Objective To observe the eotaxin expression of rat airway smooth muscle cells ( ASMCs) induced by serum from asthmatic rats, and explore the possible mechanism. Methods ASMCs isolated fromrat tracheas were cultured in vivo. Then they were treated with serum from asthmatic rats, or treated with serum and dexamethasone simultaneously. The level of eotaxin protein in supernatant and eotaxin mRNA in ASMCs were measured by ELISA and reverse transcription-polymerase chain reaction. The expression of cAMP in ASMCs was examined by radioimmunoassay. Results After the treatment with sensitized serum, the eotaxin level in supernatant and mRNA expression in ASMCs were significantly higher [ ( 107. 09 ±7. 12) ng/L vs. ( 0. 63 ±0. 56) ng/L, P lt; 0. 05; 1. 39 ±0. 04 vs. 0. 05 ±0. 01, P lt;0. 05] , and the level of cAMP in ASMCs was significantly lower compared with the control group [ ( 17. 58 ±3. 62) ng/L vs. ( 32. 39 ±3. 36) ng/L, P lt; 0. 05] . After intervened by the sensitized serum and dexamethasone simultaneously, the protein and mRNA expressions of eotaxin were lower compared with those intervened by sensitized serumalone [ ( 64. 18 ±4. 04) ng/L and 0. 77 ±0. 19] . The level of eotaxin in supernatant was negatively correlated with cAMP level in ASMCs ( r = - 0. 788, P lt; 0. 01) . Conclusions There is anautocrine function in ASMCs as inflammatory cells after stimulation with sensitized serum. Eotaxin may play an important roll in the pathogenesis of asthma via a cAMP-dependent pathway.
ObjectiveTo study immunodepression effect of bone marrow-derived mesenchymal stem cell (BMSC) on acute asthmatic airway inflammation by galectin-1 (gal-1) in vivo.MethodsEighty-five female BALB/c mice were equally randomized into normal control group, asthmatic group, BMSC treatment group, gal-1 treatment group and BMSC and gal-1 inhibitor group. Ovalbumin (OVA) was used to establish acute asthmatic model. Total cell number and differential cell analysis in each group in bronchoalveolar lavage fluid (BALF) were determined. Furthermore, hematoxylin-eosin and periodic-acid Schiff staining was used to compare airway inflammation among five groups. Measurement of cytokines, including interleukin (IL) -4, IL-5 and gal-1 in BALF and OVA specific IgE (OVA-IgE) in serum were evaluated by enzyme linked immunosorbent assay. Moreover, dendritic cell (DC) in lung tissue was sorted by immunomagnetic beads and its MAPK signal pathway was analyzed by western blotting among five groups.ResultsAccumulation of inflammation cells, particularly eosinophils around airway and in BALF was evident in asthmatic mouse model, meanwhile hyperplasia of Goblet cell was also obvious in asthmatic group. BMSC engraftment or gal-1 infusion significantly reduced airway inflammation and hyperplasia of Goblet cell and the number of inflammation cells in BALF, especially eosinophils attenuated dramatically. However, there was no effect on airway inflammation and hyperplasia of Goblet Cell by simultaneous infusion BMSC engraftment and gal-1 inhibitor. Compared to normal control group, the level of IL-4, IL-5 in BALF and OVA-IgE in serum was increased remarkably in asthmatic group, but the level of gal-1 reduced obviously. Moreover, infusion of BMSC or gal-1 could mitigate the level of IL-4, IL-5 in BALF and OVA-IgE in serum and increase the level of gal-1 in asthmatic mouse. However, infusion with both BMSC and gal-1 inhibitor exerted no effect on cytokine and OVA-IgE in asthmatic mouse. DC was sorted by immunomagnetic beads and western blotting was used to detect the expression of MAPK signal pathway among five groups. The expression of ERK phosphorylation in asthmatic group was much lower than that in normal control group. On the contrary, the expression of p38 phosphorylation was much higher than that in normal control group. BMSC engraftment or gal-1 infusion significantly activated the ERK pathway and inhibited the p38 MARP pathway on asthmatic mouse DC. Nevertheless, the expression of ERK phosphorylation and p38 phosphorylation for group with BMSC and gal-1 inhibitor infusion was between the level of asthmatic group and normal control group.ConclusionsBMSC infusion alleviates airway inflammation in asthmatic mouse, especially weakens eosinophils infiltration, and the underlying mechanism might be protective effect of gal-1 secreted by BMSC which plays a role in lung tissue DC and regulates the DC expression of MAPK signal pathway.
