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关键词： 胸腺基质淋巴细胞生成素(TSLP)   纤维化   慢性难愈性创面(CRW)   成纤维细胞   综述  

摘要： 慢性难愈性创面（CRW）其形成是多因素共同作用的结果，其中纤维化在发病过程中具有双重作用：适度的纤维化可保护创面，但过度纤维化会导致病理性疤痕，加剧组织缺氧和僵硬，阻碍愈合。胸腺基质淋巴细胞生成素（TSLP）是一种重要的免疫调节细胞因子，其在过敏性疾病中发挥关键作用，近期研究发现TSLP也参与CRW纤维化的发病机制。TSLP通过调控转化生长因子β/SMA和MAD相关蛋白（TGF-β/SMAD）、无翅型小鼠乳房肿瘤病毒整合位点家族/β-连环蛋白（Wnt/β-catenin）、磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）等信号通路，影响成纤维细胞的活化、巨噬细胞的极化、趋化因子的表达以及赖氨酰氧化酶介导的胶原交联，从而在CRW纤维化中发挥重要作用。未来研究应进一步探索TSLP与其他促纤维化因子的协同效应，并设计联合疗法以平衡纤维化与修复过程，为CRW纤维化的治疗提供新的策略。

关键词： 孟德尔随机化分析   血细胞指标   脓毒症   嗜碱性粒细胞   肿瘤坏死因子  

摘要： 目的 探讨17项血细胞指标与4种不同脓毒症亚型之间的因果关联。方法 基于全基因组关联研究摘要统计数据，采用双样本孟德尔随机化（MR）分析，以乘法随机效应的逆方差加权法为主，辅以多种方法验证结果。通过盲肠结扎和穿刺建立小鼠脓毒症模型，评估肿瘤坏死因子（TNF）小分子抑制剂UCB-9260的作用。结果 MR分析显示，血细胞指标中的嗜碱性粒细胞计数（BASO#）与脓毒症发生风险呈显著负相关(OR=0.814,P=1.15×10-4)。既往研究报道，小鼠体内嗜碱性粒细胞来源的TNF在脓毒症过程中发挥保护作用；TNF-/-小鼠在发生脓毒症后存活率明显降低。与这些结果相一致的是，在小鼠体内全身性抑制TNF显著降低了血液细菌清除率（P=0.0286），并显著升高死亡率（P=0.0304）。结论 嗜碱性粒细胞可能是脓毒症的保护因素，嗜碱性粒细胞-TNF轴有望成为脓毒症干预的关键靶点。

关键词： Cell membranes  

摘要： The interaction between human leukocyte antigens (HLAs) and T cell receptor (TCR) is essential for adaptive immune recognition. While it is known that one TCR can map to multiple HLA alleles, the extent of this cross-reactivity remains poorly understood. Here, we introduce THNet, a TCR-based HLA similarity network, and present a comprehensive analysis of HLA-TCR cross-reactivity, which is built upon more than 9 million significantly associated HLA-TCR pairs. We created similarity networks for both class I and class II HLA alleles, illustrating how peptide cross-presentation contributes to HLA-TCR cross-reactivity. Our analysis revealed disease susceptibilities missed by single-HLA enrichment analyses, especially in the Black population. Last, we demonstrated that THNet can prioritize optimal HLA mismatch candidates across different transplantation contexts, supporting its potential utility in donor selection strategies. In summary, our investigation of the HLA-TCR cross-reactive network provides useful insights into autoimmune risk prediction and improved transplantation outcomes. © (2025), (American Association for the Advancement of Science). All rights reserved.

关键词： Cytokines   Lung injury   Oxidative stress   Salvigenin   Sepsis  

摘要：

关键词： alloanti-D immunization   D antigen   HLA   Rh system  

摘要： Alloanti-D is still one of the most common causes of severe hemolytic disease of the fetus and newborn in China, as rhesus immunoglobulin (RhIG) prophylaxis is not a routine practice throughout China. HLA plays an important role in the susceptibility to alloimmunisation against red blood cell antigens. This study was designed to identify susceptible and protective HLA alleles for alloanti-D immunisation after pregnancy in the southern Chinese D-negative (D-) pregnant women. In this study, a cohort of 116 true D- pregnant females who had not received prophylactic RhIG prophylaxis, had two or more pregnancies, and did not produce alloanti-D (non-responders group), and 122 true D- pregnant women with alloanti-D immunisation (D responders group), were enrolled. HLA genotyping (HLA-A, -B, -C, -DRB1, -DPA1, -DPB1, -DQA1, and -DQB1) was performed by third generation sequencing with nanopore technology. The phenotypic frequencies of HLA alleles were compared between the D responders group and non-responders group. The results showed that the phenotypic frequencies of HLA-DRB1*08:03 and HLA-DQA1*01:03 alleles in the D responders group were significantly lower than those in the non-responders group: 1.7% versus 13.1% [Odds Ratio (OR): 0.116, 95% CI: 0.026-0.518;p c = 0.029] for HLA-DRB1*08:03 allele, and 5.2% versus 18.8% (OR: 0.235, 95% CI: 0.092-0.600, p c = 0.019) for HLA-DQA1*01:03 allele. Our findings indicated that the presence of HLA-DRB1*08:03 or HLA-DQA1*01:03 alleles can be considered as a protective factor for alloanti-D immunisation in the southern Chinese D- pregnant women.

