published_or_final_version / abstract / Dentistry / Master / Master of Philosophy

More than half of the women aged from 45-55 suffer from menopausal symptoms which can seriously affect the quality of life of the midlife women. The menopause transition has become a very active research area in healthy aging in the last several decades. In recent years, more and more women have turned to traditional Chinese medicine (TCM) to manage their menopausal symptoms. Among various Chinese medicine formulae, Er-Xian Decoction (EXD) is one of the most acceptable Chinese medicine formulae to relieve menopausal symptoms. Although EXD is popular in the management of menopausal symptoms, its effectiveness has not been evaluated by strictly designed clinical study. A systematic review was conducted to evaluate the current evidence to assess the efficacy and safety of EXD as a basic formula for menopausal symptoms. A total of 12 randomized controlled trials (RCTs) were included for further analysis. The results of these studies suggested that EXD was more effective than the control interventions, which included various HRT and other Chinese herbal medicine. Seven of the studies compared EXD with HRT and the meta-analysis seemed to suggest that EXD as a basic formula was superior to hormone replacement therapy. However, the included studies were insufficient in methodological quality and had a high probability of bias. A double-blind randomized controlled clinical trial was then conducted to assess the efficacy and safety of EXD for menopausal symptoms. Of 557 recruited women, 108 subjects were eligible to participate in the study and 101 subjects finished the study. Comparisons between placebo and EXD groups were conducted by using an analysis of covariance (ANCOVA) with baseline as covariate. EXD granules when compared with placebo significantly reduced the frequency and severity of hot flushes and night sweats. EXD compared with placebo significantly reduced the frequency of hot flushes (P=0.041) and the hot flush severity score (P=0.016). Superiority of EXD over placebo was also observed in greater improvement in total scores of MRS (P=0.028) and MENQOL questionnaires (P=0.021). There were no differences between EXD and placebo group in serum hormones and bone markers. There were no serious adverse events and the safety indices of whole blood counts, renal and liver functions were normal before and after the treatment. Both EXD and placebo were well tolerated. In summary, this Chinese herbal formula EXD was found to be superior to placebo in reducing hot flushes and improving menopausal symptoms in Hong Kong perimenopausal women. It was well tolerated, with no serious adverse events noted during the study period. / published_or_final_version / Chinese Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / Chinese Medicine / Master / Master of Philosophy

Chan, Chun Kit. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 147-161). / Abstracts in English and Chinese. / Chapter Chaper 1 --- Introduction --- p.1 / Chapter 1.1 --- General introduction to cerebral stroke --- p.1 / Chapter 1.2 --- Different types of cerebral stroke --- p.2 / Chapter 1.3 --- Statistics --- p.3 / Chapter 1.4 --- Symptoms of cerebral stroke --- p.4 / Chapter 1.5 --- Complications of cerebral stroke --- p.5 / Chapter 1.6 --- Risks and preventions of cerebral stroke --- p.6 / Chapter 1.7 --- Cerebral stroke treatment --- p.8 / Chapter 1.8 --- Post stroke rehabilitation --- p.11 / Chapter 1.9 --- Mechanisms of stroke --- p.15 / Chapter 1.9.1 --- Energy production failure and loss of ionic homeostasis --- p.15 / Chapter 1.9.2 --- Excitotoxicity --- p.16 / Chapter 1.9.3 --- Calcium ions mediated toxicity --- p.17 / Chapter 1.9.4 --- Passive neuronal cell death --- p.18 / Chapter 1.9.5 --- Oxidative stress --- p.19 / Chapter 1.9.6 --- Inflammation --- p.22 / Chapter 1.9.7 --- Apoptosis --- p.25 / Chapter 1.10 --- Potential therapeutic agents for cerebral stroke --- p.24 / Chapter 1.10.1 --- Anti-oxidative enzyme and free radical scavengers --- p.24 / Chapter 1.10.2 --- Ions channel blockers and glutamate antagonists --- p.26 / Chapter 1.10.3 --- Anti-inflammatory agent --- p.28 / Chapter 1.10.4 --- Anti-apoptotic agent --- p.28 / Chapter 1.11 --- Experimental model of cerebral ischemia-reperfusion --- p.29 / Chapter 