Search

Abstract Per‐ and poly‐fluoroalkyl substances (PFAS), which are long‐lasting environmental contaminants that are released into the environment during the e‐waste disassembly process, pose a threat to human health. Human milk is a complex and dynamic mixture of endogenous and exogenous substances, including steroid hormones and PFAS. Therefore, in this study, we aimed to investigate the association between PFAS and steroid hormones in human milk from women living close to an e‐waste disassembly area. In 2021, we collected milk samples from 150 mothers within 4 weeks of delivery and analyzed them via liquid chromatography‐tandem mass spectrometry to determine the levels of 21 perfluorinated compounds and five steroid hormones (estrone, estriol, testosterone, progesterone, and androstenedione [A‐dione]). We also performed multiple linear regression analysis to clarify the association between maternal PFAS exposure and steroid hormone concentrations. Our results indicated that PFOA and PFOS were positively associated with estrone (β, 0.23; 95% CI, 0.08–0.39) and A‐dione (β, 0.186; 95% CI, 0.016–0.357) concentrations in human milk, respectively. Further, the average estimated daily intake of PFOA and PFOS were 36.5 ng/kg bw/day (range, 0.52–291.7 ng/kg bw/day) and 5.21 ng/kg bw/day (range, 0.26–32.3 ng/kg bw/day), respectively. Of concern, the PFAS intake of breastfeeding infants in the study area was higher than the recommended threshold. These findings suggested that prenatal exposure to PFAS from the e‐waste disassembly process can influence steroid hormones levels in human milk. Increased efforts to mitigate mother and infant exposure to environmental pollutants are also required.

Objectives: This study aimed to analyze the possible role of rDNA copy number variation in the association between hexavalent chromium [Cr (VI)] exposure and semen quality in semen donors and further confirm this association in mice. Methods: In this cross-sectional study, whole blood and semen samples were collected from 155 semen donors in the Zhejiang Human Sperm Bank from January 1st to April 31st, 2021. Adult C57BL/6 J male mice were treated with different doses of Cr (VI) (0, 10, or 15 mg/kg b.w./day). Semen quality, including semen volume, total spermatozoa count, sperm concentration, progressive motility, and total motility, were analyzed according to the WHO laboratory manual. Cr concentration was detected using inductively coupled plasma mass spectrometry. The rDNA copy number was measured using qPCR. Results: In semen donors, whole blood Cr concentration was negatively associated with semen concentration and total sperm counts. Semen 5 S and 45 S rDNA copy numbers were negatively associated with whole blood Cr concentration and whole blood 5.8 S rDNA copy number was negatively associated with semen Cr concentration. In mice, Cr (VI) damaged testicular tissue, decreased semen quality, and caused rDNA copy number variation. Semen quality was related to the rDNA copy number in whole blood, testicular tissue, and semen samples in mice. Conclusion: Cr (VI) was associated with decreased semen quality in semen donors and mice. Our findings suggest an in-depth analysis of the role of the rDNA copy number variation in the Cr (VI)-induced impairment of semen quality.

Abstract Background Several studies have provided evidence about adverse pregnancy outcomes of nurses involved in occupational exposure. However, the pregnancy outcomes among nurses in middle-income countries are not well demonstrated. The main aim of this study is to present the prevalence and influencing factors of pregnancy outcomes among female nurses in China. Methods We included 2243 non-nurse health care workers, and 4230 nurses in this national cross-sectional study in China. Information on occupational exposures and pregnancy outcomes was collected using a face-to-face investigation. Odds ratios (ORs) were estimated through logistic regression. Results The proportion of threatened abortion, spontaneous abortion, and stillbirth of female nurses was 2.6%, 7%, and 2.1%, respectively. We found an increased risk of threatened abortion among nurses with overtime work (OR = 1.719, 95% CI 1.158–2.550). The risk of threatened abortion and spontaneous abortion was elevated among nurses handling disinfectant (OR = 2.293 and 1.63, respectively). We found a nearly twofold increased risk of premature birth (OR = 2.169, 95% CI 1.36–3.459) among nurses handling anti-cancer drugs. Conclusions Our findings suggested that maternal occupational exposures might be associated with the risk of adverse pregnancy outcomes among female nurses in China. We recommend that policy-markers and hospital managers work together to reduce exposure to occupational hazards and improve pregnancy outcomes among female nurses.

