SIRT1 attenuates endoplasmic reticulum stress and apoptosis in rat models of COPD.

The present study aimed to investigate the protective role of sirtuin 1 (SIRT1) and oxygen regulated protein 150 (ORP150) in a rat COPD model by inducing changes in ER stress and apoptosis. We separated 48 Sprague Dawley (SD) rats into four groups randomly: the control group, resveratrol group, COPD group and the resveratrol intervention group. Rats were challenged with cigarette smoke and lipopolysaccharide with resveratrol (a selective activator of SIRT1). The lung functions of the rats were measured and recorded. The expression levels of SIRT1 and ORP150 in lung tissues were examined by western blot and RTq PCR. The expression levels of the ER stress apoptosis-associated protein were determined .The apoptotic level of lung tissues was analyzed. The results suggest that SIRT1 attenuated apoptosis and ER stress in the lung tissues of rats with COPD. During this process, a positive correlation was identified between SIRT1 and ORP150.

Allergic Bronchopulmonary Aspergillosis With Elevated CEA Is Infrequent / La aspergilosis broncopulmonar alérgica con niveles elevados de antígeno carcinoembrionario (CEA) es infrecuente

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The relationship between HbA1c control levels and antituberculosis treatment effects: a meta-analysis.

BACKGROUND: Multiple studies of tuberculosis (TB) treatment have indicated that patients with diabetes mellitus (DM) may experience poor outcomes. We performed a meta-analysis to summarize evidence for the relationship between HbA1c control levels and anti-TB treatment effects in patients afflicted with both TB and DM. METHODS: Both English and Chinese databases were searched. Chinese databases included CNKI, WanFang, SinoMed, and VIP. PubMed, Ovid MEDLINE, Embase, Cochrane Library, and Web of Science were searched for English articles. We included studies that were restricted to the relationship between HbA1c levels and anti-TB treatment effects (sputum conversion rate [SCR] and TB focus absorption) in diabetic patients receiving treatment for TB. We used RevMan 5.3 software to analyze the data. RESULTS: We included 12 studies, of which five reported SCR at 2 months, seven reported the conversion at 3 months, and seven reported TB focus absorption. According to the five studies which reported 2 months-SCR, patients with diabetes and TB had an odds ratio (OR) of 2.14 (95% CI: 0.84-5.43) for the 2 months-SCR between controlled (HbA1c <7.0) and uncontrolled diabetes (HbA1c ≥7.0). However, additional seven studies reporting 3 months-SCR showed that controlled diabetics had higher SCR than uncontrolled (OR 3.39, 95% CI: 2.12-5.43). Moreover, seven of the 12 studies demonstrated that there were differences in TB focus absorption between controlled and uncontrolled diabetes (OR 2.69, 95% CI: 1.91-3.79). CONCLUSION: HbA1c control levels influence the SCR at 3 months and the TB focus absorption at the end of the anti-TB intensive treatment phase. This study highlights a need for increased attention to HbA1c or glucose control in patients afflicted with both TB and DM.

Propylthiouracil-induced organizing pneumonia: A case report.

RATIONALE: Propylthiouracil (PTU) is a common antithyroid drug which can treat hyperthyroidism effectively. PTU is, however, associated to multiple adverse effects. In rare case, PTU can cause interstitial pneumonia. PATIENT CONCERNS: A 40-year-old woman presented with dyspnea and was diagnosed with pulmonary infection at the first time. After the treatment with moxifloxacin, her symptoms still got worse. DIAGNOSIS: The lung tissues biopsy confirmed the diagnosis of organizing pneumonia (OP) and the administration of PTU suggested the diagnosis of PTU-induced OP. INTERVENTION: Withdrawal of PTU and the administration of methylprednisolone. OUTCOMES: The patient's symptoms relieved significantly 1 month later and lung computed tomography (CT) scan also demonstrated significant reduction of lung lesions. LESSONS: Here we report the first case of histologically confirmed OP induced by PTU and conduct a literature review of the cases of PTU-induced interstitial pneumonia. The awareness of PTU-induced OP can help physicians reduce the possibility of misdiagnosis.

