Pancreatic ductal adenocarcinoma (PDAC) is classified as a cancer with high metastasis so that its mortality rate is high and most of the patients could not survive longer than 5 years. RAS signaling participate in cellular processes, so it has a key role in PDAC.RAS activation is associated via three different signaling pathway including somatic oncogenic point mutations in KRAS, upstream signaling like EGFR, oncogenic activation of the downstream B-RAF molecule. Several targeted therapies have been developed against kinase effectors particularly those in the MAPK and PI3K (phosphoinositide 3-kinase)/mTOR signaling pathways and several inhibitors are undergoing clinical studies at the moment. However, because it is highly metastatic and frequently diagnosed at advanced disease stages, pancreatic cancer continues to be a challenging cancer to treat. This article will explore therapeutic approaches that focus on oncogenic KRAS signaling in pancreatic cancer and provide an updated synopsis of our knowledge of how mutant KRAS function in the illness.

目的:探讨非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)与结肠腺瘤性息肉的相关性及NAFLD严重程度与结肠腺瘤性息肉发生风险之间的关系,为临床诊治NAFLD及结肠肿瘤提供依据.方法:回顾性分析2017年-2019年在陆军第七十三集团军医院消化内科行结肠镜检查及肝脏影像学检查的1371例患者的临床资料,诊断非酒精性脂肪肝组470例,对照组A 901例;其中诊断脂肪肝组按照肝脏影像学检查(包括超声及CT检查)结果分为轻度脂肪肝组176例、中度214例、重度80例;同时根据结肠镜检查及病理组织学检查提示1371例患者中存在结肠腺瘤组638例,对照组B 733例.分析各组间基线资料的差异,再进一步分析NAFLD严重程度与结肠腺瘤性息肉发病风险的关系.结果:NAFLD组与对照组A相比,年龄、BMI、收缩压、舒张压、谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(GGT)、碱性磷酸酶(AKP)、白蛋白(WB)、球蛋白(STB)、心率、血红蛋白(Hb)、白细胞计数(WBC)、红细胞计数(RBC)、血小板计数(PLT)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、尿酸(BUA)、空腹血糖(FBG)、载脂蛋白(ApoA)差异均有统计学意义(P<0.05).腺瘤组与对照组B相比,性别、年龄、BMI、收缩压、舒张压、AST、GGT、AKP、STB、血尿素氮(BUN)、血肌酐(CR)、心率、Hb、RBC、PLT、TG、TC、LDL-C、BUA、FBG、甲胎蛋白(AFP)差异均有统计学意义(P<0.05).通过二元Logistic回归结果显示,分别校正不同的因素建立三个模型,三个模型均显示重度脂肪肝组与对照组A比较,结肠腺瘤的风险会增加(P<0.05),轻、中度脂肪肝组与对照组A比较差异无统计学意义(P>0.05).结论:NAFLD与结肠腺瘤性息肉发生密切相关,重度NAFLD患者应定期行结肠镜检查,早期诊断治疗,降低结肠肿瘤发病率和死亡率.

目的 探讨在缺氧微环境下Pokemon对肝细胞癌血管形成的影响.方法 选取肝细胞癌细胞株HepG2和Huh7,采用短发夹RNA稳定转染并筛选稳定沉默Pokemon基因表达的肝细胞癌细胞株.通过RT-PCR验证沉默Pokemon之后血管形成相关基因的表达.在缺氧条件下通过Western blot法验证Pokemon基因沉默后缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)表达的影响.结果 成功构建Pokemon干扰质粒.HepG2和Huh7细胞在Pokemon基因沉默后,血管形成相关基因促血管生成素2(angiopoietin-2,ANG2)、血管内皮生长因子A(vascular endothelial growth factor A,VEGFA)以及血管内皮生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR2)的mRNA表达均受到抑制(均P<0.05).在缺氧条件下,HepG2和Huh7细胞在Pokemon基因沉默后HIF-1α蛋白表达均下调(均P<0.05).将HIF-1α质粒瞬转至Hela细胞36 h后,通过Western blot检测发现HIF-1α的表达增加(P<0.05),而Pokemon的表达变化差异没有统计学意义(P>0.05).结论 在缺氧微环境下Pokemon上调HIF-1α表达促进肝细胞癌血管形成,促进肝细胞癌的发生及发展.

