Li Yan

Tianjin Medical University, T’ien-ching-shih, Tianjin Shi, China

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Publications (105)262.04 Total impact

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    ABSTRACT: Objective: To clarify the quantitative relationship of body mass index (BMI) change from early adulthood to midlife with presence of type 2 diabetes mellitus (T2DM) after midlife. Methods: This study included 120,666 middle-aged and elderly, whose retrospectively self-reported body weight at 20 and 40 years and measured height were available. BMI at 20 and 40 years and BMI change in between were defined as early-adulthood BMI, midlife BMI, and early-adulthood BMI change. Results: The odds ratio (OR) for T2DM associated with an 1-unit increment of early-adulthood or midlife BMI was 1.08 (95% confidence interval (CI), 1.07-1.08) and 1.09 (95% CI, 1.09-1.10) respectively. In the cross-tabulation of both early-adulthood BMI and BMI change, the prevalence of T2DM increased across both variables. Compared with participants with normal early-adulthood weight and BMI increase/decrease ≤1, the OR (95% CI) for T2DM of participants with early-adulthood overweight/obesity and BMI increase ≥4 kg/m(2) was 3.49 (3.05-4.00). For participants with early-adulthood underweight and BMI increase/decrease ≤ 1, the OR (95% CI) was 0.85 (0.75-0.97). Subgroup analysis according to sex and age showed similar trends. Conclusions: Early-adulthood BMI may influence T2DM prevalence after midlife independent of current BMI. T2DM prevalence after midlife was positively associated with early-adulthood weight gain and inversely related to early-adulthood weight loss, while early-adulthood weight loss could not completely negate the adverse effect of early-adulthood overweight/obesity on diabetes.
    No preview · Article · Feb 2016 · Obesity
  • Meng Ren · Kan Sun · Feng Li · Yi qin Qi · Diao zhu Lin · Na Li · Yan Li · Li Yan
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    ABSTRACT: Aims: The effects of obesity on the micro vascular diseases have drawn much attention. The aim of the study was to investigate the relationship between obesity measures and albuminuria in Chinese population. Methods: We conducted a population-based cross-sectional study in 8600 subjects aged 40years or older from a community in Guangzhou. Urinary albumin excretion and creatinine were measured and urinary albumin-to-creatinine ratio (ACR) was calculated as urinary albumin divided by creatinine. Low-grade albuminuria was classified as the highest quartile of ACR in participants without increased urinary albumin excretion. Increased urinary albumin excretion was defined according to the ACR ranges greater or equal than 30mg/g. Results: Pearson's correlation analysis and multivariate linear regression analysis revealed that body mass index (BMI), waist circumference and body fat content were significantly correlated with ACR (all P<0.01). Prevalence of low-grade albuminuria and increased urinary albumin excretion gradually increased across the BMI, waist circumference and body fat content quartiles (all P for trend<0.0001). Compared with participants in quartile 1 of BMI, waist circumference and body fat content, participants in quartile 4 had increased prevalence of low-grade albuminuria and increased urinary albumin excretion in logistic regression analysis after adjustment for age, sex, physical activity, fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol and HbA1c (all P<0.05). Conclusion: Obesity measures are associated with urinary albumin excretion in middle-aged and elderly Chinese.
