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Wu T.,Beijing Institute of Geriatrics | Long X.,Beijing Normal University | Wang L.,Capital Medical University | Hallett M.,U.S. National Institutes of Health | And 3 more authors.
Human Brain Mapping | Year: 2011

Parkinson's disease (PD) patients have difficulty in initiating movements. Previous studies have suggested that the abnormal brain activity may happen not only during performance of self-initiated movements but also in the before movement (baseline or resting) state. In the current study, we investigated the functional connectivity of brain networks in the resting state in PD. We chose the rostral supplementary motor area (pre-SMA) and bilateral primary motor cortex (M1) as "seed" regions, because the pre-SMA is important in motor preparation, whereas the M1 is critical in motor execution. FMRIs were acquired in 18 patients and 18 matched controls. We found that in the resting state, the pattern of connectivity with both the pre-SMA or the M1 was changed in PD. Connectivity with the pre-SMA in patients with PD compared to normal subjects was increased connectivity to the right M1 and decreased to the left putamen, right insula, right premotor cortex, and left inferior parietal lobule. We only found stronger connectivity in the M1 with its own local region in patients with PD compared to controls. Our findings demonstrate that the interactions of brain networks are abnormal in PD in the resting state. There are more connectivity changes of networks related to motor preparation and initiation than to networks of motor execution in PD. We postulate that these disrupted connections indicate a lack of readiness for movement and may be partly responsible for difficulty in initiating movements in PD. © 2010 Wiley-Liss, Inc.


Jin J.,Beijing Institute of Geriatrics | Niu X.,Beijing Hospital | Zou L.,Beijing Institute of Geriatrics | Li L.,Beijing Hospital | And 5 more authors.
Cancer Letters | Year: 2016

Circulating tumor cells (CTCs) quantification may be helpful for evaluating cancer dissemination, predicting prognosis and assessing therapeutic effectiveness and safety. In the present study, CTCs from blood samples of 72 patients with hepatocellular carcinoma (HCC) were enriched with anti-EpCAM nanoparticles. AFP mRNA level was detected by nested polymerase chain reaction (PCR) after enrichment of CTCs from HCC blood samples at 0, 3, 6, 9 and 12 months after hepatectomy, respectively. AFP mRNA expression in CTCs was positive in 43 patients (59.7%) and negative in 29 patients (40.3%) before hepatectomy. Among 43 patients with positive AFP mRNA expression in CTCs before hepatectomy, 10 and 11 were diagnosed as intrahepatic/extrahepatic metastasis before and after hepatectomy, respectively. In addition, these 21 patients with metastasis had persisting positive AFP mRNA of CTCs during the whole tested year. Specifically, 3 patients with AFP mRNA negative in CTCs before hepatectomy changed to be positive at 6 and 9 months, and 2 of them were diagnosed as metastasis 12 months after hepatectomy. We conclude that the positive AFP mRNA of CTCs can be a pivotal predictor for HCC metastasis before and after hepatectomy. The release of AFP expression from hepatocellular carcinoma cells into circulation must be a major source of HCC metastasis. © 2016 Elsevier Ireland Ltd


Chen S.,Beijing Institute of Technology | Senlin L.,Beijing Institute of Technology | Pan L.,Beijing Institute of Technology | Zhang T.,Beijing Institute of Geriatrics | And 2 more authors.
Bio-Medical Materials and Engineering | Year: 2014

The aim of this study is to quantitatively analyze the influence of risk factors on the blood glucose level, and to provide theory basis for understanding the characteristics of blood glucose change and confirming the intervention index for type 2 diabetes. The quantitative method is proposed to analyze the influence of risk factors on blood glucose using back propagation (BP) neural network. Ten risk factors are screened first. Then the cohort is divided into nine groups by gender and age. According to the minimum error principle, nine BP models are trained respectively. The quantitative values of the influence of different risk factors on the blood glucose change can be obtained by sensitivity calculation. The experiment results indicate that weight is the leading cause of blood glucose change (0.2449). The second factors are cholesterol, age and triglyceride. The total ratio of these four factors reaches to 77% of the nine screened risk factors. And the sensitivity sequences can provide judgment method for individual intervention. This method can be applied to risk factors quantitative analysis of other diseases and potentially used for clinical practitioners to identify high risk populations for type 2 diabetes as well as other disease. © 2014 - IOS Press and the authors. All rights reserved.


PubMed | Beijing Institute of Geriatrics and Beijing Institute of Technology
Type: | Journal: Computers in biology and medicine | Year: 2014

A simulation based computational method was conducted to reflect the effect of intervention for those at high risk of type 2 diabetes. Hierarchy Support Vector Machines (H-SVMs) were used to classify high risk. The proportion transitioning from the high risk state to moderate state, low state or the normal state was calculated. When Body Mass Index (BMI) decreased by 5% (weight loss 3-5kg), the proportion of Class A transferring to a lower state was 15-25%, and risk also appeared reduced for Class B1. In Class C, when cholesterol (CHOL) was decreased by 2.5% (0.13-0.34mmol/L), 10-25% transitioned to a lower risk state. The method could help determine risk transition by the adjustment of sensitive risk factors. This might provide the basis for implementing intervention in cases in a high risk state.


