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Epidemiological evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) is associated with lipid profile levels, but with inconsistent conclusions from different studies. The aim of this study was to conduct a meta-analysis of the relationship between PFAS exposure and lipid profile levels based on population-based epidemiological studies. Embase, PubMed, Ovid database, The Cochrane Library and Web of Science database were used to search appropriate studies (before September 6, 2022) on the correlation between PFAS exposure and lipid profile levels. ß value, odd ratio (OR) and 95â¯% confidence intervals (CIs) were extracted from studies. In this study, we found that higher low-density lipoprotein (LDL) levels were associated with exposure to perfluoroundecanoic acid (PFUnDA) (ß value=0.13, 95â¯% CIs: 0.02, 0.24) and perfluorooctane sulfonic acid (PFOS) (ß value=0.13, 95â¯% CIs: 0.04, 0.21). PFOA, PFOS and PFNA exposure were significantly related to the higher levels of total cholesterol (TC) with the pooled effect estimates of 0.08 (95â¯% CI: 0.02, 0.14), 0.13 (95â¯% CI: 0.05, 0.21) and 0.14 (95â¯% CI: 0.08, 0.20) respectively. In sum, our results identified that PFOA, PFOS, PFNA and PFUnDA were the most important risk factors for abnormal levels of lipid profile, indicating that we should prevent cerebrovascular disease by reducing and controlling PFAS exposure.
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What is already known about this topic?: Pneumoconiosis, recognized as one of the most detrimental occupational diseases in China, exhibits a multimorbidity profile due to a plethora of comorbidities and complications. These factors significantly influence the treatment outcomes, progression, prognosis, and overall quality of life of the afflicted patients. What is added by this report?: The present study examined the prevalence and types of comorbidities, encompassing 13 common diseases or conditions, within cases of pneumoconiosis across 27 provincial-level administrative divisions (PLADs) in China. Distinctions in multimorbidity distribution by gender, urban vs. rural areas, stages of pneumoconiosis, and the smoking index were considered. Furthermore, the study investigated the patterns of multimorbidity. What are the implications for public health practice?: This study serves as a reference point for the formulation of treatment strategies and health policy development concerning pneumoconiosis in China.
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What is already known about this topic?: The application of whole lung lavage (WLL) for the clinical treatment of pneumoconiosis is prevalent in China. Several scholars have reported success in the treatment of early-stage pneumoconiosis. Nonetheless, the overall efficacy of WLL in the management of pneumoconiosis remains ambiguous. What is added by this report?: The preliminary evaluation of the effects of WLL on pneumoconiosis patients was conducted using follow-up data from 2020 to 2022, after controlling for confounding factors via propensity score matching. While the study found that WLL may improve some pneumoconiosis symptoms, no significant enhancements were observed in overall health status or quality of life. What are the implications for public health practice?: The findings of this research indicate limited efficacy of WLL in treating patients with pneumoconiosis, thereby suggesting that it should not be utilized as a standard treatment procedure for this condition.
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Introduction: Pneumoconiosis emerges as the most critical and prevalent occupational disease in China at present, according to research. Studies indicate that pneumoconiosis may indeed impact the body's phospholipid metabolism. Methods: In this study, serum samples were taken from 46 paired participants, which included patients with pneumoconiosis and dust-exposed workers. We employed ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology in targeted lipidomics to investigate serum target phospholipids. Initially, a pilot study was conducted with a selection of 24 pneumoconiosis patients and 24 dust-exposed workers, using both univariate and multivariate statistical analyses to preliminarily identify significant differences in phospholipids. Subsequent to this, the remaining subjects were engaged in a validation study, wherein receiver operating characteristic (ROC) analysis was performed to further substantiate the screening potency of potential lipid biomarkers for pneumoconiosis. Results: The pilot study revealed significantly reduced serum levels of 16â¶0 lysophosphatidylcholines (Lyso PC), 18â¶0-18â¶1 phosphatidylglycerol (PG), 18â¶0-18â¶1 phosphatidylethanolamine (PE), 18â¶0 PE, and 18â¶1 lysophosphatidylethanolamineï¼Lyso PE) in the case group in comparison to the control group. Additionally, 18â¶0 PE, 18â¶0-18â¶1 PE, and 18â¶1 Lyso PE emerged as significant phospholipids with superior diagnostic values [area under the curve (AUC)>0.7]. A diagnostic model was established, built on 16â¶0 PC and 18â¶0 PE (AUC>0.8). In the ROC analyses of validation studies, the 18â¶0-18â¶1 PE and this diagnostic model demonstrated excellent screening efficiency (AUC>0.7). Discussion: A significant divergence in phospholipid metabolism has been observed between pneumoconiosis patients and dust-exposed workers. The 18â¶0-18â¶1 PE present in serum could potentially function as a lipid biomarker for pneumoconiosis. Additionally, diagnostic models were developed relying on 16â¶0 PC and 18â¶0 PE, proving to have superior screening efficiency.
