Sodium Valproate-lnduced Cardiovascular Abnormalities in the JchlCR Mouse Fetus

Sodium valproate was administered to Jcl:ICR mice in order to evaluate teratogenicity in the cardiovascular system. A single dose of 600mg/kg of sodium valproate was injected intraperitoneally on gestational day 6, 7, 8 or 9. On day 18 of gestation, dams were laparotomized to observe incidence and type of cardiovascular abnormality in live fetuses. Cardiovascular abnormalities were found most frequently in the group treated on day 7, being recognized in 86% of litters (19/22) and in 29% of live fetuses (70/238). Among these, there were 28 cases of transposition of the great arteries, 13 of double outlet right ventricle, 11 of endocardial cushion defect, 9 of ventricular septal defect, 5 of tricuspid atresia, and 4 of hypoplastic left heart syndrome.     

瑞德西韦对感染肠道病毒71型的人横纹肌瘤细胞和 ICR乳鼠的抗病毒活性

探讨瑞德西韦（RDV）在细胞与动物水平对肠道病毒71型（EV71）的抗病毒活性，并阐明其抗病毒作用机制。     

The Possibility of Using the ICR Mouse as an Animal Model to Assess Antimonkeypox Drug Efficacy

As a result of the conducted experimental studies on intranasal challenge of ICR mice, rabbits and miniature pigs (even in the maximum variant) with the doses of 4.0–5.5 lg PFU of monkeypox virus (MPXV), some clinical signs such as purulent conjunctivitis, blepharitis and ruffled fur were found only in mice. The 50% infective dose (_CID₅₀) of MPXV for these animals estimated by the presence of external clinical signs was 4.8 lg PFU, and _LID₅₀ estimated by the virus presence in the lungs of mice 7 days post‐infection taking into account its 10% application in the animal respiratory tract was 1.4 lg PFU. When studying the dynamics of MPXV propagation in mice challenged intranasally with 25 _LID₅₀ of MPXV, the maximum pathogen accumulation was revealed in nasal cavity, lungs and brain: 5.7 ± 0.1, 5.5 ± 0.1 and 5.3 ± 0.3 lg PFU/ml, respectively. The pathomorphological examination of these animals revealed the presence and replication of the pathogen in the traditional primary target cells for MPXV (mononuclear phagocyte system cells and respiratory tract epitheliocytes) as well as in some other types of cells (endothelial cells, reticular cells, connective tissue cells). Our use of these animals to assess the antiviral efficacy of some drugs demonstrated the agreement of the results (a significant positive effect of NIOCH‐14 and ST‐246) with those described in scientific literature, which opens up the prospects of using ICR mice as animal models for monkeypox to develop preventive antismallpox drugs.     

ICR小鼠卵母细胞通过旁分泌机制促进排卵关键过程

目的:利用国内医学研究常用ICR品系小鼠,在构建用于研究卵母细胞-卵丘细胞交互作用培养模型的基础上,研究卵母细胞及其产生的旁分泌因子生长分化因子9(GDF9)和骨形态发生蛋白15(BMP15)对排卵过程中的关键事件——卵丘扩展的调控作用?方法:通过显微手术制备摘除卵母细胞后的卵丘细胞复合体(OOX),并通过与卵母细胞共培养或GDF9和BMP15 处理研究卵母细胞及其特异释放的旁分泌因子对表皮生长因子(EGF)诱导卵丘扩展过程的调控?结果:成功构建了ICR小鼠OOX培养模型,发现卵母细胞及其释放的旁分泌因子GDF9和BMP15为EGF诱导卵丘扩展所必需?结论:ICR小鼠卵母细胞通过旁分泌机制促进排卵关键过程?     

