal pathway analysis of cell models after treatment with the Chinese medicine to be evaluated

[0111] (1) Treatment of human non-small cell lung cancer A549 cells with Chinese herbal extracts

[0112] The single medicine includes Corydalis cyrtomium, Polygonum cuspidatum, Perilla leaf, Astragalus, Ophiopogon japonicus, Ganoderma lucidum, donkey-hide gelatin, Licorice, White Peony Root, Bupleurum, Albizzia bark, Charcoal Areca, Ginger, Schisandra, Lotus Leaf, Nepeta Spike, Bombyx Batryticatus, Angelica dahurica, Eucommia ulmoides, Polygala tenuifolia, etc. The above-mentioned medicinal materials are water-extracted by ultrasound and Soxhlet method, and freeze-dried powder is prepared by freeze dryer. The extract mother solution is prepared by weighing an appropriate amount of freeze-dried powder and dissolving it in PBS at a concentration of 50 mg / mL. During the logarithmic growth phase of A549 cells, a cell culture bottle is taken from the incubator, pancreatin is added to the culture bottle, and the entire cell surface is gently covered with pancreatin, and the cell is placed in the incubator for digestion until the cells partially float, and complete medium is added to terminate digestion, and the culture medium is blown with a Pasteur pipette to make the cells fall off, centrifuge, discard the supernatant, add culture medium to gently blow and mix the cells, and count with a cell counting plate. For suspended cells, when the logarithmic growth phase is reached, after centrifugation to collect the cells, the culture medium is added to gently blow and mix the cells, and count with a cell counting plate. A549 was seeded in a 384-well plate at a seeding density of 3000 / well. After overnight attachment, 200ug / mL of drug was added for treatment for 24h.

[0113] (2) Treatment of THP1 cells with Chinese herbal medicine extracts

[0114] THP1 was inoculated in a 384-well plate at a density of 8000 / well in RPMI1640 complete medium containing 100 ng / mL PMA. After directional induction for 24-48 hours, the cells were treated with 200 μg / mL of the drug extract for 24 hours.

[0115] (3) Transcriptome sequencing and pathway analysis

[0116] The lysis, reverse transcription and amplification of drug screening cells were carried out according to the instructions for use of the relevant kits. The samples were sequenced on the machine using Illumina HiSeq X10, and 2Mreads were measured for each sample, and the data off the machine were analyzed. Gene set enrichment analysis (GSEA) was used to perform enrichment analysis of signal pathways (FDR<0.25, the pathway was considered to be significantly regulated). The standardized enrichment score of each Chinese medicine in the significantly enriched pathway was obtained. A positive NES indicates that the gene set of the Chinese medicine is enriched at the top of the gene (high expression value), and a negative NES indicates that the gene set is enriched at the bottom of the gene (low expression value).

[0117] Example 3: Prescription and prescription evaluation based on the dysregulated pathway of peripheral blood mononuclear cells in lung cancer patients

[0118] (1) Obtain the dysregulated pathways of peripheral blood mononuclear cells of patients according to the method of Example 1. As described in Example 1, a total of 17 dysregulated pathways were selected based on the transcriptome data of peripheral blood mononuclear cells of lung cancer patients in this example. The detailed pathways and the corresponding NES are shown in the following table: As shown in Table 1.

[0119] Table 1

[0120]

[0121]

[0122] (2) Pathways after Chinese medicine treatment of cell models

[0123] The transcriptome data and signal pathways of the cell model treated with the Chinese medicine to be evaluated were obtained according to the method of Example 2. The NES of the 17 dysregulated pathways of lung cancer patients described in Example 1 in two cell models, A549 cells and THP1 cells, were obtained.

[0124] (3) Prescription composition and evaluation based on disordered pathways

[0125] For a specific abnormal signaling pathway, when the NES of a single drug is in the opposite direction to the NES of a patient, it means that the single drug can reverse (or inhibit) the abnormality of this signaling pathway in the patient, and the pharmacodynamic enrichment of the single drug on this pathway is divided into |NES|. When the NES value of a single drug is in the same direction as the NES value of a patient, it means that the single drug can enhance (or upregulate) the abnormality of this signaling pathway in the patient, and the pharmacodynamic enrichment of the single drug on this pathway is divided into -|NES|.

