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[Diabetic Charcot neuroarthropathy initially misdiagnosed as rheumatoid arthritis and gout: A case report]. [糖尿病Charcot神经关节病最初误诊为类风湿关节炎和痛风1例]。
Q3 Medicine Pub Date : 2025-12-18
Jingyan Gu, Xinyi Li, Jinxia Zhao, Rong Mu

Charcot neuroarthropathy (CN) is a rare but severely disabling complication most commonly seen in patients with longstanding diabetic peripheral neuropathy. CN is characterized by progressive destruction, dislocation, and deformity of the foot and ankle joints, often accompanied by altered biomechanics, chronic ulceration, secondary infection, and, in advanced cases, a high risk of amputation or even mortality. The early clinical presentation of CN is frequently atypical, with mild or painless swelling, warmth, and erythema due to underlying sensory deficits, which can easily lead to misdiagnosis as other rheumatic or autoimmune joint disorders such as rheumatoid arthritis and gout. In this report, we present the case of a 60-year-old woman with a 12-year history of type 2 diabetes mellitus who developed persistent swelling and pain in her left ankle for eight months, along with progressive numbness in her left foot for six months. Her initial laboratory and imaging findings suggested a diagnosis of rheumatoid arthritis combined with gout, resulting in the administration of anti-rheumatic and uric acid-lowering therapies, which proved ineffective. Further diagnostic workup, including advanced imaging modalities, neuroelec-trophysiological testing, and synovial biopsy, ultimately confirmed the diagnosis of diabetic Charcot neuroarthropathy, revealing severe joint dislocation, bone fragmentation, and extensive osteolysis. The patient received comprehensive management, including strict glycemic control, anti-osteoporosis treatment, neurotrophic support, and ultimately underwent left ankle multi-joint fusion surgery. During postoperative follow-up, the patient demonstrated significant improvement in limb function, with no recurrence of ulcers or infection. This case highlights the importance of considering CN in diabetic patients with unilateral, painless joint swelling, deformity, and sensory disturbance. Accurate differential diagnosis from rheu-matic and autoimmune diseases, early recognition, and standardized intervention are crucial to prevent irreversible deformity and reduce the risk of amputation, ultimately improving patient outcomes. Early multidisciplinary management and individualized treatment strategies play a key role in optimizing prognosis for patients with diabetic CN.

Charcot神经关节病(CN)是一种罕见但严重致残的并发症,最常见于长期糖尿病周围神经病变患者。CN的特征是足部和踝关节的进行性破坏、脱位和畸形,常伴有生物力学改变、慢性溃疡、继发感染,晚期患者截肢甚至死亡的风险很高。CN的早期临床表现通常是非典型的,由于潜在的感觉缺陷,有轻微或无痛的肿胀、发热和红斑,这很容易导致误诊为其他风湿性或自身免疫性关节疾病,如类风湿关节炎和痛风。在本报告中,我们报告了一名60岁的2型糖尿病患者,她患有12年的2型糖尿病病史,左脚踝持续肿胀和疼痛8个月,同时左脚进行性麻木6个月。她最初的实验室和影像学检查结果显示诊断为类风湿关节炎合并痛风,因此给予抗风湿和降尿酸治疗,但证明无效。进一步的诊断检查,包括先进的影像学检查、神经电生理检查和滑膜活检,最终证实了糖尿病性Charcot神经关节病的诊断,发现严重的关节脱位、骨碎裂和广泛的骨溶解。患者接受全面治疗,包括严格控制血糖、抗骨质疏松治疗、神经营养支持,最终行左踝关节多关节融合手术。术后随访期间,患者肢体功能明显改善,无溃疡或感染复发。本病例强调了在伴有单侧、无痛性关节肿胀、畸形和感觉障碍的糖尿病患者中考虑CN的重要性。风湿病和自身免疫性疾病的准确鉴别诊断、早期识别和标准化干预对于预防不可逆畸形和降低截肢风险,最终改善患者预后至关重要。早期多学科管理和个体化治疗策略对优化糖尿病合并胆管癌患者的预后起着关键作用。
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引用次数: 0
[Effect of aquaporin 5 on TLR4/MyD88/NF-κB signaling pathway in Sjögren syndrome rats]. [水通道蛋白5对Sjögren综合征大鼠TLR4/MyD88/NF-κB信号通路的影响]。
Q3 Medicine Pub Date : 2025-10-18
Lixiu Zhu, Renli Chen, Sujuan Zhou, Ye Lin, Yirong Tang, Zhen Ye

Objective: To investigate the effect of aquaporin 5 (AQP5) on Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor κB (NF-κB) signaling pathway in Sjögren syndrome (SS) rats.

Methods: The SS gene expression data sets GSE406611 and GSE84844 were extracted from the Gene Expression Omnibus (GEO), and the AQP5 mRNA expression was analyzed by R software. The rat SS model was constructed. The successfully modeled rats were divided into SS group, SS+NC group, and SS+pc group, 10 rats in each group; and 10 rats were set as Normal group. The rats in the SS+NC group were injected with 10 μg of rno-pcDNA3.1-AQP5-NC at the submandibular gland, subcutaneously every day for 28 days. The rats in the SS+pc group were injected with 10 μg of rno-pcDNA3.1-AQP5 at the submandibular gland, subcutaneously every day for 28 days. The enzyme-linked immunosorbent assay (ELISA) kit was used to detect the content of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the serum. High-throughput sequencing was used to identify the target genes. Quantitative real-time PCR (qPCR) and Western blot were used to detect the mRNA and protein expressions of AQP5, TLR4, MyD88, and NF-κB in the rat submandibular gland tissue.

Results: In the SS dataset GSE406611 and GSE84844, the mRNA expression of AQP5 in SS was significantly reduced. Compared with the Normal group, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS group were significantly increased, the mRNA and protein expressions of AQP5 were significantly decreased. After overexpression of AQP5, the content of TNF-α and IL-1β in the serum, the mRNA and protein expressions of TLR4, MyD88, and NF-κB in the SS+pc group were significantly decreased, the mRNA and protein expressions of AQP5 were significantly increased. The differences were statistically significant (all P < 0.05).

Conclusion: The expression of AQP5 is involved in the progression of SS. Increasing the expression of AQP5 can significantly inhibit inflammatory stress and reduce the pathological damage of submandibular gland tissue. This may be related to the inhibition of TLR4/MyD88/NF-κB conduction.

