The effect of the nucleolar protein ZNF385A on the ribosomal DNA copy number variation in response to Cr(VI)-induced DNA damage.

Hexavalent chromium [Cr(VI)] is a widely distributed carcinogen in industrial contexts and general environmental contexts. Emerging research highlights the central role of ribosomal DNA (rDNA) in DNA Damage Responses (DDRs). However, there remains a lack of investigation into the potential dose-dependent relationship between exposure to Cr(VI) and alterations in rDNA copy number (CN), as well as the related mechanisms underlying these effects. A molecular epidemiological investigation involving 67 workers exposed to Cr(VI) and 75 unexposed controls was conducted. There was a notable increase in ZNF385A expression, variations in rDNA CN, and elevated γH2AX levels in the peripheral blood of Cr(VI)-exposed workers. Restricted cubic spline (RCS) models showed that blood Cr levels in the exposed population exhibited non-linear dose-dependent relationships with γH2AX, rDNA CN, and ZNF385A. Of considerable interest, there were robust and positive associations between ZNF385A and both γH2AX and rDNA CN. Further in vitro experiments provided concrete evidence that Cr(VI) simultaneously caused an increase in ZNF385A expression and variations in rDNA CN. ZNF385A-depleted cells showed increased sensitivity to Cr(VI)-mediated DDRs and alterations in rDNA CN. This study indicated that ZNF385A played a highly significant role in the rDNA CN variation in response to Cr(VI)-induced DNA damage.

Integrated DNA methylation analysis of peripheral blood from asbestos exposed populations and patients with malignant mesothelioma reveals novel methylation driver genes of diagnostic and prognostic relevance.

Effective biomarkers are paramount importance for the early detection and prognosis prediction of malignant mesothelioma (MM) which mainly caused by asbestos exposure, and DNA methylation has been demonstrated to be a potentially powerful diagnostic tool. To elucidate the relationship between asbestos exposure and alterations in DNA methylation patterns, as well as the potential diagnostic and prognostic value of differentially methylated regions and CpG sites (DMRs/DMCs) in the progression of MM. The current study employed reduced representation bisulfite sequencing (RRBS) to examine the genome-wide DNA methylation profiles in the peripheral blood of individuals exposed to asbestos and those diagnosed with MM, in comparison to the controls, and DMRs/DMCs were subsequently validated by targeted bisulfite sequencing (TBS). Our results suggested that there were 12 DMRs/DMCs exhibiting a consistent change trend of DNA methylation in both RRBS and TBS results. Significant correlations were observed between DNA methylation levels of DMRs/DMCs and the duration of occupational asbestos exposure. The evaluation of the receiver operating characteristic (ROC) curve suggested that the DNA methylation status of FHIT, CCR12P and CDH15 may serve as diagnosis indicator in distinguishing MM patients from healthy controls and those exposed to asbestos. Our findings offer a foundation for the role of DNA methylation in the development of MM induced by asbestos exposure. The potential significance of FHIT, CCR12P and CDH15 DNA methylation alterations in the pathogenesis and advancement of MM disease suggests their potential as diagnostic and prognostic biomarkers.

Association Between Prenatal Exposure to Per- and Poly-Fluoroalkyl Substances From Electronic Waste Disassembly Areas and Steroid Hormones in Human Milk Samples.

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 (ß, 0.23; 95% CI, 0.08-0.39) and A-dione (ß, 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.

Cr (VI)-induced ribosomal DNA copy number variation is associated with semen quality impairment: Evidence from human to animal study.

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.

Exosomal proteomics and cytokine analysis distinguish silicosis cases from controls.

