Upon encountering allergens, CD4+ T cells differentiate into IL-4-producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL-5 and IL-13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells. We found that an increase in reactive oxygen species (ROS) in immune cells infiltrating the lungs is necessary for the development of eosinophilic asthma and polyfunctional Th2 cells in vivo. Deletion of the ROS sensor NRF2 specifically in T cells, but not in dendritic cells, significantly abolished eosinophilia and polyfunctional Th2 cells in the airway. Mechanistically, NRF2 intrinsic to T cells is essential for inducing optimal oxidative phosphorylation and glycolysis capacity, thereby driving Th2 cell polyfunctionality independently of IL-33, partially by inducing PPARγ. Treatment with an NRF2 inhibitor leads to a substantial decrease in polyfunctional Th2 cells and subsequent eosinophilia in mice and a reduction in the production of Th2 cytokines from peripheral blood mononuclear cells in asthmatic patients. These findings highlight the critical role of Nrf2 as a spatial and temporal metabolic hub that is essential for polyfunctional Th2 cells, suggesting potential therapeutic implications for allergic diseases.

Goats are often affected by respiratory diseases and, despite ultrasonography can assess lung consolidations in several species, it is rarely used in these animals. So, this study evaluated the effectiveness of on-farm lung ultrasonography in detecting lung consolidations on 27 goats. The goats, scheduled for slaughter, underwent complete clinical examinations and lung ultrasonography. For the latter, both sides of the thorax were divided in four quadrants and examined using convex and linear probes before and after shaving the hair. Each quadrant was classified based on presence/absence of lung consolidation and maximum consolidation\'s depth (4-point scale: 0 healthy; 1 depth < 1 cm; 2 depth < 3 cm; 3 depth > 3 cm). The lungs were examined at necropsy, 66% of goats exhibited lung consolidations and sensitivity (83%-89%), specificity (100%), and κ coefficient values (0.67-0.72) were high with all techniques. An higher (p ≤ 0.01) percentage of class 1 lesions were found at necropsy compared to all the ultrasonographic techniques. All the ultrasonographic techniques effectively detected lung consolidation deeper than 1 cm. So, ultrasonography seems an effective tool for lung examination in goats with chronic pneumonia. The examination using the linear or the convex probes without shaving the hair could be a promising tool for the on-field diagnosis of pneumonia, although further research on larger sample sizes are necessary to validate these findings.

UNASSIGNED: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes.
UNASSIGNED: Clinical data and PRGs of COPD patients were sourced from the GEO database. The \"ConsensusClusterPlus\" package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT - PCR to detect the expression levels of eight genes in COPD patient and normal.
UNASSIGNED: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them.
UNASSIGNED: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.

There is a reciprocal relationship between extracellular matrix (ECM) remodelling and inflammation that could be operating in the progression of severe COVID-19. To explore the immune-driven ECM remodelling in COVID-19, we in this explorative study analysed these interactions in hospitalised COVID-19 patients. RNA sequencing and flow analysis were performed on peripheral blood mononuclear cells. Inflammatory mediators in plasma were measured by ELISA and MSD, and clinical information from hospitalised COVID-19 patients (N=15) at admission was included in the analysis. Further, we reanalysed two publicly available datasets: (1) lung tissue RNA-sequencing dataset (N=5) and (2) proteomics dataset from PBCM. ECM remodelling pathways were enriched in PBMC from COVID-19 patients compared to healthy controls. Patients treated at the intensive care unit (ICU) expressed distinct ECM remodelling gene profiles compared to patients in the hospital ward. Several markers were strongly correlated to immune cell subsets, and the dysregulation in the ICU patients was positively associated with plasma levels of inflammatory cytokines and negatively associated with B-cell activating factors. Finally, our analysis of publicly accessible datasets revealed (i) an augmented ECM remodelling signature in inflamed lung tissue compared to non-inflamed tissue and (ii) proteomics analysis of PBMC from severe COVID-19 patients demonstrated an up-regulation in an ECM remodelling pathway. Our results may suggest the presence of an interaction between ECM remodelling, inflammation, and immune cells, potentially initiating or perpetuating pulmonary pathology in severe COVID-19.

