基于器官功能保全的局部进展期直肠癌诊治新策略

局部进展期直肠癌（locally advanced rectal cancer, LARC）的治疗进入肿瘤学效果和功能并重的时代，传统“三明治”治疗模式的利弊凸显，通过高分辨率核磁共振成像，可以将LARC按照局部复发风险进一步分成不同危险度组别，从而施行个体化治疗模式，是保障疗效和功能的最优化策略。部分危险度稍低的LARC可以通过直接进行高质量手术、单纯术前化疗来避免术前放疗带来的功能损害。而对于根治性手术可能带来较大功能损害的LARC，通过结合各种不同的术前治疗策略，乃至全程新辅助治疗（TNT）策略，强化肿瘤退缩，甚至获得肿瘤完全缓解来改变原有的手术方式，从不可保肛的根治性腹会阴联合切除术变为可保肛的低位/极低位前切除术、括约肌间切除术等根治性手术，或从全直肠系膜切除术变为经肛局部切除术，乃至最后不需要手术的“观察＆等待”，从而最大限度保全患者的器官功能。     

磁锚定技术辅助腹腔镜阑尾切除术的实验研究

目的:验证自行设计加工的磁锚定装置在减戳孔腹腔镜阑尾切除术中应用的可行性。方法:设计加工适用于辅助减戳孔腹腔镜阑尾切除术的磁锚定装置,该装置包括内置抓钳和锚定磁体2个部分。以6只健康雄性Beagle犬为模型,用磁锚定装置代替传统腹腔镜阑尾切除术中的副操作孔抓钳,经主操作孔置入磁锚定内置抓钳并钳夹于阑尾尖部,体外放置锚定磁体,锚定磁体与内置抓钳的靶磁体相吸,移动锚定磁体即可改变内置抓钳的牵拉方向,从而有效牵拉暴露手术术野,完成减戳孔腹腔镜阑尾切除手术。记录手术操作时间、术中出血量,评价利用磁锚定装置进行阑尾切除时操作的安全性和可行性。结果:6只Beagle犬均顺利完成磁锚定技术辅助减戳孔腹腔镜阑尾切除,手术时间27~38 min,出血量均小于10 ml,术后实验犬状态良好,未出现并发症。结论:磁锚定装置用于减戳孔腹腔镜阑尾切除手术操作简单、安全可行,在相关设计进一步优化基础上,可尝试或试验性用于临床。     

Rabs and axonal regeneration

Membrane trafficking processes are presumably vital for axonal regeneration after injury, but mechanistic understanding in this regard has been sparse. A recent loss-of-function screen had been carried out for factors important for axonal regeneration by cultured cortical neurons and the results suggested that the activity of a number of Rab GTPases might act to restrict axonal regeneration. A loss of Rab27b, in particular, is shown to enhance axonal regeneration in vitro, as well as in C. elegans and mouse central nervous system injury models in vivo. Possible mechanisms underlying this new finding, which has important academic and translational implication, are discussed.     

多原发结直肠癌的临床特征和预后

目的探讨多原发结直肠癌的临床特征和预后。方法回顾性分析南京医科大学第一附属医院2013年1月至2018年12月收治的42例多原发结直肠癌患者的临床资料,对其临床病理特征、诊治及预后进行总结。结果符合多原发结直肠癌诊断的患者42例,占同期收治的所有结直肠癌患者的1.20%(42/3499),病理类型以腺癌为主。其中,同时性多原发癌32例,年龄38~86岁,中位年龄66岁,共发现73处结直肠癌灶,多位于近端结肠、乙状结肠及直肠;共检出淋巴结527枚,阳性10枚(1.9%),淋巴结阳性患者占同时性多原发癌的37.5%(12/32);27例为双原发癌,3例为三原发癌,2例为五原发癌;1、3年总生存率分别为83.75%和74.38%。异时性多原发癌10例,年龄33~86岁,第一癌多位于直肠和乙状结肠区域,第二癌多位于升结肠区域;共检出淋巴结276枚,阳性率12.3%(34枚),1、3年总生存率分别为100.00%和66.67%。结论多原发结直肠癌在临床上不少见,其分布有一定规律。临床中应引起重视,提高早期诊断率。应早期手术治疗以提高患者的生存率。     

Protein kinase Cδ mediates trimethyltin-induced neurotoxicity in mice in vivo via inhibition of glutathione defense mechanism

