The Resistance of Cancer Cells to Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, is Mediated by the ABCB1 Transporter.

Palbociclib was approved by the United States Food and Drug Administration for use, in combination with letrozole, as a first-line treatment for estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) postmenopausal metastatic breast cancer. However, recent studies show that palbociclib may be an inhibitor of the ABCB1 transporter, although this remains to be elucidated. Therefore, we conducted experiments to determine the interaction of palbociclib with the ABCB1 transporter. Our in vitro results indicated that the efficacy of palbociclib was significantly decreased in the ABCB1-overexpressing cell lines. Furthermore, the resistance of ABCB1-overexpressing cells to palbociclib was reversed by 3 µM of the ABCB1 inhibitor, verapamil. Moreover, the incubation of ABCB1-overexpressing KB-C2 and SW620/Ad300 cells with up to 5 µM of palbociclib for 72 h, significantly upregulated the protein expression of ABCB1. The incubation with 3 µM of palbociclib for 2h significantly increased the intracellular accumulation of [3H]-paclitaxel, a substrate of ABCB1, in ABCB1 overexpressing KB-C2 cells but not in the corresponding non-resistant parental KB-3-1 cell line. However, the incubation of KB-C2 cells with 3 µM of palbociclib for 72 h decreased the intracellular accumulation of [3H]-paclitaxel due to an increase in the expression of the ABCB1 protein. Palbociclib produced a concentration-dependent increase in the basal ATPase activity of the ABCB1 transporter (EC50 = 4.73 µM). Molecular docking data indicated that palbociclib had a high binding affinity for the ABCB1 transporter at the substrate binding site, suggesting that palbociclib may compete with other ABCB1 substrates for the substrate binding site of the ABCB1. Overall, our results indicate that palbociclib is a substrate for the ABCB1 transporter and that its in vitro anticancer efficacy is significantly decreased in cancer cells overexpressing the ABCB1.

VKNG-1 Antagonizes ABCG2-Mediated Multidrug Resistance via p-AKT and Bcl-2 Pathway in Colon Cancer: In Vitro and In Vivo Study.

The emergence of multidrug resistance (MDR) to chemotherapeutic drugs is a major problem in the therapy of cancer. Knowledge of the mechanisms of drug resistance in cancer is necessary for developing efficacious therapies. ATP-binding cassette (ABC) transporters are transmembrane proteins that efflux chemotherapeutic drugs from cancer cells, thereby producing MDR. Our research efforts have led to the discovery of VKNG-1, a compound that selectively inhibits the ABCG2 transporter and reverses resistanctabe to standard anticancer drugs both in vitro and in vivo. VKNG-1, at 6 µM, selectively inhibited ABCG2 transporter and sensitized ABCG2-overexpressing drug-resistant cancer cells to the ABCG2 substrate anticancer drugs mitoxantrone, SN-38, and doxorubicin in ABCG2-overexpressing colon cancers. VKNG- 1 reverses ABCG2-mediated MDR by blocking ABCG2 efflux activity and downregulating ABCG2 expression at the mRNA and protein levels. Moreover, VKNG-1 inhibits the level of phosphorylated protein kinase B (PKB/p-AKT), and B-cell lymphoma-2 (Bcl-2) protein which may overcome resistance to anticancer drugs. However, the in vitro translocation of ABCG2 protein did not occur in the presence of 6 µM of VKNG-1. In addition, VKNG-1 enhanced the anticancer efficacy of irinotecan in ABCG2- overexpressing mouse tumor xenografts. Overall, our results suggest that VKNG-1 may, in combination with certain anticancer drugs, represent a treatment to overcome ABCG2-mediated MDR colon cancers.

Role of B-Cell Lymphoma 2 Ovarian Killer (BOK) in Acute Toxicity of Human Lung Epithelial Cells Caused by Cadmium Chloride.