    No preview · Article · Dec 2015 · Journal of diabetes and its complications
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    ABSTRACT: Background: Although dyslipidemia is related to the pathogenesis of renal insufficiency, which routinely available lipid measure is more applicable in estimation of kidney function is still uncertain. Our objective was to evaluate inconsistent associations of lipid profiles with both albuminuria and chronic kidney disease (CKD). Methods: We performed a population-based study in 9730 subjects aged 40 years or older. Definitions of abnormalities in albumin excretion were according to the latest guidelines of American Diabetes Association's Standards of Medical Care. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m(2) or the presence of albuminuria. Results: There were 2274 (23.4 %) participants categorized as low-grade albuminuria, 639 (6.6 %) participants categorized as increased urinary albumin excretion and 689 (7.1 %) participants categorized as CKD. Triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), Non HDL-C to HDL-C ratio, TG to HDL-C ratio were significantly correlated with urinary albumin to creatinine ratio (ACR), serum creatinine and eGFR (all P < 0.0001). Compare with other lipid parameters, TG to HDL-C ratio have shown the strongest correlation with increased odds of both increased urinary albumin excretion and CKD. No significant associations between lipid parameters and low-grade albuminuria were observed after adjustments for potential confounding factors. Conclusion: Our study lends support to discordant associations of lipid parameters with albuminuria and renal function. TG to HDL-C ratio is a better marker than other routine lipid measures for identifying renal insufficiency and should be given more consideration in the clinical practice.
    Preview · Article · Nov 2015 · Lipids in Health and Disease
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    ABSTRACT: Our objective was to evaluate the associations between habitual daytime napping and diabetes and whether it varies by sex, menopause, and sleep quality. We conducted a population-based cross-sectional study in 8621 eligible individuals aged 40 years or older. Information on daytime napping hours, night-time sleep duration, history of menstruation, and sleep quality was self-reported. Diabetes was diagnosed according to the 1999 World Health Organization diagnostic criteria. The prevalence of diabetes was 19.4 % in men and 15.6 % in women. Increased daytime napping hours were positively associated with parameters of glycometabolism in women, such as fasting plasma glucose, oral glucose tolerance test (OGTT) 2-h plasma glucose, and Hemoglobin A1c (HbA1c, all P for trend <0.05). In women, the prevalence of diabetes in no-habitual daytime napping group, 0-1-h daytime napping group, and more than 1-h daytime napping group were 14.5, 15.6, and 20.8 %, respectively (P for trend = 0.0004). A similar trend was detected in postmenopausal women (P for trend = 0.002). In multivariate logistic regression analysis, compared with no-habitual daytime napping postmenopausal women, those with daytime napping more than 1 h had higher prevalent diabetes (odds ratios 1.36, 95 % confidence interval, 1.04-1.77). In subgroup analysis of postmenopausal women, associations of daytime napping levels and prevalent diabetes were detected in older, overweight participants with good sleep quality who have not retired from work. In conclusion, our study suggests that habitual daytime napping is associated with prevalence of diabetes in postmenopausal women.
    No preview · Article · Oct 2015 · Endocrine
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    ABSTRACT: The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China.
    No preview · Article · Oct 2015 · Journal of Clinical Lipidology
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    ABSTRACT: This study aimed to identify carcinogenic potential-related molecular mechanisms in cancer stem cells (CSCs) in lung cancer. CD133(+) and CD133(-) subpopulations were sorted from A549 cells using magnetic-activated cell sorting. The abilities to form sphere and clone, proliferate, migrate, and invade were compared between CD133(+) and CD133(-) cells, as well as drug sensitivity. Thereafter, microRNA (miRNA) profiles were performed to identify differentially expressed miRNAs between CD133(+) and CD133(-) subpopulation. Following, bioinformatic methods were used to predict target genes for differentially expressed miRNAs and perform enrichment analysis. Furthermore, the mammalian target of rapamycin (mTOR) signaling pathways and CSC property-associated signaling pathways were explored and visualized in regulatory network among competitive endogenous RNA (ceRNA), miRNA, and target gene. CD133(+) subpopulation showed greater oncogenic potential than CD133(-) subpopulation. In all, 14 differentially expressed miRNAs were obtained and enriched in 119 pathways, including five upregulated (hsa-miR-23b-3p, -23a-3p, -15b-5p, -24-3p, and -4734) and nine downregulated (hsa-miR-1246, -30b-5p, -5096, -6510-5p, has-miR-7110-5p, -7641, -3197, -7108-5p, and -6791-5p). For mTOR signaling pathway, eight differential miRNAs (hsa-miR-23b-3p, -23a-3p, -15b-5p, -24-3p, -4734, -1246, -7641, and -3197) and 39 target genes (e.g., AKT1, AKT2, PIK3CB, PIK3CG, PIK3R1, PIK3CA, and PIK3CD) were involved, as well as some ceRNAs. Besides, for CSC property-related signaling pathways, six miRNAs (hsa-miR-1246, -15b-5p, -30b-5p, -3197, -4734, and -7110-5p) were dramatically enriched in Hedgehog, Notch, and Wnt signaling pathways via regulating 108 target genes (e.g., DVL1, DVL3, WNT3A, and WNT5A). The mTOR and CSC property-associated signaling pathways may be important oncogenic molecular mechanisms in CD133(+) A549 cells.
