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HM30181A,a potent P-glycoprotein inhibitor,potentiates the absorption and in vivo antitumor efficacy of paclitaxel in an orthotopic brain tumor model

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Cancer Biology & Medicine 2020年第4期17卷 986-1001页

作者： Wu Zeng Betty Yuen Kwan Law Vincent Kam Wai Wong Denise So Bik Chan Simon Wing Fai Mok Joyce Jia Ying Gao Rebecca Ka Yan Ho Xu Liang Jia Hao Li Ming Tsung Lee Weng Li Yoon Michael P Smolinski Johnson Yiu Nam lau Christopher Wai kei Lam Manson Fok State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina At he nex Hong Kong Irmo vative Limited Hong Kong China Faculty of Medici ne Macao Un iversity of Science and TechnologyMacaoChina Athenex Inc. New York 14203USA

Objective:Delivery of chemotherapeutic drugs to the brain has remained a major obstacle in the treatment of glioma,owing to the presence of the blood-brain barrier and the activity of P-gp,which pumps its substrate back into the systemic *** aim of the present study was to develop an intravenous formulation of HM30181 A(HM)to inhibit P-gp in the brain to effectively deliver paclitaxel(PTX)for the treatment of malignant ***:Two formulations of solubilized HM were designed on the basis of different solid dispersion strategies:i)spray-drying[polyvinlypyrrolidone(PVP)-HM]and ii)solvent evaporation[HP-β-cyclodextrin(cyclodextrin)-HM].The P-gp inhibition of these 2 formulations was assessed on the basis of rhodamine 123 uptake in cancer *** and brain pharmacokinetic parameters were also determined,and the antitumor effect of cyclodextrin-HM with PTX was evaluated in an orthotopic glioma xenograft mouse ***:Although both PVP-HM and cyclodextrin-HM formulations showed promising P-gp inhibition activity in vitro,cyclodextrin-HM had a higher maximum tolerated dose in mice than did *** study of cyclodextrin-HM revealed a plasma concentration plateau at 20 mg/kg,and the mice began to lose weight at doses above this ***-HM(10 mg/kg)administered with PTX at 10 mg/kg showed optimal antitumor activity in a mouse model,according to both tumor volume measurement and survival time(Pmay have potential for glioma therapy in humans.

关键词： HM30181A glioma pharmacokinetics paclitaxel P-glycoprotein

What can implementation science offer civil society in their efforts to drive rights-based health reform?

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Global Health Research and Policy 2023年第1期8卷 548-554页

作者： Diya Uberoi Tolulope Ojo Abi Sriharan Lincoln lau Faculty of Law McGill University3644 Peel StMontrealQC H3A 1W9Canada Dalla Lana School of Public Health University of Toronto155 College StreetToronto M5T 3M7Canada

Over the years,civil society organizations(CSOs)have made tremendous efforts to ensure that state policies,programmes,and actions facilitate equitable access to *** CSOs are key actors in the realization of the right to health,a systematic understanding of how CSOs achieve policy change is *** science,a discipline focused on the methods and strategies facilitating the uptake of evidence-based practice and research can bring relevant,untapped methodologies to understand how CSOs drive health *** article argues for the use of evidence-based strategies to enhance civil society *** hold that implementation science can offer an actionable frame to aid CSOs in deciphering the mechanisms and conditions in which to pursue rights-based actions most *** empirical studies are needed to generate evidence and CSOs have already indicated the need for more data-driven solutions to empower activists to hold policymakers to *** implementation science may not resolve all the challenges CSOs face,its frameworks and approaches can provide an innovative way for organizations to chart out a course for reform.

