用于高分辨率成像的肺器官芯片构建及肺炎模型应用研究

肺是人体呼吸系统的重要组成部分,气道上皮是肺与外界接触的第一道屏障,参与抵御外来的颗粒物、病原体等,可将异物以痰的形式排出体外,对维护呼吸道正常功能起到至关重要的作用。 常用的体外细胞培养模型和哺乳动物模型尚不能完全模拟人体肺-气道微环境,在人体细胞与病原体相互作用研究和药物研发应用方面具有一定的局限性。该研究设计制作了一种基于微流控技术的双通道肺器官芯片,通过改进制备工艺使其能够满足高倍镜极短工作距离的要求,用于高分辨率成像;实现了模拟人体肺-气道微环境的气液界面气道上皮培养,并且能够实时观察细胞与细菌的共培养过程,为体外研究气道上皮和病原微生物的相互作用提供一个有力平台。     

Detection of COVID-19 and its pulmonary stage using Bayesian hyperparameter optimization and deep feature selection methods

Since the first case of COVID-19 was reported in December 2019, many studies have been carried out on artificial intelligence for the rapid diagnosis of the disease to support health services. Therefore, in this study, we present a powerful approach to detect COVID-19 and COVID-19 findings from computed tomography images using pre-trained models using two different datasets. COVID-19, influenza A (H1N1) pneumonia, bacterial pneumonia and healthy lung image classes were used in the first dataset. Consolidation, crazy-paving pattern, ground-glass opacity, ground-glass opacity and consolidation, ground-glass opacity and nodule classes were used in the second dataset. The study consists of four steps. In the first two steps, distinctive features were extracted from the final layers of the pre-trained ShuffleNet, GoogLeNet and MobileNetV2 models trained with the datasets. In the next steps, the most relevant features were selected from the models using the Sine–Cosine optimization algorithm. Then, the hyperparameters of the Support Vector Machines were optimized with the Bayesian optimization algorithm and used to reclassify the feature subset that achieved the highest accuracy in the third step. The overall accuracy obtained for the first and second datasets is 99.46% and 99.82%, respectively. Finally, the performance of the results visualized with Occlusion Sensitivity Maps was compared with Gradient-weighted class activation mapping. The approach proposed in this paper outperformed other methods in detecting COVID-19 from multiclass viral pneumonia. Moreover, detecting the stages of COVID-19 in the lungs was an innovative and successful approach.     

Non-Intensive Care Unit Acquired Pneumonia: A New Clinical Entity?

Hospital-acquired pneumonia (HAP) is a frequent cause of nosocomial infections, responsible for great morbidity and mortality worldwide. The majority of studies on HAP have been conducted in patients hospitalized in the intensive care unit (ICU), as mechanical ventilation represents a major risk factor for nosocomial pneumonia and specifically for ventilator-associated pneumonia. However, epidemiological data seem to be different between patients acquiring HAP in the ICU vs. general wards, suggesting the importance of identifying non ICU-acquired pneumonia (NIAP) as a clinical distinct entity in terms of both etiology and management. Early detection of NIAP, along with an individualized management, is needed to reduce antibiotic use and side effects, bacterial resistance and mortality. The present article reviews the pathophysiology, diagnosis, treatment and prevention of NIAP.     

Review of pulmonary toxicity of indium compounds to animals and humans

Due to the increased production of ITO, the potential health hazards arising from occupational exposure to this material have attracted much attention. This review consists of three parts: 1) toxic effects of indium compounds on animals, 2) toxic effects of indium compounds on humans, and 3) recommendations for preventing exposure to indium compounds in the workplace.Available data have indicated that insoluble form of indium compounds, such as ITO, indium arsenide (InAs) and indium phosphide (InP), can be toxic to animals. Furthermore, InP has demonstrated clear evidence of carcinogenic potential in long-term inhalation studies using experimental animals. As for the dangers to humans, some data are available concerning adverse health effects to workers who have been exposed to indium-containing particles. The Japan Society for Occupational Health recommended the value of 3 μg/L of indium in serum as the occupational exposure limit based on biological monitoring to preventing adverse health effects in workers resulting from occupational exposure to indium compounds. Accordingly, it is essential that much greater attention is focused on human exposure to indium compounds, and precautions against possible exposure to indium compounds are most important with regard to health management among indium-handling workers.     

