目的 探究脐动脉血流动力学指标、血脂、促甲状腺激素(TSH)对妊娠期糖尿病患者分娩结局的影响研究。方法 选取我院2021年1月—2021年11月收治的妊娠期糖尿病患者138例,采用随机数字表法分为对照组和研究组,每组各69例。比较2组患者体内脐动脉血流动力学指标、血脂指标及TSH相关指标表达水平差异及妊娠结局,并通过多元线性回归分析探究脐动脉血流动力学指标、血脂指标、TSH等相关指标与妊娠期糖尿病患者不良妊娠结局的相关性。结果 研究组孕妇脐动脉峰值流速/舒张末期流速(S/D)、阻力指数(RI)、三酰甘油(TG)、低密度脂蛋白(LDL)、TSH水平高于对照组,游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)水平低于对照组(P<0.05);研究组孕妇巨大儿、剖宫产、新生儿低血糖发生率及新生儿体质量均高于对照组(P<0.05);多元线性回归方程显示:S/D、RI、TG、LDL、TSH水平变化均与不良妊娠结局存在相关性(R²=0.224,调整R²=0.201;F=9.504,P<0. 05),且影响顺序由大到小依次为 TG、TSH、RI、S/D、LDL。结论 妊娠期糖尿病孕妇体内的S/D、RI、TG、LDL、TSH水平异常可能会影响妊娠结局,临床可通过监测上述指标的变化,及时采取干预措施。

Objective To investigate the effects of umbilical artery hemodynamic indexes, blood lipids and thyroid stimulating hormone (TSH) on delivery outcomes in patients with gestational diabetes mellitus. Methods A total of 138 patients with gestational diabetes mellitus who were admitted to our hospital from January 2021 to November 2021 were selected and divided into a control group and a study group by random digital table, with 69 cases in each group. The differences in umbilical artery hemodynamic indexes, blood lipid indexes and TSH-related indexes and pregnancy outcomes were compared between the two groups, and multiple linear regression analysis was used to explore the relationship between umbilical artery hemodynamic indexes, blood lipid indexes, TSH, other related indexes and adverse pregnancy outcomes in patients with gestational diabetes mellitus. Results The systolic and diastolic peak volume ratio (S/D), resistive index (RI) of umbilical artery, triglyceride (TG), low density lipoprotein (LDL) and TSH in the study group were higher than those in the control group, while the levels of free triiodothyronine (FT3) and free thyroxine (FT4) were lower than those in the control group (P<0.05). The incidences of macrosomia, cesarean section, neonatal hypoglycemia and neonatal weight in study group were significantly higher than those in the control group (P<0.05). The multiple linear regression equation showed that the adverse pregnancy outcomes were correlated with changes of TG, TSH, RI, S/D, LDL levels (R²=0.224, adjusted R²=0.201; F=9.504, P<0.05), in descending order. Conclusions Abnormal levels of S/D, RI, TG, LDL, TSH and FT4 in pregnant women with gestational diabetes mellitus may affect the pregnancy outcomes. Clinical intervention measures can be taken by monitoring the changes of the above indicators.

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.

目的 探究长链非编码RNA SNHG12在乙肝病毒X蛋白(HBx)诱导肝癌发生过程中的作用。方法 把课题组构建的肝前体细胞14-19、EGFP-14-19、HBx-EGFP-14-19通过小鼠肝门静脉注射到体内;采用 qRT-PCR、Western blot 方法检测30 d,90 d,180 d,360 d小鼠肝脏组织及细胞模型中HBx、SNHG12以及下游调节基因的mRNA和蛋白表达情况;使用si-SNHG12干扰其表达,并通过CCK-8、划痕实验、transwell实验、流式细胞术观察其对体外表型影响;检测SNHG12及下游的 mRNA 和蛋白表达;HE染色观察小鼠肝组织切片。结果 qRT-PCR结果表明SNHG12、Notch1、Hes1在HBx-EGFP-14-19细胞及各时间段的小鼠肝组织中均上调(F=48.808,P<0.000 1;F=13.322,P<0.000 1);Western blot结果显示在HBx过表达细胞及动物模型中,受HBx诱导SNHG12表达升高后Notch1信号通路被激活,促凋亡因子Bax下调,抗凋亡因子Bcl-2上调,细胞周期因子CDK2和Cyclin E上调;抑制SNHG12表达后,qRT-PCR、Western blot实验结果显示SNHG12(t=22.746,P<0.000 1)及其上述基因表达均扭转,CCK-8实验显示细胞增殖受到明显抑制,流式细胞术检测显示细胞凋亡增多,划痕及transwell实验表明细胞迁移及侵袭减弱。结论 HBx通过上调SNHG12诱导Notch1表达,导致细胞增殖、周期和凋亡异常,从而促进肝癌的发生。

