课程文献中心 更多>>

关键词： 糖尿病足溃疡   中医外治法   细胞因子  

摘要： 糖尿病足溃疡（Diabeticfootulcer，DFU)作为糖尿病的一种严重并发症，其发病率随着社会老龄化的进程不断攀升。正常创面的愈合是一个复杂的过程，包括炎症阶段、增殖阶段和组织重塑阶段，这三个阶段相互重叠，共同促进伤口的愈合。然而，糖尿病足溃疡创面在愈合过程中的表现却常常显得异常。近年来，中医外治法在治疗DFU方面取得了显著的疗效，尤其在局部创面处理上表现出了显著的优势。然而，尽管中医外治法在临床实践中表现出色，但其具体的作用机制及作用靶点却尚未完全明确。细胞因子如白细胞介素、干扰素、生长因子等在创面愈合过程中发挥着重要作用。中医外治法通过调节如AGEs/RAGE、NF-κB、PI3K/Akt等信号通路，影响相关细胞因子的表达，从而干预不同的愈合阶段，促进糖尿病创面的愈合。因此，深入探究中医外治法修复DFU创面的作用机制及靶点，不仅有助于揭示中医外治法的科学内涵，也有助于推动其在临床上的进一步推广和应用。本文将从细胞因子的角度，对中医外治法修复DFU创面的相关研究进行回顾和总结。

关键词： COVID-19   diagnostic   HLA   subacute thyroiditis   treatments  

摘要： Subacute thyroiditis (SAT) is an inflammatory thyroid disease that is often associated with viral infections. In particular, SARS-COV-2 and its vaccine were found to cause SAT during the recent COVID-19 pandemic. However, the pathogenesis, clinical features, and processes still need further profiling. Recently, there are new findings and understanding about the pathogenic mechanisms of SAT. Some HLA genes have been shown to increase the risk of SAT development, and inflammatory cytokine storms could promote the progression of SAT. Some new diagnostic criteria for SAT have been proposed to facilitate clinicians' diagnosis of SAT when facing atypical symptoms in a manner of rapidity and accuracy. Plus, new treatments for SAT with herbal medicines have been proposed recently as an addition to the conventional steroidal drugs and NSAIDs. This review will provide a summary of these recent progresses of SAT on pathogenesis, diagnosis, and therapies with emphasis on the role of a variety of virus pathogens, including the COVID-19 virus.

关键词： 过敏性哮喘   医药共管   抗IgE单克隆抗体   奥马珠单抗  

摘要： 目的 进一步规范抗IgE单克隆抗体治疗过敏性哮喘的合理应用。方法 通过系统检索和临床经验总结抗IgE单克隆抗体治疗管理的相关问题，按照证据分级进行质量评价，并运用德尔菲法就共识建议达成共识，形成《抗IgE单克隆抗体治疗过敏性哮喘的医药共管专家共识》（简称《共识》）。结果 《共识》以奥马珠单抗为代表，形成了12条建议，涵盖了医药共管的工作模式、工作路径、分级诊疗和培训考核等内容，明确奥马珠单抗治疗过敏性哮喘医药共管的规范化管理路径。结论 该共识为药师参与奥马珠单抗治疗过敏性哮喘的管理提供切实有效的建议，有助于提高患者的用药依从性和疾病预后，实现抗IgE单克隆抗体的医疗价值。

关键词： “邵氏五针法”   哮喘   气道重塑   白细胞介素-4、白细胞介素-6   转化生长因子-β1、Smad家族成员2 mRNA  

摘要： 目的 观察针刺“肺俞”“大椎”“风门”对哮喘大鼠血清中白细胞介素（IL）-4、IL-6及肺组织中转化生长因子-β1（TGF-β1）和Smad家族成员（Smad）2基因表达的影响。方法 选取40只大鼠分为空白组、模型组、针刺组和地塞米松组，共4组每组各10只。通过腹腔注射卵蛋白加氢氧化铝混合物并用卵蛋白滴鼻激发的方法来制备慢性哮喘大鼠模型，空白组用生理盐水代替。针刺组每周针刺“肺俞”“大椎”“风门”3次，每次20min，地塞米松组每周腹腔注射3次，空白组和模型组仅陪同抓取固定，不进行治疗。干预结束24h后取材，苏木精-伊红（HE）染色对肺组织进行病理学检查；酶联免疫吸附试验（ELISA）检测血清中IL-4、IL-6的表达；实时荧光定量聚合酶链式反应（RT-PCR）测定TGF-β1和Smad2 mRNA在大鼠肺组织中的表达情况。结果 与空白组相比，模型组大鼠支气管管壁和平滑肌可见明显的增厚、管腔变窄，并有较多的炎性细胞浸润，大鼠血清中IL-4、IL-6和肺组织中TGF-β1、Smad2 mRNA的表达量显著升高（P＜0.01）；与模型组相比，针刺组和地塞米松组大鼠气道炎症程度均降低，血清中IL-4、IL-6和肺组织中TGF-β1、Smad2 mRNA的表达量均显著降低（P＜0.01）。结论 “邵氏五针法”可以通过下调大鼠血清中IL-4、IL-6及肺组织中TGF-β1、Smad2 mRNA的表达，减轻炎症细胞浸润，抑制平滑肌增厚和气道重塑，可作为针刺抗哮喘效应的机理之一。

