Faculty Of Education UNHI

Faculty Of Education UNH

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

TB STIGMA – MEASUREMENT GUIDANCE

TB is the most deadly infectious disease in the world, and stigma continues to play a significant role in worsening the epidemic. Stigma and discrimination not only stop people from seeking care but also make it more difficult for those on treatment to continue, both of which make the disease more difficult to treat in the long-term and mean those infected are more likely to transmit the disease to those around them. TB Stigma – Measurement Guidance is a manual to help generate enough information about stigma issues to design and monitor and evaluate efforts to reduce TB stigma. It can help in planning TB stigma baseline measurements and monitoring trends to capture the outcomes of TB stigma reduction efforts. This manual is designed for health workers, professional or management staff, people who advocate for those with TB, and all who need to understand and respond to TB stigma

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

The Future of Medicine: Frontiers in Integrative Health and Medicine

Contemporary healthcare trends indicate that many chronic and communicable diseases are related to lifestyle, stress, personal choices and systemic factors. In response to the shortfalls of modern medicine regarding the prevention of these diseases and the promotion of whole-person health, providers and consumers worldwide are exploring integrative, natural and complementary approaches to prevention, treatment and health promotion. These trends harbor the future of medicine. The issues of clinician burnout, high rates of adverse effects, high cost, and lack of rigorous methods to promote individual and collective immunity are addressed by leading physicians and scientists from around the world. The original research and reviews in this volume investigate efficacy, molecular mechanisms and hypotheses that suggest that traditional systems of medicine and health, e.g., Ayurveda, yoga, traditional Chinese medicine, and mind–body–lifestyle medicine, may offer preventive and cost-effective solutions to contemporary health care challenges. Integrating innovative health approaches with conventional medicine offers a whole system of medicine that encompasses the individual, family, community and environment—from single person to planetary health

Health Communication Research Among the Chinese Hui Ethnic Minority Group in Shenyang City

This dissertation aims to contribute to the development of health communication in China by reporting on the results of explorative empirical research conducted among the Chinese Hui people in Shenyang City

The emergence of clusters in societal transition : a coevolutionary perspective on the TCM cluster at Tonghua/China