    No preview · Article · Aug 2015 · Tumor Biology
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    ABSTRACT: To investigate dynamic changes in plantar pressure in Chinese diabetes mellitus patients and to provide a basis for further preventing diabetic foot. This is a cross-sectional investigation including 649 Chinese diabetes mellitus patients (diabetes group) and 808 "normal" Chinese persons (nondiabetes group) with normal blood glucose levels. All the subjects provided a complete medical history and underwent a physical examination and a 75-g oral glucose tolerance test. All subjects walked barefoot with their usual gait, and their dynamic plantar forces were measured using the one-step method with a plantar pressure measurement instrument; 5 measurements were performed for each foot. No significant differences were found in age, height, body weight, or body mass index between the two groups. The fasting blood glucose levels, plantar contact time, maximum force, pressure-time integrals and force-time integrals in the diabetes group were significantly higher than those in the nondiabetes group (p < 0.05). However, the maximum pressure was significantly higher in the nondiabetes group than in the diabetes group (p < 0.05). No difference was found in the contact areas between the two groups (p > 0.05). The maximum plantar force distributions were essentially the same, with the highest force found for the medial heel, followed by the medial forefoot and the first toe. The peak plantar pressure was located at the medial forefoot for the nondiabetes group and at the hallucis for the diabetes group. In the diabetes group, the momentum in each plantar region was higher than that in the nondiabetes group; this difference was especially apparent in the heel, the lateral forefoot and the hallucis. The dynamic plantar pressures in diabetic patients differ from those in nondiabetic people with increased maximum force and pressure, a different distribution pattern and significantly increased momentum, which may lead to the formation of foot ulcers.
    No preview · Article · Jun 2015 · Wound Repair and Regeneration
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    ABSTRACT: MiRNAs associated with the metastasis of lung cancer remains largely unexplored. In this study gene and miRNA expression profiling were performed to analyze the global expression of mRNAs and miRNAs in human high- and low- metastatic lung cancer cell strains. By developing an integrated bioinformatics analysis, six miRNAs (miR-424-3p, miR-450b-5p, miR-335-5p, miR-34a-5p, miR-302b-3p, miR-206) showed higher target gene degrees in the miRNA-gene –network and might be the potential metastasis related miRNAs. Using qRT-PCR method, the six miRNAs were further confirmed significant expression difference between human lung cancer and normal tissue samples. Since miR-206 was lower expression both in lung cancer tissues and cell lines, it was used as an example for further functional verification.,Wound healing assay and transwell invasion assay showed that miR-206 mimics significantly inhibited cell migration and invasion of high-metastatic lung cancer 95D cell strain. One of its predicted targets in our miRNA-gene-network, MET, was also obviously decreased at protein level when miR-206 was overexpressed. Instead, miR-206 inhibitors increased MET protein expression, cell migration and invasion of low-metastatic lung cancer 95C cell strain. Meanwhile, luciferase assay showed that MET was direct target of miR-206. Furthermore, MET gene silence showed a similar anti-migration and anti-invasion effect with miR-206 mimics in 95D cells and could partially attenuated the migration- and invasion-promoting effect of miR-206 inhibitors in 95C cells, suggesting miR-206 targeting MET in the lung cancer metastasis. Finaly, we also demonstrated that miR-206 can significantly inhibit lung cancer proliferation and metastasis in mouse models. In conclusion, our study provided a miRNA-gene regulatory network in lung cancer metastasis and further demonstrate the roles of miR-206 and MET in this process, which enhanced the understanding of regulatory mechanism in lung cancer metastasis. The miRNAs in the network could be considered as potential target genes in lung cancer anti-metastasis therapy.
