Comparison of disinfection quality in nurseries of Nanjing during 2019-2021 / 中国学校卫生

Objective@#To analyze the disinfection quality and influencing factors of nurseries in Nanjing during 2019-2021, so as to provide a scientific basis for optimizing preventive disinfection strategies and measures in nurseries.@*Methods@#Environmental samples from 389 nurseries in Nanjing from January 2019 to December 2021 were tested, and the change of disinfection quality qualification rate was compared.@*Results@#The overall disinfection qualification rate of nurseries of year 2019-2021 were 96.32%, 95.85% and 94.60%, respectively, showing a downward trend ( χ 2 trend =8.67, P <0.05). Specifically, disinfection qualification rate of object surfaces, staff hands and tableware showed a downward trend, while the disinfection qualification rate of dynamic air showed an upward trend, and the differences were statistically significant ( χ 2 trend =23.17, 12.32, 5.37, 21.48, P <0.05). The total qualification rate of disinfection in Jiangning and Liuhe districts increased during 2019-2021( χ 2 trend =21.46, 24.05, P <0.05).@*Conclusion@#Disinfection quality of nurseries in Nanjing has declined by year during 2019-2021, especially the object surfaces and staff hands. It is urgent to optimize and refine the strategies and measures for preventive disinfection in nurseries, strengthen the training of personnel on disinfection knowledge, and ensure the quality of disinfection in nurseries.

Sharp injuries: a cross-sectional study among health care workers in a provincial teaching hospital in China.

BACKGROUND: The objectives of this study are to investigate the incidence and reporting behavior of sharp injuries among healthcare workers (HCWs) and identify the risk factors associated with these injuries. METHODS: A cross-sectional survey was conducted in February 2017 in a provincial teaching hospital in China. Data were collected from 901 HCWs using a self-administered questionnaire which included demographic information, experience, and reporting behavior of sharp injuries. Stepwise logistical regression was used to analyze the risk factors. RESULTS: HCWs (248 [27.5%]) had sustained a sharp injury in the previous year. Factors including seniority, job category, title, education, department, and training programs were associated with the occurrence of sharp injuries. According to the stepwise logistical regression, seniority, and training programs were the risk factors associated with the occurrence of sharp injuries. Of 248 sharp injuries, 130 HCWs were exposed to blood. Only 44 (33.9%) HCWs reported their injuries to the concerned body. The main reasons for not reporting the sharp injuries were as follows: perception that the extent of the injury was light (30.2%), having antibodies (27.9%), and unaware of injury (16.3%). CONCLUSIONS: Sharp injuries in the studied hospital were common and were likely to be underreported. Therefore, an effective reporting system and sufficient education on occupational safety should be implemented by the relevant institutions. Moreover, it is important to take effective measures to manage sharp injuries in HCWs and provide guidance for their prevention.

HIF-2α, acting via miR-191, is involved in angiogenesis and metastasis of arsenite-transformed HBE cells.

Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested that hypoxia-inducible factors (HIFs) and microRNAs (miRNAs) are involved in human lung cancer; however, their molecular mechanisms that causally contribute to arsenite-caused malignant transformation of cells remain unclear. To elucidate the mechanisms of angiogenesis and metastasis of lung cancer caused by arsenite, we investigated the role of HIF-2α regulation of miRNA-191 (miR-191) in the angiogenic and metastatic properties of human bronchial epithelial (HBE) cells transformed by arsenite. In HBE cells, HIF-2α binds to the hypoxia response element (HRE) in the promoter region of miR-191 and initiates transcription of miR-191. Blocking of HIF-2α with siRNA inhibited the up-regulation of miR-191, Wilms' tumor 1 (WT1) protein, matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), and the down-regulation of brain acid-soluble protein 1 (BASP1). In arsenite-transformed HBE (T-HBE) cells, down-regulation of HIF-2α by siRNA blocked the process of angiogenesis and decreased their neoplastic properties and metastatic capacity, which were reversed by over-expression of miR-191 or by up-regulating WT1. Thus, HIF-2α up-regulates WT1 via miR-191, both of which are involved in the angiogenesis and metastasis of T-HBE cells. The results present a better understanding of the processes involved in lung cancer caused by arsenite exposure.

