目的 探讨抑制甲胎蛋白(AFP)表达对肝癌模型小鼠肝脏损伤修复的影响及相关机制.方法 注射Walker-256癌肉瘤细胞株细胞悬液0.1 mL(约2×107个细胞)至小鼠肝脏组织建立移植性肝癌模型.将45只肝癌模型小鼠按随机数字表法分为3组-模型组、对照组与AFP组.AFP组与对照组采用EntransterTM-in vivo体内转染shRNA-AFP与shRNA-NC,模型组以等剂量的磷酸盐缓冲液进行转染,7 d 1次,共转染4次.观察与记录小鼠体重、血液学指标与肝脏p53表达水平变化情况.结果 AFP组治疗第14天与治疗第28天的体重高于模型组与对照组,瘤体直径、血清AFP含量、CD8+T细胞比率低于模型组与对照组,差异有统计学意义(P<0.05),模型组与对照组比较差异无统计学意义(P>0.05).AFP组治疗第28天的肝脏组织中p53蛋白相对水平均低于模型组与对照组,差异有统计学意义(P<0.05),模型组与对照组比较,差异无统计学意义(P>0.05).结论 抑制AFP表达能促进肝癌模型小鼠肝脏损伤修复,增加小鼠体重,抑制肝脏组织p53的表达与肿瘤生长,改善小鼠的免疫状态.

目的 分析结核分枝杆菌(MTB )介导TWIK2 - NLRP3通路参与小鼠肺泡巨噬细胞损伤.方法 将40只昆明小鼠按照随机数字表法分为卡介苗组和H37Rv组,每组20只.2组分别经尾静脉给予一次性注射MTB活菌卡介苗和H37Rv菌悬液制备小鼠感染模型,剂量均0.3 mL.2组小鼠于感染后1、3、7、14 d脱颈处死,采用磷酸盐缓冲液对气管、肺泡进行灌洗,收集的感染小鼠肺泡巨噬细胞以激光共聚焦显微镜技术、MTT、流式细胞术、酶联免疫吸附实验(ELISA )、实时聚合酶链式反应(RT-PCR)及蛋白质印迹(Western blotting )等技术对2组小鼠不同时间点巨噬细胞的吞噬能力、凋亡率、乳酸脱氢酶(LDH)表达量、炎性因子含量、K+浓度、钾离子通道蛋白(TWIK2)、炎症小体(NLRP3 )及凋亡相关斑点样蛋白(ASC )的mRNA和蛋白表达量进行检测、对比.结果 感染后1、3、7、14 d,2组小鼠肺泡巨噬细胞吞噬菌种的量、凋亡率以及LDH表达量均随时间显著增加,K+浓度则随时间显著降低,且均在在感染后7d达到最高或最低.感染7d后,与卡介苗组相比,H37Rv组小鼠中TWIK2、NLRP3及ASC mRNA和蛋白的相对表达量以及炎性因子白细胞介素-lβ( IL-1β)、白细胞介素-18( IL-18 )和肿瘤坏死因子-a( TNF-a)含量均显著升高,差异有统计学意义(P ＜0.05 ).结论 MTB和卡介苗菌株均介导TWIK2-NLRP3通路参与小鼠肺泡巨噬细胞损伤.小鼠体内注入适量MTB可被肺泡巨噬细胞吞噬,MTB可促进肺泡巨噬细胞的凋亡与损伤,其作用机制可能与TWIK2的激活密切相关..

