目的 探索α-突触核蛋白（α-Syn）干预对人单核细胞白血病细胞系（THP-1）巨噬细胞源性泡沫细胞的影响。方法 通过佛波酯（PMA）和氧化型低密度脂蛋白（ox-LDL）构建THP-1巨噬细胞源性泡沫细胞模型,使用不同浓度（33、66、100、133 nmol/L）α-Syn处理泡沫细胞,随后检测细胞胆固醇含量和炎症因子白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）及白细胞介素-8（IL-8）的mRNA表达以及核因子κB（NF-κB）和凝集素样氧化低密度脂蛋白受体-1（LOX-1）的蛋白表达变化。结果 高剂量（100和133 nmol/L）α-Syn处理可以减少THP-1巨噬细胞源性泡沫细胞内胆固醇的含量（P<0.05）,并且减少IL-1β、IL-6和IL-8的mRNA表达（P<0.05）。进一步发现（100 nmol/L和133 nmol/L）α-Syn可以降低THP-1巨噬细胞源性泡沫细胞p-NF-κB和LOX-1的蛋白表达（P<0.05）。结论 α-Syn可以降低THP-1源性巨噬细胞泡沫细胞胆固醇蓄积和炎症反应,可能是通过下调p-NF-κB和LOX-1蛋白表达。

      Objective To explore the effects of α-synuclein（α-Syn）intervention on human monocytic leukemia cell（THP-1）macrophage-derived foam cells．Methods The THP-1 macrophage-derived foam cell model was constructed by phorbol 12-myristate 13-acetate（PMA）and oxidized low-density lipoprotein（ox-LDL）．Foam cells were treated with different concentrations（33, 66, 100, and 133 nmol/L）of α-Syn, and the cellular cholesterol contents, as well as the mRNA expression of IL-1β、IL-6 and IL-8 were detected．Subsequently,alternation in protein expression of NF-κB and LOX-1 was measured．Results High-dose（100 and 133nmol/L）α-Syn treatment significantly reduced the levels of intracellular cholesterol in THP-1-derived macrophage foam cells（P<0.05）and decreased the mRNA expression of IL-1β、IL-6 and IL-8（P<0.05）．It was further found that（100 nmol/L and 133 nmol/L）α-Syn decreased the protein expression of p-NF-κB and LOX-1 in THP-1 macrophage-derived foam cells（P<0.05）．Conclusions The results of the present study suggest that α-Syn reduces cholesterol accumulation and inflammatory response in THP-1-derived macrophage foam cells, possibly by down-regulating p-NF-κB and LOX-1 protein expression．

       目的   探讨溶酶体相关膜蛋白3（LAMP3）与肾癌发病风险之间的因果关系，为肾癌的分子致病机制提供新的理论依据。方法   基于全基因组关联研究（GWAS）数据，采用孟德尔随机化分析方法，评估LAMP3基因表达与肾癌的因果关系。并通过GEPIA2分析LAMP3表达对肾癌总体生存期（OS）及无病生存期（DFS）的关系。结果  LAMP3基因变异与肾癌风险呈正相关，提示LAMP3的表达可能增加肾癌的发病风险。此外，GEPIA2分析进一步显示，LAMP3的高表达与肾癌患者的低总体生存期（OS）及无病生存期（DFS）显著相关。结论   本研究通过孟德尔随机化分析探讨了LAMP3基因表达与肾癌的因果关系，结果表明LAMP3可能是肾癌的潜在致病因子，并与肾癌预后相关。这为肾癌的分子致病机制研究提供了重要的理论依据，并为未来的生物标志物和靶向治疗策略的开发提供了新的思路。