NETs promote ALI/ARDS inflammation by regulating alveolar macrophage polarization.

Neutrophils activated during acute lung injury (ALI) form neutrophil extracellular traps (NETs) to capture pathogens. However, excessive NETs can cause severe inflammatory reactions. Macrophages are classified as M1 macrophages with proinflammatory effects or M2 macrophages with anti-inflammatory effects. During ALI, alveolar macrophages (AMs) polarize to the M1 phenotype. This study tested the hypothesis that NETs may aggravate ALI or acute respiratory distress syndrome (ARDS) inflammation by promoting alveolar macrophage polarization to the M1 type. Our research was carried out in three aspects: clinical research, animal experiments and in vitro experiments. We determined that NET levels in ARDS patients were positively correlated with M1-like macrophage polarization. NET formation was detected in murine ALI tissue and associated with increased M1 markers and decreased M2 markers in BALF and lung tissue. Treatment with NET inhibitors significantly inhibitor NETs generation, downregulated M1 markers and upregulated M2 markers. Regardless of LPS pre-stimulation, significant secretion of proinflammatory cytokines and upregulated M1 markers were detected from bone marrow-derived macrophages (M0 and M2) cocultured with high concentrations of NETs; conversely, M2 markers were downregulated. In conclusion, NETs promote ARDS inflammation during the acute phase by promoting macrophage polarization to the M1 phenotype. We propose that NETs play an important role in the interaction between neutrophils and macrophages during the early acute phase of ALI.

MS-275 potentiates the effect of YM-155 in lung adenocarcinoma via survivin downregulation induced by miR-138 and miR-195.

BACKGROUND: YM-155 has been proven to be an efficient antitumor suppressor in non-small cell lung cancer (NSCLC) cells. However, the suppressive effect of YM-155 on the expression of survivin is not sufficient and has a short half-life. MS-275, a histone deacetylase inhibitor, has significant antitumor capacity with a relatively long half-life. Our study explored whether MS-275 could enhance the inhibitory effect of YM-155 on LUAD proliferation. METHODS: To investigate the synergistic effect of MS-275 and YM-155, we employed methyl thiazolyl tetrazolium and colony formation assays to access the inhibition effect of MS-275, YM-155, or a combination in A549 and HCC827 cell lines. We then detected the effect of MS-275 and YM-155 on the expression of survivin and pro-apoptotic proteins by Western blot and miR-138 or miR-195 expression by quantitative PCR. We also analyzed the methylation level of microRNAs (miRNAs) using methylation-sensitive quantitative PCR. Finally, we investigated the interaction between miRNAs and survivin by luciferase reporter assay. RESULTS: MS-275 facilitated an inhibitory effect of YM-155 on lung adenocarcinoma cell proliferation. MS-275 can upregulate the level of acetylated H3, promote the degradation of DNA methyltransferases, and inhibit the methylation of miR-138 and miR-195 genes to elevate the expression of miR-138 and miR-195. Moreover, miR-138 and miR-195 showed a synergistic effect with YM-155 by directly binding to the 3 untranslated region of survivin to attenuate its expression. CONCLUSION: For the first time, we report the synergistic effective of MS-275 and YM-155 and suggest a new direction for the future application of YM-155.

Correction: Resveratrol reduces the apoptosis induced by cigarette smoke extract by upregulating MFN2.

[This corrects the article DOI: 10.1371/journal.pone.0175009.].

Resveratrol reduces the apoptosis induced by cigarette smoke extract by upregulating MFN2.