BackgroundWith the rise and deepening of positive psychology research, theoretical research on job burnout is also deepening worldwide, and some new theoretical models are proposed, such as the burnout-engagement continuum, but there is still a lack of empirical research and application in China. ObjectiveTo analyze the current situation and influencing factors of five profiles in the burnout-engagement continuum in working populations of China: job engagement, ineffective, overextended, disengaged, and burnout. MethodsFrom August to October 2019 and June to September 2020, a total of 27344 subjects of key occupations in six typical industries, including teachers, firefighters, manufacturing workers, medical staff, flight attendants, and traffic police, were selected from 10 provinces (cities) in the eastern, middle, and western regions of China by multistage stratified cluster sampling method for cross-sectional investigation. Maslach Burnout Inventory-General Survey and Core Occupational Stress Scale were used to evaluate job burnout and occupational stress respectively. χ2 test was used to compare rates of count data. Binary logistic regression was used for multivariate analysis of the five profiles. ResultsAmong the subjects, 24.4%, 61.9%, 31.9%, 12.7%, and 11.8% were the prevalence rates of job engagement, ineffective, overextended, disengaged, and burnout, respectively. Flight attendants (35.7%), firefighters (29.0%), traffic police (28.5%), and manufacturing workers (26.5%) had high prevalence rates of job engagement profile. Medical stuff (62.9%) and manufacturing workers (61.8%) had high prevalence rates of ineffective profile. Teachers (39.2%), traffic police (37.2%), and medical stuff (35.5%) had high prevalence rates of overextended profile. Traffic police (17.9%), medical staff (14.3%), and teachers (13.4%) had high prevalence rates of disengaged profile. Traffic police (16.9%), medical staff (13.4%), and teachers (13.3%) had high prevalence rates of burnout profile. The results of multivariate analysis showed that gender, age, education level, marital status, weekly working hours, length of service, income per month, shift work, smoking, drinking, industry, and occupational stress entered into the regression equations of job engagement, ineffective, overextended, disengaged, and burnout. The risks of overextended (OR=1.456-2.970), disengaged (OR=1.306-4.092), and burnout (OR=1.302-4.102) among the high rating groups of the four factors of occupational stress were higher than those among the low rating groups. Flight attendants (OR=0.296) and firefighters (OR=0.329) had lower risks of burnout than teachers, and flight attendants (OR=0.392) and firefighters (OR=0.466) had lower risks of disengaged than teachers. ConclusionAmong the prevalence rates of the five profiles in the burnout-engagement continuum in the 6 typical occupational populations in China, ineffective profile is the highest, followed by overextended, and burnout is the lowest. Gender, age, education level, marital status, weekly working hours, length of service, income per month, shift work, smoking, drinking, industry, and occupational stress have different effects on the five profiles, but industry and occupational stress have greater impacts on job burnout.

BackgroundAs one of the common tools for job burnout assessment, Maslach Burnout Inventory-General Survey (MBI-GS), its reliability and validity across different populations in China have not been examined yet.ObjectiveTo evaluate the reliability and validity of General Burnout Scale (GBS) by multiple occupational groups through the translation and preliminary test of MBI-GS.MethodsBased on the Special Project of Occupational Hazards in Key Populations led by the Institute of Occupational Health and Poison Control, China CDC, key occupational groups in five typical industries were selected by multi-stage stratified cluster sampling, including teachers, firefighters, manufacturing workers, medical staff, and traffic police. Confirmatory factor analysis (CFA) was used to evaluate the construct validity of GBS by single-factor, two-factor, and three-factor structure models. The model fitness was assessed by ratio of the chi-square statistic to the respective degrees of freedom (χ2/ν), root mean square error of approximation (RMSEA), goodness-of-fit index (GFI), comparative fit index (CFI), and parsimony-adjusted non-normed fit index (PNFI). Spearman correlation analysis was used to calculate the criterion validity of GBS with occupational stress, depressive symptoms, and sleep disorders. Cronbach's α coefficient and composite reliability (CR) coefficient were used to evaluate the internal consistency reliability of GBS.ResultsA total of 3485 subjects were surveyed in this study, 3375 valid questionnaires were recovered with a valid response rate of 96.84%. The results of CFA showed that in the adjusted three-factor structure model of GBS (exhaustion, cynicism, and professional efficacy), the χ2/ν < 4, the RMSEA ranged from 0.032 to 0.069, the GFI > 0.90, the CFI > 0.90, and the PNFI > 0.70, which illustrated a good fitness than that of the single- or the two-factor structure models in different occupational groups. The Spearman correlation analysis results showed that occupational stress, depressive symptoms, and sleep disorders were positively correlated with exhaustion and cynicism dimensions, and negatively correlated with professional efficacy dimension of the GBS, with the \begin{document}$ \left| r \right| $\end{document} ranging from 0.139 to 0.662 (P0.05). The Cronbach's α coefficients ranged from 0.819 to 0.899, and the CR values ranged from 0.941 to 0.978 in different occupational groups.ConclusionThe GBS shows high reliability and validity, as well as good application effects in different occupational groups.