1.11.1 --- In vitro model (oxygen and glucose deprivation model) --- p.29 / Chapter 1.11.2 --- In vivo model (Middle cerebral artery occlusion) --- p.31 / Chapter 1.12 --- Traditional Chinese Medicine (TCM) --- p.32 / Chapter 1.12.1 --- General Introduction to Traditional Chinese Medicine --- p.32 / Chapter 1.12.2 --- TCM and cerebral stroke --- p.33 / Chapter 1.12.3 --- Chinese compound formula --- p.34 / Chapter 1.12.4 --- Introduction to individual herb --- p.34 / Chapter 1.12.4.1 --- Astragali Radix (Pinyin name: Huangqi) --- p.34 / Chapter 1.12.4.2 --- Rhizoma Chuanxiong (Pinyin name: Chuanxiong) --- p.35 / Chapter 1.12.4.3 --- Radix Salviae Miltorrhizae (Pinyin name: Danshen) --- p.35 / Chapter 1.12.4.4 --- Cassia Obtusifolia Linne (Pinyin name: Jue Ming Zi) --- p.36 / Chapter 1.12.4.5 --- Radix Glycyrrhizae (Pinyin name: Gancao) --- p.37 / Chapter 1.12.4.6 --- Radix Angelicae Sinensis (Pinyin name: Dongquai) --- p.37 / Chapter 1.12.4.7 --- Paeoniae Veitchii Radix (Pinyin name: Chi Shao) --- p.38 / Chapter 1.12.5 --- Salvianolic acid B --- p.39 / Chapter 1.13 --- Aim of study --- p.40 / Chapter Chapter 2 --- Materials and Methods --- p.41 / Chapter 2.1 --- Materials --- p.41 / Chapter 2.1.1 --- Drug --- p.41 / Chapter 2.1.1.1 --- Herbal Medicine --- p.41 / Chapter 2.1.1.2 --- Herbal extraction of PSR --- p.42 / Chapter 2.1.1.3 --- Herbal extraction of individual herb --- p.43 / Chapter 2.1.1.4 --- Salvianolic acid B --- p.43 / Chapter 2.1.2 --- Chemical --- p.44 / Chapter 2.1.3 --- Animal --- p.48 / Chapter 2.2 --- Methods --- p.49 / Chapter 2.2.1 --- (AAPH)- induced erythrocyte hemolysis --- p.49 / Chapter 2.2.2 --- Cell Culture study --- p.51 / Chapter 2.2.2.1 --- Cell Line --- p.51 / Chapter 2.2.2.2 --- Cell differentiation --- p.52 / Chapter 2.2.2.3 --- In vitro model of ischemia - Oxygen glucose deprivation (OGD) experiment --- p.53 / Chapter 2.2.2.4 --- Cell viability assay --- p.54 / Chapter 2.2.3 --- In vivo Study --- p.54 / Chapter 2.2.3.1 --- Cerebral blood flow (CBF) measurement --- p.54 / Chapter 2.2.3.2 --- In vivo transient focal cerebral ischemia model - Middle cerebral artery occlusion (MCAo) --- p.55 / Chapter 2.2.3.3 --- Administration of PSR --- p.57 / Chapter 2.2.3.4 --- Administration of salvianolic acid B (SAB) --- p.59 / Chapter 2.2.3.5 --- Measurement of brain infarct volume --- p.60 / Chapter 2.2.3.6 --- In vivo anti-oxidative enzyme activity determination in the brain --- p.61 / Chapter 2.2.3.6.1 --- Brain tissue preparation --- p.61 / Chapter 2.2.3.6.2 --- Tissue homogenization and protein extraction --- p.61 / Chapter 2.2.3.6.3 --- Protein concentration determination --- p.63 / Chapter 2.2.3.6.4 --- Catalase activity determination in the brain --- p.63 / Chapter 2.2.3.6.5 --- Glutathione Peroxidase (GPx) activity determination in the brain --- p.64 / Chapter 2.2.3.6.6 --- The Superoxide Dismutase (SOD) activity determination in the brain --- p.65 / Chapter 2.2.3.7 --- Behavioral Evaluation --- p.66 / Chapter 2.2.3.7.1 --- Neurological behavioural test --- p.66 / Chapter 2.2.3.7.2 --- Shuttle box escape experiment --- p.67 / Chapter 2.3 --- Statistical analyses --- p.71 / Chapter Chapter 3 --- Results --- p.72 / Chapter 3.1 --- In vitro model of ischemia - Oxygen glucose and deprivation (OGD) experiment --- p.72 / Chapter 3.2 --- AAPH assay of PSR --- p.75 / Chapter 3.3 --- AAPH assay of individual herb --- p.77 / Chapter 3.4 --- Brain slices after middle cerebral artery occlusion (MCAo) experiment --- p.81 / Chapter 3.5 --- Brain infarct volume of single dose protocol --- p.83 / Chapter 3.6 --- Neurological behavioural test of single dose protocol --- p.85 / Chapter 3.7 --- Brain infarct volume of double doses protocol --- p.87 / Chapter 3.8 --- Neurological behavioural test of double doses protocol --- p.89 / Chapter 3.9 --- Determination of superoxide dismutase (SOD) activity in the brain --- p.91 / Chapter 3.10 --- Determination of glutathione peroxidase (GPx) activity in the brain --- p.93 / Chapter 3.11 --- Determination of catalase activity in the brain --- p.95 / Chapter 3.12 --- Brain infarction volume of Salvianolic acid B (SAB) treatment --- p.98 / Chapter 3.13 --- Neurological behavioural test of SAB treatment --- p.100 / Chapter 3.14 --- Shuttle box performance in training and testing series --- p.102 / Chapter 3.15 --- Change in shuttle box performance (% avoidance c.f. last day of training) in testing series --- p.104 / Chapter 3.16 --- Escape latency in testing and training series --- p.107 / Chapter 3.17 --- Change in escape latency (c.f. last day of training) in testing series --- p.109 / Chapter 3.18 --- Brain infarct volume of shuttle box escape experiment --- p.112 / Chapter 3.19 --- Neurological score in shuttle box escape experiment --- p.114 / Chapter Chapter 4 --- Discussion --- p.117 / Chapter 4.1 --- The protective effect of PSR in in vitro oxygen and glucose deprivation (OGD) on human neuroblastoma SH-SY5Y cell line --- p.117 / Chapter 4.1.1 --- OGD model and cell line --- p.117 / Chapter 4.1.2 --- Protective effect of PSR in OGD experiment --- p.118 / Chapter 4.1.3 --- Free radical scavenging property of PSR --- p.120 / Chapter 4.2 --- The protective effects of PSR in in vivo middle cerebral artery (MCAo) model --- p.121 / Chapter 4.2.1 --- The shortcomings of in vitro OGD model --- p.121 / Chapter 4.2.2 --- Development of in vivo MCAo model and TTC staining --- p.122 / Chapter 4.2.3 --- Protective effect of PSR in MCAo experiment (single dose protocol) --- p.124 / Chapter 4.2.4 --- Protective effect of PSR in MCAo experiment (double doses protocol) --- p.125 / Chapter 4.2.5 --- The effect of PSR toward neurological deficits --- p.127 / Chapter 4.2.6 --- Anti-oxidative effects of PSR in MCAo model --- p.128 / Chapter 4.3 --- The protective effects of SAB in in vivo middle cerebral artery (MCAo) model --- p.130 / Chapter 4.3.1 --- Free radical scavenging property of different herbs --- p.130 / Chapter 4.3.2 --- Selection of pure compound that used to treat stroke --- p.131 / Chapter 4.3.3 --- Protective effect of Salvianolic B in MCAo experiment --- p.132 / Chapter 4.3.4 --- The effect of SAB toward neurological deficits --- p.133 / Chapter 4.4 --- The effects of PSR and SAB on stroked rats' performance in shuttle box escape experiment --- p.134 / Chapter 4.4.1 --- Establishment of shuttle box escape experiment --- p.134 / Chapter 4.4.2 --- Effects of PSR and SAB on avoidance performance --- p.135 / Chapter 4.4.3 --- Effects of PSR and SAB on escape latency --- p.138 / Chapter 4.5 --- Assessment on the contribution of SAB to the protective effect of PSR --- p.140 / Chapter 4.6 --- Comparison of acute and chronic testing --- p.140 / Chapter 4.6.1 --- The protective effect of the drugs (Histopathological examination) --- p.140 / Chapter 4.6.2 --- The severity of motor deficit (Neurological score) --- p.141 / Chapter Chapter 5 --- Conclusion and Future prospect --- p.143 / Chapter 5.1 --- Conclusion --- p.143 / Chapter 5.2 --- Future prospect --- p.144 / References --- p.147

 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

published_or_final_version / Computer Science and Information Systems / Master / Master of Philosophy

University of Macau / Institute of Chinese Medical Sciences

At present, there is no cure for bone metastasis. The current goals in patient care are to palliate pain, prevent pathological bone fracture and increase the strength and function of bone, so as to extend the life expectancy and maintain a good quality of life. Bisphosphonate treatment is the currently standard therapy of bone metastasis and is commonly used by physicians; it alleviates the tumour-induced hypercalcemia in 90% of patients and reduces the metastatic bone pain in 50% of patients. Moreover, it also prevents the pathological fracture of the affected bones. However, while effective, bisphosphonate injections are very costly, though its oral formulation is less expensive it is also less efficacious, and causes gastrointestinal discomfort. Furthermore, prolonged use of bisphosphonate treatment may lead to certain adverse effects, including hypocalcemia. These factors will prohibit the longterm use of such medication as it can negatively affect the treatment outcome. / Based on enormous medical potentials illustrated by the aforementioned findings, BBYNG deserves wider clinical application, large-scale clinical study on its preventive effect against bone metastasis and detailed investigation of its mode(s) of action in the body. / Based on the above-described understanding of Chinese medicine and bone metastasis, supplementing the kidney and strengthening bone could be the basic