目的 研究苦参碱对膀胱癌模型大鼠前列腺素脱氢酶(prostaglandin dehydrogenase,PGDH)、血管内皮生长因子(vascular endothelial cell growth factor,VEGF)以及细胞膜磷脂酶A2(cytosolic phospholipasesA2,cPLA2)相对蛋白表达量的影响.方法 选将60只大鼠采用随机数字表法分为模型组、实验组和空白组,每组各20只.模型组、实验组两组大鼠采取灌胃的形式服用致癌剂N-丁基-N-(4-羟丁基)亚硝基胺,剂量200 mg/mL每只,连续灌胃8周.实验组大鼠给予苦参碱灌胃治疗,空白组和实验组两组大鼠给予等体积的生理盐水,灌胃,1d/次,连续治疗35周.对所有大鼠进行肿瘤细胞凋亡指数观察,并对各组大鼠VEGF、cPLA2、PGDH相对蛋白表达量进行检测.对p16INK4a与CyclinD1及CDK4表达水平关系进行研究.结果 空白组和实验组PGDH表达水平显著高于模型组,差异有统计学意义(P＜0.05);模型组VEGF水平显著高于实验组和空白组,差异有统计学意义(P＜0.05);模型组cPLA2水平显著高于实验组和空白组,差异有统计学意义(P＜0.05);空白组大鼠肿瘤细胞凋亡指数明显低于实验组和模型组,差异有统计学意义(P＜0.05),实验组大鼠肿瘤细胞凋亡指数高于模型组,差异有统计学意义(P＜0.05);模型组大鼠肿瘤细胞增殖指数高于实验组和空白组大鼠,差异有统计学意义(P＜0.05);空白组大鼠p16INK4a蛋白表达水平明显高于实验组和模型组.3组实验数据比较,差异有统计学意义(P＜0.05).结论 苦参碱对大鼠膀胱癌有抑制生长的作用,可能作用机制是通过抑制前列腺素通路相关蛋白cPLA2、PGDH蛋白表达,有助于p16INK4a蛋白表达上调.

Objective To compare the prognostic factors and adverse effects of elderly patients with esophageal cancer between radiotherapy alone and concurrent chemoradiotherapy. Methods A total of 479 patients with esophageal squamous cell carcinoma aged 70 years or older were analyzed retrospectively at our institute, from January 2008 to December 2017. The patients were divided into radiotherapy alone group ( 359 cases ) and concurrent chemoradiotherapy group ( 120 cases ) . After Propensity Score Matching ( PSM) , data from matched patients with 102 cases in each group was analyzed. The overall survival (OS) rates, the prognostic factors and adverse effects were assessed. Results The 1, 3, 5-year of OS in radiotherapy alone group after PSM were 77. 4％, 40. 1％, 22. 7％, respectively, and median overall survival time (mOS) was 26. 9 months (95％ CI:18. 7 - 35. 2 months). The chemoradiotherapy group after PSM were 79. 5％, 47. 6％, 35. 7％ and 35. 6 months (95％ CI:23. 2-48.0 months), respectively, while there was no significant difference between the groups (P >0. 05). Subgroup analysis showed that the 1, 3, 5-year of OS and mOS of the patients aged 70 -75 years in radiotherapy alone group were 79. 4％, 41. 0％, 26. 2％ and 29. 2 months, respectively. The patients aged 70-75 years in chemoradiotherapy group were 86. 5％, 56. 1％, 47. 6％ and 48. 9 months, respectively. There was statistically significance between the groups after PSM(χ2 =4. 746, P<0. 05). The univariate prognostic analysis showed that the age, T stage, N stage, clinical stage, short-term efficacy and performance status were influencing factors for OS (χ2 =6. 714-42. 900, P<0. 05). The clinical stage and short-term efficacy were independent prognostic factors for OS (χ2 =5. 007 -9. 181, P<0. 05). In addition , the risk of non-tumor related death of the patients aged 75 years or older in the chemoradiotherapy group was higher than those in the radiotherapy alone group(χ2 =5. 630, P<0. 05). The prevalence of toxicities (≥grade 3) including bone marrow suppression, radiation esophagitis and radiation pneumonia in the chemoradiotherapy group were higher than that in the radiotherapy alone group (χ2 =4. 701 -28. 318, P<0. 05). Conclusions Concurrent chemoradiotherapy, compared with radiotherapy alone, may improve the prognosis of patients aged 70-75 years with esophageal squamous cell carcinoma.