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Objective To investigate the serum expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1) and C1q/tumor necrosis factor-related protein 3 (CTRP3) in type II diabetic rats with atherosclerosis and to undermine the interventional mechanism of simvastatin. Methods SD rats were randomly divided into normal diet (NC) group (n=8), high-fat diet (HFD) group (n=8), high-fat diet intervention (HFD+S) group (n=8), model (M) group (n=18) and model intervention (M+S) group (n=16). The diabetic atherosclerosis model was established by streptozotocin (STZ)+ Vitamin D3 (VitD3)+High-fat diet. The group HFD+S and group M+S rats were administrated with simvastatin at 20 mg/(kg⋅d)intragastrically as intervention while distilled water [20 mL/(kg⋅d)] were given to other groups. Serum levels of fasting plasma glucose (FPG), blood lipid, fasting insulin (FINS), VEGF, TGF-β1 and CTRP3 were compared between each groups. Results Characteristics of atheromatous plaque were seen in group M and group M + S whose pathological change were markedly attenuated compared to group M. Serum levels of VEGF, TGF-β1 and CTRP3 were significantly higher in rats from Group HFD than those in rats from group NC. Serum levels of VEGF and TGF-β1 were significantly higher in rats from Group M than those in rats from group NC. Serum level of VEGF was significantly higher in rats from Group M than it in rats from group HFD. Serum level of CTRP3 was significantly lower in rats from Group M than it in rats from group HFD. Moreover, serum levels of TGF-β1 and CTRP3 were significantly higher in rats from Group HFD+S than those in rats from group HFD after the intervention with simvastatin. Serum level of VEGF was significantly lower in rats from Group M+S than it in rats from group M, and serum levels of TGF-β1 and CTRP3 were significantly higher in rats from group M+S than those in rats from group M after the intervention with simvastatin. Conclusion VEGF, TGF-β1 and CTRP3 may participate in development of diabetic atherosclerosis. In addition to its hypolipidemic role, Simvastatin can also down regulate serum level of VEGF and up regulate serum levels of TGF-β1 and CTRP3 to exert a significant protective effect on diabetic atherosclerosis. [ABSTRACT FROM AUTHOR]

Soft tissue sarcomas (STSs) are a rare and fascinating group of diseases that can be subdivided into specific reciprocal translocations in STSs (SRTSs) and nonspecific reciprocal translocations in STSs (NRTSs). PTEN mutations are rare in STSs, suggesting that PTEN expression may be lost by alternative mechanisms such as methylation. In order to reveal whether aberrant PTEN methylation occurs in STSs, MassARRAY Spectrometry was carried to detect methylation patterns of PTEN in STSs. We evaluated methylation levels in 41 CpG sites from −2,515 to −2,186 bp (amplicon A) and −1,786 to −1,416 bp (amplicon B) relative to the translation initiation site in 110 different cases (46 cases of SRTSs, 40 cases of NRTSs, and 24 cases of normal controls). In addition, immunohistochemistry (IHC) was used to detect the loss of PTEN to determine whether PTEN alterations were responsible for decreased PTEN expression. Our data showed that expression of PTEN was diminished in 49 (57%) STSs, whereas the remaining cases (43%) were classified as high expression. Our previous results found that only 2 of 86 cases (2.3%) had a PTEN mutation suggesting that PTEN may be mainly downregulated in STSs by methylation, but not by mutation of PTEN itself. We observed that amplicon A was hypermethylated in STSs with low PTEN expression, whereas normal controls had low methylation levels (P<0.0001), which was not present in amplicon B (P>0.05), nor were there significant differences in the methylation levels in PTEN between SRTS and NRTS cases. The majority of individual CpG units within two amplicons was demonstrated to be hypermethylated. These findings indicate that PTEN hypermethylation is a common event in STSs suggesting that the inactivation of PTEN may be due to hypermethylation in the promoter of PTEN. The aberrant methylation of the CpG sites within PTEN promoter may serve as a potential candidate biomarker for STSs. [ABSTRACT FROM AUTHOR]

The article presents a study on the enhanced green fluorescent protein (EGFP) expression in transgenic chickens. The ability of the 2-(kilobyte) kb promoter fragment of the chicken ovalbumin gene to elicit tissue-specific expression of a foreign EGFP gene in chickens. The study projected potential of chicken ovalbumin promoter for the production of biologically active proteins in egg whites.

Abstract\nSIGNIFICANCE STATEMENTKeratinocyte and fibroblast dysfunctions contribute to delayed healing of diabetic wounds. Small extracellular vesicles (sEV) are key mediators of intercellular communication and are involved in the pathogenesis of several diseases. Recent findings suggest that sEV derived from high-glucose-treated keratinocyte (HaCaT-HG-sEV) can transport LINC01435 to inhibit tube formation and migration of HUVECs, thereby delaying wound healing. This study aimed to elucidate sEV-related communication mechanisms between keratinocytes and fibroblasts during diabetic wound healing. HaCaT-HG-sEV treatment and LINC01435 overexpression significantly decreased fibroblast collagen level and migration ability but significantly increased fibroblast autophagy. However, treatment with an autophagy inhibitor suppressed LINC01435 overexpression-induced decrease in collagen levels in fibroblasts. In diabetic mice, HaCaT-HG-sEV treatment decreased collagen levels and increased the expression of the autophagy-related proteins Beclin-1 and LC3 at the wound site, thereby delaying wound healing. Conclusively, LINC01435 in keratinocyte-derived sEV activates fibroblast autophagy and reduces fibroblast collagen synthesis, leading to impaired diabetic wound healing.Diabetic foot ulcers are a serious complication of diabetes and can lead to amputation and death. Therefore, it is crucial to comprehensively elucidate the mechanisms of delayed diabetic wound healing, with emphasis on the role of keratinocyte-derived small extracellular vesicles. In vivo and in vitro experiments showed that keratinocyte-derived small extracellular vesicles suppressed diabetic wound healing, which is partly attributed to the effects of their content (LINC01435) in fibroblasts. This study suggests that LINC01435 could be targeted to regulate diabetic wound healing. [ABSTRACT FROM AUTHOR]

