Vascular dementia (VaD), the second most common cause of dementia, causes substantial distress to patients and represents a significant burden to their families and communities. Currently, there is no effective treatment to reverse the brain damage associated with VaD. In general the drugs available for the management of cognitive problems in VaD are expensive and outcomes are uncertain. It is, therefore, important to seek out alternative approaches, which may prove effective, cheaper and safer. Chinese herbal medicine (CHM) has been used for the treatment of dementia-like disorders for centuries. Data from many preclinical studies and some clinical studies have suggested the potential effectiveness of CHM for the treatment of VaD. Based on the literature review conducted as part of this thesis, however, most of the studies were published in Chinese literature and failed to demonstrate methodological rigour or to report sufficient methodological detail. Randomised controlled trials (RCTs) using scientific methods of diagnosis and outcome measures are urgently needed. Wei Nao Kang (WNK) is a three-herb formula developed by Xi Yuan Hospital, China Academy of Chinese Medical Sciences. Preclinical experiments of WNK have demonstrated significant improvement in learning and memory function in VaD animal models in rats and mice. Human case studies have also signalled the potential value of WNK in VaD. Although the results of these studies were encouraging, strong scientific evidence from a well-designed RCT is still required. A rigorous clinical trial methodology, including scientific diagnostic criteria and outcome measures, was designed and applied to the evaluation of WNK for VaD. The trial was successfully conducted over a two-year period. Cognitive functions, as evidenced by the ADAS-cog, were significantly improved in the study group taking WNK herbal medication compared with the placebo group. The ADAS-cog was simultaneously validated as a measure of cognitive function in VaD. Blinding was verified and no major adverse effects were found related to WNK treatment. However, neither group demonstrated long-lasting effect on a 16 weeks follow-up after completion of treatment. WNK demonstrated a significant effect on quality of life (measured by SF-36) and some effect on activities of daily living (measured by ADCS-ADL) in VaD patients. The SF-36 was validated as a measure of general health status and the ADCS-ADL as a measure of activities of daily living in patients with VaD. Both scales were proven sensitive to the presence of VaD, and provided useful supplementary outcome measures for VaD. A cerebral perfusion study was conducted to identify changes in cerebral blood flow and its relationship with clinical symptoms. The study showed that WNK had marked increases in blood flow in the inferior frontal and anterior temporal regions, both of which are closely related to cognitive function in human brains. This study has provided scientific evidence in support of the clinical effect of WNK on VaD. In addition, it validated several outcome measures in assessing improvements in cognitive functions, activities of daily living and quality of life in VaD patients. One of the highlights of this study is the application of SPECT scans as an outcome measure. This provided an excellent objective parameter for assessing the effects of WNK. To the best of our knowledge, SPECT scanning has never been used in VaD trials of herbal medicines. / Doctor of Philosophy (PhD)

This thesis examines the medical case records of the Imperial Qing Palace. The case records were examined with a view to see how Chinese medicine was practised in the Qing period in China. I also analysed the role of medical cases as another way of adding to an understanding of history. My primary sources were the archive medical case records of the Qing Imperial Palace as compiled by Chen Keji. I also used selected secondary sources, particularly research by Chang Che-Chia on the Qing cases. I concentrated my research on selected emperors and the Empress Dowager. I analysed the case records of Kangxi, Qianlong, Tongzhi, Guangxu and Cixi. Each of these figures were analysed using medical analysis and historical analysis. Using clinical knowledge, I analysed each of these political figures considering the historical and social context of the time. While analysing selected cases I also analysed the medical approach and style of one doctor of the nineteenth century, Ma Peizhi. This physician was selected as representative of elite doctors in China in the late Qing period. Using the methodology of textual analysis I supplemented analysis of the primary sources with examination of secondary sources such as biographies and other journals. In medical terms, I found that the practice of Chinese medicine changes according to social and historical circumstances. In line with the social norms of the elite at the time in Qing China, medicine was practised with the approach of gentleness and balance. This distinctive style, practised by Ma Peizhi, saw the root of physical disease in mental unease. In historical terms, I found that the medical records provided primary evidence for trends in Qing history. The Kangxi emperor looked askance at Chinese medicine, while avidly practising his Manchu shamanic rituals. His grandson, Qianlong, in contrast, presented himself as a patron of Chinese classical learning, of which he saw Chinese medicine as an important component. This was evidence that the sinification of the Manchu conquerors was almost complete. A key finding of the thesis was that the realities of the Qing emperors and the Empress Dowager Cixi differed from the personas they had projected to the public. The Qing emperors and the Empress Dowager were, on the whole, frail in health, psychologically vulnerable and suffering from chronic anxiety, if not depression. The Qing images of power did not fit the reality.

Thesis (Ph.D.)--University of California, Riverside, 1993. / Source: Dissertation Abstracts International, Volume: 54-03, Section: A, page: 0987. Chairman: Eugene N. Anderson, Jr. Includes bibliographical references.

