目的 通过生物信息分析途径,从分子水平揭示非酒精性脂肪性肝病（NAFLD）的发病发展机制,为NAFLD研究提供新的思路。方法 从公共数据库GEO中下载NAFLD相关的基因芯片数据GSE48452,利用Transcriptome Analysis Console软件筛选差异表达基因,FunRich软件和STRING在线分析工具对差异基因进行下一步的生物信息学分析。结果 正常组与NAFLD组差异基因52个,正常组与非酒精性脂肪性肝炎（NASH）基因64个,共同差异基因15个。这些差异表达基因参与脂质转运、胆汁酸合成、脂质和脂蛋白代谢、生物氧化等过程。通过通路分析及蛋白质相互作用分析进一步筛选出与NAFLD发病发展密切相关的18个差异表达基因。结论 通过生物信息学分析筛选出MSN、CDC45、ANXA5、PIK3CG和DTL基因可能为研究乃至阻断NAFLD发展进程的重要靶点,需进一步验证。

Objective To explore the molecular mechanism of nonalcoholic fatty liver disease （NAFLD） with bioinformatics analysis. Methods The microarray data of NAFLD were downloaded from the Gene Expression Omnibus （GEO） database and analyzed using Transcriptome Analysis Console （TAC） for screening differentially expressed genes. The further analysis of differentially expressed genes was conducted by FunRich software and the online tool STRING. Results For the comparison of control group vs. NAFLD group,52 genes have differentially expressed,while control groups vs. nonalcoholic steatohepatitis （NASH） group,64 genes have differentially expressed. 15 differentially expressed genes were found in both comparisons. These genes were involved in the biological pathway of lipid transport,bile acid biosynthesis,metabolism of lipids and lipoproteins and biological oxidations. With biological pathway analysis and protein-protein interaction analysis,18 differentially expressed genes were found closely associated with the progression of NAFLD. Conclusion MSN、CDC45、ANXA5、PIK3CG and DTL may be the important target for study the progression of NAFLD,which needs a further study to confirm.

目的 研究BAG-1基因与乳腺癌他莫昔芬(TAM)治疗敏感性的相关性。方法 以58例乳腺癌患者为观察组,50例乳腺良性肿瘤患者为对照组。予以观察组患者TAM治疗,检测并统计2组患者肿瘤组织BAG-1基因的阳性率;并根据检测结果将观察组患者分为BAG-1阳性组与阴性组,对比分析观察组BAG-1阳性者与阴性者的临床预后及血清肿瘤标志物水平,包括癌胚抗原(CEA)、糖类抗原153(CA153)。结果 观察组BAG-1基因阳性率为74.14%,对照组为12%,2组比较, P＜0.05。观察组BAG-1阳性组患者临床缓解率为46.51%,阴性组为66.67%,2组比较,P＜0.05;BAG-1阳性组患者临床控制率为67.44%,阴性组为86.67%,2组比较,P＜0.05。观察组BAG-1阳性组患者平均OS为(1.55±0.86)a,PFS为(1.02±0.31)a,阴性组依次为(2.76±0.95)a、(2.06±0.82)a,2组比较,差异均有统计学意义(P＜0.05)。治疗后,观察组BAG-1阴性组患者血清CEA、CA153指标值均低于对照组(P＜0.05)。结论 BAG-1基因与乳腺癌TAM治疗敏感性密切相关,BAG-1阳性者行TAM治疗的临床效果及预后均较阴性者差。

Objective To study the correlation between BAG-1 gene and the sensitivity of tamoxifen (TAM) in breast cancer. Methods 58 cases of breast cancer patients as the observation group, 50 cases of benign breast cancer patients as the control group.The positive rate of BAG-1 gene in two groups of patients was detected and statistically analyzed by TAM. The patients in the observation group were divided into BAG-1 positive group and negative group according to the test results, and the positive rate of BAG- (CEA), carbohydrate antigens 153 (CA153) and carcinoembryonic antigen (CEA). Results The positive rate of BAG-1 gene was 74.14% in the observation group and 12% in the control group, P<0.05. The clinical response rate of BAG-1 positive group was 46.51% and negative group was 66.67%, P<0.05; The clinical control rate of BAG-1 positive group was 67.44%, negative group was 86.67%. Compared 2 groups , it was P<0.05. The mean OS was (1.55±0.86) years, PFS was(1.02±0.31) years in the BAG-1 positive group and (2.76±0.95) years in the negative group and (2.06±0.82) years in the negative group, (P<0.05). After treatment, the serum CEA and CA153 values in the negative group of BAG-1 were lower than those in the control group (P<0.05). Conclusion BAG-1 gene and breast cancer TAM treatment sensitivity is closely related to BAG-1 positive TAM treatment of clinical efficacy and prognosis were worse than negative.

