目的 应用生物信息学的方法筛选参与星型胶质细胞瘤的预后生物标志物。方法 首先,下载GEO(gene expression omnibus,GEO)数据库中星型胶质细胞瘤的基因芯片数据,通过R语言将来自4个数据集的基因芯片数据进行合并,将合并后的194人来源的脑组织样本分为:星型胶质细胞瘤组和正常组。然后对原始基因芯片数据进行批次效应去除和标准化处理,并使用密度图和主成分分析监测处理前后的效果。利用R语言中的limma包对处理后的基因芯片数据进行差异表达分析,从而筛选得到星型胶质细胞瘤组和正常组中之间的差异表达基因(differentially expressed genes,DEGs)。接着对差异表达基因进行GO(gene ontology,GO)分析和KEGG(kyoto encyclopedia of genes and genomes,KEGG)分析,并对所有基因的表达矩阵进行GSEA(gene set enrichment analysis,GSEA)分析。通过STRING数据库构建差异表达基因的蛋白—蛋白相互作用网络(protein-protein interaction,PPI),通过Cytoscape中的cytoHubba插件筛选Hub基因。为了探索Hub基因在星型胶质细胞中的诊断价值和预后价值,我们下载TCGA(the cancer genome atlas,TCGA)数据库中的基因表达数据和临床预后资料,使用ROC曲线评价Hub基因的诊断价值,并对诊断价值较高的Hub基因进行COX回归,筛选HR值最有意义的基因进行总生存分析(overall survival,OS)。结果 通过limma包总共分析得到1 043个差异表达基因。GO分析结果表明差异表达基因主通过影响神经突触的功能而发挥作用。KEGG分析结果显示钙信号通路、cAMP信号通路、MAPK信号通路、PI3K-Akt信号通路、Rap1信号通路和Ras信号通路等通路等在星型胶质细胞瘤中发挥着重要的作用。GSEA富集分析结果主要富集于细胞因子-细胞因子受体相互作用、JAK-STAT信号通路、逆行内源性大麻素信号、神经活性配体-受体相互作用、GABA能突触和钙信号通路等通路。通过PPI网络总共分析得到ADCY1、ANXA1和PENK等20个Hub基因。通过对Hub基因的诊断价值和预后价值进行评价,发现SST在星型胶质细胞瘤既可作为诊断标志物,也可作为预后生物标志物。结论 我们通过生物信息学分析发现SST可作为星型胶质细胞的预后生物标志物,又预测了Rap1信号通路有可能成为星型胶质细胞分子机制中的新通路。

Objective To screen biomarkers involved in the prognosis of astrocytoma by bioinformatics. Methods Firstly,the gene chip data of astrocytoma in GEO database were downloaded. The gene chip data from four data sets were combined by R language. The combined 194 human brain samples were divided into astrocytoma group and normal group. Then,the original microarray data were processed by batch effect removal and standardization,and the effects before and after processing were monitored by density map and principal component analysis. The differentially expression genes (DEGs) between astrocytoma group and normal group were screened by using limma package of R language to analyze the differentially expression of the processed gene chip data. Then gene ontology(GO) analysis and Kyoto encyclopedia of genes and genes (KEGG) analysis were carried out for the differentially expressed genes,and gene set enrichment analysis (GSEA) was carried out for the expression matrix of all genes. The protein-protein interaction (PPI) network of differentially expressed genes was constructed by using string database,and the Hub gene was screened by using the cytohubba plug-in of Cytoscape. In order to explore the diagnostic value and prognostic value of Hub gene in astrocytes,we downloaded the gene expression data and clinical prognostic data in the Cancer Genome Atlas(TCGA) database,used ROC curve to evaluate the diagnostic value of hub gene,and Cox regression for Hub gene with high diagnostic value,and screen the most significant gene of HR value for overall survival(OS) analysis. Results A total of 1 043 differentially expressed genes were obtained by limma analysis. Go analysis showed that the differentially expressed genes played an important role by affecting the function of synapses. KEGG analysis showed that calcium signaling pathway,cAMP signaling pathway,MAPK signaling pathway,PI3K Akt signaling pathway,Rap1 signaling pathway and Ras signaling pathway played an important role in astrocytoma. The results of GSEA enrichment analysis were mainly enriched in cytokine cytokine receptor interaction,JAK-STAT signaling pathway,retrograde endogenous cannabinoid signaling,neuroactive ligand receptor interaction,GABAergic synapse and calcium signaling pathway. A total of 20 Hub genes such as ADCY1,ANXA1 and PINK were obtained by PPI network analysis. By evaluating the diagnostic and prognostic value of hub gene,we found that SST could be used as both a diagnostic marker and a prognostic biomarker in astrocytoma. Conclusion We found that SST could be used as a biomarker for the prognosis of astrocytes by bioinformatics analysis,and predicted that Rap1 signaling pathway may be a new pathway in the molecular mechanism of astrocytes.

