甲醛致大鼠鼻腔癌与K-ras癌基因活化相关

为探讨甲醛致大鼠鼻腔癌的分子机制,对甲醛诱发的大鼠鼻腔癌细胞系FAT7中的转化序列进行检测.采用的实验方法,包括肿瘤细胞DNA与选择标志基因(neo)共转染、裸鼠成瘤性分析、Southern杂交、聚合酶链反应(PCR)和序列分析等.结果发现:在第二轮裸鼠肿瘤DNA中含有大鼠源性的K-ras基因序列,而无大鼠源性的H-ras、N-ras和p53基因序列.这表明甲醛诱发的大鼠鼻腔癌细胞系FAT7中所含的转化序列与H-ras、N-ras及p53基因无关,K-ras癌基因的活化可能参与甲醛致大鼠鼻腔癌.     

Bmp4 gene is expressed at the putative site of fusion in the midfacial region

The molecular mechanisms by which the primordia of the midface grow and fuse to form the primary palate portion of the craniofacial region are not well characterized. This is in spite of the fact that failure of growth and/or fusion of these primordia leads to the most common craniofacial birth defect in humans (i.e. clefts of the lip and/or palate). Bmp4 plays a critical role during early embryonic development and has previously been shown to play a role in epithelial-mesenchymal interactions in the craniofacial region of chicks. We analyze the expression of bmp4 in mouse as the midfacial processes undergo fusion to form the primary palate. We show that bmp4 is expressed in a very distinct manner in the three midfacial processes (lateral nasal, LNP, medial nasal, MNP, and maxillary processes, MxP) that ultimately fuse to form the midface. Prior to fusion of the midfacial processes, bmp4 is expressed in the ectoderm of the LNP, MNP, and MxP in a distinct spatial and temporal manner near and at the site of fusion of the midface. Bmp4 appears to demarcate the cells in the LNP and MNP that will eventually contact and fuse with each other. As fusion of the three prominences proceeds, some bmp4 expressing cells are trapped in the fusion line. Later, the expression of bmp4 switches to the mesenchyme of the midface underlying its initial expression in the ectoderm. The switch occurs soon after fusion of the three processes. The pattern of expression in the midfacial region implicates the important role of bmp4 in mediating the fusion process, possibly through apoptosis of cells in the putative site of fusion, during midfacial morphogenesis.     

Real-time monitoring of nasal mucosal pH during carbon dioxide stimulation: implications for stimulus dynamics

Carbon dioxide is a commonly employed irritant test compound in nasal chemesthetic studies because it is essentially free of olfactory stimulus properties. CO(2) is thought to act via hydration to H(2)CO(3) and dissociation to H(+) in nasal mucus, with resulting activation of acid sensors. However, transient changes in nasal mucosal pH have not been documented during CO(2) stimulation in humans. We placed a small pH probe on the floor of the right anterior nasal cavity during CO(2) stimulation in eight human subjects with historically high (>30%) and low (< or =20%) CO(2) detection thresholds. Three second pulses of CO(2) (15-45% v/v) paired with air in random order (12-15 s inter-stimulus interval; 60 s inter-trial interval) were administered by nasal cannula at 5 l/min. in an ascending series. For each subject, both a CO(2) detection threshold and suprathreshold psychophysical ratings [psi; labeled magnitude scale] were generated. All subjects showed phasic drops in pH associated with CO(2) stimulation (DeltapH). For all subjects combined, a positive correlation was apparent between applied [CO(2)] and both DeltapH and psi, as well as between DeltapH and psi themselves (P < 0.0001 for each comparison). Subjects with historically low CO(2) thresholds showed steeper dose-response curves for psi as a function of both applied [CO(2)] and DeltapH, but not for DeltapH as a function of applied [CO(2)]. For the six of eight subjects with measurable pH changes at threshold, DeltapH was positively related to log [CO(2) threshold] (P < 0.01). These data imply that variability in CO(2) detection thresholds and suprathreshold rating may derive from intrinsic differences in neural sensitivity, rather than differences in stimulus activation to hydrogen ion.     