BackgroundManufacturing industry is the main body of China's national economy, and manufacturing employees provide solid guarantee and support for the vigorous development of China's manufacturing industry. The research on job burnout of manufacturing employees is helpful to prevent or alleviate the health damage and economic loss caused by job burnout. ObjectiveTo investigate the status and influencing factors of job burnout among manufacturing employees in China, and evaluate the potential mediating effect of job burnout between job stress and depressive symptoms. MethodsA cross-sectional study was performed from August to October 2019 and from June to September 2020 in seven provinces of China. Study participants were recruited from 21 manufacturing companies covering 11 manufacturing subdivisions using multistage stratified cluster sampling. General Burnout Scale, Core Occupational Stress Scale, and Patient Health Questionnaire-9 were used to evaluate job burnout, job stress, and depressive symptoms. Mann-Whitney U test and Kruskal-Wallis H test were used to compare data between two independent samples and multiple independent samples of measurement data; Pearson χ2 test was used to compare the rate of enumeration data; Spearman rank correlation analysis was used to evaluate correlation between selected variables; binary logistic regression was used for multivariate analysis; stepwise regression and bias-corrected Bootstrap method were used to test potential mediating effect. ResultsA total of 10973 valid questionnaires were collected. The M (P25, P75) scores of exhaustions, cynicism, professional efficacy, job burnout, job stress, and depressive symptoms were 1.6 (0.4, 3.0), 1.0 (0.2, 2.2), 4.8 (3.2, 5.7), 1.6 (0.8, 2.5), 45.0 (40.0, 50.0), and 7.0 (4.0, 11.0), respectively. The positive rates of job burnout, job stress, and depressive symptoms were 53.4% (5865/10973), 28.4% (3116/10973), and 29.4% (3231/10973), respectively. The influencing factors of job burnout were gender (versus male; OR for female=0.852), age (versus≤25 years old; ORs for 26-30, 31-40, 41-50, 51-60 years old=0.824, 0.819, 0.738, 0.677), education level (versus junior high school or below; ORs for senior high school/technical secondary school, junior college/vocational college, graduate school or above=1.119, 1.345, 1.331), income per month (versus＜3000 yuan; ORs for 3000-4999, 5000-6999, 7000-8999, 9000-10999, ≥11000 yuan=0.513, 0.470, 0.430, 0.375, 0.411), position (versus assembly line; OR for non-assembly line=0.814), average weekly working hours (versus ≤40 h; ORs for 61-70, ＞70 h=1.199, 1.519), and drinking (versus non-drinking; OR for drinking=1.261). Job burnout was positively correlated with job stress and depressive symptoms (r=0.556, 0.508, P

Abstract Electronic waste that has not been properly treated can lead to environmental contamination including of heavy metals, which can pose risks to human health. Infants, a sensitive group, are highly susceptible to heavy metals exposure. The aim of this study was to investigate the association between prenatal heavy metal exposure and infant birth outcomes in an e‐waste recycling area in China. We analyzed cadmium (Cd), chromium (Cr), manganese (Mn), lead (Pb), copper (Cu), and arsenic (As) concentrations in 102 human milk samples collected 4 weeks after delivery. The results showed that 34.3% of participants for Cr, which exceeds the World Health Organization (WHO) guidelines, as well as the mean exposure of Cr exceeded the WHO guidelines. We collected data on the birth weight (BW) and length of infants and analyzed the association between metal concentration in human milk and birth outcomes using multivariable linear regression. We observed a significant negative association between the Cd concentration in maternal milk and BW in female infants (β = −162.72, 95% CI = −303.16, −22.25). In contrast, heavy metals did not associate with birth outcomes in male infants. In this study, we found that 34.3% of participants in an e‐waste recycling area had a Cr concentration that exceeded WHO guidelines, and there was a significant negative association between prenatal exposure to the Cd and infant BW in females. These results suggest that prenatal exposure to heavy metals in e‐waste recycling areas may lead to adverse birth outcomes, especially for female infants.

