A brief overview of traditional Chinese medicine prescription powered by artificial intelligence

Traditional Chinese medicine prescription is one of the treasures of traditional Chinese medicine(TCM).There are tens of thousands TCM prescriptions accumulated in the past thousands of years,corresponding to different diseases,symptoms and therapeutic goals.The correspondences are so complicated that there is an urgent need to leverage new technologies such as artificial intelligence(AI)to analyze,understand and utilize them effectively.In this paper,we present a brief overview of this direction,where current research progress on TCM prescription powered by AI is summarized.Our summarization focuses on three aspects,TCM prescription mining that aims at understanding the TCM prescription,TCM prescription or herb knowledge base construction that aims at extracting knowledge to support the TCM prescription-related study,and TCM prescription discovery that aims at utilizing AI technologies to further energize TCM.It is encouraging to see that steady progress in this direction has been made recently.Besides,a toy experiment on image-based TCM herb recognition by using convolutional neural networks is also conducted.It basically verifies that it is promising to use AI technologies to address challenging tasks in TCM.We also point out several research topics that could be cooperatively performed by researchers from the two disciplines.

Prescription and treatment rules for the prescriptions containing Poria cocos and Atractylodes macrocephala couplet medicine based on traditional Chinese Medicine inheritance support platform

Objectives:To provide a theoretical basis for the development of the new products of Poria cocos-Atractylodes macrocephala couplet medicine.Methods:All prescription preparations containing Poria cocos and Atractylodes macrocephala were collected from the Drug Standards of the Ministry of Public Health Drug Standard·Traditional Chinese Medicine Set Prescription Preparation(called Traditional Chinese Medicine Set Prescription Preparation for short).After standardization,the information of each prescription preparation was input into the Chinese Traditional Medicine Inheritance Support Platform(V2.5),and the relevant rules of the software were adopted.Data mining methods were used to analyze the frequency of drugs,main symptoms and diseases in prescriptions,and to analyze the regularity of prescriptions.The prescription rules of top 2 high frequency attending syndromes and diseases were analyzed.Results:There were total of 337 prescription preparations containing couplet medicine of Poria cocos and Atractylodes macrocephala,107 kinds of main symptoms and 66 kinds of diseases.The high frequency syndromes were deficiency of Qi and blood and weakness of spleen and stomach,and the high frequency syndromes were anorexia and irregular menstruation.Conclusion:The couplet medicine of Poria cocos-atractylodes macrocephala prescription is mainly used to treat digestive tract diseases and gynecological diseases;it mostly takes tonifying deficiency efficat.It can treat different diseases being compatible with different medicinal materials.The study can provide theoretical basis for clinical application and new drug development of the couplet medicine of Poria cocos-atractylodes macrocephala.

Network Pharmacology Approach to Investigate the Preventive Mechanism of Hunan Expert Group Recommended Chinese Medicine Prevention No.2 Prescription Against COVID-19

Objective To explore the possible preventive mechanism of Hunan expert group recommended Chinese medicine prescription of No.2(Pre-No.2)against coronavirus disease 2019(COVID-19)by network pharmacology method.Methods The target proteins of effective components and active compounds in Pre-No.2 were screened by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).A component-target-disease interaction network of Pre-No.2 was constructed by Cytoscape 3.7.2,gene ontology(GO)analysis,and Kyoto encyclopedia of genes and genomes(KEGG)analysis of target protein pathway by DAVID.Results A total of 163 compounds and 278 target protein targets in Pre-No.2 were collected from the TCMSP database.Kaempferol,wogonin,7-methoxy-2-methyl isoflavone,formononetin,isorhamnetin,and licochalcone A were the most frequent targets in the regulatory network.GO enrichment analysis showed that Pre-No.2 regulated response to virus,viral processes,humoral immune responses,defense responses to virus and viral entry into host cells.KEGG enrichment analysis showed that the formula regulated the NF-κB signaling pathway,B cell receptor signaling pathway,viral carcinogenesis,T cell signaling pathway and FcγR-mediated phagocytosis signaling pathway.Conclusions Pre-No.2 may play a preventive role against COVID-19 through regulation of the Toll-like signaling,T cell signaling,B cell signaling and other signaling pathways.It may regulate the immune system to protect against anti-influenza virus.

