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 探讨Ki-67、微小染色体维持蛋白2（MCM2）、p16在宫颈鳞状上皮内病变中的表达及其临床意义。方法 采用免疫组化检测Ki-67、MCM2、p16在宫颈炎症组14例、低级别鳞状上皮内病变（LSIL）组47例、高级别鳞状上皮内病变（HSIL）组49例中的表达情况,以病理结果作为金标准,对结果进行统计分析。结果 HSIL组中Ki-67、MCM2、p16阳性率均高于炎症组和LSIL组（均P<0.017）。HSIL组中Ki-67、MCM2过表达率均显著高于炎症组和LSIL组（均P<0.017）。随着宫颈病变级别增加,Ki-67及MCM2阳性范围从基底层至表层逐渐扩大。MCM2及Ki-67在LSIL组中表达模式多为基底层的非过表达模式,HSIL组多为中层及以上的过表达模式。Spearman相关性分析显示,MCM2和Ki-67在宫颈鳞状上皮内病变中的表达强度之间呈正相关（r=0.801,P<0.05）;p16与MCM2在宫颈鳞状上皮内病变中的表达呈正相关（r=0.559,P<0.05）;p16与Ki-67在宫颈鳞状上皮内病变中的表达呈正相关（r=0.478,P<0.05）。结论 p16阳性提示宫颈高级别鳞状上皮内病变。MCM2与Ki-67在宫颈鳞状上皮内病变中的表达具有较高一致性,MCM2可作为宫颈鳞状上皮内病变新的增殖标志物。

Objective To investigate the expression and significance of Ki-67,MCM2 and p16 in cervical intraepithelial lesions．Methods The expressions of Ki-67,MCM2 and p16 in cervicitis group（14 cases）,low-grade squamous intraepithelial lesion（LSIL） group（47 cases）and high-grade squamous intraepithelial lesion（HSIL） group（49 cases）were detected by immunohistochemistry．The pathological results were used as the gold standard for statistical analysis．Results The positive rates of Ki-67,MCM2 and p16 in HSIL group were significantly higher than those in cervicitis group and LSIL group（P<0.017）．The over-expression rates of Ki-67,MCM2 in HSIL group were significantly higher than those in cervicitis group and LSIL group（P<0.017）．With the increase of cervical lesion grade,the positive range of Ki-67 and MCM2 gradually expanded from basal layer to surface layer．The expression patterns of MCM2 and Ki-67 in LSIL group were mostly non-overexpressed in the basal layers,while those in HSIL group were mostly overexpressed in the middle layer and above．Spearman correlation analysis showed that the expression intensity of MCM2 and Ki-67 in cervical squamous intraepithelial lesions was positively correlated（r=0.801,P<0.05）．There was a positive correlation between the expression of p16 and MCM2 in cervical squamous intraepithelial lesions（r=0.559,P<0.05）．There was a positive correlation between the expression of p16 and Ki-67 in cervical squamous intraepithelial lesions（r=0.478,P<0.05）．Conclusions Positive p16 indicates high-grade squamous intraepithelial lesion．The expression of MCM2 and Ki-67 in cervical intraepithelial lesions is highly consistent．MCM2 can be used as a new proliferative marker for cervical intraepithelial lesions．

目的 探究血清多配体蛋白聚糖-1（SCD-1）与可溶性血管内皮生长因子受体-2（sVEGFR-2）表达水平在老年慢性心力衰竭患者预后评估的判定价值。方法 选取2023年1月—2024年3月珠海市第五人民医院检验科收治的110例老年慢性心力衰竭患者,检测其血清SCD-1和sVEGFR-2水平,对患者进行随访调查,了解其再次由于心力衰竭住院、心源性死亡的情况。运用多因素Logistic回归分析,探究老年慢性心力衰竭患者预后影响因素。结果 Logistic回归分析显示,心功能分级（OR=3.433,95%CI：0.934~6.431）、B型脑钠肽升高（OR=2.462,95%CI：0.861~4.765）、血清SCD-1升高（OR=3.795,95%CI：0.972~6.894）、血清sVEGFR-2升高（OR=3.842,95%CI：0.942~6.912）为影响老年慢性心力衰竭患者预后不良的重要因素（P<0.05）;联合血清SCD-1和sVEGFR-2曲线下面积0.962与B型脑肽钠曲线下面积0.844,相较于单一SCD-1曲线下面积0.658、sVEGFR-2曲线下面积0.712明显偏高（P<0.05）。结论 经研究证实,老年慢性心力衰竭患者预后效果不理想,其血清SCD-1和sVEGFR-2监测水平异常升高,和老年慢性心力衰竭预后不佳存在关联性,可视为老年慢性心力衰竭患者判定预后效果的主要标志物。

