Increasing radiofrequency ablation volumes with the use of internally cooled electrodes and injected hydrochloric acid in ex vivo bovine livers

Purpose: We used an impedance-controlled generator with an internally cooled electrode to perform radiofrequency ablation (RFA) in ex vivo bovine livers, with a single injection of either 38.5% sodium chloride (NaCl) or 10% hydrochloric acid (HCl), to determine the relative effects of these two solutions on tissue impedance, temperature and ablation volume.

Materials and methods: We performed 10 ablations each with injections of NaCl (NaCl-RFA), HCl (HCl-RFA) or nothing (RFA-alone), with a power setting of 200 W for 15?minutes. We recorded tissue impedance before and after injection. We logged temperatures obtained from thermocouple probes positioned 5, 10, 15 and 20?mm from the internally cooled RF electrode. After ablation, we measured ablation zone longitudinal and transverse diameters, and we calculated a spherical ratio (SR) for each ablation.

Results: Mean post-injection impedance of 30.3 (standard deviation [SD] 2.5) ohms for HCl was significantly lower than that of 55.4 (SD 3.5) ohms for NaCl (p?<?.001). Mean maximum temperatures recorded at each respective distance from the RFA electrode were all highest for HCl-RFA and lowest for RFA-alone (p?<?.001). Mean longitudinal and transverse diameters after HCl-RFA (5.50 [SD 0.25] cm and 5.28 [SD 0.22] cm, respectively) were significantly larger than those after NaCl-RFA (4.24 [SD 0.35] cm and 3.55 [SD 0.43] cm, respectively) and after RFA-alone (3.60 [SD 0.10] cm and 2.70 [SD 0.13] cm, respectively) (p?<?.001). Mean SR after HCl-RFA (0.93, SD 0.02) was significantly higher than mean SR after NaCl-RFA (0.76, SD 0.06) and RFA-alone (0.72, SD 0.04) (p?<?.001).

Conclusion: Monopolar, impedance-controlled RFA, with an internally cooled electrode and a single 10% HCl injection may allow larger tumors to be treated, potentially resulting in improved patient outcomes.     

生物电阻抗矢量法评估血液透析合并高血压患者的容量负荷

目的应用生物电阻抗矢量法评估血液透析合并高血压患者的容量负荷,探讨高容量负荷状态对高血压患者预后的影响。方法研究对象来自南京医科大学附属明基医院透析前收缩压(6次透析治疗前平均收缩压值)>160 mmHg的血液透析患者。用生物电阻抗矢量法评估患者容量状态,并根据患者容量状态分为容量增加组和非容量增加组(包括容量正常和容量下降的患者)。比较两组患者临床资料、实验室指标、细胞内液比例(ICW)、细胞外液比例(ECW)、体细胞质量、瘦体重、干瘦体重及其占总体重的百分比、脂肪含量占总体重的百分比、阻抗/身高、容抗/身高、相位角、疾病指数的差异。采用Kaplan⁃Meier生存曲线比较两组患者生存率的差异。结果共51例血液透析合并高血压患者入选本研究,容量增加组19例,非容量增加组32例(容量正常27例,容量下降5例)。容量增加组患者的血白蛋白、前白蛋白、血红蛋白、血细胞比容、血磷较非容量增加组显著下降,淋巴细胞比例明显升高,组间比较差异均有统计学意义(均P<0.05)。容量增加组的细胞外液比例、疾病指数显著高于非容量增加组(均P<0.01);相位角、阻抗/身高、容抗/身高显著低于非容量增加组(均P<0.01)。临床追踪20个月,容量增加组患者血压达标率(透析前收缩压<160 mmHg)低于非容量增加组(26.3%比43.8%),但差异无统计学意义。容量增加组患者全因死亡率高于非容量增加组(26.3%比15.6%),Kaplan⁃Meier生存曲线分析提示两组生存率的差异尚无统计学意义。结论容量负荷增加的血液透析合并高血压患者细胞外液增加明显,营养状态评估指标较非容量增加的高血压患者明显下降,而淋巴细胞比例升高,可能与患者微炎症状态有关。容量负荷增加的高血压患者血压更加难以控制,临床预后可能不及非容量增加的患者。     

