BACKGROUND:Haemoglobin H (HbH) disease is caused by a disorder of α-globin synthesis, and it results in a wide range of clinical symptoms. M6A methylation modification may be one of the mechanisms of heterogeneity. Therefore, this article explored the role of methyltransferase like 16 (METTL16) in HbH disease. METHOD:The results of epigenetic transcriptome microarray were analysed and verified through bioinformatic methods and qRT-PCR, respectively. The overexpression or knock down of METTL16 in K562 cells was examined to determine its role in reactive oxygen species (ROS), cell cycle processes or iron overload. YTH domain family protein 3 (YTHDF3) was knocked down in K562 cells and K562 cells overexpressing METTL16 via siRNA to investigate its function. In addition, haemoglobin expression was detected through benzidine staining. qRT-PCR, WB, methylated RNA Immunoprecipitation (MeRIP) and (RNA Immunoprecipitation) RIP experiments were conducted to explore the mechanism of intermolecular interaction. RESULTS:METTL16, YTHDF3 and solute carrier family 5 member 3 (SLC5A3) mRNA and the methylation level of SLC5A3 mRNA were downregulated in HbH patients. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) mRNA expression was negatively correlated with HGB content among patients with HbH-CS disease. Overexpression of METTL16 increased ROS and intracellular iron contents in K562 cells, changed the K562 cell cycle, reduced hemin-induced haemoglobin synthesis, increased the expressions of SLC5A3 and HBG and increased SLC5A3 mRNA methylation levels. Knockdown of METTL16 reduced ROS and intracellular iron contents in K562 cells. Hemin treatment of K562 cells for more than 14 days reduced the protein expressions of METTL16 and SLC5A3 and SLC5A3 mRNA methylation levels. Knockdown of YTHDF3 rescued the intracellular iron content changes induced by the overexpression of METTL16. The RIP experiment revealed that SLC5A3 mRNA can be enriched by METTL16 antibody. CONCLUSION:METTL16 may affect the expression of SLC5A3 by changing its m6A modification level and regulating ROS synthesis, intracellular iron and cycle of red blood cells. Moreover, METTL16 possibly affects the expression of haemoglobin through IGF2BP3, which regulates the clinical phenotype of HbH disease.

目的:探究铁死亡关键基因在不明原因复发性流产(URSA)发生发展中的作用,初步确定潜在生物标志物.方法:从基因表达综合(GEO)数据库下载数据集GSE26787,利用GEO2R筛选差异表达基因(DEGs);从FerrDbV2数据库下载铁死亡相关基因;DEGs与铁死亡基因取交集获得URSA铁死亡相关基因;利用DAVID数据库对URSA铁死亡相关基因进行基因本体(GO)富集及京都基因与基因组百科全书(KEGG)通路分析;利用String数据库和Cytoscape软件分析蛋白互作网络,筛选Hub基因;采用实时荧光定量PCR(RT-qPCR)检测Hub基因在人工流产组及URSA组患者蜕膜组织中mRNA的表达水平.结果:共筛选出55个URSA铁死亡基因;GO功能富集提示URSA铁死亡相关基因主要在自噬调节、RNA聚合酶Ⅱ启动子转录正调控、膜的整体组分、酶及p53蛋白受体结合富集.KEGG通路分析显示URSA铁死亡基因富集最明显的为FoXO信号通路.采用String数据库及Cytoscape软件筛选出的URSA铁死亡关键基因分别为EGFR、SRC、KRAS、MDM2.RT-qPCR检测结果显示,EGFR、SRC、MDM2在URSA组中的表达均低于人工流产组(均P＜0.05);KRAS在URSA组和人工流产组中表达无统计学差异(P＞0.05).结论:铁死亡相关基因EGFR、SRC、MDM2可作为诊治URSA的潜在生物标志物.