目的:探讨水通道蛋白5 (AQP5)对Sjögren综合征(SS)大鼠toll样受体4 (TLR4)/髓样分化因子88 (MyD88)/核因子κB (NF-κB)信号通路的影响。方法:从gene expression Omnibus (GEO)中提取SS基因表达数据集GSE406611和GSE84844,用R软件分析AQP5 mRNA的表达。建立大鼠SS模型。将成功造模的大鼠分为SS组、SS+NC组和SS+pc组,每组10只;10只大鼠为正常组。SS+NC组大鼠每天在颌下腺皮下注射rno-pcDNA3.1-AQP5-NC 10 μg,连续28 d。SS+pc组大鼠每天在颌下腺皮下注射rno-pcDNA3.1-AQP5 10 μg,连续28 d。采用酶联免疫吸附试验(ELISA)试剂盒检测血清中肿瘤坏死因子-α (TNF-α)和白细胞介素-1β (IL-1β)的含量。采用高通量测序技术鉴定目的基因。采用实时荧光定量PCR (qPCR)和Western blot检测大鼠颌下腺组织中AQP5、TLR4、MyD88、NF-κB mRNA和蛋白的表达。结果:在SS数据集GSE406611和GSE84844中,AQP5在SS中的mRNA表达量显著降低。与正常组比较,SS组大鼠血清中TNF-α、IL-1β含量显著升高,TLR4、MyD88、NF-κB mRNA和蛋白表达显著升高,AQP5 mRNA和蛋白表达显著降低。过表达AQP5后,SS+pc组大鼠血清中TNF-α、IL-1β含量及TLR4、MyD88、NF-κB mRNA和蛋白表达量显著降低,AQP5 mRNA和蛋白表达量显著升高。差异均有统计学意义(P < 0.05)。结论:AQP5的表达参与了SS的进展,增加AQP5的表达可显著抑制炎症应激,减轻颌下腺组织的病理损伤。这可能与抑制TLR4/MyD88/NF-κB传导有关。
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引用次数: 0
[Comparation of anterior maxilla and whole maxilla clockwise rotation to improve paranasal aesthetic defects of skeletal Class Ⅲ maxillofacial deformity]. [上颌前牙与全颌顺时针旋转改善骨类颌面畸形鼻旁审美缺陷的比较]。
Q3 Medicine Pub Date : 2025-10-18
Fengqi Song, Xinyu Xu, Xiaojing Liu, Zili Li

Objective: To compare the aesthetic effects of anterior maxilla clockwise rotation combined with segmental Le Fort Ⅰ osteotomy and whole maxilla clockwise rotation on improving paranasal concavity in patients with Class Ⅲ maxillofacial deformity.

Methods: A non-randomized controlled trial was designed, and 21 patients diagnosed with skeletal Class Ⅲ maxillofacial deformity were included. In the study, 11 patients in the test group were treated by segmental Le Fort Ⅰ osteotomy combined with anterior maxilla clockwise rotation, and 10 patients in the control group were treated by whole maxilla clockwise rotation. The CBCT and 3D photography of preoperative (T0), 2 weeks postoperative (T1), and 6 months postoperative (T2) were collected respectively, and the three-dimensional cephalometry was carried out. The differences of specific parameters between the two groups were compared by independent sample t-test, including saggital displacement of the cheek mass point (CK) and subalare point (SA), nasolabial angle, occlusal plane angle and labial inclination angle of the upper incisor.

Results: There were no significant differences of the parameters on T0 between the two groups. The average sagittal displacement of the upper incisors of the test group was (-0.71±1.67) mm and smaller than that of control group [(2.26±1.68) mm], t=-4.052, P < 0.05. The average angle of the occlusal plane clockwise rotation of the test group was 1.46°±2.38° and smaller than that of the control group (4.31°±1.83°), t=-3.047, P < 0.05. The angle of anterior maxilla clockwise rotation was 11.73°±2.81° during the surgery. The average saggital displacement of the paranasal soft tissue landmarks of the test group from T0 to T2 was larger than that of the control group [CK point, (4.96±1.18) mm vs. (2.01± 1.50) mm, P < 0.05;SA point, (5.19±1.17) mm vs. (2.69±1.45) mm, P < 0.05]. The labial inclination angle of the upper incisor of the test group was 112.15°±5.40° in T2 and significantly smaller than that of the control group (122.38°±8.83°), t=-3.237, P < 0.05. The nasolabial angle of the test group was 106.54°±12.82° in T2 and significantly larger than that of the control group (93.90°±12.46°), t=2.288, P < 0.05.

Conclusion: Compared with whole maxilla clockwise rotation, anterior maxilla clockwise rotation combined with segmental Le Fort Ⅰ osteotomy can increase the saggital displacement of the paranasal soft tissue, correct labial inclination of the upper incisors and the acute naso-labial angle and better improve the paranasal aesthetic defects in patients with Class Ⅲ maxillofacial deformity with less changing on the saggital orientation of the upper incisors and the occlusal plane angle.

目的:比较上颌前牙顺时针旋转联合节段性Le FortⅠ截骨术与整个上颌顺时针旋转治疗Ⅲ类颌面畸形患者鼻副凹陷的美学效果。方法:设计非随机对照试验,纳入21例骨骼类Ⅲ颌面畸形患者。实验组11例采用Le FortⅠ节段截骨联合前上颌顺时针旋转治疗,对照组10例采用全颌顺时针旋转治疗。分别收集术前(T0)、术后2周(T1)和术后6个月(T2)的CBCT和3D照片,并进行三维头颅测量。采用独立样本t检验比较两组患者颊肿块点(CK)和颌下点(SA)矢状位移、鼻唇角、咬合平面角、上切牙唇倾角等具体参数的差异。结果:两组患者T0指标无显著性差异。试验组上切牙矢状位平均位移为(-0.71±1.67)mm,小于对照组(2.26±1.68)mm, t=-4.052, P < 0.05。试验组牙合平面顺时针旋转的平均角度为1.46°±2.38°,小于对照组(4.31°±1.83°),t=-3.047, P < 0.05。术中上颌前牙顺时针旋转角度为11.73°±2.81°。试验组T0 ~ T2鼻旁软组织标志矢状位平均移位量大于对照组[CK点,(4.96±1.18)mm vs(2.01±1.50)mm, P < 0.05;SA点,(5.19±1.17)毫米和(2.69±1.45)毫米,P < 0.05)。试验组T2时上切牙唇倾角为112.15°±5.40°,显著小于对照组(122.38°±8.83°),t=-3.237, P < 0.05。试验组鼻唇角在T2时为106.54°±12.82°,显著大于对照组(93.90°±12.46°),t=2.288, P < 0.05。结论:与全颌顺时针旋转相比,上颌前牙顺时针旋转联合Le FortⅠ节段截骨术可以增加鼻旁软组织矢状位移,矫正上切牙唇倾和鼻唇角,更好地改善Ⅲ类颌面畸形患者的鼻旁美学缺陷,且上切牙矢状位和咬合平面角变化较小。
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引用次数: 0
[Artificial intelligence in stomatology: Innovations in clinical practice, research, education, and healthcare management]. 【口腔医学中的人工智能:临床实践、研究、教育和医疗管理方面的创新】。
Q3 Medicine Pub Date : 2025-10-18
Xuliang Deng, Mingming Xu, Chenlin DU

