Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapies and poorly defined cross-tissue immune mechanisms. We performed single-cell RNA sequencing and TCR profiling of paired lung, lymph node, and peripheral blood samples from patients with IPF, combined with functional coculture assays and mouse model. We identified GZMK-high CD8⁺ T cells enriched in fibrotic lungs, displaying inflammatory but low-cytotoxic features. TCR and trajectory analyses indicated that these cells originate from lymph-node CD8_HSPA1A cells and migrate to the lung. Higher GZMK⁺CD8⁺ T-cell levels correlated with impaired lung function and worse outcomes. Mechanistically, GZMK-overexpressing CD8⁺ T cells promoted fibroblast-to-myofibroblast differentiation and proliferation through TGF-β1 signalling, while GZMK inhibition reduced fibroblast activation and collagen deposition. Pharmacological blockade of TGFβR1/ALK4 with TEW suppressed fibroblast activation in vitro and significantly attenuated pulmonary fibrosis in vivo. Together, these findings identify a lymph node-to-lung migration axis of GZMK⁺CD8⁺ T cells that drives fibroblast activation through TGFβR1/ALK4 signalling, highlighting GZMK as a potential biomarker and therapeutic target in IPF. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by National Key R&D Program of China (Noncommunicable Chronic Diseases-National Science and Technology Major Project; 2023YFC2507100 to Jingyu Chen) and Leading Talents Program of Zhejiang Province (2024C03185 to Man Huang), Nature Science Foundation of China (82470431 to Jun Yang). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Ethics Committee of The Second Affiliated Hospital Zhejiang University School of Medicine (ID: 2024-1416). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The scRNA-seq and scTCR-seq data supporting the findings of this study have been deposited at GSA-Human (HRA013103) under accession code PRJCA032809.

We describe in detail a novel surgical technique for repairing donor anterior left atrial wall defect in vivo by rotating the posterior atrial flap during lung transplantation. This method can safely and effectively address the most common type of donor left atrial cuff defect: the anterior wall defect, with the intact posterior wall, typically retained when the donor heart is also used. During atrial cuff anastomosis in lung transplantation, the excess donor posterior atrial wall is trimmed into an atrial flap. After the posterior wall anastomosis is completed, the atrial flap is rotated 180° and used as a patch for anterior wall reconstruction anastomosis. After restoring blood flow, the flow rate of the pulmonary vein is normal and smooth as confirmed by transesophageal echocardiography. Compared with the traditional patch reconstruction method, the new method effectively reduces the atrial cuff anastomosis time. Our results showed no significant difference in pulmonary vein obstruction after reconstruction. Pulmonary artery systolic blood pressure was significantly lower and pulmonary function improved postoperatively in all groups, with no significant differences among the groups. The new technique provides a feasible strategy for the reconstruction of left atrial cuff defects and can improve the effective utilization rate of donor lungs.

目的 评价连续性肾脏替代治疗在边缘性供肺维护中的应用价值.方法 2019年1月1日～2019年10月31日经无锡市人民医院肺移植中心维护的脑死亡边缘性供肺30例,根据维护方法 不同,将其分为两组,实验组12例,在获取前予以常规+持续性肾脏替代治疗(CRRT)联合方案维护48小时;对照组18例,仅进行常规方案维护.两组每24小时留取外周血样,行胸片及气道纤支镜检查,动态监测并对比两种维护方式在血流动力学、氧合指数、感染指标、气道黏膜水肿以及供肺最终使用情况等的差异.结果 经两种方法 维护后,两组供肺质量均较前有不同程度改善,实验组和对照组氧合指数增加分别为(93.58±16.92)％ 和(57.72±11.41)％,C-反应蛋白(CRP)下降分别为(36.04±22.30)mg/L和(18.01±6.78)mg/L,降钙素原(PCT)下降分别为1.09±0.45和0.59±0.82,两组比较,差异有统计学意义(P<0.05).实验组肺影像学的渗出改变、气道黏膜水肿程度改善显著.实验组中8例、对照组中5例达到供肺使用标准,实验组使用率显著高于对照组(P<0.05).结论 早期予以CRRT联合方案,能显著改善边缘性供肺肺功能,提高供体器官利用率.

Abstract Background A pathologically confirmed negative margin is required when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma. However, the optimal margin distance to ensure complete tumor resection while preserving healthy lung tissue remains unknown. We aimed to establish a reliable distance range for negative margins. Methods A total of 52 intraoperative para-cancer tissue specimens from patients with peripheral lung adenocarcinoma with pathological tumors ≤2 cm in size were examined. Depending on the distance from the tumor edge (D), the para-cancer tissues were divided into the following five groups: D < 0.5 cm (group I); 0.5 cm ≤ D < 1.0 cm (group II); 1.0 cm ≤ D < 1.5 cm (group III); 1.5 cm ≤ D < 2.0 cm (group IV); and D ≥ 2.0 cm (group V). During pathological examination of the specimens under a microscope, the presence of atypical adenomatous hyperplasia or more severe lesions was considered unsafe, whereas the presence of normal lung tissue or benign hyperplasia was considered safe. Results Group V, in which the margin was the farthest from the tumor edge, was the safest. There were significant safety differences in between groups I and V (χ2 = 26.217, P < 0.001). Significant safety differences also existed between groups II and V (χ2 = 9.420, P < 0.005). There were no significant safety differences between group III or IV and group V (P = 0.207; P = 0.610). Conclusions We suggest that when performing sublobar resection in patients with early stage peripheral lung adenocarcinoma with pathological tumor sizes ≤2 cm, the resection margin distance should be ≥1 cm to ensure a negative margin.