目的 应用iTRAQ联合质谱技术筛选COPD大鼠肺组织差异表达蛋白。方法 20只雄性SD大鼠(200~220 g),随机分为对照组和模型组,每组10只,采用熏烟法建立COPD大鼠模型。观察大鼠肺组织病理学改变,测定肺功能,BALF白细胞数,肺组织总蛋白iTRAQ标记后质谱鉴定,用生物信息学方法分析蛋白表达变化。结果 与对照组相比,模型组大鼠支气管黏膜下肌层增厚,肺内可见大量炎性细胞浸润,肺功能降低,BALF白细胞数升高(均P<0.05)。质谱鉴定出4 916种蛋白,筛选出468个差异表达蛋白,其中285个表达上调,183个表达下调。筛选了上皮细胞粘着连接蛋白、fMLP、整合素等与COPD相关蛋白。结论 基于iTRAQ技术的蛋白质组学方法筛选出COPD大鼠差异表达蛋白,为进一步研究COPD的发生机制奠定了基础。

Objective iTRAQ and mass spectrometry were used to screen the differentially expressed proteins in the lung of COPD rats. Methods 20 male SD rats (200-220g)were randomly divided into control group and treatment group, with 10 rats in each group. COPD rat model was established by smoking. The lung function, the number of BALF leukocytes, the total protein iTRAQ in lung tissue were measured and identified by mass spectrometry. The differentially expressed proteins were identified by bioinformatic analysis. Results Compared with the control group, the submucous layer of bronchus in the model group was thickened, a large number of inflammatory cells were seen in the lung, the lung function was reduced, and the number of BALF leukocytes was increased. 4 916 proteins were identified by mass spectrometry, 468 differentially expressed proteins were screened, 285 of which were up-regulated and 183 down regulated. Among them, the important COPD related proteins were epithelial adhesion connexin, fMLP and integrins. Conclusion iTRAQ technology screened out the differentially expressed proteins of COPD rats, which laid the foundation for the further study of COPD mechanism

目的 筛选结直肠癌（CRC）差异性表达的长链非编码RNA（lncRNA）,并进行临床标本验证,研究其对结肠癌细胞HCT116功能的作用。方法 利用lncRNA PCR芯片对3对CRC组织和癌旁对照组织筛选差异性表达的lncRNA,确定候选研究lncRNA GAPLINC,RT-qPCR对21例临床样本进行验证其表达的差异性;同时构建GAPLINC表达质粒及其沉默体siRNA转染HCT116细胞,研究其对细胞凋亡、迁移及侵袭能力的影响。结果 lncRNA芯片实验结果提示CRC组织中存在大量的差异性表达的lncRNA,其中GAPLINC在CRC组织表达稳定增加,21例临床样本进一步验证了其在肿瘤组织中表达增加（P<0.05）;转染GAPLINC表达质粒后,HCT116细胞凋亡被抑制,同时其迁移及侵袭能力增强,转染siRNA抑制GAPLINC的表达后,则出现相反的结果。结论 利用lncRNA芯片可对CRC差异性表达lncRNA进行批量筛选,GAPLINC在CRC组织中表达稳定增加,具有促癌作用,在CRC发生发展中可能起着重要作用。