[0126] The NES value of a Chinese medicine combination on a certain pathway = the sum of the NES values ​​of each single herb on the pathway. For example, if Chinese medicine combination X contains three Chinese medicines, namely Chinese medicine 1, Chinese medicine 2, and Chinese medicine 3, then the NES value of Chinese medicine combination X on pathway 1 = the NES value of Chinese medicine 1 + the NES value of Chinese medicine 2 + the NES value of Chinese medicine 3. Similar to single drugs, when the NES value of the Chinese medicine combination is in the opposite direction to the NES value of the patient, it means that the Chinese medicine combination can reverse (or inhibit) the abnormality of this signaling pathway of the patient, and the pharmacodynamic enrichment score of the Chinese medicine combination on this pathway is |NES|. When the NES value of the Chinese medicine combination is in the same direction as the NES value of the patient, it means that the Chinese medicine combination can enhance (or upregulate) the abnormality of this signaling pathway of the patient, and the pharmacodynamic enrichment score of the Chinese medicine combination on this pathway is -|NES|. (4) For patient-specific disease-related disordered pathways, calculate the standardized enrichment score and disordered pathway reversal rate of single or Chinese medicine combination. The reversal rate of a single herb is the number of signal pathways reversed (or inhibited) in the patient / the number of signal pathways in the patient*100%. The pharmacodynamic enrichment score of a Chinese medicine composition on a specific pathway is the sum of the pharmacodynamic enrichment scores of all single herbs. The pharmacodynamic enrichment score of a Chinese medicine composition is the sum of the pharmacodynamic enrichment scores of all pathways;

[0127] (5) Chinese medicine combination: For the signal pathway of the patient's first blood sampling, calculate the reversal rate and efficacy enrichment score of A549 cells and / or THP1 of all Chinese medicine combinations, and prefer the prescription with higher reversal rate and efficacy enrichment score. In this case, the patient's lung cancer with systemic metastasis is accompanied by activity disorders, anemia, poor appetite, bone metastasis cancer pain, insomnia, venous thrombosis, and occult blood. Based on the Chinese medicine treatment principles of strengthening the body and eliminating evil, and treating according to syndrome differentiation, it improves lung function, immunity, and mental state.

[0128] The recommended prescription composition is: 9g of Rhizoma Cynomorii, 15g of Polygonum Cuspidatum, 10g of Perilla Leaf, 30g of Astragalus, 12g of Ophiopogon, 12g of Ganoderma Lucidum, 9g of Donkey-hide Gelatin, 6g of Licorice, 15g of White Peony Root, 10g of Bupleurum, 12g of Albizzia Cocobolo, 10g of Charred Areca Nut, 9g of Ginger, 6g of Schisandra Chinensis, 10g of Lotus Leaf, 10g of Schizonepeta Spike, 10g of Bombyx Batryticatus, 10g of Angelica dahurica, 10g of Eucommia ulmoides, and 10g of Polygala Tenuifolia. In the prescription, Rhizoma Cynomorii, Polygonum Cuspidatum, and Perilla Leaf can detoxify and regulate Qi, Astragalus, Ophiopogon, Ganoderma Lucidum, Donkey-hide Gelatin, and Licorice can invigorate Qi and nourish blood, White Peony Root, Bupleurum, and Albizzia Cocobolo can soften the liver and relieve depression, Poria, Charred Areca Nut, and Ginger can invigorate the spleen and harmonize the stomach, Schisandra Chinensis, Lotus Leaf, and Schizonepeta Spike can astringe and stop bleeding, Bombyx Batryticatus and Angelica dahurica can relieve pain and disperse nodules, and Eucommia ulmoides and Polygala Tenuifolia can nourish the kidney and calm the mind.

