Association between per- and polyfluoroalkyl substances and sex hormone levels in males based on human studies.

BACKGROUND: Per- and poly-fluoroalkyl substances (PFAS) are ubiquitous chemicals in the environment and our daily lives. Several epidemiological studies have revealed that PFAS exposure is linked to male sex hormone levels; however, the conclusions are inconsistent across studies. Consequently, we performed a meta-analysis to systematically evaluate the association between PFAS exposure and male sex hormones. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) standards were followed during the meta-analysis. PubMed, Wed of Science, Embase, Cochrane Library, and Ovid databases were used to identify suitable articles before June 2023. The 95% CI and ß values were calculated to assess the association between male sex hormone levels and PFAS exposure. Heterogeneity among the included studies was tested using inconsistency statistics (I2). RESULTS: The literature search identified 12 published articles that met our search criteria, involving 7506 participants. Our results revealed that perfluorononanoic acid (PFNA) and perfluorooctanoic acid (PFOA) exposures were negatively correlated with testosterone (ß = -0.05; 95% CI: -0.09, -0.02, P = 0.003) and (ß = -0.04; 95% CI: -0.08, 0.00, P = 0.049), respectively. CONCLUSION: Exposure to PFNA and PFOA is negatively correlated with changes in male testosterone levels. This correlation suggests that we need to pay attention in the future to whether they are potential risk factors for male reproductive health.

Shift patterns, physical exercise, and Type 2 diabetes mellitus (T2DM): a prospective cohort study in China.

To examine the relationships between different shift patterns and Type 2 diabetes mellitus (T2DM) risk, and determine whether physical exercise reduced the incidence of T2DM in shift workers in the oil industry. Baseline data were collected from participants in May 2013 who were then followed for 4 years in a prospective cohort study. The cohort initially consisted of 3,002 workers and ultimately included 2,827 people. Baseline and follow-up questionnaires were sent to participants every 2 years (in May 2015 and May 2017) to update medical and lifestyle information during the follow-up period. The risk of T2DM among two shift workers [relative risk (RR) = 3.442, 95% CI: 1.904-6.799)], three shift workers (RR = 2.534, 95% CI: 1.484-4.571), and four shift workers (RR = 4.230, 95% CI: 2.680-7.518) was higher than that among day workers. An increasing trend was observed with respect to T2DM risk, with the lowest risk in three shift workers, moderate risk in two shift workers, and highest risk in four shift workers. In the interactive analysis between shift work and physical exercise, taking part in mild physical exercise increased the risk of T2DM for workers. Four shift workers who took part in mild physical exercise had an increased risk of T2DM. The relative excess risk due to interaction (RERI) was 33.769 (0.398-67.140). The attributable proportion due to interaction [API (%)] was 0.704 (0.529-0.880). The synergy index (SI) was 3.563 (1.900-6.683). Shift work is significantly correlated with increased incidence of T2DM. Risk of T2DM is lowest risk in three shift workers, moderate in two shift workers, and highest in four shift workers. Shift workers who participated in moderate and severe physical exercise had reduced risk of developing T2DM.

This study investigated the role of different shift patterns and physical exercise on type 2 diabetes mellitus (T2DM) risk factors of shift workers. We hypothesized that shift patterns would be correlated with the incidence of type 2 diabetes and that physical exercise would reduce the risk of type 2 diabetes. We studied 2,827 workers using a cohort study design following for 4 years. The study sample consisted of 1,249 fixed-day-shift workers, 650 three-shift workers, 297 two-shift workers, and 631 four-shift workers. We found that compared with fixed day shift workers, alternating shift workers were at an increased risk for developing T2DM. And moderate and severe physical exercise reduced the risk of T2DM in shift workers. We concluded that physical exercise is associated with decreased type 2 diabetes risk in shift workers, particularly when physical exercise is moderate and severe. The findings of the current study may assist enterprise management departments in developing diabetes interventions among shift workers.

The relationships of shift work, hair cortisol concentration and dyslipidaemia: a cohort study in China.

