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Causal Inference of Different Smoke Exposure Statuses and Influenza Risk: Insights From a Mendelian Randomization Study
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-05-13 DOI: 10.1111/crj.70083
Yanqi Guo, Haixia Chen, Shijie Wu, Jiesen Zhou, Zhihua Chen

Introduction

Previous observational studies have suggested a potential association between smoking exposure and influenza infection risk. However, the impact of different smoke exposure statuses on susceptibility to influenza infection remains insufficiently explored. This study employs Mendelian randomization analysis to investigate the causal relationship between smoking exposure statuses, including current tobacco use, household smoking exposure, past smoking history, and the risk of influenza infection.

Methods

The summary-level data for this study were obtained from the FinnGen Consortium R11 and Neale Lab, both outcomes and exposures. To ensure robust results, we employed multiplicative random-effects inverse variance weighting, MR-Egger, and weighted median (WM) methods to analyze single-nucleotide polymorphisms (SNPs). We also conducted Cochran's Q test, MR-PRESSO, and the MR-Egger intercept test to assess heterogeneity and horizontal pleiotropy, ensuring accurate and reliable findings.

Results

Our analysis demonstrated that elevated exposure to current tobacco smoking causally increased the risk of influenza infection, with (OR = 2.032, 95% CI 1.672–2.538, p < 0.001) or without pneumonia (OR = 2.081, 95% CI 1.824–2.338, p = 0.015). No reverse causal relationship was found, and no bidirectional effects were observed for past smoking (OR = 1.108, 95% CI 0.543–2.258, p = 0.779) or household exposure (OR = 1.127, 95% CI −0.209–2.462, p = 0.939).

Conclusion

This analysis identified a significant causal association between current tobacco smoking and increased risk of influenza infection. However, no significant association was observed for other smoking exposures (e.g., former or household smoking). These findings emphasized the importance of considering different types of smoking exposure in clinical influenza prevention and treatment strategies.

先前的观察性研究表明,吸烟暴露与流感感染风险之间存在潜在关联。然而,不同的烟雾暴露状态对流感感染易感性的影响仍未得到充分探讨。本研究采用孟德尔随机化分析,探讨吸烟暴露状况(包括当前烟草使用情况、家庭吸烟暴露、既往吸烟史)与流感感染风险之间的因果关系。方法本研究的汇总数据来自FinnGen Consortium R11和Neale Lab,包括结果和暴露。为了确保结果的稳稳性,我们采用乘法随机效应逆方差加权、MR-Egger和加权中位数(WM)方法来分析单核苷酸多态性(snp)。我们还进行了Cochran’s Q检验、MR-PRESSO和MR-Egger截距检验,以评估异质性和水平多效性,确保结果准确可靠。结果:我们的分析表明,当前吸烟增加会导致流感感染的风险增加(OR = 2.032, 95% CI 1.672-2.538, p < 0.001)或不会导致肺炎(OR = 2.081, 95% CI 1.824-2.338, p = 0.015)。未发现反向因果关系,既往吸烟(OR = 1.108, 95% CI 0.543-2.258, p = 0.779)或家庭暴露(OR = 1.127, 95% CI - 0.209-2.462, p = 0.939)未观察到双向影响。结论:该分析确定了当前吸烟与流感感染风险增加之间存在显著的因果关系。然而,没有观察到其他吸烟暴露(例如,以前或家庭吸烟)的显著关联。这些发现强调了在临床流感预防和治疗策略中考虑不同类型吸烟暴露的重要性。
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引用次数: 0
Correction to “The Relationship of Vitamin A and Neonatal Respiratory Diseases: A Meta-Analysis” 对“维生素A与新生儿呼吸系统疾病的关系:荟萃分析”的更正
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-05-06 DOI: 10.1111/crj.70078

Y. Li, R. Zhang, X. Li, Q. Zhai, “ The Relationship of Vitamin A and Neonatal Respiratory Diseases: A Meta-Analysis,” Clinical Respiratory Journal 18, no. 10 (2024), https://doi.org/10.1111/crj.70030.

