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Metabolic memory:mechanisms and diseases

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1086-1114页

作者： Hao Dong Yuezhang Sun Lulingxiao Nie Aimin Cui Pengfei Zhao wai keung leung Qi Wang State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Department of Prosthodontics West China Hospital of StomatologySichuan UniversityChengduChina Periodontology and Implant Dentistry Division Faculty of DentistryThe University of Hong KongHong KongChina

Metabolic diseases and their complications impose health and economic burdens *** from past experimental studies and clinical trials suggests our body may have the ability to remember the past metabolic environment,such as hyperglycemia or hyperlipidemia,thus leading to chronic inflammatory disorders and other diseases even after the elimination of these metabolic *** long-term effects of that aberrant metabolism on the body have been summarized as metabolic memory and are found to assume a crucial role in states of health and *** molecular mechanisms collectively participate in metabolic memory management,resulting in different cellular alterations as well as tissue and organ dysfunctions,culminating in disease progression and even affecting *** elucidation and expansion of the concept of metabolic memory provides more comprehensive insight into pathogenic mechanisms underlying metabolic diseases and complications and promises to be a new target in disease detection and ***,we retrace the history of relevant research on metabolic memory and summarize its salient *** provide a detailed discussion of the mechanisms by which metabolic memory may be involved in disease development at molecular,cellular,and organ levels,with emphasis on the impact of epigenetic ***,we present some of the pivotal findings arguing in favor of targeting metabolic memory to develop therapeutic strategies for metabolic diseases and provide the latest reflections on the consequences of metabolic memory as well as their implications for human health and diseases.

关键词： diseases metabolism alterations

p53-independent pRB degradation contributes to a drug-induced apoptosis in AGS cells

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Cell Research 2005年第9期 20-28页

作者： wai keung leung,Joseph Jao-Yiu SUNG Department of Medicine and Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital Shatin Hong Kong SAR China Department of Medicine and Therapeutics The Chinese University of Hong Kong Prince of Wales Hospital Shatin Hong Kong SAR China

The retinoblastoma (RB) tumor suppressor protein, pRB, plays an important role in the regulation of mammalian cell cycle. Furthermore, several lines of evidence suggest that pRB also involves in the regulation of apoptosis. In the present study, the degradation of pRB was observed in apoptotic gastric tumor cells treated with a new potent anti-tumor component, tripchlorolide (TC). The inhibition of pRB degradation by a general cysteine protease inhibitor IDAM resulted in the reduction of the apoptotic cells. Furthermore, the survival of the gastric tumor cells under the TC treatment was enhanced by an over-expression of exogenous pRB. These results suggest that the pRB degradation of the gastric tumor cells under the TC treatment involves in the apoptotic progression. In addition, the same extent of TC- induced pRB-degradation was detected in the gastric tumor cells containing a p53 dominant-negative construct, indicat- ing that this kind of pRB degradation is p53-independent.

关键词： pRB degradation p53 apoptosis.

Follow up of serial urea breath test results in patients after consumption of antibiotics for non-gastric infections

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World Journal of Gastroenterology 2002年第4期8卷 703-706页

作者： wai-keung leung Lawrence Cheung-Tsui Hung Carrie Ka-Li Kwok Rupert Wing-Loong Leong Daniel Kwok-keung Ng Joseph Jao-Yiu Sung Department of Medicine & Therapeutics Prince of Wales Hospitalthe Chinese University of Hong KongShatinHong KongChina Department of Paediatrics Kwong Wah HospitalKowloonHong KongChina