Peripheral primitive neuroendodermal tumors (PNETs) and Ewing's sarcoma belong to the Ewing family of tumors and are small round-cell malignancies originating from spinal cord cells. These tumors account for 5% of all small round-cell malignant neoplasms. PNETs that arise from the lung parenchyma without pleural or chest wall involvement are very rare. We report a case of an adult female with a large pulmonary PNET who had given birth just 1 month prior to the diagnosis. She had cough and expectoration for 6 months, and the preoperative examination showed no metastases. Thus, we performed radical pneumonectomy and lymph node dissection. The patient recovered well without surgical complications and was discharged 7 days after the surgery. Postoperative pathology confirmed that the tumor was a small round-cell malignancy, and the tumor cells were positive for CD99, Friend leukemia virus integration 1 (FLI-1), and neuron-specific enolase (NSE), which was consistent with the diagnosis of a PNET. For primary large pulmonary PNETs, radical pneumonectomy may be a safe surgical method, worthy of further application in clinical practice.

Background and Objectives:The influence of age at diagnosis of breast cancer upon the prognosis of patients with different immunohistochemical (IHC)-defined subtypes is still incompletely defined. Our study aimed at examining the association of age at diagnosis and risk of breast cancer-specific mortality (BCSM). Methods:172,179 eligible breast cancer patients were obtained for our study cohort using the Surveillance, Epidemiology, and End Results database from 2010 to 2015. Patients were classified into four IHC-defined subtypes according to their ER, PgR, and HER2 status. Kaplan-Meier plots were used to describe BCSM among patients in different age groups. A Cox proportional hazards model was used for multivariate analysis. A multivariable fractional polynomial model within the Cox proportional hazards model was used to evaluate the relationship between age at diagnosis and the risk of BCSM. Results:For the whole cohort, the median follow-up time was 43 months. Patients younger than 40 years and those older than 79 years presented with the worst BCSM (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.03-1.23, and HR 3.52, 95% CI 3.23-3.83, respectively,p< 0.01, with age 40-49 years as the reference). The log hazard ratios of hormone receptor (HoR)(+)/HER2(-) patients formed a quadratic relationship between age at diagnosis and BCSM, but not in the other three subtypes of breast cancer. In the HoR(+)/HER2(-) subtype, patients younger than 40 years had worse BCSM than those aged at 40-49 years (HR 1.26, 95% CI 1.10-1.45, andp< 0.01). Conclusions:Women diagnosed with HoR(+)/HER2(-) breast cancer younger than 40 years or older than 79 years of age suffer higher rates of cancer-specific mortality. Young age at diagnosis may be particularly prognostic in HoR(+)/HER2(-) breast cancer.

目的 通过肺结节交互印证式诊断,提高术前影像诊断的准确率,选择合适的手术时机,指导肺小结节的随访时间.方法 回顾性分析单中心2016年7月至2019年10月厦门大学附属第一医院胸外科1 368例肺结节手术患者的临床资料,男531例、女837例,年龄44(21～67)岁.选择肺结节直径≤2 cm,术前行多学科会诊,详细阅读胸部CT,术中切开病灶剖面进行分析,快速病理诊断肺结节性质,术后常规行病理诊断.随后将肺结节影像特征、术中剖面特征与病理结果一一对照,通过两两对应,交互印证,把肺结节的影像病理及病变切面表现为一个动态变化的过程.结果 在1 368例肺小结节患者中,影像学表现为纯磨玻璃样结节的有376例(27.5％),混合性磨玻璃样结节共有729例(53.3％),实性结节共有263例(19.2％).在纯磨玻璃样结节患者中,原位腺癌(adenocarcinoma in situ,AIS)占比最高,为156例,微浸润性腺癌(microinvasive adenocarcinoma,MIA)和不典型腺瘤样增生(atypical adenomatous hyperplasia,AAH)比例相当,分别为90例和85例,其它良性肿瘤共20例.在混合性磨玻璃样结节中,浸润性腺癌(invasive adenocarcinoma,IA)共495例,其次是MIA 207例;且在实性结节中,病理结果主要为IA和其它良性肿瘤,分别为213例和50例,实性结节病理无AAH、AIS及MIA.结论 肺结节交互印证式诊断可以提高术前诊断的准确率,对选择手术时机、随访时间的判断具有重要意义.