Objective To screen the differentiational expression of lncRNA in CRC tissue,confirm it in large simple of clinical specimens,and study its effects on human colorectal cells HCT116 cell line. Methods We screened the lncRNA which expressed differently in 3 CRC tissues and their pair-non carcinour tissues by lncRNA arrays;chose the over expressed lncRNA which played the potential role of oncogene for further researching,and tested the difference in 21 clinical specimens by RT-qPCR. We cultured the HCT166 cells,and then constructed expressed plasmids pcCDNA3.1-GAPLINC and synthesized GAPLINC siRNA,transfected the plasmids and siRNA into HCT116 cells;to study the changes of HCT116 cells behavior,the transwell assays were carried on;the changes of apoptosis of HCT116 cells were tested by flow cytometry. Results There existed many lncRNA which expressed differently between CRC tissues and normal control tissues by lncRNA arrays,there were 21 lncRNA down expressed,and 3 lncRNA up expressed;among these lncRNA,GAPLINC over expressed stably,and its high level of expression was approved in 21 clinical specimens by the test of RT-qPCR. We constructed the expressed plasmids pcCDNA3.1-GAPLINC and synthesizing GAPLINC siRNA successfully;after transfecting pcCDNA3.1-GAPLINC into HCT116 cells,the over expression of GAPLINC increased the migration and invasion of the HCT166 cells （P<0.05）,decreased the proportion of cell apoptosis （P <0.05）;by contraries,knocked down the expression of GAPLINC inhibited invasion and migration of HCT116 cells （P<0.05）,and promoted the apoptosis of the HCT116 cells （P <0.05）. Conclusion It could screen the different expression of lncRNA in large quantities by lncRNA arrays,and GAPLINC expressed highly and stably in CRC tissues. GAPLINC played a role of oncogene,which promoted the proliferation and invasion of CRC cells,and inhibited the apoptosis of CRC cells,which meant playing an important role in the carcinoma and development of CRC.

目的 探讨Graf法超声在6个月以内婴儿发育性髋关节异常筛查及随访中的应用价值。方法 选取我院2014年1月—2017年6月2 000例0～6个月婴儿(4 000个髋关节)为标本,采用Graf法超声检查进行筛查,检测发病率,并对部分髋关节异常的婴儿进行随访。结果 Ⅰ型髋关节3 572例(89.3%),Ⅱ型336例(8.4%),Ⅲ型92例(2.3%)。随访的272例发育性髋关节异常婴儿中,86例Ⅱ型转化为Ⅰ型,42例Ⅲ型转化为Ⅰ型,46例Ⅱa型转化为Ⅱb型,98例Ⅱ型无转化。结论 Graf法超声检查在婴儿髋关节异常筛查以及随访中有较高的使用价值。Graf法超声检查安全性好、有效率高,有助于发育性髋关节异常疾病的早期诊断及早期治疗。

目的 探究聚乙二醇筛查法在高泌乳血症诊断中的临床意义。方法 选取260例HP患者作为观察组以及80例健康体检者作为对照组。应用雅培I2000全自动化学发光检测仪对两组标本进行PRL浓度测定,并将标本进行PEG筛查法沉淀后再次进行PRL浓度测定,将所得数据进行对比。结果 观察组检出MP67例,检出率25.77%,对照组检出MP3例,检出率3.75%,二者差异有统计学意义(P＜0.05);HP组、MP组和对照组之间PEG沉淀前PRL浓度差异有统计学意义(P＜0.05),沉淀后HP组和MP组以及对照组差异有统计学意义(P＜0.05),MP组和对照组差异无统计学意义(P＞0.05);MP在HP引起的各种临床疾病中检出情况差异无统计学意义(P＞0.05)。结论 应用聚乙二醇筛查法对于排除MPRL对HP诊断的干扰具有可行性,对降低HP的误诊率有着重要的意义。

Objective To explore the clinical signification of polyethylene glycol screening method on the diagnosis of hyperprolactinemiat.Methods We selected 260 patients with hyperprolactinemia as observation group and 80 healthy individuals as control group. The two groups were measured with Abbott laboratories I2000 automatic chemiluminescence detector about the concentration of PRL. Then the groups were measured again after they were precipitated by the polyethylene glycol and the result data were analyzed.Results 78 cases of MP were checked out from the observation group and 3 cases were checked out from the control group. The proportion was 25.77% and 3.75% respectively, and the differences were statistically significant (P＜0.05). The difference of the concentration of PRL before precipitated by PEG among the HP group, the MP group and the control group were statistically significant (P＜0.05). After precipitating, the difference of the concentration of PRL between the HP group and the MP group were statistically significant (P＜0.05), as well as the HP group and the control group. However, there was no difference between the MP group and the control group (P＞0.05). The checking conditions of MP in some diseases caused by HP had no difference(P＞0.05).Conclusion The use of polyethylene glycol screening method is a practicable method to eliminate the interference of MPRL on the diagnosis in HP. It has significance reducing misdiagnosis rate of HP.