PURPOSE: The aim of this study was to investigate the effect of resveratrol (RSV) on cigarette smoke extract (CSE)-induced cell apoptosis and mitochondrial dysfunction in vitro, as well as changes in the MFN2 expression level. METHODS: Cultured human bronchial epithelial (HBE) cells were initially treated with CSE to induce apoptosis, followed by incubation either with or without RSV. Numerous techniques were used to evaluate the outcomes of the present study, including a cell counting kit-8 assay, real-time quantitative polymerase chain reaction (real-time qPCR), western blotting, JC-1 fluorescence, Hoechst 33342 staining, Annexin V-PI flow cytometry apoptosis analyses, and siRNA technology. RESULTS: A 24 h incubation in 3.5% CSE induced apoptosis in HBE cells, and pretreatment of HBE cells with RSV (20 µM) significantly suppressed the CSE-induced apoptosis, prevented the CSE-induced decrease in MFN2 levels, suppressed BAX translocation to the mitochondria, and prevented mitochondrial membrane potential loss and cytochrome C release. However, following the transfection of MFN2 siRNA, the anti-apoptotic effects of RSV were significantly attenuated. CONCLUSION: The results of the present study demonstrated that RSV may protect bronchial epithelial cells from CS-induced apoptosis in vitro by preventing mitochondrial dysfunction, and MFN2 may be associated with the anti-apoptotic functions of RSV in HBE cells.

Multinodule abnormalities of the tracheobronchus: bronchoscopy findings and clinical diagnosis.

BACKGROUND AND AIMS: Bronchoscopy is an important method for diagnosing respiratory disease. Multiple tracheobronchial nodules are rarely reported and their causes remain unclear. OBJECTIVES: The aim of this study was to describe the clinical characteristics of multiple nodule tracheobronchial abnormalities found under bronchoscopy caused by different diseases. METHODS: Eighty-seven patients with multiple tracheobronchial nodules were enrolled in this study. The characteristics of the multinodule lesions and the patient were diagnosed based on the pathology findings in our hospital. Chest computed tomography images were retrospectively reviewed by pulmonologists and radiologist. RESULTS: In 55 patients with definite pathological diagnosis, 16 (29%) patients were diagnosed as tuberculosis (TB) granuloma; 23 (41.8%) cases were diagnosed as malignant disease; 12 (21.8%) cases were diagnosed as tracheobronchopathia osteochondroplastica; 2 (3.6%) cases were diagnosed as sarcoidosis; and one case (1.8%) was diagnosed as lymphoma and one case (1.8%) as fungal infection. There were 32 cases of chronic inflammation. There was no relationship between nodule distribution and the pathological diagnosis. Malignant nodules usually smaller with a pale outlook, while nodules with larger size and smooth and intact mucosa usually turn out to be granuloma of unknown reason. CONCLUSION: The major causes of mutinodule lesions observed using bronchoscopy are tumor and TB. The presence of multiple endotracheobronchial nodules suggest that pulmonary lesion is present, and biopsy should be performed. Malignant nodules can be diagnosed by appearance and biopsy. Pathology results of TB, sarcoidosis and fungal infection can turn out to be granuloma of unknown reason. Further diagnosis needs other clinical materials.

A multi-center phase II study of nintedanib as second-line therapy for patients with advanced non-small-cell lung cancer in China.

PURPOSE: This study examined the efficacy and safety of using nintedanib as single-regimen in 2(nd)-line chemotherapy for Chinese patients with advanced (beyond stage IIIB) non-small-cell lung cancer (NSCLC). METHODS: Chinese patients were those with stage IIIB or IV NSCLC and had unsuccessful 1(st)-line platinum based chemotherapy. Patients received two oral intakes of 200 mg nintedanib everyday from day 1 to day 21, on every 4-week cycle. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and disease control rate. RESULTS: There were 62 eligible patients enrolled in the study. Half of the patients were male (n = 31, 50.0%). The median age was 64.2 years with youngest age of 33 years and oldest age of 83 years. Median PFS was 3.9 months (95% CI, 2.7-6.4 months). Median OS was 6.7 months (95% CI, 4.8-10.1 months). No patients (0.0%) had complete response. Thirty-one patients (50.0%) had stable disease and 23 patients (37.1%) had partial response. The most common severe adverse events (AEs), graded as 3 or 4, were heart failure (n = 12, 19.4%), hypertension (n = 7, 11.8%) and diarrhea (n = 6, 9.8%). CONCLUSION: NSCLC Patients in 2(nd)-line chemotherapy reached similar PFS, as compared with other FDA-approved second-line regimens. Also, the toxicity of nintedanib was well tolerated. Thus, nintedanib may be used as a standard regimen for 2(nd)-line chemotherapy for patients with advanced NSCLC.