Objective: Colorectal cancer (CRC) is the leading cause of mortality worldwide. Growing evidence suggests that the current pathological staging system is inadequate for efficient and accurate prognosis. In this study, we aim to build a prognosis model to predict the survival outcome of CRC patients by using gene expression profiles from The Cancer Genome Atlas (TCGA). Materials and Methods: Univariate and multivariate Cox regression analysis were used to assess the relationship between clinical factors and P4HA1 expression regarding the prognosis of patients with colon adenocarcinoma (COAD). The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to select prognostic differential expression genes (DEGs) for the construction of prognostic risk score model. Kaplan-Meier and receiver operating characteristic (ROC) survival analysis were used to assess the performance of the model on both TCGA cohort and an independent dataset GSE39582. Results: Overexpression of P4HA1 was confirmed to be associated with poor clinical outcome of colon cancer patients in both TCGA and GSE39582 cohorts. Using the TCGA cohort, we identified 1528 DEGs related to elevated P4HA1 expression, and we established a 11-gene panel to construct the prognostic risk score model by LASSO Cox regression analysis based on their expression profiles. The 11-gene signature was further validated in the independent dataset GSE39582. Time-dependent ROC curves indicated good performance of our model in predicting 1, 2, and 3-years overall survival in COAD patients. Additionally, gene set enrichment analysis indicated that the 11-gene signature was related to pathways involved in tumor progression. Conclusions: Together, we have established a 11-gene signature significantly associated with prognosis in COAD patients, which could serve as a promising tool for clinical application in the future.

目的 研究分析幽门螺杆菌(Hp)根除性治疗在慢性胃炎治疗中的应用效果,为后续临床治疗提供数据参考.方法 104例慢性胃炎患者,随机分为对照组和研究组,各52例.对照组采用常规治疗,研究组采取Hp根除性治疗.比较两组患者临床疗效、Hp根除率、治疗前后炎性因子及胃泌素水平.结果 研究组患者治疗总有效率96.15％高于对照组的78.85％,差异具有统计学意义(P<0.05).研究组Hp根除率96.15％高于对照组的84.62％,差异具有统计学意义(P<0.05).治疗后,研究组患者胃泌素、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平分别为(70.12±11.42)ng/L、(6.46±2.96)mg/L、(40.12±5.04)IU/ml、(140.23±7.62)ng/L,均低于对照组的(102.23±15.26)ng/L、(9.55±2.75)mg/L、(59.26±6.64)IU/ml、(162.22±8.74)ng/L,差异均具有统计学意义(P<0.05).结论 Hp根除性治疗慢性胃炎临床疗效理想,具有推广价值.

目的:研究临床在丙泊酚麻醉下透明帽辅助肠镜对肥大肛乳头切除的临床效果.方法:选取79例实施肛乳头肥大切除的患者作为研究对象,按照手术方法的不同,将79例患者分为两组,其中研究组42例患者实施透明帽辅助无痛肠镜下行肛乳头肥大切除,对照组37例患者采用肛门局部利多卡因胶浆涂抹,无透明帽辅助切除.对两组患者手术时间,切除肛乳头数目及大小,麻醉复苏后的疼痛情况,术后相关并发症的发生情况进行比较分析.结果:治疗后,研究组患者的效果更好.研究组的手术时间低于对照组(P<0.05),研究组患者的术后相关并发症发生率低于对照组且术后疼痛评分低于对照组患者(P<0.05).结论:透明帽辅助无痛肠镜下行肛乳头肥大切除的临床应用效果较好,可以明显缓解患者的症状,且手术时间短,疗效可靠,较为安全.

