The link between smoking, emphysema, and fibrosis: A retrospective cohort study.

INTRODUCTION: The presence of emphysema is common in patients with interstitial lung disease (ILD), which is designated as combined pulmonary fibrosis and emphysema (CPFE). This study aimed to examine the association between smoking, emphysema, and fibrosis in ILD patients. METHODS: A total of 800 patients hospitalized for ILD at the affiliated hospital of Qingdao University, Shandong, Qingdao, China, from December 2012 to December 2020 were included in our retrospective cohort study. Participants were divided into CPFE and non-CPFE groups. The patients' clinical presentations and radiographic and laboratory findings were reviewed and compared. The two groups were then divided and compared based on smoking status. Kaplan-Meier survival analysis with log-rank testing and multivariable Cox proportional hazards regression analysis were used to compare all-cause mortality. RESULTS: Emphysema was present in 188 (23.5%) ILD patients. Smoking was associated with increased odds of CPFE (adjusted odds ratio, AOR=2.13; 95% CI: 1.33-3.41, p=0.002). The CPFE patients had a comparable risk of death to non-CPFE patients (adjusted hazard ratio, AHR=0.89; 95% CI: 0.64-1.24, p=0.493). Smoking was not a risk prognostic factor in the whole group (AHR=1.34; 95% CI: 0.90-1.99, p=0.152) or the CPFE group (AHR=0.90; 95% CI: 0.43-1.86, p=0.771). However, a significant prognostic difference between smokers and non-smokers was found in the non-CPFE group (AHR=1.62; 95% CI: 1.02-2.58, p=0.042). In ILD patients, smoking pack-years were weakly correlated with total centrilobular emphysema (CLE) scores and total fibrosis scores (TFS), but not with total emphysema scores (TES); TFS were weakly correlated with TES. CONCLUSIONS: CPFE did not affect the prognosis of ILD. Smoking was a risk but not a prognostic factor for CPFE. However, smoking was associated with worse survival in non-CPFE patients. There was an intricate association among smoking, emphysema, and fibrosis in ILD patients.

Diabetes mellitus and idiopathic pulmonary fibrosis: a Mendelian randomization study.

BACKGROUND: The question as to whether or not diabetes mellitus increases the risk of idiopathic pulmonary fibrosis (IPF) remains controversial. This study aimed to investigate the causal association between type 1 diabetes (T1D), type 2 diabetes (T2D), and IPF using Mendelian randomization (MR) analysis. METHODS: We used two-sample univariate and multivariate MR (MVMR) analyses to investigate the causal relationship between T1D or T2D and IPF. We obtained genome-wide association study (GWAS) data for T1D and T2D from the European Bioinformatics Institute, comprising 29,652 T1D samples and 101,101 T1D single nucleotide polymorphisms (SNPs) and 655,666 T2D samples and 5,030,727 T2D SNPs. We also used IPF GWAS data from the FinnGen Biobank comprising 198,014 IPF samples and 16,380,413 IPF SNPs. All cases and controls in these datasets were derived exclusively from European populations. In the univariate MR analysis, we employed inverse variance-weighted (IVW), weighted median (WM), and MR-Egger regression methods. For the MVMR analysis, we used the multivariate IVW method primarily, and supplemented it with multivariate MR-Egger and multivariate MR- least absolute shrinkage and selection operator methods. Heterogeneity tests were conducted using the MR-IVW and MR-Egger regression methods, whereas pleiotropic effects were assessed using the MR-Egger intercept. The results of MR and sensitivity analyses were visualized using forest, scatter, leave-one-out, and funnel plots. RESULTS: Univariate MR revealed a significant causal relationship between T1D and IPF (OR = 1.118, 95% CI = 1.021-1.225, P = 0.016); however, no significant causal relationship was found between T2D and IPF (OR = 0.911, 95% CI = 0.796-1.043, P = 0.178). MVMR analysis further confirmed a causal association between T1D and IPF (OR = 1.133, 95% CI = 1.011-1.270, P = 0.032), but no causal relationship between T2D and IPF (OR = 1.009, 95% CI = 0.790-1.288, P = 0.950). Sensitivity analysis results validated the stability and reliability of our findings. CONCLUSION: Univariate and multivariate analyses demonstrated a causal relationship between T1D and IPF, whereas no evidence was found to support a causal relationship between T2D and IPF. Therefore, in clinical practice, patients with T1D should undergo lung imaging for early detection of IPF.

