Dust ; Humans ; Inflammation ; metabolism ; Intercellular Signaling Peptides and Proteins ; metabolism ; Silicon Dioxide ; adverse effects ; Silicosis ; metabolism

Objective: To investigate the effects of crystalline silica with different exposure patterns on lung fibrosis in rats. Methods: A total of 20 adult male Wistar rats were randomly divided into 4 groups consisting of five animals each and received intratracheal instillation of sterile saline or silica suspension in different patterns: saline once at day 0, saline once/week, crystalline silica 50 mg at day 0, crystalline silica 6.25 mg/week. The rats were sacrificed at 8 weeks. The lung tissues were collected for pathological analyses, and determining mRNA and protein levels of related fibrogenic molecules. Results: The collagen deposition induced by crystalline silica in lung tissues were increased. The mRNA levels of IL-1β and Col I in group c were significantly elevated than those in group saline once at day 0 (all P<0.05). Compared with group saline once/week, the mRNA levels of IL-1β, TGF-β, Col I, Col III and CTGF were significantly increased in group crystalline silica 6.25 mg/week (P<0.05) . The mRNA levels of Col I and CTGF were significantly increased in group crystalline silica 6.25 mg/week in comparison with those in group crystalline silica 50 mg at day 0 (P<0.05) . Conclusion Given the same cumulative dose of crystalline silica, multiple exposures were likely to induce more severe lung fibrosis.

Objective: To investigate the modulation role of Gas6 in silica-induced inflammatory effect on human macrophages. Methods: Differentiated THP-1 macrophages were exposed to different concentrations of silica for 6 h and 24 h. Additionally, silica-activated macrophages were treated with different concentrations of recombine human Gas6 and Gas6 antibody respectively. Cell viabilities were determined by CCK-8 kit. Expression levels of Gas6 and inflammatory cytokines (TNF-α, IL-1β and IL-6) were measured by ELISA assay kits. Results: Silica particles induced clear dose-dependent decreases of cell viability and Gas6 expression at both 6 h and 24 h. The cell viability of 24 h is lower than 6 h at the same concentration of silica (P<0.05). Furthermore, silica activated macrophages treated with Gas6 antibody induced significant decreases of Gas6 both at 6 h and 24 h (P<0.05). After pretreated with various concentrations of Gas6 antibody, silica induced higher expressions of inflammatory cytokines (TNF-α, IL-1β, IL-6) in dose-dependent manners at two time points. Addition of exoge-nous Gas6 significantly suppressed silica-induced inflammatory cytokines concentrations mentioned above in the cell culture supernatants in clear dose-dependent manners. Conclusion Exogenous Gas6 could inhibit the secre-tion of inflammatory cytokines in macrophages, while the block of Gas6 might enhance this inflammation.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

OBJECTIVE：To in vestigate the effects of dexmedetomidine （Dex）on SIRT 1/Akt/GSK3β/β-catenin signaling pathway in cerebral injury of sepsis model rats ，and explore the mechanism of its protecitve effect on cerebral injury. METHODS ： A total of 80 male SD rats were randomly divided into sham operation group （Sham group ），sepsis group （CLP group ），CLP+Dex group（10 μg/kg Dex），CLP+Dex+Sirtinol group （10 μg/kg Dex+2 μL/100 g SIRT 1 inhibitor sirtinol ），with 20 mice in each group. Two hours before modeling ，CLP+Dex+Sirtinol group was injected with sirtinol via lateral ventricle. Sepsis model was induced by cecal ligation and perforation in each group （in sham group ，only operation was performed but no ligation was performed）. At 0，3，6 h after modeling ，CLP+Dex group and CLP+Dex+Sirtinol group were given Dex （10 μg/kg） intraperitoneally，Sham group and CLP group were given constant volume of normal saline intraperitoneally. Cerebral tissue water content，Evans blue （EB）content，apoptosis in cerebral cortex ，the levels of IL- 1β and TNF-α in cerebral tissue as well as the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were detected 24 h after last medication. RESULTS ： Compared with Sham group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were increased significantly（P＜0.05），while the protein expression of SIRT 1， p-Akt，p-GSK3β and β-catenin in hippocampus were decreased significantly （P＜0.05）. Compared with CLP group ，cerebral tissue water content ，EB content ，the number of apoptotic cells in cerebral cortex as well as the levels of IL- 1β and TNF-α in cerebral tissue were decreased significantly in CLP+Dex group （P＜0.05），while the protein expression of SIRT 1，p-Akt，p-GSK3β and β-catenin in hippocampus were increased significantly （P＜0.05）. Sirtinol could significantly reverse the above-mentioned cerebral protection and factor regulation effects of Dex （P＜0.05）. CONCLUSIONS ：Dex can protect the cerebral tissue of sepsis model rats，which may play an anti-inflammatory and anti-apoptotic role by activating SIRT 1/Akt/GSK3β/β-catenin signaling pathway ，so as to reduce cerebral edema ，protect blood-brain barrier and reduce cerebral injury.

