In Silico Screening of Potential Inhibitors against dPLA2 from Named Chinese Herbs for Identification of Compounds with Antivenom Effects Due to Deinagkistrodon acutus Snake Bites

Phospholipase A2 (PLA2) is the key enzyme to the venom from Deinagkistrodon acutus which is one of the highly venomous snakes in China. In addition to being a catalyst for the hydrolysis of phospholipases A2 from snake venom, its well known that it possesses a broad spectrum of pharmacological activities, such as myotoxicity, neurotoxicity, cardiotoxicity, and hemolytic, anticoagulant and antiplatelet activities. However, snakebites are not efficiently treated by conventional serum therapy. Acute wounds can still cause poisoning and death. In order to find effective inhibitors of Deinagkistrodon venom acid phospholipase A2 (dPLA2), we obtained 385 compounds in 9 Chinese herbs from the TCMSP. These compounds were further performed to virtual screen using in silico tools like ADMET analysis, molecular docking and molecular dynamics (MD) simulation. After Pharmacokinetics analysis, we found 7 candidate compounds. Besides, analysis of small molecule interactions with dPLA2 confirmed that the amino acid residues HIS47 and GLY29 are key targets. Because they bind not only to the natural substrate phosphatidylcholine and compounds known for having inhibitory functions, but also for combining with potential antidote molecules in Chinese herbal medicine. This study is the first to report experience with virtual screening for possible inhibitor of dPLA2, such as the interaction spatial structure, binding energy and binding interaction analysis, these experiences not only provide reference for further experimental research, but also have a guideline for the study of drug molecular mechanism of action.

Topology and Semantic Information Fusion Classification Network Based on Hyperspectral Images of Chinese Herbs

Most methods for classifying hyperspectral data only consider the local spatial relation-ship among samples,ignoring the important non-local topological relationship.However,the non-local topological relationship is better at representing the structure of hyperspectral data.This paper proposes a deep learning model called Topology and semantic information fusion classification network(TSFnet)that incorporates a topology structure and semantic information transmis-sion network to accurately classify traditional Chinese medicine in hyperspectral images.TSFnet uses a convolutional neural network(CNN)to extract features and a graph convolution network(GCN)to capture potential topological relationships among different types of Chinese herbal medicines.The results show that TSFnet outperforms other state-of-the-art deep learning classification algorithms in two different scenarios of herbal medicine datasets.Additionally,the proposed TSFnet model is lightweight and can be easily deployed for mobile herbal medicine classification.

Cell-Based Biological Markers for Blood-Enriching Chinese Herbs: Erythropoietin Production in HepG2 Cells and Nitric Oxide Release in Human Umbilical Vein Endothelial Cells (HUVECs)

Chinese tonifying herbs, which are classified into four functional categories (namely, Yang, Qi, Yin, Blood) are commonly used for restoring normal body function and the prevention of diseases. To explore cell-based biological markers for Blood-enriching Chinese herbs, we investigate the effect of 11 commonly used Blood-enriching herbs on erythropoietin (EPO) production in HepG2 cells. Herbs for nourishing Yin were tested for determining the specificity of Blood-enriching herbs in inducing EPO production. In addition, the effects of Blood-enriching herbs on nitric oxide (NO) production in both HepG2 cells and human umbilical vein endothelial cells (HUVECs) were also investigated. The results indicated that methanolic extracts of Blood-enriching herbs (but not Yin-nourishing herbs) showed characteristic pharmacological activity in inducing EPO production in HepG2 cells and NO release in HUVECs. The experimental findings, therefore, support the use of cell-based EPO production and NO release as biological markers for Blood-enriching Chinese tonifying herbs.