Association of lactate/albumin ratio with in-hospital mortality in ICU patients with acute respiratory failure: A retrospective analysis based on MIMIC-IV database.

We aimed to investigate the association between the lactate/albumin ratio (LAR), and in-hospital mortality in critically ill patients with acute respiratory failure. This retrospective cohort study was conducted based on the medical information mart for intensive care-IV database, which included critically ill adult patients with acute respiratory failure whose primary endpoint was in-hospital death. The analyses included curve fitting, a logistic multivariate regression model, and subgroup analysis. In this study, 6028 intensive care unit patients with acute respiratory failure were analyzed. Of these, 1843 (30.57%) died. After adjusting for confounding factors, a nonlinear relationship between LAR and in-hospital mortality was observed, and the risk of death was found to decrease by 81% with a reduction of 1 unit of LAR when it was < 4.46. The association between LAR and in-hospital mortality was not statistically significant when LAR was > 4.46. Hence, the relationship between LAR and in-hospital mortality could only be observed when the LAR was < 4.46. There is a nonlinear relationship between LAR and the risk of in-hospital death in intensive care unit patients with acute respiratory failure, and there is a saturation effect.

The Co-Occurrence of Anthracosis with Interstitial Lung Disease.

Objective: Anthracosis is defined as deposition of black pigments in the bronchial mucosa or lung parenchyma. The aim of this study was to investigate the clinical features of patients with coexisting anthracosis and interstitial lung diseases (ILDs). Methods: A total of 335 ILDs patients who underwent bronchoscopy at the affiliated hospital of Qingdao University were included in our study. We enrolled 71 patients who diagnosed with anthracosis by bronchoscopy. The clinical presentations, radiographic features, and bronchoscopic findings of the patients were reviewed. Results: Compared with the non-anthracosis group, biomass exposure (48, 67.6% vs. 153, 53.9%, p=0.041), the median pressure of carbon dioxide before six-minute test (42.00 mmHg vs. 40.00 mmHg, P=0.001), the mean peak expiratory flow (115.21 ±23.55 %predicted vs. 104.20±26.17%pre-dicted, P=0.048), the mean level of triglyceride (1.79±1.27 mmol/L vs. 1.51 ±0.74 mmol/L, P=0.034) were significantly increased and the mean oxygen saturation after six-minute test (95.49 ±2.72% vs. 96.56 ±1.27%, P=0.028), the mean cardiac ejection fraction (61.22±2.07% vs.62.08±2.89%, P=0.019) were significantly decreased in the anthracosis group. However, we didn't find significant difference between the two groups in lymph node calcification (p=0.620) and lymphadenectasis (p=0.440). Conclusions: Biomass smoke is a risk factor for anthracosis. Anthracosis produce a bad effect on the oxygenation, cardiac function and lipid metabolism in ILDs patients. The ILDs patients should decrease the exposure of biomass.

HIPK2 attenuates bleomycin-induced pulmonary fibrosis by suppressing the Wnt/ß-catenin signaling pathway.

