Tissue-resident immune cells play a crucial role in chronic lung diseases, yet a comprehensive profile of these cells in human lungs is lacking. Here, we explore alterations of resident immune cells in idiopathic pulmonary fibrosis (IPF), a fatal lung disease characterized by tissue inflammation and progressive scarring. Utilizing ex-vivo human lung perfusion with single-cell RNA-sequencing, we successfully segregate the resident immune cells. By analyzing approximately 100,000 resident immune cells from seven patients with IPF and five healthy control lungs, we identify 13 distinct cell types. Previously unrecognized aberrant lymphocyte phenotypes are uncovered. Specifically, among T lymphocytes, we observe an enrichment of GZMK+ CD8+ T cells in IPF lungs, possessing a potential pro-fibrotic function. The fraction of pro-inflammatory HSPhi CD4+ conventional T cells increases in IPF lungs, while the quiescent subset decreases. Despite an increased presence of Tregs in IPF lungs, these cells show reduced expression of genes associated with immune suppression. Moreover, significant B cell expansion and activation occur, with continuous differentiation into IgG-producing plasma cells. Stromal niche interaction analysis shows that IPF fibroblasts, especially the CTHRC1hi subset, exert stronger effects on lymphocytes. These findings provide evidence of dysregulated immune cell populations in IPF, advancing our understanding of its immunopathology.

Tissue-resident immune cells are crucial in chronic lung diseases, yet a comprehensive profile in human lungs is lacking. Here, we defined alterations of resident immune cells in idiopathic pulmonary fibrosis (IPF), a fatal interstitial lung disease characterized by tissue inflammation and progressive scarring. Utilizing ex-vivo human lung perfusion coupled with single-cell RNA-sequencing, we successfully segregated the resident immune cells. Analyzing approximately 100,000 resident immune cells from 7 IPF and 5 control lungs, we identified 13 distinct cell types. Previously unrecognized aberrant lymphocyte phenotypes were uncovered. Specifically, among T lymphocytes, we observed an enrichment of GZMK + CD8 + T cells in IPF lungs, possessing a potential pro-fibrotic function. The fraction of pro-inflammatory HSP hi CD4 + T cells was increased in IPF lungs, while the quiescent subset decreased. Despite an increased presence of Tregs in IPF lungs, these cells showed reduced expression of genes associated with immune suppression. Moreover, significant B cell expansion and activation occurred, with continuous differentiation into IgG-producing plasma cells. Stromal niche interaction analysis showed that IPF fibroblasts, especially the CTHRC1 hi subset, exerted stronger effects on lymphocytes. These findings offer novel insights into dysregulated immune populations in IPF, advancing understanding of its immunopathology.

Pediatric lung transplant (pLTX) is a rare procedure globally; its characteristics and survival outcomes in China remain unknown. This retrospective study analyzed data from pLTX recipients aged ≤ 17 years between January 2019 and December 2023 from the China Lung Transplantation Registry. Pre-, intra-, and post-operative characteristics were described and compared between children aged 2–11 years and 12–17 years and between pLTX conducted in centers with high and low transplant volumes. The Kaplan‒Meier method was used to estimate the postoperative survival rates and 95

BackgroundFew studies have investigated the relationship between sarcopenia and the incidence of major adverse cardiovascular events (MACE), which are common complications in maintenance hemodialysis (MHD) patients. This study thus explored the association between sarcopenia and MACE in a prospective cohort with mediation analysis.MethodsAdult MHD patients in Jiangdu People’s Hospital in December 2019 were screened. The exposure was sarcopenia, as defined by the 2019 Asian Working Group. The primary endpoint was the occurrence of MACE, defined as the composite of all-cause mortality or hospital admission with a primary diagnosis of acute myocardial infarction, stroke, or heart failure during a 3-year follow-up period. Multivariate Cox regression analyses were used to test the association between sarcopenia and subsequent MACE incidence. Mediation analyses were used to investigate whether potential mediators influenced the association between sarcopenia and MACE.ResultsOf the 230 patients enrolled, 57% were male, with a median age of 57 years (interquartile range [IQR]: 50 to 66), and a median dialysis vintage of 67 months (IQR: 32 to 119). The prevalence of sarcopenia was 45.2%. The presence of sarcopenia was significantly correlated with age (Spearman’s r = 0.47, p < 0.001), C-reactive protein (Spearman’s r = 0.13, p = 0.044), serum albumin (Spearman’s r = −0.22, p < 0.001), 25(OH) vitamin D (Spearman’s r = −0.26, p < 0.001), and coronary artery calcification score (Spearman’s r = 0.20, p = 0.002). Over the 3-year follow-up period, MACE were observed in 59/104 (56.7%) patients with sarcopenia and 38/126 (30.2%) patients without sarcopenia (log-rank p < 0.001). After accounting for potential confounders, patients with sarcopenia presented a 66% (4–168%, p = 0.035) increase in their risk of MACE incidence as compared to non-sarcopenic individuals. However, adjusted mediation analyses did not detect any indication of a causal mediation pathway linking the effects of sarcopenic status on coronary artery calcification score, C-reactive protein, serum albumin, or 25(OH) vitamin D levels to MACE outcomes. Conversely, sarcopenia exhibited a potential direct effect (average direct effect range: −1.52 to −1.37, all p < 0.05) on MACE incidence.ConclusionThese results revealed that the presence of sarcopenia was associated with a higher incidence of MACE in MHD patients. The putative effects of sarcopenia on this cardiovascular endpoint are possibly not mediated by any causal pathways that include vascular calcification, inflammation, hypoalbuminemia, or vitamin D.