Occupational silica exposure caused a serious disease burden of silicosis. There is currently a lack of sensitive and effective biomarkers for silicosis, and the pathogenesis of silicosis is unclear. Exosomes were significant in the pathogenesis of silicosis, and our study was carried out from exosomal proteomics and cytokine analysis. Firstly, the plasma levels of cytokines were detected using a Luminex multiplex assay, and the results indicated that the plasma levels of TNF-α, IL-6, CCL2, CXCL10, and PDGF-AB were significantly higher in silicosis patients than in silica-exposed workers and controls (p < 0.05). After correlation analysis, the plasma levels of cytokines were positively correlated with exosomal protein concentration. Secondly, data-independent acquisition (DIA) was performed on plasma-derived exosomes in the screening population, which identified 88, 151, 293, and 53 differentially expressed proteins (DEPs) in exposure/control, silicosis/control, silicosis/exposure, and silicosis stage Ⅲ/silicosis stage Ⅰ groups respectively. After parallel reaction monitoring (PRM) in an independent verification population, the results indicated that the changing trend of 15 DEPs was coincident in screening and verification results. The result of correlation analysis indicated that the plasma level of TNF-α was negatively correlated with the expression of exosomal DSP, KRT78, SERPINB12, and CALML5. The AUC of combined determination of TNF-α and CALML5 reached 0.900, with a sensitivity of 0.714 and a specificity of 0.933. Overall, our study revealed the exosomal proteomic profiling of silicosis patients, silica-exposed workers, and controls, indicating that exosomes were significant in the pathogenesis of silicosis. It also revealed that the combined of the plasma levels of cytokines and the expression of exosomal DEPs could increase determination efficiency. This study provided directions for the development of silicosis biomarkers and a scientific basis for the pathogenesis research of silicosis in the future.

Expression of RIPK1 and FADD are associated with chemosensitivity and survival in head and heck squamous cell carcinoma via tanshinone IIA-mediated modulation of the RIPK1-FADD-Caspase 8 complex.

Tanshinone IIA (Tan IIA), a main active ingredient of salvia miltiorrhiza, has a wide range of antitumor effects, while its specific role and mechanism in head and neck squamous cell carcinomas (HNSCC) is not fully understood. Totally 59 primary HNSCC patients underwent two courses of induction chemotherapy before surgery. The association between expression of Fas-Associated Death Domain (FADD) and receptor interacting protein kinase 1 (RIPK1) and chemotherapy resistance and survival were evaluated. The cell counting kit-8 was used to detect the effect of Tan IIA on the activity of cisplatin in chemoresistant HNSCC cells through a series of in vitro experiments. The quantitative real-time reverse-transcription polymerase chain reaction, Western blot analysis and flow cytometry were used. FADD and RIPK1 expressions were differentially expressed in Chemosensitive and drug-resistant patients. Furthermore, patients with tumors exhibiting high expression of FADD and RIPK1 had significantly greater risk for chemoresistance and mortality than patients with tumors that had low levels of these proteins. Moreover, Tan IIA reduced the expression of RIPK1 and FADD in HNSCC chemoresistant cell lines, which could increase the chemosensitivity of cisplatin and promote apoptosis. Overexpression of RIPK1 led to attenuation of therapeutic effects of Tan IIA, which were mainly realized through regulation of the RIPK1-FADD-Caspase 8 complex. This study is the first to demonstrate the clinical value and role of FADD and RIPK1 in the treatment of HNSCC. This work establishes the proapoptotic effects of Tan IIA and its potential to enhance chemosensitivity in HNSCC by modulating the RIPK1-FADD-Caspase 8 complex.

Effects of the SEMA4B gene on hexavalent chromium [Cr(VI)]-induced malignant transformation of human bronchial epithelial cells.

Our previous study identified the potential of SEMA4B methylation level as a biomarker for hexavalent chromium [Cr(VI)] exposure. This study aimed to investigate the role of the SEMA4B gene in Cr(VI)-mediated malignant transformation of human bronchial epithelial (BEAS-2B) cells. In our population survey of workers, the geometric mean [95% confidence intervals (CIs)] of Cr in blood was 3.80 (0.42, 26.56) µg/L. Following treatment with various doses of Cr(VI), it was found that 0.5 µM had negligible effects on the cell viability of BEAS-2B cells. The expression of SEMA4B was observed to decrease in BEAS-2B cells after 7 days of treatment with 0.5 µM Cr(VI), and this downregulation continued with increasing passages of Cr(VI) treatment. Chronic exposure to 0.5 µM Cr(VI) enhanced the anchorage-independent growth ability of BEAS-2B cells. Furthermore, the use of a methylation inhibitor suppressed the Cr(VI)-mediated anchorage-independent growth in BEAS-2B cells. Considering that Cr levels exceeding 0.5 µM can be found in human blood due to occupational exposure, the results suggested a potential carcinogenic risk associated with occupational Cr(VI) exposure through the promotion of malignant transformation. The in vitro study further demonstrated that Cr(VI) exposure might inhibit the expression of the SEMA4B gene to promote the malignant transformation of BEAS-2B cells.

