目的  探讨TAP水平与乳腺癌分子亚型及临床病理参数之间的相关性。方法  以2021年3月—2025年1月期间收治的150例乳腺癌病例为样本，采用静脉采血方式测定TAP凝聚物表面积指标，通过免疫组织化学EnVision双步染色技术，对雌激素受体（ER）、雄激素受体（AR）、孕激素受体（PR）、Ki-67及p53等表达水平进行分析，采用荧光原位杂交（FISH）对人表皮生长因子受体2（HER2）基因扩增状态进行检测。结果  150例患者中，TAP强阳性131例，TAP弱阳性15例，TAP阴性4例，TAP阳性率97.33%。免疫表型：ER阴性43例，ER阳性107例；AR阳性133例，AR阴性17例；PR阴性60例，PR阳性90例；p53阳性73例，p53阴性77例；HER2强阳性41例，HER2弱阳性89例，HER2阴性20例；Ki-67增殖指数≥20% 116例，Ki-67增殖指数＜20% 34例。FISH对65例免疫组织化学检测结果为HER2（2+ ）的乳腺癌病例进行基因扩增状态分析，其中阳性7例，阴性58例。Ki-67高增殖组TAP表达水平显著高于低增殖组（P＜0.05）；不同临床分期患者TAP表达水平存在差异（P＜0.05）；三阴型、HER2阳性型、Luminal A型和Luminal B型的患者之间的TAP表达水平存在差异（P＜0.05），各分子分型（HER2阳性型、三阴型、Luminal A型和Luminal B型）与其对应非分型组的TAP表达均无统计学差异（均P＞0.05）。结论  TAP在乳腺癌中广泛表达，且与Ki-67增殖指数、临床分期呈正相关。虽然不同分子分型间TAP表达存在总体差异，但具体亚型对比未显示显著性，后期需扩大样本量验证。

       Objective  To explore the relationship between tumor abnormal protein（TAP）level and molecular typing and clinicopathological features of breast cancer．Methods  A total of 150 breast cancer cases admitted from March 2021 to January 2025 were enrolled in this study．The surface area of TAP condensates was measured using venous blood samples．The expression levels of estrogen receptor（ER），androgen receptor（AR），progesterone receptor（PR），Ki-67，and P53 were analyzed via immunohistochemistry（IHC）using the EnVision two-step staining technique．The amplification status of the human epidermal growth factor receptor 2（HER2+）gene was determined using fluorescence in situ hybridization（FISH）．Results  Among 150 patients，131 cases were strongly positive，15 cases were weakly positive and 4 cases were negative，with a positive rate of 97.33%．Immunophenotype：ER positive in 107 cases and ER negative in 43 cases，133 cases were  positive for AR and  17 cases were negative，PR was positive in 90 cases and negative in 60 cases，73 cases were positive for p53 and 77 cases were negative．HER2 is strongly positive in 41 cases，weakly positive in 89 cases and negative in 20 cases．There were 116 cases with Ki-67 proliferation index ≥ 20% and 34 cases with Ki-67 proliferation index ＜ 20%．Sixty-five cases of breast cancer HER2（2 ）were detected in the later stage．by FISH，of which 7 cases were positive and 58 cases were negative．The expression level of TAP in patients with high Ki-67 proliferation index was higher than that in patients with low Ki-67 proliferation index（P＜0.05）．The expression level of TAP in patients with different clinical stages was different（P＜0.05）．There were differences in TAP expression levels among patients with triple negative type，HER2 positive type，Luminal A type and Luminal B type（P＜0.05）．There was no statistical difference in TAP expression between each molecular type（triple negative type，HER2 positive type，Luminal A type and Luminal B type）and its corresponding non-typing group（all P＞0.05）．Conclusions  TAP is widely expressed in breast cancer，and it is positively correlated with Ki-67 proliferation index and clinical stage．Although there is a general difference in TAP expression among different molecular typing，the comparison of specific subtypes shows no significance，and it needs to be verified by expanding the sample size 