Background: Research has shown that gonadal hormones are involved in metabolic pathways relevant to metabolic syndrome (MetS). Nevertheless, no longitudinal study has been conducted on the association between SHBG and MetS in Chinese. The objective of our study was to determine whether there is any association between middle-aged and elderly males in China., Methods: A total of 531 eligible male subjects, aged above 40 years or older, without MetS at baseline, were recruited. Sex hormone binding globulin (SHBG), total testosterone (TT), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured. A harmonized definition and recommended thresholds for the Chinese population were used to determine metabolic syndrome., Results: During 3.2 years of follow-up, 20.7% of subjects had developed MetS. Compared with the non-MetS group, subjects in the new-onset MetS group had significantly lower SHBG (43.5 nmol/L [28.8, 74.9] vs 53.7nmol/L [33.8, 115.0], P=0.0018), TT (18.1nmol/L [13.6-21.7] vs 19.5nmol/L[15.0-23.6], P=0.0204), and LH (5.13mIU/L [3.63-7.29] vs 5.87mIU/L [4.05-8.36]) at baseline. The incidence of MetS was decreased according to elevated SHBG quartiles (Q1:26.9%, Q2:22.7%, Q3:21.1%, Q4:12.1%, P for trend =0.0035), TT (Q1: 25.2%, Q2:23.7%, Q3: 17.3%, Q4: 16.7%, P for trend=0.0425), and LH (Q1:25.0%, Q2:21.8%, Q3: 21.8%, Q4: 14.3%, P for trend=0.0411). Compared with those in quartile 4, the OR[CI] of incident MetS for participants in Quartile 1 was 2.33[1.13-4.79] after multiple adjustments. But associations between incident MetS and different quartiles of LH, TT, and FSH were not observed after multiple adjustments. In the subgroup analyses, the significant association between SHBG level and Mets was detected in subjects over 60 years or older, with normal BMI, without insulin resistance, and with eGFR ≥90 mL/min per 1.73m2., Conclusion: Compared with TT, LH, and FSH, a lower level of SHBG is significantly related to the incidence of MetS among middle-aged and elderly males in China., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Chen, Li, Huang, Lin, Wang, Wang, You, Li, Li, Liang, Xiao, Yan, Lao and Sun.)

Purpose: To investigate the effect of grape seed extract on pathological changes of aorta in rats with chronic periodontitis and arteriosclerosis, and to analyze the possible mechanism., Methods: Fifteen SPF male rats with chronic periodontitis and arteriosclerosis were randomly divided into three groups, i.e., model group(n=5), low dose of grape seed extract group (n=5), high dose of grape seed extract group (n=5) , and control group (n=10). The rats in the low and high dose groups were treated with 40 mg·kg-1·d-1 and 80 mg·kg-1·d-1 for 4 weeks respectively, while the rats in the normal control group and the model group were treated with the same amount of normal saline at the same time. The maximal intima-media thickness(IMT) of abdominal aorta was measured by H-E staining, the activity of SOD and the content of MDA in serum were measured by colorimetry, the content of GSH-px in serum and serum levels of inflammatory factor (TNF-α) and interleukin-6(IL-6) were detected by ELISA. p38 mitogen-activated protein kinase/nuclear transcription factor Kappa B p65(p38 MAPK/NF-κB p65) pathway was detected by Western blotting. SPSS 20.0 software package was used for statistical analysis., Results: In the model group, the intima of abdominal aorta was irregularly thickened, with a lot of inflammatory cell infiltration, and arterial lesions appeared. In the low-and high-dose groups of grape seed extract, the plaque of abdominal aorta intima decreased and inflammatory cells reduced significantly, arterial vascular disease was improved, and the improvement was more obvious in high dose group than in low dose group. Compared with the control group, the levels of IMT, serum MDA, TNF-α, IL-6, p-p38MAPK/p38MAPK, NF-κB p65 and serum SOD and GSH-px in the model group were increased, while those in the model group were decreased(P＜0.05); the levels of IMT, serum MDA, TNF-α, IL-6, p-p38MAPK/p38MAPK, NF-κB p65 and SOD, GSH-px were decreased in the low and high dose groups(P＜0.05)., Conclusions: Grape seed extract can inhibit the oxidative stress level and inflammatory reaction in serum of chronic periodontitis with arteriosclerosis rats, thus improving the intimal lesion of aorta, possibly by inhibiting the activation of p38MAPK/NF-κB p65 pathway.

Dysregulation of macroautophagy/autophagy contributes to the delay of wound healing in diabetic skin. N 6 -methyladenosine (m 6 A) RNA modification is known to play a critical role in regulating autophagy. In this study, it was found that SQSTM1/p62 (sequestosome 1), an autophagy receptor, was significantly downregulated in two human keratinocyte cells lines with short-term high-glucose treatment, as well as in the epidermis of diabetic patients and a db/db mouse model with long-term hyperglycemia. Knockdown of SQSTM1 led to the impairment of autophagic flux, which was consistent with the results of high-glucose treatment in keratinocytes. Moreover, the m 6 A reader protein YTHDC1 (YTH domain containing 1), which interacted with SQSTM1 mRNA, was downregulated in keratinocytes under both the acute and chronic effects of hyperglycemia. Knockdown of YTHDC1 affected biological functions of keratinocytes, which included increased apoptosis rates and impaired wound-healing capacity. In addition, knockdown of endogenous YTHDC1 resulted in a blockade of autophagic flux in keratinocytes, while overexpression of YTHDC1 rescued the blockade of autophagic flux induced by high glucose. In vivo , knockdown of endogenous Ythdc1 or Sqstm1 inhibited autophagy in the epidermis and delayed wound healing. Interestingly, we found that a decrease of YTHDC1 drove SQSTM1 mRNA degradation in the nucleus. Furthermore, the results revealed that YTHDC1 interacted and cooperated with ELAVL1/HuR (ELAV like RNA binding protein 1) in modulating the expression of SQSTM1 . Collectively, this study uncovered a previously unrecognized function for YTHDC1 in modulating autophagy via regulating the stability of SQSTM1 nuclear mRNA in diabetic keratinocytes. Abbreviations: ACTB: actin beta; AGEs: glycation end products; AL: autolysosome; AP: autophagosome; ATG: autophagy related; AKT: AKT serine/threonine kinase; ANOVA: analysis of variance; BECN1: beclin 1; Co-IP: co-immunoprecipitation; DEGs: differentially expressed genes; DM: diabetes mellitus; ELAVL1: ELAV like RNA binding protein 1; FTO: FTO alpha-ketoglutarate dependent dioxygenase; G: glucose; HaCaT: human keratinocyte; GO: Gene Ontology; GSEA: Gene Set Enrichment Analysis; HE: hematoxylin-eosin; IHC: immunohistochemical; IRS: immunoreactive score; KEAP1: kelch like ECH associated protein 1; KEGG: Kyoto Encyclopedia of Genes and Genomes; m 6 A: N 6 -methyladenosine; M: mannitol; MANOVA: multivariate analysis of variance; MAP1LC3: microtubule associated protein 1 light chain 3; MAP1LC3B: microtubule associated protein 1 light chain 3 beta; MeRIP: methylated RNA immunoprecipitation; METTL3: methyltransferase 3, N6-adenosine-methytransferase complex catalytic subunit; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin complex 1; NBR1: NBR1 autophagy cargo receptor; NFE2L2: nuclear factor, erythroid 2 like 2; NG: normal glucose; NHEK: normal human epithelial keratinocyte; OE: overexpressing; p-: phospho-; PI: propidium iodide; PPIN: Protein-Protein Interaction Network; RBPs: RNA binding proteins; RIP: RNA immunoprecipitation; RNA-seq: RNA-sequence; RNU6-1 : RNA, U6 small nuclear 1; ROS: reactive oxygen species; siRNAs: small interfering RNAs; SQSTM1: sequestosome 1; SRSF: serine and arginine rich splicing factor; T2DM: type 2 diabetes mellitus; TEM: transmission electron microscopy; TUBB: tubulin beta class I; WT: wild-type; YTHDC1: YTH domain containing 1.