Objective Although the mechanism underlying preeclampsia (PE) has been widely explored, the mechanisms related to senescence have not yet been fully revealed. Therefore, we investigated the role of the miR-494/longevity protein Sirtuin 1 (SIRT1) axis in PE.Methods Human placental tissue was obtained from severe preeclampsia (SPE) (n = 20) and gestational age-matched normotensive pregnancies (n = 20), and senescence-associated β-galactosidase (SAβG) and SIRT1 expression levels were measured. The TargetScan and miRDB databases predicted candidate miRNAs targeting SIRT1, and intersected with differentially expressed miRNAs in the GSE15789 dataset (p < 0.05, |log2FC|≥1.5). Subsequently, we showed that miRNA (miR)-494 expression was significantly elevated in SPE, revealing miR-494 as a candidate SIRT1-binding miRNA. A dual-luciferase assay confirmed the targeting relationship between miR-494 and SIRT1. The senescence phenotype, migration, cell viability, reactive oxygen species (ROS) production levels and inflammatory molecule expression levels were measured after miR-494 expression was altered. We conducted a rescue experiment using SIRT1 plasmids to further demonstrate the regulatory relationship.Results SIRT1 expression was lower(p < 0.01) and miR-494 expression was higher (p < 0.001) in SPE, and SaβG staining showed premature placental aging in SPE (p < 0.001). Dual-luciferase reporter assays revealed that miR-494 targeted SIRT1. Compared to control cells, HTR-8/SVneo cells with upregulation of miR-494 had remarkably downregulated SIRT1 expression (p < 0.001), more SAβG-positive cells (p < 0.001), cell cycle arrested (p < 0.05), and upregulated P21 and P16 expression (p < 0.01). miR-494 overexpression also decreased HTR-8/SVneo cell migration (p < 0.05) and ATP synthesis (p < 0.001), increased ROS levels (p < 0.001), and upregulated NLRP3 and IL-1β expression (p < 0.01). SIRT1-overexpressing plasmids partially reversed the effects of miR-494 overexpression in HTR-8/SVneo cells.Conclusion The miR-494/SIRT1 interaction plays a role in the mechanism of premature placental aging in PE patients.

The involvement of circRNAs in β-thalassemia and their actions on fetal hemoglobin (HbF) is unclear. Here, the circRNAs in β-thalassemia carriers with high HbF levels were comprehensively analyzed and compared with those of healthy individuals. Differential expression of 2183 circRNAs was observed and their correlations with hematological parameters were investigated. Down-regulated hsa-circRNA-100466 had a strong negative correlation with HbF and HbA2. Bioinformatics was employed to construct a hsa-circRNA-100466‑associated competing endogenous RNA (ceRNA) network to identify hub genes and associated miRNAs. The hsa-circRNA-100466▁miR-19b-3p▁SOX6 pathway was identified using both present and previously published data. The ceRNA network was verified by qRT-PCR analysis of β-thalassemia samples, RNA immunoprecipitation of K562 cell lysates, and dual-luciferase reporter analysis. qRT-PCR confirmed that hsa-circRNA-100466 and SOX6 were significantly down-regulated, while miR-19b-3p was up-regulated. Hsa-circRNA-100466, miR-19b-3p, and SOX6 were co-immunoprecipitated by anti-argonaute antibodies, indicating involvement with HbF induction. A further dual-luciferase reporter assay verified that miR-19b-3p interacted directly with hsa-circRNA-100466 and SOX6. Furthermore, spearman correlation coefficients revealed their significant correlations with HbF. In conclusion, a novel hsa-circRNA-100466▁miR-19b-3p▁SOX6 pathway was identified, providing insight into HbF induction and suggesting targets β-thalassemia treatment.

目的:探讨基于微信平台下的seminar教学法对妇产科见习课程学习效果的影响.选取我校2015级54名学生为实验组,51名学生为对照组,实验组采用基于微信平台下的seminar教学法,对照组采用传统教学法.从两组学生的测试成绩及调查问卷等方面比较两组的教学效果.结果:①实验组测试中分析题成绩及总成绩均高于对照组,但两组分析题成绩及总成绩均无统计学差异(P>0.05);②实验组学生对基于微信平台下的seminar教学法的各个项目满意度均达到80％及以上,总体教学满意度达到96％.

