Background Due to the lack of large sample evidence-based medical studies, the surgical approach for radical resection of rectal neuroendocrine tumors is controversial. Methods We retrospectively collected the medical records of rectal neuroendocrine tumors patients who underwent radical resection at 17 large tertiary care hospitals in China, from January 1, 2010 to April 30, 2022. All patients were divided into laparoscopic surgery group and open surgery group. After propensity score matching was used to reduce confounders, postoperative and oncologic outcomes were compared between the groups. Results We enrolled 174 patients with rectal neuroendocrine tumors who underwent radical surgery. After random matching, 124 patients were included in the comparison (62 in the laparoscopic surgery group vs. 62 in the open surgery group). The laparoscopic surgery group had fewer complications(14.5% vs. 35.5%, P = 0.048) and superior relapse-free survival (P = 0.048). There was no significant difference in the R0 resection rate, operation time, and postoperative hospital stay. Subgroup analysis revealed that the laparoscopic surgery group had fewer complications (10.9% vs 34.7%, P = 0.004), shorter postoperative hospital stays (9.56 ± 5.21 days vs 12.31 ± 8.61 days, P = 0.049) and superior relapse-free survival (P = 0.025) in the rectal neuroendocrine tumors ≤ 4 cm subgroup. Conclusions Laparoscopic surgery is associated with improved postoperative outcomes and oncologic prognosis for patients with rectal neuroendocrine tumors ≤ 4 cm and can serve as a safe and feasible option of radical surgery of rectal neuroendocrine tumors.

BACKGROUND:Studies on grade 2 rectal neuroendocrine tumors are limited, and the optimal treatment for these tumors is not well established. OBJECTIVE:We aimed to compare the oncologic results of local excision versus radical resection for the treatment of grade 2 rectal neuroendocrine tumors. DESIGN:Retrospective multicenter propensity score-matched study to minimize heterogeneity between groups and focus on the differences between surgery strategies. SETTINGS:Seventeen large-scale Chinese medical centers participated in this study. PATIENTS:A total of 144 patients with pathologically confirmed grade 2 rectal neuroendocrine tumors were retrospectively analyzed. MAIN OUTCOME MEASURES:Cancer-specific survival and relapse-free survival were assessed to compare surgery strategies. RESULTS:A total of 144 patients with grade 2 rectal neuroendocrine tumors were enrolled in this study. Twenty-seven patients underwent endoscopic resection, 55 underwent transanal excision, 50 underwent radical resection, and 12 underwent palliative surgery or biopsy for distant metastasis. Of the 50 patients who underwent radical resection, 30 (60.0%) had clinically positive lymph nodes on the basis of the histopathology results. The optimal cutoff value for tumor size to predict cancer-specific survival was 1.5 cm. In patients with grade 2 rectal neuroendocrine tumors of ≤1.5-cm size, there were no significant differences in cancer-specific survival and relapse-free survival between local excision and radical resection groups ( p > 0.05). In patients with grade 2 rectal neuroendocrine tumors of >1.5-cm size, relapse-free survival was significantly lower in the local excision group than in the radical resection group ( p = 0.04). LIMITATIONS:The nature of retrospective reviews and a relatively short follow-up period are limitations of this study. CONCLUSIONS:Grade 2 rectal neuroendocrine tumors have a nonnegligible rate of lymph node metastasis. Local excision is a feasible choice for tumors of ≤1.5 cm size without metastasis, whereas radical resection is more beneficial in those of >1.5 cm size. See Video Abstract . ESCISIN LOCAL VERSUS RESECCIN RADICAL PARA TUMORES NEUROENDOCRINOS RECTALES GRADO ANLISIS MULTICNTRICO CON PUNTUACIN DE PROPENSIN COINCIDENTE:ANTECEDENTES:Los estudios sobre los tumores neuroendocrinos rectales de grado 2 son limitados y el tratamiento óptimo para estos tumores no está bien establecido.OBJETIVO:Comparar los resultados oncológicos de la escisión local versus la resección radical para el tratamiento de tumores neuroendocrinos rectales grado 2.DISEÑO:Estudio multicéntrico retrospectivo emparejado por puntuación de propensión para minimizar la heterogeneidad entre grupos y centrarse en la diferencia entre estrategias quirúrgicas.ESCENARIO:Diecisiete centros médicos chinos de gran tamaño participaron en este estudio.PACIENTES:Se analizaron retrospectivamente un total de 144 pacientes con tumores neuroendocrinos rectales grado 2 patológicamente confirmados.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron la supervivencia específica del cáncer y la supervivencia libre de recaída para comparar las estrategias quirúrgicas.RESULTADOS:En este estudio se inscribieron un total de 144 pacientes con tumores neuroendocrinos rectales grado 2. Veintisiete pacientes se sometieron a resección endoscópica, 55 a escisión transanal, 50 a resección radical y 12 a cirugía paliativa o biopsia por metástasis a distancia. De los 50 pacientes que se sometieron a resección radical, 30 (60,0%) tenían ganglios linfáticos clínicamente positivos según los resultados histopatológicos. El valor de corte óptimo para el tamaño del tumor para predecir la supervivencia específica del cáncer fue de 1,5 cm. En pacientes con tumores neuroendocrinos rectales grado 2 ≤ 1,5 cm, no hubo diferencias significativas en la supervivencia específica del cáncer y la supervivencia libre de recaída entre los grupos de escisión local y resección radical ( p >0,05). En pacientes con tumores neuroendocrinos rectales grado 2 > 1,5 cm, la supervivencia libre de recaída fue significativamente menor en el grupo de escisión local que en el grupo de resección radical ( p = 0,04).LIMITACIONES:La naturaleza de la revisión retrospectiva y el período de seguimiento relativamente corto son limitaciones de este estudio.CONCLUSIONES:Los tumores neuroendocrinos rectales grado 2 tienen una tasa no despreciable de metástasis en los ganglios linfáticos. La escisión local es una opción factible para tumores ≤ 1,5 cm sin metástasis, mientras que la resección radical es más beneficiosa en aquellos > 1,5 cm. (Traducción-Dr. Felipe Bellolio ).

