A novel, effective machine learning-based RNA editing profile for predicting the prognosis of lower-grade gliomas.

Patients with low-grade glioma (LGG) may survive for long time periods, but their tumors often progress to higher-grade lesions. Currently, no cure for LGG is available. A-to-I RNA editing accounts for nearly 90% of all RNA editing events in humans and plays a role in tumorigenesis in various cancers. However, little is known regarding its prognostic role in LGG. On the basis of The Cancer Genome Atlas (TCGA) data, we used LASSO and univariate Cox regression to construct an RNA editing site signature. The results derived from the TCGA dataset were further validated with Gene Expression Omnibus (GEO) and Chinese Glioma Genome Atlas (CGGA) datasets. Five machine learning algorithms (Decision Trees C5.0, XGboost, GBDT, Lightgbm, and Catboost) were used to confirm the prognosis associated with the RNA editing site signature. Finally, we explored immune function, immunotherapy, and potential therapeutic agents in the high- and low-risk groups by using multiple biological prediction websites. A total of 22,739 RNA editing sites were identified, and a signature model consisting of four RNA editing sites (PRKCSH|chr19:11561032, DSEL|chr18:65174489, UGGT1|chr2:128952084, and SOD2|chr6:160101723) was established. Cox regression analysis indicated that the RNA editing signature was an independent prognostic factor, according to the ROC curve (AUC = 0.823), and the nomogram model had good predictive power (C-index = 0.824). In addition, the predictive ability of the RNA editing signature was confirmed with the machine learning model. The sensitivity of PCI-34051 and Elephantin was significantly higher in the high-risk group than the low-risk group, thus potentially providing a marker to predict the effects of lung cancer drug treatment. RNA editing may serve as a novel survival prediction tool, thus offering hope for developing editing-based therapeutic strategies to combat LGG progression. In addition, this tool may help optimize survival risk assessment and individualized care for patients with low-grade gliomas.

Analysis of the differential expression and prognostic relationship of DEGs in AML based on TCGA database.

BACKGROUND: Acute myeloid leukemia (AML) is a common and lethal hematological malignant hyperplastic disease originating from hematopoietic stem cells. The purpose of this study is to obtain the key differentially expressed gene (DEG) related to the survival of AML by The Cancer Genome Atlas (TCGA) database and to verify these genes by a clinical follow-up investigation, in order to identify valuable predictive and prognostic biomarkers for early diagnosis of AML and predict the survival rates. METHODS: The RNA sequencing (RNA-Seq) data and clinical information of TCGA-LAML were downloaded from the TCGA database. After that we (1) screened the survival-related DEGs by Cox regression analysis, (2) selected the cytogenetics risk-related DEGs by DESeq2 R package, and (3) filtrated the genes in the top10 pathways of up-regulated and down-regulated of Normalization Enrichment Score (NES) by Gene Set Enrichment Analysis (GSEA). Finally, we focused the intersectional genes of above three parts as the key gene of the present study. The following Multivariate.

Machine learning assessment of white blood cell counts in workers exposed to benzene: a historical cohort study.

To explore the fitting effect of the ARIMA, GM(1,1), and RANSAC model in the changes of white blood cells (WBC) in benzene-exposed workers, and select the optimal model to predict the WBC count of workers. Among 350 employees in an aerospace process manufacturing enterprise in Nanjing, workers with 10 years of benzene exposure were selected, and used Excel software to organize the WBC data, and the ARIMA model and RANSAC model were established by R software, and the GM(1, 1) model was established by DPS software, and the magnitude of the mean absolute percentage error (MAPE) of fitting three models to WBC counts was compared. The MAPE based on the ARIMA(2,1,2) model is 6.78%, the MAPE based on the GM(1,1) model is 5.19%, and the MAPE based on the RANSAC model is 6.37%, so the GM( 1,1) model was more suitable for fitting the trend of WBC counts in benzene exposed workers in this study. The GM(1,1) model is suitable for fitting WBC counts in a small sample size and can provide a short-term prediction of WBC counts in benzene-exposed workers and provide basic information for occupational health risk assessment of workers.