Wang Y.-H.,Wenzhou Medical College | Pan P.-P.,Beijing Institute of Geriatrics | Dai D.-P.,Beijing Hospital and Beijing Institute of Geriatrics | Wang S.-H.,Beijing Institute of Geriatrics | And 3 more authors.
Xenobiotica | Year: 2014

1. CYP2C9 is an important member of the cytochrome P450 enzyme superfamily, with 57 CYP2C9 allelic variants being previously reported. Among these variants, we recently identified 21 novel alleles in the Han Chinese population. The aim of this study was to assess the catalytic activities of 36 CYP2C9 variants found in the Chinese population toward losartan in vitro. 2. Insect microsomes expressing the 36 CYP2C9 variants were incubated with 0.5-25μM losartan for 30min at 37°C. Next, the products were extracted, and signal detection was performed using high-performance liquid chromatography. 3. Compared with wild-type CYP2C9.1, the intrinsic clearance (Vmax/Km) values of all variants except for CYP2C9.56 were significantly altered. One variant exhibited markedly increased values (>250%), whereas 33 variants exhibited significantly decreased values (from 20 to 96%) due to increased Km and/or decreased Vmax values. 4. These findings suggest that more attention should be paid to subjects carrying these infrequent CYP2C9 alleles when administering losartan in the clinic. © 2014 Informa UK Ltd.


Woo J.,Chinese University of Hong Kong | Zheng Z.,Beijing Institute of Geriatrics | Leung J.,Chinese University of Hong Kong | Chan P.,Beijing Institute of Geriatrics
BMC Geriatrics | Year: 2015

Background: Frailty predicts dependence and mortality, and is an important health indicator for aging populations. Comparing frailty prevalence between populations of the same ethnicity but different socioeconomic, lifestyle, health and social care systems, and environmental characteristics would address the role of these factors in contributing to frailty. Methods: We compare frailty prevalence and contributory factors across three Chinese populations: Beijing rural, Beijing urban, and Hong Kong (urban). Older people aged 65 years and above living in the community were invited to respond to a general health questionnaire covering demographic, socioeconomic, medical and drug histories, geriatric syndromes, assessment of physical and cognitive functioning, psychological wellbeing and nutritional status. Frailty is defined as an index calculated from multiple deficits > = 0.25 (FI). The ratio of FI/life expectancy at birth was used as an indicator of compression of morbidity. Risk factors and attributable fraction for frailty were compared across the three cohorts. Results: The prevalence of frailty increases with age in all three cohorts, and was lower among rural compared with urban (Beijing and Hong Kong) populations. The highest FI/LE ratio was observed in the Beijing urban population, followed by Hong Kong, with the Beijing rural population having the lowest ratio. Risk factors for frailty were similar in all three populations. Those having the highest ORs were multi-morbidity (number of diseases > = 3), polypharmacy (number of drugs > = 4), age 85+, female gender, followed by low education level, and physical inactivity. For all three cohorts, age and multi-morbidity constitute the highest attributable fraction, and were highest in the Beijing rural cohort. A major difference between the Beijing and Hong Kong cohorts is the high AF from polypharmacy in Beijing and the 'protective' contribution of being married; and the effect of being a teetotaler in the Hong Kong cohort. Conclusions: This comparison draws attention to the importance of frailty prevention for ageing populations. © 2015 Woo et al.


Chen X.,Beijing Institute of Geriatrics | Xu X.,Beijing Hospital | Xiao F.,Beijing Institute of Geriatrics
Frontiers of Medicine in China | Year: 2013

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality throughout the world and is mainly characterized by persistent airflow limitation. Given that multiple systems other than the lung can be impaired in COPD patients, the traditional FEV1/FVC ratio shows many limitations in COPD diagnosis and assessment. Certain heterogeneities are found in terms of clinical manifestations, physiology, imaging findings, and inflammatory reactions in COPD patients; thus, phenotyping can provide effective information for the prognosis and treatment. However, phenotypes are often based on symptoms or pathophysiological impairments in late-stage COPD, and the role of phenotypes in COPD prevention and early diagnosis remains unclear. This shortcoming may be overcome by the potential genotypes defined by the heterogeneities in certain genes. This review briefly describes the heterogeneity of COPD, with focus on recent advances in the correlations between genotypes and phenotypes. The potential roles of these genotypes and phenotypes in the molecular mechanisms and management of COPD are also elucidated. © 2013 Higher Education Press and Springer-Verlag Berlin Heidelberg.


