Effects of bronchial thermoplasty and cryoablation on airway smooth muscle.

BACKGROUND: The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma. This study compared the effects of BT and cryoballoon ablation (CBA) therapy on the airway smooth muscle (ASM). METHODS: Eight healthy male beagle dogs were included in this experiment. In the preliminary experiment, one dog received BT treatment for both lower lobe bronchus, another dog received CBA treatment for 7 s on the upper and lower lobe of right bronchus, and 30 s on the left upper and lower lobe. The treatments were performed twice at an interval of 1 month. In subsequent experiments, the right lower lobe bronchus was treated with BT, and the left lower lobe bronchus was treated with CBA. The effects of treatment were observed after 1 (n = 3) month and 6 months (n = 3). Hematoxylin-eosin staining, Masson trichrome staining, and immunohistochemical staining were used to compare the effects of BT and CBA therapy on the ASM thickness, collagen fibers synthesis, and M3 receptor expression after treatment. One-way analysis of variance with Dunnett post hoc test was used to analyze the differences among groups. RESULTS: In the preliminary experiment, the ASM ablation effect of 30-s CBA was equivalent to that of 7-s CBA (ASM thickness: 30.52 ±â€Š7.75 µm vs. 17.57 ±â€Š15.20 µm, P = 0.128), but the bronchial mucociliary epithelium did not recover, and large numbers of inflammatory cells had infiltrated the mucosal epithelium at 1-month post-CBA with 30-s freezing. Therefore, we chose 7 s as the CBA treatment time in our follow-up experiments. Compared with the control group (35.81 ±â€Š11.02 µm), BT group and CBA group (13.41 ±â€Š4.40 µm and 4.81 ±â€Š4.44 µm, respectively) had significantly decreased ASM thickness after 1 month (P < 0.001). Furthermore, the ASM thickness was significantly lower in the 1-month post-CBA group than in the 1-month post-BT group (P = 0.015). There was no significant difference in ASM thickness between the BT and CBA groups after six months (9.92 ±â€Š4.42 µm vs. 7.41 ±â€Š7.20 µm, P = 0.540). Compared with the control group (0.161 ±â€Š0.013), the average optical density of the ASM M3 receptor was significantly decreased in 6-month post-BT, 1-month post-CBA, and 6-month post-CBA groups (0.070 ±â€Š0.022, 0.072 ±â€Š0.012, 0.074 ±â€Š0.008, respectively; all P < 0.001). There was no significant difference in the average optical density of ASM M3 receptor between the BT and CBA therapy groups after six months (P = 0.613). CONCLUSIONS: CBA therapy effectively ablates the ASM, and its ablation effect is equivalent to that of BT with a shorter onset time. A neural mechanism is involved in both BT and CBA therapy.

Evaluation of the predictive value of red blood cell distribution width for onset of cerebral infarction in the patients with obstructive sleep apnea hypopnea syndrome.

Red blood cell distribution width (RDW) is a risk factor for the complications caused by obstructive sleep apnea hypopnea syndrome (OSAHS). This study was aimed to evaluate the predictive value of RDW for the occurrence of cerebral infarction in patients with OSAHS.We conducted a prospective study of 129 consecutive patients who were admitted to the Sleep Laboratory of in the Tenth People's Hospital of Shanghai (China) with complaints of snoring, apnea, or daytime sleepiness. All patients underwent polysomnography between June 2011 and May 2012. In total, 90 patients met the study criteria and were included in the study; there are 71 men and 19 women.RDW correlated positively with the apnea hypopnea index (AHI) (P = .00, r = 0.76). Logistic regression analysis showed correlations between each variation and cerebral infarction, high blood pressure (odds ratio [OR] = 4.72, P = .220), diabetes (OR = 2.67, P = .490), hyperlipidemia (OR = 7.42, P = .190), RDW (OR = 58.24, P = .020), and AHI (OR = 243.92, P = .001). RDW ≥ 15% showed a higher predictive value for the occurrence of cerebral infarction in patients with OSAHS (area under curve 0.837; sensitivity 0.919; specificity 0.755), with positive and negative predictive values of 0.697 and 0.938, respectively.RDW correlates positively with AHI. RDW values ≥15% are predictive for the occurrence of cerebral infarction in patients with OSAHS.

Mesenchymal stem cells suppress lung inflammation and airway remodeling in chronic asthma rat model via PI3K/Akt signaling pathway.

BACKGROUND: Mesenchymal stem cells (MSCs) came out to attract wide attention and had become one of the hotspots of most diseases' research in decades. But at present, the mechanisms of how MSCs work on chronic asthma remain undefined. Our study aims at verifying whether MSCs play a role in preventing inflammation and airway remodeling via PI3K/AKT signaling pathway in the chronic asthma rats model. METHODS: First, an ovalbumin (OVA)-induced asthma model was built. MSCs were administered to ovalbumin-induced asthma rats. The total cells in a bronchial alveolar lavage fluid (BALF) and inflammatory mediators in BALF and serum were measured. Histological examination of lung tissue was performed to estimate the pathological changes. Additionally, the expression of phosphorylated-Akt (p-Akt) in all groups was measured by western blot and immunohistochemistry (IHC). RESULTS: Compared to normal control group, the degree of airway inflammation and airway remodeling was significantly increased in asthma group. On the contrary, they were obviously inhibited in MSCs transplantation group. Moreover, the expression of p-Akt was increased in lung tissues of asthmatic rats, and suppressed by MSCs transplantation. CONCLUSION: Our results demonstrated that MSCs transplantation could suppress lung inflammation and airway remodeling via PI3K/Akt signaling pathway in rat asthma model.