The present study explored the mechanism of Qingwei Powder(QP) in the treatment of periodontitis based on chromatography-mass spectrometry and network pharmacology-molecular docking techniques. UPLC-Q-TOF-MS and GC-MS were used to identify the chemical constituents of QP. The active components and targets were screened out through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and their targets were predicted using SwissTargetPrediction. Targets related to periodontitis were obtained from GeneCards, OMIM, and DisGeNET. Venn diagram was constructed using Venny 2.1 to obtain the intersection targets. Cytoscape 3.7.2 was used to construct the &quot;chemical component-target-disease&quot; network. The targets were analyzed for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by clusterProfiler R, and the &quot;chemical component-target-pathway&quot; network was constructed. The binding activity of the active components to the target proteins was verified by molecular docking. A total of 189 chemical components were obtained by UPLC-Q-TOF-MS and GC-MS, including 39 active components with 180 potential targets related to periodontitis. Target enrichment analysis of the active components yielded 92 KEGG pathways. Twenty KEGG pathways, 34 active components, and 99 targets were involved in the &quot;chemical component-target-pathway&quot; network. Molecular docking verified a good binding ability of the key targets to the key compounds. This study preliminarily indicates that QP is effective in treating periodontitis through multiple components, multiple targets, and multiple pathways, which reflects the complex system of Chinese medicine. This study provides the theoretical foundation for the subsequent research on the material basis and key quality attributes of QP.

Objectives: This study utilized personal noise measurements and fit-testing to evaluate the association between noise exposures and personal attenuation rating (PAR) values among participating workers, and second, to compare the attenuated exposure levels received by the workers and the British Standards Institute's recommended noise exposure range of 70 to 80 dBA., Design: We measured hearing protection device (HPD) attenuation among a sample of 91 workers at 2 US metal manufacturing facilities, through performance of personal noise dosimetry measurements and HPD fit-testing over multiple work shifts. We compared this testing with participant questionnaires and annual audiometric hearing threshold results., Results: The average 8-hr time-weighted average noise exposures for study participants was 79.8 dBA (SD = 7.0 dBA), and the average PAR from fit-testing was 20.1 dB (±6.7 dB). While differences existed between sites, 84% of the 251 PAR measurements resulted in effective protection levels below the recommended 70 dBA (indicating overprotection), while workers were underprotected (i.e., effective exposures >80 dBA) during <1% of monitored shifts. Our results also demonstrated a significant positive relationship between measured noise exposure and PAR among non-custom-molded plug users (p = 0.04). Non-custom-molded plug wearers also showed a significant increase in PAR by sequential fit-test interaction (p = 0.01), where on average, subsequent fit-testing resulted in increasingly higher HPD attenuation. Workers at site 1 showed higher PARs. PARs were significantly related to race, even when adjusting for site location. While age, hearing threshold level, task, and self-reported tinnitus showed no significant effect on individual PAR in an unadjusted model, site, race, and sand- or water-blasting activities were significant predictors in adjusted models. Within-worker variability in time-weighted averages and PARs across repeated measurements was substantially lower than variability between workers., Conclusions: Careful selection of HPDs is necessary to minimize instances of overprotection to workers in low and moderate occupational noise environments. The use of fit-testing in hearing conservation programs to evaluate PAR is recommended to avoid overprotection from noise exposure while also minimizing instances of under-attenuation.

Objectives: Noise is one of the most common exposures, and occupational noise-induced hearing loss (NIHL) is highly prevalent. In addition to NIHL, noise is linked to numerous non-auditory health effects. The Occupational Safety and Health Administration (OSHA) maintains the Integrated Management Information System (IMIS) database of compliance-related measurements performed in various industries across the USA. The goal of the current study was to describe and analyse personal noise measurements available through the OSHA IMIS, identifying industries with elevated personal noise levels or increasing trends in worker exposure over time., Methods: Through a Freedom of Information Act request, we obtained OSHA's noise measurements collected and stored in IMIS between 1979 and 2013 and analysed permissible exposure limit (PEL) and action level (AL) criteria measurements by two-digit industry code., Results: The manufacturing industry represented 87.8% of the 93 920 PEL measurements and 84.6% of the 58 073 AL measurements. The highest mean noise levels were found among the agriculture, forestry, fishing and hunting industry for PEL (93.1 dBA) and the mining, quarrying and oil and gas extraction group for AL (93.3 dBA). Overall, measurements generally showed a decreasing trend in noise levels and exceedances of AL and PEL by year, although this was not true for all industries., Conclusions: Our results suggest that, despite reductions in noise over time, further noise control interventions are warranted both inside and outside of the manufacturing industry. Further reductions in occupational noise exposures across many industries are necessary to continue to reduce the risk of occupational NIHL., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Phosphatase and tension homolog deleted on chromosome 10 (PTEN) was considered as a promising target in type 2 diabetes mellitus (T2DM) because of its negative effects on insulin resistance. Alteration in DNA methylation is thought to play a role in the pathogenesis of T2DM. The aim of the present study was to quantitatively evaluate the promoter methylation of PTEN in Uyghur patients with mild T2DM. We evaluated methylation levels in 21 CpG sites from -2515 bp to -2186 bp relative to the translation initiation site in 55 cases of T2DM and 50 cases of normal glucose tolerance (NGT) using the MassARRAY spectrometry. In addition, PTEN mRNA and protein levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting to determine whether DNA methylation alterations were responsible for PTEN expression. Compared with NGT groups, the PTEN mRNA expression was significantly higher in Uyghur patients with mild T2DM groups. We also showed that PTEN protein expression was upregulated in Uyghur patients with mild T2DM groups, but the level of protein kinase B (AKT) was downregulated. PTEN methylation in T2DM patients was significantly lower than that in NGT groups. In addition, 2 CpG units demonstrated a significant difference between the NGT and Uyghur patients with mild T2DM groups. Furthermore, there was a negative association between promoter methylation and PTEN expression. Together, these findings suggest that epigenetic inactivation of PTEN plays an important role in Uyghur patients with mild T2DM. The aberrant methylation of CpG sites within the PTEN promoter may serve as a potential candidate biomarker for T2DM in the Uyghur population.

