Objective : To investigate the mechanisms of bromodomain-containing protein 4(BRD4) in TGF-β1-induced epithelial-mesenchymal transition in alveolar type II epithelial cells. Methods : MLE-12 cells were stimulated with different concentrations(5 ng/ml, 10 ng/ml) of TGF-β1 for 48 h to establish an EMT cell model. The cells were pretreated with 50 nmol/L BRD4 inhibitor JQ-1, 100 μmol/L high mobility group box 1 protein(HMGB1)inhibitor glycyrrhizin acid(GA), and 3 μg/ml rHMGB1. The experimental groups were divided as follows: control group, TGF-β1 group, JQ-1 group, JQ-1+TGF-β1 group, GA group, GA+TGF-β1 group, and JQ-1+TGF-β1+rHMGB1 group. The effect of JQ-1 on cell viability was examined using cell counting kit-8(CCK-8). The protein expression levels of CDH1, ZO-1, Vimentin, α-SMA, BRD4, HMGB1, TGF-β1, Smad2/3 and p-Smad2/3 were detected by Western blot. The cell migration ability was detected by a scratch test. Results : Compared with the control group, the levels of Vimentin and α-SMA in the TGF-β1 group increased, and the levels of CDH1 and ZO-1 protein decreased, suggesting that the EMT model was successfully established. In this model, the expression of BRD4 and HMGB1 significantly increased. Different concentrations of JQ-1 could inhibit the cell viability of MLE-12 in a concentration-dependent manner. Both JQ-1 and GA could effectively alleviate TGF-β1-induced EMT, and reduce the increase in HMGB1 expression and the activation of TGF-β1/Smad2/3 pathway caused by TGF-β1. Moreover, rHMGB1 treatment could reduce the effects of JQ-1 on EMT and the TGF-β1/Smad2/3 pathway. Additionally, both JQ-1 and glycyrrhizin could effectively decrease TGF-β1-induced cell migration, whereas rHMGB1 could alleviate the inhibitory effect of JQ-1 on the rate of cell migration. Conclusion BRD4 can regulate epithelial-mesenchymal transition in alveolar type II epithelial cells via HMGB1/TGF-β1/Smad2/3 signaling cascade, and BRD4 may be a potential target for inhibition of pulmonary fibrosis.

OBJECTIVE To investigate the current status of air quality in clean operating rooms in Xi'an and explore the possible influencing factors,thus to provide data support for improving the quality of operating room manage-ment.METHODS According to GB50333-2013"Architectural technical code for hospital clean operating depart-ment",on-site monitoring was conducted from 2017 to 2021 on the air quality of 242 clean operating rooms in 41 hospitals in Xi'an,and the results were compared and analyzed.RESULTS Among the operating rooms being sur-veyed,130 were from secondary hospitals,112 from tertiary hospitals;seventy-nine were ClassⅠoperating rooms,26 were ClassⅡ,137 were ClassⅢ.The pass rate for settling bacterial was 98.35%,with 94.94%for ClassⅠoperating rooms,which was significantly lower than that in ClassⅡand ClassⅢ operating rooms(χ2=6.565,P=0.022).The pass rate for dust particles was 69.01%,with 43.04%for ClassⅠoperating rooms,and there was significant difference among different levels of operating rooms(χ2=37.304,P<0.001).The pass rate for dust particles in tertiary hospitals was 61.61%,lower than that in secondary hospitals(75.38%;χ2=5.340,P=0.021).The pass rate for dust particles≥0.5μm and≥5μm were 85.12%and 74.79%,respectively.Among the operating rooms with unqualified dust particles,those with both≥0.5 μm and≥5 μm dust particles not meeting standards accounted for 29.33%,and those with only≥0.5 μm dust particles not meeting standards accounted for 18.67%.Multivariate logistic regression analysis showed that influencing factors for air quality in clean operating rooms included the year of monitoring and the level of the operating room,while the sampling area and hospital level were not statistically associated with the outcomes.CONCLUSION The overall air quality of op-erating rooms in Xi'an is not optimistic,the pass rate is affected by the year of monitoring and the clean levels of the operating rooms,indicating a need to strengthen routine management and monitoring of clean operating rooms.

