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

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

Comparison of different prediction tools for the risk of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a propensity-matched analysis

Objective To compare the predictive performance of the current clinical prediction models for predicting intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). Methods We retrospectively analysed upper tract urothelial carcinoma patients who underwent radical nephroureterectomy in our centre from January 2009 to December 2019. We used the propensity score matching (PSM) method to adjust the confounders between the IVR and non-IVR groups. Additionally, Xylinas’ reduce model and full model, Zhang’s model, and Ishioka’s risk stratification model were used to retrospectively calculate predictions for each patient. Receiver operating characteristic (ROC) curves were generated, and the areas under the curves (AUCs) were compared to identify the method with the highest predictive value. Zesults We included 217 patients with a median follow-up of 41 months, of which 57 had IVR. After PSM analysis, 52 pairs of well-matched patients were included in the comparative study. No significant difference was found in clinical indicators besides hydronephrosis. The model comparison showed that the AUCs of the reduced Xylinas’ model for 12 months, 24 months, and 36 months were 0.69, 0.73, and 0.74, respectively, and those of the full Xylinas’ model were 0.72, 0.75, and 0.74, respectively. The AUC of Zhang’s model for 12 months, 24 months, and 36 months was 0.63, 0.71, and 0.71, respectively, the performance of Ishioka’s model is that the AUC of 12 months, 24 months and 36 months was 0.66, 0.71, and 0.74, respectively. Conclusion The external verification results of the four models show that more comprehensive data and a larger sample size of patients are needed to strengthen the models’ derivation and updating procedure, to better apply them to different populations (AU)

Comparison of different prediction tools for the risk of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma: a propensity-matched analysis.

OBJECTIVE: To compare the predictive performance of the current clinical prediction models for predicting intravesical recurrence (IVR) after radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). METHODS: We retrospectively analysed upper tract urothelial carcinoma patients who underwent radical nephroureterectomy in our centre from January 2009 to December 2019. We used the propensity score matching (PSM) method to adjust the confounders between the IVR and non-IVR groups. Additionally, Xylinas' reduce model and full model, Zhang's model, and Ishioka's risk stratification model were used to retrospectively calculate predictions for each patient. Receiver operating characteristic (ROC) curves were generated, and the areas under the curves (AUCs) were compared to identify the method with the highest predictive value. RESULTS: We included 217 patients with a median follow-up of 41 months, of which 57 had IVR. After PSM analysis, 52 pairs of well-matched patients were included in the comparative study. No significant difference was found in clinical indicators besides hydronephrosis. The model comparison showed that the AUCs of the reduced Xylinas' model for 12 months, 24 months, and 36 months were 0.69, 0.73, and 0.74, respectively, and those of the full Xylinas' model were 0.72, 0.75, and 0.74, respectively. The AUC of Zhang's model for 12 months, 24 months, and 36 months was 0.63, 0.71, and 0.71, respectively, the performance of Ishioka's model is that the AUC of 12 months, 24 months and 36 months was 0.66, 0.71, and 0.74, respectively. CONCLUSION: The external verification results of the four models show that more comprehensive data and a larger sample size of patients are needed to strengthen the models' derivation and updating procedure, to better apply them to different populations.

Tolterodine ameliorates inflammatory response and ferroptosis against LPS in human bladder epithelial cells.

Bacterial endotoxin lipopolysaccharide (LPS)-induced inflammatory response and ferroptosis play an important role in urinary tract infections. Tolterodine has been used as a urinary tract antispasmodic and anticholinergic agent. However, the effects of Tolterodine against LPS-induced insults in human bladder epithelial cells (hBECs) have not been reported before. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase release assays to determine the cell viability, reactive oxygen species (ROS) and malondialdehyde level detection were used to determine the level of oxidative stress, enzyme-linked immunosorbent assay and Western blot analysis were used to detect the protein level. In the current study, we found that Tolterodine ameliorated LPS-induced production of ROS and lipid oxidation in hBECs. Interestingly, Tolterodine inhibited the production of interleukin 6, interleukin-1ß, and tumor necrosis factor α. Also, Tolterodine reduced the levels of Fe2+ and suppressed ferroptosis by reducing the levels of glutathione peroxidase 4, prostaglandin-endoperoxide synthase 2, and acyl-CoA synthetase long-chain family member 4 in LPS-challenged bladder epithelial cells. Mechanistically, it was shown that Tolterodine restored the nuclear factor E2-related factor 2 (Nrf2)/nuclear factor-κB signaling. Importantly, inhibition of Nrf2 with its specific inhibitor ML385 abolished the protective effects of Tolterodine in the inflammatory response and ferroptosis, suggesting that the effects of Tolterodine are mediated by Nrf2. Based on these findings, we conclude that Tolterodine might serve as a promising agent for the treatment of LPS-induced bladder inflammation.