Epigenetic silencing of microRNA-218 via EZH2-mediated H3K27 trimethylation is involved in malignant transformation of HBE cells induced by cigarette smoke extract.

Abnormal expression of miRNAs has been implicated in the pathogenesis of human lung cancers, most of which are attributable to cigarette smoke. The mechanisms of action, however, remain obscure. Here, we report that there are decreased expression of miR-218 and increased expression of EZH2 and H3K27me3 during cigarette smoke extract (CSE)-induced transformation of human bronchial epithelial (HBE) cells. Depletion of EZH2 by siRNA or by the EZH2 inhibitor, 3-deazaneplanocin A, attenuated CSE-induced decreases of miR-218 levels and increases of H3K27me3, which epigenetically controls gene transcription, and BMI1, an oncogene. Furthermore, ChIP assays demonstrated that EZH2 and H3K27me3 are enriched at the miR-218-1 promoter in HBE cells exposed to CSE, indicating that EZH2 mediates epigenetic silencing of miR-218 via histone methylation. In addition, miR-218 directly targeted BMI1, through which miR-218 ablates cancer stem cells (CSCs) self-renewal in transformed HBE cells. In CSE-transformed HBE cells, the protein level of Oct-4 and mRNA levels of CD133 and CD44, indicators of the acquisition of CSC-like properties, were reduced by over-expression of miR-218, and over-expression of miR-218 decreased the malignancy of transformed HBE cells. Thus, we conclude that epigenetic silencing of miR-218 via EZH2-mediated H3K27 trimethylation is involved in the acquisition of CSC-like properties and malignant transformation of HBE cells induced by CSE and thereby contributes to the carcinogenesis of cigarette smoke.

STAT3-regulated exosomal miR-21 promotes angiogenesis and is involved in neoplastic processes of transformed human bronchial epithelial cells.

Although microRNA (miRNA) enclosed in exosomes can mediate intercellular communication, the roles of exosomal miRNA and angiogenesis in lung cancer remain unclear. We investigated functions of STAT3-regulated exosomal miR-21 derived from cigarette smoke extract (CSE)-transformed human bronchial epithelial (HBE) cells in the angiogenesis of CSE-induced carcinogenesis. miR-21 levels in serum were higher in smokers than those in non-smokers. The medium from transformed HBE cells promoted miR-21 levels in normal HBE cells and angiogenesis of human umbilical vein endothelial cells (HUVEC). Transformed cells transferred miR-21 into normal HBE cells via exosomes. Knockdown of STAT3 reduced miR-21 levels in exosomes derived from transformed HBE cells, which blocked the angiogenesis. Exosomes derived from transformed HBE cells elevated levels of vascular endothelial growth factor (VEGF) in HBE cells and thereby promoted angiogenesis in HUVEC cells. Inhibition of exosomal miR-21, however, decreased VEGF levels in recipient cells, which blocked exosome-induced angiogenesis. Thus, miR-21 in exosomes leads to STAT3 activation, which increases VEGF levels in recipient cells, a process involved in angiogenesis and malignant transformation of HBE cells. These results, demonstrating the function of exosomal miR-21 from transformed HBE cells, provide a new perspective for intervention strategies to prevent carcinogenesis of lung cancer.

Epigenetic silencing of p21 by long non-coding RNA HOTAIR is involved in the cell cycle disorder induced by cigarette smoke extract.

Long noncoding RNAs (lncRNAs), which are epigenetic regulators, are involved in human malignancies. Little is known, however, about the molecular mechanisms for lncRNA regulation of genes induced by cigarette smoke. We recently found that, in human bronchial epithelial (HBE) cells, the lncRNA, Hox transcript antisense intergenic RNA (HOTAIR), is associated with changes in the cell cycle caused by cigarette smoke extract (CSE). In the present study, we report that increased expression of HOTAIR and enhancer of zeste homolog 2 (EZH2), and tri-methylation of Lys 27 of histone H3 (H3K27me3), affect cell cycle progression during CSE-induced transformation of HBE cells. Inhibition of HOTAIR and EZH2 by siRNAs attenuated CSE-induced decreases of p21 levels. Further, ChIP assays verified that HOTAIR and EZH2 were needed to maintain the interaction of H3K27me3 with the promoter regions of p21; combined use of a HOTAIR plasmid and EZH2 siRNA supported this observation. Thus, HOTAIR epigenetic silencing of p21 via EZH2-mediated H3K27 trimethylation contributes to changes in the cell cycle induced by CSE. These observations provide further understanding of the regulation of CSE-induced lung carcinogenesis and identify new therapeutic targets.

