Li Yan

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (85)178.85 Total impact

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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.
    Diabetes 11/2014; · 7.90 Impact Factor
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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.
    Metabolism 08/2014; · 3.10 Impact Factor
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    ABSTRACT: Abstract The aim of the study was to discuss the effect of intensive nursing education on the prevention of diabetic foot ulceration among patients at high risk for diabetic foot. One hundred eighty-five diabetes patients at high risk for foot diseases were enrolled in this study and provided with intensive nursing education, including individualized education about diabetes mellitus and diabetic foot diseases, instruction in podiatric care (the right way of washing the foot, the care of foot skin, appropriate choice of shoes and socks, intense examinations and records of feet by patients themselves every day, and the assistant management of calluses). Study subjects were followed up for 2 years. Once the foot ulceration developed, the inducing factors of foot ulceration were inquired about, the ulcers were evaluated, and the incidence of foot ulceration was analyzed before and after the intensive nursing education according to self-paired data. Results showed there were highly statistically significant improvements in the intensive treatment group compared with the control group in plasma glucose, blood pressure, and high-density lipoprotein cholesterol levels. More important is that intensive nursing education helps to prevent diabetic foot ulceration and to decrease the rate of amputation among patients at high risk for diabetic foot.
    Diabetes Technology &amp Therapeutics 07/2014; · 2.21 Impact Factor
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    ABSTRACT: Objective Progressive β-cell dysfunction hinders the maintenance of glycaemic control in type 2 diabetes, but comparative data on β-cell-protective therapies are lacking in the early stage of type 2 diabetes. Here we evaluated the comparative glycaemic efficacy and impact on β-cell function of three antihyperglycaemic agents that have a β-cell-protective effect, exenatide, insulin and pioglitazone, in newly diagnosed type 2 diabetes patients.Design and methodsIn this 48-week, multicentre, parallel-group study, 416 patients newly diagnosed with type 2 diabetes were randomly assigned 1:1:1 to receive exenatide, insulin or pioglitazone. The primary endpoint was the change in glycosylated haemoglobin (HbA1c) from baseline. Secondary endpoints included effects on weight, blood pressure, lipid profiles and β-cell function assessed by homeostasis model assessment, fasting proinsulin:insulin (PI/I), disposition index (DI) and acute insulin response (AIR).ResultsAt week 48, mean [95% confidence interval (CI)] HbA1c changes from baseline were –1.8% (–1.55% to –2.05%) with exenatide, –1.7% (–1.52% to –1.96%) with insulin and –1.5% (–1.23% to –1.71%) with pioglitazone. Treatment differences were –0.20% (95% CI –0.46% to 0.06%) for exenatide versus insulin (P = 0.185), and –0.37% (95% CI –0.63% to –0.12%) for exenatide versus pioglitazone (P = 0.002). Significant improvements from baseline in AIR, PI/I and DI were observed with all treatments, with the greatest improvements in DI, as well as weight, blood pressure and lipid profile, observed with exenatide.Conclusions All three agents showed efficacy regarding glycaemic control and metabolic benefits; however, exenatide showed the greatest efficacy. β-cell function improved in all treatment groups, hence early initiation of β-cell-protective therapy may halt the decline in β-cell function in type 2 diabetes.This article is protected by copyright. All rights reserved.
    Journal of Internal Medicine 07/2014; · 6.46 Impact Factor
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    ABSTRACT: Epidemiological evidence suggests that passive smoke exposure is related to the development of diabetes. However, data on this issue are controversial. We conducted a meta-analysis to provide a quantitative assessment of the association between passive smoking and the risk of diabetes. We searched the Medline and Embase databases up to October 2013 to identify prospective cohort studies related to passive smoke exposure and incident diabetes. Summary effect estimates with 95 % confidence intervals (CI) were derived using a fixed or random effects model, depending on the heterogeneity of the included studies. Six prospective studies that span three continents involving 154,406 participants (ages 18-74) with 7,116 new diabetes cases were included in the meta-analysis. On the basis of the Newcastle Ottawa Scale system, five studies were identified as relatively high-quality. In our primary analysis, compared to never smokers without passive smoke exposure, never smokers reporting passive smoke exposure was associated with increased risk of diabetes (pooled relative risk 1.21, 95 % CI 1.07-1.38). Such association persisted in the dose-response analysis. No indications of significant heterogeneity and publication bias were detected. Estimates of total effects were generally consistent in the sensitivity and subgroup analyses. Findings of the present meta-analysis suggest that passive smoke exposure is independently associated with the risk of diabetes. The conclusion may have a far-reaching significance for public health in countries of high smoking intensity and high incident diabetes.