Objective In order to explore the role of long non-coding RNA SNHG12 in hepatitis B virus X protein (HBx) induced hepatocarcinogenesis. Methods The liver precursor cells 14-19, EGFP-14-19 and HBx-EGFP-14-19 constructed by the research group was injected into the body through the hepatic portal vein of KM mice; qRT-PCR and Western blot were used to detect the mRNA and protein expression of HBx, SNHG12 and downstream regulatory genes in liver tissues of 30 d, 90 d, 180 d and 360 d mice and cell models. Si-SNHG12 was used to interfere with SNHG12 expression in vitro, the mRNA and protein expression of SNHG12 and downstream genes were detected, and its effect on phenotype in vitro was observed by CCK-8, flow cytometry, scratch test and transwell test. HE staining was used to observe the liver sections of mice. Results qRT-PCR showed that SNHG12, Notch1 and Hes1 were up-regulated in HBx overexpression cells and mouse liver tissue at each time point (F=48.808,P<0.000 1;F=13.322,P<0.000 1); the results of Western blot showed that in HBx over-expressing cells and animal models, the expression of SNHG12 was increased induced by HBx, resulting in the activation of Notch1 signal pathway, the down regulation of pro-apoptotic factor Bax, anti-apoptotic factor Bcl-2, and the up-regulation of cell cycle factors CDK2, cyclin E. After inhibiting the expression of SNHG12, the results of qRT-PCR and Western blot showed that SNHG12 (t=22.746,P<0.000 1) and the above genes were inhibited; CCK-8 experiment showed that cell proliferation was significantly inhibited, flow cytometry showed that cell apoptosis increased, scratch experiment and transwell experiment showed that cell migration and invasion decreased. Conclusions HBx induced Notch1 expression by up regulating SNHG12, resulting in abnormal cell proliferation, cycle and apoptosis, so as to promote the occurrence of liver cancer.

临床研究中,我们会经常遇到多重检验的问题。当同时检验多个假设时,如何控制犯Ⅰ类错误的概率,保证结果的准确性,是研究者面对的首要问题。然而未对多重检验进行校正的文章比例仍较大。本文从简单的单个检验假设出发,回答为什么需要进行多重校正,何时进行多重校正,同时介绍总体错误率(FWER)和错误发现率(FDR)两种重要的错误率以及在此基础上的Bonferroni和Benjamini-Hochberg校正方法,从而避免因多重检验问题带来的混乱。

In clinical research, we often encounter the problem of multiple testing. When testing many hypotheses at the same time, how to control the type I error to ensure the accuracy of the results is the primary problem faced by researchers. However, the proportion of articles that didn't correct the multiple testing remains substantial. Starting with the simple hypothesis of a single test, this article provides an introduction to multiple testing issues, answers why and when multiple corrections are needed, introduces two important error rates which are family-wise error rate (FWER) and false discovery rate (FDR), and the Bonferroni and Benjamini-Hochberg correction methods based on them, thereby avoiding confusion caused by multiple testing.

近年来,由于抗生素的不合理使用,导致新型耐药性细菌不断出现,严重危害人类健康,迫使我们急需发现新型抗菌药物来对抗耐药性细菌引起的感染。FtsZ蛋白是细菌分裂的必需蛋白,在细菌分裂增殖过程中起着关键作用。当FtsZ的功能受到抑制时,细菌的分裂增殖亦会被抑制,最终导致细菌死亡。FtsZ蛋白是目前热门的抗菌新靶点之一。本文回顾了FtsZ蛋白的生物学功能,总结了以FtsZ为靶标的新型抗菌分子的研究进展。

Antibiotic-resistant bacterial infection has become epidemic all over the world. To overcome the drug resistance problem, antibacterial agents targeting at new binding sites become critical. FtsZ, a bacterial cell division protein, has become a new attractive target for antibacterial agents’ discovery because it is the most important and conserved protein in bacterial cell division. Cell division will be inhibited when the functions of FtsZ were disturbed. In this article, the biological functions of FtsZ have been reviewed, and recent advances in discovery of FtsZ inhibitors were summarized.

