This study plans to prepare lipid bilayer-coated mesoporous silica nanoparticles (LMSNs) which are pH sensitive with core-shell structure to improve the tumor cell lethality of antitumor drug. The lipid coated mesoporous silica nanoparticles loaded with irinotecan (CPT-11) (CPT-11-LMSNs) were prepared by hot water-film hydration method, and the characterized its morphology, particle size and release in vitro. Meanwhile, the intracellular uptake and cell toxicity of CPT-11-LMSNs and intracellular accumulation of CPT-11 were evaluated on human breast carcinoma cell line (MCF-7). The results indicated that the mean diameter of the spherical LMSNs was (120.27 +/- 5.91) nm. The slow release in simulated normal physiological conditions and a rapid release under simulated intracellular condition demonstrated the pH sensitivity of CPT-11-MSNs in vitro. Moreover, the CPT-11-LMSN could improve the intracellular CPT-11 cumulant 2.1 times and reduce half maximal inhibitory concentration (IC50) values of CPT-11 1.4 times compared with CPT-11-MSNs, demonstrating a stronger cell lethality.

Objective To improve the success rate of insertion of gastric lavage canal in patientswith tracheal intubation. Methods 70 patients with organophosphoms pesticide intoxication who neededgastric lavage after tracheal intubation were randomized into the test group and the control group, 35 easesin each. In test group, lavage canal was inserted through bite block orally and the bedside was raised till 70to 80 in angle. While in the control group, lavage canal was inserted directly through mouth with the posi-tion of hypsokinesis. The success rate of intubation was compared between the two groups. Results One-time success rate was 94.2% in the test group,which was statistically different from that of the control group(37.1%), P < 0.01. The complication of intubation in the test group was also lower than that of the controlgroup,which had statistical difference. Conclusions Through improvement of position to raise the bedsidetill 70 to 80 in angle, the insertion of gastric lavage canal through bite block orally was much better than thenormal one and it is worth applying.

In this work, we developed PEO-PPO-PEO micelles loaded with irinotecan hydrochloride (CPT-11) using breast cancer resistance protein (BCRP) inhibitory material PEO20-PPO70-PEO20, and studied its mechanism of decreasing CPT-11 induced delayed diarrhea and intestinal toxicity. BCRP-overexpressing MDCKII (MDCKII/BCRP) cells were used to evaluate the effect of PEO20-PPO70-PEO20 and PEO-PPO-PEO micelles on transmembrane transport of CPT-11 in vitro. The biliary excretion, delayed diarrhea and intestinal damage of CPT-11 loaded PEO-PPO-PEO micelles of rats were investigated. The results showed that the obtained micelles could decrease the biliary excretion of CPT-11, ameliorate delayed diarrhea and intestinal toxicity of rats through inhibiting BCRP-mediated CPT-11 efflux. PEO-PPO-PEO micelles were promising carriers to reduce intestinal toxicity of CPTs.

Background The influencing factors of noise hazards in the automotive manufacturing industry are complex, diverse, and mutually correlated, resulting in significant health impacts on workers. Objective To explore the application of generalized estimating equations (GEE) to analyze the factors affecting high-frequency hearing loss among noise-exposed workers in an automotive manufacturing company, guiding enterprises to scientifically carry out employee hearing protection programs. Methods The data of occupational health field evaluation and occupational health surveillance of an automobile manufacturing company for five consecutive years from 2018 to 2022 were collected, and 806 noise-exposed workers with pure tone hearing test results for all five consecutive years were selected as study participants. The retrieved indicators were gender, physical examination year, noise intensity, blood pressure, white blood cell counts, red blood cell counts, platelet counts, concentrations of hemoglobin, alanine transaminase, aspartate aminotransferase, smoking, drinking, etc. Gender, noise intensity, blood pressure, white blood cell counts, red blood cell counts, concentrations of hemoglobin, platelet counts, glutamate aminotransferase, glutamate aminotransferase, smoking, and drinking were set as independent variables, and occurrence of high-frequency hearing loss was set as a dependent variable, and GEE were constructed by using the statistical software of SPSS 20.0 to analyze the influencing factors of high-frequency hearing loss. Results Of the 806 workers, 698 were male (86.6%) and 108 were female (13.4%). The detection rates of high-frequency hearing loss in each year from 2018 to 2022 were 66.4% (535/806), 69.8% (563/806), 70.0% (564/806), 68.9% (555/806), and 68.2% (550/806), respectively. The detection rate of high-frequency hearing loss in the company was varied significantly by gender, lowered white blood cell counts, lowered red blood cell counts, lowered platelet counts, smoking, and drinking (P<0.05). The results of GEE analysis showed that after adjusting for selected confounding factors and excluding interaction effects, the risk of high-frequency hearing loss was higher in men than in women (P=0.001; OR=1.907, 95%CI: 1.286, 2.829); it was higher in workplace with disqualified noise intensity than in those without (P=0.043; OR=1.289, 95%CI: 1.009, 1.648); it was also higher in smokers than in non-smokers (P=0.004; OR=1.507, 95%CI: 1.137, 1.999). Conclusion Gender, noise intensity, and smoking are the main influencing factors of high-frequency hearing loss in noise-exposed workers in this automobile manufacturing company. Controlling smoking and reducing noise exposure intensity may reduce the occurrence of high-frequency hearing loss in workers.