Prevalence and risk factors analysis for low back pain among occupational groups in key industries of China.

BACKGROUND: With the acceleration of industrialization and population aging, low back pain (LBP) has become the leading cause of life loss years caused by disability. Thus, it places a huge economic burden on society and is a global public health problem that needs urgent solution. This study aimed to conduct an epidemiological investigation and research on a large sample of workers in key industries in different regions of China, determine the incidence and distribution characteristics of LBP, explore the epidemic law, and provide a reference basis for alleviating global public health problems caused by LBP. METHODS: We adopted a modified epidemiological cross-sectional survey method and a stratified cluster sampling method. All on-duty workers who fulfill the inclusion criteria are taken as the research participants from the representative enterprises in key industries across seven regions: north, east, central, south, southwest, northwest, and northeast China. The Chinese version of the musculoskeletal disease questionnaire, modified by a standardized Nordic questionnaire, was used to collect information, and 57,501 valid questionnaires were received. Descriptive statistics were used, and multivariate logistic regression analysis (p < 0.05) was performed to explore the association between musculoskeletal disorders and potential risk factors. RESULTS: LBP annual incidence among workers in China's key industries is 16.4%. There was a significant difference in LBP incidence among occupational groups across different industries (p < 0.05). The multivariate regression model showed the following as risk factors for LBP: frequent repetitive movements with the trunk, working in the same positions at a high pace, trunk position, frequently turning around with your trunk, often working overtime, lifting heavy loads (i.e., more than 20 kg), education level, staff shortage, working age (years), cigarette smoking, use of vibration tools at work, body mass index, lifting heavy loads (i.e., more than 5 kg), and age (years). Physical exercise, often standing at work, and absolute resting time were protective factors. CONCLUSION: LBP incidence among key industries and workers in China is high. Thus, it is urgent to take relevant measures according to the individual, occupational, and psychosocial factors of LBP to reduce the adverse impact of LBP on workers' health.

The Potential Key Role of the NRF2/NQO1 Pathway in the Health Effects of Arsenic Pollution on SCC.

Arsenic is widely present in nature and is a common environmental poison that seriously damages human health. Chronic exposure to arsenic is a major environmental poisoning factor that promotes cell proliferation and leads to malignant transformation. However, its molecular mechanism remains unclear. In this study, we found that arsenite can promote the transformation of immortalized human keratinocyte cells (HaCaT) from the G0/G1 phase to S phase and demonstrated malignant phenotypes. This phenomenon is accompanied by obviously elevated levels of NRF2, NQO1, Cyclin E, and Cyclin-dependent kinase 2 (CDK2). Silencing the NRF2 expression with small interfering RNA (siRNA) in arsenite-transformed (T-HaCaT) cells was shown to reverse the malignant phenotype. Furthermore, the siRNA silencing of NQO1 significantly decreased the levels of the cyclin E-CDK2 complex, inhibiting the G0/G1 to S phase cell cycle progression and transformation to the T-HaCaT phenotypes. Thus, we hypothesized that the NRF2/NQO1 pathway played a key role in the arsenite-induced malignancy of HaCaT cells. By increasing the expression of Cyclin E-CDK2, the NRF2/NQO1 pathway can affect cell cycle progression and cell proliferation. A new common health effect mechanism of arsenic carcinogenesis has been identified; thus, it would contribute to the development of novel treatments to prevent and treat skin cancer caused by arsenic.

Occupational health risk assessment of the benzene exposure industries: a comprehensive scoring method through 4 health risk assessment models.