Potential Preventive and Therapeutic Effects of Traditional Chinese Medicine Compound Prescription and Traditional Chinese Medicine Products on COVID-19

This paper mainly analyzes the traditional Chinese medicine compound prescription and traditional Chinese medicine products with remarkable epidemic prevention effect since the outbreak of COVID-19,and discusses their potential prevention and treatment effects,so as to provide a basis for the further development and application of traditional Chinese medicine compound prescription and traditional Chinese medicine products against COVID-19.

A study on the medication law of oral administration of traditional Chinese medicine in treating breast carbuncle based on the Traditional Chinese Medicine Prescription Dictionary

Objective:Based on the database of Traditional Chinese Medicine Prescription Dictionary,the prescription medication rules of oral administration of traditional Chinese medicine in the treatment of breast carbuncle were explored by using the software of Traditional Chinese Medicine Inheritance Support System(V2.5).Methods:To screen and retrieve the prescriptions for treating breast carbuncle in the Traditional Chinese Medicine Prescription Dictionary,and data mining was carried out by using association rule algorithm,complex system entropy clustering and so on.Results:A total of 208 prescriptions which met the inclusion criteria were selected,involving 175 traditional Chinese medicines.Among them,23 medicines were found to be more than 21 times in the treatment of breast carbuncle.The nature of the medicine is mainly cold or warm,the flavour of the medicine is mainly bitter or sweet,most of them belong to the spleen,liver,stomach.15 commonly used drug combinations and 9 new prescriptions were obtained.Conclusion:The key pathogenesis of breast carbuncle is liver depression and Qi stagnation,stomach heat blocking collaterals,the treatment is mainly to clear heat and detoxify,regulate Qi to diffuse the knot,which provides reference for the choose of traditional Chinese medicine prescription in treating breast carbuncle.

China Association of Chinese Medicine Paper notice for seminar on clinical application of TCM classic prescriptions and herbs in the treatment of emotional diseases

Hosted by ChinaAssociation of Chinese Medicine,and organized by World Journal of Integrated traditional and western Medicine,seminar on clinical application of TCM classic prescriptions and herbs in the treatment of emotional diseaseis planned to be held in Yichang,Hubei province from June 22nd to 24th.

Effects of Traditional Chinese Herbal Medicine on Immune Organ Indexes and Macrophages Phagocytic Indexes in Chickens Infected by Infectious Bronchitis Virus

[ Objective] To study the therapeutic effects of traditional Chinese medicine prescriptions on infectious bronchitis （IB） and find a novel avenue for prevention and treatment of viral diseases in poultry. [Method] A total of 160 cockerels at the age of 15 d were divided into four groups randomly, including traditional Chinese medicine group, moroxydine control group, challenge control group and healthy control group. Except the healthy control group, other groups were challenged with infectious bronchitis virus （IBV） on Day 15. After 48 h post challenge, the traditional Chinese medicine groupand moroxydine control group were respectively administrated with Chinese herbal medicine prescription and moroxydine, continuously for 5 d. The immune organ indexes and macrephage phagocytic indexes were detected on Day 18, 24 and 30, respectively. [ Result] The immune organ indexes and macrophage phagocytic indexes were not significantly different between traditional Chinese medicine group and moroxydine control group on Day 18. But all the indexes of the traditional Chinese medicine groups were increased significantly （ P 〈 0.05） on Day 24 and 30, and showed extremely significant difference （ P 〈 0.01 ） with those of challenge control group on Day 30. [ Conclusion] The traditional Chinese herbal medicine can enhance macrophage phagocytic indexes and immune organs indexes of chickens infected by IBV.

