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Insulin exerts direct, IGF-1 independent actions in growth plate chondrocytes

Bone Research 2014年第2期2卷 121-130页

作者： Fengjie Zhang Qiling He wing pui tsang W Timothy Garvey Wai Yee Chan Chao Wan Ministry of Education Key Laboratory for Regenerative Medicine School of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong School of Biomedical Sciences Core Laboratory Institute of Stem Cell Genomics and Translational Research Shenzhen Research Institute The Chinese University of Hong Kong Departments of Microbiology and Pathology University of Alabama at Birmingham AL USA Department of Nutrition Sciences University of Alabama at Birmingham AL USA

Insufficient insulin production or action in diabetic states is associated with growth retardation and impaired bone healing, while the underling mechanisms are unknown. In this study, we sought to define the role of insulin signaling in the growth plate. Insulin treatment of embryonic metatarsal bones from wild-type mice increased chondrocyte proliferation. Mice lacking insulin receptor （IR） selectively in chondrocytes （CartIR-/-） had no discernable differences in total femoral length compared to control littermates. However, CartIR-/- mice exhibited an increase in chondrocyte numbers in the growth plate than that of the controls. Chondrocytes lacking IR had elevated insulin-like growth factor （IGF）-IR mRNA and protein levels. Subsequently, IGF-1 induced phosphorylafion of Akt and ERK was enhanced, while this action was eliminated when the cells were treated with IGF-1R inhibitor Picropodophyllin. Deletion of the IR impaired chondrogenic differentiation, and the effect could not be restored by treatment of insulin, but partially rescued by IGF-1 treatment. Intriguingly, the size of hypertrophic chondrocytes was smaller in CartIR-/- mice when compared with that of the control littermates, which was associated with upregnlation of tuberous sclerosis complex 2 （TSC2）. These results suggest that deletion of the IR in chondrocytes sensitizes IGF-1R signaling and action, IR and IGF-1R coordinate to regulate the proliferation, differentiation and hypertrophy of growth plate chondrocytes.

关键词： IGF-1 independent actions in growth plate chondrocytes Insulin exerts direct

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Psoralen prevents osteoporosis progression through inhibiting NFATc1-mediated osteoclastogenesis

Psoralen prevents osteoporosis progression through inhibitin...

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世界中医药学会联合会老年医学专业委员会2021年学术年会暨中国中西医结合学会慢病防治与管理专业委员会第四次学术年会

作者： Yanyan Wang Fengjie Zhang wing pui tsang Chao Wan Key Laboratory of Regenerative Medicine Ministry of Education School of Biomedical Sciences Faculty of Medicine The Chinese University of Hong Kong Key Laboratory of Regenerative Medicine Ministry of Education (Shenzhen Base) School of Biomedical Sciences Core LaboratoryShenzhen Research Institute The Chinese University of Hong Kong

With population aging, osteoporosis becomes an important public health issue affecting the elderly. Osteoporosis is a common metabolic bone disease characterized by decreased bone mass and increased risk of bone fractures. Discovery of novel therapeutic molecules or targets remains a significant clinical demand. Natural products from traditional Chinese medicines have been considered as an alternative source of candidate molecules for discovery of novel anti-osteoporosis drugs. Psoralen(PS), a coumarin derivative compound extracted from the seeds of Psoralea croylifolia Lnn., is shown to possess osteoprotective effect. However, the underlying pharmacological mechanisms of PS in prevention or treatment of osteoporosis remain unclear. In this study, we performed systemic in vitro and in vivo analyses to examine the cellular and molecular mechanisms of PS on osteoclast differentiation and function as well as its therapeutic efficacy in the ovariectomy(OVX) induced osteoporosis model in mice. The animals were divided into four groups: control, low, middle and high doses. Our data showed that PS dose-dependently inhibited bone marrow mononuclear cells(BMMNCs) derived osteoclast formation. Meanwhile, PS inhibited F-actin ring formation and suppressed osteoclastic bone resorption activity. PS attenuated the expression of osteoclast marker genes including nuclear factor of activated T-cells cytoplasmic 1(NFATc1), TRAP, calcitonin receptor(CTR), cathepsin K(CtsK), carbonic anhydrase Ⅱ(CAII) and matrix metalloproteinases 9(MMP9). Mechanistically, PS suppressed receptor activator of nuclear factor-κB ligand(RANKL)-induced activation of AKT and transcription factors including NFATc1, c-Fos and c-Jun that control osteoclast differentiation. Intraperitoneal delivery of PS at high dose for eight weeks prevented bone loss in the OVX mice accompanied by increased bone volume/total volume, trabecular number, decreased trabecular separation, osteoclast numbers and serum level of TRACP