BACKGROUND There is currently a shortage of accurate, efficient, and precise predictive instruments for rectal neuroendocrine neoplasms (NENs). AIM To develop a predictive model for individuals with rectal NENs (R-NENs) using data from a large cohort. METHODS Data from patients with primary R-NENs were retrospectively collected from 17 large-scale referral medical centers in China. Random forest and Cox proportional hazard models were used to identify the risk factors for overall survival and progression-free survival, and two nomograms were constructed. RESULTS A total of 1408 patients with R-NENs were included. Tumor grade, T stage, tumor size, age, and a prognostic nutritional index were important risk factors for prognosis. The GATIS score was calculated based on these five indicators. For overall survival prediction, the respective C-indexes in the training set were 0.915 (95% confidence interval: 0.866-0.964) for overall survival prediction and 0.908 (95% confidence interval: 0.872-0.944) for progression-free survival prediction. According to decision curve analysis, net benefit of the GATIS score was higher than that of a single factor. The time-dependent area under the receiver operating characteristic curve showed that the predictive power of the GATIS score was higher than that of the TNM stage and pathological grade at all time periods. CONCLUSION The GATIS score had a good predictive effect on the prognosis of patients with R-NENs, with efficacy superior to that of the World Health Organization grade and TNM stage.

The miR-497-195 cluster facilitates the occurrence and development of cancer. This study aims to investigate whether the miR-195-497 cluster could regulate the progression of colorectal cancer by regulating the common target gene, FOS-related antigen 1 ( FRA1 ). Overexpression of the miR-195/497 vector was used to evaluate the effect of overexpression of miR-195-497 clusters on the biological behavior of colon cancer cells. In animal experiments, tumor growth and metastasis were recorded by constructing a nude mouse model of a subcutaneously implanted tumor. miR-195 and miR-497 were expressed to varying degrees in Caco-2, LoVo, and HT-29 cells. Overexpression of miR-195/497 and inhibition of FRA1 decreased HT-29 cell proliferation, inhibited cell invasion and migration, and promoted Epithelial-mesenchymal transition (EMT). In vivo experiments showed that the overexpression of miR-195/497 or inhibition of FRA1 inhibited tumor growth, affected EMT in tumor cells, and inhibited the expression of FRA1 . Additionally, the aforementioned conditions had the best effect when used together. The miR-195-497 cluster can regulate the proliferation, EMT, invasion, and migration of colorectal cancer cells by regulating the common target gene FRA1 , thereby affecting the development of colorectal cancer.