Quantitative analysis of the dynamic properties of thoraco-abdominal organs such as lungs during respiration could lead to more accurate surgical planning for disorders such as Thoracic Insufficiency Syndrome (TIS). This analysis can be done from semi-automatic delineations of the aforesaid organs in scans of the thoraco-abdominal body region. Dynamic magnetic resonance imaging (dMRI) is a practical and preferred imaging modality for this application, although automatic segmentation of the organs in these images is very challenging. In this paper, we describe an auto-segmentation system we built and evaluated based on dMRI acquisitions from 95 healthy subjects. For the three recognition approaches, the system achieves a best average location error (LE) of about 1 voxel for the lungs. The standard deviation (SD) of LE is about 1-2 voxels. For the delineation approach, the average Dice coefficient (DC) is about 0.95 for the lungs. The standard deviation of DC is about 0.01 to 0.02 for the lungs. The system seems to be able to cope with the challenges posed by low resolution, motion blur, inadequate contrast, and image intensity non-standardness quite well. We are in the process of testing its effectiveness on TIS patient dMRI data and on other thoraco-abdominal organs including liver, kidneys, and spleen.

暂无摘要。

BACKGROUND: Point-of-Care Ultrasound (POCUS) consists of a range of increasingly important imaging modalities across a variety of specialties. Despite a variety of accreditation pathways available in the UK, lung POCUS training remains difficult to deliver and accreditation rates remain suboptimal. We describe a multidisciplinary, multi-centre, and multi-pronged approach to lung POCUS education within a region.
METHODS: A survey was conducted in a region. From these results, bottlenecks were identified for improvement. We utilised key stages in an established accreditation pathway, and the Action Learning process. Analysing participant feedback, consensus amongst the team, regional educational needs, and leveraging the expertise within the faculty, we implemented several solutions which were multidisciplinary, multi-centre, and multi-pronged. We also set up a database across several accreditation pathways to facilitate supervision and assessment of rotational trainees.
RESULTS: Utilising the Action Learning process, we implemented several improvements at elements of the lung ultrasound accreditation pathways. An initial regional survey identified key barriers to accreditation: lack of courses (52%), lack of mentors (93%), and difficulty arranging directly supervised scans (73%). A multidisciplinary team of trainers was assembled. Regular courses were organised and altered based on feedback and anecdotal educational needs within the region. Courses were set up to also facilitate continuing professional development and exchange of knowledge and ideas amongst trainers. The barrier of supervision was removed through the organisation of regular supervision sessions, facilitating up to fifty scans per half day per trainer. We collected feedback from courses and optimised them. Remote mentoring platforms were utilised to encourage asynchronous supervision. A database of trainers was collated to facilitate triggered assessments. These approaches promoted a conducive environment and a commitment to learning. Repeat survey results support this.
CONCLUSIONS: Lung ultrasound accreditation remains a complex educational training pathway. Utilising an education framework, recruiting a multidisciplinary team, ensuring a multi-pronged approach, and fostering a commitment to learning can improve accreditation success.

Pulmonary toxicity is a serious side effect of some specific anticancer drugs. Bleomycin is a well-known anticancer drug that triggers severe reactions in the lungs. It is an approved drug that may be prescribed for the treatment of testicular cancers, Hodgkin\'s and non-Hodgkin\'s lymphomas, ovarian cancer, head and neck cancers, and cervical cancer. A large number of experimental studies and clinical findings show that bleomycin can concentrate in lung tissue, leading to massive oxidative stress, alveolar epithelial cell death, the proliferation of fibroblasts, and finally the infiltration of immune cells. Chronic release of pro-inflammatory and pro-fibrotic molecules by immune cells and fibroblasts leads to pneumonitis and fibrosis. Both fibrosis and pneumonitis are serious concerns for patients who receive bleomycin and may lead to death. Therefore, the management of lung toxicity following cancer therapy with bleomycin is a critical issue. This review explains the cellular and molecular mechanisms of pulmonary injury following treatment with bleomycin. Furthermore, we review therapeutic targets and possible promising strategies for ameliorating bleomycin-induced lung injury.