Resveratrol exerts an anti-apoptotic effect on human bronchial epithelial cells undergoing cigarette smoke exposure.

Cigarette smoke can cause endoplasmic reticulum stress and induce apoptosis, both of which are important pathogenic factors contributing to chronic obstructive pulmonary disease. The aim of the present study was to produce a cigarette smoke extract (CSE)­induced apoptosis human bronchial epithelial cell (HBEpC) model, to investigate the protective effects of resveratrol (RES). The role of oxygen­regulated protein 150 (ORP150) in the RES­induced activation of Sirtuin 1 (SIRT1) was additionally studied. Cultured HBEpCs were initially treated with CSE to induce apoptosis, followed by an incubation either with or without RES. Numerous techniques were used to evaluate the outcomes of the present study, including cell counting kit­8 assay, quantitative polymerase chain reaction, western blotting, Hoechst 33342 staining and AnnexinV­PI flow cytometry apoptosis analyses, and gene knockdown. It was identified that 24 h 2% CSE incubation induced apoptosis in HBEpC, accompanied by an overexpression of the apoptosis molecular markers CCAAT­enhancer­binding protein homologous protein, caspase 4 and caspase 3. Pre­treatment of the cells with RES markedly alleviated the severity of apoptosis, as confirmed by apoptosis analyses and the expression levels of the apoptosis molecular markers. SIRT1 was shown to be overexpressed following RES treatment. However, following the gene knockdown of ORP150, the anti­apoptotic effects of RES were significantly attenuated. The results of the present study demonstrate that RES may have a protective effect against CSE­induced apoptosis, and a molecular pathway involving SIRT1 and ORP150 may be associated with the anti­apoptotic functions of RES in HBEpC.

Differences in distribution and drug sensitivity of pathogens in lower respiratory tract infections between general wards and RICU.

BACKGROUND: Lower respiratory tract infections (LRTIs) are common among patients in hospitals worldwide, especially in patients over the age of 60. This study investigates the differences in distribution and drug sensitivity of pathogens in LRTIs. METHODS: The clinical and laboratory data of 4,762 LRTI patients in the general ward and respiratory intensive care unit (RICU) of Xiangya Hospital (Changsha) were retrospectively analyzed. RESULTS: The infection rate of Gram-negative bacteria was significantly higher than that of Gram-positive bacteria in both the general ward and RICU (P<0.05). The incidence of Gram-negative bacteria infection was significantly higher in the RICU than in the general ward (P<0.05), whereas the incidence of Gram-positive bacteria infection is less in the RICU than in the general ward (P<0.05). In the general ward, the incidence of Gram-negative bacteria infection significantly increased (P<0.05) over time, whereas the incidence of Gram-positive bacteria infection significantly decreased from 1996 to 2011 (P<0.05). In the RICU, the incidence of Gram-positive bacteria infection decreased, while Gram-negative bacteria infections increased without statistical significance (P>0.05). Staphylococcus pneumoniae and Staphylococcus aureus were found to be the predominant Gram-positive strains in the general ward (34.70-41.18%) and RICU (41.66-54.87%), respectively (P>0.05). Pseudomonas aeruginosa and Acinetobacter baumannii were the predominant gram negative strains in the general ward (19.17-21.09%) and RICU (29.60-33.88%), respectively (P>0.05). Streptococcus pneumoniae is sensitive to most antibiotics with a sensitivity of more than 70%. Staphylococcus aureus is highly sensitive to vancomycin (100%), linezolid (100%), chloramphenicol (74.36-82.19%), doxycycline (69.57-77.33%), and sulfamethoprim (67.83-72.46%); however, its sensitivity to other antibiotics is low and decreased each year. Sensitivity of Pseudomonas aeruginosa to most ß-lactam, aminoglycoside, and quinolone group antibiotics decreased each year. CONCLUSIONS: The distribution and drug sensitivity of LRTI pathogens exhibit a high divergence between the general ward and RICU. Streptococcus pneumoniae may not be the predominant pathogen in LRTIs in some areas of China.

[Resveratrol attenuates endoplasmic reticulum stress and alveolar epithelial apoptosis in a rat model of chronic obstructive pulmonary disease].

