Publications by authors named "Kan Sun"

94 Publications

Mixed neuroendocrine-non-neuroendocrine neoplasm of the gallbladder: case report and literature review.

Diagn Pathol 2022 Jun 17;17(1):51. Epub 2022 Jun 17.

Hospital Information Center of Heilongjiang Province Affiliated to Harbin Institute of Technology, Harbin, 150001, Heilongjiang Province, China.

Background: Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of the gallbladder are rare malignancies. Here we presented two cases and reviewed the related literature.

Case Presentation: Our two patients were postoperatively diagnosed with gallbladder MiNENs, which pathologically consisted of a large cell neuroendocrine carcinoma and papillary adenocarcinoma. After cholecystectomy, one patient had a survival time of 30 months, while the other remained alive through 12 months of follow-up. In the literature, a total of 72 cases of gallbladder MiNENs were identified, and with our two patients included, we calculated a male-to-female ratio of 0.22 and a mean age of 64.5 years for the 74 reported cases. About one-half of these patients were found to have gallstones and presented with abdominal pain or discomfort in a relatively early stage. The preoperative diagnosis of these 74 cases mainly relied on abdominal ultrasound, contrast-enhanced computed tomography (CT) scanning, and magnetic resonance imaging or positron emission tomography/CT. However, the final diagnosis was established based upon the pathological evidence and expression of synaptophysin (Syn) and/or chromogranin A identified by immunohistochemical staining or neurosecretory granules detected by electron microscopy. Fifty-eight patients (78.4%) underwent various operations including simple cholecystectomy (n = 14), en bloc cholecystectomy (n = 9), standard or non-standard radical cholecystectomy (n = 25), or extended radical cholecystectomy (n = 6). The mean size of the resected gallbladder masses was 50.8 ± 36.1 mm (n = 63) with regional lymph node metastasis in 37 patients (52.1%), liver invasion or staging greater than T3 in 33 patients (45.8%), and hepatic metastasis in 26 patients (35.1%). The postoperative median survival time was 36 ± 11.42 months (95% confidence interval, 13.62 to 58.38 months). The log-rank analysis did not find that postoperative adjuvant chemotherapy contributed to a longer survival time relative to that among the patients who did not receive chemotherapy (numbers of patients, 15 versus 43; survival times, 36 months versus 30 months, p > 0.05).

Conclusions: Our two cases and the cases in the literature suggest that MiNENs of the gallbladder predominantly occur in women; are associated with early lymph node metastasis, local hepatic invasion, and hepatic metastasis; and can be managed by various surgeries as well as chemotherapy combined with somatostatin analogs.
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http://dx.doi.org/10.1186/s13000-022-01231-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206291PMC
June 2022

Potential Novel Serum Metabolic Markers Associated With Progression of Prediabetes to Overt Diabetes in a Chinese Population.

Front Endocrinol (Lausanne) 2021 5;12:745214. Epub 2022 Jan 5.

Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.

Background: Identifying the metabolite profile of individuals with prediabetes who turned to type 2 diabetes (T2D) may give novel insights into early T2D interception. The purpose of this study was to identify metabolic markers that predict the development of T2D from prediabetes in a Chinese population.

Methods: We used an untargeted metabolomics approach to investigate the associations between serum metabolites and risk of prediabetes who turned to overt T2D (n=153, mean follow up 5 years) in a Chinese population (REACTION study). Results were compared with matched controls who had prediabetes at baseline [age: 56 ± 7 years old, body mass index (BMI): 24.2 ± 2.8 kg/m2] and at a 5-year follow-up [age: 61 ± 7 years old, BMI: 24.5 ± 3.1 kg/m2]. Confounding factors were adjusted and the associations between metabolites and diabetes risk were evaluated with multivariate logistic regression analysis. A 10-fold cross-validation random forest classification (RFC) model was used to select the optimal metabolites panels for predicting the development of diabetes, and to internally validate the discriminatory capability of the selected metabolites beyond conventional clinical risk factors.

Findings: Metabolic alterations, including those associated with amino acid and lipid metabolism, were associated with an increased risk of prediabetes progressing to diabetes. The most important metabolites were inosine [odds ratio (OR) = 19.00; 95% confidence interval (CI): 4.23-85.37] and carvacrol (OR = 17.63; 95% CI: 4.98-62.34). Thirteen metabolites were found to improve T2D risk prediction beyond eight conventional T2D risk factors [area under the curve (AUC) was 0.98 for risk factors + metabolites vs 0.72 for risk factors, P < 0.05].

Interpretations: Use of the metabolites identified in this study may help determine patients with prediabetes who are at highest risk of progressing to diabetes.
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http://dx.doi.org/10.3389/fendo.2021.745214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766640PMC
March 2022

Association of education levels with the risk of hypertension and hypertension control: a nationwide cohort study in Chinese adults.

J Epidemiol Community Health 2022 Jan 7. Epub 2022 Jan 7.

Department of Endocrinology, Shanghai National Research Center for Endocrine and Metabolic Disease, State Key Laboratory of Medical Genomics, Shanghai Institute for Endocrine and Metabolic Disease, Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China.

Background: Education attainment can improve life expectancy and guide healthy behaviours throughout an entire lifetime. A nationwide longitudinal study of the association of education status with the risk of hypertension and its control in China is lacking.

Methods: The China Cardiometabolic Disease and Cancer Cohort Study is a multicentre, population-based, prospective cohort study. We performed the baseline survey from 2011 to 2012. A follow-up visit was conducted during 2014-2016. 101 959 subjects were included in the final data analyses. Cox proportional hazards regression was used to examine the associations of education levels with the risk of hypertension and uncontrolled hypertension.