目的 探究多囊卵巢综合征不孕患者采用定经汤加减联合穴位埋线治疗的临床价值。方法 研究对象为我院2020年3月—2021年3月收治的90例多囊卵巢综合征不孕患者,并采取随机抽签法分为对照组和研究组,对照组枸橼酸氯米芬胶囊治疗,研究组采用定经汤加减联合穴位埋线法治疗。对比2组患者治疗效果。结果 对比2组患者激素水平,干预前,对照组患者睾酮素(T)、黄体生成激素(LH)、卵泡生成激素(FSH)水平与研究组差异不具有统计学意义(P>0.05);干预后,研究组在改善FSH、LH、T水平方面优于对照组(P<0.05);干预前,2组患者中医症状积分对比差异不具有统计学意义(P>0.05);干预后,研究组患者中医证候分析较对照组改善(P<0.05);对照组患者子宫内膜厚度、排卵率及妊娠率均低于研究组患者(P<0.05)。结论 定经汤加减联合穴位埋线能够有效改善多囊卵巢综合征不孕患者性激素水平,促进排卵、提高临床妊娠率,具备临床应用价值。

目的 本文主要分析乳腺癌患者应用蒽环类药物序贯曲妥珠单抗治疗对其心脏毒性的相关危险因素,并按照危险因素选择合适患者的治疗方案。方法 研究纳入了2019年6月—2022年6月在本院接受治疗的300例乳腺癌患者,患者接受蒽环类药物序贯曲妥珠单抗治疗,按照患者治疗期间是否发生心脏毒性进行分组,即为11例发生心脏毒性(观察组),289例患者未发生心脏毒性(对照组)。记录2组患者个人基础资料、肿瘤分期、病史、蒽环类药物以及联合化疗等因素,通过Logistic回归逐一对各项因素展开分析,了解相关危险因素。结果 在本次研究分析中,心脏毒性发生例数为11例,发生率为3.67%。其中289例患者未出现心脏毒性,患者用药后未出现相关反应。2组患者在联合放疗、高脂血症、蒽环类药物种类均有差异,差异有统计学意义(P<0.05)。结论 乳腺癌患者应用蒽环类药物序贯曲妥珠单抗后,发生心脏毒性的几率升高,其危险因素主要包括高脂血症史、应用表柔比星治疗以及左胸放疗史。

目的 探讨我国南方地区鲍曼不动杆菌流行株ST457毒力进化方向。方法 收集南方地区5家大型三甲医院2012年—2015年血和/或痰标本来源的鲍曼不动杆菌菌株,运用不同毒力实验,比较ST457与其他CC92流行克隆株与非流行克隆株的毒力差异。结果 ST457感染患者早期死亡率高;ST457菌株平均产生物膜能力低于ST195和ST208;83.3%的鲍曼不动杆菌临床分离菌株在血清的存活率大于60%,其中43.3%的菌株可在血清内快速繁殖,不同ST型组间、菌血症组和非菌血症组间无差异;不同ST型菌株竞争后,ST457未展现出竞争优势。结论 与传统CC92流行株相比,ST457毒力表型与传统的CC92流行株类似,提示CC92克隆株共进化能力。部分流行株短时间内在血清中快速繁殖,提示其条件致病后潜在的血流感染的能力。

Objective To investigate the virulence of the prevalent clone ST457 of Acinetobacter baumannii in Southern China. Methods Isolates from sputum and/or blood samples from 2012 to 2015 in 5 large differences between clonal complex 92(CC92) and non-CC92 were estimated by biofilm assay, competition assay and serum assay. Results Patients with ST457 infection had high early mortality. The average biofilm production of ST457 was significantly lower than that of ST195 and ST208. In serum assay, 83.3% isolates survived in the serum with over 60% survival rate, of which 43.3% strains reproduced in the serum, with no difference between STs or between bacteremia and non-bacteremia group. After competing with different ST strains, ST457 shows no competitive advantage. Conclusions ST457 had a similar virulence phenotype with the traditional prevalent CC92 clone, suggesting the co-evolutionary ability for CC92 clone. Some clinical isolates were survived in human serum, suggesting the potential capacity of bloodstream infection.