关键词： delta-Catenin   IL-17A   inflammation   miRNA   psoriasis  

摘要： Psoriasis is an immune-mediated inflammatory dermatological disorder characterized by the interaction between immune cells and keratinocytes, which perpetuates cutaneous inflammation and cellular hyperproliferation. In this study, we identified a strong delta-catenin signature in psoriatic skin;however, the precise role of delta-catenin remains to be elucidated. Additionally, we observed that Interleukin (IL)-17A, a pivotal cytokine involved in the development of psoriatic lesions, induces delta-catenin expression in HEKn and HACAT cells. From a mechanistic perspective, delta-catenin initiated NF-kappa B signaling, subsequently leading to the activation of IL-6 and IL-8 production. Furthermore, silencing delta-catenin expression mitigated IL-17A-induced hyperproliferation of keratinocytes through the NF-kappa B pathway. Our study further identified miR-101 and miR-122 as upstream regulators of delta-catenin, exerting their effects by downregulating delta-catenin protein levels. We demonstrated that miR-101 and miR-122 can inhibit the hyperproliferation of keratinocytes induced by delta-catenin. These findings validate the role of delta-catenin in the pathogenesis of psoriasis, particularly in keratinocyte-mediated inflammatory responses and cellular hyperproliferation. Consequently, miR-101 and miR-122 hold potential as therapeutic agents in the treatment of psoriasis.

关键词： humans   lipolysis   tocilizumab   interleukin-6   fatty acids   obesity   homeostasis   fasting   nutrients   isotopes  

摘要： Interleukin-6 (IL-6) knockout mice and humans treated with IL-6 receptor blockade gain adipose tissue mass. This study investigates whether basal IL-6 activity (resting IL-6 levels) influences fat storage during fasting and postprandial states. Using stable-isotope tracer techniques and IL-6 receptor blockade with tocilizumab, we examine fat kinetics in humans. Blocking basal IL-6 activity reduces fasting whole-body lipolysis, decreases hormone-sensitive lipase (HSL) phosphorylation and fatty acid release in adipose tissue, and impairs postprandial fatty acid uptake in the leg. These results suggest diminished fatty acid uptake and oxidation in skeletal muscle, along with enhanced fatty acid entrapment in adipose tissue, which may account for the increased adiposity in the absence of IL-6 activity. Additionally, IL-6 blockade increases the escape of meal-derived fatty acids into the bloodstream. Whether this affects fatty acid storage and lipotoxicity in other tissues warrants further investigation. This study was registered at *** (NCT04687540).

摘要： Recipients' age has emerged as a key factor that impacts on acute renal allograft rejection and graft survival. Age-related functional and structural changes in the immune system have been observed, yet the precise influence of aged immunity on kidney transplant remains unclear. In an initial retrospective analysis of clinical data gathered from two major centers in China and Germany, we found a correlation between aging and mitigated rejection outcomes in kidney recipients. To study the mechanism, we performed kidney transplantation on mice and observed attenuated allograft rejection in senescent recipients. Single-cell transcriptome analysis of allograft kidneys indicated a protective role of p21high macrophages in aged mice. Supernatant collected from p21high macrophage primary culture inhibited the cytotoxic function and proliferation of CD8+ T cells. Zfp36 is highly expressed in senescent p21high macrophages. To determine its role in renal allograft rejection, we studied mice with Zfp36 conditionally deleted in macrophages (Zfp36-cKO). These mice developed exacerbated allograft rejection with enhanced IL-27 production and CD8+ T cell hyperactivation. Inhibition of IL-27 with neutralizing antibody or deletion of IL-27 receptor on CD8+ T cells reversed acute renal allograft rejection in Zfp36-cKO mice. Moreover, in vitro silencing Zfp36 with siRNA led to impaired degradation of IL-27 p28 mRNA and a subsequent increase of IL-27 in p21high macrophages. In conclusion, senescent macrophages protect renal allograft rejection by suppressing CD8+ T cells via a Zfp36/IL-27-dependent mechanism. These findings may provide innovative therapeutic strategies for addressing kidney allograft rejection.

关键词： Medical risk factors   Immune suppression   Graft survival   Renal transplantation   Antigens   Diabetes mellitus   Immunology   Transplantation immunology  

摘要： Background HLA-DQ antibodies are the most prevalent de novo donor-specific antibodies (dnDSAs) after kidney transplantation (KT). The immunogenicity and impact of each HLA-DQ mismatch on graft outcomes can vary considerably. Methods This retrospective cohort study investigated the prevalence and risk factors for dnDSA development in patients who underwent KT at Siriraj Hospital between 2006 and 2020 and had HLA-DQB1 mismatches. Our center employed a protocol for post-KT dnDSA surveillance. The impact of dnDSAs on late rejection and graft survival was evaluated. Results In our cohort of 491 KT recipients, 59 (12.02%) developed dnDSAs to HLA-DQB1 at a median time of 4.2 years after KT. The risk of dnDSA occurrence was significantly higher among recipients with HLA-DQ7 mismatch (HR: 2.8;95% CI: 1.21-6.52;P = 0.017) and HLA-DQ9 mismatch (HR: 2.63;95% CI: 1.11-6.27;P = 0.028). Recipients who developed dnDSAs were younger (P = 0.009), had higher rates of medication nonadherence (P = 0.031), had pre-KT panel reactive antibody levels above 20% (P = 0.044), and received non-tacrolimus immunosuppression (P < 0.001) compared to those without. Recipients who developed dnDSAs to HLA-DQ exhibited a significantly higher incidence of late graft rejection (HR: 7.76;95% CI: 5-12.03;P < 0.0001) and inferior death-censored graft survival than those without dnDSAs (log rank P < 0.001). Conclusion The patients with HLA-DQ7 and HLA-DQ9 mismatches exhibit the highest risk of developing dnDSAs. Individualized immunosuppression adjustment and kidney allocation based on specific HLA-DQ mismatch may enhance long-term graft survival.