    No preview · Article · Jun 2015 · Molecular BioSystems
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    ABSTRACT: To investigate the association between the level of serum testosterone and atherosclerosis in middle-aged and elderly men. We conducted a population-based study of 413 males aged 40-75 years in a community in Guangzhou. We obtained the sociodemographic characteristics, clinical data, physical measurements, and laboratory results of sex hormones, blood glucose, and blood lipid of the subjects. We also measured the carotid intima media thickness (CIMT) by color Doppler ultrasonography. The subjects were divided into a carotid atherosclerosis (CAS) group (CIMT ≥ 0.9 mm) and a non-CAS group (CIMT < 0.9 mm). The medians of free testosterone (FT) were 57.41 and 59.72 pmol/L in the CAS and non-CAS groups, respectively (P = 0.005), and no significant difference was found between the two groups in total testosterone (TT). The levels of serum FT and TT were negatively correlated to CIMT, with Spearman's rank correlation coefficients of -0.126 (P = 0.011) and -0.188 (P < 0.001), respectively. The incidence rates of CAS were 23.30, 13.46, 17.48, and 7.77% in the Q1, Q2, Q3, and Q4 groups, respectively according to the quartile of FT (P for trend = 0.008) and 17.48, 18.27, 16.50, and 9.71% respectively according to the quartile of TT (P for trend = 0.116). Based on the quartile of FT and after adjustment for age, waist circumference, systolic blood pressure, and HbAlc, the risk of CAS was significantly increased in the Q1 group as compared with Q4 (OR = 2.491, 95% CI 1.01-6.149), but no statistically significant differences were observed according to the quartile of TT. A low serum FT level may be a risk factor of atherosclerosis in Chinese men aged 40 years or older.
    No preview · Article · Jun 2015 · Zhonghua nan ke xue = National journal of andrology
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    Full-text · Dataset · May 2015
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    ABSTRACT: Advanced glycation end products(AGEs) played an important role for the development of diabetic foot. In the present study we tried to show the mevalonate pathway and the key demethylation site(s) in the MMP-9 cis-promoter to component of MMP-9 by AGEs in keratinocyte. Human keratinocyte cell line (HaCaT) cells were exposed to AGE-BSA. The Plasmid construction and site-directed mutagenesis, Dual-luciferase reporter assays, Immunoblot, Zymography,pull down, Bisulfite sequencing PCR analysis and Western Blotting were application. The AGE-BSA could increase and more activate the MMP9 in keratinocyte. The RhoA and ROCK1 also could be activated. These affects were blocked by the simvastatin. Meanwhile, the CpG site at -562 site was largely demethylated with AGE-BSA treated. The cis-promoter sequences with -562bp site methylated had a lower activity change, which had a highest expression activity and was decreased by simvastatin. Moreover, Site-directed mutagenesis of CpG site (-562bp) in the recombinant plasmid pCpGL-571 brought more reduction of activity, and the activity of methylated mutation pCpGL-571 remain to decrease. The cis-promoter regions of MMP9 would be methylated by AGE-BSA in keratinocyte through the mevalonate pathway, special the -562bp site. Copyright © 2015. Published by Elsevier Ireland Ltd.