Results: During follow-up, 11 189 (19.9%) participants had developed hypertension among subjects without hypertension at baseline. Among the participants with hypertension at baseline, only 40.6% had controlled hypertension. Compared with the participants' education level at elementary school and below, the multivariable-adjusted HR for incident hypertension was 0.76 (95% CI, 0.72 to 0.80) in those with a middle school education level and 0.67 (95% CI, 0.63 to 0.70) in those with a high school degree or above. Correspondingly, multivariable-adjusted HRs associated with uncontrolled hypertension were 0.90 (95% CI, 0.87 to 0.92) in participants with a middle school education level and 0.85 (95% CI, 0.82 to 0.88) in participants with a high school degree or above level.

Conclusion: Participants with education attainment at elementary school and below exhibited excess risks of newly diagnosed hypertension and worse blood pressure control compared with individuals with education attainment at middle school or above.
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http://dx.doi.org/10.1136/jech-2021-217006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995829PMC
January 2022

mA reader YTHDC1 modulates autophagy by targeting SQSTM1 in diabetic skin.

Autophagy 2022 06 17;18(6):1318-1337. Epub 2021 Oct 17.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Dysregulation of macroautophagy/autophagy contributes to the delay of wound healing in diabetic skin. N-methyladenosine (mA) 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 led to the impairment of autophagic flux, which was consistent with the results of high-glucose treatment in keratinocytes. Moreover, the mA reader protein YTHDC1 (YTH domain containing 1), which interacted with mRNA, was downregulated in keratinocytes under both the acute and chronic effects of hyperglycemia. Knockdown of affected biological functions of keratinocytes, which included increased apoptosis rates and impaired wound-healing capacity. In addition, knockdown of endogenous resulted in a blockade of autophagic flux in keratinocytes, while overexpression of rescued the blockade of autophagic flux induced by high glucose. , knockdown of endogenous or inhibited autophagy in the epidermis and delayed wound healing. Interestingly, we found that a decrease of YTHDC1 drove 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 . Collectively, this study uncovered a previously unrecognized function for YTHDC1 in modulating autophagy via regulating the stability of nuclear mRNA in diabetic keratinocytes. 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; mA: N-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; : 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.
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http://dx.doi.org/10.1080/15548627.2021.1974175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225222PMC
June 2022

The association of adiponectin with risk of pre-diabetes and diabetes in different subgroups: cluster analysis of a general population in south China.

Endocr Connect 2021 Nov 3;10(11):1410-1419. Epub 2021 Nov 3.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.

Objective: Adiponectin is an adipocyte-derived hormone with an important role in glucose metabolism. The present study explored the effect of adiponectin in diverse population groups on pre-diabetes and newly diagnosed diabetes.

Methods: A total of 3300 individuals were enrolled and their data were collected in the analyses dataset from December 2018 to October 2019. Cluster analysis was conducted based on age, BMI, waistline, body fat, systolic blood pressure, triglycerides, and glycosylated hemoglobin 1c. Cluster analysis divided the participants into four groups: a young-healthy group, an elderly-hypertension group, a high glucose-lipid group, and an obese group. Odds ratio (OR) and 95% CIs were calculated using multivariate logistic regression analysis.

Results: Compared with the first quartile of adiponectin, the risk of pre-diabetes of fourth quartile was decreased 61% (aOR = 0.39, 95% CI (0.20-0.73)) in the young-healthy group; and the risk of diabetes of fourth quartile was decreased 85% (aOR = 0.15, 95% CI (0.02-0.67)) in the obese group. There were no significant correlations between the adiponectin level and diabetes/pre-diabetes in the other two groups. Additionally, receiver operating characteristic curve analysis indicated that adiponectin could significantly improve the diagnosis based on models in the young-healthy group (from 0.640 to 0.675) and the obese group (from 0.714 to 0.761).

Conclusions: Increased adiponectin levels were associated with decreased risk of pre-diabetes in the young-healthy population, and with a decreased the risk of diabetes in the obese population. An increased adiponectin level is an independent protective factor for pre-diabetes and diabetes in a specific population in south China.
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http://dx.doi.org/10.1530/EC-21-0235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8630761PMC
November 2021

Galectin-3/adiponectin as a new biological indicator for assessing the risk of type 2 diabetes: a cross-sectional study in a community population.

Aging (Albany NY) 2021 06 7;13(11):15433-15443. Epub 2021 Jun 7.

Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, People's Republic of China.

Objective: This study aimed to explore the association between the risk of newly diagnosed type 2 diabetes and galectin-3 and adiponectin and to investigate whether their joint action shows a favorable diabetes assessment performance.

Methods: We conducted a community-based study in 135 newly diagnosed patients with type 2 diabetes and 270 age- and sex-matched nondiabetic patients. Odds ratios and 95% confidence intervals were determined using logistic regression analysis. Receiver operating characteristic curve, decision curve analysis and calibration plot were used to explore their efficacy and clinical utility for models.

Results: High quartiles of galectin-3/adiponectin (quartile 4 vs 1: OR 2.43 [95% CIs: 1.21-5.00]) showed the strongest correlation with an increased risk of type 2 diabetes in the total population, which was consistent in the older population (age≥50 years old) in adjustment models. The combination + lipids + galectin-3/adiponectin model (AUC = 0.72 [95% CIs: 0.66-0.77]) displayed better diabetes assessment performance than the other two models.

Conclusions: High galectin-3 and low adiponectin levels were associated with the high risk of diabetes, and their joint action was a superior promising factor for evaluating diabetes risk. The diabetes discriminative strength of galectin-3/adiponectin was better in the older population than the younger.
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http://dx.doi.org/10.18632/aging.203101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221326PMC
June 2021

Association between uric acid lowering and renal function progression: a longitudinal study.

