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 评估调脂药物靶点所介导的脂质表型（HMGCR、PCSK9和NPC1L1）与高血压肾病风险之间潜在的因果相关性。方法 使用来自欧洲人群公开可获得的全基因组关联研究（GWAS）汇总数据进行孟德尔随机化（MR）分析。采用与低密度脂蛋白胆固醇（LDL-C）相关的遗传变异,根据选定的调脂药物靶基因筛选工具变量,使用逆方差加权法作为主要MR分析方法,并进行敏感性分析确保结果的稳健性。结果 基因预测的LDL-C水平与较高的高血压肾病风险相关（OR=1.19,95% CI：1.03~1.38,P=0.021）。较高的HMGCR介导的LDL-C水平与高血压肾病风险存在正向因果相关性（OR=4.08,95% CI：2.86~5.81;P<0.001）。然而,PCSK9和NPC1L1介导的LDL-C水平与高血压肾病风险无相关性。Cochran Q检验、MR-PRESSO检测和MR-Egger截距测试显示工具变量之间不存在异质性或水平多效性。结论 HMGCR介导的LDL-C与高血压肾病的发病风险存在因果相关性,针对HMGCR基因的他汀类药物在高血压肾病的防治中可能具有潜在益处。

Objective To assess the potential causal relationship between lipid phenotypes mediated by lipid-lowering drug targets（HMGCR,PCSK9 and NPC1L1）and the risk of hypertensive nephropathy．Methods Mendelian randomization（MR）analysis was conducted using summary data from publicly available European ancestry genome-wide association studies（GWAS）．Genetic variants associated with low-density lipoprotein cholesterol（LDL-C）were used as instrumental variables based on selected lipid-lowering drug target genes screening tools．Inverse variance weighting was selected as the main MR analysis method,with sensitivity analyses conducted to ensure the robustness of the results．Results Genetically predicted LDL-C levels were associated with a higher risk of hypertensive nephropathy（OR=1.19,95% CI：1.03~1.38,P=0.021）．Higher LDL-C levels mediated by HMGCR were positively causally related to increased risk of hypertensive nephropathy（OR=4.08,95% CI：2.86~5.81;P<0.001）．However,LDL-C levels mediated by PCSK9 and NPC1L1 showed no significant association with the risk of hypertensive nephropathy．Cochran’s Q test,MR-PRESSO,and MR-Egger intercept tests showed no heterogeneity or horizontal pleiotropy among instrumental variables．Conclusions The findings of this study support the causal relationship between LDL-C mediated by HMGCR and increased risk of hypertensive nephropathy,suggesting potential benefits of statin therapy for hypertensive nephropathy．

目的 探讨双靶点微创联合尼莫地平治疗丘脑出血破入脑室患者的安全性及对NIHSS评分的影响。方法 选择2017年1月—2020年1月期间本院收治的54例丘脑出血破入脑室患者作为研究资料,随机分组各27例,对照组行单纯侧脑室体外引流术治疗,观察组行立体定向下侧脑室联合丘脑血肿双靶点微创穿刺引流术治疗,均实施尼莫地平治疗,观察两组手术并发症,测定治疗不同阶段患者NIHSS评分、ADL评分、神经损伤指标、创伤应激指标变化。结果 并发症率比较,观察组7.41%低于对照组29.63%,P＜0.05;治疗后,观察组NSE、NGF、β-EP、Cor均降低,且低于对照组,P＜0.05;治疗后,观察组NIHSSL评分降低且低于对照组,ADL评分升高且高于对照组,P＜0.05。结论 针对丘脑出血破入脑室患者采取立体定向下侧脑室联合丘脑血肿双靶点微创穿刺引流术及尼莫地平治疗可进一步改善神经功能及生活质量,且手术安全性高,创伤应激恢复改善,神经损伤恢复快,并发症少,值得推广。

Objective To investigate the safety of double target minimally invasive surgery combined with nimodipine in the treatment of patients with thalamic hemorrhage breaking into ventricle and its influence on NIHSS score. Methods From January 2017 to January 2020, 54 patients with thalamic hemorrhage ruptured into ventricles in our hospital were selected as the research data, and they were randomly divided into 27 cases in each group. The control group was treated with external drainage of lateral ventricle alone, and the observation group was treated with stereotactic double target minimally invasive puncture and drainage of hypothalamic hematoma. The changes of NIHSS score, ADL score, nerve injury index and trauma stress index in different stages of treatment were determined. Results The complication rate of the observation group was 7.41%, lower than that of the control group 29.63%, P<0.05; after treatment, NSE, NGF, β-EP, Cor in the observation group were decreased, and lower than those in the control group, P<0.05; after treatment, NIHSSL score of the observation group was decreased, lower than that of the control group, ADL score was increased and higher than that of the control group, P<0.05. Conclusion For patients with thalamic hemorrhage breaking into ventricles, stereotactic double target minimally invasive puncture drainage combined with thalamic hematoma and nimodipine treatment may further improve the neurological function and patients’ quality of life, and the operation safety is high, the recovery of traumatic stress is improved, the recovery of nerve injury is quick, and the complications are less, which is worthy of promotion.