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A Selection of Commonly Used Species in [ 28 ]. In it set up a programme to standardise terms used in TCM and its derivatives such as kampo Japanese herbal medicines derived from TCM , as the beginning of its efforts to create an evidence base for traditional medicine and to provide an international platform to harmonise information exchange on traditional medicines [ 29 ]. Over the years, international journals and public media sensed the historic opportunities and challenges in TCM. In the Lancet , for example, a number of aspects of TCM, such as acupuncture [ 34 - 36 ], TCM diagnostic methods [ 2 , 37 ], herb-drug and herb-immunoassay interactions [ 38 , 39 ], as well as therapeutic and sometimes severe adverse effects of TCM drugs and adulterants [ 40 - 44 ] were reported.

In recognition of the political, historic and cultural impacts on the development of TCM [ 4 , 5 , 45 , 46 ], the Lancet highlighted the development of TCM in different countries and regions, characterised by global perspectives [ 2 , 37 , 42 , 47 - 49 ]. Governmental and non-governmental efforts within and outside China have coincided with new breakthroughs in modern science.

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Representative examples to illustrate the main achievements of these thirty years with international and scientific perspectives are given below. From to , China conducted a series of nationwide surveys on the substances used in TCM practice across the country. According to the official data published by the SATCM, 11, botanical and 1, zoological species, as well as 80 minerals were used [ 50 ]. In volumes and more than , pages, more than classic monographs are included, making it the most comprehensive compilation of TCM and Chinese materia medica classics dating back to BC - AD.

This collection not only highlights the value of TCM as a rich source for knowledge-based medical rediscovery due to its continuous documentation of clinical experiences for thousands of years, but also implies the huge task to dissect out the very best parts of TCM for modern innovation. The recognition of the need to standardise materials used in TCM is evidenced in the nine editions of the Chinese Pharmacopoeia, with each edition containing updated information about the medicinal products used in TCM. In its latest edition published in , Volume I is fully dedicated to TCM drugs, representing the most comprehensive official monographs in this field.

Peigen Xiao, the founding director of the Institute of Medicinal Plant Development in Beijing, was a pioneer in systematic studies of TCM resources, especially Chinese medicinal plants. He built bridges between Chinese and Western pharmacognosy and introduced Chinese medicinal plants to the rest of the world. His work resulted in the discovery of new species and the publication of hundreds of scientific papers and more than 25 books, e. In response to the European use of TCM products, Hildebert Wagner, Rudolf Bauer and Peigen Xiao started a joint project in to elaborate chemical fingerprint analytical methods for the identification of Chinese herbs in Western pharmacies, leading to the publication of two volumes of books [ 55 ].

The US Pharmacopoeia has also included some Chinese herbs in their monographs. TCM has continuous records of thousands of years. Cover image of the volume one. In the s, randomised, controlled clinical trials began to successfully investigate claims for a series of TCM drugs. Atherton and colleagues conducted a series of such trials in the UK, investigating the efficacy of a TCM formula in the treatment of atopic eczema [ 41 , 57 ]. In Japan, double-blind placebo-controlled trials showed two kampo drugs to be both safe and efficacious in the treatment of constipation and perennial nasal allergy [ 48 ].

In Australia, two TCM products were shown to be efficacious in the treatment of irritable bowel syndrome and hepatitis C [ 58 , 59 ]. These clinical trials, among others, set important milestones for the overseas use of Chinese herbal medicine. In , Kanglaite, a botanical drug derived from Coix lacryma-jobi L. On the other hand, according to Cochrane and other independent reviews, many clinical trials on TCM were inconclusive, at least partially because of the low quality of many trials conducted in China [ 62 ]. Similarly, the quality of systematic reviews and data meta-analysis has also been criticised [ 63 ].

This situation is about to change. Since the mids, China has accelerated its steps in joining the international community of evidence-based medicine and clinical trials conducted in China have begun to be published in leading clinical journals [ 49 , 64 , 65 ]. Nevertheless, many challenges remain [ 43 ].

Some challenges are specific to TCM including the practice of personalised medicine and the difficulties in designing quality controls for TCM practices and drugs, about which international collaborations such as GP-TCM have led to the development of practical guidelines [ 66 , 67 ]. Traditional use, however, is only an indication but certainly not a proof of safety as dreadful mid-term and long-term toxicities have a low chance of being detected [ 68 ].

