香叶天竺葵挥发油的化学成分及抗瘤作用

用高分离效能的交联石英毛细管柱气相色谱法和气相色谱/质量选择检测器分离和鉴定了三种香叶油,并作了对比。结果表明这些香叶油的化学成分极为相似,但某些成分的含量却有明显差别。香茅醇、香叶醇、甲酸香茅酯和乙酸香茅酯均有一定的抗瘤活性。     

Antenatal counselling for prospective parents whose fetus has a neurological anomaly: part 2, risks of adverse outcome in common anomalies

After diagnosis of a fetal neurological anomaly, prospective parents want to know the best and worst-case scenarios and an estimation of the risk to their infant of having an atypical developmental outcome. The literature on developmental outcomes for fetal neurological anomalies is poor: studies are characterized by retrospective design, small sample size, often no standardized assessment of development, and differing definitions of anomalies. This review provides an aide-memoir on the risks of adverse neurodevelopmental outcome for ventriculomegaly, cortical anomalies, microcephaly, macrocephaly, agenesis of the corpus callosum, posterior fossa anomalies, and myelomeningocele, to assist healthcare professionals in counselling. The data in this review should be used alongside recommendations on counselling and service design described in part 1 to provide antenatal counselling.     

IFN-β is a potent inhibitor of insulin and insulin like growth factor stimulated proliferation and migration in human pancreatic cancer cells

Introduction: Pancreatic cancer is a highly aggressive malignancy with few treatment options. The overexpression of several growth factors, including insulin and insulin-like growth factors (IGFs), can underlie the aggressive nature of this disease. Previous research has demonstrated potent effects of interferon (IFN)-β on pancreatic cancer cell growth, however up till now it is unknown whether IFN-β is able to counteract IGF1, IGF2 and insulin-induced pancreatic cancer cell proliferation and migration. Methods: Expression of IGF- and insulin receptors was determined and the stimulatory effects of IGF1, IGF2 and insulin on cell proliferation and migration, as well as the inhibitory effects of IFN-β were evaluated in 3 human pancreatic adenocarcinoma cell lines. Results: Both the insulin- and the IGF1 receptor were variably expressed in the cell lines. IGF1, IGF2 and insulin were capable of stimulating cell proliferation in all three cell lines, however cell migration was significantly enhanced only in the BxPC-3 cell line. IFN-β significantly inhibited IGF1-, IGF2- and insulin-stimulated proliferation in all three cell lines in a dose and time dependent manner. Furthermore, in the BxPC-3 cell line IFN-β significantly inhibited both basal and IGF1-, IGF2- and insulin-stimulated cell migration. Conclusion: Both IGF1, -2 and insulin were capable of stimulating proliferation and migration in human pancreatic cancer cells irrespective of the type of receptor expressed. This study demonstrates that insulin, in addition to IGF1 and IGF2, may play an important role in the progression of pancreatic cancer. Moreover, IFN-β strongly inhibits growth factor stimulated cell proliferation and migration. Our study supports previous findings which have suggested that IFN-β can be a potential promising anti-cancer agent in pancreatic cancer.     

Interprotomer disulfide-stabilized variants of the human metapneumovirus fusion glycoprotein induce high titer-neutralizing responses

Human metapneumovirus (HMPV) is a major cause of respiratory disease worldwide, particularly among children and the elderly. Although there is no licensed HMPV vaccine, promising candidates have been identified for related pneumoviruses based on the structure-based stabilization of the fusion (F) glycoprotein trimer, with prefusion-stabilized F glycoprotein trimers eliciting significantly higher neutralizing responses than their postfusion F counterparts. However, immunization with HMPV F trimers in either prefusion or postfusion conformations has been reported to elicit equivalent neutralization responses. Here we investigate the impact of stabilizing disulfides, especially interprotomer disulfides (IP-DSs) linking protomers of the F trimer, on the elicitation of HMPV-neutralizing responses. We designed F trimer disulfides, screened for their expression, and used electron microscopy (EM) to confirm their formation, including that of an unexpected postfusion variant. In mice, IP-DS–stabilized prefusion and postfusion HMPV F elicited significantly higher neutralizing responses than non–IP-DS–stabilized HMPV Fs. In macaques, the impact of IP-DS stabilization was more measured, although IP-DS–stabilized variants of either prefusion or postfusion HMPV F induced neutralizing responses many times the average titers observed in a healthy human cohort. Serological and absorption-based analyses of macaque responses revealed elicited HMPV-neutralizing responses to be absorbed differently by IP-DS–containing and by non–IP-DS–containing postfusion Fs, suggesting IP-DS stabilization to alter not only the immunogenicity of select epitopes but their antigenicity as well. We speculate the observed increase in immunogenicity by IP-DS trimers to be related to reduced interprotomer flexibility within the HMPV F trimer.

