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关键词： 带状疱疹后神经痛   脉冲射频   局部注射  

摘要： 目的 评价局部药物注射联合脉冲射频治疗带状疱疹后神经痛的临床疗效及IL-1β、IL-6、TNF-α的影响。方法 采用前瞻性随机对照研究方法，选取2023年6月-2024年6月襄阳市中心医院疼痛科符合纳入标准的带状疱疹后神经痛病人，随机分为P组（PulseRadiationFrequencyPRF）、B组（BTX-A皮下注射联合PRF）和L组（利多卡因皮内注射联合PRF）。评价三组病人治疗后第1、4、12周疼痛数字分级评分法(Visualanaloguescale，VAS)评分、阿森斯失眠量表(AthensInsomniaScale，AIS）评分，比较三组病人治疗后1周IL-1β、IL-6、TNF-α水平。结果 符合纳入标准的PHN病人共159例，P组（n=53）、B组（n=53）、L组（n=53）。治疗后第1周B组病人VAS、AIS评分下降，与P组、L组比较差异有统计学意义（P＜0.01），P组与L组比较差异无统计学意义（P＞0.05）。第4、12周P组与B组、L组病人VAS、AIS评分比较，差异有统计学意义（P＜0.01），B组病人与L组病人VAS评分、AIS评分比较，差异无统计学意义（P＞0.05）。与基础值相比，三组病人在第1、4、12周VAS、AIS评分均显著降低（P＜0.001）。治疗后1周，三组病人IL-1β、IL-6、TNF-α水平，三组组间比较差异有统计学意义（P＜0.01），与基础值相比，均显著降低（P<0.001）。结论 PRF能够有效减轻带状疱疹后神经痛，改善生活质量，BTX-A皮下注射联合PRF较单纯PRF或利多卡因皮内注射联合PRF治疗效果更显著，安全性更高。

关键词： Anticalin proteins   interleukin (IL)-23   severe asthma  

摘要： Severe asthma is a syndromic label assigned to patients based on clinical parameters, yet there are diverse underlying molecular endotypes in severe asthma pathobiology. Immunophenotyping of asthma biospecimens commonly includes a mixture of granulocytes and lymphocytes. Recently, a subset of patients with severe asthma was defined as non-type 2 with neutrophil-enriched inflammation associated with increased Th17 CD4+ T cells and IL-17 levels. Here, we used an allergen-driven mouse model of increased IL-17 and mixed granulocyte lung inflammation to determine the impact of upstream regulation by an Anticalin protein that specifically binds IL-23. Airway administration of the IL-23-binding Anticalin protein (AcIL-23) decreased lung neutrophils, eosinophils, macrophages, lymphocytes, IL-17+ CD4 T cells, mucous cell metaplasia, and methacholine-induced airway hyperresponsiveness. Selective targeting of IL-23 with a monoclonal antibody (IL-23p19;alpha IL-23) also decreased macrophages, IL-17+ CD4 T cells, and airway hyperresponsiveness. In contrast, a monoclonal antibody against IL-17A (alpha IL-17A) had no significant effect on airway hyperresponsiveness but did decrease lung neutrophils, macrophages, and IL-17+ CD4 T cells. Targeting the IL-23 pathway did not significantly change IL-5+ or IL-13+ CD4 T cells. Together, these data indicate that airway AcIL-23 mirrored the activity of systemic anti-IL-23 antibody to decrease airway hyperresponsiveness in addition to mixed granulocytic inflammation and that these protective actions were broader than blocking IL-17A or IL-5 alone, which selectively decreased airway neutrophils and eosinophils, respectively. NEW & NOTEWORTHY This is the first report of an Anticalin protein engineered to neutralize IL-23 (AcIL-23). Airway administration of AcIL-23 in mice regulated allergen-driven airway inflammation, mucous cell metaplasia, and methacholine-induced airway hyperresponsiveness. In mixed granulocytic allergic lung inflammation,

摘要： INTRODUCTION:Juvenile idiopathic arthritis (JIA) is one of the most common chronic diseases of childhood and presents with various clinical phenotypes. A multifactorial and complex interaction of genetic and environmental factors are responsible for JIA, of which the proinflammatory cytokine genes are of particular research interest. This meta-analysis investigates the association between IL-1A and IL-1B gene polymorphisms and susceptibility to JIA. EVIDENCE ACQUISITION:A total of eight studies, involving 1633 patients and 2309 controls were included, and a meta-analysis was performed on the association between IL1A -889 C/T, IL1B -511 C/T, and IL1B +3954 C/T, and susceptibility to JIA. EVIDENCE SYNTHESIS:There was no significant association between the presence of IL1A -889 C/T, IL1B -511 C/T, and IL1B +3954 C/T polymorphisms and JIA, under any genetic model or in any ethnicity subgroups. CONCLUSIONS:Results of this study suggest that these three IL-1 variants do not increase the susceptibility to JIA. However, the limited number of studies and the considerable level of heterogeneity must be taken into account before interpretation.

关键词： 大黄灵仙胶囊   PI3K、TGF-α、IL-1β   炎性反应   大鼠   动物实验  

摘要： 目的：观察大黄灵仙胶囊对胆管炎性模型大鼠胆管组织磷脂酰肌醇3-激酶（Phosphoinositide3，PI3K）、转化生长因子α(Transforminggrowthfactor，TGF-α)、白细胞介素1β（interleukin，IL-1β）表达的影响。方法：选择18只清洁级健康SD大鼠，按随机数字表法分成3组：假手术组、模型组、大黄灵仙组，每组6只。除假手术组外，其余两组均采用脂多糖 （LPS）诱导构建大鼠胆管动物模型，大黄灵仙组大鼠在制备胆管炎性模型前给予大黄灵仙胶囊颗粒溶液灌胃2天，在制备胆管炎性模型后给予大黄灵仙胶囊颗粒溶液灌胃3天，给药剂量为320mg/（kg·d），空白组、模型组大鼠每天给予等量蒸馏水灌胃，每天2次，连续干预5天。处死各组大鼠，采用HE染色观察各组胆管病理形态改变，Westernblot法检测PI3K、TGF-α、IL-1β的蛋白表达量，实时PCR 法检测PI3K、TGF-α、IL-1β的mRNA表达。结果：HE染色显示采用大黄灵仙胶囊颗粒溶液灌胃大鼠的胆管组织病理炎性反应下降。与假手术组比较，模型组片内可见汇管区炎细胞浸润，个别区域可见肝细胞点状坏死，大鼠胆管组织的PI3K、TGF-α、IL-1β mRNA表达以及蛋白表达量均升高(P﹤0.05)。与模型组比较，大黄灵仙组大鼠片内可见汇管区少量炎细胞浸润，较模型组炎细胞减少，个别区域仍可见肝细胞点状坏死，炎细胞浸润面积显著减小，大黄灵仙PI3K、TGF-α、IL-1β mRNA表达和蛋白表达量均降低（P﹤0.05）。结论：大黄灵仙胶囊可能通过减少胆管组织中PI3K、TGF-α、IL-1β表达，改善组织病理损害，最终发挥保护胆管组织的作用。

关键词： HLA-1   MHC-I   Merkel Cell   TCRδ   biomarker   gamma delta   immunotherapy   tumor immune-microenvironment  

摘要： Merkel Cell Carcinoma (MCC) is an aggressive cutaneous malignancy with a poor prognosis. One of the major mechanisms of immune evasion in MCC involves downregulation of MHC-I. Anti-PD-1/PD-L1 checkpoint inhibitors (CKIs) have revolutionized treatment for MCC, producing objective responses in ∼50% of patients, and are now standard of care; however, a substantial proportion of patients either fail to respond or develop resistance to CKIs. Given these recent successes, identification of other targetable immune checkpoints in the MCC tumor microenvironment (TME) is of great interest. Additionally, γ-delta (γδ) T cells may play critical roles in the response to MHC-I deficient cancers; therefore, evaluating γδ-T cells as a prognostic biomarker is warranted. We characterized the expression of PD-L1, PD-1, CD3, CD8, LAG-3, MHC-I, and γδ-T cells by IHC in a pre-immunotherapy retrospective cohort of 54 cases of MCC, and quantified expression levels and marker density via HALO. The increased density of LAG-3 and γδ-T cells correlated with other markers of an inflamed TME, with significant positive associations across all six markers (p<.002). Reflective of their putative role in the response to MHC-I suppressed cancers, cases with low HLA-I density showed a trend towards a higher ratio of γδ-T cells:CD3+ T cells (Spearman's r=-0.1582, p=0.21). Importantly, high CD3 density (HR=0.23, p=0.002), LAG-3 density (HR=0.47, p=0.037), γδ-T cell density (HR=0.26, p=0.02), and CD8 density (HR=0.27, p=0.03) showed associations with improved progression-free survival. Conditional tree analysis demonstrated that high CD8 and TCRδ expression were non-significant predictors of improved PFS and OS. Overall, LAG-3 is expressed in MCC infiltrates and is prognostic in pre-immunotherapy MCC, suggesting a potential role for LAG-3 inhibition in MCC. Additionally, CD8 and γδ-T cells may play a critical role in the response to MCC, and γδ-T cell density may represent a novel biomarker in MCC.