This is being increasingly recognised since when Vanherweghem and colleagues reported rapidly progressive interstitial renal fibrosis in women who had followed a slimming regimen inadvertently containing Aristolochia sp roots. Aristolochic acids were identified as mediators of not only the Aristolochia -induced renal fibrosis, the endemic Balkan nephropathy, but also Aristolochia -induced urothelial cancer [ 69 , 70 ]. These studies, together with some other reports, such as those on herb-drug interactions [ 38 ], aconite poisoning [ 44 ] and the hepato- and genotoxicity of pyrrolizidine alkaloids [ 72 ], gave an impetus to research the adverse effects of herbal medicines.

Given the number of herbal products on the market and relatively low budgets available for research so far, safety assessment has been carried out on relatively few herbs according to modern guidelines [ 68 ]. This emphasises the importance of pharmacovigilance in detecting any unfortunate adverse events [ 73 , 74 ]. Given the importance of ensuring quality of TCM drugs and safety of patients, legislation and regulation of TCM practitioners and products are equally important.

In the EU, the Committee on Herbal Medicinal Products HMPC of the European Medicines Agency EMA regulates the use of herbals and publishes herbal monographs and lists, which present a documented scientific opinion on the safety and efficacy data of herbal substances and their preparations intended for medicinal use [ 76 ].

Specifically, the HMPC evaluates scientifically all available information including non-clinical and clinical data but also documents long-standing use and experience in the EU. The different approaches of regulating herbal products have been also recognised as an important issue by the FP7 GP-TCM Consortium, which compiled a more comprehensive global comparison of herbal regulation practices in order to promote harmonisation in the future [ 61 ].

For the future development of TCM, raw materials must be produced in a sustainable way. Cultivation under good agricultural practice GAP should be the goal [ 78 , 79 ]. The scientific principles of daodi should be also considered — Daodi medicinal materials are those produced and assembled in specific geographic regions with designated natural conditions and ecological environment, with particular attention to cultivation technique, harvesting and processing, and thus regarded as superior in quality and effects as compared to materials of the same species obtained from other regions [ 80 ].

The identity and pharmaceutical quality of herbal medicinal products must be controlled in Europe and China according to the pharmacopoeia standards [ 81 ]. Due to the complex chemical composition of TCM drugs and many sources of variations that could lead to batch-to-batch inconsistency, classical quality control measures such as those applied to purified chemical drugs are often not suited to ensure quality of TCM materials and products. Sometimes DNA based methods may be needed for unambiguous authentication [ 82 ], but do not yield any information on the qualitative and quantitative chemical profiles.

In order to focus not only on single quality marker compounds, more holistic concepts need to be developed such as metabolic fingerprinting [ 83 , 84 ]. The FP7 GP-TCM Consortium have recognised authentication and quality control of research materials used in clinical, animal and in-vitro studies as an area that needs urgent improvement and have developed a checklist and good practice guidelines [ 67 , 86 ]. Funding bodies, journals, academia and commercial suppliers must collaborate closely to address this fundamental issue.

Post-harvest treatment and processing paozhi are common features in Chinese herbal medicine. In order to provide plant material of consistent quality, these processes need to be scientifically investigated and standard operating procedures and specific endpoints need to be defined and implemented [ 87 ]. Beyond the success in isolating new chemical entities amenable to drugs, such as artemisinin, emerging evidence suggested that multiple compounds from herbals might demonstrate synergism.


In vitro , the antimicrobial action of berberine was potentiated by multidrug pump inhibitors biosynthesised by the same plants that produce berberine or by different plants [ 88 , 89 ]. In acute promyelocytic leukaemia APL animal models and in APL cell lines, synergism among three active compounds isolated from the three components of a TCM formula was also demonstrated [ 90 ].

Until recently, the project focused on development of systematic separation methodology for resolving and analysing the complex components in Chinese herbal medicine and establishment of a comprehensive resource library [ 95 ]. This project might eventually help to understand the chemical basis of the active constituents of TCM drugs, be they single or multiple compounds. Clinical trials on treatment of pain and other diseases, adverse effects, mechanisms of action and discussions on the roles for the placebo effect in acupuncture continued to be active.