Benzene is one of the most common occupational hazards in the working environment which was in the list of group 1 carcinogens. This study applied four occupational health risk assessment models: EPA model; MOM model of Singapore; the International Council on Mining and Metals (ICMM) model, and the Technical guide WS/T 777-2021 of China. The models assessed both non-carcinogenic and carcinogenic effects of benzene for 1629 employees in 50 factories in Jiangsu Province (China) who were exposed to benzene in the working environment and analysis the risk between industries by principal component analysis (PCA) method. The highest occupational health hazard of benzene among the five industries is petroleum processing industry, then followed by chemical products manufacturing industry, special equipment manufacturing industry, wood processing and products industry, and at last the pharmaceutical manufacturing industry. The population of abnormal routine blood parameters in the subjects was mostly in the "wood products industry" group, and the concentration of benzene in "wood products industry" group is the lowest in 5 groups. The industries with low exposure concentration have higher blood abnormality rates; this may be caused by the fact that blood damage is more secretive under low occupational health risk.

Proteomic profiling reveals differentially expressed proteins associated with amylose accumulation during rice grain filling.

BACKGROUND: Amylose accumulation in rice grains is controlled by genetic and environmental factors. Amylose content is a determinant factor of rice quality in terms of cooking and eating. Great variations in amylose content in indica rice cultivars have been observed. The current study was to identify differentially expressed proteins in starch and sucrose metabolism and glycolysis/gluconeogenesis pathways and their relationships to amylose synthesis using two rice cultivars possess contrasting phenotypes in grain amylose content. RESULTS: Synthesis and accumulation of amylose in rice grains significantly affected the variations between rice cultivars in amylose contents. The high amylose content cultivar has three down-regulated differentially expressed proteins, i.e., LOC_Os01g62420.1, LOC_Os02g36600.1, and LOC_Os08g37380.2 in the glycolysis/gluconeogenesis pathway, which limit the glycolytic process and decrease the glucose-1-phosphate consumption. In the starch and sucrose metabolic pathway, an up-regulated protein, i.e., LOC_Os06g04200.1 and two down-regulated proteins, i.e., LOC_Os05g32710.1 and LOC_Os04g43360.1 were identified (Figure 4). Glucose-1-phosphate is one of the first substrates in starch synthesis and glycolysis that are catalyzed to form adenosine diphosphate glucose (ADPG), then the ADPG is catalyzed by granule-bound starch synthase I (GBSS I) to elongate amylose. CONCLUSIONS: The results indicate that decreasing the consumption of glucose-1-phosphate in the glycolytic process is essential for the formation of ADPG and UDPG, which are substrates for amylose synthesis. In theory, amylose content in rice can be regulated by controlling the fate of glucose-1-phosphate.

Salt-Inducible Kinase 3 Haplotypes Associated with Noise-Induced Hearing Loss in Chinese Workers.

INTRODUCTION: Noise-induced hearing loss (NIHL) is a common occupational disease that represents an irreversible hearing damage to the auditory system. It has been identified as a complicated disease involving both environmental and genetic factors. More efforts need to be made to explore the genes associated with susceptibility to NIHL. The main aim of this research is to detect the associations between SIK3 polymorphisms and NIHL susceptibility in Han people in China. METHODS: A case-control study was performed in 586 cases and 639 controls in a textile factory matched for sex, age, smoking, drinking, work time with noise, and intensity of noise exposure. Three single nucleotide polymorphisms (SNPs) (rs493134, rs6589574, and rs7121898) of SIK3 were genotyped in the participants. Then, the main influences of the SNPs on and their interactions with NIHL were assessed. RESULTS: Under the allelic model, distributions of rs493134 T, rs6589574 G, and rs7121898 A in the NIHL group are statistically different from those of the normal group (p = 0.001, p < 0.001, and p = 0.019, respectively). The following haplotype analysis shows that TAA (rs493134-rs6589574-rs7121898) may have a protective effect, while TGA (rs493134-rs6589574-rs7121898) (OR = 1.49, 95% CI = 1.25-1.79) may be a risk factor for NIHL. Multifactor dimensionality reduction analysis shows that the interaction of the 3 selected SNPs is associated with NIHL susceptibility (OR = 1.88, 95% CI = 1.50-2.36). CONCLUSION: The results suggest that 3 SNPs (rs493134, rs6589574, and rs7121898) of SIK3 may be an important part of NIHL susceptibility and can be applied in the prevention, early diagnosis, and treatment of NIHL in noise-exposed Chinese workers.

