妊娠期甲状腺癌多学科综合治疗

妊娠期甲状腺癌的诊治是目前甲状腺疾病诊治的热点和难点问题之一。妊娠期发现甲状腺癌对临床医生和孕妇都是一个极大的挑战，应通过多学科协作，尽快明确诊断，全面、合理的评估孕妇和胎儿的情况，选择最合适的治疗和随诊方式，避免对孕妇和胎儿产生副反应，维持正常孕期，获得最佳的治疗效果。     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

Transarterial Chemoembolization vs Radioembolization for Neuroendocrine Liver Metastases: A Multi-Institutional Analysis

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蒜氨酸抗菌机制研究

目的 检测蒜氨酸最低抑菌浓度（MIC）与最低杀菌浓度（MBC），探讨蒜氨酸体内外抗菌机制。方法 体外微量稀释法检测蒜氨酸MIC和MBC，荧光显微镜观察菌体表面蒜氨酸，探讨蒜氨酸抗菌机制。体内蒜氨酸和青霉素分别治疗金葡菌感染家兔脓肿，检测脓汁标本中细菌存活情况，探讨体内蒜氨酸抗菌作用。结果 蒜氨酸对大肠杆菌、伤寒杆菌、金黄色葡萄球菌、白色葡萄球菌的MIC分别为3.047 μg·mL^-1、6.094 μg·mL^-1、0.386 μg·mL^-1、0.386 μg·mL^-1，蒜氨酸体外无杀菌活性。浓汁标本：死菌率蒜氨酸治疗组显著高于阴性对照组（P < 0.01），与青霉素治疗组无明显差异（P > 0.05）；活菌率蒜氨酸治疗组显著低于阴性对照组（P < 0.01），与青霉素治疗组无明显差异（P > 0.05）。结论 蒜氨酸与菌体蛋白、细菌酶蛋白结合阻断细菌与环境物质交换，抑制细菌生命活动，具有较强的抑菌作用，无杀菌活性；蒜氨酸体内代谢成大蒜素，具有较强杀菌作用。     

安息香药材化学成分、药理作用研究进展及质量标志物预测分析＊

安息香为安息香科白花树Styrax tonkinensis （Pierre） Craib ex Hart.的干燥树脂，主要化学成分为香脂酸类和三萜类物质，及少数木脂素类物质，其中香脂酸类化合物是其主要活性成分。安息香主要药理活性有抗炎解热、抗肿瘤、血脑屏障保护等。本文对安息香药材的化学成分和药理作用进行了综述，并从多角度分析预测了安息香可能的质量标志物，为安息香药材的质量控制、合理开发与利用提供参考。     

基于网络药理学与分子对接技术的石菖蒲治疗癫痫作用机制研究＊

目的 利用网络药理学和分子对接技术研究石菖蒲抗癫痫的有效成分及作用机制。方法 运用中药系统药理数据库及分析平台检索石菖蒲有效成分及主要靶点，通过GeneCards数据库收集癫痫疾病的相关潜在作用靶点，运用Cytoscape.3.7.1和 String绘制石菖蒲-癫痫靶点互作关系图，运用Metascape数据库进行GO和KEGG信号通路富集分析。运用AutoDock Vina 1.1.2软件对石菖蒲主要有效成分与癫痫相关靶标进行分子对接验证；通过构建戊四唑诱导的癫痫模型初步评价石菖蒲提取物及潜在有效成分的抗癫痫作用。结果 由 TCMSP 筛选得到4个有效成分及76个主要靶点。癫痫疾病以“Score”大于1.5分进行筛选得到3685个靶标。GO富集分析得到BP条目10个，细胞CC条目9个，MF条目10个（P<0.01），主要涉及核受体活性、离子通道活性、激素结合、神经递质受体活性、蛋白激酶活性、钙调蛋白结合等。KEGG 富集得到14条通路，主要涉及c型凝集素受体信号通路、雌激素信号通路、Ca²⁺信号通路、逆行内源性大麻素信号通路等。分子对接结果显示，桉脂素、山奈酚和8-异戊烯基山奈酚与癫痫关键靶标GABRA2、PPARG等具有良好的结合活性。动物实验结果表明，石菖蒲水提取物及主要潜在有效成分桉脂素和山奈酚在PTZ致小鼠癫痫模型上显示出较好的抗癫痫活性。结论 本研究通过动物实验验证了石菖蒲提取物和潜在有效成分的抗癫痫活性，并且运用网络药理学和分子对接技术探讨了其抗癫痫作用机制，发现石菖蒲可通过多个成分如桉脂素、山奈酚、8-异戊烯基山奈酚，多靶点如GABA_A、PPARG等，多条通路如雌激素信号通路、钙信号通路对机体产生协调效应从而抑制癫痫的发作。该研究提示石菖蒲治疗癫痫具有多成分、多靶点、多通路特点，为石菖蒲的进一步研究提供数据支撑。     

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.