In recent years, China has continued to face a high prevalence of oral diseases, along with uneven access to high-quality dental care. Against this backdrop, artificial intelligence (AI), as a data-driven, algorithm-supported, and model-centered technology system, has rapidly expanded its role in transforming the landscape of stomatology. This review summarizes recent advances in the application of AI in stomatology across clinical care, biomedical and materials research, education, and hospital management. In clinical settings, AI has improved diagnostic accuracy, streamlined treatment planning, and enhanced surgical precision and efficiency. In research, machine learning has accelerated the identification of disease biomarkers, deepened insights into the oral microbiome, and supported the development of novel biomaterials. In education, AI has enabled the construction of knowledge graphs, facilitated personalized learning, and powered simulation-based training, driving innovation in teaching methodologies. Meanwhile, in hospital operations, intelligent agents based on large language models (LLMs) have been widely deployed for intelligent triage, structured pre-consultations, automated clinical documentation, and quality control, contributing to more standardized and efficient healthcare delivery. Building on these foundations, a multi-agent collaborative framework centered around an AI assistant for stomatology is gradually emerging, integrating task-specific agents for imaging, treatment planning, surgical navigation, follow-up prediction, patient communication, and administrative coordination. Through shared interfaces and unified knowledge systems, these agents support seamless human-AI collaboration across the full continuum of care. Despite these achievements, the broader deployment of AI still faces challenges including data privacy, model robustness, cross-institution generalization, and interpretability. Addressing these issues will require the development of federated learning frameworks, multi-center validation, causal reasoning approaches, and strong ethical governance. With these foundations in place, AI is poised to move from a supportive tool to a trusted partner in advancing accessible, efficient, and high-quality stomatology services in China.

近年来,中国继续面临口腔疾病的高患病率,以及获得高质量牙科保健的机会不均衡。在此背景下,人工智能作为一种数据驱动、算法支持、以模型为中心的技术体系,在改变口腔医学格局方面的作用迅速扩大。本文综述了人工智能在口腔临床护理、生物医学和材料研究、教育和医院管理等方面的应用进展。在临床环境中,人工智能提高了诊断准确性,简化了治疗计划,提高了手术精度和效率。在研究中,机器学习加速了疾病生物标志物的识别,加深了对口腔微生物组的了解,并支持了新型生物材料的开发。在教育领域,人工智能使知识图谱的构建成为可能,促进了个性化学习,并为基于模拟的培训提供了动力,推动了教学方法的创新。同时,在医院运营中,基于大型语言模型(llm)的智能代理已广泛用于智能分类、结构化预会诊、自动化临床文档和质量控制,有助于实现更标准化和更高效的医疗保健服务。在此基础上,以口腔医学人工智能助手为中心的多智能体协作框架正在逐渐出现,该框架整合了特定任务的智能体,用于成像、治疗计划、手术导航、随访预测、患者沟通和行政协调。通过共享界面和统一的知识系统,这些智能体支持在整个连续护理过程中实现人类与人工智能的无缝协作。尽管取得了这些成就,但人工智能的广泛部署仍然面临着包括数据隐私、模型鲁棒性、跨机构泛化和可解释性在内的挑战。解决这些问题需要开发联邦学习框架、多中心验证、因果推理方法和强有力的道德治理。有了这些基础,人工智能将从一个支持工具转变为一个值得信赖的合作伙伴,在中国推进可获得、高效和高质量的口腔医学服务。
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引用次数: 0
[Development and dissemination of precision medicine approaches in gastric cancer management]. [精准医学在胃癌治疗中的发展与推广]。
Q3 Medicine Pub Date : 2025-10-18
Zhemin Li, Jiafu Ji, Guoxin Li, Ziyu Li, Zhaode Bu, Xiangyu Gao, Di Dong, Lei Tang, Xiaofang Xing, Shuqin Jia, Ting Guo, Lianhai Zhang, Fei Shan, Xin Ji, Anqiang Wang

Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.

胃癌是严重威胁中国公众健康的高发恶性肿瘤,其发病率和死亡率均位居癌症前三位。大多数患者在晚期被诊断出来,导致治疗选择有限和预后不良。为了解决胃癌诊断和治疗中的关键挑战,北京大学肿瘤医院季家富教授领导的研究团队专注于“胃癌管理中精准医学方法的发展和传播”项目。通过一系列高质量的多中心临床研究,团队在围手术期治疗、个体化药物选择、智能无创诊断、新型免疫治疗策略等方面建立了一套新的国际标准。这些进展显著提高了胃癌患者的治疗效果,减少了手术创伤,在诊断、治疗和机制认识方面取得了关键技术突破,系统地改善了胃癌患者的预后。该项目的研究结果具有广泛的国际影响,包括主办了中国首届国际胃癌大会。通过全国推广,推动胃癌精准诊疗学科发展,牵头制定国家卫健委胃癌诊疗指南。该项目获2024年中国医学科学技术奖一等奖,以表彰其成果。
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引用次数: 0
[Impact of palliative care on medication use and medical utilization in patients with advanced cancer]. [姑息治疗对晚期癌症患者用药和医疗利用的影响]。
Q3 Medicine Pub Date : 2025-10-18
Dingyi Chen, Haoxin DU, Yichen Zhang, Yanfei Wang, Wei Liu, Yuanyuan Jiao, Luwen Shi, Xiaodong Guan, Xinpu Lu

Objective: To evaluate the effect of palliative care on drug use, medical service utilization and medical expenditure of patients with advanced cancer.

