Ontologies and Computational Methods for Traditional Chinese Medicine

Perinteinen kiinalainen lääketiede (PKL) on tuhansia vuosia vanha hoitomuoto, jonka tarkoituksena on terveyden ylläpito, tautien ennaltaehkäisemisen ja terveydellisten ongelmien hoito. Useat vuosittain julkaistavat tutkimukset tukevat hoitojen tehokkuutta ja PKL onkin jatkuvasti kasvattamassa suosiotaan maailmanlaajuisesti. Kiinassa PKL ollut suosittu hoitomuoto jo pitkään ja nykyään sitä harjoitetaan rinnakkain länsimaisen lääketieteen kanssa. Viime vuosikymmeninä tapahtuneen tietotekniikan kehityksen ja yleistymisen myötä myös PKL:n menetelmät ovat muuttuneet ja tietotekniikkaa on alettu hyödyntämään PKL:n tutkimuksessa. PKL:n tietoa on tallennettu digitaaliseen muotoon, minkä seurauksena on syntynyt suuri määrä erilaisia tietokantoja. Tieto on jakautunut eri tietokantoihin, joiden terminologia ei ole yhtenevää. Tämä aiheuttaa ongelmia tiedon löytämisessä ja tietoa hyödyntävien sovellusten kehittämisessä. Tässä työssä selvitetään, mitä PKL on, ja mikä sen asema on nykyään Kiinassa ja muualla maailmalla. Työn tarkoituksena on tutkia PKL:n tietoteknisten sovelluksen kehittämistä ja siihen liittyviä haasteita. Työssä perehdytään PKL:n ontologioiden ja semanttisten työkalujen toimintaan, sekä PKL:n laskennallisiin menetelmiin ja niiden tarjoamiin mahdollisuuksiin. Lisäksi kerrotaan uusimmista kansainvälisesti merkittävistä projekteista ja pohditaan tulevaisuuden näkymiä. Jo kehitetyt PKL:n tietotekniset sovellukset tarjoavat uusia mahdollisuuksia tiedon etsimiseen ja parantavat tutkijoiden mahdollisuutta jakaa tietoa ja tehdä yhteistyötä. Tietokoneavusteiset diagnoosityökalut ja asiantuntijajärjestelmät tarjoavat mahdollisuuksia lääkärin tekemän diagnoosin varmistamiseen. Tulevaisuudessa laskennallisia menetelmiä hyödyntäen voitaisiin tarjota terveyttä ja hyvinvointia edistäviä palveluja verkossa.Traditional Chinese Medicine (TCM) has been used for thousands of years in China for the purposes of health maintenance, disease prevention and treatment of health problems. Several published studies support the effectiveness of TCM treatments and the global use of TCM is constantly increasing. In China, Western and Chinese medicine are practiced in parallel. During the past few decades, the use of information technology in medicine has increased rapidly. The development of information technology has opened up new possibilities for information storage and sharing, as well as communication and interaction between people. Along with the growing use of information technology, a wide variety of patient databases and other electronic sources of information have emerged. However, the information is fragmented and dispersed, and the terminology is ambiguous. The objective of the thesis is to examine the position of TCM today, and to find out what changes and new opportunities the modern information technology brings for different aspects of TCM. This study describes how ontologies and semantic tools can be utilized when collecting existing knowledge and combining different databases. Also different computational methods and TCM expert systems are introduced. Finally, the most recent projects in the field of TCM are discussed and the future challenges are reflected. The computational methods for TCM, such as diagnostic tools and expert systems, could be very useful in anticipating and preventing health problems. E-science and knowledge discovery offer new ways for knowledge sharing and cooperation. TCM expert systems can be used to generate diagnosis or automatic clinical alerts. In the future, a comprehensive and easily accessible online health service system could be developed and used to improve the health and well-being of people

Conceptual graph-based knowledge representation for supporting reasoning in African traditional medicine