University of Macau / Institute of Chinese Medical Sciences

University of Macau / Institute of Chinese Medical Sciences

University of Macau / Institute of Chinese Medical Sciences

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

 As the aging in reproductive system proceeds, females will eventually enter the period of menopause, during which a series of physiological changes occurs. The decline of estrogen level during menopausal transition is thought to associate with various menopausal symptoms. Although hormone replacement therapy can be adopted to deal with the estrogen-deficient state, side effects such as cancer risk cannot be overlooked. Alternatively, Erxian Decoction (EXD), a Chinese medicine formula for treating menopausal symptoms has been used clinically for more than 60 years without adverse effects reported. Some pharmacological properties of EXD have been reported in previous research, which are thought to be contributed by its multiple bioactive components. Thus in the present study, the pharmacological properties of EXD have been further evaluated. The drug compatibility of Traditional Chinese Medicine (TCM) formula, EXD, was also demonstrated. At last, a novel approach for identification of bioactive components from Chinese medicine formula was introduced using EXD as study model. To evaluate the multiple pharmacological properties of EXD, proteins involved in steroidogenesis in ovaries of aged female rats were measured by immunoblotting analysis. On top of that, serum lipid profiles and the related proteins were determined by colorimetric assay and immunoblotting analysis respectively. Also, anti-osteoporotic properties and drug compatibility of EXD were evaluated by in vitro methods such as proliferation assay, osteoclast differentiation assay, ELISA assay or immunoblotting analysis. Lastly, a novel approach for identification of bioactive components in relation to the subsequent bioactivity from traditional Chinese medicinal formula was introduced using HPLC profiles. From the results, it was demonstrated that EXD can modulate steroidogenesis in aged female rat model at least through up-regulation of ovarian aromatase, protein kinase B and estrogen receptor beta at protein level. Besides, EXD also exerts antihyperlipidemic effects in aged female rats as reflected from the decreased serum total cholesterol and LDL-cholesterol levels via regulation of HMG CoA reductase and LDL-receptor, the key proteins for cholesterol synthesis and LDL-cholesterol clearance. In vitro study has also demonstrated the anti-osteoporotic properties of EXD through stimulation of osteoblast proliferation and inhibition of proliferation and differentiation of osteoclast precursor cells. The later was proved to be mediated by down-regulation of NFATc1 proteins, a key protein for osteoclastogenesis. The roles of the drugs categories according to the drug compatibility of traditional Chinese medicine contributing to the optimal anti-osteoporotic properties of EXD were also elucidated. Since the diverse pharmacological properties of a Chinese medicinal formula are often the results of the effects of complex bioactive constituents in the extract, yet identification of the bioactive components has been a tedious task. Thus in the last part of the study, a novel approach for identification of bioactive component from Chinese medicinal formula has been developed. By comparing the HPLC profiles of EXD extracted by different decoction method in relation to their pharmacological properties, six bioactive chemicals were successfully identified which may contribute to the stimulatory effect of EXD on ovarian aromatase and hepatic catalase expression. / published_or_final_version / Chinese Medicine / Master / Master of Philosophy

abstract / Chinese Medicine / Doctoral / Doctor of Philosophy

Over the 30 years since it was first identified, the HIV/AIDS epidemic has had historically unprecedented severity and impact. There are approximately 33.4 million people living with HIV-1/AIDS which urges to seek novel approaches for HIV-1 diagnosis and HIV-1 therapy. Men who have sex with men (MSM) are severely affected by HIV-1 and constitute a large proportion of HIV-infected individuals. In Hong Kong, the transmission route of homosexual and bisexual contacts accounted for nearly 50% of incidence in 2012. To investigate HIV-1 prevalence among MSM in Hong Kong, the combination of fast antibody test (FAT) and real-time dried-blood-spot-based quantitative polymerase chain reaction (DBS-qPCR) was employed for 474 participants chosen randomly from community testing sites of MSM within a one-year period which showed a 4.01% (19/474) rate of HIV-1 prevalence among MSM in Hong Kong with three cases at the acute phase among the newly infected participants. The new survey demonstrated that the risk factors of MSM are mostly correlated with the receptive role during anal sex and syphilis infection. In this study, two traditional Chinese herbal medicines (TCHM), Sanguisorba officinalis (SO) and Spatholobus suberectus (SS), inhibited the infection of model cell lines expressing HIV-1 targets by HIV-1 pseudoviruses, while the anti-HIV-1 properties of SO were demonstrated for the first time. Both SO and SS were able to block not only infection by pseudoviral HIV-1 CCR5-tropic and CXCR4-tropic strains, but also RT and PI drug-resistant strains. Mechanistic studies revealed that SO and SS interact with the viral envelope to prevent the infection of target cells by HIV-1. Two compounds derived from SO and SS, named Gallic acid (GA) and Jiazhi (JZ), retained anti-HIV-1 properties and blocked HIV-1 infection by acting on the viral envelope. Small molecules derived from TCHM were also investigated for their capacity to activate HIV-1 from latency. A small molecule derived from SS, Daidzein (DDZ), demonstrated the potentials to trigger HIV-1 reactivation in latently infected cell lines. DDZ enhanced gene expression from HIV-1 LTR in which the Sp1 binding site plays an important role. The Akt pathway is also involved in the initiation of DDZ-induced activation. Phosflow analysis revealed that DDZ activated the Akt pathway in various subpopulations of T cells, including memory CD4+ T cells which are considered to be a major reservoir for HIV-1. The structure-activity relationships (SARs) study demonstrated the 4'-hydroxyisoflavone as bio-functional core structure. Addition of a hydroxyl group on C-5 position significantly decreases its biological function of HIV-1 latency activation. In summary, this study investigates HIV prevalence and incidence using an assay for early HIV-1 diagnosis and performs an analysis of risk factors of behavior which contributes to the effective control of HIV transmission in Hong Kong and its neighbors in Asia. It also demonstrates a drug research sourced from traditional Chinese herbal medicines that which sheds lights on drug discovery from traditional herbal medicines and facilitates mechanistic drug design for HIV-1 eradication. / published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy