Clinicopathological features,diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF‐mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to “interval cancers” and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.     

产前分娩预演对初产妇自然分娩成功率及产后并发症的影响

[目的]探讨产前分娩预演对初产妇自然分娩成功率和产后并发症的影响.[方法]收集2016年9月至2018年10月在本院妇产科分娩的初产妇86例,按产前分娩教育方式分为观察组(n=42)和对照组(n=44).对照组孕妇产前接受常规产前健康教育课程培训,观察组在对照组的基础上进行分娩预演实践.比较两组自我效能感量表(GSES)、抑郁自评量表(SDS)和焦虑自评量表(SAS)评分及自然分娩成功率和产后并发症发生率等.[结果]与对照组相比,观察组分娩总产程和第一、二、三明显缩短;新生儿窒息率和产后SDS、SAS评分均明显降低;自然分娩成功率、GSES评分均明显提高,其差异均有统计学意义(P<0.05).观察组产后出血、感染、尿潴留、乳汁淤积发生率及总并发症发生率均低于对照组(P<0.05).[结论]采用常规产前健康教育培训结合产前分娩预演实践的产前管理方式,可有效提高初产妇自然分娩成功率,缩短产程,减少产后并发症的发生,值得临床推广应用.     

依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.     

热疗对肿瘤免疫微环境中免疫细胞及免疫相关细胞因子的影响

随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。     

3D打印模型在儿童先天性脊柱侧凸治疗中的应用研究

目的探讨3D打印模型在儿童先天性脊柱侧凸治疗中的应用疗效。方法回顾性分析2015年12月至2016年12月于首都医科大学附属北京儿童医院接受手术治疗的83例先天性脊柱侧凸患儿临床及影像学资料,根据是否使用3D打印模型分为试验组(n=44)和对照组(n=39),比较两组手术时间、术中透视次数、置钉准确性、矫形效果及并发症情况。结果本研究共纳入83例先天性脊柱侧凸患儿,其中男童47例,女童36例,平均手术年龄5.98 (1.5~13)岁。行半椎体切除术40例,Ponte截骨术31例,经椎弓根截骨术8例,全脊椎切除术4例。随访时间24~35个月。试验组患儿手术时间短于对照组[(180.92±16.74) min (201.51±27.60) min],差异有统计学意义(t=2.798,P<0.05),试验组术中出血量[(340.23±89.52) mL vs.(392.64±100.41) mL]及术中透视次数(4.36±0.89 6.05±1.28)明显少于对照组,差异有统计学意义(P<0.05);试验组置钉准确率高于对照组(93.55%vs 79.91%)(X^2=218.00,P<0.05),平均置钉时间明显短于对照组[(4.24±1.05) min vs.(8.35±2.29) min],差异有统计学意义(t=10.71,P<0.05)。两组患儿矫形率无明显差异(t=-1.135,P=0.272)。试验组与对照组患儿术后胸膜损伤、硬膜损伤发生率无明显差异(P>0.05)。结论 3D打印模型能清晰、直观显示先天性脊柱侧凸患儿的脊柱结构及形态,为制定手术计划及手术置钉提供帮助,从而提高置钉准确率,减少术中透视次数,缩短手术时间,减少术中出血量。