    No preview · Article · Apr 2015 · Molecular and Cellular Endocrinology
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    ABSTRACT: The follicular helper T cell (Tfh) and IL-21 have been shown to play an important role in many autoimmune diseases. However, less is known about their role in Graves' disease (GD). This study aimed to investigate the expression of Tfhs and related factors (IL-21, IL-21R, CXCR5, and CXCL13) in GD thyroid tissues and to explore the effect of IL-21 on thyroid follicular cells (TFCs). The expression of Tfh-related factors in GD and normal thyroid tissues was validated using immunohistochemistry, real-time polymerase chain reaction and Western blotting. Confocal microscopy confirmed the presence of Tfh and IL-21R on CD4(+)T-/CD19(+)B cell in GD thyroid tissues. Furthermore, the effect of IL-21 on cAMP production in TFCs upon thyroid-stimulating antibody (TSAb) stimulation was also examined by an in vitro bioassay. The increased expression of Tfh-related factors was observed in GD thyroid tissues compared to control subjects. Confocal microscopy further confirmed the presence of Tfhs and the expression of IL-21R on CD4(+)T cells and CD19(+)B cells in GD thyroid tissues. Moreover, the expression of IL-21mRNA in GD thyroid tissues was correlated with the levels of thyroid autoantibodies. Additionally, IL-21 could indirectly promote cAMP production upon TSAb stimulation in TFCs when cooperating with lymphocytes, and GD TFCs were more sensitive to IL-21 stimulation than normal TFCs. There is increased expression of Tfhs and related factors (IL-21, IL-21R, CXCR5, and CXCL13) in GD thyroid tissues, and the expression of IL-21mRNA in GD thyroid tissues was found to correlate with the serum levels of thyroid autoantibodies and thyroid hormones. Moreover, IL-21 could indirectly enhance the biological activity of TFCs upon TSAb stimulation when cooperating with lymphocytes in vitro, particularly in GD TFCs, suggesting that Tfh and IL-21 might be involved in the pathogenesis of GD.
    No preview · Article · Apr 2015 · Immunologic Research
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    ABSTRACT: Severe aplastic anemia is a rare autoimmune disease characterized by severe pancytopenia and bone marrow failure, which is caused by activated T lymphocytes. Tregs are believed to control development and progression of autoimmunity by suppressing autoreactive T cells. This study aims at understanding the quantity and function of peripheral Tregs in SAA. The expression of related biomarkers on Treg cell surface were determined by flow cytometry. The frequency of Tregs and the expression of CTLA-4 in SAA was significantly decreased than that in normal controls. The expression of perforin in SAA was significantly increased than that in controls, while expression of CD39, CD73 and GITR in Tregs did not show any significant difference between the two groups. These data revealed that CTLA-4 could be responsible for Treg abnormalities in SAA, but suppression mediated by perforin, CD39, CD73 and GITR, and survival capability of single Treg cell may not be injured. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · Apr 2015 · Cellular Immunology
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    ABSTRACT: Aims: To determine the annual incidence and clinically relevant risk factors for foot ulceration in a large cohort study of diabetic foot ulcer (DFU) patients and diabetes mellitus (DM) patients in China.Methods: To investigate a cohort of 1333 patients comprising 452 DFU patients and 881 DM patients, who underwent foot screening, physical examination and laboratory tests in eight hospitals. The patients were assessed at baseline in terms of their demographic information, medical and social history, peripheral neuropathy disease (PND) screening, periphery artery disease (PAD) screening, assessment of nutritional status and diabetic control. One year later, the patients were followed up to determine the incidence of new foot ulcers, amputation and mortality. By univariate analysis, statistically significant differences were found in age, location, gender, living alone (yes/no), occupation, smoking, hypertension, PND, PAD, nephropathy, retinopathy, cataracts, duration of diabetes, Glycosylated Hemoglobin A (HbA1c), fasting plasma glucose level, postprandial blood glucose level, insulin level, blood urea nitrogen, creatinine, cholesterol, triglyeride, high density lipoprotein (HDL), serum albumin, white blood cell, and body mass index (BMI). A binary logistic regression model was used to examine which of these risk factors were independent risk factors for foot ulceration.Results: A total of 687 (51.5%) of the 1333 patients were followed up for