关键词： Right to health Access to medicines Implementation science Civil society

Numerical Simulation of the Genesis of Typhoon Durian (2001) over the South China Sea:the Effect of Sea Surface Temperature

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Journal of Ocean University of China 2010年第2期9卷 99-115页

作者： WANG Lei lau Kai-Hon FUNG Chi-Hung Department of Mathematics Hong Kong University of Science and Technology Hong Kong P. R. China Institute for the Environment Hong Kong University of Science and Technology Hong Kong P. R. China

Typhoon Durian (2001),which formed over the South China Sea (SCS),was simulated by using the Weather Research and Forecasting (WRF) model. The genesis of typhoon Durian which formed in the monsoon trough was reproduced by numerical simulations. The simulated results agree reasonably well with observations. Two numerical experiments in which the sea surface temperature (SST) was either decreased or increased were performed to investigate the impact of the SST on the genesis of the ty-phoon. When the SST was decreased by 5℃ uniformly for all grids in the model,the winds calculated became divergent in the lower troposphere and convergent in the upper troposphere,creating conditions in which the amount of total latent heat release (TLHR) was low and the tropical cyclone (TC) could not be formed. This simulation shows the importance of the convergence in the lower tropo-sphere and the divergence in the upper troposphere for the genesis of the initial vortex. When the SST was increased by 1℃ uni-formly for all grids,a stronger typhoon was generated in the results with an increase of about 10 m s-1 in the maximum surface wind speed. Only minor differences in intensity were noted during the first 54 h in the simulation with the warmer SST,but apparent dif-ferences in intensity occurred after 54 h when the vortex began to strengthen to typhoon strength. This experiment shows that warmer SST will speed the strengthening from tropical storm strength to typhoon strength and increase the maximum intensity reached,while only minor impact can be seen during the earlier stage of genesis before the TC reaches the tropical storm strength. The results sug-gest that the amount of TLHR may be the dominant factor in determining the formation and the intensification of the TC.

关键词： tropical cyclone WRF numerical simulation cyclone genesis

Non-regular Employment of Women,Fertility Rate,and Economic Growth

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Economics World 2018年第3期6卷 217-227页

作者： kei Murata Shizuoka University ShizuokaJapan

This study analyzes the interaction between non-regular employment of women and economic growth patterns by an overlapping-generations *** Birthrate White Paper-Cabinet Office(2013)shows the ideal number of children per household is 2.42 compared to the current number of 2.07,which is the lowest so far in *** main reason households do not have the ideal number of children is“the costs burden of childcare and education”and the ratio amounts to 60.4%.In recent years in Japan,households in which both the husband and the wife work are increasing,whereas those in which only the husband works are ***,although women have same educational background and abilities as men,most women become non-regular employees after marriage and childbirth,which reduces household *** such a situation,raising the rate of pension insurance will be a big burden for the household and the declining birthrate may be caused by high levels of educational expenditure and pension *** Japanese government has discussed raising the wages of non-regular *** paper finds that a rise in the wage rate of non-regular employment is needed under the public pension policy that raises the rate of pension insurance,and it must be at an adequate *** is,there is a high risk that this policy will have a negative effect on Japan’s economic growth if an adequate level is not achieved.

关键词： overlapping-generations employment of women fertility rate public pension policy human capital economic growth

Low serum amylase and obesity, diabetes and metabolic syndrome: A novel interpretation

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World Journal of Diabetes 2016年第6期7卷 112-121页

作者： kei Nakajima Department of Metabolism Kuki General Hospital Division of Clinical Nutrition Department of Medical Dietetics Faculty of Pharmaceutical Sciences Josai University

For the last decade, low serum amylase(hypoamylasemia) has been reported in certain common cardiometabolic conditions such as obesity, diabetes(regardless of type), and metabolic syndrome, all of which appear to have a common etiology of insufficient insulin action due to insulin resistance and/or diminished insulin secretion. Some clinical studies have shown that salivary amylase may be preferentially decreased in obese individuals, whereas others have revealed that pancreatic amylase may be preferentially decreased in diabetic subjects with insulin dependence. Despite this accumulated evidence, the clinical relevance of serum, salivary, and pancreatic amylase and the underlying mechanisms have not been fully elucidated. In recent years, copy number variations(CNVs) in the salivary amylase gene(AMY1), which range more broadly than the pancreatic amylase gene(AMY2A and AMY2B), have been shown to be well correlated with salivary and serum amylase levels. In addition, low CNV of AMY1, indicating low salivary amylase, was associated with insulin resistance, obesity, low taste perception/satiety, and postprandial hyperglycemia through impaired insulin secretion at early cephalic phase. In most populations, insulin-dependent diabetes is less prevalent(minor contribution) compared with insulin-independent diabetes, and obesity is highly prevalent compared with low body weight. Therefore, obesity as a condition that elicits cardiometabolic diseases relating to insulin resistance(major contribution) may be a common determinant for low serum amylase in a general population. In this review, the novel interpretation of low serum, salivary, and pancreas amylase is discussed in terms of major contributions of obesity, diabetes, and metabolic syndrome.