BACKGROUND B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) is a Bcl-2 family member with sequence homology to pro-apoptotic BAX and BAK, but its physiological and pathological roles remain largely unclear. Exposure of cells to cadmium may cause DNA damage, decrease DNA repair capacity, and increase genomic instability. MATERIAL AND METHODS The present study investigated the effects of BOK on the toxicity of cadmium chloride (CdCl2) to human bronchial epithelial (16HBE) cells. We constructed BOK over-expressing (16HBE-BOK) cells and BOK knockdown (16HBE-shBOK) cells using the BOK-ORF plasmid and BOK-siRNA. qRT-PCR for BOK mRNA expression. We used Trypan blue exclusion assay for cell growth, MTT colorimetric assays for cells inhibition rate, and Comet assays for detecting damaged DNA. RESULTS CdCl2, at various concentrations and exposure times, increased BOK mRNA. 16HBE-BOK cells (BOK over-expressing) proliferated more than 16HBE cells after 72 h; 16HBE-shBOK (BOK knockdown) cells proliferated less. In addition, BOK deficiency enhanced cell death induced by CdCl2. Similarly, CdCl2- and H2O2-induced DNA damage was greater in BOK-deficient cells. CONCLUSIONS These findings support a role for BOK in CdCl2-induced DNA damage and cell death.

Spatiotemporal variability of polybrominated diphenyl ether concentration in atmospheric fine particles in Shenzhen, China.

Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants for various products and have become ubiquitous pollutants in environmental media. However, little is known about PBDE levels in Shenzhen, a manufacturing center of electronic products. This study aimed to investigate spatiotemporal variability of PBDE concentration in atmospheric fine particles (PM2.5) and to estimate the daily inhalation exposure doses for local residents in Shenzhen, China. A total of 36 samples were collected and 8 PBDE compounds (BDE-28, 47, 99, 100, 153, 154, 183 and 209) were analyzed by isotope dilution high-resolution gas chromatograph/high-resolution mass spectrometer (HRGC/HRMS). Mean concentrations of Σ8PBDEs and BDE-209 in PM2.5 in Shenzhen were 33.47 pg/m3 and 24.75 pg/m3, respectively, which were lower than those for other reported cities from China. The mean concentration of Σ8PBDEs was higher in the winter + spring than that in summer + autumn, and both concentrations of BDE-28 and BDE-47 in PM2.5 were significantly higher in winter + spring than those in summer + autumn. Among the 8 congeners, BDE-209 was predominant, accounting for 73.9% of the Σ8PBDEs concentrations. Traffic area, industrial area, residential area and discharge of electronic industries had significant positive influences on PBDE concentrations in PM2.5. Both vegetation area and water area were significantly negatively correlated with PBDE levels in PM2.5. Significantly negative correlation was also found between PBDE concentrations in PM2.5 and the relative humidity. The ranking of estimated inhalation exposure doses of PBDEs via PM2.5 inhalation were toddlers (1.74 pg/kg b.w./day) > children (1.33 pg/kg b.w./day) > adults (1.26 pg/kg b.w./day) > teenagers (0.64 pg/kg b.w./day), and toddlers had a highest risk to expose to PBDEs by PM2.5. To our knowledge, the present study is the first to reveal the spatiotemporal variability of PBDEs in PM2.5 of Shenzhen, China.

Epidermal growth factor receptor (EGFR) inhibitor PD153035 reverses ABCG2-mediated multidrug resistance in non-small cell lung cancer: In vitro and in vivo.

