A benchmark dose study of prenatal exposure to di(2-ethylhexyl) phthalate and behavioral problems in children

IntroductionPrenatal exposure to di(2-ethylhexyl) phthalate (DEHP) has been reported to be associated with adverse effects on neurodevelopment that yield behavior syndromes in young children with an estimated median exposure lower than the currently recommended tolerable daily intake (TDI) and reference dose (RfD).ObjectivesOur aim was to derive the benchmark dose for prenatal exposure to DEHP for the neurodevelopmental health in children.MethodsA total of 122 mother-child pairs from the Taiwan Maternal and Infant Cohort Study were analyzed for the dose-response relationship between maternal exposure to DEHP and children's behavioral syndromes evaluated at 8 years (n = 122, 2009), 11 years (n = 96, 2012), and 14 years (n = 78, 2015) of age. We employed a multivariate regression model to assess the statistical associations between the estimated maternal average daily intake of DEHP and child's individual CBCL scores for boys and girls at each separate age, followed by a mixed model for all the children across three ages accounting for individual variations. We then employed structural equation models by combining the children's specific behavioral problem scores at different ages and obtained a simulated overall latent score in relation to maternal exposure. Based on the established dose-response relationship, we derived the benchmark dose (BMD) and the lower limit (BMDL).ResultsAssociations of maternal DEHP exposure (median 4.54$\mu g/kg\_bw/day$) with the Child Behavior Checklist (CBCL) scores were all significant, except for somatic complaints, adjusting for child's age, gender, IQ, and family income. The BMDL, given a benchmark response of 0.10 (0.05) and a background response of 0.05, was 6.01 (2.16) $\mu g/kg\_bw/day$for an integrated CBCL score.ConclusionsThe current TDI (RfD) of 50 (20) $\mu g/kg\_bw/day$ for DEHP might not protect pregnant women for their children from behavioral problems. There remains the lack of comparable toxicological data. Further investigations are needed.     

RPLU、FURL及PCNL治疗输尿管上段嵌顿性结石的疗效研究

目的探讨后腹腔镜切开取石术（retroperitoneal laparoscopic lithotomy，RPLU）、输尿管软镜碎石清石术（lithotripsy with flexible ureteroscope，FURL）及经皮肾镜碎石清石术（percutaneous nephrolithotomy，PCNL）种不同方法治疗输尿管上段嵌顿性结石的疗效，以明确直径大于1.5 cm的输尿管上段嵌顿性结石的最佳处理方案。 方法回顾性分析159例输尿管上段嵌顿性结石，收集其术前术中资料，按术式不同分为RPLU组56例、FURL组55例、PCNL组48例。对手术时间、术后住院时间、结石清除率、术后并发症等数据进行统计学分析。 结果FURL组手术时间和术后住院时间明显短于RPLU组和PCNL组，差异均有统计学意义（P＜0.05）。RPLU组术后3 d和术后1个月的结石清除率（100%，100%）稍高于FURL组（90.9%，94.5%）和PCNL组（93.8%，93.8%），3组患者术后无严重并发症出现，差异均无统计学意义（P＞0.05）。 结论3种不同手术方法治疗嵌顿性输尿管上段结石均安全有效，FURL组手术时间及住院时间更短，患者术后恢复更快，更具有优势。     