Occupational Mercury Exposure at a Thermometer Facility - Jiangsu Province, 2019.

WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: Mercury is still used in the manufacture of some thermometers in China. This may pose health risks if exposure is not properly prevented and controlled. WHAT IS ADDED BY THIS REPORT?: An onsite investigation of a workplace at a thermometer facility in Jiangsu Province in 2019 found heavily elevated airborne and urinary mercury levels among a massive number of workers exposed to mercury. Traditional and obsolete technology as well as inadequate protection measures for occupational hazards caused this high level of exposure. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Employers at thermometer producing facilities need to adopt effective protection measures and implement strict management. Monitoring exposure, adopting better engineering controls, diligent cleaning, and providing recommended personal protective equipment (PPE) along with training to their workers properly can alleviate mercury exposure at their facilities. In addition, transitioning to mercury-free thermometers would eliminate the risk of mercury exposure.

Research and Discussion on the Relationships between Noise-Induced Hearing Loss and ATP2B2 Gene Polymorphism.

Long-term and continuous noise exposure can result in noise-induced hearing loss (NIHL), which is a worldwide problem resulting from the interaction of environmental and genetic factors. The ATP2B2 gene polymorphism can destroy cochlear hair cells and increase the risk of NIHL. A case-control study of 760 Chinese textile workers was conducted to investigate the relationship between ATP2B2 polymorphisms and NIHL susceptibility. Venous blood was collected and questionnaires were conducted by professional physicians. A case group and a control group which were typed by individuals' pure-tone audiometry test results were set. Three polymorphism sites of ATP2B2 were genotyped by using the PCR technique. Analysis results revealed that the C allele of rs3209637 (95%CI = 1.08-2.58, odds ratio (OR) = 1.67, P = 0.027) was a dangerous factor and could add to risks of NIHL in the Chinese employees. The data of stratified analysis revealed that individuals who are exposed to noise > 95 dB with the rs3209637 C genotype have a higher susceptibility to NIHL (OR = 1.34, 95%CI = 1.07-1.68). Multifactor dimensionality reduction analysis revealed that the interaction between rs14154 and rs3209637 is linked to increased NIHL risk, and for the interaction among rs14154, smoking and drinking had the same function (OR = 1.54 and 1.77, 95%CI = 1.15-2.07, 1.33-2.37, and P = 0.0037 and P < 0.0001, respectively). Our results suggest that genetic polymorphism rs3209637 C within ATP2B2 is a risk factor for NIHL among Chinese employees and rs3209637 C could be a potential biomarker for NIHL patients.

Analysis of Polymorphisms Associated with Base Excision Repair in Patients Susceptible and Resistant to Noise-Induced Hearing Loss.

OBJECTIVE: Noise-induced hearing loss (NIHL) is one of the most common occupational health risks in both developed and industrialized countries. It occurs as a result of interactions between genetic and environmental factors. Nevertheless, inherited genetic factors contributing to NIHL are not well understood. Therefore, we aim to investigate whether genetic mutations in three important base excision repair genes (OGG1, APEX1, and XRCC1) may influence susceptibility to NIHL. METHODS: Three SNPs in OGG1, APEX1, and XRCC1 were genotyped from 1170 noise-exposed workers and were classified into 117 most susceptible and 117 most resistant individuals. RESULTS: Results showed that the rs1799782 TT genotype located in the XRCC1 coding region and rs1130409 GG/GT in the APEX1 coding region were associated with increased risk for NIHL in a Chinese population. Compared to the rs1799782 C allele frequency, the T allele frequency was increased in the sensitive group (adjusted OR = 1.51, 95%CI = 1.01 to 2.26, P = 0.043). The rs1130409 G allele frequency was also increased in the sensitive group compared to the resistant group (adjusted OR = 1.59, 95%CI = 1.10 to 2.31, P = 0.015). Moreover, rs1130409 and drinking had a statistically significant interaction (P = 0.0002), while rs1799782, rs1130409, and smoking also had a statistically significant interaction (P < 0.0001). CONCLUSIONS: XRCC1 rs1799782 and APEX1 rs1130409 may have potential as biomarkers for the screening of susceptibility to NIHL in workers exposed severe noise.