目的 探讨以问题为导向的教学方法(PBL)联合以案例为基础的教学方法(CBL)在胃肠外科规培生教学中的应用价值.方法 将2018年在武汉大学人民医院胃肠外科进行住院医师规范化培训的学员作为对照组(n=50),采用传统教学方法,2019年的学员采用PBL+CBL教学方法作为实验组(n=54).比较两组学员的基础理论,操作技能,病例分析能力等出科考试成绩.同时进行问卷调查,比较两组学员的学习积极性,自主学习能力,团队合作能力,语音表达能力,文献查找能力.结果 PBL+CBL教学方法组学员基础理论,操作技能,病例分析得分均较传统教学方法组高(P<0.05).同时,PBL+CBL组学员的学习积极性、自主学习能力、团队合作能力、语音表达能力、文献查找能力也较传统教学方法组高,差异有统计学意义(P<0.05).结论 PBL+CBL教学法能够提高胃肠外科规培生的教学效果,同时能激发学员的主动性和积极性,具有较好的应用价值.

Background. Early diagnosis of anastomotic leakage (AL) after rectal surgery can reduce the adverse effects of AL, thereby reducing morbidity and mortality. Currently, there are no accepted indicators or effective scoring systems that can clearly identify patients at risk of anastomotic leakage. Methods. A prospective study with assessment of the diagnostic accuracy of oxidative stress level (CAT, SOD, MDA) in serum and drain fluid compared to white blood cell count (WBC), C-reactive protein (CRP), and neutrophil percentage (NEUT) in prediction of AL in patients undergoing elective rectal surgery with anastomosis. Results. Most of the oxidative stress indicators we detected are of considerable significance in the diagnosis of anastomotic leakage. The level of MDA on postoperative day (POD)3 (areas under the curve (AUC): 0.831) and POD5 (AUC: 0.837) in the serum and on POD3 (AUC: 0.845) in the drain fluid showed the same excellent diagnostic accuracy as the level of CRP on the POD3 (AUC: 0.847) and POD5 (AUC: 0.896). Conclusions. The overall level of oxidative stress in serum and drain fluid is a reliable indicator for the early diagnosis of anastomotic leakage after rectal surgery. More specifically, among the redox indicators analyzed, MDA has almost the same predictive value as CRP, which provides another useful biomarker for the early diagnosis of anastomotic leakage.

OBJECTIVE:To explore the value of the heart rate, body temperature, and respiratory rate in the early prediction of anastomotic leakage after rectal cancer surgery.METHODS:Clinical data from patients with rectal cancer who underwent anterior rectal resection in the Department of Gastroenterology, Renmin Hospital of Wuhan University, from January 2017 to December 2019 were collected and analyzed retrospectively. Based on the occurrence of anastomotic leakage after surgery, the patients were divided into two groups: those with and without anastomotic leakage. The quantitative values of the heart rate, body temperature, and respiration rate at day 7 postsurgery were compared between the two groups. The ROC curve was used to analyze their role in the early prediction of anastomotic leakage.RESULTS:Among 441 patients with rectal cancer, 30 (6.81%) had clinical anastomotic leakage and were diagnosed at 7 ± 3 days postsurgery. Within 7 days postsurgery, the heart rate, body temperature, and respiratory rate in the anastomotic leakage group were higher than those in the nonanastomotic leakage group. The differences in heart rate (1-5 d), body temperature (2-7 d), and respiratory rate (1-7 d) were statistically significant (P < 0.05). The three ROC curves were drawn, respectively. The predictive value of the heart rate is greatest at days 2-3 postsurgery. The predictive value of the body temperature is greatest at days 4-6 postsurgery. The predictive value of the respiratory rate is best at days 1-4 postsurgery.CONCLUSION:The changes of vital signs (heart rate, body temperature, and respiratory rate) have a certain value in the early prediction of anastomotic leakage after rectal cancer surgery. Observation of postoperative vital signs at 7 days postsurgery is helpful for the early diagnosis of anastomotic leakage.