Traditional Chinese medicine prescriptions and herbs for the treatment of hypothyroidism:a narrative review

The increasing prevalence of hypothyroidism,which can cause endocrine dysfunction,abnormal neurological function,and cardiovascular and cerebrovascular injuries,poses serious health problems.Thyroid hormone supplementation constitutes the current main therapeutic method for hypothyroidism,yet it has many limitations and risks and is not suitable for everyone.Therefore,it is necessary to seek alternative and complementary treatment methods.It has been proven in practice that traditional Chinese medicine(TCM)possesses multi-channel comprehensive characteristics for the treatment of hypothyroidism and has more advantages than single thyroid hormone supplementation.Through a comprehensive examination of existing literature about TCM efficacy in addressing hypothyroidism,we have meticulously consolidated the most recent research findings on prescriptions and herbal substances employed in the treatment of this condition.Furthermore,we have explicated their respective functions in the management of hypothyroidism,thereby offering valuable perspectives and recommendations for the prospective utilization of natural remedies in its treatment.

Five commonly used traditional Chinese medicine formulas in the treatment of ulcerative colitis:A network meta-analysis

BACKGROUND Currently,traditional Chinese medicine(TCM)formulas are commonly being used as adjunctive therapy for ulcerative colitis in China.Network meta-analysis,a quantitative and comprehensive analytical method,can systematically compare the effects of different adjunctive treatment options for ulcerative colitis,providing scientific evidence for clinical decision-making.AIM To evaluate the clinical efficacy and safety of commonly used TCM for the treatment of ulcerative colitis(UC)in clinical practice through a network metaanalysis.METHODS Clinical randomized controlled trials of these TCM formulas used for the adjuvant treatment of UC were searched from the establishment of the databases to July 1,2022.Studies that met the inclusion criteria were screened and evaluated for literature quality and risk of bias according to the Cochrane 5.1 standard.The methodological quality of the studies was assessed using ReviewManager(RevMan)5.4,and a funnel plot was constructed to test for publication bias.ADDIS 1.16 statistical software was used to perform statistical analysis of the treatment measures and derive the network relationship and ranking diagrams of the various intervention measures.RESULTS A total of 64 randomized controlled trials involving 5456 patients with UC were included in this study.The adjuvant treatment of UC using five TCM formulations was able to improve the clinical outcome of the patients.Adjuvant treatment with Baitouweng decoction(BTWT)showed a significant effect[mean difference=36.22,95%confidence interval(CI):7.63 to 65.76].For the reduction of tumor necrosis factor in patients with UC,adjunctive therapy with BTWT(mean difference=−9.55,95%CI:−17.89 to−1.41),Shenlingbaizhu powder[SLBZS;odds ratio(OR)=0.19,95%CI:0.08 to 0.39],and Shaoyao decoction(OR=−23.02,95%CI:−33.64 to−13.14)was effective.Shaoyao decoction was more effective than BTWT(OR=0.12,95%CI:0.03 to 0.39),SLBZS(OR=0.19,95%CI:0.08 to 0.39),and Xi Lei powder(OR=0.34,95%CI:0.13 to 0.81)in reducing tumor necrosis factor and the recurrence rate of UC.CONCLUSION TCM combined with mesalazine is more effective than mesalazine alone in the treatment of UC.

Synergistic effects of carbon cycle metabolism and photosynthesis in Chinese cabbage under salt stress

Chinese cabbage(Brassica rapa ssp. pekinensis) has a long cultivation history and is one of the vegetable crops with the largest cultivation area in China. However, salt stress severely damages photosynthesis and hormone metabolism, nutritional balances, and results in ion toxicity in plants. To better understand the mechanisms of salt-induced growth inhibition in Chinese cabbage, RNA-seq and physiological index determination were conducted to explore the impacts of salt stress on carbon cycle metabolism and photosynthesis in Chinese cabbage. Here, we found that the number of thylakoids and grana lamellae and the content of starch granules and chlorophyll in the leaves of Chinese cabbage under salt stress showed a time-dependent response, first increasing and then decreasing. Chinese cabbage increased the transcript levels of genes related to the photosynthetic apparatus and carbon metabolism under salt stress, probably in an attempt to alleviate damage to the photosynthetic system and enhance CO_(2) fixation and energy metabolism. The transcription of genes related to starch and sucrose synthesis and degradation were also enhanced;this might have been an attempt to maintain intracellular osmotic pressure by increasing soluble sugar concentrations. Soluble sugars could also be used as potential reactive oxygen species(ROS) scavengers, in concert with peroxidase(POD)enzymes, to eliminate ROS that accumulate during metabolic processes. Our study characterizes the synergistic response network of carbon metabolism and photosynthesis under salt stress.

Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Systems Theory-Driven Framework for AI Integration into the Holistic Material Basis Research of Traditional Chinese Medicine

This paper introduces a systems theory-driven framework to integration artificial intelligence(AI)into traditional Chinese medicine(TCM)research,enhancing the understanding of TCM’s holistic material basis while adhering to evidence-based principles.Utilizing the System Function Decoding Model(SFDM),the research progresses through define,quantify,infer,and validate phases to systematically explore TCM’s material basis.It employs a dual analytical approach that combines top-down,systems theory-guided perspectives with bottom-up,elements-structure-function methodologies,provides comprehensive insights into TCM’s holistic material basis.Moreover,the research examines AI’s role in quantitative assessment and predictive analysis of TCM’s material components,proposing two specific AIdriven technical applications.This interdisciplinary effort underscores AI’s potential to enhance our understanding of TCM’s holistic material basis and establishes a foundation for future research at the intersection of traditional wisdom and modern technology.

A chromosome-level genome assembly for Chinese plum‘Wushancuili'reveals the molecular basis of its fruit color and susceptibility to rain-cracking

Chinese plum(Prunus salicina Lindl.)originates from China and makes a large contribution to the global production of plums.The P.salicina‘Wushancuili'has a green coloration and high fruit quality and is economically important in eliminating poverty and protecting ecology in the Yangtze River Three Gorges Reservoir.However,rain-induced cracking(rain-cracking,literally skin cracking caused by rain)is a limitation to‘Wushancuili'fruit production and causes severe losses.This study reported a high-quality‘Wushancuili'genome assembly consisting of a 302.17-Mb sequence with eight pseudo-chromosomes and a contig N50 of 23.59 Mb through the combination of Illumina sequencing,Pacific Biosciences HiFiⅢsequencing,and high-throughput chromosome conformation capture technology.A total of 25109 protein-coding genes are predicted and 54.17%of the genome is composed of repetitive sequences.‘Wushancuili'underwent a remarkable orthoselection during evolution.Gene identification revealed that loss-of-function in four core MYB10 genes results in the anthocyanin deficiency and absence of red color,revealing the green coloration due to the residual high chlorophyll in fruit skin.Besides,the occurrence of cracking is assumed to be closely associated with cell wall modification and frequently rain-induced pathogen enrichment through transcriptomic analysis.The loss of MYB10 genes might render fruit more susceptible to pathogen-mediated cracking by weakening the epidermal strength and reactive oxygen species(ROS)scavenging.Our findings provided fundamental knowledge regarding fruit coloration and rain-cracking and will facilitate genetic improvement and cultivation management in Chinese plums.

Understandings of Urban Sustainability in China:a Bibliometric Analysis Using Chinese Literatures

Cities hold a critical responsibility for achieving the Sustainable Development Goals(SDGs)due to their high population density,extensive resource consumption,and significant economic contributions.To examine the present state of understandings regarding urban sustainability(SDG 11:Sustainable Cities and Communities)within Chinese research communities,this study collected 15950 papers from 1994 to 2022 on the 12 indicators of SDG 11,from the China National Knowledge Infrastructure(CNKI),a hub of Chinese academic papers,that directly relate to policymaking.Significant research topics on SDG 11 were identified for each indicator using bibliometrics analysis approaches.The high-frequency keywords and clusters of keywords over the last three decades reveal that existing studies primarily concentrated on the physical aspects,such as transportation and environment,while there is a lack of consideration of societal aspects.This indicates a limited and biased understanding of the urban sustainability within the Chinese academic community.Hence,it is crucial to prioritize the societal aspects in order to develop a research agenda that further advances urban sustainability.