Effects of occupational exposure to dust on chest radiograph, pulmonary function, blood pressure and electrocardiogram among coal miners in an eastern province, China.

BACKGROUND: Coal dust is one of the most serious risk factor that leads to respiratory diseases and cardiovascular diseases in miners. This study aimed to observe the effects of occupational dust exposure on chest radiograph, pulmonary function (PF), blood pressure (BP) and electrocardiogram (ECG) indexes in coal miners and explore the related risk factors. METHODS: In the Chinese Occupational Disease Monitoring and Occupational Health Risk Assessment Program, a total of 11,061 subjects in 2015 and 12,597 subjects in 2016 were recruited in this study. The chest radiograph, PF, BP and ECG of coal miners were surveyed using radiograph machine, spirometer, sphygmomanometer and electrocardiograph, respectively. RESULTS: The prevalence of aberrant BP was the highest in coal miners, followed by abnormal ECG, PF and radiograph. Significant differences in abnormal BP, ECG, PF and radiograph of coal miners were closely associated with age, years of dust exposure, smoking, drinking, working types and size of mines. A total of 80 persons diagnosed with coal workers' pneumoconiosis (CWP) in 2015-2016, which occupied 0.34% of the coal miners. CONCLUSION: Abnormal BP, ECG, PF and radiograph of coal miners are highlighted health problems in China and require serious attention. Feasible health promotion and protective facilities should be adopted to guarantee coal miners' health.

Association of genetic variations in FOXO3 gene with susceptibility to noise induced hearing loss in a Chinese population.

Noise induced hearing loss (NIHL), a multifactorial disease involving both genetic and environmental factors, is one of the most important occupational health hazards. Nonetheless, the influence of FOXO3 variants on NIHL risk have not been illuminated. This research was conducted to explore the effects of FOXO3 polymorphisms on individual susceptibility to NIHL. A total of 2689 industrial workers from one textile factory of east China were recruited to participate in the current research. Venous blood was collected, questionnaire and pure-tone audiometry (PTA) was conducted by specialist physicians. Then, we performed genotyping of three selected SNPs (rs2802292, rs10457180, and rs12206094) in FOXO3 gene in 566 NIHL patients and 566 controls. Subsequently, the main effects of genotype and its interactions were evaluated. Our results revealed that individuals with the G allele of rs2802292, G allele of rs10457180, T allele of rs12206094 (OR = 1.43, 1.43, and 1.31 respectively) and the haplotype GAC and others (TGT/GGT/GGC/GAT) (rs2802292-rs10457180-rs12206094) (OR = 1.49 and 2.09 respectively) are associated with an increased risk of NIHL in a Chinese population. Stratified analysis showed that an increased NIHL risk was found in the subjects who exposed to noise >16 years with rs2802292 GG/GT and rs10457180 AG/GG genotype with an OR of 1.62 and 1.66 respectively. Multifactor dimensionality reduction analysis indicated that rs10457180, rs2802292, and rs12206094 have interactions and are related to increased NIHL risk (OR = 1.53). The genetic polymorphism rs2802292, rs10457180, and rs12206094 within FOXO3 gene are associated with an increased risk of NIHL in a Chinese population and have potential to be biomarkers for noise exposed workers.