       目的  观察补肾益气方肾俞膏摩治疗结直肠癌康复期癌因性疲乏的临床疗效。方法  收集2023年6月—2024年6月结直肠癌康复期的80例住院及门诊患者，随机平均分为两组。行常规对症支持治疗的为对照组；在常规对症支持治疗上加用补肾益气方肾俞膏摩的为干预组；两组均连续治疗14天。于开始治疗前1天和治疗结束后1天分别进行疗效评估相关指标检测。于治疗前1天、治疗第7天和第14天进行不良反应检测。结果 干预组治疗后Piper评分、中医证候总积分、PSQI评分、KPS评分及免疫功能指标（CD₃⁺  、CD₄⁺、CD₈⁺  、CD₄⁺ /CD₈⁺ ）较治疗前均有明显改善；干预组发生不良反应少于对照组。结论  补肾益气方肾俞膏摩治疗能够有效改善结直肠癌患者的癌因性疲乏的治疗效果，提高生活质量和免疫功能，减少不良反应。

       Objective  To observe the clinical observation of Shenshu Tuina combined with Bushen Yiqi herbal ointment in the treatment of cancer-induced fatigue in the convalescent stage of colorectal cancer and evaluate the efficacy．Methods  From June 2023 to June 2025，80 inpatients and outpatients of colorectal cancer in the  recovery period were collected and  randomly divided into two groups．The patients who received routine symptomatic supportive treatment were enrolled as the control group．The intervention group was given Shenshu Tuina combined with Bushen Yiqi herbal ointment on the basis of control group．The relevant indicators for efficacy evaluation were tested one day before treatment and one day after the end of treatment．Adverse reactions were detected on the day before treatment，theseventh day and 14th day during treatment．Results  The efficacy evaluation indexes of the intervention group after treatment were obviously improved compared with those before treatment．Adverse  reactions occurred less in the intervention group than in the control group．Conclusions  Shenshu Tuina combined with Bushen Yiqi herbal ointment can effectively improve the treatment effect of cancer-induced fatigue in patients with colorectal cancer，improve the quality of life and immune function，reduce adverse reactions．

      目的 探讨肺癌根治术后患者康复期的症状体验与心理感受, 为完善症状管理和制定个性化康复干预方案提供依据。方法 采用现象学研究法,对15例肺癌根治术后康复期患者进行半结构式访谈, 运用Colaizzi 7步分析法进行归纳和提炼主题。结果 归纳出5个主题, 12个亚主题：多重躯体症状负担持续存在（术后疼痛综合征、顽固性刺激性咳嗽、劳力性呼吸困难、持续性疲劳感）; 负性心理情绪困扰（病耻感、疾病不确定感与复发恐惧）; 心理调适过程（诊断冲击与认知失调、角色适应与主动应对）; 创伤后成长与健康行为转变（生命意义感提升、健康促进行为强化）; 强烈的康复信息支持需求（自我保健知识需求、结构化康复锻炼指导需求）。结论 医护人员应关注肺癌根治术后患者康复期的症状体验, 动态评估患者的身心状况, 制定精准、有效的个性化干预方案, 帮助患者树立康复信心, 改善术后康复体验和提高生活质量。

       Objective  To explore the symptom experience and psychological feelings of patients during the rehabilitation period after radical resection of lung cancer, aiming to provide a basis for improving symptom management and formulating personalized rehabilitation interventions．Methods The phenomenological research method was used to conduct semi-structured interviews with 15 patients in the rehabilitation period after radical surgery for lung cancer．Colaizzi's 7-step analysis method was used to summarize and extract themes．Results Five themes and 12 sub-themes were summarized：Persistent burden of multiple physical symptoms（postoperative pain syndrome, refractory irritative cough, exertional dyspnea, persistent fatigue）; negative emotional experiences（stigma of illness, illness uncertainty and fear of recurrence）; psychological adjustment processes（diagnostic shock and denial, role acceptance and active coping）; post-traumatic growth and health behavior transformation（enhanced sense of meaning in life, strengthened health-promoting behaviors）; strong demand for rehabilitation information support（self-care knowledge, rehabilitation exercise knowledge）．Conclusions Medical staff should pay attention to the symptom experience of patients during the recovery period after radical lung cancer surgery, dynamically assess their physical and mental conditions, develop precise and effective personalized intervention plans, help patients build confidence in recovery, and thereby improve their postoperative rehabilitation experience and quality of life．

