先天性肺气道畸形 Wnt7B 和 BMP4 表达模式分析
- 作者列表："Zhu H","Liu D","Jia H
BACKGROUND:Congenital pulmonary airway malformation (CPAM) is a rare disorder characterized by aberrant overgrowth of terminal bronchioles. The objective of this study was to describe wingless-type MMTV integration site family 7B (Wnt7B) and bone morphogenetic protein 4 (BMP4) expression patterns in human CPAM lesions and to explore the possible roles of Wnt7B and BMP4 in the pathogenesis of CPAM. METHODS:Fifteen tissue samples from patients with CPAM were obtained from the Pathology Department of Shengjing Hospital of China Medical University. Samples representing CPAM lesions and adjacent normal lung tissues were collected and Wnt7B and BMP4 expression was detected through immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. RESULTS:IHC revealed that Wnt7B immunopositive cells were only detected in epithelial cells, whereas BMP4 immunopositive cells were detected in epithelial and mesenchymal cells. Expression of Wnt7B and BMP4 immunopositive cells was higher in CPAM lesions than that in adjacent normal lung tissue. qRT-PCR and Western blotting showed that Wnt7B and BMP4 mRNA and protein expression were significantly higher in CPAM lesions than in adjacent normal lung tissue (P ＜ 0.05). Overall, the level of BMP4 was higher than that of Wnt7B. Conclusions: Increased expression of Wnt7B and BMP4 appear to be related to the pathogenesis of CPAM and abnormal pulmonary development. Upregulation of Wnt7B and BMP4 could play an important role in the development of the bronchial‐alveolar structures that characterize CPAM.
背景: 先天性肺气道畸形 (CPAM) 是一种以终末细支气管异常过度生长为特征的罕见疾病。本研究的目的是描述无翅型 MMTV 整合位点 7B (Wnt7B) 和骨形态发生蛋白 4 (BMP4) 人 CPAM 病变中的表达模式，并探讨 Wnt7B 和 BMP4 在 CPAM 发病机制中的可能作用。 方法: 15 例 CPAM 患者的组织标本来自中国医科大学附属盛京医院病理科。收集代表 CPAM 病变和癌旁正常肺组织的标本，通过免疫组织化学 (IHC) 染色、实时定量聚合酶链反应 (qRT-PCR) 检测 Wnt7B 和 BMP4 的表达,和 Western blotting。 结果: IHC 显示 Wnt7B 免疫阳性细胞仅在上皮细胞中检测到，而 BMP4 免疫阳性细胞在上皮细胞和间充质细胞中检测到。CPAM 病变中 Wnt7B 和 BMP4 免疫阳性细胞表达高于癌旁正常肺组织。QRT-PCR 和 Western blotting 检测显示，CPAM 病变组 Wnt7B 和 BMP4 mRNA 和蛋白表达明显高于癌旁正常肺组织 (p <0.05)。总体而言，BMP4 水平高于 Wnt7B。 结论: Wnt7B 和 BMP4 表达增高与 CPAM 的发病及肺发育异常有关。Wnt7B 和 BMP4 的上调可能在描述 CPAM 的支气管-肺泡结构的发展中发挥重要作用。
METHODS:Background Dye localization is a useful method for the resection of unidentifiable small pulmonary lesions. This study compares the transbronchial route with augmented fluoroscopic bronchoscopy (AFB) and conventional transthoracic CT-guided methods for preoperative dye localization in thoracoscopic surgery. Methods Between April 2015 and March 2019, a total of 231 patients with small pulmonary lesions who received preoperative dye localization via AFB or percutaneous CT-guided technique were enrolled in the study. A propensity-matched analysis, incorporating preoperative variables, was used to compare localization and surgical outcomes between the two groups. Results After matching, a total of 90 patients in the AFB group ( N = 30) and CT-guided group ( N = 60) were selected for analysis. No significant difference was noted in the demographic data between both the groups. Dye localization was successfully performed in 29 patients (96.7%) and 57 patients (95%) with AFB and CT-guided method, respectively. The localization duration (24.1 ± 8.3 vs. 21.4 ± 12.5 min, p = 0.297) and equivalent dose of radiation exposure (3.1 ± 1.5 vs. 2.5 ± 2.0 mSv, p = 0.130) were comparable in both the groups. No major procedure-related complications occurred in either group; however, a higher rate of pneumothorax (0 vs. 16.7%, p = 0.029) and focal intrapulmonary hemorrhage (3.3 vs. 26.7%, p = 0.008) was noted in the CT-guided group. Conclusion AFB dye marking is an effective alternative for the preoperative localization of small pulmonary lesions, with a lower risk of procedure-related complications than the conventional CT-guided method.