红霉素对解脲支原体肺炎的疗效及对细胞亚群和肝功能的影响

目的: 探讨红霉素对解脲支原体肺炎的疗效及对细胞亚群、肝功能的影响。方法: 收集我院2016年5月至2017年5月收治的41例解脲支原体肺炎患儿作为试验组,静脉滴注10 mg/kg红霉素与适量5%葡萄糖注射液,每天2次,疗程7～10 d,同期选取41例健康体检儿童,比较健康组与试验组治疗前后细胞亚群及肝功能,并分析试验组疗效及安全性。结果: 治疗前,试验组CD4+、CD4+/CD8+分别为（41.95±5.71）%、1.26±0.18,低于健康组的（48.13±7.21）%、1.79±0.20,试验组CD8+为（35.10±4.41）%,高于健康组的（26.56±3.13）%,试验组谷丙转氨酶、乳酸脱氢酶、总胆汁酸、胆红素、总胆固醇、甘油三酯、谷草转氨酶、谷丙转氨酶/谷草转氨酶分别为（136.71±17.20）U/L、（439.67±54.45）U/L、（28.39±3.72）U/L、（68.05±8.95）μmol/L、（7.82±0.95）mmol/L、（1.70±0.24）mmol/L、（113.37±14.25）U/L、1.24±0.14,高于健康组的（45.26±4.88）U/L、（397.98±47.20）U/L、（22.24±2.66）U/L、（36.71±4.83）μmol/L、（4.26±0.46）mmol/L、（1.24±0.17）mmol/L、（62.51±9.19）U/L、0.77±0.12;治疗后,试验组CD4+、CD4+/CD8+显著上升,CD8+、谷丙转氨酶、乳酸脱氢酶、总胆汁酸、胆红素、总胆固醇、甘油三酯、谷草转氨酶、谷丙转氨酶/谷草转氨酶显著下降,且两组比较无统计学差异（P>0.05）。结论: 红霉素对解脲支原体肺炎的疗效肯定,能够利于细胞亚群及肝功能的缓解。     

重症肺炎支原体肺炎肺泡灌洗液中TNF-α、IL-6、IL-8、IL-10水平观察

目的检测重症肺炎支原体肺炎患者支气管肺泡灌洗液（bronchial tube pul monary alveolus syringe fluid,BALF）中肿瘤坏死因子-α（Tumor necrosis factor-α,TNF-α）、白细胞介素-6（Interleukin-6,IL-6）、白细胞介素-8（In-terleukin-8,IL-8）白细胞介素-10（Interleukin-10,IL-10）浓度,探讨其临床意义。方法收住ICU的重症肺炎支原体肺炎患者36例,其CPIS评分〉6分为CPIS高分组共15例,CPIS评分〈6分为CPIS低分组共21例;正常对照组24例。取支气管肺泡灌洗液检测TNF-α、IL-6、IL-8、IL-10水平。结果重症肺炎支原体肺炎无论CPIS高分组和CPIS低分组支气管肺泡灌洗液中TNF-α、IL-6、IL-8、IL-10水平明显高于对照组,差异有统计学意义（P〈0.01）,CPIS高分组TNF-α、IL-6、IL-8水平高于CPIS低分组,差异有统计学意义（P〈0.01）,CPIS高分组IL-10水平稍高于CPIS低分组,差异无统计学意义（P〉0.05）。2组治疗后恢复期TNF-α、IL-6、IL-8、IL-10水平均明显下降（P〈0.01）。结论 TNF-α、IL-6、IL-8、IL-10在重症肺炎的发生发展中起重要作用,是重症肺炎支原体肺炎诊断的重要因素之一。利用支气管肺泡灌洗液检测TNF-α、IL-6、IL-8、IL-10水平变化对临床诊断治疗及预后有一定的临床价值。     