Methods: A cohort of patients including pal-liative care and standard care was constructed using the medical records of the patients in Peking University Cancer Hospital from 2018 to 2020, and coarsened exact matching was used to match the two groups of patients. The average monthly opioid consumption, hospitalization rate, intensive care unit (ICU) rate and operation rate, and the average monthly total cost were selected to evaluate drug use, medical service utilization and medical expenditure. Chi-square test and Wilcoxon signed rank test were used to compare the differences between the two groups before and after exposure and the change in the palliative care group. The net impact of palliative care on the patients was calculated using the difference-in-differences analysis.

Results: In this study, 180 patients in the palliative care group and 3 101 patients in the stan-dard care group were finally included in the matching, and the matching effect of the two groups was good (L1 < 0.1). Before and after exposure, the average monthly opioid consumption in the palliative care group was significantly higher than that in the standard care group (Before exposure: 0.3 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; After exposure: 0.7 DDD/person-month vs. 0.1 DDD/person-month, P < 0.01; DDD refers to defined daily dose), palliative care significantly increased the average monthly opioid consumption in the patients (0.3 DDD/person-month, P < 0.01). The hospitalization rate (48.9% vs. 74.3%, P < 0.01) and operation rate (3.9% vs. 8.8%, P < 0.01) of the patients in palliative care group were significantly lower than those in standard care group, and the ICU rate became similar between the two groups (1.1% vs. 1.6%, P=0.634). Palliative care significantly reduced the patients ' hospitalization rate (-25.6%, P < 0.01), ICU rate (-4.9%, P < 0.01) and operation rate (-14.5%, P < 0.01). Before and after exposure, the average monthly total costs of pal-liative care group were slightly higher than those of standard care group (Before exposure: 20 092.3 yuan vs. 19 132.8 yuan, P=0.725; After exposure: 9 719.8 yuan vs. 8 818.8 yuan, P=0.165). Palliative care increased the average monthly total cost by 2 208.8 yuan, but it was not statistically significant (P=0.316).

Conclusion: Palliative care can increase the opioid consumption in advanced cancer patients, reduce the rates of hospitalization, ICU and surgery, but has no significant effect on medical expenditure.

