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[Interpretation of the"Guidelines for the diagnosis and treatment of insomnia disorder (2025 edition)"]. 【《失眠诊断与治疗指南(2025年版)》解读】。
Q3 Medicine Pub Date : 2025-12-16 DOI: 10.3760/cma.j.cn112137-20250928-02520
X Luo, B Zhang

Since the publication of the "Chinese guidelines for the diagnosis and treatment of insomnia disorder" in 2017, the diagnostic and treatment system for insomnia has achieved significant advances in precision medicine, digital therapeutics, and multidisciplinary integration. The Chinese Sleep Research Society organized domestic experts from relevant fields to develop the"Guidelines for the diagnosis and treatment of insomnia disorder (2025 edition)", which features significant updates in both diagnostic classification and treatment strategies. The guidelines adopt the International Classification of Sleep Disorders-Third Edition, Text Revision diagnostic classification, systematically introduce insomnia subtype classification, and expand coverage of digital cognitive behavioral therapy for insomnia, novel medications, and individualized management strategies for special populations including children/adolescents, women, and elderly patients. This article aims to elucidate the core updates and clinical implications of the guidelines by examining the revisions to the diagnostic system and advancements in treatment strategies, thereby providing a reference for promoting standardized and precision-based diagnosis and treatment of insomnia in China.

自2017年《中国失眠症诊疗指南》发布以来,失眠诊疗体系在精准医学、数字化治疗、多学科融合等方面取得重大进展。中国睡眠研究会组织国内相关领域专家制定了《失眠症诊疗指南(2025版)》,在诊断分类和治疗策略上都有重大更新。指南采用《国际睡眠障碍分类-第三版》文本修订诊断分类,系统引入失眠亚型分类,扩大失眠数字认知行为治疗、新型药物、针对儿童/青少年、妇女、老年患者等特殊人群的个性化管理策略的覆盖范围。本文旨在通过分析诊断体系的修订和治疗策略的进展,阐明该指南的核心更新和临床意义,从而为促进中国失眠的规范化、精准化诊断和治疗提供参考。
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引用次数: 0
[Effect of CD4+T cell-specific methyltransferase-like 3 gene knockout on calcipotriol-induced atopic dermatitis in mice]. [CD4+T细胞特异性甲基转移酶样3基因敲除对钙三醇诱导的小鼠特应性皮炎的影响]。
Q3 Medicine Pub Date : 2025-12-16 DOI: 10.3760/cma.j.cn112137-20250614-01455
Q Y Chen, L Cui, Z Y Chen, J L Y Cai, H Mei, C Y Guo, Y L Shi

Objective: To investigate the regulatory role of methyltransferase-like protein 3 (Mettl3) within CD4+T cells in a mouse model of atopic dermatitis (AD) induced by calcipotriol (MC903). Methods: The C57BL/6 mouse model with CD4+T cell-specific Mettl3 knockout (Mettl3-/-) was constructed (cKO group, n=4), with Mettl3flox/flox mice lacking CD4-Cre recombinase serving as the control group (WT group, n=4). An AD-like dermatitis model was induced by topical application of MC903 to the ventral side of the right ear. The characteristics of AD-like dermatitis were assessed based on erythema and scaling at the lesion site, epidermal and dermal thickness, and the scoring of AD (SCORAD). The mRNA expression levels of key cytokines [interleukin (IL)-4, IL-10, etc.] and filaggrin (FLG) in the skin lesions, as well as the proportions of CD4+T cell subsets in the draining lymph nodes, were measured. Results: In the MC903-induced AD-like skin inflammation model, compared with the WT group, the cKO group exhibited less severe AD-like skin lesions, reduced skin thickening, decreased epidermal thickness [(45.4±16.3) μm vs (59.6±2.9) μm], less edema, and lower SCORAD scores. The mRNA expression level of IL-4 in the skin lesions was lower [(0.7±0.1) vs (1.0±0.1)], while the mRNA expression levels of FLG and IL-10 were higher [(2.7±1.3) vs (1.0±0.1) and (1.4±0.3) vs (1.0±0.1), respectively] (all P<0.05). The proportion of regulatory T cells in the draining lymph nodes was significantly higher in the cKO group [(5.7%±1.3%) vs (2.4%± 0.3%), P<0.05]. The proportion of T helper 2 cells (Th2) was lower, with no significant difference [(0.7%±0.2%) vs (0.8%±0.7%), P>0.05]. Conclusion: CD4+T cell-specific deletion of Mettl3 modulates IL-4, IL-10, and FLG expression, alters the Th2/Treg cell ratio, and thereby attenuates MC903-induced AD-like dermatitis in mice.

