Li Yan

Sun Yat-Sen University, Guangzhou, Guangdong Sheng, China

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Publications (76)126.43 Total impact

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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: 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; · 1.42 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; · 1.42 Impact Factor
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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; · 1.42 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: 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
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    ABSTRACT: To investigate the relationship of erectile dysfunction (ED) with blood vessel-, nerve- and androgen-related factors in young and middle-aged men with type 2 diabetes mellitus (T2DM) in order to provide some clinical evidence for early prevention and treatment of ED. We divided 53 male T2DM patients under 50 years into an ED group (IIEF-5 score < or = 21, n = 28) and a non-ED (NED) group (IIEF-5 score > or = 22, n = 25). We detected the levels of blood lipid, glucose, total testosterone (TT), sex hormone-binding globulin (SHBG), sulfate dehydroepiandrosterone (DHEA-S), calculated free testosterone (cFT), and examined the complications of macroangiopathy (MA), diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN), and compared the above indicators between the two groups. There were no significant differences between the two groups in age, diabetes duration, body mass index, blood pressure, and blood lipid and glucose levels (P > 0.05). The incidence rate of DR was significantly higher in the ED than in the NED group (39.3% vs 4.0%, P < 0.05), but no statistically significant differences were found in the levels of TT, cFT, SHBG and DHEA-S and the incidence rates of MA and DPN between the two groups (P > 0.05). The incidence of ED is closely related to DR in young and middle-aged men with T2DM. Therefore particular attention should be paid to the erectile function of T2DM patients with DR as early as possible.
    Zhonghua nan ke xue = National journal of andrology 10/2012; 18(10):904-8.
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    ABSTRACT: OBJECTIVE: To compare plasma concentrations of biomarkers of endothelial dysfunction between patients with primary aldosteronism (PA) and essential hypertension (EH), and to determine whether elevated levels of these biomarkers could predict development of early organ damage. METHODS: Thirty-six PA patients and 39 EH patients matched for age, sex, blood pressure and duration of hypertension were included in this study. Plasma levels of biomarkers reflecting endothelial dysfunction (von Willebrand factor, vWF; soluble intercellular adhesion molecule 1, sICAM-1; and oxidized low density lipoprotein, ox-LDL) were detected and compared between PA and EH patients. Left ventricular mass index (LVMI) determined by echocardiography, 24-hour urinary protein quantitative determination and urinary albumin excretion rate (UAER) were analyzed to evaluate early organ damage. Left ventricular hypertrophy was defined as LVMI > 125 g/m(2) in men and > 120 g/m(2) in women, and UAER between 20 µg/min and 200 µg/min was defined as microalbuminuria. RESULTS: vWF [(122.3 ± 53.8)% vs. (113.1 ± 68.3)%], sICAM-1 [(401.0 ± 74.1) µg/L vs. (300.9 ± 87.0) µg/L], ox-LDL [(13.6 ± 10.0) U/L vs. (8.1 ± 5.9) U/L], LVMI [(124.7 ± 33.6) g/m(2) vs. (109.1 ± 25.7) g/m(2)], 24-hour urinary protein quantitation [24 h UPQ, (0.17 ± 0.10) g vs. (0.09 ± 0.04) g] and UAER [(25.9 ± 7.7) µg/min vs. (9.7 ± 5.9) µg/min] were significantly higher in PA group than in EH group (all P < 0.05). Elevated plasma vWF, sICAM-1 levels and plasma aldosterone concentration independently predicted microalbuminuria. Whereas, elevated plasma vWF and ox-LDL levels, plasma aldosterone concentration and systolic blood pressure independently predicted left ventricular hypertrophy. CONCLUSION: Patients with PA have severer endothelial dysfunction reflected by multiple biomarkers and earlier organ damage than patients with EH, and plasma aldosterone concentration and multiple endothelial dysfunction biomarkers could independently predict early organ damage.
    Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 08/2012; 40(8):640-644.
