纤毛是细胞表面的重要细胞器，广泛参与细胞运动、感知外界信号和维持器官功能等生理过程。纤毛的形成，即纤毛发生（ciliogenesis）是一个高度复杂且受精密调控的过程，涉及大量与纤毛结构和功能相关基因的表达与调控。近年来，随着基因组学和发育生物学的发展，越来越多的研究揭示了多种关键转录因子在纤毛发生中的调控作用，包括RFX家族、FOXJ1、MCIDAS、GEMC1、MYB、E2F等。这些转录因子共同构成了一个多层次、多通路交织的调控网络，调控纤毛组装、基体复制、纤毛定位和功能维持等多个方面。本文系统综述了纤毛相关基因转录调控的研究进展，特别是关键转录因子的功能、相互作用及其在纤毛病中的作用，为深入理解纤毛的发育机制和疾病治疗提供参考。

       Cilia are crucial cell-surface organelles involved in cell movement，signal sensing，and organ function maintenance．Their formation，or ciliogenesis，is a complex and  precisely controlled  process that  requires the expression and regulation of numerous cilia-related genes．Recent advances in genomics and developmental biology have uncovered the  regulatory roles of key transcription factors like the RFX family，FOXJ1，MCIDAS，GEMC1，MYB，and E2F in ciliogenesis．These factors form a multi-level，interconnected regulatory network that oversees cilium assembly，basal body replication，ciliary positioning，and function preservation．This review systematically examines current research on transcriptional regulation of ciliary genes，with a focus on the roles，interactions，and contributions of these key transcription factors to ciliopathies，offering insights into ciliary development and disease treatment．

       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   免疫球蛋白A肾病（IgAN）与炎症性肠病（IBD）的相互作用机制尚未阐明。本研究旨在解析IBD与IgAN共病的关键特征基因及核心信号通路，以揭示肠－肾轴的分子调控网络。方法   于GEO数据库获取IBD（GSE75214）和IgAN（GSE93798）基因表达谱，筛选差异表达基因（DEGs）。通过蛋白互作网络（PPI）和拓扑算法（MCC、MNC、Degree、EPC等）识别核心特征基因，并结合公共数据库（CTD、DISEASES和GeneCards）和单细胞转录组测序（GSE171314）进行验证。通过Nephroseq数据库验证基因表达与临床表型的相关性。结果   共筛选出17个IBD-IgAN共病DEGs，PPI网络分析等确定以FOS、EGR1、CXCL2和JUNB为核心特征基因。功能富集分析显示白细胞介素-17（IL-17）信号通路显著激活。单细胞测序验证FOS、EGR1、CXCL2和JUNB基因在IgAN特异性高表达，并通过Nephroseq数据库验证其与尿蛋白和估算的肾小球滤过率下降（eGFR）显著相关。结论  本研究揭示IBD与IgAN共享IL-17通路异常激活及FOS、EGR1、CXCL2和JUNB的基因网络，为开发基于肠－肾轴调控的靶向治疗策略提供理论依据。

       Objective  The complex interplay between immunoglobulin A nephropathy（IgAN）and inflammatory bowel disease（IBD）remains poorly understood．This  study  aimed to identify  key  cross-talk  genes  and  pivotal  signaling pathways shared between IBD and IgAN，thereby elucidating the molecular regulatory network underlying the gut-kidney axis．Methods  Transcriptomic datasets for IBD（GSE75214）and IgAN（GSE93798）were retrieved from the GEO database．Differentially expressed genes（DEGs）were screened，and shared DEGs were intersected．Protein-protein interaction（PPI）networks were constructed using STRING and Cytoscape，with topological algorithms applied to identify hub genes．Gene expression profiles were validated through（CTD，DISEASES and GeneCards）and single-cell RNA sequencing（GSE171314）and the Nephroseq database，focusing on clinical correlations with proteinuria and estimated glomerular filtration rate（eGFR）．Results  Seventeen shared DEGs were identified between IBD and IgAN．PPI network analysis revealed FOS，EGR1，CXCL2 and JUNB as core hub genes．Functional enrichment analysis demonstrated significant activation of the interleukin-17（IL-17）signaling pathway．Single-cell sequencing confirmed the specific upregulation of these genes in renal tubular epithelial cells of IgAN patients，which was further validated to correlate with proteinuria and eGFR decline．Conclusions  IBD and  IgAN share aberrant activation of the IL-17 pathway and a co-regulatory gene network involving FOS，EGR1，CXCL2 and JUNB，providing a theoretical foundation for developing therapeutic strategies centered on the gut-kidney axis．