The Funding section is incomplete and should be revised to:

Funding: This work was financially supported by the Scientific Research Project of Weifang Health Committee of Shandong Province (wfwsjk2019-182), Weifang Youth Medical Talent Support Project, and Weifang Clinical Medical Research Center Cultivation Project (Clinical Medical Research Center for Neonatal Diseases).

The other elements of the paper remain the same.

We apologize for this error.

李艳,张荣,翟强,“维生素A与新生儿呼吸系统疾病的关系:meta分析”,《临床呼吸杂志》,第18期。10 (2024), https://doi.org/10.1111/crj.70030。资助部分内容不完整,应修改为:资助:本工作由山东省潍坊市卫生健康委员会科研项目(wfwsjk2019-182)、潍坊市青年医学人才支持项目、潍坊市临床医学研究中心培养项目(新生儿疾病临床医学研究中心)资助。论文的其他要素保持不变。我们为这个错误道歉。
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引用次数: 0
USP7-Mediated ICAM1 Facilitates Lipopolysaccharide-Induced Human Pulmonary Microvascular Endothelial Cell Injury to Accelerate Pediatric Acute Respiratory Distress Syndrome usp7介导的ICAM1促进脂多糖诱导的人肺微血管内皮细胞损伤加速儿童急性呼吸窘迫综合征
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-05-06 DOI: 10.1111/crj.70079
Jing Li, Jing Wu, Lili Zhao, Lian Liu

Background

Intercellular cell adhesion molecule 1 (ICAM1) has been confirmed to be abnormally expressed in acute respiratory distress syndrome (ARDS) patients. However, its role and mechanism in pediatric ARDS process need further revealed.

Methods

Serum samples were selected from pediatric ARDS patients and age-matched healthy individuals. Lipopolysaccharide (LPS)-induced human pulmonary microvascular endothelial cells (HPMECs) were used to mimic ARDS cell models. Cell proliferation and apoptosis were tested by cell counting kit 8 assay, EdU assay, and flow cytometry. Oxidative stress and inflammation were assessed by corresponding kits. M1 macrophage polarization was evaluated via measuring CD86 positive cell rate. The expression levels of ICAM1, ubiquitin-specific peptidase 7 (USP7), and NF-κB pathway-related markers were detected by quantitative real-time PCR and western blot. The interaction between USP7 and ICAM1 was analyzed by Co-IP assay.

Results

LPS induced apoptosis, inflammation, oxidative stress, and M1 macrophage polarization, while suppressed proliferation in HPMECs. ICAM1 was upregulated in pediatric ARDS patients, and its knockdown alleviated HPMEC injury induced by LPS. USP7 positively regulated ICAM1 protein expression through deubiquitination. USP7 overexpression aggravated LPS-induced HPMEC apoptosis, inflammation, oxidative stress, and M1 macrophage polarization. Besides, ICAM1 upregulation could eliminate the inhibitory effect of USP7 knockdown on LPS-induced HPMEC injury. In addition, USP7 activated NF-κB pathway by promoting ICAM1 expression.

Conclusion

USP7-mediated ICAM1 upregulation could promote LPS-induced HPMEC injury by activating NF-κB pathway, which provided a new idea for the treatment of pediatric ARDS.