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

BACKGROUND: Several studies have provided evidence about adverse pregnancy outcomes of nurses involved in occupational exposure. However, the pregnancy outcomes among nurses in middle-income countries are not well demonstrated. The main aim of this study is to present the prevalence and influencing factors of pregnancy outcomes among female nurses in China. METHODS: We included 2243 non-nurse health care workers, and 4230 nurses in this national cross-sectional study in China. Information on occupational exposures and pregnancy outcomes was collected using a face-to-face investigation. Odds ratios (ORs) were estimated through logistic regression. RESULTS: The proportion of threatened abortion, spontaneous abortion, and stillbirth of female nurses was 2.6%, 7%, and 2.1%, respectively. We found an increased risk of threatened abortion among nurses with overtime work (OR = 1.719, 95% CI 1.158-2.550). The risk of threatened abortion and spontaneous abortion was elevated among nurses handling disinfectant (OR = 2.293 and 1.63, respectively). We found a nearly twofold increased risk of premature birth (OR = 2.169, 95% CI 1.36-3.459) among nurses handling anti-cancer drugs. CONCLUSIONS: Our findings suggested that maternal occupational exposures might be associated with the risk of adverse pregnancy outcomes among female nurses in China. We recommend that policy-markers and hospital managers work together to reduce exposure to occupational hazards and improve pregnancy outcomes among female nurses.

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

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

Do patients with metastatic renal cell carcinoma obtain survival benefits from cytoreductive nephrectomy? A population-based study.

PURPOSE: This study aimed to explore the value of cytoreductive nephrectomy (CN) and develop nomograms to predict the prognosis of metastatic renal cell carcinoma (mRCC) patients with receiving radiology therapy or/and chemotherapy (RT/&CT). METHODS: Clinical data of patients with mRCC between 2010 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Prognostic nomograms were constructed to predict the overall survival (OS) and cancer-specific survival (CSS) probability for 1-, 3-, and 5- years in patients with mRCC. A series of validation methods were used to validate the accuracy and reliability of the model, including area under the receiver operating curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA). RESULTS: 1394 patients were enrolled in this study. All patients were randomly divided into the training cohort (n = 976) and the validation cohort (n = 418). In the training cohort, multivariate Cox regression analysis suggested that pathology grade, histology type, T stage, N stage, surgery, and distant metastasis were independent risk factors for OS and CSS. The AUC and C-index were both over 0.65 in both cohorts, indicating that the nomograms for OS and CSS had satisfactory discriminative power. The calibration curves revealed that the predictive nomograms had a good consistency between the observed and the predicted survival. CONCLUSION: This study provided evidence that mRCC patients underwent RT/&CT could gain survival benefits from CN. The prognostic nomogram constructed in our study is reliable and practical, may help guide clinical strategies in the treatment of mRCC.

Occupational hazards and the onset of natural menopause.

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

Effect of hexavalent chromium-induced ribosomal DNA copy number variation on DNA damage response in various cell lines / 预防医学