BACKGROUND: Currently, cardiovascular disease is the leading cause of death, and dyslipidaemia is an independent and modifiable major risk factor. Previous studies on shift work with dyslipidaemia and hair cortisol concentration (HCC) have yielded conflicting results. The aim of this study was to clarify the association between shift work, dyslipidaemia, and HCC. We further explored the mediating effect of HCC. METHODS: In this cohort study, baseline data were collected from participants in May 2013. The cohort included 2170 participants- 1348 shift workers and 822 non-shift workers- who were followed up for 6 years with four questionnaire surveys from July 2014, October 2015, and May to December 2019. Hair samples were collected from 340 participants during the baseline period for HCC testing with an automated radioimmunoassay. Dyslipidaemia was defined using the National Cholesterol Education Program Adult Treatment Panel III diagnostic criteria. RESULTS: Shift workers had a higher risk of dyslipidaemia than workers on the fixed day shift (two-shift RR = 1.408, 95% CI: 1.102-1.798; three-shift RR = 1.478, 95% CI: 1.134-1.926; four-shift RR = 1.589, 95% CI: 1.253-2.015). Additionally, shift workers had higher HCC levels than fixed day shift workers, with geometric mean concentration (GMC) ± geometric standard difference (GSD) = 2.625 ± 2.012 ng/g, two-shift GMC ± GSD = 3.487 ± 1.930 ng/g, three-shift GMC ± GSD = 2.994 ± 1.813 ng/g, and four-shift GMC ± GSD = 3.143 ± 1.720 ng/g. High HCC was associated with a high incidence of dyslipidaemia. After controlling for confounding factors, this study showed that HCC played a role in mediating dyslipidaemia in shift workers and accounted for 16.24% of the effect. CONCLUSIONS: Shift work was linked to increased risk of dyslipidaemia compared with fixed day shift work. Higher HCC was associated with a higher prevalence of dyslipidaemia. HCC had a significant mediating effect on dyslipidaemia in shift workers.

Association between sleep disorders and shift work: a prospective cohort study in the Chinese petroleum industry.

Objective. This study aimed to understand the prevalence of sleep disorders among shift workers and analyze the relationship between sleep disorders and shift work. Methods. Baseline data were collected from subjects who were then followed for 2 years in a prospective cohort study. The cohort ultimately included 2453 people starting in May 2013, and follow-up with questionnaires was performed in July 2014 and October 2015. Sleep disorders were assessed with the Pittsburgh sleep quality index. Results. The risk of sleep disorders among two-shift workers (relative risk [RR] = 1.318, 95% confidence interval [CI] [1.025, 1.695]), three-shift workers (RR = 1.326, 95% CI [1.048, 1.679]) and four-shift workers (RR = 1.334, 95% CI [1.062, 1.675]) was higher than that among non-shift workers, and an increasing trend was observed in sleep disorders as the number of shifts increased. Conclusions. Shift workers have a higher incidence of sleep disorders than non-shift workers. An increasing linear trend was observed between the number of shifts and sleep disorders. In the petroleum industry, it is necessary to decrease the frequency of shifts to reduce the incidence of sleep disorders among shift workers.

Relationships among N,N-dimethylformamide exposure, CYP2E1 and TM6SF2 genes, and non-alcoholic fatty liver disease.

OBJECTIVE: This study aimed to examine the relationships among N, N-dimethylformamide (DMF) exposure, cytochrome P4502E1 (CYP2E1) single nucleotide polymorphisms (SNPs) (rs2031920, rs3813867, rs6413432), transmembrane 6 superfamily member 2 (TM6SF2) SNP rs58542926 and non-alcoholic fatty liver disease (NAFLD). METHODS: Baseline data were collected from participants who were then followed for 5 years in a prospective cohort study. The cohort initially consisted of 802 workers and ultimately included 660 people, all of whom underwent annual occupational health examinations from 2010 to 2015. RESULTS: The above-threshold group (≥7.3 mg/m³ adjusted relative risk (RR)= 3.620, 95%CI 2.072-6.325) was significantly more likely to develop NAFLD than the below-threshold group (<7.3 mg/m³). The TM6SF2 SNP rs58542926 CT (adjusted RR=3.921, 95% CI 2.329-6.600, P = 0.000) and CT+TT (adjusted RR=4.385, 95% CI 2.639-7.287, P = 0.000) genotypes were risk factors for NAFLD, as compared with the TM6SF2 rs58542926 CC genotype. Each dose group (below-threshold group and above-threshold group) interacting with the genotype of TM6SF2 SNP rs58542926 had an adjusted RR from 7.764 (95% CI 3.272-18.420, P = 0.000) to 24.022 (95% CI 8.971-64.328, P = 0.000). The T allele of rs58542926 in the TM6SF2 gene may be a risk factor for susceptibility to DMF-induced NAFLD. CONCLUSION: Polymorphisms of TM6SF2 SNP rs58542926 may play an important role in susceptibility to NAFLD after exposure to DMF.