特发性非特异性间质性肺炎的光镜和电镜观察

目的：观察特发性非特异性间质性肺炎(INSIP)的显微和超微结构特点以及与肺纤维化发生的关系。方法：对7例INSIP患者经电视胸腔镜(VATS)取肺病理活检组织进行光镜和透射电镜观察。结果：光镜观察肺间质呈不同程度的炎症和纤维化,浸润的细胞主要是淋巴细胞和浆细胞。电镜观察查见Ⅱ型肺泡上皮增生,基底膜增厚,肺泡中隔内纤维细胞增生和胶原纤维沉积,淋巴细胞、浆细胞和巨噬细胞浸润,肥大细胞脱颗粒;纤维化型有明显的平滑肌和肌纤维母细胞增生。结论：INSIP以成熟的纤维细胞增生为主,多种细胞成分参与了肺纤维化的发生过程。     

Mesenchymal Stem Cell-Based Therapy as an Alternative to the Treatment of Acute Respiratory Distress Syndrome: Current Evidence and Future Perspectives

Acute respiratory distress syndrome (ARDS) represents a current challenge for medicine due to its incidence, morbidity and mortality and, also, the absence of an optimal treatment. The COVID-19 outbreak only increased the urgent demand for an affordable, safe and effective treatment for this process. Early clinical trials suggest the therapeutic usefulness of mesenchymal stem cells (MSCs) in acute lung injury (ALI) and ARDS. MSC-based therapies show antimicrobial, anti-inflammatory, regenerative, angiogenic, antifibrotic, anti-oxidative stress and anti-apoptotic actions, which can thwart the physiopathological mechanisms engaged in ARDS. In addition, MSC secretome and their derived products, especially exosomes, may reproduce the therapeutic effects of MSC in lung injury. This last strategy of treatment could avoid several safety issues potentially associated with the transplantation of living and proliferative cell populations and may be formulated in different forms. However, the following diverse limitations must be addressed: (i) selection of the optimal MSC, bearing in mind both the heterogeneity among donors and across different histological origins, (ii) massive obtention of these biological products through genetic manipulations of the most appropriate MSC, (iii) bioreactors that allow their growth in 3D, (iv) ideal culture conditions and (v) adequate functional testing of these obtaining biological products before their clinical application.     

High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia

Numbers of patients with coronavirus disease 2019 (COVID-19) have increased rapidly worldwide. Plasma levels of full-length galectin-9 (FL-Gal9) and osteopontin (FL-OPN) as well as their truncated forms (Tr-Gal9, Ud-OPN, respectively), are representative inflammatory biomarkers. Here, we measured FL-Gal9, FL-OPN, Tr-Gal9, and Ud-OPN in 94 plasma samples obtained from 23 COVID-19-infected patients with mild clinical symptoms (CV), 25 COVID-19 patients associated with pneumonia (CP), and 14 patients with bacterial infection (ID). The four proteins were significantly elevated in the CP group when compared with healthy individuals. ROC analysis between the CV and CP groups showed that C-reactive protein had the highest ability to differentiate, followed by Tr-Gal9 and ferritin. Spearman’s correlation analysis showed that Tr-Gal9 and Ud-OPN but not FL-Gal9 and FL-OPN, had a significant association with laboratory markers for lung function, inflammation, coagulopathy, and kidney function in CP patients. CP patients treated with tocilizumab had reduced levels of FL-Gal9, Tr-Gal9, and Ud-OPN. It was suggested that OPN is cleaved by interleukin-6-dependent proteases. These findings suggest that the cleaved forms of OPN and galectin-9 can be used to monitor the severity of pathological inflammation and the therapeutic effects of tocilizumab in CP patients.