PeerJ 2021 24;9:e11073. Epub 2021 Mar 24.

Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: This study aimed to explore the association between uric acid lowering and renal function.

Materials And Methods: We conducted a population-based cohort study with 1,534 subjects for 4 years from 2012 to 2016. The population was divided into four groups according to the interquartile range of changes in serum uric acid with quartile 1 representing lower quarter. Renal function decline was defined as eGFR decreased more than 10% from baseline in 2016. Renal function improvement was defined as eGFR increased more than 10% from baseline in 2016. Cox regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI).

Results: In the adjusted Cox regression models, compared to quartile 4, quartile 1 (HR = 0.64, 95% CI [0.49-0.85]), quartile 2 (HR = 0.65, 95% CI [0.50-0.84]) and quartile 3 (HR = 0.75, 95% CI [0.58-0.96]) have reduced risk of renal function decline. An increasing hazard ratio of renal function improvement was shown in quartile 1 (HR = 2.27, 95% CI [1.45-3.57]) and quartile 2 (HR = 1.78, 95% CI [1.17-2.69]) compared with quartile 4.

Conclusions: Uric acid lowering is associated with changes in renal function. The management of serum uric acid should receive attention in clinical practice and is supposed to be part of the treatment of chronic kidney disease.
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http://dx.doi.org/10.7717/peerj.11073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000451PMC
March 2021

Associations of GDF-15 and GDF-15/adiponectin ratio with odds of type 2 diabetes in the Chinese population.

Endocrine 2021 05 12;72(2):423-436. Epub 2021 Mar 12.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, 510120, People's Republic of China.

Purpose: We elucidate the effect of Growth differentiation factor-15(GDF-15)/adiponectin ratio in improving the assessment value for odds of type 2 diabetes.

Methods: Cross-sectional design. A total of 405 participants (135 patients with newly diagnosed type 2 diabetes, 135 age- and sex-matched participants with prediabetes, and 135 healthy controls) were collected from Guangzhou and Dongguan, China. The serum GDF-15 and adiponectin levels were measured by ELISA and latex-enhanced immunoturbidimetry. Logistic regression analysis and restricted cubic splines were used to evaluate the associations between diabetes and the indicators.

Results: The low level of adiponectin and high GDF-15/adiponectin ratio were significantly associated with increased odds of type 2 diabetes, but not for GDF-15. Three clusters were identified based on the K-means clustering analysis. Compared to the lowest quartiles of adiponectin, the OR and 95% CI of the highest adiponectin with type 2 diabetes was 0.24 (0.07-0.74, p trend = 0.004) after adjusting for sex, age, BMI, and DBP only in cluster 1. After adjusting for confounding factors, subjects with the highest GDF-15/adiponectin ratio quartiles had 3.9 times (OR = 3.85, 95% CI = 0.76-24.25) and 3.8 times (OR = 3.80, 95% CI = 1.02-14.68) higher odds of type 2 diabetes in cluster 2 and cluster 3, respectively. The association between the GDF-15/adiponectin ratio and type 2 diabetes was attenuated, but still remarkable (OR = 3.18, 95% CI = 1.11-10.18), in cluster 1.

Conclusions: Higher GDF-15/adiponectin ratio is independently associated with increased odds of type 2 diabetes for all study populations, suggesting that the GDF-15/adiponectin ratio may be a better indicator of type 2 diabetes.
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http://dx.doi.org/10.1007/s12020-021-02632-1DOI Listing
May 2021

Association of metabolic syndrome with the incidence of low-grade albuminuria: a cohort study in middle-aged and elderly Chinese adults.

Aging (Albany NY) 2021 03 3;13(5):7350-7360. Epub 2021 Mar 3.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People' s Republic of China.

Background: Individuals with metabolic syndrome have elevated risks of micro- and macro-albuminuria as well as chronic kidney disease (CKD).

Objective: To assess the influence of metabolic abnormalities on the presence of low-grade albuminuria (below the threshold for microalbuminuria). Design, participants, and main outcome measures: This community-based cohort study included 3,935 eligible individuals aged 40 years or older. The presence of low-grade albuminuria was detected in those without micro- or macro-albuminuria and analyzed according to the highest quartile of the baseline urinary albumin-to-creatinine ratio (ACR ≥11.13 mg/g). CKD was defined by an estimated glomerular filtration rate <60 mL/min/1.73 m or the new presence of albuminuria (ACR ≥30 mg/g).

Results: Overall, 577 (14.7%) participants developed low-grade albuminuria and 164 (4.2%) participants developed CKD during a mean follow-up period of 3.6 years. Compared with participants without metabolic syndrome, those with metabolic syndrome had greater risks of low-grade albuminuria [adjusted odd ratio (OR) and 95% confidence interval (95% CI): 1.30 (1.05-1.61)] and CKD [1.71 (1.20-2.44)]. Moreover, the incidence rates of low-grade albuminuria and CKD increased as the number of metabolic syndrome components increased (P for trend <0.0001).

Conclusions: The presence of metabolic syndrome is associated with increased incidence rates of low-grade albuminuria and CKD the middle-aged and elderly Chinese populations.
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http://dx.doi.org/10.18632/aging.202592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993658PMC
March 2021

Association of gonadal hormones and sex hormone binding globulin with risk of diabetes: A cohort study in middle-aged and elderly Chinese males.

Int J Clin Pract 2021 May 21;75(5):e14008. Epub 2021 Jan 21.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Aim: Late-onset hypogonadism in men is related to the development of diabetes. The association of gonadal hormones, sex hormone binding globulin with diabetes has been studied in various studies. However, there is no cohort study on the relationship between gonadal hormone, sex hormone binding globulin and diabetes in Chinese. We aimed to provide an insight into the possible association in middle-aged and elderly Chinese males.