[0129] In addition, based on the patient signal pathway, the regulatory effect of Qingfei Sanjie Pills on the patient signal pathway was also evaluated. According to the instructions for Qingfei Sanjie Pills, it has the effects of clearing the lungs and dispersing knots, promoting blood circulation and relieving pain, and detoxifying and resolving phlegm. It is used for lung cancer with qi and yin deficiency, phlegm heat and blood stasis syndrome, and can also be used as an auxiliary medicine for lung cancer surgery, radiotherapy and chemotherapy. The results showed that Qingfei Sanjie Pills performed well on the A549 cell line and THP1 cell line, reversing 88% and 59% of the patient signal pathways, respectively. However, compared with Qingfei Sanjie Pills, the invention of this patent can regulate more abnormal signal pathways in patients.

[0130] The specific evaluation results are as follows:

[0131] Table 2

[0132]

[0133]

[0134] Example 4: Dynamic detection of dysregulated pathways in peripheral blood mononuclear cells of lung cancer patients and evaluation of therapeutic effects

[0135] In Example 1, after 2 weeks of treatment, the patient's wheezing symptoms were significantly improved, his mental state improved, his appetite increased, his eating situation improved compared to before treatment, his sleep improved, and he could only stay in bed and could carry out short-term activities. The patient's second blood was taken to analyze the relevant pathways. It can be seen that some pathway abnormalities were improved, such as platelet activation, P53 signaling pathway, long-term depression and other pathways. The positive expression of P53 protein in lung cancer tissue was significantly higher than that in paracancerous tissue, and was significantly correlated with lymph node metastasis, distant metastasis, invasion range and clinical stage. Regulating the P53 signaling pathway is of great significance in the treatment of lung cancer. It can not only enhance chemotherapy sensitivity, but also be used as one of the strategies for targeted therapy. By restoring the function of p53, the treatment effect of lung cancer can be improved, bringing better prognosis to patients. The improvement of the asthma pathway is also consistent with the improvement of wheezing symptoms. After the patient's symptoms were significantly improved, his mental state improved, which was consistent with the improvement of the long-term depression pathway in the second test result. In addition, some pathways related to tumor metastasis and immunity, such as cell adhesion molecule pathway, TH17 cell differentiation pathway, TH1 and TH2 cell differentiation pathway, have been regulated and improved. Figure 1 As shown, red indicates up-regulated pathways, blue indicates down-regulated pathways, and white indicates no significant enrichment pathways.

[0136] Example 5: Inhibitory effect of prescription on A549

[0137] During the logarithmic growth phase of A549 cells, a cell culture bottle is taken from an incubator, pancreatin is added to the culture bottle, and the entire cell surface is covered with pancreatin, and the incubator is put into the digestion until the cell part floats, and complete medium is added to terminate digestion, and the culture medium is blown and beaten using a Pasteur pipette to make the cells fall off, centrifuged, and the supernatant is discarded, and the cells are gently blown and mixed, and counted with a cell counting plate. For suspended cells, when the logarithmic growth phase is reached, after centrifugation and collection of cells, culture medium is added and the cells are gently blown and mixed, and counted with a cell counting plate. A549 is inoculated in 384 orifice plates at a density of 3000 / well, and after overnight attachment, the extract of the prescription described in Example 3 is added to process 24h.

[0138] The A549 cells were taken out of the incubator and the culture medium was slowly discarded. The culture medium containing CCK-8 reagent was added. After culturing for 3 hours, the absorbance of each well was measured using an ELISA reader (wavelength 450nm), and the cell survival rate was calculated according to the reagent instructions. The results showed that the prescription 1 described in the present invention had an inhibitory effect on lung cancer A549 cells, such as Figure 2 shown.