背景细胞间细胞粘附分子1 (ICAM1)在急性呼吸窘迫综合征(ARDS)患者中表达异常。但其在小儿ARDS过程中的作用及机制有待进一步研究。方法选取小儿ARDS患者和年龄匹配的健康人的血清样本。采用脂多糖(LPS)诱导的人肺微血管内皮细胞(hpmes)模拟ARDS细胞模型。采用细胞计数试剂盒8法、EdU法和流式细胞术检测细胞增殖和凋亡。采用相应试剂盒检测氧化应激和炎症反应。通过检测CD86阳性细胞率评价M1巨噬细胞极化。采用实时荧光定量PCR和western blot检测ICAM1、泛素特异性肽酶7 (USP7)、NF-κB通路相关标志物的表达水平。采用Co-IP法分析USP7与ICAM1的相互作用。结果LPS诱导细胞凋亡、炎症、氧化应激、M1巨噬细胞极化,抑制细胞增殖。ICAM1在小儿ARDS患者中表达上调,其下调可减轻LPS诱导的HPMEC损伤。USP7通过去泛素化正向调节ICAM1蛋白的表达。USP7过表达加重了lps诱导的HPMEC凋亡、炎症、氧化应激和M1巨噬细胞极化。此外,ICAM1上调可消除USP7下调对lps诱导的HPMEC损伤的抑制作用。此外,USP7通过促进ICAM1表达激活NF-κB通路。结论usp7介导的ICAM1上调可通过激活NF-κB通路促进lps诱导的HPMEC损伤,为儿童ARDS的治疗提供了新的思路。
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引用次数: 0
Development of a Nomogram Model to Predict Mortality in ANCA-Associated Vasculitis Patients With Pulmonary Involvement 建立预测肺部受累的 ANCA 相关性血管炎患者死亡率的提名图模型
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-04-22 DOI: 10.1111/crj.70067
Qifang Guo, Yijia Shao, Le Yu, Xiuling Zhang, Jingjing Shang, Xueqin Feng, Wei Zhou, Xinwang Duan

Objective

Risk assessment and prognosis prediction are crucial for patients with pulmonary involvement in antineutrophil cytoplasimc antibody associated vasculitis (AAV). This study was conducted to create and internally validate a prognostic model for mortality of pulmonary involvement in patients with AAV that provides individualized risk assessments.

Methods

A cohort of 150 patients diagnosed with AAV at the Second Affiliated Hospital of Nanchang University Hospital between January 2013 and July 2022 was included, using data obtained from the Chinese Rheumatism Data Center (CRDC). The model was developed using Cox proportional hazards regression and the least absolute shrinkage and selection operator. To validate the model, assessments were conducted for discrimination, calibration, and through decision curve analysis.

Results

The mean survival time of lung involvement AAV patients was 57.0 ± 4.1 months. In the final predictive model for death, four clinical variables were included: age at baseline, history of tumors, baseline hemoglobin level, and the level of the percentage of forced vital capacity to the normal predicted value. One-, two-, and three-year AAV patients with pulmonary involvement mortality probability-predictive nomogram were established. Internal validation of the model was conducted, yielding Harrell's concordance index (0.884), a Brier score of 0.088, and a calibration curve indicating satisfactory performance.

Conclusion

We constructed a risk model utilizing easily accessible clinical risk factors, which could accurately forecast the future mortality risk associated with pulmonary involvement in AAV patients.

目的抗中性粒细胞细胞质抗体相关性血管炎(AAV)累及肺部患者的风险评估和预后预测至关重要。本研究旨在建立并内部验证AAV患者肺部受累死亡率的预后模型,该模型可提供个性化的风险评估。方法纳入2013年1月至2022年7月在南昌大学附属第二医院诊断为AAV的150例患者,数据来自中国风湿病数据中心(CRDC)。采用Cox比例风险回归、最小绝对收缩和选择算子建立模型。为了验证模型,进行了判别、校准和决策曲线分析的评估。结果累及肺的AAV患者的平均生存时间为57.0±4.1个月。在最终的死亡预测模型中,包括4个临床变量:基线年龄、肿瘤史、基线血红蛋白水平和强迫肺活量与正常预测值的百分比水平。建立1年、2年和3年AAV累及肺的患者死亡率概率预测图。对模型进行内部验证,得到Harrell的一致性指数为0.884,Brier评分为0.088,校准曲线显示满意的性能。结论利用易于获取的临床危险因素构建风险模型,可以准确预测AAV患者肺部累及相关的未来死亡风险。
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引用次数: 0
A Case of Lung Squamous Cell Carcinoma Harboring TP53 Mutation and PLPP5-FGFR1 Fusion Gene 肺鳞状细胞癌携带TP53突变和PLPP5-FGFR1融合基因1例
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-04-17 DOI: 10.1111/crj.70074
Meng Xiao-ru, Shi Xiao-Xiong, Gao Qian, Qu Ya-jing, Huo Li-li, Gao Yan-Yan, Xu Peng-peng, Ma Guan-nan, Ren Gui-bing