Objective: A dramatic gap exists between the clinical practice and guidelines for the dyslipidemia control in patients with diabetes. It is still uncertain which routinely available lipid measure is more applicable in estimation of insulin sensitivity and blood glucose control. The present study aims to investigate associations of routine lipid profiles with insulin resistance and diabetes, respectively., Methods: We conducted a population-based study in 9764 Chinese participants. The homeostasis model assessment of insulin resistance was calculated to estimate insulin sensitivity. Diabetes was diagnosed according to the 1999 World Health Organization diagnostic criteria., Results: Participants with insulin resistance or diabetes presented with significantly higher triglycerides (TG), Non-high-density lipoprotein cholesterol (Non-HDL-C), Non-HDL-C/HDL-C, TG/HDL-C and lower HDL-C when compared with control subjects (all P < 0.0001). Such lipid measures were significantly correlated with fasting insulin, fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) 2 h glucose and Hemoglobin A1c (HbA1c) in Pearson's correlation analysis and multivariate linear regression analysis (all P < 0.0001). In logistic regression analysis, subjects were more likely to have prevalent insulin resistance and diabetes with the elevated quartiles of TG, Non-HDL-C, Non-HDL-C/HDL-C and TG/HDL-C (all P < 0.05). TG/HDL-C ratio, compare with other lipid parameters, have shown the strongest correlation with increased odds of insulin resistance and diabetes., Conclusion: Our study suggests a discordant association of lipid parameters with blood glucose level and TG/HDL-C is a better marker for evaluating insulin resistance and diabetes in Chinese population when compared with other routine lipid measures., (Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Diabetes elevates matrix metalloproteinase (MMP)-9 levels in the skin and its keratinocytes, and activated MMP-9 impairs skin wound healing. Epigenetic regulation of the DNA methylation status within the MMP-9 promoter plays an important role in the alteration of MMP-9 expression. Our aim was to investigate the role and mechanism of growth arrest and DNA damage-inducible 45a (GADD45a), a well-known DNA demethylation regulatory protein that mediates DNA methylation, in the regulation of MMP-9 expression. In this study, we showed that GADD45a was markedly upregulated in skin tissues from patients with diabetic foot ulcers, in diabetic rats, and in human keratinocyte (HaCaT) cells exposed to advanced glycation end products. We observed a substantial positive correlation between the levels of GADD45a and MMP-9 expression. Knockdown of GADD45a ameliorated the increase in MMP-9 transcription induced by a diabetic condition by inhibiting demethylation in the MMP-9 promoter and promoted diabetic HaCaT cell migration, but GADD45a knockdown did not affect HaCaT cell proliferation or apoptosis. Additionally, we demonstrated that overexpression of GADD45a activated MMP-9 expression by inducing promoter demethylation. Moreover, we found that GADD45a binds to the promoter of MMP-9 and recruits thymine-DNA glycosylase for base excision repair-mediated demethylation in diabetic HaCaT cells and diabetic rat skin. Our results reveal a mechanism in which GADD45a is required for demethylation of the MMP-9 promoter and the induction of diabetic wound healing. The inhibition of GADD45a might be a therapeutic strategy for diabetic foot ulcers., (Copyright © 2018 Endocrine Society.)

Epigenetics may affect the susceptibility for type 2 diabetes mellitus (T2DM). Previously, our studies have shown that the hypomethylation of human miR-375 promoter may contribute to the pathogenesis of T2DM. However, the methylation pattern of miR-375 promoter in T2DM is not yet fully understood. In this study, the DNA methylation status of the different region of miR-375 promoter in Chinese Han population with T2DM were explored. 100 Han patients with T2DM and 100 Han healthy controls with normal glucose tolerance (NGT) were collected. Then the transcription level of pre-miR-375 and mature miR-375 were examined using quantitative real-time PCR and the methylation status of 27 CpG sites in the miR-375 promoter was determined by MassARRAY Spectrometry. The relative expression of mature miR-375 was shown as fold difference relative to miR-16 (3.0-fold, P =0.0260) and pre-miR-375 was markedly unregulated (2.6-fold, P =0.0415) in Han T2DM samples. Aberrant methylation was significantly higher within the amplicon of the miR-375 promoter in T2DMs than in NGTs, an average of 10.27% and 7.24% (P=0.0004; Figure 3A), respectively. Further, one CpG unit (CpG&#95;26.27) was significantly hypermethylated in T2DM samples compared with NGT. Together, our results highlights for the first time that aberrant hypermethylation is a common event in Han T2DM, suggesting that the aberrant methylation of the CpG sites within miR-375 promoter may serve as a potential candidate biomarker for T2DM in the Chinese Han population., Competing Interests: None., (IJCEP Copyright © 2017.)

Purpose: There is a paucity of biomarkers to predict failure in human papillomavirus-positive (HPV + ) oropharyngeal squamous cell carcinoma (OPSCC) following curative therapy. E6/E7 viral oncoproteins are constitutively expressed in HPV + tumors and highly immunogenic, resulting in readily detected serum antibodies. The purpose of this study is to determine whether serum E6 and E7 antibody levels can potentially serve as a biomarker of recurrence in patients with HPV+OPSCC. Experimental Design: We evaluated E6/E7 antibody levels in patients with previously untreated, advanced stage (III, IVa-b), HPV+OPSCC receiving definitive chemoradiation under a uniform protocol from 2003 to 2010. Baseline and longitudinal serum samples were obtained from our archived repository. E6/E7 serum levels were measured using a glutathione- S -transferase capture ELISA and quantified by approximating the area under the dilution curve, and were analyzed using ANOVA and linear mixed model for longitudinal analysis. Results: We compared 22 HPV+OPSCC patients who developed recurrence with 30 patients who remained disease-free. There were no differences in T classification, N classification, disease subsite, or smoking status between the groups. In a longitudinal analysis, recurrent patients had significantly higher E6 and E7 serum antibody levels than the nonrecurrent patients over the follow-up period ( P = 0.02 and P = 0.002, respectively). Patients who recurred had a lower clearance of E7 antibody than patients who remained disease-free ( P = 0.0016). Conclusions: Patients with HPV+OPSCC whose disease recurs have a lower clearance of E6 and E7 antibodies than patients who do not have recurrence. The ratio of E7 antibody at disease recurrence compared with baseline is potentially a clinically significant measurement of disease status in HPV+OPSCC. Clin Cancer Res; 23(11); 2723-9. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Overexpression of matrix metalloproteinase-9 (MMP-9) is critical for diabetic chronic wounds involved in the refractory wound healing process. We aimed to develop a strategy through RNAi to decrease MMP-9 expression and improve diabetic wound healing. We had explored β-CD-(D 3 ) 7 as a gene carrier to take siRNA and effectively interfere with MMP-9 expression. It has been proven that β-CD-(D 3 ) 7 could be used as an effective siRNA delivery system. In this study, we want to know about the efficiency and safety of β-CD-(D 3 ) 7 /MMP-9 siRNA for improving wound healing in diabetic rats. β-CD-(D3)7/MMP-9 siRNA treated animals show lower levels of MMP-9 expression, which induce faster wound-close rates. Histological evaluation indicates that β-CD-(D3)7/MMP-9 siRNA significantly increases the content of collagen around the injured tissues. The number of neutrophilic ganulocytes was significantly decreased through treatment of β-CD-(D3)7/MMP-9 siRNA. In vivo fluorescence imaging assessment shows that β-CD-(D3)7/MMP-9 siRNA could not cause organ damage and organ accumulation. The results suggest that β-CD-(D 3 ) 7 /MMP-9 siRNA might be developed as a novel topical agent for the diabetic wounds treatment.