[目的]观察抗氧化物MnTE-2-PyP对大鼠新辅助放化疗肠切除-吻合术(以下简称"手术")后直肠吻合口愈合的影响.[方法]75只大鼠随机分为5组:对照组、模拟放化疗组、模拟放化疗+MnTE-2-PyP组、放化疗组及放化疗+MnTE-2-PyP组,每组15只.对照组:标准手术;模拟放化疗组:模拟放化疗+手术+腹腔注射磷酸盐缓冲液;模拟放化疗+MnTE-2-PyP组:模拟放化疗+手术+腹腔注射MnTE-2-PyP;放化疗组:放化疗+手术+腹腔注射磷酸盐缓冲液;放化疗+MnTE-2-PyP组:放化疗+手术+腹腔注射MnTE-2-PyP.各组术后第7天测量吻合口破裂压力,免疫组织化学染色观察微血管密度,天狼星红染色检测吻合口处胶原沉积.[结果]与对照组相比,新辅助放化疗降低大鼠术后直肠吻合口破裂压力(P＜0.05)及羟脯氨酸水平(P＜0.01).经过MnTE-2-PyP处理后,肠吻合口的破裂压力(P＜0.05)和羟脯氨酸水平(P＜0.01)均显著增加.此外,吻合口组织CD34免疫组织化学染色结果表明MnTE-2-PyP促进吻合口处微血管新生(P＜0.05),天狼星红染色提示MnTE-2-PyP增加吻合口处胶原沉积(P＜0.05),有利于吻合口愈合.[结论]MnTE-2-PyP通过促进微血管形成及胶原合成,增强大鼠新辅助放化疗术后肠吻合口强度,减少吻合口漏的发生.

BACKGROUND:Metastasis and invasion are the main causes of mortality in gastric cancer. To improve the treatment of gastric cancer, the development of effective and innovative antitumor agents toward invasion and proliferation is needed. Alpha-lipoic acid (ALA), a naturally occurring thiol antioxidant, showed antiproliferative and cytotoxic effects on several cancers. So it is feasible to explore whether ALA can be used to inhibit proliferation and invasion in human gastric cancer.METHODS:The expression of MUC4 in human gastric cancer tissues was assayed by immunohistochemistry. Then, we performed in vitro cell proliferation and invasion analysis to explore the antitumor effect of ALA using AGS, BGC-823, and MKN-28 cells. To further explore the mechanism of ALA-mediated downregulation of MUC4, we cotransfected human gastric cancer cells with STAT3 siRNA and STAT3 overexpression construct. ChIP assays were carried out to find the relationship between MUC4 and STAT3.RESULTS:We found that the MUC4 gene was strongly expressed in human gastric cancer tissues. Meanwhile, ALA reduced proliferation and invasion of human gastric cancer cells by suppressing MUC4 expression. We also found that STAT3 was involved in the inhibition of MUC4 by ALA. Mechanistically, ALA suppressed MUC4 expression by inhibiting STAT3 binding to the MUC4 promoter region.CONCLUSION:ALA inhibits both proliferation and invasion of gastric cancer cells by suppression of STAT3-mediated MUC4 gene expression.