目的:探讨甲基转移酶样蛋白3 (methyltransferase-like protein 3, Mettl3)在钙三醇(MC903)诱导的小鼠特应性皮炎(AD)模型中CD4+T细胞中的调控作用。方法:构建CD4+T细胞特异性敲除Mettl3 (Mettl3-/-)的C57BL/6小鼠模型(cKO组,n=4),缺失CD4- cre重组酶的Mettl3flox/flox小鼠作为对照组(WT组,n=4)。右耳腹侧外用MC903诱导ad样皮炎模型。根据病变部位的红斑和鳞屑、表皮和真皮厚度以及AD评分(SCORAD)来评估AD样皮炎的特征。检测皮肤病变组织中关键细胞因子[白细胞介素(IL)-4、IL-10等]和聚丝蛋白(FLG) mRNA表达水平,以及引流淋巴结中CD4+T细胞亚群比例。结果:在mc903诱导的ad样皮肤炎症模型中,与WT组相比,cKO组ad样皮肤病变较轻,皮肤增厚减轻,表皮厚度降低[(45.4±16.3)μm vs(59.6±2.9)μm],水肿减轻,SCORAD评分较低。皮损组织中IL-4 mRNA表达量较低[(0.7±0.1)vs(1.0±0.1)],FLG和IL-10 mRNA表达量较高[分别为(2.7±1.3)vs(1.0±0.1)和(1.4±0.3)vs(1.0±0.1)](均PPP>0.05)。结论:CD4+T细胞特异性缺失Mettl3可调节IL-4、IL-10和FLG的表达,改变Th2/Treg细胞比例,从而减轻mc903诱导的小鼠ad样皮炎。
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引用次数: 0
[Call for attention on evaluation of bone quality based on three-dimensional interconnected bone trabecular network in radiology]. [呼吁在放射学中重视基于三维互联骨小梁网络的骨质量评价]。
Q3 Medicine Pub Date : 2025-12-16 DOI: 10.3760/cma.j.cn112137-20250818-02111
P Zhang, J Li, W M Guan, S F Li, W B Xia, Z C Wang

Bone trabeculae are key components of bone microstructure, and their complex three-dimensional interconnected microarchitecture is closely related to bone mechanical properties. Traditional imaging studies have been mostly limited to two-dimensional morphological analysis of bone trabeculae, with insufficient attention paid to their interconnected topology, making it difficult to comprehensively reflect bone quality characteristics. The development of ultra-high resolution CT (U-HRCT) technology has brought revolutionary breakthroughs to three-dimensional imaging of bone microstructure. Its spatial resolution can reach up to 50 μm, enabling clear visualization of the three-dimensional structure of bone trabeculae and providing a technical foundation for in vivo assessment of the interconnected trabecular network. Placing emphasis on imaging assessment of bone quality based on three-dimensional interconnected bone microstructure is of great significance for innovating the diagnosis and treatment paradigm of osteoporosis and improving the accuracy of fracture risk prediction. On the basis of systematically reviewing research progress on the three-dimensional interconnected microarchitecture of bone trabeculae, this article focuses on commenting on the technical advantages of U-HRCT in bone microstructure imaging, analyzes the equipment and technical feasibility of evaluation based on the three-dimensional interconnected trabecular network, proposes developing new pathways for bone quality imaging assessment, constructs novel imaging parameters that reflect interconnected topological features, and establishes new bone quality assessment models by integrating multi-level information. It also points out current challenges, including lack of standardization, lengthy imaging durations, and complex data processing, and emphasizes that clinical translation still requires multidisciplinary integration and collaborative advancement across endocrinology, orthopedics, radiomics, biomechanics, and AI.

骨小梁是骨微观结构的关键组成部分,其复杂的三维互联微结构与骨力学性能密切相关。传统的影像学研究多局限于骨小梁的二维形态分析,对其相互联系的拓扑结构关注不足,难以全面反映骨质量特征。超高分辨率CT (U-HRCT)技术的发展为骨微观结构三维成像带来了革命性的突破。其空间分辨率可达50 μm,可清晰显示骨小梁的三维结构,为骨小梁互联网络的体内评估提供技术基础。重视基于三维互联骨微观结构的骨质量影像学评估,对于创新骨质疏松症的诊疗模式,提高骨折风险预测的准确性具有重要意义。本文在系统回顾骨小梁三维互联微结构研究进展的基础上,重点评述了U-HRCT在骨微结构成像中的技术优势,分析了基于三维互联小梁网络的评估设备及技术可行性,提出了开发骨质量成像评估新途径。构建反映互联拓扑特征的新型成像参数,整合多层次信息建立新的骨质量评估模型。它还指出了目前的挑战,包括缺乏标准化,成像时间长,数据处理复杂,并强调临床翻译仍然需要多学科整合和协作推进,包括内分泌学,骨科,放射组学,生物力学和人工智能。
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引用次数: 0
[Expert consensus on the standardized application of emulated target trials in clinical research (2025 edition)]. [关于在临床研究中规范应用模拟靶试验的专家共识(2025年版)]。
Q3 Medicine Pub Date : 2025-12-16 DOI: 10.3760/cma.j.cn112137-20250722-01821

The emulated target trial (TTE) is a real-world data-based research approach that seeks to emulate randomized controlled trials within observational datasets to enable relatively high-quality causal inference. In recent years, with the accumulation of medical big data and real-world cohort data, an increasing number of clinical studies have adopted TTE designs following the principles of randomized controlled trials. However, the methodological rigor and quality of such studies remain uneven. In this context, a multidisciplinary group composed of the Rehabilitation Big Data Working Committee of Chinese Association of Rehabilitation Medicine and experts and scholars from institutions across China-with expertise in clinical medicine, epidemiology and biostatistics, research methodology, evidence-based medicine, and data science-conducted extensive literature reviews and multiple rounds of expert consultation and discussion. This process culminated in the development of the Expert Consensus on the Standardized Application of Emulated Target Trials in Clinical Research (2025 edition). This consensus explicitly proposes 17 recommendations, systematically defining the concept, applicable scenarios, and core components of TTE, and comprehensively addressing key methodological aspects of TTE studies, including selection of data sources, new-user design, determination of time zero, and choice of post-hoc randomization methods. It fills an important gap in China's methodological standards for TTE applications, offering scientific guidance for the rigorous implementation of TTE designs and making a meaningful contribution to the advancement of clinical research.

模拟目标试验(TTE)是一种基于真实世界数据的研究方法,旨在模拟观察数据集中的随机对照试验,以实现相对高质量的因果推理。近年来,随着医学大数据和现实世界队列数据的积累,越来越多的临床研究采用了遵循随机对照试验原则的TTE设计。然而,这些研究方法的严谨性和质量仍然参差不齐。在此背景下,由中国康复医学协会康复大数据工作委员会和来自全国各机构的临床医学、流行病学与生物统计学、研究方法学、循证医学、数据科学等方面的专家学者组成的多学科小组开展了广泛的文献综述和多轮专家咨询和讨论。这一过程最终形成了《模拟靶试验在临床研究中的标准化应用专家共识》(2025年版)。该共识明确提出了17项建议,系统地定义了TTE的概念、适用场景和核心组成部分,并全面解决了TTE研究的关键方法学方面的问题,包括数据源的选择、新用户设计、时间零点的确定和事后随机化方法的选择。它填补了中国TTE应用方法学标准的重要空白,为TTE设计的严格实施提供了科学指导,为推进临床研究做出了有意义的贡献。
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引用次数: 0
[Expert consensus on neurosurgical robot-assisted deep brain stimulation surgery (2025 edition)]. 【神经外科机器人辅助深部脑刺激手术专家共识(2025年版)】。
Q3 Medicine Pub Date : 2025-12-12 DOI: 10.3760/cma.j.cn112137-20251014-02648

Robot-assisted deep brain stimulation (DBS) surgical systems in neurosurgery have demonstrated significant advantages in enhancing operative precision, reducing complications, and improving clinical outcomes. With advancements in robot-assisted surgical systems and evolving surgical techniques, coupled with their wider adoption in DBS procedures, there is a growing need to further refine and standardize surgical workflows and technical details. This consensus specifically focuses on robot-assisted DBS surgery. Through proposing recommendation questions, summarizing and evaluating evidence, formulating recommendations, and incorporating expert discussions and clinical practice, eight recommendations were developed covering aspects such as indications, preoperative preparation, surgical planning, registration, anesthesia, key operative steps, and postoperative assessment. The aim is to enhance surgical precision and safety, improve patient outcomes, comprehensively present the latest research progress in robot-assisted DBS surgery, and integrate the collective expertise and opinions of experts in the field, thereby providing guidance for the clinical practice of DBS surgery.

在神经外科中,机器人辅助脑深部刺激(DBS)手术系统在提高手术精度、减少并发症和改善临床结果方面具有显著的优势。随着机器人辅助手术系统的进步和手术技术的发展,再加上它们在DBS手术中的广泛应用,进一步完善和标准化手术工作流程和技术细节的需求越来越大。这一共识特别关注机器人辅助DBS手术。通过提出推荐问题、总结和评估证据、制定建议、结合专家讨论和临床实践,形成8项建议,涵盖适应证、术前准备、手术计划、挂号、麻醉、关键手术步骤、术后评估等方面。旨在提高手术精度和安全性,改善患者预后,全面介绍机器人辅助DBS手术的最新研究进展,整合该领域专家的集体专业知识和意见,为DBS手术的临床实践提供指导。
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引用次数: 0
[Analysis of related factors for intestinal contents refluxing into the bile duct after endoscopic retrograde biliary drainage]. 【内镜逆行胆道引流术后肠内容物返流到胆管的相关因素分析】。
Q3 Medicine Pub Date : 2025-12-02 DOI: 10.3760/cma.j.cn112137-20250714-01731
H L Zhang, C Zhang, C Qiu, B S Zhang, A H Huang, H Hu, Y L Yang

Objective: To analyze the related factors for intestinal contents refluxing into the biliary tract following endoscopic retrograde biliary drainage (ERBD). Methods: A total of 620 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) to remove biliary stents and perform biliary tract cleaning at the Shanghai East Hospital Gallstone Disease Center from March 2019 to October 2024 were included in this study. Patients were divided into a case group and a control group based on the presence or absence of chyme-fibrin reflux into the biliary tract. Clinical data were collected for all patients, and univariate and multivariate logistic regression analyses were performed to identify related factors for intestinal contents reflux into the biliary tract. Results: A total of 620 patients were included: 397 in the control group, aged 61.0 (51.0, 71.0) years, with 198 males; and 223 in the case group, aged 62.0 (51.0, 70.0) years, with 89 males. The control group had a longer duration of biliary stent placement [3.0 (2.1, 3.5) vs 2.6 (1.8, 3.2) months], a higher proportion of male patients [49.9% (198/397) vs 39.9% (89/223)], history of ERCP procedures [16.4% (65/397) vs 10.3% (23/223)], and hypertension [36.0% (143/397) vs 26.5% (59/223)] compared with the case group (all P>0.05). The proportion of pancreaticobiliary maljunction (PBM)in the case group was higher than that in the control group [10.8% (24/223) vs 4.8% (19/397), P=0.005]. The incidence of endoscopic sphincterotomy (EST) [82.5% (184/223) vs 75.3% (299/397)] and endoscopic papillary balloon dilatation (EPBD) [94.5% (207/223) vs 87.1% (343/397)] was higher in the case group than in the control group (both P<0.05); the total number of biliary stents placed was higher in the control group (10.1% vs 4.9%) than in the case group (P=0.023). Multivariate logistic regression analysis identified PBM (OR=2.00, 95%CI: 1.05-3.81),female gender (OR=1.45, 95%CI: 1.02-2.07), duration of biliary stent placement (OR=0.87, 95%CI: 0.80-0.96) and hypertension (OR=0.61, 95%CI: 0.42-0.89) as related factors for post-ERBD intestinal contents reflux into the biliary tract. Conclusion: Female gender and PBM are related factors for post-ERBD intestinal contents reflux into the biliary tract.