The IL-6/STAT3 pathway via miR-21 is involved in the neoplastic and metastatic properties of arsenite-transformed human keratinocytes.

Inflammation and microRNAs are involved in human skin cancer; however, their molecular mechanisms remain unclear. Further, a concern in skin cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. To explore new biomarkers of chemical exposure in risk assessment of chemical carcinogenesis and arsenite-induced skin cancer, we investigated the roles of interleukin-6 (IL-6) regulation of microRNA-21 (miR-21), functioning via activation of signal transducers and activators of transcription 3 (STAT3), in neoplastic and metastatic properties of immortalized human keratinocytes (HaCaT cells) transformed by arsenite. In HaCaT cells, arsenite caused increases of IL-6 and miR-21 levels and activation of STAT3, which induced the epithelial-mesenchymal transition (EMT). Blocking IL-6 with anti-IL-6 antibody inhibited the activation of STAT3 and increases of miR-21 levels. Knock-down of STAT3 by siRNA blocked the increases of miR-21. In arsenite-transformed HaCaT (HaCaT-30T) cells, down-regulation of STAT3 by siRNA blocked the process of EMT and decreased their neoplastic properties and migratory capacity, effects that were antagonized by over-expression of miR-21.Thus, the IL-6/STAT3 pathway via miR-21 is involved in EMT, neoplastic properties, and migratory capacity of arsenite-transformed HaCaT cells. The results may lead to development of biomarkers for early diagnosis and accurate prognosis of arsenite-induced skin cancer.

MicroRNA-191, by promoting the EMT and increasing CSC-like properties, is involved in neoplastic and metastatic properties of transformed human bronchial epithelial cells.

Lung cancer is the leading cause of cancer mortality worldwide. A common interest in lung cancer research is the identification of biomarkers for early diagnosis and accurate prognosis. There is increasing evidence that microRNAs (miRNAs) are involved in lung cancer. To explore new biomarkers of chemical exposure in risk assessment of chemical carcinogenesis and lung cancer, we analyzed miRNA expression profiles of human bronchial epithelial (HBE) cells malignantly transformed by arsenite. High-throughput microarray analysis showed that 51 miRNAs were differentially expressed in transformed HBE cells relative to normal HBE cells. In particular, miR-191 was up-regulated in transformed cells. In HBE cells, arsenite induced increases of miR-191 and WT1 levels, decreased BASP1 expression, and activated the Wnt/ß-catenin pathway, effects that were blocked by miR-191 knockdown. In addition, a luciferase reporter assay indicated that BASP1 is a direct target of miR-191. By inhibiting the expression of BASP1, miR-191 increased the expression of WT1 to promote activation of Wnt/ß-catenin pathway. In transformed cells, inhibition of miR-191 expression blocked the epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties of cells and decreased their migratory capacity and neoplastic properties. Thus, these results demonstrate that miR-191 modulates the EMT and the CSC-like properties of transformed cells and indicate that it is an onco-miR involved in the neoplastic and metastatic properties of transformed cells.

Epithelial-mesenchymal transition and cancer stem cells, mediated by a long non-coding RNA, HOTAIR, are involved in cell malignant transformation induced by cigarette smoke extract.

The incidence of lung diseases, including cancer, caused by cigarette smoke is increasing, but the molecular mechanisms of gene regulation induced by cigarette smoke remain unclear. This report describes a long noncoding RNA (lncRNA) that is induced by cigarette smoke extract (CSE) and experiments utilizing lncRNAs to integrate inflammation with the epithelial-mesenchymal transition (EMT) in human bronchial epithelial (HBE) cells. The present study shows that, induced by CSE, IL-6, a pro-inflammatory cytokine, leads to activation of STAT3, a transcription activator. A ChIP assay determined that the interaction of STAT3 with the promoter regions of HOX transcript antisense RNA (HOTAIR) increased levels of HOTAIR. Blocking of IL-6 with anti-IL-6 antibody, decreasing STAT3, and inhibiting STAT3 activation reduced HOTAIR expression. Moreover, for HBE cells cultured in the presence of HOTAIR siRNA for 24h, the CSE-induced EMT, formation of cancer stem cells (CSCs), and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates HOTAIR in an autocrine manner, contributes to the EMT and to CSCs induced by CSE. These data define a link between inflammation and EMT, processes involved in the malignant transformation of cells caused by CSE. This link, mediated through lncRNAs, establishes a mechanism for CSE-induced lung carcinogenesis.

MicroRNA-21, up-regulated by arsenite, directs the epithelial-mesenchymal transition and enhances the invasive potential of transformed human bronchial epithelial cells by targeting PDCD4.

Arsenic is well established as a human carcinogen, but the molecular mechanisms leading to arsenic-induced carcinogenesis are complex and elusive. It is not been determined if the epithelial-mesenchymal transition (EMT) contributes to carcinogen-induced malignant transformation and subsequent tumor formation. We have found that, during the neoplastic transformation induced in human bronchial epithelial (HBE) cells by a low concentration (1.0µM) of arsenite, the cells undergo an EMT and show enhanced invasion and migration. With longer times for transformation of HBE cells, there was increased miR-21 expression. Further, during the transformation of HBE cells, inhibition of miR-21 with an miR-21 inhibitor increased levels of PDCD4, an inhibitor of neoplastic transformation; reduced Twist1, a transcription factor involved in cell differentiation; and inhibited cell invasion and migration. In addition, PDCD4 interacted with Twist1 and inhibited its expression function, which is involved in arsenite-induced EMT. Thus, miR-21, acting on PDCD4, which interacts with Twist1 and represses the expression of Twist1, contributes to the EMT induced by arsenite. These observations add to an understanding of the processes involved in arsenite-induced carcinogenesis.

The acquisition of cancer stem cell-like properties and neoplastic transformation of human keratinocytes induced by arsenite involves epigenetic silencing of let-7c via Ras/NF-κB.

Exposure of humans to inorganic arsenic can cause skin cancer. The acquisition of cancer stem cell-like properties is involved in the initiation of some cancers, and there are changes in let-7 levels in some tumors. The mechanisms of action, however, remain obscure. Here, we report that there are decreased levels of let-7a, let-7b, and let-7c in human keratinocyte HaCaT cells during malignant transformation induced by a low concentration (1.0µM) of arsenite. The process by which arsenite reduces the level of let-7c apparently involves methylation, for 5-aza-2'-deoxycytidine, an inhibitor of methyltransferases, prevents arsenite-induced hypermethylation, decreases the level of let-7c, and thereby blocks arsenite-induced activation of the Ras/NF-κB signal pathway. Let-7c is an up-stream regulator of the Ras/NF-κB signal pathway and down-regulates activation of this pathway. In arsenite-transformed HaCaT cells, the acquisition of cancer stem cell-like properties is prevented by over-expression of let-7c, and over-expression of let-7c decreases the malignancy of transformed HaCaT cells. Thus, we conclude that epigenetic silencing of let-7c via Ras/NF-κB is involved in the acquisition of cancer stem cell-like properties and neoplastic transformation of HaCaT cells induced by arsenite, which contribute to the tumorigenesis of arsenite.

Cell cycle changes mediated by the p53/miR-34c axis are involved in the malignant transformation of human bronchial epithelial cells by benzo[a]pyrene.

Characterization of aberrant microRNA (miRNA) expression during carcinogen-induced cell transformation will lead to a better understanding of the role of miRNAs in cancer development. In this investigation, we evaluated changes in p53 function and its downstream target miRNAs in benzo[a]pyrene (BaP)-induced transformation of human bronchial epithelial (HBE) cells. Chronic exposure to BaP induced malignant transformation of cells, in which there were increased levels of mutant p53 (mt-p53) and reduced expression of wild-type p53 (wt-p53) and phosphorylated p53 (p-p53). With acute (12h) exposure to BaP, p-p53 was increased, and with increasing time of exposure (24h), the increase in p-p53 at a concentration of 1µM BaP was followed by a decline with increasing concentrations; wt-p53 and mt-p53 did not change. With prolonged exposure (48h), p-p53 and wt-p53 decreased, but mt-p53 increased. At different exposure times, the levels of miR-34c were consistent with p-p53. Over-expression of miR-34c resulted in inhibition of the BaP-induced G1-to-S transition and diminished up-regulation of cyclin D. Further, up-regulation of miR-34c or silencing of cylin D prevented BaP-induced malignant transformation. Thus, changes in the cell cycle mediated by the p53/miR-34c axis are involved in the transformation cells induced by BaP.