Earlier reports of adverse effects were usually related to insufficient basic medical knowledge, low hygienic standard and inadequate acupuncture education [ 96 ]. With disposable sterile needles and improved training and regulation of acupuncturists, more recent data from large surveys in the UK [ 97 , 98 ] and Germany [ 99 , ] have shown that adverse events after acupuncture are uncommon and acupuncture is a safe therapy in the hands of well trained professionals.

A placebo needle that does not penetrate the skin was introduced for sham acupuncture [ 35 ], a plausible tool to differentiate placebo effects caused by non-penetrating sham acupuncture [ , ]. A number of large-scale trials on the efficacy [ - ] and effectiveness [ , ] of acupuncture, as well as randomised controlled trials on the efficacy of combined therapy of acupuncture and Chinese herbal medicine [ ], have been published; a recent meta-analysis, that pooled the data of 29 clinical trials on chronic pain, concluded that acupuncture is statistically superior to sham acupuncture [ ].

However, debates about acupuncture point specificity, acupuncture techniques and placebo effects will likely continue. Nevertheless, a growing body of evidence had clinical implications. A number of physiological changes were documented as consequences of acupuncture needling, which might direct to possible mechanisms of action of acupuncture.

Scientific Study of Chinese Medicine

This was followed by a paper suggesting that adenosine, after breakdown of ATP in the skin, acted as a prejunctional modulator of nociceptive sensory pathways [ ]. The start of Phase III coincided with the announcements of three prestigious international awards for scientists involved in different aspects of TCM research [ - ]:.

In October , another highlight of the beginning of phase III was the final outputs from the FP7 GP-TCM project, which brought together a large collaborative network of over scientists and clinicians, more than institutions and 24 countries to work on the future directions of TCM. The main conclusions of this FP7 project were published in a special open-access issue of the Journal of Ethnopharmacology , in which good practice was defined, guidelines collated, information updated and priorities, challenges and opportunities agreed [ ].

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In the scientific context of TCM, integrity is defined as good practice and rigour, a concept of consistency of actions, values, methods, measures, principles, expectations and outcomes;. The word refers to an approach towards wholeness by either bringing parts together or by removing barriers; and. The word refers to renewal or change, as well as introducing better or more effective products, processes, services, technologies, or ideas, etc.

As a holistic medicine, TCM considers the human body as a whole, emphasises the importance of functions and emotions and considers patients as part of a system interacting with its environmental factors, such as diet, climate and life style. This is embodied in TCM diagnosis, prescriptions and life style interventions. Since the era of Sun Simiao — A. Now, TCM ethics should apply to not only TCM practitioners, but also the agricultural, industrial and scientific communities, and all stakeholders.

Conflict of interests should be avoided, stated and properly regulated. In such epic efforts, collaboration and sharing must be encouraged and we must strive for consensus while respecting differences.


Good practice is especially required in authentication, quality control, safety assessments and sustainable use of TCM drugs and materials; agricultural and manufacturing practices; commercial and clinical practices; basic and clinical research of TCM; application of routine and emerging technologies; as well as differentiation between valuable knowledge and superstitious, erroneous and misleading anecdotes [ , ]. Integration of these three important aspects was one of the most important achievements in modernisation of TCM and this must continue.

TCM is an important part of Chinese culture and is guided by Chinese philosophy. Thus, researchers of the scientific, cultural and philosophical values of TCM should collaborate with and learn from each other. In China and some other countries, TCM and Western medicine are both in mainstream healthcare and intend to complement each other.

Bringing evidence-based medicine to recognise the value of TCM will have to integrate a thorough rethinking of both Western and TCM practices to generate scientifically and statistically convincing evidence of the TCM-based approaches. Due to the complexity and the vast range of TCM, collaborations between different regions, different business sectors, as well as different areas of knowledge must be encouraged in order to share resources and expertise and join forces to meet the challenges together.