Chinese herbal medicine combined with Western medicine for Mycoplasma pneumoniae pneumonia in children:An overview of systematic reviews

Objective:To summarize the characteristics and evaluate the quality of the methodology and evidence within systematic reviews(SRs)of Chinese herbal medicine(CHM)for Mycoplasma pneumoniae pneumonia(MPP)inchildren.Methods:SRs of randomized controlled trials were searched using PubMed,the Cochrane Library,Embase,the Chinese National Knowledge Infrastructure Databases(CNKI),the Chinese Scientific Journals Database(VIP),Wanfang,and the SinoMed Database.SRs on the use of CHM alone or in combination with Western medications for MPP in children were included.The study compared the effects of Western medicine alone with those of CHM.The evidence quality using the A Measurement Tool to Assess Systematic Reviews(AMSTAR)2,the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)2020,and the Grading of Recommendations,Assessment,Development,and Evaluation(GRADE)criteria.The primary indicators were the total effective rate,fever subsidence time,and cough disappearance time.The secondary outcomes were pulmonary rale disappearance time,average hospitalization time,lung X-ray infiltrate disappearance time,immunological indices,and inflammatory cytokine levels.Results:Twelve relevant SRs were included;75%(9/12)were assessed as very low quality,and 25%(3/12)Were rated as low quality using the AMSTAR 2 criteria.According to the PRISMA 2020 checklist,the average SR score was 20.3 out of a 27 point maximum.In all SRs,CHM demonstrated improvement in symptoms and signs among children with MPP.The evidence quality using the GRADE criteria ranged from"very low"(>50%)to"moderate"(<5%).The most common downgrading factor was imprecision,followed by publication bias and inconsistency.Conclusion:This overview highlights the limited quality of the methodology and evidence of the included SRs.Although the included studies showed the beneficial effects of CHM on MPP in children,it was difficult to draw firm conclusions owing to methodological flaws.

Exploring the transformative impact of traditional Chinese medicine on depression:Insights from animal models

Depression,a prevalent and complex mental health condition,presents a significant global health burden.Depression is one of the most frequent mental disorders;deaths from it account for 14.3%of people worldwide.In recent years,the integration of complementary and alternative medicine,including traditional Chinese medicine(TCM),has gained attention as a potential avenue for addressing depression.This comprehensive review critically assesses the efficacy of TCM interventions in alleviating depressive symptoms.An in-depth look at different research studies,clinical trials,and meta-analyses is used in this review to look into how TCM practices like herbal formulations,acupuncture,and mindbody practices work.The review looks at the quality of the evidence,the rigor of the methods,and any possible flaws in the current studies.This gives us an idea of where TCM stands right now in terms of treating depression.This comprehensive review aims to assess the efficacy of TCM interventions in alleviating depressive symptoms.In order to learn more about their possible healing effects,the study also looks into how different types of TCM work,such as herbal formulas,acupuncture,and mind-body practices.

Research progress on insomnia treated by traditional Chinese medicine and acupuncture based on microbial-gut-brain axis theory

Insomnia,as one of the emotional diseases,has been increasing in recent years,which has a great impact on people's life and work.Therefore,researchers are eager to find a more perfect treatment.The microbiome-gut-brain axis is a new theory that has gradually become popular abroad in recent years and has a profound impact in the field of insomnia.In recent years,traditional Chinese medicine(TCM)has played an increasingly important role in the treatment of insomnia,especially acupuncture and Chinese herbal medicine.It is the main method of TCM in the treatment of insomnia.This paper mainly reviews the combination degree of"microorganism-gut-brain axis"theory with TCM and acupuncture under the system of TCM.To explore the mechanism of TCM and acupuncture in the treatment of insomnia under the guidance of"microorganismgut-brain axis"theory,in order to provide a new idea for the diagnosis and treatment of insomnia.

Machine learning-based comparison of factors influencing estimated glomerular filtration rate in Chinese women with or without nonalcoholic fatty liver