关键词： Artificial intelligence   Chronic Kidney Disease   Clinical registry   Integrated care   Prevention  

摘要： The PIRP Project (Progressive Renal Insufficiency Prevention), launched in Emilia-Romagna in the early 2000s, was created to establish a network between general practitioners and nephrologists aimed at the early identification of chronic kidney disease (CKD), slowing its progression, and improving clinical outcomes. The project included several phases: a training phase for general practitioners, the establishment of dedicated outpatient clinics, and the creation of a regional electronic registry, which today includes more than 38,000 patients. The results have shown a reduction in CKD progression, fewer urgent dialysis starts, and better control of comorbidities. PIRP differs from the national PDTA for CKD in its operational and regional approach, based on real-world data and multidisciplinary co-management, whereas the PDTA represents a general regulatory framework. The project has developed predictive models (such as CT-PIRP), inspired comparative European studies, and today stands as a model of integrated healthcare, useful for the implementation of nephroprotective drugs and artificial intelligence. Twenty years after its inception, PIRP remains an example of proactive and collaborative medicine, anticipating modern paradigms of population health management.

关键词： HLA   HLA-A*02:1233   novel allele   sequence-based typing   Taiwanese  

摘要： One nucleotide mutation in exon 2 of HLA-A*02:07:01:01 results in the novel allele, HLA-A*02:1233.

关键词： 结肠炎相关结肠癌   上皮间质转化   虎杖苷   IL-17A   Wnt/β-catenin信号通路  

摘要： 目的：通过构建偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）诱导的结肠炎相关结直肠癌（CAC）小鼠模型及体外细胞实验，探究虎杖苷延缓CAC进展的作用及潜在机制。方法：选取54只雄性C57BL/6J小鼠为实验对象，将小鼠随机分为正常组、模型组、虎杖苷组(0.045g·kg-1)。采用AOM/DSS构建CAC小鼠模型，分别在造模后的4、7、10周三个时间点取材。分析小鼠的体质量变化率、疾病活动指数（DAI）及肿瘤形成情况；苏木素-伊红（H&E）染色观察小鼠肠组织病理损伤；免疫组织化学（IHC）观察结肠组织闭锁小带蛋白-1（ZO-1）的表达及蛋白免疫印迹法（Westernblot）检测结肠上皮细胞E-钙黏蛋白（E-cadherin）、N-钙黏蛋白（N-cadherin）和波形蛋白（Vimentin）的表达；实时荧光定量聚合酶链式反应（Real-timePCR）检测结肠组织中白细胞介素-17A（IL-17A）、Wnt3a、β-连环蛋白（β-catenin）、T细胞因子1（Tcf1）、E-cadherin、N-cadherin和Vimentin的mRNA表达；流式细胞术检测肿瘤中CD8+T细胞比例及耗竭相关分子的表达。将人结肠癌细胞（DLD-1）置于含虎杖苷的培养环境中刺激培养，细胞划痕实验观察愈合速率变化；Real-timePCR检测细胞白细胞介素-17受体A（IL-17RA）、Wnt3a、β-catenin、Tcf1、E-cadherin、N-cadherin和Vimentin的mRNA表达。结果：与正常组比较，3个阶段模型组小鼠体质量变化率均明显下降（P<0.01）、结肠长度显著缩短（P<0.01），DAI评分显著升高（P<0.01）；H&E染色显示模型组结肠黏膜下层炎细胞浸润显著，伴上皮细胞异型增生；结肠组织紧密连接蛋白ZO-1表达显著减少（P<0.01）；促炎因子（IL-17A）及Wnt/β-catenin通路关键分子（Wnt3a、β-catenin、Tcf1）的mRNA表达显著升高（P<0.05）；上皮-间质转化（EMT）标志物N-cadherin和Vimentin的mRNA及蛋白表达显著上调（P<0.05），E-cadherin的mRNA及蛋白表达显著下调（P<0.05）；表达免疫抑制性分子（TIM-3、LAG-3、PD-1）的肿瘤浸润CD8+T细胞比例显著升高（P<0.05）。与模型组比较，虎杖苷组体质量及DAI 评分均有显著改善（P<0.01），结肠长度与结肠组织损伤明显修复；结肠组织ZO-1蛋白表达明显升高（P<0.01），IL-17A、Wnt3a、β-catenin、Tcf1、N-cadherin和Vimentin相对表达量显著下降（P<0.05），E-cadherin的表达量显著上调（P<0.01）；表达免疫抑制性分子的肿瘤浸润CD8+T细胞显著下降（P<0.05）。体外实验显示，虎杖苷显著抑制DLD-1细胞迁移（P<0.01），并逆转IL-17RA、Wnt3a、β-catenin、N-cadherin和Vimentin的mRNA上调（P<0.05）及E-cadherin的mRNA下调（P<0.05）。结论：虎杖苷可抑制IL-17A的分泌和IL-17RA的表达，同时改善免疫微环境、阻断Wnt/β-catenin信号通路和上皮间质转化标志（N-cadherin和Vimentin）的表达，恢复肠上皮紧密连接蛋白的表达，延缓小鼠从结肠炎向结肠癌进展的过程。

