目的:探究STAT3 miR-146-b反馈回路抑制IL-6的NF-κB信号轴调控结直肠癌细胞的干性机制.方法:用Dulbecco改良的Eagle培养基(DMEM)培养结直肠癌细胞HCT116和正常人结肠上皮细胞CCD 841 CoN细胞.通过免疫荧光检测IL-6和NF-κB信号轴.通过Western blot检测p-STAT3、p-JAK2和miR-146-b蛋白表达水平.通过Transwell分析法检测细胞迁移能力,通过TUNEL染色检测细胞凋亡.通过CCK-8评估不同处理组细胞活力.通过Western blot检测EMT间充质标志物波形蛋白(Vimentin,VIM),SNAIL和ZEB1及上皮标志物E-钙粘蛋白(CDH1)水平.通过PCR检测CRC标志物CD44、CD133、NANOG和Lgr5mRNA的表达.结果:与对照组相比,CRC组IL-6和NF-κB表达水平均升高(P<0.05),而IL-6抑制剂组较CRC组IL-6和NF-κB表达水平均降低(P<0.05).与对照组相比,CRC组p-STAT3、p-JAK2和miR-146-b蛋白含量均升高(P<0.05),而IL-6抑制剂组较CRC组p-STAT3、p-JAK2和miR-146-b蛋白含量均降低(P<0.05).与对照组相比,CRC组细胞迁移能力增加,细胞凋亡降低(P<0.05),而IL-6抑制剂组较CRC组细胞迁移能力降低,细胞凋亡增加(P<0.05).与对照组相比,CRC组0 h细胞活力无差异(P>0.05),24、48和72 h细胞活力均增加(P<0.05),而IL-6抑制剂组较CRC组0 h细胞活力无差异(P>0.05),24、48和72 h细胞活力均降低(P<0.05).与对照组相比,CRC组VIM、SNAIL和ZEB1蛋白含量均升高,CDH1蛋白含量降低(P<0.05),而IL-6抑制剂组较CRC组VIM、SNAIL和ZEB1蛋白含量均降低,CDH1蛋白含量升高(P<0.05).与对照组相比,CRC组CD44、CD133、NANOG和Lgr5 mRNA的表达均升高(P<0.05),而IL-6抑制剂组较CRC组CD44、CD133、NANOG和Lgr5 mRNA的表达均降低(P<0.05).结论:STAT3 miR-146-b反馈回路抑制IL-6的NF-κB信号轴调控结直肠癌细胞的干性.IL-6/STAT3/miR-146-b轴可以作为CRC的诊断标记,并为结肠癌治疗提供治疗靶标.

肠道生态系统的改变会影响人类的健康,甚至引发结直肠癌.大量证据表明,在结直肠癌患者的肠道中普遍存在一种病理性微生物群失衡状态.本综述从免疫与炎症反应、肠道微生物代谢产物和基因损伤三个方面总结了肠道微生物引发结直肠癌的机制,介绍了肠道微生物群相关的结直肠癌诊断标志物,分析了肠道微生物在结直肠癌放化疗及免疫治疗中的新进展,希望为结直肠癌的防治及诊疗提供新的机会.

目的 探讨锌指E盒结合同源盒1通过抑制sirtuin3影响结肠癌细胞能量代谢和转移复发的机制.方法 使用慢病毒介导的方法沉默锌指E盒结合同源盒1(ZEB1),并使用海马细胞通量分析仪测量ZEB1和甲基CpG结合域蛋白1(MBD1)对有氧糖酵解的影响,反应性氧种类和线粒体膜电位.ZEB1和MBD1之间的相互作用通过免疫共沉淀和免疫荧光测定法进行评估.ZEB1和MBD1相互作用对sirtuin 3(SIRT3)表达的影响通过定量聚合酶链反应、Western印迹、双荧光素酶和染色质免疫沉淀法验证.结果 ZEB1是胰腺癌中有氧糖酵解的正向调节剂.ZEB1通过与MBD1的相互作用使SIRT3转录沉默.结论 SW620癌细胞中的ZEB1通过与MBD1相互作用沉默SIRT3表达,从而导致线粒体能量代谢功能障碍,最终影响细胞转移复发,可能是细胞对治疗更加敏感的治疗策略.