Objective To investigate the effects of smoking intensity, duration and cessation on mRNA and protein expressions of matrix metalloproteinase-9 ( MMP-9) in tracheal epitheliumof rats, and the relationship between smoking or smoking cessation and airway remodeling in chronic obstructive pulmonary disease ( COPD) . Methods Forty Wistar rats were randomly divided into 5 groups, ie. a normal control group, a long termheavy smoking group, a short termheavy smoking group, a long termlight smoking group,and a smoking cessation group which was exposed to room air for 10 weeks after long term heavy smoking.The expressions of MMP-9 mRNA and protein in tracheal epithelium of rats were detected by in situ hybridization and munohistochemistry respectively. Results ( 1) The pathological changes of emphysema were observed in the lung tissue of every smoking rat, and were most sever in the long term heavy smoking group. ( 2) Compared with the normal control group [ ( 0. 88 ±0. 88) PU, ( 2. 80 ±1. 66) PU] , the expressions of MMP-9 mRNA and proteins in tracheal epithelium were remarkable elevated in the long term heavy smoking group [ ( 22. 01 ±2. 86) PU, ( 20. 81 ±2. 46) PU] , the short term heavy smoking group [ ( 14. 94 ±3. 46) PU, ( 13. 68 ±2. 00) PU] , the long term light smoking group [ ( 6. 92 ±2. 71) PU,( 8. 84 ±1. 80) PU] and the smoking cessation group [ ( 19. 00 ±3. 36) PU, ( 14. 82 ±1. 74) PU] ( P lt;0. 01) . Compared with the long term heavy smoking group, the expressions of MMP-9 in tracheal epithelium were decreased in other three smoking groups ( P lt; 0. 05) . Conclusions Smoking could increase the expression of MMP-9 in tracheal epithelium and cause trachea damage and remodeling with intensity and duration in rats. Smoking cessation could decrease the MMP-9 expression and alleviate trachea remodeling,suggesting its role in the prevention of COPD.
0bjective To evaluate the efficacy of FEV6 and FEV1／FEV6 as surrogates for FVC and FEV1／FVC in the spirometric diagnosis of airway obstruction，and to determine the fixed cut-off point of FEV1／FEV6 which can be used as an alternative for FEV1／FVC lt; 70％.Methods Spirometry measurements were perform ed in 128 participants．FEV1，FEV6，FVC，FEV1％pred，FVC％pred，FEV1／FVC and FEV1／FEV6 were measured and analyzed.FEV1／FVClt;70％ was used as the“gold standard”。Severity of obstruction was based on FEV ％ pred．From ROC curve analysis，the FEV1／FEV6 ratio，which corresponded to optimal combination of sensitivity and specificity，was determined．Correlation between FEV1／FVC and FEV1／FEV6 was studied．Results Of 128 participants，there were 65(51％)with FEV1／FVC ≥70％ ．Of the 63 participants with FEV1／FVC lt;70％ ，there were 5 with FEV1／FEV6 between 70.09％ to 71％。There was no significant difference between the mean value of FVC and that of FEV ．Lifear correlation was revealed between FEV1／FVC and FEV1／FEV6 with the value close to 1(r=0.9979，Plt;0.0001)．From ROC curve analysis，the FEV1／FEV6lt;71.14％ was the best cut-off point coresponding to FEV1／FVC lt;70％ ．Conclusion These results suggest that FEV1／FEV6 is a valid alternative to FEV1／FVC for spirometric diagnosis of airw ay obstruction．There is a b corelation between FEV1／FEV6 and FEV1／FVC．
ObjectiveTo analyze the disease burden and temporal trends of chronic obstructive pulmonary disease (COPD) attributable to air pollution in China from 1990 to 2021. MethodsUtilizing data from the Global Burden of Disease Study 2021 (GBD 2021), we assessed the burden of COPD attributable to air pollution in China through metrics including death counts, disability-adjusted life years (DALYs), age-standardized mortality rate (ASMR), age-standardized DALY rate (ASDR), annual percentage change (APC), and average annual percentage change (AAPC). A Bayesian Age-Period-Cohort (BAPC) model was employed to project future trends in COPD burden attributable to air pollution. ResultsIn 2021, China’s ASMR and ASDR for COPD attributable to air pollution were 32.57 and 533.84 per 100 000 population, respectively, exceeding global averages. From 1990 to 2021, both ASMR and ASDR exhibited significant declining trends, with AAPCs of −5.24% (95% CI −5.78% to −4.70%) and −5.28% (95% CI −5.75% to −4.81%), respectively. The burden intensified with advancing age and was disproportionately higher among males compared to females. BAPC projections indicate a continued decline in COPD burden from 2022 to 2035, with ASMR expected to decrease from 56.40 to 23.02 per 100 000 and ASDR from 900.14 to 408.64 per 100 000. Conclusion Despite sustained reductions in the burden of COPD attributable to air pollution in China from 1990 to 2021, with further declines anticipated through 2035, national rates remain elevated relative to global benchmarks. Male and elderly populations bear the highest burden, underscoring the urgency for targeted interventions to mitigate air pollution exposure and address health disparities in vulnerable demographics.