目的 了解新生儿先天性心脏病的患病情况,为制定和采取干预措施提供依据。方法 对2015年10月—2016年9月分娩的5 769名新生儿进行心脏彩超检查,根据筛查结果进行统计分析。结果 共筛查出182例新生儿先天性心脏病,患病率3.15%,先天性心脏病新生儿中女婴比例较高,差异边缘显著,早产儿比例较高,差异有统计学意义,产母年龄和正常组分布相近。先天性心脏病类型中室间隔缺损和房间隔缺损的构成比分别排第一位(48.90%)和第二位(38.46%),严重先天性心脏病仅占5.43%。结论 新生儿先心病的发病率较高,采用心脏彩超筛查可尽早发现先心病患儿,同时需做好先心病患儿的随访工作,及时进行干预。

Objective To investigate the prevalence of neonatal congenital heart diseases (CHD) and providing basis for integrating efficient interventions. Methods The color Doppler echocardiography screening were applied to 5 769 newborns from Oct 2015 to Sep 2016, and the data was collected and analyzed. Results 182 cases of neonatal CHD were detected, and the prevalence rate of neonatal CHD was 3.15%. The proportion of girls and premature infants in the newborns with CHD was significantly higher than normal newborns, but the age distribution of their mothers was similar. In the 182 CHD cases, ventricular septal defect(48.90%) and atrial septal defect(38.46%) accounted for the most, while the constituent ratio of severe CHD was only 5.43%. Conclusion The prevalence of neonatal CHD was relatively high, and the color Doppler echocardiography screening could find out neonatal CHD earlier. The follow-up examinations and interventions should be conducted in time.

目的 探讨妇科门诊宫颈癌高危人群采取阴道镜检查后配合宫颈细胞学检查对宫颈癌筛查价值。方法 选取2016年2月—2017年4月我院妇科门诊就诊合并宫颈癌高危患者387例为研究对象,所有患者均行阴道镜检查和宫颈细胞学检查,以最终病理检查为诊断“金标准”,探究阴道镜、宫颈细胞学检查在宫颈癌中筛查灵敏度、特异度及阳性符合率。结果 387例纳入研究宫颈癌高危患者,经病理诊断后明确诊断为宫颈癌51例,占13.18%。细胞学检查在宫颈癌中筛查灵敏度为72.55%,特异度为90.48%,阳性符合率为88.11%。阴道镜检查在宫颈癌中筛查灵敏度为50.98%,特异度为94.64%,阳性符合率为88.89%。宫颈癌筛查中,细胞学检查灵敏度高于阴道镜检查,特异度低于阴道镜检查(P＜0.05),两者检查阳性符合率比较差异无统计学意义(P＞0.05)。结论 妇科门诊宫颈癌高危患者宫颈筛查中,阴道镜筛查具有较高特异度,细胞学检查具有较高灵敏度,联合检查能提高筛查价值。

目的 探讨血清胃蛋白酶原在胃癌筛查中的价值。方法 用ELISA方法对1102名患者血清PG水平进行检测,并行内镜病理组织学检查,采用ROC曲线确定PG筛查胃癌的最佳界定值。结果 与对照组、萎缩性胃炎组、胃良性溃疡组相比,早期胃癌组、进展期胃癌组PGI、PGR下降(P＜0.05),进展期胃癌组PGI、PGR较早期胃癌组下降(P＜0.05)。与对照组相比,早期胃癌组、进展期胃癌组、胃良性溃疡组PGII升高(P＜0.05)。PGI及PGR在ROC曲线下面积为0.920和0.831,对胃癌的诊断价值较高。PGI≤71.50 μg/L或PGR≤4.50作为筛查标准时,对胃癌高危人群筛查的灵敏度为83.33%,特异度为82.25%。结论 血清PGI、PGR在不同胃部病变中的表达水平不一致,对胃癌的早期筛查和早期诊断具有重要价值。PGI≤71.50 μg/L或PGR≤4.50是东莞地区筛查胃癌较合适的界定值。