principle for the treatment of bone metastasis using Chinese medicine. In view of this theory, and in addition to the clinical observation and a thorough search of the available literature, we selected relevant kidney-tonifying Chinese herbs, namely (Fructus Ligustri Lucidi), (Rhizoma Drynariae), (Herba Epimedii), (Psoralea Corylifolia) and wide-spectrum anticancer herbs (Herba Hedyotidis Diffusae) for the preparation of a combined formula--BBYNG. / Chinese medicine has long been used to treat cancers. Its advantages reside in its holistic properties, which bring palliative, corrective and convalescing functions against damage caused by radiotherapy, chemotherapy and surgery. These features position Chinese medicines as the adjuvant to orthodox cancer treatment. During the late stage of tumour development, when standard therapy is no longer effective, Chinese medicine plays a critical role as an integrated therapy. Searching for a safe, inexpensive and effective Chinese medicine preparation suitable for prolonged use as adjunct therapy in late cancer cases is of paramount importance. / Clinical results. Both Chinese medicine and Western medicine treated patients showed no significant change in their blood parameters or liver and kidney examinations before and after drug administration; Male subjects on BBYNG, their bone mass density remained stable after 6 months treatment and the subjects on OSTAC showed slightly decreased In females, subjects on BBYNG remained stable, but subjects on OSTAC slightly increased. / Clinical study. The study was designed as a randomized, parallel-group comparison between BBYNG formula and Bisphosphonate. The patients who meet the inclusion/exclusion criteria were randomly assigned to receive either BBYNG granules, which was prepared by a GMP manufacturer, or Clodronic acid. The treatment period was 6 months (24 weeks). For both groups, various clinical parameters such as body functions, blood examinations, bone density (BMD) assessment, X-ray examinations, pain intensity and quality of life were evaluated and compared. / Conclusions. (1) As an adjuvant to patients with bone metastases, BBYNG is effective in relieving the metastatic bone pain, improving the quality of life. (2) In the animal model, BBYNG reduced the metastatic bone damage, prolonged the survival and enhanced the T lymphocyte immunity in the tumour-bearing mice. (3) In vitro study on the breast and lung cancer cell lines showed that BYYNG could induce apoptosis and prevent tumour cell invasion. It suggests that BYYNG may restrict tumour growth and development, thus reducing the occurrence of bone metastasis. / In accordance with Chinese medicine, bone metastasis can be categorized into "bone tumour" "bone erosion" "bone wilting" "bone necrosis" and "bone impediment". The main cause of bone metastasis is twofold: cancer toxicity, and in Chinese medicine theory, the kidney governs the bone marrow, if the kidney is not functioning in balance, then the bone will become weak. Cancer toxicity is the "pathogenic cause" to skeletal metastases, while kidney weakness decreases the body defence against the cancer. A vicious cycle ensues when cancer and kidney deficiency and bone weakness occurs simultaneously coincidently and worsens the conditions. / In vitro study on tumour cell lines. The anticancer effects of different concentrations of BBYNG formula and various single components against human breast cancer and lung cancer cell lines were evaluated by cell viability test (MTT assay), cell apoptosis test and invasion suppression test. / In vitro study results. BBYNG and the aqueous extracts of its component herbs at very low drug concentrations stimulated the growth of three tumour cell lines tested. When the concentrations were slightly increased, they showed an inhibitory effect on cancer cell proliferation. As the drug concentrations further increased, the extracts showed cytotoxic effects on these tumor cells. At the noncytotoxic dose, the extracts could trigger apoptosis and enhance the caspase-3 activity in all three tumour cell lines. In addition, at this "non toxic" concentration, the extracts markedly inhibited the in vitro invasive property of the 4T1 breast cancer cell lines in our Matrigel invasion model. Thus these in vitro results suggested that BBYNG possess