目的:评价姑息治疗对晚期癌症患者用药、医疗服务利用及医疗支出的影响。方法:利用2018 - 2020年北京大学肿瘤医院患者病历,构建姑息治疗与标准治疗患者队列,采用粗化精确匹配方法对两组患者进行匹配。选取月平均阿片类药物使用量、住院率、重症监护病房(ICU)使用率和手术率以及月平均总费用来评价用药情况、医疗服务利用情况和医疗支出情况。采用卡方检验和Wilcoxon符号秩检验比较两组暴露前后的差异及姑息治疗组的变化。姑息治疗对患者的净影响采用差异中差异分析来计算。结果:本研究最终将姑息治疗组180例患者和标准治疗组3101例患者纳入匹配,两组匹配效果良好(L1 < 0.1)。暴露前后,姑息治疗组阿片类药物月平均用量显著高于标准治疗组(暴露前:0.3 DDD/人月vs. 0.1 DDD/人月,P < 0.01;暴露后:0.7 DDD/人月vs. 0.1 DDD/人月,P < 0.01; DDD为限定日剂量),姑息治疗显著提高了患者阿片类药物月平均用量(0.3 DDD/人月,P < 0.01)。姑息治疗组患者住院率(48.9% vs. 74.3%, P < 0.01)和手术率(3.9% vs. 8.8%, P < 0.01)均显著低于标准治疗组,两组患者ICU率基本持平(1.1% vs. 1.6%, P=0.634)。姑息治疗显著降低患者住院率(-25.6%,P < 0.01)、ICU率(-4.9%,P < 0.01)和手术率(-14.5%,P < 0.01)。暴露前后,姑息治疗组平均每月总费用略高于标准治疗组(暴露前:20 092.3元对19 132.8元,P=0.725;暴露后:9 719.8元对8 818.8元,P=0.165)。姑息治疗使患者平均每月总费用增加2 208.8元,但差异无统计学意义(P=0.316)。结论:姑息治疗可增加晚期癌症患者阿片类药物的消耗,降低住院率、ICU率和手术率,但对医疗支出无显著影响。
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引用次数: 0
[Expression of lumican protein in serum of patients with rheumatoid arthritis and its correlation with disease and immune activities]. [类风湿关节炎患者血清中lumican蛋白的表达及其与疾病和免疫活动的相关性]。
Q3 Medicine Pub Date : 2025-10-18
Ju Yang, Jing Xu, Juhua Dai, Lianjie Shi
<p><strong>Objective: </strong>To investigate the serum level of lumican (LUM) and its clinical correlation with disease and immune activities in patients with rheumatoid arthritis (RA).</p><p><strong>Methods: </strong>The serum LUM levels in both RA patients and health controls (HCs) were detected by enzyme-linked immunosorbent assay (ELISA). The clinical and laboratory data of the patients were collected. The LUM levels in the patients with different clinical features were analyzed. The correlation between the clinical data, laboratory parameters, and serum LUM levels were also analyzed. Independent samples <i>t</i> test, Spearman correlation were used for statistical analysis. Analysis of variance and Kruskal-Wallis test, the least significant difference (LSD)-<i>t</i> test and Bonferroni correction were used for statistical analysis. The Pearson Chi-square test was used for comparison of the rates between the groups. Statistical significance was set at <i>P</i> < 0.05.</p><p><strong>Results: </strong>The levels of LUM were elevated in the RA patients than in the HCs (<i>P</i> < 0.000 1). Serum LUM levels were correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A (IgA), titers of platelet (PLT) and 28-joint disease activity score (DAS28, all <i>P</i> < 0.05). Next, we compared the serum LUM levels in the RA patients with different characteristics, and no difference was found in serum LUM levels between early-RA and RA, the same to RA with different gender (<i>P</i>>0.05). The levels of serum LUM were elevated in the RF positive patients (<i>P</i> < 0.000 1), and in the RF and anti-CCP positive patients (<i>P</i> < 0.05) than in the RA patients with negative RF whether the anti-CCP was positive. In addition, no differences were found between the RA patients with negative RF whether the anti-CCP was positive (<i>P</i>>0.05). All the levels of serum LUM were elevated in the RA patients with different CRP or ESR than in the HCs (<i>P</i> < 0.05), and the serum LUM levels in the RA patients with elevated ESR and CRP were significantly elevated in those with normal ESR and CRP (<i>P</i> < 0.05). Additionally, the results demonstrated that serum LUM levels were positively associated with RA disease activity, and they were declined in RA sustained remission than those in middle or high disease activity (<i>P</i> < 0.05). Furthermore, no difference was found between the RA patients in remission and HCs (<i>P</i>>0.05). No differences were found in the RA patients with and without complications including interstitial pneumonia disease, Sjögren's syndrome, thyroid gland diseases and osteoporosis (<i>P</i>>0.05). The LUM positivity rates were significantly elevated in the RF positive patients than the RF negative patients in RA (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>LUM, a cyclocitrullinated protein, might be a promising biomarker which could reflect both disease activit
目的:探讨类风湿关节炎(RA)患者血清lumican (LUM)水平及其与疾病及免疫活动的临床相关性。方法:采用酶联免疫吸附试验(ELISA)检测RA患者和健康对照者血清LUM水平。收集患者的临床和实验室资料。分析不同临床特征患者的LUM水平。分析临床资料、实验室参数与血清LUM水平的相关性。采用独立样本t检验、Spearman相关进行统计分析。采用方差分析、Kruskal-Wallis检验、LSD -t检验和Bonferroni校正进行统计学分析。采用Pearson卡方检验比较两组间的发生率。差异有统计学意义,P < 0.05。结果:类风湿关节炎患者中LUM水平明显高于hcc患者(P < 0.0001)。血清LUM水平与红细胞沉降率(ESR)、c反应蛋白(CRP)、类风湿因子(RF)、免疫球蛋白A (IgA)、血小板滴度(PLT)、28关节疾病活动性评分(DAS28)相关,均P < 0.05。接下来,我们比较了不同特征RA患者的血清LUM水平,发现早期RA与RA之间血清LUM水平无差异,不同性别RA之间血清LUM水平无差异(P < 0.05)。RF阳性患者血清LUM水平升高(P < 0.000 1), RF和抗ccp阳性患者血清LUM水平均高于RF阴性RA患者(P < 0.05)。此外,RF阴性的RA患者抗ccp是否阳性,差异无统计学意义(P < 0.05)。不同CRP、ESR组RA患者血清LUM水平均高于hc组(P < 0.05), ESR、CRP升高组RA患者血清LUM水平显著高于ESR、CRP正常组(P < 0.05)。此外,结果显示血清LUM水平与RA疾病活动性呈正相关,并且RA持续缓解时其水平低于中度或高度疾病活动性(P < 0.05)。此外,缓解期RA患者与hcc患者之间无差异(P < 0.05)。合并间质性肺炎、Sjögren综合征、甲状腺疾病、骨质疏松等并发症的RA患者与不合并间质性肺炎、Sjögren综合征、甲状腺疾病、骨质疏松的RA患者无统计学差异(P < 0.05)。RF阳性患者的LUM阳性率明显高于RF阴性患者(P < 0.05)。结论:环腈氨酸化蛋白LUM可能是一种有前景的生物标志物,可以反映RA的疾病活动性和免疫活性。
{"title":"[Expression of lumican protein in serum of patients with rheumatoid arthritis and its correlation with disease and immune activities].","authors":"Ju Yang, Jing Xu, Juhua Dai, Lianjie Shi","doi":"","DOIUrl":"","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the serum level of lumican (LUM) and its clinical correlation with disease and immune activities in patients with rheumatoid arthritis (RA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The serum LUM levels in both RA patients and health controls (HCs) were detected by enzyme-linked immunosorbent assay (ELISA). The clinical and laboratory data of the patients were collected. The LUM levels in the patients with different clinical features were analyzed. The correlation between the clinical data, laboratory parameters, and serum LUM levels were also analyzed. Independent samples &lt;i&gt;t&lt;/i&gt; test, Spearman correlation were used for statistical analysis. Analysis of variance and Kruskal-Wallis test, the least significant difference (LSD)-&lt;i&gt;t&lt;/i&gt; test and Bonferroni correction were used for statistical analysis. The Pearson Chi-square test was used for comparison of the rates between the groups. Statistical significance was set at &lt;i&gt;P&lt;/i&gt; &lt; 0.05.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The levels of LUM were elevated in the RA patients than in the HCs (&lt;i&gt;P&lt;/i&gt; &lt; 0.000 1). Serum LUM levels were correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), immunoglobulin A (IgA), titers of platelet (PLT) and 28-joint disease activity score (DAS28, all &lt;i&gt;P&lt;/i&gt; &lt; 0.05). Next, we compared the serum LUM levels in the RA patients with different characteristics, and no difference was found in serum LUM levels between early-RA and RA, the same to RA with different gender (&lt;i&gt;P&lt;/i&gt;&gt;0.05). The levels of serum LUM were elevated in the RF positive patients (&lt;i&gt;P&lt;/i&gt; &lt; 0.000 1), and in the RF and anti-CCP positive patients (&lt;i&gt;P&lt;/i&gt; &lt; 0.05) than in the RA patients with negative RF whether the anti-CCP was positive. In addition, no differences were found between the RA patients with negative RF whether the anti-CCP was positive (&lt;i&gt;P&lt;/i&gt;&gt;0.05). All the levels of serum LUM were elevated in the RA patients with different CRP or ESR than in the HCs (&lt;i&gt;P&lt;/i&gt; &lt; 0.05), and the serum LUM levels in the RA patients with elevated ESR and CRP were significantly elevated in those with normal ESR and CRP (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Additionally, the results demonstrated that serum LUM levels were positively associated with RA disease activity, and they were declined in RA sustained remission than those in middle or high disease activity (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). Furthermore, no difference was found between the RA patients in remission and HCs (&lt;i&gt;P&lt;/i&gt;&gt;0.05). No differences were found in the RA patients with and without complications including interstitial pneumonia disease, Sjögren's syndrome, thyroid gland diseases and osteoporosis (&lt;i&gt;P&lt;/i&gt;&gt;0.05). The LUM positivity rates were significantly elevated in the RF positive patients than the RF negative patients in RA (&lt;i&gt;P&lt;/i&gt; &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;LUM, a cyclocitrullinated protein, might be a promising biomarker which could reflect both disease activit","PeriodicalId":8790,"journal":{"name":"北京大学学报(医学版)","volume":"57 5","pages":"911-918"},"PeriodicalIF":0.0,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Influence of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis]. [长期生物治疗对中重度斑块型银屑病代谢生化参数的影响]。