Alzheimer′s disease (AD) is a degenerative disorder of the central nervous system. In the early stages of AD, i.e. when cognitive impairment is mild or absent but biomarkers are present, patients show abnormal neuroelectric activity. Repetitive transcranial magnetic stimulation (rTMS) is an important method of non-invasively regulating neuroelectric activity in the brain. It does so by inducing microcurrents to change the membrane potential of nerve cells in the brain based on electromagnetic induction. In this review, the characteristics of neuroelectric activity of AD patients and AD model mice in the early stage of AD were mainly introduced, and the regulation of rTMS on the neuroelectric activity of early AD was discussed.

OBJECTIVE To investigate the current status of air quality in clean operating rooms in Xi'an and explore the possible influencing factors,thus to provide data support for improving the quality of operating room manage-ment.METHODS According to GB50333-2013"Architectural technical code for hospital clean operating depart-ment",on-site monitoring was conducted from 2017 to 2021 on the air quality of 242 clean operating rooms in 41 hospitals in Xi'an,and the results were compared and analyzed.RESULTS Among the operating rooms being sur-veyed,130 were from secondary hospitals,112 from tertiary hospitals;seventy-nine were ClassⅠoperating rooms,26 were ClassⅡ,137 were ClassⅢ.The pass rate for settling bacterial was 98.35%,with 94.94%for ClassⅠoperating rooms,which was significantly lower than that in ClassⅡand ClassⅢ operating rooms(χ2=6.565,P=0.022).The pass rate for dust particles was 69.01%,with 43.04%for ClassⅠoperating rooms,and there was significant difference among different levels of operating rooms(χ2=37.304,P<0.001).The pass rate for dust particles in tertiary hospitals was 61.61%,lower than that in secondary hospitals(75.38%;χ2=5.340,P=0.021).The pass rate for dust particles≥0.5μm and≥5μm were 85.12%and 74.79%,respectively.Among the operating rooms with unqualified dust particles,those with both≥0.5 μm and≥5 μm dust particles not meeting standards accounted for 29.33%,and those with only≥0.5 μm dust particles not meeting standards accounted for 18.67%.Multivariate logistic regression analysis showed that influencing factors for air quality in clean operating rooms included the year of monitoring and the level of the operating room,while the sampling area and hospital level were not statistically associated with the outcomes.CONCLUSION The overall air quality of op-erating rooms in Xi'an is not optimistic,the pass rate is affected by the year of monitoring and the clean levels of the operating rooms,indicating a need to strengthen routine management and monitoring of clean operating rooms.

Background Silicosis is an occupational disease mainly characterized by pulmonary progressive fibrosis induced by the accumulation of free silica (SiO₂) in the lungs due to long-term exposure to SiO₂ dust. It has been shown that neutrophil extracellular traps (NETs) are increased in the lung tissues of silicotic mice after 28 d SiO₂ exposure, but it is unclear how the levels of NETs change throughout entire progression of silicosis in mice. Objective To observe the levels of NETs and pathological changes in the lungs of silicotic mice after different duration of SiO₂ exposure, and to confirm the possible role and significance of NETsin the development of SiO₂-induced pulmonary fibrosis. Methods A total of 28 SPF male C57BL/6J mice were randomly divided into a control group, and a model group, and the model group was subdivided into, a 2 d model group, a 7 d model group, and a 28 d model group, with 7 mice in each group. The mice in the model groups were given intratracheal instillation with 10 mg SiO₂ suspension (50 μL), and the mice in the control group were received same volume of saline. Mice were sacrificed and samples were collected at designed time points. The pathological changes of lung tissues of mice were observed after hematoxylin-eosin (HE) and Van Gieson (VG) staining. Immunofluorescence was used to observe the NETs markers citrullination histone H3 (CitH3) and myeloperoxidase (MPO) in bronchoalveolar lavage fluid (BALF), and the percentage of NETs-positive cells was calculated. PicoGreen fluorescent dye kit was used to detect the content of extracelluar DNA (ex-DNA) in mouse BALF, and the expression levels of fibrosis-related proteins α-smooth muscle actin (α-SMA) and fibronectin (FN) and NETs marker CitH3 in lung tissues of mice were detected by Western blot (WB). Results Compared with the control group, inflammatory cells accumulation, alveolar wall thickening, and collagen deposition were obviously observed in the lungs of the silicosis model groups, and a large number of silicone nodules were recorded in the lung tissues in the 28 d group. Compared with the control group, the expressions of α-SMA and FN in the lung tissue of the 28 d group were significantly increased (P<0.05). The percentages of NETs in BALF increased significantly in the 2 d and the 7 d model group, then decreased in the 28 d model group (P<0.05). Compared with the control group (7.434±0.258) ng·mL⁻¹, the ex-DNA levels in BALF of mice in the 2 d [(35.110±6.331) ng·mL⁻¹], the 7 d [(39.491±6.948) ng·mL⁻¹], and the 28 d [(23.360±4.809) ng·mL⁻¹] model groups were increased (P<0.05), and the increase of ex-DNA in the 2 d and the 7 d model groups were statistically significant (P<0.05). In comparison with the control group, the protein level of CitH3 was significantly increased in the lung tissues of mice in the 7 d model group (P<0.05). Conclusion The content of NETs increases significantly and reaches a peak in the early inflammatory stage of silicosis, and decreases as the disease progresses to the fibrotic stage, suggesting that NETs may play a role in early stage of silicosis.

