[Analysis of the status of occupational disease prevention and control of enterprises in mining and manufacturing industries in China in 2019].

Objective: To analyze the status of prevention and treatment of occupational diseases among mining and manufacturing industries in China in 2019, provide the scientific basis for the formulation and revision of policies and standards of prevention and treatment of occupational diseases. Methods: In May 2022, Collecting data of a project named Surveillance of Occupational Hazards in the Workplace in 2019 through the National Surveillance System for Occupational Hazards in the workplace. Compare the status of prevention and treatment of occupational diseases in 63 563 enterprises of mining and manufacturing industries among different dimensions. Results: The training rate of managers was 76.17% and that of occupational health managers was 76.97%. The rate of reporting of occupational diseases hazardous items was 67.58%, the rate of launching of the detection of occupational hazards was 57.16%, and the rate of launching of occupational health examination was 62.42%. Excluding the distribution rate of dust mask, the installation rate of various occupational prevention facilities and the distribution rate of gas mask and hearing protector were less than 80%. The differences in all the indicators among different areas, enterprise scales, economic types were statistically significant (P<0.05) . Conclusion: There are still some enterprises which are relatively weak in the ability of the prevention and treatment of occupational diseases in China. Measures such as special support, guidance and strengthen supervision should be taken towards those enterprises toimprove the awareness of prevention and treatment of occupational diseases and the level of that.

[Analysis of dust and noise exposure levels in the mining industry from the national surveillance program in 2019].

Objective: To understand the exposure level of dust and noise in the mining industry and provide data support for revising policy for the prevention and control of occupational diseases. Methods: In May 2022, Data was collected through the National Surveillance Program for Occupational Hazards in the Workplace. Descriptive analysis was conducted for dust and noise levels by industry type and enterprise size from 7, 679 enterprises in the mining industry among 29 provincial regions nationwide. Results: The enterprises in the mining industry included in the National Surveillance Program for Occupational Hazards in the Workplace are mainly small and micro, accounting for 47.97% (3684/7679) and 30.00% (230/7679) respectively. The industry is mainly compred of employers in the non-metallic ming and beneficiation industry, accounting for 50.25% (3859/7679). Among the enterprises with silica dust, coal dust, and noise hazards, the proportion of enterprises where total dust concentration and noise intensity exceed the standard is higher than 50%. 30% of the posts are with an exposure level of silica dust, coal dust, and noise that exceeds the standard. The exceedance rate and the median of the time-weighted average concentration of total coal dust among large and medium-sized enterprises are higher than those among small and micro-sized enterprises (P<0.05) . Conclusion: The dust and noise hazards in the mining industry are lower than in the past in China, but more than 25% of workers are still at a high risk of occupational pneumoconiosis and noise deafness. Therefore, intervention and surveillance strategies should be strengthened in the future.

Jade-1: its structure, regulation and functions in the renal cancer.

Jade-1 is originally identified by the yeast two-hybrid system as a protein partner of von Hippel-Lindau (pVHL) tumor suppressor, a well-known renal tumor suppressor. In cellular signaling pathways, many upstream Jade-1 regulators, such as pVHL, CK1α, PC1, and NPHP4, can control its activity by stabilization, phosphorylation, and nuclear translocation. Numerous downstream effectors, including ß-catenin, AKT, p21, and Bcl-2, are well modulated by Jade-1, which mainly regulates cell proliferation and apoptosis. Jade-1 is also deemed to be a candidate of transcriptional co-activator associated with histone acetyltransferase (HAT) activity. This review focuses on the anticancer role of Jade-1 in clear cell renal carcinoma and the inhibitory effect of Jade-1 on cystic renal diseases. This review aims to provide a basis of disease prevention or therapy.

The role of 3D computed tomography (CT) imaging in the diagnosis of foreign body aspiration in children.

OBJECTIVE: The aim of this study was to improve the understanding of FBA in children and to decrease the rate of misdiagnosis, missed diagnosis and morbidity. PATIENTS AND METHODS: We analyzed the clinical features and the three-dimensional reconstructed CT images of 590 children with foreign body aspiration (FBA) in the Xuzhou area of the Jiangsu province. RESULTS: CT imaging revealed common complications of FBA including emphysema (n = 379), pneumonia (n = 174), and atelectasis (n = 26). The remaining 120 patients had no visible complications on the three-dimensional reconstructed CT images. Serious complications including pneumothorax, pneumomediastinum, subcutaneous emphysema, pneumatorrhachis could also be observed. The types of foreign bodies were diverse: the most common were peanuts and sunflower seeds. The diagnostic accuracy of the three-dimensional CT imaging was high, with a sensitivity and specificity of 99.83% and 99.89%, respectively. CONCLUSIONS: 3D CT imaging is an accurate, non-invasive technique to evaluate children with suspected FBA that can help decrease the rate of misdiagnosis and eliminate a delay in treatment for this potentially life-threatening condition.