Objective To investigate the prognostic value of serum syndecan-1（SCD-1）and soluble vascular endothelial growth factor receptor-2（sVEGFR-2）expression levels in elderly patients with chronic heart failure. Methods A total of 110 elderly patients with chronic heart failure admitted to our hospital were selected,with a time interval of January 2023 to March 2024．Serum SCD-1 and sVEGFR-2 levels were detected and follow-up investigations were conducted to understand their re hospitalization and cardiogenic death due to heart failure．Multiple logistic regression analysis was used to explore the prognostic factors affecting elderly patients with chronic heart failure. Results According to logistic retrospective analysis,heart function grading（OR=3.433,95%CI：0.934-6.431）,elevated B-type brain natriuretic peptide（OR=2.462,95%CI：0.861-4.765）,elevated serum SCD-1（OR=3.795,95%CI：0.972-6.894）,and elevated serum sVEGFR-2（OR=3.842,95%CI：0.942-6.912）were important factors affecting the poor prognosis of elderly patients with chronic heart failure,with differences P<0.05．The area under the curve of combined serum SCD-1 and sVEGFR-2 was 0.962,and the area under the curve of B-type brain peptide sodium was 0.844,which was significantly higher than that of a single SCD-1 curve of 0.658 and sVEGFR-2 curve of 0.712,with a difference of P<0.05. Conclusions Research has confirmed that the prognosis of elderly patients with chronic heart failure is not satisfied,and their serum SCD-1 and sVEGFR-2 monitoring levels are abnormally elevated,which is related to the poor prognosis of elderly patients with chronic heart failure．It can be regarded as the main biomarker for defining the prognosis of elderly patients with chronic heart failure．

目的 探讨转录因子E盒结合锌指蛋白1（ZEB1）、溶酶体相关膜蛋白5（LAMP5）在结直肠癌组织中的表达水平分析及预后预测价值。方法 选取驻马店市中心医院2018年1月—2020年1月收治的120例结直肠癌患者,分别采取所有患者的结直肠癌组织及癌旁组织进行免疫组化染色,对比ZEB1、LAMP5阳性率。对比不同病理特征结直肠癌患者ZEB1、LAMP5表达水平差异。对所有患者进行4年随访,依照随访结果将患者分为2个亚组,即预后不良组（n=35）和预后良好组（n=85）,对比两组患者一般临床特征及ZEB1、LAMP5表达水平,应用Logistic回归分析ZEB1、LAMP5对结直肠癌预后的预测价值。结果 结直肠癌组织ZEB1、LAMP5相对表达量（38.26±5.49、26.77±3.85）与ZEB1、LAMP5阳性率（86.67%、72.22%）高于癌旁组织（15.46±2.54、8.04±1.59、23.33%、15.56%],对比差异有统计学意义（t=41.280,χ²=25.437;t=49.255,χ²=16.071;P<0.05）。不同TNM分期[Ⅰ~Ⅱ期（35.55±4.13）、Ⅲ~Ⅳ期（42.32±4.75）]、淋巴结转移患者[是（44.37±4.28）、否（35.84±3.77）]、肿瘤分化程度[低分化（35.27±4.57）、中高分化（41.34±4.60）]ZEB1相对表达量对比差异有统计学意义（t=-8.281,P<0.001;t=10.746,P<0.001;t=-7.253,P<0.001）;不同TNM分期[Ⅱ期（24.88±3.37）、Ⅲ~Ⅳ期（29.61±2.57）]、淋巴结转移[是（30.72±2.19）、否（25.21±3.19）]、肿瘤分化程度[低分化（24.57±3.62）、中高分化（29.04±2.55）]患者LAMP5相对表达量对比差异有统计学意义（t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,<0.001）;预后良好组与预后不良组患者性别、年龄、大体类型、肿瘤大小对比差异无统计学意义（P>0.05）,预后良好组与预后不良组患者TNM分期、淋巴结转移、肿瘤分化程度、ZEB1、LAMP5阳性比例对比差异有统计学意义（P<0.05）;Logistic回归分析显示：淋巴结转移、ZEB1阳性、LAMP5阳性为结直肠癌预后不良独立预测因素（P<0.05）。结论 ZEB1、LAMP5在结直肠癌组织中呈现高表达状态,且与结直肠癌的发生有关,同时ZEB1、LAMP5是结直肠癌预后的独立预测因素,两者有希望成为结直肠癌的治疗靶点。