目的 对 2017—2021年护理岗位人员的职业倦怠相关领域文献中的研究热点进行分析,以期让相关研究人员和卫生行政管理人员更加全面了解护理人员的职业倦怠情况。方法 本文基于共词聚类的研究方法,将从CNKI数据库中获取的护理人员职业倦怠研究文献运用BICOMB、gcluto 2.0和VOSviewer软件进行热点分析。结果 共有1 218篇护理人员职业倦怠相关文献纳入研究,分布在199本期刊中,共有关键词1 495个,出现频次≥10的关键词共有78个。通过共词聚类分析,护理人员职业倦怠研究可归纳为4大聚类热点:巴林特小组改善护理人员职业倦怠、心理资本与护理人员职业倦怠中介作用、护理人员工作压力、心理弹性及社会支持与职业倦怠、护理人员职业倦怠现状、影响因素及应对方式等。 结论 研究揭示了我国护理人员职业倦怠研究领域的研究现状及热点。

Objective Through the analysis of the research hotspots in the literature about job burnout of nursing staff from 2017 to 2021, relevant researchers and health administrators were expected to have a more comprehensive understanding of job burnout of nursing staff. Methods Based on the research method of co-word clustering, this paper used BICOMB and gcluto 2.0 and VOSviewer software to analyze the literatures on nursing burnout obtained from CNKI database. Results A total of 1 218 nursing staff burnout related literatures were included in the study, distributed in 199 journals, with 1 495 high-frequency subject words, 78 words with frequency≥10 times. Through word clustering analysis, nurses' job burnout research can be summarized as four clustering hotspots: bahrain's team to improve nurses' job burnout, psychological capital and the intermediary role of nurses' job burnout, nurses work pressure, resilience and social support and job burnout, nurses' job burnout status, influencing factors and coping methods, etc. Conclusions This study reveals the current situation and hotspots of nursing staff burnout research in China.

目的 探讨血沉(ESR)对川崎病(KD)冠状动脉病变(CAL)的预测价值。方法 收集 2017 年 5 月— 2021 年 6 月收治入院的KD患儿的临床资料,分析ESR对KD患儿CAL发生的预测作用。结果 纳入272例KD患儿,70例KD患儿合并CAL,202例KD患儿无CAL。KD患儿的ESR升高。单因素分析提示CAL组的ESR低于非CAL组,差异有统计学意义(P＜0.05)。ROC曲线下的面积为0.586,提示ESR可作为CAL的预测因子(P＜0.05)。ESR预测川崎病冠脉病变发生的临界值为76.5 mm/h。二分类Logistic回归分析显示,ESR是KD患儿发生CAL的独立危险因素(P＜0.05),当ESR＜76.5 mm·h^-1时,KD患儿CAL发生风险增加 (OR=2.38,95% CI: 1.25~4.53)。结论 KD急性期的ESR水平可用于预测KD患儿CAL的发生,ESR＜76.5 mm·h^-1时,提示KD患儿可能会出现CAL。

Objective To investigate the predictive value of erythrocyte sedimentation rate (ESR) on coronary artery lesions (CAL) in Kawasaki disease (KD). Methods Clinical data of children with KD admitted to the hospital from May 2017 to June 2021 were collected to analyze the predictive value of ESR on the occurrence of CAL in children with KD. Results Of the 272 enrolled children with KD, 70 children with CAL and 202 children without CAL. ESR was significantly higher in children with KD. Univariate analysis suggested that ESR was lower in the CAL group than in the non-CAL group, and the difference was statistically significant (P<0.05). The area under the ROC curve was 0.586, suggesting that ESR could be a predictor of CAL (P<0.05). The critical value of ESR for predicting the occurrence of CAL in KD was 76.5 mm/h. Dichotomous Logistic regression analysis showed that ESR was an independent risk factor for the development of CAL in children with KD (P<0.05), and the risk of CAL in children with KD was significantly increased when ESR was<76.5 mm/h. (OR = 2.38, 95% CI: 1.25-4.53). Conclusions ESR levels in the acute phase of KD can be used to predict the development of CAL in children with KD, and ESR <76.5 mm/h suggests that children with KD may develop CAL.