Objective@#To investigate the effect of ribosomal DNA (rDNA) copy number variation caused by hexavalent chromium exposure on DNA damage response in different cell lines, so as to provide insights into the involvement of hexavalent chromium-induced rDNA copy number variation in DNA damage responses. @*@#Methods Human lung epithelial BEAS-2B cells and human embryonic lung MRC-5 cells were treated with 2 μmol/L potassium dichromate for 24 hours, and then cells were transferred to fresh media for further incubation, while cells treated with the same volume of phosphate buffer solution served as controls. Cells treated with potassium dichromate for 24 hours, and 3 and 7 days post-detoxification, were harvested, and rDNA copy number was quantified in cells using a quantitative fluorescent real-time PCR assay. Cell cycle, apoptosis and DNA damage were detected using a Muse cell analyzer, and the DNA damage was evaluated with the proportion of ataxia telangiectasia-mutated (ATM) gene activation, proportion of double-strand DNA breaks and the percentage of the H2A.X variant histone phosphorylatio.@*@# Results The 45S and 5S rDNA copy numbers of were significantly higher in MRC-5 cells than in BEAS-2B cells [(1.54±0.26) vs. (1.02±0.18), P<0.05; (6.97±1.07) vs. (3.00±0.15), P<0.05]. The 45S rDNA copy number was lower in MRC-5 cells 3 days post-detoxification (0.80±0.04) than in controls (P<0.05), and was higher in BEAS-2B cells 3 days post-detoxification (1.43±0.07) than in controls (P<0.05) . G0/G1 phase arrest was found in MRC-5 cells 24 hours post-treatment, and the apoptotic rates were significantly higher in MRC-5 cells 3 and 7 days post-detoxification than in controls [(11.53±1.53)%, (18.33±0.70)% vs. (3.53±0.93)%, P<0.05]. The overall apoptotic rates 24 hours post-treatment and 3 days post-detoxification [(2.80±0.17)%, (3.33±0.57)% vs. (1.53±0.61)%, P<0.05], proportion of ATM gene activation 3 days post-detoxification [(3.37±0.67%) vs. (1.18±0.22)%, P<0.05], proportion of double-strand DNA breaks 3 days post-detoxification [(4.45±0.85)% vs. (0.97±0.21)%, P<0.05] and percentage of the H2A.X variant histone phosphorylation 3 days post-detoxification [(1.68±0.56)% vs. (0.29±0.06)%, P<0.05] in BEAS-2B cells were higher than in controls. @*Conclusions@#Hexavalent chromium-induced rDNA copy number variation affects DNA damage response in different cell lines. A stronger DNA damage response is found in BEAS-2B cells with a low rDNA copy number, and a relative stable response is observed in MRC-5 cells with a high rDNA copy number.

Mortality due to respiratory system disease and lung cancer among female workers exposed to chrysotile in Eastern China: A cross-sectional study.

Female workers in the asbestos processing industry of Eastern China are at high risk of developing multiple types of cancer, and more data are urgently needed to better understand and address this issue. Death certificate data were selected from an asbestos processing city in China from 2005 to 2006. Information was investigated using the relatives of those individuals who had died as sources of information. Individuals were classified into one of three asbestos exposure levels. Standardized mortality ratio and 95% confidence interval were calculated. A total of 2,964 individual deaths were identified from 2005 to 2006; of these, 21.4% were occupationally exposed to asbestos. The main cause of death was circulatory system diseases (21.2%). The proportion of individuals with respiratory system diseases increased by age among each exposure subgroup (P trend < 0.01). Among females, a significant trend was observed between increased asbestos exposure and mortality due to respiratory system diseases and lung cancer. Our study indicated that asbestos exposure was associated with excess mortality from lung cancer and respiratory diseases, particularly among female workers in an asbestos processing area in Eastern China.

Association of occupations with decreased semen quality in eastern China: a cross-sectional study of 12 301 semen donors.

OBJECTIVES: This study aims to examine the association between occupational factors and semen quality in semen donors in eastern China. METHODS: We recruited 12 301 semen donors from 2006 to 2020 as the studying population. A self-designed questionnaire was applied for collecting lifestyle and work style information. Semen samples were analysed according to WHO guidelines. A crude and adjusted linear regression model was used to analyse the association between occupational factors and semen quality. RESULTS: College students accounted for 36.2% of all semen donors. The majority (81.3%) of semen donors were between 18 year and 30 years. Soldiers or the police had the highest semen volume (the median value=3.8 mL), however, they had the lowest sperm concentration (53.6×106/ml) and sperm motility (45.5%). Workers in finance or insurance had an elevated risk of low semen volume, sperm concentration and total sperm count (OR=1.43, 1.57 and 1.98, respectively). Unemployed men had a high risk of low sperm concentration and low total sperm count (OR=1.84 and 1.58, respectively). Working in the information technology industry had a deleterious effect on the progressive motility of sperm (OR=1.27, 95% CI 1.03 to 1.57). CONCLUSION: Our study indicated that sedentary work style and intensive sports in certain professions might be associated with decreased semen quality. We reported evidence of becoming unemployed on the damage to semen quality. Hence, we advocate a healthy work style to improve semen quality in eastern China.