       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 明确亚甲基四氢叶酸还原酶（MTHFR）C677T、A1298C基因多态性与成人患者使用大剂量甲氨蝶呤（MTX）治疗急性淋巴细胞白血病（ALL）毒性反应和24、48、72 h MTX血药浓度关系。方法 收集2014年6月—2020年6月就诊于新疆医科大学第一附属医院成人急性淋巴细胞白血病75例患者血样检测MTHFR C677T及A1298C基因多态性, 根据抗癌药物常见毒性反应分级标准对毒性反应进行分级,采用非条件Logistic回归分析MTHFR C677T、A1298C基因多态性与HD-MTX毒性反应及血药浓度的关系。结果 MTHFR 677TT型发生贫血风险显著高于CC型（P=0.027, OR=4.694, 95%CI：1.195~18.438）; 未发现MTHFR C677T与白细胞减少、血小板计数减少、中性粒细胞计数减少、淋巴粒细胞计数减少、骨髓抑制、谷丙转氨酶升高、谷草转氨酶升高、肝功能损伤、急性肾损伤及黏膜损伤、24 h、48 h及72 h MTX血药浓度有相关性（P>0.05）; 未发现MTHFR A1298C与HD-MTX毒性反应及血药浓度有相关性（P>0.05）。结论 MTHFR C677T基因多态性与成人急性淋巴细胞白血病患者大剂量MTX化学治疗后血液毒性存在相关性。

Objective To determine the relationship among C677T and A1298C gene polymorphisms of methyltetrahydrofolate reductase（MTHFR）and adult acute lymphocytic leukemia（ALL）, the relationship between the toxicity of high-dose methotrexate（HD-MTX）after chemotherapy and the MTX blood concentration of 24 h, 48 h and 72 h in patients with ALL．Methods Blood samples were collected from 75 adult patients with ALL who were treated at the First Affiliated Hospital of Xinjiang Medical University from June 2014 to June 2020．The samples were used to detect the genetic polymorphisms of MTHFR C677T and A1298C, and the toxic reactions were graded according to the common toxic reaction classification criteria of anti-cancer drugs．Unconditional Logistic regression was used to analyze the relationship between MTHFR C677T and A1298C gene polymorphisms and HD-MTX toxic reactions and blood drug concentration．Results The risk of anemia in MTHFR 677TT was significantly higher than that in CC type（P=0.027, OR=4.694, 95% CI：1.195-18.438）．No correlation was found between MTHFR C677T and leukopenia, thrombocytopenia, neutropenia, lymphogranulocytopenia, bone marrow suppression, elevated alanine aminotransferase, elevated aspartate aminotransferase, liver function injury, acute kidney injury and mucosal injury, 24 h, 48 h and 72 h MTX plasma concentrations（>0.05）．No correlation was found among MTHFR A1298C and HD-MTX toxicity and blood concentration（P>0.05）．Conclusions MTHFR C677T gene polymorphism is associated with hematotoxicity after HD-MTX chemotherapy in adult patients with ALL．

目的 探讨骨肉瘤（OS）和软组织肉瘤（STS）的关键核心基因（Hub基因）及其潜在作用,为肿瘤诊断和预后提供新依据。方法 从基因表达综合数据库（GEO）获得OS数据集GSE16088及STS数据集GSE21122,采用GEO2R在线工具筛选GSE16088和GSE21122数据集的差异表达基因（DEGs）。通过韦恩图获得2个数据集共同DEGs。选取2个数据集中差异表达最显著的上调和下调基因各20个,分别绘制聚类热图。通过使用注释、可视化和综合发现数据库（DAVID）对2个数据集的共同DEGs进行功能（GO）和通路（KEGG）富集分析。构建蛋白互作网络并使用最大中心度（MCC）算法筛选排名最前的10个基因作为潜在的关键Hub基因。采用受试者工作特征（ROC）曲线探讨关键Hub基因对肉瘤患者的诊断价值。通过Kaplan-Meier Plotter进行生存期分析。通过实时荧光定量PCR技术对得分靠前的5个Hub基因进行验证。结果 GSE16088数据集筛选出5 210个DEGs,其中上调和下调的DEGs分别为1 028、4 182个;GSE21122数据集共筛选出1 224个DEGs,其中上调和下调的DEGs分别为451、773个;2个数据集共获得498个共同DEGs。共同DEGs参与到多个生物学过程和信号通路。基于PPI网络和MCC算法最终获得10个关键Hub基因,ROC曲线验证结果符合预期,且生存期分析10个关键Hub基因与肉瘤预后显著相关（P<0.05）。Hub基因在mRNA表达水平和生物信息学分析结果一致（P<0.05）。结论 10个关键Hub基因可用于肉瘤的诊断和预后,为后续免疫治疗提供新视野。