Lung squamous cell carcinoma (LUSC) is one of the most common subtype of lung cancer and is associated with the poor prognoses. The fibroblast growth factor receptor (FGFR) family is known to be activated through fusions with various partners across multiple cancer types, including nonsmall cell lung cancer (NSCLC). FGFR inhibitors are currently undergoing clinical evaluation for the treatment of tumors harboring these fusions. While FGFR1 amplification has been well-documented in numerous NSCLC datasets, the characterization of specific FGFR fusion variants remains limited. In this study, we identified a novel PLPP5-FGFR1 fusion in a 65-year-old male patient with lung squamous cell carcinoma through targeted RNA sequencing. The fusion junction was located between exon 1 of PLPP5 and exon 5 of FGFR1, and the result was validated by Sanger sequencing. To our knowledge, this is the first reported case of a PLPP5-FGFR1 fusion coexisting with a TP53 mutation in LUSC. These findings broaden the spectrum of potential translocation partners in FGFR1 fusions, and the clinical implications of this novel fusion on treatment outcomes and prognosis warrant further investigation and long-term follow-up.

肺鳞状细胞癌(LUSC)是最常见的肺癌亚型之一,与预后不良有关。已知成纤维细胞生长因子受体(FGFR)家族通过与多种癌症类型的各种伙伴融合而被激活,包括非小细胞肺癌(NSCLC)。FGFR抑制剂目前正在进行治疗含有这些融合物的肿瘤的临床评估。虽然FGFR1扩增已在许多NSCLC数据集中得到充分记录,但特异性FGFR融合变体的表征仍然有限。在这项研究中,我们通过靶向RNA测序在一名65岁男性肺鳞状细胞癌患者中发现了一种新的PLPP5-FGFR1融合。融合结位于PLPP5的外显子1和FGFR1的外显子5之间,结果通过Sanger测序得到验证。据我们所知,这是首次报道的LUSC中PLPP5-FGFR1融合与TP53突变共存的病例。这些发现扩大了FGFR1融合中潜在易位伴侣的范围,这种新型融合对治疗结果和预后的临床意义值得进一步研究和长期随访。
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引用次数: 0
Effects of Physical Exercises in Asthma: An Umbrella Review of Systematic Review and Meta-Analysis 体育锻炼对哮喘的影响:系统综述和荟萃分析的综合综述
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-04-17 DOI: 10.1111/crj.70075
Fuchun Huang, Shuang Yang, Mingxuan Ma, Jialin Zhang, Hua Liu

Background

As a disease-modifying strategy, physical exercise has been demonstrated to significantly improve quality of life, exercise capacity, and lung function in individuals with asthma. However, the quality and robustness of this evidence has not been thoroughly examined in many large-scale investigations. In order to assess the evidence addressing the effects of physical exercise in patients with asthma, we therefore carried out an umbrella review.

Methods

A comprehensive search of the PubMed, Web of Science, and Cochrane databases for systematic reviews and meta-analyses of the effects of physical activity on asthma was conducted up to December 31, 2022. The study was registered in Prospero (CRD42023382921). For every qualified systematic review and meta-analysis, we extracted information on the main characteristics and general findings. The GRADE tool was utilized to quantify the strength of the evidence, and the AMSTAR2 score was employed to evaluate the methodological quality.

Results

A total of 1254 articles were searched, and 42 independent results were identified as eligible in the 11 articles that were included. Of the 42 unique outcomes, two were rated as high, two as medium, and the rest as low or very low. Physical exercise is beneficial for improving QoL, exercise capacity, and lung function in patients with asthma.

