Nanomedicine for acute respiratory distress syndrome: The latest application,targeting strategy,and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air–blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.     

类风湿关节炎患者肺泡灌洗液检测结果分析

目的通过对类风湿关节炎（RA）患者进行高分辨CT（HRCT）和肺泡灌洗液检测（BLAF）,探讨诊断类风湿肺间质病变的有效方法。方法选择RA患者31例,进行高分辨CT、肺泡灌洗液检测。结果 31例患者中,HRCT检测发现肺间质病变1例（阳性率为3.2%）,BLAF检测发现肺间质病变4例（阳性率为12.9%）;BLAF的肺间质病变阳性检出率高于HRCT,但差异无统计学意义（χ2=1.957 9,P〉0.05）。结论 BLAF是探询早期发现及明确类风湿性关节炎引发呼吸系统损害的更为有效的检查方法,比HRCT能更好地明确肺间质病变病变的病理类型,有助于治疗方案的制定。     

Femur chondrosarcoma misdiagnosed as acute knee arthritis and osteomyelitis—Further developing a hitherto unreported complication of tumor embolic ischemic ileal perforation after arthroscopic lavage

The differentiation between osteomyelitis and bone tumor may be difficult due to their overlapping clinical and radiological features. A 25-year-old lady presented with left knee pain and joint effusion associated with redness and hotness. A sub-optimally taken plain radiograph showed mixed osteolytic and osteoblastic lesion in the left lower femur with surrounding soft tissue swelling. Since the clinical diagnosis was acute osteomyelitis and arthritis, arthroscopic lavage was performed as a diagnostic and therapeutic procedure. The removed loose bodies and fibrinous tissue showed pathological features suspicious of chondrosarcoma. Subsequent MRI revealed an infiltrative tumor eroding through the cortex and joint cartilage. En bloc excision of the left lower femur, upper tibia including the knee joint and patella was performed, and the final diagnosis was grade 2 chondrosarcoma. The patient developed bilateral pulmonary metastasis 33 months after operation. Five months later, she suffered from a hitherto undescribed complication of ischemic perforation of the terminal ileum secondary to tumor embolic arterial obstruction with no macroscopic intestinal or peritoneal tumor deposit. The patient developed multiple brain metastases and died 43 months after initial presentation.Our case illustrates that malignant bone tumor as a differential diagnosis of acute osteomyelitis and arthritis merits recognition and exclusion before arthroscopic lavage, which may enhance tumor dissemination and in our patient results in embolic ischemic ileal perforation.     

毛大丁草抗卵清蛋白诱导的小鼠支气管哮喘作用的活性部位筛选

目的 通过卵清蛋白(ovalbumin，OVA)诱导的支气管哮喘小鼠模型，筛选毛大丁草抗哮喘的活性部位。方法 采用D101大孔吸附树脂法对毛大丁草50%乙醇提取物进行分段富集，依次洗脱得到水、60%乙醇、95%乙醇3个洗脱部位。小鼠通过腹腔注射OVA致敏、雾化吸入OVA激发来复制哮喘动物模型，在激发阶段连续6 d进行灌胃给药治疗。采用行为学评分考察不同部位对哮喘行为学的影响，利用酶联免疫吸附法测定血清、肺泡灌洗液(bronchoalveolar lavage fluid，BALF)中IL-5的浓度和血清免疫球蛋白IgE的浓度，采用HE染色对肺组织进行组织病理学评价。结果 模型组小鼠哮喘症状评分升高，血清中IgE和IL-5的水平显著升高，BALF中IL-5的水平显著升高；与模型组比较，60%乙醇段高剂量组小鼠哮喘症状明显改善，血清中IL-5的水平显著降低，BALF中IL-5的水平也显著降低。结合病理学切片观察，60%乙醇段治疗的小鼠较之模型组小鼠肺泡间隔增厚程度降低，血管周围和支气管周围炎症细胞浸润显著减少。结论 毛大丁草50%乙醇提取物的60%乙醇洗脱部位为其抗哮喘的活性部位，其化学成分主要是酚酸类、黄酮类和香豆素类。     

支气管肺泡灌洗在小儿肺部疾病中的应用进展

支气管肺泡灌洗是用液体直接灌注，将支气管、肺泡内的分泌物、积滞物通过稀释、吸引迅速排除，起到了类似外科清创、引流排毒的作用，并以此缓解气道阻塞、改善呼吸功能、控制感染。该项技术在肺部疾病的诊断和治疗应用方面已成为主要手段之一。由于该项技术较为安全且相对无损伤，在肺科领域得到了较为广泛的应用，并日益受到临床的高度重视。该文对支气管肺泡灌洗术在小儿肺部疾病方面的临床应用研究进展进行了综述。     

