Model informed precision medicine of Chinese herbal medicines formulas-A multi-scale mechanistic intelligent model

Recent trends suggest that Chinese herbal medicine formulas(CHM formulas)are promising treatments for complex diseases.To characterize the precise syndromes,precise diseases and precise targets of the precise targets between complex diseases and CHM formulas,we developed an artificial intelligence-based quantitative predictive algorithm(DeepTCM).DeepTCM has gone through multilevel model calibration and validation against a comprehensive set of herb and disease data so that it accurately captures the complex cellular signaling,molecular and theoretical levels of traditional Chinese medicine(TCM).As an example,our model simulated the optimal CHM formulas for the treatment of coronary heart disease(CHD)with depression,and through model sensitivity analysis,we calculated the balanced scoring of the formulas.Furthermore,we constructed a biological knowledge graph representing interactions by associating herb-target and gene-disease interactions.Finally,we experimentally confirmed the therapeutic effect and pharmacological mechanism of a novel model-predicted intervention in humans and mice.This novel multiscale model opened up a new avenue to combine“disease syndrome”and“macro micro”system modeling to facilitate translational research in CHM formulas.

Exploring the compatibility theory of traditional Chinese medicine formulae:the disassembled prescriptions study

Traditional Chinese medicine(TCM)has become very popular in the treatment of complex diseases worldwide in recent decades.Despite the promising performance of TCM,how herbs work synergistically in a formula and their therapeutic targets remain ambiguous.This largely limits the correct use and modernization of TCM formulas clinically.The study of disassembled prescriptions is important for investigating the compatibility theory of Chinese medicines.By dissecting the mechanisms of TCM formulae,the compatibility principles of some well-known formulae,such as Realgar-Indigo naturalis,have been elucidated to a certain extent.In this review,several common methods of disassembled prescription studies are summarized,including those of single herb or mineral,sub-prescription,active ingredients or effective parts,large formulae,and systems pharmacology studies,as well as the methods of grouping based on the properties or efficacy of Chinese medicines,in order to provide evidence for formulae study.Moreover,some challenges to be addressed in disassembled prescriptions studies have been identified in this review.

Compatibility mechanism of Chinese medicine formula:state of the art and perspectives

Traditional Chinese medicine(TCM)has been practiced in China and surrounding countries for thousands of years and has gradually attracted the attention of Western countries.After reasonable compatibility,TCMs could play the key role of enhancing efficacy and reducing toxicity,which has significant therapeutic advantages in the treatment of complex diseases in clinical practice.While the TCM compatibility is not the simple addition of drugs.Under the appropriate dosage ratio,multiple TCMs can play a synergistic role to realize the overall regulation of TCM treatment.Therefore,it is of critical essential to study the compatibility of TCM formula to promote TCM modernization,new drug development and clinical application.Recently,under the guidance of TCM theory,many researches on the composition,pharmacodynamic activity and pharmacokinetic properties of TCM formula have emerged by integrating new technologies and new methods,revealing the scientific connotation of the compatibility of TCM formula from different perspectives and levels.This paper introduces the research progress of compatibility rules from different levels of compatibility,compatibility for synergistic enhancement and detoxification,and application of cutting-edge technology,with representative cases,in order to provide ideas and references for further study on TCM compatibility.

Analysis of Adverse Reactions in the Treatment of COVID-19 with Three Chinese Patent Medicines and Three Herbal Formulas

Objective To explore the rules and characteristics of the adverse drug reactions(ADRs)of three Chinese patent medicines and three herbal formulas for the treatment of COVID-19,and to provide a reference for clinical safe medication.Methods The cases and ADR reports of the three Chinese patent medicines and three herbal formulas in PubMed,Web of Science,Springer Link,CNKI,Wanfang and VIP database were retrieved from December 2019 to May 2021.Then we extracted and analyzed the effective information included in the literature.Results and Conclusion According to the pre-developed retrieval plan,a total of 136 documents were obtained,and a total of 6 documents met the inclusion criteria finally.553 patients used three Chinese patent medicines and three herbal formulas,and there were 133 cases of adverse reactions.The adverse reactions of patients taking the three Chinese patent medicines and three herbal formulas can all be explained under the theory of traditional Chinese medicine,and the adverse reactions can be eliminated by adding or subtracting the flavor of the medicine or stopping the medicine.