RPA1 expression in esophageal carcinoma and its influence on radiosensitivity of esophageal carcinoma TE-1 cells.

AIM: To determinate the RPA1 expression in esophageal carcinoma and the paired tumor-adjacent tissue, and to explore the influence of RPA1 on radiosensitivity of esophageal carcinoma TE-1 cells. METHODS: Firstly, the RPA1 expression of 40 cases esophageal carcinoma and their adjacent tissues were detected by immunohistochemistry. Secondly, The esophageal carcinoma cell subline-radiation resistance model (TE-1R) was constructed by radiation-induction, the RPA1 expression and proliferation activity of TE-1 and TE-1R cells were detected by Western blot and MTT assay respectively. After radiation, the expression of RPA1 and cell apoptosis were detected by Western blot and FACS respectively. Cell clone formation and survival rate were detected by clonogenic assay. Thirdly, Inhibiting RPA1 expression by siRNA in TE-1 cells, the expression of RPA1 was detected by RT-PCR and Western blot, Cell proliferation inhibition ratio and cell apoptosis after radiation were detected by MTT assay and FACS respectively. RESULTS: The RPA1 expression in esophageal carcinoma was significantly higher than that in the tumor-adjacent tissues, which was associated with tumor invasion and lymph node metastasis. The RPA1 expression in TE-1R cells was higher than that in TE-1 cells, while the proliferation activity of TE-1R cells was lower than that of TE-1 cells, and the apoptosis rate of TE-1R cells after radiation was less than that of TE-1 cells. In addtion, the clone formation and survival rate of TE-1R cells were higher than that of TE-1 cells. Moreover, inhibiting RPA1 expression by siRNA-RPA1 could promoted proliferation inhibition ratio and apoptosis rate of TE-1 cells after radiation. CONCLUSION: The over-expression of RPA1 in esophageal carcinoma was related with progression and metastasis. Moreover, radiation induced the excessive expression RPA1 in TE-1 cells, and the radiosensitivity of TE-1R cells was less than that of TE-1 cells. Furthermore, inhibiting RPA1 expression could increase radiosensitivity of TE-1 cells. Overall, RPA1 could influence radiosensitivity and might be one important mechanism of radiation resistance in TE-1 cells.

Potent anti-tumour activity of a novel conditionally replicating adenovirus for melanoma via inhibition of migration and invasion.

BACKGROUND: Conditionally replicating adenoviruses (CRAds) represent a novel class of oncological therapeutic agents. One strategy to ensure tumour targeting is to place the essential viral genes under the control of tumour-specific promoters. Ki67 has been selected as a cancer gene therapy target, as it is expressed in most malignant cells but is barely detectable in most normal cells. This study aimed to investigate the effects of a Ki67 promoter-controlled CRAd (Ki67-ZD55-IL-24) on the proliferation and apoptosis of melanoma cells. METHODS: Melanoma cells were independently treated with Ki67-ZD55-IL-24, ZD55-IL-24, Ki67-ZD55, and ZD55-EGFP. The cytotoxic potential of each treatment was assessed using cell viability measurements. Cell migration and invasion were assayed using cell migration and invasion assays. Apoptosis was assayed using the annexin V-FITC assay, western blotting, reverse transcriptase PCR (RT-PCR), haematoxylin and eosin (H&E) staining, and the TUNEL assay. RESULTS: Our results showed that Ki67-ZD55-IL-24 had significantly enhanced anti-tumour activity as it more effectively induced apoptosis in melanoma cells than the other agents. Ki67-ZD55-IL-24 also caused the most significant inhibition of cell migration and invasion of melanoma cells. Furthermore, apoptosis was induced more effectively in melanoma xenografts in nude mice. CONCLUSIONS: This strategy holds promising potential for the further development of an effective approach to treat malignant melanoma.

Cullin1 is a novel marker of poor prognosis and a potential therapeutic target in human breast cancer.