目的 研究EGFR基因突变与系列肿瘤标志物在160例原发性肺癌患者及51例肺部良性占位病变患者中的表达状况,为肺部占位病变的诊断、鉴别诊断和治疗提供参考依据。方法 160例肺癌患者取新鲜病理组织标本,采用扩增阻滞突变系统荧光PCR(ARMS-PCR)技术检测EGER基因突变;160例肺癌患者和51例良性占位病变患者取外周静脉血用化学发光法检测系列肿瘤标志物,用χ²检验统计分析数据。结果 160例肺癌病例中,EGFR基因野生型比率为47.56%(78/164),EGFR基因突变型比率为52.44%(86/164),突变型中21L858R点突变占23.17%(38/164),19Del缺失突变占22.56%(37/164)。肺癌组中系列肿瘤标志物较良性占位组具显著高表达,P＜0.01。差异有统计学意义。结论 肺癌致病与EGFR基因突变、肿瘤标志物高表达有显著正相关,通过肿瘤标志物和EGFR基因突变检测,结合影像学检查,将有助于肺部占位病变诊断和鉴别诊断,并为治疗手段选择提供参考依据。

Objective To research EGFR gene mutation and series of tumor markers expression in 160 patients with primary lung cancer and 51 patients with lung benign placeholder lesions, provide some references for the diagnosis, differential diagnosis and treatment in lung placeholder lesions. Methods We took fresh pathological tissue specimens from 160 cases of patients with lung cancer, Then used ARMS PCR technique to detect EGER gene mutations. We took the peripheral venous blood in 160 patients with lung cancer and 51 patients with lung benign placeholder lesions, with chemiluminescence method to detect series of tumor markers,and used thechi-square test to statistic and analysis data. Results In 160 cases of lung cancer patients,The EGFR gene wild type rate was 47.56%(78/164).The EGFR gene mutation type rate was 52.44%(86/164).In EGFR gene mutation type,The proportion of 21L858R mutation was 23.17%(38/164),19del mutation was 22.56%(37/164). Series of tumor markers had significantly higher expression in lung cancer group than in benign placeholder lesions group. P＜0.01.The difference was statistically significant. Conclusion Lung cancer pathogenesis and EGFR gene mutations, tumor markers high expression was significantly positive correlation. Through a series of tumor markers and EGFR mutation testing, combined with imaging examination, it will contribute to the diagnosis and differential diagnosis in lung placeholder lesions, and provide the basis for treatment.

目的 探讨原发性肉碱缺乏症的诊断与治疗方案,对2例原发性肉碱缺乏症患儿及其家系行SLC22A5基因检测,确定基因突变位点,为家系提供遗传疾病的咨询。方法 用串联质谱技术对1例疑似患儿进行游离肉碱及多种酰基肉碱检测,对游离肉碱降低的患儿行SLC22A5基因突变检测,确诊PCD,对其姐姐行上述检查。对2例确诊PCD患儿补充左旋肉碱治疗,随访11个月。并对其家系行SLC22A5基因检测。结果 2例确诊PCD患儿,1例为临床患儿,另1例为其姐姐,无明显临床表现。2例患儿均检测到基因突变。2例患儿血游离肉碱水平低于参考值,伴多种酰基肉碱显著降低,均给予补充左旋肉碱治疗,1例治疗2月后症状改善,另1例未曾未发病,血游离肉碱及其他酰基肉碱水平上升至正常。2例患儿SLC22A5 c.760C>T,(p.Arg254X)纯合,致病突变;患儿父母亲SLC22A5基因的c.760C位点检测,发现:均携带c.760C>T,(p.Arg254X)杂合突变。结论 应用串联质谱技术检测血游离肉碱、多种酰基肉碱水平及SLA22A5基因突变检测诊断了2例PCD,均补充左旋肉碱取得较好疗效。SLC22A5基因c.760C>T,(p.Arg254X)突变是本家系中患有PCD的致病突变,用错义突变和剪切改变的分析手段对SLC22A5基因的外显子编码区进行直接测序可为PCD家系提供遗传咨询。