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    ABSTRACT: Matrix metalloproteinases (MMPs) degrade extracellular matrix components. Increased MMP-9 content in diabetic skin contributes to skin vulnerability and refractory foot ulcers. To identify ways to decrease MMP-9 levels in skin, inhibition of MMP-9 expression in dermal fibroblasts using small interfering RNA was investigated in vitro. A full-thickness wound was created on the midback of streptozotocin-induced diabetic rats; skin biopsies were performed 3 days later. Skin MMP-9 expression was observed by immunohistochemical analysis. Dermal fibroblasts from 1-day-old normal Sprague Dawley rats cultured with high glucose and homocysteine concentrations were transfected with small interfering RNA complexes. Cells were collected 30, 48, and 72 hours after transfection, and reverse transcription-polymerase chain reaction, Western blot analysis, and gelatin zymography for MMP-9 were performed. Expression of MMP-9 was increased in diabetic rat skin, especially around wounds. After 30-, 48-, and 72-hour transfection with each MMP-9-specific small interfering RNA, reverse transcription-polymerase chain reaction showed markedly decreased MMP-9 messenger RNA expression, protein abundance, and activity. Of four MMP-9 small interfering RNAs, one sequence had a stable high inhibition rate (>70% at 30 and 48 hours after transfection). Expression of MMP-9 was increased in diabetic rat skin, especially around wounds, and was markedly inhibited after MMP-9 small interfering RNA transfection in vitro (P < .05). These findings may provide new treatments for diabetic skin wounds.
    Journal of the American Podiatric Medical Association 07/2012; 102(4):299-308. · 0.77 Impact Factor
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    ABSTRACT: We sought to develop new recombinant human epidermal growth factor (rhEGF)-containing hydrogels and to investigate their biological activity and therapeutic effects on wound healing in diabetic rats. Levels of rhEGF released from hydrogels were measured by enzyme-linked immunosorbent assay. The cellular proliferating activity of released rhEGF was evaluated by MTT assay. Fifty-six wounded diabetic rats were randomly divided into four groups with different topical treatment daily. The therapeutic effects were evaluated by wound area measurement, histologic analysis, immunohistochemical assessment of proliferating cell nuclear antigen and B-cell lymphoma/leukemia-2, and Western blotting of EGF receptor. The rhEGF released from the hydrogel matrix kept its bioactivity on stimulating proliferation of the BALB/c3T3 cell line. Wound closure rates on postoperative day 14 were 75.8% in the negative control group, 82.83% in the group treated with hydrogel matrix, 85.87% in the group treated with rhEGF-containing hydrogel, and 81.18% in the group treated with rhEGF solution. Compared with hydrogel matrix, rhEGF-containing hydrogel had an additional effect on induction of EGF receptor expression (P < .05). Compared with negative controls, protein expression of B-cell lymphoma/leukemia-2 was higher in the rhEGF-containing groups (P < .05). Proliferating cell nuclear antigen was induced at its highest level on day 7 in the rhEGF-containing hydrogel-treated group (P < .05). These data from in vitro release and diabetic animal models highlight the efficacy of hydrogels as a controlled releasing system for topical application of EGFs. The rhEGF-containing hydrogel we developed holds the merits of prolonged and sustained releasing of bioactive rhEGF and therapeutic potential in enhancing diabetic wound healing.
    Journal of the American Podiatric Medical Association 03/2012; 102(2):89-98. · 0.77 Impact Factor
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    ABSTRACT: To evaluate the effects of aldosterone with or without high sodium intake on blood pressure, myocardial structure and left ventricular function in rats, and to investigate the mechanisms underlying the effects. Eight-week-old male Sprague-Dawley rats were randomly divided into 3 groups: (1) control (CON) group fed a normal sodium diet, (2) aldosterone (ALD) group receiving aldosterone infusion and a normal sodium diet, and (3) high sodium plus aldosterone (HS-ALD) group receiving 1% NaCl diet in conjunction with aldosterone infusion. Aldosterone was administered through continuously subcutaneous infusion with osmotic minipump at the rate of 0.75 μg/h for 8 weeks. The myocardium structure was observed using transthoracic echocardiography and transmission electron microscopy. The collagen deposition in left ventricle was evaluated with Masson's trichrome staining. The expression of IL-18, p22phox, and p47phox proteins was examined using Western blot analysis. The systolic blood pressure in the ALD and HS-ALD groups was significantly higher than that in the CON group after 2-week treatment. But the blood pressure showed no significant difference between the HS-ALD and ALD groups. The left ventricular hypertrophy, myocardial collagen deposition and oxidative stress were predominantly found in the HS-ALD and ALD group. Furthermore, the breakdown of myocardial structure and oxidative stress were more apparent in the HS-ALD group as compared with those in the ALD group. Long-term infusion of aldosterone results in hypertension and profibrotic cardiovascular responses in rats fed a normal sodium diet, which were mediated by oxidative stress. High-sodium intake could aggravate myocardial injuries induced by aldosterone.