One of the major mediators of multidrug resistance (MDR) in non-small cell lung cancer (NSCLC) is the overexpression of ATP-binding cassette subfamily G member 2 (ABCG2). In this study, we conducted in vitro and in vivo experiments to determine whether PD153035, an inhibitor of EGFR, could reverse ABCG2-mediated MDR in human NSCLC and transfected cells overexpressing ABCG2. The efficacy of SN-38, topotecan, and mitoxantrone (MX) were significantly increased by PD153035, PD153035 significantly reversed ABCG2-mediated MDR by attenuating the efflux activity of this transporter. In addition, PD153035 significantly down-regulated the expression of the ABCG2 transporter protein. Furthermore, a combination of PD153035 and topotecan, exhibited significant synergistic anticancer activity against mice xenografted with human H460/MX20 cells. These results, provided that they can be extrapolated to humans, suggest that the combination of topotecan and PD153035 could be a promising therapeutic strategy to attenuate the resistance to topotecan, as well as other anticancer drugs, mediated by the overexpression of ABCG2.

Validation of the chinese version of the EORTC QLQ-CR29 in patients with colorectal cancer.

AIM: To assess the validity and reliability of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Colorectal Cancer 29 (EORTC QLQ-CR29) in Chinese patients with colorectal cancer (CRC). METHODS: From March 2014 to January 2015, 356 patients with CRC from four different hospitals in China were enrolled in the study, and all patients self-administered the EORTC QLQ-CR29 and the quality of life core questionnaire (EORTC QLQ-C30). Evaluation of the scores was based on the Karnofsky Performance Scale (KPS). The reliability and validity of the questionnaires were assessed by Cronbach's α coefficient, the Spearman correlation test and Wilcoxon rank sum test. RESULTS: The EORTC QLQ-CR29 showed satisfactory reliability (α > 0.7), although the urinary frequency and blood and mucus in stool dimensions had only moderate reliability (α = 0.608). The multitrait scaling analyses showed good convergent (r > 0.4) and discriminant validity. Significant differences were obtained for each item in the different KPS subgroups (KPS ≤ 80; KPS > 80). Body image and most single-item dimensions showed statistically significant differences in patients with a stoma compared with the rest of the patients. CONCLUSION: The EORTC QLQ-CR29 exhibits high validity and reliability in Chinese patients with CRC, and can therefore be recommended as a valuable tool for the assessment of quality of life in these patients.

[Effects of hexabromocyclododecanes on retinoid X receptor α, pregnane X receptor and peroxisome proliferator-activated receptor γ].

OBJECTIVE: To investigate the effect of hexabromocyclododecanes( HBCDs) on cell proliferation and the expression of the three important cell nuclear receptor of retinoic X receptor α( RXRα), peroxisome proliferator-activated receptor-γ( PPARγ), pregnane X receptor( PXR) and their interaction in Neuro-2a(N2a). METHODS: Neuro-2a cells were treated with different concentrations of diastereoisomers, of HBCDs which were α-HBCD, ß-HBCD, γ-HBCD, respectively, and cell toxicity was analyzed using the cell counting kit-8( CCK-8) assay. The impact of HBCDs on cell cycles of Neuro-2a were analyzed by flow cytometry analysis, and the expression levels in mRNA and protein for the three nuclearreceptors( RXRα, PPARγ, PXR andits target genes CYP3A11) were determined by RT-PCR and Western blot, respectively. The interaction between the receptors of RXRα, PXR, PPARγ was explored by immunoprecipitation. RESULTS: Cytotoxicity of ß-HBCD was the greatest among the three diastereoisomers, it was significantly greater than α-HBCD, however cytotoxicity of γ-HBCD for the Neuro-2a cells couldn 't be determined. Moreover α-HBCD, ß-HBCD induced significant cytotoxicity in a time-dose-response relationship to Neuro-2a cells( P < 0. 05), IC_(50) of α-HBCD, ß-HBCD to Neuro-2a cells were 60. 07 and 10. 52 µmol/L, respectively. α-, ß-HBCD blocked the cell cycle at G2/M phase. The expression levels in mRNA and protein of RXRα, PPARγ, PXR, CYP3A11 were significantly increased after cells exposure to α-HBCD and ß-HBCD 24 h. An interaction between RXRα, PPARγ and PXR in Neuro-2a cells existed no matter before and after exposure to HBCD. CONCLUSION: α-HBCD, ß-HBCD inhibit proliferation of Neuro-2a cells, cell cycle mainly was arrested at G2/M phase. α-HBCD, ß-HBCD could up-regulated the expression levels of RXRα, PPARγ, PXR. Meanwhile, the expression of CYP3A11 which is downstream gene of PXR also significantly increased( P < 0. 05). Interaction between RXRα, PPARγ and PXR exist whether or not exposure to α-, ß-HBCD. The molecular mechanisms of interaction between the receptors need further study.