OBJECTIVE: To investigate alveolar epithelial cell apoptosis induced by endoplasmic reticulum stress in a rat model of chronic obstructive pulmonary disease (COPD) and the potential protective effect of resveratrol. METHODS: The COPD rat model was established by intratracheal instillation of lipopolysaccharide (LPS) and exposure to cigarette smoke daily. Forty-eight male Sprague-Dawley rats were randomly divided into 4 groups (n = 12 each): a normal control group, a resveratrol control group (resveratrol 25 mg × kg⁻¹ × d⁻¹ gavage), a COPD group (COPD rat model established), and a resveratrol intervention group (COPD model rats receiving resveratrol 25 mg × kg⁻¹ × d⁻¹ gavage). Spirometry was conducted and the lung pathological changes were observed. The protein expression of CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-12 were detected by immunohistochemistry and Western blot, and alveolar epithelial apoptosis was analyzed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). Statistical analysis among groups were carried out by one way analysis of variance followed by LSD-t test between 2 groups. RESULTS: Significant decrease of FEV0.3/FVC [(59 ± 4)%] and dynamic lung compliance [(0.154 ± 0.013) ml/cm H2O, 1 cm H2O = 0.098 kPa] and increase of airway resistance [(0.651 ± 0.046) cm H2O × ml⁻¹× s⁻¹] were found in the COPD group when compared with the normal control group [(82 ± 4)%, (0.401 ± 0.033) ml/cm H2O, (0.404 ± 0.033) cm H2O × ml⁻¹ × s⁻¹] (t = -14.48, 16.48, P < 0.05). The FEV0.3/FVC [(71 ± 5)%] and dynamic lung compliance [(0.302 ± 0.023) ml/cm H2O] of the resveratrol intervention group were significantly improved when compared with those of the COPD group, and the airway resistance [(0.442 ± 0.036) cm H2O × ml⁻¹ × s⁻¹] also decreased (t = -10.02-10.37, P < 0.05). Significant small airway inflammation and emphysema were seen in the lung tissue of COPD group, while significant improvement was observed in the resveratrol intervention group when compared with COPD group. The lung tissue immunohistochemistry integrated optical density (IOD) of CHOP and caspase-12 (9 778 ± 217, 12 009 ± 346) of the COPD group increased significantly when compared with the normal control group (960 ± 94, 1 124 ± 112) (t = -100.43, - 90.43, P < 0.05), while the IODs of the resveratrol intervention group (5 799 ± 177, 6 720 ± 173) decreased significantly when compared with the COPD group (t = 45.32, 43.93, P < 0.05). Western blot results showed that the relative quantification of CHOP (0.910 ± 0.053) and caspase-12 (1.104 ± 0.026) increased in the COPD group when compared with the normal control group (0.204 ± 0.021, 0.133 ± 0.013, t = -36.04, -115.03, P < 0.05), while the ratios of the resveratrol intervention group (0.462 ± 0.037, 0.642 ± 0.011) decreased significantly when compared with COPD group (t = 24.22, 60.59, P < 0.05). Higher apoptosis index was seen in the COPD group [(39.8 ± 1.6)%] when compared with the resveratrol intervention group [(26.3 ± 1.5)%] and the normal control group [(6.4 ± 0.6)%] (t = 20.21, -49.94, P < 0.05). CONCLUSIONS: Endoplasmic reticulum stress, which induced apoptosis of alveolar epithelial cells, was observed in this COPD model. Resveratrol was shown to alleviate endoplasmic reticulum stress and attenuate alveolar epithelial apoptosis.

The effect of tai chi on chronic obstructive pulmonary disease: a pilot randomised study of lung function, exercise capacity and diaphragm strength.