控制性低中心静脉压在原发性肝癌伴肝炎后肝硬化患者腹腔镜肝切除中的应用

背景与目的:在肝脏切除手术中采用控制性低中心静脉压(CLCVP)技术可有效减少肝断面出血,然而,低中心静脉压(CVP)所产生的相对低血压和潜在低灌注可能造成不良影响,这使其推广应用受到一定程度的限制。本研究探讨CLCVP技术在原发性肝癌伴肝炎后肝硬化患者腹腔镜肝切除手术中的应用效果和安全性。方法:回顾性分析2017年4月—2019年3月在安徽医科大学第一附属医院肝胆胰外科行全腹腔镜解剖性肝切除手术的44例原发性肝癌伴肝炎后肝硬化患者临床资料,所有患者均接受同一组医生手术,其中24例患者术中采用CLCVP技术(观察组),另外20例患者术中未采用CLCVP对照组(对照组),分析并比较两组术前、术中、术后的相关临床资料。结果:两组患者术前资料包括性别、年龄、BMI、Child分级、肝硬化程度、肝肾功能指标差异均无统计学意义(均P0.05)。两组手术均顺利完成,无围手术期死亡病例。观察组术中、术后均未见低CVP相关气栓、肝肾损伤等并发症。与对照组比较,观察组术中动脉收缩压、CVP明显降低,手术时间与肝门阻断时间明显缩短、术中出血和手术输血率明显降低,但术中乳酸指标明显升高(均P0.05)。两组的术后出血、感染、胸腔积液、胆汁漏的发生率以及肝肾功能指标、拔管时间、住院时间方面均无统计学差异(均P0.05),但观察组患者术后引流量多于对照组(P0.05);两组术后复发率亦无统计学差异(P0.05)。结论:在做好术前肝功能评估和术中密切观测患者灌注指标的前提下,CLCVP技术对肝炎后肝硬化患者腹腔镜肝切除手术是安全可靠的,虽然低CVP会使机体灌注减少,机体无氧代谢增强,乳酸含量增高,但对肝肾功能及肝癌的复发无明显影响,而且较低的CVP能够有效减少术中出血量和输血量,缩短手术时长和肝门阻断时间,降低长时间缺血缺氧对肝脏的打击。总之,在无严重心、肺、脑、肾基础疾病的肝炎后肝硬化患者腹腔镜肝切除手术中,CLCVP是一种值得推荐的控制肝断面出血技术。     

The key role of macrophage depolarization in the treatment of COPD with ergosterol both in vitro and in vivo

Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo. Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients.     

白藜芦醇治疗结直肠癌的机制研究进展

【摘要】白藜芦醇是一种天然的多酚化合物，有预防心血管疾病，预防衰老，抗炎，抗癌等作用。该文总结了近年来白藜芦醇作用于结直肠癌的机制的研究进展，为白藜芦醇的进一步研究提供依据。     

程序性细胞死亡蛋白配体1在结直肠癌免疫治疗中的研究进展

近年来,抗程序性细胞死亡蛋白1(PD-1)药物在转移性结直肠癌患者错配修复缺陷治疗中的成功使得该疾病的免疫治疗得以重视。然而,失配修复缺陷的结直肠癌患者仅占结肠癌患者的一部分。目前的研究重点是将免疫治疗应用到疾病的早期阶段,包括辅助一线治疗,以及检测免疫检查点抑制剂治疗的敏感性。然而,哪些患者能够从该免疫治疗中获益仍是值得商榷的问题,因为这类药物具有自身免疫毒性。PD-1的配体之一程序性细胞死亡蛋白配体1(PD-L1)作为一种检测生物标记物,其检测可以通过免疫组化来实现。但其免疫组化的检测存在一些混杂因素,包括应用不同的检测抗体、不同的免疫组化临界值、肿瘤组织的采集准备方式不同、处理过程的不同、原发与继发的活检标本、肿瘤源性或诱导的PD-L1表达,以及肿瘤与免疫细胞的染色等。目前的结果表明,免疫组化检测肿瘤过表达PD-L1的患者在接受抗PD-L1治疗时临床效果更理想,而有些低表达的肿瘤也对该治疗有所缓解,这使PD-L1的分析中存在复杂性。阐明宿主免疫系统与肿瘤微环境的机制则能够更好地解释针对PD-L1药物是否让患者受益。     

The effects of grape seed extract on glycemic control,serum lipoproteins,inflammation, and body weight: A systematic review and meta‐analysis of randomized controlled trials

The aim of this systematic review and meta‐analysis was to analyze the effects of grape seed extract (GSE) on glycemic control and serum lipoproteins, inflammation and body weight. Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until May 30, 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I‐square (I²) statistic. Data were pooled using a random‐effects model and weighted mean difference (WMD) was considered as the overall effect size. Fifty trials were included in this meta‐analysis. Pooling effect sizes from studies demonstrated a significant decrease in fasting plasma glucose (FPG) (WMD): ?2.01; 95% confidence interval (CI): ?3.14, ?0.86), total cholesterol (TC; WMD: ?6.03; 95% CI: ?9.71, ?2.35), low‐density lipoprotein (LDL) cholesterol (WMD: ?4.97; 95% CI: ?8.37, ?1.57), triglycerides (WMD: ?6.55; 95% CI: ?9.28, ?3.83), and C‐reactive protein (CRP) concentrations (WMD: ?0.81; 95% CI: ?1.25, ?0.38) following GSE therapy. Grape seed did not influence HbA1c, HDL cholesterol levels, and anthropometric measurements. This meta‐analysis demonstrated that GSE intake significantly reduced FPG, TC, LDL cholesterol, triglycerides, and CRP levels.