METHODS:Background The use of artificial intelligence, including machine learning, is increasing in medicine. Use of machine learning is rising in the prediction of patient outcomes. Machine learning may also be able to enhance and augment anesthesia clinical procedures such as airway management. In this study, we sought to develop a machine learning algorithm that could classify vocal cords and tracheal airway anatomy real-time during video laryngoscopy or bronchoscopy as well as compare the performance of three novel convolutional networks for detecting vocal cords and tracheal rings. Methods Following institutional approval, a clinical dataset of 775 video laryngoscopy and bronchoscopy videos was used. The dataset was divided into two categories for use for training and testing. We used three convolutional neural networks (CNNs): ResNet, Inception and MobileNet. Backpropagation and a mean squared error loss function were used to assess accuracy as well as minimize bias and variance. Following training, we assessed transferability using the generalization error of the CNN, sensitivity and specificity, average confidence error, outliers, overall confidence percentage, and frames per second for live video feeds. After the training was complete, 22 models using 0 to 25,000 steps were generated and compared. Results The overall confidence of classification for the vocal cords and tracheal rings for ResNet, Inception and MobileNet CNNs were as follows: 0.84, 0.78, and 0.64 for vocal cords, respectively, and 0.69, 0.72, 0.54 for tracheal rings, respectively. Transfer learning following additional training resulted in improved accuracy of ResNet and Inception for identifying the vocal cords (with a confidence of 0.96 and 0.93 respectively). The two best performing CNNs, ResNet and Inception, achieved a specificity of 0.985 and 0.971, respectively, and a sensitivity of 0.865 and 0.892, respectively. Inception was able to process the live video feeds at 10 FPS while ResNet processed at 5 FPS. Both were able to pass a feasibility test of identifying vocal cords and tracheal rings in a video feed. Conclusions We report the development and evaluation of a CNN that can identify and classify airway anatomy in real time. This neural network demonstrates high performance. The availability of artificial intelligence may improve airway management and bronchoscopy by helping to identify key anatomy real time. Thus, potentially improving performance and outcomes during these procedures. Further, this technology may theoretically be extended to the settings of airway pathology or airway management in the hands of experienced providers. The researchers in this study are exploring the performance of this neural network in clinical trials.
METHODS:BACKGROUND:The optimal mode of delivering topical anesthesia during flexible bronchoscopy remains unknown. This article compares the efficacy and safety of nebulized lignocaine, lignocaine oropharyngeal spray, or their combination. METHODS:Consecutive subjects were randomized 1:1:1 to receive nebulized lignocaine (2.5 mL of 4% solution, group A), oropharyngeal spray (10 actuations of 10% lignocaine, group B), or nebulization (2.5 mL, 4% lignocaine) and two actuations of 10% lignocaine spray (group C). The primary outcome was the subject-rated severity of cough according to a visual analog scale. The secondary outcomes included bronchoscopist-rated severity of cough and overall procedural satisfaction on a visual analog scale, total lignocaine dose, subject's willingness to undergo a repeat procedure, adverse reactions to lignocaine, and others. RESULTS:A total of 1,050 subjects (median age, 51 years; 64.8% men) were included. The median (interquartile range) score for subject-rated cough severity was significantly lower in group B compared to group C or group A (4 [1-10] vs 11 [4-24] vs 13 [5-30], respectively; P < .001). The bronchoscopist-rated severity of cough was also the least (P < .001), and the overall satisfaction was highest in group B (P < .001). The cumulative lignocaine dose administered was the least in group B (P < .001). A significantly higher proportion of subjects (P < .001) were willing to undergo a repeat bronchoscopy in group B (73.7%) than in groups A (49.1%) and C (59.4%). No lignocaine-related adverse events were observed. CONCLUSIONS:Ten actuations of 10% lignocaine oropharyngeal spray were superior to nebulized lignocaine or their combination for topical anesthesia during diagnostic flexible bronchoscopy. TRIAL REGISTRY:ClinicalTrials.gov; No.: NCT03109392; URL: www.clinicaltrials.gov.