Clinical efficacy and safety of TCM prescriptions combined with nucleoside(acid)analogues in treating chronic hepatitis B:a meta-analysis

Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely clear.This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.Methods We searched Chinese databases the China National Knowledge Infrastructure(CNKI),Wanfang Data,and China Science and Technology Journal Database(VIP),as well as English databases Pub Med and Cochrane Library,from time of establishment to April 14,2021.Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network.Rev Man 5.3 and Stata 12.0 software were used to perform this research.Results A total of 23 articles,3282 patients,and 25 TCM prescriptions were included in this study.NAs plus TCM remarkably improved the clinical total effective rate[Odds ratio(OR)=3.92,P<0.00001],TCM syndrome score(Mean difference=-3.73,P<0.00001),hepatitis B virus(HBV)DNA negative conversion rate(OR=1.49,P=0.0001),hepatitis Be antigen(HBe Ag)negative conversion rate(OR=2.03,P<0.00001),alanine aminotransferase levels[Std mean difference(SMD)=-0.95,P<0.00001],and aspartate aminotransferase levels(SMD=-0.70,P=0.0004).Adverse reaction rates did not increase in the combined treatment group(OR=0.97,P=0.84).A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.Conclusion TCM in combination with NAs,demonstrated better clinical efficacy against CHB than NAs alone.In addition,the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy.However,more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM.

Diagnosis and Treatment of Yeast Mastitis in Dairy Cattle

[Objective] Study on the yeast mastitis in dairy cattle cases which have been ineffectively treated by multiple antibiotics through traditional Chinese medicine prescription. [ Method] The isolated pathogenic fungi from milk were used for drug sensitivity testing and the ones proved were clinically treated by self-made traditional Chinese medicine prescription ＂Ruxiaotang＂. [ Result] 19 cases of 20 selected dairy cattle cases were diagnosed as yeast mastitis and cured with the except of a Candida tropicalis case. [ Conclusion] The results provide a new reference for curing yeast mastitis.

Value and influencing factors of valid Traditional Chinese Medicine compound prescription patents for mammary gland hyperplasia

OBJECTIVE: To explore the value and factors influencing the maintenance of valid Traditional Chinese Medicine compound prescription patents for the management of mammary gland hyperplasia. METHODS: The State Intellectual Property Office Patents Database, China Patent Information Center Patents Database, Soopat Patent Search Platform, and CNIPR Search Platform of Chinese and Foreign Patent Database were searched to identify Traditional Chinese Medicine compound prescription patents for mammary gland hyperplasia that had been maintained for at least 5 years. Logistic regression analysis was used to detect the factors influencing the maintenance of valid patents. RESULTS: From 1 January 1993 to 31 December 2019, a total of 1228, Traditional Chinese Medicine compound prescription patents for mammary gland hyperplasia were authorized. Of these applications, 381 patents were granted and only 176 patents were maintained for more than 5 years. The five independent variables assessed in this study all had significant explanatory functions. CONCLUSIONS: The maintenance of valid patents for Traditional Chinese Medicine compound prescriptions for treating mammary gland hyperplasia is of great importance. The maintenance of such patents depends on many factors, such as the concentration of effective herbs, number of dependent claims, provision of new dosage forms and detailed experimental data, and transfer of patent rights.

Discovery of Regularities in the Use of Herbs in Chinese Medicine Prescriptions

Chinese medicine （CM） is a discipline with its own distinct methodologies and philosophical principles. The main method of treatment in CM is to use herbal prescriptions. Typically, a number of herbs are combined to form a formula and different formulae are prescribed for different patients. Regularities in the mixture of herbs in the prescriptions are important for both clinical treatment and novel patent medicine development. In this study, we analyze CM formula data using latent tree （LT） models. Interesting regularities are discovered. Those regularities are of interest to students of CM as well as pharmaceutical companies that manufacture medicine using Chinese herbs.