Background. As a key step in enhancing cancer cell invasion and metastasis, epithelial-mesenchymal transition (EMT) plays an important role in colorectal cancer progression. EMT is triggered by a variety of signaling pathways, among which the transforming growth factor β (TGF-β) signaling pathway has been implicated as a primary inducer. Accumulating evidence demonstrates that MnTE-2-PyP (chemical name: manganese(III) meso-tetrakis-(N-ethylpyridinium-2-yl), a superoxide dismutase (SOD) mimetic, inhibits TGF-β signaling; however, its ability to inhibit TGF-β-induced EMT in colorectal cancer has not yet been explored. Methods. To verify our hypothesis that MnTE-2-PyP attenuates TGF-β-induced EMT, human colorectal cancer cells were treated with TGF-β in the presence or absence of MnTE-2-PyP. Cells were analyzed by several techniques including western blotting, real-time quantitative PCR, transwell assay, and wound healing assay. Results. MnTE-2-PyP reverses cell phenotypes induced by TGF-β in colon cancer cells. MnTE-2-PyP treatment significantly reduced the expression of mesenchymal markers but maintained epithelial marker expression. Mechanistically, MnTE-2-PyP suppressed the phosphorylated Smad2/3 protein levels induced by TGF-β in SW480 cells, but MnTE-2-PyP failed to suppress TGF-β-induced Slug and Snail expression in colorectal cells. Furthermore, MnTE-2-PyP effectively suppressed TGF-β-mediated cell migration and invasion and the expression of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in colorectal cells. Conclusion. Taken together, we provide an in-depth mechanism by which MnTE-2-PyP inhibits colorectal cancer progression, supporting an important role for MnTE-2-PyP as an effective and innovative antitumor agent to enhance treatment outcomes in colorectal cancer.

目的 探讨低位直肠间质瘤的临床特征及治疗方法 .方法 回顾性分析32例接受手术治疗的低位直肠间质瘤病人的临床资料,按手术方法分为两组.接受Dixon及Miles手术的为扩大手术组,接受内镜下切除、经肛切除,经骶切除及经会阴切除者,为局部切除组.其中扩大切除组14例,局部切除组18例,比较两组的临床特征及术后复发转移情况.结果 扩大切除组的手术时间是(152.4±46.2)分钟,出血量是(76.1±36.6)ml,肛门排气时间(3.8±0.6)天,住院时间(10.2±1.6)天;局部切除组分别是(54.1±17.9)分钟,(41.1±20.3)ml,(2.9±0.8)天和(6.3±1.3)天,两组比较差异均有统计学意义(P＜0.05).两组间手术并发症,术后局部复发及远处转移比较,差异无统计学意义(P＞0.05).结论 低位直肠间质瘤采用局部切除联合伊马替尼治疗未增加局部复发及远处转移的风险,但手术时间,出血量,住院时间显著降低,局部切除联合伊马替尼能明显减少创伤及改善病人生活质量.

Cancer-associated fibroblasts comprise the major stromal cell populations in gastric cancer, which is a significant contributor to cancer-related death worldwide. As a member of the serine protease family, HTRA1 is reportedly involved in malignant transformation of various tumor types. In the present study, we observed that HTRA1 is positively correlated with α-SMA expression in gastric cancer tissues, which was also confirmed by correlation analysis and Gene Set Enrichment Analysis (GSEA) using the GEO database. Upregulation of HTRA1 in gastric cancer cell lines induces expression of α-SMA in normal fibroblasts. To explore how HTRA1 activates normal fibroblasts, an ELISA assay was performed. Secretion of bFGF/FGF2 from gastric cancer cells was significantly increased in response to HTRA1 overexpression. However, upreguation of α-SMA in normal fibroblasts induced by HTRA1 was restored by inhibiting the expression of bFGF. Furthermore, HTRA1 promotes bFGF/FGF2 expression through activation of NF-κB signaling in gastric cancer cells. Inhibition of the NF-κB signaling pathway partially restored baseline expression levels of α-SMA induced by HTRA1. In conclusion, HTRA1 promotes transdifferentiation of normal fibroblasts to cancer-associated fibroblasts by increasing bFGF/FGF2 expression, which is dependent upon activation of NF-κB signaling in gastric cancer.