A meta-analysis of diabetes risk prediction models applied to prediabetes screening.

AIM: To provide a systematic overview of diabetes risk prediction models used for prediabetes screening to promote primary prevention of diabetes. METHODS: The Cochrane, PubMed, Embase, Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for a comprehensive search period of 30 August 30, 2023, and studies involving diabetes prediction models for screening prediabetes risk were included in the search. The Quality Assessment Checklist for Diagnostic Studies (QUADAS-2) tool was used for risk of bias assessment and Stata and R software were used to pool model effect sizes. RESULTS: A total of 29 375 articles were screened, and finally 20 models from 24 studies were included in the systematic review. The most common predictors were age, body mass index, family history of diabetes, history of hypertension, and physical activity. Regarding the indicators of model prediction performance, discrimination and calibration were only reported in 79.2% and 4.2% of studies, respectively, resulting in significant heterogeneity in model prediction results, which may be related to differences between model predictor combinations and lack of important methodological information. CONCLUSIONS: Numerous models are used to predict diabetes, and as there is an association between prediabetes and diabetes, researchers have also used such models for screening the prediabetic population. Although it is a new clinical practice to explore, differences in glycaemic metabolic profiles, potential complications, and methods of intervention between the two populations cannot be ignored, and such differences have led to poor validity and accuracy of the models. Therefore, there is no recommended optimal model, and it is not recommended to use existing models for risk identification in alternative populations; future studies should focus on improving the clinical relevance and predictive performance of existing models.

Prenatal Exposure to Heavy Metals and Adverse Birth Outcomes: Evidence From an E-Waste Area in China.

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 (ß = -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.

Associations between maternal occupational exposures and pregnancy outcomes among Chinese nurses: a nationwide study.

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.

MtDNA Copy Number in Oral Epithelial Cells Serves as a Potential Biomarker of Mitochondrial Damage by Neonicotinoid Exposure: A Cross-Sectional Study.

As the mitochondrial DNA copy number (mtDNAcn) has been reported to be a biomarker for mtDNA damage in honeybees when exposed to sublethal neonicotinoids, the feasibility of using human mitochondria as a predictor upon neonicotinoid exposure remains elusive. This study investigated the association between the urinary neonicotinoid and the relative mtDNAcn (RmtDNAcn) of oral epithelial cells collected in a cross-sectional study with repeated measurements over 6 weeks. The molecular mechanism underlying neonicotinoid-caused mitochondrial damage was also examined by in vitro assay. Herein, the average integrated urinary neonicotinoid (IMIRPF) concentration ranged from 8.01 to 13.70 µg/L (specific gravity-adjusted) during the sampling period. Concomitantly, with an increase in the urinary IMIRPF, the RmtDNAcn significantly increased from 1.20 (low group) to 1.93 (high group), indicating potential dose-dependent mitochondrial damage. Furthermore, the linear regression analysis confirmed the significant correlation between the IMIRPF and RmtDNAcn. Results from in vitro assays demonstrated that neonicotinoid exposure led to the inhibition of the genes encoding mitochondrial oxidative phosphorylation (OXPHOS) complexes I and III (e.g., ND2, ND6, CytB, and CYC1), accompanied by increased reactive oxygen species production in SH-SY5Y cells. Conjointly, neonicotinoid exposure led to mitochondrial dysfunction and a resulting increase in the RmtDNAcn, which may serve as a plausible biomarker in humans.

The prevalences and levels of occupational exposure to dusts and/or fibres (silica, asbestos and coal): A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

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.

Performance of a prediabetes risk prediction model: A systematic review.

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.

Hexavalent chromium [Cr(VI)]-induced ribosomal DNA copy number variation and DNA damage responses and their associations with nucleolar protein HRAS in humans and cells.