Although African patients use both conventional or modern and traditional healthcare simultaneously, it has been proven that 80% of people rely on African traditional medicine (ATM). ATM includes medical activities stemming from practices, customs and traditions which were integral to the distinctive African cultures. It is based mainly on the oral transfer of knowledge, with the risk of losing critical knowledge. Moreover, practices differ according to the regions and the availability of medicinal plants. Therefore, it is necessary to compile tacit, disseminated and complex knowledge from various Tradi-Practitioners (TP) in order to determine interesting patterns for treating a given disease. Knowledge engineering methods for traditional medicine are useful to model suitably complex information needs, formalize knowledge of domain experts and highlight the effective practices for their integration to conventional medicine. The work described in this paper presents an approach which addresses two issues. First it aims at proposing a formal representation model of ATM knowledge and practices to facilitate their sharing and reusing. Then, it aims at providing a visual reasoning mechanism for selecting best available procedures and medicinal plants to treat diseases. The approach is based on the use of the Delphi method for capturing knowledge from various experts which necessitate reaching a consensus. Conceptual graph formalism is used to model ATM knowledge with visual reasoning capabilities and processes. The nested conceptual graphs are used to visually express the semantic meaning of Computational Tree Logic (CTL) constructs that are useful for formal specification of temporal properties of ATM domain knowledge. Our approach presents the advantage of mitigating knowledge loss with conceptual development assistance to improve the quality of ATM care (medical diagnosis and therapeutics), but also patient safety (drug monitoring)

Network Pharmacology Approaches for Understanding Traditional Chinese Medicine

Traditional Chinese medicine (TCM) has obvious efficacy on disease treatments and is a valuable source for novel drug discovery. However, the underlying mechanism of the pharmacological effects of TCM remains unknown because TCM is a complex system with multiple herbs and ingredients coming together as a prescription. Therefore, it is urgent to apply computational tools to TCM to understand the underlying mechanism of TCM theories at the molecular level and use advanced network algorithms to explore potential effective ingredients and illustrate the principles of TCM in system biological aspects. In this thesis, we aim to understand the underlying mechanism of actions in complex TCM systems at the molecular level by bioinformatics and computational tools. In study Ⅰ, a machine learning framework was developed to predict the meridians of the herbs and ingredients. Finally, we achieved high accuracy of the meridians prediction for herbs and ingredients, suggesting an association between meridians and the molecular features of ingredients and herbs, especially the most important features for machine learning models. Secondly, we proposed a novel network approach to study the TCM formulae by quantifying the degree of interactions of pairwise herb pairs in study Ⅱ using five network distance methods, including the closest, shortest, central, kernel, as well as separation. We demonstrated that the distance of top herb pairs is shorter than that of random herb pairs, suggesting a strong interaction in the human interactome. In addition, center methods at the ingredient level outperformed the other methods. It hints to us that the central ingredients play an important role in the herbs. Thirdly, we explored the associations between herbs or ingredients and their important biological characteristics in study III, such as properties, meridians, structures, or targets via clusters from community analysis of the multipartite network. We found that herbal medicines among the same clusters tend to be more similar in the properties, meridians. Similarly, ingredients from the same cluster are more similar in structure and protein target. In summary, this thesis intends to build a bridge between the TCM system and modern medicinal systems using computational tools, including the machine learning model for meridian theory, network modelling for TCM formulae, as well as multipartite network analysis for herbal medicines and their ingredients. We demonstrated that applying novel computational approaches on the integrated high-throughput omics would provide insights for TCM and accelerate the novel drug discovery as well as repurposing from TCM.Perinteinen kiinalainen lääketiede (TCM) on ilmeinen tehokkuus taudin hoidoissa ja on arvokas lähde uuden lääkkeen löytämiseen. TCM: n farmakologisten vaikutusten taustalla oleva mekanismi pysyy kuitenkin tuntemattomassa, koska TCM on monimutkainen järjestelmä, jossa on useita yrttejä ja ainesosia, jotka tulevat yhteen reseptilääkkeeksi. Siksi on kiireellistä soveltaa Laskennallisia työkaluja TCM: lle ymmärtämään TCM-teorioiden taustalla oleva mekanismi molekyylitasolla ja käyttävät kehittyneitä verkkoalgoritmeja tutkimaan mahdollisia tehokkaita ainesosia ja havainnollistavat TCM: n periaatteita järjestelmän biologisissa näkökohdissa. Tässä opinnäytetyössä pyrimme ymmärtämään monimutkaisten TCM-järjestelmien toimintamekanismia molekyylitasolla bioinformaattilla ja laskennallisilla työkaluilla. Tutkimuksessa kehitettiin koneen oppimiskehystä yrttien ja ainesosien meridialaisista. Lopuksi saavutimme korkean tarkkuuden meridiaaneista yrtteistä ja ainesosista, mikä viittaa meridiaaneihin ja ainesosien ja yrtteihin liittyvien molekyylipiirin välillä, erityisesti koneen oppimismalleihin tärkeimmät ominaisuudet. Toiseksi ehdoimme uuden verkon lähestymistavan TCM-kaavojen tutkimiseksi kvantitoimisella vuorovaikutteisten yrttiparien vuorovaikutuksen tutkimuksessa ⅱ käyttämällä viisi verkkoetäisyyttä, mukaan lukien lähin, lyhyt, keskus, ydin sekä erottaminen. Osoitimme, että ylä-yrttiparien etäisyys on lyhyempi kuin satunnaisten yrttiparien, mikä viittaa voimakkaaseen vuorovaikutukseen ihmisellä vuorovaikutteisesti. Lisäksi Center-menetelmät ainesosan tasolla ylittivät muut menetelmät. Se vihjeitä meille, että keskeiset ainesosat ovat tärkeässä asemassa yrtteissä. Kolmanneksi tutkimme yrttien tai ainesosien välisiä yhdistyksiä ja niiden tärkeitä biologisia ominaisuuksia tutkimuksessa III, kuten ominaisuudet, meridiaanit, rakenteet tai tavoitteet klustereiden kautta moniparite-verkoston yhteisön analyysistä. Löysimme, että kasviperäiset lääkkeet samoilla klusterien keskuudessa ovat yleensä samankaltaisia ominaisuuksissa, meridiaaneissa. Samoin saman klusterin ainesosat ovat samankaltaisempia rakenteissa ja proteiinin tavoitteessa. Yhteenvetona tämä opinnäytetyö aikoo rakentaa silta TCM-järjestelmän ja nykyaikaisten lääkevalmisteiden välillä laskentatyökaluilla, mukaan lukien Meridian-teorian koneen oppimismalli, TCM-kaavojen verkkomallinnus sekä kasviperäiset lääkkeet ja niiden ainesosat Osoitimme, että uusien laskennallisten lähestymistapojen soveltaminen integroidulle korkean suorituskyvyttömiehille tarjosivat TCM: n näkemyksiä ja nopeuttaisivat romaanin huumeiden löytöä sekä toistuvat TCM: stä