关键词： Psoralen osteoporosis aging

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Can a cardiorespiratory field parameter assess both cardiovascular and respiratory fitness in schoolchildren?

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Health 2014年第1期6卷 33-43页

作者： Louisa Ming Yan Chung Lina pui Yu Chow Eric Cheuk Kuen tsang Joanne Wai Yee Chung Department of Health and Physical Education The Hong Kong Institute of Education Hong Kong China

Background: Cardiorespiratory fitness involves both cardiovascular and respiratory capacities. However, existing methods have been criticised for reflecting cardiovascular fitness, but not pulmonary fitness. The objective of this study was to investigate the relationship between these two testing parameters. Methods: A cross-sectional population-based physical fitness assessment was conducted in 23 schools. The body height and weight, lung capacity, and step test results of students aged 10-18 were recorded. Criterion-referenced standards from the China Sports Bureau were adopted, as they include separate measurements for cardiovascular and pulmonary fitness. Results: The Pearson coefficients of lung capacity and the step test index from 13,028 schoolchildren ranged from 0.007 to 0.086 and from 0.026 to 0.105 for boys and girls, respectively, showing that poor correlations exist between the two parameters. Cluster analysis resulted in three clusters of children with similar characteristics. A good degree of similarity was found between the two parameters in children obtaining an “excellent” grade, but only a moderate degree of similarity between the two parameters in those obtaining a “good”, “pass” or “fail” grade. Conclusion: When cardiovascular fitness and pulmonary fitness are considered separately, there is a poor correlation between them, thus indicating further studies of cardiopulmonary fitness measurements is necessary.

关键词： Cardiovascular Fitness Pulmonary Fitness Cardiorespiratory Fitness Field Assessment Schoolchildren

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Comparing 11 early warning scores and three shock indices in early sepsis prediction in the emergency department

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World Journal of Emergency Medicine 2024年第4期15卷 273-282页

作者： Rex pui Kin Lam Zonglin Dai Eric Ho Yin Lau Carrie Yuen Ting Ip Ho Ching Chan Lingyun Zhao Tat Chitsang Matthew Sik Hon Tsui Timothy Hudson Rainer Department of Emergency Medicine School of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina School of Public Health Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina Accident and Emergency Department Queen Mary HospitalHong KongChina

BACKGROUND:This study aimed to evaluate the discriminatory performance of 11 vital sign-based early warning scores(EWSs)and three shock indices in early sepsis prediction in the emergency department(ED).METHODS:We performed a retrospective study on consecutive adult patients with an infection over 3 months in a public ED in Hong *** primary outcome was sepsis(Sepsis-3 definition)within 48 h of ED *** c-statistics and the DeLong test,we compared 11 EWSs,including the National Early Warning Score 2(NEWS2),Modified Early Warning Score,and Worthing Physiological Scoring System(WPS),etc.,and three shock indices(the shock index[SI],modified shock index[MSI],and diastolic shock index[DSI]),with Systemic Inflammatory Response Syndrome(SIRS)and quick Sequential Organ Failure Assessment(qSOFA)in predicting the primary outcome,intensive care unit admission,and mortality at different time ***:We analyzed 601 patients,of whom 166(27.6%)developed ***2 had the highest point estimate(area under the receiver operating characteristic curve[AUROC]0.75,95%CI 0.70-0.79)and was significantly better than SIRS,qSOFA,other EWSs and shock indices,except WPS,at predicting the primary ***,the pooled sensitivity and specificity of NEWS2≥5 for the prediction of sepsis were 0.45(95%CI 0.37-0.52)and 0.88(95%CI 0.85-0.91),*** discriminatory performance of all EWSs and shock indices declined when used to predict mortality at a more remote time ***:NEWS2 compared favorably with other EWSs and shock indices in early sepsis prediction but its low sensitivity at the usual cut-off point requires further modification for sepsis screening.