The carcinogenicity of hexavalent chromium [Cr(VI)] and its compounds has been widely recognized, yet the mechanism of genetic damage is still not fully understood. The ribosomal DNA (rDNA) copy number is recently considered a potential marker of cancer-associated stress. To investigate the roles of rDNA copy number variation (CNV) in DNA damage responses (DDRs) induced by Cr(VI) and the potential mechanism from nucleolar protein HRAS, a cross-sectional study in Cr(Ⅵ)-exposed workers and an in vitro experiment using HeLa cells were conducted. Our results showed increased levels of rDNA CNV, DDRs, and HRAS expression in Cr(VI)-exposed workers. Generalized linear regression analyses showed that Cr(VI) exposure was significantly positively associated with increased levels of rDNA CNV, DDRs, and HRAS expression in Cr(VI)-exposed workers. Moreover, there were pairwise associations between rDNA CNV, DDRs, and HRAS levels. Mediation analyses found that rDNA CNV significantly mediated the association between Cr(VI) exposure and DDRs. The in vitro experiments further confirmed that Cr(VI) treatment induced increased levels of rDNA CNV, DDRs, and HRAS expression in HeLa cells. Cr(VI)-induced rDNA CNV, ATM activation, and apoptosis damage were then strongly enhanced by HRAS depletion with siRNA in vitro, suggesting the important role of HRAS in CNV and DDRs caused by Cr(VI). The combined results of the human and cell line studies indicated that Cr(VI) exposure might enhance rDNA CNV by regulation of HRAS expression, which leads to Cr(VI)-induced genetic damage.

Multiple exposures to heavy metals and changes in steroid hormones production in 4-year-old children.

BACKGROUND: Prenatal exposure to multiple heavy metals can interfere with early neurodevelopment, lead to changes in sex hormone concentrations in children, and affect female reproductive health. To date, the influence of prenatal exposure to heavy metals on the endocrine system of children in Chinese electronic waste (e-waste) recycling areas has not been elucidated. METHODS: Four weeks after delivery, 10 mL of human milk was collected for analysis of three heavy metals (lead (Pb), cadmium (Cd), and mercury (Hg)) via inductively coupled plasma mass spectrometry (ICP-MS). Four serum steroid hormones, including progesterone, testosterone, androstenedione (A-dione), and dehydroepiandrosterone (DHEA), were analyzed in 4-year-old children (25 boys and 17 girls). A multiple linear regression (MLR) model was implemented to investigate the association between each individual metal and serum steroid hormone. The exposure-response relationships were explored by generalized additive models (GAMs). Additionally, a Bayesian kernel machine regression (BKMR) model was used to assess the effects of multiple heavy metal exposures on each steroid hormone. RESULTS: The MLR results show a significant positive association between a natural log unit increase in Hg and DHEA levels after adjusting for confounders (ß = 65.50, 95% confidence interval (CI) = 4.37, 126.62). According to the GAM, the univariate exposure-response relationship of Hg on DHEA was almost linear. However, this association was attenuated based on the multiple metal MLR and BKMR results after accounting for multiple heavy metal exposures. SIGNIFICANCE: Prenatal Hg exposure may affect sex hormones in children by affecting DHEA levels. IMPACT STATEMENT: Prenatal maternal exposure to Hg may have long-term effects on the next generation. Hence, regulatory measures to reduce Hg exposure and long-term monitoring of children's health in e-waste areas are needed.

Occurrence, distribution and potential risk to infants of neonicotinoids in breast milk: A case study in Hangzhou, China.

The pervasive use of neonicotinoid insecticides (neonics) has led to increasing concerns regarding the potential health risks associated with them. Breast milk is the main food source of infants, and thus, the presence of chemicals in breast milk has a greater impact on infant health. However, there have only been few reports regarding the presence of neonics in breast milk. Herein, eight neonics were detected in breast milk samples using ultraperformance liquid chromatography-mass spectrometry and their Pearson correlation was analyzed. The potential health risks of neonics to infants were assessed using the relative potency factor (RPF) method. The results revealed that neonics were widely detected in the breast milk samples from Hangzhou, with at least one neonics being detected in >94 % of the breast milk samples. The most frequently detected neonics included thiamethoxam (70.8 %) followed by imidacloprid (IMI) (62.0 %) and clothianidin (46.0 %). The residual concentrations of neonics in the breast milk samples ranged from

Occupational hazards and the onset of natural menopause.