关键词： amyloidosis   ankylosing spondylitis   familial Mediterranean fever   HLA-B27   MEFV   spondyloarthritis  

摘要： This study investigated the coexistence of familial Mediterranean fever (FMF) and spondyloarthritis (SpA), aiming to provide a comprehensive understanding of their clinical, radiological, and genetic features. A total of 127 patients with both FMF and SpA were evaluated, with data collected on demographic, clinical, and laboratory characteristics, including human leukocyte antigen (HLA)-B27 status, Mediterranean fever (MEFV) gene variants, and acute phase reactants. Pelvic radiographs and sacroiliac joint magnetic resonance imaging scans were reviewed when available. The median age of the cohort was 39 years (interquartile range: 30-50), and 48% were female, showing an equal sex distribution. Ankylosing spondylitis was the most common SpA subtype (76.4%), followed by nonradiographic axial SpA (10.2%), peripheral SpA (5.5%), undifferentiated SpA (6.3%), and psoriatic arthritis (1.6%). Most patients exhibited intermittent (90.8%) and oligoarticular (76.7%) joint involvement, typically affecting large joints of the lower extremities, while 23.6% had chronic arthritis. Patients with grade 4 sacroiliitis, chronic arthritis, or hip arthroplasty had a longer disease duration (P < .05). HLA-B27 positivity was identified in 30.4% of patients and was strongly associated with AA amyloidosis (odds ratio = 13.3, 95% confidence interval: 4-43.9). The most frequent MEFV mutation was homozygous M694V (69.3%), followed by M694V/M680I (14.7%) and M680I/V726A (5.3%). MEFV mutations were present in 83.1% of HLA-B27-negative patients. Collectively, these findings indicate that FMF-SpA coexistence defines a distinct clinical and genetic entity characterized by balanced sex distribution, lower HLA-B27 frequency compared to classic SpA, and a strong link between HLA-B27 positivity and amyloidosis risk, underscoring a complex genetic interaction between MEFV variants and HLA-B27 in disease expression. Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.

关键词： children   diagnostic value   interleukin-6   Mycoplasma pneumoniae   risk factors   signal transduction and transcriptional activation factor 3  

摘要： This study analyzes the risk factors for mycoplasma pneumoniae infection in children and the expression of interleukin-6 (IL-6)/signaling and transcriptional activating factor 3 (STAT3) pathway. Seventy-three children diagnosed with mycoplasma pneumoniae infection were admitted to Jinzhou Medical University Hospital between April 2021 and April 2023, forming the study group. Additionally, 730 healthy children who underwent physical examinations during the same period were selected as the control group. A comparison of clinical data between the 2 groups was conducted to analyze the risk factors associated with mycoplasma pneumoniae infection in children. Furthermore, the diagnostic value of IL-6, STAT3, white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT) in children with mycoplasma pneumoniae infection was assessed using receiver operating characteristic (ROC) curve analysis. A history of recurrent upper respiratory tract infections and living in close quarters are identified as risk factors for mycoplasma pneumoniae infection in children (OR = 1.988, 2.123, P < .05). The study group exhibited elevated levels of IL-6, STAT3 mRNA, WBC, CRP, and PCT compared to the control group (P < .05). Analysis of the ROC curve revealed that using IL-6, STAT3, WBC, CRP, and PCT levels individually or in combination yielded area under the curve values of 0.829, 0.813, 0.852, 0.759, 0.849, and 0.953, respectively. The combined detection method demonstrated a sensitivity of 86.30% and specificity of 90.40%. The IL-6/STAT3 pathway is known to be activated in children with mycoplasma pneumoniae infection, leading to an upregulation in the expression of white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT). Utilizing a combination of IL-6, STAT3, WBC, CRP, and PCT levels can aid in the diagnosis of mycoplasma pneumoniae infection in children. Additionally, a history of recurrent upper respiratory tract infections and living in close quarters wi