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Some studies have suggested that perfluoroalkyl and polyfluoroalkyl substance (PFAS) exposure may be associated with semen quality in the general population, but with inconsistent results. To identify a more precise relationship between them, a meta-analysis was performed. We searched Embase, the PubMed, The Cochrane Library, Ovid databases, and Web of Science databases (before March 2022) for appropriate studies on the correlations of PFAS exposure with semen parameters. We extracted ß value and 95% confidence intervals (CIs) to conduct meta-analysis. Subgroup analyses was performed by sample size, geographic location, and sample type. A total of seven articles involving 2190 participants were included in this study. The concentrations of perfluorooctanoic acid (PFOA) (ß value = - 1.38; 95% CI: - 2.44, - 0.32) and perfluorononanoic acid (PFNA) (ß value = - 1.31, 95% CI: - 2.35, - 0.26) were negatively associated with sperm progressive motility. Subgroup analysis revealed that PFNA exposure was related to sperm morphology in studies with the sample size exceeding 200 people (ß value = - 0.14; 95% CI: - 0.26, - 0.01). Our study supports that exposure to some PFASs (e.g., PFNA, PFOA) may be associated with semen quality, such as lower sperm progressive motility. Therefore, it is of great significance for the prevention of male infertility by control the use of PFASs.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Humanos , Masculino , Análisis de Semen , SemenRESUMEN
Long-term inhalation of welding fume at high exposure can cause welder's pneumoconiosis, and metals in welding dust are associated with respiratory dysfunction. This cross-sectional study, which contains 384 Chinese male workers who were or had been working in a container factory, aimed to assess the potential risk of haemal and urinary metal content in welder's pneumoconiosis. Further, we investigated their effects on lung function parameters. Metal content and lung function were measured using inductively coupled plasma-mass spectrometry (ICP-MS) and spirometer, respectively. The concentration and metal content of respirable dust as well as total dust were collected at this container factory. Lung function of cases with welder's pneumoconiosis was significantly worse, as indicated by lower values of FVC, FVC% predicted, FEV1, FEV1% predicted, MEF25% predicted, and MMEF% predicted (p < 0.05). Results of logistic regression models showed that haemal Cr and Zn were risk factors of welder's pneumoconiosis (OR = 4.98, 95%CI: 1.73-21.20, p = 0.009 for Cr; OR = 5.23, 95%CI: 1.56-41.08, p = 0.033 for Zn) after adjusted with age, BMI, working years, welding dust exposure years, and smoking status. Multiple linear regression models showed that several metals (haemal Cd and Pb; urinary Cd and Fe) were significantly associated with different lung function indices in the welder's pneumoconiosis group. Compared to non-welders, welders were exposed to considerably higher levels of respirable dust, total dust, and six kinds of metals (p < 0.05). In conclusion, haemal Cr and Zn are positively related to welder's pneumoconiosis. Meanwhile, Cd and Pb might worsen lung function in welder's pneumoconiosis.