目的 观察胃癌组织中丝氨酸蛋白酶1(HTRA1)的表达并探讨其意义.方法 收集有完整临床病理资料及随访记录的胃癌切除术患者石蜡包埋标本108例份,应用免疫组化法进行染色,检测胃癌组织和远癌组织中HTRA1蛋白表达.另收集行胃癌切除的新鲜组织标本32例份,采用RT-PCR方法检测胃癌组织及远癌组织中HTRA1 mRNA表达.分析HTRA1表达与胃癌患者临床病理特征的关系,采用Kaplan-Meier方法绘制生存曲线,观察HTRA1表达对胃癌患者预后的影响.结果 HTRA1在胃癌、远癌组织中的阳性表达率分别为17.6％(19/108)、82.4％(89/108),二者比较,P<0.001.在32例新鲜组织标本中,有24例HTRA1 mRNA在胃癌中的表达较相应远癌组织中下降(P=0.002).HTRA1表达与肿瘤大小(P=0.047)、浸润深度(P=0.007)有关.HTRA1阳性表达者生存时间长于阴性表达者(P=0.012).结论 胃癌组织中HTRA1表达下调,HTRA1低表达的胃癌患者预后较差.

目的 探讨腹内型侵袭性纤维瘤病的临床特点、治疗方法和预后.方法 回顾性分析2007年1月～2017年6月武汉大学人民医院收治的26例腹内型侵袭性纤维瘤病患者的临床资料,所有患者均经病理诊断证实.分析接受根治性手术患者和仅行放化疗患者的生存率,并将肿瘤直径≥10 cm组(8例)与肿瘤直径<10 cm(18例)组分别采用Kaplan-Meier法绘制生存曲线,两组生存率比较采用χ2检验,生存曲线采用Log-rank检验.结果 26例患者术前均行CT或MRI检查,仅1例考虑为腹腔内侵袭性纤维瘤病.22例接受根治性切除术的患者中,随访期间仅1例死亡,总生存率为95.45％;而未能切除仅行放化疗的4例患者中,随访期间有3例死亡,总生存率为25.00％,两组总生存率比较,差异有高度统计学意义(P<0.01).肿瘤直径≥10 cm组与肿瘤直径<10 cm组的预后比较,差异有统计学意义(P=0.033).结论 腹内型侵袭性纤维瘤病术前诊断困难,初治时是否首选手术治疗、肿瘤大小、能否行根治性切除是影响其预后的关键性因素.

目的观察小鼠克罗恩病模型外周血单核细胞及结肠组织中白细胞介素(IL) 17、叉头状/翅状螺旋蛋白3(Foxp3)的表达,探讨其在2,4,6-三硝基苯磺酸(TNBS)诱导的克罗恩病小鼠急性炎症中的作用.方法 共40只6～8周龄雌性Bal/c小鼠,采用随机数字表法随机分为两组,20只以TNBS/乙醇溶液灌肠诱导克罗恩病模型(实验组),另外20只小鼠以同等浓度的乙醇氯化钠灌肠(正常对照组).干预1周后行疾病活动指数(DAI),结肠病理组织学评分(TDI)和结肠大体形态损伤指数(CMDI)评价,以实时荧光定量反转录聚合酶链反应(RT-PCR)检测小鼠外周血单核细胞IL-17mRNA、Foxp3 mRNA的表达,采用免疫印迹法检测小鼠结肠组织IL-17蛋白、Foxp3蛋白的表达.结果 与正常对照组相比,实验组的DAI、TDI、CMDI显著升高[DAI(5.41±0.48)比(0.85±0.07),TDI(5.63±0.74)比(0.74±0.08),CMDI(6.88±0.84)比(0.91±0.06),P＜0.01],外周血单核细胞的IL-17 mRNA显著升高[(1.118±0.145)比(1.000±0.000),P＜0.01],与其DAI、TDI及CMDI呈正相关(r =0.875,0.935,0.825,P＜0.01),Foxp3 mRNA显著降低[(0.797±0.271)比(1.000±0.000),P＜0.01],与其DAI、TDI及CMDI呈负相关(r=-0.885,-0.734,r-0.812,P＜0.01),结肠组织IL-17蛋白显著上升[(0.631±0.331)比(0.272±0.112),P＜0.01],与其DAI、TDI及CMDI呈正相关(r =0.765,0.778,0.734,P＜0.01),Foxp3蛋白显著降低[(0.274±0.112)比(0.592±0212),P＜0.01],与DAI、TDI及CMDI呈负相关(r=-0.889,-0.809,-0.851,P＜0.01).结论在TNBS诱导的结肠炎中,Th17/Treg轴的免疫偏倚是导致克罗恩病发生和发展的重要因素.