Q3 Medicine Pub Date : 2025-10-18
Xiangxian Liu, Yi Lin, Jinzhu Guo
<p><strong>Objective: </strong>To assess the impact of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis patients.</p><p><strong>Methods: </strong>The study included patients over 18 years old who had been treated by biological agents for at least 24 weeks for moderate to severe plaque psoriasis from Novermber 2015 to January 2024. According to the biological agents the patients used, they were divided into three groups: interleukin-17 (IL-17) inhibitor group, IL-23 and IL-12/23 inhibitor group and tumor necrosis factor-α (TNF-α) inhibitor group. The metabolic biochemical parameters of each group were evaluated and compared before and after the administration of the biologic therapies.</p><p><strong>Results: </strong>A total of 174 patients with moderate to severe plaque psoriasis were included in the long-term treatment with biologics, including 127 males (73.00%), 47 females (27.00%), with a median age of 38.00 (31.50, 49.00) years and a median duration of psoriasis of 12.00 (10.00, 20.00) years. The median duration of biologic treatment was 61.00 (49.00, 96.25) weeks, ranging from 26 to 301 weeks. There were 101 patients in the IL-17 inhibitor group, 38 patients in the IL-23 and IL-12/23 inhibitor group, and 35 patients in the TNF-α inhibitor group. After long-term treatment with IL-17 inhibitors, no statistically significant changes were observed in body weight, body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose (GLU), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with baseline measurements (<i>P</i>>0.05). However, low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced [(2.90±0.75) mmol/L <i>vs</i>. (3.05±0.79) mmol/L, <i>t</i>=-2.100, <i>P</i>=0.038], while uric acid (UA) levels showed a significant increase [(401.13±99.13) μmol/L <i>vs</i>. (364.94±91.11) μmol/L, <i>t</i>=5.215, <i>P</i> < 0.001]. The group with normal UA levels before treatment showed a significant increase after long-term application of biological agents compared with before treatment [(370.69± 89.59) μmol/L <i>vs</i>. (324.66±64.50) μmol/L, <i>t</i>=5.856, <i>P</i> < 0.001]. Following long-term application of IL-23 and IL-12/23 inhibitors, no statistically significant differences were observed in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C and UA levels when compared with baseline measurements (<i>P</i>> 0.05). However, LDL-C levels exhibited a significant reduction from baseline [(2.85±0.74) mmol/L <i>vs</i>. (3.12±0.68) mmol/L, <i>t</i>=-2.082, <i>P</i>=0.045]. After long-term treatment with TNF-α inhibitor, there were no significant differences in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C, LDL-C and UA compared with baseline measurements (<i>P</i>>0.05).</p><p><strong>Conclusion: </strong>Long-term application of IL-17 inhibitors in moderate to severe plaque psoriasis patients
目的:探讨长期生物治疗对中重度斑块型银屑病患者代谢生化指标的影响。方法:研究纳入了2015年11月至2024年1月期间接受生物制剂治疗至少24周的18岁以上中重度斑块型银屑病患者。根据患者使用的生物制剂分为3组:白细胞介素-17 (IL-17)抑制剂组、IL-23和IL-12/23抑制剂组和肿瘤坏死因子-α (TNF-α)抑制剂组。对各组患者给予生物治疗前后的代谢生化指标进行评价和比较。结果:共纳入174例中重度斑块型银屑病患者,其中男性127例(73.00%),女性47例(27.00%),中位年龄38.00(31.50,49.00)岁,中位银屑病病程12.00(10.00,20.00)年。生物治疗的中位持续时间为61.00(49.00,96.25)周,范围为26 ~ 301周。IL-17抑制剂组101例,IL-23和IL-12/23抑制剂组38例,TNF-α抑制剂组35例。长期使用IL-17抑制剂治疗后,体重、体重指数(BMI)、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、空腹血糖(GLU)、总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白胆固醇(HDL-C)与基线值相比无统计学意义变化(P < 0.05)。低密度脂蛋白胆固醇(LDL-C)水平显著降低[(2.90±0.75)mmol/L vs(3.05±0.79)mmol/L, t=-2.100, P=0.038],尿酸(UA)水平显著升高[(401.13±99.13)μmol/L vs(364.94±91.11)μmol/L, t=5.215, P < 0.001]。治疗前正常组长期应用生物制剂后UA水平较治疗前显著升高[(370.69±89.59)μmol/L vs(324.66±64.50)μmol/L, t=5.856, P < 0.001]。长期应用IL-23和IL-12/23抑制剂后,体重、BMI、ALT、AST、GLU、TC、TG、HDL-C、UA水平与基线比较,差异均无统计学意义(P < 0.05)。然而,LDL-C水平较基线有显著降低[(2.85±0.74)mmol/L vs(3.12±0.68)mmol/L, t=-2.082, P=0.045]。经TNF-α抑制剂长期治疗后,体重、BMI、ALT、AST、GLU、TC、TG、HDL-C、LDL-C、UA与基线比较无显著差异(P < 0.05)。结论:中重度斑块型银屑病患者长期应用IL-17抑制剂可导致尿酸水平升高,尤其是治疗前尿酸水平正常的患者。长期使用IL-17抑制剂、IL-23抑制剂或IL-12/23抑制剂可能降低LDL-C水平。
{"title":"[Influence of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis].","authors":"Xiangxian Liu, Yi Lin, Jinzhu Guo","doi":"","DOIUrl":"","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To assess the impact of long-term biologic therapy on metabolic biochemical parameters in moderate to severe plaque psoriasis patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The study included patients over 18 years old who had been treated by biological agents for at least 24 weeks for moderate to severe plaque psoriasis from Novermber 2015 to January 2024. According to the biological agents the patients used, they were divided into three groups: interleukin-17 (IL-17) inhibitor group, IL-23 and IL-12/23 inhibitor group and tumor necrosis factor-α (TNF-α) inhibitor group. The metabolic biochemical parameters of each group were evaluated and compared before and after the administration of the biologic therapies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 174 patients with moderate to severe plaque psoriasis were included in the long-term treatment with biologics, including 127 males (73.00%), 47 females (27.00%), with a median age of 38.00 (31.50, 49.00) years and a median duration of psoriasis of 12.00 (10.00, 20.00) years. The median duration of biologic treatment was 61.00 (49.00, 96.25) weeks, ranging from 26 to 301 weeks. There were 101 patients in the IL-17 inhibitor group, 38 patients in the IL-23 and IL-12/23 inhibitor group, and 35 patients in the TNF-α inhibitor group. After long-term treatment with IL-17 inhibitors, no statistically significant changes were observed in body weight, body mass index (BMI), alanine aminotransferase (ALT), aspartate aminotransferase (AST), fasting glucose (GLU), total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) compared with baseline measurements (&lt;i&gt;P&lt;/i&gt;&gt;0.05). However, low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced [(2.90±0.75) mmol/L &lt;i&gt;vs&lt;/i&gt;. (3.05±0.79) mmol/L, &lt;i&gt;t&lt;/i&gt;=-2.100, &lt;i&gt;P&lt;/i&gt;=0.038], while uric acid (UA) levels showed a significant increase [(401.13±99.13) μmol/L &lt;i&gt;vs&lt;/i&gt;. (364.94±91.11) μmol/L, &lt;i&gt;t&lt;/i&gt;=5.215, &lt;i&gt;P&lt;/i&gt; &lt; 0.001]. The group with normal UA levels before treatment showed a significant increase after long-term application of biological agents compared with before treatment [(370.69± 89.59) μmol/L &lt;i&gt;vs&lt;/i&gt;. (324.66±64.50) μmol/L, &lt;i&gt;t&lt;/i&gt;=5.856, &lt;i&gt;P&lt;/i&gt; &lt; 0.001]. Following long-term application of IL-23 and IL-12/23 inhibitors, no statistically significant differences were observed in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C and UA levels when compared with baseline measurements (&lt;i&gt;P&lt;/i&gt;&gt; 0.05). However, LDL-C levels exhibited a significant reduction from baseline [(2.85±0.74) mmol/L &lt;i&gt;vs&lt;/i&gt;. (3.12±0.68) mmol/L, &lt;i&gt;t&lt;/i&gt;=-2.082, &lt;i&gt;P&lt;/i&gt;=0.045]. After long-term treatment with TNF-α inhibitor, there were no significant differences in body weight, BMI, ALT, AST, GLU, TC, TG, HDL-C, LDL-C and UA compared with baseline measurements (&lt;i&gt;P&lt;/i&gt;&gt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Long-term application of IL-17 inhibitors in moderate to severe plaque psoriasis patients ","PeriodicalId":8790,"journal":{"name":"北京大学学报(医学版)","volume":"57 5","pages":"934-940"},"PeriodicalIF":0.0,"publicationDate":"2025-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12549349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145353695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
[Neuroendocrine carcinoma with significantly vacuolar nucleus at the esophagogastric junction: A case report]. 食管胃交界处神经内分泌癌伴明显空泡核1例。
Q3 Medicine Pub Date : 2025-10-18
Weihua Hou, Shujie Song, Zhongyue Shi, Lu Liu, Mulan Jin