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large number of individual experts. Evidence from human, animal and mechanistic data suggests that occupational exposure to dusts and/or fibres (silica, asbestos and coal dust) causes pneumoconiosis. In this paper, we present a systematic review and meta-analysis of the prevalences and levels of occupational exposure to silica, asbestos and coal dust. These estimates of prevalences and levels will serve as input data for estimating (if feasible) the number of deaths and disability-adjusted life years that are attributable to occupational exposure to silica, asbestos and coal dust, for the development of the WHO/ILO Joint Estimates. Objectives: We aimed to systematically review and meta-analyse estimates of the prevalences and levels of occupational exposure to silica, asbestos and coal dust among working-age (≥ 15 years) workers. Data sources: We searched electronic academic databases for potentially relevant records from published and unpublished studies, including Ovid Medline, PubMed, EMBASE, and CISDOC. We also searched electronic grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews and included study records; and consulted additional experts. Study eligibility and criteria: We included working-age (≥ 15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (< 15 years) and unpaid domestic workers. We included all study types with objective dust or fibre measurements, published between 1960 and 2018, that directly or indirectly reported an estimate of the prevalence and/or level of occupational exposure to silica, asbestos and/or coal dust. Study appraisal and synthesis methods: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, then data were extracted from qualifying studies. We combined prevalence estimates by industrial sector (ISIC-4 2-digit level with additional merging within Mining, Manufacturing and Construction) using random-effects meta-analysis. Two or more review authors assessed the risk of bias and all available authors assessed the quality of evidence, using the ROB-SPEO tool and QoE-SPEO approach developed specifically for the WHO/ILO Joint Estimates. Results: Eighty-eight studies (82 cross-sectional studies and 6 longitudinal studies) met the inclusion criteria, comprising > 2.4 million measurements covering 23 countries from all WHO regions (Africa, Americas, Eastern Mediterranean, South-East Asia, Europe, and Western Pacific). The target population in all 88 included studies was from major ISCO groups 3 (Technicians and Associate Professionals), 6 (Skilled Agricultural, Forestry and Fishery Workers), 7 (Craft and Related Trades Workers), 8 (Plant and Machine Operators and Assemblers), and 9 (Elementary Occupations), hereafter called manual workers. Most studies were performed in Construction, Manufacturing and Mining. For occupational exposure to silica, 65 studies (61 cross-sectional studies and 4 longitudinal studies) were included with > 2.3 million measurements collected in 22 countries in all six WHO regions. For occupational exposure to asbestos, 18 studies (17 cross-sectional studies and 1 longitudinal) were included with > 20,000 measurements collected in eight countries in five WHO regions (no data for Africa). For occupational exposure to coal dust, eight studies (all cross-sectional) were included comprising > 100,000 samples in six countries in five WHO regions (no data for Eastern Mediterranean). Occupational exposure to silica, asbestos and coal dust was assessed with personal or stationary active filter sampling; for silica and asbestos, gravimetric assessment was followed by technical analysis.Risk of bias profiles varied between the bodies of evidence looking at asbestos, silica and coal dust, as well as between industrial sectors. However, risk of bias was generally highest for the domain of selection of participants into the studies.The largest bodies of evidence for silica related to the industrial sectors of Construction (ISIC 41–43), Manufacturing (ISIC 20, 23–25, 27, 31–32) and Mining (ISIC 05, 07, 08). For Construction, the pooled prevalence estimate was 0.89 (95% CI 0.84 to 0.93, 17 studies, I2 91%, moderate quality of evidence) and the level estimate was rated as of very low quality of evidence. For Manufacturing, the pooled prevalence estimate was 0.85 (95% CI 0.78 to 0.91, 24 studies, I2 100%, moderate quality of evidence) and the pooled level estimate was rated as of very low quality of evidence. The pooled prevalence estimate for Mining was 0.75 (95% CI 0.68 to 0.82, 20 studies, I2 100%, moderate quality of evidence) and the pooled level estimate was 0.04 mg/m3 (95% CI 0.03 to 0.05, 17 studies, I2 100%, low quality of evidence). Smaller bodies of evidence were identified for Crop and animal production (ISIC 01; very low quality of evidence for both prevalence and level); Professional, scientific and technical activities (ISIC 71, 74; very low quality of evidence for both prevalence and level); and Electricity, gas, steam and air conditioning supply (ISIC 35; very low quality of evidence for both prevalence and level).For asbestos, the pooled prevalence estimate for Construction (ISIC 41, 43, 45,) was 0.77 (95% CI 0.65 to 0.87, six studies, I2 99%, low quality of evidence) and the level estimate was rated as of very low quality of evidence. For Manufacturing (ISIC 13, 23–24, 29–30), the pooled prevalence and level estimates were rated as being of very low quality of evidence. Smaller bodies of evidence were identified for Other mining and quarrying (ISIC 08; very low quality of evidence for both prevalence and level); Electricity, gas, steam and air conditioning supply (ISIC 35; very low quality of evidence for both prevalence and level); and Water supply, sewerage, waste management and remediation (ISIC 37; very low quality of evidence for levels).For coal dust, the pooled prevalence estimate for Mining of coal and lignite (ISIC 05), was 1.00 (95% CI 1.00 to 1.00, six studies, I2 16%, moderate quality of evidence) and the pooled level estimate was 0.77 mg/m3 (95% CI 0.68 to 0.86, three studies, I2 100%, low quality of evidence). A small body of evidence was identified for Electricity, gas, steam and air conditioning supply (ISIC 35); with very low quality of evidence for prevalence, and the pooled level estimate being 0.60 mg/m3 (95% CI −6.95 to 8.14, one study, low quality of evidence). Conclusions: Overall, we judged the bodies of evidence for occupational exposure to silica to vary by industrial sector between very low and moderate quality of evidence for prevalence, and very low and low for level. For occupational exposure to asbestos, the bodies of evidence varied by industrial sector between very low and low quality of evidence for prevalence and were of very low quality of evidence for level. For occupational exposure to coal dust, the bodies of evidence were of very low or moderate quality of evidence for prevalence, and low for level. None of the included studies were population-based studies (i.e., covered the entire workers’ population in the industrial sector), which we judged to present serious concern for indirectness, except for occupational exposure to coal dust within the industrial sector of mining of coal and lignite. Selected estimates of the prevalences and levels of occupational exposure to silica by industrial sector are considered suitable as input data for the WHO/ILO Joint Estimates, and selected estimates of the prevalences and levels of occupational exposure to asbestos and coal dust may perhaps also be suitable for estimation purposes.Protocol identifier:https://doi.org/10.1016/j.envint.2018.06.005.PROSPERO registration number:CRD42018084131.