ObjectiveTo investigate the synergistic effect of cold stress plus particulate matter 2.5 (PM2.5) co-exposure on the occurrence of respiratory inflammation and the possible post-transcriptional regulation mechanism of cold inducible RNA-binding protein (CIRP).MethodsIn vivo and in vitro experiments were carried out, and the lung tissue specimens from human surgical resection were observed. The rat model and cultured airway epithelial cells 16HBE were respectively divided into four groups (n=8), namely blank control group, 5 °C/18 °C group, PM2.5 group and 5 °C/18 °C+PM2.5 group. The expression of mRNA and protein of representative inflammatory cytokines and CIRP of cultured airway epithelial cells and rat bronchial/pulmonary tissues were respectively detected by ELISA, qPCR, and Western blot. Furthermore, the temporal dynamics of CIRP distribution were observed by cellular immunofluorescence. Finally, immunohistochemical method was used to observe the localization and expression of CIRP in rat and human bronchial/pulmonary tissues at the same time.ResultsIn vivo experiments, the mRNA and protein expression levels of CIRP, interleukin-6, and tumor necrosis factor-α in 5 °C group and PM2.5 group were significantly higher than those in the control group (all P<0.05), while the expression level of mRNA and protein in 5 °C+PM2.5 group were increased most obviously (all P<0.01). The same rule also appeared in the experimental results of each group in the vitro experiment. In addition, CIRP was mainly located in the cell nucleus; compared with the control group, the intracellular shift of CIRP appeared in 18 °C group and PM2.5 group, while the migration phenomenon was most obvious in the 18 °C+PM2.5 group. In the immunohistochemistry of rat bronchus/pulmonary tissue, the expressions of CIRP in the 5 °C group and in the PM2.5 group were significantly higher than those in the control group, and the CIRP expression in 5 °C+PM2.5 group was increased most evidently. Moreover, CIRP was expressed in the bronchial epithelial mucosa of normal people and patients with chronic obstructive respiratory disease (COPD), and it is mainly located in the nucleus of airway mucosal epithelial cells. The CIRP expression of COPD patients was significantly higher than that in the normal population.ConclusionCold stress has a sensitizing effect on airway epithelial inflammatory response induced by PM2.5, and post-transcriptional regulation of CIRP translocation from nucleus to cytoplasm may be an important mechanism.