[0139] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for constructing an individualized evaluation model for traditional Chinese medicine prescriptions, characterized in that: The steps include: Step 1: Obtain transcriptome data of peripheral blood mononuclear cells of patients; Step 2: Obtain normal human peripheral blood mononuclear cell transcriptome data; Step 3: By comparing the transcriptome data of the patient's peripheral blood mononuclear cells with the transcriptome data of the normal person's peripheral blood mononuclear cells, a signal pathway enrichment analysis is performed using a gene set-based enrichment analysis method to obtain a standardized enrichment score of a specific dysregulated pathway in the patient's peripheral blood mononuclear cells, that is, the patient's signal pathway NES of the specific signal pathway, and the positive or negative value of the NES represents the direction of the patient's signal pathway; Select signaling pathways that are significantly enriched in all or part of the patient's peripheral blood mononuclear cells as the patient's dysregulated pathways; Step 4: Build a disease cell model; Step 5: Obtain the transcriptome data of the signaling pathway effect of the Chinese medicine to be evaluated on the cell model; Obtain transcriptome data of the cell model of the Chinese medicine to be evaluated; Obtain transcriptome data of the control group cell model; By comparing the transcriptome data of the cell model after the Chinese medicine to be evaluated acts on the cell model with the transcriptome data of the control group cell model, GSEA is used to perform enrichment analysis of the signal pathway to obtain the NES of the Chinese medicine to be evaluated on the specific pathway, that is, the drug signal pathway NES of the specific signal pathway, and the positive or negative value of NES represents the direction of the drug signal pathway; Step 6: Calculate the intensity of action, regulation direction and reverse regulation ratio of a single drug; Step 7: Calculate the effect intensity, regulation direction and reverse regulation ratio of the Chinese medicine composition.

2. The method for isolating peripheral blood mononuclear cells from patients and constructing a transcriptome library according to claim 1, characterized in that: The method for obtaining the transcriptome data of peripheral blood mononuclear cells of patients in step 1 is: real-time and dynamic collection of peripheral blood mononuclear cells of patients, extraction of total RNA of peripheral blood mononuclear cells, construction of transcriptome sequencing library, and high-throughput sequencing; The method for obtaining normal human peripheral blood mononuclear cell transcriptome data described in step 2 is: collecting peripheral blood mononuclear cells from normal healthy people, extracting total RNA of peripheral blood mononuclear cells, constructing a transcriptome sequencing library, and performing high-throughput sequencing.

3. The construction method according to claim 1 or 2, characterized in that: The method for obtaining the transcriptome data after the cell model is acted upon by the Chinese medicine to be evaluated in step 5 is: taking the extract of the Chinese medicine to be evaluated to treat the disease cell model, extracting total RNA, constructing a transcriptome sequencing library, and performing high-throughput sequencing; The method for obtaining the transcriptome data of the control group cell model in step 5 is: taking the solvent of the extract of the Chinese medicine to be evaluated as the control group to treat the disease cell model, extracting total RNA, constructing a transcriptome sequencing library, and performing high-throughput sequencing.

4. The construction method according to any one of claims 1 to 3, characterized in that: In step 6-7, for a specific abnormal signal pathway, when the drug signal pathway NES of the single drug or Chinese medicine composition to be evaluated is opposite to the NES of the patient's signal pathway, that is, the direction of the drug signal pathway is opposite to the direction of the patient's signal pathway, it means that the single drug or Chinese medicine composition to be evaluated can reverse or inhibit the abnormality of this signal pathway of the patient; When the drug signal pathway NES of the Chinese medicine to be evaluated is in the same direction as the patient signal pathway NES, that is, the drug signal pathway direction is the same as the patient signal pathway direction, it means that the Chinese medicine to be evaluated can enhance or upregulate the abnormality of this signal pathway of the patient.

5. The construction method according to any one of claims 1 to 4, characterized in that: In step 6-7, the proportion of pathways reversely regulated by the single drug or Chinese medicine combination to be evaluated (reversal rate), reversal rate = number of reversed pathways / number of disordered pathways in the patient*100%; In step 6-7, the regulatory strength of the single drug or Chinese medicine combination to be evaluated on the disordered pathway, i.e., the drug efficacy enrichment score; Pharmacodynamic enrichment score = the sum of the pharmacodynamic enrichment scores of all single drugs in a single drug or Chinese medicine combination on all patient signal pathways; the positive or negative value of the pharmacodynamic enrichment score indicates the regulatory direction of the single drug or Chinese medicine combination on the disordered pathway set.