For example, the various distribution channels encountered in different countries must be connected in order to develop harmonised pharmacovigilance procedures suitable to rapidly and globally detect and assess warning signals for adverse events. TCM emphasises holistic and relationist approaches of thinking, while Western medicine is largely based on analytical and reductionist approaches. To see both the trees and the wood, these approaches must be integrated. These three most important aspects of TCM are so much interrelated that future training and research must further integrate these crucial elements to better ensure safety and efficacy.

Although some achievements have already arisen through studying TCM using a Western approach, e. Among all aspects of TCM, holistic TCM diagnosis has probably the most complementary elements to modern medical practice, including its function-oriented description of organ systems and diagnostic approach leading to syndrome differentiation , its emphasis on modulation of functional balance, its comprehensive categorisation and interpretation of tongue and pulse patterns, its characteristic categorisation of the nature of diseases and drugs, etc.

These could be important sources for developing and validating innovative mindset, methods, tools and strategies that could complement biology-based diagnosis [ , ]. TCM is characterised by both pre-emptive approaches and interventions with multiple components. It emphasises intervention before disease arises and often combines dietary advice, physical exercises such as Taijiquan Tai Chi Chuan [ , ], meditation, herbal medicines, massage, acupuncture and moxibustion, etc. The values of these individualised and integrated approaches are important directions for future public health.

The complexity of TCM demands novel and more robust ways of thinking, approaches, tools and methods. For example, the individualised and holistic nature of TCM requires tools for complexity research, research of the science of individuality and personalised medicine, as well as novel statistics [ ]. It also awaits the maturation of omics, systems biology and other systems-based technologies [ ].

In view of the vast areas of TCM yet to be explored and the limited resources available for such an emerging area of research in the global context, prioritisation and focus become the key to achieving real innovation. After 60 years of development, modernisation of TCM has arrived at a new era. To achieve this, especially to reach the goals of better quality, safety and efficacy, the proposed rules of integrity , integration and innovation must be followed. Acute promyelocytic leukaemia; ATP: Higher education institutions; HMPC: Investigational new drug; ISO: International Organization of Standardization; LC: The World Health Organization.

QX contributed to the overall conceptualisation and project plan, coordinated various sections of the paper, synthesised the findings and coordinated the writing of the paper. RB contributed to the overall writing and revision, especially on milestones outside China and in sections on TCM resources, quality control and standardisation. PJH and BMH contributed to the overall conceptualisation, synthesised the findings and played central roles in discussion and revision of the manuscript.

T-PF contributed to the overall revision and provided some very critical references and ideas. PD contributed to the writing and critical revision of the whole manuscript, especially the toxicology section. CMW and NR gathered literature and information and wrote part of the acupuncture section, as well as contributed to the overall discussion and revision process. MSJS did literature analysis for the whole paper and contributed to the overall discussion and revision of the manuscript. DG provided some useful discussions and revisions on the manuscript.

All authors read and approved the final manuscript. We thank all project members for their contributions that have inspired this manuscript and in particular, we gratefully acknowledge the following colleagues for their critical discussions on this manuscript: National Center for Biotechnology Information , U. Published online Jun Author information Article notes Copyright and License information Disclaimer.

M ; Claudia M Witt: Received Feb 17; Accepted May This article has been cited by other articles in PMC. Introduction Traditional Chinese medicine TCM is a holistic medical system for diagnosis, prevention and treatment of diseases and has been an integral part of Asian cultures for thousands of years. Review These past 60 years can be divided into two year phases, which are followed by a prospective phase III that will be crucial for the scientific prospects of TCM.

Phase II ss This phase was especially characterised by the following main hallmarks: TCM resources From to , China conducted a series of nationwide surveys on the substances used in TCM practice across the country. Open in a separate window. Efficacy and effectiveness of Chinese herbal medicine In the s, randomised, controlled clinical trials began to successfully investigate claims for a series of TCM drugs. Legislation and regulation of Chinese herbal medicine Given the importance of ensuring quality of TCM drugs and safety of patients, legislation and regulation of TCM practitioners and products are equally important.