目的 探讨P4HA1对胃癌发生发展的影响及分子机制.方法 构建P4HA1干扰质粒,稳定转染胃癌MKN-28细胞株;采取Western blot验证P4HA1干扰效率;MTT检测P4HA1干扰前后细胞增殖变化;Western blot检测增殖相关蛋白Akt和ERK表达水平;通过裸鼠移植瘤模型探讨P4HA1对成瘤生长的影响.结果 成功构建P4HA1干扰质粒并稳转胃癌MKN-28细胞株,P4HA1表达抑制后MKN-28细胞增殖受到抑制;Akt和ERK蛋白表达降低,移植瘤实验组中P4HA1干扰后裸鼠肿瘤生长受到抑制.结论 P4HA1通过调节Akt和ERK途径促进胃癌细胞增殖.

目的:探讨原发性胆汁反流性胃炎(primary bile reflux gastritis,PBRG)的胃黏膜损伤情况及与胃幽门螺杆菌(Helicobacter pylori,Hp)感染的关系.方法:选取PBRG患者48例为PBRG组,以及慢性非萎缩性胃炎(chronic non-atrophic gastritis,CNAG)患者50例为对照组.根据PBRG患者胃黏膜胆染情况将其胆汁反流程度分为Ⅰ、Ⅱ、Ⅲ级.所有研究对象均行胃镜检查,记录胃镜及病理特点,并予胃黏膜组织活检苏木素染色法、13C-尿素呼气试验法、血清Hp抗体ELISA法同时检测其Hp感染情况.结果:病理组织学表现,PBRG组胃黏膜慢性炎症、萎缩、肠化生检出率均明显高于对照组(P<0.05).胆汁反流程度加重,慢性炎症检出率升高,萎缩加重、肠化生检出率也升高.PBRG组Hp检出率为47.92％,对照组Hp检出率42.00％,两组差异无统计学意义(P>0.05),且胆汁反流程度加重,Hp检出率无明显升高或下降趋势.PBRG组患者Hp阳性胃黏膜萎缩检出率明显高于Hp阴性.PBRG组患者Hp阳性血清G-17水平也明显高于Hp阴性,差异有统计学意义(P<0.05).结论:胆汁反流可导致胃黏膜慢性炎症、萎缩、肠化生的发生率明显升高.PBRG与Hp感染无明显相关,但PBRG患者合并Hp感染时,可加速胃黏膜的萎缩及加重高胃泌素血症,导致胆汁反流的迁延不愈,因此建议PBRG患者积极抗Hp治疗.

目的 探讨酪酸梭菌治疗非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)的效果.方法 选取2016年1月至2018年1月我院收治的NAFLD患者100例,随机分为对照组和治疗组,每组50例.对照组给予安慰剂,治疗组给予酪酸梭菌活菌片,干预过程为3个月.观察所有患者干预前后肝功能、肿瘤坏死因子 α(TNF-α)、内毒素水平变化,并同期检测肝脏受控衰减参数(CAP)及肝脏彩超,评估脂肪肝的情况.结果 治疗组干预后肝功能、TNF-α、内毒素水平较干预前明显下降,肝脏脂肪含量明显下降,差异有统计学意义(P<0.05).两组干预后,治疗组的肝功能、TNF-α、内毒素水平较对照组明显下降,肝脏脂肪含量明显下降,差异均有统计学意义(P<0.05).结论 酪酸梭菌可改善患者肠道屏障功能,降低炎症反应,减轻肝脏损伤及脂肪沉积,且未见明显不良反应,治疗NAFLD疗效安全确切.