目的:分析内镜下胆道逆行引流术(ERBD)后肠内容物返流到胆道的相关因素。方法:选取2019年3月至2024年10月在上海东方医院胆结石疾病中心行内窥镜逆行胆管造影(ERCP)取下胆道支架并行胆道清扫术的620例患者。根据食糜纤维蛋白返流进入胆道的存在与否,将患者分为病例组和对照组。收集所有患者的临床资料,并进行单因素和多因素logistic回归分析,以确定肠内容物反流到胆道的相关因素。结果:共纳入620例患者:对照组397例,年龄61.0(51.0,71.0)岁,其中男性198例;病例组223例,年龄62.0(51.0,70.0)岁,男性89例。与病例组相比,对照组胆道支架置入时间更长[3.0 (2.1,3.5)vs 2.6(1.8, 3.2)个月],男性患者比例更高[49.9% (198/397)vs 39.9% (89/223)], ERCP手术史[16.4% (65/397)vs 10.3%(23/223)],高血压[36.0% (143/397)vs 26.5%(59/223)](均P < 0.05)。病例组胰胆管畸形(PBM)比例高于对照组[10.8% (24/223)vs 4.8% (19/397), P=0.005]。病例组的内镜下括约肌切开术(EST)[82.5%(184/223)对75.3%(299/397)]和内镜下乳头球囊扩张术(EPBD)[94.5%(207/223)对87.1%(343/397)]的发生率均高于对照组(PP均=0.023)。多因素logistic回归分析发现PBM (OR=2.00, 95%CI: 1.05-3.81)、女性(OR=1.45, 95%CI: 1.02-2.07)、胆道支架置入时间(OR=0.87, 95%CI: 0.80-0.96)和高血压(OR=0.61, 95%CI: 0.42-0.89)是erbd后肠内容物返流到胆道的相关因素。结论:女性和PBM是erbd后肠内容物返流到胆道的相关因素。
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引用次数: 0
[The effect of different coronary artery flow isolation techniques in off-pump coronary artery bypass grafting]. 不同冠状动脉血流隔离技术对非体外循环冠状动脉搭桥术的影响
Q3 Medicine Pub Date : 2025-12-02 DOI: 10.3760/cma.j.cn112137-20250621-01515
L H Guo, J C Zhang, Z X Liang, Y Pei, S Hao

Objective: To explore the clinical effect of different coronary artery flow isolation methods in off-pump coronary artery bypass grafting (OPCABG). Methods: A total of 60 patients who accepted OPCABG in the Department of Cardiovascular Surgery, the First Affiliated Hospital of Zhengzhou University from June 2021 to June 2024 were randomly divided into three groups by computer. The different coronary flow isolation methods were used in three groups. The coronary artery was occluded with tourniquets in the occlusion group (n=20). The coronary artery was shunted with shunt in the shunt group (n=20). The coronary artery was selectively shunted or occluded according to the different blood flow conditions of each target vessel in the combined group (n=20). The anastomosis time and the amount of bleeding were observed and compared. The serum levels of cardiac troponin T (cTnT) and N-terminal pro B-type natriuretic peptide (NT-ProBNP) were detected after eight hours of operation. Results: Among the 60 patients with coronary artery disease, 48 patients were male and 12 patients were female. The anastomotic time of each anastomosis in the shunt group was longer than that in the occlusion group and the combined group [(18.4±2.8) min vs (12.3±2.2) min, (14.3±2.9) min, both P<0.017]. There was no statistically significant difference in anastomotic time between the occlusion group and the combined group (P=0.176). Postoperative serum cTnT in the occlusion group was higher than that in the shunt group and the combined group [(0.28±0.07) μg/L vs (0.16±0.03) μg/L, (0.17±0.04) μg/L, both P<0.017]. There was no statistically significant difference in postoperative serum cTnT between the shunt group and the combined group (P=0.152). Postoperative serum NT-ProBNP in the combined group was lower than that in the occlusion group and the shunt group [(254±27) ng/L vs (481±19) ng/L, (373±42) ng/L, both P<0.017]. Postoperative serum NT-ProBNP in the shunt group was lower than that in the occlusion group [(373±42) ng/L vs (481±19) ng/L, P=0.001]. There were no significantly differences in the amount of bleeding among the three groups (P=0.191). Conclusion: The selected method of occlusion or shunting depending on the flow condition of target coronary artery in OPCABG can decrease anastomosis time and myocardial injury.