We investigated whether protein kinase C (PKC) is involved in trimethyltin (TMT)-induced neurotoxicity. TMT treatment (2.8 mg/kg, i.p.) significantly increased PKCδ expression out of PKC isozymes (i.e., α, βI, βII, δ, and ?) in the hippocampus of wild-type (WT) mice. Consistently, treatment with TMT resulted in significant increases in cleaved PKCδ expression. Genetic or pharmacological inhibition (PKCδ knockout or rottlerin) was less susceptible to TMT-induced seizures than WT mice. TMT treatment increased glutathione oxidation, lipid peroxidation, protein oxidation, and levels of reactive oxygen species. These effects were more pronounced in the WT mice than in PKCδ knockout mice. In addition, the ability of TMT to induce nuclear translocation of Nrf2, Nrf2 DNA-binding activity, and upregulation of γ-glutamylcysteine ligase was significantly increased in the PKCδ knockout mice and rottlerin (10 or 20 mg/kg, p.o. × 6)-treated WT mice. Furthermore, neuronal degeneration (as shown by nuclear chromatin clumping and TUNEL staining) in WT mice was most pronounced 2 days after TMT. At the same time, TMT-induced inhibition of phosphoinositol 3-kinase (PI3K)/Akt signaling was evident, thereby decreasing phospho-Bad, expression of Bcl-xL and Bcl-2, and the interaction between phospho-Bad and 14-3-3 protein, and increasing Bax expression and caspase-3 cleavage were observed. Rottlerin or PKCδ knockout significantly protected these changes in anti- and pro-apoptotic factors. Importantly, treatment of the PI3K inhibitor LY294002 (0.8 or 1.6 µg, i.c.v.) 4 h before TMT counteracted protective effects (i.e., Nrf-2-dependent glutathione induction and pro-survival phenomenon) of rottlerin. Therefore, our results suggest that down-regulation of PKCδ and up-regulations of Nrf2-dependent glutathione defense mechanism and PI3K/Akt signaling are critical for attenuating TMT neurotoxicity.     

农村青少年不同时期家庭逆境与精神病理症状的关联

目的探讨家庭逆境致精神病理症状结局的累积性与关键期效应,为预防与干预逆境伤害提供依据。方法2017年12月,采用方便抽样的方法选取安徽省阜阳地区2所农村学校的710名青少年。采用《童年期不良经历问卷》评估家庭逆境,《MacArthur健康与行为问卷》评价内化症状和外化症状。采用多元线性回归分析家庭逆境发生时间与数量和精神病理症状的关联。结果持续家庭逆境组与内化症状、外化症状增加均有相关性[β值(95%CI)分别为0.35(0.15~0.54),0.16(0.01~0.32)]。家庭逆境数量为2和≥3与内化症状[β值(95%CI)分别为0.20(0.04~0.36),0.42(0.24~0.60)]、外化症状[β值(95%CI)分别为0.14(0.01~0.26),0.23(0.09~0.37)]增加有关。在仅童年期家庭逆境中,家庭逆境数量为2和≥3的内化症状[β值(95%CI)分别为0.23(0.06~0.41),0.34(0.11~0.58)]、外化症状[β值(95%CI)分别为0.17(0.02~0.31),0.21(0.02~0.39)]的风险增高。在持续家庭逆境组中,逆境数量≥3与内化症状、外化症状相关[(β值(95%CI)分别为0.56(0.31~0.82),0.24(0.02~0.45)]。仅青春期家庭逆境与精神病理症状无关。结论家庭逆境的多次发生可增加精神病理症状风险,童年期可能是家庭逆境致精神病理症状的关键期。     

胃癌患者术前应用含ω-3不饱和脂肪酸的肠内营养制剂的临床效果观察

目的探讨术前应用含ω-3不饱和脂肪酸的肠内营养制剂对胃癌患者营养状况和炎症因子水平的影响,并对其进行安全性评价。方法前瞻性纳入2014年1~6月期间四川大学华西医院收治的60例胃癌患者,随机分为试验组(30例)和对照组(30例)。试验组术前以含ω-3不饱和脂肪酸的营养制剂(瑞能)作为肠内营养制剂,对照组进食等热卡等氮的均浆膳,术前均连续服用5 d,至术前1 d。检测患者入院时、术前1 d、术后3 d及术后5 d血清中的炎症因子指标和营养相关指标,检测患者入院时和术前1 d的肝肾功能指标以作为安全性评价指标;记录患者呕吐、腹泻等不良反应,以及术后感染相关并发症的发生情况。结果术后3 d试验组患者的白介素-6(IL-6)和α-1酸性糖蛋白(AAG)水平均低于对照组(P<0.05),术后5 d试验组的C反应蛋白(CRP)水平低于对照组(P<0.05),其余各时点2组患者的各指标比较差异均无统计学意义(P>0.05)。在肠内营养支持期间,试验组患者发生腹胀1例,腹泻1例,对照组患者未出现腹胀、腹泻等不适。2组患者的不良反应发生率比较差异无统计学意义(P>0.05)。术后试验组发生切口感染1例(3.3%);对照组发生切口感染3例(10.0%),腹腔感染1例(3.3%),尿路感染1例(3.3%),肺部感染2例(6.7%),共计7例(23.3%)。2组患者的腹腔感染、切口感染、尿路感染及肺部感染发生率比较差异均无统计学意义(P>0.05),但试验组的总并发症发生率低于对照组(P=0.026)。结论术前应用含ω-3不饱和脂肪酸的营养制剂降低了胃癌患者术后的感染并发症发生率,且安全性较高。