an average of 12 months; there were 458 DM patients and 229 DFU patients. A total of 46 patients died during the follow-up period; 13 were DM patients, and 33 were DFU patients. Of the 641 patients, 445(69.4%) patients were DM patients, and 196(30.6%)were DFU patients. At follow-up, 36/445 DM patients (8.1%), and 62/196 DFU patients (31.6%), developed new ulcers; 10/196 DFU patients underwent an amputation. The annual incidence of ulceration for DM patients and amputation for DFU patients were 8.1% and 5.1%, respectively. The annual mortality of the DM patients and DMF patients were 2.8% and 14.4%, respectively. A binary logistic regression model was used to examine which risk factors were independent risk factors for foot ulceration during the follow-up period, and the final results showed that nephropathy (odds ratio 2.32), insulin level (odds ratio 3.136, 2.629), and decreased HDL (odds ratio 0.427) were associated with increased risks for foot ulceration.Conclusions: Complications of diabetes affecting the feet represent a serious problem in China. The incidence of foot ulcers and amputation are much higher than that of Western countries. More intensive surveillance and aggressive care following a diagnosis of DFU and earlier referral to specialty care might improve the patient outcome. This article is protected by copyright. All rights reserved.
    No preview · Article · Feb 2015 · Wound Repair and Regeneration
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    ABSTRACT: Implantation of embryonic stem cells (ESC)-derived insulin-producing cells has been extensively investigated for treatment of diabetes in animal models. However, the in vivo behavior and migration of transplanted cells in diabetic models remains unclear. Here we investigated the location and migration of insulin-producing cells labeled with superparamagnetic iron oxide (SPIO) using a dynamic MRI tracking method. SPIO labeled cells showed hypointense signal under the kidney subcapsules of diabetic mice on MRI, and faded gradually over the visiting time. However, new hypointense signal appeared in the spleen 1 week after transplantation, and became obvious with the time prolongation. Further histological examination proved the immigrated cells were insulin and C-peptide positive cells which were evenly distributed throughout the spleen. These intra-spleen insulin-producing cells maintained their protective effects against hyperglycemia in vivo, and these effects were reversed upon spleen removal. Transplantation of insulin-producing cells through spleen acquired an earlier blood glucose control as compared with that through kidney subcapsules. In summary, our data demonstrate that insulin-producing cells transplanted through kidney subcapsules were not located in situ but migrated into spleen, and rescues hyperglycemia in diabetic models. MRI may provide a novel tracking method for preclinical cell transplantation therapy of diabetes continuously and non-invasively.
    Preview · Article · Dec 2014 · Scientific Reports
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    ABSTRACT: Serum γ - glutamyltransferase (GGT) is implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. Albuminuria is a marker of endothelial damage and correlated with structural and functional integrity of the vasculature. Our objective was to evaluate the association between serum GGT level and prevalence of albuminuria in a Chinese population. We conducted a population-based cross-sectional study in 9,702 subjects aged 40 years or older. Increased urinary albumin excretion was defined according to the urinary albumin-to-creatinine ratio (ACR) ranges greater or equal than 30 mg/g. Low-grade albuminuria was defined according to the highest quartile of ACR in participants without increased urinary albumin excretion. The prevalence of low-grade albuminuria and increased urinary albumin excretion were respectively 23.4% and 6.6% in this population and gradually increased across the sex-specific serum GGT quartiles (all P for trend <0.05). In logistic regression analysis, compared with subjects in the lowest quartile of serum GGT level, the adjusted odds ratios (ORs) in the highest quartile was 1.22 [95% confidence interval (CI), 1.04-1.43] for low-grade albuminuria and 1.55 (95% CI, 1.18-2.04) for increased urinary albumin excretion. In subgroup analysis, significant relationship of serum GGT level with both low-grade albuminuria and increased urinary albumin excretion were detected in women, younger subjects, overweight subjects and in those with hypertension or glomerular filtration rate greater than 90 (all P <0.05). Serum GGT level is associated with urinary albumin excretion in middle-aged and elderly Chinese.