    Endocrine 02/2014; · 3.53 Impact Factor
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    ABSTRACT: Obesity and insulin resistance are risk factors for cardiovascular diseases. Whether insulin-sensitive obese individuals are at higher risk for cardiovascular diseases is still debated. We aim to investigate whether insulin-sensitive obesity associates with prevalent cardiovascular diseases and 10-year coronary heart disease (CHD) risk. At the baseline of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study, 211,641 participants aged 40years or older were recruited from 25 communities across the China mainland, in 2011 to 2012. Participants were categorized by insulin-sensitive/resistant and general/abdominal obese status. Cardiovascular diseases included CHD, stroke, and myocardial infarction. Framingham risk score (FRS) was calculated according to National Cholesterol Education Program-Adult Treatment Panel III and FRS greater than 20% or cardiovascular diseases were identified as high risk for 10-year CHD. Controlling for potential confounders, compared with insulin-sensitive normal weight individuals, insulin-sensitive general obese individuals had increased risks for prevalent cardiovascular diseases (men: OR, 2.55, 95% CI, 2.04-3.18; women: 1.73, 1.45-2.06) and 10-year Framingham risk for CHD (men: 2.26, 1.86-2.76; women: 1.73, 1.46-2.06). Compared with insulin-sensitive normal waist subgroup, insulin-sensitive abdominal obesity was associated with higher risks for prevalent cardiovascular diseases (men: 1.32, 1.20-1.46; women: 1.36, 1.27-1.47) and 10-year Framingham risk for CHD (men, 1.34, 1.23-1.45; women, 1.37, 1.27-1.47). Both general and abdominal obesity were associated with elevated prevalent cardiovascular diseases and 10-year CHD risk, regardless of the presence or absence of insulin resistance.
    International journal of cardiology 01/2014; · 6.18 Impact Factor
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    ABSTRACT: A longitudinal prospective study was undertook to investigate the effect of multifactorial target control, recommended by the American Diabetes Association (ADA), on macrovascular disease in patients with short-duration type 2 diabetes. Patients who were newly diagnosed with type 2 diabetes or within 1 year and had no previous vascular diseases or atherosclerosis plaques were enrolled in the present study. All patients received multifactorial intervention, with pharmacologic therapy targeting hyperglycemia, hypertension, dyslipidemia, along with secondary prevention of vascular disease with aspirin when necessary according to the ADA recommendation. Patients were followed up for 8 years (2002-2010). The ultrasounds of arteries (carotid, iliac and femoral arteries) were measured every year. The primary endpoint was the time to the first occurrence of atherosclerosis plaques of the arteries. The second endpoint was clinical evidence of cardiovascular diseases. One hundred and forty-three patients were recruited, and the mean age was 50 (6.92) years. During the study, atherosclerosis plaques occurred in 49 patients. Systolic blood pressure less than 130 mmHg [hazard ratio (HR), 0.236; 95 % confidence interval (CI) 0.076-0.734; P = 0.013] and fasting plasma glucose less than 7 mmol/l (HR, 0.457; 95 % CI 0.210-0.994; P = 0.048) were significantly associated with decreased onset of atherosclerosis plaques. Simultaneous target control of systolic blood pressure and fasting plasma glucose reduced the risk of atherosclerosis plaques by 18 % (P = 0.097) and cardiovascular diseases by 16 % (P = 0.046). Multifactorial target treatment in patients with short-duration type 2 diabetes can effectively reduce the risk of macrovascular complications.
    Endocrine 01/2014; · 3.53 Impact Factor
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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.
    Scientific reports. 01/2014; 4:7586.
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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.
    PLoS ONE 01/2014; 9(12):e114970. · 3.53 Impact Factor
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    ABSTRACT: 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.