肺移植手术是治疗终末期肺病的唯一有效手段[1-3],自1990年起,全球已完成超过70000例[4].近年来,肺移植技术在我国快速发展,但同时也面临着许多阻碍.其中,供肺短缺是目前影响肺移植发展最主要的问题.据报道,目前我国的供肺利用率仅为 6％,远低于国际15％ ～ 20％的平均利用率,因此在临床实践中,综合评估并利用符合扩展标准的边缘供肺,以扩大供者池变得尤为重要.

To the Editor: The lung is the most frequent site of extrahepatic hepatocellu-lar carcinoma(HCC)recurrence after liver transplantation(LT).Pul-monary metastasis from hepatocellular carcinoma(PM-HCC)car-ries a poor prognosis as the patient could finally die of pulmonary failure secondary to the tumor despite maintaining ideal liver func-tion.

STIP1-homologous U-Box containing protein 1 (STUB1) is involved in the development of immune pathologies and the regulation of T cell. However, the potential role of STUB1 in the pathogenesis of rheumatoid arthritis (RA), especially in the regulation of T cells, remains elusive. Here we show that STUB1 promotes the imbalance of Th17/Treg cells through non-degradative ubiquitination of aryl hydrocarbon receptor (AHR). Using Western blot and flow cytometry analysis, we observe that the level of STUB1 was increased in RA patients compared with healthy controls. In particular, the expression of STUB1 protein was different in Th17 cells and Treg cells of RA patients. We also demonstrated that STUB1 facilitates Th17/Treg imbalance by up- or downregulating the expression of STUB1. In a subsequent series of in vitro experiments, we revealed that STUB1 promoted the imbalance of Th17 and Treg cells through non-degradative ubiquitination of AHR. Both knockdown of the AHR expression by siRNA and assays of CYP1A1 enzymatic activity by ethoxyresorufin-O-deethylase (EROD) supported this conclusion. Furthermore, we explored the ubiquitination sites of AHR responsible for STUB1-mediated ubiquitination and revealed that STUB1 promotes ubiquitination of AHR via K63 chains. Together, STUB1 may induce the imbalance of Th17/Treg cells via ubiquitination of AHR and serve as a potential therapeutic target for RA.

1 离体肺脏机械灌注技术简介 离体肺脏灌注技术(ex vivo lung perfusion, EVLP)是一种在体外模拟肺脏生理环境,通过机械泵提供肺循环血流动力,辅以保护性通气,达到体外保存和评估供肺的手段[1-2].现代EVLP的概念最早由Lund团队提出,并由多伦多Cypel团队等推广至临床应用.EVLP包含了灌注容器、泵管系统、血栓过滤器、氧合器、控温装置、呼吸机及配套管路等核心组件,采用以白蛋白右旋糖苷溶液为基础的无细胞灌注液.其原理是通过肺保护性通气氧合灌注液,经肺静脉流出至氧合器去氧后,微栓过滤,泵入肺动脉构成肺循环.在肺灌注的过程中可实时监测灌注液血气、顺应性等指标反应供肺质量,达到评估供肺的目的.也可进行多种途径的治疗,达到修复供肺的目的.不同于直接移植发生的快速再灌注过程,EVLP具有缓慢的程序性复温和复灌的特点.经EVLP评估合格的供肺将再次冷藏保存后用于临床移植.

Previous studies have suggested a correlation between uric acid (UA) and lung lesion in some diseases. However, it remains unknown whether UA contributes to the lung injury in rheumatoid arthritis (RA). Our study aimed to investigate the clinical value of the UA level in the severity of rheumatoid arthritis–associated interstitial lung disease (RA-ILD). We measured UA in serum and bronchoalveolar lavage fluid (BALF), and UA levels of subjects were compared. As for the role of UA on ILD, we incubated A549 cells with UA and the expression of EMT markers was measured by immunofluorescence staining. The concentrations and messenger RNA expression of IL-1, IL-6, and transforming growth factor-β (TGF-β) were measured by ELISA and RT-PCR, respectively. We observed that serum UA levels in RA were significantly higher than those in controls. And, higher UA was measured in both serum and BALF of patients with RA-ILD, particularly those with interstitial pneumonia (UIP) pattern. Additionally, the correlation of the serum and BALF UA levels with serum KL-6, a biomarker of ILDs, in RA was significant ( r = 0.44, p < 0.01; r = 0.43, p < 0.01). And, the negative correlations of UA, in both serum and BALF, with forced vital capacity ( r = −0.61, p < 0.01; r = −0.34, p < 0.01) and diffusing capacity for carbon monoxide ( r = −0.43, p < 0.01; r = −0.30, p < 0.01) were measured in patients. In the ROC curve analysis, the AUC value of UA for RA-ILD was 0.744 (95% CI: 0.69–0.80; p < 0.01), and the AUC of serum UA for predicting UIP pattern of patients with RA-ILD was 0.845 (95% CI: 0.78–0.91; p < 0.01), which showed the significance of the UA in clinical settings. Also, the in vitro experiment showed that UA induced epithelial-to-mesenchymal transition (EMT) and production of IL-1, IL-6, and TGF-β in A549 cells. Therefore, the elevated UA levels may be a diagnostic marker in RA-ILD, particularly RA-UIP.