Identification of differential plasma miRNA profiles in Chinese workers with occupational lead exposure.

Elevated lead absorptions are hazardous factors in lead-related workers. Previous studies have found its toxic impacts on nervous, circulatory, and metabolic systems. We hypothesized that alteration of miRNAs profile in plasma was closely associated with lead exposure. We analyzed to identify lead-related miRNAs in workers occupationally exposed to lead. Microarray assay was performed to detect plasma miRNA between workers with high and minimal lead exposure in the discovery stage. The following prediction of miRNAs' candidate target genes was carried out by using miRecords, STRING, and KEGG databases. We finally identified four miRNAs significantly associated with high level of blood lead. miR-520c-3p (*P=0.014), miR-211 (*P=0.019), and miR-148a (*P=0.031) were downexpressed in workers with high lead exposure and with high blood lead level (BLL), while miR-572(*P=0.027) displayed an opposite profile. Functional analysis of miRNAs displayed that these miRNAs could trigger different cellular genes and pathways. People under chronic lead exposure had a diverse 'fingerprint' plasma miRNA profile. Our study suggested that miR-520c-3p, miR-211, miR-148a, and miR-572 were the potential biomarkers for lead susceptibility in Chinese.

Survival Analysis of Coal Workers' Pneumoconiosis (CWP) Patients in a State-Owned Mine in the East of China from 1963 to 2014.

To investigate the mortality probability, life expectancy of coal workers' pneumoconiosis (CWP), and related factors of life expectancy, a total of 495 patients with CWP were diagnosed and reported from 1963 to 2014 in a state-owned mine in the east of China. The life table method, log rank method, and Cox regression model were used for survival analysis. 95 out of 495 CWP died during this period. The mortality rate was 19.19%. The average life span was 12.1 (0.0-33.2) years and average death age was 57.4 (33.0-83.0) years. The life table indicated that overall mortality probability increased with the age of CWP patients. Life expectancy of CWP patients was prolonged to 4.3, 1.4, 1.2, and 1.4 years without death caused by pneumoconiosis, tuberculosis, lung cancer, and pulmonary heart disease respectively. The survival curve of CWP patients without pulmonary tuberculosis was higher (average 37.9 years) than patients with pulmonary tuberculosis (average 34.1 years). There was significant difference observed (χ² = 6.196, p < 0.05). Three risk factors that include initial dust exposure year, age of onset, and first diagnostic stage were put into the Cox regression model for evaluation. The data indicated that prevention and treatment of CWP complication is important to improve patients' survival rates.

Involvement of water channel Aquaporin 5 in H2S-induced pulmonary edema.

Acute exposure to hydrogen sulfide (H2S) poses a significant threat to life, and the lung is one of the primary target organs of H2S. However, the mechanisms involved in H2S-induced acute pulmonary edema are poorly understood. This study aims to investigate the effects of H2S on the expression of water channel aquaporin 5 (AQP5) and to elucidate the signaling pathways involved in AQP5 regulation. In an in vivo study, C57BL6 mice were exposed to sub-lethal concentrations of inhaled H2S, and histological injury of the lungs and ultrastructure injury of the epithelial cells were evaluated. With real-time PCR and western blot assays, we found that H2S exposure contributed to a significant decrease in AQP5 expression both in murine lung tissue and the A549 cell line, and the ERK1/2 and p38 MAPK signaling pathways were demonstrated to be implicated in AQP5 regulation. Therefore, adjusting AQP5 protein levels could be considered a therapeutic strategy for the treatment of APE induced by H2S and other hazardous gases.

Analysis of plasma microRNA expression profiles in a Chinese population occupationally exposed to benzene and in a population with chronic benzene poisoning.