        Objective  To investigate the causal  relationship  between LAMP3 expression and  renal cancer  risk  using Mendelian randomization analysis，providing a theoretical basis for understanding the molecular mechanisms underlying renal cancer．Methods  This study utilized data from genome-wide association studies（GWAS）and employed Mendelian randomization analysis to assess the causal relationship between LAMP3 gene expression and renal cancer．Additionally，GEPIA2 was used to examine the association between LAMP3 expression and overall survival（OS）and disease-free survival（DFS）in renal cancer patients．Results  Variants in the LAMP3 gene were positively correlated with renal cancer risk，suggesting that LAMP3 expression may increase the likelihood of developing renal cancer．Furthermore，GEPIA2 analysis  revealed that high expression of LAMP3 was significantly associated with lower OS and DFS in renal cancer patients．Conclusions  This study explored the causal  relationship between LAMP3 gene expression and renal cancer through Mendelian randomization analysis．The results indicate that LAMP3 may be a potential pathogenic factor in renal cancer and is associated with poor prognosis．These findings provide important theoretical insights into the molecular mechanisms of  renal cancer and offer new perspectives for the development of biomarkers and targeted therapeutic strategies in the future．

      目的   采用两样本孟德尔随机化以及Meta分析研究趋化因子C-X3-C基序配体1（CX3CL1）表达水平与系统性红斑狼疮（SLE）发病风险的因果关系。方法   获取CX3CL1表达水平与SLE的全基因组关联研究（GWAS）数据，将单核苷酸多态性（SNP）作为工具变量并选择敏感的SNPs进行分析。通过逆方差加权法（IVW）、加权中位数法（WM）、MR-Egger回归法进行两样本MR分析，以OR值评估CX3CL1表达水平与SLE之间的因果关系，并对结果进行异质性和多效性检验。最后利用R软件Meta包进行Meta分析。利用coloc包进行共定位分析。结果   纳入9个SLE作为结局变量，其中4个变量ebi-a-GCST90018917（OR=2.14，95%CI：1.50~3.06），ebi-a-GCST003156（OR=2.25，95%CI：1.00~5.06），ebi-a-GCST90014238（OR=3.02，95%CI：1.54~5.94），finn-b-SLE_NOS（OR=1.81，95%CI：1.01~3.22）表明CX3CL1表达水平与SLE之间存在因果关系。关于 OR 95% CI 的森林图显示 SLE 患者的CX3CL1表达水平显著高于健康人群（OR=1.87，95%CI：1.53~2.29，P＜0.001）。共定位分析结果提示CX3CL1表达水平和SLE表型之间有共享的遗传变异位点（rs170364）。结论  CX3CL1表达水平与SLE存在正向因果关系，CX3CL1表达水平的升高使得SLE的发病风险升高。

       Objective  To investigate the causal  relationship  between CX3CL1 levels and the  risk of  systemic lupus erythematosus（SLE）using two-sample Mendelian randomization and Meta-analysis methods．Methods  Genome-Wide Association Study（GWAS）data for CX3CL1 levels and SLE were obtained．Single nucleotide polymorphisms（SNPs）were used as instrumental variables，and sensitive SNPs were selected for analysis．Two-sample Mendelian  randomization was performed using the inverse variance weighted（IVW）method，weighted median（WM）method，and MR-Egger  regression to evaluate the causal relationship between CX3CL1 levels and SLE，with OR values assessing this relationship．Heterogeneity and pleiotropy tests were conducted on the results．Meta-analysis was performed using the Meta package in R software，and colocalization analysis was conducted using the coloc package．Results  Nine SLE outcomes were included as outcome variables，with four variables（ebi-a-GCST90018917［OR=2.14，95%CI：1.50-3.06］，ebi-a-GCST003156［OR=2.25，95%CI：1.00-5.06］，ebi-a-GCST90014238［OR=3.02，95%CI：1.54-5.94］，finn-b-SLE_NOS［OR=1.81，95%CI：1.01-3.22］）indicating a causal relationship between CX3CL1 expression levels and SLE．The forest plot for OR 95%CI showed that CX3CL1 expression levels in SLE patients were significantly higher than in healthy individuals（OR=1.87［95%CI：1.53-2.29］，P＜0.001）．Colocalization analysis suggested that there was shared genetic variation sites（rs170364）between CX3CL1 expression levels and SLE phenotype．Conclusions  There is a positive causal relationship between CX3CL1 expression levels and SLE，with increased CX3CL1 levels elevating the risk of developing SLE．