关键词： Sepsis Emergency department Clinical prediction rule Early warning score Shock index

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Clinical Characteristics,Laboratory Identification,and In Vitro Antifungal Susceptibility of Yarrowia(Candida)lipolytica Isolates Causing Fungemia

Clinical Characteristics,Laboratory Identification,and In Vi...

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中华医学会第十二次全国临床微生物学术年会暨第十一次全球华人临床微生物学与感染症学术年会

作者：赵颖 Jasper Fuk-Woo Chan Chi-Ching tsang He Wang Dawen Guo Yuhong Pan Yuling Xiao Na Yue Jonathan Hon-Kwan Chen Susanna Kar-pui Lau Yingchun Xu Patrick Chiu-Yat Woo Department of Clinical Laboratory Peking Union Medical College HospitalChinese Academy of Medical Sciences State Key Laboratory of Emerging Infectious Diseases Department of MicrobiologyResearch Centre of Infection and Immunologyand Carol Yu Centre for InfectionThe University of Hong Kong Department of Microbiology the First Affiliated HospitalHarbin Medical University Department of Clinical Laboratory Fujian Medical University Union Hospital Division of Clinical Microbiology Department of Laboratory MedicineWest China HospitalSichuan University Laboratory Center General Hospital of Tianjin Medical University

目的研究引起真菌血症的解脂念珠菌的相关临床病例特征,实验室鉴定和体外真菌药敏试验。方法对2009-2012年CHIF-NET中分离到的15株解脂念珠菌进行临床病例分析。采用Vitek 2 YSTID Card,API 20C AUX system和MALDI-TOF MS.对菌株进行生...

目的研究引起真菌血症的解脂念珠菌的相关临床病例特征,实验室鉴定和体外真菌药敏试验。方法对2009-2012年CHIF-NET中分离到的15株解脂念珠菌进行临床病例分析。采用Vitek 2 YSTID Card,API 20C AUX system和MALDI-TOF MS.对菌株进行生化鉴定研究。采用Sensititre YeastOne微量肉汤稀释法进行9种抗真菌药物的体外药敏试验。结果这些菌株的临床病例分析提示对于不复杂的解脂念珠菌导管相关性感染可以采用仅移除导管而不

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音位配列规律对粤英双语者感知声音序列的影响

中国语音学报

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中国语音学报 2023年第1期19卷 166-174页

作者：吴漪嫚李明兴曾霈铫 Hong Kong Baptist University China Department of English Language and Literature at Hong Kong Baptist University China

对一门语言语音系统的习得包括对其音位配列规律的习得,前人研究中广泛地发现了已习得语言音位配列规律对语音感知的影响。例如Dupoux et al.(1999)对日语母语者的感知研究发现,他们在听辅音丛(*CC)时,可能在中间幻听到元音,这与日语中... 详细信息