Background We designed a meta-analysis to evaluate the clinical significance and efficacy of circulating noncoding RNAs (ncRNAs) in the early prediction of preeclampsia. Methods PubMed, Embase and the Cochrane Library were used to search for literature. The combined prediction performance was evaluated by calculating the area under the summary receiver operator characteristic (SROC) curve. The potential sources of heterogeneity were analysed by meta-regression analysis and subgroup analysis. All statistical analyses and mapping were performed by RevMan 5.3 and Stata 12.0. Results A total of 41 studies from 14 articles, including 557 preeclampsia patients and 842 controls, were included in our meta-analysis. All studies collected blood before onset. NcRNAs in blood performed relatively well in predicting preeclampsia. The combined sensitivity was 0.71, the specificity was 0.84, and the area under the SROC curve (AUC) was 0.86. Peripheral blood mononuclear cell (PBMC) samples showed the best diagnostic accuracy. The combined AUC was 0.93. Combined detection was better than single detection, and miRNA was better than circRNA. The heterogeneity of the study was determined by sample size, lncRNA characteristics, lncRNA source and race. Conclusion Circulating ncRNAs can be valuable biomarkers used as candidates for noninvasive early predictive biomarkers of preeclampsia and have great clinical application prospects. The clinical value of ncRNAs needs to be tested by further multicentre, comprehensive and prospective studies, and the test criteria should be established.

目的:医学生培养中Seminar小组学习法的影响因素探讨.方法:选取广西医科大学2015级临床医学大四学生共143名,每10-13名同学成一小组,共分成12组,进行Seminar小组学习,学期结束进行问卷调查.统计分析调查问卷的可信度、主因子分析影响因素,比较各主因子间的相关性.结果:获有效问卷138份.总量表的Cronbach α系数﹥0. 7,达到内部一致性信度要求.主因子分析结果与问卷设计的课程影响因素吻合.五个因素归纳为:教师表现、Seminar内容、学生准备程度、团队互动和互联网,其中教师表现、Seminar内容与团队互动之间具有显著的相关性(p<0. 01).在互联网影响因素下的Seminar小组学习方法备受学生肯定.结论:优化医学专业Seminar小组学习法的影响因素可以提升课堂质量.

目的 研究双胎生长不一致和小于胎龄儿(SGA)的流行病学情况.方法 对2017年1月至2018年12月在该院出生的147对双胎临床特征进行回顾性分析,评估双胎生长不一致和双胎SGA的发病率及相关因素.结果 双胎生长不一致为23对(15.65％),纳入双胎生长不一致组.双胎生长一致组(124例,84.35％)和双胎生长不一致组的单绒毛膜和双绒毛膜比较,差异无统计学意义(P>0.05).高龄孕妇发生双胎生长不一致的概率升高,差异无统计学意义(P=0.102).妊娠高血压和胎盘异常是双胎生长不一致的高危因素.双胎生长不一致与双胎红细胞压积(HCT)不一致呈较弱的正相关(r2=0.103,P=0.000).按照双胎的不同胎龄体重百分位图标准进行评判,SGA为40例(13.61％).双胎生长不一致的小胎儿出生后发生SGA风险较高.结论 双胎生长不一致需要临床重点关注,其中小胎儿发生SGA相关的不良结局概率增加.建议选取适合双胎的不同胎龄体重百分位图用于临床保健工作.

目的 分析不同年龄层次孕妇双胎妊娠的母婴风险.方法 回顾性分析2012年6月至2017年12月在广西医科大学第一附属医院分娩的335例双胎妊娠孕妇的临床资料,分析不同年龄段的母婴结局.结果 (1)无论低龄组还是高龄组,辅助生殖技术双胎受孕率均占总数的一半以上,双绒毛膜双胎占90％以上,其中年龄大于或等于40岁的孕妇辅助生殖技术双胎受孕率迭100％.(2)高龄组(≥35岁)与低龄组(＜35岁)平均分娩孕周35周左右,高龄组在28+0～31+6周发生早产以及早产时间小于34周的孕妇比例升高,但与低龄组比较差异无统计学意义(P＞0.05).年龄大于或等于40岁的双胎妊娠孕妇发生早产时间小于34周者比例升高,28+0～31+6周分娩率、32+0～33+6周分娩率与35～39岁组、低龄组比较升高(P＜0.05),新生儿平均出生体质量偏低.(3)妊娠期糖尿病患病率高龄组较低龄组明显升高(P＜0.05).新生儿不均衡生长的发生率在高龄组中增加,而其他不良母婴结局与低龄组比较差异无统计学意义.结论 高龄双胎虽然是高危妊娠,但做好孕前、孕期保健,其围生期不良结局与低龄组相比并没有显著增加,母婴严重疾病的发生率很低,总体情况良好.