       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   探讨临床特征联合外周血血管内皮生长因子（VEGF）与α-羟基丁酸脱氢酶（α-HBDH）对卵巢癌的诊断价值。方法   选取2022年6月—2024年6月在天津市中心妇产科医院妇科接收的84例卵巢癌恶性肿瘤患者纳入观察组，同期选取84例卵巢良性病变患者纳入对照组。对比两组患者临床资料及VEGF、α-HBDH水平的差异，分析VEGF、α-HBDH水平与卵巢癌恶性肿瘤患者临床特征的相关性。采用二元Logistics回归分析卵巢癌恶性肿瘤的独立危险因素，并采用受试者工作特征（ROC）曲线分析VEGF、α-HBDH水平诊断卵巢癌恶性肿瘤的价值。结果   观察组年龄、身体质量指数（BMI）及血清CA125、HE4、VEGF、α-HBDH水平显著高于对照组（P＜0.05），VEGF与α-HBDH水平与国际妇产科联盟（FIGO）分期、分化等级及淋巴结转移均呈正相关关系（P＜0.05）。将年龄、BMI、VEGF、α-HBDH作为自变量纳入二元Logistic回归，结果显示BMI、VEGF、α-HBDH是卵巢癌恶性肿瘤的影响因素（P＜0.05），ROC曲线分析显示，联合检测VEGF和α-HBDH的AUC达0.921，灵敏度和特异度分别为81.0%和91.7%，优于单独检测（VEGF：AUC=0.702；α-HBDH：AUC=0.796）。结论  BMI联合VEGF与α-HBDH检测可为卵巢癌的诊断提供高效、无创的辅助手段，具有重要临床应用潜力。

      Objective  To explore the  diagnostic value of clinical features combined with  peripheral  blood vascular endothelial growth factor（VEGF）and α-hydroxybutyrate dehydrogenase（α-HBDH）levels in ovarian cancer．Methods  A total of 84 patients with malignant ovarian cancer admitted to the gynecology department of Tianjin Central Hospital of Gynecology and Obstetrics from June 2022 to June 2024 were included in the observation group，and 84 patients with benign ovarian lesions during the same period were included in the control group．The clinical data and VEGF，α-HBDH levels of the two groups were compared．Pearson analysis was used to explore the correlation between VEGF，α-HBDH levels，and clinical characteristics of patients with malignant ovarian cancer．Binary Logistic regression analysis was conducted to identify independent risk factors for malignant ovarian cancer，and receiver operating characteristic（ROC） curves were used to analyze the diagnostic value of VEGF and α-HBDH levels for malignant ovarian cancer．Results  The observation group had significantly higher age，BMI，and serum CA125，HE4，VEGF，α-HBDH levels compared to the control group（P＜0.05）．VEGF and α-HBDH levels were significantly positively correlated with FIGO stage，differentiation grade，and lymph node metastasis（P＜0.05）．Age，BMI，VEGF，and α-HBDH were included as independent variables in binary Logistic regression，and the results showed that BMI，VEGF，and α-HBDH levelswere independent risk factors for malignant ovarian cancer（P＜0.05）．ROC curve analysis  revealed that the AUC for combined detection of VEGF and α-HBDH reached 0.921，with sensitivity and specificity of 81.0% and 91.7%，respectively，significantly superior to individual detection（VEGF：AUC=0.702；α-HBDH：AUC=0.796）．Conclusions  The detection of BMI combined with VEGF and α-HBDH levels can provide an efficient and noninvasive auxiliary means for the diagnosis of ovarian cancer，which has important clinical application potential．