Background: Vitamin D status is related to obesity-related metabolic disorders. We investigated the risk of 25-hydroxyvitamin D [25(OH)D] deficiency among different metabolic phenotypes., Methods: This prospective cross-sectional study evaluated 1,292 individuals who were ≥40 years old. Participants were classified as metabolically healthy and normal weight (MHNW), metabolically obese but normal weight (MONW), metabolically healthy but obese (MHO) or metabolically unhealthy and obese (MUO). The demographic and clinical characteristics, as well as plasma 25(OH)D levels, were compared between the 4 groups., Results: The prevalences of MHNW, MONW, MHO and MUO were 32.1%, 19.3%, 17.9% and 30.7%, respectively. Approximately 58.5% participants had vitamin D deficiency, and vitamin D deficiency was more common in the MONW (68.7%) and MUO (73.6%) groups (MHNW, 42.7 and MHO, 50.2%). The MONW and MUO groups had lower 25(OH)D levels (versus the MHNW and the MHO groups). Among vitamin D-deficient participants, the MONW group exhibited increased risks of abdominal obesity (odds ratio [OR]: 3.28, P = 0.005), hypertension (OR: 3.08, P = 0.003) and elevated C-reactive protein (OR: 1.97, P = 0.03). In addition, the MUO group exhibited increased risks of hypertriglyceridemia (OR: 2.57, P = 0.001), insulin resistance (OR: 2.37, P = 0.001) and elevated C-reactive protein level (OR: 2.09, P = 0.003)., Conclusions: Individuals who were MONW and MUO had increased risks of vitamin D deficiency (versus MHNW and MHO), and individuals with vitamin D deficiency had worse metabolic status. Vitamin D supplementation may improve the metabolic status of individuals who are MONW or MUO., (Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

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.

Introduction: Firefighters have high rate of injuries and illnesses, as well as exposures to high levels of noise. This study explored the relationship between noise exposure and injury among firefighters., Methods: We recruited firefighters undergoing vehicle extrication and structural collapse emergency response training at a highly realistic training facility. Demographics, health status, body mass index (BMI), and history of serious injuries (i.e. injuries requiring first aid treatment, treatment in a medical clinic or office, or treatment at a hospital) were assessed at baseline, and daily activities, injury events, and near misses were assessed daily via surveys. Participants' noise exposures were monitored for one 24-h period using noise dosimeters. We used a mixed-effects logistic regression model to estimate the odds of injury events and near misses associated with noise exposure as an independent variable., Results: Of 56 subjects, 20 (36%) reported that they had ever suffered a serious injury during firefighting activities, and 9 (16%) reported a serious injury within the past year. We estimated rates of 6.6 lifetime serious injuries per 100 FTE 16.1 serious injuries per 100 FTE within the past year. Our models indicated a significant increase in injury events and near misses among those with higher BMI, and as well as a dose-response relationship between near misses/injuries and increasing noise levels. Noise levels >90 dBA in the 30 min prior to time of injury or near miss were associated with substantially increased odds ratios for injury or near miss. Our models further indicated that perceived job demands were significantly associated with increased risk of injury or near miss., Conclusion: Our results suggest that noise exposures may need to be incorporated into injury prevention programs for firefighters to reduce injuries among this high-risk occupational group., (© The Author 2015. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

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 40 years 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 30 mg/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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The thermoresponsive double-hydrophilic glycopolymer (DHG), Poly (6-O-vinyl-nonanedioyl-D-galactose-co-N-vinylcaprolactam) (P(OVNG-co-NVCL)) was synthesized via a chemo-enzymatic process and a free radical copolymerization and the resulting nanofibers were fabricated using an electrospinning process. The desired lower critical solution temperature (LCST) between 32 and 40 °C of the DHG polymers was achieved by adjusting the molar fraction of galactose monomer in the copolymers during the synthesis. The thermoresponsive DHG polymers were found to have good cytocompatibility with Hela cells as determined by the MTT assay, and special recognition of the protein peanut agglutinin (PNA). The drug release properties of these newly designed thermoresponsive DHG P(OVNG-co-NVCL) nanofibers are temperature regulated, can target specific proteins and have the potential application in the field of sustained drug release., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Steps in the genetic basis of pancreatic cancer (PC) have been recently identified, however, Studies focusing on the relationship between Jab1 and Smad4 in PC are rarely reported. This study was performed to examine the expression patterns and association of Jab1 and Smad4 in PC cells for gaining a further understanding of PC pathogenesis., Methods: Human pancreatic cancer cell line PANC-1 cells were infected with retrovirus vector containing GFP, HA-Jab1, siGFP, and siJab1 respectively. The expression of Jab1 and Smad4 in PANC-1 cells was analyzed by Western blot and immunocytochemistry. Subsequently, the effect of overexpression of Jab1 on cell proliferation inhibition mediated by TGF-β was examined with MTT colorimetry., Results: The expression of Smad4 in PANC-1 cells was inhibited after the overexpression of Jab1. Inversely, the expression of Smad4 was increased after the down-regulation of Jab1 silenced by SiRNA. Smad4 expression in PANC-1 cells was negatively correlated with Jab1 expression. In addition, the cell proliferation inhibitory effect induced by TGF-β in PANC-1 cells was attenuated after the overexpression of Jab1., Conclusions: The reverse correlation of Jab1 and Smad4 in PANC-1 cells may be involved in the Pathogenesis of PC. Jab1 can cause degradation of Smad4 via TGF-β signal pathway, consequently contributing to the proliferation of PC cells.

Objective: To compare the difference of glycosylated hemoglobin (HbA1c) for diagnosing type 2 diabetes mellitus (T2DM) between Chinese Uyghurs and Hans in xinjiang., Methods: we collected 707 subjects, including 456 Uyghurs and 251 Hans in Xinjiang Kashi region. All the subjects were underwent oral glucose tolerance test (OGTT) for diagnosing T2DM, at the same time their clinical biochemical markers and HbA1c levels were also measured. Then the data were analyzed, the receiver operating characteristic (ROC) curve was plotted and correlation analysis were made by SPSS 19.0 software., Results: 1. The levels of body mess index (BMI), 2-hour plasma glucose (2 h PG), diastolic blood pressure (DBP) total cholestero (TC) and triglycerides (TG) were 26.6±4.75 kg/m(2), 14.3±6.2 mmol/l, 81.6±13.4 mmHg, 4.5±1.3 mmol/l and 4.3±2.8 mmol/l in Uyghurs, moreover those were higher than Hans [25.4±13.3 kg/m(2), 13.1±6.9 mmol/l, 78.4±9.9 mmHg, 2.3±2.1 mmol/l and 2.0±1.4 mmol/l, (P<0.05)]. 2. Otherwise, the optimal cut-off value for HbA1c to diagnose T2DM was 6.95% in Uyghurs. At this cut-off value, the sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR) and the area under the ROC curve (AUC) were 98.3%, 97.7%, 43.64, 0.017 and 0.997. While the optimal cut-off value was 7.05% in Hans, and, the sensitivity, specificity, +LR, -LR and AUC separately were 91.1%, 92.8%, 0.971, 12.6, 0.096 and 0.971. 3. The correlation analysis was made in two populations. It demonstrated that HbA1c was positively correlated with BMI, TC and TG in Uyghurs (r=0.138, 0.273, 0.482, P<0.05). However, in Hans, the HbA1c only was positively correlated with TG (r=0.178, P<0.05)., Conclusion: The Uyghurs have higher metabolic markers, for example, BMI, TC, DBP and TG. It reveals that Uyghurs may have more severe insulin resistance (IR) comparing with Hans. And then, the cut-off value of HbA1c for diagnosing and screening T2DM is different between Uyghurs and Hans in Xinjiang.