Backgrounds: The prediabetes population is large and easily overlooked because of the lack of obvious symptoms, which can progress to diabetes. Early screening and targeted interventions can substantially reduce the rate of conversion of prediabetes to diabetes. Therefore, this study systematically reviewed prediabetes risk prediction models, performed a summary and quality evaluation, and aimed to recommend the optimal model. Methods: We systematically searched five databases (Cochrane, PubMed, Embase, Web Of Science, and CNKI) for published literature related to prediabetes risk prediction models and excluded preprints, duplicate publications, reviews, editorials, and other studies, with a search time frame of March 01, 2023. Data were categorized and summarized using a standardized data extraction form that extracted data including author; publication date; study design; country; demographic characteristics; assessment tool name; sample size; study type; and model-related indicators. The PROBAST tool was used to assess the risk of bias profile of included studies. Findings: 14 studies with a total of 15 models were eventually included in the systematic review. We found that the most common predictors of models were age, family history of diabetes, gender, history of hypertension, and BMI. Most of the studies (83.3%) had a high risk of bias, mainly related to under-reporting of outcome information and poor methodological design during the development and validation of models. Due to the low quality of included studies, the evidence for predictive validity of the available models is unclear. Interpretation: We should pay attention to the early screening of prediabetes patients and give timely pharmacological and lifestyle interventions. The predictive performance of the existing model is not satisfactory, and the model building process can be standardized and external validation can be added to improve the accuracy of the model in the future.

Abstract Background Multi-walled carbon nanotube (MWCNT) is one of the most widely used manufactured nanomaterials, however, its potential harmful effect on human health is of great concern. Previously we have shown the acute and chronic exposure to MWCNT induced different responses in human mesothelial MeT-5A cells. In the current study, MeT-5A cells were continuously subjected to MWCNT exposure at 10 μg/cm2 for 48 h per passage, up to a whole year, to further clarify the carcinogesis and its potential mechanisms of MWCNT. Results After one-year MWCNT treatment, MeT-5A cells exhibited neoplastic-like properties, including morphological changes, anchorage-independent growth, increased cell proliferation and cell migration. Further examination revealed the expression of microRNA 221 (miR221) was gradually decreased, while the annexin a1 expression was increased at both the mRNA and protein level during the exposure. Bioinformatic analysis indicated that annexin a1 is a target for miR221 regulation, and it was confirmed by transfecting cells with miR221 mimics, which resulted in the downregulation of annexin a1. Detailed analyses demonstrated miR221 was involved in the regulation of cell migration, e.g., downregulation of miR221 or overexpression of ANNEXIN A1, contributed to the increased cell migration. In contrast, overexpression of miR221 or downregulation of ANNEXIN A1 slowed cell migration. Conclusions Taken together, these results point to a neoplastic-transforming property of MWCNT, and the miR221-annexin a1 axis is involved in the regulation of cell migration in the transformed cells.

Female workers in the asbestos processing industry of Eastern China are at high risk of developing multiple types of cancer, and more data are urgently needed to better understand and address this issue. Death certificate data were selected from an asbestos processing city in China from 2005 to 2006. Information was investigated using the relatives of those individuals who had died as sources of information. Individuals were classified into one of three asbestos exposure levels. Standardized mortality ratio and 95% confidence interval were calculated. A total of 2,964 individual deaths were identified from 2005 to 2006; of these, 21.4% were occupationally exposed to asbestos. The main cause of death was circulatory system diseases (21.2%). The proportion of individuals with respiratory system diseases increased by age among each exposure subgroup (Ptrend < 0.01). Among females, a significant trend was observed between increased asbestos exposure and mortality due to respiratory system diseases and lung cancer. Our study indicated that asbestos exposure was associated with excess mortality from lung cancer and respiratory diseases, particularly among female workers in an asbestos processing area in Eastern China.

Objectives This study aims to examine the association between occupational factors and semen quality in semen donors in eastern China.Methods We recruited 12 301 semen donors from 2006 to 2020 as the studying population. A self-designed questionnaire was applied for collecting lifestyle and work style information. Semen samples were analysed according to WHO guidelines. A crude and adjusted linear regression model was used to analyse the association between occupational factors and semen quality.Results College students accounted for 36.2% of all semen donors. The majority (81.3%) of semen donors were between 18 year and 30 years. Soldiers or the police had the highest semen volume (the median value=3.8 mL), however, they had the lowest sperm concentration (53.6×106/ml) and sperm motility (45.5%). Workers in finance or insurance had an elevated risk of low semen volume, sperm concentration and total sperm count (OR=1.43, 1.57 and 1.98, respectively). Unemployed men had a high risk of low sperm concentration and low total sperm count (OR=1.84 and 1.58, respectively). Working in the information technology industry had a deleterious effect on the progressive motility of sperm (OR=1.27, 95% CI 1.03 to 1.57).Conclusion Our study indicated that sedentary work style and intensive sports in certain professions might be associated with decreased semen quality. We reported evidence of becoming unemployed on the damage to semen quality. Hence, we advocate a healthy work style to improve semen quality in eastern China.

DNA is essential for the development and function of organisms. A number of factors affect DNA integrity and cause DNA damages, such as ultraviolet light, ionizing radiation and hydrogen peroxide. DNA damages activate a series of intracellular reactions, called DNA damage response, which play a crucial role in the pathogenesis of cancers and other diseases. MiRNA is a type of evolutionarily conserved non-coding RNA and affects the expression of target genes by post-transcriptional regulation. Increasing evidences suggested that the expression of some miRNAs was changed in tumor cases. MiRNAs may participate in DNA damage response and affect genomic stability via influencing the processes of cell cycle, DNA damage repair and apoptosis, thus ultimately impact on tumorigenesis. Therefore, the role of miRNA in DNA damage response is reviewed, to provide a theoretical basis for the mechanism of miRNAs’ effects on DNA damage response and for the research of new therapies for diseases.

