Screening of Organophosphate Flame Retardants with Placentation-Disrupting Effects in Human Trophoblast Organoid Model and Characterization of Adverse Pregnancy Outcomes in Mice

Background: Abnormal placental development may result in adverse pregnancy outcomes and metabolic diseases in adulthood; however, it remains unknown whether and how xenobiotics affect human placentation.Objectives: This study aimed to screen and identify placentation-disrupting chemicals in commonly used organophosphate flame retardants (OPFRs) and, if identified, to investigate potential adverse effects on placentation in relation to adverse pregnancy outcomes and metabolic disorder in offspring in mice.Methods: We devised a high-throughput immunofluorescence screening assay based on human trophoblast organoids and used it to screen OPFRs that inhibit the proliferation of organoids. One identified chemical was assessed for its effects on placentation by evaluating villous cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts using immunofluorescence and a mitochondrial stress test after 2 d of exposure. A 10-d exposure study was further performed to observe the dynamic effect of the OPFR on the structure of the organoids. RNA-sequencing and western blotting experiments were performed to explore the associated pathways, and a potential binding protein was identified by immunoprecipitation and in vitro kinase activity assays. Animal studies were performed to determine whether the findings in organoids could be replicated in mice and to observe adverse pregnancy outcomes.Results: The proliferation of organoids exposed to three aryl-OPFRs was significantly lower than the proliferation of control organoids. Further analysis demonstrated that one such chemical, 2-ethylhexyl-diphenyl phosphate (EHDPP), disrupted placentation in organoids. Mechanistically, EHDPP interfered with insulin-like growth factor 1 receptor (IGF1R) to inhibit aerobic respiration. Mice exposed to EHDPP at a physiological human concentrations exhibited immature and mature placental disorders, which correlated with fetal growth restriction, implantation failure, stillbirth, and impaired glucose tolerance.Conclusions: The human trophoblast organoid model showed that the commonly used OPFRs disrupted placentation via IGF1R, indicating that its use may contribute to adverse pregnancy outcomes and metabolic disorders in offspring. https://doi.org/10.1289/{"type":"entrez-protein","attrs":{"text":"EHP10273","term_id":"372009658","term_text":"EHP10273"}}EHP10273     

三康胶囊对高原移居青年体力作业效率的影响

目的探讨在高原服用三康胶囊对移居青年体力作业效率的影响。方法对进驻海拔3 700 m 1年的10名青年在服药前和服药15d后分别用EGM-Ⅱ型踏车功量计做坐位踏车运动,初始负荷功率为50 W,每3 m in递增50 W,以60 r/m in连续踏车至200 W 3 m in后终止。用直线回归法计算每位受试者的PMC170,HR90w、功率200 W时的HR及SaO2,运动终止5 m in后恢复HR,按公式计算心功能指数。结果服药后各项检测指标较服药前均有非常显著性差异(P<0.01)。结论服用三康胶囊能明显提高高原移居青年的体力作业效率。     

海拔1400m某部官兵睡眠呼吸暂停低通气综合征患病率调查

目的调查某部官兵睡眠呼吸暂停低通气综合征(SAHS)的患病率,为进一步了解移居不同海拔高度不同时间人群的患病情况提供参照,并为制定该病的防治策略提供依据。方法采用整群抽样的方法对驻守海拔1 400 m的某部官兵进行睡眠问卷调查,根据打鼾程度及日间嗜睡评分保守估计人群SAHS患病率。结果在调查的348人中打鼾的发生率为39.08%,中度打鼾者占5.17%,无重度鼾症患者。吸烟和饮酒与打鼾程度相关。有高原接触史的被调查者打鼾发生率高于未曾上过高原者(χ2=7.122,P=0.028)。不同程度的打鼾患者,日间的嗜睡评分有显著性差异(F=3.689,P=0.013)。结论如果仅依据日间Epworth嗜睡量表(ESS)评分≥9分为标准,保守估计驻守海拔1 400 m某部官兵的SAHS患病率为4.02%,打鼾及SAHS是严重危害健康的疾病之一,但未引起人们的重视,需要搞好宣传教育工作。     

氟伐他汀对老年动脉粥样硬化所致肾动脉狭窄的临床疗效观察

目的观察氟伐他汀对老年肾动脉粥样硬化所致肾动脉狭窄(ARAS)的治疗作用及其抗炎机制。方法将在我院门诊及住院的54例老年ARAS患者,随机分为治疗组及对照组,对照组给予常规降压治疗,治疗组每晚加服氟伐他汀40 mg。比较两组治疗前及治疗后尿蛋白排泄率(UAER)、血肌酐(Scr)、C反应蛋白(CRP)及肾脏血管多普勒超声中肾动脉收缩期峰值速度(PSV)、肾动脉血流加速度时间(AT),肾动脉峰值流速与肾动脉开口处腹主动脉流速之比(RAR)等指标。结果观察期间,两组上述指标均呈下降趋势,治疗组UAER,PSV,AT,RAR下降较对照组明显(P<0.05,P<0.01),治疗组CRP下降明显(P<0.05,P<0.01),对照组CRP变化不明显(P>0.05)。而且在两组血脂正常的老年ARAS所致肾动脉狭窄的患者进行比较分析也得出类似结果。结论氟伐他汀因降低CRP的致炎效应而改善肾动脉狭窄,且不依赖氟伐他汀的降血脂作用。     