       目的   初步探讨生长因子受体结合蛋白14（GRB14）在肺腺癌患者预后中的具体作用机制。方法   通过TIMER数据库、UALCAN数据库及GEPIA数据库，探讨GRB14 mRNA在肺腺癌及正常肺组织中的表达。运用免疫组织化学通过组织芯片（75例肺腺癌患者和75例癌旁组织）检测其蛋白表达水平，收集国外肿瘤研究团队上传至TCGA数据库229例肺腺癌患者的临床数据，分析评估GRB14在肺腺癌患者的表达及其临床特征及生存预后之间的关系。应用TIMER数据库对GRB14肺腺癌患者进行免疫浸润分析。String数据库探讨GRB14与其他蛋白之间是否存在相互作用。结果  TIMER数据库分析显示，相比正常组织，GRB14 mRNA在多种实体肿瘤和肺腺癌组织中高表达（P＜0.05）。使用UALCAN数据库和GEPIA数据库以正常样本为对照组，肺腺癌患者的GRB14的表达均增加（P＜0.01）。免疫组织化学检测组织芯片结果显示，GRB14蛋白在肺腺癌的表达高于正常肺组织（肺腺癌6.07±1.01 vs 癌旁组织4.80±1.22；P＜0.01）。TCGA数据库分析显示，肺腺癌患者中GRB14高表达组和低表达组的中位总生存期分别为（41.59±5.20）月和（88.67±16.69）月；结合TCGA数据库绘制ROC曲线，发现GRB14的表达对肺腺癌患者具有一定的诊断价值。单因素回归分析结果显示，肿瘤分期（Ⅲ-Ⅳ）（P＜0.01）、肿瘤原发灶的情况（T3-4）（P＜0.01）、淋巴结转移（N1-3）（P＜0.01）和GRB14表达（P＜0.01）是影响肺腺癌中位总生存期的因素；Cox多因素回归分析显示，淋巴结转移（N1-3）（P＜0.05）和GRB14表达（P＜0.01）是影响肺腺癌中位总生存时间的因素。TIMER数据库分析显示，GRB14 mRNA 表达与巨噬细胞（r=-0.164，P＜0.01）、中性粒细胞（r=-0.175，P＜0.01）和树突状细胞（r=-0.148，P＜0.01）具有相关性。通过String数据库分析发现与GRB14相互作用的蛋白质包括EGFR、HRAS、FGFR1、INSR、CNGA1、COBLL1、LYPLAL1、TNKS2、TNKS、PRKCZ。结论  GRB14表达增加与肺腺癌患者预后不良相关。

       Objective  To assess the specific mechanism of growth factor receptor-bound protein 14（GRB14）in the prognosis of lung adenocarcinoma（LUAD）patients．Methods  The expression of GRB14 mRNA in LUAD and normal lung tissue was explored using TIMER database，UALCAN database，and GEPIA database．The expression of GRB14 protein was examined by immunohistochemistry using a tissue microarray．Then，the associations of GRB14 expression with clinicopathological features and clinical outcomes of LUAD were validated by analyzing TCGA database at the mRNA level and statistically evaluating the results．TIMER database was used to analyze immune infiltration of GRB14 in LUAD．Protein-protein interaction of GRB14 were analyzed using the String database．Results  Using the TIMER database，we found that GRB14 mRNA was highly expressed in various solid tumors and LUAD tissues compared to normal tissues（P＜0.05）．Comparing with the normal group，the expression of GRB14 was increased in LUAD（P＜0.01）via using UALCAN database and GEPIA database．The expression level of GRB14 protein in the LUAD tissues was significantly higher than that in the noncancerous LUAD tissues（LUAD［6.07±1.01］ vs benign，［4.80±1.22］；P＜0.01）in tissue microarray ．Median overall survival in the high and low GRB14 expression groups in LUAD was（41.59±5.2）and（88.67±16.69）months respectively．We plotted the ROC curves of 3-year survival rate and 5-year survival rate which again suggested that the model had good predictive performance．Univariate analysis revealed that individual cancer stages（Ⅲ-IV）（P＜0.01），tumor（T3-4）（P＜0.01），lymph node metastasis（N1-3）（P＜0.05）and GRB14 expression（P＜0.01）were risk factors affecting the median overall survival time of LUAD．According to Cox multiple regression analysis，we found that lymph node metastasis（N1-3）（P＜0.05）and GRB14 expression（P＜0.01）were  risk factors affecting the median overall survival time of LUAD．Using TIMER database analysis，the mRNA level of GRB14 was significantly correlated with macrophages（r=-0.164，P＜0.01），neutrophils（r=-0.175，P＜0.01）and dendritic cells（r=-0.148，P＜0.01）．Through analysis of the String database，it was found that proteins that interacted with GRB14 including EGFR，HRAS，FGFR1，INSR，CNGA1，COBLL1，LYPLAL1，TNKS2，TNKS，PRKCZ．Conclusions  The results of the present study suggest that GRB14 may efficiently predict poor survival in LUAD patients．