BACKGROUND: Circulating microRNA (miRNA) has attractive interests as a non-invasive biomarker of physiological and pathological conditions. Our study aimed to investigate the potential effects of chronic benzene poisoning (CBP) and benzene exposure on miRNA expression, and identify CBP-related miRNAs. METHODS: In the discovery stage, we used a microarray assay to detect the miRNA expression profiles among pooled plasma samples from ten CBP patients, ten healthy benzene-exposed individuals and ten non-benzene exposed individuals. Subsequently, we conducted an expanded validation of six candidate miRNAs in 27 CBP patients- low blood counts, 54 healthy benzene-exposed individuals and 54 non-exposed individuals. Moreover, we predicted the biological functions of putative target genes using a Gene Ontology (GO) function enrichment analysis and KEGG pathway analysis. RESULTS: In the discovery stage, compared with non-exposures, 36 and 12 miRNAs demonstrated at least a 1.0-fold differential expression in the CBP patients and the benzene exposures, respectively. And compared with benzene exposures, 58 miRNAs demonstrated at least a 1.0-fold differential expression in the CBP patients. In the expanded validation stage, compared with non-exposures as well as exposures, miR-24-3p and miR-221-3p were significantly up-regulated (1.99- and 2.06-fold for miR-24-3p, 2.19- and 3.93-fold for miR-221-3p, P<0.01) while miR-122-5p and miR-638 were significantly down-regulated (-3.45- and -2.60-fold for miR-122-5p, -1.82- and -3.20-fold for miR-638, P<0.001) in the CBP patients; compared with non-exposures, the plasma level of miR-638 was significantly up-regulated (1.38-fold, P<0.01) while the plasma levels miR-122-5p and miR-221-3p were significantly down-regulated (-0.85- and -1.74-fold, P<0.01) in the exposures, which were consistent with the results of microarray analysis. CONCLUSIONS: The four indicated plasma miRNAs may be biomarkers of indicating responses to benzene exposure. Further studies are warranted to verify our findings with a large sample and to confirm the underlying mechanisms.

[Study on relationships between biomarkers in workers with low-level occupational lead exposure].

OBJECTIVE: To investigate the lead exposure, its effects, and the relationships between biomarkers of susceptibility in the workers with low-level occupational lead exposure, and to explore its sensitivity and practical value to evaluate the health hazard. METHODS: The concentrations of lead fume and lead dust in workplaces of a lead acid storage battery enterprise in Jiangsu Province, China, were measured by occupational health monitoring method. The blood samples of 233 workers with occupational lead exposure and 76 non-occupational lead exposure were collected to measure the blood lead (Pb-B) level using graphite furnace atomic absorption spectrometry (GFAAS), the zinc Protoporphyrin (ZPP) level with blood fluorescence assay, and the delta-aminolevulinic acid dehydratase (ALAD) concentration by a spectrophotometer, and to determine the gene polymorphism of ALAD with TaqMan real-time polymerase chain reaction. At the same time, their urine samples were collected to measure urine lead (Pb-U) concentration with GFAAS and delta-aminolevulinic acid (ALA-U) concentration with a spectrophotometer. The correlations between the above indices were analyzed by multiple linear regression method. RESULTS: The concentration of lead fume in 18 testing sites and the concentration of lead dust in 30 testing sites were 0.002-0.019 mg/m3 and 0.004-0.013 mg/m3, respectively. Pb-B level was positively correlated with Pb-U concentration (r=0.62, P<0.01) and ZPP level (r=0.47, P<0.01) and was negatively correlated with ALAD concentration (r=-0.77, P<0.01) in 233 workers with occupational lead exposure. Among 233 workers, 218 (93.6%) had ≤70 µg/L Pb-U, and 15 (6.9%) had ≥400≥g/L Pb-B. Pb-B level was not correlated with ZPP level as Pb-B level was <190 µg/L (r=0.18, P=0.068 ), while Pb-B level was positively correlated with ZPP level as Pb-B level was ≥190 µg/L (r=0.36, P<0.01). Pb-U concentration was positively correlated with ALA-U concentration (r=0.49, P<0.01) and ZPP level (r=0.47, P<0.01). ZPP level was negatively correlated with ALAD concentration (r=-0. 19, P<0.01), and was positively correlated with ALA-U concentration (r=0.27, P<0.01). ALAD concentration was not correlated with ALA-U concentration (r =-0. 11, P>0.05). And in 233 workers with occupational lead exposure, there were no significant differences in Pb-B level, ZPP level, and ALAD activity between the workers with ALAD1-2 genotype and the workers with ALAD1-1 genotype (P>0.05). In 76 workers with non-occupational lead exposure, there was no significant difference in Pb-B level between the workers with ALAD1-2 genotype and the workers with ALAD1-1 genotype (P >0.05). The workers with ALAD1-2 genotype had a significantly lower ALAD activity, and a significantly higher ZPP level compared with those ALAD1-1 genotype (P<0.01). CONCLUSION: In the workers with low-level occupational lead exposure, ZPP level is positively correlated with Pb-B level when Pb-B level was ≥190 µ/L. ALAD could be used as an effect biomarker of low Pb-B level. ALAD gene polymorphism shows different effects on the Pb-B level and the toxic effects between the workers with occupational lead exposure and the workers with non-occupational lead exposure.