    International Journal of Nanomedicine 01/2014; 9:3377-87. · 4.20 Impact Factor
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    ABSTRACT: 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.
    World journal of emergency medicine. 01/2014; 5(2):139-43.
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    ABSTRACT: Graves' disease (GD) is a common autoimmune disease mainly caused by thyroid-stimulating antibodies (TSAbs). Interleukin 21 (IL-21) has recently been reported to play a vital role in the production of pathogenic autoantibodies in several autoimmune diseases, but less is known about GD. This study aimed to investigate the serum levels of IL-21 in GD patients and to explore their association with disease activity. We performed a case-control association study of 152 patients with GD and 32 healthy controls. All patients were further classified into three subgroups: the GD-untreated group (n = 70), the GD-recurrence group (n = 41), and the GD-remission group (n = 41). Serum IL-21 levels were assayed with ELISA. TSAb activity was measured by an in vitro bioassay. Changes in serum IL-21 were also observed in 12 GD patients before and after treatment. Additionally, correlations among the serum IL-21 and free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb), thyrotropin receptor antibody (TRAb), and TSAb were also analyzed. The serum IL-21 levels in all GD patients were significantly higher than those in the control group (P < 0.001), and specifically, both the GD-untreated and GD-recurrence groups had elevated serum IL-21 compared to the control group (P < 0.001). Moreover, serum IL-21 in newly diagnosed patients markedly decreased after treatment (P < 0.001). Additionally, the serum IL-21 levels in GD-goiter patients were higher than those of the GD-non-goiter patients (P < 0.001). However, no significant differences were found in the serum IL-21 levels in patients with or without Graves' ophthalmopathy. Importantly, serum IL-21 positively correlated with FT3, FT4, TPOAb, TGAb, and TRAb (r = 0.5053, r = 0.3266, r = 0.1792, r = 0.2445, and r = 0.4096, respectively; all P < 0.0001), and particularly with TSAb activity (r = 0.8171, P < 0.0001), negatively correlated with TSH (r = -0.2713, P < 0.0001). Serum IL-21 levels were significantly elevated in patients with GD and decreased after treatment; moreover, IL-21 may be associated with the clinical disease activity. These observations suggest that IL-21 may play an important role in the pathogenesis of GD.
    Endocrine 11/2013; · 3.53 Impact Factor
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    ABSTRACT: To demonstrate whether abnormal glucose metabolism (diabetes and prediabetes) is associated with increased risk for cancer in the Chinese population and to identify factors that modify the risk of cancer among individuals with abnormal glucose metabolism. Between 2011 and 2012, 259,657 community-dwelling adults, aged 40 years and older, were recruited from 25 centers across the mainland China to participant in the baseline survey of REACTION study, with follow-up investigations performed 3, 5, 10 years later. Detailed questionnaire about lifestyles, physical and biochemical measurement, bio-samples including serum, urine, and whole blood for DNA extraction were collected for all the participants. The mean±SD age of this cohort was 57±10 years. And the prevalence of preexisting and newly diagnosed diabetes was 10.32% and 10.57%, respectively. A total of 4,511 prevalent cancer cases (988 men and 3,523 women) were identified, the prevalence was 1.79. Comparing to those with normal glucose metabolism, men with diabetes had a significantly lower adjusted prevalence ratio (PR) of stomach cancer (PR: 0.38, 95% CI: 0.16-0.89), and women with diabetes had significantly higher adjusted PRs of cancer of all sites (PR: 1.36, 95% CI: 1.20-1.56), and cancer of the breast (PR: 1.56, 95% CI: 1.21-2.00), the endometrium (PR: 1.58, 95% CI: 1.16-2.15), and the thyroid (PR: 1.53, 95% CI: 1.03-2.27). The multi-center Reaction study has captured a broad range of data on physical, psychological and metabolic function as well as health status, biochemical and lifestyle information in 259,657 adults from the general population across the China.