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Exposición Profesional , Neumoconiosis , Soldadura , Masculino , Humanos , Estudios Transversales , Pulmón , Cadmio/análisis , Plomo/análisis , Neumoconiosis/epidemiología , Polvo/análisis , China , Exposición Profesional/efectos adversos , Exposición Profesional/análisisRESUMEN
BACKGROUND: Polypharmacy increases the risk of potential drug-drug interactions (pDDIs). This retrospective analysis was conducted to detect pDDIs and adverse drug reactions (ADRs) among older adults with psychiatric disorder, and identify pDDIs with clinical significance. METHODS: A retrospective analysis was carried out based on the medical records of older adults with psychiatric disorders. Data on demographic characteristics, substance abuse, medical history, and medications were extracted. The Lexi-Interact online database was used to detect pDDIs. The minimal clinically important difference (MCID) was set as the change in the Treatment Emergent Symptom Scale (TESS) score between admission and discharge. The median and interquartile ranges were used for continuous variables, and frequencies were calculated for dichotomous variables. Poisson regression was implemented to determine the factors influencing the number of ADR types. The influencing factors of each ADR and the clinical significance of the severity of the ADR were analysed using binary logistic regression. P < 0.05 was considered statistically significant. RESULTS: A total of 308 older adults were enrolled, 171 (55.52%) of whom had at least 1 pDDI. Thirty-six types of pDDIs that should be avoided were found, and the most frequent pDDI was the coadministration of lorazepam and olanzapine (55.5%). A total of 26 ADRs induced by pDDIs were identified, and the most common ADR was constipation (26.05%). There was a 9.4 and 10.3% increase in the number of ADR types for each extra medical diagnosis and for each extra drug, respectively. There was a 120% increase in the number of ADR types for older adults hospitalized for 18-28 days compared with those hospitalized for 3-17 days. There was an 11.1% decrease in the number of ADR types for each extra readmission. The length of hospitalization was a risk factor for abnormal liver function (P < 0.05). The use of a large number of drugs was a risk factor for gastric distress (P < 0.05) and dizziness and fainting (P < 0.05). None of the four pDDIs, including coadministrations of olanzapine and lorazepam, quetiapine and potassium chloride, quetiapine and escitalopram, and olanzapine and clonazepam, showed clinical significance of ADR severity (P > 0.05). CONCLUSIONS: pDDIs are prevalent in older adults, and the rate is increasing. However, many pDDIs may have no clinical significance in terms of ADR severity. Further research on assessing pDDIs, and possible measures to prevent serious ADRs induced by DDIs is needed to reduce the clinical significance of pDDIs.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Trastornos Mentales , Anciano , Interacciones Farmacológicas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Humanos , Lorazepam , Trastornos Mentales/tratamiento farmacológico , Olanzapina , Fumarato de Quetiapina , Estudios RetrospectivosRESUMEN
In this work, untargeted lipidomics was employed to analyze the effects of coal dust exposure on serum metabolite profiles. Furthermore, the potential of differential metabolites as novel biomarkers for diagnosis was investigated by binary logistic classification model. Nineteen differential metabolites were found among the three groups. The compounds were enriched in pathways associated with linoleic acid metabolism and pyrimidine metabolism. Fifty-three differential metabolites were found in coal dust-exposed people and CWP patients, and they were mainly enriched in glycerophospholipid metabolism. Three differential metabolites were correlated with lung function values. The diagnostic model, composed of lysoPI (16:0/0:0), bilirubin, and lysoPC (24:1/0:0), showed strong discrimination ability between dust-exposed people and CWP patients. The sensitivity, specificity, and AUC values of the model were 0.869, 0.600, and 0.750, respectively. The results suggest that coal worker's pneumoconiosis causes abnormal lipid metabolism in the body. A diagnostic model may aid current CWP diagnostic methods, and lysoPI (16:0/0:0), bilirubin, and lysoPC (24:1/0:0) can be used as potential CWP biomarkers. Further study is warranted to validate the findings in larger populations.