Neoplasms characterized by the expression of markers of neuroendocrine differentiation in neoplastic cells are defined as neuroendocrine neoplasms. A case of neuroendocrine carcinomas (NECs) with a small amount of papillary adenocarcinoma and significantly vacuolar nucleus at the esophagogastric junction was reported in this article. A 77-year-old male had dysphagia for one week. Endoscopy revealed early-stage esophagogastric junction carcinoma, and biopsy was diagnosed as poorly differentiated carcinoma. Endoscopic submucosal dissection was performed. Histologically, the papillary adenocarcinoma progresses from typically branching papillary structures (well-differentiated) to hyperplasia of the lining epithelium of the papilla to form a cribriform structure (moderately differentiated), to solid area lacking papillary structures (poorly differentiated). There was a continuous process, and during this process, the vacuoles in the nuclei of tumor cells showed progressive changes from mild to obvious and finally to significant vacuoles. The tumor was mainly composed of solid areas (about 95%), with single cell, large cell, round or oval to irregular nuclei, and significantly vacuolar nuclei, nuclei with larger vacuoles appeared in a loop, a few thin weakly basophilic or weakly eosinophilic fine particles could be seen in the vacuoles, and the vacuoles had rough edges. The nucleus chromatin at the outer edge of the vacuoles was fine particles, and mitosis was common (20-30/mm2), atypical mitosis could be seen, and nucleoli could be seen easily, the cytoplasm was weakly eosinophilic, and the boundaries of cells were unclear. The cells were arranged in a nested, trabecular, or diffuse sheet shape, with some arranged in a glandular tube shape. Tumor thrombus was found in the vein of submucosa; the interstitial tissue rich in capillaries within the tumor was accompanied by a large number of neutrophil infiltration. Immunohistochemical staining showed that the solid area of the tumor was positive for synaptophysin (Syn) and chromogranin A (CgA), while papillary adenocarcinoma was negative. Mucin 5AC (MUC5AC) was diffusely positive in papillary adenocarcinoma, while the proportion of positive cells in the solid area of the tumor was about 10% to 15%. In a word, this case showed the extreme situation of the vacuolar nuclear characteristics of NECs, extremely rare, in a sense, this case expanded the boundary of the morphological spectrum of NECs. Understanding the extreme vacuolar features of this nucleus is helpful to make a correct pathological diagnosis.