BACKGROUND: To investigate the role of Cullin1 (Cul1) in the development of breast cancer, we examined the expression of Cul1 in breast cancer tissues and analyzed the correlation between Cul1 expression and clinicopathologic variables and patients survival. PATIENTS AND METHODS: We evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) which includes 393 breast cancer tissues. We also studied the role of Cul1 in breast cancer cell proliferation, migration and invasion by carrying out CCK8 cell proliferation assay, cell migration and invasion assay. RESULTS: The Cul1 expression was significantly correlated with breast cancer histology grade (P = 0.000), estrogen receptor status (P = 0.001), progesterone receptor status (P = 0.001) and human epidermal growth factor receptor 2 status (P = 0.002). Furthermore, we showed a strong correlation between high Cul1 expression and worse 5-year overall and disease-specific survival rates in breast cancer patients (P = 0.026 and P = 0.015, respectively). Finally, we found that Cul1 knockdown inhibits cell proliferation, migration and invasion abilities. CONCLUSIONS: Cul1 overexpression is significantly correlated with breast cancer progression and predicts worse survival. Cul1 regulates breast cancer cell proliferation, migration and invasion.

Isolation and identification of renal cell carcinoma-derived peptides associated with GP96.

We determined the possible associated determinants and analyzed whether gp96-_associated antigenic peptides can be found in renal cell carcinoma (RCC). The gp96-peptide complexes were chromatographically purified from resected tumor tissue of RCC patients. SDS-PAGE and Western blot analysis confirmed gp96 using the gp96 monoclonal antibody, and its concentration was measured using BCA. Approximately 20 to 50 µg gp96-peptide complexes was obtained from 1 g RCC tissue. The mass spectrometry (MS) analysis of the eluted peptides included the initial profiling using matrix-assisted laser desorption/ionization time-of-flight MS. Quadrupole time-of-flight MS combined with the Mascot search engine was used to identify the peptides and find proteins from primary sequence databases. MS analysis results demonstrated that the mass range of peptide associated with gp96 was from 1046.48 to 3501.56 Da. Further research confirmed the sequences of two gp96-associated peptides, namely, LVPLEGWGGNVM and PPVYYVPYVVL. However, the original protein of the two peptides could not be found. The results demonstrated that the gp96-associated peptides are small molecular peptides, and the two peptides are deduced to be RCC-associated peptides. The identified peptides were confirmed to be associated with gp96 using the protocols described above. However, the specificity and relevance of the association to the immunogenicity of gp96 remains to be examined. Further analysis must be accomplished before the findings can be applied in peptide vaccine.

Strategies to improve the killing of tumors using temozolomide: targeting the DNA repair protein MGMT.

Alkylating agents such as temozolomide (TMZ) are effective anticancer drugs for treating a variety of solid tumors including melanoma, glioma, and astrocytoma. TMZ exerts its effects mainly via the mutagenic product O(6)-methylguanine, a cytotoxic DNA lesion. This damage may be repaired by the DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT), a key player in the resistance of cancers to TMZ. Several strategies are presently being pursued to improve the killing of tumor cells by TMZ, with inhibition of MGMT being the most promising. In this review, we provide an overview of recent advances in this field.

Oncolytic adenovirus expressing interleukin-18 induces significant antitumor effects against melanoma in mice through inhibition of angiogenesis.

It has been shown that interleukin 18 (IL-18) exerts antitumor activity. In this study, we investigated whether oncolytic adenovirus-mediated gene transfer of IL-18 could induce strong antitumor activity. A tumor-selective replicating adenovirus expressing IL-18 (ZD55-IL-18) was constructed by insertion of an IL-18 expression cassette into the ZD55 vector, which is based on deletion of the adenoviral E1B 55-kDa gene. It has been shown that ZD55-IL-18 exerted a strong cytopathic effect and significant apoptosis in tumor cells. ZD55-IL-18 significantly decreased vascular endothelial growth factor and CD34 expression in the melanoma cells. Treatment of established tumors with ZD55-IL-18 showed much stronger antitumor activity than that induced by ZD55-EGFP (enhanced green fluorescent protein) or Ad-IL-18. These data indicated that oncolytic adenovirus expressing IL-18 could exert potential antitumor activity through inhibition of angiogenesis and offer a novel approach to melanoma therapy.

Inhibition of renal cancer cell growth in vitro and in vivo with oncolytic adenovirus armed short hairpin RNA targeting Ki-67 encoding mRNA.

RNA interference (RNAi) has been proved to be a powerful tool for gene knockdown purpose and holds great promise for the treatment of cancer. Our previous study demonstrated that the reduction of Ki-67 expression by means of chemically synthesized siRNAs and shRNAs expressed from plasmid resulted in proliferation inhibition in human renal carcinoma cells. In this study, we constructed a novel oncolytic adenovirus-based shRNA expression system, ZD55-Ki67, and explored ZD55-Ki67-mediated RNAi for Ki-67 gene silencing. Our results showed that ZD55-Ki67 could induce silencing of the Ki-67 gene effectively, allow for efficient tumor-specific viral replication and induce the apoptosis of tumor cells effectively in vitro and in nude mice. We conclude that combining shRNA gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and shRNA antitumor responses.