目的 检测微小RNA（miR）在人黑色素瘤中的表达情况,研究miR-412通过抑制性别确定区Y框转录因子6（SOX6）的表达影响黑色素瘤细胞增殖及侵袭能力的变化。方法 癌症基因组图谱（TCGA）数据库分析发现miR-412在黑色素瘤中异常表达,为研究其表达与肿瘤的相关性,采用Transwell小室,非锚定独立生长实验分析miR-412对黑色素瘤细胞增殖及侵袭能力的影响。软件预测SOX6可能为其靶向基因,采用荧光素酶报告分析及Western blot实验检测SOX6与miR-412的靶向调节情况。结果 TCGA数据库分析黑色素瘤组织中miR-412表达水平高于正常对照组,表达越高,生存时间越短。Transwell小室,非锚定独立生长实验显示miR-412过表达后促进细胞增殖及侵袭能力,而下调miR-412后抑制黑色素瘤细胞增殖及侵袭能力;通过靶点预测miR-412结合SOX6基因3’-非翻译区（UTR）,导致SOX6蛋白因miR-412表达增高而下调;同时在miR-412下调的细胞中抑制SOX6表达可恢复黑色素瘤细胞的增殖及侵袭能力。结论 miR-412过表达后促进黑色素瘤细胞增殖及侵袭能力,反之则抑制黑色素瘤细胞增殖及侵袭能力。 miR-412通过靶向调控SOX6影响黑色素瘤细胞增殖及侵袭,提示miR-412在黑色素瘤的发病过程中起重要作用,是潜在的治疗靶点。

Objective To assess the expression of miR-412 in human melanoma and investigate how miR-412 modulates melanoma cell proliferation and invasive capacity by inhibiting SRY-Box Transcription Factor 6,（SOX6） expression．Methods Analysis of the TCGA（The Cancer Genome Atlas）database identified aberrant miR-412 expression in melanoma．To explore its relevance to tumorigenesis,we conducted Transwell chamber and non-adherent independent growth assays to examine the effects of miR-412 on melanoma cell proliferation and invasion．Software predictions highlighted SOX6 as a potential target gene．We performed luciferase reporter assays and Western blot experiments to elucidate the regulatory interactions between SOX6 and miR-412．Results TCGA database analysis revealed significantly elevated miR-412 expression levels in melanoma tissues compared to the normal control group．Moreover,higher miR-412 expression correlated with shorter survival times．Functional assays using Transwell chambers and non-adherent independent growth assays demonstrated that overexpressing miR-412 enhanced cell proliferation and invasive capabilities．Conversely,reducing miR-412 expression restrained these attributes in melanoma cells． Target prediction analysis indicated that miR-412 binds to the 3’-UTR region of SOX6,resulting in decreased SOX6 protein levels due to increased miR-412 expression．Intriguingly,inhibiting SOX6 expression concurrently amplified the proliferation and invasive potential of melanoma cells,which was initially dampened by miR-412 downregulation．Conclusions Elevated miR-412 expression augments melanoma cell proliferation and invasive capabilities,while its suppression diminishes these traits．Through its targeted regulation of SOX6,miR-412 exerts a significant influence on melanoma cell proliferation and invasion．These findings underscore the pivotal role of miR-412 in melanoma pathogenesis and underscore its potential as a promising therapeutic target．