       目的   了解育龄期乳腺癌患者对子代健康和遗传风险担忧现状及其对癌症诊断前后生育意愿改变的影响。方法   于2019年11月—2020年9月，采用中文版癌症后生育忧虑量表（RCAC）-子女健康亚量表对广州市某三甲医院的230例育龄期乳腺癌患者进行调查，应用SPSS 26.0及PSM插件对结果进行统计分析。在进行子女健康亚量表得分低分组和中高分组患者的生育意愿改变率的比较时，应用倾向性评分匹配法控制混杂因素。结果   育龄期乳腺癌患者对子代健康和遗传风险担忧得分为（11.40±2.99）分；匹配前后不同子女健康亚量表得分分组的患者在癌症诊断前后生育意愿改变率的差异均不具有统计学意义（P＞0.05）。结论   育龄期乳腺癌患者对子代健康和遗传风险的担忧虽然没有显著影响其生育意愿的改变，但其对子代健康和遗传风险担忧处于较高水平，临床医护人员应提高对这一现象的重视，可通过多渠道科普相关知识，开展遗传咨询服务以减轻患者的担忧。

      Objective  To explore the current status of childbearing age breast cancer patients’  concerns  about their children’s health and genetic risk and its influence on the change of fertility intention before and after cancer diagnosis．Methods  From November 2019 to September 2020，the Chinese version of the Reproductive Concern After Cancer Scale（RCAC）- Children’s Health Sub-scale was used to interview 230 patients with breast cancer of childbearing age in a tertiary hospital in Guangzhou，and SPSS 26.0 and PSM plug-in were used to analyze the results statistically．The  propensity  score matching method was used to control confounding factors when comparing the change  rate of fertility intention of patients with low scores and those with medium and high scores in the children health subscale．Results  The score of concern for the health and genetic risk of children in breast cancer patients of childbearing age was（11.40±2.99）．There was no statistically significant difference in the change  rate of fertility intention before and after cancer diagnosis among patients with different subscale scores of children’s health．Conclusions   Despite not significantly impacting fertility intentions，the notably high level of concern regarding children’s health and genetic risks among childbearing-age breast cancer patients necessitates increased clinical awareness．It is recommended that healthcare professionals address this through multi-channel education and genetically focused counseling within a collaborative model to mitigate patient distress．

      目的   通过生物信息学手段筛选非小细胞肺癌（NSCLC）中的关键靶点基因，识别预后标志物NDC80，并探讨其在NSCLC中的表达意义，进而分析NDC80作为NSCLC基因治疗靶点的可行性。方法   采用癌症基因组图谱（TCGA）TCGA数据库检索NSCLC相关数据，进行加权基因共表达网络分析（WGCNA）以识别关键基因，并进行差异表达分析、相关性分析和蛋白互作网络构建。对筛选出的关键基因进行功能分析。利用免疫组化染色法检测癌组织及癌旁组织中NDC80蛋白的表达水平，并进一步探究其与临床病理特征的关系。采用Kaplan-Meier法分析NDC80表达与NSCLC患者无进展生存时间（PFS）的关系。结果   共筛选出20个与NSCLC高度关联的关键基因，包括CDC20、CDK1、MCM4、CDC6、MCM2、PLK1、NDC80、CCNB1、CDC45、AURKA、MCM8、BUB1、CDT1、ORC1、CCNA2、CASC5、MAD2L1、BUB1B、CENPA、AURKB。免疫组化验证显示，NDC80蛋白在NSCLC组织中高表达，其在NSCLC组（阳性表达率88.6%）显著高于癌旁组（50.0%）（P＜0.05）。NDC80蛋白的阳性表达率在TNM分期（Ⅲ期+Ⅳ期）、低分化、淋巴结转移的NSCLC组高于TNM分期（Ⅰ期+Ⅱ期）、高分化及中分化以及未发生淋巴结转移的NSCLC组（P＜0.05）。NDC80蛋白的阳性表达率在不同性别、年龄、病灶大小分类的NSCLC组织中无显著差异（P＞0.05）。Kaplan-Meier分析显示，NDC80蛋白高表达组的PFS中位数为（9.00±0.27）个月，明显低于低表达组（11.00±0.79）个月（P＜0.05）。结论   本研究发现的关键基因在NSCLC干细胞的维持中发挥重要作用。免疫组化结果显示，NDC80蛋白在NSCLC组织中高表达，且与肿瘤分化、TNM分期及淋巴结转移密切相关。NDC80蛋白高表达组的PFS明显低于低表达组，提示NDC80可能成为NSCLC筛查、治疗和预后评估的潜在生物标志物。