微小膜壳绦虫感染对ICR小鼠小肠LY6A(Sca-1)及IFN-γ、STAT1表达的影响

目的 探讨微小膜壳绦虫感染ICR小鼠小肠组织中LY6A及IFN-γ、STAT1的表达情况。方法 采集微小膜壳绦虫成虫标本并收集虫卵制作悬液。将ICR小鼠随机分为对照组和实验组,实验组以定量1 000个/只虫卵灌胃感染,于感染后第2 d和第8 d按照编号处死小鼠获取小肠组织。采用HE染色进行小肠组织病理学观察,RT-PCR技术检测LY6A、IFN-γ和STAT1的mRNA相对表达量,免疫组织化学技术检测小肠中LY6A蛋白阳性细胞的表达,并用PRM技术对LY6A蛋白和STAT1蛋白进行相对丰度定量。结果 HE染色结果显示感染后第8 d在肠腔内发现成虫节片,并且虫体寄生处出现急性炎症反应。RT-PCR检测显示感染第2 d实验组LY6A(t=12.57,P<0.001)和STAT1(t=12.13,P<0.001)的mRNA相对表达量低于对照组,而IFN-γ的mRNA相对表达量高于对照组(t=7.78,P<0.01);感染后第8 d实验组LY6A(t=10.01,P<0.001)和STAT1(t=11.19,P<0.001)的mRNA相对表达量高于对照组;而IFN-γ的mRNA相对表达量低于对照组(t=26.47,P<0.001)。免疫组化结果显示感染后第2 d实验组LY6A阳性细胞百分比高于对照组(t=4.26,P<0.01),感染后第8 d实验组LY6A蛋白阳性细胞百分比高于对照组(t=8.18,P<0.001)。PRM检测结果显示感染后第2 d实验组LY6A蛋白相对表达量低于对照组(t=6.55,P<0.05),实验组STAT1蛋白与对照组相比无统计学差异,感染后第8 d实验组LY6A蛋白(t=4.95,P<0.05)和STAT1(t=2.91,P<0.05)蛋白的相对表达量均高于对照组。结论 微小膜壳绦虫感染ICR小鼠小肠后LY6A(Sca-1)的mRNA水平和蛋白水平在幼虫侵入早期呈低表达,成虫期呈高表达;IFN-γ对LY6A的表达不起主导作用,而STAT1可能对LY6A(Sca-1)的表达起诱导作用。     

弓形虫PRU株感染妊娠期小鼠动物模型的建立

目的：探讨建立弓形虫生殖毒性妊娠期小鼠动物模型的方法。方法：将妊娠期ICR小鼠随机分为孕早期感染组、孕晚期感染组及相应对照组,孕早期和孕晚期感染组小鼠再分别分为3小组,分别以灌胃方式感染弓形虫PRU株包囊10、20及40个,对照组灌胃生理盐水,观察各组小鼠不良妊娠结局及产仔数量。结果：弓形虫PRU株感染数量为10个包囊时,孕早期感染组孕鼠的死亡率为36.36%,出现阴道流血、流产、早产等现象,不良妊娠结局高达85.71%,与对照组比较差异有统计学意义（ P<0.05）;感染20包囊和40包囊时,孕早期感染组孕鼠的死亡率高达50%和100%;孕晚期感染组孕鼠在妊娠期发病不明显,产仔鼠数量较对照组减少,但差异无统计学意义（ P>0.05）;结论：用10个PRU株包囊灌胃能建立妊娠期弓形虫感染小鼠动物模型,为研究弓形虫PRU株所致生殖毒性奠定基础。     

A novel de novo point mutation of the OCT‐binding site in the IGF2/H19‐imprinting control region in a Beckwith–Wiedemann syndrome patient

The IGF2/H19‐imprinting control region (ICR1) functions as an insulator to methylation‐sensitive binding of CTCF protein, and regulates imprinted expression of IGF2 and H19 in a parental origin‐specific manner. ICR1 methylation defects cause abnormal expression of imprinted genes, leading to Beckwith–Wiedemann syndrome (BWS) or Silver–Russell syndrome (SRS). Not only ICR1 microdeletions involving the CTCF‐binding site, but also point mutations and a small deletion of the OCT‐binding site have been shown to trigger methylation defects in BWS. Here, mutational analysis of ICR1 in 11 BWS and 12 SRS patients with ICR1 methylation defects revealed a novel de novo point mutation of the OCT‐binding site on the maternal allele in one BWS patient. In BWS, all reported mutations and the small deletion of the OCT‐binding site, including our case, have occurred within repeat A2. These findings indicate that the OCT‐binding site is important for maintaining an unmethylated status of maternal ICR1 in early embryogenesis.     