To set up a new method, which is sensitive, low cost, rapid and suitable for clinical application for FTO gene rs9930506 variant genotyping basing on high resolution melting (HRM) platform, and to preliminarily put into practice in susceptibility analysis for metabolic syndrome (MS) in Beijing. Unlabelled probe with C3-spacer block specific for rs9930506 variant has been designed according to the Refseq from GenBank. With LC-Green plus dye pre-mixed, we scanned the signal for the genotype analysis after PCR amplification and HRM reaction. Restriction fragment length polymorphism (RFLP) and PCR-sequencing methods were designed as 2 control genotyping methods for the evaluation of accuracy and convenience. Afterwards, the HRM-based method was put into practice in metabolic syndrome patients (n = 500) and control groups (n = 500) for rs9930506 genotyping, and primarily study the association between rs9930506 and MS. All the 3 methods could genotype rs9930506 appropriately, although the 2 control methods seemed to be a little time-inefficient. The call rate of HRM-method was 100% and sampling accuracy reached 99.3% according to sequencing results. In the MS group, AA, AG and GG genotypes were found in 290, 185 and 25 cases, respectively. And in the control group, those were found in 344, 138 and 18 cases. No genotype distribution difference was detected between control group and HapMap-CHB data (P = 0.520). The genotype distributions were all in Hardy-Weinberg equilibrium in each group. AA genotype of rs9930506 seemed to reduce the risk for MS (OR = 0.626, 95%CI = 0.483 - 0.812). The AA genotype of rs9930506 variant in FTO might be a protective factor for MS in Beijing population. The susceptibility related genotyping in clinical samples could be more rapid, precise and inexpensive with the development of HRM in genotyping.


PubMed | Beijing Institute of Geriatrics
Type: Journal Article | Journal: Diabetes research and clinical practice | Year: 2011

This study was to test the hypothesis that enhanced oxidative stress is induced in monocytes with over-activated NADPH oxidase during the development of type 2 diabetes mellitus.Levels of glucose and lipids were analyzed in 73 diabetic patients and 36 controls. Superoxide dismutase (SOD), malondialdehyde (MDA), reactive oxygen species (ROS) and protein carbonylation were tested. Expression of NADPH oxidase was examined and p47phox translocation was assessed.With the abnormality of glucose and lipid metabolism, diabetic patients showed a higher oxidative stress state indicated by decreased SOD activity but elevated MDA and protein carbonylation level. Monocytes in diabetes also showed elevated ROS generation and protein carbonylation level. Furthermore, NADPH oxidase was highly activated in monocytes represented by p22phox up-regulation and p47phox translocation. Significant positive bivariate correlation was found between glucose and MDA level as well as p22phox expression. In vitro experiments also indicated that glucose could stimulate ROS generation in a NADPH oxidase dependent manner. Moreover, we carried out same measurement in 40 diabetic patients with anti-diabetic intervention and obtained the reinforced results.Hyperglycemia is the main factor which induces oxidative stress mainly by activation of NADPH oxidase in monocytes of diabetic patients.


To set up a new method, which is sensitive, low cost, rapid and suitable for clinical application for FTO gene rs9930506 variant genotyping basing on high resolution melting (HRM) platform, and to preliminarily put into practice in susceptibility analysis for metabolic syndrome (MS) in Beijing.Unlabelled probe with C3-spacer block specific for rs9930506 variant has been designed according to the Refseq from GenBank. With LC-Green plus dye pre-mixed, we scanned the signal for the genotype analysis after PCR amplification and HRM reaction. Restriction fragment length polymorphism (RFLP) and PCR-sequencing methods were designed as 2 control genotyping methods for the evaluation of accuracy and convenience. Afterwards, the HRM-based method was put into practice in metabolic syndrome patients (n = 500) and control groups (n = 500) for rs9930506 genotyping, and primarily study the association between rs9930506 and MS.All the 3 methods could genotype rs9930506 appropriately, although the 2 control methods seemed to be a little time-inefficient. The call rate of HRM-method was 100% and sampling accuracy reached 99.3% according to sequencing results. In the MS group, AA, AG and GG genotypes were found in 290, 185 and 25 cases, respectively. And in the control group, those were found in 344, 138 and 18 cases. No genotype distribution difference was detected between control group and HapMap-CHB data (P = 0.520). The genotype distributions were all in Hardy-Weinberg equilibrium in each group. AA genotype of rs9930506 seemed to reduce the risk for MS (OR = 0.626, 95%CI = 0.483 - 0.812).The AA genotype of rs9930506 variant in FTO might be a protective factor for MS in Beijing population. The susceptibility related genotyping in clinical samples could be more rapid, precise and inexpensive with the development of HRM in genotyping.

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