Methods: We included a population sample of 673 subjects aged 40 years or older. Total testosterone (TT), sex hormone binding globulin (SHBG), follicle-stimulating hormone (FSH) and luteinising hormone (LH) were detected. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to estimate insulin sensitivity. Diabetes was diagnosed according to the 2010 American Diabetes Association criteria.

Results: With an average follow-up time of 3.2 ± 0.5 years, 9.8% of participants had developed diabetes. The prevalence of diabetes was decreased according to increasing SHBG quartiles (Q1:13.1%, Q2: 12.0%, Q3: 11.2%, Q4: 3.0%, P for trend < .0001) and TT (Q1:16.0%, Q2: 7.9%, Q3: 9.0%, Q4: 6.4%, P for trend < .0001). The ORs of diabetes for increasing SHBG quartiles were 4.52 (95% CI 1.40-14.57), 4.32 (95% CI 1.33-14.06), 3.89 (95% CI 1.21-12.50) and 1.00 (reference) respectively. But the odds of prevalent diabetes were not increased in different quartiles of TT, FSH and LH. In subgroup analyses, the relationship between SHBG and risk of incident diabetes was significantly increased in the population aged over 60, without insulin resistance and with eGFR < 90 mL/min per 1.73 m .

Conclusions: Compared with gonadal hormones, a lower level of SHBG is independently associated with the risk of diabetes in middle-aged and elderly Chinese males.
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http://dx.doi.org/10.1111/ijcp.14008DOI Listing
May 2021

Cyclovirobuxine D inhibits colorectal cancer tumorigenesis via the CTHRC1‑AKT/ERK‑Snail signaling pathway.

Int J Oncol 2020 07 3;57(1):183-196. Epub 2020 Apr 3.

Department of Colorectal Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.

Cyclovirobuxine D (CVB‑D) is an alkaloid, which is mainly derived from Buxus microphylla. It has been reported that CVB‑D has positive effects on breast cancer, gastric cancer and other malignant tumors. However, to the best of our knowledge, there are no reports regarding the effects of CVB‑D on colorectal cancer (CRC). The purpose of the present study was to determine the anticancer effects of CVB‑D and further elucidate its molecular mechanism(s). DLD‑1 and LoVo cell lines were selected to evaluate the antitumor effect of CVB‑D. Cytotoxicity, viability and proliferation were evaluated by the MTT and colony formation assays. Flow cytometry was used to detect the effects on apoptosis and the cell cycle in CVB‑D‑treated CRC cells. The migration and invasion abilities of CRC cells were examined by wound healing and Transwell assays. In addition, RNA sequencing, bioinformatics analysis and western blotting were performed to investigate the target of drug action and clarify the molecular mechanisms. A xenograft model was established using nude mice, and ultrasound was employed to assess the preclinical therapeutic effects of CVB‑D in vivo. It was identified that CVB‑D inhibited the proliferation, migration, stemness, angiogenesis and epithelial‑mesenchymal transition of CRC cells, and induced apoptosis and S‑phase arrest. In addition, CVB‑D significantly inhibited the growth of xenografts. It is notable that CVB‑D exerted anticancer effects in CRC cells partly by targeting collagen triple helix repeat containing 1 (CTHRC1), which may be upstream of the AKT and ERK pathways. CVB‑D exerted anticancer effects through the CTHRC1‑AKT/ERK‑Snail signaling pathway. Targeted therapy combining CTHRC1 with CVB‑D may offer a promising novel therapeutic approach for CRC treatment.
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http://dx.doi.org/10.3892/ijo.2020.5038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252468PMC
July 2020

Obesity-associated secondary hypogonadism in young and middle-aged men in Guangzhou: A single-centre cross-sectional study.

Int J Clin Pract 2020 Aug 8;74(8):e13513. Epub 2020 May 8.

Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China.

Aim: Male obesity-associated secondary hypogonadism (MOSH) is becoming a public health issue. We aimed to know MOSH among young and middle-aged men in our hospital, to analyse their sex hormones and other index, and to determine leptin as a risk factor for MOSH.

Methods: In total, 258 men (ages ranging from 20 to 60, mean 38 ± 15) were enrolled in this study, and 242 of these men had their complete data, body mass index (BMI), waist circumference and sex hormones retrospectively investigated. The leptin and lipid levels were also evaluated, and comparisons were made between young (20-39 years old) and middle-aged (40-60 years old) men.

Results: Among all the participants, 7 were thin, with a BMI < 18.5 kg/m , 95 had a normal BMI (18.5 ≤ BMI < 23.9 kg/m ), 87 (35.9%) were overweight (24 ≤ BMI ≤ 27.9 kg/m ) and 53 (21.9%) were obese (BMI ≥ 28 kg/m ), 173 (71.5%) had a waist sized ≥ 85 cm. Among the 242 men, 104 (43%) had hypogonadism (TT ≤ 331.412 ng/dL). Compared with the men of normal weight, the level of testosterone of the obese men decreased (P = .006), while the level of serum lipids (including total cholesterol, TG and low-density lipoprotein cholesterol, P < .05) was elevated, higher UA, FSH and leptin were also present in the obese men. There were 83 (34.2%) men with MOSH. Compared with middle-aged men with MOSH, the FSH in young men was significantly reduced (P < .05); no significant increase in estradiol was observed in the MOSH group. The leptin levels in the MOSH group were significantly higher than those in the hypogonadism only group (P < .001).

Conclusion: Obesity increases the prevalence of hypogonadism. The decrease in testosterone levels in young men maybe due to inhibition of the hypothalamic pituitary gonadal axis. Leptin is an independent risk factor for MOSH.
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http://dx.doi.org/10.1111/ijcp.13513DOI Listing
August 2020

Lipid accumulation product and late-onset hypogonadism in middle-aged and elderly men: results from a cross-sectional study in China.