      Objective  To screen the key target genes in non-small cell lung cancer（NSCLC）by bioinformatics，identify the prognostic marker NDC80，and explore its expression significance in NSCLC，so as to analyze the feasibility of NDC80 as a gene therapy target for NSCLC．Methods  TCGA database was used to retrieve NSCLC-related data，and weighted gene co-expression network analysis（WGCNA）was used to identify key genes，and differential expression analysis，correlation analysis and protein-protein interaction network construction were carried out．The function of the selected key genes was analyzed．Immunohistochemical staining was used to detect the expression level of NDC80 protein in cancer tissues and adjacent tissues，and to further explore its relationship with clinicopathological features．Kaplan-Meier method was used to analyze the relationship between NDC80 expression and progression-free survival （PFS）of NSCLC patients．Results  A total of 20 key genes highly associated with NSCLC were screened out，which were CDC20，CDK1，MCM4，CDC6，MCM2，PLK1，NDC80，CCNB1，CDC45，AURKA，MCM8，BUB1，CDT1，ORC1，CCNA2，CASC5，MAD2L1，BUB1B and CENPA．Immunohistochemical  verification  showed that NDC80 protein was highly expressed in NSCLC tissue，and its positive expression rate in NSCLC group（88.6%）was significantly higher than that in adjacent cancer group（50.0%，P＜0.05）．The positive expression rate of NDC80 protein in NSCLC with TNM staging（Ⅲ+Ⅳ），low differentiation and lymph node metastasis was higher than that in NSCLC with TNM staging（Ⅰ+Ⅱ），high differentiation and moderate differentiation and no lymph node metastasis（P＜0.05）．There was no significant difference in the positive expression rate of NDC80 protein among NSCLC tissues with different gender，age and lesion size（P＞0.05）．Kaplan-Meier analysis showed that the median PFS of high expression group of NDC80 protein was（9.00±0.27）months，which was significantly lower than that of low expression group（11.00±0.79）months（P＜0.05）．Conclusions  The key genes found in this study play an important role in the maintenance of NSCLC stem cells．Immunohistochemical results showed that NDC80 protein was highly expressed in NSCLC，and it was closely related to tumor differentiation，TNM staging and lymph node metastasis．The PFS of high expression group of NDC80 protein was significantly lower than that of low expression group，suggesting that NDC80 may become a potential biomarker for screening，treatment and prognosis evaluation of NSCLC．