Objective To investigate the value of serum pepsinogen PG detection for screening of gastric cancer. Methods PG was detected by ELISA of 1102 people, gastrointestinal endoscopy and biopsy pathology were also carried on. Using ROC curve to establish the PG screening standard, and verified its' value at high risk population of gastric cancer. Results Compared with control group, atrophic gastritis group and benign gastric ulcer group, serum PGI and PGR in early gastric cancer group and advanced gastric cancer group decreased significantly(P＜0.05). Serum PGI and PGR in advanced gastric cancer group were lower than early gastric cancer group(P＜0.05). Serum PGII in early gastric cancer group, advanced gastric cancer group and benign gastric ulcer group were higher than control group(P＜0.05). The area under ROC curve of PGI and PGII was 0.920 and 0.831 respectively, both of them showed high value for the diagnosis of gastric cancer. Took PGI≤71.50μg/L or PGR≤4.50 as the diagnosis criteria, the sensitivity was 83.33% and specificity was 82.25% at high risk population of gastric cancer. Conclusion Serum PGI and PGR were inconsistent in different gastric disease, which showed high sensitivity and specificity in the screening of gastric cancer,and have important value in early screening and early diagnosis of gastric cancer. PGI≤71.50μg/L or PGR≤4.50 were established as the appropriate standard for PG screening.

目的 研究探讨南沙区宫颈癌HPV筛查的认知程度及干预工程的效果。方法 选取2014年7月—2015年6月通过随机抽样抽取的南沙区21～60岁的妇女1000例为研究对象,通过问卷对其宫颈癌认知情况进行调查,并且根据筛查结果进行有针对性的干预措施。结果 南沙区的妇女只有35%既往有按时定期进行宫颈癌的筛查,只有13%做过HPV的筛查。筛查的900例中,HPV感染率6.78%,其中CIN1级为0.78%,CIN2级为0.44%,CIN3级为0.33%,疑浸润癌为0.11%。结论 南沙区妇女对宫颈癌HPV筛查的认知程度较低,通过对育龄妇女实施HPV筛查及干预工程,能够针对不同人群给予有针对性的干预措施,对农村育龄妇女的宫颈癌早期诊断及预防具有积极的意义。

目的 了解惠州市早产儿视网膜病变的发病状况,并探讨相关危险因素。方法 回顾分析我院在2015年1月—2015年9月776例(1552只眼)早产儿和低体重儿的眼病筛查资料。结果 776例早产儿中,发现各期ROP共27例,检出率3.479%,其中包括1期11例(18只眼),2期11例(22只眼),3期2例(4只眼),AP-ROP3例(6只眼)。统计学分析显示,ROP组和无ROP组在出生胎龄、出生体重、吸氧史间比较,差异有统计学意义,提示早产、低出生体重与ROP的发生密切相关。结论 惠州地区ROP发病率3.479%,出生体重、出生胎龄、吸氧史及宫内缺氧、母体慢性高血压合并妊娠等孕期母体因素都是影响其发生的高危因素。

Objective To study the incidence of retinopathy of prematurity and to analyse the risk factors for ROP. Methods A retrospective analysis was conducted on 776 premature children from January 2015 to September 2015. Results In the 776 premature babies examinaion, 26 cases(54 eyes, 3.479%)developed ROP, including 11 cases (18 eyes) suffering from stage 1,11 cases (22 eyes) from stage 2,2 cases (4 eyes) from stage 3,3cases (6 eyes) from AP-ROP. The results of statistical analysis showed that gestational age, birth weight and oxygen therapy were significantly to ROP. Clinical analysis indicated that prematurity, low birth weight and oxygen therapy were closely related to the occurrence of ROP. Conclusion The incidence of ROP in Huizhou city is 3.479%. The gestational age, birth weight ,intrauterine hypoxia, and maternal prenatal factors such as chronic hypertension with pregnancy are the high risk factors of ROP.