同种异体或自体造血干细胞移植是各种血液系统疾病的主要治疗手段，并显著提高了患者的生存率。但是同种异体造血干细胞移植后机体出现的移植物抗宿主病是降低患者生活质量和长期生存率的关键因素。移植物抗宿主病多表现为多器官受累，其中迟发性非感染性肺部并发症是造血干细胞移植后死亡的重要原因。在这些并发症中，闭塞性细支气管炎综合征是一种由进行性小气道疾病定义的独特临床实体，是最普遍和最具特征的晚期并发症，也是目前唯一被正式认定为肺部移植物抗宿主病的疾病实体。本文报道了1例急性白血病患者异体骨髓移植术后1年半出现移植物抗宿主病——闭塞性细支气管炎，后因重症肺炎致呼吸功能障碍行肺移植术。对患者全肺切除标本进行病理学检查，显微镜下观察见典型的闭塞性细支气管炎，此外见脏层胸膜广泛显著纤维化以及脏层胸膜下肺间质纤维化。本例受体肺病理学检查拓展了对造血干细胞移植后慢性移植物抗宿主病的肺部病理学特征的认识，为进一步临床诊疗提供可靠的病理学依据。.

Objective: To investigate and summarize pediatric patients with severe Mycoplasma pneumoniae pneumonia (MPP) presenting with varied clinical and chest imaging features in order to guide the individualized treatment. Methods: This was a retrospective cohort study. Medical records of clinical, imaging and laboratory data of 505 patients with MPP who were admitted to the Department Ⅱ of Respirology Center, Beijing Children\'s Hospital, Capital Medical University from January 2016 to October 2023 and met the enrollment criteria were included. They were divided into severe group and non-severe group according to whether lower airway obliterans was developed. The clinical and chest imaging features of the two groups were analyzed. Those severe cases with single lobe ≥2/3 consolidation (lobar consolidation) were further divided into subtype lung-necrosis and subtype non-lung-necrosis based on whether lung necrosis was developed. Comparison on the clinical manifestations, bronchoscopic findings, whole blood C-reactive protein (CRP) and other inflammatory indicators between the two subtypes was performed. Comparisons between two groups were achieved using independent-sample t-test, nonparametric test or chi-square test. Univariate receiver operating characteristic (ROC) curve analyses were performed on the indicators such as CRP of the two subtypes. Results: Of the 505 cases, 254 were male and 251 were female. The age of the onset was (8.2±2.9) years. There were 233 severe cases, among whom 206 were with lobar consolidation and 27 with diffuse bronchiolitis. The other 272 belonged to non-severe cases, with patchy, cloudy infiltrations or single lobe <2/3 uneven consolidation or localized bronchiolitis. Of the 206 cases (88.4%) severe cases with lobar consolidation, 88 harbored subtype lung-necrosis and 118 harbored subtype non-lung-necrosis. All 206 cases (100.0%) presented with persistent high fever, among whom 203 cases (98.5%) presented with inflammatory secretion obstruction and plastic bronchitis under bronchoscopy. Of those 88 cases with subtype lung-necrosis, there were 42 cases (47.7%) with dyspnea and 39 cases (44.3%) with moderate to massive amount of pleural effusion. There were 35 cases (39.8%) diagnosed with lung embolism during the disease course, of which other 34 cases (38.6%) were highly suspected. Extensive airway mucosal necrosis was observed in 46 cases (52.3%), and the level of their whole blood CRP was significantly higher than that of subtype non-lung-necrosis (131.5 (91.0, 180.0) vs. 25.5 (12.0, 43.1) mg/L, U=334.00, P<0.001). They were regarded as subtype \"lung consolidation-atelectasis-necrosis\". Of those 118 cases with subtype non-lung-necrosis, 27 cases (22.9%) presented with dyspnea and none were with moderate to massive amount of pleural effusion. Sixty-five cases (55.1%) presented with plastic bronchitis and localized airway mucosal necrosis was observed in 32 cases (27.1%). They were deemed as subtype \"lung consolidation-atelectasis\". ROC curve analyses revealed that whole blood CRP of 67.5 mg/L on the 6-10 th day of disease course exhibited a sensitivity of 0.96, a specificity of 0.89, and an area under the curve of 0.97 for distinguishing between these two subtypes among those with lobar consolidation. Conclusions: Pediatric patients with severe MPP present with lobar consolidation or diffuse bronchiolitis on chest imaging. Those with lobar consolidation harbor 2 subtypes as \"lung consolidation-atelectasis-necrosis\" and \"lung consolidation-atelectasis\". Whole blood CRP of 67.5 mg/L can be applied as an early discriminating indicator to discriminate between these two subtypes.
目的： 总结临床和影像学等不同表现的儿童重症肺炎支原体肺炎（MPP）的临床表型。 方法： 回顾性队列研究。纳入2016年1月至2023年10月在首都医科大学附属北京儿童医院呼吸中心临床部二病区住院的505例MPP患儿的临床、影像学和实验室数据等资料。根据是否遗留下气道闭塞分为重症和非重症组，分析组间的临床和影像学特征；根据重症组影像学表现为单个肺叶≥2/3的肺实变（大叶实变）的患儿是否发生肺组织坏死分为肺组织坏死亚型及肺组织未坏死亚型，比较两个亚型的临床表现、支气管镜下表现和全血C反应蛋白（CRP）等炎症指标。组间比较采用独立样本t检验、非参数检验或χ²检验。对两个亚型的CRP等炎症指标进行单因素受试者工作特征（ROC）曲线分析。 结果： 505例MPP患儿中，男254例、女251例，起病年龄（8.2±2.9）岁。重症组233例，其中影像学表现为大叶实变206例，弥漫性细支气管炎27例；非重症组272例，影像学表现均有斑片、云絮影或单个肺叶<2/3的不均匀实变或局限性细支气管炎。206例大叶实变患儿中，肺组织坏死亚型88例、肺组织未坏死亚型118例；持续高热206例（100.0%），支气管镜下存在炎性分泌物阻塞和塑形性支气管炎203例（98.5%）。88例肺组织坏死亚型中呼吸困难42例（47.7%），合并中-大量胸腔积液39例（44.3%），病程中明确合并肺栓塞35例（39.8%），另有34例（38.6%）高度可疑，支气管镜下可见气道较为广泛的黏膜坏死46例（52.3%）；肺组织坏死亚型的全血CRP水平高于肺组织未坏死亚型［131.5（91.0，180.0）比25.5（12.0，43.1）mg/L，U=334.00，P<0.001］，称为“肺实变-不张-坏死型”。118例肺组织未坏死亚型中呼吸困难27例（22.9%），中-大量胸腔积液0例，支气管镜下可见塑形性支气管炎65例（55.1%），可见气道黏膜少量坏死32例（27.1%），称为“肺实变-不张型”。ROC曲线分析示病程第6~10天的全血CRP 67.5 mg/L对于在大叶实变患儿中识别出“肺实变-不张-坏死型”的灵敏度0.96，特异度0.89，曲线下面积0.97。 结论： 儿童重型MPP的影像学表现为大叶实变或弥漫性细支气管炎，其中大叶实变可分为“肺实变-不张-坏死型”和“肺实变-不张型”两个亚型，病程第6~10天的全血CRP 67.5 mg/L可作为两个亚型的早期区分指标。.