INTRODUCTION: The present study aimed to investigate the effect of homeodomain interacting protein kinase 2 (HIPK2) on pulmonary fibrosis and the probable mechanisms. MATERIAL AND METHODS: We constructed a mouse model of bleomycin-induced pulmonary fibrosis and up-regulated the expression of HIPK2 in the lung by in vivo transfection. Lung tissues were collected for the detection of mesenchymal markers (α-SMA, collagen I, collagen III) and the expression of ß-catenin as assessed by RT-PCR, western blot, and immunohistochemistry. Mouse lung fibroblasts (MLFs) with upregulation or downregulation of HIPK2 were successfully constructed and XAV939 was used to downregulate ß-catenin expression. Then, we evaluated the activation of MLFs and the Wnt/ß-catenin pathway under various conditions. RESULTS: The results showed that in the bleomycin-induced mouse model group, the lung alveolar structure was severely damaged, the amount of collagen fibers was increased in alveolar speta, and the expression of HIPK2 in the fibrotic area was found to be reduced. After upregulating HIPK2 in the lungs of the mouse fibrosis model we found that pulmonary fibrosis was attenuated and the expression of ß-catenin and mesenchymal markers was reduced. The upregulation of HIPK2 inhibited the proliferation and migration of MLFs induced by TGF-ß1, promoted apoptosis of MLFs, and reduced the expression of mesenchymal markers and ß-catenin. Meanwhile, downregulation of HIPK2 promoted the proliferation and migration of MLFs, inhibited apoptosis, and promoted mesenchymal markers and ß-catenin expression. XAV939 treatment of MLFs silencing HIPK2 inhibited their proliferation and activation via silencing HIPK2, promoted apoptosis, and reduced interstitial markers and ß-catenin expression. CONCLUSIONS: HIPK2 can attenuate bleomycin-induced pulmonary fibrosis by inhibiting the Wnt/ß-catenin pathway in mouse lung fibroblasts.

Positron emission tomography/computed tomography and endobronchial ultrasound-guided transbronchial needle aspiration to evaluate the status of N2 in preoperative non-small cell lung cancer: a diagnostic test.

Background: As a minimally invasive method, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was more accurate than non-invasive methods such as positron emission tomography (PET) and computed tomography (CT) to evaluate the lymph nodes in preoperative non-small cell lung cancer (NSCLC). PET/CT has more anatomical advantages than PET scanning and is more accurate in lung cancer staging. However, no relevant studies have comparatively evaluated PET/CT and EBUS-TBNA for NSCLC patients. Methods: A total of 112 patients were included in this retrospective analysis. The golden diagnosis of N2 status was postoperative pathological results. In EBUS-TBNA puncture specimens, if clear malignant tumor cells could be seen, the results were taken as positive. In PET/CT image analysis, the CT values, short diameter, and maximum standardized uptake value (SUVmax) of each lymph node were recorded to evaluate N2 status. The results of PET/CT and EBUS-TBNA were compared with the final pathological results, and respective sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated. - Then, the patients were divided into adenocarcinoma group and squamous cell carcinoma group -and the results were calculated and compared with the above method. Results: The results showed that EBUS-TBNA had a higher diagnostic value for mediastinal lymph nodes than PET/CT, and the difference was statistically significant (P<0.001). In NSCLC patients, the results showed that the sensitivity (P=0.013), specificity (P<0.001), PPV (P<0.001), NPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than that of PET/CT (AUC =0.954 and 0.636, respectively). In adenocarcinoma cases, specificity (P<0.001), PPV (P<0.001), NPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than that of PET/CT (AUC =0.957 and 0.596, respectively).In cases with squamous cell carcinoma, specificity (P=0.003), PPV (P<0.001), and accuracy (P<0.001) of EBUS-TBNA were higher than PET/CT (AUC =0.952 and 0.657, respectively). Conclusions: For preoperative diagnosis of mediastinal lymph node metastases in NSCLC, EBUS-TBNA is more accurate than PET/CT. For those patients with suspected mediastinal lymph node metastasis, EBUS-TBNA should be preferred method to evaluate the status of mediastinal lymph nodes.

Yellow nail syndrome accompanied by minimal-change nephrotic syndrome: A case report.

BACKGROUND: In most cases of yellow nail syndrome (YNS), the classic triad of yellow nails, lymphedema and respiratory manifestations rarely manifest simultaneously. Therefore, diagnosis is delayed or frequently missed. CASE SUMMARY: We report a 62-year-old YNS patient presenting with bilateral pleural, pericardial and peritoneal effusions who, 2 mo later, developed minimal-change nephrotic syndrome. After treatment with vitamin E, clarithromycin and prednisone for 3 mo, effusions in the chest, pericardium and abdominal cavity decreased while urine protein levels returned to within normal ranges. CONCLUSION: Clinicians should consider the possibility of YNS for patients presenting with multiple serous effusions and nephrotic syndromes.

A Predicting Nomogram for Mortality in Patients With COVID-19.