Survival analysis of 36 patients with malignant mesothelioma / 预防医学

Objective @#To analyze the survival of patients with malignant mesothelioma, so as to provide insights into the management of malignant mesothelioma.@*Methods @#Totally 36 patients with malignant mesothelioma admitted to Cixi Third People’s Hospital from October 2012 to January 2021 were enrolled, and the demographic features, exposure to asbestos, and diagnosis and treatment were retrospectively reviewed. The survival rate and median survival time were calculated with the life-table method, and the factors affecting the survival rate of malignant mesothelioma were identified using the Kaplan-Meier estimate and log-rank test.@*Results @#The 36 patients with malignant mesothelioma included 6 men ( 16.67% ) and 30 women ( 83.33% ), and had a median age of 61 ( interquartile range, 14 ) years. There were 30 cases with pleural malignant mesothelioma ( 83.33% ) and 6 cases with peritoneal malignant mesothelioma ( 16.67% ), 32 cases ( 88.89% ) with a history of occupational exposure to asbestos, and 26 cases ( 72.22% ) receiving palliative treatment. The 1-, 2- and 3-year cumulative survival rates were 30%, 15% and 3%, respectively, and the median survival time was 0.71 years. In addition, there were no significant differences in the survival period among patients with malignant mesothelioma in terms of gender, age, route of asbestos exposure, duration of asbestos exposure, pathogenic site and treatment regimens ( P>0.05 ).@*Conclusion @#The 36 patients with malignant mesothelioma had a median survival period of 0.71 years, and no association was found between the survival period and asbestos exposure or pathogenic site.

Effect of asbestos exposure on oxidative stress / 预防医学

Objective @#To examine the effect of asbestos exposure on oxidative stress, so as to provide insights into the elucidation of pathogenesis and management of asbestos-related diseases. @*Methods @#Totally 245 subjects were recruited from an asbestos manufacturing area in Zhejiang Province, and their gender, age and history of asbestos exposure were collected through a questionnaire survey. The serum levels of 8-hydroxy-2'deoxyguanosine ( 8-OHdG ), glutathione ( GSH ), malondialdehyde ( MDA ), superoxide dismutase ( SOD ) and total antioxidative capacity ( TAOC ) were measured using an enzyme-linked immunosorbent assay ( ELISA ), and the levels of catalase ( CAT ), peroxiredoxin 2 ( PRX2 ), SOD1, SOD2 and thioredoxin-1 ( TRX1 ) were detected in peripheral white blood cells ( WBCs ) using a liquid-chip assay. Multivariable linear regression analysis was performed to identify the association between asbestos exposure and oxidative stress parameters. @*Results @#There were 50 subjects without a history of asbestos exposure (unexposed group), 102 subjects with asbestos exposure for less than 10 years ( AE<10-year group ) and 93 subjects with asbestos exposure for 10 years and more ( AE≥10-year group ). No significant differences were found among the three groups in terms of age, gender, proportion of smokers or proportion of alcohol consumers ( P>0.05 ). Significantly higher 8-OHdG and MDA in serum, and higher PRX2 in peripheral WBCs were detected in the AE≥10-year group than in the unexposed group ( P<0.05 ); lower GSH and TAOC in serum, and lower CAT in peripheral WBCs were detected in the AE≥10-year group than in the unexposed group ( P<0.05 ); higher 8-OHdG and MDA in serum, and higher PRX2 in peripheral WBCs were detected in the AE≥10-year group than in the AE<10-year group ( P<0.05 ). Multivariable linear regression analysis showed that asbestos exposure significantly correlated with 8-OHdG, MDA and TAOC in serum, and CAT and PRX2 in peripheral WBCs ( P<0.05 ). @*Conclusion @#Asbestos exposure may induce the oxidative stress damage, suggesting that oxidative stress may be involved in asbestos-related diseases.

Genome wide profiling of miRNAs relevant to the DNA damage response induced by hexavalent chromium exposure (DDR-related miRNAs in response to Cr (VI) exposure).

AIM: We aimed to explore the expression of miRNAs and their potential roles in the DNA damage response (DDR) induced by Cr (VI) exposure in human B lymphoblast cells (HMy2.CIR cells) and in a population of Cr (VI)-exposed humans. METHODS: Differentially expressed miRNAs were found by a combination of miRNA sequencing and RT-qPCR validation in HMy2.CIR cells treated with K2Cr2O7. Differentially expressed miRNAs related to DDR were selected for functional study. The expression levels of differential miRNAs were also investigated in chromate workers. RESULTS: A total of 214 differentially expressed miRNAs were identified by sequencing, and the expression of 5 miRNAs among 25 associated with DDR was found to be consistent between sequencing and validation studies.Functional studies showed that miR-148a-3p, miR-21-5p, and miR-424-3p might be related to Cr (VI)-induced cell apoptosis, and miR-221-3p might participate in Cr (VI)-induced DDR. We also found that the expression of miR-21-5p and miR-424-3p was upregulated in chromate workers. CONCLUSIONS: Cr (VI) exposure could significantly impact miRNAs expression in vitro and in chromate workers. Functional studies showed that miR-148a-3p, miR-21-5p and miR-221-3p might take a crucial role in the cellular DDR induced by Cr (VI) exposure.