Human metapneumovirus (HMPV) is a globally widespread respiratory pathogen (1–13) primarily affecting infants, the elderly, and those that are immune compromised (reviewed in ref. 14). Disease symptoms are similar to those of the closely related respiratory syncytial virus (RSV) (15), with rates of hospitalization in older adults approaching those of influenza (6). Phylogenetic analysis (SI Appendix, Fig. S1) shows HMPV to comprise two related subtypes, A and B, which are closely related to avian metapneumoviruses, from which HMPV might have evolved (1, 16, 17).There is currently no licensed vaccine or treatment for HMPV (2–4, 18). Recently, promising vaccine candidates for RSV as well as for parainfluenza viruses types 1 through 4 have been developed using structure-based vaccine design, in which prefusion-stabilized versions of the fusion (F) glycoprotein have been used to induce high titer-neutralizing responses; this approach has succeeded in animal models (19–23) and for RSV in recent human clinical trials (24). Unfortunately, prefusion F-based stabilization with the HMPV F glycoprotein does not induce improved neutralization titers compared to postfusion HMPV F (18, 25, 26).In the absence of a difference in titers induced by prefusion versus postfusion forms of HMPV F, we explored whether there was a structure-based vaccine approach that might increase neutralizing titers elicited by HMPV F. With both human and bovine RSV F, stabilization in the prefusion conformation with multiple disulfide bonds significantly increased neutralizing titers (27, 28). The increase was especially evident with interprotomer disulfides (IP-DSs), covalently cross-linking together protomers within the trimer (27). We therefore sought to test the impact of disulfides—and especially IP-DSs—on the elicitation of HMPV-neutralizing responses. We evaluated the prefusion HMPV F structure (PDB ID 5WB0) (26) for sites suitable for the introduction of either intraprotomer- or IP-DS–bonding mutations, which we then synthesized, expressed, and tested antigenically. We determined cryoEM structures to delineate F conformation and atomic-level details of stabilization and assessed immunogenicity in mice and rhesus macaques. Overall, IP-DSs—of both prefusion and postfusion F—induced significantly higher HMPV-neutralizing responses than non–IP-DS–stabilized variants, suggesting that in addition to fixing a particular conformation, IP-DSs appear to be capable of enhancing the immunogenicity of neutralizing responses.     

肝细胞生长因子诱导前软骨干细胞向软骨细胞的分化

目的:探讨肝细胞生长因子诱导前软骨干细胞向软骨细胞分化的机制。方法:实验于2005-12/2006-03在河南省正骨研究院完成。①实验材料:普通级新生兔10只,平均体质量3kg。②实验干预:采用免疫磁珠分离技术分离新生兔长骨干骺端前软骨干细胞。利用肝细胞生长因子(浓度分别为0.5,1,2,4μg/L)作用前软骨干细胞;另以2μg/L肝细胞生长因子作用前软骨干细胞,对照用相同剂量的培养基,检测前软骨干细胞Ⅱ型胶原及Ⅱ型胶原mRNA的表达。③实验评估:采用光学显微镜观察前软骨干细胞形态及生长情况;四甲基偶氮唑盐比色法检测前软骨干细胞的增殖;免疫荧光检测Ⅱ型胶原表达;反转录-聚合酶链反应检测Ⅱ型胶原mRNA的表达。结果:①前软骨干细胞形态及生长情况:分离纯化的前软骨干细胞贴壁稳定,在光学显微镜下呈多角和梭形,生长旺盛,曲光度好。②前软骨干细胞增殖情况:细胞增殖率上升,在24,48,72h内呈时间浓度依赖。③Ⅱ型胶原表达:肝细胞生长因子作用第5天前软骨干细胞出现Ⅱ型胶原蛋白的表达。④Ⅱ型胶原mRNA的表达:在肝细胞生长因子刺激3d开始出现表达,并且5d,7d逐渐增加。结论:肝细胞生长因子作用前软骨干细胞后,出现软骨特征标志抗原Ⅱ型胶原的表达,细胞增殖活性上升,表明肝细胞生长因子能诱导前软骨干细胞向软骨细胞方向分化。其机制可能是前软骨干细胞也存在肝细胞生长因子受体。     