BMJ Open 2020 02 10;10(2):e033991. Epub 2020 Feb 10.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Guangzhou, China

Objectives: Hypogonadism in men is related to the deterioration of general health. However, the association between lipid overaccumulation and ageing-related hypogonadism remains an undetermined concept. We aimed to provide an insight into the possible links between the lipid accumulation product (LAP) and late-onset hypogonadism (LOH).

Setting: Sun Yat-sen Memorial Hospital of Sun Yat-sen University.

Participants: We included a population sample of 997 subjects aged 40 years or older.

Primary And Secondary Outcome Measures: The LAP was calculated by gender-specific equations using waist circumference (WC) and triglyceride (TG). LOH was defined by the presence of androgen deficiency symptoms and low serum total testosterone levels.

Results: The prevalence of LOH was 9.4% in this population and gradually increased according to increasing LAP quartiles. Compared with subjects without LOH, ageing men with LOH had higher body mass index, WC, systolic blood pressure, percentage of subjects currently smoking, TG and follicle stimulating hormone and lower low-density lipoprotein cholesterol and sex hormone binding globulin. In multivariate logistic regression analysis, the adjusted ORs of LOH for increasing LAP quartiles 1-4 were 1.00 (reference), 1.10 (95% CI 0.45-2.69), 2.15 (95% CI 0.93-4.94) and 3.83 (95% CI 1.73-8.45), respectively.

Conclusion: Body lipid accumulation evaluated by the LAP is independently associated with the prevalence of LOH in middle-aged and elderly Chinese men.
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http://dx.doi.org/10.1136/bmjopen-2019-033991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045028PMC
February 2020

Corrigendum to "A novel long non-coding RNA-ARA: Adriamycin resistance-associated" [Biochem. Pharmacol. 87 (2014) 254-283].

Biochem Pharmacol 2020 02 21;172:113732. Epub 2019 Dec 21.

Comprehensive Breast Health Centre, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address:

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http://dx.doi.org/10.1016/j.bcp.2019.113732DOI Listing
February 2020

Parity is associated with albuminuria and chronic kidney disease: a population-based study.

Aging (Albany NY) 2019 12 2;11(23):11030-11039. Epub 2019 Dec 2.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People's Republic of China.

Background And Aims: Epidemiological studies have shown that increasing parity is associated with risk of hypertension and diabetes in parous women. However, the relationship between the parity degree with chronic kidney disease (CKD) is still unknown.

Results: Parous women with higher parity had increased age, body mass index, waist circumference, systolic blood pressure, fasting plasma glucose, fasting insulin and decreased high-density lipoprotein cholesterol, eGFR and education levels. Compared with women with one-child birth, those with more than two-child births had greater prevalence of increased urinary albumin excretion (odds ratios [ORs] 1.53, 95% confidence intervals [CI], 1.03 - 2.28) and CKD (ORs 1.79, 95% CI, 1.24 - 2.58) after multiple adjustments. In dose-response analysis, a nonlinear relationship of parity degree with albuminuria and CKD was detected.

Conclusion: Parity is associated with higher prevalence of albuminuria and CKD in middle-aged and elderly Chinese women.

Methods: We conducted a community-based study in 6,946 women to investigate the association of parity with albuminuria and CKD. Increased urinary albumin excretion was defined as albumin-to-creatinine ratio (ACR) greater or equal than 30 mg/g. CKD was defined as estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m² or presence of albuminuria.
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http://dx.doi.org/10.18632/aging.102507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932874PMC
December 2019

TET2-interacting long noncoding RNA promotes active DNA demethylation of the MMP-9 promoter in diabetic wound healing.

Cell Death Dis 2019 10 25;10(11):813. Epub 2019 Oct 25.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.

Wound healing in diabetic skin is impaired by excessive activation of matrix metalloproteinase-9 (MMP-9). MMP-9 transcription is activated by Ten-eleven translocation 2 (TET2), a well-known DNA demethylation protein that induces MMP-9 promoter demethylation in diabetic skin tissues. However, how TET2 is targeted to specific loci in the MMP-9 promoter is unknown. Here, we identified a TET2-interacting long noncoding RNA (TETILA) that is upregulated in human diabetic skin tissues. TETILA regulates TET2 subcellular localization and enzymatic activity, indirectly activating MMP-9 promoter demethylation. TETILA also recruits thymine-DNA glycosylase (TDG), which simultaneously interacts with TET2, for base excision repair-mediated MMP-9 promoter demethylation. Together, our results suggest that the TETILA serves as a genomic homing signal for TET2-mediated demethylation specific loci in MMP-9 promoter, thereby disrupting the process of diabetic skin wound healing.
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http://dx.doi.org/10.1038/s41419-019-2047-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6814823PMC
October 2019

Number of parity is associated with low-grade albuminuria in middle-aged and elderly Chinese women.

BMC Womens Health 2019 10 7;19(1):117. Epub 2019 Oct 7.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No.107 Yanjiang West Road, Guangzhou, 510120, People's Republic of China.

Background: Women with a higher number of pregnancies have a higher risk of developing cardiovascular diseases. Subtle fluctuations in albumin excretion could be related to pathophysiologic changes in the vascular system. We aimed to investigate the possible association of parity with low-grade albuminuria.

Methods: We conducted a community-based study in 6495 women aged 40 years or older. Low-grade albuminuria was defined according to the highest quartile of urine albumin-to-creatinine ratio in participants free of micro- or macro-albuminuria.