Objective To analyze the basic characteristics and variation trend of death causes of permanent residents in Enshi City during 2013-2018, to assess the burden of different diseases, and to provide a scientific basis for formulating disease prevention and control strategies. Methods The death monitoring data of permanent residents in Enshi City, Hubei Province from 2013 to 2018 was collected. The crude mortality, standardized mortality, life expectancy, potential years of life loss (PYLL), standard potential years of life loss (SPYLL), average years of life lost (AYLL), and annual percentage change (APC) were calculated to describe the distribution and trend of death causes. Results The average annual crude death rate and standardized death rate of residents in Enshi City from 2013 to 2018 were 679.43 per 100 000 and 615.02 per 100 000, respectively. The top 5 causes of death were circulatory system diseases, respiratory system diseases, malignant tumors, injuries, and digestive system diseases, accounting for 91.2% of the total deaths. Analysis of life expectancy found that the average life expectancy of local residents from 2013 to 2018 was 78.02 years, and the value in the male group (75.57 years) was lower than that in the female group (80.78 years). Life loss analysis revealed that PYLL caused by various diseases was 171 620 person-years, SPYLL was 171 284.62 person-years, and AYLL was 15.03 years/person in Enshi City from 2013 to 2018. Among all the death causes, the top five in terms of life loss were injuries, malignant tumors, circulatory diseases, respiratory diseases and digestive diseases. Conclusion From 2013 to 2018, the death rate of residents in Enshi City was relatively higher compared with those in other cities in China, the average annual crude death rate was on the rise, and the average annual standardized death rate was on the decline, indicating a highly ageing region. Chronic diseases such as circulatory system diseases, malignant tumors, and respiratory diseases, as well as injuries were the main death causes and caused a heavy burden of diseases, which should be the focus of future prevention and control work. Considering the higher levels of death and life loss indicators of male residents than those of women, targeted prevention and control measures should be taken to narrow the gap between men and women and improve the overall life quality of the whole population.

Objectives To investigate the effects of low level of ambient NO₂ on the death of cardiovascular and cerebrovascular diseases in Enshi city and to identify sensitive population, so as to provide a scientific basis for formulating health policies. Methods The data of air pollutants, meteorological factors and death of cardiovascular and cerebrovascular diseases in Enshi city from 2015 to 2018 were collected. The generalized additive model based on Poisson distribution was used to analyze the effects of low ambient NO₂ level on the death risk of cardiovascular and cerebrovascular diseases in Enshi city. A subgroup analysis was performed on age, gender, and season. Results The average concentrations of major gaseous air pollutants in Enshi city from 2015 to 2018 were NO₂ (21.40 μg/m³), SO₂ (9.68 μg/m³), CO (0.88 mg/m³), and O₃ (61.21 μg/m³), respectively, all of which did not exceed the national secondary standard. The results of single pollutant model analysis showed that each 1 μg/m3 increase in NO₂ concentration in lag0 day was associated with a 0.33% increase (95% CI: 0.06 - 0.72) (P>0.05) in mortality risk of cardiovascular and cerebrovascular diseases. In the female population, each 1 μg/m3 increase in NO2 concentration in lag01 day was associated with a 0.92% increase (95% CI: 0.26 - 1.56) (P<0.05) in mortality risk of cardiovascular and cerebrovascular diseases. In the cold season, each 1 μg/m3 increase in NO₂ concentration in lag0 day was associated with a 0.62% increase (95% CI: 0.12 - 1.12) (P<0.05) in mortality risk of cardiovascular and cerebrovascular diseases. The results of the two-pollutant model showed that after controlling other gaseous pollutants (SO₂, CO or O₃), the effect of NO₂ on the mortality risk of cardiovascular and cerebrovascular diseases in women and the whole population in cold season still existed. Conclusion The low ambient level of NO₂ in Enshi city was significantly associated with increased mortality risk of cardiovascular and cerebrovascular diseases in female population as well as in cold seasons in the whole population. Attention should be paid to the health protection of special populations in areas with low ambient pollution level of NO₂ in special seasons.

Programmed death factor-1 (PD-1) is a promising target molecule for clinical tumor immunotherapy in recent years. Recent studies suggest that PD-1 and related signaling pathways (PI3K/AKT, JAK/STAT3, p38MAPK, ERK, etc.) played a key regulatory role in the process of pulmonary fibrosis. Silicosis is a systemic disease caused by inhalation of free silicon dioxide dust, which is mainly characterized by extensive pulmonary nodular fibrosis and seriously endangers the health of patients. Dissecting the role of PD-1 in the pathogenesis of silicosis may be of great significance in the mechanism research and clinical diagnosis and treatment of silicosis. This paper reviews the regulation of PD-1 molecule on related signaling pathways and its role in pulmonary fibrosis, and looks forward to the potential application of these mechanistic studies in silicosis research.