Traditional Chinese medicine for transformation of gastric precancerous lesions to gastric cancer:A critical review

Gastric cancer(GC)is a common gastrointestinal tumor.Gastric precancerous lesions(GPL)are the last pathological stage before normal gastric mucosa transforms into GC.However,preventing the transformation from GPL to GC remains a challenge.Traditional Chinese medicine(TCM)has been used to treat gastric disease for millennia.A series of TCM formulas and active compounds have shown therapeutic effects in both GC and GPL.This article reviews recent progress on the herbal drugs and pharmacological mechanisms of TCM in preventing the transformation from GPL to GC,especially focusing on antiinflammatory,anti-angiogenesis,proliferation,and apoptosis.This review may provide a meaningful reference for the prevention of the transformation from GPL to GC using TCM.

Progress on traditional Chinese medicine in improving hepatic fibrosis through inhibiting oxidative stress

Hepatic fibrosis is a common pathological process that occurs in the development of various chronic liver diseases into cirrhosis and liver cancer,characterized by excessive deposition of the extracellular matrix.In the past,hepatic fibrosis was thought to be a static and irreversible pathological process.In recent years,with the rapid development of molecular biology and the continuous in-depth study of the liver at the microscopic level,more and more evidence has shown that hepatic fibrosis is a dynamic and reversible process.Therefore,it is particularly important to find an effective,simple,and inexpensive method for its prevention and treatment.Traditional Chinese medicine(TCM)occupies an important position in the treatment of hepatic fibrosis due to its advantages of low adverse reactions,low cost,and multi-target effectiveness.A large number of research results have shown that TCM monomers,single herbal extracts,and TCM formulas play important roles in the prevention and treatment of hepatic fibrosis.Oxidative stress(OS)is one of the key factors in the occurrence and development of hepatic fibrosis.Therefore,this article reviews the progress in the understanding of the mechanisms of TCM monomers,single herbal extracts,and TCM formulas in preventing and treating hepatic fibrosis by inhibiting OS in recent years,in order to provide a reference and basis for drug therapy of hepatic fibrosis.

Rheumatic valvular heart disease treated with traditional Chinese medicine:A case report

BACKGROUND Rheumatic heart disease(RHD)is an autoimmune disease that leads to irreversible valve damage and heart failure.Surgery is an effective treatment;however,it is invasive and carries risks,restricting its broad application.Therefore,it is essential to find alternative nonsurgical treatments for RHD.CASE SUMMARY A 57-year-old woman was assessed with cardiac color Doppler ultrasound,left heart function tests,and tissue Doppler imaging evaluation at Zhongshan Hospital of Fudan University.The results showed mild mitral valve stenosis with mild to moderate mitral and aortic regurgitation,confirming a diagnosis of rheumatic valve disease.After her symptoms became severe,with frequent ventricular tachycardia and supraventricular tachycardia>200 beats per minute,her physicians recommended surgery.During a 10-day preoperative waiting period,the patient asked to be treated with traditional Chinese medicine.After 1 week of this treatment,her symptoms improved significantly,including resolution of the ventricular tachycardia,and the surgery was postponed pending further follow-up.At 3-month follow-up,color Doppler ultrasound showed mild mitral valve stenosis with mild mitral and aortic regurgitation.Therefore,it was determined that no surgical treatment was required.CONCLUSION Traditional Chinese medicine treatment effectively relieves symptoms of RHD,particularly mitral valve stenosis and mitral and aortic regurgitation.

