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Development of systemic therapy for hepatocellular carcinoma at 2013:Updates and insights

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World Journal of Gastroenterology 2014年第12期20卷 3135-3145页

作者： Stephen L chan Winnie Yeo Department of Clinical Oncology The Chinese University of Hong KongPrince of Wales Hospital State Key Laboratory in Oncology in South China

A growing number of multi-targeted tyrosine kinase inhibitor (TKI) has undergone testing for hepatocellular carcinoma (HCC). Unfortunately, this enthusiasm has recently been discouraged by a number of negative phase III studies on several anti-angiogenic TKIs in HCC. Several postulations have been made to account for this phenomenon, namely the plateau effects of anti-angiogenesis approach, the heterogeneity of HCC in terms of background hepatitis/cirrhosis and tumor biology, as well as the way how clinical trials are designed. Regardless of the underlying reasons, these results suggested that alternative strategies are necessary to further develop systemic therapy for HCC. Several new strategies are currently evaluated: for examples, molecular agents with activities against targets other than vascular endothelial growth factor receptor are being evaluated in on-going clinical trials. In addition, different approaches of targeted agents in combination with various treatment modalities, such as concurrently with another molecular agent, cytotoxic chemotherapy or transarterial chemoembolization, are being developed. This review aims to give a summary on the results of recently released clinical trials on TKIs, followed by discussion on some of the potential novel agents and combinational approaches. Future directions for testing innovative systemic agents for HCC will also be discussed.

关键词： Liver neoplasms Systemic treatment Biologics Staging Clinical trial

Measurement of calprotectin in ascitic fluid to identify elevated polymorphonuclear cell count

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World Journal of Gastroenterology 2013年第13期19卷 2028-2036页

作者： Emanuel Burri Felix Schulte Jürgen Muser Rémy Meier Christoph Beglinger Gastroenterology and Hepatology University Hospital Basel Gastroenterology Hepatology and Clinical NutritionCantonal Hospital Central Laboratories Cantonal Hospital

AIM: To evaluate the diagnostic capability of calprotectin in ascitic fluid for detecting a polymorphonuclear (PMN) cell count > 250/μL ascites. METHODS: In this prospective observational study, a total of 130 ascites samples were analysed from 71 consecutive patients referred for paracentesis. Total and differential leukocyte cell counts were determined manually with a Neubauer chamber and gentianviolet stain. Calprotectin was measured in 1 mL ascetic fluid by enzyme-linked immunosorbent assay (ELISA) and a point-of-care (POC) lateral flow assay with the Quantum Blue Reader (Bühlmann Laboratories). All measurements were carried out in a central laboratory by senior personnel blinded to patient history. A PMN count > 250/μL was the primary endpoint of the study. The diagnostic value of ascitic calprotectin measurement was assessed by comparing to the final diagnosis of each patient that had been adjudicated by investigators blinded to calprotectin values. RESULTS: The PMN count was > 250/μL in 19 samples (14.6%) from 15 patients (21.1%) and varied widely among the study population (range 10-19 800/mL and 1-17 820/mL, respectively). Spontaneous bacterial peritonitis (SBP) was the final diagnosis in four patients (5.6%). All patients with PMN ≤ 250/μL had negative bacterial culture. PMN count was elevated in five patients with peritoneal carcinomatosis, three with lymphoma, one with neuroendocrine carcinoma, and two with secondary peritonitis due to abdominal perforation. PMN cell counts correlated with ascitic calprotectin values (Spearman's rho; r = 0.457 for ELISA, r = 0.473 for POC). A considerable range of ascitic calprotectin concentrations was detected by ELISA [median 0.43 μg/mL, interquartile range (IQR) 0.23-1.23 (range 0.10-14.93)] and POC [median 0.38 μg/mL, IQR 0.38-0.56 (range 0.38-13.31)]. Ascitic calprotectin levels were higher in samples with PMN > 250/μL, by both ELISA [median (IQR) 2.48 μg/mL (1.61-3.65) vs 0.10 μg/mL (0.10-0.36), P < 0.001] and POC