目的 探讨LIMD1对食管癌发生发展的影响及分子机制.方法 构建LIMD1干扰质粒,稳定转染食管癌细胞KYSE30;采取Western blot验证LIMD1干扰效率;MTT检测LIMD1干扰前后细胞增殖变化;Western blot检测增殖相关蛋白Akt和ERK表达水平;裸鼠移植瘤模型探讨LIMD1对成瘤生长的影响.结果 成功构建LIMD1干扰质粒并稳转食管癌细胞KYSE30细胞株.与对照组比较,实验组干扰LIMD1转染后KYSE30细胞的增殖能力受到明显增强(P<0.01),且Akt和ERK蛋白表达水平均明显增加.较对照组而言,移植瘤实验显示实验组裸鼠肿瘤生长增快(P<0.01).结论 LIMD1通过调节Akt和ERK途径抑制食管癌细胞增殖.

目的 探讨LAMβ1基因对人胆管癌细胞QBC939裸鼠皮下移植瘤生长的影响.方法 构建重组慢病毒LAMβ1过表达载体;将24只裸鼠按随机数字表分为3组,分别为实验组(转染LV-LAMβ1)、阴性对照组(空载慢病毒)以及空白对照组,每组8只.制备密度为1×107/ml胆管癌QBC939细胞悬液,取0.2ml分别注入裸鼠皮下,每3d测量瘤体大小,4周后处死裸鼠取出裸鼠皮下瘤体.采用RT-PCR、免疫组化检测瘤组织LAMβ1及VEGF表达.结果 成功构建过表达慢病毒LAMβ1载体;与阴性对照组和空白对照组比较,实验组裸鼠皮下移植瘤生长受到抑制,重量与体积明显减小(F体积=18.04,P＜0.01;F重量=42.87,P＜0.01);实验组裸鼠瘤组织中LAMβ1 mRNA和蛋白水平较阴性对照组及空白对照组增高,转移因子VEGF mRNA和蛋白水平下降(P＜0.05).结论 LAMβ1基因过表达通过下调转移因子VEGF表达抑制胆管癌裸鼠皮下移植瘤的生长.

目的 探讨乳头旁憩室对内镜下括约肌切开术(endoscopic sphincterotomy,EST)治疗胰管结石及术后并发症的影响.方法 回顾性分析194例胰管结石行内镜逆行胰胆管造影术(endoscopic retrograde cholangio-pancreatography,ERCP)治疗病例,其中无乳头旁憩室的胰管结石患者148例为对照组,46例合并乳头旁憩室为试验组;比较两组ERCP插管成功率、EST胰管取石成功率及并发症发生率.结果 试验组与对照组ERCP插管成功率比较,差异无统计学意义(89.13％ vs 89.19％,P＞0.05),试验组EST取石成功率明显降低(90.24％vs 97.73％,P＜0.05),试验组EST术后创面出血显著增多(13.04％ vs 8.78％,P＜0.01),术后胰腺炎及结石复发两组差异无统计学意义(P＞0.05).结论 乳头旁憩室对EST治疗胰管结石有一定影响;EST仍是治疗乳头旁憩室胰管结石的一种相对安全、有效的手段.

目的:探讨非诺贝特联合血液滤过治疗高脂血症性胰腺炎患者的临床疗效。方法:选取2012年2月至2018年3月我院收治110例高脂血症性胰腺炎患者,研究分为常规治疗组43例,血液滤过组32例:在常规治疗基础上予血液滤过治疗;联合治疗组35例:常规治疗基础上血液滤过联合非诺贝特治疗。比较三组腹痛平均消失时间、平均住院时间、血C-反应蛋白（CRP）、甘油三酯（TG）、血清淀粉酶（AMP）水平变化情况。结果:联合治疗组患者治疗总有效率为88.57%（31/35）,显著高于血液滤过组84.38%（27/32）及常规治疗组72.09%（31/43）,差异有统计学意义（P＜0.05）;联合治疗组患者腹痛平均消失时间及平均住院时间分别为（4.3±1.2） d、（9.6±1.4） d,均明显短于血液滤过组（5.9±1.8） d、（11.3±1.8） d以及常规治疗组（6.8±1.1） d、（14.2±1.3） d,差异均有统计学意义（P＜0.05）;治疗5 d后联合治疗组患者的CRP、TG及AMP水平分别为（6.3±2.2） mg/L、（4.3±2.3） mmol/L、（421.3±97.2） U/L,均明显低于血液滤过组的（12.7±2.4） mg/L、（10.2±2.9） mmol/L、（475.8±83.5） U/L及常规治疗组的（16.2±1.6） mg/L、（14.9±2.4） mmol/L、（513.7±96.4） U/L,差异均有统计学意义（P＜0.05）。结论:在常规治疗基础上非诺贝特联合血液滤过治疗可提高高脂血症性胰腺炎临床效果,值得进一步推广应用。

