Inhibition of the Hedgehog Signaling Pathway Depresses the Cigarette Smoke-Induced Malignant Transformation of 16HBE Cells on a Microfluidic Chip / 中华医学杂志(英文版)

<p><b>Background</b>The hedgehog signaling system (HHS) plays an important role in the regulation of cell proliferation and differentiation during the embryonic phases. However, little is known about the involvement of HHS in the malignant transformation of cells. This study aimed to detect the role of HHS in the malignant transformation of human bronchial epithelial (16HBE) cells.</p><p><b>Methods</b>In this study, two microfluidic chips were designed to investigate cigarette smoke extract (CSE)-induced malignant transformation of cells. Chip A contained a concentration gradient generator, while chip B had four cell chambers with a central channel. The 16HBE cells cultured in chip A were used to determine the optimal concentration of CSE for inducing malignant transformation. The 16HBE cells in chip B were cultured with 12.25% CSE (Group A), 12.25% CSE + 5 μmol/L cyclopamine (Group B), or normal complete medium as control for 8 months (Group C), to establish the in vitro lung inflammatory-cancer transformation model. The transformed cells were inoculated into 20 nude mice as cells alone (Group 1) or cells with cyclopamine (Group 2) for tumorigenesis testing. Expression of HHS proteins was detected by Western blot. Data were expressed as mean ± standard deviation. The t-test was used for paired samples, and the difference among groups was analyzed using a one-way analysis of variance.</p><p><b>Results</b>The optimal concentration of CSE was 12.25%. Expression of HHS proteins increased during the process of malignant transformation (Group B vs. Group A, F = 7.65, P < 0.05). After CSE exposure for 8 months, there were significant changes in cellular morphology, which allowed the transformed cells to grow into tumors in 40 days after being inoculated into nude mice. Cyclopamine could effectively depress the expression of HHS proteins (Group C vs. Group B, F = 6.47, P < 0.05) and prevent tumor growth in nude mice (Group 2 vs. Group 1, t = 31.59, P < 0.01).</p><p><b>Conclusions</b>The activity of HHS is upregulated during the CSE-induced malignant transformation of 16HBE cells. Cyclopamine can effectively depress expression of HHS proteins in vitro and prevent tumor growth of the transformed cells in vivo.</p>

Research on the relationship between obstructive sleep apnea hypopnea syndrome and gastroesophageal reflux / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the relationship between obstructive sleep apnea and nocturnal gastroesophageal reflux (GER).</p><p><b>METHODS</b>Seventy-six patients with obstructive sleep apnea hypopnea syndrome (OSAHS) underwent polysomnography (PSG) and nocturnal distal esophageal pH monitoring, to assess the prevalence of GER in OSAHS patients. Among these patients, thirty-two OSAHS patients with GER disease had been operated on. Surgical treatment included uvulopalatopharyngoplasty (UPPP), inferior turbinate reduction, nasal septoplasty et al. After 6 months of surgical treatment, the PSG and pH probe testing were rechecked. The pre and post operative apnea-hypopnea index (AHI), micro-arousal index (MAI), lowest artery oxygen saturation (LSaO2), acidified index of distal esophagus (pHI) and percentage of acid contact time of esophagus were compared. The correlation analysis was also employed.</p><p><b>RESULTS</b>The AHI of 76 OSAHS patients was (38.6 +/- 29.5)/h (average +/- s), GER was present in 48 patients (63.2 %). The pre and post operative AHI, MAI, LSaO2, pHI and percentage of ACT in 32 OSAHS patients associated with GER were (51.2 +/- 23.1)/h and (17.3 +/- 10.3)/h, (38.3 +/- 21.4 )/h and (14.5 +/- 10.0)/h, 0.698 +/- 0.107 and 0.858 +/- 0.076, (12.5 +/- 6.6)/h and (6.3 +/- 4.2)/h, (10.3 +/- 5.2)% and (4.5 +/- 2.9)%. The differences were statistically significant by matching t test (t were 10.95, 7.82, 15.97, 6.12, 7.62 respectively, P < 0.001). There were positive relationships between the reductions of AHI, MAI and the reductions of pHI (r were 0.775, 0.764, P < 0.001). The improved levels of AHI and MAI were correlated with the reduction of the percentage of ACT (r were 0.607, 0.730, P < 0.001).</p><p><b>CONCLUSIONS</b>GER is prevalent in OSAHS patients. Surgical treatment of OSAHS has significant reduction in AHI, MAI as well as marked improvement in the GER, which suggests that nocturnal gastroesophageal reflux is correlated with the disorder of sleep respiration and the sleep disturbances.</p>