目的 探讨链霉菌抗生物素蛋白-过氧化物酶（SP）免疫组化染色检测胰岛素样生长因子-1（IGF-1）及组织P53蛋白的表达在结直肠腺癌中意义。方法 选取乌鲁木齐市中医医院2020年1月—2023年12月收治的169例结直肠腺癌患者为恶性组,另选取我院同期收治的169例良性结直肠肿瘤患者为良性组。取手术或活检病理组织应用SP免疫组化染色检测2组肿瘤组织IGF-1及P53蛋白表达水平,对比良性组与恶性组间差异,分析不同临床分期、淋巴结转移情况及组织分化程度患者的IGF-1水平、IGF-1mRNA及P53蛋白阳性率。结果 SP免疫组化染色检测IGF-1阳性率、P53蛋白阳性率,恶性组（72.78%、47.93%）均高于良性组（14.79%、6.51%）,对比差异有统计学意义（χ²=115.440、χ²=73.180,P<0.05）;Ⅳ期患者IGF-1阳性率（96.77%）及P53蛋白阳性率（77.42%）高于Ⅲ期（85.11%、63.83%）、Ⅱ期（62.69%、31.34%）及Ⅰ期患者（45.83%、25.00%）,对比差异有统计学意义（χ²=24.860,χ²=28.000,P<0.05）,各亚组两两比较差异无统计学意义（IGF-1阳性与阴性,Ⅰ期 vs Ⅲ期,χ²=12.110,P<0.001;Ⅰ期 vs Ⅳ期,χ²=16.060,P<0.001;Ⅱ期 vs Ⅲ期,χ²=6.880,P=0.009;P53蛋白阳性与阴性Ⅰ期 vs Ⅲ期,χ²=9.580,P<0.002;Ⅰ期 vs Ⅳ期,χ²=14.9990,P<0.001;Ⅱ期 vs Ⅲ期,χ²=11.790,P=0.001;）;有淋巴结转移患者IGF-1阳性率（85.71%）及P53蛋白阳性率（71.43%）高于无淋巴结转移患者（14.79%、40.94%）,对比差异有统计学意义（χ²=4.720、11.740,P<0.05）;低分化患者IGF-1阳性率（93.48%）及P53蛋白阳性率（71.74%）高于中分化患者（81.18%、54.12%）、高分化患者（52.63%、31.58%）,对比差异有统计学意义（χ²=21.250、13.510,P<0.05）。结论 SP免疫组化染色检测提示结直肠腺癌患者IGF-1、P53蛋白阳性率高于良性肿瘤患者,且临床分期高、淋巴结转移与肿瘤组织低分化者的IGF-1、P53蛋白阳性率高,因此IGF-1、P53有望成为结直肠腺癌诊治的重要检测指标。

Objective Exploring the significance of immunohistochemical staining with streptavidin-perosidase（SP）to detect the expression of insulin-like growth factor-1（IGF-1）and tissue P53 in colorectal adenocarcinoma．Methods A total of 169 patients with colorectal adenocarcinoma admitted to a hospital from January 2020 to December 2023 were selected and divided into the malignant group．Other 169 patients with benign colorectal tumors admitted to a hospital during the same period were selected and divided into the benign group．SP immunohistochemistry staining was used to detect and compare the expression levels of IGF-1 and P53 proteins in two groups of tumor tissues obtained in surgery or biopsy．And the IGF-1 levels,IGF-1 mRNA,and P53 positivity rates in patients with different clinical stages,lymph node metastasis,and tissue differentiation levels were compared．Results There was a significant difference in the positive rates of IGF-1mRNA and P53 detected by SP immunohistochemistry staining,and malignant group（72.78%,47.93%）were higher than the benign group（14.79%,6.51%）,which were statistically significant（χ²=115.440,73.180,P<0.05）．The positive rates of IGF-1 and P53 were 96.77% and 77.42% in stage IV,which were higher than those in Stage III（85.11%,63.83%）,II（62.69%,31.34%）and I（45.83%,25.00%）,the differences were statistically significant（χ²=24.860,28.000,P<0.05）．The expression levels of IGF-1 and P53 in colorectal adenocarcinoma patients with different lymph node metastases showed significant differences,the positive rates of IGF-1（85.71%）and P53（71.43%）in patients with lymph node metastasis were higher than those without lymph node metastasis（14.79%,40.94%）,and the differences were statistically significant（χ²=4.720,11.740,P<0.05）．There were significant differences in the expression levels of IGF-1 and P53 among patients with colorectal adenocarcinoma of different degrees of differentiation,the positive rates of IGF-1（93.48%）and P53（71.74%）were significantly higher than those of moderately differentiated（81.18%,54.12%）and well differentiated（52.63%,31.58%）,and the differences were statistically significant（χ²=21.250,13.510,P<0.05）．Conclusion sThrough SP immunohistochemical staining,it was found that the positivity rates of IGF-1 and P53 in colorectal adenocarcinoma patients were higher than those in benign tumor patients,and those with high the clinical stage,lymph node metastasis,and low differentiation of tumor tissue,had higher the positivity rates of IGF-1 and P53．Therefore,IGF-1 and P53 are expected to become important monitoring indicators for the diagnosis and treatment of colorectal adenocarcinoma．