Objective To explore the Hub genes of osteosarcoma（OS）and soft tissue sarcoma（STS）and their potential roles,and to provide evidence for tumor diagnosis and prognosis．Methods The GSE16088 dataset and the GSE21122 dataset were screened in the Gene Expression Omnibus database of the National Center for Biotechnology Information in the United States．The online editing tool GEO2R was used to screen the DEGs of the GSE16088 dataset and the GSE21122 dataset and the Veen map was drawn to find the common DEGs of the GSE16088 dataset and the GSE21122 dataset．20 up-regulated and 20 down-regulated genes with the most significant differential expression were selected from 2 datasets,and heatmaps were drawn for each．The Database for Annotation,Visualization and Integrated Discovery was used to perform GO function enrichment analysis and KEGG pathway enrichment analysis on DEGs of GSE16088 dataset and GSE21122 dataset．PPI network of DEGs was constructed by STRING．PPI sub-modules and Hub genes with high connectivity were screened．Maximal clique centrality（MCC）score was used to select the Hub genes in the protein interaction network．The predictive value of 10 Hub genes in sarcoma patients was analyzed by receiver operating characteristic（ROC）curve．Survival analysis was performed by means of the Kaplan-Meier Plotter．The top five core genes were verified by real-time fluorescence quantitative PCR．Results A total of 5 210 genes were screened in GSE16088 dataset,including 1 028 and 4 182 genes with upregulated and downregulated expression．A total of 1 224 genes were selected from the GSE21122 dataset,including 451 and 773 genes with upregulated and downregulated expression．The cluster heatmap was used to show the top 20 DEGs with high and low expression in GSE16088 and GSE21122 datasets．By differential analysis of gene expression between the two datasets,498 co-DEGs were obtained．GO and KEGG enrichment showed that common DEGs were associated．Ten Hub genes were obtained by PPI and MCC algorithm,the ROC curve verification results were as expected．Survival analysis showed that 10 Hub genes were significantly associated with the prognosis of sarcoma（P<0.05）．The mRNA expression level of Hub genes was the same as the results of bioinformatics analysis（P<0.05）．Conclusions The 10 Hub genes can be used for the diagnosis and prognosis of osteosarcoma,and provide a new vision for subsequent immunotherapy．

血友病是一种由于X染色体上凝血因子基因突变所致的遗传性出血性疾病,目前主要的治疗方法是凝血因子替代疗法。但长期频繁的注射用药往往导致患者依从性差,容易产生抑制性抗体,从而影响治疗效果。虽然现在延长半衰期的新型凝血因子药物、人源化双特异性抗体以及抗组织因子途径抑制剂单克隆抗体等用于疾病治疗,在给药方式和作用持续时间上已有很大进步,但它们仍无法治愈血友病。因此,以疾病根治为重要目标的基因治疗被设计出来,近年来受到了广泛的关注。该文介绍了血友病基因治疗的原理、基因治疗载体的选择、基因治疗预处理方案,总结了现阶段基因治疗临床应用的安全性和有效性;最后讨论基因治疗目前存在的问题以及未来发展方向。

Hemophilia is a genetic bleeding disorder resulting from mutations in coagulation factor genes on the X chromosome．The mainstay of current treatment is coagulation factor replacement therapy．However,frequent and long-term injections often lead to poor patient compliance,easy inhibitor development,and compromised therapeutic efficacy．Despite advancements in delivery methods and prolonged action of novel agents such as extended half-life coagulation factor concentrates,humanized bispecific antibodies,and anti-tissue factor pathway inhibitor monoclonal antibodies,these approaches still fall short of curing hemophilia．Consequently,gene therapy,aiming for disease eradication,has garnered significant attention in recent years．This review delves into the principles of gene therapy,the selection of gene therapy vectors,and gene therapy preconditioning regimens．It summarizes the safety and efficacy of gene therapy in current clinical applications and discusses challenges and future directions in this field．

