Associations among neighborhood walkability, metal exposure, and sex steroid hormone levels: Results from Hangzhou Birth Cohort Study â ¡.

BACKGROUND: Neighborhood walkability may influence maternal-fetal exposure to environmental hazards and maternal-fetal health (e.g., fetal growth restriction, reproductive toxicity). However, few studies have explored the association between neighborhood walkability and hormones in pregnant women. METHODS: We included 533 pregnant women from the Hangzhou Birth Cohort Study II (HBCS-II) with testosterone (TTE) and estradiol (E2) measured for analysis. Neighborhood walkability was evaluated by calculating a walkability index based on geo-coded addresses. Placental metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). TTE and E2 levels in umbilical cord blood were measured using chemiluminescence microparticle immunoassay (CMIA). Linear regression model was used to estimate the relationship between the walkability index, placental metals, and sex steroid hormones. Effect modification was also assessed to estimate the effect of placental metals on the associations of neighborhood walkability with TTE and E2. RESULTS: Neighborhood walkability was significantly linked to increased E2 levels (P trend=0.023). Compared with participants at the first quintile (Q1) of walkability index, those at the third quintiles (Q3) had lower chromium (Cr) levels (ß = -0.212, 95% CI = -0.421 to -0.003). Arsenic (As), cobalt (Co), manganese (Mn), molybdenum (Mo), nickel (Ni), lead (Pb), antimony (Sb), selenium (Se), tin (Sn), and vanadium (V) were linked to decreased TTE levels, and cadmium (Cd) was linked to increased TTE levels. No metal was significantly associated with E2 levels in trend analysis. In the analysis of effect modification, the associations of neighborhood walkability with TTE and E2 were significantly modified by Mn (P = 0.005) and Cu (P = 0.049) respectively. CONCLUSION: Neighborhood walkability could be a favorable factor for E2 production during pregnancy, which may be inhibited by maternal exposure to heavy metals.

Occupational Hearing Loss Associated With Non-Gaussian Noise: A Systematic Review and Meta-analysis.

OBJECTIVES: Epidemiological characteristics of occupational noise-induced hearing loss (NIHL) associated with non-Gaussian noise are still unclear and have been rarely reported in the literature. METHODS: The relationships between non-Gaussian noise exposure and occupational NIHL were analyzed based on the published papers. Systematic review and meta-analysis of epidemiological studies were performed. RESULTS: Of 78 epidemiological studies (47,814 workers) selected, there were seven cohort studies and 71 cross-sectional studies. The incidence of high-frequency NIHL (HFNIHL) and speech-frequency NIHL (SFNIHL) in the seven cohort studies was 10.9 and 2.9%, respectively. In 71 cross-sectional studies, the prevalence of HFNIHL and SFNIHL was 34.2 and 18.9%, respectively. The average hearing threshold level at the high frequencies was 42.1 ± 17.4 dB HL. Workers exposed to non-Gaussian noise had a higher risk of developing HFNIHL than those not exposed to noise (overall-weighted odds ratio [OR] = 4.46) or those exposed to Gaussian noise (overall-weighted OR = 2.20). The Chi-square trend test demonstrated that the prevalence of HFNIHL was positively correlated with age, cumulative noise exposure, and exposure duration (p < 0.001). CONCLUSIONS: Workers exposed to non-Gaussian noise suffered from greater NIHL than those exposed to Gaussian noise or not exposed to noise. Age, exposure duration, noise level, and noise temporal structure were the main risk factors for occupational NIHL. The A-weighted equivalent continuous sound pressure level (LAeq) is not a sufficient measurement metric for quantifying non-Gaussian noise exposure, and a combination of kurtosis and noise energy metrics (e.g., LAeq) should be used. It is necessary to reduce the exposure of non-Gaussian noise to protect the hearing health of workers.

New Metrics Needed in the Evaluation of Hearing Hazard Associated With Industrial Noise Exposure.