目的 探讨移动CT(mobile CT,MCT)在肺小结节术前及术中定位中的价值.方法 2017年9月～2018年1月我们对50例62个肺小结节术前在MCT引导下用Hook-wire定位针进行肺小结节定位,根据定位行肺小结节切除术,所有肺小结节均送术中冰冻病理检查,若Hook-wire脱落或移位术中再次利用MCT扫描定位.结果 62个肺小结节术前定位成功59个,2个脱钩,1个移位,成功率95.2％(59/62),脱落、移位率4.8％(3/62),术中再次利用MCT扫描定位,最终62个肺结节病灶均成功切除.术中冰冻病理结果显示肿物距离切缘2 cm.定位时间(15.2±5.1)min.定位后少量气胸11例,肺出血1例,肋间血管出血1例,均未特殊处理.结论 MCT在肺小结节术前及术中定位准确、快速,值得推荐.

The study aimed to retrospectively evaluate the success rate, utility, practicality and results of pre-operative CT (computed tomography)–guided semi-rigid single hook-wire placement and the pathology results of small pulmonary nodules (SPN). Seventy-four patients with 81 small pulmonary nodules underwent CT-guided semi-rigid single hook wire localization consecutively between 2016 and 2017 were reviewed. VATS (video-assisted thoracoscopic surgery) resection of lung tissue containing each pulmonary nodule and were performed in the direction of hook wire. The success rate and utility of the localization, hook wire related complications, the histopathology of SPN are analyzed. The semi-rigid hook wire was performed successfully in all 81 small pulmonary nodules within mean time of 10 min (8–13 min, SD: 1.58 min). Compared with solid nodules, GGOs (ground-glass opacity) were more frequently malignant (p < 0.05), with an OR (odds ratio) 8.59 (95%CI, 0.967, 412.845). Of the pure GGOs, 9 (25%) nodules were classified as AIS, 10 (27.8%) nodules were classified as MIA and 22 (57.9%) of the mGGOs were lung cancer. According to multivariate analysis, the malignant hazard was as high as 6.533-fold higher in nodules with a size larger than 10 mm compared with those smaller than 10 mm. GGOs with tiny blood vessels showed a statistically significant correlation with malignancy. Surprisingly, no statistically significant difference in the incidence of lung cancer in age. No major complication occurred. Preoperative localization of small pulmonary nodules using semi-rigid single hook wire was found to be practical and safe, which allows for proper diagnosis. Incidental small pulmonary nodule, especially GGO larger than 10 mm needs to be taken seriously.

髓外造血(extramedullary hematopoiesis ,EMH)是一种罕见疾病,为骨髓外出现造血成分,其中以腹部髓外造血最为常见,主要累及肝和脾,也可见于肾和肾上腺. 发生于纵隔脊髓旁的髓外造血极为少见.本文报道1例54岁男性,CT检查发现后纵隔肿物,影像学检查均考虑神经源性肿瘤或淋巴瘤,穿刺病理未能确定诊断,于2017年10月行胸腔镜手术完整切除,术后病理诊断为髓外造血,进一步查β-地中海贫血基因,检出β基因IVS-II-654 (C-T)突变杂合子,术后随访1年,无胸背部不适,贫血无加重.

Objective To explore the clinical value of video-assisted thoracoscopic surgery(VATS)for coinstantaneous primary carcinoma of esophagus and lung. Methods A retrospective analysis was made on 17 cases of VATS for coinstantaneous primary carcinoma of esophagus and lung in our hospital from July 2005 to December 2015.The surgical approach was chosen mainly based on the location of lung lesions and intraoperative frozen-section examinations.Generally, if the preoperative lung biopsies confirmed cancer,the surgical wedge resection, pulmonary segmentectomy or pulmonary lobectomy was performed firstly, and then thoracoscopic resection of esophageal carcinoma was carried out on the right side.When preoperative lung tumor pathology was not clear,thoracoscopic pulmonary wedge or segment resection was performed,and then according to the intraoperative rapid pathological examination,segment resection with lymph node biopsy for carcinoma in situ or lobectomy with mediastinal lymph node dissection for invasive carcinoma was conducted, followed by thoracoscopic radical surgery for esophageal carcinoma on the right side. Results The concurrent operation was accomplished in all the 17 cases.One patient died of pulmonary embolism on the 7th day.The complications contained 1 case of anastomotic leakage,2 cases of hoarseness,and 1 case of lung infection, all of which were cured. Postoperative pathology results showed that 17 cases of esophageal cancer were all squamous cell carcinoma,and among the 17 cases of lung cancer there were 13 cases of adenocarcinoma,3 cases of adenosquamous carcinoma,and 1 case of small cell carcinoma.Eight patients died in the period from 12 to 36 months,with a mean survival time of 33.6 months.The other 8 patients were followed up for 12 -60 months(mean, 45.6 months). Conclusions Concurrent video-thoracoscopic surgery in the treatment of esophageal carcinoma complicated with pulmonary cancer has a good perioperative treatment effect prognosis and acceptable risks.The surgical method is safe and feasible.