目的 探讨男性人乳头瘤病毒（HPV）基因分型感染情况。方法 收集采用聚合酶链式反应反向斑点杂交法进行28种HPV基因分型检测的1 137例男性检查结果,进行回顾性分析。结果 1 137例男性患者中阳性441例,阳性率为38.79%,感染率居前5位的亚型依次为HPV6（11.35%）、HPV11（7.92%）、HPV16（5.10%）、HPV52（3.52%）、HPV43（2.64%）;就诊人群以20~39岁为主,感染人数也最多,各年龄组间阳性率比较差异无统计学意义（P>0.05）,≥50岁组HPV52型阳性率高于20~29岁组（P<0.05）和30~39岁组（P<0.05）。单一感染占67.35%,多重感染占32.65%,单一感染中低危型占比最多（41.27%）,多重感染中,二重感染占比最多（19.50%）,高低危混合感染为各种类型感染之首（15.87%）。结论 1 137例样本中HPV阳性率为38.79%,感染亚型以HPV6、HPV11、HPV16、HPV52、HPV43为主,单一低危型感染较为常见,各年龄组间阳性率相近。

Objective To investigate the genotypes of human papillomavirus（HPV）infection．Methods A total of 1 137 male patients’ diagnoses were collected and analyzed retrospectively,which came from the detections using polymerase chain reaction reverse dot blot hybridization to genotype 28 HPV．Results Among 1 137 male patients,441 were HPV positive,with a positive rate of 38.79%,the infections of top five HPV types were HPV6（11.35%）,HPV11（7.92%）,HPV16（5.10%）,HPV52（3.52%）,HPV43（2.64%）．The majority of the patients were the 20-39 age group,and the number of infections was also the highest．There was no statistical significance on the difference in the positive rate among different age groups（P>0.05）．The positive rate of HPV52 in ≥50 years old group was higher than the groups of aged 20~29（P<0.05）and 30~39（P<0.05）．The single and multiple infections accounted for 67.35% and 32.65%．The low-risk HPV accounted for the highest proportion（41.27%）in single infections,while in patients with multiple infections,the proportion of dual infections was the largest（19.50%）and the high- and low-risk HPV mixed infections was the maximum of the infection types（15.87%）．Conclusions The detection rate of positive HPV in 1 137 male patients was 38.79%,mainly were type 6,type 11,type 16,type 52 and type 43,and the single low-risk HPV infected was common．Positive rates were similar among different age groups．

目的 探讨唐氏综合征血清学筛查风险值异常孕妇选择接受无创产前基因检测（NIPT）的影响因素,为临床制定对应策略提供参考依据。方法 选取2022年1月—2022年12月唐氏综合征血清学筛查风险值异常孕妇229例,根据是否接受NIPT分为接受组（195例）与不接受组（34例）。收集两组临床资料,采用Lasso-Logistic回归分析唐氏综合征血清学筛查风险值异常孕妇接受NIPT的影响因素。结果 单因素分析显示,年龄、文化水平、居住地、家庭平均月收入、孕前优生优育检查、孕前合并生殖相关疾病、受孕方式、不良孕产史、家族史、补充叶酸、配偶意愿、NIPT认知水平、血清学风险等级是血清学筛查异常孕妇接受NIPT的影响因素（P<0.05）;Lasso回归分析筛选出7个变量,分别为年龄、文化水平、家庭平均月收入、不良孕产史、家族史、NIPT认知水平、血清学风险等级;Logistic回归分析,年龄（OR=6.269,95%CI：2.413~16.285）、文化水平（OR=4.119,95%CI：1.627~10.430）、家庭平均月收入（OR=5.102,95%CI：2.067~12.594）、不良孕产史（OR=5.247,95%CI：1.833~15.021）、家族史（OR=7.416,95%CI：2.952~18.629）、NIPT认知水平（OR=5.751,95%CI：2.338~14.146）、血清学风险等级（OR=7.866,95%CI：3.057~20.238）是血清学筛查异常孕妇接受NIPT的影响因素（P<0.05）。结论 唐氏综合征血清学筛查风险值异常孕妇选择接受NIPT的影响因素较多,包括年龄、文化水平、家庭平均月收入、不良孕产史、家族史、NIPT认知水平、血清学风险等级,能为临床提高NIPT接受度提供指导信息。