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Antracosis , Minas de Carbón , Neumoconiosis , Humanos , Neumoconiosis/complicaciones , Neumoconiosis/diagnóstico , Lipidómica , Antracosis/complicaciones , Carbón Mineral , Polvo , Biomarcadores , BilirrubinaRESUMEN
Prolonged exposure to hard metal dust results in hard metal lung disease (HMLD) characterized by respiratory symptoms. Understanding the pathogenesis and pathological process of HMLD would be helpful for its early diagnosis and treatment. In this study, we established a mouse model of hard metal-induced acute lung injury through one-time intratracheal instillation of WC-Co dust suspension. We found that WC-Co treatment damaged the lungs of mice, leading to increased production of IL-1ß, TNF-α, IL-6 and IL-18, inflammatory cells infiltration and apoptosis. In vitro, WC-Co induced cytotoxicity, inflammatory response and apoptosis in macrophages (PMA-treated THP-1) and epithelial cells (A549) in a dose-dependent manner. Moreover, RNA-sequence and validation experiments verified that Pentraxin 3 (PTX3), an important mediator in the regulation of inflammation, was elevated both in vivo and in vitro induced by WC-Co. Functional experiments confirmed the PTX3, which was located on the membrane of apoptotic cells, promoted macrophage efferocytosis efficiently. This progress could help block the lung inflammation and contribute to the rapid recovery of WC-Co-induced acute lung injury. These observations provide a further understanding of the molecular mechanism of WC-Co-induced pulmonary injury and disclose PTX3 as a new potential therapeutic approach to relieve WC-Co-induced acute lung injury via efferocytosis.
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Long-term exposure to inhaled silica dust induces pneumoconiosis, which remains a heavy burden in developing countries. Modern industry provides new resources of occupational SiO2 leading to artificial stone silicosis especially in developed countries. This study aimed to characterize the serum metabolic profile of pneumoconiosis and artificial stone silicosis patients. Our case-control study recruited 46 pairs of pneumoconiosis patients and dust-exposed workers. Nontargeted metabolomics and lipidomics by ultra-high-performance liquid chromatography-tandem mass spectrometry platform were conducted to characterize serum metabolic profile in propensity score-matched (PSM) pilot study. 54 differential metabolites were screened, 24 of which showed good screening efficiency through receiver operating characteristics (ROC) in pilot study and validation study (both AUC > 0.75). 4 of the 24 metabolites can predict pneumoconiosis stages, which are 1,2-dioctanoylthiophosphatidylcholine, phosphatidylcholine(O-18:1/20:1), indole-3-acetamide and l-homoarginine. Kynurenine, N-tetradecanoylsphingosine 1-phosphate, 5-methoxytryptophol and phosphatidylethanolamine(22:6/18:1) displayed the potential as specific biomarkers for artificial stone silicosis. Taken together, our results confirmed that tryptophan metabolism is closely related to pneumoconiosis and may be related to disease progression. Hopefully, our results could supplement the biomarkers of pneumoconiosis and provide evidence for the discovery of artificial stone silicosis-specific biomarkers.
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Antracosis/sangre , Antracosis/metabolismo , Pueblo Asiatico , Dióxido de Silicio/toxicidad , Silicosis/sangre , Silicosis/metabolismo , Adulto , Antracosis/epidemiología , Biomarcadores/sangre , Estudios de Casos y Controles , China/epidemiología , Polvo , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Silicosis/epidemiologíaRESUMEN
BACKGROUND: Patients with pneumoconiosis have an elevated risk of contracting pulmonary tuberculosis (PTB) and need particular attention. However, extensive population-based studies on the prevalence of PTB in patients with pneumoconiosis have not been reported in China since 1992. This study aimed to investigate the epidemiological characteristics of PTB in patients with pneumoconiosis based on its social determinants and risk factors in China. METHODS: Based on the Commission on Social Determinants of Health (CSDH) framework, data were obtained from a questionnaire survey of patients with pneumoconiosis from China's 27 provinces (autonomous regions, municipalities) from December 2017 to June 2021. By chi-square and multivariate logistic regression analyses, the epidemiological characteristics of PTB in the patients were identified based on its prevalence and odds ratio (OR) and associated social determinants and risk factors. The population attributable fractions (PAFs) of significant risk factors were also calculated. RESULTS: The prevalence of PTB in patients with pneumoconiosis ( n â=â10,137) was 7.5% (95% confidence interval [CI]: 7.0-8.0%). Multivariate logistic regression analysis showed that risk factors included in-hospital exposure to patients with PTB (ORâ=â3.30, 95% CI: 2.77-3.93), clinically diagnosed cases (ORâ=â3.25, 95% CI: 2.42-4.34), and northeastern regions (ORâ=â2.41, 95% CI: 1.76-3.31). In addition, lack of work-related injury insurance (WRII), being born in a rural area, being unemployed, living in western regions, household exposure to patients with PTB, smoking, being underweight, complications of pulmonary bullae or pneumothorax, hospitalization history, and former drinkers among the rural patients were also statistically significant risk factors. Being born in a rural area, lack of WRII and in-hospital exposure to patients with PTB had higher PAFs, which were 13.2% (95% CI: 7.9-18.5%), 12.5% (95% CI: 8.3-16.7%), and 11.6% (95% CI: 8.8-14.3%), respectively. CONCLUSION: The prevalence of PTB in pneumoconiosis remains high in China; it is basically in line with the CSDH models and has its characteristics.