LncRNA-MALAT1 as a novel biomarker of cadmium toxicity regulates cell proliferation and apoptosis.

Cadmium (Cd) and its compounds are well-known human carcinogens, but the mechanisms underlying the carcinogenesis are not well understood. This study aimed to investigate whether lncRNA-MALAT1 could serve as a novel biomarker of Cd toxicity in cells, animals and Cd-exposed workers, and regulate cell proliferation, apoptosis, migration and invasion. MALAT1 expression increased gradually in CdCl2 transformed 16HBE cells. The cell apoptosis, migration and invasion were significantly inhibited, and the mRNA and protein expression of FOXC2, STAT, BAX, EGFR, and TGF-ß1 reduced, but BCL-2 increased (P < 0.05) after silencing MALAT1 by siRNA in CdCl2 treated 16HBE cells of 15th and 35th passages. Cadmium increased MALAT1 expression in the lung of Cd-exposed rats in a dose-dependent manner. A significant positive correlation was observed between blood MALAT1 expression and urinary/blood Cd concentrations, and there were significant correlations of MALAT1 expression with the expressions of target genes in the lung of Cd-exposed rats and the blood of Cd exposed workers. This study suggests that the expression of MALAT1 is upregulated and regulates the cell cycle progression, proliferation, apoptosis, migration and invasion in Cd toxicity. MALAT1 may serve as a novel valuable biomarker of cadmium exposure and cadmium toxicity.

Sleep quality and health service utilization in Chinese general population: a cross-sectional study in Dongguan, China.

OBJECTIVES: The aims of this study were to explore the Pittsburgh Sleep Quality Index (PSQI) and health service utilization in Chinese general population, to investigate the association between PSQI and health service utilization and to identify the independent contributions of social demographic variables, health related factors and PSQI to health service utilization. METHODS: In a cross-sectional community-based health survey using a multi-instrument questionnaire, 4067 subjects (≥15 years old) were studied. The Chinese version of the PSQI was used to assess sleep quality. Health service utilization was measured by recent two-week physician visit and annual hospitalization rates. RESULTS: Higher PSQI scores were associated with more frequent health service utilization. Higher scores in subjective sleep quality were associated with higher rate of recent two-week physician visit (adjusted OR = 1.24 per SD increase, P = 0.015). Higher scores in habitual sleep efficiency (adjusted OR = 1.24 per SD increase, P = 0.038) and sleep disturbances (adjusted OR = 2.09 per SD increase, P < 0.001) were associated with more frequent annual hospitalization. The independent influence of PSQI on the risk of recent two-week physician visit was 0.7%, and that of annual hospitalization 31.4%. CONCLUSIONS: Poorer sleep quality predicted more frequent health service utilization. The independent contribution of PSQI on health service utilization was smaller than social demographic variables.

Serum albumin level is associated with the recurrence of acute ischemic stroke.

