Bile reflux, resulting from pancreaticobiliary reflux (PBR), not only alters the chemical of bile but also constitutes a significant risk factor for the occurrence and development of gallbladder cancer. In previous studies, the authors identified a marked elevation of palmitic acid (PA) levels in the bile of patients with PBR. This study seeks to elucidate the mechanisms of promoting the migration of gallbladder cancer cells, with the objective of contributing novel strategies and theoretical foundations for the treatment of gallbladder cancer. We performed a cytotoxicity screening on the NOZ and GBC-SD human gallbladder cancer cell line using varying concentrations of palmitic acid. These following methodologies were employed to investigate the mechanism of PA in NOZ and GBC-SD cells. Intracellular lipid droplet accumulation was assessed using Oil red O staining, while cell migration capability was evaluated through the Transwell migration assay. Reactive oxygen species (ROS) levels were quantified using the superoxide anion fluorescent probe, Dihydroethidium (DHE), in conjunction with a ROS detection kit. The expression levels of relevant genes and proteins were analyzed using Western blot (WB), quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence (IF) techniques. In NOZ and GBC-SD cells, it was observed that palmitic acid facilitates the accumulation of intracellular lipid droplets and diminishes cellular activity while augmenting the cells’ migratory capacity. Furthermore, elevated concentrations of PA have been shown to increase ROS levels in NOZ and GBC-SD cells. This elevation also activates the Nuclear factor-kappa B (NF-κB) and the Nuclear factor erythroid 2-related factor 2 (NRF2)/Antioxidant Response Element (ARE) signaling pathways. The addition of the ROS inhibitor N-acetylcysteine (NAC) to NOZ and GBC-SD cells treated with high concentrations of PA effectively inhibits the enhancement of cell migration and epithelial-mesenchymal transition (EMT) induced by PA. PA promotes EMT in human gallbladder cancer cells by overproducing ROS and activating the NF-κB and NRF2/ARE signaling pathways, thereby facilitating increased migration.

Hypoxia is a hallmark of solid tumors. Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment, and CAF-derived exosomes are involved in cancer genesis and progression. Here, this work investigated the role and mechanism of exosomal circHIF1A derived from hypoxia-induced CAFs in hepatocellular carcinoma (HCC) tumorigenesis. CAFs isolated from fresh HCC tissues were incubated in normoxia or hypoxia condition (N/CAFs or H/CAFs), and then the exosomes from N/CAFs or H/CAFs were isolated for functional analysis. Cell proliferation, migration and invasion were analyzed by cell counting kit-8, colony formation, and transwell assays. Immune evasion was evaluated by measuring the cytotoxicity and viability of CD8+T cells. qRT-PCR and western blotting analyses were used for the level measurement of genes and proteins. The binding between Hu antigen R (HuR) and circHIF1A or Programmed death ligand 1 (PD-L1) was analyzed by RNA immunoprecipitation assay. Functionally, we found that CAFs, especially CAFs under hypoxic stress (H/CAFs), promoted the proliferation, migration, invasion and EMT progression in HCC cells, as well as induced immune escape by suppressing CD8+T cell cytotoxicity and activity in an exosome-dependent manner. H/CAFs-derived exosomes showed highly expressed circHIF1A, and could secrete circHIF1A into HCC cells via exosomes. The oncogenic effects of H/CAFs-secreted exosomes were abolished by circHIF1A knockdown. Mechanistically, circHIF1A interacted with HuR to stabilize PD-L1 expression in HCC cells. Meanwhile, circHIF1A silencing suppressed HCC cell proliferation, mobility and immune escape by regulating PD-L1 expression. In all, exosomal circHIF1A derived from hypoxic-induced CAFs promoted the proliferation, migration, invasion, EMT progression and immune escape in HCC cells by up-regulating PD-L1 expression in a HuR-dependent manner.