Experimental and numerical determination of odorant solubility in nasal and olfactory mucosa

Odorant deposition in the nasal and olfactory mucosas is dependent on a number of factors including local air/odorant flow distribution patterns, odorant mucosal solubility and odorant diffusive transport in the mucosa. Although many of these factors are difficult to measure, mucosal solubility in the bullfrog mucus has been experimentally determined for a few odorants. In the present study an experimental procedure was combined with computational fluid dynamic (CFD) techniques to further describe some of the factors that govern odorant mucosal deposition. The fraction of odorant absorbed by the nasal mucosa (eta) was experimentally determined for a number of odorants by measuring the concentration drop between odorant 'blown' into one nostril and that exiting the contralateral nostril while the subject performed a velopharyngeal closure. Odorant concentrations were measured with a photoionization detector. Odorants were delivered to the nostrils at flow rates of 3.33 and 10 l/min. The velopharyngeal closure nasal air/odorant flows were then simulated using CFD techniques in a 3-D anatomically accurate human nose modeland the mucosal odorant uptake was numerically calculated. The comparison between the numerical simulations and the experimental results lead to an estimation of the human mucosal odorant solubility and the mucosal effective diffusive transport resistance. The results of the study suggest that the increase in diffusive resistance of the mucosal layer over that of a thin layer of water seemed to be general and non-odorant-specific; however, the mucosa solubility was odorant specific and usually followed the trend that odorants with lower water solubility were more soluble in the mucosa than would be predicted from water solubility alone. The ability of this approach to model odorant movement in the nasal cavity was evaluated by comparison of the model output with known values of odorant mucosa solubility.     

Polarized cultures of human airway epithelium from nasal scrapings and bronchial brushings

Airway epithelial cultures are generally derived from tracheas postmortem or from surgical specimens of nasal polyps or turbinates. Scrapings of the mucosal surface have been little used as starting material for cultures because of their low yield of epithelial cells and their contamination with mucous secretions, blood, and underlying connective tissue. For the first time, we report that human airway epithelial cells obtained from nasal scrapings or bronchial brushings can be grown in culture to produce polarized cell sheets suitable for studies of vectorial transport.     

嗜酸性粒细胞、调节性T细胞对慢性鼻窦炎伴鼻息肉的诊断及预后预测价值分析

摘要 目的：探讨嗜酸性粒细胞、调节性T细胞对慢性鼻窦炎伴鼻息肉的诊断及预后预测价值。方法：选取我院2020年3月到2023年3月收治的100例慢性鼻窦炎伴鼻息肉患者作为研究对象,将其分为慢性鼻窦炎伴鼻息肉组,选取同期来我院治疗的100例单纯慢性鼻窦炎患者作为慢性鼻窦炎组,另选取同期来我院体检的100名健康志愿者作为对照组。对比三组受检者嗜酸性粒细胞、调节性T细胞表达水平,并建立受试者工作特征（ROC）曲线,分析嗜酸性粒细胞、调节性T细胞对慢性鼻窦炎伴鼻息肉的诊断效能。随后对100例性鼻窦炎伴鼻息肉患者手术治疗后进行1年随访,依照患者的复发情况评价其预后情况,并分为两个亚组,将术后1年内复发的21例患者分为预后不良组,两未复发的79例患者分为预后良好组,对比两组患者一般临床情况,嗜酸性粒细胞、调节性T细胞表达水平,并分析嗜酸性粒细胞、调节性T细胞对慢性鼻窦炎伴鼻息肉的预后预测价值。结果：三组受检者嗜酸性粒细胞、调节性T细胞表达水平对比差异显著,慢性鼻窦炎伴鼻息肉组患者嗜酸性粒细胞（EOS）个数高于慢性鼻窦炎组和对照组,调节性T细胞（Tregs）水平低于慢性鼻窦炎组和对照组（P＜0.05）;通过绘制ROC曲线,确定EOS、Tregs其对慢性鼻窦炎伴鼻息肉的诊断效能,结果显示,EOS、Tregs两者联合对慢性鼻窦炎伴鼻息肉的诊断效能优于单一检测（P＜0.05）;预后良好组与预后不良组患者性别、年龄、BMI、吸烟史、饮酒史、白细胞介素-35（IL-35）、转化生长因子-β（TGF-β）、白细胞介素-1β（IL-1β）表达水平对比无明显差异（P＞0.05）,预后良好组与预后不良组患者病程、合并哮喘、合并变应性鼻炎、组织淋巴细胞占比、白细胞介素-10（IL-10）、肿瘤坏死因子-α（TNF-α）、EOS个数以及Tregs表达水平对比差异显著（P＜0.05）;logistic回归分析结果表明：合并哮喘、组织淋巴细胞占比、EOS个数以及Tregs为慢性鼻窦炎伴鼻息肉的预后独立影响因素（P＜0.05）。结论：嗜酸性粒细胞、调节性T细胞不仅对慢性鼻窦炎伴鼻息肉的临床诊断具有重要价值,而且能够预测慢性鼻窦炎伴鼻息肉患者的预后情况,因此临床上对于EOS个数增加,Tregs降低的患者要及时改善治疗措施,预防患者预后不良的发生。     