6. The construction method according to any one of claims 1 to 5, characterized in that: Step 6 is as follows: For a specific abnormal signal pathway, when the direction of the drug signal pathway of the Chinese medicine to be evaluated is opposite to that of the patient's signal pathway, it means that the Chinese medicine to be evaluated can reverse or inhibit the abnormality of this signal pathway, which is marked as a reversal pathway, and the pharmacodynamic enrichment of the Chinese medicine on this pathway is divided into |NES|; when the direction of the drug signal pathway of the Chinese medicine to be evaluated is the same as that of the patient's signal pathway, it means that the Chinese medicine to be evaluated can enhance or upregulate the abnormality of this signal pathway of the patient, which is marked as an enhancement pathway, and the pharmacodynamic enrichment of the Chinese medicine on this pathway is divided into -|NES|; For single Chinese medicine: for the disordered pathway of the patient described in step 3, calculate the effect strength of the single Chinese medicine: drug effect enrichment score = the sum of drug effect enrichment scores of the single medicine in all pathways; The proportion of pathway disorders of a single Chinese medicine was calculated, and the reversal rate = the number of reversal pathways / the number of signal pathways in the patient, and the reverse regulation ratio was obtained; Step 7 is as follows: For a specific abnormal signal pathway, the drug signal pathway NES of all single drugs in the traditional Chinese medicine composition are added together to serve as the drug signal pathway NES of the traditional Chinese medicine composition on the specific abnormal signal pathway; For a specific abnormal signal pathway, when the direction of the drug signal pathway of the Chinese medicine composition to be evaluated is opposite to that of the patient's signal pathway, it means that the Chinese medicine composition to be evaluated can reverse or inhibit the abnormality of this signal pathway, which is marked as a reversal pathway, and the pharmacodynamic enrichment of the Chinese medicine composition on this pathway is divided into |NES|; when the direction of the drug signal pathway of the Chinese medicine composition to be evaluated is the same as that of the patient's signal pathway, it means that the Chinese medicine composition to be evaluated can enhance or upregulate the abnormality of this signal pathway of the patient, which is marked as an enhancement pathway, and the pharmacodynamic enrichment of the Chinese medicine composition on this pathway is divided into -|NES|; For the Chinese medicine composition: for the disordered pathway set described in step 3, calculate the effect strength of the Chinese medicine composition (marked as the drug effect enrichment score): drug effect enrichment score = the sum of the drug effect enrichment scores of all single drugs on all patient signal pathways; the positive or negative value of the drug effect enrichment score indicates the regulation direction of the Chinese medicine composition on the disordered pathway set; The ratio of reverse regulation pathways (reversal rate) of the Chinese medicine composition was calculated, where reversal rate = number of reversed pathways / number of disordered pathways in the patient, to obtain the reverse regulation ratio.

7. The construction method according to any one of claims 1 to 6, characterized in that: The disease suffered by the patient includes but is not limited to cancer, acute disease or chronic disease; Preferably, the cancer includes but is not limited to lung cancer; Preferably, the acute disease includes but is not limited to infectious diseases; more preferably, the acute disease includes novel coronavirus infection; Preferably, the chronic disease includes but is not limited to chronic obstructive pulmonary disease; Preferably, the disease involves the nervous system, digestive system, circulatory system, respiratory system, urogenital system, skeletal muscle system, blood system, endocrine system, skin or appendages; Preferably, the disease includes but is not limited to metabolic diseases or rheumatic diseases.

8. An evaluation method for individualized intelligent Chinese medicine prescriptions, characterized in that: Based on the evaluation model constructed by the construction method according to any one of claims 1 to 7, the Chinese medicine to be tested that reverses the disordered pathway is selected to obtain a Chinese medicine composition.

9. A processor, the processor being used to run a program, characterized in that: When the program is run, the construction method according to any one of claims 1 to 7 or the evaluation method according to claim 8 is executed.

10. An electronic device or apparatus, characterized in that The electronic device comprises: a memory and a processor as claimed in claim 9; Wherein, one or more computer programs are stored in the memory, and the one or more computer programs include instructions; when the instructions are executed by the processor, the electronic device executes the construction method according to any one of claims 1 to 7 or the evaluation method according to claim 8; The device comprises one or more components, and the one or more components implement the construction method according to any one of claims 1 to 7 or the evaluation method according to claim 8.

11. A Chinese medicine composition for treating lung cancer, characterized in that: In parts by weight, it includes the following components:

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