BACKGROUND:Studies have shown that coagulation and fibrinolysis (CFR) are correlated with Hepatocellular carcinoma (HCC) progression and prognosis. We aim to build a model based on CFR-correlated genes for risk assessment and prediction of HCC patient. METHODS:HCC samples were selected from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases respectively. The Molecular Signatures Database (MSigDB) was used to select the CFR genes. RiskScore model were established by single sample gene set enrichment analysis (ssGSEA), weighted correlation network analysis (WGCNA), multivariate Cox regression analysis, LASSO regression analysis. RESULTS:PCDH17, PGF, PDE2A, FAM110D, FSCN1, FBLN5 were selected as the key genes and designed a RiskScore model. Those key genes were Differential expressions in HCC cell and patients. Overexpression PDE2A inhibited HCC cell migration and invasion. The higher the RiskScore, the lower the probability of survival. The model has high AUC values in the first, third and fifth year prediction curves, indicating that the model has strong prediction performance. The difference analysis of clinicopathological features found that a great proportion of high clinicopathological grade samples showed higher RiskScore. RiskScore were positively correlated with immune scores and TIDE scores. High levels of immune checkpoints and immunomodulators were observed in high RiskScore group. High RiskScore groups may benefit greatly from taking traditional chemotherapy drugs. CONCLUSIONS:We screened CFR related genes to design a RiskScore model, which could accurately evaluate the prognosis and survival status of HCC patients, providing certain value for optimizing the clinical treatment of cancer in the future.

Background: Circulating tumor cells (CTCs) can adsorb and activate platelets to form a microthrombus protective barrier around them, so that therapeutic drugs and immune cells cannot effectively kill CTCs. The platelet membrane (PM) bionic carrying drug system has the powerful ability of immune escape, and can circulate in the blood for a long time.Materials and methods: we developed platelet membrane coated nanoparticles (PM HMSNs) to improve the precise delivery of drugs to tumor sites and to achieve more effective immunotherapy combined with chemotherapy strategy.Results: Successfully prepared aPD-L1-PM-SO@HMSNs particles, whose diameter is 95-130 nm and presenting the same surface protein as PM. Laser confocal microscopy and flow cytometry experimental results showed that the fluorescence intensity of aPD-L1-PM-SO@HMSNs was greater than SO@HMSNs that are not coated by PM. Biodistribution studies in H22 tumor-bearing mice showed that due to the combined action of the active targeting effect and the EPR effect, the high accumulation of aPD-L1-PMSO@HMSNs in the local tumor was more effective in inhibiting tumor growth than other groups of therapeutic agents.Conclusion: Platelet membrane biomimetic nanoparticles have a good targeted therapeutic effect, which can effectively avoid immune clearance and have little side effects. It provides a new direction and theoretical basis for further research on targeted therapy of CTCs in liver cancer.& COPY; 2023 Elsevier Inc. All rights reserved.

The emergence of targeted drugs brings hope to patients with advanced liver cancer. However, due to the complex and diverse environment in the human body, the overall response rate of targeted drugs is not high. Therefore, how to efficiently deliver targeted drugs to tumor sites is a major challenge for current research. The project intends to construct mPEG-PLGA nanoparticles loaded with Sora and encapsulate them with exosomes for targeted therapy of hepatocellular carcinoma. mPEG-PLGA drug-loaded nanoparticles were prepared by the dialysis method and characterized by TEM and DLS. The obtained nanoparticles were incubated with the exosomes of liver cancer cells, and the exosomes-encapsulated drug-loaded nanoparticles (Exo-Sora-NPs) were obtained under pulsed ultrasound conditions, and they were characterized by Western blot, transmission electron microscopy (TEM), and dynamic light scattering (DLS). The toxic effect of Exo-Sora-NPs on liver cancer cells was detected by the CCK-8 experiment. The uptake efficiency of nanoparticles by liver cancer cells was detected by a confocal microscope. The accumulation and infiltration depth of nanomedicine in liver cancer tissues were observed by confocal microscope on frozen sections of liver cancer tissue after the H22 liver cancer subcutaneous tumor transplantation model was constructed. The tumor size, body weight, pathology, and serology analysis of mice were measured after administration. The mPEG-PLGA polymer drug-loaded particles encapsulated by exosomes have high targeting ability and biosafety. To a certain extent, they can target the drug to the tumor site with a smaller systemic response and have a highly effective killing effect on the tumor. Nanodrug-loaded particles encapsulated by exosomes have great potential as drug carriers.

目的 探讨慢性HBV感染者和肝细胞癌患者细胞毒性T淋巴细胞相关抗原-4(cytotoxic T lymphocyte associated antigen-4,CTLA-4)和T细胞免疫球蛋白及黏蛋白分子-3(T cell immunoglobulin and mucin domain-3,TIM-3)的基因多态性分布,以及二者的联合作用.方法 通过病例对照研究方法,提取439例慢性HBV感染者(无症状携带者48例,慢性肝炎154例,肝硬化134例和肝癌103例)和220例健康对照者的基因组DNA,限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测所有患者DNA的CTLA-4+49 A/G和TIM-3-1516 G/T基因型分布频率,采用χ2检验分析基因型频率、等位基因频率在HBV感染组与对照组的分布情况以及在肝癌组与非肝癌组的分布情况.结果 HBV感染组的CTLA-4+49含A基因型(GA+AA)频率高于对照组(P<0.001,OR=1.924).HBV感染组的TIM-3-1516含T基因型(GT+TT)频率高于对照组(P=0.002,OR=2.263).CTLA-4+49 GG/TIM-3-1516 GG基因型组合在HBV感染组中的分布频率低于对照组(P<0.001,OR=0.242).非肝癌组(无症状携带者、慢性肝炎和肝硬化患者)的CTLA-4+49 GA和AA基因型频率高于肝癌组(分别为P<0.001,OR=2.433和P=0.003,OR=2.798).非肝癌组的TIM-3-1516 GG基因型频率高于肝癌组(P=0.042,OR=1.725).CTLA-4+49 GA/TIM-3-1516 GG和CTLA-4+49 AA/TIM-3-1516 GG基因型组合在非肝癌组的分布频率高于肝癌组(分别为P=0.001,OR=3.728和P=0.003,OR=4.032).结论 CTLA-4+49含A基因型和TIM-3-1516含T基因型可能是慢性HBV感染的危险因素,基因型组合增加了慢性HBV感染的发病风险.CTLA-4+49 GG基因型和TIM-3-1516 GT+TT基因型可能与HCC发生相关,基因型组合也增加了HCC发生的风险.CTLA-4和TIM-3基因多态性可能各自并联合地增加慢性HBV感染和肝细胞癌的风险.

Background Increasing evidence suggests that taurine upregulated gene 1 (TUG1) is crucial for tumor progression; however, its role in hepatocellular carcinoma (HCC) and the underlying mechanisms are not well characterized. Methods The expression levels of TUG1, miR-524-5p, and sine oculis homeobox homolog 1 (SIX1) were determined using quantitative real-time PCR. The regulatory relationships were confirmed by dual-luciferase reporter assay. Cell proliferation and invasion were assessed using Cell Counting Kit 8 and transwell assays. Glucose uptake, cellular levels of lactate, lactate dehydrogenase (LDH), and adenosine triphosphate (ATP) were detected using commercially available kits. Silencing of TUG1 or SIX1 was performed by lentivirus transduction. Protein levels were measured by immunoblotting. Results Cancer-associated fibroblasts (CAFs)-secreted exosomes promoted migration, invasion, and glycolysis in HepG2 cells by releasing TUG1. The promotive effects of CAFs-secreted exosomes were attenuated by silencing of TUG1. TUG1 and SIX1 are targets of miR-524-5p. SIX1 knockdown inhibited the promotive effects of miR-524-5p inhibitor. Silencing of TUG1 suppressed tumor growth and lung metastasis and therefore increased survival of xenograft model mice. We also found that TUG1 and SIX1 were increased in HCC patients with metastasis while miR-524-5p was decreased in HCC patients with metastasis. Conclusions CAFs-derived exosomal TUG1 promoted migration, invasion, and glycolysis in HCC cells via the miR-524-5p/SIX1 axis. These findings may help establish the foundation for the development of therapeutics strategies and clinical management for HCC in future.

目的 探讨慢性HBV感染者PD-1和CTLA-43′UTR的基因多态性分布,以及二者之间的交互作用.方法 通过病例对照研究方法,PCR-RFLP技术检测慢性HBV感染者433例,健康对照者208例,PD-1 rs10204525和CTLA-4 rs3087243的基因型分布频率,采用χ2检验分析HBV感染组与健康对照组的基因型频率、等位基因频率、基因间的交互作用、与疾病严重程度的关系.结果 PD-1 rs10204525:与GG基因型相比,慢性HBV感染组的AA基因型频率明显高于健康对照组(P=0.019,OR=2.231,95％CI=1.127～4.418),A等位基因频率明显高于健康对照组(P=0.033,OR=1.334,95％CI=1.024～1.739).CTLA-4 rs3087243:与AA基因型相比,慢性HBV感染组的GG基因型频率明显高于健康对照组(P=0.016,OR=2.196,95％CI=1.145～4.214),G等位基因频率明显高于健康对照组(P=0.040,OR=1.320,95％CI=1.012～1.723).PD-1和CTLA-4的基因型交互后,在HBV感染组和健康对照组中的差异、与疾病严重程度、与肝癌的关系均有统计学意义.结论 PD-1 rs10204525的A A基因型和A等位基因可能是慢性HBV感染的危险因素,CTLA-4 rs3087243的GG基因型和G等位基因可能是慢性HBV感染的危险因素.联合基因型可增加慢性HBV感染的危险因素.CTLA-4 rs3087243的GG基因型和G等位基因可能与HCC感染相关.

An eco-friendly biosynthesized Ag NPs immobilized Hibiscus rosa-sinensis extract has been introduced. The as-prepared nanoparticles were characterized using UV–Vis, SEM, and FT-IR analysis. In the FT-IR test, the presence of many antioxidant compounds with related bonds caused the excellent condition for reducing of silver in the silver nanoparticles. In UV–Vis, the clear peak in the wavelength of 428 nm indicated the formation of silver nanoparticles. The synthesized nanoparticles had very low cell viability and high anti-liver cancer activities dose-dependently against pleomorphic hepatocellular carcinoma (SNU-387), hepatic ductal carcinoma (LMH/2A), morris hepatoma (McA-RH7777), and novikoff hepatoma (N1-S1 Fudr) cell lines without any cytotoxicity on the normal cell line (HUVEC). The synthesized nanoparticles inhibited half of the DPPH molecules in the concentration of 78 µg/mL. Perhaps notable anti-liver cancer activities of the synthesized nanoparticles against common liver cancer cell lines are linked to their antioxidant activities.

目的 探讨miR-223、miR-324-5p与慢性乙肝肝纤维化的关系,以及其对慢性乙肝感染及肝纤维化程度的临床诊断价值.方法 选取本院2018年1月至2019年12月收治的80例慢性乙型肝炎患者为乙肝组,80例健康者为对照组,采用RT-PCR法检测所有受试者血清中miR-223、miR-324-5p相对表达水平.根据肝组织活检Metavir评分标准将乙肝组分为无肝纤维化组(n=20)和肝纤维化组(n=60),采用二元Logistics回归分析miR-223、miR-324-5p与乙型肝炎肝纤维化的关系.随后再将乙肝组分为轻中度肝纤维化组(n=44)和重度肝纤维化组(n=36),绘制ROC曲线研究miR-223、miR-324-5p相对表达水平对乙型肝炎病毒感染和重度肝纤维化的诊断效能.结果 乙肝组患者血清中miR-223和miR-324-5p水平均显著高于对照组,差异均有统计学意义(P<0.05).肝纤维化组患者血清中miR-223和miR-324-5p水平均显著高于无肝纤维化组,差异均有统计学意义(P<0.05).二元Logistics回归分析提示miR-223水平是乙型肝炎患者肝纤维化的危险因素.重度肝纤维化患者血清中miR-223和miR-324-5p水平均显著高于轻中度肝纤维化患者,差异均有统计学意义(P<0.05).在乙型肝炎的诊断中,miR-223、miR-324-5p及两者联合的ROC曲线下面积分别为0.855,0.818,0.879,均有统计学意义(P<0.05).在重度肝纤维化的诊断中,miR-223、miR-324-5p及两者联合的ROC曲线下面积分别为0.792,0.676,0.830,均有统计学意义(P<0.05).诊断效能统计结果显示,miR-223和miR-324-5p联合检测诊断乙型肝炎的准确度、特异度均优于各指标单独检测;miR-223和miR-324-5p联合检测诊断重度肝纤维化的准确度、敏感度均优于各指标单独检测.结论 miR-223水平可能是乙型肝炎患者肝纤维化的危险因素,具有进一步研究价值.外周血miR-223和miR-324-5p水平可有效反映乙型肝炎病毒的感染情况和肝纤维化程度,同时监测两者表达水平,有助于对乙型肝炎的诊断和对肝纤维化程度的判断.