关键词： Calprotectin Ascites Liver cirrhosis Spontaneous bacterial peritonitis Polymorphonuclear cells

Genipin and geniposide from Gardenia jasminoides:An overview of their anti-cancer and other pharmacological properties

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Journal of Chinese Pharmaceutical Sciences 2022年第1期31卷 1-12页

作者： Eric Wei Chiang chan Siu Kuin Wong Hung Tuck chan Faculty of Applied Sciences UCSI University56000 CherasKuala LumpurMalaysia School of Foundation Studies Xiamen University MalaysiaBandar Sunsuria43900 SepangSelangorMalaysia Secretariat of International Society for Mangrove Ecosystems(ISME) Faculty of AgricultureUniversity of the RyukyusOkinawa 903-0129Japan

Genipin and geniposide are iridoids from the fruits of Gardenia *** compounds have a methyl acetate(-COOCH_(3))group at C4 and a hydroxyl(-OH)group at *** an iridoid glucoside with a glucose moiety at C1,geniposide is also known as genipin-1-O-β-*** the glucose moiety,genipin is an iridoid and the aglycone of ***-OH group at C1 of genipin is responsible for its cytotoxic *** without the-OH group at C1 lacks the cytotoxic *** are more publications on the anti-cancer properties of genipin than *** have reported the potentiation of genipin when used in combination with anti-cancer *** anti-cancer properties of geniposide have been investigated using human intestinal microflora that hydrolyzes geniposide to *** genipin and geniposide exert antiproliferative and apoptotic activities via different molecular targets and *** pharmacological properties of genipin and geniposide include antidepressant,antidiabetic,anti-inflammatory,anti-obesity,anti-thrombotic,hepatoprotective,and neuroprotective *** research on genipin and geniposide is suggested.

关键词： Iridoid Iridoid glucoside Anti-cancer Cytotoxicity

Alpinia zerumbet, a ginger plant with a multitude of medicinal properties： An update on its research findings

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Journal of Chinese Pharmaceutical Sciences 2017年第11期26卷 775-788页

作者： Eric Wei Chiang chan Siu Kuin Wong Hung Tuck chan Faculty of Applied Sciences UCSI University Cheras 56000 Kuala Lumpur Malaysia School of Science Monash University Sunway Petaling Jaya 46150 Selangor Malaysia Secretariat International Society for Mangrove Ecosystems c/o Faculty of Agriculture University of the Ryukyus 903-0129 Okinawa Japan

In this review, the botany and uses of Alpinia zerumbet(yan shan jiang) are described, and the current knowledge of its phytochemistry, pharmacological properties, and clinical trials is summarized. An important ginger crop in East Asia, A. zerumbet has many uses, both medicinal and non-medicinal. Leaves are used to produce essential oils and herbal teas. Rhizomes are consumed as spices, and stem fibers are made into paper, fabrics, and handicrafts. In Brazil, tea from A. zerumbet leaves is believed to have hypotensive, diuretic, and anti-ulcerogenic properties. This species possesses many medicinal properties due to its chemical constituents, including flavonoids, phenolic acids, phenylpropanoids, kava pyrones, sterols, and terpenoids. Extracts of A. zerumbet display antioxidant, antimicrobial, insecticidal, anthelmintic, tyrosinase and melanogenesis inhibitory, anti-atherogenic, anti-aging, anti-glycation, integrase and neuraminidase inhibitory, lifespan prolongation, hair growth promotion, anticancer, antidepressant, anxiolytic, anti-obesity, analgesic, anti-inflammatory, hypolipidemic, anti-ulcerogenic, anti-platelet, osteoblastic, osteogenic, thrombolytic, and cardiac arrhythmogenic activities. Essential oils of A. zerumbet leaves have antimicrobial, larvicidal, antinociceptive, hypotensive, vasorelaxant, myorelaxant, antispasmodic, antidepressant, anxiolytic, anti-neuraminidase, anti-atherogenic, anti-aging, anti-melanogenic, anti-tyrosinase, cytoprotective, cardiodepressive, antipsychotic, analgesic, anti-inflammatory, and tissue healing activities. Clinical trials conducted in Brazil showed that extracts of A. zerumbet have hypotensive and diuretic effects whereas topical application of the essential oil has positive therapeutic effects on patients with fibromyalgia. Spanning two continents of Asia and South America, A. zerumbet is truly a multi-purpose ginger plant with promising medicinal properties.