Objective: To investigate the association between the level of serum testosterone and atherosclerosis in middle-aged and elderly men., Methods: 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., Results: 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., Conclusion: A low serum FT level may be a risk factor of atherosclerosis in Chinese men aged 40 years or older.

Objective: To explore the direct regulation effects and mechanisms of glucagon in insulin secretion of MIN6 cells that in the kind of the islet β cells. Methods ICUE3 and PCDNA3.1 plasmid were transfected to the MIN6 cells by electroporation transfection, and then treated with different concentrations of glucagon (Glg) and glucose (Glu). Biosensor technology that based on the fluorescence resonance energy transfer (FRET) was used to monitor the change of cAMP quantitatively and real-time. The level of cAMP and insulin were measured by the enzyme-linked immunosorbent assay (ELISA)., Results: The receptor of Glg was mainly located on the cell membrane in MIN6 cells. Compared with the 0 ng/L Glg group in the Glu-free state, the average value of CFP/YFP increased 4%±0.02 in the 500 ng/L Glg group, and the value in the 1000 ng/L Glg group increased 6%±0.03 (P>0.05). While in the high-Glu (16.7 mmol/L) state, the value increased 11%±0.02 in the 500 ng/L Glg group, and increased 23%±0.06 in the 1000 ng/L Glg group when compared with the 0 ng/L Glg group (P<0.01). The levels of the cAMP of 1000 ng/L and 500 ng/L Glg group were higher than those of the 100 ng/L and 0 ng/L Glg group in the condition of Glu-free (81.27±6.29, 76.73±2.10,39.45±2.83, 40.36±4.20; P<0.01). The levels of the cAMP of 1000 ng/L, 500 ng/L and 100 ng/L Glg group were higher than those of the 0 ng/L Glg group, at the meanwhile, the levels of the cAMP of 1000 ng/L and 500 ng/L Glg group were also higher than 100 ng/L Glg group in the condition of low-Glu (2.8 mmol/L) (92.91±7.35, 90.36±3.15, 65.82±10.49, 46.73±1.05; P<0.01). And this trend in the condition of high-Glu was almost to the low-Glu (106.75±7.26, 94.18±2.99, 83.09±1.16, 55.60±5.51, P<0.01). The levels of the insulin of 1000 ng/L, 500 ng/L and 100 ng/L Glg group were higher than those of the 0 ng/L Glg group. While 1000 ng/L Glg group was higher than that of the 500 ng/L and 100 ng/L Glg group in the condition of Glu-free (1844.02±200.93, 1387.94±483.12, 1251.817±60.30, 787.33±81.72; P<0.01). The levels of the insulin of 1000 ng/L and 500 ng/L Glg group were higher than those of the 100 ng/L and 0 ng/L Glg group, and the 1000 ng/L and was also higher than 500 ng/L Glg group in the condition of low-Glu (1552.31±81.20, 1285.62±131.67, 1020.85±42.60, 762.89±26.94, P<0.01). And this trend in the condition of high-Glu was almost to the low-Glu (1898.337±169.03, 1399.30±148.66, 1061.735±9.13, 972.89±22.19; P<0.01). The levels of cAMP and insulin secretion of MIN6 cells had a positive correlation in different Glu conditions (r2=0.559, P<0.01)., Conclusion: Glg may stimulate insulin secretion by increasing cAMP levels in the way of concentration gradient within the islet β cell lines--MIN6 cells. And the increasing trend was Glu dependent.

Objective: To investigate whether celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, can attenuate proliferation, migration, invasion and MMP-14 expression in pancreatic cancer cells PANC-1 and the possible anti-tumor mechanism of celecoxib., Methods: Human pancreatic cancer cell line PANC-1 cells were treated with diverse concentrations of celecoxib (20, 60, 100 μmol/L). Cell proliferation, invasion and migration capabilities were measured by MTT colorimetry, transwell invasion assay, and scratch assay separately. At the same time, the protein expression of COX-2 and MMP-14 was assessed by ELISA., Results: The capabilities of proliferation, invasion and migration in PANC-1 cells were attenuated in a concentration-dependent manner after treated with celecoxib, followed by the down-regulation of the protein expression of COX-2 and MMP-14. In addition, MMP-14 expression was significantly positively correlated with COX-2 expression., Conclusions: COX-2 inhibitor celecoxib can inhibit the proliferation, invasion and migration of PANC-1 cells via down-regulating the expression of MMP-14 in a concentration-dependent manner, thus contributing to its anti-tumor effect in pancreatic cancer.

Objectives: There have been no previous reports concerning functions of miR-103a in gastric cancer (GC) cells. Thus the aim of the study was to investigate its expression and role in development of this tumour., Materials and Methods: Real-time RT-PCR was performed to detect expression of miR-103a in GC cell lines and clinical cancer specimens. To further understand its role, we restored expression of miR-103a in MGC-803 cell line by transfection with miR-103a mimics or inhibitors. Effects of miR-103a on cell proliferation, migration and invasion on targets were also determined., Results: miR-103a was down-regulated in both GC cell lines and clinical cancer specimens. Meanwhile, its level was closely associated with pM or pTNM stage of GC. Overexpression of miR-103a markedly suppressed proliferation, migration, and invasion of GC cells, while its inhibition significantly accelerated cell proliferation, migration and invasion. Moreover, c-Myb was identified to be a functional downstream target of miR-103a, ectopic expression of which partially reversed suppression of cell proliferation and invasion., Conclusions: Thus our observations suggest that miR-103a functioned as a tumour suppressor by targeting c-Myb. These findings indicate that miR-103a might play a significant role in pathogenesis of GC., (© 2014 John Wiley & Sons Ltd.)

Context: Fetuin-A is an abundant plasma protein known to inhibit insulin signaling and pathologic calcification, has emerged as a promising candidate biomarker for diabetes risk., Objective: The objective of this study was to investigate the relationships between plasma Fetuin-A level with clinical characteristics in patients with new-onset type 2 diabetes mellitus (nT2DM)., Subjects and Methods: Plasma Fetuin-A levels, and clinical characteristics were assessed in 100 patients with nT2DM and 100 normal glucose tolerance (NGT)., Results: nT2DM subjects had significantly higher Fetuin-A levels than NGT subjects (368.5 ± 15.6 vs 152.7 ± 7.1 mg/ml, P < 0.01). In the Pearson's correlation coefficients, Fetuin-A levels and clinical parameters. Fetuin-A was positively correlated with HOMA-insulin resistance index (HOMA-IR), carotid intima media thickness(CIMT), HbA1c, triglyceride (TG), Low-density lipoprotein cholesterol (LDL-C), body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FBG) and 2 h post-glucose load blood glucose (2 h OGTT) (P < 0.05 and P < 0.01), but negatively with fasting plasma insulin (FINS), 2 h plasma insulin after glucose overload (PINS), High-density lipoprotein cholesterol (HDL-C) and HOMA-beta-cell insulin secretion index (HOMA-IS) (P < 0.05 and P < 0.01). However, no significant relationships were observed between plasma Fetuin-A levels and estimated glomerular filtration rate (eGFR), age and gender in nT2DM subjects. In a multiple linear regression analysis, Fetuin-A levels were independently associated with FBG, 2 h OGTT, HOMA-IS, TG, and CIMT (R(2) = 0.6760). CIMT were negatively associated with FINS and HDL-C (r = -0.33, P = 0.008; r = -0.31, P = 0.01, respectively) in the Pearson's analyses. Moreover, they were positively associated with HOMA-IR (r = 0.28, P = 0.03). It showed significant correlations of plasma CIMT with FINS, PINS and HOMA-IR (R(2) = 0.6760)., Conclusions: Our study suggests that the plasma Fetuin-A levels may be associated with macroangiopathies in nT2DM patients. Therefore, detecting early plasma Fetuin-A levels nT2DM provides an opportunity to intervene of carotid artery disease in diabetic patients and giving timely treatment for the prevention of diabetic vascular complications.