Quality control and standardisation of Chinese herbal medicine For the future development of TCM, raw materials must be produced in a sustainable way. Mechanisms and herbalome Beyond the success in isolating new chemical entities amenable to drugs, such as artemisinin, emerging evidence suggested that multiple compounds from herbals might demonstrate synergism. Acupuncture Clinical trials on treatment of pain and other diseases, adverse effects, mechanisms of action and discussions on the roles for the placebo effect in acupuncture continued to be active. The start of phase III — and the future The start of Phase III coincided with the announcements of three prestigious international awards for scientists involved in different aspects of TCM research [ - ]: These concepts are further expanded and interpreted below.

Conclusions After 60 years of development, modernisation of TCM has arrived at a new era. Competing interest The authors declare that they have no competing interests. Six surrounding words were collected for each instance of an entity, three before and three after the instance. After removing the infrequent words, distinct words remained. We then defined a feature function for each of the words, to indicate the frequency that each word appeared around the two end-entities of a relation.

Determining the latent semantic relatedness of the two end-entities may also be helpful for identifying a relation.

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For calculating semantic distance, we first need to represent the semantic meanings of each entity. Distributed vector representations facilitate learning word meanings from large collections of text. Each word is learned as a distinct pattern of continuous values over a single, large vector, with each dimension corresponding to a latent topic. We can then measure the semantic relatedness among words in terms of distances in the resulting vector space.

We used word2vec 40 https: We then defined a feature function on each dimension by using the absolute value of the difference between the values of the dimensions of the two end-entities. Except for the above three categories of features, syntactic structure ie, dependency relation is another type of information that is useful for relation extraction. However, being able to determine syntactic structure requires that the two end-entities co-occur within one single sentence.

So, we did not take syntactic structure into account in this study. Illustration of the transitive property of triadic closures. We propose using a semi-supervised learning algorithm to estimate the parameters of the model see Supplementary Appendix A , which enables us to predict the labels of unknown edges based on the estimated parameters see Supplementary Appendix B. We trained and evaluated our proposed HFGM on the dataset we collected and annotated.

Five types of relations — herb-syndrome, herb-disease, formula-syndrome, formula-disease, and syndrome-disease — were extracted from the TCM literature we analyzed. The entire semi-supervised learning and inference process took about 4. A traditional classification approach was employed as the baseline, in which the co-occurring frequency, lexical context, as well as the aforementioned semantic distance were taken as the classification features.

Because the number of features involved in this approach was very large, we used an SVM 41 www. We designed an iterative SVM classifier in our experiments that takes the results of the basic SVM classifier as the initiate values of all the labels, then iteratively updates the label of each relation by simultaneously using its observed features and inferred neighboring label values, until the labels no longer change. In this study, we also defined iterative features based on the transitive property of triadic closures.

Specifically, we calculated the numbers of triadic closures with different sums ie, 0, 1, 2, and 3, as shown in Figure 4 that were formed by each relation with its neighboring relations. We performed a five-fold cross-validation to evaluate the performance of our model. Table 3 shows the performance of the HFGM as compared with that of two other approaches. To further determine the effectiveness of our approach, we plotted receiver operating characteristic curves of the basic SVM and HFGM approaches as shown in Figure 5 , where the y -axis represents the rate of predicated positive labels in all the positive samples, and the x -axis represents the rate of predicted positive labels in all the negative samples.

Receiver operating characteristic curves of different approaches for extracting a herb-syndrome, b herb-disease, c formula-syndrome, d formula-disease, and e syndrome-disease relations. The y -axis represents the true positive rate and the x -axis represents the false positive rate. After performing an in-depth analysis of some specific instances, we found that our HFGM significantly improves the accuracy of relation extraction in the following cases in which traditional classifiers have difficult identify relations:. The context is very short. For a candidate relation, we took the co-occurring frequency of the two end-entities appearing in the same documents and the frequencies of their surrounding words as the classification features, so if a relation only appears once in a single, short document, then the context information will not be enough to identify the relation.

The context contains confusing information. In some TCM treatment experiments, one or more control groups are used to compare the effectiveness of different treatments, which often misleads traditional classifiers to extract some relations from the control groups that are not actually present. Several different studies are reported on in the same document. Occasionally, several studies will be covered within a single article or even a single sentence. The name of an entity is a polysemous word. Some Chinese names for TCM entities have other meanings.

Scientific Study of Chinese Medicine

The effectiveness of the HFGM demonstrates the existence of correlations among different types of relations. In addition, using the transitive property of triadic closures to model the dependencies among the labels of edges in the network is a reasonable and practicable approach. However, some of our results can be improved upon, and some of the approaches we employ can be expanded upon in the future. Firstly, some other types of important TCM entities, such as symptoms, are not incorporated into our model.

This is because there is not a standard or unified terminology glossary for TCM symptoms, so entity recognition techniques are needed to detect the instances of symptom entities in text. If we can bring such entities into our unified model in the future, then more types of relations can be extracted. Another challenge is that the computational complexity of learning the HFGM is very high, because multiple rounds of approximate inferences are required over the entire dataset see Algorithm 1 of the online supplementary data.

Consequently, we need to develop efficient learning approaches. In addition, other approximation techniques, such as the pseudolikelihood measure, 42 , 43 may also be used in our collective inference methods. Our approach also be directly applied to relation extraction in the field of biomedical text mining. We can construct heterogeneous networks between biomedical entities eg, proteins, genes, phenotypes, biological targets, diseases, drugs, treatments gathered from biomedical literature or clinical records, then employ the HFGM to extract biomedical relations in the context of these heterogeneous biomedical networks.

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  4. The HFGM model proposed in this article is only suitable for heterogeneous entity networks that contain at least three kinds of entities, because we use triadic closures formed by three kinds of entities to construct compatibility factors in the model. Another limitation of the current version of our model is that it can only extract one class of relations between the same two types of entities at the same time, because we treat the relation extraction problem as a binary classification problem in this study.

    In this article, we examine the problem of automatically extracting meaningful entity relations from TCM literature and propose an HFGM that exploits the power of collective inference in the context of heterogeneous entity networks to simultaneously and globally extract all types of relations eg, herb-syndrome, herb-disease, formula-syndrome, formula-disease, and syndrome-disease relations from the entire corpus of TCM data.

    We propose using a semi-supervised learning algorithm to estimate the parameters of the model. The results of our analysis of a professionally annotated dataset show that our approach is superior to traditional classification methods in extracting multiple types of relations from TCM literature.

    This work was mainly done while the first author was visiting KU Leuven, Belgium. The work was a collaboration between all the authors. All the authors have made valuable contributions to revising and approving the manuscript. Supplementary material is available online at Supplementary Data.

    Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Sign In or Create an Account. Close mobile search navigation Article navigation. Extracting relations from traditional Chinese medicine literature via heterogeneous entity networks Huaiyu Wan. Abstract Objective Traditional Chinese medicine TCM is a unique and complex medical system that has developed over thousands of years. View large Download slide.

    Then, the joint probability can be factorized as follows: The joint probability defined in Equation 1 can be rewritten as: We defined one category of feature functions for compatibility factors based on the transitive property of triadic closures. Figure 4 gives an illustration of the transitive property, in which the labels of three edges form a triad closure. According to the transitive property, we can define the feature function as follows: Integrating next-generation sequencing and traditional tongue diagnosis to determine tongue coating microbiome.

    Text mining for traditional Chinese medical knowledge discovery: Automated acquisition of disease-drug knowledge from biomedical and clinical documents: Large scale application of neural network based semantic role labeling for automated relation extraction from biomedical texts. Consolidating the set of known human protein-protein interactions in preparation for large-scale mapping of the human interactome. Automated extraction of information on protein-protein interactions from the biological literature. Automatic extraction of relations between medical concepts in clinical texts.

    Extraction of semantic biomedical relations from text using conditional random fields. Semantic retrieval for the accurate identification of relational concepts in massive textbases. Mining of relations between proteins over biomedical scientific literature using a deep-linguistic approach. All-paths graph kernel for protein-protein interaction extraction with evaluation of cross-corpus learning.

    Protein-protein interaction extraction by leveraging multiple kernels and parsers. Text mining for finding functional community of related genes using TCM knowledge. The directed closure process in hybrid social-information networks, with an analysis of link formation on Twitter. Distributed representations of words and phrases and their compositionality. A community-based pseudolikelihood approach for relationship labeling in social networks. For Permissions, please email: Email alerts New issue alert. Receive exclusive offers and updates from Oxford Academic.

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