关键词： Serum amylase Salivary Pancreas Diabetes Metabolic syndrome Obesity AMY1 AMY2 Insulin resistance

Hong Kong female's breast cancer awareness measure: Cross-sectional survey

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World Journal of Clinical Oncology 2019年第2期10卷 98-109页

作者： may Pui Shan Yeung Emily Ying Yang Chan Samuel Yeung Shan Wong Benjamin Hon kei Yip Polly Suk-Yee Cheung Division of Global Health and Humanitarian Medicine the Jockey Club School of Public Health and Primary Care the Chinese University of Hong Kong Prince of Wales Hospital Division of Family Medicine and Primary Healthcare the Jockey Club School of Public Health and Primary Care The Chinese University of Hong Kong Prince of Wales Hospital Hong Kong Breast Cancer Foundation

BACKGROUND In women worldwide, breast cancer is the most common cancer. Breast cancer accounted for 26.6% of all new cancers in females diagnosed in 2015 in Hong *** To examine women's awareness, perception, knowledge, and screening practice of breast cancer in Hong *** We carried out a population-based survey using random telephone interviews to women aged 18 or above using the United Kingdom Cancer Research Breast Cancer Awareness Measure(United Kingdom CAM). The data was analysed using proportions, chi-square test(χ~2-test) and adjusted odds ratios(ORs).RESULTS A total of 1000 participants completed the CAM questionnaire from 1,731 responses(response rate = 57.8%) from September to October 2017. One in five and one in four respondents recalled ≥ 3 early warning signs and ≥ 2 risk factors of breast cancer respectively. The majority(62.6%) reported they were not confident that they would notice a change in their breasts. Among the respondents, 16.8% would have regular mammography at least every two *** general, 4 in 10 women had tried practices on preventing breast *** with better result in recalling breast cancer signs and symptoms were more likely to seek immediate medical help when noticed a change in their breasts(χ2-test P = 0.038), and more likely had tried prevention practice(χ~2-test P< 0.001). Respondents received higher education(secondary school or above) had higher breast cancer awareness(OR = 2.83, CI: 1.61-4.97), more frequent screening(OR = 2.64, CI: 1.63-4.26) and more had tried prevention practices(OR = 2.80, CI:1.96-4.02) when compared to those with lower education. Those in age groups 31-45 and 46-60 had higher percentages in performing breast self-exam and mammography when compared to the 18-30 and 61 or above age *** Population-wide public health initiatives should emphasize on prevention and early detection of breast cancer in women, with targeted strategy for those with low education level and a

关键词： Breast cancer Cancer Awareness Measure Awareness Screening practice Behaviour Attitude

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重塑钻石梦 034

The ion balance of Shotokuseki extract promotes filaggrin fragmentation and increases amino acid production and pyrrolidone carboxylic acid content in three-dimensional cultured human epidermis

21世纪经济报道

作者： Wed lau Gary may

“中国的钻石市场仍在不断拓宽，钻石消费在中小型城市的穿透力也很强，但钻石品牌对中国珠宝市场的占领仍然不全面。”9月17日，钻石业巨头戴比尔斯公司（De Beers）在香港发布了《钻石市场前景报告》。De Beers全球CEO Philippe Mell...