Background: Concerns regarding the use of selected bone marrow stem cells (BMSCs) in the field of cardiac repair after acute ischemic events have been raised. The current meta-analysis aimed to assess the efficacy and safety of selected BMSC transplantation in patients with acute myocardial infarction (AMI) based on published randomized controlled trials (RCTs)., Methods: A systematic literature search of PubMed, Ovid LWW, BIOSIS Previews, and the Cochrane library from 1990 to 2014 was conducted. Results from RCTs involving subjects with AMI receiving selected BMSC therapy and followed up for at least 6 months were pooled., Results: Eight trials with a total of 262 participants were included. Data were analyzed using a random effects model. Overall, selected BMSC therapy improved left ventricular ejection fraction (LVEF) by 3.17% (95% confidence interval [CI] 0.57-5.76, P=0.02), compared with the controls. There were trends toward reduced left ventricular end-systolic volume (LVESV) and fewer major adverse cardiac events (MACEs). Subgroup analysis revealed a significant difference in LVEF in favor of selected BMSC therapy with bone marrow mesenchymal stem cells (BMMSCs) as the cell type., Conclusions: Transplantation of selected BMSCs for patients with AMI is safe and induces a significant increase in LVEF with a limited impact on left ventricular remodeling., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2014. Published by Elsevier Inc.)

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.

Background & Aims: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2013. Published by Elsevier Ltd.)

Background & Aims: Evidence has suggested that low serum potassium concentration or low dietary potassium intake can result in many metabolic disorders. Our objective was to evaluate the association between serum potassium level and risk of prevalent metabolic syndrome., Methods: We conducted a cross-sectional study in 10,341 participants aged 40 years or older. Metabolic syndrome was defined according to guidelines from the National Cholesterol Education Program with modification., Results: The prevalence rate of metabolic syndrome was 51.7% in participants with hypokalemia and 37.7% in those with normokalemia. With the reduction of serum potassium quartiles, participants were tended to have higher level of triglycerides and uric acid, lower level of high-density lipoprotein cholesterol (HDL-C), larger waist circumference and more severe insulin resistance. Serum potassium level significantly decreased with the increasing number of metabolic syndrome components. Compared with subjects in the highest quartile of serum potassium level, multivariate adjusted odds ratios for prevalent metabolic syndrome in the lowest quartile was 1.48 (95% confidence interval, 1.16-1.87). Moreover, compared with subjects without central obesity, hypertriglyceridemia, low HDL-C and elevated fasting plasma glucose, those with each of these metabolic syndrome components have lower level of serum potassium after adjusted for age and sex., Conclusions: Low serum potassium level significantly associated with prevalence of metabolic syndrome in middle-aged and elderly Chinese., (Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: Patients with type 2 diabetes (T2D) are at a high risk of developing microvascular complications, such as diabetic retinopathy (DR). Previous studies have shown that low serum bilirubin concentrations in T2D patients may increase the risk of diabetic complications. Thus, the aim of the present was to investigate the association between the prevalence of DR and serum concentrations of total bilirubin in a Chinese population., Methods: The present study was a population-based cross-sectional study on 1761 T2D patients aged ≥40 years from the Jiading district of Shanghai, China. Fundus photographs were taken to confirm the presence and severity of DR. Subjects were assigned to quartiles based on serum total bilirubin concentrations (Quartile (Q) 1 <0.60 mg/dL; Q2 0.60-0.76 mg/dL; Q3 0.77-0.99 mg/dL; Q4 >0.99 mg/dL). Logistic regression models were used to explore the association between bilirubin concentrations and the prevalence of DR., Results: The prevalence of DR in the entire study population was 9.6%. The prevalence of DR was significantly lower in Q4 compared with the other three quartiles (Ptrend  = 0.004). After adjustment for multiple confounding factors, T2D patients in Q4 (i.e. serum bilirubin >0.99 mg/dL) were less likely (odds ratio 0.55; 95% confidence interval 0.33-0.91) to suffer from DR than patients in Q1 (i.e. serum bilirubin <0.60 mg/dL)., Conclusion: Serum bilirubin concentrations were inversely associated with DR in an elderly Chinese population, independent of traditional risk factors for microvascular complications., (© 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.)

Recent studies have shown that DNA methylation in the promoter of microRNA-375 (miR-375) downregulates its expression during tumorigenesis. However, it is not known if CpG methylation of the miR-375 promoter also has a role in the pathogenesis of type 2 diabetes mellitus (T2DM). In this study, the expression level and CpG methylation status of miR-375 in patients with T2DM were analyzed. Plasma samples from 100 patients with T2DM and 100 healthy controls with normal glucose tolerance (NGT) were collected. The plasma levels of miR-375 were examined using quantitative polymerase chain reaction (qPCR) and the methylation status of 17 CpG sites in the promoter of the miR-375 were determined using MassARRAY spectrometry. The plasma levels of miR-375 were found to be upregulated in patients with T2DM compared with controls with NGT (P<0.05). Overall, the methylation levels of the miR-375 promoter in patients with T2DM were not significantly different compared with controls with NGT; however, further studies revealed that four of the eight analyzed individual CpG units within the amplicon were significantly hypomethylated in T2DM samples compared with the NGT samples. This study demonstrated for the first time, to the best of our knowledge, that miR-375 is overexpressed in plasma in patients with T2DM, and this may be used as a novel biomarker to distinguish between patients with T2DM and healthy individuals. It was also demonstrated in this study that the miR-375 promoter is hypomethylated, in patients with T2DM, which may regulate the expression of miR-375 and contribute to the pathogenesis of T2DM.

Objective: Study of Once-daily LeVEmir(®) (SOLVE(TM)) was a 24-week international observational study to evaluate the safety and effectiveness of initiating once-daily insulin detemir (Levemir) as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who failed treatment of oral anti-diabetic drugs (OAD)., Methods: The present study was derived from the data of Chinese cohort. A total of 3272 patients with T2DM failing OAD were enrolled in the study. Determir were prescribed to the patients by the decision of the physician. Clinical data were collected at baseline, week 12 and week 24 to evaluate the safety and effectiveness of detemir., Results: The age of the patients was (56.2 ± 10.8) years with a diabetes duration of (7.1 ± 5.2) years. Their BMI was (25.3 ± 3.3) kg/m(2). No patient experienced any major or nocturnal hypoglycaemic event during the study. After 24 weeks of treatment, the glycosylated hemoglobin A1c (HbA1c) decreased from (8.33 ± 1.69)% to (7.16 ± 1.18)% with a mean change of -1.17%, the fasting plasma glucose decreased from (9.52 ± 2.59) mmol/L to (6.84 ± 1.42) mmol/L with a mean change of -2.7 mmol/L, and the 7-point blood glucose profile improved overall. Totally 49.1% of patients achieved HbA1c < 7%. The mean body weight decreased by 0.15 kg., Conclusions: Insulin detemir administered once daily as add-on therapy in patients with T2DM failing OAD regimen significantly reduces the risk of major hypoglycemia, improves glycemic control, increases the percentage of patients achieving treatment target with neutral effect on body weight.