BACKGROUND: Previous studies have confirmed that low serum albumin levels in acute ischemic stroke patients increased the risk for poor outcome and death, demonstrating the neuroprotective role of albumin. However, there are few studies investigating the relationship between albumin levels and recurrence of stroke. The aim of this study was to evaluate the effect of serum albumin level on the risk of recurrence in patients with acute ischemic stroke. METHODS: Seven hundred fifty-three consecutive patients with acute first-ever ischemic stroke were recruited in this study. Recurrent outcome was measured 1 year after stroke through home interviews (n = 692). RESULTS: Patients with recurrence had significantly lower serum albumin level than those without recurrence (37.07 ± 4.21 vs 38.91 ± 3.25). The multiple logistic regression adjustment for confounding factors showed that the association remained significant for patients in the second albumin quartile, the third quartile, and the fourth quartile compared with patients in the first quartile (adjusted odds ratio [aOR] = 0.543, 95% confidence interval [CI]: 0.307-0.959, P= .036; aOR = 0.449, 95% CI: 0.249-0.812, P= .008; and aOR = 0.290, 95% CI: 0.148-0.570, P < .001). CONCLUSION: Lower serum albumin level increases the risk of recurrence in patients with acute ischemic stroke, suggesting that serum albumin level might be used as an indicator for stroke recurrence.

Dietary intake and urinary level of cadmium and breast cancer risk: A meta-analysis.

Cadmium, a human carcinogenic heavy metal, has been reported to be associated with breast cancer risk; however, the results from the epidemiological studies are not always consistent. The objective of this study was to quantitatively summarize the current evidence for the relationship between cadmium exposure and breast cancer risk using meta-analysis methods. Six studies determining the dietary cadmium intake level and five studies evaluating the urinary cadmium level were identified in a systematic search of MEDLINE and PubMed databases, and the associations between these levels and breast cancer risk were analysed. The pooled estimates under the random-effects model suggested that higher urinary cadmium levels were associated with an increased risk for breast cancer (highest versus lowest quantile, pooled odds ratio [OR]=2.24, 95% confidence interval [95%CI]=1.49-3.35) and a 1µg/g creatinine increase in urinary cadmium led to a 1.02-fold increment of breast cancer (pooled OR=2.02, 95%CI=1.34-3.03); however, pooled estimates for dietary cadmium intake found no significant association between cadmium exposure and breast cancer risk (highest versus lowest quantile, pooled relative risk [RR]=1.01, 95%CI=0.89-1.15). These results suggest that cadmium exposure may lead to an increased risk of breast cancer, and urinary cadmium levels can serve as a reliable biomarker for long-term cadmium exposure and may predict the breast cancer risk.

Reliability and Construct Validity of Two Versions of Chalder Fatigue Scale among the General Population in Mainland China.

The 14-item Chalder Fatigue Scale (CFS) is widely used, while the 11-item version is seldom to be found in current research in mainland China. The objectives of the present study is to compare the reliability and construct validity between these two versions and to confirm which may be better for the mainland Chinese setting. Based on a cross-sectional health survey with a constructive questionnaire, 1887 individuals aged 18 years or above were selected. Socio-demographic, health-related, gynecological data were collected, and 11-item and 14-item Chalder Fatigue Scale (CFS) were used to assess fatigue. Confirmatory factor analysis and exploratory structural equation modeling (ESEM) were performed to test the fit of models of the two versions. Confirmatory factor analysis of the two versions of CFS did not support the two-factor theorized models. In addition, a three-factor ESEM model of the 11-item version, but not the 14-item version, showed better factor structure and fitness than the other models examined. Both the versions had good internal consistency reliability and a satisfactory internal consistency (Ω = 0.78-0.96, omega coefficient indicates the internal consistency reliability) was obtained from the optimal model. This study provided evidence for satisfactory reliability and structural validity for the three-factor model of the 11-item version, which was proven to be superior to the 14-item version for this data.

eIF3 regulates migration, invasion and apoptosis in cadmium transformed 16HBE cells and is a novel biomarker of cadmium exposure in a rat model and in workers.