目的 观察电子束照射对体外培养的细粒棘球蚴形态结构、死亡率及其p38 mRNA表达的影响。方法 采集自然感染的绵羊肝中的细粒棘球蚴原头蚴,随机分成3组,分别用0 Gy、30 Gy、60 Gy的不同剂量的6 MeV电子束各照射1次,照射后连续培养3 d、14 d,光镜观察虫体的大体变化及死亡率,qRT-PCR法测定p38基因的表达水平。结果 60 Gy组较0 Gy、30 Gy组原头蚴变性坏死数目明显增多,死亡率有差异（P<0.0125）,连续培养天数（3 d、14 d）对虫体死亡率无影响。经电子束照射后,30 Gy、60 Gy组原头蚴p38 mRNA表达水平较0 Gy组升高（P<0.05）。结论 体外培养的原头蚴经电子束照射后大体形态结构发生明显变化、死亡率升高,且与电子束的剂量存在量效关系;p38 mRNA的表达量随着电子束的剂量的增加而升高,p38基因可能参与电子束所致体外杀伤棘球蚴的作用机制。

Objective To observe the effect of 6 MeV electron beam on the morphological structure,mortality rate and expression of p38 mRNA and in Echinococcus granulosus．Methods Einococcus granulosus was collected from natural infected sheep liver and divided into 3 groups randomly,then irradiated by 6 MeV electron beam of 0 Gy,30 Gy and 60 Gy,respectively．After culturing for 3 and 14 days,the gross change and mortality of worms were observed by light microscopy and the expression level of p38 gene was determined by qRT-PCR．Results In 60 Gy group,compared with 0 Gy and 30 Gy group,the gross morphology and structure have changed significantly,the mortality rate was significantly different（P <0.0125）．Days of culture（3 days,14 days）had no obvious effect on mortality,and the p38 mRNA expression levels in 30 Gy and 60 Gy group were significantly higher than 0 Gy group（P <0.05）．Conclusions The gross morphology,structure changes and mortality of Einococcus granulosus increases significantly after electron beam irradiation and has obvious quantitative and effective relationship with the electron beam dose,the p38 gene may be involved in the mechanism of in vitro killing by electron beam.

目的 分析TIMELESS、鼠肉瘤病毒家族相关蛋白2A（RAB2A）、异常纺锤体样小头畸形相关基因（ASPM）在乳腺癌组织中的表达及与临床特征相关性。方法 选取2019年2月—2021年2月我院乳腺癌组织标本84例作为研究组、正常乳腺组织标本53例作为对照组,采用荧光定量聚合酶测定TIMELESS、ASPM,采用Western blot检测RAB2A蛋白表达情况,分析上述三个指标在乳腺癌中表达及与临床特征相关性。结果 对比对照组,研究组TIMELESS、ASPM表达较高,RAB2A较低（P<0.05）。TIMELESS、RAB2A、ASPM与乳腺癌淋巴结浸润、TNM分期、分化程度相关（P<0.05）。TIMELESS、RAB2A、ASPM为影响乳腺癌发生的危险因素（P<0.05）。TIMELESS、RAB2A负相关（r=-0.383、P=0.001）;TIMELESS、ASPM正相关（r=0.397、P=0.001）;RAB2A、ASPM负相关（r=-0.257、P=0.018）。对比TIMELESS、RAB2A、ASPM单一检测,三者联合检测对乳腺癌的诊断价值较高（P<0.05）。结论 乳腺癌患者TIMELESS、ASPM呈高表达,RAB2A呈低表达,上述三个指标与乳腺癌高度相关,可作为乳腺癌发生的检测指标。