Objective To explore the diagnosis and treatment of primary carnitine deficiency. To identify potential mutation of SLC22A5 gene in two children affected with primary carnitine deficiency and provide genetic counseling. Methods We measured the free camitine(Co)and acylcamitine levels in a suspected clinical inherited metabolic diseases by tandem mass spectrometry. The SLC22A5 gene mutations were tested to the children with low Co level and the diagnosis was made. Then, We measured the free camitine(Co)and acylcamitine levels and SLC22A5 gene mutations in her sister. The children with PCD were treated with carnitine and followed up for 11 months. The SLC22A5 gene was detected in their family. Results In two children affected with PCD, 1 case was clinical children, another case of their sister was no obvious clinical manifestations. Mutations were found in all of them.The average C0 level in patients was lower than the reference value,along with decreased level of different acylcamitines. Two cases were treated with earnitine. Their clinical symptoms reduced 2 months later. Another case had not been sick. The CO level and different acylcamitines level in the blood rose to normal. A homozygous mutation C. 760C>T (P. Arg254X)of the SLC22A5 gene was detected in the two cases.Heterozygous mutation C. 760C>T (P.Arg254X) was also found in other family members. Conclusion Two patients were diagnosed with PCD by the test levels of free carnitine and acylcarnitines in blood with tandem mass spectrometry,and gene mutation test. L-carnitine supplement had a good effect in treatment of the PCD patients.C.760C> T (P.Arg254X) mutations of the SLC22A5 gene is the deleterious mutations for PCD families, The analysis method of the wrong mutagenesis and shear changes which is used to directly sequence the exons codes of the SLC22A5 gene can provide genetic counseling for PCD families.

目的 探讨逍遥散治疗首发抑郁症的疗效与5-HT2A受体基因多态性的关联。方法 采用病例对照研究方法,以120例首发抑郁症患者(研究组)和120例正常人(对照组)为研究对象,研究组予逍遥散治疗,疗程8周。于治疗前后采用汉密顿抑郁量表评定。采用高温连接酶检测反应法(LDR)检测5-HT2A受体基因,分析其与抗抑郁药物疗效的关系。结果 5-HT2A受体基因(T102C)T／C基因型、C／C基因型频率及等位基因频率与对照组相比差异无统计学意义(P﹥0.05)。不同基因型的疗效无差异(P﹥0.05)。结论 5-HT2A受体基因(T102C)多态性与逍遥散治疗抑郁症的疗效无关联。

目的 了解中山市7家医院金黄色葡萄球菌感染的临床分布,并对耐药基因进行检测,为临床经验治疗金黄色葡萄球菌感染提供用药及分子生物学依据。方法 收集2015年1月—2015年6月中山市7家医院分离到的金黄色葡萄球菌,使用ATB半自动细菌鉴定及药敏分析仪(法国梅里埃)对分离到的菌株进行鉴定及药敏试验,使用PCR技术对耐甲氧西林金黄色葡萄球菌(MRSA)的耐药基因进行检测。结果 7家医院共分离到89株金黄色葡萄球菌,其中MRSA检出33株,检出率为37.1%。金黄色葡萄球菌主要来源于呼吸内科(32株,36.0%)、骨科(20株,22.5%),主要分离自痰(41株,46.1%),伤口分泌物(16株,18%),对万古霉素、替考拉宁、奎奴普丁/达福普丁、复方新诺明、左氧氟沙星、诺氟沙星具有较高敏感性,MRSA对常用抗菌药物耐药率高于甲氧西林敏感金黄色葡萄球菌。共有32株MRSA检出bla_mecA基因,检出率为97%。结论 MRSA耐药情况较为严峻,临床科室应根据微生物培养报告合理使用抗菌药物。bla_mecA基因在MRSA检出较高,是MRSA主要的耐药机制。

Objective To analyze clinical distribution of Staphylococcus aureus infections from 7 hospitals in Zhongshan city, as well as to provide basis of empirical treatment and molecular biology for Staphylococcus aureus infections. Methods Staphylococcus aureus were collected from January 2015 to June 2015 in Zhongshan city, and then the strains were identified and tested antibiotic susceptibility by using ATB semiautomatic analyzer(Merieux). Resistance gene of methicillin-resistant Staphylococcus aureus(MRSA) was detected by polymerase chain reaction. Results 89 strains of Staphylococcus aureus were isolated from 7 hospitals and with prevalence of 33 strains of MRSA. Of all strains, 32(36.0%) were isolated from respiratory medicine and 20(22.5%) from orthopedics. 41(46.1%) strains of Staphylococcus aureus were isolated from sputum and 16(18.0%) from wound secretion. 89 strains of Staphylococcus aureus had highly susceptibility to vancomycin, teicoplanin, quinupristin/dalfopristin, cotrimoxazole, levofloxacin, norfloxacin. Resistance rates to commonly used antimicrobial drugs of MRSA were significantly higher than methicillin-sensitive. A total of 32 MRSA were detected carrying bla_mecA gene with the detection rate of 97%. Conclusion Clinical departments should be based on microbial culture report for rational use of antibiotics because of MRSA with more serious drug resistance. The gene of bla_mecA is the main mechanism of resistance for MRSA.