OBJECTIVES: To evaluate (1) the accuracy of the International Organization for Standardization (ISO) standard ISO 1999 [(2013), International Organization for Standardization, Geneva, Switzerland] predictions of noise-induced permanent threshold shift (NIPTS) in workers exposed to various types of high-intensity noise levels, and (2) the role of the kurtosis metric in assessing noise-induced hearing loss (NIHL). DESIGN: Audiometric and shift-long noise exposure data were acquired from a population (N = 2,333) of screened workers from 34 industries in China. The entire cohort was exclusively divided into subgroups based on four noise exposure levels (85 ≤ LAeq.8h < 88, 88 ≤ LAeq.8h < 91, 91 ≤ LAeq.8h < 94, and 94 ≤ LAeq.8h ≤ 100 dBA), two exposure durations (D ≤ 10 years and D > 10 years), and four kurtosis categories (Gaussian, low-, medium-, and high-kurtosis). Predicted NIPTS was calculated using the ISO 1999 model for each participant and the actual measured NIPTS was corrected for age and sex also using ISO 1999. The prediction accuracy of the ISO 1999 model was evaluated by comparing the NIPTS predicted by ISO 1999 with the actual NIPTS. The relation between kurtosis and NIPTS was also investigated. RESULTS: Overall, using the average NIPTS value across the four audiometric test frequencies (2, 3, 4, and 6 kHz), the ISO 1999 predictions significantly (p < 0.001) underestimated the NIPTS by 7.5 dB on average in participants exposed to Gaussian noise and by 13.6 dB on average in participants exposed to non-Gaussian noise with high kurtosis. The extent of the underestimation of NIPTS by ISO 1999 increased with an increase in noise kurtosis value. For a fixed range of noise exposure level and duration, the actual measured NIPTS increased as the kurtosis of the noise increased. The noise with kurtosis greater than 75 produced the highest NIPTS. CONCLUSIONS: The applicability of the ISO 1999 prediction model to different types of noise exposures needs to be carefully reexamined. A better understanding of the role of the kurtosis metric in NIHL may lead to its incorporation into a new and more accurate model of hearing loss due to noise exposure.

Associations between prenatal metal exposure and growth rate in children: Based on Hangzhou Birth Cohort Study.

BACKGROUND: It has been reported that prenatal metal exposure is associated with child anthropometry. However, studies focusing on the growth rate of anthropometry among children have not been conducted. This study aimed to examine associations between the exposure of multiple metals during pregnancy and the growth rate of anthropometry among offspring. METHODS: 743 mother-child pairs from the Hangzhou Birth Cohort Study (HBCS) were included. Levels of eleven metals in mother's blood during pregnancy were measured. Offspring had a mean of 5.7 measurements on anthropometric indicators including weight, length/height, head circumference, and body mass index (BMI) within 1.5 years of birth. Generalized estimating equation (GEE) model was used to investigate the associations between maternal metal exposure and growth rate of anthropometric indicators in children. Stratification analysis by sex was also examined. RESULTS: Levels of selenium (Se, ß = 0.213, 95 % CI = 0.017 to 0.409, P = 0.033) were positively associated with length/height gain per month in children. Levels of chromium (Cr, ß = 0.025, 95 % CI = 0.018 to 0.033, P < 0.001) were positively associated with the rate of weight gain. Levels of manganese (Mn, ß = -0.030, 95 % CI = -0.052 to -0.008, P = 0.009) and cobalt (Co, ß = -0.012, 95 % CI = -0.024 to -0.000, P = 0.044) were inversely associated with growth rate of head circumference. Children with higher maternal Mn levels had a lower BMI change rate. Associations between metals and growth rate were stronger in girls than in boys. Besides, significant associations between metal mixtures and growth rate were found. CONCLUSION: Prenatal exposure to Se, Cr, Mn, and Co was associated with growth rate in children, with sex-specific disparities. Our results suggested important effects of maternal exposure to multiple metals on development in offspring.

Occupational health risk assessment methods in China: A scoping review.

