1504-siRNA对EphA3表达肿瘤细胞HCT116的抑制作用研究

目的研究原癌基因EphA3的小干扰RNA(small interfering RNA)1504-siRNA对高表达结肠癌细胞HCT116的增殖抑制作用。方法将1504-siRNA质粒用Vigofect转染试剂瞬时转染HCT116细胞,36～48 h后,收集蛋白,用Western印迹检测EphA3及AKT信号通路中的蛋白分子表达,收集细胞,进行噻唑蓝(MTT)实验、平板克隆形成实验和软琼脂克隆形成实验。结果 1504-siRNA能抑制HCT116细胞的EphA3蛋白水平,抑制其增殖、平板克隆和软琼脂克隆的形成,抑制pmTOR、p-c-Raf、pAKT、p-4ebp1等信号分子的表达。结论 1504-siRNA抑制HCT116细胞的增殖、存活能力和恶性程度,这可能是通过抑制AKT信号通路来实现,它有望作为肿瘤治疗的候选药物。     

Cbl suppresses B cell receptor-mediated phospholipase C (PLC)-gamma2 activation by regulating B cell linker protein-PLC-gamma2 binding

Accumulating evidence indicates that the Cbl protein plays a negative role in immune receptor signaling; however, the mode of Cbl action in B cell receptor (BCR) signaling still remains unclear. DT40 B cells deficient in Cbl showed enhanced BCR-mediated phospholipase C (PLC)-gamma2 activation, thereby leading to increased apoptosis. A possible explanation for the involvement of Cbl in PLC-gamma2 activation was provided by findings that Cbl interacts via its Src homology 2 (SH2) domain with B cell linker protein (BLNK) after BCR ligation. BLNK is a critical adaptor molecule for PLC-gamma2 tyrosine phosphorylation through its binding to the PLC-gamma2 SH2 domains. As a consequence of the interaction between Cbl and BLNK, the BCR-induced recruitment of PLC-gamma2 to BLNK and the subsequent PLC-gamma2 tyrosine phosphorylation were inhibited. Thus, our data suggest that Cbl negatively regulates the PLC-gamma2 pathway by inhibiting the association of PLC-gamma2 with BLNK.     

Pituitary hormones and the small bowel: effect of hypophysectomy on intestinal adaptation to small bowel resection in the rat*

Abstract. The influence of pituitary hormones on intestinal adaptation to small bowel resection was studied by examining jejunal and ileal structure and function in control and in sham-operated rats, and in animals with 50% proximal or distal resection which were divided into three main groups: normally-fed, hypophysectomized, and pair-fed. The pituitary was removed 2 weeks before intestinal surgery and gut structure and function were studied 4 weeks later. The effectiveness of hypophysectomy was confirmed by histological examination of the aspirated pituitary, and by showing a significant subsequent reduction in weight of the testes and adrenals. Food intake and body weight fell significantly after removing the pituitary; intestinal surgery caused a transient further decrease in food intake. Measurements of intestinal villus height and crypt depth, indices of mucosal mass (mucosal wet weight, protein and DNA content/cm intestine), measurements of mucosal a-glucosidase activity, and in vivo galactose absorption/unit length of intestine all showed comparable results. In rats with an intact intestine, resection resulted in mucosal hyperplasia and increased segmental absorption. Following hypophysectomy, there was marked mucosal hypoplasia and hypofunction which seemed to be due largely to associated hypophagia since comparable changes were found in the pair-fed, sham-operated rats. However following pituitary removal, both distal jejunum and proximal ileum retained their capacity to regenerate though the magnitude of this adaptive change was much greater in the resected, pair-fed rats suggesting that hypophagia alone cannot explain the diminished adaptation to resection after hypophysectomy. By inference, pituitary hormones do influence the adaptive response to resection.     

Factors influencing extrauterine growth retardation in singleton-non-small for gestational age infants in China: A prospective multicenter study