Results: Parous women with a higher number of pregnancies had increased age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), fasting plasma glucose (FPG), and fasting insulin, as well as decreased high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR) levels, and proportion of menopause. The prevalence of low-grade albuminuria in parous women gradually increased with parity number. Compared with women with one childbirth, those with more than two childbirths were independently associated with a higher prevalent low-grade albuminuria (odds ratios [ORs] 1.41, 95% confidence interval [CI], 1.09-1.81) after multiple adjustments. In subgroup analysis after multiple adjustments, significant relation between parity number and prevalent low-grade albuminuria was detected in subjects age 55 years or older.

Conclusion: Number of parity is associated with prevalent low-grade albuminuria in middle-aged and elderly Chinese women without micro- or macro-albuminuria.
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http://dx.doi.org/10.1186/s12905-019-0814-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781324PMC
October 2019

Burden associated with nonfatal slip and fall injuries in the surface stone, sand, and gravel mining industry.

Saf Sci 2019 Dec 13;120:625-635. Epub 2019 Aug 13.

Pittsburgh Mining Research Division, National Institute for Occupational Safety and Health, 626 Cochrans Mill Road, Pittsburgh, PA 15236, USA.

Slips, trips, and falls (STFs) pose a significant financial burden to employers and account for over 33% of the total nonfatal workers' compensation cost in the United States. Previous analyses documenting the burden of STF incidents in the mining industry have focused on occupational fatalities or STFs during equipment ingress, egress. There is limited information on the burden of nonfatal STF incidents in the mining industry and most of it is outdated. Hence, to increase awareness and highlight the importance of STFs in the mining industry, this analysis documents the burden associated with nonfatal STF incidents at surface stone, sand, and gravel (SSG) mines from 2008 through 2017. In this time frame, nonfatal STF incidents occurred at a rate of 62 per 10,000 full-time equivalent (FTE) employees per year. Pits had a higher prevalence of injuries, but plants had a higher incidence rate. In addition, nonfatal STF incidents at surface SSG mines led to approximately 23,800 total days lost per year with an estimated cost to the mining industry of $17.5 million per year. Assessed violations that are not related to reported injuries but are related to STF hazards identified during Mine Safety and Health Administration (MSHA) inspections cost the mining industry approximately $3 million per year from 2013 through 2017. Based on the data analyzed in this study, falls to the lower level pose a higher burden in terms of cost; however, falls to the same level have a higher number of incidents and incidence rate.
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http://dx.doi.org/10.1016/j.ssci.2019.08.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6760904PMC
December 2019

Assessment of adiposity distribution and its association with diabetes and insulin resistance: a population-based study.

Diabetol Metab Syndr 2019 27;11:51. Epub 2019 Jun 27.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, 510120 People's Republic of China.

Background: Rational measures in estimating adiposity distribution in diabetic patients has yet to be validated. This study aims to provide insight about the possible links between routinely available body adiposity parameters and the development of both diabetes and insulin resistance.

Methods: We performed a population-based cross-sectional study in 9496 subjects aged 40 years or older. All of the body adiposity measures including body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist-height ratio (WHtR), visceral adiposity index (VAI), body adiposity index (BAI) and lipid accumulation product index (LAP) were separately evaluated according to standard measurement methods. Diabetes was diagnosed according to the American Diabetes Association 2010 criteria.

Results: All tested body adiposity measurements were significantly associated with fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) 2 h glucose, HbA1c and fasting insulin. Compared with other adiposity phenotypes, LAP have shown the relatively strongest while BAI have shown the relatively weakest association with increased odds of both diabetes and insulin resistance across all logistic regression models. Additionally, LAP provided the best discrimination accuracy for diabetes [area under the curve (AUC): 0.658 95% confidence intervals (CI) 0.645-0.671] and insulin resistance (AUC: 0.781 95% CI 0.771-0.792) when compared with other body adiposity parameters.

Conclusions: The LAP index seems to be a better indicator than other adiposity measures tested in the study to evaluate the association of visceral fat mass with diabetes and insulin resistance, which should be given more consideration in the clinical practice.
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http://dx.doi.org/10.1186/s13098-019-0450-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598265PMC
June 2019

Risk assessment of recordable occupational hearing loss in the mining industry.

Int J Audiol 2019 11 8;58(11):761-768. Epub 2019 Jul 8.

Pittsburgh Mining Research Division, National Institute for Occupational Safety and Health , Pittsburgh , PA , USA.

To evaluate the hearing loss risk in different sectors and subunits in the mining industry and to identify associated occupations, in an attempt to locate gaps between hearing conservation efforts and hearing loss risks. Descriptive statistics and frequency tables were generated by commodity types, subunit operations, and/or occupations. Temporal trends of the incidences of hearing loss were reported by commodity types. The MSHA Accident/Injury/Illness and MSHA Address/Employment databases from 2000 to 2014 were used. Incidence rate of OHL was reported highest in the coal sector compared to other commodity types. Those members of the workforce that entered the mining industry after the year 2000 accounted for 6.5% and 19.0% of the total hearing loss records for coal and non-coal, respectively. High-risk occupations found in all three commodity sectors (coal; stone, sand, and gravel; and metal/non-metal) were electrician/helper/wireman, mechanic/repairman/helper, bulldozer/tractor operator, and truck driver. Hearing loss risks were not uniform across mining sectors, subunit operations, and occupations. In addition to the continuous efforts of implementing engineering controls to reduce machinery sound level exposure for operators, a multi-level approach may benefit those occupations with a more dynamic exposure profile - e.g., labour/utilityman/bullgang, electrician/helper/wireman, and mechanic/repairman/helper.
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http://dx.doi.org/10.1080/14992027.2019.1622041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007233PMC
November 2019

Endothelial cell-derived small extracellular vesicles suppress cutaneous wound healing through regulating fibroblasts autophagy.