Objective To analyze the expression of TIMELESS,murine sarcoma virus family related protein 2A（RAB2A）and abnormal spindle like microcephaly related gene（ASPM）in breast cancer tissues and their correlation with clinical features．Methods A total of 84 breast cancer tissue samples from our hospital from February 2019 to February 2021 were selected as the study group and 53 normal breast tissue samples were selected as the control group．Time,ASPM and RAB2A protein expression were determined by fluorescent quantitative polymerase,and RAB2A protein expression was detected by Western blot．The expression of the above three indicators in breast cancer and their correlation with clinical characteristics were analyzed．Results Compared with the control group,the study group had higher TIMELESS and ASPM expression levels and lower RAB2A level（P<0.05）．TIMELESS,RAB2A and ASPM expressions were correlated with lymph node infiltration,TNM stage and differentiation of breast cancer（P<0.05）．TIMELESS,RAB2A and ASPM were the risk factors of breast cancer（P<0.05）．TIMELESS and RAB2A were negatively correlated（r=-0.383,P=0.001）;TIMELESS and ASPM were positive correlated（r=0.397、P=0.001）;RAB2A and ASPM were negatively correlated（r=-0.257,P=0.018）．Compared with the single detection of TIMELESS,RAB2A and ASPM,the combined detection had higher diagnostic value for breast cancer（P<0.05）．Conclusions Patients with breast cancer had high expression of TIMELESS and ASPM,and low expression of RAB2A．The above three indicators were highly correlated with breast cancer and can be detection indicators for breast cancer．

目的 研究核因子-κB激活剂1（Act1）对高糖诱导肾小管上皮细胞炎症反应及细胞外基质表达的调控作用。方法 培养肾小管上皮细胞MK2,设置对照组和高糖组,处理12 h、24 h、48 h、72 h后检测细胞中Act1的mRNA和蛋白表达水平;设置si-NC组（5.5 mmol/L葡萄糖培养基中转染NC siRNA）、si-NC+高糖组（30 mmol/L葡萄糖培养基中转染NC siRNA）、si-Act1+高糖组（30 mmol/L葡萄糖培养基中转染Act1 siRNA）,48 h后检测细胞中Act1、E-钙黏蛋白（E-cadherin）、N-钙黏蛋白（N-cadherin）、I型胶原（Col-I）、III型胶原（Col-III）的mRNA和蛋白表达水平以及培养基中肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）、干扰素-γ（IFN-γ）的含量。结果 高糖组处理12 h、24 h、48 h、72 h时细胞中Act1的mRNA和蛋白表达水平均高于对照组（P<0.05）;si-NC+高糖组处理48h时细胞中Act1、N-cadherin、Col-I、Col-III的mRNA和蛋白表达水平以及培养基中TNF-α、IL-1β、IFN-γ的含量均高于si-NC组,细胞中E-cadherin的mRNA和蛋白表达水平均低于si-NC组（P<0.05）;si-Act1+高糖组处理48h时细胞中Act1、N-cadherin、Col-I、Col-III的mRNA和蛋白表达水平以及培养基中TNF-α、IL-1β、IFN-γ的含量均低于si-NC+高糖组,细胞中E-cadherin的mRNA和蛋白表达水平均高于si-NC+高糖组（P<0.05）。结论 Act1表达增加对高糖诱导肾小管上皮细胞炎症反应激活和细胞外基质增多具有促进作用。