International expert consensus on clinical application of traditional Chinese medicine formula granules

Guided by the theory of traditional Chinese medicine(TCM),TCM formula granules are made through the optimal process of extraction,concentration,drying,and granulation by combining modern new preparation technologies and pharmaceutical technologies.TCM formula granules are stable,safe,convenient,and effective.Compared with TCM decoction pieces,TCM formula granules can achieve the full process control of its industry chain from field to workshop and standardize the management of the origin of medicinal materials,processing of decoction pieces,processing technology,quality inspection,sales,and products distribution.TCM formula granules can partially replace Chinese patent medicines.Only available for around 800 common varieties of TCM,TCM formula granules cannot replace decoction pieces for many types which are not commonly used in clinical practice.A large number of formula granules are used in clinical and animal studies so that investigators no longer need to extract and control the quality of TCM decoction pieces.How to improve the production process,establish the quality standard,perfect the regulatory system,and expand the clinical application are the problems we need to solve as soon as possible for the better development of formula granules.

Efficacy and safety of traditional Chinese medicine kidney-nourishing formula for Alzheimer's disease in comparison with donepezil:a systematic review and meta-analysis

Objective:Finding an effective therapy against Alzheimer’s disease(AD)has been associate increasingly pressing issue and traditional Chinese medicine(TCM)is widespread in the prevention and treatment of AD in China.The aim of this study was to judge the efficaciousness and safety of TCM kidney-nourishing(the changes of pathological state of kidney deficiency by means of TCM treatment and so on)formula(TKNF)for AD in comparison with donepezil.Methods:The retrieval period of seven databases was from the establishment of each database to April 2019.Two authors independently identified randomized controlled trials(RCTs),fetched data and assessed bias risk.Comprehensive analysis process was conducted with review manager for eligible and appropriate RCTs.Results:A complete of 981 AD patients from 13 studies were enclosed.Meta-analysis of RCTs showed that there was no significant difference in the improvement of Alzheimer's disease assessment scale-cognitive subscale score between 2 groups in short term,but the effect of long-term treatment may exceed donepezil;there was a significant difference in the improvement of activities of daily living score between 2 groups;there was a significant difference in TCM curative efficacy between 2 groups with long-term treatment.There was no significant difference in the incidence of adverse events between 2 groups.The quality of the evidence was high or moderate.Conclusion:Compared with donepezil,TKNF was an effective drug for AD patients and the clinical application of TKNF was safe.TKNF's long-term benefits need more evidence to verify.

Analysis of new therapeutic strategies for diabetes mellitus based on traditional Chinese medicine'xiaoke'formulae

Objective:To develop new therapeutic strategies for diabetes mellitus(DM)by analyzing the mechanisms of action of traditional Chinese medicine(TCM)'xiaoke'formulae(TCM prescriptions for remedying xiaoke).Methods:We characterized 291 xiaoke formulae,including the herbs contained,chemical composition,constituents'targets,and corresponding genes.Xiaoke-related genes were retrieved based on the relationships of constituents'targets and xiaoke formulae,and a threshold of over 95.88%occurrence of each constituent target in the 291 TCM formulae served as a definition for xiaoke-related genes.Upon comparison with DM-related genes in the DisGeNET database,the genes differing in expression between cases administered TCM and synthetic drugs were explored using a TCM grammar system.Results:The results showed that xiaoke formulae and 14 exclusively xiaoke-related genes were significantly associated with multiple biological processes closely related to DM and diabetic complications(P<.01).Moreover,intervention in the expression of these xiaoke-related genes would affect DM-related genes directly or indirectly.Conclusion:The 14 xiaoke-related genes APEX1,EHMT2,TSHR,CBX1,FEN1,GMNN,JUN,KMT2A,MAPT,POLl,USP1,PIN1,POLB,and POLK can serve as candidate genes for antidiabetic drug design.Compared with DM-related genes in DisGeNET,intervention in the expression of 14 xiaoke-related genes by TCM formulae has the potential to not only lower blood glucose,but also reduce the occurrence of some side effects and inhibit the development of diabetic complications.These findings will contribute to the discovery of new strategies for treating DM.