目的 探讨单倍体亲缘异基因造血干细胞移植治疗重型再生障碍性贫血(SAA)的可行性。方法 对1例诊断SAA 4年余,先后经CsA治疗、脐血移植治疗均无效并反复输注红细胞、血小板的12岁男性患者进行单倍体亲缘异基因造血干细胞移植,供者为其胞兄,高分辨HLA基因型5/10相合,预处理方案为BU+CTX+ATG:BU 3.2 mg/kg×2 d,CTX 50 mg/kg×4 d,ATG 2.5 mg/kg×4 d。干细胞来源为G-CSF动员的骨髓+外周造血干细胞,共计输注单个核细胞(MNC)4.055×10⁸/kg(受者体重),CD 34 2.331×10⁶/kg。GVHD预防:-1 d采用与受者HLA部分相合的第三方脐带血细胞,术后联合应用环孢素A、短程氨甲碟呤、霉酚酸酯。结果 造血缓慢重建,术后22天(+22 d)ANC>0.5×10⁹/L,术后3月血小板脱离输注。+26天DNA指纹图全部表现为供者基因型。+40天血型转为供者型“O”型。+29 d出现急性移植物抗宿主病aGVHD(胃肠型,Ⅲ度),+31 d、+34 d及+42 d予巴利昔单抗20 mg静滴,+40 d、+44 d、+63 d输注间充质干细胞,患者急性GVHD逐渐控制。期间曾出现肺部感染、口腔黏膜炎及巨细胞病毒血症,经抗感染后可控制。现随访3年,血象正常稳定,Kamofsky评分100分。结论 单倍体亲缘异基因造血干细胞移植治疗SAA,对无相合供者(包括亲缘或非亲缘)且强效免疫抑制治疗失败的患者,可考虑进行,GVHD和感染为主要并发症,需根据患者病情采用相应措施。

Objective To investigate the feasibility of haploid genetic allogeneic hematopoietic stem cell transplantation in the treatment of severe aplastic anemia(SAA) in our hospital. Methods A 12-year-old patient with acquired SAA for 4 years showed no response to CsA and cord blood transplant treatment and was transfusion-dependent. Lacking an HLA-identical sibling donor, the patient was treated with HSCT from his brother 5/10 matched at the generic level. Theconditioning regimen was BU+CTX+ATG:BU 3.2 mg/kg×2 d,CTX 50 mg/kg×4 d,ATG 2.5 mg/kg×4 d. Stem cells were the source of G-CSF mobilization of bone marrow and peripheral blood stem cells, dose of stem cells infused: mononuclear cells (MNC) 4.055×10⁸/kg (body weight of subject), CD34 2.331×10⁶/kg. Prevention of GVHD: -1 d Third-party umbilical cord blood cells which were HLA partially matched were used. Postoperative joint use included cyclosporine A, short-course methotrexate, mycophenolate mofetil. Results Hematopoiesis was slowly rebuilding, 22 d after surgery (+22 d) ANC> 0.5×10⁹/L, after three months departing from transfusion of platelets. +26 d suggesting that the DNA fingerprints showed donor genotypes. +40 d into donor blood type “O” type. + 29 d occurred acute GVHD (GI type, Ⅲ degrees), + 31 d, + 34 d + 42 d infusion of basiliximab 20mg, + 40 d, + 44 d, + 63 d infusion of mesenchymal stem cells. Gradually acute GVHD was controlled in the patient, who had lung infections, oral mucositis and cytomegalovirus viremia, could be controlled with anti-infective. Now followed up for 3 years, hemogram change has been normal and stable. Kamofsky score was 100 points. Conclusion It may be considered to have haploid genetic allogeneic hematopoietic stem cell transplantation for treatment of SAA, for those patients who have non-matched donor (including relatives and non-relatives) and potent immunosuppressive therapy failure. GVHD and infection are major complications. Need to adopt appropriate measures in accordance with the patient's condition.