甲磺酸阿帕替尼片用于标准治疗失败后卵巢癌治疗的有效性和安全性

目的:观察甲磺酸阿帕替尼用于标准治疗失败后卵巢癌的有效性和安全性，为多线耐药的卵巢癌患者提供一种治疗方式。方法:选取2015年6月至2018年3月二线及二线后化疗失败的晚期卵巢癌患者26例，口服甲磺酸阿帕替尼后观察疗效及毒副反应。结果:1例患者CR，17例患者PR,2例患者SD,6例患者PD，客观有效率69%，疾病控制率77%，中位PFS达4.3个月。患者总体耐受性良好，常见的不良反应为1-3级的胃肠道反应，包括腹痛、恶心及呕吐，其中以腹痛最为常见。结论:对于经标准治疗失败后的晚期卵巢癌患者，阿帕替尼具有良好的疗效和安全性。     

黄酮类化合物及其纳米制剂在肿瘤防治中的研究进展

传统的肿瘤治疗方法依然存在肿瘤组织可及性差和药物不良反应普遍的问题。黄酮类化合物已被证实对多种类型肿瘤有效，但其安全性和作用部位特异性尚未被评估。然而，膳食黄酮类化合物因溶解度小、代谢快、口服吸收差等特点限制了其在体内抗肿瘤活性的发挥。此外，黄酮类化合物在某些情况下还能通过生物转化等作用与药物相互作用而影响生物利用度。纳米载体因可改变药物的药动学和药效学特征而被设计用于靶向药物传递，提高难溶性药物的生物利用度，将大分子传递到细胞内的作用位点，同时还能减少药物不良反应。体内、外研究均表明，纳米类黄酮制剂，特别是槲皮素、柚皮素、芹菜素、儿茶素和非瑟酮等在多种肿瘤的预防和治疗方面具有潜在作用，但其临床应用价值仍有待阐明。本文就纳米类黄酮制剂在提高生物利用度、肿瘤治疗效果和安全性方面的作用展开综述，为肿瘤治疗药物的开发利用提供新思路。     

农村订单定向医学生培养第二课堂的形式与教学

根据农村订单定向医学生免费本科医学教育人才培养模式改革试点的要求，落实卓越医生教育培养计划目标，以第二课堂为载体，以建立居民健康档案与开展居民健康管理为教学形式和教学内容，通过建立档案、病种筛选、自主学习、教师指导、健康管理、家庭访视、信息维护等方式，为农村订单定向医学生打下基层医疗卫生服务的坚实基础，并促进综合实践能力全面提升。     

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain-dependent regulation of Wnt/β-catenin signaling

Sex-determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor-related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss-of-function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β-catenin signaling as well as its target genes, c-Myc and cyclin D1. Interesting, the tumor-suppressive function of SOX6 was proved to be dependent on its specific high-mobility-group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β-catenin signaling pathway in an HMG domain-dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.     

Activation of CD3+ T cells by Helicobacter pylori DNA vaccines in potential immunotherapy of gastric carcinoma

Most of gastric carcinoma (GC) is attributed to infection by Helicobacter pylori (H. pylori) but there is increasing evidence that the positive H. pylori status correlates with better prognosis in GC. The H. pylori-induced cellular immune response may suppress cancer and in this work, recombinant pcDNA3 plasmids encoding various fragments of H. pylori virulence genes of cagA, vacA and babA are constructed and combined into groups to immunize BALB/c mice. The activated splenic CD3⁺ T cells are purified and the anticancer effects are investigated in vitro and in vivo. The H. pylori DNA vaccines induce a shift in the response from Th1 to Th2 that mimicks the immune status in patients of GC with chronic H. pylori infection. The stimulated CD3⁺ T cells inhibit the growth of human GC cells in vitro and adoptive transfusions of the CD3⁺ T cells suppress the growth of GC xenograft in vivo. The effects may be caused by the larger ratios of infiltrated CD8⁺/CD4⁺ T cells, reduced infiltration of regulatory FOXP3⁺ T cells, and enhanced apoptosis induced by upregulation of Caspase-9/Caspase-3 and downregulation of Survivin. Our results reveal the potential immunotherapeutic value of H. pylori vaccine-activated CD3⁺ T cells in those with advanced GC.