BACKGROUND The prevalence of non-alcoholic fatty liver(NAFLD)has increased recently.Subjects with NAFLD are known to have higher chance for renal function impairment.Many past studies used traditional multiple linear regression(MLR)to identify risk factors for decreased estimated glomerular filtration rate(eGFR).However,medical research is increasingly relying on emerging machine learning(Mach-L)methods.The present study enrolled healthy women to identify factors affecting eGFR in subjects with and without NAFLD(NAFLD+,NAFLD-)and to rank their importance.AIM To uses three different Mach-L methods to identify key impact factors for eGFR in healthy women with and without NAFLD.METHODS A total of 65535 healthy female study participants were enrolled from the Taiwan MJ cohort,accounting for 32 independent variables including demographic,biochemistry and lifestyle parameters(independent variables),while eGFR was used as the dependent variable.Aside from MLR,three Mach-L methods were applied,including stochastic gradient boosting,eXtreme gradient boosting and elastic net.Errors of estimation were used to define method accuracy,where smaller degree of error indicated better model performance.RESULTS Income,albumin,eGFR,High density lipoprotein-Cholesterol,phosphorus,forced expiratory volume in one second(FEV1),and sleep time were all lower in the NAFLD+group,while other factors were all significantly higher except for smoking area.Mach-L had lower estimation errors,thus outperforming MLR.In Model 1,age,uric acid(UA),FEV1,plasma calcium level(Ca),plasma albumin level(Alb)and T-bilirubin were the most important factors in the NAFLD+group,as opposed to age,UA,FEV1,Alb,lactic dehydrogenase(LDH)and Ca for the NAFLD-group.Given the importance percentage was much higher than the 2nd important factor,we built Model 2 by removing age.CONCLUSION The eGFR were lower in the NAFLD+group compared to the NAFLD-group,with age being was the most important impact factor in both groups of healthy Chinese women,followed by LDH,UA,FEV1 and Alb.However,for the NAFLD-group,TSH and SBP were the 5th and 6th most important factors,as opposed to Ca and BF in the NAFLD+group.

Advances in the treatment of diabetic peripheral neuropathy by modulating gut microbiota with traditional Chinese medicine

Diabetic peripheral neuropathy(DPN)is one of the strongest risk factors for diabetic foot ulcers(neuropathic ulcerations)and the existing ulcers may further deteriorate due to the damage to sensory neurons.Moreover,the resulting numbness in the limbs causes difficulty in discovering these ulcerations in a short time.DPN is associated with gut microbiota dysbiosis.Traditional Chinese medicine(TCM)compounds such as Shenqi Dihuang Decoction,Huangkui Capsules and Qidi Tangshen Granules can reduce the clinical symptoms of diabetic nephropathy by modulating gut microbiota.The current review discusses whether TCM compounds can reduce the risk of DPN by improving gut microbiota.

ISO releases a standard for a Chinese medicinal material

Rehmannia glutinosa root is one of the most commonly used herbs in traditional Chinese medicine. It has a long history in East and Southeast Asian countries for relieving heat and cooling the blood, nourishing yin and body fluid.

Research progress of traditional Chinese medicine in the treatment of endocrine metabolic diseases in 2023

This study aimed to provide a comprehensive review of the research progress in Chinese medicine in the treatment of endocrine metabolic diseases in 2023,covering traditional Chinese medicine(TCM)monomers,TCM extracts,and TCM combinations,including non-alcoholic fatty liver disease,type 2 diabetes mellitus and its complications,obesity,hyperuricaemia,and thyroid disorders.After systematic sorting and summary,we found that in 2023,the research focusing on the application of TCM for endocrine metabolic diseases was still on the mechanism of action at the cellular and molecular levels,which not only influenced the classical pathways of lipid metabolism,but also delved into the key mechanisms of anti-inflammation,anti-oxidation,anti-insulin resistance,and so on.Additionally,TCM has shown remarkable results in the treatment of endocrine metabolic diseases by improving intestinal flora disorders and abnormal cellular iron death.These research results provide valuable ideas,methods,and tools for TCM in the prevention and treatment of endocrine metabolic diseases,and provide important references and guidance for future research and practice.