目的 探讨Foxp3-924(rs2232365)基因位点多态性与产后抑郁的相关性。方法 选取211例在越秀区光塔街社区卫生服务中心分娩的产妇进行回访研究,所有产妇均经PCR-SSP技术对Foxp3-924(rs2232365)基因位点分型。结果 对比产后抑郁组与对照组产妇Foxp3-924各种基因型频率,结果显示均无差异(P>0.05)。结论 产后抑郁和Foxp3-924(rs2232365)位点基因多态性无较大关联。

Objective To investigate the distribution of-924(rs2232365) genotypes and to explore the correlation between gene loci polymorphism and postpartum depression. Methods In puerpera in Yuexiu district Guangta street community health center, there were 211 cases of childbirth study visits, who were confirmed by PCR-SSP technique Foxp3-924 (rs2232365) gene locus genotyping. Results Compared postpartum depression group and control groupFoxp3-924 various genotypes, it showed no great difference (P> 0.05). Conclusion It has no greater relevance between postpartum depression and Foxp3-924 (rs2232365) polymorphism loci.

目的 对不同周龄的KO小鼠与WT小鼠进行悬尾实验进行观察,探讨KO小鼠与WT小鼠的行为差别。方法 采用健康的试验动物180只分两组:①KO组(4、6、8周龄,各周龄30只,雌雄各半,共90只)②WT组(4、6、8周龄,各周龄30只,雌雄各半,共90只);通过悬尾实验观察性别,年龄对不动时间的影响。结果 同龄KO雌性小鼠比雄性小鼠的静止时间差别不大;随着年龄增大,静止时间增长。 同龄同性别的KO鼠比WT鼠的不动时间长。P<0.05;同龄雄性小鼠比雌性小鼠的不动时间短; 随年龄增长各种系小鼠不动时间增长,KO鼠的不动时间比WT鼠长,P<0.05。结论 KO小鼠存在抑郁行为表型。

Objective To observe tail suspension test in Fmr1 gene knockout mice and to explore whether there are differences in mobility of KO and WT mice. Methods 180 test mice were divided into two groups: ① KO group (4,6,8 weeks old, each age group of mice is 30, male and female in half, a total of 90) ② WT group (4,6, 8 weeks old, each group of mice is 30, male and female on half, a total of 90). Through forced swimming test and tail suspension test to observe gender, age effect on immobility time. Results With the same age of the same sex,the KO mice's immobility time was longer than WT mice's. P<0.05. With the same age,the male mice's immobility time was shorter than female mice's. With the age increase, the immobility time of KO mice was longer than WT mice. P<0.05. Conclusion Fmr1 gene knockout mice have anxiety and depressive behavior.

目的 探讨CYP2C19不同基因分型对急性冠状动脉综合征(ACS)患者服用氯吡格雷后血小板聚集率的影响。方法 选取2015年1月—2016年3月入住心内科的ACS患者258例为研究对象。入院时及服用氯吡格雷三日后分别抽取静脉血检测血小板聚集率及CYP2C19基因型。结果 快代谢型组(extensive metabolisers, EM)和中代谢型组(intermediate metabolisers, IM)服药前后血小板最大聚集率分别为(58.76±15.45)% vs(35.17±10.26)%和(59.35±11.58)% vs(47.66±12.59)%(P<0.05), 而慢代谢型组(poor metabolisers, PM)的血小板最大聚集率无明显降低。快代谢型组的最大血小板聚集率的降低幅度比慢代谢型组大(23.58±12.39% vs 11.65±13.56%,P<0.05)。 共有33例(12.79%)患者为氯吡格雷抵抗, 其中快代谢型组中氯吡格雷抵抗者2例(1.67%), 中代谢型组中氯吡格雷抵抗者3例(2.80%), 慢代谢型组中氯吡格雷抵抗者28例(90.32%) (三组比较P=0.038)。结论 ACS患者CYP2C19基因分型与服用氯吡格雷后血小板最大聚集率有关,与氯吡格雷抵抗有关。

Objective To explore the relationship between platelet aggregation rate and CYP2C19 gene polymorphisms. Methods A total of 258 cases diagnosed as acute coronary syndrome (ACS) from January 2015 to March 2016. The platelet aggregation rate was tested before and 3 days after taking clopidogrel. CYP2C19 gene polymorphisms was tested by Gene chip hybridization technique. Results The platelet aggregation rate before and after taking clopidogrel was(58.76±15.45)% vs(35.17±10.26)% and(59.35±11.58)% vs(47.66±12.59)%(P<0.05)in EM group and IM group. But there was no change in PM group. The PM group were associated with a significant increase risk of clopidogrel resistance compared with EM group and IM group. Conclusion CYP2C19 gene polymorphisms influence the rate of platelet aggregation rate after taking clopidogrel and are associated with clopidogrel resistance in ACS patients.