Objective:To analyze the differential expressions of proteins in aqueous humor in patients with exfoliation syndrome (XFS).Methods:A total of 20 patients were enrolled in the Department of Ophthalmology, People's Hospital of Hotan District from June 2020 to January 2021, including 10 patients with age-related cataract and 10 XFS patients combined with cataract, which were classified as cataract group and XFS group, respectively.A total of 50 to 100 μl aqueous humor was obtained in the middle of the anterior chamber through the intraoperative phacoemulsification channel.The proteins extracted from aqueous humor were analyzed by label-free quantitative proteomics technology.The cataract group was set as the control group, and the differentially expressed proteins (DEPs) in XFS group were screened according to P<0.05 and fold change >1.5.Gene ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were used to explore the function and regulatory signaling pathways of DEPs in the XFS group.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY[L]-21).Written informed consent was obtained from each subject. Results:In comparison with the cataract group, 25 DEPs were identified in the XFS group, primarily involved in cell adhesion, receptor, hydrolase, and molecular transport.Specifically, there were 14 down-regulated proteins including complement factor H-related protein 1 (CFHR1), endoplasmic reticulum chaperone BiP (HSPA5), biglycan (BGN), FRAS1-related extracellular matrix protein 2 (FREM2), hemoglobin subunit delta (HBD), hemoglobin subunit gamma-1 (HBG1), lysosomal thioesterase PPT2 (PPT2) etc., and 11 up-regulated proteins including latent-transforming growth factor beta-binding protein 2 (LTBP2), very low-density lipoprotein receptor (VLDLR), laminin subunit alpha-2 (LAMA2), coagulation factor Ⅸ (F9).Among them, FREM2 was the most significantly differentially expressed protein in XFS group with consistent expression levels across individual samples.GO analysis revealed that these DEPs mainly localized to the extracellular matrix of collagen, bound globin-hemoglobin complex, plasma lipoprotein particles and lysosomes.Molecular functions and biological processes showed that HBD and HBG1 were involved in cellular detoxification, PPT2 in hydrolase activity, and BGN and LTBP2 in glycosaminoglycan binding.KEGG signaling pathway analysis indicated that CFHR1 and F9 were associated with complement and coagulation cascade pathways, and FREM2 and LAMA2 were linked to the extracellular matrix interaction pathway.Conclusions:Disease progression of XFS may be associated with changes in extracellular matrix proteins, disruption of the blood-aqueous humor barrier, and potential inflammatory responses.The significant down-regulation of FREM2 protein may be a potential biomarker for XFS.