Objective To study the regulation effect of nuclear factors-κB activator 1（NF-κB activator 1,Act1）on high glucose induced inflammatory response and extracellular matrix expression in renal tubular epithelial cells．Methods Renal tubular epithelial cells MK2 were cultured and control group and high glucose group were set．The mRNA and protein expression of Act1 were detected after treatment for 12,24,48 and 72 hours．MK2 were divided into si-NC group（transfected with NC siRNA in 5.5 mmol/L glucose medium）,si-NC+high glucose group（transfected with NC siRNA in 30 mmol/L glucose medium）and si-Act1+high glucose group（transfected with Act1 siRNA in 30 mmol/L glucose medium）．The mRNA and protein expression of Act1,E-cadherin,N-cadherin,type I collagen（Col-I）,and type III collagen（Col-III）and the contents of tumor necrosis factor-α（TNF-α）,interleukin-1β（IL-1β）,interferon-γ（IFN-γ）in culture medium were detected．Results The mRNA and protein expression levels of Act1 in cells of high glucose group were higher than those of control group at 12 h,24 h,48 h and 72 h（P<0.05）．The mRNA and protein expression levels of Act1,N-cadherin,CoL-I,Col-III in cells and the contents of TNF-α,IL-1β,IFN-γ in culture medium of si-NC+high glucose group were higher than those of si-NC group,the mRNA and protein expression levels of E-cadherin in cells were lower than those of si-NC group at 48 h（P<0.05）．The mRNA and protein expression levels of Act1,N-cadherin,CoL-I,Col-III in cells and the contents of TNF-α,IL-1β,IFN-γ in culture medium of si-Act1+high glucose group were lower than those of si-NC+high glucose group,the mRNA and protein expression levels of E-cadherin in cells were higher than those of si-NC+high glucose group at 48 h（P<0.05）．Conclusions The increased expression of Act1 promotes the activation of inflammatory response and the increase of extracellular matrix in renal tubular epithelial cells induced by high glucose．

目的 观察2型糖尿病大鼠肝脏组织中circRNA-0003340的表达,并探讨与糖尿病的关系。方法 选取健康雄性SD大鼠30只,随机分为2组,正常对照组（NC组,n=10）与2型糖尿病组（T2DM组,n=20）,检测FPG、FINs、HbA1c、TC、TG、HDL-C、LDL-C、AST、ALT;行腹腔注射糖耐量实验和胰岛素耐量实验,计算胰岛素抵抗指数（HOMA-IR）;HE染色观察胰岛细胞形态;RT-PCR检测大鼠肝脏组织circRNA-000334的表达量。结果 与NC组比较,T2DM组的AST、ALT、FPG、HAb1c、FINs、HOMA-IR、TG、TC、LDL-C均升高（P<0.05）,HDL-C降低（P<0.05）。circRNA-0003340在T2DM组肝脏组织中的表达较NC组肝脏组织中的表达是下调的,差异有统计学意义（P<0.05）。Sperman相关分析示大鼠肝脏组织中circRNA-0003340表达水平与FPG、TG及TC呈负相关（P<0.05）。结论 circRNA-003340的表达水平可能与T2DM大鼠的糖脂代谢密切相关,circRNA-003340在肝脏组织中的表达水平下调可能参与T2DM的发生发展。

Objective To observe the expression of circRNA-0003340 in the liver tissue of type 2 diabetes mellitus （T2DM）rats and to explore its relationship with diabetes．Methods A total of 30 healthy male SD rats were randomly divided into two groups,normal control group（NC group,n=10）and T2DM group（n=20）,and fasting plasma glucose（FPG）,fasting insulins（FINS）,glycated hemoglobin（HbA1c）,total cholesterol（TC）,triglyceride (TG）,high-density lipoprotein cholesterol（HDL-C）,low-density lipoprotein cholesterol（LDL-C）,aspartate aminotransferase（AST）,alanine aminotransferase（ALT）levels were detected．Intraperitoneal glucose tolerance test and insulin tolerance test were performed to calculate the insulin resistance index（HOMA-IR）,HE staining was used to observe islet cell morphology,the expression of circRNA-000334 in rat liver tissue was detected by RT-PCR．Results Compared with the NC group,the T2DM group had increased AST,ALT,FPG,HAb1c,FINs,HOMA-IR,TG,TC,LDL-C（P<0.05）and decreased HDL-C（P<0.05）．The expression of circRNA-0003340 in liver tissue in T2DM group was down-regulated compared with that in NC group,with statistically significant difference（P<0.05）．Sperman correlation analysis showed that the expression level of circ-0003340 in rat liver tissue was negatively correlated with FPG,TG and TC（P<0.05）．Conclusions The expression level of circRNA-003340 may be closely related to the glycolipid metabolism of T2DM rats,and the downward regulation of the circRNA-003340 expression level in liver tissues may be involved in the occurrence and development of T2DM．