目的:探讨非体外循环冠状动脉旁路移植术中不同冠状动脉血流隔离方法的临床效果。方法:选取2021年6月至2024年6月郑州大学第一附属医院心血管外科行OPCABG的患者60例,通过计算机随机分为3组。三组采用不同的冠状动脉血流隔离方法。闭塞组用止血带闭塞冠状动脉(n=20)。分流术组冠状动脉分流术(n=20)。联合组根据各靶血管血流情况的不同,选择性分流或闭塞冠状动脉(n=20)。观察吻合时间和出血量,并进行比较。术后8 h检测血清心肌肌钙蛋白T (cTnT)和n端前b型利钠肽(NT-ProBNP)水平。结果:60例冠心病患者中,男性48例,女性12例。分流组各吻合时间均长于闭塞组和联合组[(18.4±2.8)min vs(12.3±2.2)min,(14.3±2.9)min,两者PP=0.176]。闭塞组术后血清cTnT高于分流组和联合组[(0.28±0.07)μg/L vs(0.16±0.03)μg/L,(0.17±0.04)μg/L, PP均=0.152]。联合组术后血清NT-ProBNP低于闭塞组和分流组[(254±27)ng/L vs(481±19)ng/L,(373±42)ng/L, PP均=0.001]。三组患者出血量比较差异无统计学意义(P=0.191)。结论:OPCABG中根据靶冠状动脉血流情况选择闭塞或分流的方法可缩短吻合时间,减少心肌损伤。
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引用次数: 0
[Comprehensive bioinformatics analysis and machine learning to investigate the regulatory mechanism and clinical value of secreted phosphoprotein 1 gene in lung squamous cell carcinoma]. [综合生物信息学分析与机器学习探讨分泌磷酸化蛋白1基因在肺鳞癌中的调控机制及临床价值]。
Q3 Medicine Pub Date : 2025-12-02 DOI: 10.3760/cma.j.cn112137-20250901-02267
L Shi, Y D Xu, J Liu, X D Zhu, Y Zhang, H N Jiang, Q Y Hong
<p><p><b>Objective:</b> This study aimed to comprehensively investigate the regulatory mechanism and clinical value of secreted phosphoprotein 1 (SPP1) in the three-stage progression of "smoking-chronic obstructive pulmonary disease (COPD)-carcinogenesis" in lung squamous cell carcinoma (LUSC) through integrated bioinformatics analysis and machine learning. <b>Methods:</b> The datasets for the three stages of LUSC were downloaded from the Gene Expression Omnibus (GEO) database, including GSE18385 (containing lung tissue samples from 31 healthy smokers and 21 healthy non-smokers), GSE38974 (containing lung tissue samples from 23 smoking COPD patients and 9 healthy smokers), and GSE12472 (containing lung tissue samples from 18 LUSC patients with COPD and 17 smoking COPD patients). The Cancer Genome Atlas (TCGA)-LUSC dataset (comprising 504 samples, including lung tissue samples from LUSC patients and their matched normal lung tissue samples) was downloaded from TCGA database for further analysis. Samples and follow-up information from 208 non-small cell lung cancer patients who underwent radical resection and mediastinal lymph node dissection at Zhongshan Hospital, Fudan University in 2005 were selected for prognostic analysis and validation. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to screen stage-specific module genes. Differentially expressed genes (DEGs) were identified through differential expression analysis. The CIBERSORT algorithm and Gene Set Enrichment Analysis (GSEA) were used to characterize the immune microenvironment. Eight machine learning algorithms and protein-protein interaction (PPI) network analysis were combined to screen for core regulatory targets. <b>Results:</b> Results from WGCNA and differential analysis of the GEO datasets indicated that SPP1 is consistently highly expressed across the three stages of LUSC. Analysis of the TCGA-LUSC dataset further verified that the relative expression level of SPP1 in lung tissues of LUSC patients was significantly higher than in normal lung tissues (9.13±2.01 vs 4.68±1.64, <i>P</i><0.001). Furthermore, SPP1 expression was significantly higher in patients with TNM stage Ⅲ than in those with stage Ⅱ (9.59±2.09 vs 8.80±2.15, <i>P</i>=0.045). Male LUSC patients with high smoking exposure exhibited higher SPP1 expression levels than those with low smoking exposure (9.56±2.23 vs 8.60±2.04, <i>P</i>=0.032). Survival prognosis analysis revealed that among male patients, the difference in median overall survival (OS) between the high SPP1 expression group and the low expression group was statistically significant [2.90 (95%<i>CI</i>: 2.11-4.64) years vs 4.69 (95%<i>CI</i>: 2.95-7.34) years, <i>P</i>=0.032). Data validation from Zhongshan Hospital, Fudan University, also showed that the 5-year survival rate of lung cancer patients with high SPP1 expression was lower than that of patients with low SPP1 expression (49.3% vs 62.6%, <i>P</i>=0.042). Results from the CIBERSORT
目的:本研究旨在通过综合生物信息学分析和机器学习,全面探讨分泌磷酸化蛋白1 (SPP1)在肺鳞状细胞癌(LUSC)“吸烟-慢性阻塞性肺疾病(COPD)-癌变”三期进展中的调控机制及临床价值。方法:从Gene Expression Omnibus (GEO)数据库中下载LUSC三个阶段的数据集,包括GSE18385(包含31名健康吸烟者和21名健康非吸烟者的肺组织样本)、GSE38974(包含23名吸烟COPD患者和9名健康吸烟者的肺组织样本)和GSE12472(包含18名LUSC合并COPD患者和17名吸烟COPD患者的肺组织样本)。从TCGA数据库下载癌症基因组图谱(TCGA)-LUSC数据集(包括504个样本,包括LUSC患者的肺组织样本及其匹配的正常肺组织样本)进行进一步分析。选取2005年在复旦大学中山医院行根治和纵隔淋巴结清扫术的208例非小细胞肺癌患者的样本和随访资料进行预后分析和验证。加权基因共表达网络分析(Weighted Gene Co-expression Network Analysis, WGCNA)用于筛选阶段特异性模块基因。通过差异表达分析鉴定差异表达基因(DEGs)。利用CIBERSORT算法和基因集富集分析(GSEA)表征免疫微环境。结合八种机器学习算法和蛋白质-蛋白质相互作用(PPI)网络分析来筛选核心调控靶点。结果:来自WGCNA和GEO数据集的差异分析结果表明,SPP1在LUSC的三个阶段一致高表达。TCGA-LUSC数据集分析进一步验证了SPP1在LUSC患者肺组织中的相对表达水平显著高于正常肺组织(9.13±2.01 vs 4.68±1.64,PP=0.045)。男性LUSC高吸烟暴露者SPP1表达水平高于低吸烟暴露者(9.56±2.23 vs 8.60±2.04,P=0.032)。生存预后分析显示,在男性患者中,SPP1高表达组与低表达组的中位总生存期(OS)差异有统计学意义[2.90 (95%CI: 2.11 ~ 4.64)年vs 4.69 (95%CI: 2.95 ~ 7.34)年,P=0.032]。复旦大学中山医院的数据验证也显示,SPP1高表达肺癌患者的5年生存率低于SPP1低表达肺癌患者(49.3% vs 62.6%, P=0.042)。结论:SPP1可能通过抑制NTN1或激活CX3CL1介导M2巨噬细胞极化,从而促进LUSC的进展,提示SPP1可能作为高危男性吸烟者的预后生物标志物和治疗靶点。
{"title":"[Comprehensive bioinformatics analysis and machine learning to investigate the regulatory mechanism and clinical value of secreted phosphoprotein 1 gene in lung squamous cell carcinoma].","authors":"L Shi, Y D Xu, J Liu, X D Zhu, Y Zhang, H N Jiang, Q Y Hong","doi":"10.3760/cma.j.cn112137-20250901-02267","DOIUrl":"https://doi.org/10.3760/cma.j.cn112137-20250901-02267","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; This study aimed to comprehensively investigate the regulatory mechanism and clinical value of secreted phosphoprotein 1 (SPP1) in the three-stage progression of \"smoking-chronic obstructive pulmonary disease (COPD)-carcinogenesis\" in lung squamous cell carcinoma (LUSC) through integrated bioinformatics analysis and machine learning. &lt;b&gt;Methods:&lt;/b&gt; The datasets for the three stages of LUSC were downloaded from the Gene Expression Omnibus (GEO) database, including GSE18385 (containing lung tissue samples from 31 healthy smokers and 21 healthy non-smokers), GSE38974 (containing lung tissue samples from 23 smoking COPD patients and 9 healthy smokers), and GSE12472 (containing lung tissue samples from 18 LUSC patients with COPD and 17 smoking COPD patients). The Cancer Genome Atlas (TCGA)-LUSC dataset (comprising 504 samples, including lung tissue samples from LUSC patients and their matched normal lung tissue samples) was downloaded from TCGA database for further analysis. Samples and follow-up information from 208 non-small cell lung cancer patients who underwent radical resection and mediastinal lymph node dissection at Zhongshan Hospital, Fudan University in 2005 were selected for prognostic analysis and validation. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to screen stage-specific module genes. Differentially expressed genes (DEGs) were identified through differential expression analysis. The CIBERSORT algorithm and Gene Set Enrichment Analysis (GSEA) were used to characterize the immune microenvironment. Eight machine learning algorithms and protein-protein interaction (PPI) network analysis were combined to screen for core regulatory targets. &lt;b&gt;Results:&lt;/b&gt; Results from WGCNA and differential analysis of the GEO datasets indicated that SPP1 is consistently highly expressed across the three stages of LUSC. Analysis of the TCGA-LUSC dataset further verified that the relative expression level of SPP1 in lung tissues of LUSC patients was significantly higher than in normal lung tissues (9.13±2.01 vs 4.68±1.64, &lt;i&gt;P&lt;/i&gt;&lt;0.001). Furthermore, SPP1 expression was significantly higher in patients with TNM stage Ⅲ than in those with stage Ⅱ (9.59±2.09 vs 8.80±2.15, &lt;i&gt;P&lt;/i&gt;=0.045). Male LUSC patients with high smoking exposure exhibited higher SPP1 expression levels than those with low smoking exposure (9.56±2.23 vs 8.60±2.04, &lt;i&gt;P&lt;/i&gt;=0.032). Survival prognosis analysis revealed that among male patients, the difference in median overall survival (OS) between the high SPP1 expression group and the low expression group was statistically significant [2.90 (95%&lt;i&gt;CI&lt;/i&gt;: 2.11-4.64) years vs 4.69 (95%&lt;i&gt;CI&lt;/i&gt;: 2.95-7.34) years, &lt;i&gt;P&lt;/i&gt;=0.032). Data validation from Zhongshan Hospital, Fudan University, also showed that the 5-year survival rate of lung cancer patients with high SPP1 expression was lower than that of patients with low SPP1 expression (49.3% vs 62.6%, &lt;i&gt;P&lt;/i&gt;=0.042). Results from the CIBERSORT","PeriodicalId":24023,"journal":{"name":"Zhonghua yi xue za zhi","volume":"105 44","pages":"4065-4075"},"PeriodicalIF":0.0,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Genomic profiles of primary and acquired MET mutations in NSCLC and the impact of co-mutations on treatment outcomes]. [NSCLC原发性和获得性MET突变的基因组图谱以及共突变对治疗结果的影响]。
Q3 Medicine Pub Date : 2025-12-02 DOI: 10.3760/cma.j.cn112137-20250924-02479
Y L Long, K F Huang, S S Huang, Y H Yan, Y C Xia, F F Liu, T Q Chu, Q Chu
<p><p><b>Objective:</b> To analyze the mutational landscape of primary and acquired mesenchymal to epithelial transition factor (MET) mutations in non-small cell lung cancer (NSCLC) and investigate the impact of co-mutations on the therapeutic efficacy. <b>Methods:</b> A total of 316 pathologically confirmed NSCLC patients with MET gene mutations treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Shanghai Chest Hospital, Shanghai Jiao Tong University, between January 2012 and May 2023 were retrospectively enrolled. Demographics, clinicopathological characteristics, and treatment outcomes were collected. Patients were classified into primary MET mutation and acquired MET mutation groups according to the timing of mutation occurrence, and intergroup differences were compared. Treatment responses were evaluated according to the Response Evaluation Criteria in Solid Tumors criteria. Follow-up data on efficacy and progression-free survival (PFS) were collected through telephone calls and medical record review. The follow-up continued until January 2024. Kaplan-Meier survival curves were generated, and log-rank tests were used to compare PFS between patients with different co-mutations receiving tyrosine kinase inhibitor (TKI) or immune checkpoint inhibitor (ICI) therapy. <b>Results:</b> Compared to the acquired mutation group, patients with primary MET mutations were significantly older[median (<i>Q</i><sub>1</sub>, <i>Q</i><sub>3</sub>) age: 65 (58, 71) vs 59 (51, 64) years; <i>P</i><0.001], had a higher proportion of males [62.4% (141/226) vs 48.9% (44/90), <i>P</i>=0.028] and a higher proportion of never-smokers [48.7% (110/226) vs 30% (27/90), <i>P</i>=0.002]. In the primary mutation group, TP53 was the most common co-mutation gene (43%, 51/118), followed by EGFR (32%, 38/118) and KRAS (9%, 11/118). In the acquired mutation group, 89% (69/73) of patients retained the EGFR mutation. Aside from EGFR, the most common co-mutation genes were TP53 (63%, 46/73) and CDK4 (12%, 9/73). Among the 62 patients treated with MET-TKI, those with concurrent EGFR-sensitive mutations had a median PFS of 3.1 (95%<i>CI</i>: 2.4-7.2) months, significantly shorter than that of EGFR wild-type patients [18.2 (95%<i>CI</i>: 9.2-22.1) months, <i>P</i><0.001]. Patients with TP53 co-mutations had a median PFS of 7.5 (95%<i>CI</i>: 6.4-not reached) months, which was significantly longer than TP53 wild-type patients [3.4 (95%<i>CI</i>: 1.8-4.3) months, <i>P</i>=0.035]. Among the 57 patients treated with ICI, those with EGFR-sensitive mutations had a median PFS of 5.3 (95%<i>CI</i>: 2.0-8.2) months, which was significantly shorter than EGFR wild-type patients [10.4 (95%<i>CI</i>: 5.2-not reached) months, <i>P</i>=0.027]. Patients with TP53 co-mutations had a median PFS of 5.9 (95%<i>CI</i>: 3.8-20.4) months, which was longer than TP53 wild-type patients [3.0 (95%<i>CI</i>: 2.0-4.5) months], although the difference was not stati
目的:分析非小细胞肺癌(NSCLC)原发性和获得性间充质上皮转化因子(MET)突变的突变格局,探讨共突变对治疗效果的影响。方法:回顾性分析2012年1月至2023年5月在华中科技大学同济医学院同济医院和上海交通大学上海胸科医院就诊的经病理证实MET基因突变的非小细胞肺癌患者316例。收集人口统计学、临床病理特征和治疗结果。根据突变发生时间将患者分为原发性MET突变组和获得性MET突变组,比较组间差异。根据实体瘤标准中的反应评价标准对治疗反应进行评价。通过电话和病历回顾收集疗效和无进展生存期(PFS)的随访数据。后续工作一直持续到2024年1月。生成Kaplan-Meier生存曲线,并使用log-rank检验比较不同共突变患者接受酪氨酸激酶抑制剂(TKI)或免疫检查点抑制剂(ICI)治疗的PFS。结果:与获得性突变组相比,原发性MET突变患者明显更老[中位年龄(Q1, Q3): 65岁(58,71)vs 59岁(51,64);PP=0.028],从不吸烟者的比例更高[48.7% (110/226)vs 30% (27/90), P=0.002]。在原发性突变组中,TP53是最常见的共突变基因(43%,51/118),其次是EGFR(32%, 38/118)和KRAS(9%, 11/118)。在获得性突变组中,89%(69/73)的患者保留了EGFR突变。除EGFR外,最常见的共突变基因是TP53(63%, 46/73)和CDK4(12%, 9/73)。在接受MET-TKI治疗的62例患者中,同时存在EGFR敏感突变的患者的中位PFS为3.1 (95%CI: 2.4-7.2)个月,显著短于EGFR野生型患者[18.2 (95%CI: 9.2-22.1)个月,PCI: 6.4-未达到)个月],显著长于TP53野生型患者[3.4 (95%CI: 1.8-4.3)个月,P=0.035]。在57例接受ICI治疗的患者中,EGFR敏感突变患者的中位PFS为5.3 (95%CI: 2.0-8.2)个月,显著短于EGFR野生型患者[10.4 (95%CI: 5.2-未达到)个月,P=0.027]。TP53共突变患者的中位PFS为5.9 (95%CI: 3.8 ~ 20.4)个月,高于TP53野生型患者的中位PFS [3.0 (95%CI: 2.0 ~ 4.5)个月],但差异无统计学意义(P=0.344)。结论:原发性和获得性MET突变在非小细胞肺癌中表现出不同的基因组特征。在非小细胞肺癌中同时存在EGFR突变的患者在MET-TKI和ICI治疗中获益较少,而在接受MET-TKI治疗时,与TP53野生型非小细胞肺癌患者相比,TP53共突变的患者往往获得更有利的结果。
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引用次数: 0
[Clinical efficacy and safety of Holmium laser combined with balloon dilation in treating benign bile duct columnar stenosis]. 钬激光联合球囊扩张治疗良性胆管柱状狭窄的临床疗效及安全性。
Q3 Medicine Pub Date : 2025-12-02 DOI: 10.3760/cma.j.cn112137-20250912-02374
D X Li, W He, X Dai, K Dong, X C Zhao, F Li, M D Li, Y Y Xu