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Neumoconiosis , Tuberculosis Pulmonar , Humanos , Estudios Transversales , Determinantes Sociales de la Salud , Factores de Riesgo , Tuberculosis Pulmonar/epidemiología , Neumoconiosis/epidemiología , China/epidemiologíaRESUMEN
Airborne particulate matter (PM) is a complex mixture containing various kinds of harmful components. Exposure to air PM is associated with childhood respiratory disease, but epidemiological data are limited concerning the circulating respiratory injury protein on the etiology of childhood respiratory disease. Specifically, the role of PM toxic components or its biological effective dose (adduct) in respiratory injury remains unclear. To demonstrate the dose-response relationship and the main mechanism on circulating club cell secretory protein (CC16) from PM compositions among children, we enrolled 273 boarding schoolchildren in China, including 110 and 163 children of whom were in the low- and high-PM exposed areas, respectively. In this study, we measured the internal exposure levels, including serum polycyclic aromatic hydrocarbons (PAH) adduct, urinary metals, and AhR expression, and detected the serum CC16 level as a lung injury marker. Environmental tobacco exposure in children was assessed by urinary cotinine. We found that significantly higher levels of serum CC16, benzo[a]pyridin-7,8-dihydroglycol-9,10-epoxide (BPDE)-albumin adduct, urinary molybdenum, selenium, arsenic, cadmium and barium, and lower level of AhR expression in high-PM exposed group. There was a good association between serum BPDE-albumin adduct and CC16 (ß = 0.222, P = 0.006). There was no association on urinary metals and serum CC16. BPDE-albumin adduct was directly associated with serum CC16 alternation [direct effect = 0.2044, 95% confidence interval (CI) = (0.0426, 0.36)]. PM could cause serum CC16 increased in children. PAH and its adduct might play a key role in lung injury during PM exposure.
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Material Particulado , Hidrocarburos Policíclicos Aromáticos , Niño , China/epidemiología , Exposición a Riesgos Ambientales , Humanos , Epidemiología Molecular , Material Particulado/análisis , Material Particulado/toxicidad , Hidrocarburos Policíclicos Aromáticos/análisis , Hidrocarburos Policíclicos Aromáticos/toxicidadRESUMEN
WHAT IS ALREADY KNOWN ON THIS TOPIC?: Asbestos is classified as a Class I Carcinogen by the International Agency for Research on Cancer (IARC) because exposure causes mesothelioma and lung cancer in addition to asbestosis and plaques. So far, asbestos has been banned in 67 countries, but chrysotile, a commonly encountered form of asbestos, is still widely used in China and most developing countries. Most asbestos-caused cancers are not reported, recorded, and compensated in many countries. WHAT IS ADDED BY THIS REPORT?: Enterprises manufacturing asbestos products have been migrating from economically developed Eastern China to relatively underdeveloped central and western regions between 2010 and 2019. Asbestosis cases reported in Tianjin, Beijing, Shandong, Xinjiang, Gansu, Qinghai, and Sichuan accounted for a large proportion of the total cases in China, which was inconsistent with the distribution of asbestos-related enterprises (AREs). The reported asbestosis cases versus total pneumoconiosis cases declined from 2.81% to 0.39% from 2006-2017, and this proportion reached 0.69% in 2018. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Robust occupational and environmental health assessments and reporting are needed to define the epidemiology of asbestos-related lung diseases, and management of using asbestos and existing products containing asbestos need strengthening and follow-up. Enterprises should be encouraged to use safer substitutes and gradually ban asbestos materials in China.