Objective To evaluate the risk of hearing loss of assembly workers in an automobile manufacturing factory. Methods An 8-hour equivalent sound level monitoring was carried out for assembly posts in an automobile factory. The risk of noise-induced hearing loss of assembly workers was measured using the method specified in ISO 1999:2013(E). The risk of noise-induced hearing loss was assessed in a graded manner according to the Guidelines for the Management of Occupational Disease Hazards from Noise. The results were statistically analyzed using Pearson correlation analysis. Results The average 8-hour equivalent sound level of the assembly work post in this automobile manufacturing factory was 89.5 dB (A). At 4000 Hz, the hearing loss N₅₀ (dB) of assembly workers reached the maximum. The longer the exposure time, the higher the risk of high-frequency standard hearing threshold shift. The risk of high-frequency standard hearing threshold shift was at a relatively high level at 30 years of work, while the risk of noise deafness reached a higher level after 40 years of work. Conclusion The 8-hour equivalent sound level (L_EX,8h) of assembly workers in the automobile factory exceeds the occupational exposure limit. With the increase of exposure years, the risk of high-frequency standard hearing threshold shift and noise deafness increases.

Aim To investigate the effect of colchicine on lipopolysaccharide (LPS) induced endothelial to mesenchymal transition (EndMT) in human umbilical vein vascular endothelial cells (HUVECs) and its related mechanisms. Methods The EndMT model was established by treating HUVECs with LPS. Cell proliferation rate was detected by CCK-8 assay, cytotoxicity was detected by LDH assay, and the optimal drug concentration was screened. The cells were divided into the normal control group, the normal control + colchicine (10 nmol • L) group, the LPS (10 mg • L) model group, and the LPS + colchicine (10 nmol • L) group. The morphologic changes of the cells were observed under an inverted microscope, the cell migration ability was detected by Transwell assay, and the ability of tube formation was analyzed by tube formation assay. The expression of endothelial markers (CD31/ VE-cadherin) and mesenchymal cell markers (a-SMA/FSP-1) were detected by Western blot. NF-KB inhibitor was used to detect the changes in related signaling pathways. Results CCK-8 and LDH experiments showed that 10 nmol • L colchicine was the optimal concentration. LPS could induce morphological changes in HUVECs, and colchicine could reverse morphological changes in HUVECs to a certain extent. Transwell experiment showed that the migration ability of HUVECs in the LPS treatment group was significantly enhanced (P < 0. 05), and colchicine could significantly reverse this phenomenon (P < 0. 05) . Tube formation experiment showed that LPS decreased the endothelial tube formation ability of HUVECs (P < 0. 05), while colchicine treatment markedly improved LPS-induced tube formation defects (P < 0. 05) . Western blot assay showed that after colchicine co-cultured with LPS, the expression levels of CD31 and VE-cadherin significantly increased compared with the model group (P < 0. 05), while the expression levels of a-SMA and FSP-1 significantly decreased compared with the model group (P < 0. 05) . During the induction of EndMT by LPS, colchicine could inhibit the activation of the NF-KB/Snail signaling pathway. Conclusions Colchicine can effectively inhibit EndMT induced by LPS, and the mechanism may be related to the regulation of the NF-KB/Snail signaling pathway.

Objective To monitor the indoor radon concentration of urban residents in Shiyan, China, and to analyze the related influencing factors. Methods From April to July, 2019, RSKS standard detectors were used to measure the indoor radon concentration of 125 households in Shiyan, and the results were analyzed. Results The indoor radon concentration of residents in Shiyan showed a skewed distribution, ranging from 13.8 to 145 Bq/m³, and M (P₂₅,P₇₅) was 38.3 (29.0,62.0) Bq/m³. The estimated annual effective dose of radon and radon daughters from inhalation was 0.52-5.50 mSv, and M (P₂₅,P₇₅) was 1.45 (1.10, 2.36) mSv, which was consistent with literature. Building structure (H = 14.10, P < 0.001), floor (H = 24.41, P < 0.001), and geographical region (H = 8.963, P < 0.05) were influencing factors of indoor radon concentration, and the differences were significant. Conclusion The indoor radon concentration of urban residents in Shiyan is lower than the national standard limit. However, in daily life, it is still necessary to take appropriate measures to reduce the concentration of indoor radon as much as possible.