Translation (eukaryotic) initiation factor 3 (eIF3 or TIF3) has been found to be a proto-oncogene in cadmium (Cd) response both in vitro and vivo, but whether eIF3 may serve as a biomarker of Cd exposure is still unclear. This study aimed to investigate whether eIF3 could serve as a novel biomarker of Cd toxicity in cells, animals and workers, and regulate the apoptosis, migration and invasion in human bronchial epithelial cell (16HBE cells) transformation with cadmium chloride (CdCl2). In CdCl2 transformed 16HBE cells, eIF3 expression increased gradually, and sequencing did not identify mutation and methylation of eIF3. In 16HBE cells with eIF3 silencing by siRNA and CdCl2 treated 16HBE cells of the 15th and 35th generations, the apoptosis, migration and invasion were significantly inhibited, and the expressions of relevant genes were also altered (P < 0.05). In CdCl2 treated rats, eIF3 mRNA expression increased to different extents in the blood, liver, kidney, heart and lung, and this increase was dependent on the Cd concentration (P < 0.05). The eIF3 mRNA expression was related to the mRNA expressions of AKT, BAX, BCL-2, E-CADHERIN, CASPASE-3, EGFR, FOXC2, STAT3, TGF-ß1 and VIMENTIN (P < 0.05). In 181 workers with Cd exposure, the eIF3 mRNA expression was positively related to the blood Cd, urine Cd and ß2-microglobulin content (P < 0.05). This study showed that abnormally expressed eIF3 may regulate the apoptosis, migration and invasion of 16HBE cells with Cd toxicity. This suggests that eIF3 may become a novel and valuable biomarker of Cd toxicity and Cd-induced effects, and may regulate apoptosis, migration and invasion of 16HBE cells. Thus, the detection of eIF3 expression is important for the monitoring of Cd toxicity in humans.

The Effect on Sodium/Iodide Symporter and Pendrin in Thyroid Colloid Retention Developed by Excess Iodide Intake.

It is well known that excess iodide can lead to thyroid colloid retention, a classic characteristic of iodide-induced goiter. However, the mechanism has not been fully unrevealed. Iodide plays an important role in thyroid function at multiple steps of thyroid colloid synthesis and transport among which sodium/iodide symporter (NIS) and pendrin are essential. In our study, we fed female BALB/c mice with different concentrations of high-iodine water including group A (control group, 0 µg/L), group B (1500 µg/L), group C (3000 µg/L), group D (6000 µg/L), and group E (12,000 µg/L). After 7 months of feeding, we found that excess iodide could lead to different degrees of thyroid colloid retention. Besides, NIS and pendrin expression were downregulated in the highest dose group. The thyroid iodide intake function detected by urine iodine assay and thyroidal (125)I experiments showed that the urine level of iodine increased, while the iodine intake rate decreased when the concentration of iodide used in feeding water increased (all p < 0.05 vs. control group). In addition, transmission electron microscopy (TEM) indicated a reduction in the number of intracellular mitochondria of thyroid cells. Based on these findings, we concluded that the occurrence of thyroid colloid retention exacerbated by excess iodide was associated with the suppression of NIS and pendrin expression, providing an additional insight of the potential mechanism of action of excess iodide on thyroid gland.

Workplace Violence and Job Performance among Community Healthcare Workers in China: The Mediator Role of Quality of Life.

OBJECTIVE: To explore the impact of workplace violence on job performance and quality of life of community healthcare workers in China, especially the relationship of these three variables. METHODS: From December 2013 to April 2014, a total of 1404 healthcare workers were recruited by using the random cluster sampling method from Community Health Centers in Guangzhou and Shenzhen. The workplace violence scale, the job performance scale and the quality of life scale (SF-36) were self-administered. The structural equation model constructed by Amos 17.0 was employed to assess the relationship among these variables. RESULTS: Our study found that 51.64% of the respondents had an experience of workplace violence. It was found that both job performance and quality of life had a negative correlation with workplace violence. A positive association was identified between job performance and quality of life. The path analysis showed the total effect (ß = -0.243) of workplace violence on job performance consisted of a direct effect (ß = -0.113) and an indirect effect (ß = -0.130), which was mediated by quality of life. CONCLUSIONS: Workplace violence among community healthcare workers is prevalent in China. The workplace violence had negative effects on the job performance and quality of life of CHCs' workers. The study suggests that improvement in the quality of life may lead to an effective reduction of the damages in job performance caused by workplace violence.