OBJECTIVE: To identify occupational hazards associated with earlier onset of natural menopause. STUDY DESIGN: A national cross-sectional study was conducted to explore the reproductive health of Chinese female workers. The final sample size was 17,948. MAIN OUTCOME MEASURES: Participants completed a self-report instrument that recorded working conditions, chemical and physical agents in the occupational environment, socioeconomic factors, lifestyle, reproductive history, and occupational information. A Cox regression model was used to examine the association between each occupational hazard and onset of menopause. RESULTS: Abnormal workload (19.31 %), aromatic compounds (7.95 %), and noise (24.94 %) were the three most frequently self-reported occupational hazards in the three categories of working conditions, chemical agents, and physical agents, respectively. Abnormal workload (HR = 1.133, p = 0.038), noise (HR = 1.233, p < 0.001), and heat stress (HR = 1.178, p = 0.041) were associated with earlier age at natural menopause in the analyses of each hazard, after adjustment. Only noise (HR = 1.187, p = 0.003) remained statistically significant after including all possible occupational hazards. CONCLUSIONS: In a national survey of 17,948 female workers, this study investigated the association of age at natural menopause with multiple occupational hazards, some of which have not been addressed. Occupational noise was identified as a risk factor for reproductive senescence for the first time. However, further research is needed to confirm our findings.

Partitioning behavior-oriented health risk assessment on internal organophosphorus flame retardants exposure.

Though the partitioning behavior of organophosphorus flame retardants (OPFRs) has been recognized in vitro incubation assay, health risk assessment on those internal exposure with or without partitioning indexes in human blood is still unclear. In this study, nine commonly used OPFRs were quantified in 96 pairs of plasma and blood cell samples from Chinese volunteers. Non-carcinogenic and carcinogenic risk (CR) assessment building upon two distinct scenarios were conducted and compared. The dominant OPFRs in both plasma and blood cells were TBEP, TBP and TPHP. TCEP was the most enriched compound in plasma with Fplasma nearly to 1.0 (0.92), followed by TCPP, TBEP, TPHP, TBP and TEHP (from 0.61 to 0.76). The partitioning behavior of TCP in plasma was equivalent to blood cells with Fplasma at 0.50. When fully considered the Fplasma, the estimated average daily intake (DI) of ∑OPFRs (638.44 ng/kg BW/day) reached nearly 1.48-fold higher than the conventional calculation (dividing the concentration of plasma (Cplasma) by a factor of 2.0). Accordingly, we found the average hazard quotation (index) of TBP, TPHP and ∑OPFRs was underrated 1.50-fold when neglected the partitioning behaviors. Notably, the average CR of TCEP exceeded 10-6 at the highest concentration (1.19 × 10-6 ng/mL in plasma) only when the Fplasma was introduced. These data conjointly demonstrated that most of the DI levels and the corresponding risk index of OPFRs would be underestimated without factoring Fplasma into calculation, especially for those of low plasma partitioning. To our best knowledge, this study initially uncovered the gap between introducing Fplasma and dividing Cplasma by 2.0 during health risk assessment on internal OPFRs exposure.

Dosimetric advantages of robust optimization combined with flattening filter free in treating cancer of the left breast.

OBJECTIVE: By comparing the target dose distribution with or without the robust optimization, the dosimetric advantages of robust optimization and flattening filter free (FFF) in radiation therapy for postmastectomy cancer of the left breast was explored when part of the chest wall target was moved out in case of respiratory motion. MATERIALS AND METHODS: This is a retrospective study. The data of 21 postmastectomy patients with cancer of the left breast from 2019 to 2020 were retrospectively collected. The planned target volume (PTV) dose was prescribed 50 Gy/25 fractions and the treatment plans were designed using 6 MV FFF X ray and volumetric modulated arc therapy (VMAT) technology in RayStation treatment planning system (TPS), with and without robust optimization. The movement of the target area of the internal chest wall (0.50 cm) caused by respiratory movement was simulated by moving the isocenter of the beams. RESULTS: When the chest wall target moved outward, the PTV target area D98, D95, D2, conformity index (CI) and homogeneity index (HI) with robust optimization were better than those without robust optimization. The coverage rate of Planned Target Volume-Chest (PTV-T) V50 with robust optimization was significantly higher than that with no-robust optimization (P<0.001). Clinical target volume (CTV) V50 coverage with robust optimization was 14.49% higher than that with no-robust optimization. In terms of organ-at-risk parameters, the average spinal cord dose of the plan with robust optimization was 13.19% lower than that of the plan with no-robust optimization, and the Lung-L V5 of the plan with no-robust optimization was slightly (1.94%) lower than that of the plan with robust optimization. There was no significant difference in machine execution efficiency between the two groups (P>0.05). CONCLUSIONS: Robust optimization could be adopted in the postoperative radiotherapy planning for cancer in the left breast, for it ensures that the target dose coverage and the dose limit of organ-at-risk still meet the clinical requirements under condition of chest wall displacement caused by respiratory movement.