Conclusions

According to our research, physical activity benefits QoL of patients with asthma, exercise tolerance, and lung function. In the future, further evidence from superior prospective studies will be required because the quality of the available evidence is now insufficient.

作为一种疾病改善策略,体育锻炼已被证明可以显著改善哮喘患者的生活质量、运动能力和肺功能。然而,在许多大规模调查中,这一证据的质量和稳健性尚未得到彻底的检验。为了评估体育锻炼对哮喘患者影响的证据,我们进行了一项综合综述。方法全面检索PubMed、Web of Science和Cochrane数据库,对体育锻炼对哮喘的影响进行系统评价和荟萃分析,截止到2022年12月31日。该研究已在Prospero注册(CRD42023382921)。对于每一个合格的系统评价和荟萃分析,我们提取了主要特征和一般发现的信息。GRADE工具用于量化证据的强度,AMSTAR2评分用于评估方法学质量。结果共检索1254篇文献,在纳入的11篇文献中筛选出42个独立结果。在42个独特的结果中,两个被评为高,两个被评为中等,其余的被评为低或非常低。体育锻炼有利于改善哮喘患者的生活质量、运动能力和肺功能。结论根据我们的研究,体育活动有利于哮喘患者的生活质量、运动耐量和肺功能。在未来,由于现有证据的质量不足,将需要来自优质前瞻性研究的进一步证据。
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引用次数: 0
A Comment on ‘Screening for Obstructive Sleep Apnea Before Coronary Angiography’ 对“冠状动脉造影前阻塞性睡眠呼吸暂停筛查”的评论
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-04-13 DOI: 10.1111/crj.70077
Baris Demirkol, Celal Satici

Obstructive sleep apnea (OSA) is closely associated with cardiovascular diseases, and its impact on coronary heart disease (CHD) has been increasingly investigated [1, 2]. The pathophysiological mechanisms of OSA, such as recurrent nocturnal hypoxemia and increased sympathetic nervous system activation, can lead to endothelial dysfunction and early atherosclerotic changes, thereby heightening the risk of CHD [2-4]. Additionally, OSA shares common characteristics with other major cardiovascular risk factors, including hypertension, obesity, and metabolic syndrome, further underscoring the strong relationship between these conditions [5, 6]. Therefore, effective screening and management of OSA may play a significant role in the prevention and treatment of CHD.

We have reviewed with great interest the study by Guo Pei et al., titled “Screening for Obstructive Sleep Apnea Before Coronary Angiography,” which highlights the importance of OSA screening prior to coronary angiography [7]. While this valuable study contributes to the literature, we believe it could yield more impactful results with some refinements.

First, since the primary focus of the study is the importance of OSA screening, selecting OSA rather than CHD as the primary endpoint might be more appropriate. This adjustment could better align the study with its focus on assessing the clinical implications of OSA and provide a more coherent framework for its objectives. Presenting and comparing the characteristics of OSA (+) and OSA (−) groups, along with conducting a multivariable analysis of these data, could also enhance the clarity and interpretability of the findings. Logistic regression analyses based on these groups could more effectively evaluate the independent predictors of OSA detection.

The current multivariable analysis model includes parameters with high collinearity (e.g., total cholesterol, LDL, HDL), which may adversely affect the model's accuracy and result in multicollinearity issues. Evaluating the model's fit using measures such as the Hosmer–Lemeshow test and considering alternative models could help better elucidate the independent effects of each parameter.

Lastly, performing a receiver operating characteristic (ROC) analysis to clarify the relationship between OSA screening and Gensini scores could provide a more precise determination of a cut-off value with high sensitivity for OSA. This additional analysis would facilitate a more practical interpretation of the results and enhance the study's clinical applicability.

Baris Demirkol and Celal Satici contributed to the study's design and implementation, the evaluation and analysis of the results, and the drafting of the manuscript.

The authors declare no conflicts of interest.