腹主动脉瘤腔内修复术治疗现状

目的 综合分析国内外腹主动脉瘤腔内修复术治疗现状。方法 检索国内外腹主动脉瘤腔内修复术相关文献,选择其中病例数较大或试验较规范的文章,结合本院经验,进行分析、评价。结果 腔内修复术是一种治疗腹主动脉瘤有效、可行的新方法,近期研究发现该法具有创伤小、失血量小、病人易接受等优点,移位、内漏及转为肝腹手术是目前的主要问题。结论 腔内修复术是治疗腹主动脉瘤一种可供选择的方法,术后随访极其重要。     

Evaluation of risk assessment questions used to target blood lead screening in Illinois

OBJECTIVE: Beginning in 1995, Illinois law permitted targeted-as opposed to universal-blood lead screening in low-risk areas, which were defined by ZIP code characteristics. State guidelines recommended specific lead risk assessment questions to use when targeting screening. This study was designed to evaluate the sensitivity and specificity of Illinois lead risk assessment questions. DESIGN: Parents bringing their 9- or 10- or 12-month and 24-month-old children for health supervision visits at 13 pediatric practices and parents of children (aged 6 through 25 months and who needed a blood lead test) receiving care at 5 local health departments completed a lead risk assessment questionnaire concerning their child. Children had venous or capillary blood lead testing. Venous confirmation results of children with a capillary level >/=10 micrograms/dL were used in analyses. CHILDREN: There were 460 children with both blood and questionnaire data recruited at the pediatric practices (58% of eligible) and 285 children (51% of eligible) recruited at local health departments. Of the 745 children studied, 738 provided a ZIP code that allowed their residence to be categorized as in a low-risk (n = 456) or high-risk (n = 282) area. RESULTS: Sixteen children (3.5%) living in low-risk areas versus 34 children (12.1%) living in high-risk areas had a venous blood lead level (BLL) >/=10 micrograms/dL; 1.8% and 5.3%, respectively, had a venous BLL >/=15 micrograms/dL. For children living in low-risk areas, Illinois mandated risk assessment questions (concerning ever resided in home built before 1960, exposure to renovation, and exposure to adult with a job or hobby involving lead) had a combined sensitivity of.75 for levels >/=10 micrograms/dL and.88 for levels >/=15 micrograms/dL; specificity was.39 and.39, respectively. The sensitivity of these questions was similar among children from high-risk areas; specificity decreased to.27 and.28, for BLLs >/=10 micrograms/dL and >/=15 micrograms/dL, respectively. The combination of items requiring respondents to list house age (built before 1950 considered high risk) and indicate exposure to renovation had a sensitivity among children from low-risk areas of.62 for BLLs >/=10 micrograms/dL with specificity of.57; sensitivity and specificity among high-risk area children were.82 and.36, respectively. For this strategy, similar sensitivities and specificities for low and high-risk areas were found for BLLs >/=15 micrograms/dL. CONCLUSIONS: The Illinois lead risk assessment questions identified most children with an elevated BLL. Using these questions, the majority of Illinois children in low-risk areas will continue to need a blood lead test. This first example of a statewide screening strategy using ZIP code risk designation and risk assessment questions will need further refinement to limit numbers of children tested. In the interim, this strategy is a logical next step after universal screening.