在医学教育中使用模拟技术能显著提高医生实践水平:一项病例对照研究

随着现代制造工艺、电子技术的水平提升,医学模拟技术在功能性和仿真性方面日趋完善,种类也极大丰富,在医学教育中有越来越广泛的应用前景.为了验证在医学教育中应用模拟教育是否可以直接提高医生在实际临床工作中的医疗水平,美国西北大学Feinberg医学院的研究人员进行了一项针对其附属医院的心脏停搏诊疗团队的回顾性病例对照研究.     

Loss-of-function mutations in the immunoglobulin superfamily member 1 gene (IGSF1) cause a novel,X-linked syndrome of central hypothyroidism and testicular enlargement

BackgroundCongenital central hypothyroidism occurs either as isolated thyroid-stimulating hormone (TSH) deficiency or in conjunction with other pituitary hormone deficits. Undetected central hypothyroidism is associated with developmental delay in children and adverse cardiometabolic sequelae in adults. Hitherto, mutations in the thyrotropin-releasing hormone receptor gene (TRHR) or the TSHb subunit gene (TSHB) are the only known causes of isolated TSH deficiency.MethodsUsing whole exome and candidate gene sequencing, we have studied 11 unrelated families with males exhibiting isolated TSH deficiency, testicular enlargement, and variably low serum prolactin levels.FindingsWe have identified eight distinct mutations and two whole gene deletions disrupting the X-linked immunoglobulin superfamily member 1 gene (IGSF1) in affected males. IGSF1 encodes a pituitary-enriched plasma membrane glycoprotein; disease-associated mutations block trafficking of IGSF1 from the endoplasmic reticulum to the membrane, consistent with loss-of-protein function. Adult male IGSF1 null mice exhibit central hypothyroidism with decreased pituitary TSH content and circulating T3 levels; TSH secretion in response to TRH is blunted and pituitary TRHR mRNA levels are decreased, suggesting that impaired TRH signalling may provide the basis for hypothyroidism.InterpretationOur observations delineate a novel X-linked syndrome in which loss-of-function mutations in IGSF1 cause central hypothyroidism, testicular enlargement, and variable prolactin deficiency, and identify a previously unsuspected role for IGSF1 in hypothalamic-pituitary control of thyroid and testicular function. Variable biochemical penetrance in these families highlights the importance of genetic ascertainment in this syndrome, so that asymptomatic affected individuals can benefit from early initiation of thyroxine treatment.FundingWellcome Trust and National Institute for Health Research Biomedical Research Centre.     

血吸虫对吡喹酮抗药性的研究Ⅴ吡喹酮对曼氏血吸虫吡喹酮抗性株和敏感株成虫皮层的损伤

目的 体内比较吡喹酮对曼氏血吸虫吡喹酮抗性株与敏感株成虫皮层的损伤程度。方法 用各虫株尾蚴分别感染小鼠,感染后第57天,以300mg/kg微粒化吡喹酮悬液对小鼠作灌胃治疗;在灌药后10、30min和1、12、24h后剖杀感染小鼠,门静脉灌注收集成虫,按常规方法制成扫描电镜标本,扫描电镜下观察成虫体表的变化。结果 吡喹酮诱导的皮层损伤主要为虫体表形成泡状结构的薄壁隆起;给药10min,敏感株雄虫皮层可见较多小泡状物,而抗性株则少见;1h后,敏感株虫体表可见大量的泡状物,泡状物溃破可形成皮层损伤灶,抗性株仅见少量的泡状物;24h后,敏感株雄虫体表完全受损,部分皮层剥落,暴露出肌肉层,而抗性株仅见少量泡状物和破损的泡状物。给药1h后,敏感株雌虫开始出现少量泡状物,抗性株雌虫体表未见泡状损伤;12h后,敏感株雌虫泡状物数量增加,抗性株仅在有限区域见少量泡状物。结论 抗性株和敏感株成虫体表吡喹酮诱导的皮层损伤程度存在明显差异,敏感株的损伤程度重于抗性株,雄虫重于雌虫。     

