黄芩素调控 NLRP3 / Caspase-1 通路对牙周炎大鼠牙槽骨吸收的影响

目的 探索黄芩素调控核苷酸结合寡聚化结构域样受体蛋白 3 ( nucleotide-binding oligomerization domain-like receptor protein 3, NLRP3) / 半胱氨酸天冬氨酸蛋白酶 1 ( cysteine aspartate protease 1, Caspase1) 通路对牙周炎大鼠牙槽骨吸收的影响。 方法 将 40 只牙周炎大鼠随机分为模型组、 黄芩素组、 激活剂 组、 黄芩素 + 激活剂组, 另取 10 只正常作为对照组。 检测大鼠釉牙骨质界到牙槽嵴顶 (CEJ-AC) 的距离、 血清中白细胞介素-6 (IL-6)、 转化生长因子-β (TGF-β) 含量以及牙周组织病理变化、 IL-6、 TGF-β 阳性 表达和 NLRP3、 Caspase-1 蛋白表达。 结果 模型组大鼠 CEJ-AC、 NLRP3、 Caspase-1、 IL-6、 TGF-β 水平及 阳性表达水平以及蛋白表达水平均升高 (P< 0. 05); 经黄芩素干预后, 各项指标均降低 (P< 0. 05); 引入 激活剂明显削弱了黄芩素对牙周炎大鼠的抗炎作用。 结论 黄芩素通过抑制 NLRP3 / Caspase-1 通路减轻炎性反应, 控制牙槽骨吸收。     

Phase 0 Study of Vandetanib-Eluting Radiopaque Embolics as a Preoperative Embolization Treatment in Patients with Resectable Liver Malignancies

PurposeTo assess the safety and tolerability of a vandetanib-eluting radiopaque embolic (BTG-002814) for transarterial chemoembolization (TACE) in patients with resectable liver malignancies.Materials and MethodsThe VEROnA clinical trial was a first-in-human, phase 0, single-arm, window-of-opportunity study. Eligible patients were aged ≥18 years and had resectable hepatocellular carcinoma (HCC) (Child-Pugh A) or metastatic colorectal cancer (mCRC). Patients received 1 mL of BTG-002814 transarterially (containing 100 mg of vandetanib) 7–21 days prior to surgery. The primary objectives were to establish the safety and tolerability of BTG-002814 and determine the concentrations of vandetanib and the N-desmethyl vandetanib metabolite in the plasma and resected liver after treatment. Biomarker studies included circulating proangiogenic factors, perfusion computed tomography, and dynamic contrast-enhanced magnetic resonance imaging.ResultsEight patients were enrolled: 2 with HCC and 6 with mCRC. There was 1 grade 3 adverse event (AE) before surgery and 18 after surgery; 6 AEs were deemed to be related to BTG-002814. Surgical resection was not delayed. Vandetanib was present in the plasma of all patients 12 days after treatment, with a mean maximum concentration of 24.3 ng/mL (standard deviation ± 13.94 ng/mL), and in resected liver tissue up to 32 days after treatment (441–404,000 ng/g). The median percentage of tumor necrosis was 92.5% (range, 5%–100%). There were no significant changes in perfusion imaging parameters after TACE.ConclusionsBTG-002814 has an acceptable safety profile in patients before surgery. The presence of vandetanib in the tumor specimens up to 32 days after treatment suggests sustained anticancer activity, while the low vandetanib levels in the plasma suggest minimal release into the systemic circulation. Further evaluation of this TACE combination is warranted in dose-finding and efficacy studies.     

双源CT多定量参数对胃癌的诊断价值及与HER2的相关性

目的:探讨门脉期双源CT多个定量参数与胃腺癌病理分化程度及HER2的相关性。方法: 回顾性分析2018年7月至2019年4月间于陕西省人民医院行双源CT双能量扫描的48例经胃镜活检(21例)或手术病理证实（27例）的胃腺癌及30例正常胃的影像学资料，其中27例HER2指标明确，通过西门子第二代双源CT扫描获得静脉期双能量图像，利用syngo.via软件获得曲线斜率、门脉期碘浓度、标准化碘浓度；将患者分为胃腺癌与正常胃壁组，高、中、低分化胃腺癌组，HER2阳性组（+，++，+++）与HER2阴性组（-）。统计学方法采用Kappa一致性检验、ROC曲线法、两独立样本t检验及方差分析。结果:活检与术后病理结果具有较强的一致性（Kappa系数为0.701），两者无明显差异；胃腺癌与正常胃壁两组间能谱曲线斜率（1.35±0.24、2.19±0.71）及标准化碘浓度（0.31±0.079、0.54±0.157）均具有统计学意义（P<0.05），曲线下面积分别为0.992、0.919；低分化、中分化及高分化胃腺癌能谱曲线斜率值（3.07±0.67，2.63±0.57，2.01±0.39）组间及组内差异均具有统计学意义（P<0.05），低分化、中分化及高分化胃腺癌门脉期标准化碘浓度(0.60±0.167，0.52±0.089，0.36±0.039)组间差异具有统计学意义（P<0.05），中分化组与低分化组差异无统计学意义（P>0.05），高分化组与中、低分化组均具有统计学差异（P<0.05）。HER2阳性组与阴性组的能谱曲线斜率及标准化碘浓度值无统计学差异（P>0.05）。结论:能谱曲线斜率及门脉期标准化碘浓度值有助于对胃腺癌进行诊断并推测病理分化程度；双源CT定量参数与免疫组化指标HER2无相关性。