BACKGROUND: Although the benefits of exercise on the health of patients with chronic obstructive pulmonary disease (COPD) have been widely reported, the effect of Tai Chi as an alternative exercise has not been thoroughly evaluated in patients with COPD. This study reported a randomised controlled trial, which investigated the effects of Tai Chi on lung function, exercise capacity, and diaphragm strength in patients with COPD. TRIAL DESIGN: Single blind randomised controlled study. SETTING: Department of Respiratory Medicine, Xiangya Hospital, Central South University. METHODS: Forty patients with COPD were randomised into either a control group or Tai Chi intervention group. Participants in the control group received only routine care, while participants in the Tai Chi group received routine care and completed a six-month Tai Chi exercise program. OUTCOMES: Lung function parameters, blood gas parameters, 6-min walking distance (6MWD), and diaphragm strength parameters. RESULTS: Lung function parameters (FEV1: 1.43 ± 0.08 and FEV1 (%) predicted: 47.6 ± 4.76), 6MWD (476 ± 15) and diaphragm strength parameters (TwPes: 1.17 ± 0.07, TwPga: -1.12 ± 0.06, and TwPdi: 1.81 ± 0.09) were found to be significantly increased in participants who successfully completed the six-month Tai Chi program compared to participants in the control group who only received routine care (p<0.05). These parameters were also found to be significantly increased in participants who completed the Tai Chi exercise program compared to the baseline (p<0.05). In contrast, no significant differences in PaO2 and PaCO2 were observed in participants before or after completing a Tai Chi program or between Tai Chi group and control group (p>0.05). CONCLUSIONS: Tai Chi enhances lung function, exercise capacity, and diaphragm strength. However, this is only preliminary research data and a larger trial is needed for more detailed results.

Cigarette smoke extract induces the expression of GRP78 in A549 cells via the p38/MAPK pathway.

Apoptosis of alveolar epithelial cells has been implicated in the pathogenesis of chronic obstructive pulmonary disease. To determine the involvement of glucose­regulated protein 78 (GRP78) in the cigarette smoke extract (CSE)­induced apoptosis of alveolar epithelial cells and the potential mechanisms underlying this effect, A549 cells that originate from alveolar type II epithelial cells were exposed to various CSE conditions in the present study. GRP78 expression and its effect on the apoptosis of A549 cells were investigated using techniques such as RT-PCR, western blot analysis, gene knockdown by GRP78 siRNA interference and the terminal deoxynucleotidyl transferase dUTP nick­end labeling assay. The activity of the p38/mitogen­activated protein kinase (MAPK) pathway and its involvement in GRP78 expression were also analyzed using SB203580, a p38/MAPK pathway inhibitor. It was demonstrated that GRP78 expression in the cells was significantly upregulated following CSE exposure and a 12­h exposure of 5% CSE was the most efficient in inducing GRP78 expression. This CSE­induced GRP78 expression was significantly attenuated by GRP78 siRNA or by the use of SB203580. The downregulation of GRP78 expression by GRP78 siRNA also led to the increased expression of caspase-3 and an increased apoptotic index (AI, P<0.05 vs. other groups). These results suggested that CSE induced GRP78 expression in A549 cells. This study demonstrated that upregulated GRP78 expression may be anti­apoptotic effects and the p38/MAPK pathway was involved in the process of CSE­induced GRP78 expression in A549 cells.

Salubrinal protects against cigarette smoke extract-induced HBEpC apoptosis likely via regulating the activity of PERK-eIF2α signaling pathway.

BACKGROUND AND AIMS: Endoplasmic reticulum (ER) stress plays an important role in cigarette smoke extract (CSE)-induced apoptotic cell death, which is an important pathogenic factor of chronic obstructive pulmonary disease (COPD). The aim of this study was to explore the role of the PERK-eIF2 pathway in CSE-induced human bronchial epithelial (HBE) cell apoptosis and to evaluate the protective effects and possible mechanism of salubrinal (Sal) on CSE-induced HBE cell apoptosis. METHODS: Normal human bronchial epithelial cells (HBEpC) were cultured and then treated with CSE alone or together with Sal or preincubated with or without PERK siRNA. Expressions of p-PERK/PERK, p-eIF2α/eIF2α, and caspase 3 and 4 were detected with PCR, Western blot, and immunofluorescence. Apoptosis was detected using AnnexinV-PI flow cytometry. RESULTS: CSE induced apoptotic cell death and caused a dynamic change in PERK-eIF2α pathway activity following the course of CSE exposure. The knockdown of PERK suppressed the expression of both PERK and p-eIF2a and caused a great increase in cell apoptosis. Sal could eliminate the effects of PERK knockdown, protecting the cells against the CSE insult, and this protection was accomplished through maintaining the homeostasis of PERK- eIF2α pathway. CONCLUSIONS: PERK-eIF2α pathway mediates the CSE-induced HBE cell apoptosis. The intactness of PERK-eIF2α pathway is crucial for HBE cell survival under CSE insult. Sal can protect against CSE-induced HBE cell apoptosis, and this effect is likely achieved through maintaining the homeostasis of PERK- eIF2α pathway.

