旋覆代赭汤对反流性食管炎大鼠模型TLR4/NF-κB的影响

目的观察旋覆代赭汤对反流性食管炎(RE)模型大鼠食管黏膜与脂多糖(LPS)、Toll样受体4(TLR4)、核因子κB(NF-κB)表达的影响。方法将60只雄性Wistar大鼠按随机数字表法分为正常对照组、模型组、旋覆代赭汤组(简称中药组,9.89 g/kg)、西药(奥美拉唑+莫沙比利,2.58 mg/kg)组,每组15只。除正常对照组外大鼠采用“4.2 mm幽门夹+2/3胃底结扎术”制备酸碱混合反流RE大鼠模型。术后第7天予相应药物干预,持续干预14天。利用光学显微镜观察大鼠食管下段黏膜组织形态学变化;应用ELISA法检测定外周血中LPS含量;采用Western Blot法与RT-PCR法检测食管黏膜组织中TLR4、NF-κB蛋白和基因表达。结果与正常对照组比较,模型组大鼠食管黏膜镜下损伤最为严重,食管黏膜呈炎性改变,可见急慢性炎细胞浸润,病理积分和外周血中LPS含量升高(P<0.05),食管组织中TLR4、NF-κB蛋白和基因表达升高(P<0.05)。与模型组比较,中药组、西药组病理积分和外周血中LPS含量降低(P<0.05),食管组织中TLR4、NF-κB蛋白和基因表达亦明显降低(P<0.05)。结论旋覆代赭汤能够减轻RE模型大鼠食管黏膜的损伤,抑制TLR4、NF-κB的表达,促进食管黏膜损伤的恢复。     

结外NK/T细胞淋巴瘤患者鼻腔菌群失调与预后的关系

目的 探讨鼻腔菌群失调与结外NK/T细胞淋巴瘤（extranodal NK/T-cell lymphoma，ENKTCL）预后的相关性。方法 回顾性分析244例初治ENKTCL患者的临床资料及鼻拭子培养结果，根据是否存在鼻腔菌群失调将患者分为菌群正常组（n=114）和菌群失调组（n=130），并分析菌群失调与患者临床病理特征、治疗效果及预后的关系。结果  菌群失调组患者共培养出409株优势菌株，以金黄色葡萄球菌、草绿色链球菌、表皮葡萄球菌及铜绿假单胞菌为主。菌群失调组患者的乳酸脱氢酶升高比例高于菌群正常组（P=0.044），预后评分PINK≥1的中危或高危患者比例亦高于菌群正常组（P=0.003）。治疗结束时，菌群失调组患者的完全缓解率显著低于菌群正常组（45.5% vs 61.4%，P<0.05），5年无疾病进展生存率亦低于菌群正常组（48.4% vs 63.9%，P=0.048）。亚组分析显示，早期及PINK低危患者中，菌群失调与否与患者的无疾病进展生存期有关（P=0.022， 0.011）。结论 鼻腔菌群失调与ENKTCL患者预后密切相关，针对鼻腔菌群失调的措施可能进一步改善ENKTCL的治疗效果及预后。     

胸腺瘤术后辅助放疗的现状及进展

手术切除是胸腺瘤最重要的治疗手段,然而,术后辅助放疗的作用一直存在不同争议。二维放疗时代多数获益不明显,精准放疗技术已使肿瘤放疗发生了较大的变化,胸腺瘤术后放疗价值也可能在改变。目前,放疗在手术切缘阳性或无法行手术切除者的作用是肯定的;在完整手术切除者中,Masaoka-Koga分期Ⅰ期患者无需术后辅助放疗,Ⅱ期患者术后辅助放疗作用争议较大,如果放疗宜考虑Ⅱb期、大体积、B2/B3型等因素;Ⅲ期术后辅助放疗也存在争议,但是多数结果倾向行术后放疗。术后辅助放疗宜采用精准放疗技术,照射范围建议瘤床三维外扩0.5 cm,肿瘤累及的纵隔胸膜及沿纵隔胸膜前后、头脚方向0.5～1.0 cm,肺侧纵隔胸膜为0.5 cm以内,以及肿瘤周血管壁和部分血管间隙,避免包括过多的正常组织。剂量在完全切除时为45~50Gy,非完全切除为54~60Gy或稍高,可能会使放疗获益增加和风险下降。质子、重离子等新型放疗技术的应用可获得剂量学方面的优势,是否能转化为临床获益还需进一步探究。     

circRNA_001569通过miR-145/HBXIP轴影响乳腺癌细胞的恶性生物学行为

目的：探讨 circRNA_001569 通过 miR-145/HBXIP 轴在乳腺癌细胞增殖、侵袭、迁移中发挥的作用。方法:收集2016年1月至2019年1月期间衡水市人民医院收治的30例乳腺癌患者的癌组织和癌旁组织。qPCR检测circRNA_001569在乳腺癌组织、癌旁组织以及细胞系中的表达。生物信息学工具预测miR-145的靶基因，RNA免疫沉淀（RNA immunoprecipitation，RIP）和双荧光素酶报告基因实验检测 miR-145 或靶基因之间的相互作用 ；向乳 腺 癌 MDA-MB-231 和 MCF-7细胞中转染si-circRNA_001569、miR-145 mimics或miR-145 inhibitor，建立基因过表达或沉默的细胞模型，qPCR和Western blotting分别检测转染对相关基因和蛋白表达的影响，CCK-8法、Transwell实验检测转染对细胞增殖、侵袭和迁移的影响。结果:在乳腺癌组织和乳腺癌细胞中，circRNA_001569 和 HBXIP 均呈高表达、miR-145 呈低表达。RIP 分析和双荧光素酶实验证实了 miR-145 与circRNA_001569和HBXIP之间的靶向关系；circRNA_001569或HBXIP过表达促进MDA-MB-231和MCF-7细胞的增殖、侵袭和迁移（均 P<0.01），而 miR-145 过表达起相反的作用（均 P<0.01）。结论:circRNA_001569 可能通过下调 miR-145 的表达、上调HBXIP的表达从而促进乳腺癌细胞的增殖、侵袭和迁移。     