To evaluate the efficacy and safety of Holmium laser combined with balloon dilation in treating benign bile duct columnar stenosis, a retrospective analysis was performed on the clinical data of 58 patients diagnosed with benign biliary strictures at Sichuan Provincial People's Hospital from October 2019 to October 2022. Among these patients, 31 patients underwent minimally invasive holmium laser combined with balloon dilation treatment as the study group, with an age of (58.3±5.1) years, including 13 males; 27 patients underwent hepatic segment resection as the control group, with an age of (56.3±4.9) years, including 11 males. The median follow-up time was 17.5 months (range: 12-26 months). The study group showed shorter recovery time of gastrointestinal function [(1.0±0.5) vs (3.2±1.0) d], lower medical costs [(1.2±0.2) vs (2.7±0.6) ten thousand yuan], lower incidence of cholangitis [6.5% (2/31) vs 22.2% (6/27)], lower rates of bile leakage [3.2% (1/31) vs 18.5% (5/27)], shorter hospitalization duration [(5.6±0.5) vs (8.4±1.2) d], shorter operative time [(68.5±20.5) vs (145.2±50.5) min], reduced intraoperative blood loss [(5.0±0.4) vs (80.4±17.1) ml], and lower incision infection rate [3.2% (1/31) vs 14.8% (4/27)], and lower recurrence rate of biliary stricture [6.4% (2/31) vs 33.3% (9/27)] compared to the control group (all P<0.05). The study group achieved a higher biliary stricture relief rate than the control group [96.7% (30/31) vs 85.2% (23/27), P=0.037]. The study results indicate that the combination of holmium laser and balloon dilation is effective in treating benign biliary strictures, reduces the incidence of surgical complications and recurrence of biliary strictures, and is safe and reliable, with potential for clinical application and promotion.