以肿瘤细胞表达神经内分泌分化标志物为特征的肿瘤被定义为神经内分泌肿瘤。本文报告1例神经内分泌癌(NECs)伴少量乳头状腺癌,并在食管胃交界处有明显的空泡核。77岁男性,有吞咽困难1周。内镜检查发现早期食管胃交界癌,活检诊断为低分化癌。内镜下粘膜夹层。组织学上,乳头状腺癌从典型的分枝状乳头状结构(高分化)发展到乳头内膜上皮增生形成筛状结构(中度分化),再到缺乏乳头状结构的实区(低分化)。这是一个连续的过程,在这个过程中,肿瘤细胞核内的液泡由轻微到明显,最后到显著的液泡变化。肿瘤以实区为主(约95%),有单细胞、大细胞、圆形或卵圆形至不规则核,可见明显的空泡核,较大的空泡核呈环状,空泡内可见少量薄的弱嗜碱性或弱嗜酸性细颗粒,空泡边缘粗糙。液泡外缘核染色质呈细颗粒状,有丝分裂常见(20 ~ 30/mm2),可见非典型有丝分裂,易见核仁,细胞质嗜酸性弱,细胞边界不清。细胞呈巢状、小梁状或弥散片状排列,部分细胞呈腺管状排列。粘膜下静脉可见肿瘤血栓;肿瘤内毛细血管丰富的间质组织伴大量中性粒细胞浸润。免疫组化染色显示肿瘤实区突触素(Syn)和嗜铬粒蛋白A (CgA)阳性,乳头状腺癌阴性。Mucin 5AC (MUC5AC)在乳头状腺癌中呈弥漫性阳性,肿瘤实区阳性细胞比例约为10% ~ 15%。总之,本病例显示了NECs液泡核特征的极端情况,极为罕见,从某种意义上说,本病例拓展了NECs形态学谱的边界。了解该核的极端空泡特征有助于做出正确的病理诊断。
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引用次数: 0
[Protein biomarker screening and functional analysis of salivary exosomes in patients with ulcerative colitis]. 溃疡性结肠炎患者唾液外泌体的蛋白生物标志物筛选和功能分析
Q3 Medicine Pub Date : 2025-10-18
Congyi Yang, Xiaowen Zheng, Jingyi Chen, Jun Xu, Feng Chen, Yang Chen, Ning Chen
<p><strong>Objective: </strong>To identify protein markers that may be associated with ulcerative colitis (UC) by analyzing differential proteins in the salivary exosomes from newly diagnosed patients with active UC and healthy controls (HC), and to investigate the function of salivary exosome-specific high-expression proteins in UC patients and their potential role in the pathogenesis of UC.</p><p><strong>Methods: </strong>All patients and healthy controls were recruited from Peking University People' s Hospital. Whole saliva was obtained from 37 patients with newly diagnosed active ulcerative colitis (<i>n</i>=37) and apparently healthy controls (<i>n</i>=10). Salivary exosomes were extracted from samples, and the proteins within the exosomes were identified by liquid chromatograph-mass spectrometer (LC-MS/MS). The differentially expressed protein genes underwent gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis using the DAVID tool. <i>In vitro</i>, macrophages were co-cultured with salivary exosomes from UC group and those from HC group, respectively, and real-time quantitative polymerase chain reaction (qPCR) was used to detect levels of CD80<sup>+</sup> and CD86<sup>+</sup>. Additionally, ELISA was performed to measure secretion levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) in the cell supernatant.</p><p><strong>Results: </strong>A total of 259 proteins were co-expressed in saliva exosomes from UC group and HC group, among which 11 proteins were highly expressed in the UC group, including PDIA4, A2M, EEF2, C3, PSMA2, PSMB6, PSMA1, IGHG1, IGHG3, IGHG4 and SERPING1, while 4 proteins were lowly expressed in UC group, including TCN1, SLPI and SERPING. Functional analysis of these 15 proteins, along with 129 specific proteins found only in the UC patients and 69 specific proteins found only in HC patients, respectively, was conducted using GO/KEGG. The results revealed that in the UC group, proteasome-related proteins such as PSMA1, PSMA2 and PSMB6 expressions were increased in salivary exosomes while many key molecules involved in complement cascade pathways, such as C3 were up-regu-lated. <i>In vitro</i> co-culture experiments demonstrated that compared with healthy controls, the salivary exosomes of the UC patients in active stage could play a pro-inflammatory role by promoting the transformation of macrophages into M1 type cells that secrete inflammatory factors IL-1β, IL-6 and TNF-α.</p><p><strong>Conclusion: </strong>Salivary exosomes in the UC patients may have the function of promoting inflammation. Analysis of protein levels in the saliva of the UC patients and healthy controls revealed significant differences in the expression levels of 15 co-expressed proteins between the two groups. Among them, C3, PSMA2, PSMB6 and PSMA1 were found to be mainly related to immune and inflammatory reactions in the UC group. These findings suggest that proteins with high s
目的:通过分析新诊断的活动性UC患者和健康对照组(HC)唾液外泌体的差异蛋白,发现可能与UC相关的蛋白标志物,探讨UC患者唾液外泌体特异性高表达蛋白的功能及其在UC发病机制中的潜在作用。方法:在北京大学人民医院招募所有患者和健康对照者。从37例新诊断为活动性溃疡性结肠炎的患者(n=37)和表面健康的对照组(n=10)中获得全唾液。提取唾液外泌体,采用液相色谱-质谱联用(LC-MS/MS)对外泌体中的蛋白质进行鉴定。差异表达蛋白基因使用DAVID工具进行基因本体(GO)和京都基因基因组百科全书(KEGG)富集分析。体外分别与UC组和HC组唾液外泌体共培养巨噬细胞,采用实时定量聚合酶链反应(qPCR)检测CD80+和CD86+水平。ELISA法检测细胞上清液中白细胞介素-6 (IL-6)、白细胞介素-1β (IL-1β)、肿瘤坏死因子-α (TNF-α)的分泌水平。结果:UC组和HC组唾液外泌体共表达259个蛋白,其中UC组高表达11个蛋白,包括PDIA4、A2M、EEF2、C3、PSMA2、PSMB6、PSMA1、IGHG1、IGHG3、IGHG4和SERPING1, UC组低表达4个蛋白,包括TCN1、SLPI和SERPING。使用GO/KEGG对这15种蛋白以及仅在UC患者中发现的129种特异性蛋白和仅在HC患者中发现的69种特异性蛋白进行功能分析。结果显示,UC组唾液外泌体中PSMA1、PSMA2、PSMB6等蛋白酶体相关蛋白表达增加,补体级联通路中C3等关键分子表达上调。体外共培养实验表明,与健康对照组相比,活动期UC患者唾液外泌体可通过促进巨噬细胞向分泌炎性因子IL-1β、IL-6和TNF-α的M1型细胞转化而发挥促炎作用。结论:UC患者唾液外泌体可能具有促炎作用。对UC患者和健康对照组唾液中蛋白质水平的分析显示,两组之间15种共表达蛋白的表达水平存在显著差异。其中C3、PSMA2、PSMB6、PSMA1在UC组中主要与免疫和炎症反应相关。这些发现表明,UC患者唾液外泌体中高特异性表达的蛋白有可能作为UC诊断的疾病标志物,并可能参与UC的发病机制。
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引用次数: 0
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北京大学学报(医学版)
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