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Identifying sensitive and specific biomarkers for early detection of cancer is immensely imperative for early diagnosis and treatment and better clinical outcome of cancer patients. This study aimed to construct a specific DNA methylation pattern of cancer suppressor genes and explore the feasibility of applying cell-free DNA based methylation as a biomarker for early diagnosis of esophageal squamous cell carcinoma (ESCC). We recruited early stage ESCC patients from Yangzhong County, China. The Illumina Infinium 450K Methylation BeadChip was used to construct a genome-wide DNA methylation profile. Then, differentiated genes were selected for the validation study using the Sequenom MassARRAY platform. The frequency of methylation was compared between cancer tissues, matched cell-free DNAs and normal controls. The specific methylation profiles were constructed, and the sensitivity and specificity were calculated. Seven CG sites in three genes CASZ1, CDH13 and ING2 were significantly hypermethylated in ESCC as compared with normal controls. A significant correlation was found between the methylation of DNA extracted from cancer tissues and matched plasma cell-free DNA, either for individual CG site or for cumulative methylation analysis. The sensitivity and specificity reached 100% at an appropriate cut-point using these specific methylation biomarkers. This study revealed that aberrant DNA methylation is a promising biomarker for molecular diagnosis of esophageal cancer. Hypermethylation of CASZ1, CDH13 and ING2 detected in plasma cell-free DNA can be applied as a potential noninvasive biomarker for diagnosis of esophageal cancer.
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This study assesses the effects of long-term exposure to ambient air pollutants on inflammatory response and lung function. We selected 390 male coke oven workers with exposure to polycyclic aromatic hydrocarbons (PAHs) and fine particulate matter (PM2.5) and 115 control workers. The average duration in the exposed group was 9.10 years. The total amount of PAHs was more enriched in PM2.5 which collected from the coke oven workshops compared with the control areas. Correspondingly, the internal PAHs exposure indicated by urinary 1-hydroxypyrene (1-OHP) in the exposure group increased 25.7-fold compared to that of the control group. Moreover, the increasing level of urinary 1-OHP was associated with the decrease of forced expiratory volume in 1 s to forced vital capacity ratio (FEV1/FVC). In non-current smokers of exposure group, inverse correlation of 1-OHP with FEV1/FVC was also found. Particularly, an exposure duration-dependent decline in FEV1/FVC and mean forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%) indicated that small airways were functionally obstructed. Furthermore, the increasing serum high-sensitivity C-reactive protein (hs-CRP) was correlated with the decline in pulmonary function in all subjects. These findings provide a clue that long-term exposure to PAHs-enriched PM2.5 impairs pulmonary function in occupational population.
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Contaminantes Atmosféricos , Coque , Exposición Profesional , Hidrocarburos Policíclicos Aromáticos , Humanos , Masculino , Material Particulado , PirenosRESUMEN
BACKGROUND: Little is known about the prevalence of latent tuberculosis infection (LTBI) among coal workers' pneumoconiosis (CWP) patients. To estimate the prevalence of LTBI and identify its associated risk factors among CWP patients. METHODS: A cross-sectional study was conducted to assess the prevalence of LTBI. Participants were screened for active TB or a history of TB by X-ray and those that underwent QuantiFERON-TB Gold In-Tube (QFT) test. A standardized questionnaire was completed and risk factors were assessed for acquiring TB. Log-binomial regression was used to estimate the LTBI prevalence ratio (PR) in relation to risk factors. RESULTS: Of 244 individuals with CWP (median age 67 years; all male), 162 (66.4%) were QFT positive. In Multivariate analysis, poor workplace ventilation (adjusted prevalence ratio [APR] = 1.26) and intake of fruits regularly (≥4 days of every week) (APR = 0.81) (all p < 0.05) were associated with a decreased risk of QFT. CONCLUSIONS: This study showed a high prevalence of LTBI among individuals with CWP in China. Poor workplace ventilation may be an important contributing factor for LTBI. Regular monitoring and dust control measures need to be improved in workplaces to ensure the safety of workers. Moreover, intake of fruits regularly may be a protective factor for LTBI. However, the effect of fruits should be further studied.