    Preview · Article · Dec 2014 · PLoS ONE
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    ABSTRACT: Diabetic foot ulcer (DFU), caused by impaired wound healing, is a common vascular complication of diabetes. The present study revealed that plasma levels of pigment epithelium-derived factor (PEDF) were elevated in Type 2 diabetic patients with DFU and in db/db mice. To test whether elevated PEDF levels contributes to skin wound healing delay in diabetes, endogenous PEDF was neutralized with an anti-PEDF antibody in db/db mice. Our results showed that neutralization of PEDF accelerated wound healing, increased angiogenesis in the wound skin, and improved functions and numbers of endothelial progenitor cells (EPCs) in the diabetic mice. Further, PEDF deficient mice showed higher baseline blood flow in the skin, higher density of cutaneous micro-vessels, increased skin thickness, improved circulating numbers and functions of EPCs, and accelerated wound healing, compared to the Wt mice. Over-expression of PEDF suppressed the Wnt signaling pathway in the wound skin. Lithium chloride-induced Wnt signaling activation at downstream of the PEDF-interaction site attenuated the inhibitory effect of PEDF on EPCs and rescued the wound healing deficiency in diabetic mice. Taken together, these results suggest that elevated circulating PEDF levels contribute to impaired wound healing on the process of angiogenesis and vasculogenesis through inhibition of Wnt/β-catenin signaling.
    Full-text · Article · Nov 2014 · Diabetes
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    ABSTRACT: Background: The high level of matrix metalloproteinase 9 (MMP9) is thought to slow down the healing of diabetic foot ulcers. Whether it can influence the biological behaviors of skin fibroblasts and affect wound healing is still unclear. The present study aimed to observe changes in the biological behaviors of rat dermal fibroblasts induced by high expression of MMP9 and to clarify the possible mechanisms of wound healing for diabetic foot. Methods: A cell model of skin fibroblast with high expression of MMP9 was established by co-culture of high glucose (22.0 mmol/L) and homocysteine (100 μmol/L). A control group was incubated with normal glucose (5.5 mmol/L). Realtime PCR, ELISA and gelatin zymography were used to detect the MMP9 mRNA, protein expression and activity of MMP9. Flow cytometry, CCK-8, ELISA assay, scratch test and transwell were used to detect cell proliferation, viability, collagen (hydroxyproline) secretion, horizontal migration and vertical migration of cells. The data were expressed as mean±SD. P value less than 0.05 was considered statistically significant. Results: The expression of MMP9 mRNA, protein levels and the activity of MMP9 were much higher in the high MMP9 group than in the control group (7.05±1.02 vs. 1.00±0.00, 206.9±33.6 pg/mL vs. 40.4±5.9 pg/mL, and 1.47±0.13 vs. 0.57±0.12, respectively, P<0.01). The proportion of S-phase cells, proliferation index, cell viability, collagen (hydroxyproline) secretion, horizontal migration rate and the number of vertical migration cells were lower in the high MMP9 group than in the control group (P<0.01). Conclusion: Fibroblasts with a high expression of MMP9 decreased proliferation, activity, secretion and migration of collagens, suggesting that MMP9 may inhibit the biological behaviors of fibroblasts.