Abstract Fibulin-3 is an extracellular matrix glycoprotein widely expressed in various tissues. Tissue fibulin-3 expression have never been reported in association with prognosis of mesothelioma. Hence, we sought to determine the association between fibulin-3 expression and mesothelioma survival. We made a tissue microarray, which was comprised of cancer and normal tissue from mesothelioma patients (n = 82) during the period 1998–2017 in China. Fibulin-3 and HGMB1 expression were analyzed by immunohistochemistry method. Kaplan–Meier method and Cox proportional hazard models were used for analyzing survival data. Overall, 61 cases (74.4%) were female; 90.2% were of epithelioid type; the median overall survival time was 12.5 months. Fibulin-3 and HMGB1 were highly expressed in tumor tissue rather than adjacent tissue. The expression of fibulin-3 in tissue was correlated with that of HMGB1 (r = 0.32, P = 0.003). High expression of fibulin-3 in tumor tissue could predict poor survival in patients with mesothelioma (P = 0.02). This remained true in a multivariate model, with a significant hazard ratio of 1.91. We demonstrated that fibulin-3 in tumor tissue was a novel biomarker of poor survival of mesothelioma, suggesting it may be a relevant target for therapeutic intervention.

Aim: We aimed to explore the expression of miRNAs and their potential roles in the DNA damage response (DDR) induced by Cr (VI) exposure in human B lymphoblast cells (HMy2.CIR cells) and in a population of Cr (VI)-exposed humans. Methods: Differentially expressed miRNAs were found by a combination of miRNA sequencing and RT-qPCR validation in HMy2.CIR cells treated with K2Cr2O7. Differentially expressed miRNAs related to DDR were selected for functional study. The expression levels of differential miRNAs were also investigated in chromate workers. Results: A total of 214 differentially expressed miRNAs were identified by sequencing, and the expression of 5 miRNAs among 25 associated with DDR was found to be consistent between sequencing and validation studies. Functional studies showed that miR-148a-3p, miR-21-5p, and miR-424-3p might be related to Cr (VI)-induced cell apoptosis, and miR-221-3p might participate in Cr (VI)-induced DDR. We also found that the expression of miR-21-5p and miR-424-3p was upregulated in chromate workers. Conclusions: Cr (VI) exposure could significantly impact miRNAs expression in vitro and in chromate workers. Functional studies showed that miR-148a-3p, miR-21-5p and miR-221-3p might take a crucial role in the cellular DDR induced by Cr (VI) exposure.

Abstract Background Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and lethal malignancies. Long non-coding RNAs (lncRNAs) are being found to play crucial roles in ATC progression. Herein, we focused on the role of nuclear paraspeckle assembly transcript 1 (NEAT1) on ATC progression under hypoxia and underlying mechanisms governing it. Methods The expression levels of NEAT1, miR-206 and miR-599 were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Cell migration and invasion abilities were detected using transwell assays. Glucose consumption and lactate production were determined using a corresponding commercial assay kit. Western blot was performed to evaluate the level of hexokinase 2 (HK2). The targeted interplays between NEAT1 and miR-206 or miR-599 were confirmed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft model was established to observe the effect of NEAT1 on tumor growth in vivo. Results Our data indicated that NEAT1 was highly expressed in ATC tissues and cells, and hypoxia induced NEAT1 expression in ATC cells. NEAT1 depletion repressed ATC cell migration, invasion and glycolysis under hypoxia. Mechanistically, NEAT1 acted as a molecular sponge of miR-206 and miR-599. Moreover, the repressive effects of NEAT1 knockdown on ATC cell migration, invasion and glycolysis under hypoxia were mediated by miR-206 or miR-599. Additionally, NEAT1 knockdown weakened tumor growth in vivo. Conclusion In conclusion, our study suggested that a low NEAT1 expression suppressed the migration, invasion, and glycolysis in ATC cells under hypoxia at least partially through modulating miR-206 and miR-599, providing new therapeutic strategies for ATC treatment.

Hexavalent Chromium [Cr (VI)] is an established toxicant, carcinogen, and a significant source of public health concern. The multicopy ribosomal DNA (rDNA) array is mechanistically linked to aging and cancer, is the most evolutionarily conserved segment of the human genome, and gives origin to nucleolus, a nuclear organelle where ribosomes are assembled. Here we show that exposure to Cr (VI) induces instability in the rDNA, triggering cycles of rapid, specific, and transient amplification and contraction of the array in human cells. The dynamic of environmentally responsive rDNA copy number (CN) amplification and contraction occurs at doses to which millions of individuals are regularly exposed. Finally, analyses of human populations occupationally exposed to Cr (VI) indicate that environmental exposure history and drinking habits but not age shape extensive naturally occurring rDNA copy number variation. Our observations identify a novel pathway of response to hexavalent chromium exposure and raise the prospect that a suite of environmental determinants of rDNA copy number remain to be discovered.