关键词： Alpinia zerumbet Shell ginger Phytochemistry Pharmacology Clinical trials

An Overview of Chemical Constituents, Medicinal Properties, Clinical Trials, and Patents of Twigs of Morus alba(Ramulus Mori)

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 149-158页

作者： Eric Wei Chiang chan Hung Tuck chan Siu Kuin Wong Department of Food Science and Nutrition Faculty of Applied SciencesUCSI UniversityCherasKuala LumpurMalaysia Secretariat of International Society for Mangrove Ecosystems Faculty of AgricultureUniversity of the RyukyusOkinawaJapan School of Foundation Studies Xiamen University MalaysiaSepangSelangorMalaysia

The rich chemical constituents and diverse pharmacological properties of Ramulus Mori(RM) or the twig of Morus alba with evidence supported by clinical trials and patents are reviewed. Known as Sangzhi in Chinese, RM is widely used in traditional Chinese medicine to treat gout, arthritis, and rheumatism. Chemical constituents include flavonoids, benzofurans, alkaloids, stilbenes, chalcones, phenolic acids, and coumarins. Bioactivities of RM include antidiabetic, anti-obesity, anti-inflammatory, antityrosinase, neuroprotective, antioxidant, hepatoprotective, cytoprotective, renoprotective, antihyperuricemic, analgesic, antifungal, DNA protective, anticancer, gastroprotective, cardioprotective, anti-hair aging, anti-arthritic, and antiplatelet aggregation properties. The most active compounds from RM are mulberrin, oxyresveratrol, and mulberroside A. All four clinical trials on RM are focused on the treatment of diabetes. The patents entail using RM extracts as cosmetics for skin whitening and as agents for hypoglycemia. Topics for further research on RM are suggested.

关键词： Clinical trials mulberrin mulberroside A oxyresveratrol patents Sangzhi

An overview of Pu-erh tea and its health-promoting effects of lipid-lowering and anti-obesity

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Journal of Chinese Pharmaceutical Sciences 2021年第8期30卷 623-633页

作者： Eric Wei Chiang chan Siu Kuin Wong Hung Tuck chan Faculty of Applied Sciences UCSI University56000 Cher asKuala LumpurMalaysia School of Foundation Studies Xiamen University MalaysiaBandar Sunsuria43900 SepangSelangorMalaysia Secretariat of International Society for Mangrove Ecosystems(ISME) Faculty of AgricultureUniversity of the RyukyusOkinawa 903-0129Japan

As a dark tea,Pu-erh tea(PET)is produced from sun-dried leaves of Camellia sinensis *** mainly in Yunnan Province of *** microorganisms are involved in the fermentation of *** them,Aspergillus niger is most *** is believed that the longer the preservation period,the better is the quality and taste of PET,which is commercially available as loose,compressed or instant tea *** components of PET include flavones,flavanols,flavonols,phenolic acids,alkaloids and *** this overview,the lipid-lowering and anti-obesity effects of PET were discussed based on animal models and human trials,and our study provided some insights into possible mechanisms of bioactive compounds,such as theabrownin,catechins,lovastatin and gallic *** bioactivities of PET and some information on Fuzhuan brick tea were also *** of information cited were from Google Scholar,Pub Med,Pub Med Central,Science Direct,J-Stage,Pub Chem,Directory of Open Access Journals(DOAJ),and China National Knowledge Infrastructure(CNKI).