Background Arsenic exposure is a common and important environmental and occupational hazardous factor in China, and arsenic-induced insulin resistance (IR) has attracted widespread attention as a negative health outcome to the population. Objective To explore part of the mechanism of hepatic IR induced by arsenic exposure based on the peroxisome proliferators-activated receptors γ (PPARγ)/ glucose transporter 4 (GLUT4) pathway, and to investigate potential effects of Ginkgo biloba extract (GBE) on hepatic IR induced by arsenic exposure and associated mechanism of action. Methods The target of drug action was predicted by network pharmacology and verified by in vivo and in vitro experiments. In vivo experiments: 48 SPF C57BL/6J male mice were divided into 4 groups, including control group, 50 mg·L⁻¹ NaAsO₂ model group (NaAsO₂), 50 mg·L⁻¹ NaAsO₂+10 mg·kg⁻¹ GBE intervene group (NaAsO₂+GBE), and 10 mg·kg⁻¹ GBE group (GBE), 12 mice in each group. The animals were given free access to purified water containing 50 mg·L⁻¹ NaAsO₂, or given intraperitoneal injection of normal saline containing 10 mg·kg⁻¹ GBE once per week. After 6 months of exposure, blood glucose detection, intraperitoneal glucose tolerance test (IPGTT), and insulin tolerance test (ITT) were performed. Serum and liver tissues were collected after the mice were neutralized, liver histopathological sections were obtained, serum insulin levels, liver tissue glycogen content, glucose content were detected by enzyme linked immunosorbent assay (ELISA), and the expression of PPARγ and GLUT4 proteins was detected by Western blot (WB). In vitro experiments: HepG2 cells were divided into 4 groups, including control group, 8 μmol·L⁻¹ NaAsO₂ group (NaAsO₂), 8 μmol·L⁻¹ NaAsO₂ + 200 mg·L⁻¹ GBE intervene group (NaAsO₂+GBE), and 200 mg·L⁻¹ GBE group (GBE). The levels of glycogen and glucose were detected by ELISA, and the expression of PPARγ and GLUT4 proteins was detected by WB. Results A strong binding effect between GBE and PPARγ was revealed by network pharmacology. In in vivo experiments, the NaAsO₂ group exhibited an elevated blood glucose compared to the control group, and the NaAsO₂+GBE group showed a decreased blood glucose compared to the NaAsO₂ group (P<0.01). The histopathological sections indicated severe liver structural damage in the arsenic exposure groups (NaAsO₂ group and NaAsO₂+GBE group), with varying staining intensity, partial liver cell necrosis, and diffuse red blood cell appearance. Both results of in vitro and in vivo experiments showed a decrease in glycogen synthesis and glucose uptake in the NaAsO₂ groups compared to the control groups, which was alleviated in the NaAsO₂+GBE group (P<0.01). The results of WB revealed inhibited PPARγ expression and reduced GLUT4 levels on the cell membrane, and all these changes were alleviated in the NaAsO₂+GBE group (P<0.01). Conclusion This study findings suggest that GBE antagonizes arsenic exposure-induced hepatic IR by regulating the PPARγ/GLUT4 pathway, indicating that GBE has a protective effect on arsenic exposure-induced hepatic IR, and PPARγ may be a potential therapeutic target for arsenic exposure-induced hepatic IR.