New industries are recognized as new impetus to national wealth. At the same time, they are increasingly becoming geographically concentrated in some well defined areas. But current studies on the emergence of industrial clusters tend to analyze favorable driving factors. This dissertation takes the example of a Chinese endogenous industrial cluster, the traditional Chinese medicine (TCM) cluster at Tonghua, a small peripheral city in Northeastern China, to contribute to the theoretical understanding of the emergence of industrial cluster as a co-evolutionary process of organizations, institutions and firms, or, to put it more broadly, as economic evolution embedded in complex socio-economic contexts. The recent advance in evolutionary and co-evolutionary economics which considers the economy and economic landscape as dynamic process instead of equilibrium can be regarded as a part of broader and more intellectual turn of quest for history in social sciences. Although the principle of "history matters" is widely acknowledged, it tends to be reduced to a quite simple concept of "path dependence". However, path dependence cannot offer space for new path creation, except from an external shock. Accordingly, the role of human conscious action or Schumpeterian innovation should be added to path analysis through the concept of path creation. Furthermore, and more importantly, history should be understood as context, and historical context can be explored through the understanding of multi-paths and interaction among them over time. So path inter-dependence (co-evolution between paths) would be useful to better understand the complexity of real history. Since the industrial cluster is composed of interconnected firms and is also subject to changes in institution and technology, I will focus on the multi-way causal relationship between firm, institution and technology. The theorizing is not entirely new, but most of the theoretical and empirical discussions are at the national or industrial level, not regional or local one. A competitive cluster can be regarded as a co-evolutionary hotspot in which multiple populations actively interact and are interconnected. Co-evolution itself is a dynamic and evolutionary process. So I will adopt a dynamic and evolutionary view to examine co-evolutionary degree or co-evolutionary effects in the Tonghua pharmaceutical cluster through time. After a brief introduction which deals with the national institutional changes that are highly associated with new venture creation, entrepreneurship, and innovation, with registrations on drug and healthcare system, and with changes in market demand of China’s pharmaceutical industry and geographical distribution, I will collect evidences from three aspects based upon field survey and second hand data, i.e., the history of the enterprises, the origin of entrepreneurship, and the knowledge of evolution, linking their respective generative relationships through the genealogical method. In this volume, the evolution of the Tonghua pharmaceutical firm organization, the formation of local entrepreneurship, historical accumulation of knowledge, and particular knowledge of transfer among generations of firms will be discussed, then I will probe into co-adaption and co-evolution between local formal and informal institutions and organizations in Tonghua’s TCM industry. In addition, I will try to understand the co-evolutionary process at different geographical levels (namely, national and local). In summary, my main findings include the following several points. Firstly, in the course of the emergence of Tonghua’s pharmaceutical industry, local social networks and the traditional alliance between enterprises and government have played important roles. Secondly, the most important factor that influences the evolution of endogenous industrial clusters such as the Tonghua pharmaceutical industry in transitional countries is not the change in technology, but the change in fundamental national institutions. Thirdly, the success of the Tonghua pharmaceutical industry can be ascribed to the creation of multiple paths largely based on initial conditions, which implies that economic policy should have historical consciousness, namely, new economic innovation should make full use of both historical legacies and existing assets. Finally, it is co-adaption and co-selection of firm organization, institution, and technology that have jointly made Tonghua’s pharmaceutical industry become highly competitive, which means that whether one region can grasp new opportunities partially depends on its capabilities to coordinate a varity of development agents.Neue Industrien werden im Allgemeinen als Impuls der Entwicklung zu nationalem Wohlstand verstanden. Zugleich sind sie überwiegend an einigen geographisch genau definierten Orten konzentriert. Aktuelle Studien zur Emergenz dieser Industrie-Cluster neigen dazu, entsprechende begünstigende Faktoren zu analysieren. Mit dem Beispiel eines endogenen Clusters in China, dem Cluster der Traditionellen Chinesischen Medizin (TCM) in Tonghua, will diese Dissertation zum theoretischen Verständnis der Emergenz von Industrie-Clustern unter der Perspektive eines ko-evolutorischen Prozesses von Form der Organisation, Institutionen und Unternehmen beitragen. Oder, um es etwas breiter auszudrücken, diese Emergenz als ökonomische Evolution zu verstehen, die in einen komplexen sozio-ökonomischen Kontext eingebettet ist. Obgleich der Vorstellung, Geschichte habe eine Bedeutung („history matters“), überwiegend in der Forschung zugestimmt wird, bleibt diese oft auf das Konzept der Pfadabhängigkeit beschränkt. Das aber eröffnet keinen Raum für die Betrachtung endogener Pfad-Bildung. Dem Konzept der Pfad-Bildung entsprechend sollte jedoch die Pfadanalyse ergänzt werden um bewusste Handlungen des Menschen oder auch um Innovationen im Schumpeterschen Sinn. Wichtiger ist außerdem, dass Geschichte als ein Kontext verstanden werden sollte, in dem mehrere Pfade ko-existieren und im Zeitverlauf auch interagieren. So wäre ein Konzept der Pfad-Interdependenz (oder der Ko-Evolution von Pfaden) nützlich zum besseren Verständnis der Komplexität „wirklicher“ Geschichte. Weil das Industriecluster sich aus untereinander verflochtenen Unternehmen zusammen setzt und zugleich Gegenstand von Änderungen in den Institutionen und der Technologie ist, konzentriert sich die Dissertation auf vielseitige kausale Beziehungen von Unternehmen, Institutionen und Technologie. Ein wettbewerbsfähiges Cluster kann aus geographischer Sicht als ein „hot spot“ der Ko-evolution betrachtet werden, in dem verschiedenartige Populationen aktiv untereinander agieren und daher miteinander verflochten sind. Ko-Evolution selbst ist dann ein dynamischer und evolutorischer Prozess. Die Arbeit wählt diese Perspektive, um das Maß und die Wirkungen der Ko-Evolution im Pharma-Cluster von Tonghua im Zeitverlauf zu analysieren. Die Dissertation fußt auf empirischen Erhebungen, ergänzt um eine Dokumenten-Analyse, zur Geschichte der Unternehmen, der Herkunft der Unternehmerschaft sowie der Evolution von Wissen. Sie diskutiert die Evolution in den Organisationsformen der Pharma-Unternehmen in Tonghua, die Bildung einer lokalen Unternehmerschaft, die historische Akkumulation von Wissen und den besonderen Wissenstransfer zwischen Generationen von Unternehmen. Schließlich untersucht sie die Ko-Adaption und Ko-Evolution von lokalen formalen und informellen Institutionen und Organisationen der TCM-Industrie in Tonghua. Die folgenden Punkte betreffen die wichtigsten Ergebnisse der Dissertation: Erstens haben sehr langfristige und dichte lokale soziale Netzwerke eine erhebliche Rolle im Lauf der Emergenz der Pharma-Industrie in Tonghua gespielt. Zweitens ist der wichtigste Faktor in der Pharma-Industrie nicht im technologischen Fortschritt durch Anstrengungen bei Forschung und Entwicklung (FuE) zu sehen, sondern im institutionellen Wandel sowohl auf nationaler als auch auf lokaler Ebene. Drittens kann der Erfolg der Pharma-Industrie in Tonghua der Bildung multipler Pfade zugeschrieben werden, die auf bestimmten Anfangsbedingungen gründen. Das bedeutet, dass die neue ökonomische Entwicklungspolitik sowohl das historische Erbe als auch bestehende Aktivposten in vollem Umfang nutzen sollte. Schließlich ist festzustellen, dass Ko-Adaption und Ko-Selektion der Unternehmens-Organisation, von Institutionen und Technologie zusammen die Pharma-Industrie von Tonghua in hohem Maße wettbewerbsfähig gemacht haben. Ob eine Region neue Gelegenheiten ergreifen kann, hängt folglich teilweise von ihrer Fähigkeit ab, eine Vielfalt von Entwicklungs-Agenten zu koordinieren