Emergent quality issues in the supply of Chinese medicinal plants: A mixed methods investigation of their contemporary occurrence and historical persistence

Quality issues that emerged centuries ago in Chinese medicinal plants (CMP) were investigated to explore why they still persist in an era of advanced analytical testing and extensive legislation so that a solution to improve CMP quality could be proposed. This is important for 85% of the world’s population who rely on medicinal plants (MP) for primary healthcare considering the adverse events, including fatalities that arise from such quality issues. CMP are the most prevalent medicinal plants globally. This investigation used mixed-methods, including 15 interviews with CMP expert key informants (KI), together with thematic analysis that identified the main CMP quality issues, why they persisted, and informed solutions. An unexplained case example, Eleutherococcus nodiflorus (EN), was analysed by collection of 106 samples of EN, its known toxic adulterant Periploca sepium (PS), and a related substitute, Eleutherococcus senticosus (ES), across mainland China, Taiwan and the UK. Authenticity of the samples was determined using High-performance thinlayer chromatography. Misidentification, adulteration, substitution and toxicity were the main CMP quality issues identified. Adulteration was found widespread globally with 57.4% EN found authentic, and 24.6% adulterated with cardiotoxic PS, mostly at markets and traditional pharmacies. The EN study further highlighted that the reason CMP quality issues persisted was due to the laboratory-bound nature of analytical methods and testing currently used that leave gaps in detection throughout much of the supply chain. CMP quality could be more effectively tested with patented analytical technology (PAT) and simpler field-based testing including indicator strip tests. Education highlighting the long-term economic value and communal benefit of delivering better quality CMP to consumers was recommended in favour of the financial motivation for actions that lead to the persistence of well-known and recurrent CMP quality issues