    No preview · Article · Sep 2014
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    ABSTRACT: Objective Our objective was to evaluate the association between habitual daytime napping and the prevalence of metabolic syndrome. Materials and Methods We conducted a population-based study of 8,547 subjects aged 40 years or older. Metabolic syndrome was defined according to a harmonized definition from a joint statement and the recommended thresholds for the Chinese population. Information about sleep duration was self-reported. Results The prevalence of metabolic syndrome in the no daytime napping group, the 0 to 1 hour daytime napping group and the more than 1 hour daytime napping group were 35.0%, 36.0% and 44.5% among the females (P < 0.0001). Increased daytime napping hours were positively associated with parameters of metabolic syndrome in the female subjects, including waist circumference, systolic blood pressure, triglycerides and fasting plasma glucose (P < 0.05 for all). Multivariate adjusted logistic regression analysis revealed that, compared to the no habitual daytime napping females, napping for more than 1 hour was independently associated with an increased prevalence of metabolic syndrome (odds ratio 1.39, 95% confidence interval, 1.13 - 1.72). Compared to the female subjects in the no daytime napping group, those habitually napped for more than 1 hour exhibited 46% and 26% increases in the prevalence of central obesity and hypertriglyceridemia (all P < 0.05). No statistically significant associations were detected between daytime napping hours and metabolic syndrome among the male subjects. Conclusion Daytime napping is associated with an increased prevalence of metabolic syndrome in middle-aged non-obese Chinese women.
    No preview · Article · Aug 2014 · Metabolism
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    ABSTRACT: Background Excessive expression of matrix metalloproteinase-9 (MMP-9) is deleterious to the cutaneous wound-healing process in the context of diabetes. The aim of the present study was to explore whether a cationic star-shaped polymer consisting of β-cyclodextrin (β-CD) core and poly(amidoamine) dendron arms (β-CD-[D3]7) could be used as the gene carrier of small interfering RNA (siRNA) to reduce MMP-9 expression for enhanced diabetic wound healing. Methods The cytotoxicity of β-CD-(D3)7 was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MMT) method in the rat CRL1213 skin fibroblast cell line. The transfection efficiency of β-CD-(D3)7/MMP-9-small interfering RNA (siRNA) complexes was determined by confocal microscopy and flow cytometry. Quantitative real time (RT) polymerase chain reaction was performed to measure the gene expression of MMP-9 after the transfection by β-CD-(D3)7/MMP-9-siRNA complexes. The β-CD-(D3)7/MMP-9-siRNA complexes were injected on the wounds of streptozocin-induced diabetic rats. Wound closure was measured on days 4 and 7 post-wounding. Results β-CD-(D3)7 exhibited low cytotoxicity in fibroblast cells, and easily formed the complexes with MMP-9-siRNA. The β-CD-(D3)7/MMP-9-siRNA complexes were readily taken up by fibroblast cells, resulting in the downregulation of MMP-9 gene expression (P<0.01). Animal experiments revealed that the treatment by β-CD-(D3)7/MMP-9-siRNA complexes enhanced wound closure in diabetic rats on day 7 post-wounding (P<0.05). Conclusion β-CD-(D3)7 may be used as an efficient carrier for the delivery of MMP-9-siRNA to reduce MMP-9 expression in skin fibroblast cells and promote wound healing in diabetic rats.
    Full-text · Article · Jul 2014 · International Journal of Nanomedicine

Publication Stats

1k Citations
262.04 Total Impact Points

Institutions

  • 2015
    • Tianjin Medical University
      T’ien-ching-shih, Tianjin Shi, China
  • 2003-2015
    • Sun Yat-Sen University
      • • Department of Endocrinology
      • • Department of Chemical Engineering
      Shengcheng, Guangdong, China
  • 2008-2014
    • Zhongshan University
      中山, Guangdong, China
  • 2010-2011
    • University of Maryland, Baltimore County
      • Department of Computer Science and Electrical Engineering
      Baltimore, Maryland, United States
  • 2002-2010
    • Sun Yat-Sen University of Medical Sciences
      • Department of Endocrinology
      Shengcheng, Guangdong, China
  • 2009
    • China-Japan Friendship Hospital
      Peping, Beijing, China
  • 2007
    • Shantou University
      Swatow, Guangdong, China
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China
    • 306th Hospital Of PLA
      Peping, Beijing, China
    • Maternal and Children Health Hospital of Guangxi Zhuang Autonomous Region
      Yung-ning, Guangxi Zhuangzu Zizhiqu, China
  • 2005
    • Beijing Jiaotong University
      Peping, Beijing, China