Background: The global COVID-19 epidemic remains severe, with the cumulative global death toll reaching more than 207,170 as of May 2, 2020 (1). Purpose: Our research objective is to establish a reliable nomogram to predict mortality in COVID-19 patients. The nomogram can help us distinguish between patients who are at high risk of death and need close attention. Patients and Methods: For the single-center retrospective study, we collected 21 cases of patients who died in the critical illness area of the Optical Valley Branch of Tongji Hospital, Huazhong University of Science and Technology, from February 9 to March 10. Additionally, we selected 99 patients discharged during this period for analysis. The nomogram was constructed to predict the mortality for COVID-19 patients using the primary group of 120 patients and was validated using an independent cohort of 84 patients. We used multivariable logistic regression analysis to construct the prediction model. The nomogram was evaluated for calibration, differentiation, and clinical usefulness. Results: The predictors included in the nomogram were c-reactive protein, PaO2/FiO2, and cTnI. The areas under the curves of the nomogram were 0.988 (95% CI: 0.972-1.000) and 0.956 (95% CI, 0.874-1.000) in the primary and validation groups, respectively. Decision curve analysis suggests that the nomogram may have clinical usefulness. Conclusion: This study provides a nomogram containing c-reactive protein, PaO2/FiO2, and cTnI that can be conveniently used to predict individual mortality in COVID-19 patients. Next, we will collect as many cases as possible from multiple centers to build a more reliable nomogram to predict mortality for COVID-19 patients.

CXXC5 Attenuates Pulmonary Fibrosis in a Bleomycin-Induced Mouse Model and MLFs by Suppression of the CD40/CD40L Pathway.

OBJECTIVE: To investigate the role of CXXC5 and the CD40/CD40L pathway in lung fibrosis. METHODS: (1) We constructed mouse models of bleomycin-induced pulmonary fibrosis and transfected them with a CXXC5 overexpression vector to evaluate the severity of pulmonary fibrosis. (2) Mouse lung fibroblast (MLF) models stably overexpressed or knockout of CXXC5 vector were constructed. After transforming growth factor-ß1 (TGF-ß1) stimulation, we examined the proliferation and apoptosis of the MLF model and evaluated the expression of mesenchymal markers and the CXXC5/CD40/CD40L pathway. RESULTS: (1) Compared with other groups, the overexpressed CXXC5 group had less alveolar structure destruction, thinner alveolar septum, and lower Ashcroft score. (2) In bleomycin-induced mice, the expression of CD40 and CD40L increased at both transcriptional and protein levels, and the same changes were observed in α-smooth muscle actin (α-SMA) and collagen type I (Colla I). After upregulation of CXXC5, the increase in CD40, CD40L, α-SMA, and Colla I was attenuated. (3) Stimulated with TGF-ß1, MLF proliferation was activated, apoptosis was suppressed, and the expression of CD40, CD40L, α-SMA, and Colla I was increased at both transcriptional and protein levels. After upregulation of CXXC5, these changes were attenuated. CONCLUSION: CXXC5 inhibits pulmonary fibrosis and transformation to myofibroblasts by negative feedback regulation of the CD40/CD40L pathway.

Effect of the alteration of Tribbles homologue 3 expression on epithelial­mesenchymal transition of transforming growth factor ß1­induced mouse alveolar epithelial cells through the Wnt/ß­catenin signaling pathway.

The aims of the present study were to elucidate the regulatory effect of exogenous Tribbles homologue 3 (TRB3) expression on the Wnt/ß­catenin signaling pathway and epithelial­mesenchymal transition (EMT) in transforming growth factor­ß1 (TGF­ß1)­induced mouse alveolar epithelial cells (MLE­12) and investigate the underlying regulatory mechanisms. TRB3 expression was upregulated and downregulated using gene overexpression and RNA interference techniques, respectively. TGF­ß1­stimulated MLE­12 cells were examined for EMT and activation condition of the Wnt/ß­catenin signaling pathway using Cell Counting Kit­8, flow cytometry, western blotting, reverse transcription­quantitative PCR, ELISA and immunofluorescence techniques. During TGF­ß1­induced EMT, TRB3 expression was found to be significantly upregulated (P<0.05). In the TRB3 overexpression group, upregulated expression of ß­catenin and EMT­related genes and proteins was observed (P<0.05), and an increase in fibrosis­related factors in the cell culture supernatant was detected (P<0.05); however, the results were the opposite in the TRB3 downregulated group (P<0.05). TRB3 may be involved in the regulation of EMT in TGF­ß1­induced MLE­12 cells through the Wnt/ß­catenin signaling pathway.