AIM: The widespread use of antibacterial therapy hasbeen suggested to be the cause for the decline in theprevalence of Helicobacter pyloriinfection. This studyexamine the serial changes of urea breath test resultsin a group of hospitalized patients who were givenantibacterial therapy for non-gastric ***: Thirty-five hospitalized patients who weregiven antibacterial therapy for clinical infections,predominantly chest and urinary infections, werestudied. Most (91%) patients were given singleantibiotic of either a penicillin or cephalosporin *** 13C-urea breath tests were performed within 24hours of initiation of antibiotics, at one-week and atsix-week post-therapy. H. pylori infection wasdiagnosed when one or more urea breath tests ***: All 35 patients completed three serial ureabreath tests and 26 (74 %) were H. pylori-positive. Ten(38 %) H. pylori-infected patients had at least onenegative breath test results during the study *** medium delta 13C values were significantly lowerat baseline (8.8) than at one-week (20.3) and six-week(24.5) post-treatment in H. pylori-positive individuals(P=0.022). Clearance of H. pyloriat six-week was onlyseen in one patient who had received anti-helicobactertherapy from another ***: Our results suggested that one-third ofH. pylori-infected individuals had transient false-negative urea breath test results during treatment withantibacterial agent. However, clearance of H. pyloriinfection by regular antibiotic consumption is rare.

关键词：抗生素 HP感染连续尿素呼吸试验耐药

Clinical significance of hepatic derangement in severe acute respiratory syndrome

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World Journal of Gastroenterology 2005年第14期11卷 2148-2153页

作者： Henry Lik-Yuen Chan Ambrose Chi-Pong Kwan Ka-Fai To Sik-To Lai Paul Kay-Sheung Chan wai-keung leung Nelson Lee Alan Wu Joseph Jao-Yiu Sung Department of Medicine and Therapeutics Chinese University of Hong Kong Hong Kong SARChina Department of Medicine Princess Margaret Hospital Hong Kong SARChina Department of Anatomical and Cellular Pathology Chinese University of Hong Kong Hong Kong SARChina Department of Microbiology Chinese University of Hong Kong Hong Kong SARChina

AIM:Elevation of alanine aminotransferase (ALT) level is commonly seen among patients suffering from severe acute respiratory syndrome (SARS). We report the progression and clinical significance of liver derangement in a large cohort of SARS patient. METHODS: Serial assay of serum ALT was followed in patients who fulfilled the WHO criteria of SARS. Those with elevated ALT were compared with those with normal liver functions for clinical outcome. Serology for hepatitis B virus (HBV) infection was checked. Adverse outcomes were defined as oxygen desaturation, need of intensive care unit (ICU) and mechanical ventilation and death. RESULTS: Two hundred and ninety-four patients were included in this study. Seventy (24%) patients had elevated serum ALT on admission and 204 (69%) patients had elevated ALT during the subsequent course of illness. Using peak ALT >5xULN as a cut-off and after adjusting for potential confounding factors, the odds ratio of peak ALT >5x ULN for oxygen desaturation was 3.24 (95%CI 1.23-8.59, P= 0.018), ICU care was 3.70 (95%CI 1.38-9.89, P= 0.009), mechanical ventilation was 6.64 (95%CI 2.22-19.81, P = 0.001) and death was 7.34 (95%CI 2.28-24.89, P= 0.001). Ninety-three percent of the survived patients had ALT levels normalized or were on the improving trend during follow-up. Chronic hepatitis B was not associated with worse clinical outcomes. CONCLUSION: Reactive hepatitis is a common complication of SARS-coronavirus infection. Those patients with severe hepatitis had worse clinical outcome.

关键词： SARS Hepatitis Hepatitis B virus Coronavirus

Contents of four active components in different commercial crude drugs and preparations of Danshen (Salvia miltiorrhiza)

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Acta Pharmacologica Sinica 2002年第12期23卷 110-115页

作者： Susan wai Sum leung,Yaw Loong SIOW,Ricky Ying keung MAN Department of Pharmacology Faculty of Medicine University of Hong Kong 21 Sassoon Road Hong Kong China Department of Pharmacology Faculty of Medicine University of Hong Kong 21 Sassoon Road Hong Kong China Department of Pharmacology Faculty of Medicine University of Hong Kong 21 Sassoon Road Hong Kong China Department of Pharmacology University of Hong Kong 21 Sassoon Road Hong Kong China