NIA0004Unsaturated fatty acids diminish the detrimental effects of saturated fatty acids on insulin signalling in human muscle by decreasing de novo ceramide production

Insulin resistance in skeletal muscle is associated with impaired oxidative capacity and reduced size, number and function of mitochondria. Insulin‐resistant individuals have lower adiponectin concentrations, a characteristic predating the development of type‐2 diabetes (T2D). The aim of this study was to test the potential role of adiponectin in mitochondrial bioenergetics in individuals predisposed to develop T2D, in adiponectin KO mice and in primary muscle cell culture. Individuals with a family history of T2D displayed lower plasma adiponectin concentration (P = 0.03), reduced PGC1β (P = 0.04) and mtFAM (P = 0.03) mRNA, lower mitochondrial content (P = 0.006), citrate synthase (P = 0.02) and (‐HAD (P = 0.03) activity, suggesting defective mitochondrial bioenergetics in skeletal muscle. In addition, AdipoR1 was the principle correlate of mitochondrial content (r² = 0.81), suggesting an important role in mitochondrial biogenesis. Knock out of adiponectin in mice was associated with low PGC1α and PPARδ mRNA (both, P < 0.05), reduced mitochondrial content (P < 0.05) and COX II activity (P < 0.05) and markers for type‐1 oxidative fibers in skeletal muscle. This suggests that mitochondrial function is dependent on circulating adiponectin. In primary cultures of human myotubes, treatment with adiponectin induced AMPKK/ AMPK activity, PGC1α protein, mitochondrial biogenesis (P < 0.05), palmitate oxidation (P < 0.05), citrate synthase (P < 0.05) and SOD activity (P < 0.05), and reduced mitochondrial membrane potential and the production of ROS (P < 0.05). The inhibition of adiponectin receptor expression by siRNA or of AMPK by a pharmacological agent blunted the induction in mitochondrial function. Our findings indicate a novel pathway in skeletal muscle by which adiponectin increase mitochondrial number and function and exerts an insulin sensitizing effect.     

THE LIMA SUCCESS STORY — WHITHER OTHER ARTERIAL GRAFTS — ARE VEIN GRAFTS OBSOLETE ?

SUMMARY The long-term benefit of myocardial revascularisation depends largely upon the continued patency of bypass grafts, but the long-term patency of vein grafts is poor. To improve the results of myocardial revascularisation, either measures to increase the patency of saphenous vein grafts or alternative conduits are required. Use of the left internal mammary artery as a graft is known to increase survival, and this has prompted wider use of other arterial grafts in the expectation that they will further enhance the long-term results of coronary artery bypass. This policy is based upon sound theory, but convincing evidence that it improves survival is lacking. Meanwhile, advances in the understanding of the pathology of vein graft occlusion have given rise to new methods of increasing vein graft patency. While these techniques are, as yet, only experimental, if translated into clinical practice, the places of arterial and venous grafts may require further assessment.     