Overexpression of adenylate cyclase-associated protein 1 may predict brain metastasis in non-small cell lung cancer.

This study was designed to establish a biomarker risk model for predicting brain metastasis (BM) in non-small cell lung cancer (NSCLC). The model comprises 120 cases of NSCLC that were treated and followed up for 4 years. The patients were divided into the BM (n=50) and non-BM (other visceral metastasis and those without recurrence) (n=70) groups. Immunohistochemical and western blot analyses were performed in metastatic tissues of NSCLC. Multivariate regression analysis was performed to correlate the immunoreactive cyclase-associated protein 1 (CAP1) signal with BM. Survival analyses were performed by using the Kaplan-Meier method. CAP1 protein content and immunoreactivity were significantly increased in BM specimens compared to other-metastatic specimens. The survival analysis revealed that CAP1 overexpression was significantly associated with survival (P<0.05). The ROC test suggested that the area under the curve was 73.33% (P<0.001; 95% CI, 63.5-83.2%). When P=0.466, the sensitivity and specificity reached 79.5 and 67.1%, respectively. These findings suggested that CAP1 is involved in the BM of NSCLC, and that elevated levels of CAP1 expression may indicate a poor prognosis for patients with BM. The CAP1 molecular model may be useful in the prediction of the risk of BM in NSCLC.

Relationship between expression of matrix metalloproteinase-9 and adenylyl cyclase-associated protein 1 in chronic obstructive pulmonary disease.

OBJECTIVE: To investigate the relationship between expression of matrix metalloproteinase (MMP)-9 and expression of adenylyl cyclase-associated protein (CAP)-1 in chronic obstructive pulmonary disease (COPD). METHODS: Patients with possible respiratory disease were recruited into the study and divided into a COPD group and a non-COPD group on diagnosis. Pulmonary function tests were performed and serum concentrations of MMP-9 were measured using an enzyme-linked immunosorbent assay. MMP-9 and CAP1 expression were analysed in lung tissue and bronchoalveolar lavage fluid in all available samples using immunohistochemistry and Western blot, respectively. In addition, expression of MMP-9 and CAP1 in vitro was investigated using immunofluorescence. Expression of CAP1 in response to MMP-9 was measured in the human alveolar epithelial cell line HP-AEpiC, using Western blot. RESULTS: A total of 90 patients were included in the study: 52 were in the COPD group and 38 in the non-COPD group. Serum MMP-9 concentrations were significantly higher in the COPD than in the non-COPD group. MMP-9 serum concentrations were negatively correlated with forced expiratory volume in 1 s (FEV1), FEV1 as a percentage of the normal predicted value and the ratio of FEV1 to forced vital capacity, and were positively correlated with residual volume (RV), total lung capacity (TLC) and RV/TLC values. In lung tissue and bronchoalveolar lavage fluid samples, MMP-9 and CAP1 expression were inversely related. This relationship was confirmed in HP-AEpiC cells. High expression of MMP-9 and low expression of CAP1 was demonstrated in the COPD group compared with the non-COPD group. CONCLUSIONS: This study demonstrated an inverse relationship between CAP1 and MMP-9 expression, and high expression of MMP-9 and low expression of CAP1 in those with COPD compared with the non-COPD group. Overexpression of MMP-9 in lung tissue and its interaction with CAP1 is likely to play a major role in airway obstruction in COPD.

Prophylactic cranial irradiation may impose a detrimental effect on overall survival of patients with nonsmall cell lung cancer: a systematic review and meta-analysis.

PURPOSE: To determine the role of brain metastases (BM) and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) by performing a meta-analysis of the RCTs (randomized controlled clinical trials) and non-RCTs (non-randomized controlled clinical trials) published in the literature. METHODS: A meta-analysis was performed using trials identified through PubMed, EMBASE and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included BM, OS, median survival (MS), response rate (RR), Hazard ratios (HRs) and odds ratios (ORs), and their 95% confidence intervals (CIs) were pooled using ReMan software. RESULTS: Twelve trials (6 RCTs and 6 non-RCTs) involving 1,718 NSCLC patients met the inclusion criteria. They were grouped on the basis of study design for separate Meta-analyses. The results showed that prophylactic cranial irradiation (PCI) reduced the risk of BM as compared with non-PCI in NSCLC patients (OR = 0.30, 95% [CI]: 0.21-0.43, p<0.00001). However, HRs for OS favored non-PCI (HR = 1.19, 95% [CI]: 1.06-1.33, p = 0.004), without evidence of heterogeneity between the studies. CONCLUSION: Our results suggest that although PCI decreased the risk of BM, it may impose a detrimental effect on OS of NSCLC patients.