Background: Over the decades, many assessment methods have been developed around the world and used for occupational health risk assessment (OHRA). This scoping review integrated the literature on methodological studies of OHRA in China and aimed to identifies the research hot-spots and methodological research perspectives on OHRA in China. Methods: A scoping review of literature was undertaken to explore the research progress on OHRA methods in China. Focusing on OHRA methods, the authors systematically searched Chinese and English databases and relevant guideline websites from the date of establishment to June 30, 2022. Databases included Web of Science, PubMed, Scopus, the China National Knowledge Internet, WanFang Database. Some other websites were also searched to obtain gray literature. The extracted information included the author, year, region of first author, the target industry, risk assessment model, study type, the main results and conclusions. Results: Finally, 145 of 9,081 studies were included in this review. There were 108 applied studies, 30 comparative studies and 7 optimization studies on OHRA in China. The OHRA methods studied included: (1) qualitative methods such as Romanian model, Australian model, International Council on Mining and Metals model, and Control of Substances Hazardous to Health Essentials; (2) quantitative methods such as the U. S. Environmental Protection Agency inhalation risk assessment model, Physiologically Based Pharmacokinetic, and Monte Carlo simulation; (3) semi-quantitative methods such as Singapore model, Fuzzy mathematical risk assessment model, Likelihood Exposure Consequence method and Occupational Hazard Risk Index assessment method; (4) comprehensive method (Chinese OHRA standard GBZ/T 298-2017). Each of the OHRA methods had its own strengths and limitations. In order to improve the applicability of OHRA methods, some of them have been optimized by researchers. Conclusions: There is a wide range of OHRA methods studied in China, including applied, comparative, and optimization studies. Their applicability needs to be further tested through further application in different industries. Furthermore, quantitative comparative studies, optimization studies, and modeling studies are also needed.

Epidemiological characteristics and survival analysis on patients with occupational pneumoconiosis in Zhejiang Province from 1987 to 2019.

Objective: To evaluate risk factors affecting survival in patients diagnosed with pneumoconiosis and propose strategies to improve the quality of life in these patients. Methods: The basic patient information was obtained from the pneumoconiosis report card. Disease types, regions, and industry distribution of pneumoconiosis were analyzed. The Kaplan-Meier survival curves and the Cox proportional risk regression model was used for survival analysis. Results: A total of 13,812 patients were diagnosed with pneumoconiosis in Zhejiang province from 1987 to 2019. The overall survival rate at the end of life table analysis was 83%. Kaplan-Meier analyses showed that there were significant differences between survival curves depending on the stage of first diagnosis, age at first diagnosis, type of pneumoconiosis, industry, and duration of dust exposure (P < 0.05). The results of Cox proportional hazards regression analysis showed that pneumoconiosis stage of first diagnosis, age at first diagnosis, industry, and duration of dust exposure were risk factors affecting patient survival (P < 0.05). Conclusions: The patients with high stage of pneumoconiosis at first diagnosis, older age, and long duration of dust exposure should be followed up and monitored as key population, and the industries with high incidence of pneumoconiosis such as mining and construction should be supervised as key industries.

Epidemiological characteristics of hearing loss associated with noise temporal structure among manufacturing workers.

Objective: This study aimed to investigate the epidemiological characteristics of occupational noise-induced hearing loss (NIHL) among manufacturing workers, and to provide evidence for diagnosing and preventing occupational hearing loss caused by complex noise, which is different from Gaussian noise in temporal structure. Methods: One thousand and fifty manufacturing workers exposed to occupational noise were recruited in a cross-sectional survey. Exposure characteristics and epidemiological distribution of hearing loss and noise exposure metrics (noise energy and kurtosis) were investigated, and the relationship between noise exposure and hearing loss was analyzed. The effects of kurtosis on hearing threshold shift across different frequencies and on NIHL development with exposure duration and noise intensity were also investigated. Results: Each type of work had specific noise exposure metrics. Noise intensity and kurtosis were independent parameters (r = -0.004, p = 0.885). The prevalence of NIHL and the hearing threshold level had a specific distribution in different types of work. Kurtosis deepened the hearing notch at high frequencies and accelerated the formation of early hearing loss. The effect of exposure duration and noise intensity on the prevalence of high-frequency NIHL (i.e., at 3, 4, 6, and 8 kHz) for manufacturing workers increased with kurtosis in workers with noise exposure duration of less than 10 years and with LAeq.8h between 80 and 90 dB(A). Male (OR = 1.557, 95%CI = 1.141-2.124), age (OR = 1.033, 95%CI = 1.014-1.052), exposure duration (OR = 1.072, 95%CI = 1.038-1.107), kurtosis (OR = 1.002, 95%CI = 1.001-1.003), and noise intensity (LAeq.8h; OR = 1.064, 95%CI = 1.044-1.084) were risk factors for high-frequency NIHL. The speech-frequency NIHL (i.e., at 0.5, 1, and 2 kHz) risk of workers exposed to manufacturing noise was related to age (OR = 1.071, 95%CI = 1.043-1.100). There were no statistically significant associations between speech-frequency NIHL and sex, noise exposure duration, kurtosis, and noise intensity (LAeq.8h). Conclusion: The high-frequency NIHL prevalence among manufacturing workers is associated with sex, age, exposure duration, noise intensity, and temporal structure of noise, while the speech-frequency NIHL prevalence is associated with age. Kurtosis strengthens the association of noise exposure duration and noise intensity with high-frequency hearing loss. The influence of noise temporal structure should be considered in the diagnosis and early prevention of occupational hearing loss caused by complex noise.