目的：探讨IL-33对克罗恩病（ CD）小鼠肠组织细胞因子（ IFN-γ、IL-4、IL-10、TGF-β）及转录因子（ T-bet、GATA-3、FOXP3）的影响。方法选择雌性BALB／c小鼠45只，随机分为对照组、TNBS组、IL-33组，每组15只。TNBS组、IL-33组给予TNBS／50％乙醇混合溶液灌肠建立CD模型，对照组仅予生理盐水灌肠。灌肠后TNBS组腹腔注射PBS，IL-33组腹腔注射重组鼠IL-33（rIL-33），对照组腹腔注射PBS。各组于腹腔注射第5天处死，取肠组织行HE染色，观察肠组织病理变化；采用ELISA法检测肠组织上清液IFN-γ、IL-4、IL-10、TGF-β，Western blotting法检测肠组织T-bet、GATA-3、FOXP3蛋白表达。结果与对照组比较，TNBS组肠组织炎症明显；肠组织IFN-γ水平升高，IL-4、IL-10、TGF-β水平降低（P均＜0．05）；T-bet蛋白表达升高，GATA-3、FOXP3蛋白表达降低（P均＜0．05）。与TNBS组比较，IL-33组肠组织炎症相对较轻；IFN-γ水平降低，IL-4、IL-10、TGF-β表达升高（P均＜0．05），T-bet蛋白表达降低，GATA-3、FOXP3蛋白表达升高（P均＜0．05）。结论 IL-33能缓解CD小鼠病情，其机制与抑制Th1细胞分化、诱导Th2和Treg细胞产生有关。

Objective To investigate the effect of immature dentritic cell(imDC) on the Crohn's mice models induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS).Methods The mouse were randomly divided into 4 groups:normal group,TNBS group,immature dentritic cell (imDC)group,mature dentritic cell (mDC) group.The other three gourps were administered 50％ ethanol/TNBS vain anus except control group,Each group was injected saline or cells via tail vein before and after administration of anus enema.Control group and TNBS group were injected saline.imDC group was injected imDC.mDC-group was injected mDC.Then we observe the general situation of murine.After one week,the disease activity index (DAI),tissue damage index (TDI) and colon macroscopic damage index (CMDI) were evaluated,the colon level of interleukin-10 (IL-10),transforming growth factor-β (TGF-β) determined by enzyme-linked immunosorbent assay (ELISA).The level of colon forkhead/winged helix protein 3 (Foxp3) protein was determined by Western blotting.Results The scores of DAI,CMDI,TDI in TNBS group were 5.420 ± 0.326,4.923 ± 0.226,7.200 ± 0.851,incresed significantly compared with control group (P＜0.01).And the colon tissue level of IL-10,TGF-β protein were (6.103 ± 1.140),(21.164 ±3.252) ng/L,the relatively expression of protein was 0.439 2 ±0.045 9,decresed significantly compared with crotrol group (P ＜ 0.01).ImDC can significantly decrease the scores of DAI,CMDI,TDI and increse the colon tissue level of IL-10,TGF-β,Foxp3 protein (P ＜0.05).But the mDC increased the scores of DAI,CMDI,TDI and decrese the colon tissue level of IL-10,TGF-β,Foxp3 protein (P ＜ 0.05).Conclusion We succsefully induce Crohn' s mice models by TNBS.And obseve the imDC can significantly inhabit intestinal inflammation in Crohn' s mice models and the mechanism of immune tolerance induced by imDC might be inhibit T lymphocytes responsiveness by regulatory T cells.