    Acta Pharmacologica Sinica 03/2012; 33(3):393-400. · 2.35 Impact Factor
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    ABSTRACT: To explore the effects of matrix metallopeptidase 9 (MMP-9) on the proliferation, apoptosis, type I and III procollagen synthesis of rat dermal fibroblasts. Lipopolysaccharide (LPS) at 0.1 and 1.0 µg/ml was used to stimulate fibroblasts to up-regulate the expression of MMP-9 for 18 and 48 h. And then RNA interference was employed to inhibit the high expression of MMP-9. Cell proliferation was tested by CCK-8, cell apoptosis by flow cytometry and type I and III procollagen expressions by quantitative reverse transcriptase PCR (qRT-PCR). The MMP-9 expression of fibroblasts increased after the stimulation of LPS. And the 1.0 µg/ml LPS stimulation of 48 hours was 14.25 times of mRNA expression and 2.31 times of protein expression versus that of the normal group (both P < 0.05). The RNA interference obviously inhibited the high expression of MMP-9. The mRNA expression was 1/8 and protein expression 1/3 (both P < 0.05) as compared with the control group. Cell proliferation decreased with the rising expression of MMP-9 to some extent [(1.08 ± 0.08) vs (1.18 ± 0.09), P < 0.05] and improved after the inhibition of high expression of MMP-9 [(1.78 ± 0.17) vs (1.53 ± 0.15), P < 0.01]. There was no change of apoptosis accompanied with high expression of MMP-9 (P > 0.05). Apoptosis decreased after the inhibition of high expression of MMP-9 for 48 hours (3.53% ± 0.22% vs 4.47% ± 0.46%, P < 0.05). The synthesis of type I procollagen was the same no matter up-regulation or down-regulation of MMP-9 expression (P > 0.05). As the expression of MMP-9 increased, the synthesis of type III procollagen decreased (P < 0.01), but not increased by 1.02 folds after the inhibited expression of MMP-9 (P > 0.05). MMP-9 can affect the biological behaviors of rat dermal fibroblasts.
    Zhonghua yi xue za zhi 02/2012; 92(8):564-7.
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    ABSTRACT: The serum aldosterone concentration (SAC)/plasma renin activity (PRA) ratio (ARR) is considered a useful screening test in the differential diagnosis of essential hypertension (EH) and primary aldosteronism (PA). The purpose of this study is to investigate the effect of age on ARR and compare the screening accuracy of ARR plus elevated SAC for PA screening in different age groups. Thirty-nine patients with PA, 274 patients with EH, and 153 healthy volunteers were recruited. Blood was sampled for SAC and PRA measuring under keeping upright posture for 1 h. Levels of SAC, PRA, and ARR were compared at different ages range for the respective three groups of subjects. The screening accuracy of ARR plus elevated SAC was compared in different age groups and PA patients served as the same positive subjects. In the EH group, logarithmically transformed ARR (Log-ARR) increased with advancing age and reached its peak in the ≥ 60 years group; in the normotensives group, Log-ARR reached its peak in the 40-49 years group and slightly declined with advancing age. In the PA group, Log-ARR was not age dependent. Screening accuracy increased when combined index of ARR and SAC was used in the ≥ 40 years group but not in the <40 years group. Although the number of EH patients with elevated ARR increased with advancing age, but the screening accuracy and cutoff values of ARR were not affected by age. Using the combined index of ARR and SAC increased the screening accuracy for the patients older than 40 years, but not necessary for the patients younger than 40 years.
    Endocrine 02/2012; 42(1):182-9. · 1.42 Impact Factor
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    ABSTRACT: Advanced glycation end products (AGEs) exert divergent effects on the pathogenesis of diabetes complications. Excessive expression of matrix metalloproteinases-9 (MMP-9) is deleterious to the cutaneous wound-healing process in the context of diabetes. However, the effect of AGEs on MMP-9 induction in skin cells and the exact molecular mechanisms involved are still poorly understood. In this study, we investigated the effect of AGEs on the production of MMP-9 in HaCaT keratinocytes and characterized the signal transduction pathways activated by AGEs that are involved in MMP-9 regulation. We showed that AGE-BSA increased MMP-9 expression in HaCaT cells at both the protein and mRNA levels. The stimulatory effect of AGE-BSA on MMP-9 was attenuated by inhibitors of extracellular-signal-regulated kinase (ERK1/2, U0126), p38 mitogen-activated protein kinase (MAPK, SB203580) and NF-κB, but not c-Jun N-terminal kinase. Furthermore, receptor for advanced glycation end products (RAGE) was expressed in keratinocytes, and incubation with AGE-BSA resulted in a significant upregulation of RAGE expression in a dose-dependent manner. Silencing of the RAGE gene prevented AGE-BSA-induced MMP-9 activation and the phosphorylation of ERK1/2 and p38 MAPK. We also observed the involvement of NF-κB in AGE-BSA-induced MMP-9 activation, which was not blocked by U0126 and SB203580. These results suggest that AGEs may play an important role in the impairment of diabetic wound healing by upregulating MMP-9 expression in keratinocytes via the RAGE, ERK1/2 and p38 MAPK pathways; activation of NF-κB is also involved in this process. These pathways may represent potential targets for drug interventions to improve diabetic wound healing, a process in which MMP-9 plays a critical role.