Diffuse pulmonary lymphangiomatosis: A rare case report in an adult.

RATIONALE: Diffuse pulmonary lymphangiomatos (DPL) is a rare aggressive lymphatic disorder characterized by proliferation of anastomozing lymphatic vessels and extremely rare in adult patients. PATIENT CONCERNS: We report a case of diffuse pulmonary lymphangiomatosis in 59-year-old man presented with cough and sputum for 2 months. DIAGNOSES: Combining clinical manifestations with results of radiological, bronchoscopy, and surgical lung biopsy, it was consistent with the diagnosis of DPL. INTERVENTIONS: After bronchoalveolar lavage and biopsy, symptom of cough got worse suddenly accompanied by excessive chyloptysis. The patient received an emergency surgical intervention and low fat medium chain fat treatment. OUTCOMES: The patient was discharged with a much better health condition. LESSONS: This case report is the oldest patient reported in the English literature, to the best of our knowledge. Serious complications of bronchoscopy should be considered, especially in DPL patients with severely enlarged mediastinum or with thin-walled translucent vesicles under endoscopy.

LINC00702 suppresses proliferation and invasion in non-small cell lung cancer through regulating miR-510/PTEN axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been consistently reported to be involved in the progression of non-small cell lung cancer (NSCLC). In this study, we aimed to identify aberrantly expressed lncRNAs in NSCLC, in order to explore new therapeutic targets for NSCLC. METHODS: Two pairs of NSCLC and adjacent normal tissues were first analyzed by RNA sequencing. The expressions of LINC00702 in 40 pairs patient samples and in 4 NSCLC cell lines was measured by quantitative real-time PCR. Putative target miRNAs of LINC00702 were predicted by the bioinformatics tools. The effect of LINC00702 on tumor growth in vivo was evaluated. RESULTS: LINC00702 was significantly down-regulated in patients with NSCLC, which was correlated with tumor size and metastasis. In addition, overexpression of LINC00702 markedly suppressed proliferation and metastasis in NSCLC cells via inducing apoptosis in vitro and in vivo. Moreover, bioinformatics and luciferase reporter assays demonstrated that LINC00702 functioned as a competing endogenous RNA (ceRNA) for miR-510 in NSCLC, and upregulated its target gene PTEN. CONCLUSION: Our results indicated that LINC00702 modulated the expression of PTEN gene by acting as a ceRNA for miR-510 in NSCLC. Therefore, LINC00702 may serve as a potential target for the diagnosis and treatment of patients with NSCLC.

Expression of TRB3 promotes epithelial­mesenchymal transition of MLE­12 murine alveolar type II epithelial cells through the TGF­ß1/Smad3 signaling pathway.

The aim of the present study was to investigate whether the expression of tribbles pseudokinase 3 (TRB3) is involved in pulmonary interstitial fibrosis and to examine the possible mechanisms. The expression of TRB3 in murine alveolar type II epithelial cells (MLE­12 cells) following transforming growth factor ß1 (TGF­ß1) stimulation was assessed using various techniques, including western blot and reverse transcription­quantitative polymerase chain reaction assays. TRB3 overexpression and downregulation models were used to evaluate the impact of TRB3 on the TGF­ß1­induced epithelial­mesenchymal transition (EMT) of MLE­12 cells. The downregulation of TRB3 was induced by RNA interference. The expression of TRB3 was significantly increased in MLE­12 cells following the activation of TGF­ß1 (P<0.05). The overexpression of TRB3 was found to promote activation of the TGF­ß1/Smad3 signaling pathway, EMT, and the upregulated expression of ß­catenin and EMT­related genes and proteins (P<0.05), whereas the downregulation of TRB3 attenuated the promoting effect on EMT induced by TGF­ß1. In addition, the overexpression of TRB3 inhibited MLE­12 cell proliferation by stimulating apoptosis, leading to the formation of pulmonary fibrosis (PF). The positive feedback loop demonstrated that TGF­ß1 induced the expression of TRB3, and TRB3, in turn, stimulated EMT and promoted the onset of PF through activation of the TGF­ß1/Smad3 signaling pathway. Therefore, TRB3 may promote the formation of PF through the TGF­ß1/Smad3 signaling pathway.