OBJECTIVEThe aim of this study was to investigate the effects of nucleostemin (NS) knocking down in SGC- 7901 gastric cancer cell line and investigates its correlation with the metastasis and TNM stage ingastric cancer (GC) patients.METHODSNS expression was assessed using immunohistochemistry in 421 patients with GC. The correlation between NS expression, clinicopathological features and prognosis was analyzed. NS gene silencing was performed using a specific small interfering RNA (NS-siRNA). The gene expression level of NS was evaluated by PCR. The viability and growth rate of SGC-7901 cells were determined by trypan blue exclusion test. Cell cycle distribution of the cells was analyzed by flow cytometry.RESULTSHigh NS expression was correlated with node metastasis, distant metastasis and TNM stage. Kaplan-Meier survival analysis revealed that patients with low NS expression had significantly longer survival than those with high NS expression. Moreover, our results showed that NS knocking down inhibited proliferation and viability of SGC-7901 cells in a time-dependent manner. Cell cycle studies revealed that NS depletion resulted in G1 cell cycle arrest at short times of transfection (24 h) followed with apoptosis at longer times (48 and 72 h), suggest that post-G1 arrest apoptosis is occurred in SGC-7901 cells.CONCLUSIONOverall, these results point to essential role of NS in SGC-7901 cells, thus, this gene might be considered as a promising target for treatment of GC.

Objective: The aim of this study was to investigate the effects of nucleostemin (NS) knocking down in SGC-7901 gastric cancer cell line and investigates its correlation with the metastasis and TNM stage ingastric cancer (GC) patients. Methods: NS expression was assessed using immunohistochemistry in 421 patients with GC. The correlation between NS expression, clinicopathological features and prognosis was analyzed. NS gene silencing was performed using a specific small interfering RNA (NS-siRNA). The gene expression level of NS was evaluated by PCR. The viability and growth rate of SGC-7901 cells were determined by trypan blue exclusion test. Cell cycle distribution of the cells was analyzed by flow cytometry. Results: High NS expression was correlated with node metastasis, distant metastasis and TNM stage. Kaplan-Meier survival analysis revealed that patients with low NS expression had significantly longer survival than those with high NS expression. Moreover, our results showed that NS knocking down inhibited proliferation and viability of SGC-7901 cells in a time-dependent manner. Cell cycle studies revealed that NS depletion resulted in G1 cell cycle arrest at short times of transfection (24 h) followed with apoptosis at longer times (48 and 72 h), suggest that post-G1 arrest apoptosis is occurred in SGC-7901 cells. Conclusion: Overall, these results point to essential role of NS in SGC-7901 cells, thus, this gene might be considered as a promising target for treatment of GC.

Objective:To explore HtrA1 gene expression aud its regulation in human gastric cancers.Methods:The HtrA1 mRNA levels were examined by QPCR analysis and coufirmed its expression with Northern blot analysis.The HtrA1 protein levels in all six gastric epithelial cell lines were investigated by Western blot analysis.Gene copy number was accessed and then sequenced the coding region from each mRNA in all six cell lines.The HtrA1 promoter region DNA methylation status was detected by using bisulfite sequeucing analysis.Effect of decitabine and TSA on HTRA1 expression in gastric cancer cell line was determined by RTPCR.Results:HIC analysis indicated that HtrA1 was highly expressed in normal epithelium,but dramatically down-regulated in gastric carcinoma tissues and variably expressed in tumor-adjacent tissues.HtrA1 gene expression was dramatically decreased in gastric carcinoma cells compared to nontumorigenic counterparts.The HtrA1 gene loss in any of the 4 breast cancer cell lines was not detected.Total 14 CpGs in this region were all methylated in gastric cancer cells,whereas two normal cells.GES-1 and HFI-145,were having several unmethylated cytosines in this region.HtrA1 showed as M r 44,000,Expression of HtrA1 protein was not observed in any of the four gastric caucer cell lines.BGC-823.MKN-45.SGC-7901and MKN-28.HtrA1 expression was observed in the HF1-145and GES-1 cell lines.Conclusions:The epigenetic silencing for HtrA1gene expression could provide a possible strategy for re-activating Htrt1 gene expression in gastric cancer cells.thus facilitating further investigation of HtrA1’s role in chemotherapy.