阻塞性睡眠呼吸暂停(OSA)与心血管疾病密切相关,其对冠心病(CHD)的影响已被越来越多的研究[1,2]。OSA的病理生理机制,如反复的夜间低氧血症和交感神经系统激活增加,可导致内皮功能障碍和早期动脉粥样硬化改变,从而增加冠心病的风险[2-4]。此外,OSA与其他主要心血管危险因素(包括高血压、肥胖和代谢综合征)具有共同特征,进一步强调了这些疾病之间的密切关系[5,6]。因此,对OSA进行有效的筛查和管理,对冠心病的预防和治疗具有重要意义。我们饶有兴趣地回顾了郭培等人的“冠状动脉造影前筛查阻塞性睡眠呼吸暂停”的研究,该研究强调了冠状动脉造影前OSA筛查的重要性。虽然这项有价值的研究为文献做出了贡献,但我们相信,通过一些改进,它可以产生更有影响力的结果。首先,由于本研究的主要焦点是OSA筛查的重要性,因此选择OSA而不是冠心病作为主要终点可能更合适。这一调整可以更好地将研究重点与评估OSA的临床意义结合起来,并为其目标提供更连贯的框架。提出和比较OSA(+)组和OSA(−)组的特征,以及对这些数据进行多变量分析,也可以提高结果的清晰度和可解释性。基于这些分组的Logistic回归分析可以更有效地评价OSA检测的独立预测因素。目前的多变量分析模型包括高共线性的参数(如总胆固醇、LDL、HDL),这可能会对模型的准确性产生不利影响,并导致多重共线性问题。使用Hosmer-Lemeshow检验等方法评估模型的拟合性,并考虑替代模型,可以帮助更好地阐明每个参数的独立影响。最后,进行受试者工作特征(ROC)分析,以澄清OSA筛查与Gensini评分之间的关系,可以更精确地确定OSA的高灵敏度临界值。这种额外的分析将有助于对结果进行更实际的解释,并增强研究的临床适用性。Baris Demirkol和Celal Satici对研究的设计和实施、结果的评估和分析以及手稿的起草做出了贡献。作者声明无利益冲突。
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引用次数: 0
Ruxolitinib for Emergency Treatment of COVID-19–Associated Cytokine Storm: Findings From an Expanded Access Study Ruxolitinib用于covid -19相关细胞因子风暴的紧急治疗:来自扩大准入研究的发现
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-04-08 DOI: 10.1111/crj.70050
Jeffrey Weinstein, Nikhil Jagan, Shawnta Lorthridge-Jackson, J. E. Hamer-Maansson, Peg Squier

Introduction

This expanded access program (EAP) provided ruxolitinib (oral, selective Janus kinase [JAK]1/JAK2 inhibitor) for emergency treatment of COVID-19–associated cytokine storm in patients eligible for hospitalization (NCT04355793).

Methods

Patients received ruxolitinib 5 mg twice daily (preferred regimen when tolerated) or once daily for ≤ 14 days, or until determination of no clinical benefit was made. Outcomes were clinical status, physician-assessed clinical benefit, and serious adverse event (SAE) incidence.

Results

Of 312 patients, 45.5% achieved ≥ 1-point clinical status improvement. Physician-assessed clinical benefit was reported in 42.6% of evaluable patients. SAEs occurred in 42.9%, with 2.6% experiencing an SAE suspected to be ruxolitinib related.

Conclusions

Overall, some hospitalized patients with COVID-19–associated cytokine storm who received ruxolitinib experienced clinical status improvement; ruxolitinib was well tolerated.