The Sonic Hedgehog signaling pathway regulates autophagy and migration in ovarian cancer.

BACKGROUND: The Sonic Hedgehog (SHH) signaling pathway plays an important role in various types of human cancers including ovarian cancer; however, its function and underlying mechanism in ovarian cancer are still not entirely understood. METHODS: We detected the expressions of SHH and SQSTM1 in borderline ovarian tumor tissues, epithelial ovarian cancer (EOC) tissues and benign ovarian tumor tissues. Cyclopamine (Cyp, a well-known inhibitor of SHH signaling pathway) and chloroquine (CQ, the pharmaceutical inhibitor of autophagy) were used in vivo and in vitro (autophagic flux, CCK-8 assay, wound healing assay, transwell assay, tumor xenograft model). The mechanism of action was explored through Quantitative RT-PCR and Western Blot. RESULTS: We found up-regulation of SHH and accumulation of SQSTM1/P62 in epithelial ovarian cancer. Cyp induced autophagy through the PI3K/AKT signaling pathway. Moreover, low-dose Cyp and chloroquine (CQ) significantly promoted the migratory ability of SKOV3 cells. CONCLUSIONS: Our findings suggest that inhibition of the SHH pathway and autophagy may be a potential and effective therapy for the treatment of ovarian cancer.

Hormone Replacement Therapy Reverses Gut Microbiome and Serum Metabolome Alterations in Premature Ovarian Insufficiency.

Objective: We explored the gut microbiome and serum metabolome alterations in patients with premature ovarian insufficiency (POI) and the effects of hormone replacement therapy (HRT) with the aim to unravel the pathological mechanism underlying POI. Methods: Fecal and serum samples obtained from healthy females (HC, n = 10) and patients with POI treated with (n = 10) or without (n = 10) HRT were analyzed using 16S rRNA gene sequencing and untargeted metabolomics analysis, respectively. Peripheral blood samples were collected to detect serum hormone and cytokine levels. Spearman's rank correlation was used to evaluate correlations between sex hormones and cytokines and between the gut microbiota and serum metabolites. To further confirm the correlation between Eggerthella and ovarian fibrosis, the mice were inoculated with Eggerthella lenta (E. lenta) through oral gavage. Results: The abundance of genus Eggerthella significantly increased in the fecal samples of patients with POI compared to that observed in the samples of HCs. This increase was reversed in patients with POI treated with HRT. Patients with POI showed significantly altered serum metabolic signatures and increased serum TGF-ß1 levels; this increase was reversed by HRT. The abundance of Eggerthella was positively correlated with altered metabolic signatures, which were, in turn, positively correlated with serum TGF-ß1 levels in all subjects. Estrogen ameliorated ovarian fibrosis induced by E. lenta in mice. Conclusions: The interactions between the gut microbiota, serum metabolites, and serum TGF-ß1 in patients with POI may play a critical role in the development of POI. HRT not only closely mimicked normal ovarian hormone production in patients with POI but also attenuated gut microbiota dysbiosis and imbalance in the levels of serum metabolites and TGF-ß1, which are reportedly associated with fibrosis. The findings of this study may pave the way for the development of preventive and curative therapies for patients with POI.

Occupational noise-induced hearing loss in China: a systematic review and meta-analysis.

