Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases.

As the locus for air exchange, lung tissue is perpetually exposed to a significant quantity of foreign pathogens. Consequently, lung has developed a refined and intricate immune system. Beyond their physical and chemical barrier roles, lung epithelial cells can contribute to immune defence through the expression of Toll-like receptors (TLRs) and other pattern recognition receptors, along with the secretion of cytokines. Emerging evidence demonstrates that lung epithelial cells can generate and secrete immunoglobulins (Igs), including IgM, IgA, or IgG, thus performing antibody function. Moreover, malignantly transformed lung epithelial cells have been discovered to produce high levels of Ig, predominantly IgG, which do not fulfill the role of antibodies, but instead carries out tumour-promoting activity. Structural analysis has indicated that the biological activity of IgG produced by lung cancer cells differs from that of Igs produced by normal lung epithelial cells due to the unique glycosylation modification. Specifically, the sialylated IgG (SIA-IgG), characterised by a non-traditional N-glycosylation modification at the Asn162 site of Igγ CH1, is highly expressed in tumour stem cells. It has been demonstrated that SIA-IgG relies on this unique sialylation modification to promote tumorigenesis, metastasis, and immune evasion. Current results have proven that the Ig produced by lung epithelial cells has multifaceted biological activities, including immune defence functions under physiological conditions, while acquiring tumour-promoting activity during malignant transformation. These insights possess potential for the diagnosis and treatment of lung cancer as novel biomarkers and targets.

BACKGROUND: The canine influenza virus (CIV) outbreak has garnered considerable attention as it poses a significant threat to dog health. During the H3N2 CIV evolution in beagles, the virus formed a new clade after 2019 and gradually became more adaptable to other mammals. Therefore, successfully elucidating the biological characteristics and constructing a canine influenza infection model is required for CIV characterization.
METHODS: We performed genetic analyses to examine the biological characteristics and infection dynamics of CIV.
RESULTS: The genotype of our H3N2 CIV strain (from 2019 in Shanghai) belonged to the 5.1 clade, which is now prevalent in China. Using MDCK cells, we investigated viral cytopathic effects. Virus size and morphology were observed using transmission electron microscopy. Beagles were also infected with 104, 105, and 106 50% egg-infectious doses (EID50). When compared with the other groups, the 106 EID50 group showed the most obvious clinical symptoms, the highest virus titers, and typical lung pathological changes. Our results suggested that the other two treatments caused mild clinical manifestations and pathological changes. Subsequently, CIV distribution in the 106 EID50 group was detected by hematoxylin and eosin (H&E) and immunofluorescence (IF) staining, which indicated that CIV primarily infected the lungs.
CONCLUSIONS: The framework established in this study will guide further CIV prevention strategies.

OBJECTIVE: To explore the correlation between asthma risk and genetic variants affecting the expression or function of lipid-lowering drug targets.
METHODS: We conducted Mendelian randomization (MR) analyses using variants in several genes associated with lipid-lowering medication targets: HMGCR (statin target), PCSK9 (alirocumab target), NPC1L1 (ezetimibe target), APOB (mipomersen target), ANGPTL3 (evinacumab target), PPARA (fenofibrate target), and APOC3 (volanesorsen target), as well as LDLR and LPL. Our objective was to investigate the relationship between lipid-lowering drugs and asthma through MR. Finally, we assessed the efficacy and stability of the MR analysis using the MR Egger and inverse variance weighted (IVW) methods.
RESULTS: The elevated triglyceride (TG) levels associated with the APOC3, and LPL targets were found to increase asthma risk. Conversely, higher LDL-C levels driven by LDLR were found to decrease asthma risk. Additionally, LDL-C levels (driven by APOB, NPC1L1 and HMGCR targets) and TG levels (driven by the LPL target) were associated with improved lung function (FEV1/FVC). LDL-C levels driven by PCSK9 were associated with decreased lung function (FEV1/FVC).
CONCLUSIONS: In conclusion, our findings suggest a likely causal relationship between asthma and lipid-lowering drugs. Moreover, there is compelling evidence indicating that lipid-lowering therapies could play a crucial role in the future management of asthma.

BACKGROUND: Primary pulmonary myxoid sarcoma (PPMS) is a rare, low-grade malignant tumor, constituting approximately 0.2% of all lung tumors. Despite its rarity, PPMS possesses distinctive histological features and molecular alterations, notably the presence of EWSR1-CREB1 gene fusion. However, its precise tissue origin remains elusive, posing challenges in clinical diagnosis.
UNASSIGNED: A 20-year-old male patient underwent a routine physical examination 6 months prior, revealing a pulmonary mass. Following surgical excision, microscopic evaluation unveiled predominantly short spindle-shaped tumor cells organized in a fascicular, beam-like, or reticular pattern. The stromal matrix exhibited abundant mucin, accompanied by lymphocytic and plasma cell infiltration, with Russell bodies evident in focal areas. Immunophenotypic profiling revealed positive expression of vimentin and epithelial membrane antigen in tumor cells, whereas smooth muscle actin and S-100, among others, were negative. Ki-67 proliferation index was approximately 5%. Subsequent second-generation sequencing identified the characteristic EWSR1-CREB1 gene fusion. The definitive pathological diagnosis established PPMS. The patient underwent no adjuvant chemotherapy or radiotherapy and remained recurrence-free during a 30-month follow-up period.
CONCLUSIONS: We report a rare case of PPMS located within the left lung lobe interlobar fissure, featuring Russell body formation within the tumor stroma, a novel finding in PPMS. Furthermore, the histomorphological characteristics of this case highlight the diagnostic challenge it poses, as it may mimic inflammatory myofibroblastic tumor, extraskeletal myxoid chondrosarcoma, or hemangiopericytoma-like fibrous histiocytoma. Therefore, accurate diagnosis necessitates an integrated approach involving morphological, immunohistochemical, and molecular analyses.

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.

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.

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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。.