Effect of Xiaobailing Decoction on Melanocytes in Vitro

To observe the effect of Xiaobailing Decoction （消白灵汤） on murine melanocytes in vitro and to explore the mechanism of Xiaobailing Decoction in the treatment of vitiligo. Methods： B-16F10 murine melanoma cells were cultured in 1640 medium and treated respectively with different concentrations （lmg/ml, 2mg/ml, 3mg/ml） of the Chinese drug Xiaobailing Decoction and its main components, the drugs for replenishing the lddney-yang, and the drugs for nourishing blood and activating blood circulation, etc. for 7 days. MMT assay was used to determine the proliferation of B-16F10 murine melanoma cells. NaOH cleavage assay was adopted to measure the melanogenesis of melanocytes. Results：Xiaobailing Decoction, the drugs for replenishing the kidney-yang and the drugs for nourishing blood and activating blood circulation at different concentrations significantly improved the proliferation of B-16F10 murine melanoma cells from the 3rd day to the 5th day （P〈0.05）, with Xiaobailing Decoction at the concentrations of lmg/ml having the most distinct action on promoting the proliferation of melanocytes on the 3rd day （P〈0.001）; And the drugs for replenishing the lodney-yang at the concentrations of 2mg/ml and 3mg/ml and the drugs for nourishing blood and activating blood circulation at 3mg/ml significantly increased melanogenesis of melanocytes （P〈0.05）. Conclusion： Xiaobailing Decoction can promote melanocytic proliferation and melanogenesis in vitro, and it is indicated that the drugs for replenishing the kidney-yang and the drugs for nourishing blood and activating blood circulation play an important role in treating vitiligo.

A Clustering Method of Chinese Medicine Prescriptions Based on Modified Firefly Algorithm

This paper is aimed to study the clustering method for Chinese medicine（CM） medical cases. The traditional K-means clustering algorithm had shortcomings such as dependence of results on the selection of initial value, trapping in local optimum when processing prescriptions form CM medical cases. Therefore, a new clustering method based on the collaboration of firefly algorithm and simulated annealing algorithm was proposed. This algorithm dynamically determined the iteration of firefly algorithm and simulates sampling of annealing algorithm by fitness changes, and increased the diversity of swarm through expansion of the scope of the sudden jump, thereby effectively avoiding premature problem. The results from confirmatory experiments for CM medical cases suggested that, comparing with traditional K-means clustering algorithms, this method was greatly improved in the individual diversity and the obtained clustering results, the computing results from this method had a certain reference value for cluster analysis on CM prescriptions.

Letter to the editor: Comment on the Regulatios of the Simplified Registration and Approval Management for Compound Recipe of Classical Prescription of Traditional Chinese Medicine

To the Editor:On Oct 9,2017,China Food and Drug Administration announced1~ the Regulations of the Simplified Registration and Approval Management for Compound Recipe of Classical Prescription of Traditional Chinese Medicine(Exposure Draft)which has been stirring up intense debate in the West.The article China to Roll Back Regulations for Traditional Medicine Despite Safety Concerns lately

Mechanism of Yinchenhao decoction in the treatment of jaundice based on network pharmacology

Objective:This study aimed to examine the mechanism of classic ancient prescription of Chinese medicine Yinchenhao decoction in treating jaundice based on network pharmacology.Method:An oral bioavailability of≥30%,a drug likeness of≥0.18,and literature studies were used to screen for Yinchen(Artemisiae scopariae herba),Zhizi(Gardeniae fructus),Dahuang(Rhei radix et rhizome)in the Chinese Medicine System Pharmacology Database and Analysis Platform.The active ingredient was introduced into the PubChem database to collect drug component targets and import into the Uniprot database for gene standardization.The target gene of Yinchen(Artemisiae scopariae herba)was screened via Human Gene Database(GeneCards).Then,use the Cytoscape 3.7.2 software was used for network visualization analysis,and the R3.6.1 software was used for gene ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses.Results:We collected a total of 47 active constituents of classic ancient prescription of Chinese medicine Yinchenhao decoction,of which 17 were related to jaundice;189,9 targets of jaundice were screened,of which 41 were interdigitated with the targets of classic ancient prescription of Chinese medicine Yinchenhao decoction.Gene ontology functional enrichment analysis revealed 111 biological processes,14 cellular components,and 28 molecular functions,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed 34 Kyoto Encyclopedia of Genes and Genomes pathways including hepatocellular carcinoma,PI3K-Akt signaling pathway,HIF-1 signaling pathway,prolactin signaling pathway,and non-alcoholic fatty liver disease.Conclusion:Based on the network pharmacology,the analysis of jaundice and classic ancient prescription of Chinese medicine Yinchenhao decoction provides a novel idea and direction for the study of classic ancient prescription of Chinese medicine Yinchenhao decoction in the treatment of jaundice.