AIM: To detect the contents of four active components of Salvia miltiorrhiza in various commercially available danshen crude drugs and preparations. METHODS: Commercially available danshen crude drugs from different sources, as well as danshen pills and intravenous injection preparations containing danshen alone or in combination with other herbs were collected. The composition of these danshen samples was analyzed using HPLC. Specifically, the amounts of magnesium tanshinoate B (MTB), danshensu, isotanshinone IIA, and ctyptotanshinone were determined. In some of these samples, the content of MTB was further confirmed by liquid chromatography-tandem mass spectrometer (LC-MS)/MS method. RESULTS: There were great variations in the amount of the four active ingredients in the commercially available danshen crude drugs and drug preparations in this study. The amount of MTB was the highest among the four components measured in the crude drugs. However, the amounts of MTB in all danshen preparations were much

关键词： Salvia miltiorrhiza magnesium tanshinoate B (MTB) high pressure liquid chromatography

Investigation of drinking water bacterial community through high-throughput sequencing

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Journal of Environmental Sciences 2015年第11期27卷 154-156页

作者： Tsz wai Ng Guocheng Huang Po keung Wong School of Life Sciences The Chinese University of Hong Kong

Delivery of safe and pathogen-free drinking water is crucial to public ***,there exist challenges to the maintenance of the sterility of drinking water throughout the drinking water distribution systems（DWDS）.Microbial growth in DWDS,such as growth of opportunistic pathogenic microorganisms,can lead to severe health problems in consumers（Berry et al.,2006;Brettar and Hofle,2006;Lu et al.,2014;Zhang et al.,2015）.

关键词： Drinking water distribution systems Microbial community High-throughput sequencing Water safety

Gastrointestinal stromal tumors in a cohort of Chinese patients in Hong Kong

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World Journal of Gastroenterology 2006年第14期12卷 2223-2228页

作者： Kam Hoi Chan Chun Wing Chan wai Hung Chow wai keung Kwan Chi Kwan Kong Ka Fung Mak Miu Yi leung Lin Kiu Lau Department of Medicine Yan Chai Hospital Tsuen Wan Hong Kong SAR China Department of Surgery Yan Chai Hospital Tsuen Wan Hong Kong SAR China Department of Radiology Yah Chai Hospital Tsuen Wan Hong Kong SAR Chin Department of Pathology Yah Chai Hospital Tsuen Wan Hong Kong SAR China

AIM： To investigate the prevalence and clinical pattern of gastrointestinal stromal tumors （GISTs） in Hong Kong Chinese, and to assess the impact of introduction of CD117 on the disease incidence. METHODS： From the database of the Department of Pathology of Yan Chai Hospital, 47 patients, with GISTs from September 1995 to December 2003 were included in this study. Ten GISTs were diagnosed before the introduction of CD117. The clinical features, tumor characteristics, and treatment were analyzed. Factors predicting tumor related death or recurrence were studied with Cox proportional hazard model. RESULTS： The patients included 26 males and 21 females, with a mean age of 66.6 years （SD 13.1, range 29-87 years）. The estimated prevalence of GISTs was 13.4-15.6 per 100 000 people, with an annual inddence of 1.68-1.96 per 100 000 people. The annual incidence of GISTs before and after the introduction of CD117 was 1.1 per 100 000 people and 2.1 per 100 000 people respectively. Stomach （34 patients, 72.3%） was the most common location for the tumor, followed by the small intestine （8 patients, 17.0%）, esophagus （2 patients, 4.3%）, omentum （2 patients, 4.3%） and colon （1 patient, 2.1%）. Thirty-one patients （66%） had complete tumor resection. Eleven out of 16 deaths （23%） were tumor-related. The median survival time was 26 too. Five-year survival rate was 61.3%. The significant factors associated with tumor-related death or recurrence were incomplete resection, tumor size 5 cm or above, invasion to the adjacent organ or presence of metastasis, CONCLUSION： The incidence of GIST in Hong Kong is comparable to that in the United States but lower than that in Finland. The true incidence of GISTs could be underestimated before the introduction of CD117. Incomplete resection, tumor size 5 cm or above, invasion to the adjacent organ or presence of metastasis are factors predicting tumor-related death or recurrence.