Epigastric pain syndrome: What can traditional Chinese medicine do? A randomized controlled trial of Biling Weitong Granules

BACKGROUND Recent research suggests that although prokinetic agents,acid suppressors,and radical treatment for Helicobacter pylori infection may be effective in patients with functional dyspepsia(FD),a large proportion of patients still fail to respond to these treatments or may suffer from severe adverse reactions.Many traditional Chinese medicinal herbs can regulate the status of the entire body and have special advantages in the treatment of functional diseases.The present study was designed to verify the efficacy of Biling Weitong Granules(BLWTG),a traditional Chinese medicinal herbal compound formula,in alleviating epigastric pain syndrome(EPS)in FD patients,in an attempt to provide an effective prescription for the clinical treatment of this disease.AIM To evaluate the clinical efficacy and safety of BLWTG in treating EPS in patients with FD.METHODS In this multicenter,stratified,randomized,double-blind,placebo-controlled,parallel group clinical trial,eligible patients were randomized into the BLWTG and placebo groups who were treated for 6 wk.Efficacy indicators including the severity and frequency of EPS and the time to pain resolution and safety indicators including adverse events were observed and compared.RESULTS The baseline demographic data and clinical characteristics,such as epigastric pain symptoms,pain intensity,and frequency of attacks,were matched between the two groups before randomization.After 6 wk of treatment and after the center effect was eliminated,the epigastric pain was significantly improved in 28.33%and 85.59%of the patients in the placebo and BLWTG groups,respectively(P<0.05).At 6 wk,the resolution rate of epigastric pain was 15%and 69.49%in the placebo and BLWTG groups,respectively(P<0.05).The differences of total FD clinical score between these two groups were significant(P<0.05)at 2,4,and 6 wk(P<0.05).The scores of each item and the total score in the Functional Digestive Disorders Quality of Life Questionnaire showed significant differences between the two groups at 6 wk after both the center and interaction effects were eliminated(P<0.05).There was no significant difference in the incidence of adverse events between the two groups,and no serious adverse event was noted during the observation.CONCLUSION Compared with placebo,BLWTG markedly improved EPS in FD patients without causing serious adverse reactions.

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

Traditional Chinese medicine(TCM) has played a positive role in the management of hepatocarcinoma. Hepatocarcinoma patients may present Qi-stagnation, damp-heat, blood stasis, Qi-deficiency, Yin-deficiency and other TCM syndromes(Zheng). Modern treatments such as surgery, transarterial chemoembolization(TACE) and high intensity focus ultrasound treatment would influence the manifestation of TCM syndromes. Herbs with traditional efficacy of tonifying Qi, blood and Yin, soothing liver-Qi stagnation, clearing heat and detoxifying and dissolving stasis, have been demonstrated to be potent to prevent hepatocarcinogenesis. TCM has been widely used in all aspects of integrative therapy in hepatocarcinoma, including surgical resection, liver transplantation, TACE, local ablative therapies and even as monotherapy for middle-advanced stage hepatocarcinoma. Clinical practices have confirmed that TCM is effective to alleviate clinical symptoms, improve quality of life and immune function, prevent recurrence and metastasis, delay tumor progression, and prolong survival time in hepatocarcinoma patients. The effective mechanism of TCM against hepatocarcinoma is related to inducing apoptosis, autophagy, anoikis and cell senescence, arresting cell cycle, regulating immune function, inhibiting metastasis and angiogenesis, reversing drug resistance and enhancing effects of chemotherapy. Along with the progress of research in this field, TCM will contribute more to the prevention and treatment of hepatocarcinoma.

Antibacterial Effects of Chinese Herbal Medicines against Streptococcus iniae in Oreochromis niloticus

In this study, the antibacterial effects of Chinese herbal medicines against Streptococcus iniae in Oreochromis niloticus were investigated by drug sensitiv- ity test. The results indicated that Streptococcus in/ae was extremely sensitive to Calla Chinensis, Fructus Hippophae and Fructus Murne, highly sensitive to Sappan Lignum, Pericarpium Granati, Folium Eucalypti and Radix Scutellariae, moderately sensitive to Rh/zoma Coptidis, Radix et Rhizoma Rhei, Flos Caryophyllata, Cortex phellodendri and Rabdosia serra （ Maxim. ） Hara, and insensitive to Herba Portulacae , Herba Houttuyniae , Polygonum hydropiper L. , Herba Menthae , Radix Glycyrrhizae , Pericarpium Citri Reticulatae , Herba Andrographitis and Rhizoma Acori Tatarinowii. Chinese medicinal herbs which Streptococcus iniae was extremely sensitive or moderately sensitive to were selected and prepared into three Chinese herbal medicine formulae for medicated bath of Oreochromis niloticus infected arti- ficially with Streptococcus iniae. The results showed that medicated bath elicited therapeutic effects on infected Oreochromis niloticus. Formula II exhibited the best therapeutic effect with an effective percentage of 90%.