      目的   探讨肺癌伴癌性疼痛患者心理僵化现状及其影响因素，为临床制定改善患者心理僵化的针对性干预措施以及提升患者生活质量提供参考依据。方法   采用便利抽样法，选取2023年10月—12月期间焦作市某三级甲等医院收治的肺癌伴癌性疼痛患者为研究对象，采用一般资料调查问卷、疼痛心理僵化量表（PIPS）、简易疾病感知问卷（BIPQ）、家庭功能问卷（APGAR）进行调查，采用Pearson相关性分析肺癌伴癌性疼痛患者心理僵化与疾病感知、家庭功能的关系。采用多元线性回归分析肺癌伴癌性疼痛患者心理僵化的影响因素。结果   本次研究共发放问卷152份，回收有效问卷150份，有效回收率为98.68%。150例肺癌伴癌性疼痛患者心理僵化量表总分为（61.66±2.85）分，回避型经验维度得分为（45.52±1.97）分，认知融合维度得分为（19.74±1.59）分。不同文化程度、家庭人均月收入、疼痛程度的肺癌伴癌性疼痛患者心理僵化得分比较，差异有统计学意义（P＜0.05）。Pearson相关性分析结果显示：肺癌伴癌性疼痛患者心理僵化总分、经验性回避维度得分、认知融合维度得分与疾病感知得分均呈正相关关系（P＜0.001），与家庭功能得分均呈负相关关系（P＜0.001）。多元线性回归结果显示：文化程度、家庭人均月收入、疾病感知、家庭功能是肺癌伴癌性疼痛患者心理僵化的影响因素（P＜0.05），可解释肺癌伴癌性疼痛患者心理僵化43.9%的变异度。结论   肺癌伴癌性疼痛患者心理僵化处于较高水平，且受到文化程度、家庭人均月收入、疾病感知和家庭功能的影响，临床医护人员可从疾病感知、家庭支持等角度出发，采用认知干预、同伴支持等方法，加强对患者的健康教育，以缓解其对疾病的负性认知，从而缓解心理僵化，促进身心健康恢复。

       Objective  To explore the status and influencing factors of psychological  rigidity in patients with lung cancer and cancer pain，and to provide reference for clinical development of targeted interventions to improve patients’psychological rigidity andquality of life．Methods  The convenience sampling method was used to select patients with lung cancer and cancer pain who were admitted to a tertiary hospital in Jiaozuo City from October to December 2023 as the research object．The general data questionnaire，Psychological Inflexibility in Pain Scale（PIPS），Brief Illness Perception Questionnaire（BIPQ），and family function questionnaire（APGAR）were used to investigate．Pearson correlation analysis was used to analyze the relationship between psychological rigidity and disease perception and family function in patients with lung cancer and cancer pain．Multivariate linear regression was used to analyze the influencing factors of psychological rigidity in patients with lung cancer and cancer pain．Results  A total of 152 questionnaires were distributed in this study，and 150 valid questionnaires were recovered，with an effective recovery rate of 98.68 %．The total score of PIPS of 150 patients with lung cancer and cancer pain was（61.66±2.85），the score of avoidance experience dimension was（45.52±1.97），and the score of cognitive fusion dimension was（19.74±1.59）．There were statistically significant differences in the scores of psychological rigidity among lung cancer patients with cancer pain with different educational levels，family per capita monthly income，and pain degree（P＜0.05）．The  results of Pearson correlation analysis showed that the total score of PIPS，the score of empirical avoidance dimension and the score of cognitive fusion dimension were positively correlated with the score of disease perception（P＜0.001），and negatively correlated with the score of family function（P＜0.001）．The results of multiple linear regression showed that education level，family per capita monthly income，disease perception and family function were the influencing factors of psychological rigidity in patients with lung cancer and cancer pain（P＜0.05 ），which could explain 43.9 % of the variation of psychological rigidity in patients with lung cancer and cancer pain．Conclusions  The psychological rigidity of lung cancer patients with cancer pain is at a high level，and is affected by education level，family per capita monthly income，disease perception and family function．Clinical medical staff can use cognitive intervention and peer support from the perspective of disease perception and family support to strengthen the health education of patients，so as to alleviate their negative cognition of the disease，to alleviate the psychological rigidity and promote the recovery of physical and mental health．