    Journal of Diabetes 11/2013; · 2.94 Impact Factor
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    ABSTRACT: To assess the design and the Mainland China subgroup baseline characteristics of the study to evaluate the efficacy and safety of alogliptin versus placebo in subjects with type 2 diabetes (T2DM) as monotherapy, add-on to metformin or add-on to pioglitazone. This was a multi-center, randomized, double-blind, placebo-controlled, 16-week study comparing alogliptin (ALO, 25 mg, 1/d) versus placebo (PLA) as monotherapy (A), add-on to metformin (B) or add-on to pioglitazone ± metformin (C). The T2DM subjects with glycosylated hemoglobin A1c(HbA1c) between 7% and 10% and aged between 18 years and 75 years were enrolled and randomized to the alogliptin group and the placebo group in 1: 1 ratio with 16 weeks treatment. All patients were followed up every 4 weeks. The safety endpoints consisted of the incidence of hypoglycemia and other adverse events. A total of 491 patients were enrolled in the Mainland China subgroup of the study (181 in group A, 186 in group B and 124 in group C). In each treatment group, the baseline characteristics including age, gender, body mass index, diabetes duration, HbA1c, fasting plasma glucose, body weight, daily dosage of metformin and daily dosage of pioglitazone were all well balanced. The demographic data, medical history, glycemic profile and treatment regimen at baseline in Mainland China subgroup are well balanced. The result of this study will provide the clinical evidence for the use of alogliptin in Chinese T2DM patients.
    Zhonghua nei ke za zhi [Chinese journal of internal medicine] 11/2013; 52(11):932-935.
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    ABSTRACT: The best preoperative examination in Graves' disease with thyroid cancer still remains uncertain. The objectives of the present study were to investigate the prevalence of thyroid cancer in Graves' disease patients, and to identify the predictive factors and ultrasonographic features of thyroid cancer that may aid the preoperative diagnosis in Graves' disease. This retrospective study included 423 patients with Graves' disease who underwent surgical treatment from 2002 to 2012 at our institution. The clinical features and ultrasonographic findings of thyroid nodules were recorded. The diagnosis of thyroid cancer was determined according to the pathological results. Thyroid cancer was discovered in 58 of the 423 (13.7 %) surgically treated Graves' disease patients; 46 of those 58 patients had thyroid nodules, and the other 12 patients were diagnosed with incidentally discovered thyroid carcinomas without thyroid nodules. Among the 58 patients with thyroid cancer, papillary microcarcinomas were discovered in 50 patients, and multifocality and lymph node involvement were detected in the other 8 patients. Multivariate regression analysis showed younger age was the only significant factor predictive of metastatic thyroid cancer. Ultrasonographic findings of calcification and intranodular blood flow in thyroid nodules indicate that they are more likely to harbor thyroid cancers. Because the influencing factor of metastatic thyroid cancers in Graves' disease is young age, every suspicious nodule in Graves' disease patients should be evaluated and treated carefully, especially in younger patients because of the potential for metastasis.
    World Journal of Surgery 10/2013; · 2.23 Impact Factor
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    ABSTRACT: Epidemiological evidence suggests that alcohol consumption is related to the incidence and development of metabolic syndrome. However, data on this issue are unstable and controversial. We conducted a meta-analysis to provide a quantitative assessment of the association between alcohol intake and risk of metabolic syndrome. We searched the Pubmed and Embase databases up to May 2013 to identify prospective cohort studies related to alcohol consumption and metabolic syndrome. Summary effect estimates with 95% confidence intervals (CI) were derived using a fixed or random effects model, depending on the heterogeneity of the included studies. Six prospective studies involving 28,862 participants with 3305 cases of metabolic syndrome were included in the meta-analysis. On the basis of the Newcastle Ottawa Scale system, 83.3% of the studies were identified as relatively high-quality. In our primary analysis, compared with nondrinker, very light drinker was associated with decreased risk of metabolic syndrome [pooled relative risk (RR) 0.86, 95% CI: 0.75-0.99, fixed-effect model] while heavy drinker was associated with increased risk of metabolic syndrome (pooled RR 1.84, 95% CI: 1.34-2.52, fixed-effect model). No indications of heterogeneity and publication bias were found in these two groups. Estimates of total effects were generally consistent in the sensitivity and stratification analyses. The present meta-analysis of prospective studies suggested that heavy alcohol consumption might be associated with an increased risk of metabolic syndrome while very light alcohol consumption seemed to be associated with a reduced risk of metabolic syndrome.