Clin Sci (Lond) 2019 05 2;133(9). Epub 2019 May 2.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China

Diabetic foot ulcer is a life-threatening clinical problem in diabetic patients. Endothelial cell-derived small extracellular vesicles (sEVs) are important mediators of intercellular communication in the pathogenesis of several diseases. However, the exact mechanisms of wound healing mediated by endothelial cell-derived sEVs remain unclear. sEVs were isolated from human umbilical vein endothelial cells (HUVECs) pretreated with or without advanced glycation end products (AGEs). The roles of HUVEC-derived sEVs on the biological characteristics of skin fibroblasts were investigated both and We demonstrate that sEVs derived from AGEs-pretreated HUVECs (AGEs-sEVs) could inhibit collagen synthesis by activating autophagy of human skin fibroblasts. Additionally, treatment with AGEs-sEVs could delay the wound healing process in Sprague-Dawley (SD) rats. Further analysis indicated that miR-106b-5p was up-regulated in AGEs-sEVs and importantly, in exudate-derived sEVs from patients with diabetic foot ulcer. Consequently, sEV-mediated uptake of miR-106b-5p in recipient fibroblasts reduces expression of extracellular signal-regulated kinase 1/2 (ERK1/2), resulting in fibroblasts autophagy activation and subsequent collagen degradation. Collectively, our data demonstrate that miR-106b-5p could be enriched in AGEs-sEVs, then decreases collagen synthesis and delays cutaneous wound healing by triggering fibroblasts autophagy through reducing ERK1/2 expression.
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http://dx.doi.org/10.1042/CS20190008DOI Listing
May 2019

Matrix metalloproteinase 9 induces keratinocyte apoptosis through FasL/Fas pathway in diabetic wound.

Apoptosis 2019 08;24(7-8):542-551

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, 510120, Guangdong, China.

Apoptosis is a mechanism to remove unwanted cells in the tissue. In diabetic wound, which is characterized by delayed healing process, excessive apoptosis is documented and plays a crucial role. Matrix metalloproteinase 9 (MMP9), which is elevated in non-healed diabetic wound, is necessary for healing process but its abnormality resulted in a delayed healing. The classical function of MMP9 is the degradation of extracellular matrix (ECM). However, there is some literature evidence that MMP9 triggers cell apoptosis. Whether the excessive MMP9 contributes to epidermis cell apoptosis in delayed healing diabetic wound and the underlying mechanisms is not clear. In this study, we aimed to explore whether MMP9 induced keratinocyte apoptosis and investigate the plausible mechanisms. Our in vitro study showed that advanced glycation end products (AGEs) induced keratinocyte apoptosis and enhanced MMP9 level. Besides, MMP9, both intra-cellular expressions and extra-cellular supplement, promoted cell apoptosis. Further, MMP9 resulted in an increased expression of FasL, other than Fas and p53. These findings identified a novel effect that MMP9 exerted in delayed diabetic wound healing, owing to a pro-apoptotic effect on keratinocyte, which was mediated by an increase of FasL expression. This study increases understanding of elevated MMP9 which is involved in diabetic wound repair and offers some insights into novel future therapies.
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http://dx.doi.org/10.1007/s10495-019-01536-wDOI Listing
August 2019

The potential use of a NIOSH sound level meter smart device application in mining operations.

Noise Control Eng J 2019 Jan;67(1):23-30

Pittsburgh Mining Research Division, NIOSH, Pittsburgh, PA, USA.

Many mobile sound measurement applications (apps) have been developed to take advantage of the built-in or fit-in sensors of the smartphone. One of the concerns is the accuracy of these apps when compared to professional sound measurement instruments. Previously, a research team from the National Institute for Occupational Safety and Health (NIOSH) developed the NIOSH Sound Level Meter (SLM) app for iOS smart devices. The team found the average accuracy of this app to be within ±1 dBA when using calibrated external microphones with a type 1 reference device and measuring pink noise at levels from 65 to 95 dBA in 5-dBA increments. The studies were conducted in a reverberant noise chamber at the NIOSH Acoustics Laboratory in Cincinnati. However, it is still unknown how this app performs in measuring industrial/mining sound levels outside of a controlled laboratory environment. The current NIOSH study evaluates the NIOSH SLM app to measure sound levels from a jumbo drill (a large mining machine). The study was conducted in a hemi-anechoic chamber at the NIOSH Pittsburgh Mining Research Division and followed by a field evaluation in an underground metal mine. Six different iOS smart devices were used with two types of external microphones chosen from previous studies to measure sound levels during jumbo drill operations, and the results were compared with a reference device. Results show that the average sound levels measured by the NIOSH SLM app are within ±1 dBA of the reference device both in the laboratory and field. However, the type of operation being performed, the selection and use of external microphones, distance from a noise source, and environmental factors (e.g., air movement) may all influence the accuracy of the app's performance. Although additional validation is still needed, the results from this study suggest a potential for using the NIOSH SLM app, with calibrated external microphones, to measure sound levels in mining operations.
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http://dx.doi.org/10.3397/1/37673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345572PMC
January 2019

Analysis of PTEN expression and promoter methylation in Uyghur patients with mild type 2 diabetes mellitus.

Medicine (Baltimore) 2018 Dec;97(49):e13513

Department of Endocrinology and Metabolism.

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.
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http://dx.doi.org/10.1097/MD.0000000000013513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310531PMC
December 2018

Patterns and trends in OSHA occupational noise exposure measurements from 1979 to 2013.

Occup Environ Med 2019 02 27;76(2):118-124. Epub 2018 Nov 27.

Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA.

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.
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http://dx.doi.org/10.1136/oemed-2018-105041DOI Listing
February 2019

Hearing Protector Attenuation and Noise Exposure Among Metal Manufacturing Workers.