    Experimental Dermatology 02/2012; 21(2):123-9. · 3.58 Impact Factor
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    ABSTRACT: To explore the effects of the high expression of MMP9 on biological behaviors of fibroblasts. High glucose and hyperhomocysteine were used to induce MMP9 expression in skin fibroblasts. Cell proliferation was detected by flow cytometry and cell viability by CCK-8. ELISA assay was used to detect collagen (hydroxyproline) secretion. Scratch test was employed to evaluate horizontal migration of cells and transwell method to evaluate vertical migration of cells. The mRNA and protein expressions of MMP9 and its protease activity were significantly higher in cells treated with high glucose and hyperhomocysteine than those in control group. At the same time, the S-phase cell ratio, proliferation index, cell viability, collagen (hydroxyproline) secretion, horizontal migration rate, and the number of vertical migration cells decreased in high-glucose and hyperhomocysteine-treated group. Tissue inhibitor of metalloproteinase 1 (TIMP1), which inhibits the activity of MMP9, recovered the above biological behaviors. High expression of MMP9 in skin fibroblasts could be induced by cultureing in high glucose and hyperhomocysteine medium, which inhibited cell biological behaviors. Inhibitions could be reversed by TIMP1. The findings suggested that MMP9 deters the healing of diabetic foot ulcers by inhibiting the biological behaviors of fibroblasts.
    Experimental Diabetes Research 01/2012; 2012:494579. · 1.89 Impact Factor
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    ABSTRACT: Prevalence of inadequate glycaemic control among patients with type 2 diabetes mellitus (T2DM) remains high. We assessed glycaemic control in the real-life practice among people with T2DM in metropolises in China who were treated with oral antidiabetic drugs (OAD) alone and to determine factors associated with inadequate glycaemic control in this population. An observational, cross-sectional multicentre study was conducted in 16 metropolitan medical centers. People with T2DM who had been followed-up before the index visit which occurred from January to September 2007 were included in the study. All subjects were ≥ 30 years of age at the time of T2DM diagnosis and had received monotherapy or combination therapy of OAD for at least 6 months. Demographic and clinical data were collected from medical records. The main study outcome was the inadequate glucose control rate, which was calculated by the proportion of patients with haemoglobin A(1C) (HbA(1C)) ≥ 6.5% detected on the index visit. In this cohort of 455 patients with T2DM whose mean age was 60.6 years and mean disease duration was 6.1 years, 45.5% had inadequate glycaemic control. The mean (SD) HbA(1C) was 6.7% (1.3). Multivariate Logistic regression showed that physical inactivity, disease duration > 10 years, body mass index (BMI) ≥ 24 kg/m(2), low homeostasis model assessment of β-cell function (HOMA-β) index, less frequency of medical visit and hypertriglyceridaemia were independent determinants of inadequate glycaemic control. Higher incidence of self-reported hypoglycemia experience (47.1% vs. 34.8%, P = 0.008) and more fear of hypoglycemia quantified by Worry subscale of the Hypoglycaemia Fear Survey (HFS) II were happened in subjects with good glycemic control. Approximately one half of these outpatients with T2DM from the metropolitan medical centers in China had inadequate glycaemic control treated with OAD alone, which raises the need for more effective educational and therapeutic approaches on management of hypertriglycemia, enhancing physical exercise and weight control, and at the same time, lowering the hypoglycemic risk and diminishing the hypoglycemic fear of patients.
    Chinese medical journal 08/2011; 124(16):2461-8. · 0.90 Impact Factor

Publication Stats

389 Citations
126.43 Total Impact Points

Institutions

  • 2006–2013
    • Sun Yat-Sen University
      • Department of Endocrinology
      Guangzhou, Guangdong Sheng, China
  • 2002–2013
    • Sun Yat-Sen University of Medical Sciences
      • • Department of Endocrinology
      • • Sun Yat-sen Memorial Hospital
      Shengcheng, Guangdong, 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
    • Maternal and Children Health Hospital of Guangxi Zhuang Autonomous Region
      Yung-ning, Guangxi Zhuangzu Zizhiqu, China
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China