Angiogenesis, mediated by miR-21, is involved arsenite-induced carcinogenesis.

Evidence for arsenite-induced lung cancer in humans is strong, but the molecular mechanisms by which arsenite causes cancer remain to be established. Angiogenesis is a fundamental characteristic of cancer and is necessary in its multi-step progression. In this investigation, the mechanism for arsenite-induced angiogenesis was evaluated. Tumors formed from human bronchial epithelial (HBE) cells transformed by arsenite developed new blood vessels, which were prevented by the knockdown of miR-21, and cultures of human umbilical vein endothelial cells (HUVEC) exposed to arsenite developed endothelial tubes, a characteristic of angiogenesis. Also found in transformed HBE cells were up-regulation of a microRNA, miR-21, and increased levels of vascular endothelial growth factor (VEGF), which promotes angiogenesis. Down-regulation of miR-21 in these cells inhibited the arsenite-induced increases of VEGF levels. Thus, we conclude that arsenite induces tumor angiogenesis through processes mediated by miR-21.

Arsenite evokes IL-6 secretion, autocrine regulation of STAT3 signaling, and miR-21 expression, processes involved in the EMT and malignant transformation of human bronchial epithelial cells.

Arsenite is an established human carcinogen, and arsenite-induced inflammation contributes to malignant transformation of cells, but the molecular mechanisms by which cancers are produced remain to be established. The present results showed that, evoked by arsenite, secretion of interleukin-6 (IL-6), a pro-inflammatory cytokine, led to the activation of STAT3, a transcription activator, and to increased levels of a microRNA, miR-21. Blocking IL-6 with anti-IL-6 antibody and inhibiting STAT3 activation reduced miR-21 expression. For human bronchial epithelial cells, cultured in the presence of anti-IL-6 antibody for 3days, the arsenite-induced EMT and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates miR-21in an autocrine manner, contributes to the EMT induced by arsenite. These data define a link from inflammation to EMT in the arsenite-induced malignant transformation of HBE cells. This link, mediated through miRNAs, establishes a mechanism for arsenite-induced lung carcinogenesis.

NF-κB-mediated inflammation leading to EMT via miR-200c is involved in cell transformation induced by cigarette smoke extract.

Cigarette smoking constitutes a major human health hazard because it is the most important risk factor for lung cancer. Although evidence for smoking-induced lung cancer in humans is strong, the molecular mechanisms by which smoking causes cancer remain to be established. In this investigation, we evaluated the roles of inflammation and the epithelial-mesenchymal transition (EMT) in cigarette smoke extract (CSE)-induced transformation of human bronchial epithelial (HBE) cells. The results showed that chronic exposure to CSE induced EMT and transformation of these cells. Activation of nuclear factor-κB (NF-κB) by CSE increased levels of the proinflammatory interleukin-6 (IL-6), and acute and chronic exposures to CSE caused decreases in miR-200c levels. By blocking NF-κB with Bay11-7082 and IL-6 with anti-IL-6 antibody and enhancement of IL-6 with human recombinant IL-6, we found that the NF-κB signal pathway was involved in CSE-induced increases of IL-6, which suppressed miR-200c expression and promoted EMT. Moreover, IL-6 was necessary for maintenance of CSE-induced transformation and for malignant progression of HBE cells. Finally, blocking of NF-κB with Bay11-7082 prevented CSE-induced EMT and malignant transformation due to decreases of E-cadherin and miR-200c and elevations of IL-6, N-cadherin, and vimentin. Thus, we have defined a link between inflammation and EMT, processes involved in the malignant transformation of cells caused by CSE. This link, mediated through miRNAs, establishes a mechanism for CSE-induced lung carcinogenesis.

Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells.

Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß). The data also indicated that HIF-2α was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2α mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis.