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关键词： gamma delta T cells   Unconventional T cells   V delta 2   TCR   Primary biliary cirrhosis   Autoimmune liver disease   Subset   Subpopulation   Function   CXCR6   Granzyme B   PERIPHERAL-BLOOD   BIOCHEMICAL RESPONSE   LIVER   INFLAMMATION   ELEVATION  

摘要： Background and aims Gamma-delta (gamma delta) T cells are involved in the development of diverse liver and autoimmune diseases, whereas the role of gamma delta T cells in primary biliary cholangitis (PBC) remains unclear. Methods We analyzed the number, phenotypes, and functional molecules of both circulating and hepatic gamma delta T cells in PBC patients and healthy controls (HCs) by flow cytometric analysis and immunohistochemistry. Results We identified two distinct functional subsets of circulating gamma delta T cells according to the CD3/TCR gamma delta complex: the TCR gamma delta(high) and TCR gamma delta(low) subsets. Approximately, three-quarters of cells in the TCR gamma delta(high) subset were V delta 1 T cells, while V delta 2 T cells were enriched in the TCR gamma delta(low) subset in HCs. The frequency and absolute number of circulating TCR gamma delta(low) cells were significantly decreased in PBC patients compared with HCs (p < 0.001). Furthermore, the frequency of TCR gamma delta(low) cells was correlated with disease severity and ursodeoxycholic acid (UDCA) response. TCR gamma delta(low) cells exhibited a similar apoptotic and proliferative phenotype, but enhanced liver-homing chemokine receptor (CXCR6) expression in PBC patients compared with HCs. In addition, circulating TCR gamma delta(low) cells were more activated and produced higher granzyme B (GZMB) in PBC patients compared with HCs. Finally, compared with heathy liver controls, hepatic gamma delta T cells were increased and infiltrated in the inflamed portal tracts in PBC liver. Furthermore, the number of hepatic gamma delta T cells was correlated with cholestatic markers and UDCA response. Conclusion The circulating TCR gamma delta(low) subset may migrate to the liver via the CXCR6-CXCL16 axis and be involved in the pathogenesis of PBC by increasing GZMB production.

关键词： Recurrent oral squamous cell carcinoma   Salvage surgery   Oral cancer   Ablative surgery   Disease-free interval   SALVAGE SURGERY   CAVITY CANCER   NECK CANCERS   HEAD   CHEMOTHERAPY   RADIOTHERAPY   SURVIVAL   UPDATE   CHOICE  

摘要： Objectives Survival for patients with recurrent oral squamous cell carcinoma is usually poor, and the most effective treatment has not yet been clearly defined. The present study evaluates the outcome in radiotherapy-naive patients after recurrence of oral squamous cell carcinoma with respect to different treatment modalities including surgery, radiation, chemoradiation, and palliative treatment. Patients and methods In this retrospective study, we included all patients with primary oral squamous cell carcinoma who received exclusively surgical therapy between 2010 and 2020 and who suffered from locoregional recurrence in their follow-up. Patients with previous adjuvant therapy were excluded from this protocol. Clinical and pathological parameters were collected and statistically evaluated. Survival analysis was performed according to Kaplan-Meier. The primary endpoints were overall and progression-free survival in dependance of treatment strategy for recurrent tumors. Results Out of a total of 538 patients with surgically treated primary oral squamous cell carcinoma, 76 patients met the inclusion criteria. The mean follow-up was 38 +/- 32 months. Patients who received surgically based therapy had a significantly better outcome in terms of disease-free survival (DFS) and overall survival (OS) (DFS p < 0.001; OS p < 0.001). The presence of regional metastases and a short disease-free interval (DFI) between primary and recurrent cancer were significant predictors for adverse outcomes (DFI p < 0.001). Conclusion We recommend primary surgical therapy for radiotherapy-naive patients with recurrent oral squamous cell carcinoma, supplemented by risk-adapted adjuvant therapy.

关键词： Mast cells   chymase   tryptase   fibroblasts   asthma   BETA-TRYPTASE   ACTIVATION   TETRAMER   PROCOLLAGENASE   CLEAVAGE   GROWTH   TISSUE  

摘要： Background: Mast cells (MCs) have a profound impact on allergic asthma. Under such conditions, MCs undergo degranulation, resulting in the release of exceptionally large amounts of MC-restricted proteases. However, the role of these proteases in asthma is only partially understood. Objectives: We sought to test our hypothesis that MC proteases can influence the functionality of human lung fibroblasts (HLFs). Methods: Primary HLFs were treated with MC chymase or tryptase, followed by assessment of parameters related to fibroblast function. Results: HLFs underwent major morphologic changes in response to chymase, showing signs of cellular contraction, but were refractory to tryptase. However, no effects of chymase on HLF viability or proliferation were seen. Chymase, but not tryptase, had a major impact on the output of extracellular matrix-associated compounds from the HLFs, including degradation of fibronectin and collagen-1, and activation of pro-matrix metalloprotease 2. Further, chymase induced the release of various chemotactic factors from HLFs. In line with this, conditioned medium from chymase-treated HLFs showed chemotactic activity on neutrophils. Transcriptome analysis revealed that chymase induced a proinflammatory gene transcription profile in HLFs, whereas tryptase had minimal effects. Conclusions: Chymase, but not tryptase, has a major impact on the phenotype of primary airway fibroblasts by modifying their output of extracellular matrix components and by inducing a proinflammatory phenotype.

关键词： FRAGSTATS   Green Infrastructure   Landscape metrics   Nature-based solutions   Spatial analysis   Urban ecology   LANDSCAPE CONNECTIVITY   CITIES   ACCESSIBILITY   BIODIVERSITY   INDICATORS   MANAGEMENT   SPACE   STORMWATER   RESOLUTION   SERVICES  

摘要： Green Infrastructure (GI) connects different types of green features via various scales, thereby supporting urban biodiversity and service provision. This study presents a methodology capable of identifying multiple functions to assess GI in less-developed countries, where such methodologies are lacking. GI was assessed based on a high resolution land use classification using both landscape metrics and spatial data within an urbanized region of San Jose', Costa Rica, at different scales (watershed, neighbourhood, object). Results showed highly fragmented green spaces (often < 10 ha), typically unable to support high levels of biodiversity, along with a low amount of green space per inhabitant (< 7.4 m(2)) within the watershed. Substantially higher tree cover (x6) and tree density (x5) were found in the greenest neighbourhood in comparison to the least green neighbourhood. Potential areas for new GI in the form of green roofs (4.03 ha), permeable pavement (27.3), and potential retention areas (85.3) were determined. Several green spaces (n = 11) were identified as promising GI sites with the potential to increase provision (18.6 m(2)/inhabitant). The adopted methodology demonstrates the potential of GI for increasing recreational green space access, runoff reduction, and flood retentions while supporting biodiversity, validating its utility in guiding decision-making and policy generation.

关键词： Laryngopharyngeal reflux   Matrix metalloproteinase-7 (MMP-7)   Reactive oxygen species (ROS)   Mitogen-activated protein kinases (MAPK)   Transcription factor   COLORECTAL-CANCER   OXIDATIVE STRESS   MATRILYSIN   INVASION   ESOPHAGITIS   ACTIVATION   EXPRESSION   RADICALS   MMP-7  

摘要： Laryngopharyngeal reflux disease (LPRD) is caused by pharyngeal mucosal damage due to the reflux of gastric contents, including acid, pepsin, and bile juice. Our previous study has demonstrated that LPRD is associated with the cleavage of E-cadherin, which is facilitated by the acid-activated matrix metalloproteinase-7 (MMP-7); however, the mechanism by which the acid activates MMP-7 remains unclear. The purpose of this study was to investigate the mechanism by which MMP-7 is activated in the pharyngeal epithelial cells that are exposed to acid. The levels of reactive oxygen species (ROS) were measured in the epithelial cells exposed to acid. To investigate the signaling mechanism of ROS in the expression of MMP-7, the mechanism of action of the mitogen-activated protein kinase was examined. The expression of various signaling factors was determined, according to the presence or absence of each inhibitor in the acid-exposed pharyngeal epithelial cells. To identify changes in the cleavage of E-cadherin, the integrity of the mucosal membrane was assessed using a transepithelial permeability test. We found that acid exposure increased the levels of ROS, phosphorylated-extracellular signal-regulated kinase (p-ERK) 1/2, and phosphorylated-c-Jun (p-c-Jun) in pharyngeal epithelial cells. The ROS inhibitor reduced the expression of p-ERK and MMP-7, while the ERK inhibitor reduced the expression of p-c-Jun and MMP-7. Moreover, the c-Jun inhibitor reduced the expression of MMP-7 and blocked the degradation of E-cadherin. In addition, decrease in the levels of immunostained E-cadherin and increase in transepithelial permeability after acid exposure were collectively alleviated by the inhibitors of ROS, ERK, and c-Jun. The degradation of E-cadherin that occurs after human mucosal cells are exposed to acid appears to be caused by an increase in the expression of MMP-7 via the ROS/ERK/c-Jun pathway, which is thought to be an important mechanism associated with the development of

关键词： ETOPOSIDE   CHEMOTHERAPY   METHOTREXATE   IFOSFAMIDE   STAGE  

关键词： 生态功能分区   生态空间优化   西丰县  

摘要： 近年来快速城镇化导致西丰县生态环境逐渐恶化,生态安全问题突出.本次研究以西丰县为研究对象,基于西丰县生态功能区划,结合生态本底特征总结现状生态空间存在的问题,提出西丰县的生态空间优化建议及策略,对西丰县生态空间可持续健康发展具有重要意义.

摘要： 现代建筑设计理念的不断完善,改变了传统建筑设计中对于建筑结构形态的单一要求,多元视觉传达设计思想的渗透,使建筑形态呈现出多元化的趋势,其中就包括构成的视觉化传达设计在建筑立面中的应用.建筑立面设计需综合考虑多种因素,如视觉艺术效果、结构强度外,还需要关注建筑节能与成本,所以,构成的视觉化传达设计能够丰富建筑立面的设计效果.

关键词： 景观设计   场地设计   屋顶绿化   架空步道   施工技术  

摘要： 回顾荣成市少年宫项目景观专项从设计到施工的全过程,通过设置屋顶乐园、架空步道,打破当地传统种植观念,编织大地色彩,并精心设计场地,为少年宫的孩子们打造拥抱自然、享受自然的天地.