为了培养出21世纪医学高端人才,医学高等教育模式需要不断的改革."互联网+PBL"是当下一种创新学习模式,在妇产科临床教学中应用体现出以下优点:1、有效的形成师生互动协作;2、PBL课程设计个性化且更优质;3、使学习增加了趣味性和真实感;4、使老师更了解学生."互联网+PBL"教学模式应用于临床教学显著提高教学质量,值得推广.

<正>子痫前期是临床上常见的、严重危害母婴健康的妊娠期特有的疾病,其病因学及发病机制一直是产科领域研究的热点,目前发现子痫前期的发病机制与机体过度炎症反应相关。脂氧素(1ipoxins,LXs)被喻为"炎症刹车信号"。研究发现,LXs不仅对多种炎性细胞的功能和炎症相关基因的表

Objective: To investigate the expression and its significance of lipoxin A4 receptor( ALX-R) and5-lipoxygenase( 5-LOX) in placenta of patients with preeclampsia. Methods: Expression of ALX-R and 5-LOX mRNA was detected by RT-PCR in the placenta of 30 women with preeclampsia( including 10 cases of mild preeclampsia and 20 cases of severe preeclampsia) and control group( 20 cases),respectively. Results: ①The expression of ALX-R mRNA in placenta decreased significantly with disease severity. It was lower in severe preeclampsia than that in mild preeclampsia and control group( P0. 01). ②The expression of 5-LOX mRNA in placenta increased significantly with disease severity. It was higher in severe preeclampsia than that in mild preeclampsia and control group( P0. 05). Conclusions: ALX-R and 5-LOX in placenta may play an important role in the pathogenesis of preeclampsia.

Objective:The purpose of this study was to investigate the expression and its significance of an antiinflammatory lipid mediator,lipoxin A4(LXA4),and lipoxin A4 receptor(ALX-R) in placenta of patients with preeclampsia.Methods: ELISA was used to detect the expression of LXA4 in blood serum,immunohistochemistry and PCR were used to detect the expression of protein and mRNA for ALX-R in the placenta of 30 women with preeclampsia(including 10 cases of mild preeclampsia,and 20 cases of severe preeclampsia) and 20 normal full-term pregnant women,respectively.Results:(1) Levels of LXA4 in women with mild preeclampsia were high(P<0.05).There was no difference between normal pregnancy and severe preeclampsia(P>0.05).(2) The mRNA expressions of ALX-R was lower in women with preeclampsia than in control women(P<0.01),much less the expression has decreasing tendency with aggravation;(3) The expression of ALX-R protein was lower in women with preeclampsia than in control group(P<0.01).Conclusion: The abnormal expression of LXA4 and ALX-R in placenta may play an important role in the pathogenesis of preeclampsia.

Objective:To investigate the expression and its significance of lipoxin A4 receptor and the transcription factor NF-κB p65 in placenta of patients with preeclampsia.Methods:PCR and immunohistochemistry were used to detect the expression of mRNA and protein for ALX-R and NF-ΚB p65 in the placenta of 30 women with preeclampsia(including 10 cases of mild preeclampsia and 20 cases of severe preeclampsia) and 20 normal full-term pregnant women(control group),respectively.Results:(1)The expression of ALX-R mRNA in placenta was decreased significantly with disease severity,it was lower in severe preeclampsia placenta than in mild preeclampsia and control group(P<0.01) The expression of NF-ΚB p65 mRNA in placenta was increased significantly with disease severity,it was higher in severe preeclampsia placenta than in mild preeclampsia and control group(P<0.05).(2)The expression of ALX-R protein showed significant lower in placenta with preeclampsia than in control group(P<0.01),and the expression of NF-κB p65 protein showed significant higher in placenta with preeclampsia than in control group(P<0.01).(3)There was no significant correlated between the expression of ALX-R and NF-κB p65 mRNA and protein in placenta with severe preeclampsia and mild preeclampsia.There was negative correlated between with the expression of ALX-R and NF-κB p65 mRNA and protein in placenta with control group(P<0.05).Conclusion:The abnormal expressions of ALX-R and NF-κB p65 in placenta may play an important role in the pathogenesis of preeclampsia.