颈动脉粥样硬化病变在不同年龄段冠心病患者中的特点分析

目的:探讨冠状动脉粥样硬化性心脏病(冠心病)患者超声检测的颈动脉粥样硬化病变过程和年龄增长的关系.方法:根据年龄将116名冠心病患者分为5组:＜45岁为第1组,45～54岁为第2组,55～64岁为第3组,65～74岁为第4组,＞74岁为第5组,用高分辨率超声检测所有冠心病患者和11名正常对照者的颈动脉内径、IMT、斑块及其数量,计算动脉半径和IMT的比值(R/IMT).对不同年龄段冠心病患者及正常对照者的检测值进行比较.结果:除R/IMT外,冠心病患者颈动脉粥样硬化病变各指标与年龄呈直线相关,但相关程度均不高,其中IMT与年龄的相关程度明显低于无冠心病及主要危险因素者.IMT和斑块发生率呈线性相关(r=0.316).斑块发生率、斑块数、IMT和颈动脉内径在不同年龄段冠心病患者间差异显著,但R/IMT的差异仅有临界性统计学意义,两两比较结果:斑块发生率在第4组和1、2组间有显著差异,P值分别小于0.05和0.01;斑块数在1组和4、5组间有显著差异,P＜0.05,在2组和4、5组间也有显著差异,P＜0.01;IMT在1组和4、5组及2组和5组间均有显著差异,P＜0.05;颈动脉内径在4组和1、2、3组间均有显 著差异,P＜0.01;R/IMT仅在2组和5组间有显著差异,P＜0.05.结论:(1)冠心病患者超声检测的颈动脉粥样硬化病变与年龄增长有显著的相关性,但年龄增长的生理性影响较弱.(2)65岁左右颈动脉自身代偿能力可能达到最大.     

Observation on Adaptation of Respiratory Sensations to Added Inspiratory Resistance in Human

To elucidate the adaptation of respiratory sensation to added breathingresistance,changes of ventilation,breathing pattern,and perceived magnitude(PM)of respiratory sensation were observed in 11 healthy young male subjectswith inspiratory resistive loadings for 40,30,and 20 rain at rest and in light (200kg.m.rain~(-1)),and moderate(600 kg.m.rain~(-1))physical activities respectively.Themain results are as follows:(1)With inspiratory load lasting 30 and 20 rain inlight and moderate physical activities respeetively,VI_(max),VI,f,MV,Plmax.andWI increased,and TI and VTI decreased;but PETco_2 decreased apparently only atmoderate work rate due to the accompanying hyperventilation.(2)Adaptation ofrespiratory sensation occurs,if the intensity of the added inspiratory load does notexceed the“moderate”degree and for the physical load is lower than the“light”degree.     

甲状腺功能亢进对大鼠肝脾铁含量及血红素加氧酶1表达的影响

目的 通过检测甲状腺功能亢进(简称甲亢)时大鼠肝、睥组织铁含量和血红素加氧酶1(HO-1)的表达,探讨甲亢对大鼠机体铁代谢的影响.方法 将18只雌性SD大鼠分为甲亢4周组、甲亢8周组和对照组,每组6只.甲亢组灌胃给药优甲乐,对照组灌胃生理盐水.造模结束分别取各组大鼠肝、脾脏,用二氨基联苯胺增强的Perl's铁染色法检测肝、脾组织铁含量,用逆转录PCR技术检测大鼠肝、脾组织HO-1 mRNA的表达;利用Western blot和免疫组织化学染色法对大鼠肝、脾脏HG1表达进行分析.结果 甲亢模型4周、8周组大鼠的肝、脾组织铁染色均明显强于对照组,且甲亢8周组强于甲亢4组(P＜0.01);甲亢4周、8周组大鼠的肝、脾脏的HO-1 mRNA、蛋白表达均高于对照组,且甲亢8周组明显高于4周组,差异具有统计学意义(P＜0.01).结论 甲亢可引起肝、脾组织铁含量增加,HO-1表达增强.     

恶性肿瘤靶向给药的临床应用

恶性肿瘤靶向给药是指利用具有一定肿瘤靶向性的导向分子（载体）携带治疗肿瘤的药物,在肿瘤局部选择性杀伤肿瘤细胞（及转移的肿瘤细胞）,以避免药物的全身毒副作用,提高疗效的一种治疗方法．由于抗癌药物在杀伤肿瘤细胞的同时也杀伤正常细胞,增加了全身的毒副作用．因此,近几年来,对恶性肿瘤靶向治疗的研究突飞猛进,发展了人源性抗HER-2mAb、依西美坦、放射性核素、     

针刺治疗儿童自闭症疗效观察

目的观察针刺对儿童自闭症的疗效。方法以ABC量表作为观测指标，观察治疗前后的疗效变化。结果治疗后患者的临床表现明显改善，治疗前后ABC量表评分比较具有显着性差异（P〈0．01）。结论针刺治疗儿童自闭症是一种有效的治疗方法。     

实时荧光聚合酶链反应检测HBV基因型B～D方法的建立

目的建立实时荧光聚合酶链反应检测乙型肝炎病毒(HBV)基因型B～D方法并验证其准确性。方法比较GenBank中已发表的明确分型的143株HBV全序列，设计特异的组合引物探针，应用实时荧光聚合酶链反应HBV基因分型法对兰州地区128例慢性乙型肝炎患血清标本进行基因型B、C、D检测，并随机对检测的基因型各3株标本进行S基因测序验证。结果128例标本中B型检出率为20.3％(26／128)，C型71．9％(92／128)，D型7．8％(10／128)：18株HBV克隆标本S基因测序结果与本分型法完全一致。结论实时荧光聚合酶链反应HBV基因分型法能够简便、灵敏、快速、准确地鉴定HBV基因型，适宜用于HBV基因型的大规模临床和流行病学调查。