MicroRNAs-mRNAs Expression Profile and Their Potential Role in Malignant Transformation of Human Bronchial Epithelial Cells Induced by Cadmium.

BACKGROUND: Our study was designed to elucidate whether there were miRNA and mRNA aberrantly expression profiles and potential role in malignant transformation of 16HBE induced by Cd. METHODS: mRNA and miRNA expression profiles were determined in 35th Cd-induced 16HBE and untreated 16HBE by microarray. A series of bioinformatics analyses such as predicting targets, GO, KEGG were performed to find DEGs, coexpressing networks between miRNAs and mRNAs and its functions. RESULTS: 498 DEGs were found. 8 Cd-responsive novel miRNAs predicted previously were identified, and 5 of them were downregulated. 214 target genes were predicted for the Cd-responsive miRNAs, many of which appeared to regulate gene networks. Target gene CCM2 was showed reciprocal effect by miRNAs. According to the combination analysis, hsa-miR-27b-3p regulated most of the mRNAs, especially upregulated expression genes. The differentially expressed miRNAs are involved in the biological processes and channels, and these GO and KEGG enrichment analyses result were significantly enriched in the Cd-responsive. DISCUSSION: These results provided a tight link for the miRNA-mRNA integrated network and implied the role of novel miRNAs in malignant transformation of 16HBE induced by Cadmium. It is better to understand the novel molecular mechanism of cadmium-induced tumorigenesis.

Long non-coding RNAs as novel expression signatures modulate DNA damage and repair in cadmium toxicology.

Increasing evidence suggests that long non-coding RNAs (lncRNAs) are involved in a variety of physiological and pathophysiological processes. Our study was to investigate whether lncRNAs as novel expression signatures are able to modulate DNA damage and repair in cadmium(Cd) toxicity. There were aberrant expression profiles of lncRNAs in 35th Cd-induced cells as compared to untreated 16HBE cells. siRNA-mediated knockdown of ENST00000414355 inhibited the growth of DNA-damaged cells and decreased the expressions of DNA-damage related genes (ATM, ATR and ATRIP), while increased the expressions of DNA-repair related genes (DDB1, DDB2, OGG1, ERCC1, MSH2, RAD50, XRCC1 and BARD1). Cadmium increased ENST00000414355 expression in the lung of Cd-exposed rats in a dose-dependent manner. A significant positive correlation was observed between blood ENST00000414355 expression and urinary/blood Cd concentrations, and there were significant correlations of lncRNA-ENST00000414355 expression with the expressions of target genes in the lung of Cd-exposed rats and the blood of Cd exposed workers. These results indicate that some lncRNAs are aberrantly expressed in Cd-treated 16HBE cells. lncRNA-ENST00000414355 may serve as a signature for DNA damage and repair related to the epigenetic mechanisms underlying the cadmium toxicity and become a novel biomarker of cadmium toxicity.

[Levels of polychlorinated dibenzo-p-dioxins and dibenzofurans in airborne fine particulate matter and inhalation risk assessment for local residents of Shenzhen].