    Clinical nutrition (Edinburgh, Scotland) 10/2013; · 3.27 Impact Factor
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    ABSTRACT: It is estimated that there are more than 16 million adults with drug-resistant hypertension in China. Nevertheless, the prevalence of and risk factors for primary aldosteronism, a highly curable condition among adults with drug-resistant hypertension, has not been fully investigated. Between January 2010 and October 2011, a multicenter epidemiologic study was conducted among 1656 patients with resistant hypertension in 11 provinces of China. Serum aldosterone and plasma renin activity were measured in every participant and aldosterone-to-renin ratio (ARR) was calculated. Patients with ARR more than 20 underwent an intravenous (i.v.) sodium infusion test, and diagnosis of primary aldosteronism was established by the presence of unsuppressed postinfusion aldosterone (>8 ng/dl). Patients with biochemically proved primary aldosteronism then underwent adrenal computed tomography (CT) scanning and adrenal vein sampling (AVS) for subtype classification. Among the 1656 patients, 494 (29.8%) had ARR greater than 20 and underwent i.v. sodium infusion. Of these 494, 118 were diagnosed as primary aldosteronism, yielding a prevalence of 7.1% (95% confidential interval 5.9-8.3%). Seventy of the 118 patients were categorized into unilateral (39) and bilateral (31) by AVS. Generalized additive regression analysis revealed that among all the factors investigated (age of hypertension onset, BMI, family history of hypertension, cigarette smoking, alcohol consumption, diabetes, serum potassium, hyperlipidemia, and creatinine), only age of hypertension onset and serum potassium were independently associated with the presence of primary aldosteronism. The prevalence of primary aldosteronism among Chinese patients with resistant hypertension is relatively lower than that reported previously for other ethnic populations. The screening for primary aldosteronism should be focused on those with early onset hypertension and/or hypokalemia.
    Journal of Hypertension 07/2013; 31(7):1465-71; discussion 1471-2. · 4.22 Impact Factor
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    ABSTRACT: We investigated the effect of angiotensin II (Ang II) on matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) balance in regulating collagen metabolism of diabetic skin. Skin tissues from diabetic model were collected, and the primary cultured fibroblasts were treated with Ang II receptor inhibitors before Ang II treatment. The collagen type I (Coll I) and collagen type III (Coll III) were measured by histochemistry. The expressions of transforming growth factor-β (TGF-β), MMP-1, TIMP-1 and propeptides of types I and III procollagens in skin tissues and fibroblasts were quantified using polymerase chain reaction (PCR), Western blot or enzyme-linked immunosorbent assay (ELISA). Collagen dysfunction was documented by changed collagen I/III ratio in streptozotocin (STZ)-injected mice compared with controls. This was accompanied by increased expression of TGF-β, TIMP-1 and propeptides of types I and III procollagens in diabetic skin tissues. In primary cultured fibroblasts, Ang II prompted collagen synthesis accompanied by increases in the expressions of TGF-β, TIMP-1 and types I and III procollagens, and these increases were inhibited by losartan, an Ang II type 1 (AT1) receptor blocker, but not affected by PD123319, an Ang II type 2 (AT2) receptor antagonist. These findings present evidence that Ang-II-mediated changes in the productions of MMP-1 and TIMP-1 occur via AT1 receptors and a TGF-β-dependent mechanism.