目的:探索三维数字成像手术计划系统在肝切除术中的应用.方法:采用三维手术计划系统(Myrian)用于临床精准肝切除.2015年1月至2018年1月,95例肝癌患者,其中传统手术组67例采用传统肝切除,手术的设计、规划和实施都是基于传统的二维图像.3D组28例均采用三维数字成像手术计划系统指导下的精准肝切除.比较两组手术时间、出血量、住院时间和并发症.结果:(1)术前三维手术系统预估的病灶切除体积与术后肝脏实际切除体积差异无统计学意义(P>0.05);(2)3D组患者术后胸腔积液、胆漏、肺部感染、切口感染、肝衰竭的发生率以及1年生存率分别为5.26％、0、1.75％、2.6％、0、92.31％,传统手术组分别为8.9％、1.49％、4.47％、2.98％、1.49％、78.85％,两组差异无统计学意义(P>0.05).3D组肿瘤复发率(7.69％)低于传统手术组(15.38％)(P<0.05);(3)传统手术组患者术中出血量、术后住院时间、手术时间、肝血管阻断时间、围手术期死亡病例数为(628.5±124.4)mL、(11.4±4.3)d、(117.1±32.4)min、(38.4±10.2)min、1例,3D组分别为(416.7±83.8)mL、(7.6±2.4)d、(178.5±40.9)min、(48.3±12.7)min、0例,两组差异有统计学意义(P<0.05).结论:三维重建技术对肝癌患者术前评估有利于术者优化、选择精准肝切除手术方案.

Pancreatic ductal adenocarcinoma (PDAC) is presently one of the cancers with the worst survival rates. The current treatment options for PDAC are relatively scarce due to insufficient understanding of molecular characteristics and subtypes of PDAC. Based on next-generation sequencing (NGS), we firstly presented a case about a KRAS wild-type pancreatic ductal adenocarcinoma patient harboring a concurrent targetable rare somatic novel KANK1-ALK, UPP2-NTRK3 fusion, and pathogenetic germline BRCA mutation. These two novel fusion statuses were assayed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Our findings demonstrated that comprehensive and systematic screening of PDAC for actionable genomic alteration may substantially improve the therapeutic prospects for a sizeable fraction of patients with PDAC. To improve the management of PDAC in an era of precision medicine, it is important to identify ALK or NTRK fusion-positive and pathogenic germline mutation subsets of patients who can benefit from targeted therapies.

目前肝切除已成为绝大多数肝胆良恶性病变的首选治疗方式.在精准外科理念指导下,围肝门外科技术取得了长足发展,因此也对围肝门外科的术前评估和术中处理提出了更高的要求.本文就如何精准实施目标病灶的定位、定量和定构及术中处理评估作一述评,以实现精准肝切除中外科治疗的确定性、预见性和可控性.

目的 制作小型猪自体原位肝移植肝动脉热缺血再灌注动物模型.方法 采用巴马小型猪模拟自体原位肝移植手术过程,对照组仅模拟手术过程,观察组在灌注结束后分为肝动脉和门静脉同时开放组、肝动脉缺血1h组、肝动脉缺血2h组,观察各组肝功能指标及肝组织结构变化.结果 本研究成功制作巴马小型猪自体原位肝移植肝动脉热缺血再灌注模型;随着肝动脉缺血时间的延长,肝细胞缺血缺氧加重,进而导致胆汁淤积加重,并通过肝功能指标及电镜下观察结果得到验证.结论 巴马小型猪自体原位肝移植肝动脉热缺血再灌注模型能很好的模拟手术过程,并精确控制肝动脉缺血时间.

目的 探讨体外乏氧环境下低氧诱导因子-1α (hypoxia inducible factor-1α,HIF-1α)对诱导肝癌细胞逆向分化为肝癌干细胞并维持恶性生物学行为的影响.方法 采用免疫磁珠分选出HepG2细胞中的CD133阴性细胞,分为2个大组:转染组转染siRNA-HIF-1α以沉默HIF-1α基因的表达,空白对照组不转染任何siRNA片段.2类细胞分别进行常氧及乏氧条件培养,本实验共分4组.采用MTT、克隆形成实验及Transwell小室实验检测细胞的增殖和侵袭能力,采用Western blot法及RT-PCR法检测细胞中HIF-1α、CD133、CD90及CD44的mRNA及其蛋白的表达.结果 MTT实验结果显示:4组细胞的增殖率随乏氧培养时间延长而增高;24 h及以后,与空白对照组相比,经siRNA-HIF-1α转染后,转染常氧组和乏氧组的细胞增殖率降低(P＜0.05).平板克隆实验结果显示:转染常氧组与转染乏氧组、空白对照常氧组与空白对照乏氧组比较其细胞形成克隆数的差异均有统计学意义(P＜0.05).Transwell小室实验结果显示:乏氧培养后,转染组与空白对照组相比,迁移至下室的细胞数目减少(P＜0.05).Western blot及RT-PCR结果显示:空白对照乏氧组中HIF-1α及肿瘤干细胞标志物(CD133、CD90、CD44)蛋白及其mRNA的表达水平均高于其余3组(P＜0.05);经siRNA-HIF-1α转染后,转染乏氧组中HIF-1α及肿瘤干细胞标志物(CD133、CD90、CD44)蛋白及mRNA的表达水平均较转染常氧组和空白对照常氧组降低(P＜0.05).结论 在乏氧环境下,低氧诱导因子HIF-1α可促进肝癌细胞逆向分化为肝癌干细胞并增强其恶性生物学行为.

目的 探索导师制结合PBL教学模式在普通外科临床教学中的作用.方法 选择西安交通大学第二附属医院五年制见习学生,抽取2个班分为对照组与实验组,每组20人.对照组采用传统的教学方法,实验组采用导师制结合PBL教学模式,学习结束后对两组的教学效果 进行评估.结果 实验组教师教学效果评估及学生成绩评估均优于对照组(P＜0.05).结论 导师责任制结合PBL教学模式可以弥补单独使用PBL 教学模式的不足,有助于培养全面发展的适应新时代社会发展需要的高素质医学人才.

目的 探讨体素内不相干运动成像(IVIM)定量参数与直肠癌分期及分化程度的关系.方法 选取2015年3月至2019年2月西安交通大学第二附属医院收治的95例直肠癌患者,所有患者均行MRI检查,测定IVIM纯扩散系数(D)、灌注相关假扩散系数(D*)、灌注分数(f).MRI检查后2周内予以根治性手术.根据术中探查结果与术后病理报告确定患者TNM分期、分化程度、脉管神经侵犯情况.比较不同TNM分期、分化程度、脉管神经侵犯情况患者的D、D*、f值.结果 Ⅰ、Ⅱ期患者与Ⅲ、Ⅳ期患者的D、D*、f值的差异无统计学意义(P＞0.05).不同分化程度患者D *、f的差异无统计学意义(P＞0.05).高分化患者的D值显著高于中分化与低分化患者,中分化患者显著高于低分化患者(P＜0.05).脉管神经侵犯患者与未侵犯患者的D*、f的差异无统计学意义(P＞0.05).脉管神经侵犯患者的D显著低于未侵犯患者(P＜0.05).结论 IVIM-DWI参数可无创评估直肠癌恶性程度,分化程度低、发生脉管神经侵犯的D值相对更低,对直肠癌恶性程度的评估价值较高.

Colorectal cancer (CRC) is one of the most common cancers worldwide, and genetic variations exert distinct roles in its pathogenesis. Single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL1A) were reported to be correlated to the susceptibility of diverse cancers. The aim of this study was to assess the association of IL1A SNPs with the risk of colorectal cancer in a Chinese Han population. To evaluate the correlation between IL1A polymorphisms and CRC risk, Agena MassARRAY platform was used for genotype determination among 248 CRC patients and 463 controls. The relationships between IL1A variants and CRC susceptibility were examined by logistic regression analysis. Stratified analysis was conducted for the association detection in males and females. Haplotype construction and analysis were applied to evaluate the potential relationship between the genetic block and the risk of CRC. SNP functional exploration was performed with available bioinformatics datasets. After adjusting for age and gender, the “AA” genotype of rs2856838 exhibited a risk association with colorectal cancer in the recessive model (adjusted OR = 1.98, 95% CI: 1.05–3.72, p = 0.036). With stratified analysis, the recessive models of rs3783550 (OR = 2.17, 95% CI: 1.03–4.60, p = 0.043), rs2856838 (OR = 2.58, 95% CI: 1.13–5.87, p = 0.024), rs1609682 (OR = 2.20, 95% CI: 1.04–4.65, p = 0.040), and rs3783521 (OR = 2.13, 95% CI: 1.01–4.49, p = 0.048) revealed significant relationships between these variants and an increased CRC risk only in females. Bioinformatics analysis also revealed the putative functions of the selected SNPs. This study demonstrated that rs2856838 could influence the susceptibility to CRC in Chinese Han population from northwest China. IL1A variants rs3783550, rs2856838, rs1609682, and rs3783521 were associated with CRC risk only in females.

目的 探讨肠内营养支持对进展期胃癌术后营养及化疗耐受性的影响.方法 选取2015年3月-2016年3月西安交通大学第二附属医院收治的54例接受化疗的进展期胃癌患者,所有患者术后均恢复顺利,无心肺肾等伴随疾病,无代谢性疾病及免疫性疾病,实验过程中未发现肿瘤复发及转移,对照组按常规健康指导,实验组在常规指导基础上,加用肠内营养制剂,测量所有患者入院及化疗后第1、7和14天的体重指数,检测化疗前、化疗第1、7和14天的血清清蛋白、IgA和外周血白细胞计数,以及营养状况和淋巴细胞亚群情况.结果 两组患者化疗前的体重指数、清蛋白、前清蛋白、转铁蛋白、白细胞计数、IgA等指标差异无统计学意义(P>0.05),化疗后再次检查上述指标发现,各指标均较化疗前降低,化疗后第1天的清蛋白、前清蛋白及转铁蛋白差异有统计学意义(P<0.05),化疗后第7和14天的指标两组差异逐渐加大;与化疗前比较,实验组化疗后CD4+淋巴细胞亚群数量增加,实验组骨髓毒性、胃肠道反应程度较对照组减弱,差异有统计学意义(P<0.05).结论 对于进展期胃癌患者,化疗期间的营养指导及口服营养素的补充能有效提高患者的能量摄入,维持良好的营养状况,改善患者的营养状态和免疫功能,提高化疗的耐受性,取得更好的疗效.

BACKGROUND:Gastric adenocarcinoma is one of the most common and lethal cancer types and is known as the second leading cause of cancer-related death of Asian adults, early diagnosis based on either pathology or molecular biology could be one of the most efficient ways to improve the outcomes of gastric adenocarcinoma patients.METHODS:Quantitative Real-Time PCR and Western-blot were used in detection of mRNA and protein expression. Lentivirus infection was used to overexpression or knock down target gene. Alarma blue assay was used to monitor cells proliferation. Flow cytometry analysis was performed to test protein expression and apoptosis level. Immunohistochemistry was used to identify protein expression in tissue. Statistical differences between two groups are evaluated by two-tailed t-tests. The comparison among multiple groups is performed by one-way Analysis of Variance (ANOVA) followed by Dunnett's posttest. The statistical significance of the Kaplan-Meier survival plot is determined by log-rank analysis.RESULTS:MMP7 as one of the most up-regulated genes in T-DM1 resistant NCI-N87 gastric adenocarcinoma cells compared to matched naïve cell lines. T-DM1 resistant NCI-N87 cell lines by exposed to T-DM1 in vitro. Exogenous overexpression of MMP7 promotes T-DM1 resistance and tumor growth in NCI-N87 cell lines while MMP7 knockdown enhanced sensitivity to T-DM1 in T-DM1 resistant NCI-N87 cell lines established previously. MMP7 was enriched in high WHO grade GC samples and implies poor outcomes for these patients. DKK1 as one of the most correlated genes to MMP7 in gastric adenocarcinoma and knock-down of DKK1 or inhibition of Wnt/β-catenin pathway led to a decreased expression of MMP7 and resistance to T-DM1.CONCLUSION:DKK1 and Wnt/β-catenin-dependent activation of MMP7 induces T-DM1 resistance and leads to the poor prognosis of gastric adenocarcinoma, which might be a novel potential therapeutical target for T-DM1 resistant gastric adenocarcinoma.