Occupational pneumoconiosis is one of the main occupational diseases in China. Progressive massive fibrosis in pneumoconiosis should be distinguished from lung cancer for their similar imaging features which is often identified by (18)F-FDG PET-CT in clinic. Here we reported two cases of pneumoconiosis. Both of them were suspected of carrying malignant tumors by preoperative PET-CT exam, however, nodules in these two patients were all proved to be benign by intraoperative pathology which suggested that there is false-positive possibility in the distinguishment of pneumoconiosis nodules by (18)F-FDG PET-CT.

特发性肺纤维化(IPF)是一种进展性肺间质疾病,预后较差.近年来,随着对IPF的发病机制、诊断标准的深入探索,各种各样的治疗靶点被提出,但对于IPF的治疗效果均不佳,疾病最后仍会进展为终末期呼吸衰竭.目前肺移植是唯一能提高IPF患者预期寿命的干预措施.国内外已建立了非常完善的肺移植体系,确立了肺移植治疗IPF的受者、供肺相关标准,对于术前、术后各种可能发生的情况也越来越了解.但由于合适供肺的缺少、肺移植费用高昂以及手术疗效的不确定性等因素,许多患者错过了肺移植的最佳时机.因此,普及肺移植的相关知识、鼓励器官捐献以及提高手术技巧和围手术期管理将是未来工作的重点.

在2020年至2021年新型冠状病毒肺炎(新冠肺炎)疫情流行期间,全球肺移植进入新发展阶段.全球范围内,上报国际心肺移植学会(ISHLT)的肺移植数据已经超过70000例.肺移植供者和受者特征、儿童肺移植受者的适应证随着时间和医疗技术的发展,发生了巨大的变化.肺移植在新冠肺炎相关急性呼吸窘迫综合征(ARDS)患者中的治疗也受到全球瞩目.肺移植外科技术不断发展,也将与更多的新技术融合,在人工肺脏和异种移植领域获得新的突破.本文总结了全球肺移植供、受者特征研究的最新进展,并进一步展望未来发展的趋势,以期终末期肺病患者能够从肺移植技术发展中得到更多获益.

背景 类风湿关节炎(RA)常伴有血尿酸代谢异常,间质性肺病(ILD)是RA的常见关节外表现.目前国内外有关血尿酸水平与RA相关ILD(RA-ILD)关系的研究报道很少.目的 分析血尿酸与RA-ILD的关系.方法 回顾性选取2018年1月至2021年1月在南京医科大学第二附属医院住院的RA患者234例,根据是否并发ILD将其分为RA-ILD组57例和无RA-ILD组177例.采用倾向性评分匹配方法,通过1:1最邻近匹配,最终匹配到57个对子.比较匹配后两组患者一般资料、实验室检查指标;RA患者并发ILD的影响因素分析采用多因素Logistic回归分析,绘制受试者工作特征(ROC)曲线以评估血尿酸对RA患者并发ILD的预测价值.匹配后RA患者血尿酸与一般资料及实验室检查指标的相关性分析采用Pearson相关分析或Spearman秩相关分析.结果 匹配后,RA-ILD组患者高尿酸血症发生率、血尿酸、类风湿因子(RF)、抗环瓜氨酸多肽(CCP)抗体滴度、抗CCP抗体阳性率、肌酐及胱抑素C高于无RA-ILD组(P<0.05).多因素Logistic回归分析结果显示,高尿酸血症〔OR=2.883,95％CI(1.069,7.774)〕和RF〔OR=2.471,95％CI(1.088,5.613)〕是RA患者并发ILD的影响因素(P<0.05).ROC曲线分析结果显示,血尿酸预测RA患者并发ILD的曲线下面积为0.728〔95％CI(0.652,0.804)〕,最佳截断值为330μmol/L,灵敏度为45.6％、特异度为91.5％.相关性分析结果显示,匹配后RA患者血尿酸与年龄、ILD、RF、尿素、肌酐和胱抑素C呈正相关,与血清镁、血红蛋白呈负相关(P<0.05).结论 高尿酸血症是RA-ILD的危险因素,血尿酸对RA-ILD具有一定预测价值;RF、抗CCP抗体与血尿酸可能共同参与RA-ILD的发生.