OBJECTIVETo investigate oxidative stress and mitochondria-related cell apoptosis induced by silica dust in human normal bronchial epithelial 16HBE cells.

METHODSCell viability, lactate dehydrogenase (LDH), superoxide dismutase (SOD), cell apoptotic rate, the expression level of Bax and Bcl-2 mRNA were measured after 16HBE cells were exposed to 37.5, 75, 150, 300 µg/mL respirable silica dust (diameter<2 µm, d50=1 µm)for 24 h in vitro. Reactive oxygen species (ROS)were tested after 16HBE cells were exposed to silica dust at above concentrations for 1.5, 3, 6, 12 h, respectively.

RESULTSDose-dependent decreases of cell viability and the activity of SOD were observed when silica concentrations increased. The activity of LDH increased when silica concentrations elevated. Compared with the control group, cell viability significantly reduced in 75, 150, 300 µg/mL silica-treated groups (P<0.05). The activity of LDH significantly increased in 150, 300 µg/mL silica-treated groups when compared with the control group (P<0.05). The activity of SOD in all silica-treated groups were significantly lower in comparison with controls (P<0.05). Intracellular ROS levels reached peak values at 1.5 h of silica exposure and gradually dropped to the base level at 12 h. The relationship between ROS levels and silica exposure were dose-response at 1.5 h, 3 h and 6 h of exposure (P<0.05). Similar dose-dependent increase were observed for apoptotic rate and silica exposure (P<0.05). The expression levels of Bcl-2 mRNA decreased, and the expression levels of Bax mRNA increased when silica concentrations increased. The results showed that significantly positive correlations between ROS level and apoptotic rate (r=0.892,P<0.05)or the expression level of Bax mRNA (r=0.850,P<0.05). There was a negative correlation between ROS level and the expression level of Bcl-2 mRNA (r=-0.703,P<0.05).

CONCLUSIONSilica dust could induce cytotoxicity, oxidative stress and mitochondria-related cell apoptosis in 16HBE cells. Oxidative stress may play role in the processes of mitochondria-related apoptosis.

Apoptosis ; Cell Survival ; Cells, Cultured ; Dust ; Epithelial Cells ; cytology ; drug effects ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Mitochondria ; Oxidative Stress ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Reactive Oxygen Species ; metabolism ; Silicon Dioxide ; toxicity ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism

BACKGROUNDSleep deprivation (SD) has been used in treatment of depression disorder, and could effectively improve the patients' depressive symptoms.The aim of the study was to explore the effects of SD on electroencephalographic (EEG) and executive function changes in patients with depression.

METHODSEighteen depression patients (DPs) and 21 healthy controls (HCs) were enrolled in the present study. The whole night polysomnography (PSG) was recorded by Neurofax-1518K (Nihon Kohden, Japan) system before and after 36 hours of SD. The level of subjects' depression state was assessed by Visual Analogue Scale (VAS), and the executive function was assessed by Wisconsin Card Sorting Test (WCST).

RESULTSSignificantly decreased sleep latency (SL; before SD: (31.8 ± 11.1) minutes, after SD: (8.8 ± 5.2) minutes, P < 0.01) and REM sleep latency (RL; before SD: (79.8 ± 13.5) minutes, after SD: (62.9 ± 10.2) minutes, P < 0.01) were found after SD PSG in depression patients. Decreased Stage 1 (S1; before SD: (11.7 ± 2.9)%, after SD: (7.3 ± 1.1)%, P < 0.01) and Stage 2 (S2, before SD: (53.8 ± 15.5)%, after SD: (42.3 ± 14.7)%, P < 0.05) of non-rapid eye movement (NREM) sleep, and increased Stage 3 (S3, before SD: (11.8 ± 5.5)%, after SD: (23.6 ± 5.8)%, P < 0.01) and Stage 4 (S4, before SD: (8.8 ± 3.3)%, after SD: (27.4 ± 4.8)%, P < 0.01) NREM sleep were also found. After SD, the depression level in patients decreased from 6.7 ± 2.1 to 2.9 ± 0.7 (P < 0.01). In WCST, the patients showed significantly decreased Response errors (Re, before SD: 22.3 ± 2.4, after SD: 18.3 ± 2.7, P < 0.01) and Response preservative errors (Rpe, before SD: 11.6 ± 3.6, after SD: 9.3 ± 2.9, P < 0.05). Depression patients' RE (t = 2.17, P < 0.05) and Rpe (t = 2.96, P < 0.01) also decreased significantly compared to healthy controls.

CONCLUSIONSD can improve depression symptom and executive function in depression patients.

Adult ; Depression ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Polysomnography ; methods ; Sleep Deprivation ; physiopathology