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Antracosis/terapia , Tuberculosis Latente/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Antracosis/epidemiología , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
We aimed to find possible protein markers and key pathways related to bladder cancer. In total, we extracted three bladder cancer tissues and three paracancerous tissues from Jiangsu Provincial People's Hospital Urology Department, and performed mass spectrometric detection with Q Exactive. Subsequently, we screened the differentially expressed proteins in the disease group and the normal group using the LIMMA package, and performed functional enrichment analyses using DAVID. Further, we constructed protein-protein interaction (PPI) networks with Cytoscape software, and analyzed modules with ClusterONE. In total, 165 differentially expressed proteins including 19 upregulated and 146 downregulated ones were obtained. ACTA2 (Actin, Alpha 2, Smooth Muscle, Aorta), ACTN1 (Actinin, Alpha 1), and VCL (Vinculin) were significant nodes with higher degrees in the PPI network. These three nodes were also hub nodes in module 2. Besides, functional enrichment analysis suggested that ECM-receptor interaction and focal adhesion were significant pathways, and these two pathways were also enriched in three network modules. In addition, ACTN1 and VCL were enriched in the focal adhesion pathway in module 2. Thus, ACTA2, ACTN1, and VCL may play important roles in bladder cancer progression and may be protein markers for this disease. The ECM-receptor interaction pathway and the focal adhesion pathway may be involved in the progression of bladder cancer. Furthermore, ACTN1 and VCL may play roles in bladder cancer development, partly via the focal adhesion pathway.
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Biomarcadores de Tumor/metabolismo , Redes Reguladoras de Genes , Mapas de Interacción de Proteínas , Proteoma/genética , Neoplasias de la Vejiga Urinaria/genética , Actinina/genética , Actinina/metabolismo , Actinas/genética , Actinas/metabolismo , Biomarcadores de Tumor/genética , Estudios de Casos y Controles , Adhesiones Focales/genética , Adhesiones Focales/metabolismo , Humanos , Espectrometría de Masas , Proteoma/química , Proteoma/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Vinculina/genética , Vinculina/metabolismoRESUMEN
Derlin-1 is overexpressed in various types of solid tumors and has an important function in cancer progression. However, its expression pattern in and association with the clinicopathological characteristics of human bladder cancer remain unclear. In the present study, 3 pairs of fresh samples of bladder cancer tissue and paracancerous tissue were first detected by liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to screen for differentially expressed proteins. Following bioinformatics analysis and assessments by qRT-PCR and western blotting, Derlin-1 was selected as a candidate protein and was then validated in samples from patients with bladder cancer by immunohistochemistry and western blotting. The results showed that the bladder cancer tissues exhibited higher levels of Derlin-1 expression than the paracancerous tissues (P < 0.05). Positive expression of Derlin-1 was significantly correlated with tumor stage, histological grade, and lymph node metastasis (P < 0.001) but was not correlated with other clinicopathological parameters including patient age (P = 0.758) and gender (P = 0.831). Besides, Derlin-1 was highly expressed in BC cell lines (um-uc-3 and T24), and the interference of Derlin-1 could reverse EMT progression, inhibit the tumor migration and invasion in T24 cells. Further, patients with positive Derlin-1 expression had shorter overall survival than those with negative expression (P < 0.001). Taken together, our results demonstrated that Derlin-1 was overexpressed in bladder cancer and was associated with the malignancy of bladder cancer.