为评价钬激光联合球囊扩张治疗良性胆管柱状狭窄的疗效和安全性,回顾性分析2019年10月至2022年10月四川省人民医院诊断为良性胆管狭窄的58例患者的临床资料。其中31例患者行微创钬激光联合球囊扩张治疗为研究组,年龄(58.3±5.1)岁,其中男性13例;对照组行肝段切除术27例,年龄(56.3±4.9)岁,其中男性11例。中位随访时间17.5个月(12-26个月)。研究组胃肠道功能恢复时间较短[(1.0±0.5)vs(3.2±1.0)d],医疗费用较低[(1.2±0.2)vs(2.7±0.6)万元],胆管炎发生率较低[6.5% (2/31)vs 22.2%(6/27)],胆漏率较低[3.2% (1/31)vs 18.5%(5/27)],住院时间较短[(5.6±0.5)vs(8.4±1.2)d],手术时间较短[(68.5±20.5)vs(145.2±50.5)min],术中出血量减少[(5.0±0.4)vs(80.4±17.1)ml],切口感染率[3.2% (1/31)vs . 14.8%(4/27)],胆道狭窄复发率[6.4% (2/31)vs . 33.3%(9/27)]低于对照组(均PP=0.037)。本研究结果提示钬激光联合球囊扩张治疗良性胆道狭窄有效,降低手术并发症及胆道狭窄复发发生率,安全可靠,具有临床应用和推广潜力。
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