Objective To explore the influencing factors of noninvasive prenatal testing（NIPT）for pregnant women with abnormal risk value of serological screening for Down syndrome,and to provide reference for clinical development of corresponding strategies．Methods A total of 229 pregnant women with abnormal serological screening risk values for Down syndrome from January 2022 to December 2022 were selected and divided into acceptance group（195 cases）and non-acceptance group（34 cases）according to whether they received NIPT．The clinical data of the two groups were collected and Lasso-Logistic regression was used to analyze the factors influencing the acceptance of NIPT in pregnant women with abnormal serological screening risk value for Down syndrome．Results In single factor analysis,age,education level,place of residence,average monthly family income,pre-pregnancy and childbearing examination,pre-pregnancy combined with reproductive diseases,conception method,adverse pregnancy history,family history,folic acid supplementation,spouse intention,NIPT cognition level and serological risk grade were the influencing factors for the acceptance of NIPT in pregnant women with abnormal serological screening（P<0.05）．Seven variables were selected by Lasso regression analysis,which were age,education level,average monthly family income,adverse pregnancy history,family history,NIPT cognition level and serological risk level．Logistic regression analysis showed that age（OR=6.269,95%CI：2.413-16.285）,education level（OR=4.119,95%CI：1.627-10.430）,average monthly family income（OR=5.102,95%CI：2.067-12.594）,adverse pregnancy history（OR=5.247,95%CI：1.833-15.021）,family history（OR=7.416,95%CI：2.952-18.629）,NIPT cognitive level（OR=5.751,95%CI：2.338-14.146）and serological risk level（OR=7.866,95%CI：3.057-20.238）were independent influencing factors for NIPT acceptance in pregnant women with abnormal serological screening（P<0.05）．Conclusions There are many influencing factors for pregnant women with abnormal serological screening risk value to accept NIPT,including age,education level,average monthly family income,adverse pregnancy history,family history,NIPT cognition level,serological risk grade,etc．,which can provide guidance information for clinical improvement of NIPT acceptance．

目的 观察低氧对p53RFP基因表达及启动子活性的影响,探索低氧反应元件(HRE)是否参与了低氧对p53RFP基因启动子活性的调控。方法 将HEK293细胞置于低氧条件下培养,实时定量PCR及Western blot 检测p53RFP mRNA及蛋白表达水平;通过定点突变技术构建HRE突变型p53RFP启动子双荧光素酶报告基因载体并转染HEK293细胞,分别置于常氧和低氧条件下培养,双荧光素酶报告基因检测系统检测启动子活性。结果 低氧处理不同时间点p53RFP mRNA 表达水平均显著增加,差异有统计学意义(F=96.493,P<0.001);低氧组p53RFP 及HIF-1α蛋白表达量均呈时间依赖性递增。成功构建了HRE 突变型p53RFP 启动子双荧光素酶报告基因载体,双荧光素酶报告基因检测显示,与常氧组相比,低氧条件下野生型p53RFP基因启动子活性增加(t=-19.504,P<0.001),HRE单突变或双突变后启动子活性均较野生型降低(F=160.891,P<0.001)。结论 低氧可诱导p53RFP基因表达上调;成功构建了HRE 突变型p53RFP 双荧光素酶报告基因载体,HRE 位点可能在低氧调控p53RFP基因启动子活性中发挥关键作用。

Objective To investigate the effect of hypoxia on p53RFP gene expression and p53RFP promoter activity, and explore whether hypoxia responsive element (HRE) is involved in the regulation of p53RFP gene promoter activity by hypoxia. Methods HEK293 cells were cultured under normoxia and hypoxia conditions, p53RFP expressions at mRNA and protein levels were detected by real-time PCR and Western blot respectively. The HRE mutant p53RFP promoter dual luciferase reporter gene vector was constructed by site-directed mutagenesis technology and transfected into HEK293 cells under normoxia and hypoxia conditions. The promoter activities were detected by dual luciferase reporter system. Results Compared with the normoxia group, the expression of p53RFP mRNA in the hypoxia group increased significantly at different time points, and the difference was statistically significant(F=96.493,P<0.001); the expression of p53RFP and HIF-1α protein in the hypoxia group increased in a time-dependent manner. The luciferase reporter vectors containing p53RFP with mutant HRE were successfully constructed. The dual luciferase reporter gene assay showed that the activity of the wild-type p53RFP gene promoter was significantly increased under hypoxic conditions compared to normoxic condition(t=-19.504,P<0.001),and the promoter activity of p53RFP with HRE single mutation or double mutation were both significantly lower than that of wild type under hypoxic condition (F=160.891,P<0.001). Conclusions p53RFP gene expression was induced by hypoxia; the p53RFP promoter with mutant HRE dual luciferase reporter gene vectors were successfully constructed, and the HRE locus may play a key role in the hypoxia regulation of p53RFP gene promoter activity.