Analysis of two cases with bronchopulmonary neurofibromatosis.

Neurogenic tumor of lung is very rare. Only few cases have been reported in the literature. We present here two cases of bronchopulmonary neurofibromatosis in two adults. In both cases, attempts at imaging failed to diagnose the case, and it was the histological study that ensured the diagnosis of neurofibromatosis. Biopsy specimens showed bundles of spindle-shaped cells mixed with collagen, and on immunohistochemistry some cells were positive for S-100 protein.

[The effect of erythromycin on transforming growth factor-ß(1) and secretory leukocyte proteinase inhibitor in a rat model of chronic obstructive pulmonary disease].

OBJECTIVE: To study the protective mechanism of erythromycin in the process of COPD. METHODS: Thirty-six male Wistar rats, grade SPF, weight (220 ± 20) g, were randomly divided into 3 groups, 12 each: a control group, a COPD model group and an erythromycin treated group. Measurement of rat pulmonary function and the pathological changes were performed, and the expression of transforming growth factor-ß(1) (TGF-ß(1)) and secretory leukocyte proteinase inhibitor (SLPI) in the lung of rats were evaluated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Analysis of variance, pairwise comparison between groups using SNK-q test, Pearson linear correlation analysis were carried out for statistical analysis. RESULTS: The rats in the COPD model group showed sign of less activity, loss of appetite and weight, dry and yellow hair, and sometimes wheezing, which were less or milder in the group treated with erythromycin. FEV(0.3)/FVC [(58 ± 7)%] and Cdyn [(0.16 ± 0.07) L/cm H2O, 1 cm H2O = 0.098 kPa] were significantly lower in the model group as compared to the control group [(83 ± 7)% and (0.33 ± 0.16) L/cm H2O], RI [(0.69 ± 0.14) cm H2O×L(-1)×s(-1)], but was significantly higher than the control group [(0.33 ± 0.11) cm H2O×L(-1)×s(-1)]. FEV(0.3)/FVC [(65 ± 9)%] and Cdyn [(0.23 ± 0.08) L/cm H2O] were significantly higher in the erythromycin treated group as compared to the model group [(58 ± 7)% and (0.16 ± 0.07) L/cm H2O], RI [(0.50 ± 0.13) cm H2O×L(-1)×s(-1)], but was significantly lower than the model group [(0.69 ± 0.14) cm H2O×L(-1)×s(-1)]. The expression of TGF-ß(1)protein (integral optical density value) and mRNA (absorbance value) (6.7 ± 1.5 and 0.45 ± 0.13) were lower in the erythromycin treated group as compared to the model group (10.7 ± 1.9 and 0.66 ± 0.18), but the expression of SLPI protein (integral optical density value) and mRNA (absorbance value) (9.9 ± 1.7 and 0.69 ± 0.34) were higher than those of the model group (8.1 ± 1.7 and 0.41 ± 0.27). The expressions of TGF-ß(1)and SLPI were negatively associated (r = -0.686, P < 0.05). CONCLUSIONS: The expression of SLPI was decreased but the expression of TGF-ß(1)was increased significantly in the bronchial and lung tissues of rats with COPD. Airway inflammation was inhibited by erythromycin which was able to reduce the inhibitory effect of TGF-ß(1)to SLPI, indicating a partial protective effect of erythromycin.

[Endoplasmic reticulum stress and related apoptosis in the lungs of a chronic obstructive pulmonary disease rat model].