Lymphocyte subsets in bronchoalveolar lavage after exposure to Actinobacillus pleuropneumoniae in pigs previously immunized orally or by aerosol

Young pigs were immunized with the lung-pathogenic bacterium Actinobacillus (Haemophilus) pleuropneumoniae by aerosol or orally using viable and inactivated bacteria. The cellular changes in the bronchoalveolar lavage (BAL) were studied in repeated lavages after the pigs were infected with live bacteria. The nucleated cells in the BAL were differentiated and lymphocyte subsets determined. There were no major differences between the two routes of immunization or between viable and inactivated bacteria. The immunization induced an increase in all lymphocyte subsets studied and in the appearance of plasma cells and lymphoid blasts. The infection did not cause a further increase except in granulocytes. The lack of a booster-type increase in lymphocytes in the BAL might indicate a different immunologic reaction of the lung or that lymphocytes of the BAL do not represent lung lymphocytes in general. The protective effect of the immunization might be deduced from the increase in lymphocytes after immunization but not from the reaction pattern after infection. Offprint requests to: R. Pabst     

The effect of inhaled corticosteroids on bronchoalveolar lavage cells and IL-8 levels in stable COPD patients

Chronic obstructive pulmonary disease (COPD) is characterised by a chronic inflammatory process in the large and small airways, as well as in the lung parenchyma. Although the role of oral corticosteroids in the management of acute exacerbations of COPD is well documented, its role in stable COPD is not clear. We examined the anti-inflammatory effect of inhaled budesonide on the percentage of neutrophils and on interleukin-8 (IL-8) levels in bronchoalveolar lavage (BAL) and their correlation with spirometry and symptom scores. Twenty-six patients with stable COPD were randomised, in a double-blinded, placebo-controlled trial with either 800 microg of inhaled budesonide or placebo for a 6-month period. The budesonide-treated subjects had significant reductions in IL-8 levels in the BAL after therapy (mean+/-sem, 1.53+/-0.72 at baseline vs. 0.70+/-0.48 ng/ml at 6 months, P=0.004) and a reduction in the mean percentages of neutrophils (17.16+/-2.67% vs. 13.25+/-2.28% P=0.002). The improvement in sputum production was of borderline (P=0.058) significance but there was no improvement in lung function. In stable patients with COPD, treatment with inhaled budesonide for a period of 6 months has a positive effect on markers of lung inflammation, as assessed by reduction in percentage neutrophils and IL-8 concentration in BAL.     

支气管镜肺活检在肺泡蛋白沉积症中的诊断价值

目的：评价支气管镜肺活检(transbronchial lung biopsy,TBLB)在肺泡蛋白沉积症(pulmonary alveolar proteinosis,PAP)中的诊断价值和限度。方法：对2006年6月至2012年12月在中南大学湘雅二医院住院、资料完整的 TBLB病理确诊和非TBLB诊断的PAP 25例及TBLB病理误诊为PAP 4例进行回顾性分析。结果：25例PAP患者中,14例 一次TBLB病理确诊[一次TBLB阳性率为56%(14/25)],一次TBLB阴性病例中6例再次TBLB确诊[二次TBLB阳性率为 24%(6/25)],总阳性率为80%(20/25),总阴性率为20%(5/25)。其中,5例经典型CT表现及支气管肺泡灌洗液检查确 诊,并经全肺灌洗证实;而同期TBLB病理检查将其他疾病误诊为PAP者4例。结论：TBLB是很好的诊断方法,但一 次TBLB阴性不能排除PAP,条件允许可重复进行;临床和CT表现典型结合肺泡灌洗液检查阳性可作为临床诊断依 据;不典型的病例需进行TBLB。     

纤维支气管镜在新生儿重症监护室的应用分析

 目的  探讨纤维支气管镜在新生儿重症监护室(neonatal intensive care unit,NICU)中的应用指征和安全性。方法  回顾性分析2012年1月至2014年5月在上海市儿童医院NICU住院的35例患儿的纤维支气管镜检查结果及相关临床资料。结果  35例患儿中,31例存在不同程度的气道畸形。20例进行支气管肺泡灌洗液培养,其中14例与痰培养或气管插管尖端培养结果一致。23例患儿在纤维支气管镜检查前后进行影像学检查,16例提示肺部炎症改善。28例好转出院,2例死亡,5例放弃治疗出院。21例在纤维支气管镜检查前后查血气分析提示差异无统计学意义,31例检查后查血常规提示C-反应蛋白下降。结论  纤维支气管镜检对新生儿某些疾病具有诊断和治疗的双重价值,在NICU中应用相对安全。