关键词： Pu-erh tea Fuzhuan brick tea Fermentation Lipid-lowering Anti-obesity

A global typical meteorological year(Tmy)database on ERA5 dataset

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Building Simulation 2023年第6期16卷 1013-1026页

作者： Yi Wu Jingjing An Chenxi Gui chan Xiao Da Yan Building Energy Research Center School of ArchitectureTsinghua UniversityBeijing100084China School of Environment and Energy Engineering Beijing University of Civil Engineering and ArchitectureBeijing100044China National Climate Center China Meteorological AdministrationBeijingChina

The outdoor climate condition is one of the deterministic factors influencing building energy *** performance simulation(BPS)tools usually adopt typical meteorological year(Tmy)as the outdoor climate *** that many scholars and institutes have developed Tmy datasets,these datasets are usually based on distinct data sources and *** the increase of international cooperation construction projects,compatible Tmy dataset for different countries is in urgent *** paper presents a global typical meteorological year(Tmy)database covering 38,947 stations worldwide based on the fifth-generation atmospheric reanalysis product released by the European Center(ERA5).The data is created with Chinese Standard Weather Database(CSWD)method to reflect the average level of historical *** dataset is saved in a 55 GB database of compressed CSV files and a website is established where users can download their required Tmy data for certain cities according to the longitude and latitude information.A systematic validation is conducted to confirm the feasibility of ERA5 as data source and validity of generated Tmy *** Tmy-ERA5 dataset is fundamental and essential in building system designs of international construction projects,building performance simulation,especially for some countries lacking ground meteorological stations or missing meteorological year data in the building *** can be used as references for other meteorological climate studies.

关键词： typical meteorological year atmospheric reanalysis data building simulation ERA5

The Evolutional Development of Traditional Chinese Medicine (TCM) Outside the Chinese mainland: Challenges,Training, Practice, Research, and Future Development

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World Journal of Traditional Chinese Medicine 2016年第4期2卷 6-28页

作者： Kelvin chan School of Pharmacy & Biomolecular Sciences Liverpool John Moores University L3 3AF UK The National Institute of Complementary Medicine Western Sydney University NSW 2560 Faculty of Science University of Technology Sydney NSW 2007 Australia

This overview has provided an account of evolutional changes of an experience-based traditional medical practice of traditional Chinese medicine(TCM) towards modernisation to keep up with recent advances in analytical and biomedical sciences, and information technology,which may help readers to understand why applying biomedical research methodology to TCM modernisation, while maintaining the experience-based concepts, principles and heritage of TCM's personalised health and medical approaches in balancing body's functions with physical and mental harmony when facing environmental changes, can contribute to gain global appreciation and acceptance of TCM in healthcare. It is envisaged that such future development and integration with biomedicine-based main-stream medicine(MSM) in practice will provide valuable medical care in the development of future personalised health and medicine as well as TCM product development.

关键词： Evolution of MSM & TCM Challenges Training Practice Research Integrative development

Positive solutions for a Lotka-Volterra prey-predator model with cross-diffusion and Holling type-Ⅱ functional response

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Science China Mathematics 2014年第5期57卷 991-1010页

作者： ZHOU Jun KIM chan-Gyun School of Mathematics and Statistics Southwest University Department of Mathematics College of William and Mary

We consider a Lotka-Volterra prey-predator model with cross-diffusion and Holling type-II functional *** main concern is the existence of positive solutions under the combined effect of cross-diffusion and Holling type-II functional ***,a positive solution corresponds to a coexistence state of the ***,we study the sufficient conditions to ensure the existence of positive solutions by using degree theory and analyze the coexistence region in parameter *** addition,we present the uniqueness of positive solutions in one dimension ***,we study the stability of the trivial and semi-trivial solutions by analyzing the principal eigenvalue of the corresponding linearized system,and then we characterize the stable/unstable regions of semi-trivial solutions in parameter plane.

关键词： Lotka-Volterra prey-predator model Holling type-II functional response cross-diffusion positive solutions coexistence uniqueness degree theory