Simultaneous identification of multiple single genes and multi-gene prognostic signatures with higher efficacy in liver cancer has rarely been reported. Here, 1173 genes potentially related to the liver cancer prognosis were mined with Coremine, and the gene expression and survival data in 370 samples for overall survival (OS) and 319 samples for disease-free survival (DFS) were retrieved from The Cancer Genome Atlas. Numerous survival analyses results revealed that 39 genes and 28 genes significantly associated with DFS and OS in liver cancer, including 18 and 12 novel genes that have not been systematically reported in relation to the liver cancer prognosis, respectively. Next, totally 9139 three-gene combinations (including 816 constructed by 18 novel genes ) for predicting DFS and 3276 three-gene combinations (including 220 constructed by 12 novel genes ) for predicting OS were constructed based on the above genes, and the top 15 of these four parts three-gene combinations were selected and shown. Moreover, a huge difference between high and low expression group of these three-gene combination was detected, with median survival difference of DFS up to 65.01 months, and of OS up to 83.57 months. The high or low expression group of these three-gene combinations can predict the longest prognosis of DFS and OS is 71.91 months and 102.66 months, and the shortest is 6.24 months and 13.96 months. Quantitative real-time polymerase chain reaction and immunohistochemistry reconfirmed that three genes F2, GOT2, and TRPV1 contained in one of the above combinations, are significantly dysregulated in liver cancer tissues, low expression of F2, GOT2, and TRPV1 is associated with poor prognosis in liver cancer. Overall, we discovered a few novel single genes and multi-gene combinations biomarkers that are closely related to the long-term prognosis of liver cancer, and they can be potential therapeutic targets for liver cancer.

目的 探讨铅镉锰暴露及金属硫蛋白基因多态性与新生儿出生缺陷的关系,为出生缺陷的防治以及制定干预措施提供参考依据.方法 本研究采用巢式病例对照研究方法,从广西壮族人群出生队列中选取广西壮族人群聚居的平果、田东、德保、靖西、隆安等县的人民医院及妇幼保健院2015年9月-2018年4月期间纳入队列的孕妇作为研究对象.随访收集一般人口学资料、孕期产检资料、出生结局资料等.采用原子吸收分光光度计(石墨炉法)测定孕妇血浆中铅、镉、锰的含量,采用PCR-RFLP法检测金属硫蛋白基因单核苷酸多态性位点.采用多因素logistic回归模型分析孕妇血浆中铅、镉、锰暴露与金属硫蛋白基因多态性与出生缺陷的关系.结果 多因素logistic回归分析显示:孕妇血镉值升高(OR=1.93,95％CI:1.11～3.36,P＜0.05)、血锰值升高(OR=1.22,95％CI:1.12～1.34,P＜0.01)、携带MT-2Ars10636位点突变型基因型(OR=3.96,95％CI:1.02～15.39,P＜0.05)是出生缺陷发生的危险因素.金属暴露-基因多态性交互作用分析结果显示,孕妇锰暴露与MT-2A rs10636在出生缺陷发生中存在交互作用.结论 镉、锰高暴露、携带MT-2A rs10636位点突变型基因型可能是出生缺陷发生的危险因素.

目的 探讨TBX15基因在肝细胞癌中的表达及其启动子甲基化对细胞生物学行为的影响.方法 分别采用亚硫酸氢盐测序法(bisulfite sequencing PCR,BSP)和实时荧光定量PCR(qPCR)检测3种肝癌细胞系(HepG2、MHCC97H、SNU449)中TBX15基因启动子甲基化状态和表达水平,再将空白质粒、空载质粒pc3.1和TBX15过表达质粒转染肝癌SNU499细胞,通过CCK-8实验和流式细胞术检测各组肝癌细胞的增殖和凋亡情况.结果 3种肝癌细胞系中,TBX15基因在肝癌SNU449细胞中的启动子甲基化程度最高,甲基化率为89.5％,而TBX15 mRNA表达水平最低.TBX15过表达质粒组培养48 h后,肝癌SNU449细胞的增殖能力高于空载质粒组,差异有统计学意义(0.549±0.080 vs 0.457±0.506,P=0.015);TBX15过表达质粒组肝癌SNU449细胞的总凋亡比例高于空白质粒组,差异有统计学意义[(5.12±1.42)％vs(2.16±0.41)％,P=0.014].结论 启动子区异常甲基化可能是肝癌细胞TBX15基因失活的主要原因,且与肝癌恶性生物学行为密切相关.TBX15可能是预测肝癌发生发展的指标.