Background and ObjectiveRadiotherapy (RT) is the primary treatment option for nasopharyngeal carcinoma (NPC), but it is associated with radiation-induced sarcomas (RISs). This study aims to investigate clinicopathological features and head and neck RIS prognosis after NPC RT.MethodsThe medical and radiological records of the NPC patients (n =14,074) referred to Zhejiang Cancer Hospital, Hang Zhou, China between January 1995 and December 2018 were retrospectively reviewed. Among them, 22 patients were determined to have RIS after RT for NPC. The clinicopathological data, diagnosis, treatment, and follow-up results of 22 patients with RIS were analyzed in this retrospective research. All 22 patients underwent surgery as the main treatment. The levels of Overall Survival (OS) were determined through the Log-rank test and Kaplan–Meier method.ResultsAmong these patients, 13 were males and nine females with the male/female ratio of 1.44:1. The age during the primary RT of NPC ranged from 25 to 61 years old (median age: 37 years old). Patients’ ages ranged from 33 to 73 years old (median age: 52.5 years old) when diagnosed with RIS. The latency period for development of the RIS was between 3 and 36 years (median: 8.5 years) after RT. In this cohort, R0 resection was achieved in 13 cases, R1 resection in five cases, and R2 resection in four cases. During the follow-up period ranged from 2 to 102 months (median 14 months), 15 patients had died of the disease. Kaplan–Meier method showed that the 2-year, 3-year, and the 5-year cumulative OS rate was 50.3, 43.2, and 14.4%, respectively. The median survival time was 34 months. Surgical resection with R0 resection achieves a significantly better prognosis (P = 0.012). Patients under the age of 37 years old at the time of initial RT had a relatively better prognosis (P = 0.035).ConclusionsAlthough the incidence of RIS after RT of NPC is generally low, the treatment of RIS is very difficult. The RISs are associated with poor overall prognosis. R0 resection can improve the prognosis thus it should be considered as the primary and optimal choice for the treatment of RIS.

The presence of perfluoroalkyl acids (PFAAs) and chlorinated polyfluoroalkyl ether sulfonates (Cl-PFAESs) in humans has attracted great attention in recent decades. However, information on their exposure sources and the influence of age and gender on Cl-PFAES concentrations in human serum is still limited. In this study, eighty-five serum samples were collected from the general population in Anji, China, and analyzed for perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates (PFSAs), and Cl-PFAESs. Perfluorooctane sulfonate (PFOS; mean, 5.9 ng/mL) and perfluorooctanoate (PFOA; 3.3 ng/mL) were the predominant PFAAs in human serum. The serum concentrations of C8–C12 PFCAs, perfluorohexane sulfonate, and PFOS were significantly (rs = 0.40–0.98, p

The ribosomal DNA (rDNA) can act as a sensor and responder of cancer-associated stress. Here we investigated rDNA copy number in gastric cancers and its association with existing biomarkers and metals exposure. This study was performed on paired tumor and adjacent normal tissues obtained from 65 gastric cancer patients who underwent gastrectomy. Immunohistochemistry was used to assess HER-2, E-cadherin, EGFR, CK (pan), CK20, CK7, TopoⅡ, CAM5.2, P53, and Ki-67 expression. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the concentrations of 17 metals in gastric tissues. rDNA copy number was detected by qPCR in genomic DNA isolated from tissue samples. Associations between the expression of existing markers, metal concentrations, and rDNA copy number were evaluated. Within patients with gastric cancer, the copy number of the 45S rDNA components (18S, 5.8S, 28S) and the 5S rDNA in tumor tissues were significantly higher than those in adjacent normal tissues, whereas mitochondrial DNA (mtDNA) copy number was significantly lower in tumor tissues than that in adjacent normal tissues. Further analysis revealed that the increase in 18S, 5.8S, and 28S rDNA copy number in tumor tissues was diminished in the context of EGFR and P53 loss. Moreover, analysis of metals revealed particularly high concentrations of As, Cd, Cr, Cu and Fe in the gastric tissues of these patients. Intriguingly, rDNA copy number variation across individuals was correlated with the concentrations of some metals. The rDNA was amplified in tumor tissues of gastric cancer patients, and its amplification may be associated with metals exposure. The expression of EGFR and P53 may influence rDNA copy number, with diminished amplification of the rDNA in cancers that were negative for these biomarkers. Our observation further our understanding of rDNA copy number in gastric cancer and its potential as a simple and useful marker in gastric cancer monitoring. Keywords: Gastric cancer, rDNA, Markers, Metals, Carcinogenesis

The diagnostic value of the concentration of circulating cell-free DNA (cfDNA) for breast cancer has generated inconsistent results. The aim of this study was to evaluate the first diagnostic value of the concentration of cfDNA for breast cancer by meta-analysis. Studies were retrieved by searching PubMed, Cochrane Library, and Web of Science before June 2018. Sensitivity, specificity, diagnostic odds ratio (DOR), the summary receiver operating characteristic (SROC) curve, and the area under curve (AUC) were used to summarize overall diagnostic performance. The random-effects model was used to calculate the pooled statistics. Subgroup analysis and meta-regression analysis were carried out to detect the source of heterogeneity. A total of 13 studies were identified with 1,087 breast cancer patients and 720 healthy controls. Overall, the pooled sensitivity and specificity of concentration of cfDNA for breast cancer were 87% (95% CI, 73–94%) and 87% (95% CI, 79–93%), respectively. The pooled DOR was 32.93 (95% CI, 13.52–80.19) and the SROC curve revealed an AUC of 0.93 (95% CI, 0.91–0.95). Meta-regression analysis showed that no covariate had a significant correlation with relative DOR (RDOR). Publication bias was not detected in this meta-analysis. This meta-analysis indicates that the concentration of cfDNA has potential first diagnostic value for breast cancer and plasma may be a better source of cfDNA for detection of breast cancer.