OBJECTIVE: To explore the levels and congener profiles of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in airborne fine particulate matter (PM25) in Shenzhen and roughly discuss its correlations between PM25 concentration and meteorological factors. METHODS: The high volume air samplers were used to collect the samples in six sampling sites in respective winter and spring phase and summer and autumn phase. Referring to the US EPA TO-9A for dioxins detection methods, the concentrations of the 17 polychlorinated dibenzo-p-dioxins and dibenzofurans in airborne fine particulate matter were determined by HRGC/HRMS. RESULTS: The total concentrations of PCDD/Fs ranged from 0.32 to 9.35 pg/m3, with average of 2.45 pg/ m3. The TEQ concentrations ranged from 0.006 to 0.388 pg I-TEQ/m3, with average of 0.095 pg I-TEQ/m3. The four abundant congeners were found to be OCDD (36.49%), 1, 2, 3, 4, 6, 7, 8-HpCDF (14.89%), OCDF (13.34%) and 1, 2, 3, 4, 6, 7, 8-HpCDD (10.92%). 2, 3, 4, 7, 8-PeCDF was the dominant contributor to toxicity equivalent (TEQ), accounting for 34.65%. Positive relationship was found between the levels of fine particle-bound PCDD/Fs and PM2.5 concentration (r(s) = 0.794, P = 0.006), whereas no correlation was observed for temperature, humidity and atmospheric pressure. Inhalation exposure to PCDD/Fs were 0. 023 pg I-TEQ/(kg · d) for adult and 0.035 pg I-TEQ/(kg · d) for children during winter and spring and relatively higher than those during summer and autumn (0.014 pg I-TEQ/(kg · d). for adult and 0.021 pg I-TEQ/(kg · d) for children respectively). CONCLUSION: The levels of PCDD/Fs in airborne fine particle-bound samples collected in Shenzhen were lower than those in Hangzhou and Beijing.

A community-based cross-sectional study of fatigue in middle-aged and elderly women.

BACKGROUND: Fatigue has been widely studied in the general population; however, limited studies have investigated it in the female population. The objectives of this community-based study were to (1) investigate the prevalence of fatigue, (2) explore the relationship between gynecological history and experiences of fatigue, and (3) identify risk factors for fatigue in middle-aged and elderly women. METHODS: Based on a cross-sectional health study that employed a multi-instrument questionnaire, 1272 women aged 45years or older dwelling in the community were included. The Chinese version of Chalder Fatigue Scale (CFS) was used to assess fatigue, and socio-demographic, health-related, and gynecological data were also collected. Fatigue was defined as a total CFS score≥4. RESULTS: The prevalence of fatigue among women aged over 45years was 33.9%. Multivariate logistic regression analysis identified that older age, single marital status, lower education level, the presence of chronic diseases, underweight, hospitalization in the last year, postmenopause, and a higher number of live births were associated with an increased risk of fatigue (P<0.05). CONCLUSIONS: Our results indicated that fatigue was common in middle-aged and elderly females. Being postmenopausal and having more than three live births were the particular gynecological factors contributing to fatigue in the general population.

Prevalence and risk factors of posttraumatic stress disorder among survivors five years after the "Wenchuan" earthquake in China.

OBJECTIVE: The aim of this study was to investigate the prevalence of posttraumatic stress disorder (PTSD) and its risk factors among survivors in a heavily-hit area five years after the Wenchuan earthquake in 2008, China. METHODS: 684 survivors from Beichuan county, the center of the Wenchuan Earthquake in 2008, were evaluated using the PTSD Checklist-Civilian Version (PCL-C) questionnaire in 2013. RESULTS: The prevalence of PTSD among survivors was 9.2% in 2013. Significant risk factors of PTSD included gender (females 12.1%, males 5.2%), age (18-35 y 0.8%, 36-59 y 9.7%, ≥60 y 12.9%), occupation (farmers 12.2%, non-farmers 1.6%), education (less than high school 11.0%; > = high school 0.8%) and family member loss (yes: 12.4%, no: 7.3%). Multivariate logistic regression showed that females, older people, farmers and those with family member loss were significantly more likely to develop PTSD. CONCLUSIONS: Posttraumatic stress symptoms remained relatively common among survivors five years after the "5.12" Earthquake in Beichuan county, China. It is important to provide psychological aid and social support for survivors to decease health burden from PTSD, especially for females, farmers, old age survivors and those with family member loss.