Trial Registration

ClinicalTrials.gov identifier: NCT04355793

该扩大准入计划(EAP)为符合住院条件的患者提供ruxolitinib(口服,选择性Janus激酶[JAK]1/JAK2抑制剂)用于covid -19相关细胞因子风暴的紧急治疗(NCT04355793)。方法患者服用ruxolitinib 5 mg,每日2次(耐受时首选方案)或每日1次,疗程≤14天,或直至无临床获益。结果包括临床状态、医生评估的临床获益和严重不良事件(SAE)发生率。结果312例患者中,45.5%的患者临床状态改善≥1点。42.6%的可评估患者报告了经医生评估的临床获益。42.9%发生SAE,其中2.6%发生疑似与鲁索利替尼相关的SAE。结论总体而言,部分新冠肺炎相关细胞因子风暴住院患者接受鲁索利替尼治疗后,临床状况有所改善;Ruxolitinib耐受性良好。试验注册ClinicalTrials.gov标识符:NCT04355793
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引用次数: 0
Landscape of T Cells in Tuberculous Pleural Effusion 结核性胸腔积液中T细胞的分布
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-04-02 DOI: 10.1111/crj.70066
Lihui Zou, Jing Chen, Li Xie, Lili Zhang, Li Wan, Weimin Li, Hongtao Xu

The distribution and the function of T lymphocyte subsets in pleural effusion (PE) and peripheral blood (PB) in tuberculous pleural effusion (TPE) patients remain unclear. In this study, we aimed to explore the expression patterns, regulatory mechanisms, and functions of T lymphocyte subsets in TPE patients, especially the distribution of T lymphocyte subsets at the single cell level. The CD3+ T cells were isolated from PE and PB of four TPE patients for single-cell RNA sequencing (scRNA-seq) to screen T cell subsets. T-SNE projection, Gene Set Variation Analysis (GSVA), and pseudotime analysis were performed to analyze the composition, molecular and functional properties, and developmental trajectories of T cell subsets. Finally, ELISA was carried out to identify the cytokines secreted by PE and PB. We found that CD4+CD8 T lymphocytes (Th1, Th2, and FOXP3+ Treg cells) were preferentially enriched in PE. The proportion of exhausted CD4CD8+ cells in PE was higher than that in PB, while the proportion of initial and effector CD4CD8+ cells was quite the reverse. We also found a large number of unexpected double positive (DP) cells in PE and PB, among which the proportion of CD4+CD8+-C10-CCL3 cells was the most different between PE and PB. Meanwhile, CD4+CD8+-C10-CCL3 was the group with the largest number of interactions with other groups. CD4CD8 cells were mainly found in PE and may be involved in the immunomodulatory effect of PE. Furthermore, the concentrations of cytokines secreted by Th1, Th2, and Treg in PE were higher than those in PB. Our study is helpful to understand the distribution pattern and dynamic changes of T cells in PE and PB of TPE patients and further understand that the functional status and regulation of T cells will be crucial for the successful development of TPE immunotherapy.

结核性胸腔积液(TPE)患者胸膜积液(PE)和外周血(PB)中T淋巴细胞亚群的分布和功能尚不清楚。在本研究中,我们旨在探讨T淋巴细胞亚群在TPE患者中的表达模式、调控机制和功能,特别是在单细胞水平上的T淋巴细胞亚群分布。从4例TPE患者的PE和PB中分离CD3+ T细胞,进行单细胞RNA测序(scRNA-seq)筛选T细胞亚群。通过T- sne投影、基因集变异分析(GSVA)和伪时间分析来分析T细胞亚群的组成、分子和功能特性以及发育轨迹。最后,采用ELISA法对PE和PB分泌的细胞因子进行鉴定。我们发现CD4+CD8−T淋巴细胞(Th1、Th2和FOXP3+ Treg细胞)在PE中优先富集。PE中耗竭的CD4−CD8+细胞比例高于PB,而初始和效应CD4−CD8+细胞比例则相反。我们在PE和PB中也发现了大量意想不到的双阳性(DP)细胞,其中CD4+CD8+-C10-CCL3细胞的比例在PE和PB之间差异最大。同时,CD4+CD8+-C10-CCL3是与其他组相互作用最多的组。CD4−CD8−细胞主要存在于PE中,可能参与PE的免疫调节作用。此外,PE中Th1、Th2和Treg分泌的细胞因子浓度高于PB。我们的研究有助于了解TPE患者PE和PB中T细胞的分布规律和动态变化,并进一步了解T细胞的功能状态和调控对TPE免疫治疗的成功发展至关重要。
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引用次数: 0
Immunological Features and Potential Biomarkers of Systemic Sclerosis–Associated Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis 系统性硬化症相关间质性肺疾病和特发性肺纤维化的免疫学特征和潜在生物标志物
IF 1.9 4区 医学 Q3 RESPIRATORY SYSTEM Pub Date : 2025-03-31 DOI: 10.1111/crj.70072
Shuai Shao, Siyu Cao, Yusha Chen, Zhijin Zhang, Tong Zhaohui