ObjectiveTo investigate the changes of lung function after exposure to fine particulate matter (PM2.5) for 60 days and the expression of miR-146 in mice.MethodsThirty SPF BALB/c mice were treated with noninvasive tracheal instillation of fine particulate matter suspension at different doses (2.5 mg/kg, 5.0 mg/kg, 10.0 mg/kg) for 2 months (two times one week), the blank group and normal saline group were set as control groups. The mice were examined and killed on the next day after the last instillation. Histopathological changes of the lungs, pro-infammatory factors levels in the lung tissues, pulmonary functions and the relative expression of miR-146a and miR-146b in the lung tissues were detected.ResultsPeak inspiratory flow (PIF) and peak expiratory flow (PEF) were decreased significantly after PM2.5 exposure, however, lung resistance increased and maximal voluntary ventilation reduced from the general tendency without significant difference. Hematoxylin-eosin stain showed lymphocyte infiltration and macrophage infiltration by phagocytic particles, alveolar spacer widening, inflammatory response increased with the increase of PM2.5 exposure dosage. Pro-infammatory factors as interleukin-6 in the bronchoalveolar lavage fluid, interferon-γ and tumor necrosis factor-α in the lung homogenate were increased significantly by enzyme linked immunosorbent assay. The relative expressions of miR-146a and miR-146b were up-regulated remarkablely in treatment groups compared to the control group by real-time fluorescence quantitative polymerase chain reaction, which had negative relationships with PIF and PEF.ConclusionsThe lung function of mice decreases significantly after exposure to fine particulate matter, and the expression of miR-146 is up-regulated.
Abstract: ObjectiveTo explore the surgical characteristics of primary tracheal tumors treatment and its prognosis. Methods [WTBZ]We retrospectively investigated the clinical records of 38 patients with primary tracheal tumors in both Xiangya Hospital of Central South University and Hunan Provincial Tumor Hospital from Febuary 1982 to August 2009. There were 24 males and 14 females aged from 7 to 65 years. There were 2 benign lesions, 13 adenoid cystic carcinomas, 11 squamous cell carcinomas, 5 mucoepidermoid carcinomas, 4 adenocarcinomas and 3 other cell types. One patient with adenocarcinoma underwent exploratory thoracotomy only; 33 patients underwent tracheal resection and airway reconstruction, and according to the tumor growth characteristics, the surgeon applied circumferential tracheal resection with endtoend anostomosis or wedge resection; One patient had papilloma resected under fiber bronchoscopy; and three patients with locally advanced lesions underwent radiotherapy without surgery. The overall survival rate was calculated by the KaplanMeier method. The logrank method was used for comparing survival rates among different groups, characterized by cell types or surgical procedures. Results [WTBZ]The patient with exploratory thoracotomy died 3 days after surgery from respiratory failure. The perioperative mortality was 2.94% (1/34), and all the remaining 33 patients recovered and were discharged from hospital. Minor complications happened to 12 patients (35.29%), including 6 patients with pulmonary infection, 4 with atelectasis, and 2 with hoarseness. The followup time ranged from 6 months to 15 years. The followup rate was 97.29% (36/37). The threeunresected patients died within 6 months after hospital discharge. The 1, 5, and 10year survival rate for resected patients was88% （95%CI 0.77 to 0.99), 47%(95%CI 0.29 to 0.66), and 41% (95%CI 0.21 to 0.61), respectively. The survival rate of adenoid cystic carcinoma or mucoepidermoid carcinoma was significantly higher than that of squamous cell carcinoma or other tissue types (χ2=17.581, P=0.001). There was no statistical difference (χ2=0.021, P=0.886) in 5 year survival rate between wedge resection group at 63%(95%CI 0.34 to 0.91) and the segmental resection group at 77%(95%CI 0.44 to 0.99). Conclusions [WTBZ]Surgical treatment is safe and beneficial for primary tracheal tumors, and the pathological type is a significant prognostic factor after complete resection.