Objective:To compare the application effects of three different extubation techniques in patients with mechanical ventilation in intensive care unit (ICU).Methods:A prospective randomized controlled study was conducted. Mechanical ventilation patients admitted to the critical care department of the First Affiliated Hospital of Guangxi Medical University from July to November 2023 were enrolled. According to the random number table generated by Excel, the patients were divided into negative pressure group, positive pressure group 1 and positive pressure group 2, with 45 cases in each group. On the basis of routine nursing, the negative pressure group used the negative pressure extubation technique to remove the tracheal catheter. In the positive pressure group, the pressure support (PS) and positive end-expiratory pressure (PEEP) of the positive pressure group 1 were 7 cmH 2O (1 cmH 2O≈0.098 kPa) and 5 cmH 2O, and the PS and PEEP of the positive pressure group 2 were 15 cmH 2O and 10 cmH 2O. The main outcome measures were extubation related complications, including tachypnea, severe cough, sore throat, upper airway obstruction spasm, extubation failure, hypoxemia, and hypercapnia. The secondary outcome measures were the variation of heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and blood oxygen saturation before and 1, 15 and 30 minutes after extubation. Results:Finally, 42 patients were included in each group. There were no significant differences in gender, age, catheter retention days, duration of mechanical ventilation, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ), catheter model and diagnosis among the three groups, which were comparable. There were statistically significant differences in the incidence of tachypnea, severe cough, sore throat, upper airway obstruction spasm, hypoxemia and hypercapnia among the three groups, while there was no statistically significant difference in the failure rate of extubation. The incidence of tachypnea, severe cough, sore throat, upper airway obstruction spasm, hypoxemia and hypercapnia after extubation in positive pressure group 1 and positive pressure group 2 were lower than those in negative pressure group (7.14%, 9.52% vs. 33.33%; 7.14%, 4.76% vs. 28.57%; 61.90%, 52.38% vs. 88.10%; 11.90%, 19.05% vs. 45.24%; 7.14%, 7.14% vs. 30.95%; 4.76%, 2.38% vs. 28.57%; all P < 0.05). There were no significant differences in extubation related complications between group 1 and group 2. There were significant differences in the time effect of heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure and blood oxygen saturation 30 minutes after extubation among three groups ( F values were 145.792, 49.749, 22.486, 23.622 and 242.664, respectively, all P < 0.01). The intergroup effect of blood oxygen saturation was statistically significant ( F = 3.835, P = 0.024), and the blood oxygen saturation in positive pressure group 1 and positive pressure group 2 were higher than those in negative pressure group 1 minute and 30 minutes after extubation (1 minute after extubation: 0.97±0.02, 0.97±0.02 vs. 0.95±0.02; 30 minutes after extubation: 1.00±0.01, 1.00±0.01 vs. 0.99±0.02, all P < 0.05). The interaction effects of heart rate and blood oxygen saturation were statistically significant ( F values were 3.512 and 7.226, respectively, both P < 0.01). Conclusions:Compared with negative pressure extubation, positive pressure extubation can effectively reduce extubation related complications in ICU mechanically ventilated patients. It is beneficial to maintain stable blood oxygen saturation within 30 minutes after extubation, and has better clinical application effects. It is recommended to use low pressure extubation.

Fluorosis is widely prevalent worldwide, and China is one of the countries with a high incidence of endemic fluorosis. In recent years, study on non skeletal damage caused by fluorosis, especially cardiovascular system damage, has gradually increased. Fluoride can cause cardio vascular arteriosclerosis, hypertension and other diseases, while cardiovascular disease have hidden and acute onset, and the mortality rate has increased year by year in recent years. At present, the mechanism of cardiovascular diseases caused by fluoride is not yet clear, and further clarification is needed. This article provides an overview of the effects of fluoride on cardiovascular diseases from three aspect: epidemiological investigation, animals experiment, and in vitro cell experiment. It categorizes and analyzes the pathogenesis, providing new ideas for the study of cardiovascular system damage caused by fluorosis.

【Objective】 To evaluate the associations of total fat and fatty acid consumption with the risk of hypertension among rural residents in Hanzhong, Shaanxi Province. 【Methods】 A cross-sectional survey on dietary status with a semi-quantitative food frequency questionnaire was conducted among rural residents aged between 18 and 80 years old in Hanzhong of Shaanxi. Multivariate log-binomial regression models and restricted cubic spline were used to explore the associations of dietary total fat, saturated fatty acid, polyunsaturated fatty acid and monounsaturated fatty acids with hypertension and as well as association between dose and response. 【Results】 A total of 2241 individuals were included, with 774 males and 1467 females. Monounsaturated fatty acid accounted for 51.9% of total dietary fat intake, while the other two fatty acids for 48.1%. The intake of dietary fat and any fatty acid in men was significantly in men higher than in women (P<0.001). Results of multivariable log-binomial regression indicated that after adjustment of energy, socio-demographic and lifestyles, the risk of hypertension reduced significantly in Q4 group, compared with that in Q1 (PR: 0.71, 95% CI: 0.54-0.92; P-trend: 0.022) in females. A nonlinear dose-response relationship between monounsaturated fatty acids and hypertension was detected by restricted cubic spline in women (Pnon-linear<0.01). No association was observed of total fat, saturated fatty acid and polyunsaturated fatty acid with hypertension regardless of the gender. 【Conclusion】 In women, increased consumption of monounsaturated fats might play a positive role in reducing the risk of hypertension. Further research is warranted to verify the rationality of causal inference and break-point.