目的 探讨T淋巴细胞亚群和Bcl-2蛋白在食管癌组织中的表达水平及临床意义.方法 选取2015年1月—2016年12月就诊于解放军174医院消化内科的食管癌80例,按术中所取病理组织的不同,分为肿瘤组织组和癌旁组织组,每组80例.检测并比较2组T淋巴细胞亚群和Bcl-2蛋白水平,分析二者与食管癌患者临床特征的相关性.结果 2组CD4+T细胞和CD8+T细胞表达水平比较差异无统计学意义(P>0.05).肿瘤组织组调节性T细胞和Bcl-2蛋白阳性率明显高于癌旁组织组(P<0.01).合并淋巴结转移、Ⅲ期食管癌Bcl-2蛋白阳性率、CD4+T细胞和调节性T细胞显著增高(P<0.05).中低分化、食管外膜浸润的食管癌Bcl-2蛋白阳性率和调节性T细胞显著增高(P<0.05).与Bcl-2蛋白表达阴性者比较,Bcl-2蛋白表达阳性者调节性T细胞显著增高(P<0.01).结论 肿瘤组织中T细胞亚群失衡和Bcl-2蛋白高表达与食管癌的进展相关.

Objective To study the subcellular localization of PEG10 gene in colorectal cancer cells,and explore the role of PEG10 in the invasion and growth of colorectal cancer.Methods Subcellular localization of PEG10 protein was detected by laser scanning confocal microscopy imaging.PEG10-siRNA expression vector was constructed and stably transfected into SW620 cells.The expression of PEG10 gene was detected by Western-blot.The effect of PEG10 on the invasion and growth of SW620 cells was investigate with Transwell assay.Observing The tumor growth was observed when the SW620 cells after PEG10-siRNA was injected in C57BL/6 mice.Results Laser scanning confocal microscopy imaging showed that PEG10 was mainly located in the cytoplasm.The interference plasmid PEG10 was successfully constructed.Transwell cell experiments indicated that siPEG10 inhibited colorectal cancer cell SW620 invasion ability.In vivo,siPEG10 SW620 cells were injected into subcutaneous tumor inhibited colorectal cancer cells growth compared with the control group.Conclusion PEG10 can promoted the invasion and growth of colorectal cancer cell lines in vitro and in vivo.

目的 探讨胶囊内镜对回肠末端溃疡患者的诊断价值.方法 对34例回肠末端溃疡患者行胶囊内镜检查,回顾性分析其镜下表现.结果 34例患者肠道准备条件均比较满意,胶囊内镜排出时间约24～72 h;33例患者顺利完成检查,1例患者电池耗尽未进入结肠,共检出慢性非特异性炎症20例,克罗恩病11例,白塞氏病、嗜酸细胞性胃肠炎各l例.患者在整个检查中无不适反应. 结论 胶囊内镜对回肠末端溃疡患者具有较高的诊断价值,安全性高,不良反应少,易被患者接受,值得推广.

Objective To investigate the expressions and clinical significance of ECHS1 and PKM2 proteins in cholangiocarcinoma.Methods The expressions of ECHS1 and PKM2 in cholangiocarcinoma tissues and paracancerous normal bile duct tissues were detected.The relationship of expressions of ECHS1 and PKM2 proteins with clinical pathology features and prognosis of cholangiocarcinoma were analyzed.Results The positive rates of ECHS1 and PKM2 proteins were significantly higher in cholangiocarcinoma than those in normal tissues (58.8% vs 17.9%, 64.7% vs 21.4%, P<0.05).The expressions of ECHS1 and PKM2 proteins in cholangiocarcinoma were not related with sex, age and tumor size (P>0.05).However, they were related with the differentiation grade, TNM stage and postoperative survival time (P<0.05).Conclusion Both ECHS1 and PKM2 poteins may play important roles in the occurrence and development of cholangiocarcinoma.