Recent advances of traditional Chinese medicine on the prevention and treatment of COVID-19

Coronavirus disease-2019(COVID-19)is a new highly infectious disease caused by a novel coronavirus.Recently,the number of new cases infected pneumonia in the world continues to increase,which has aroused great concern from the international community.At present,there are no small-molecule specific anti-viral drugs for the treatment.The high mortality rate seriously threatens human health.Traditional Chinese medicine(TCM)is a unique health resource in China.The combination of TCM and Western medicine has played a positive and important role in combating COVID-19 in China.In this review,through literature mining and analysis,it was found that TCM has the potential to prevent and treat the COVID-19.Then,the network pharmacological studies demonstrated that TCM played roles of anti-virus,anti-inflammation and immunoregulation in the management of COVID-19 via multiple components acting on multiple targets and multiple pathways.Finally,clinical researches also confirmed the beneficial effects of TCM on the treatment of patients.This review may provide meaningful and useful information on further drug development of COVID-19 and other viral infectious diseases.

Studies on Treating Eczema by Chinese Herbal Medicine with Anti-Type Ⅳ Allergic Activity

Objective: To study Chinese herbal prescription for treatment of eczema on the basis of the suppressive effect of Chinese herbal medicine with type Ⅳ allergic reaction. Methods: Various formulae composed of Chinese herbal medicines possessing suppressive effect on murine allergic contact dermatitis were formed following the therapeutic principles of traditional Chinese medicine in treating eczema, and their effect on ear swelling, ear flake weight, dermal inflammatory infiltration cell count and plasma level of calcitonin gene related peptide ( CGRP) were examined in mice with dinitrofluorobenzene induced dermatitis. The prescription, Composite Poria Decoction was formulated and made into granule form, which was used to treat 63 cases of eczema (atopic dermatitis was excluded), and compared with 59 cases treated with antihistaminic that was aimed at the type I allergic reaction. Results: Experimental study showed that all the 4 Chinese prescriptions had the effect of anti type Ⅳ allergic reaction, among them, the formula for cooling blood and removing Heat, Wind and Dampness evil possessed the most potent effect in suppressing murine dermatitis, and it was also able to up regulate the plasma CGRP concentration. The clinical cure rate of Composite Poria Granule treatment was 47.6%, and that of the control was 22.0%. The difference was significant between the two groups ( u =2.9555, P <0.01). Conclusions: Chinese herbal medicine has the effect of anti type Ⅳ allergic reaction. Composite Poria Granule has good effect in treating eczema.