ObjectiveTo observe the clinical effect of vitrectomy with internal limiting membrane peeling and air tamponade in the treatment of idiopathic macular hole (IMH).MethodsA prospective, non-randomized controlled case cohort study. Twenty eyes of 20 patients with IMH in Ophthamology Department of The Second Hospital of Jilin University from September 2016 to January 2017 were included in this study. There were 4 males (4 eyes) and 16 females (16 eyes), with the mean age of 60.60±9.50 years and the mean disease course of 9.55±15.5 months. The stage of macular hole ranged from Ⅱ to Ⅳ. All patients underwent BCVA, intraocular pressure, spectral-domain OCT (SD-OCT) and multifocal ERG examinations. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logMAR visual acuity. The minimum diameter (MIN), bottom diameter (BD), height (H), the defective diameter of ellipsoid zone, the defective diameter of external limiting membrane (ELM) of the macular hole were measured by SD-OCT (German Heidelberg). Then the macular hole index (MHI=H/BD), hole traction index (THI=MD/BD) and hole diameter index (DHI=H/MD) were calculated. The response density in P1 wave was detected by mf-ERG. The logMAR BCVA was 1.18±0.54. There were 5 eyes with less than 400 μm MIN, 13 eyes with 400-700 μm MIN and 2 eyes with over than 700 μm MIN. All the patients were underwent vitrectomy with internal limiting membrane peeling and air tamponade. According to the SD-OCT image features after surgery, IMH closure was divided into type Ⅰ closed, type Ⅱ closed and unclosed. The follow-up was equal or greater than 3 months. The closure rate of IMH, BCVA and the changes of microstructure parameters of macular area were observed. Spearman correlation analysis was used to analyze the correlation between BCVA and the wave response density in P1 before surgery and the efficacy after IMH surgery.ResultsClosure rate of IMH: 18 eyes (90.0%) were completely closed (all type Ⅰ closed). The closure rate of macular hole with the MIN less than 400 μm was 100.0% (5/5), 400-700 μm was 92.3% (12/13), and over than 700 μm was 50% (1/2). BCVA: the mean logMAR BCVA at 1 week, 1 month, 3 months after surgery were 0.83±0.54, 0.65±0.41, 0.48±0.34, and there was statistically significant difference between preoperative and postoperative BCVA (t=3.382, 4.459, 5.250; P=0.003, 0.007, 0.004). The outcomes of SD-OCT at 3 months after surgery: 18 eyes (90.0%) with intact ELM. The defective diameter of ellipsoid zone was 260.34±272.08 μm, there was statistically significant difference between before and after surgery (t=13.545, P=0.002). The outcomes of mf-ERG: the P1 wave response density of the ring 1 and ring 2 after surgery were increased compared with before surgery (t=-16.748, -6.151; P＜0.01,＜0.01). The results of Spearman correlation analysis: there was a positive correlation between postoperative BCVA and preoperative MIN, the defective diameter of ellipsoid zone and ELM, and postoperative the defective diameter of ellipsoid zone (r=0.56, 0.59, 0.68, 0.52; P=0.010, 0.006, 0.001, 0.019). The postoperative BCVA was negatively correlated with the P1 wave response density of ring 1 and ring 2 of mf-ERG (r=－0.34, －0.16; P=0.006, 0.020). The IMH closure had a significant negative correlation with MIN and the defective diameter of ELM (r=－0.449, －0.449; P=0.047, 0.047). MHI and THI were positively correlated with the closure of the hole (r=0.474, 0.546; P=0.035, 0.013). Intraocular pressure increased in 2 eyes during the follow-up period, and returned to normal within 1 week after the administration of antihypertensive drugs. There were no complications during or after the operation.ConclusionsVitrectomy with internal limiting membrane peeling and air tamponade in the treatment of IMH is safe and effective. The MIN, MHI THI are significantly correlated with the curative effect after IMH surgery, which could be used as the index to predict and evaluate the curative effect. The response density of ring 1 and ring 2 in P1 wave of mf-ERG is signifi-cantly improved compared with before surgery, and which is negatively correlated with BCVA.
ObjectiveTo explore the effects of elafin on the regulation of mucin5AC (MUC5AC) in airway epithelial cells.MethodsAfter cultivating epithelial cells in vitro, cells were stimulated by cigarette smoke extract (CSE) and lipopolysaccharide (LPS), the intracellular MUC5AC production and extracellular secretion were assayed by immunofluorescence and ELISA, respectively.ResultsThe level of MUC5AC protein was obviously increased in the LPS stimulation group [(0.785±0.005) μg/ml vs. (0.232±0.004) μg/ml] and the CSE stimulation group [(0.803±0.005) μg/ml vs. (0.255±0.003) μg/ml] than those in the blank control groups (both P<0.01). When pretreated with elafin then stimulated by LPS and CSE, the MUC5AC productions were evidently decreased than those in the single LPS and CSE stimulation groups [(0.363±0.003) μg/ml and (0.406±0.006) μg/ml, bothP<0.01]. As compared with the blank control groups, the MUC5AC protein secretion were significantly decreased after stimulated with single elafin [(0.176±0.002) μg/ml and (0.193±0.004) μg/ml, bothP<0.05].ConclusionElafin may inhibit MUC5AC hypersecretion by blocking MUC5AC production and secretion.