Ear Hear 2019 May/Jun;40(3):680-689

Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA.

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.
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http://dx.doi.org/10.1097/AUD.0000000000000650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395583PMC
December 2019

Visceral adiposity index is associated with increased urinary albumin excretion: A population-based study.

Clin Nutr 2019 06 2;38(3):1332-1338. Epub 2018 Jun 2.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou 510120, People's Republic of China. Electronic address:

Background: The effects of visceral fat accumulation on the renal damage have drawn much attention. We aimed to investigate the possible relationship between visceral adiposity and albuminuria.

Methods: We included information from a population-based study in 9473 subjects aged 40 years or older. As a novel and valid indicator for visceral adipose function, visceral adiposity index (VAI) was determined by gender-specific equations and calculated using simple anthropometric and functional parameters. Increased urinary albumin excretion was defined as albumin-to-creatinine ratio (ACR) 30 mg/g or greater.

Results: The prevalence rate of increased urinary albumin excretion was 6.6% in this population and gradually increased across VAI quartiles. Participants with higher VAI had elevated age, blood pressure, cholesterol, fasting insulin and decreased high density lipoprotein cholesterol and estimated glomerular filtration rate (eGFR) level. In multivariate logistic regression analysis, the adjusted odds ratios (ORs) of increased urinary albumin excretion for increasing VAI quartiles were 1.00 (reference), 1.29 (95% confidence intervals [CI] 0.94-1.76), 1.46 (95% CI 1.08-1.97) and 1.79 (95% CI 1.33-2.41). In subgroup analysis and after multiple adjustments, significant relation between VAI level and prevalent increased urinary albumin excretion was detected in women, younger subjects, non-obesity subjects, those without diabetes and those with eGFR ≥60 ml/min per 1.73 m.

Conclusion: Visceral fat accumulation evaluating by VAI is independently associated with increased urinary albumin excretion in middle-aged and elderly Chinese.
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http://dx.doi.org/10.1016/j.clnu.2018.05.025DOI Listing
June 2019

Fatty liver index, albuminuria and the association with chronic kidney disease: a population-based study in China.

BMJ Open 2018 01 30;8(1):e019097. Epub 2018 Jan 30.

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Republic of China.

Objectives: The effects of lipid metabolism disorder on renal damage have drawn much attention. Using the fatty liver index (FLI) as a validated indicator of hepatic steatosis, this study aims to provide insight about the possible links between fatty liver and the development of chronic kidney disease (CKD).

Setting: Hospital.

Participants: We performed a population-based study on 9436 subjects aged 40 years or older.

Primary And Secondary Outcome Measures: FLI is calculated using an algorithm based on body mass index, waist circumference, triglycerides and γ-glutamyltransferase. Increased urinary albumin excretion was defined according to the urinary albumin to creatinine ratio ranges ≥30 mg/g. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or presence of albuminuria.

Results: There were 620 (6.6%) subjects categorised to have increased urinary albumin excretion and 753 (8.0%) subjects categorised to have CKD. Participants with higher FLI had increased age, blood pressure, low-density lipoprotein cholesterol, fasting plasma glucose, fasting insulin and decreased eGFR level. Prevalence of increased urinary albumin excretion and CKD tended to increase with the elevated FLI quartiles. In logistic regression analysis, compared with subjects in the lowest quartile of FLI, the adjusted ORs in the highest quartile were 2.30 (95% CI 1.36 to 3.90) for increased urinary albumin excretion and 1.93 (95% CI 1.18 to 3.15) for CKD.

Conclusion: Hepatic steatosis evaluated by FLI is independently associated with increased urinary albumin excretion and prevalence of CKD in middle-aged and elderly Chinese.
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http://dx.doi.org/10.1136/bmjopen-2017-019097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829809PMC
January 2018

GADD45a Promotes Active DNA Demethylation of the MMP-9 Promoter via Base Excision Repair Pathway in AGEs-Treated Keratinocytes and in Diabetic Male Rat Skin.

Endocrinology 2018 02;159(2):1172-1186

Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

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.
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http://dx.doi.org/10.1210/en.2017-00686DOI Listing
February 2018

Evaluating hearing loss risks in the mining industry through MSHA citations.

J Occup Environ Hyg 2018 03;15(3):246-262

a National Institute for Occupational Safety and Health , Pittsburgh Mining Research Division , Pittsburgh , Pennsylvania.

A new noise regulation for the mining industry became effective in 2000, providing a consistent regulatory requirement for both coal and non-coal mining divisions. The new rule required mines to implement hearing conservation programs, including a system of continuous noise monitoring, provision of hearing protection devices, audiometric testing, hearing loss training, and record keeping. The goal of this study was to assess hearing conservation program compliance, and excessive noise exposure and hearing loss risks for both coal and non-coal mining divisions through evaluating MSHA citations. We analyzed 13,446 MSHA citations from 2000-2014 pertinent to 30 CFR Part 62. Descriptive statistics were generated and comparisons were made among mines of different commodities. In addition, one-way ANOVA on ranks was conducted to estimate the correlation between excess risks and establishment size. Results showed that 25.6% of coal mines and 14.7% of non-coal mines were cited at least once during this period of time. Larger numbers of noncompliance were seen in stone, sand, and gravel mines (SSG). Results also suggested inadequate efforts in both audiometric testing and minimizing risk after excessive noise exposure. Finally, establishment size of mine was correlated with the increasing risk of noncompliance. We anticipate that this study can guide resource allocation for preventing noise-induced hearing loss, and help improve risk management in mining.
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http://dx.doi.org/10.1080/15459624.2017.1412584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5848488PMC
March 2018
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