目的 探讨血清肿瘤标志物水平与支气管镜活检组织病理学分型的关系.方法 本研究纳入2013年1月—2018年12月于哈尔滨医科大学附属肿瘤医院行支气管镜下活检病理检查,且完成相关血清肿瘤标志物(SCCA、CYFRA21-1、CEA、CA125、NSE)检测的356例肺癌患者(140例小细胞癌、122例鳞状细胞癌、94例腺癌),对患者进行回顾性分析.结果 在支气管镜活检的肺癌患者中,五种血清肿瘤标志物的组合(SCCA+CYFRA21-1+CEA+CA125+NSE,AUC=0.948,P<0.001)对小细胞肺癌与非小细胞肺癌的辅助诊断价值更高;三种(SCC+CEA+NSE,AUC=0.901,P<0.001)或四种(SCC+CYFRA21-1+CEA+NSE,AUC=0.901,P<0.001)标志物联合鉴别鳞状细胞癌与腺癌准确性更高;而在非小细胞肺癌中鉴别鳞状细胞癌与腺癌,三种标志物组合(SCCA+CEA+CA125,AUC=0.831,P<0.001)的价值更高.结论 对于不同病理分型的肺癌患者,不同血清肿瘤标志物组合对支气管镜下活检病理的分型有一定的辅助诊断价值.

Colorectal cancer is one of the most common malignant tumors in China. It poses a serious threat to health and its morbidity and mortality are increasing year by year. There are defects in early diagnostic markers and disease activity progression indi-cators for clinical applications. Lipidomics helps to analyze the etiology,pathological progression and clinical diagnosis of colorectal cancer by comparing differences in lipid metabolites in vivo,providing a new method and platform for research of colorectal cancer. This review is aimed at the application of lipidomics in colorectal cancer.

Objective The aim of this study was to investigate the application and clinical value of ultra-fine nasal endos-copy in the diagnosis and treatment of digestive tract stenosis. Methods A retrospectively investigation of 160 cases of nasogastricos-copy in esophageal,gastroduodenal and colorectal stenosis lesions,the detection rate of lesions under the stenosis and endoscopic treat-ment were analyzed from January 1,2016 to December 31,2017. Results In 102 cases of diagnostic examination,the passing rates of nasogastricoscopy in esophageal,gastroduodenum and colorectal stenosis were 76. 92% ,50. 00% and 88. 00% ,respectively. In the ca-ses which the endoscope could successfully pass the stenotic lesions, the detection rates of new lesions below the stenosis were 8. 89% ,0 and 27. 78% ,respectively,in esophageal,gastroduodenum and colorectal stenosis. A total of 58 cases of digestive tract ste-nosis were treated with endoscopic gastroscopy. Among them,46 cases had stenosis and the pass rate was 79. 31% . Conclusion Ultra-fine nasal endoscopy can significantly improve the completeness and accuracy of endoscopic diagnosis in patients with digestive tract stenosis that cannot be passed by standard gastrointestinal endoscopy. It can also be used for endoscopic treatment of digestive tract stenosis.

Paired immunoglobulin-like receptor B (Pir-B) was an inhibitory receptor expressed on the surfaces of dendritic cells (DCs). Pir-B inhibit T helper (Th) 1 response and induce Th2 cell differentiation, leading to the imbalance of Th1/Th2 cells. However, the role and potential mechanism of Pir-B on the balance of Th17/regulatory T cells (Tregs) is still largely unknown in lung cancer murine model. In the present study, the DC function and Th17/Treg balance were destroyed during the progression of lung cancer and this was accompanied by an increased expression of Pir-B. After transfection with Pir-B siRNA or administration of IL-6 in vitro, the decreased response of Th17 cells were restored, whereas the augmented differentiation of Tregs was diminished. Further, the transfer of Pir-B silenced DCs or the injection of IL-6 in vivo increased Th17 response and decreased Treg differentiation. Our study has demonstrated that Pir-B inhibits the DC function and disturbs the Th17/Treg balance via IL-6 pathway during the progression of lung cancer, contributing to inhibited antitumor immunity.

An imbalance in the various T lymphocytes, including T-helper (Th)1, Th2 and Th17 cells, and regulatory T (Treg) cells, has been associated with immune dysfunction, and may occur following thoracotomy of patients with lung cancer. The use of transcutaneous acupoint electrical stimulation (TAES) has previously been demonstrated to exert immunoregulatory effects; therefore, the present study aimed to evaluate whether TAES was able to attenuate postoperative immune suppression in patients with lung cancer. Thoracic surgical patients with lung cancer (n=27) underwent TAES (frequency, 2/100 Hz; intensity, 4-12 mA) at the bilateral large intestine 4, pericardium 6, small intestine 3 and San Jiao 6 acupuncture points for 30 min, prior to incision, and at 20, 44, 68, 92 and 116 h following thoracotomy. The number of Th1, Th2, Th17 and Treg cells, and the protein and mRNA expression levels of related cytokines were measured by flow cytometry, ELISA and polymerase chain reaction, respectively. The balance of Th1, Th2, Th17 and Treg cells in the peripheral blood of patients with lung cancer was disrupted following thoracotomy. TAES administration increased the percentage of Th1 and Th17 cells, the protein expression levels of interleukin (IL)-2 and interferon-γ, the mRNA expression levels of T-bet and RAR-related orphan receptor-γt, and decreased the percentage of Th2 cells, IL-10 protein expression levels, and GATA binding protein 3 mRNA expression levels. The results of the present study demonstrated that TAES was able to partially attenuate the postoperative immune depression of patients with lung cancer, by regulating the balance of Th1, Th2, Th17 and Treg cells, and the expression levels of related cytokines and transcription factors; therefore, TAES may be considered to be a promising strategy for treating postoperative immune dysfunction in patients with lung cancer.

Background: The accumulation of cytokines in the plasma after trauma can induce myocyte apoptosis. We aimed to identify which cytokine(s) present in the plasma responsible for myocyte apoptosis, and delineated the signal transduction mechanism in rats subjected to surgical trauma. Methods: Rats were randomized into two groups: control and trauma groups, which was divided into five subgroups: posttraumatic 0, 3, 6, 12, and 24 h subgroups. Cardiomyocytes isolated from traumatized rats were incubated with one of the factors for 12 h (normal plasma; Cytomix; TNF-α; IL-1β; IFN-γ; trauma plasma; anti-TNF-α antibody; SB203580). Myocyte apoptosis, cytokine levels, and MAPKs activation, as the primary experimental outcomes, were measured by TUNEL, flow cytometry, ELISA and Western blot, respectively. Results: Myocyte apoptosis was induced by surgical trauma during the early stage after trauma. Accompanying this change, plasma TNF-α, IL-1β, and IFN-γ levels were elevated in traumatized rats. Incubation of traumatized cardiomyocytes with cytomix or TNF-α alone induced myocyte apoptosis, and increased the activation of p38 and ERK1/2. Myocyte apoptosis and p38 activation were elevated in traumatized cardiomyocytes with trauma plasma, and these increases were partly abolished by anti-TNF-α antibody or SB203580. Conclusion: Our study demonstrated that there exists the TNF-α-mediated-p38-dependent signaling pathway that contributed to posttraumatic myocyte apoptosis of rats undergoing surgical trauma.

Surgical trauma leads to a severe deterioration of the immune system. Electroacupuncture (EA) may improve the immunodeficiency that occurs following surgery; however, the underlying signaling mechanisms require further study. In the present study, 40 rats were equally randomized into four groups: Control; Control + EA; Trauma; Trauma + EA. EA was applied at the 'Zusanli' (ST36) and 'Lanwei' (Extra37) acupoints, immediately following surgery. The splenic T cells were isolated from the rats 24 h after surgery. The apoptotic rate of the lymphocytes was measured by flow cytometric analysis, and western blotting was used to determine the protein expression levels of caspase-3, caspase-8, tumor necrosis factor (TNF)-α and TNF receptor 1 (TNFR1). The DNA binding activity of nuclear factor (NF)-κB was determined using Trans-AM® ELISA-based kits. The results of the present study showed that surgical trauma induced apoptosis of splenic lymphocytes, and significantly increased the protein expression levels of caspase-3 and caspase-8. This was accompanied by increased expression levels of TNF-α and TNFR1, and a marked reduction in the activity of NF-κB in splenic T cells. Administration of EA significantly decreased the expression levels of caspase-3, caspase-8, TNF-α and TNFR1, elevated the activity of NF-κB, and suppressed the apoptotic rate of the lymphocytes. The data suggests that EA may inhibit the apoptosis of splenic lymphocytes induced by surgical trauma, and ameliorate the postoperative immunosuppression. This may be mediated by the downregulation of TNF-α expression levels and upregulation of the activity of NF-κB.