Objective To investigate the expression levels and prognostic value of transcription factor E-box binding to zinc finger protein 1（ZEB1）and lysosomal associated membrane protein 5（LAMP5）in colorectal cancer tissues. Methods A total of 120 colorectal cancer patients admitted to a hospital from January 2018 to January 2020 were selected．Immunohistochemical staining was performed on the colorectal cancer tissues and adjacent tissues of all patients,and the positivity rates of ZEB1 and LAMP5 were compared．The expression levels of ZEB1 and LAMP5 in colorectal cancer patients with different pathological characteristics were compared．All patients were followed up for 4 years and divided into two subgroups based on the follow-up results,namely the poor prognosis group（n=35）and the good prognosis group（n=85）．The general clinical characteristics and expression levels of ZEB1 and LAMP5 were compared between the two groups．Logistic regression analysis was used to evaluate the predictive value of ZEB1 and LAMP5 for the prognosis of colorectal cancer. Results The relative expression level of ZEB 1 and LAMP 5 in colorectal cancer tissues [（38.26±5.49）,（26.77±3.85）] and the positive rate of ZEB 1 and LAMP 5（86.67%,72.22%）were significantly higher than that of adjacent tissues [（15.46±2.54）,（8.04±1.59）,23.33%,15.56%],the contrast difference was statistically significant（t=41.280,χ²=25.437;t=49.255,χ²=16.071;P<0.05）．Relative ZEBI expression levels in different TNM stages [I-Ⅱstage（35.55±4.13）,Ⅲ-Ⅳstage（42.32±4.75）],lymph node metastasis[Yes（44.37±4.28）,No（35.84±3.77）],degree of tumor differentiation [hypodifferentiated（35.27±4.57）,and middle or high differentiated（29.04±2.55）],those differences were statistically significant（t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,P<0.001）．The relative expression of LAMP 5 between different TNM stages [I-Ⅱstage（24.88±3.37）,Ⅲ-Ⅳstage（29.61±2.57）],lymph node metastasis [yes（30.72±2.19）,no（25.21±3.19）],degree of tumor differentiation [hypodifferentiated（24.57±3.62）,and middle or high differentiated（29.04±2.55）],the contrast was statistically significant（t=-8.254,P<0.001;t=9.227,P<0.001;t=-7.797,P<0.001）．There were no differences in gender,age,gross type,and tumor size between the good prognosis group and the poor prognosis group（P>0.05）,while there were differences in TNM stages,lymph node metastasis,tumor differentiation degrees,ratio of ZEB 1 and LAMP 5（P<0.05）．Logistic regression analysis showed that TNM stage,lymph node metastasis,ZEB 1 positive,and LAMP 5 positive were independent predictive factors of poor prognosis in colorectal cancer（P<0.05）. Conclusions ZEB1 and LAMP5 are highly expressed in colorectal cancer tissues and closely related to the occurrence and development of colorectal cancer．ZEB1 and LAMP5 are independent prognostic factors for colorectal cancer,and they have the potential to become therapeutic targets for colorectal cancer．

目的 探讨TRIB2在结肠癌中的表达水平及与预后及免疫浸润之间的关系。方法 TIMER数据库分析TRIB2在泛癌种中的表达;TCGA、GSE17538下载结肠癌患者RNA-seq数据和临床信息,评估其与临床病理特征的相关性;生存曲线、单因素和多因素Cox分析探讨TRIB2与预后的相关性,并构建列线图;对TRIB2进行差异基因的富集分析;分析TRIB2表达水平与免疫细胞浸润、免疫检查点、肿瘤突变负荷（TMB）以及免疫治疗敏感性之间的相关性。结果 TRIB2在结肠癌组织中高表达（P<0.05）;CMS1结肠癌患者TRIB2 mRNA表达水平最高;TRIB2是结肠癌患者的独立预后因素（单因素Cox回归分析：HR=1.397,95%CI：1.100~1.774,P=0.006;多因素Cox回归分析：HR=1.502,95%CI：1.158~1.947,P=0.002）;TRIB2与免疫细胞的浸润密切相关,并且与免疫检查点分子表达水平以及TMB正相关（r=0.39,P<0.001）;TRIB2的表达水平与免疫检查点抑制剂的疗效相关。结论 TRIB2在结肠癌中高表达且与结肠癌患者预后差和免疫微环境密切相关。

Objective To explore the expression of TRIB2 in colon cancer and its relationship with prognosis and immune cell infiltration. Methods TIMER database was used to analyse the expression of TRIB2 in pan-cancer．RNA-seq data and clinical information of colon cancer patients were downloaded from TCGA and GSE17538 to assess the correlation between TRIB2 with clinicopathological features．Survival curves,univariate and multivariate COX regression analysis were performed to explore the correlation between TRIB2 and prognosis,and a nomogram was constructed．Gene enrichment analyses were performed for TRIB2．Correlations between TRIB2 expression and immune cell infiltration,immune checkpoints,tumor mutation burden（TMB）,and immunotherapy sensitivity were analyzed．Results TRIB2 was highly expressed in colon cancer tissues（P<0.05）．The highest level of TRIB2 mRNA expression was found in CMS1．TRIB2 was an independent prognostic factor for colon cancer patients（univariate Cox regression analysis：HR=1.397,95%CI：1.100-1.774,P=0.006;multivariate Cox regression analysis：HR=1.502,95%CI：1.158-1.947,P=0.002）．TRIB2 was closely associated with immune cell infiltration and positively correlated with the expression level of immune checkpoint molecules as well as TMB（r=0.39,P<0.001）．The expression of TRIB2 was correlated with the efficacy of immune checkpoint inhibitors．Conclusions TRIB2 is highly expressed in colon cancer and is closely associated with poor prognosis and the immune microenvironment of colon cancer 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．