目的 了解壮族人群小于胎龄儿(small for gestational age,SGA)的流行情况,并探讨SGA的影响因素.方法 选择2016年1月～2018年1月在南宁市武鸣区人民医院及武鸣区妇幼保健院产检并分娩的孕妇共3 839例,收集所有研究对象基本信息和相关研究因素的资料,采用随机森林算法、x2检验和多因素Logistic回归对资料进行分析.结果 武鸣区壮族人群SGA发生率为9.6％(368/3 839),其中男婴的发生率为6.9％(142/2 049),女婴的发生率为12.6％(226/1 790).随机森林显示孕中期胎儿宫内生长受限(intrauterine growth retardation,IUGR)的重要性评分最高,孕周最低,并筛选了7个最重要的变量纳入多因素Logistic回归.多因素分析显示,初产妇、孕妇身高＜ 1.55 m、孕期增重不足及孕中期IUGR是SGA的危险因素;孕前BMI≥18.5 kg/m2及男婴则为SGA的保护因素.结论 南宁市壮族人群SGA的发生率较高,且受多因素影响,应及时评估胎儿生长发育情况,采取综合措施以减少SGA的发生.

目的 了解广西壮族人群低出生体重儿发生状况,探讨壮族孕妇孕早期肝功能指标对低出生体重儿的影响,为低出生体重儿防治提供参考依据. 方法 选取2015年12月-2017年8月在平果县妇幼保健院分娩且有完整孕检记录的壮族孕妇作为研究对象,共收集到2 943例壮族孕妇的一般人口学资料及相关孕期保健和妊娠结局资料.采用SPSS22.0统计软件进行数据分析处理,运用倾向性评分控制混杂偏倚,使用x2检验、t检验和多因素Logistic回归分析方法筛选低出生体重儿的影响因素. 结果 连续变量单因素分析显示,低出生体重儿组与正常体重组的母亲孕早期转氨酶比、总蛋白、球蛋白、白球比水平差异有统计学意义(P＜0.05);分类变量单因素分析结果显示,低出生体重儿组孕早期总蛋白正常率高于正常体重组,差异有统计学意义(P＜0.05);多因素Logistic回归分析显示,谷丙转氨酶水平升高(OR =1.06,95％ CI:1.01 ～1.11)、球蛋白水平升高(OR=1.15,95％CI:1.06～1.24)是新生儿低出生体重儿发生的可能危险因素. 结论 谷丙转氨酶水平升高、球蛋白水平升高是新生儿低出生体重儿发生的可能危险因素.

Objective: To investigate the association between the value of α-thalassemia minor and the outcomes in pregnant women. Methods: A total of 445 pregnant women with α-thalassemia minor were selected as thalassemia group in the Pingguo County Maternal and Child Health Hospital of Guangxi from January 2011 to December 2015, with ratio of 1∶4 healthy pregnant women was randomly recruited as non-thalassemia group. Clinical characteristics and pregnancy outcomes of the two groups were retrospectively analyzed using methods including t test, χ(2) test, and logistic regression model and ROC curve. Results: There were no significant differences noticed in factors as age, BMI, gestational age and educational level of the two groups. Hemoglobin of the thalassemia group was significantly lower than that of the non-thalassemia group (P<0.001). Differences on parity, ethnicities or occupation were statistically significant. Results from univariate analysis showed that the proportions of low birth weight, small for date infant and 1 min Apgar score<7 were higher in the thalassemia group, but the ratio of adverse pregnancy outcomes was comparable on parameters as preterm birth, stillbirth, macrosomia. Findings from the unconditional logistic regression showed that pregnancy complicated with α-thalassemia minor appeared a risk for both newborns with low birth weight (aOR=2.29, 95%CI: 1.32-3.95) and small for date infant (aOR= 2.11, 95%CI: 1.16-3.84). The ROC curve showed that α-thalassemia minor combined with multiple indicators presented a certain predictive value on neonatal birth weight. Conclusion: Pregnancy complicated with α-thalassemia minor was likely to increase the risk of birth weight loss in newborns, suggesting that prenatal care for pregnant women with thalassemia be strengthened, in order to reduce the incidence of adverse pregnancy outcomes.