Epithelial sodium channel is involved in H2S-induced acute pulmonary edema.

Acute pulmonary edema is one of the major outcomes of exposure to high levels of hydrogen sulfide (H2S). However, the mechanisms involved in H2S-induced acute pulmonary edema are still poorly understood. Therefore, the present study is designed to evaluate the role of epithelial sodium channel (ENaC) in H2S-induced acute pulmonary edema. The Sprague-Dawley rats were exposed to sublethal concentrations of inhaled H2S, then the pulmonary histological and lung epithelial cell injury were evaluated by hematoxylin-eosin staining and electron microscopy, respectively. In addition to morphological investigation, our results also revealed that H2S exposure significantly decreased the alveolar fluid clearance and increased the lung tissue wet-dry ratio. These changes were demonstrated to be associated with decreased ENaC expression. Furthermore, the extracellular-regulated protein kinases 1/2 pathway was demonstrated to be implicated in H2S-mediated ENaC expression, because PD98059, an ERK1/2 antagonist, significantly mitigated H2S-mediated ENaC down-regulation. Therefore, our results show that ENaC might represent a novel pharmacological target for the treatment of acute pulmonary edema induced by H2S and other hazardous gases.

[Screening and analysis of plasma microRNA profile in benzene exposed workers].

OBJECTIVE: To find out and analyze differentially expressed miRNAs in the plasma of benzene exposed workers, and explore the potential roles of plasma miRNAs in the development of hematologic toxicity induced by benzene exposure. METHODS: By individual matching, low blood cell group, unstable blood cell group and normal group of 10 benzene exposed workers in each group were taken as subjects. Microarray was used to find out differentially expressed miRNAs among three groups. Three miRNAs validated by real-time quantitative PCR. Target genes of 9 miRNAs with the high abundance and significant difference were predicted using Target scan, Picture and miRanda softwares. David 6.7 online platform was used to perform GO term enrichment and KEGG pathway analysis of those targets. RESULTS: Microarray screened out that 138 miRNAs were differentially expressed. Three significant classes of differentially expressed miRNAs were found with the cluster analysis. The detected expressions of miR-638, let-7f-5p and miR-223-3p by relative RT-qPCR was consistent with the microarray date. Pathway analysis showed that the most enriched pathway was focal adhesion, with 6 potential functional targets, including SOS2, VCL, CCND2, COL4A6, IGF1 and MAPK1. CONCLUSION: We have identified the plasma miRNA profile in benzene exposed workers, and further analysis indicates that focal adhesion-associated miRNAs play a potential role in hematologic toxicity induced by benzene exposure.