Chinese herbal medicine for insomnia : evidence and experience

Insomnia, a condition with significant medical consequences, is becoming more and more prevalent worldwide. Hypnotic drugs are associated with dependence, adverse reactions and long-term risks. Psychotherapy is time- and resource-consuming and largely unavailable. As such, many people who present with insomnia also look for alternative treatments. Recent studies show that Chinese herbal medicine (CHM), a traditional herbal medicine based on holistic theories, could be a potential alternative. The aims of this doctoral research were to explore the potential benefits of CHM for the treatment of insomnia and provide guidance in the treatment of insomnia with CHM. For practical reasons, the empirical aspect of the investigation focuses on one specific CHM product, which is Zao Ren An Shen (ZRAS). The research questions include: (1) Is ZRAS a safe and effective treatment for insomnia disorder? (2) How do Chinese medicine clinicians diagnose and treat insomnia with CHM? This doctoral research consists of a narrative review and three major studies: one systematic review, one randomised, placebo-controlled trial and one clinical experience synthesis. In the systematic review, clinical trial that assessed the efficacy and/or safety of ZRAS for insomnia were systematically searched and screened. In the clinical trial, after one week of placebo run-in, 85 participants with insomnia disorder were randomly allocated to either take ZRAS capsule or placebo for four weeks. Insomnia severity, psychological status, fatigue levels, quality of life, subjective sleep parameters, objective sleep parameters, and adverse events were assessed through the intervention period and at a four-weeks follow-up. Both the investigator and the participants were blind to the treatment allocation. In the clinical experience synthesis (CES), clinical experience reports published in the literature, which described treatment of insomnia with CHM, were systematically reviewed and screened. The systematic review shows that ZRAS is safe and effective for insomnia. The randomised trial support ZRAS capsule as a safe and acceptable treatment, yet failed to improve significantly insomnia severity in insomnia patients. These differences may be explained by the poor quality of the studies included in the systematic review. The studies included in the systematic review and the randomised trial both used a standardised intervention approach. However, Chinese medicine clinician recommend an individualised approach, which may contribute to improved outcomes across a broader range of measures

Investigating the translation of metaphors used in diagnosis and treatment in Chinese medicine classics Neijing and Shanghan Lun

The language used in Traditional Chinese Medicine (TCM) depicts a world of human physiology, pathology, diagnosis and treatment, in which metaphors serve as an essential vehicle for readers to understand fundamental but often abstract concepts in TCM. While previous work has investigated strategies for translating the TCM classics, the metaphors used to describe diagnosis and treatment and their English translations are critical in understanding TCM, and require a more systematic exploration. This study investigates the diagnosis- and treatment-related metaphors selected from two TCM classics, Neijing and Shanghan Lun, and their English renditions by translators from different professional backgrounds. The thesis also focuses on the analysis of the effectiveness of different translation strategies in delivering pertinent health-related information conveyed by the metaphors of the original texts. A multidimensional framework that combines a conceptual approach with linguistic and cultural elements was established to capture the complexity of the metaphors, particularly from the perspective of translation. The linguistic metaphors in this study were first identified from a purpose-built corpus using a CMT-based metaphor identification procedure adapted from Steen (2010). Following the conceptual metaphor inference procedure developed by Steen (2011), various conceptual metaphors were inferred from the linguistic metaphors. Corresponding English translations were also collected to investigate which translation strategies have been used and which strategy can most effectively deliver the health-related information conveyed by the metaphors. Four main strategies were employed in the English translations: 1) equivalent mapping, by which the source domain is retained; 2) using a simile to translate a metaphor; 3) direct narrative equivalence, which abandons the metaphor and narrates the medical knowledge directly; and 4) complemented equivalent translation, whereby the metaphor is explained with additional content. From the perspective of conveying health-related knowledge, equivalent mapping was effective for metaphors universally understood by Chinese and English readers. For culturally specific metaphors, especially when the metaphor relates to an important TCM concept, complemented equivalent translation, which can reconfigure the cognitive context for the reader, was most suitable. For metaphors not related to important concepts, direct narrative equivalence was found to be effective