对一门语言语音系统的习得包括对其音位配列规律的习得,前人研究中广泛地发现了已习得语言音位配列规律对语音感知的影响。例如Dupoux et al.(1999)对日语母语者的感知研究发现,他们在听辅音丛(*CC)时,可能在中间幻听到元音,这与日语中不允许辅音丛(*CC)有关。本研究关注粤语—英语双语者在感知音段序列时,是否会受到粤语和英语的影响。我们的实验设计以Dupoux et al.(1999)为基础。被试为20位粤英双语使用者,他们的第一语言为粤语,从4岁左右开始习得英语作为第二语言。实验刺激项是形为V_(1)C_(1)(V_(x))V_(2)C_(2)的假词,其中元音辅音是英语和粤语中常见的音段;刺激项中一半刺激项里C_(1)C_(2)的组合对应英语中存在的音节首辅音丛,例如[kl,gl],另一半刺激项里C_(1)C_(2)对应英语音节首中不存在的辅音丛,例如[km,gm];假词中间V_(x)的时长分为连续统上的六个长度,从0毫秒(即无元音)到95毫秒。每听到一个假词,被试判断C_(1)C_(2)中间是否有元音存在。经过线性混合模型的检验,实验结果显示:(1)就元音V_(x)的时长而言,时长越长,被试感知到元音的概率越高;(2)在V_(x)为0毫秒(即没有元音)时,粤英双语被试仍然在一定程度上感知到元音;(3)当C_(1)C_(2)组合对应英语中存在的音节首辅音丛时,例如[kl,gl],被试感知到元音的概率显著低于当C1 C2组合对应英语音节首中不存在的辅音丛的情况,例如[km,gm];(4)元音时长和C_(1)C_(2)是否对应英语辅音丛之间没有交互作用。实验结果(2)表明,在粤英双语使用者感知音段序列时,粤语的声韵搭配规律在起作用,这和Dupoux et al.(1999)等实验中日语母语者在辅音丛(*CC)中间幻听到元音相似;实验结果(3)表明,英语的音位配列规律也在起作用,影响被试的判断,使其在C_(1)C_(2)对应英语音节首辅音丛时,相对来说不易察觉到中间的元音V_(x)。另一方面,单就被试在V_(x)为0毫秒条件下的表现而言,其幻听到元音的概率低于Dupoux et al.(1999)实验中日语被试的相应概率,同时又略高于该实验中法语被试的相应概率。这似乎说明,被试的粤语和英语两种语言的音位配列规律存在相互作用,同时影响着被试对辅音间元音的感知。

关键词：音位配列规律英语粤语双语者感知

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Novel mitochondrial 16S rRNA mutation, 3200T→C, associated with adult-onset type 2 diabetes

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Chinese Medical Journal 2002年第5期115卷 753-758页

作者：杨涛林青云曾文和汤瑞芬甘尔惠陈婉珊潘妙娟巫向前彭智培 Department of Chemical Pathology the Chinese University of Hong KongHong KongChina Department of Ophthalmology&Visual Sciences the Chinese University of Hong KongHong KongChina Department of Medicine United Christian HospitalHong KongChina Department of Medical Genetics Institute of Basic Medieal SciencesChinese Acadelny of Medical Sciences&Peking Union Medieal CollegeBeijing 100005China Heahh School Shanghai Second Medical UniversityShanghai 2O0025China

Objective To investigate the role of a potential diabetes related mitochondrial region, which includes two previously reported mutations, 3243AG and 3316GA, in Chinese patients with adult onset type 2 diabetes Methods A total of 277 patients and 241 normal subjects were recruited for the study Mitochondrial nt 3116-3353, which spans the 16S rRNA, tRNA leu(UUR) and the NADH dehydrogenase 1 gene, were detected using polymerase chain reaction (PCR), direct DNA sequencing, PCR restriction fragment length polymorphism and allele specific PCR Variants were analyzed by two tailed Fisher exact test The function of the variants in 16S rRNA were predicted for minimal free energy secondary structures by RNA folding software mfold version 3 Results Four homoplasmic nucleotide substitutions were observed, 3200TC, 3206CT, 3290TC and 3316GA Only the 3200TC mutation is present in the diabetic population and absent in the control population No statistically significant associations were found between the other three variants and type 2 diabetes The 3200TC and 3206CT nucleotide substitutions located in 16S rRNA are novel variants The 3200TC caused a great alteration in the minimal free energy secondary structure model while the 3206CT altered normal 16S rRNA structure little Conclusions The results suggest that the 3200TC mutation is linked to the development of type 2 diabetes, but that the other observed mutations are neutral In contrast to the Japanese studies, the 3316GA does not appear to be related to type 2 diabetes

关键词： type 2 diabetes · mitochondrial DNA · 16S ribosomal RNA · RNA secondary structure modeling

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