TRB3 regulates pulmonary interstitial fibrosis through the MAPK signaling pathway.

This study aims to investigate the effects of TRB3 on the EMT and MAPK signaling pathways in a bleomycin (BLM)-induced pulmonary fibrosis mouse model. TRB3 adenovirus vector with green fluorescent protein (GFP) and TRB3-siRNA adenovirus vector were constructed for overexpression and down-regulation of TRB3, respectively. The pulmonary fibrosis mouse model was induced by bleomycin, and then treated with adenovirus on the next day. The mice were randomly killed at the 7th (D7), 14th (D14) and 28th (D28) day, respectively. The lung tissues were collected for histopathologic observations, hydroxyproline determination, Immunohistochemistry, western blot and RT-qPCR to detect the expression of TRB3 and EMT-related proteins. Overexpression of TRB3 caused more severe pulmonary fibrosis (P<0.05), while downregulation of TRB3 significantly reduced pulmonary fibrosis (P<0.05). The expression of MAPK pathway-related and EMT-related genes and proteins was markedly upregulated by TRB3 overexpression (P<0.05), but prominently downregulated by TRB3-shRNA (P<0.05). In conclusion, exogenous regulation of TRB3 may have effects on bleomycin-induced pulmonary fibrosis in mice.

Interaction between Pseudomonas aeruginosa and Aspergillus fumigatus in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a disease characterized by chronic airway infection with a high incidence and poor prognosis. Pseudomonas aeruginosa and Aspergillus fumigatus are pathogens commonly found in CF patients. Clinically, these two microorganisms often coexist in the airway of CF patients. Combined infection with P. aeruginosa and A. fumigatus results in worsening lung function and clinical condition. METHODS: In this review, we focus on the mutual inhibition and promotion mechanisms of P. aeruginosa and A. fumigatus in CF patients. We also summarized the mechanisms of the interaction between these pathogenic microorganisms. RESULTS: P. aeruginosa inhibits A. fumigatus growth through the effects of phenazines, the quorum sensing system, iron competition, bacteriophages, and small colony variants. P. aeruginosa induces A. fumigatus growth through volatile organic compounds and subbacteriostatic concentrations of phenazines. A. fumigatus interferes with P. aeruginosa, affecting its metabolic growth via phenazine metabolic transformation, gliotoxin production, and reduced antibiotic sensitivity. DISCUSSION: Coexistence of P. aeruginosa and A. fumigatus can lead to both mutual inhibition and promotion. In different stages of CF disease, the interaction between these two pathogenic microorganisms may shift between promotion and inhibition. A discussion of the mechanisms of P. aeruginosa and A. fumigatus interaction can be beneficial for further treatment of CF patients and for improving the prognosis of the disease.

Pirfenidone suppresses bleomycin-induced pulmonary fibrosis and periostin expression in rats.