鼻内镜术前应用枸地氯雷他定对慢性鼻窦炎的治疗效果及对患者嗅觉功能和鼻黏膜形态的影响

摘要 目的：探讨鼻内镜术前应用枸地氯雷他定对慢性鼻窦炎的治疗效果及对患者嗅觉功能和鼻黏膜形态的影响。方法：选取我院2019年1月到2022年12月收治的80例慢性鼻窦炎患者作为研究对象,分为观察组与对照组,各40例。对照组患者采取单纯鼻内镜手术治疗,观察组患者在术前应用枸地氯雷他定治疗1个月后再行鼻内镜手术,对比两组患者的临床治疗效果,治疗前后炎症因子水平,内镜下鼻粘膜形态量化评分,嗅觉功能与糖精试验时间。结果：两组患者治疗总有效率对比无差异（P＞0.05）;治疗后两组患者IL-6、IL-1、TNF-α相关炎症因子水平均降低,且观察组较对照组低（P＜0.05）;治疗前两组患者鼻漏、结痂、瘢痕、黏膜水肿、息肉、脓性分泌物等情况内镜下鼻粘膜形态量化评分对比无明显差异（P＞0.05）,治疗后两组患者鼻漏、结痂、瘢痕、黏膜水肿、息肉、脓性分泌物等情况内镜下鼻粘膜形态量化评分均降低,且观察组较对照组低（P＜0.05）;治疗前两组患者嗅觉识别阈值、糖精试验时间对比无明显差异（P＞0.05）,治疗后两组患者嗅觉识别阈值、糖精试验时间均降低,且观察组低于对照组（P＜0.05）。结论：鼻内镜术前应用枸地氯雷他定对慢性鼻窦炎具有显著临床疗效,同时能够降低患者术后炎症因子水平,改善鼻黏膜形态,提升纤毛运动功能与嗅觉功能,值得临床应用推广。     

The role of olfaction throughout juvenile development: Functional adaptations in elasmobranchs

Seven elasmobranch species, a group known for their highly‐developed sense of smell, were examined for developmental changes in the number of olfactory lamellae, the size of the surface area of the sensory olfactory epithelium and the mass of both the olfactory rosettes (primary input to the CNS), and the olfactory bulbs. Within each species, juveniles possessed miniature versions of the adult olfactory organs, visually not distinguishable from these and without any obvious structural differences (e.g., with respect to the number of lamellae and the extent of secondary folding) between differently sized individuals. The size of the olfactory organs was positively correlated with body length and body mass, although few species showed proportional size scaling. In Aetobatus narinari and Aptychotrema rostrata, olfactory structures increased in proportion to body size. With respect to the growth of the olfactory bulb, all species showed allometric but not proportional growth. Olfaction may be of particular importance to juveniles in general, which are often subjected to heavy predation rates and fierce inter/intraspecific competition. Accordingly, it would be advantageous to possess a fully functional olfactory system early on in development. Slow growth rates of olfactory structures could then be attributed to a greater reliance on other sensory systems with increasing age or simply be regarded as maintaining an already optimized olfactory system. J. Morphol., 2010. © 2009 Wiley‐Liss, Inc.     

Nasal insulin gel as an alternate to parenteral insulin: Formulation,preclinical, and clinical studies

The objective of the present study was to formulate insulin gel for intranasal administration and to evaluate with respect to in vitro release studies and hypoglycemic activity in animal model and healthy human volunteers. The insulin gel was formulated using the combination of carbopol and hydroxypropyl methylcellulose as gelling agent. The in vivo efficacy of insulin gel administered intranasally was assessed by measuring the blood glucose levels and serum insulin levels at specified time intervals in rats and humans. The use of bioadhesive nasal gel containing insulin not only promoted the prolonged contact between the drug and the absorptive sites in the nasal cavity but also facilitated direct absorption of medicament through the nasal mucosa. Absorption of the drug through the nasal mucosa was high in the first 0.5 to 1.5 hours of the study with a sharp decline in blood sugar and rise in insulin values corresponding to that decline in blood sugar. This study further demonstrates that administration of insulin intranasally in gel form is a pleasant and painless alternative to injectable insulin. Published: September 30, 2005.