关键词： Esculentoside A   MRL/lpr mice   CD19+IL-35+Breg cell   Interleukin-35   Interleukin-17   Lupus nephritis  

摘要： Introduction: Esculentoside A (EsA) is one of the main components of the traditional Chinese medicine Phytolacca esculenta. The possible mechanism of action of EsA in the treatment of lupus nephritis (LN) was explored by observing the effects of EsA on CD19(+) IL-35(+)regulatory B (IL-35(+)Breg) cells. Methods: Twenty-four MRL/lpr mice were randomly divided into control, EsA, and EsA+IL-12p35 antibody groups. Mice were administered the respective treatments intraperitoneally once a day for 4 weeks. The urine protein/ creatinine ratio (UPCR) and blood creatinine (Cr) and IL-35, IL-10, and IL-17 expression levels were measured. Body and spleen weight were measured to calculate the splenic index (SI). Flow cytometry was performed to determine the proportion of CD19(+) IL-35(+) Breg cells in the spleen. Hematoxylin-eosin and PASM-Masson staining of renal tissues were performed, and the " Austin " acute index (AI) system for LN was determined. Results: The most severe conditions were seen in mice in the control group, with the highest UPCR, Cr, and IL-17 levels and SI and AI scores;the most severe renal histopathology, and the lowest proportion of CD19(+) IL-35(+) Breg cells and IL-35 and IL-10 levels. This was followed by the EsA+IL-12p35 antibody group. The EsA group had the lowest UPCR, Cr, and IL-17 levels and SI and AI scores;the mildest renal lesions;and the highest proportion CD19(+) IL-35(+) Breg cells and IL-35 and IL-10 levels. Conclusion: EsA delayed the progression of LN by promoting the proliferation of CD19(+)IL-35(+) Breg cells, upregulating the expression of IL-35, and decreasing the secretion of IL-17.

关键词： Comorbid pain   Group III secretory phospholipase A2   Interleukin-1(3   Medial prefrontal cortex   Temporomandibular disorder   Fibromyalgia  

摘要： The medial prefrontal cortex (mPFC) has been identified as a key brain region involved in the modulation of chronic pain. Our recent study demonstrated that unilateral anterior crossbite (UAC) developed the comorbidity model of temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS), which was characterized by both orofacial and somatic hyperalgesia. In the present study, UAC rats exhibited significant changes in gene expression in the mPFC. Enrichment analysis revealed that the significantly involved pathways were cytokinescytokine receptor interaction and immune response. The expression of group III secretory phospholipase A2 (sPLA2-III) was significantly increased in the mPFC of UAC rats. Silencing sPLA2-III expression in the mPFC blocked the orofacial and somatic hyperalgesia. Immunofluorescence showed that sPLA2-III was mainly localized in neurons. The expression of interleukin-1(3 (IL-1(3) in the mPFC significantly increased after UAC. Injection of IL-1(3 antibody into the mPFC blocked orofacial and somatic hyperalgesia. IL-1(3 was mainly localized in microglia cells. Furthermore, injection of IL-1(3 antibody significantly reduced the expression of sPLA2-III. These results indicate that neuroinflammatory cascade responses induced by glial-neuron crosstalk in the mPFC may contribute to the development of TMD and FMS comorbidity, and IL-1(3 and sPLA2-III are identified as novel potential therapeutic targets for the treatment of chronic pain in the comorbidity of TMD and FMS.

关键词： thoracolumber   vertebral fracture   X-rays  

摘要： Introduction: In trauma, we can perform a lateral radiography of the lumbosacral hinge taking the femoral heads if we include it in the initial lesion assessment. Thus, the pelvic incidence informs about the type of back as described by Roussouly. Aim: To describe the clinical and radiological results of these types of back which are operated on for a thoracolumbar fracture. Methods: We recorded the clinical, radiological data and the characteristics of the fracture of 120 patient operated on for a thoracolumbar spine fracture over a period of 14 years between February 2005 and July 2019. We studied the deformation according to Regional traumatic angulation (ART), Sagittal Farcy Index (SIF), Gardner Segment Kyphotic Deformity (GSKD). Functional evaluation was carried out according to the Denis Pain Scale. Radiological evaluation was based on relative gain and loss. Results: In individuals with low pelvic incidence, a prevalence of 72% was observed for type A fracture, whereas types B and C accounted for 45.9% (P<0.05) for backs with high pelvic incidence. The Denis Pain Scale score indicated that 90% of individuals with low incidence backs had scores below 3, whereas only 65.6% of those with high incidences had scores below 3 (P<0.05). The loss of correction for backs with low incidences was measured at 1.2°, while for backs with high incidences, it was 3° (p<0.05). Conclusion: Fractures on backs with low pelvic incidence considered as stiff backs are more frequently of type A, with better functional results and less losses. © 2024 Societe Tunisienne des Sciences Medicales. All rights reserved.