Diagnostic and Prognostic Value of Serum Interleukin-6 in Colorectal Cancer

The application of serum interleukin-6 (IL-6) in the diagnosis and prognosis of colorectal cancer (CRC) has been evaluated in many studies, whereas the results were contradictive.The aim of this study was to systematically evaluate this issue.An original study was conducted to explore the diagnostic value of serum IL-6 in CRC. Pubmed, Embase, and Cochrane library databases were searched for eligible studies.For diagnostic meta-analysis, aggregate data (AD) and individual participant data (IPD) meta-analyses were both adopted. The sensitivity and specificity were pooled and a summary receiver-operating characteristic (ROC) curve was constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of IL-6 for survival were summarized. Secondary analysis of survival data was performed to synthesize the Kaplan–Meier curves.Total 17 studies (including our study) were included in this meta-analysis. The pooled sensitivity, specificity, and area under curve (AUC) of serum IL-6 were 0.72 (95% CI: 0.46–0.88), 0.74 (95% CI: 0.56–0.86), and 0.79 (95% CI: 0.75–0.82) in CRC diagnosis, respectively. Further, IPD meta-analysis strengthened the diagnostic value of serum IL-6 (the AUC, sensitivity, and specificity were 0.794, 0.606, and 0.839, respectively). For prognostic analysis, the high serum level of IL-6 was inversely associated with overall survival (OS) (pooled HR = 1.76, 95% CI: 1.42–2.19, P < 0.001) and disease-free survival (DFS) (pooled HR = 2.97, 95% CI: 1.76–5.01, P < 0.001). The synthesized Kaplan–Meier curves indicated that CRC patients with higher serum IL-6 level had a worse OS (P = 0.0027) and DFS (P < 0.001), which further support the prognostic value of serum IL-6 in CRC patients.The present study confirmed that serum IL-6 may be a potential biomarker for CRC diagnosis, and the high serum IL-6 level was associated with poor prognosis for both CRC overall survival and disease-free survival.The study has been registered in an international registry of systematic reviews PROSPERO (CRD42013006485).     

Relationship between human development and disappearance of unusually large von Willebrand factor multimers from plasma

von Willebrand factor (vWF) multimers were examined in fetal, umbilical cord, and neonatal platelet-poor plasma (PPP) specimens. Sixty-five of 65 (100%) fetal PPP samples aged less than 35 weeks and seven of ten (70%) fetal samples aged greater than 35 weeks had unusually large vWF (ULvWF) multimers. Thirty of 46 (65%) cord PPP samples from neonates ranging in gestational age from 34 to 41 weeks had ULvWF. There was no significant relationship between either gestational age at time of delivery or birth weight and likelihood of finding ULvWF multimers in cord PPP samples. No maternal PPP sample contained ULvWF multimers. Serial heelstick samples from 16 preterm and term neonates were analyzed for 8 weeks. ULvWF multimers disappeared from the PPP of ten of the neonates during this time. The PPP of four neonates had vWF patterns similar to those in normal adult PPP throughout the sampling period. The ULvWF multimeric forms of fetal and neonatal PPP samples were similar to those constitutively released from endothelial cells. They were not as slowly migrating in a very porous 0.5% agarose gel system as the ULvWF multimers released from Weibel-Palade bodies in response to the calcium ionophore A23187. A vWF protomer was present in 97% of fetal samples, 83% of cord blood specimens, and 11% of neonatal heelstick samples, but was not found in any maternal sample. These results indicate that control mechanisms operative in older children and adults to prevent circulation of ULvWF multimers and vWF protomeric forms are normally acquired late in uterine life or during the neonatal period. ULvWF multimers, which are normal components of fetal, most cord, and some neonatal plasma samples, may contribute to in utero and postnatal hemostasis.     

Inhibition of malarial parasite invasion by monoclonal antibodies against glycophorin A correlates with reduction in red cell membrane deformability

The effect of well-characterized monoclonal antibodies to red cell surface molecules on the invasion of human red cells by the malarial parasites Plasmodium falciparum and Plasmodium knowlesi was examined. Antibodies to glycophorin A (GP alpha) inhibit invasion for both parasite species, and this is highly correlated with the degree to which they decrease red cell membrane deformability as measured by ektacytometry. This effect on rigidity and invasion was also seen with monovalent Fab fragments. The closer the antibody binding site was to the membrane bilayer, the greater was its effect on inducing membrane rigidity and decreasing parasite invasion. Antibodies to the Wright determinant in particular were the most inhibitory. This differential effect of the various antibodies was not correlated with their binding affinities or the number of sites bound per cell. Antibodies to surface molecules other than GP alpha were without effect. A novel mechanism is described whereby monoclonal antibodies and their Fab fragments directed at determinants on the external surface of red cells might act to inhibit invasion by malarial parasites by altering membrane material properties.