Relationship between Tissue Distributions of Modified Wuzi Yanzong Prescription(加味五子衍宗方) in Rats and Meridian Tropism Theory

Objective： To investigate the relationship between tissue distributions of modified Wuzi Yanzong prescription（加味五子衍宗方, MWP） in rats and meridian tropism theory. Methods： A high-performance liquid chromatography with Fourier transform-mass spectrometry（HPLC-FT） method was used to identify the metabolites of MWP in different tissues of rats after continued oral administration of MWP for 7 days. The relationship between MWP and meridian tropism theory was studied according to the tissue distributions of the metabolites of MWP in rats and the relevant literature. Results： Nineteen metabolites, mainly flavanoid compounds, were detected in the different rat tissues and classified to each herb in MWP. Further, it was able to establish that the tissue distributions of the metabolites of MWP were consistent with the descriptions of meridian tropism of MWP available in literature, this result might be useful in clarifying the mechanism of MWP on meridian tropism. In the long run, these data might provide scientific evidence of the meridian tropism theory to further promote the reasonable, effective utilization, and modernization of Chinese medicine. Conclusion： The tissue distributions of MWP in vivo were consistent with the descriptions of meridian tropism of MWP.

Study on the Complex Prescription Compatibility Law of the Cold and Hot Nature of Mahuang Decoction(麻黄汤) and Its Categorized Formulae Based on the Cold-Hot Pad Differentiating Assay

Objective：To explore the complex prescription compatibility law of the cold and hot nature of Mahuang Decoction（麻黄汤,MHD） and Maxing Shigan Decoction（麻杏石甘汤,MXSGD）,both categorized formulas but with different hot/cold natures.Methods：Oxygen consumption of mice was determined among three groups：MHD,MXSGD and the control;a cold-hot pad differentiating assay was used to observe the variability of temperature tropism among the groups of mice which was treated with MHD,MXSGD,and their compositions. Meanwhile,the total anti-oxidant capability（T-AOC） activity were detected.Results：After administration of MHD, the mice showed increased oxygen consumption（P0.01）.Compared with MHD group,the remaining rate of MXSGD mice on the hot pad was found to be significantly increased with the cold-hot pad differentiating assay （P0.05）.There was no significant difference（P0.05） among the remaining rates of MXSGD,MXSGD with high dose Gypsum Fibrosum（MXHGF） group,and MXSGD with low dose Gypsum Fibrosum（MXLGF） group mice.Compared with the MHD group,T-AOC activity of the mice in the Consensus Compositons group was significantly decreased（P=0.0494）.Compared with the MXSGD group,T-AOC activity of Gypsum Fibrosum （GF） group was increased significantly（P=0.0013）.Conclusions：The differences in cold and hot nature could be represented objectively between MHD with a hot nature and MXSGD with a cold nature.The reason may be the Gypsum Fibrosum which decreased the efficacy of the consensus compositions.However,increasing or decreasing the dose of Gypsum Fibrosum will not change the cold and hot nature of MXSGD.

Simultaneous Determination of Six Compounds in Rat Plasma by Ultra-Performance Liquid Chromatography with Tandem Mass Spectrometry: Application in the Pharmacokinetic Study of Qing Gan-Shu Yu-Fang

A rapid and high selective ultra-performance liquid chromatography(UPLC)with tandem mass spectrometry method for simultaneous determination of six compounds including albiflorin,paeoniflorin,picroside I,picroside II,saikosaponin A,and saikosaponin D in rat plasma was developed and validated using butyl p-hydroxybenzoate as an internal standard.One-step direct protein precipitation with acetonitrile was used to extract the compounds from the rat plasma samples.Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column(100 mm×2.1 mm,1.7μm)at a flow rate of 0.4 m L/min,using gradient mode containing 0.1%formic acid in water and acetonitrile were used as the Mobile phase A and B.Electrospray ionization in negative ion mode and multiple reaction monitoring were used to identify and quantify active components.Calibration curves showed good linearity(R^2>0.9908)over a wide concentration range for all compounds.The intra-and interday precision(relative standard deviation)ranged 2.4%–7.0%and 2.6%–8.0%,respectively.The accuracy(relative error)was from-13.0%to 13.2%at all quality control levels.The recovery ranged from 81.1%to 92.5%.The validated method was successfully applied to pharmacokinetic study in rats after oral administration of Qing Gan-Shu Yu-Fang.The results show that one can draw a conclusion that these six active ingredients can be quickly absorbed and play a pharmacodynamic role rapidly in vivo.