Objective: To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVE(TM) study., Methods: Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study. Data on demographics, medical history, glycemic profile and treatment regimen at baseline were collected by physicians., Results: A total of 3272 patients [female 42%, male 58%, mean age (56.2 ± 10.8) years] were included in the study. Their BMI was (25.3 ± 3.3) kg/m(2). The duration of diabetes was 4.0 (0.1 - 27.0) years, and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0 (0.0 - 20.2) years. The proportions of subjects with diabetic macro- and micro-vascular complications were 15.8% (515 cases) and 27.1% (866 cases), respectively. The hemoglobin A1c (HbA1c) at baseline was (8.33 ± 1.70)%, and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L., Conclusions: A large proportion of patients with type 2 diabetes remain in poor glycemic control, and the prevalence of diabetic complications is high, which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.

p53 and PTEN are the two most frequently mutated tumor suppressors in human cancer. However, literature on the effect of the joint inactivation of tumor-suppressor genes in soft tissue sarcoma (STS) is lacking. The purpose of this study was to investigate whether p53 and PTEN mutations play a role in the carcinogenesis of STS, as well as to evaluate their mutual role in STS pathogenesis. We screened mutations of p53 and PTEN in 86 human STSs using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing, respectively. p53 mutations were detected in 25.6% (22 out of 86) of STSs: 6 cases of p53 mutations were detected in 46 cases of specific reciprocal translocations in STSs (13.0%), 16 cases were detected in 40 cases of nonspecific reciprocal translocations in STSs (40.0%); the majority of the mutations were point mutations in exon 6-7. Furthermore, PTEN mutations were observed in 2 out of 86 STSs (2.3%). Two out of 86 cases revealed a 130th codon G>A missense mutation in exon 8 of PTEN which resulted in an Arg change to Gln in the PTEN protein structure; and a 334th codon A>T missense mutation in exon 8 of PTEN, which resulted in an Asn change to Lys in the PTEN protein structure. All subjects were examined for p53 exon 5-9 mutations and for PTEN exon 5-9 mutations. However, no tumors contained an alteration of the two genes. The findings indicate that p53 mutations may be involved in the oncogenesis of STS and also suggest that p53 may function as a potential molecular marker for distinguishing between STSs with specific reciprocal translocations and nonspecific reciprocal translocations. Although the existence of PTEN mutations in STS was detected, the PTEN mutation frequency was quite low. We conclude that PTEN may have played a less prognostic role than p53 in the development and malignant transformation of STS in the patients examined.

Initially acquired memory dissipates rapidly if not consolidated. Such memory decay is thought to result either from the inherently labile nature of newly acquired memories or from interference by subsequently attained information. Here we report that a small G protein Rac-dependent forgetting mechanism contributes to both passive memory decay and interference-induced forgetting in Drosophila. Inhibition of Rac activity leads to slower decay of early memory, extending it from a few hours to more than one day, and to blockade of interference-induced forgetting. Conversely, elevated Rac activity in mushroom body neurons accelerates memory decay. This forgetting mechanism does not affect memory acquisition and is independent of Rutabaga adenylyl cyclase-mediated memory formation mechanisms. Endogenous Rac activation is evoked on different time scales during gradual memory loss in passive decay and during acute memory removal in reversal learning. We suggest that Rac's role in actin cytoskeleton remodeling may contribute to memory erasure., (2010 Elsevier Inc. All rights reserved.)

Objective: To establish the methods for isolation, purification and function identification of Syrian golden hamster islets., Methods: The Langerhans islets were isolated and purified from golden hamster pancreas by intra-ductal collagenase V perfusion and discontinuous Ficoll density gradient centrifugation. After isolation, the islet yield and purity were evaluated with DTZ staining. The islet function was assessed using glucose-stimulated insulin secretion test., Results: The total number of purified islets from one donor hamster was 359-/+35 islet equivalent (IEQ), with the purity and viability of the isolated islets of more than 90%. In response to glucose stimulations at 5.8 and 16.7 mmol/L, the secretion of insulin by the islets was 3.29-/+0.3 and 11.12-/+0.57 mU/L, respectively, showing a 2.28-fold higher insulin release by high-concentration than by low- concentration glucose stimulation (P<0.01)., Conclusion: The methods of collagenase V digestion and gradient centrifugation result in high yield and high purity of the isolated hamster islets.

Objective: To test the hypothesis that the introduction of antisense transforming growth factor beta receptor I (TBRI) plasmid and antisense tissue inhibitor of matrix metalloproteinase (TIMP-1) eukaryotic expressing plasmid into a rat liver fibrosis model may influence the progression of liver fibrosis., Methods: Fragments of TBRI cDNA and TIMP-1 cDNA were obtained by reverse transcription polymerase chain reaction (RT-PCR) and then amplified by nest PCR. pcDNA3.1(+)-antisense TBRI eukaryotic expressing plasmid was constructed by directional and inverted joins with the purified linear pcDNA3.1(+) and the purified fragment of TBRI, as well as, pcDNA3.1(+)-antisense TIMP-1 eukaryotic expressing plasmid. The recombinant was identified by restriction endonuclease digestion and DNA sequence analysis. The recombinant plasmids were encapsulated with Lipofectmine 2000, and then they were injected intraperitoneally into the liver fibrosis model rats. The protein expression of type I collagen was evaluated by immunohistochemistry. VG staining of liver slides of the rats was used for histopathological examination., Results: Compared with the empty plasmid control group and the disease control group, the deposition of type I collagen decreased in the three antisense treatment groups: antisense TBRI group (4.37+/-1.30) x 10(5), P less than 0.05; antisense TIMP-1 group (3.40+/-0.91) x 10(5), probability value less than 0.05; antisense TBRI + antisense TIMP-1 group (0.90+/-0.32) x 10(5), P less than 0.01; treatment control group (6.90+/-1.61) x 10(5); disease control group (7.34+/-1.68) x 10(5); and the normal control group (0.41+/-0.21) x 10(5)]. Significant differences in the pathological grades of fibrosis were found between the normal control group and the other five groups (P less than 0.05) and also between the disease control group and the three antisense treatment groups (antisense TBRI group P less than 0.05; antisense TIMP-1 group P less than 0.05; antisense TBRI + antisense TIMP-1 group P less than 0.01), but no difference was found between the empty plasmid control group and disease control group (P more than 0.05)., Conclusion: Both antisense TBRI eukaryotic expressing plasmid and antisense TIMP-1 eukaryotic expressing plasmid can inhibit the progress of liver fibrosis. A combined action can inhibit the progress of liver fibrosis more.