Relationships among shift work, hair cortisol concentration and sleep disorders: a cross-sectional study in China.

OBJECTIVE: The present study was designed to demonstrate the relationships among shift work, hair cortisol concentration (HCC) and sleep disorders. DESIGN: A cross-sectional study. SETTING: Three petroleum administrations in Karamay city of Xinjiang, China. PARTICIPANTS: 435 individuals including 164 males and 271 females participated in the research. OUTCOME MEASURES: Information on shift work was collected by a self-administered questionnaire. HCC was determined using an automatic radioimmunoassay instrument. Sleep quality was measured on the Pittsburgh Sleep Quality Index scale. RESULTS: Shiftwork was associated with an increased prevalence of sleep disorders compared with the fixed day shift (two shifts: OR 3.11, 95% CI 1.57 to 6.19; three shifts: OR 2.87, 95% CI 1.38 to 5.98; four shifts: OR 2.22, 95% CI 1.17 to 4.18; others: OR 3.88, 95% CI= 1.36 to 11.08). Workers with different shift patterns had higher HCC levels than day workers ((fixed day shift: geometric mean±geometric SD=2.33±1.65; two shifts: 3.76±1.47; three shifts: 3.15±1.64; four shifts: 3.81±1.55; others: 3.60±1.33) ng/g hair, η2=0.174) and high HCC was associated with the higher prevalence of sleep disorders (OR 4.46, 95% CI 2.70 to 7.35). The mediating effect of HCC on the relationship between shift work and sleep disorders was 0.25 (95% CI 0.09 to 0.41). CONCLUSION: We found that, when compared with the fixed day shift, shiftwork was associated with both the higher HCC, and also with an increased risk of sleep disorders. High HCC was associated with the occurrence of sleep disorders. In addition, HCC had mediating effect in shift work and sleep disorders. Thus, HCC can be considered as an early marker of shiftwork circadian disruption to early detection and management of sleep disorders.

miRNA sequencing reveals miRNA-4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica-related pulmonary fibrosis: A multistage study.

BACKGROUND AND OBJECTIVE: This study aimed to identify miRNA as potential diagnostic biomarkers for silica-related pulmonary fibrosis (SPF). METHODS: We first performed a comprehensive miRNA-seq screening in PBL of eight subjects exposed to silica dust (four individuals with SPF and four healthy controls). The promising miRNA were then evaluated in the first-stage validation using an independent GEO data set (GSE80555) of 6 subjects (3 individuals with SPF and 3 healthy controls), followed by a second-stage validation using 120 subjects exposed to silica dust (60 individuals with SPF and 60 healthy controls). RESULTS: Thirty-five miRNA showed strong expression differences in miRNA-seq screening, while miRNA-4508 (P = 9.52 × 10-3 ) was retained as a candidate after the first-stage validation (GSE80555), which was further confirmed in the second-stage validation with similar and strong effect (P = 9.93 × 10-17 ). ROC analysis showed that miRNA-4508 could distinguish SPF cases from healthy controls with high AUC (0.886), with sensitivity of 81.7% and specificity of 86.7%. In addition, the miRNA-4508 upstream rs6576457 mutant A allele exhibited a strong association with susceptibility to SPF (OR = 1.64, 95% CI = 1.20-2.23, P = 0.002), while eQTL analysis revealed a potential association between different genotypes of rs6576457 and miRNA-4508 expression (P = 0.068) in 60 healthy subjects with silica dust exposure. CONCLUSION: miRNA-4508 may be a potential diagnostic marker for SPF, and rs6576457, a functional variant of miRNA-4508, may affect SPF susceptibility. The detailed mechanism of action of this miRNA remains to be elucidated.