OBJECTIVE: Most of the Chinese occupational population are becoming at risk of noise-induced hearing loss (NIHL). However, there is a limited number of literature reviews on occupational NIHL in China. This study aimed to analyse the prevalence and characteristics of occupational NIHL in the Chinese population using data from relevant studies. DESIGN: Systematic review and meta-analysis. METHODS: From December 2019 to February 2020, we searched the literature through databases, including Web of Science, PubMed, MEDLINE, Scopus, the China National Knowledge Internet, Chinese Sci-Tech Journal Database (weip.com), WanFang Database and China United Library Database, for studies on NIHL in China published in 1993-2019 and analysed the correlation between NIHL and occupational exposure to noise, including exposure to complex noise and coexposure to noise and chemicals. RESULTS: A total of 71 865 workers aged 33.5±8.7 years were occupationally exposed to 98.6±7.2 dB(A) (A-weighted decibels) noise for a duration of 9.9±8.4 years in the transportation, mining and typical manufacturing industries. The prevalence of occupational NIHL in China was 21.3%, of which 30.2% was related to high-frequency NIHL (HFNIHL), 9.0% to speech-frequency NIHL and 5.8% to noise-induced deafness. Among manufacturing workers, complex noise contributed to greater HFNIHL than Gaussian noise (overall weighted OR (OR)=1.95). Coexposure to noise and chemicals such as organic solvents, welding fumes, carbon monoxide and hydrogen sulfide led to greater HFNIHL than noise exposure alone (overall weighted OR=2.36). Male workers were more likely to experience HFNIHL than female workers (overall weighted OR=2.26). Age, noise level and exposure duration were also risk factors for HFNIHL (overall weighted OR=1.35, 5.63 and 1.75, respectively). CONCLUSIONS: The high prevalence of occupational NIHL in China was related to the wide distribution of noise in different industries as well as high-level and long-term noise exposure. The prevalence was further aggravated by exposure to complex noise or coexposure to noise and specific chemicals. Additional efforts are needed to reduce occupational noise exposure in China.

Short-term recurrence and distant metastasis following robotic-assisted radical hysterectomy with pelvic lymphadenectomy and chemoradiotherapy for a stage IB1 cervical adenocarcinoma: A case report and literature review.

RATIONALE: Postoperative concurrent chemoradiotherapy (CCRT) is considered the standard treatment for patients with early stage cervical cancer with positive pelvic nodes, yet many patients with high-risk factors treated with CCRT still suffered from distant metastasis. PATIENT CONCERNS: A 48-year-old woman presented with abnormal vaginal bleeding for 5 months. Thin prep liquid-based cytology test revealed low-grade squamous intraepithelial lesion and the human papillomavirus test (type 58) was positive. Magnetic resonance imaging showed a mass measuring 17 × 15 mm, located predominantly in the posterior lip of uterine cervix. Colposcopy biopsy reported adenocarcinoma of the cervix. DIAGNOSIS: Cervical adenocarcinoma stage IB1. INTERVENTIONS: A robotic-assisted radical hysterectomy with pelvic lymphadenectomy was performed followed by postoperative CCRT. OUTCOMES: Distant metastasis was occurred shortly after postoperative CCRT and the patient died 9 months from initial diagnosis. LESSONS: In cases of new nodule in bones, lower abdominal distension and bloating occurring shortly after CCRT in early stage cervical adenocarcinoma, clinicians should bear in mind that recurrence should be considered. Development of more effective treatment to improve the survival outcomes of patients with postoperative metastasis is needed.

All-trans retinoic acid enhances cytotoxicity of CIK cells against human lung adenocarcinoma by upregulating MICA and IL-2 secretion.

To determine the growth inhibition capability of all-trans retinoic acid (ATRA) with cytokine-induced killer cells (CIKs), we evaluated their effects, alone and in combination, on human lung carcinoma A549 cells. CIKs treated with ATRA significantly inhibited cell growth. Additionally, CIK with ATRA synergistically inhibited migration and invasiveness, colony formation of A549 and NCI-H520 cells. Furthermore, analysis of apoptosis markers Bcl-2, Bax, Survivin and cleaved Caspase-3 showed that Bcl-2 and Survivin mRNA levels significantly decreased, and that Bax mRNA significantly increased, in the CIK + ATRA-treated cells, with corresponding effects on their respective proteins. The involved mechanisms may be associated with upregulated expression of MHC class I-Related Chain (MICA) and interleukin (IL)-2. These results suggest that administration of combined CIK and ATRA is a potentially novel treatment for lung carcinoma.