地龙配方颗粒多指标成分测定及质量评价

目的 建立同时测定地龙配方颗粒中次黄嘌呤、肌苷、鸟苷和腺苷含量的HPLC方法，结合测定结果和HPLC指纹图谱对地龙配方颗粒进行质量评价。方法 采用Thermo Acclaim^TM120 C₁₈色谱柱（4.6 mm×250 mm，5 μm），以乙腈-水为流动相，梯度洗脱，流速0.6 ml/min，柱温25 ℃，检测波长254 nm，对10批次样品进行4种成分含量测定和HPLC图谱采集；对所得图谱应用《中药色谱指纹图谱相似度评价系统（2012.130723版）》进行分析评价。结果 次黄嘌呤、肌苷、鸟苷和腺苷成分在各自范围内线性关系良好（r≥0.999 9），平均加样回收率99.20%~102.98%，RSD 0.26%~0.71%；10批样品中4种成分含量范围分别为：0.740 0~4.457 4 mg/g、2.132 3~7.805 0 mg/g、0.325 4~1.596 1 mg/g、0.537 2~2.222 9 mg/g；不同厂家地龙配方颗粒HPLC图谱与对照指纹图谱的相似度均大于0.91。结论 该方法可用于地龙配方颗粒中次黄嘌呤、肌苷、鸟苷和腺苷等核苷类成分的含量测定；HPLC指纹图谱可用于地龙配方颗粒的质量评价；不同厂家生产的地龙配方颗粒的HPLC指纹图谱相似度较高，但次黄嘌呤、肌苷、鸟苷和腺苷成分的含量差异较大。     

The cGAS–STING signaling in cardiovascular and metabolic diseases: Future novel target option for pharmacotherapy

The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling exert essential regulatory function in microbial-and onco-immunology through the induction of cytokines, primarily type I interferons. Recently, the aberrant and deranged signaling of the cGAS–STING axis is closely implicated in multiple sterile inflammatory diseases, including heart failure, myocardial infarction, cardiac hypertrophy, nonalcoholic fatty liver diseases, aortic aneurysm and dissection, obesity, etc. This is because of the massive loads of damage-associated molecular patterns (mitochondrial DNA, DNA in extracellular vesicles) liberated from recurrent injury to metabolic cellular organelles and tissues, which are sensed by the pathway. Also, the cGAS–STING pathway crosstalk with essential intracellular homeostasis processes like apoptosis, autophagy, and regulate cellular metabolism. Targeting derailed STING signaling has become necessary for chronic inflammatory diseases. Meanwhile, excessive type I interferons signaling impact on cardiovascular and metabolic health remain entirely elusive. In this review, we summarize the intimate connection between the cGAS–STING pathway and cardiovascular and metabolic disorders. We also discuss some potential small molecule inhibitors for the pathway. This review provides insight to stimulate interest in and support future research into understanding this signaling axis in cardiovascular and metabolic tissues and diseases.     

cGAS-STING信号通路与脓毒症肠屏障功能障碍相关性的研究进展

［摘要］　脓毒症的发病机制复杂。近年来研究证实，脓毒症发生时，cGAS-STING信号通路激活及作用机制对于改善脓毒症肠屏障功能障碍具有重要意义。该文就cGAS-STING信号通路的激活、cGAS-STING信号通路与脓毒症肠道炎症反应及cGAS-STING信号通路对肠屏障功能的影响作一综述。     

基于特征图谱结合化学计量学和一测多评法的薤白质量评价

目的 建立薤白特征图谱分析方法，并结合化学计量学和一测多评法（quantitative analysis of multi-components with a single-marker，QAMS）开展薤白质量控制研究。方法 采用HPLC方法，Agilent Eclipse Plus C₁₈色谱柱（250 mm×4.6 mm，5μm），以甲醇-超纯水溶液为流动相梯度洗脱，体积流量1.0 mL/min，柱温30℃，检测波长261 nm，进样量20 μL，建立薤白特征图谱，接着采用聚类分析（clustering analysis，CA）、主成分分析（principal component analysis，PCA）、正交偏最小二乘法-判别分析（orthogonal partial least square method-discriminant analysis，OPLS-DA）对不同批次薤白饮片进行化学模式识别分析，实现数据集的可视化。同时以腺苷为内参物建立QAMS法，建立内参物与胞苷、尿苷、鸟苷的相对校正因子，采用外标法（external standard method，ESM）与QAMS法分别测定12批次薤白样品中胞苷、尿苷、鸟苷、腺苷4种核苷类成分的含量，以验证QAMS法结果的可靠性。结果 建立的HPLC特征图谱方法较全面地反映了薤白药材的化学成分，分析方法专属性强，准确可靠；化学计量学分析结果基本一致；并通过OPLS-DA找出了3种可能的标志性成分；QAMS法与外标法测定结果之间无显著差异。结论 建立的薤白特征图谱分析方法、化学计量学方法、多指标成分QAMS法可为薤白和其他植物药的质量控制与评价提供参考。     

复杂电磁环境工作人员尿中8-羟基脱氧鸟苷和8-羟基鸟苷水平及其影响因素分析

目的 对复杂电磁环境(complex electromagnetic environment, CEE)工作人员的DNA和RNA氧化损伤情况以及其影响因素进行分析，为预防和控制职业病危害提供科学依据。方法 采用方便抽样法选择武汉某芯片厂CEE工作人员(n=133)为暴露组和办公室人员(n=56)为对照组，用稀释法和液相色谱-三重四级杆质谱仪测量氧化应激标志物8-羟基脱氧鸟苷(8-OHdG)和8-羟基鸟苷(8-OHG)在其尿液样本中的浓度。根据问卷调查结果，用logistic回归法分析影响8-OHdG的相关因素。结果 暴露组人员尿中的8-OHdG和8-OHG,经尿比重调整后浓度中位数分别为9.34 ng/ml和17.08 ng/ml。与对照组相比，暴露组8-OHdG浓度高于对照组，且差异有统计学意义(Z=-2.194,P=0.028)。CEE(OR=3.07,95%CI:1.35～7.00)、吸烟(OR=2.62,95%CI:1.13～6.08)和运动(OR=2.5,95%CI:1.04～6.00)为危险因素；女性(OR=0.09,95%CI:0.03～0.28)为保护因素。结论 长期暴...     

Targeting Rho kinase to restore endothelial barrier function following vascular scaffold implantation

Vascular scaffold implantation induces injury to the intimal layer and causes discontinuity of the regenerated endothelial monolayer, compromising barrier integrity, increasing permeability, and allowing the transmigration of leukocytes and lipoproteins into the subendothelial space. Mechanical vascular wall stretching triggers Ras homolog family member A (RhoA)/Rho kinase-mediated actomyosin contractility and destabilization of adherens junctions, leading to endothelial barrier dysfunction. Assembly of intercellular adhesion and actin cytoskeletal organization of interendothelial junctions are controlled by downregulation of RhoA guanosine triphosphatase (GTPase)-mediated barrier-disruptive activity and upregulation of repressor-activator protein 1 (Rap1) and Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase-mediated cytoskeletal reorganization, leading to endothelial barrier stabilization. This review highlights the involvement of Rho GTPases in the disruption of endothelial barrier integrity following vascular scaffold implantation and the targeting of downstream Rho-associated protein kinases, which signal the network to restore endothelial barrier integrity and stability.