关键词： Gastrointestinal tumor GIST Prognostic factors, Clinical features Incidence

Within-Cluster Variability Exponent for Identifying Coherent Structures in Dynamical Systems

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Communications in Computational Physics 2023年第3期33卷 824-848页

作者： wai Ming Chau Shingyu leung Department of Mathematics The Hong Kong University of Science and TechnologyClear Water BayHong Kong

We propose a clustering-based approach for identifying coherent flow structuresin continuous dynamical systems. We first treat a particle trajectory over a finitetime interval as a high-dimensional data point and then cluster these data from differentinitial locations into groups. The method then uses the normalized standarddeviation or mean absolute deviation to quantify the deformation. Unlike the usualfinite-time Lyapunov exponent (FTLE), the proposed algorithm considers the completetraveling history of the particles. We also suggest two extensions of the method. To improvethe computational efficiency, we develop an adaptive approach that constructsdifferent subsamples of the whole particle trajectory based on a finite time interval. Tostart the computation in parallel to the flow trajectory data collection, we also developan on-the-fly approach to improve the solution as we continue to provide more measurementsfor the algorithm. The method can efficiently compute the WCVE over adifferent time interval by modifying the available data points.

关键词： Dynamical system visualization finite time Lyapunov exponent numerical methods for differential equations k-means clustering

幽门螺杆菌治疗后长期使用质子泵抑制剂与胃癌发生的风险:以人群为基础的研究

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英国医学杂志中文版 2019年第7期22卷 422-422页

作者： Ka Shing Cheung Esther W Chan Angel Y S Wong Lijia Chen lan C K Wong wai keung leung 彭浩(译) 不详应急总医院普外肿瘤科

目的质子泵抑制剂(PPIs)与胃萎缩恶化相关,尤其是在幽门螺杆菌(HP)感染者中。我们确定了在接受抗HP治疗的HP感染者中,PPIs使用与胃癌(GC)之间的相关性。设计本研究以中国香港全区健康资料库为基础。我们首先确认出自2003至2012年间接受... 详细信息

目的质子泵抑制剂(PPIs)与胃萎缩恶化相关,尤其是在幽门螺杆菌(HP)感染者中。我们确定了在接受抗HP治疗的HP感染者中,PPIs使用与胃癌(GC)之间的相关性。设计本研究以中国香港全区健康资料库为基础。我们首先确认出自2003至2012年间接受过以克拉霉素为基础的三联疗法门诊处方的成年人。排除标准:使用该处方治疗失败的患者,HP治疗后12个月内确诊为GC的患者,以及治疗后发生胃溃疡者。GC排除前的6个月内开始PPIs或H2受体阻滞剂(H2RA)治疗,以避免原始偏倚。通过C。x比例风险模型的倾向分数调整,评估GC发生风险与质子泵抑制剂二者之间的关系。H2RA作为阴性对照暴露。结果共63 397名合格受试者入选,在平均7.6年的随访时间中,有153(0.24%)名发生GC。PPIs使用与GC发生风险增高相关[危害比(HR)2.44,95%可信区间(C/)1.42-4.20],而H2RA无相关性(“R 0.72,95%CI 0.48-1.07)0GC发生的风险随PPIs使用时间的延长而增高(PPIs使用时间/年22年和年的GC发生风险分别为:HR 5.04.95%CI 1.23-20.61;6.65,1.62-27.26和8.34,95%CI 2.02-34.41)。PPIs使用相比非PPIs使用,调整的绝对风险差为每10000人年超过4.29 GC(95%C/1.25-9.54)。结论即使在HP根除治疗后,长期使用质子泵抑制剂仍与GC的发生风险增加相关。

关键词： Cox比例风险模型质子泵抑制剂治疗失败幽门螺杆菌胃癌发生 H2受体阻滞剂人群 HP根除治疗