Functional Variant in 3'UTR of FAM13A Is Potentially Associated with Susceptibility and Survival of Lung Squamous Carcinoma.

FAM13A is associated with aging lung disease (primarily chronic obstructive pulmonary disorder and pulmonary fibrosis) and shows stable expression throughout lung development. However, a few systematic studies of FAM13A have been conducted to assess the pathogenesis of lung cancer, particularly susceptibility. We predicted that single-nucleotide polymorphisms (SNPs) in FAM13A may be associated with lung cancer development. We systematically selected five functional SNPs (rs2602120, rs3017895, rs9224, rs7657817, and rs3756050) and genotyped them with the Genesky proprietary improved Multiligase Detection Reaction multiplex SNP genotyping system in a case-control study of 626 lung cancer cases and 667 cancer-free controls. The functional effects of FAM13A and specific miRNAs (miRNA-22-5p and miRNA-1301-3p) were evaluated based on The Cancer Genome Atlas database. We found that rs9224 in the 3' untranslated region (UTR) of FAM13A was potentially associated with an increased risk of lung squamous carcinoma (LUSQ) (additive model: odds ratio = 1.47, 95% confidence interval = 1.04-2.07, p = 0.028). In addition, the results of expression quantitative trait loci analysis suggested that the rs9224 polymorphism affects the expression of FAM13A (p = 0.050) and miRNA-22-5p (p = 0.031) in LUSQ. Further, survival analysis indicated decreased overall survival in the presence of the variant alleles of rs9224 (p = 0.048). The present results indicate that variant genotypes of rs9224 in the FAM13A 3'UTR may modify LUSQ susceptibility by affecting the binding of miRNA-22-5p and predict a poor prognosis of patients with LUSQ.

Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

OBJECTIVES: In a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported. METHODS: We systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases. RESULTS: We found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls. CONCLUSIONS: The rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility.

A Novel Variant of Desmoplakin Is Potentially Associated with Silicosis Risk.

Two genome-wide association studies and one sequencing study have coincidently reported significant associations of single nucleotide polymorphisms (SNPs) in the desmoplakin (DSP) gene with the risk of pulmonary fibrosis (mainly idiopathic pulmonary fibrosis). However, these findings have not been well generalized to occupational pulmonary fibrosis (e.g., silica-related silicosis). We systematically genotyped 8 potentially functional SNPs and the previously reported rs2076295 and rs2744371 in DSP gene region and evaluated the associations between these 10 SNPs and silicosis risk in a case-control study that included 177 silicosis cases and 204 controls with similar numbers of silica dust exposure years as the cases from a Chinese population. Genotyping was performed using the improved multiligase detection reaction multiplex SNP genotyping system. The variant A allele of rs2076304 exhibited significant association with the risk of silicosis (odds ratio = 1.53, 95% confidence interval = 1.03-2.29, p = 0.036). Moreover, significant association was observed between different genotypes of rs2076304 and DSP expression (p = 1.1 × 10-7) in 383 normal lung tissues. Further functional annotation indicated that the rs2076304 might influence the binding of RHOXF1. The rs2076304 in DSP gene is associated with a significantly increased risk of silicosis in a Han Chinese population. Further studies are warranted to validate and extend our findings, especially the biological mechanisms of rs2076304 in silicosis susceptibility.