BackgroundThe incidence of extrauterine growth retardation (EUGR) varies considerably in different countries due to the distinct definitions and inclusion criteria of individual studies. Most studies included small for gestational age (SGA) very preterm infants (VPIs), resulting in a higher incidence of EUGR. Experts have suggested the accurate definition of “EUGR” in SGA infants is not “true EUGR”. The postnatal growth curve of multiple premature births also differs from that of singletons. As far as we know, there is no study about relationship between singleton-non-SGA preterm infants and EUGR.ObjectivesTo analyze the factors influencing EUGR among VPIs who were singleton-non-SGA in China.MethodsA prospective-multicenter study was conducted in 28 hospitals distributed through China from September 2019 to December 2020. The clinical data on singleton-non-SGA among VPIs were divided into EUGR group (n = 692) and non-EUGR group (n = 912).ResultsCompared to non-EUGR group, the mean gestational age (GA), mean birth weight (BW) and percentage of BW in Fenton curve in EUGR group were lower (P < 0.001 for all). The incidence of EUGR among distinct GA groups (classifications of GA < 28weeks, 28–28⁺⁶ weeks, 29–29⁺⁶ weeks, 30–30⁺⁶ weeks and 31–31⁺⁶ weeks) and distinct BW groups (classifications of BW<1000 g, 1000–1249 g, 1250–1499 g, 1500–1999g and 2000–2500 g) were statistically significant (P = 0.004 and P <.001). Logistic regression analysis indicated that later addition of human milk fortifier (HMF), later attainment of HMF sufficient fortification, later return to BW, more accumulative days of fasting, longer duration of parenteral nutrition, total duration of oxygen support and moderate/severe bronchopulmonary dysplasia (BPD) were risk factors for the development of EUGR in singleton-non-SGA VPIs (P < 0.001, P = 0.002, P < 0.001, P = 0.002, P = 0.017, P = 0.003 and P = 0.002, respectively). The use of full-course antenatal steroids, greater BW as a percentile of the Fenton curve, breastfeeding initiation and faster average velocity of weight growth effectively protected against EUGR (P = 0.008, P < 0.001, P < 0.001 and P < 0.001, respectively).ConclusionsThe overall incidence of EUGR was 43.1% among singleton-non-SGA VPIs in China. Raising the full-course antenatal steroids usage, reducing the incidence of moderate and severe BPD, attaching importance to the management of enteral nutrition in VPIs and increasing the weight growth velocity can reduce the incidence of EUGR.     

Clinical features of coeliac disease

Aim of this review is to describe the extremely variable clinical presentation of coeliac disease. Moreover due to these varying manifestations, "coeliac literature" is characterised by a very rich terminology, which has not been unified, so far To help readers, not familiar with that terminology, we have given an explanation for the most common coeliac terms.     

不同术式治疗小度数集合不足型间歇性外斜视疗效分析

目的探讨不同的手术方式对于小度数集合不足型间歇性外斜视的治疗效果。方法收集2007年1月~2014年2月在我院就诊、符合小度数集合不足型间歇性外斜视诊断的患者158例,根据所行手术方式不同分为三组。其中单眼外直肌后徙术组44例,单眼内直肌缩短术组63例,单眼少量外直肌后徙联合内直肌缩短术组51例。术后随访6~12个月观察眼位及双眼视功能恢复情况。结果三种手术方式术后远期正位率的比较:单眼少量外直肌后徙联合内直肌缩短术组,术后正位率优于单眼外直肌后徙组,χ~2=15.587,P=0.001,差异有统计学意义(P0.05);优于单眼内直肌缩短术组,χ~2=13.063,P=0.001,差异有统计学意义。术后双眼视功能恢复比较:单眼少量外直肌后徙联合内直肌缩短术组,术后视功能恢复优于单眼外直肌后徙组,χ~2=9.633,P=0.022,差异有统计学意义;优于单眼内直肌缩短术组,χ~2=10.270,P=0.016,差异有统计学意义。结论对于小度数集合不足型外斜视的患者手术宜选择单眼少量外直肌退后联合内直肌缩短,有助于改善集合功能,稳定眼位。可以作为治疗小度数集合不足型外斜视的首选术式。     

Antitumor activity of an anti‐CD98 antibody

CD98 is expressed on several tissue types and specifically upregulated on fast‐cycling cells undergoing clonal expansion. Various solid (e.g., nonsmall cell lung carcinoma) as well as hematological malignancies (e.g., acute myeloid leukemia) overexpress CD98. We have identified a CD98‐specific mouse monoclonal antibody that exhibits potent preclinical antitumor activity against established lymphoma tumor xenografts. Additionally, the humanized antibody designated IGN523 demonstrated robust tumor growth inhibition in leukemic cell‐line derived xenograft models and was as efficacious as standard of care carboplatin in patient‐derived nonsmall lung cancer xenografts. In vitro studies revealed that IGN523 elicited strong ADCC activity, induced lysosomal membrane permeabilization and inhibited essential amino acid transport function, ultimately resulting in caspase‐3 and ‐7‐mediated apoptosis of tumor cells. IGN523 is currently being evaluated in a Phase I clinical trial for acute myeloid leukemia (NCT02040506). Furthermore, preclinical data support the therapeutic potential of IGN523 in solid tumors.