    Diabetes & Vascular Disease Research 06/2013; · 2.59 Impact Factor
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    ABSTRACT: To explore the values of arginine stimulation, oral glucose-insulin release and intravenous glucose tolerance tests to assess the function of islet β-cell in individuals with differential glucose tolerance. Healthy subjects (n = 38) and those with impaired glucose regulation (IGR) without a family history of diabetes (n = 31), 32 normal glucose tolerance (NGT, n = 32) and impaired glucose regulation as first-degree relatives of type 2 diabetes mellitus (DM) (IGR, n = 36) and 35 newly-diagnosed type 2 DM (n = 35) were recruited. All of them received arginine C-peptide releasing test (AST), oral glucose-insulin release test (OG-IRT) and intravenous glucose tolerance test (IVGTT). ACRARG was used to reflect non-glucose stimulated insulin secretion function, AIR0-10 for first-phase insulin secretion function and ΔI30/ΔG30 for early insulin secretion function. The changes of islet-β-cell function indicators were detected in individuals with different glucose tolerance. (1) No significant differences existed in ACRARG among five groups (all P > 0.05). (2) In terms of AIR0-10, the patients of type 2 DM had lower levels than those with IGR and NGT with or without a family history of DM (all P < 0.01). No significant difference existed among the subjects of IGR regardless of a family history of DM (P > 0.05). However, the subjects of IGR with or without a family history of DM had lower levels than those with NGT regardless of a family history of DM (P < 0.01 or P < 0.05). The subjects of NGT with a family history of DM had lower levels than those with NGT without a family history of DM (50.0 (24.3 - 85.1) vs 69.4 (46.1 - 94.8), P < 0.05). (3) ΔI30/ΔG30: no significant difference existed between the patients of type 2 DM and IGT with a family history of DM (P > 0.05). However, the subjects of type 2 DM had lower levels than those of IGR without a family history of DM and NGT with or without a family history of DM (all P < 0.01). The subjects of IGR with or without a family history of DM had lower levels than those with NGT regardless of a family history of DM (all P < 0.01). No significant difference existed among the subjects of NGT with or without a family history of DM (P > 0.05). And it was the same with IGR group. The acute C-peptide response to arginine stimulation test may not be used to evaluate the early phase insulin secretion among the subjects of early-stage DM, impaired glucose regulation and high diabetic risks.
    Zhonghua yi xue za zhi 03/2013; 93(10):760-3.
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    ABSTRACT: Inappropriate high expression of matrix metalloproteinase 9 (MMP9) in the late stage of diabetic foot ulcers suppresses wound healing. The underlying mechanisms are not completely understood. Site-specific demethylation was reported to function in the regulation of genes, causing persistent high expression of target genes. Therefore, this study was designed to determine whether site-specific DNA demethylation was a key regulatory component of MMP9 expression in diabetic wound healing, and to further verify the crucial CpG site(s). Human keratinocyte cell line (HaCaT) cells were exposed to tumor necrosis factor a (TNFa), and changes in MMP9 expression and DNA methylation status were detected. We found TNFa treatment increased endogenous MMP9 expression in HaCaT cells and decreased the DNA methylation percentage at the -36 bp promoter site in a time-dependent manner. Bisulfite sequencing PCR (BSP) revealed differentially demethylated CpG sites in the human MMP9 promoter region, but only the change at the -36 bp site was statistically significant. Dual-luciferase reporter assays showed that promoter with only the -36 bp site demethylated had slightly higher transcriptional activity than the promoter with all other sites except the -36 bp site demethylated. Our results demonstrated that site-specific DNA demethylation plays an important role in MMP9 expression in TNFa-stimulated keratinocytes. The -36 bp site in the MMP9 gene promoter is crucial to this effect, but other CpG sites may exert synergistic effects. Collectively, these data may contribute to the future development of novel therapeutic strategies to treat diabetic foot ulcers and prevent gangrene and amputation.
    Journal of Molecular Endocrinology 02/2013; · 3.58 Impact Factor

Publication Stats

479 Citations
178.85 Total Impact Points


  • 2006–2014
    • Sun Yat-Sen University
      • Department of Endocrinology
      Shengcheng, Guangdong, China
  • 2002–2014
    • Sun Yat-Sen University of Medical Sciences
      • • Department of Endocrinology
      • • Department of Hepatobiliary Surgery
      • • Sun Yat-sen Memorial Hospital
      Shengcheng, Guangdong, China
  • 2013
    • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      Shanghai, Shanghai Shi, China
  • 2012
    • Red Cross
      Washington, Washington, D.C., United States
  • 2008
    • China-Japan Friendship Hospital
      Peping, Beijing, China
  • 2007
    • 306th Hospital Of PLA
      Peping, Beijing, China
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China
    • Maternal and Children Health Hospital of Guangxi Zhuang Autonomous Region
      Yung-ning, Guangxi Zhuangzu Zizhiqu, China