Clinical practice guideline on traditional Chinese medicine in the treatment of influenza (2021)

Influenza is a serious public health problem that endangers the health of the global human population.Traditional Chinese medicine(TCM)is rich in theory and practical experience regarding the treatment of influenza,and TCM treatments have shown good curative effects,but there is a dearth of standardized clinical guidance.It is necessary to formulate a clinical practice guide based on evidence-based medicine.To this end,the Specialty Committee of Emergency,China Association of Chinese Medicine(Beijing,China)organized a team of clinical experts,methodological experts,and other multidisciplinary experts to develop a guideline with integrated research methods in the first place of TCM.This guide includes 23 recommendations.The prescription section contains 16 recommendations,including 5 recommendations for mild cases,5 recommendations for severe cases,3 recommendations for critical cases,and 4 recommendations for the recovery period;the portion covering proprietary Chinese medicines forms a total of 7 recommendations.This guide aims to provide the best evidence for clinicians and related practitioners to make decisions about influenza diagnosis and treatment in Chinese medicine.

Comparison of Traditional Chinese Medicine with Western Medicine Cancer Therapy

The interactions among drugs,tumor and host are critical for a response to therapy and for outcome.Anticancer herbs used in Chinese medicine are classified into 4 groups based on their target (tumor,patient and drug) as follows:eliminating pathogenic factors,strengthening the body resistance,enhancing effects of chemotherapy and detoxication of chemotherapy. Correspondingly,anticancer drugs used in Western medicine can be classified into 4 groups as follows:cytotoxic drugs,biological response modifiers,chemosensitizers and chemoprotectants. Based on the theory of Chinese medicinal formulas,prescriptions are composed of four constituents,namely,primary constituent (main component of the formula prescription),minister constituent (second component of formula prescription),adjuvant constituent (adjuvant component of the formula prescription) and messenger constituent (component making the formula prescription targeting pathological tissues).To control the interaction among drugs and to modulate the interaction among the tumor,patient and drugs,we suggest that combined therapy for Western medicine might include 4 constituents,i.e.,primary,cooperative,adjuvant and modulatory constituent. Cytotoxic drugs frequently are used as primary and cooperative constituents,whereas biological response modifiers and biochemical modulators are usually regarded respectively as adjuvant drugs and modulatory constituents. We believe these new concepts may be helpful for the aim of appropriately designing,evaluating or providing combination therapy.

Prescription analysis of traditional chinese medicine for COVID-19treatment

Background:Coronavirus disease 2019 is still spreading all over the world and without any specific medicine.Traditional Chinese medicine has played an important role in the control of epidemics in China and accumulated many experiences.The aim of this study is to summarize the law of traditional Chinese medicine and provide reference for coronavirus disease 2019 traditional Chinese medicine treatment.Methods:We collected the treatment plans of traditional Chinese medicine for coronavirus disease 2019 in 24 provinces of China to evaluate the basic Chinese medicine formulas,and the efficacy types,frequency,“Four Characters”,“Five Tastes”,“Channel Tropism”of herbal medicines.Combination rules between medicines were calculated by Apriori algorithm and Clementine12.0.Results:The formulas for“Relieving Exterior Syndrome”,“Expelling Dampness”,“Clearing Heat”and“Supplementing”have highest proportion.In prevention period and medical observation period,the medicines mainly have effect for“Clearing Heat”,“Relieving Exterior Syndrome”and“Supplementing”.In treatment period,medicines for“Clearing Heat”,“Relieving Superficies”and“Relieving Dampness”had higher frequency.The“Four Characters”of Chinese medicines in all treatment plans were mainly“Cold”and“Warm”.Medicines in the treatment plans always belong to“Pungent Taste”,“Bitter Taste”and“Sweet Taste”.For“Channel Tropism”,most medicines turned over to the“Lung”,“Stoma”and“Spleen”.The common medicine combinations in the recommended formulas during the prevention period and medical observation period were medicines for“Qi-Supplementing”and“Relieving Superficies”.In treatment period(mild,moderate,severe/critical),medicines for“Dampness Expelling”,“Relieving Superficies”and“Qi-Supplementing”were combined in a high frequency.In recovery period,the medicines for“Dispelling Dampness”combined the medicines for“Promoting Blood Circulation”with highest frequency.Conclusions:We found the characteristics of medicine and prescription rules of traditional Chinese medicine for the treatment of coronavirus disease 2019 and provided scientificity and effectiveness of it.More importantly,it provides reference for the development of new clinical prescriptions for coronavirus disease 2019.