The aim of the present study was to investigate the effect of pirfenidone on bleomycin-induced lung fibrosis in rats, in order to elucidate the underlying mechanism of periostin-induced fibrosis. The lung fibrosis model was constructed using a single intratracheal instillation of bleomycin in rats. The normal rats without bleomycin administration were used as controls (n=24). Bleomycin-treated rats were randomized into the model (M) or pirfenidone (P) group (n=24 per group). Rats were sacrificed on days 7, 14 and 28 following treatment. Hematoxylin-eosin and Masson's trichrome staining were performed to analyze pulmonary alveolitis and fibrosis. Periostin location was detected by immunohistochemistry. Hydroxyproline content, and expression of periostin and transforming growth factor (TGF)-ß1 were detected by ELISA, reverse transcription-quantitative polymerase chain reaction or western blotting. Correlation of periostin expression with hydroxyproline and TGF-ß1 content was also analyzed. Histological findings demonstrated that pirfenidone significantly inhibited bleomycin-induced lung fibrosis and reduced the hydroxyproline content on day 14 and day 28 compared with the model group (P<0.05 or P<0.01). Furthermore, the bleomycin-induced increased protein expression of periostin and TGF-ß1 was also significantly suppressed by pirfenidone on days 14 (P<0.01) and 28 (data not shown). Furthermore, periostin expression was significantly correlated with hydroxyproline and TGF-ß1 content, and fibrosis score (P<0.001). The present findings suggest that the antifibrotic effect of pirfenidone may be achieved by suppression of periostin and TGF-ß1 expression in rat pulmonary fibrogenesis.

Expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/Tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary diseases and their relationships with pulmonary vascular remodelling.

OBJECTIVE: This study aims at investigating the expressions of TOLL-like receptor 4 (TLR-4) and matrix metalloproteinase 9 (MMP-9)/ tissue inhibitor of metalloproteinase 1 (TIMP-1) in pulmonary blood vessels with chronic obstructive pulmonary disease (COPD) and their relationships with pulmonary vascular remodelling (PVR). METHODS: 60 para-tumour tissues were divided into the COPD group and the control group (n=30); the inflammations, pulmonary artery wall area/total artery area (WA%), and wall thickness/vascular outer diameter (WT%) were compared. The expressions of TLR-4, MMP-9/TIMP-1, and PCNA in pulmonary vascular smooth muscle cells were detected, and their relationships with PVR were then analysed. RESULTS: The inflammations (1.6±0.8), WA% (44.0±6.4), and WT% (27.3±3.3) in the COPD group were higher than in the control group (0.3±0.5, 26.1±2.8, 15.6±1.8), and the expressions of TLR-4 (31.4±147) and MMP-9/TIMP-1 (2.2±2.6) were increased compared to the control group (4.7±4.5, 1.9±12). Correlation analysis: TLR-4 and MMP-9/TIMP-1 were positively correlated with the inflammations (r=0.18, P<0.01), WA% (r=0.68, P<0.01), and WT% (r=0.73, P<0.01), as well as positively correlated with the expression of PCNA (r=0.44, P<0.01); the upregulation of TLR-4 was positively correlated with the expressions of MMP-9 and TIMP-1. CONCLUSIONS: The upregulation of TLR-4 in the pulmonary arterial smooth muscle cells of COPD patients could promote the inflammations and the MMP-9 expression, thus causing abnormal degradation of extracellular matrix, so it played an important role in the process of PVR.

Interventions and mechanisms of N-acetylcysteine on monocrotaline-induced pulmonary arterial hypertension.

The aim of the present study was to investigate the impact of N-acetylcysteine (NAC) on the expression of activin receptor-like kinase-1 (ALK-1) and mothers against decapentaplegic homolog 1 (Smad1) in the pulmonary artery of rats with pulmonary arterial hypertension (PAH), and to explore the possible mechanisms underlying its effects on pulmonary vascular remodeling (PVR). In total, 32 Wistar rats were randomly divided into four groups: Control, model, low-dose (100 mg/kg/day) NAC and high-dose (500 mg/kg/day) NAC. Monocrotaline (MCT) was intraperitoneally injected to prepare the model, and the right ventricular hypertrophy index (RVHI) and hemodynamic parameters were detected 6 weeks later. Hematoxylin and eosin staining was used to observe the pulmonary arterial structural changes and evaluate the peri-pulmonary artery inflammation score. Additionally, western blot analysis was used to detect the protein expression of ALK-1 and Smad1 in the pulmonary artery. The results demonstrated that treatment with NAC reduced RVHI and mean pulmonary artery pressure. In addition, NAC reduced the MCT-induced PVR, pulmonary inflammation score and upregulation of ALK-1 and Smad1. These results indicate that ALK-1 and Smad1 participate in the formation of PAH and the process of PVR, and suggest that NAC may inhibit PAH by inhibiting the expression of ALK-1 and Smad1 in the pulmonary artery.