Humans ; Nasal Cavity ; Melanoma ; Skin Neoplasms ; Paranasal Sinuses

This study aimed to explore the anti-glioma effect of natural compound pterostilbene(PTE) through regulating pyroptosis and apoptosis pathways, and to analyze the possible anti-glioma pathways and targets of PTE by network pharmacology and molecular docking. In this study, the action targets of PTE and the glioma targets were obtained by network pharmacology to construct a target network and a protein-protein interaction(PPI) network to predict the possible action targets of PTE against glioma. Molecular docking was performed on the core targets by AutoDock and the action pathways of PTE against glioma were predicted by enrichment analysis. In addition, the effect of PTE on the viability of U87MG and GL261 glioma cells was detected by CCK-8 assay. Clone formation assay and cell scratching assay were used to explore the effect of different concentrations of PTE on the proliferation and migration, respectively of glioma cells. Hoechst staining was used to observe PTE-induced apoptosis in glioma cells. The changes in mitochondrial membrane potential were detected by JC-1 staining. The pyroptosis-inducing effect of PTE on glioma cells was observed by inverted microscopy and lactate dehydrogenase(LDH) assay. Hoechst 33342/PI dual staining assay was performed to detect the integrity of glioma cell membranes. The expressions of pyroptosis and apoptosis-related proteins in glioma cells after PTE induction were determined by Western blot. In this study, 37 anti-glioma targets of PTE were obtained, and enrichment analysis suggested that PTE exerted anti-glioma effects through various signaling pathways including cancer pathway, proteoglycan in cancer, PI3K/AKT pathway, and apoptosis regulatory pathway. Molecular docking revealed that PTE had good binding activity with the main targets. Compared with the control group, PTE significantly reduced the viability as well as the proliferation, migration and adhesion abilities of U87MG and GL261 cells; it induced the apoptosis of the two glioma cells and the decrease of mitochondrial membrane potential in U87MG cells, and the effects increased with the increase of drug concentration. Compared with the conditions in the control group, glioma cells in the PTE group had increased pyroptosis-specific appearance and gradually increased LDH release; the number of PI positive cells was significantly elevated with the increase of PTE concentration as revealed by Hoechst 33342/PI staining; the expression levels of apoptosis-related factors cleaved PARP1 and B-cell lymphoma-2(Bcl-2) associated X(BAX) in the PTE group were markedly up-regulated, while the expression level of Bcl-2 was markedly down-regulated; the activation levels of pyroptosis-related proteins cleaved caspase-3 and gasdermin E-N(GSDME-N) had a remarkable rise in the PTE group, while no significant changes were found in the activation levels of gasdermin D-N(GSDMD-N) and cleaved caspase-1. In summary, PTE plays an anti-glioma role by inhibiting cell viability, proliferation, and migration and activating the caspase-3/GSDME-mediated pyroptosis pathway and mitochondrial apoptosis pathway.
Pyroptosis ; Caspase 3/metabolism* ; Network Pharmacology ; Gasdermins ; Molecular Docking Simulation ; Phosphatidylinositol 3-Kinases/metabolism* ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism*

OBJECTIVETo explore the role of stromal-derived factor-1 (SDF-1) in the migration of mesenchymal stem cells (MSCs) and the underlying signal transduction mechanism.

METHODSRat bone marrow-derived MSCs were infected with 100 ml recombinant adenovirus containing human SDF-1alpha gene (Ad-hSDF-1alpha), and the cell migration changes were observed at 1, 2, and 3 days after the infection. Twelve hours after Ad-hSDF-1alpha transfection, the MSCs in separate cultures were treated with wortmannin (50 nmol/L), LY294002 (10 mmol/L), PD98059 (50 mmol/L), U73122 (10 mmol/L), AMD3100 (0.1 g/L), or verapamil (50 nmol/L), respectively, and the signal transduction pathways involved in MSC migration were analyzed.

RESULTSThe MSCs grew in colonies after transfection with Ad-hSDF-1alpha, but this growth pattern was substantially attenuated after treatment with wortmannin, LY294002, PD98059, U73122, AMD3100 and verapamil, among which U73122 and AMD3100 treatments resulted in the most conspicuous inhibitory effects.

CONCLUSIONThe effect of SDF-1 in promoting MSC migration is related to mitogen-activated protein kinase, phosphatidylinositol phospholipase C, and protein kinase signal pathways.

Adenoviridae ; genetics ; Animals ; Cell Movement ; genetics ; physiology ; Cells, Cultured ; Chemokine CXCL12 ; genetics ; physiology ; Enzyme Inhibitors ; pharmacology ; Genetic Vectors ; genetics ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; metabolism ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; Transfection ; Type C Phospholipases ; antagonists & inhibitors ; metabolism