Effectiveness and safety of glucosamine and chondroitin for the treatment of osteoarthritis: a meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the symptomatic effectiveness and safety of oral symptomatic slow-acting drugs (SYSADOAs) on the treatment of knee and/or hip osteoarthritis, such as chondroitin, glucosamine, and combination treatment with chondroitin plus glucosamine. METHODS: We searched electronic database including PubMed, Embase, Cochrane Library, and the reference lists of relevant articles published from inception to May 22, 2018. An updated meta-analysis was performed to assess the effectiveness of these slow-acting drugs for osteoarthritis. RESULTS: Twenty-six articles describing 30 trials met our inclusion criteria and were included in the meta-analysis. The estimates between chondroitin and placebo showed that chondroitin could alleviate pain symptoms and improve function. Compared with placebo, glucosamine proved significant effect only on stiffness improvement. However, the combination therapy did not have enough evidence to be superior to placebo. Additionally, there was no significant difference in the incidence of AEs and discontinuations of AEs when compared with placebo. CONCLUSIONS: Given the effectiveness of these symptomatic slow-acting drugs, oral chondroitin is more effective than placebo on relieving pain and improving physical function. Glucosamine showed effect on stiffness outcome. Regarding on the limited number of combination therapy, further studies need to investigate the accurate effectiveness. This information accompanied with the tolerability and economic costs of included treatments would be conducive to making decisions for clinicians.

The rs2609255 polymorphism in the FAM13A gene is reproducibly associated with silicosis susceptibility in a Chinese population.

BACKGROUND: Two recent genome-wide association studies (GWASs) reported that the FAM13A gene at the 4q22 locus associated with pulmonary fibrosis (defined by rs2609255) overlapping with COPD (defined by rs6837671). We hypothesized that single-nucleotide polymorphisms (SNPs) related to lung disease (especially pulmonary fibrosis) identified in this region are also associated with the risk of silicosis. METHODS: To test this hypothesis, we genotyped these two SNPs (rs2609255 and rs6837671) in a case-control study including 177 silicosis cases and 204 controls with silica dust exposure years similar to the levels for cases in a Chinese population. RESULTS: We found that rs2609255 was significantly associated with increased silicosis risk (dominant model: OR = 1.71; 95% CI = 1.01-2.92; P = 0.047). Additionally, eQTL analysis based on the GTEx database indicated that the rs2609255 polymorphism may alter the expression level of FAM13A in lung tissues (P = 1.8 × 10-4). Furthermore, interaction analyses showed that rs2609255 interacts multiplicatively with years of silica dust exposure to contribute to silicosis risk (interaction P = 0.040). CONCLUSIONS: These results indicate that rs2609255 may modify silicosis susceptibility in the Chinese population.

Comparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib for the treatment of knee and/or hip osteoarthritis: a network meta-analysis.

OBJECTIVES: To compare the efficacies of oral glucosamine, chondroitin, the combination of glucosamine and chondroitin, acetaminophen and celecoxib on the treatment of knee and/or hip osteoarthritis. METHODS: We searched electronic databases including PubMed, Embase, and Cochrane Library and the reference lists of relevant articles published from inception to October 23, 2017. A Bayesian hierarchical random effects model was used to examine the overall effect size among mixed multiple interventions. RESULTS: We identified 61 randomised controlled trials of patients with knee and/or hip osteoarthritis. There was no obvious difference in the results between the traditional meta-analysis and the network meta-analysis. The network meta-analysis demonstrated that celecoxib was most likely the best option (SMD, -0.32 [95% CI, -0.38 to -0.25]) for pain, followed by the combination of glucosamine and chondroitin. For physical function, all interventions were significantly superior to oral placebo except for acetaminophen. In terms of stiffness, glucosamine (SMD, -0.36 [95% CI, -0.67 to -0.06]) and celecoxib (SMD, -0.29 [95% CI, -0.51 to -0.08]) were significantly better compared to placebo. In view of safety, compared to placebo only, celecoxib and acetaminophen presented significant differences. CONCLUSIONS: Given the effectiveness of these non-steroidal anti-inflammatory drugs and symptomatic slow-acting drugs, oral celecoxib is more effective than placebo on relieving pain and improving physical function, followed by the combination of glucosamine and chondroitin. Acetaminophen is likely the least efficacious intervention option. This information, accompanied by the tolerability and economic costs of the included treatments, would be conducive to making decisions for clinicians.