“中国的钻石市场仍在不断拓宽，钻石消费在中小型城市的穿透力也很强，但钻石品牌对中国珠宝市场的占领仍然不全面。”9月17日，钻石业巨头戴比尔斯公司（De Beers）在香港发布了《钻石市场前景报告》。De Beers全球CEO Philippe Mellier指出，“钻石行业在未来将面临供应量减

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Natural Products and Bioprospecting 2022年第1期12卷 586-594页

作者： kei Tsukui Takuya Kakiuchi Masamitsu Suzuki Hidetomo Sakurai Yoshihiro Tokudome Laboratory of Cosmetic Sciences Graduate School of Advanced Health SciencesSaga University1 HonjoSaga 840-8502Japan Laboratory of Dermatological Physiology Faculty of Pharmacy and Pharmaceutical SciencesJosai University1-1 KeyakidaiSakadoSaitama 350-0295Japan Zeria Pharmaceutical Co. Ltd.10-11 NihonbashiKobuna-choChuo-kuTokyo 103-8351Japan Laboratory of Cosmetic Sciences Regional Innovation CenterSaga University1 HonjoSaga 840-8502Japan

Natural moisturizing factor(NMF)in the stratum corneum contributes to the retention of moisture *** purpose of this study was to determine the penetration of ions in Shotokuseki extract(SE)into the three-dimensional cultured epidermis and the effect of NMF on the biosynthesis of amino acids and pyrrolidone carboxylic acid ***-ous ions,amino acids and pyrrolidone carboxylic acid were quantified by inductively coupled plasma mass spectrom-etry,fully automatic amino acid analyzer or high-performance liquid chromatography(HPLC)in three-dimensional cultured epidermis after application of *** expression levels of profilaggrin,calpain1,caspase14,and bleomycin hydrolase,which are involved in NMF production,were determined by reverse-transcription qPCR and bleomycin hydrolase activity was determined by aminopeptidase *** application of SE increased Na,K,Mg,Ca,Al,and Fe levels in three-dimensional cultured *** mRNA levels of the starting material of amino acid synthesis profilaggrin,and calpain1 and bleomycin hydrolase,which are involved in its fragmentation,*** activity of bleomycin hydrolase also ***,the levels of amino acids and pyrrolidone carboxylic acid increased in the three-dimensional cultured *** suggests that the ionic composition of SE may be involved in its moisturizing effect on the stratum corneum.

关键词： Shotokuseki extract Epidermis Amino acid Pyrrolidone carboxylic acid Ion Gene expression

MTBSTFA derivatization-LC-MS/MS approach for the quantitative analysis of endogenous nucleotides in human colorectal carcinoma cells

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Journal of Pharmaceutical Analysis 2022年第1期12卷 77-86页

作者： Huixia Zhang Yan Li Zheng Li Christopher Wai-kei Lam Peng Zhu Caiyun Wang Hua Zhou Wei Zhang State Key Laboratory of Quality Research in Chinese Medicines Macao Institute for Applied Research in Medicine and HealthMacao University of Science and TechnologyTaipaMacaoChina

Endogenous ribonucleotides(RNs)and deoxyribonucleotides(dRNs)are important metabolites related to the pathogenesis of many *** light of their physiological and pathological significances,a novel and sensitive pre-column derivatization method with N-(t-butyldimethylsilyl)-N-methyltrifluoroacetamide(MTBSTFA)was developed to determine RNs and dRNs in human cells using high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).A one-step extraction of cells with 85%methanol followed by a simple derivatization reaction within 5 min at room temperature contributed to shortened analysis *** derivatives of 22 nucleoside mono-,di-and tri-phosphates were retained on the typical C;column and eluted by ammonium acetate and acetonitrile in 9 *** these optimal conditions,good linearity was achieved in the tested calibration *** lower limit of quantitation(LLOQ)was determined to be 0.1-0.4μM for the tested RNs and 0.001-0.1μM for *** addition,the precision(CV)wasmay be used for specific expanded studies on intracellular pharmacology in vitro.

关键词： Ribonucleotides Deoxyribonucleotides Derivatization N-(t-butyldimethylsilyl)-N-methyltrifluoroacetamide High-performance liquid chromatography tandem mass spectrometry