基于TGF-β1/p38MAPK/FN信号通路的放射性食管炎发病机制的研究

Objective To investigate the pathogenesis mechanism of radiation esophagitis from the perspective of mucosal regeneration and to determine whether it is associated with TGF-β1/p38MAPKs/FN signaling pathway. Methods The pathological analysis of esophageal specimens was performed by HE staining method. The expression of FN and TGF-β1 genes were observed by real time-PCR method, and the expression of tissue proteins TGF-β1, p38 and FN were detected by Western blot. Results The weights, food intakes and water intakes at the first week after the occurrence of radiation esophagitis were significantly decreased (P<0.05) and recovered at the fourth week. The esophageal mucosa was destructed at the first and second weeks, and the regeneration occurred in the fourth weeks; TGF-β1 and p38MAPK protein expression increased first and then decreased, while FN protein expression decreased first and then increased. Conclusion The TGF-β1/p38MAPK/FN signaling pathway may be involved in the process of mucosal repair. © 2020, CHINA RESEARCH ON PREVENTION AND TREATMENT. All rights reserved.     

SAMHD1通过调控p27表达抑制肝细胞癌细胞增殖的研究

背景与目的：不育α基序结构域和组氨酸/天冬氨酸残基双联体结构域包涵蛋白1（sterile alpha motif and histidine/aspartic acid domain-containing protein 1，SAMHD1）具有抑制多种肿瘤细胞生长的作用，但其调节肝细胞癌（hepatocellular carcinoma，HCC）细胞增殖的作用及机制尚未见报道。探究SAMHD1调控p27的表达对HCC细胞Huh7的增殖、凋亡和细胞周期的影响。方法：首先通过蛋白质印迹法（Western blot）检测正常肝细胞和不同类型HCC细胞中SAMHD1的表达情况。利用基因修饰技术构建过表达SAMHD1、dNTP酶活性位点突变体（SAMHD1-D207N）和磷酸化位点突变体（SAMHD1-T592E）的重组质粒，然后利用四甲基偶氮唑蓝（methyl thiazolyl tetrazolium，MTT）法检测过表达SAMHD1及其突变体或siRNA干扰沉默SAMHD1对HCC细胞增殖的影响，采用流式细胞术检测细胞周期与细胞凋亡情况。在癌症基因组图谱（The Cancer Genome Atlas，TCGA）数据库中分析SAMHD1和p27表达的相关性。结果：HCC细胞中SAMHD1表达上调，过表达SAMHD1、SAMHD1-D207N和SAMHD1-T592E可以抑制Huh7细胞增殖，细胞周期停滞在G ₁ /G ₀ 期；相反，干扰SAMHD1后细胞增殖加快，细胞周期停滞在G ₂ /M期。机制研究表明，SAMHD1上调细胞周期蛋白激酶抑制因子p27的表达。在HCC组织中，p27的表达与SAMHD1表达呈正相关。结论：过表达SAMHD1可以上调p27的表达，导致细胞周期停滞在G ₁ /G ₀ 期，从而抑制HCC细胞增殖，这种抑制作用不依赖于其dNTP酶活性和磷酸化修饰。     

Borderline or locally advanced pancreatic adenocarcinoma: A single center experience on the FOLFIRINOX induction regimen

IntroductionThis study aimed to determine the impact of FOLFIRINOX neoadjuvant therapy on patients with non-metastatic borderline/locally advanced (BL/LA) pancreatic ductal adenocarcinoma (PDAC), in current practice.Material and methodsFrom 2010 to 2017, 258 patients with BL/LA PDAC from a single high-volume institution received FOLFIRINOX neoadjuvant treatment.ResultsThe 258 patients received a median number of 6 cycles of FOLFIRINOX (range, 3–16); 98 (38%) patients underwent curative surgery, and 160 (62%) continued medical treatment. A venous resection was performed in 57 patients (58%), and an arterial resection in 12 (12%). The postoperative 30- and 90-day mortality rates were 6.1% and 8.2%, respectively. Adjuvant chemotherapy was performed in 57 patients (59%). The median overall survival (OS) in patients who did (n = 98) or did not (n = 160) undergo surgical resection were 39 months and 19 months, respectively (P < 0.001). In resected patients, the ASA 3 score (P < 0.01), venous resection (P < 0.01), hemorrhage (P < 0.01), and R1 margin status (P = 0.03) were found to negatively influence the OS. The median OS was significantly higher in patients who did not require a venous resection (not reached vs. 26.5 months, P < 0.001).ConclusionsNeoadjuvant FOLFIRINOX provided a survival benefit in BL/LA PDAC patients, particularly in those who did not ultimately require venous resection.