Background

This study aims to summarize the similarities and differences in immune cell characteristics, and potential therapeutic targets between systemic sclerosis-associated interstitial lung disease (SSc-ILD) and idiopathic pulmonary fibrosis (IPF).

Methods

This study included SSc-ILD and SSc-nonILD patients who were admitted to Beijing Chaoyang Hospital between April 4th, 2013, to June 30th, 2023. Publicly available datasets, including peripheral blood monocular cell (pbmc) single-cell data, SSc, SSc-ILD pbmc transcriptome data, and SSc-ILD, IPF lung tissue transcriptome data were analyzed. Statistical analyses were conducted using the SPSS and R software, employing standard statistical methods and bioinformatics packages such as Seurat, DESeq2, enrichR, and CellChat.

Results

The results revealed that the CD4+/CD8+ T cell ratio of pbmc in SSc-ILD patients was significantly higher than in SSc-nonILD patients. In IPF patients, an elevated CD4+/CD8+ T cell ratio was also observed in progressive group, and Treg and mature CD4+ T cells might cause this change. JAK–STAT pathway and the cytokine–cytokine receptor interaction pathway were activated in peripheral blood T cells of IPF patients. The CD30, CD40, and FLT3 signaling pathways were found to play crucial roles in T cell interactions with other immune cells among IPF patients. SPA17 as a commonly upregulated gene among SSc, SSc-ILD, and IPF pbmc and lung, with its expression correlating positively with disease severity and lung function progression.

Conclusion

CD4+/CD8+ T cell ratio might associate with ILD initiation and progression; Treg cells and mature CD4+ T cells play key roles of it. SPA17 might serve as a pan-ILD marker and associated with lung function progression.

本研究旨在总结系统性硬化症相关间质性肺疾病(SSc-ILD)和特发性肺纤维化(IPF)在免疫细胞特征和潜在治疗靶点上的异同。方法本研究纳入2013年4月4日至2023年6月30日在北京朝阳医院收治的SSc-ILD和ssc -非ild患者。公开可用的数据集,包括外周血单眼细胞(pbmc)单细胞数据、SSc、SSc- ild pbmc转录组数据和SSc- ild、IPF肺组织转录组数据进行了分析。采用标准统计方法和生物信息学软件包Seurat、DESeq2、enrichment R、CellChat,采用SPSS和R软件进行统计分析。结果SSc-ILD患者pbmc CD4+/CD8+ T细胞比值明显高于ssc -非ild患者。在IPF患者中,进展组也观察到CD4+/CD8+ T细胞比例升高,Treg和成熟CD4+ T细胞可能导致这种变化。IPF患者外周血T细胞JAK-STAT通路和细胞因子-细胞因子受体相互作用通路被激活。发现CD30、CD40和FLT3信号通路在IPF患者的T细胞与其他免疫细胞的相互作用中起关键作用。SPA17是SSc、SSc- ild和IPF pbmc和肺中常见的上调基因,其表达与疾病严重程度和肺功能进展呈正相关。结论CD4+/CD8+ T细胞比值可能与ILD的发生和发展有关;Treg细胞和成熟的CD4+ T细胞在其中起关键作用。SPA17可能作为泛ild标志物,与肺功能进展相关。
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引用次数: 0
期刊
Clinical Respiratory Journal
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