Use of a triple antibiotic solution affects the healing process of intentionally delayed replanted teeth in mice

ObjectiveA mixture of ciprofloxacin, metronidazole, and minocycline (3Mix) has been reported to be effective against oral bacteria from carious and endodontic lesions in vitro and in vivo. The objective of this study was to establish an animal model using mice for the application of 3Mix following intentionally delayed tooth replantation and to investigate the effects of 3Mix on the healing process of dental pulp and periodontal tissues.MethodsUpper first molars of ICR mice were extracted, immersed in 3Mix solution at different concentrations for 5–60 min with or without the use of a transfer solution (phosphate buffer solution (PBS)), in addition to transfer solution alone, and subsequently repositioned in the sockets. Immunohistochemistry for nestin and Ki-67, histochemistry for TRAP, and TUNEL assay were performed to assess pulpal healing during days 7–21.ResultsIncreased apoptosis was observed in the PBS group at week 1, followed by cell proliferation at week 2, and tertiary dentin and/or bone-like tissue formation at week 3. In contrast, nestin-positive, newly differentiated, odontoblast-like cells began to align along the pulp–dentin border following the appearance of Ki-67- and TUNEL-positive cells during weeks 1–2 in the 3Mix groups, suggesting that pulpal healing was accelerated. Severe root ankylosis was observed exclusively in the 3Mix groups. Rinsing with PBS before replantation partially rescued the viability of the periodontal ligament, but pulpal healing was delayed.ConclusionsThe application of 3Mix promotes pulpal regeneration of intentionally delayed replanted teeth; however, its use may induce severe damage to periodontal tissues.     

4种疫苗引起小鼠异常毒性检查中腹膜刺激症状的原因探讨

目的:探讨4种疫苗引起小鼠异常毒性检查中腹膜刺激症状的原因。方法:按照2010年版《中国药典》(三部)"异常毒性检查法"项下规定,除阳性对照组(0.6%冰醋酸溶液)的给药剂量为每只0.2 ml外,其余组剂量均为每只0.5 ml,每组5只小鼠,给药方式为腹腔注射。分别进行甲型肝炎灭活疫苗(简称甲肝疫苗)、重组乙型肝炎疫苗(CHO细胞,简称乙肝疫苗)、流感病毒裂解疫苗(简称流感疫苗)、麻疹风疹联合减毒活疫苗(简称麻疹疫苗)、阴性对照(0.9%氯化钠注射液)、阳性对照的ICR小鼠异常毒性检查;甲肝疫苗、流感疫苗的ICR和昆明种小鼠异常毒性检查;甲肝疫苗、吸附前甲肝疫苗、吸附后甲肝疫苗、氢氧化铝佐剂、0.1%甲醛溶液、阳性对照、阴性对照的ICR小鼠异常毒性检查。观察出现腹膜刺激的动物数、出现时间、消失时间、其他异常表现以及7 d后体质量变化情况。结果:甲肝疫苗、乙肝疫苗和阳性对照均致3⁵只小鼠出现腹膜刺激,出现时间在15只小鼠出现腹膜刺激,出现时间在1¹5 min,消失时间除阳性对照外均在30 min内,麻疹疫苗和阴性对照均未引起腹膜刺激;甲肝疫苗和流感疫苗均致所有ICR和昆明种小鼠出现腹膜刺激,出现时间在115 min,消失时间除阳性对照外均在30 min内,麻疹疫苗和阴性对照均未引起腹膜刺激;甲肝疫苗和流感疫苗均致所有ICR和昆明种小鼠出现腹膜刺激,出现时间在1⁵ min,消失时间在85 min,消失时间在8¹0 min;甲肝疫苗、吸附后甲肝疫苗、氢氧化铝佐剂和阳性对照均致所有小鼠出现腹膜刺激,出现时间在110 min;甲肝疫苗、吸附后甲肝疫苗、氢氧化铝佐剂和阳性对照均致所有小鼠出现腹膜刺激,出现时间在1⁵ min,消失时间除阳性对照外均在12 min内,全部小鼠均无其他异常表现且体质量正常。结论:疫苗中的氢氧化铝佐剂可能是导致小鼠腹膜刺激症状出现的原因。     

特发性髁突吸收患者髁突形态特征的CBCT研究

目的:探讨特发性髁突吸收(ICR)患者髁突的三维形态特征.方法:选取符合ICR诊断的患者26例为实验组,无关节疾患的骨性Ⅰ类错(牙合)患者26例为对照组,对颞下颌关节(TMJ)行CBCT扫描,利用Mimics 17.0行三维重建,测量髁突大小及形态,并进行统计学分析.结果:实验组髁突体积、表面积变小(P＜0.01),前后径、内外径变短(P＜0.01),高度降低(P＜0.01),对照组及双侧发病组左右侧对比无明显差异(P＞0.05).结论:ICR患者髁突相比正常髁突,表现出三维方向上的形态改变,可用来评估ICR的进展、疗效及预后.