Cr(VI) exposure could produce kinds of intermediates and reactive oxygen species, both of which were related to DNA damage. Hyaluronan (HA) has impressive biological functions and was reported to protect corneal epithelial cells against oxidative damage induced by ultraviolet B, benzalkonium chloride, and sodium lauryl sulfate. So the aim of our study was to investigate HA protection on human corneal epithelial (HCE) cells against Cr(VI)-induced toxic effects. The HCE cell lines were exposed to different concentrations of K2Cr2O7 (1.875, 3.75, 7.5, 15.0, and 30 μM) or a combination of K2Cr2O7 and 0.2% HA and incubated with different times (15 min, 30 min, and 60 min). Our data showed that Cr(VI) exposure could cause decreased cell viability, increased DNA damage, and ROS generation to the HCE cell lines. But incubation of HA increased HCE cell survival rates and decreased DNA damage and ROS generation induced by Cr(VI) in a dose- and time-dependent manner. We report for the first time that HA can protect HCE cells against the toxicity of Cr(VI), indicating that it will be a promising therapeutic agent to corneal injuries caused by Cr(VI).

The benchmark dose (BMD) method has been increasingly used to assess the health risks of cadmium (Cd) in epidemiological studies. The aim of our study was to estimate the threshold levels of urinary Cd (UCd) using the BMD method in a general population of Jiangshan City, Zhejiang Province of China. In our study, a total of 934 people (469 men, 465 women) were recruited and morning urine samples were collected from all the participants. Levels of Cd, creatinine, and renal dysfunction indicators such as retinol binding protein (RBP), β2-microglobulin (β2-MG), and N-acetyl-b-glucosaminidase (NAG) in urine were detected for analysis of BMD and BMD low (BMDL) of UCd. RBP, β2-MG, and NAG in urine all correlated significantly (P < 0.001) with UCd except of age (P = 0.767). When the benchmark response (BMR) was 5%, the BMD/BMDL of UCd for RBP, β2-MG, and NAG was 1.69/ 0.89, 1.24/0.62, 0.85/0.49 μg/g Cr in men and 1.70/0.76, 1.35/0.64, 1.36/0.65 μg/g Cr in women, respectively. If the BMR was set at 10%, the BMD/BMDL of UCd for RBP, β2-MG, and NAG was 2.44/1.59, 2.09/1.30, 1.80/1.04 μg/g Cr in men and 2.43/1.53, 2.10/1.34, 2.31/1.37 μg/g Cr in women, respectively. Our results provided evidence for Cd-induced tubular effects in cadmium non-polluted areas in China. Both β2-MG and NAG were more sensitive than RBP in response to Cd exposure. But β2-MG was the most sensitive indicator in women, and NAG was the most sensitive one in men.

High mobility group box 1 (HMGB1), which has become one of the most intriguing molecules in inflammatory disorders and cancers and with which ligand-activated peroxisome proliferator-activated receptors (PPARs) are highly associated, is considered as a therapeutic target. Of particular interest is the fact that certain PPAR ligands have demonstrated their potent anti-inflammatory activities and potential anticancer effects. In this review article we summarize recent experimental evidence that PPAR ligands function as suppressors that target biological actions of HMGB1, including intracellular expression, receptor signaling cascades, and extracellular secretion of HMGB1 in cell lines and/or animal models. We also propose the possible mechanisms underlying PPAR involvement in inflammatory disorders and discuss the future therapeutic value of PPAR ligands targeting HMGB1 molecule for cancer prevention and treatment.

Hexavalent chromium [Cr(IV)], a well-known industrial waste product and an environmental pollutant, is recognized as a human carcinogen. But its mechanisms of carcinogenicity remain unclear, and recent studies suggest that DNA methylation may play an important role in the carcinogenesis of Cr(IV). The aim of our study was to investigate the effects of Cr(IV) on cell cycle progress, global DNA methylation, and DNA methylation of p16 gene. A human B lymphoblastoid cell line and a human lung cell line A549 were exposed to 5-15 µM potassium dichromate or 1.25-5 µg/cm² lead chromate for 2-24 hours. Cell cycle was arrested at G₁ phase by both compounds in 24 hours exposure group, but global hypomethylation occurred earlier than cell cycle arrest, and the hypomethylation status maintained for more than 20 hours. The mRNA expression of p16 was significantly up-regulated by Cr(IV), especially by potassium dichromate, and the mRNA expression of cyclin-dependent kinases (CDK4 and CDK6) was significantly down-regulated. But protein expression analysis showed very little change of p16 gene. Both qualitative and quantitative results showed that DNA methylation status of p16 remained unchanged. Collectively, our data suggested that global hypomethylation was possibly responsible for Cr(IV)-induced G₁ phase arrest, but DNA methylation might not be related to up-regulation of p16 gene by Cr(IV).