Objective To study the changes of CD4 +/CD8 +T cells ratio and TGF -β,IL-4,IL-6 levels in lung cancer patients during the perioperative period and to analyze the clinical significance .Methods Flow cytometer and Elisa were used to analyze the CD 4 +/CD8 +T cells ratio and TGF-β,IL-4,IL-6 levels in peripheral blood sapmles from 20 patients with lung cancer during the perioperative period and 10 healthy con-trolsR. esults Before operation ,the ratios of CD4 +T and CD8 +T cells from 20 patients with lung cancer were (46.26 ±4.26)%and(43.15 ±5.18)%, respectively.On the fifth day after operation ,the ratios of CD4 +T and CD8 +T cells were(44.30 ±4.25)%and(39.80 ±2.53)%.TGF-β,IL-4 and IL-6 levels in 20lung cancer patients were(240.51 ±46.37)pg/mL,(19.85 ±2.52)pg/mL,and(129.28 ±33.06)pg/mL,respectively.On the fifth day after operation,TGF-β,IL-4 and IL-6 levels were(210.79 ±36.94)pg/mL,(17.37 ±2.57) pg/mL,and(107.28 ±27.83) pg/mL.The differences of above parameters between the preoperative period and the fifth day after operation were statistically significant ( P<0.05) . Conclusion The immune suppression oc-curs before its recovery during perioperative period ,the changes of CD4 +/CD8 +T cells ratio and TGF-β,IL-4 and IL-6 levels have significance on monitoring the progress and prognosis of patients with tumor .

Objective: To investigate the effect of transcutaneous electrical acupoint stimulation(TEAS) on T lymphocyte subgroup, natural killer cell(NK cells) and its related cytokines secretion in perioperative lung cancer patients undergoing lobectomy.Method: Forty patients with pulmonary carcinoma were randomly divided into surgical group and TEAS surgical group. The patients in TEAS surgical group received TEAS stimulation for 30 min from 30 min before operation to 1, 2 and 3 days after operation. The levels of blood CD3+, CD4+, CD8+and CD4+/CD8+ratio as well as NK cells, and the concentrations of sIL-2R, IL-2, IFN-γ and IL-10 were determined at 30 min before operation, at the end of operation and at 1, 3 and 5 d after operation.Result: The levels of CD3+, CD4+, CD4+/CD8+ratio and NK cells in TEAS surgical group increased significantly at postoperative 1, 3 and 5 days compared with in surgical group. The expressions of CD8+, sIL-2R and IL-10 decreased significantly at postoperative 3 and 5 days, while the expressions of IL-2 and IFN-γ increased significantly(P0.05).Conclusion: TEAS may enhance the immune function of perioperative patients with lung cancer, strengthen the postoperative analgesia effect and reduce the analgesic consumption of postoperation.

Objective To investigate the dynamic changes of Th 17 ,NK and IFN-γ,IL-17 in periop-erative patients with lung cancer .Methods Twenty cases of patients with lung cancer surgery were chosen ran-domly.Ten cases of healthy were used as control .We detected the express of Th17,NK,IFN-γand IL-17.Re-sults Compared with the control group , the levels of Th17 and IL -17 increased significantly in lung cancer group(P<0.05);Compared with the pre -operation,the levels of Th17 and IL-17 increased significantly after 1st day of lung cancer surgery .However,the levels of NK and IFN -γdecreased significantly .The expression of Th17 and IL-17 decreased obviously after 5 days of lung cancer surgery .However,the levels of IFN -γin-creased significantly(P<0.05).The correlation analysis showed that there was a positive correlation between Th17 and IL-17A,NK and IFN-γof peripheral blood with lung cancer patients (P<0.01),negative correla-tion between Th17 and NK,IFN-γof peripheral blood with lung cancer patients (P<0.05).Conclusion The immune suppress before activating at perioperative ,it is important for lung cancer patients to detect the levels of Th17,IL-17,NK,IFN-γin peripheral blood .

A novel multifunctional theranostic agent has been successfully fabricated by loading iron oxide nanoparticles into poly(lactic acid) (PLA) microcapsules followed by surface functionalization with graphene oxide. Both in vitro and in vivo experiments proved that the resulting microcapsules could serve as contrast agents to simultaneously enhance ultrasound, magnetic resonance and photoacoustic imaging. The composite microcapsules show good biocompatibility and rapid response to magnetic fields. Due to the strong absorption of the near-infrared light, the composite microcapsules could efficiently kill cancer cells upon NIR laser irradiation. In addition, it was found that such a photothermal effect could be obviously enhanced by applying an external magnetic field. In a nutshell, this multifunctional microcapsule can be developed as a promising platform that integrates multimodality imaging and therapy capabilities for effective cancer theranostics.

目的 探讨Kruppel样因子6(Kruppel-like factor6,KLF6)蛋白在胃腺癌组织中的表达及其临床病理意义.方法 采用免疫组织化学法分别检测90例胃腺癌及60例正常胃粘膜组织中KLF6蛋白的表达情况,并分析其表达水平与其临床病理参数的关系.结果 KLF6蛋白的阳性表达率在胃腺癌组织中为28.9%,明显低于正常胃粘膜组织的46.7%(P＜0.05),KLF6蛋白在胃腺癌组织中的表达与淋巴结转移密切相关(P＜0.05).Kaplan-Meier法生存分析显示胃腺癌患者KLF6蛋白表达阳性与阴性的累积生存率差异有统计学意义(P＜0.05),且2年以上生存率差别明显.结论 KLF6蛋白的低表达可能与胃腺癌的发生、发展、转移及预后有关,在某些程度上可以作为判断胃腺癌预后的重要指标之一.

>小细胞肺癌恶性程度较高,占肺癌的10%～20%,多数为男性吸烟者,发病中位年龄约60岁。该病能分泌激素引起类癌综合征,常以肺外转移症状或副癌综合征为首发表现,致使临床表现不典型。70%～90%的患者被确诊时已有淋巴结转移和(或)远处转移,其中最多见的为纵隔淋巴结转移,其次是肝、脑、骨、肾上腺转移,而肺癌直肠

To represent the complex behavior of a human pilot operating a fighter aircraft, an agent-based modeling and simulation method is proposed in this paper. First a live virtual constructive simulation platform including an agent-based avionics system model is introduced as a test-bed. Through refining the interface information flow between a pilot and avionics system, employing fuzzy reasoning to mimic the information processing of human, and applying Bayesian network to situation assessment, then using fuzzy Petri-net to make decisions and plan actions, the hybrid agent-based pilot model will sense, think, learn and act as a human pilot do. The ongoing effort indicates its feasibility and validity.

[Objective] To investigate the bronchoscope instead of gastroscopy in diagnosis and treatment of esophageal stenosis in patients.[Method] Bronchoscopy has only attracting pipeline,no water supply to the gas pipeline,the case group was designed the oxygen pass nasal oxygen tube and bronchoscopic biopsy pipeline connected to the air supplying method to make the bronchoscopy like the nasal gastroscope on esophageal stenosis at the comprehensive observation and diagnosis.[Results] 14 cases of patients with endoscopic findings and disease diagnosis coincidence rate was 100%.The improved bronchoscope instead of gastroscopy,can achieve the same effect of the diagnosis and treatment of nasal endoscopy,and fewer complications.[Conclusions] Bronchoscope instead of conventional gastroscopy gastroscopy is complementary,can enter the fine cavity treatment,in patients with esophageal strictures in the diagnosis and treatment play an important role,so that the accuracy of diagnosis,treatment for higher security,in the absence of nasal endoscopy hospitals can carry out.

目的 检测Ezrin蛋白和HIF-1α在胃癌组织中的表达情况,探讨二者在胃癌血管形成中的作用.方法 应用免疫组织化学法检测60例胃癌、20例癌旁组织中HIF-1α和Ezrin蛋白的表达及微血管密度(MVD).结果 Ezrin蛋白在胃癌组织中阳性率表达为73.3%(44/60),HIF-1在胃癌组织中的表达率为76.7%(46/60),MVD平均计数为21.15±7.61.Ezrin蛋白表达与组织分化程度、淋巴结转移及预后相关(P＜0.05).HIF-1α表达与癌组织的大小、浸润深度、淋巴结转移和TNM分期及预后相关(P＜0.05).Ezrin蛋白和HIF-1α在胃癌中的表达呈正相关(r=0.380,P=0.003＜0.05).Ezrin蛋白和HIF-1α阳性组MVD值显著高于阴性组(P＜0.05).结论 Ezrin蛋白和HIF-1有可能作为评估胃癌恶性程度及判断预后的指标.Ezrin蛋白和HIF-1α可促进胃癌血管生成,可能参与胃癌的进展.