OBJECTIVE: To study the endoplasmic reticulum stress (ERS) and the apoptosis of alveolar epithelial cells in a COPD rat model. METHODS: Twenty-four Wistar rats were divided into a control group and a COPD group at random. The COPD rat model was established by intratracheal instillation of lipopolysaccharide (LPS) twice and exposure to cigarette smoke daily. The spirometry was conducted and the pathological changes were observed after the model was established. The levels of glucose regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of GRP78, CHOP and caspase-12 was detected by Western blot. TdT-mediated dUTP nick end labeling (TUNEL) was used to analyze alveolar epithelial cell apoptosis. Comparisons between the two groups were performed by t-test. RESULTS: Significant decrease of FEV(0.3)/FVC [(60 ± 6)%] and dynamic compliance of lung (CLdyn) [(0.17 ± 0.02) cm H2O×ml(-1)×s(-1)], and increase of airway resistance [(0.64 ± 0.07) ml/cm H2O] were found in the COPD group compared with the control group [(83 ± 7)%, (0.31 ± 0.03) cm H2O×ml(-1)×s(-1), (0.32 ± 0.03) ml/cm H2O] (t = -14.532 - 11.619, P < 0.05). GRP78 mRNA and CHOP mRNA densitometry [(0.65 ± 0.07), (0.79 ± 0.06)] were significantly increased in the COPD group compared with the control group [(0.21 ± 0.04), (0.07 ± 0.04), respectively] (t = -19.102 and -32.573, P < 0.05). GRP78, CHOP, and active caspase-12 protein densitometry (0.83 ± 0.06, 0.82 ± 0.06 and 0.81 ± 0.07) were significantly increased in the COPD group compared with the control group [(0.33 ± 0.05, 0.05 ± 0.03 and 0.24 ± 0.06), respectively] (t = -40.866 - -22.070, P < 0.05). More apoptotic alveolar epithelial cells were found in the COPD group [(32.4 ± 3.7)%] than in the control group [(6.2 ± 0.9)%] (t = -23.852, P < 0.05). CONCLUSIONS: ERS was triggered in the lung tissues of COPD rats, especially in the alveolar epithelial cells. Alveolar epithelial cell apoptosis was increased in the COPD group. The ERS mediated apoptosis pathway may participate in the alveolar epithelial cell apoptosis in COPD.

Clinical analysis of 68 patients with pulmonary mycosis in China.

BACKGROUND: Due to the lack of specific clinical manifestations and imaging features, the diagnosis of pulmonary mycosis is difficult. This study aimed to investigate the pathogens, clinical manifestations, imaging features, diagnosis and management of pulmonary mycosis. METHODS: Data on 68 patients diagnosed as pulmonary mycosis in Xiang Ya hospital from January 2001 to December 2010 were collected and their clinical manifestations, radiographic characterization, diagnostic methods and management were analyzed. RESULTS: All patients were diagnosed by pathological examination. Of the 68 cases, 38 (55.9%) had pulmonary aspergillosis and 19 (27.9%) pulmonary cryptococcosis. Open-lung surgery was performed in 38 patients (55.9%), transbronchial biopsy in 15 (22.0%), and computerized tomography (CT) guided percutaneous needle biopsy in 11 (16.2%). Main symptoms were as follows: cough in 51 cases (75.0%), expectoration in 38 (55.9%), hemoptysis in 25 (37.8%), fever in 20 (29.4%), while 6 cases (11.1%) were asymptomatic. X-ray and chest CT showed masses or nodular lesions in 52 cases (76.5%), patchy lesions in 10 (14.7%), cavity formation in 15 (22.0%), and diffuse miliary nodules in 1 case. In 51 cases (75.0%) misdiagnosis before pathological examination occurred. Surgical resection was performed in 38 patients (55.9%). In 25 patients (36.7%) systemic antifungal therapy was administered, and 20 patients (29.4%) experienced complete responses or partial responses. CONCLUSION: The main pathogens of pulmonary mycosis are Aspergillus, followed by cryptococcosis. Final diagnosis of pulmonary mycosis mainly depends on pathological examination. The clinical manifestations, imaging features, diagnostic methods and management differ depending on the pathogens. Satisfactory therapy can be obtained by both antifungal and surgical treatment.