Associations of age at natural menopause and occupations in Chinese female workers: A cross-sectional study.

AIMS: To investigate the impact of occupation types on age at natural menopause. METHODS: This is a nation-wide cross-sectional study based on 17,948 female workers aged over 40, who come from different industries or organizations. A face-to-face standardized questionnaire was conducted in all participants with the help of occupational hygienists. Occupational titles were coded according to the International Standard Classification of Occupations (2008) (ISCO08). Cox regression model was used to assess the association between each independent occupation and menopausal timing. Models were adjusted for marriage, education, average annual family income, parity, cigarette smoking, alcohol consumption. RESULTS: Higher risks of earlier age at natural menopause was found among legislators and senior officials (ISCO Minor group:111, HR = 2.328, P < 0.001), among other health associated professionals (ISCO Minor group: 325, HR = 1.477, P = 0.003), the workers involved in mining and mineral processing (ISCO Minor group: 811, HR = 1.515, P = 0.048) and metal processing and finishing (ISCO Minor group: 812, HR = 1.722, P < 0.001). Reduced risks of earlier age at natural menopause, including: finance professionals (ISCO Minor group: 241, HR = 0.751, P = 0.021), manufacturing and construction supervisors (ISCO Minor group: 312, HR = 0.477, P = 0.002), administrative and specialized secretaries (ISCO Minor group: 334, HR = 0.788, P = 0.045), cleaners and helpers (ISCO Minor group: 911, HR = 0.633, P = 0.01). CONCLUSIONS: This is the first study to address the influence of occupation types on reproductive aging, showing some specific occupations could be associated with age at natural menopause. Further investigations are necessary to clarify whether it is chance finding or a true association.

Exploration of identifying novel serum biomarkers for malignant mesothelioma using iTRAQ combined with 2D-LC-MS/MS.

Malignant mesothelioma (MM) is an aggressive cancer linked to asbestos exposure. Its poor prognosis makes early diagnosis extremely important, which would provide an opportunity for early treatment and potentially changing outcomes. This study aimed to explore the underlying mechanisms of MM and discover novel noninvasive biomarkers for the diagnosis of malignant mesothelioma. Using Isobaric tags for relative and absolute quantitation (iTRAQ) combined with two-dimensional liquid chromatography/tandem mass spectrometry (2D LC-MS/MS), a total of 145 differentially expressed serum proteins were identified between MM patients and healthy controls. The identified proteins were further analyzed by bioinformatics, out of which three candidate biomarkers (Filamin A (FLNA), Fibulin 1 (FBLN1) and Thrombospondin-1 (TSP-1)) were validated in large cohorts of patients with asbestos-related diseases including MM patients by ELISA assay. Receiver operating characteristic (ROC) curve analysis showed that serum FLNA, FBLN1 and TSP-1 had high diagnostic values in distinguishing MM patients from healthy controls, individuals with asbestos exposure (AE), and patients with pleural plaques (PP) or asbestosis. Meanwhile, serum FBLN1 and TSP-1 possessed good diagnostic values in distinguishing asbestosis patients from healthy controls and individuals with AE. The combination of FLNA, FBLN1, and TSP-1 proteins had higher sensitivity and specificity in discriminating patients with MM, PP and asbestosis. Our findings indicated that analysis of serum proteome using iTRAQ is a feasible strategy for biomarker discovery, and serum FLNA, FBLN1 and TSP-1 may be promising candidates for diagnosis of malignant mesothelioma and screening of at-risk individuals.

Progress in imaging diagnosis of pneumoconiosis / 预防医学

@#Pneumoconiosis is a serious occupational disease in China. Early imaging examination is one of the important measures for the diagnosis, treatment and prevention of pneumoconiosis. Digital radiography (DR) and computed tomography (CT) play an important role in the screening and diagnosis of pneumoconiosis, as well as the recent rise of artificial intelligence (AI) technology. This paper reviews the latest progress in technical parameter debugging and quality control of DR, optimization of AI computer-aided system and CT-aided diagnosis of pneumoconiosis, summarizes the advantages and problems in the application of the three technologies, providing research directions for imaging diagnosis of pneumoconiosis.