Objective To investigate the role of ECHS1 on the Warburg effect in cholangiocarcinoma and the growth of the human cholangiocarcinoma in transplanted nude mice.Methods The subjects were divided into the experi mental group and control group.ECHS1 gene was silenced in Experimental group.ECHS1 gene was normal in Control group.The effect of ECHS1 on the glucose metabolism of cholangiocarcinoma QBC939 cells was determined by using a microplate reader.The expression of PKM2 was detected in both experimental group and control group by western blot.Furthermore,we transfected ECHS1 siRNA to human cholangiocarcinoma cell line QBC939,established its subcutaneous transplantation tumor model in a nude mice and observed the effects of ECHS1 siRNA on growth of QBC939 cell in vivo.Results Microplate reader shows glucos uptaken was significantly lower than that in the control group (P＜0.05) (P＜ 0.05).Immunohistochemical results shown that interference ECHS1 can decrease PKM2 expression compared with cholangiocarcinoma QBC939 ceils in the control group (P＜0.05).Inhibit ECHS1 expression could decrease the nude mice subcutaneous tumor size (P＜0.05).Conclusion ECHS1 affects Warburg effect of cholangiocarcinoma QBC939 cells by regulating the expression of PKM2 protein and plays an important role in the growth of choriocarcinoma.inhibition of its expression by siRNA can reduce the growth of QBC939 cells in vivo.

目的 比较经口内镜下肌切开术(peroral esophageal myotomy,POEM)与腹腔镜Heller手术治疗贲门失驰缓症的临床疗效.方法 收集中国人民解放军第1 74医院2004年1月-2013年2月收治的贲门失弛缓症患者,根据手术方式,分为POME组和腹腔镜Heller手术组(腹腔镜组),比较两组治疗后临床症状缓解率、食管最大宽度下降幅度、并发症发生率及复发率.结果 共纳入60例贲门失驰缓症患者,POME组27例,腹腔镜组33例,术后随访1个月,两组症状均明显缓解,食管最大宽度下降幅度分别为(2.5±1.2)cm、(2.2±1.3) cm,两组相比,差异无统计学意义(P＞0.05).POEM组出现2例(7.4％)并发症,腹腔镜Heller手术组出现2例(6.1％)并发症,两组相比,差异无统计学意义(P＞005).随访1个月后POEM组出现2例(7.4％)胃食管反流病患者,随访1年2例(7.4％)复发,腹腔镜组术后未出现明显不适,两组术后并发症发生率和复发率相比,差异均无统计学意义(P＞0.05).结论 腹腔镜Heller手术与POME治疗贲门失弛缓症有效性及安全性相当.

Objective To evaluate the expressions of DPC4 in colorectal cancer and the relationship with the clinicopathologic fea-tures. Methods The expression of DPC4 was determined by the immunohistochemical method in total of 60 cases of colorectal cancer diagonosed by pathology. The correlation with clinicopathologic features was analyzed. Thirty cases of normal colorectal tissues were as the control. Results The expression ratio of DPC4 in colorectal cancer was 35. 5%,and the intense positive ratio was 6. 2%. The expression ratio of DPC4 in normal colorectal tissues was 100%,the intense positive ratio was 86. 9%. DPC4 expression in colorectal cancer was lower than that in normal colorectal tissues(P<0. 05). The expression of DPC4 in colorectal cancer was significantly related with differentiation,lymph node and Duke′s stage. Conclusion The expression of DPC4 in colorectal cancer is related to carcinogenesis and metastasis which can be used to determine the biological behavior and prognosis of colorectal cancer.