Clinical evidence and potential mechanisms of Chinese medicines for the treatment of diabetic retinopathy

糖尿病视网膜病变是导致患者视力损害和失明的主要原因之一.目前,由于抗VEGF制剂、类固醇激素、激光光凝和玻璃体手术在治疗糖尿病视网膜病变中的局限性,使得人们越来越重视中医药在糖尿病视网膜病变中的治疗作用.本文就中药配方（包括复方制剂、专利药和古方）的组成及其特点,中药在糖尿病视网膜病变中临床应用及作用机制方面的研究进行综述.由于中药的复杂性,关于中药的作用机制、副作用以及药物之间的相互作用等方面的问题,需要进一步深入的研究.中医药可防止病变进一步发展和恶化,保护残余视力,延缓病变发展;在糖尿病视网膜病变的预防和治疗中存在显著优势.

Reporting guidelines of Chinese medicine:Current situation and future development

Objective:Reporting research is as important a part of a study as its design or analysis.Reporting guidelines(RGs)provide structured advice on how to report research studies clearly and adequately.This study aimed to review the development of RGs of Chinese medicine(CM)and to provide recommen-dations for improvement.Methods:Through a systematic search of the Enhancing the QUAlity and Transparency Of health Research(EQUATOR)Network and electronic databases up to January 1,2022,we identified a total of 15 RGs of CM,and further summarized their characteristics and applications.In addition,we reviewed the development of international RGs and analyzed its impact for CM.Results:Compared with the generic RGs,the reporting standards of CM have been rapidly developed over the last 10 years,of which 57%were issued in recent 3 years(2019-2021).Currently,the system of RGs of CM has been established,especially for clinical trials,including various CM interventions and covering the guidelines from trial registration,protocol,results publication to the evidence synthesis and clinical practice guideline.However,the application of RGs of CM is suboptimal.Conclusion:It is necessary to take further measures to promote practical application,improve journals’endorsement,and establish quality monitoring procedures for RGs of CM in the future.

Pharmaceutical Rules of Traditional Chinese Medicine For Stroke Based on Dictionary of Prescriptions and Complex Network Analysis

Objective:Taking the Dictionary of Prescriptions as a clue,we collected effective prescriptions for treating Stroke,and systematically summarized the medication and compatibility rules of the core Chinese medicines for treating Stroke.Methods:A database of prescriptions for stroke based on complex relationship analysis system of traditional Chinese medicine was established.From the point of view of complex network,the hierarchy of drug compatibility rules of compound prescriptions(such as courtiers and envoys)was analyzed,the statistical characteristics of complex networks were analyzed,and an attempt was made to explain the characteristics of complex networks of drugs for stroke.Results:A total of 974 prescriptions were collected,including 1040 Chinese herbs.The core Chinese herbal medicines with nodal degree(>500)for Stroke were divaricate saposhnikovia root,liquorice root,Chinese angelica,tall gastrodia tuber,incised notopterygium rhizome and root.The compatibility relationship of the core Chinese medicines in the treatment of stroke is divaricate saposhnikovia root-liquorice root,ephedra-divaricate saposhnikovia root,divaricate saposhnikovia root-sichuan lovage rhizome,divaricate saposhnikovia root-Chinese angelica in order of frequency.Conclusion:Through the analysis of the common network structure of effective prescriptions for Stroke,the core prescription compatibility structure reflecting the prescription thinking and clinical characteristics was found.