Overexpression of fibulin-3 in tumor tissue predicts poor survival of malignant mesothelioma patients from hand-spinning asbestos exposed area in eastern China.

Fibulin-3 is an extracellular matrix glycoprotein widely expressed in various tissues. Tissue fibulin-3 expression have never been reported in association with prognosis of mesothelioma. Hence, we sought to determine the association between fibulin-3 expression and mesothelioma survival. We made a tissue microarray, which was comprised of cancer and normal tissue from mesothelioma patients (n = 82) during the period 1998-2017 in China. Fibulin-3 and HGMB1 expression were analyzed by immunohistochemistry method. Kaplan-Meier method and Cox proportional hazard models were used for analyzing survival data. Overall, 61 cases (74.4%) were female; 90.2% were of epithelioid type; the median overall survival time was 12.5 months. Fibulin-3 and HMGB1 were highly expressed in tumor tissue rather than adjacent tissue. The expression of fibulin-3 in tissue was correlated with that of HMGB1 (r = 0.32, P = 0.003). High expression of fibulin-3 in tumor tissue could predict poor survival in patients with mesothelioma (P = 0.02). This remained true in a multivariate model, with a significant hazard ratio of 1.91. We demonstrated that fibulin-3 in tumor tissue was a novel biomarker of poor survival of mesothelioma, suggesting it may be a relevant target for therapeutic intervention.

Comparing different kidney stone scoring systems for predicting percutaneous nephrolithotomy outcomes: A multicenter retrospective cohort study.

OBJECTIVE: To compare the predictive performance of five previously described scoring systems (i.e., S.T.O.N.E., Guy's, Clinical Research Office of the Endourological Society (CROES), the Seoul National University Renal Stone Complexity (S-RESC) and the new Stone Kidney Size (SKS) score) for postoperative outcomes regarding stone-free rate (SFR) and complications in adult patients. METHODS: Data from 349 patients who underwent percutaneous nephrolithotomy (PCNL) in three urology departments were analyzed. SKS, S.T.O.N.E., S-ReSC, CROES and Guy's nephrolithometry scoring systems were used to retrospectively calculate predictions for each patient. Univariate and multivariate analyses were performed to evaluate factors associated with SFR and complication rates. Receiver operating characteristic (ROC) curves were generated and areas under curves (AUC) were compared to identify the method with the highest predictive value. RESULTS: Median SKS, S.T.O.N.E., S-ReSC, CROES and Guy's scores were 4, 7, 3, 170.8 and 2, respectively. Overall, SFR was 67.0% (234/349) with a complications rate of 36.7% (128/349). AUCs of each method for predicting stone-free status, highlighted reasonable predictive capabilities with 0.709, 0.806, 0 0.869, 0.207, and 0.735, respectively; however, the S-ReSC scoring system had the best discriminative performance. According to multivariate logistic regression and AUC results, none were effectively capable of predicting complications. CONCLUSIONS: All scoring systems correlated significantly with stone-free status; although, S-ReSC appears to have the greatest predictive ability. This method is also relatively easy to implement and highly reproducible. However, none of the methods analyzed are able to accurately predict postoperative complications.

Circulating differential miRNAs profiling and expression in hexavalent chromium exposed electroplating workers.

Hexavalent chromium [Cr (Ⅵ)] has extensive applications in industries, and long-term occupational exposure to Cr (Ⅵ) may lead to lung carcinoma and other cancers. While microRNA (miRNA) can take part in carcinogenesis, little is known about its expression profile in the population with Cr (Ⅵ) exposure. Thus, this study aimed to explore miRNA expression profiles in Cr (Ⅵ) exposed workers and to identify the potential biological function of differentially expressed miRNAs. A total of 45 significant differentially expressed miRNAs were identified by the miRNA array. The results of validation showed that miR-19a-3p, miR-19b-3p, and miR-142-3p were downregulated and miR-590-3p and miR-941 were upregulated in the exposure group. Multivariate analysis demonstrated that age, exposure duration and urinary chromium level were associated with one or more miRNAs expression. Target gene analysis indicated that these miRNAs might participate in the regulation of DNA damage-related signaling pathways. Taken together, Cr (Ⅵ) exposure can result in differential expression of miRNAs in occupational workers, and the expression of these miRNAs is correlated with the level and duration of Cr (Ⅵ) exposure, and the differentially expressed miRNAs may participate in DNA damage response.