       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 探讨长链非编码核糖核酸肺腺癌转移相关转录本 1（LncMALAT1）通过竞争性结合微小RNA-506-3p（miR-506-3p）调控Zeste同源物增强子2（EZH2）影响膀胱癌增殖的机制。方法 收集2023年1月—2024年10月的92例外科手术切除的膀胱癌组织及对应的癌旁组织标本, 利用Western blot和定量实时逆转录聚合酶链式反应（qRT-PCR）方法检测LncMALAT1和EZH2的表达情况。根据患者预后分为不良组（n=34）和良好组（n=58）, 收集患者的性别、年龄、肿瘤直径、血管侵袭情况、TNM分期、远处转移情况等临床指标, 结合临床病理指标分析LncMALAT1和EZH2与膀胱癌患者预后的关系。通过体外实验,包括qRT-PCR、Western blot、平板克隆和EdU实验,验证LncMALAT1对EZH2表达和膀胱癌细胞增殖的影响。利用生物信息学技术预测LncMALAT1与miR-506-3p的相互作用,并通过qRT-PCR验证在膀胱癌细胞中上调LncMALAT1表达后miR-506-3p的表达变化。结果 单因素结果显示, 血管侵袭情况、TNM分期、远处转移情况、LncMALAT1及EZH2表达水平均与膀胱癌患者预后不良有关, 差异有统计学意义（均P<0.05）。分析结果发现LncMALAT1与EZH2在膀胱癌组织中的表达呈正相关。体外实验结果显示, 上调LncMALAT1表达后, EZH2的表达显著上调, 且膀胱癌细胞的增殖能力显著提高（均P<0.05）。qRT-PCR验证表明,上调LncMALAT1表达后,miR-506-3p的表达显著下调（P<0.05）, 提示LncMALAT1通过竞争性结合miR-506-3p调控EZH2,进而影响膀胱癌细胞的增殖进展。结论 LncMALAT1通过竞争性结合miR-506-3p调控EZH2促进膀胱癌增殖功能,进而加快膀胱癌细胞的增殖进展, 可为膀胱癌的治疗提供新的潜在靶点。

Objective To explore the mechanism of long non-coding ribonucleic acid metastasis - associated lung adenocarcinoma transcript 1（LncMALAT1）regulating enhancer of Zeste homolog 2（EZH2）through competitive combination with microRNA-506-3p（miR-506-3p）to affect the proliferation of bladder cancer．Methods A total of 92 pairs of bladder cancer tissues and corresponding adjacent normal tissues were collected from surgical resections between January 2023 and October 2024．The expression levels of LncMALAT1 and EZH2 were detected using Western blot and qRT-PCR．The patients were divided into poor group（n=34）and good group（n=58）according to their prognosis．Clinical data, such as gender, age, tumor diameter, vascular invasion, TNM stage, and distant metastasis were collected, and the relationship between LncMALAT1 and EZH2 and the prognosis of bladder cancer patients was analyzed with clinical pathological indicators．Through in vitro experiments, including qRT-PCR Western blot, plate cloning and EdU experiment were conducted to verify the effect of LncMALAT1 on EZH2 expression and bladder cancer cell proliferation．Bioinformatics technology was used to predict the interaction between LncMALAT1 and miR-506-3p, and qRT-PCR was used to verify the change of miR-506-3p expression after up regulating LncMALAT1 expression in bladder cancer cells．Results The univariate results showed that vascular invasion, TNM stage, distant metastasis, LncMALAT1 and EZH2 expression levels were related to the poor prognosis of bladder cancer patients, and the difference was statistically significant（all P<0.05）．The results showed that the expression of LncMALAT1 and EZH2 in bladder cancer was positively correlated．In vitro experiment results showed that after up regulating LncMALAT1 expression, EZH2 expression was significantly up-regulated, and the proliferation ability of bladder cancer cells was significantly improved（all P<0.05）．QRT-PCR validation showed that the expression of miR-506-3p was significantly down regulated after the expression of LncMALAT1 was up-regulated（P<0.05）, suggesting that LncMALAT1 could regulate EZH2 through competitive combination with miR-506-3p, thereby affecting the proliferation and progression of bladder cancer cells．Conclusions LncMALAT1 can promote the proliferation of bladder cancer cells by competitively combining with miR-506-3p to regulate EZH2, and then accelerate the proliferation of bladder cancer cells, which can provide a new potential target for the treatment of bladder cancer．