Effect of Modified Biochar with Organic Fertiliser on the Growth and Development of Chinese Rose

In order to reduce the waste of resources and environmental pollution caused by excessive application of chemical fertilizers, improve the utilization rate of fertilizers, and promote the large-scale and high-quality development of the Chinese rose industry. In this experiment, corn stover biochar, phosphoric acid modified biochar and organic fertilizer were used as test materials, and the effects of mixed application of modified biochar and organic fertilizer on the growth and development of Chinese rose as well as soil physicochemical properties were investigated by using the method of pot planting test. The results showed that modified biochar with organic fertilizer had the most significant effect on the enhancement of soil pH, organic matter content and soil carbon-to-nitrogen ratio. After 120 d of planting, modified biochar with organic fertilizer had the most significant effect on the enhancement of plant height and crown width of Chinese rose;both organic fertilizer and modified biochar with organic fertilizer significantly increased the chlorophyll content of Chinese rose. The number of flowers and the number of branches were the highest in the modified biochar with organic fertilizer treatment. In conclusion, the application of modified biochar with organic fertilizer can better improve the soil pH, and increase the soil organic matter content and carbon-to-nitrogen ratio to change the biological traits of Chinese rose. The results of this study provide a theoretical basis for the reduction of chemical fertilizers and the resource utilization of agricultural wastes and guarantee the sustainable development of the cut flower industry.

Evidence-based Clinical Chinese Medicine:What Has Changed Over the Past 20 Years

Chinese medicine has been used for centuries to treat a range of health conditions.This history has produced a wealth of classical literature,case studies and clinical research data detailing its use and effectiveness.However,high-quality and conclusive evidence that meets modern requirements for clinical decision support is lacking.This evidence gap limits the integration of Chinese medicine with contemporary medicine,which in turn limits global access and acceptance of Chinese medicine as a form of safe and effective health care.Over the past 20 years,researchers and organisations around the world,including the World Health Organization(WHO)and United Nations,have worked to support the integration of traditional medicines,such as Chinese medicine,with conventional medicines to improve global health care.This paper provides an overview of Chinese medicine studies published in the top four general medical journals(BMJ,JAMA,Lancet and New England Journal of Medicine)from February 2005 to February 2024 in the past 20 years to highlight the progress in the development of this evidence base.It also highlights key actions taken to promote evidence-based clinical Chinese medicine,including product and practitioner regulation,formalising education standards,and international collaborations.Research conducted at the China-Australia International Research Centre for Chinese Medicine demonstrates the benefits of such a collaboration.Through development of its unique and inclusive‘whole-evidence’approach,plus clinical studies and systematic reviews,the Centre has significantly contributed to the evidence base for clinical Chinese medicine.In addition,its high-impact papers and groundbreaking monographs have been cited in international conventional medicine guidelines.While progress has certainly been made during the past 20 years to build a stronger evidence base for clinical Chinese medicine,there is still a considerable gap that limits its integration with conventional medicine.Future funding and research are needed to continue this work and achieve to safe,effective and accessible traditional medicine as part of the WHO’s Universal Health Coverage strategy.

Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management

BACKGROUND Type 2 diabetes mellitus(DM)is an independent risk factor for hepatocellular carcinoma(HCC),while insulin is a potent mitogen.Identifying a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for researchers.AIM To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control.METHODS We used data acquired from the Taiwan,Chinaese National Health Insurance research database between 2000 and 2017.We identified patients with DM who were prescribed insulin for>3 months.The herb user group was further defined as patients prescribed herbal medication for DM for>3 months per annum during RESULTS We initially enrolled 657144 DM patients with regular insulin use from 2000 to 2017.Among these,46849 patients had used a herbal treatment for DM,and 140547 patients were included as the matched control group.The baseline variables were similar between the herb users and nonusers.DM patients with regular herb use had a 12%decreased risk of HCC compared with the control group[adjusted hazard ratio(aHR)=0.88,95%CI=0.80–0.97].The cumulative incidence of HCC in the herb users was significantly lower than that of the nonusers.Patients with a herb use of>5 years cumulatively exhibited a protective effect against development of HCC(aHR=0.82,P<0.05).Of patients who developed HCC,herb users exhibited a longer survival time than nonusers(aHR=0.78,P=0.0001).Additionally,we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the constituents.Our analysis indicated that Astragalus propinquus(Huang Qi)plus Salvia miltiorrhiza Bunge(Dan Shen),and Astragalus propinquus(Huang Qi)plus Trichosanthes kirilowii Maxim.(Tian Hua Fen)were the most frequent combination of single herbs.Meanwhile,Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and formulas.CONCLUSION This large-scale retrospective cohort study reveals that herbal medicine may decrease HCC risk by 12%in DM patients with regular insulin use.