anticancer, invasion-inhibitory and anti-metastatic activities. / In vivo animal study results. (Tumour growth was slower in the BBYNG treatment group when compared to the OSTAC and control groups, but this was not significantly difference) BBYNG significantly delayed tumour growth in tumour bearing mice, but it did not minimize the tumour size markedly. Moreover, BBNYG did minimize the mobility restriction caused by tumours, reduce the damage to bones, prolong the survival time and enhanced the T lymphocyte immunity. / In vivo animal study. A well-established animal model for breast cancer was used to evaluate and compare the pharmacological effects of BBYNG formula and Clodronic acid, as shown by different indicators such as tumour progression, animal's mobility, survival time, bone metastasis-induced fracture intensity and the immunological status of the tumour-bearing mice. / Malignant tumour is characterized by early metastasis. Among them 37 to 80 (depending on which type of cancer) patients show tendency of bone metastasis. Bone metastasis is usually accompanied by various complications, such as severe pain, pathological bone fracture, hypercalcemia, and bone marrow suppression, which can substantially affect the quality of life of the patients. Thus, the prevention and treatment of bone metastasis in cancer is an issue worth pursuing. / Malignant tumours leading to high mortality and morbidity are a serious threat to human health. It is the leading cause of death in China. In Hong Kong, there are over 20 thousand new cancer cases and more than 1100 people die due to cancers every year. / Study objectives. To elucidate the efficacy and some pharmacological aspects of BBYNG in regard to the treatment of bone metastasis through clinical observation and different laboratory experiments. This study would be of significant reference value to the disease-oriented drug formulation and application, mechanistic study and research methodology of the treatment of bone metastasis using Chinese medicines. / The clinical and laboratory experimental results are summarized as below: / The research study is composed of three parts, the clinical study, in vivo animal study and in vitro study on tumour cell lines. The research methods used are as follows: / Those on BBYNG treatment showed more a stable and satisfactory quality of life than those in the Western medicine-treated group. For the Clodronic acid treatment group, patients generally showed worsened symptoms and quality of life deteriorated. The ECOG index of the BBYNG group was statistically better than that of the Clodronic acid group. Within the 72-week clinical observational period, the mortality of Clodronic acid group is significantly higher that of the BBYNG group. The effects of BBYNG group as presented in relieving the pain-induced influence on patients' emotion, interpersonal relationship and entertainment was more pronounced than that in the Clodronic acid group. / Wu Ka. / 論文(哲學博士)--香港中文大學, 2006. / 參考文獻(p. 299-324). / Adviser: Leung Ping Chung. / Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1570. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in Chinese and English. / School code: 1307. / Lun wen (zhe xue bo shi)--Xianggang Zhong wen da xue, 2006. / Can kao wen xian (p. 299-324). / Wu Ka.

The project developed a web-based application that provides a user-friendly interface to assist practitioners of traditional Chinese medicine in determining the correct diagnosis. Traditional Chinese Medicine On-line Diagnosis System (TCMODS) allows a diagnostician to enter a patient's symptoms using a series of questionnaires to determine health status, which will then be stored in the database as part of the patient's medical records. The database will also differentiate among the patterns of syndromes known in traditional Chinese medicine and search and match these with the patient's data to the known uses of Chinese herbs. TCMODS will then generate that patient's medical record, including the symptoms of the ailment, the syndrome, and a prescription. User identification and access privileges were differentiated in order to maintain the integrity of the patient medical data and the information needed to make the diagnoses. The project was designed to function across platforms and was written using HTML, JSP, and MySQL.