治疗股骨转子间骨折时头颈拉力螺钉不同置入位置的有限元计算

背景：课题组总结发现,股骨转子间骨折股骨近端髓内钉置入内固定治疗后出现髋内翻的病例中,除小部分由于股骨转子部粉碎性骨折和个别存在复位问题之外,绝大多数出现并发症的患者术后复查X射线片可见,2枚头颈拉力螺钉位置均位于股骨颈中上部。 目的：通过有限元计算,验证股骨近端髓内钉头颈拉力螺钉不同置入位置的生物力学性能,从而指导股骨近端髓内钉置入以减少置入后并发症的发生。 方法：利用MIMICS中的布尔运算将股骨近端髓内钉置入骨折模型,建立三维模型。实验分为2组：中下组股骨近端髓内钉头颈拉力螺钉置于股骨颈中下1/3处;中上组股骨近端髓内钉头颈拉力螺钉置于股骨颈中上1/3处。利用有限元软件计算头颈拉力螺钉于不同方向置入时股骨及股骨近端髓内钉的应力分布情况。 结果与结论：骨折断端应力分布结果显示,中下组小转子处所受压应力小于中上组,并且中下组股骨近端髓内钉各钉所受最大应力平均值大于中上组。骨折断面张开角测量结果显示,加载后中下组骨折断面张开角小于中上组。载荷与位移关系分析结果显示,加载后中下组股骨上部合位移小于中上组。说明2枚头颈拉力螺钉置入股骨颈中下1/3处时,生物力学性能更好,结构相对更稳定,受力更合理,在临床中具有重要的参考价值。     

诱导多能干细胞建系及体外造血祖细胞定向分化体系的建立

背景：目前,大量文献报道了诱导多能性干细胞系的建立,但大规模体外诱导分化造血祖细胞的研究还缺乏深入的探讨。 目的：建立诱导多能性干细胞体外定向诱导形成造血祖细胞的方法。 方法：采用慢病毒感染的方法将含有Oct4、Sox2、Nanog和Lin28全能性基因的慢病毒颗粒转导人皮肤成纤维细胞,获得了诱导多能性干细胞;在诱导分化体系中添加了 Y-27632,克服干细胞扩增中的凋亡现象;运用OP9细胞产生的条件培养液建立诱导多能性干细胞体外定向分化形成造血祖细胞的分化体系。 结果与结论：①前3代细胞克隆传代时,诱导多能性干细胞发生凋亡的现象很多,很难大规模扩增培养。培养基中添加阻断 ROCK活化的抑制剂,能够明显抑制胚胎干细胞的凋亡。②诱导多能性干细胞在 OP9细胞条件培养液作用下,经过体外诱导分化,形成CD34＋造血祖细胞。     

In vivo Doppler optical coherence tomography of mucocutaneous telangiectases in hereditary hemorrhagic telangiectasia

BACKGROUND: Hereditary hemorrhagic telangiectasia is characterized by mucocutaneous telangiectases and visceral arteriovenous malformations. Knowledge is limited concerning the development hemodynamics of mucocutaneous telangiectases. Doppler optical coherence tomography can demonstrate microvascular blood flow at flow rates as low as 20 microm/second, which is up to approximately 100 times more sensitive than Doppler US. The aims of this study were to collect in vivo Doppler optical coherence tomography images of mucocutaneous telangiectases and normal surrounding mucosa and skin, and to gain experience for an in vivo GI endoscopic study. It was hypothesized that visibly normal areas may have occult telangiectases and that mucocutaneous telangiectases that have bled may have a higher rate of blood flow than mucocutaneous telangiectases with no history of bleeding. METHODS: Twelve patients with hereditary hemorrhagic telangiectasia and mucocutaneous telangiectases were studied. Two to 3 visible mucocutaneous telangiectases on the digits, lips, and tongue were imaged with Doppler optical coherence tomography, along with visually normal surrounding areas at each site. The Doppler optical coherence tomography images were obtained in 0.5 second by using 1310 nm light. RESULTS: A total of 67 mucocutaneous telangiectases from the 12 patients were imaged (38 digit, 16 lip, 13 tongue). Blood flow was demonstrated within every mucocutaneous telangiectasis imaged. Doppler optical coherence tomography did not identify any abnormal vasculature within visually normal areas. Mucocutaneous telangiectases with a history of bleeding (n = 18) were situated closer to the surface, compared with mucocutaneous telangiectases with no bleeding history (n = 49), but there was no difference in the Doppler flow appearance. CONCLUSIONS: Visually normal areas in patients with hereditary hemorrhagic telangiectasia did not appear to have abnormal vasculature. Mucocutaneous telangiectases with a history of bleeding were more superficial but were otherwise similar to mucocutaneous telangiectases with no bleeding history.     

Somatostatin receptors 2 and 5 are the major somatostatin receptors in insulinomas: an in vivo and in vitro study

Somatostatin (SRIF) receptors (sst) are present on normal pancreatic endocrine beta-cells. However, the use of SRIF analogs in the scintigraphic imaging of insulinomas and in the medical management of these tumors seems to be restricted to a subgroup of patients. The aim of this study was to determine the prevalence of sst expression in vitro and characterize sst subtype binding in insulinomas and its correlation with in vivo sst receptor scintigraphy (SRS). In vitro studies were performed on 27 insulinomas from 25 patients: 22 with benign and three with malignant tumors. Semiquantitative RT-PCR of sst mRNAs was performed for 20 of these insulinomas. Sst2 and sst5 were expressed in 70%, sst1 in 50%, and sst3 and sst4 subtypes only in 15-20% of the tumors. (125)I-Tyr(0)DTrp(8)SRIF(14) binding was assessed by quantitative autoradiography in 18 insulinomas, and competition experiments were performed with SRIF(14) and L797-591, L779-976, L796-778, L803-087, L817-818, selective agonists of the five sst subtypes, and BIM23244, a selective agonist of sst2 and sst5. Significant specific binding was observed in 72% of the insulinomas. Displacement experiments with ligands of higher affinity for each of the sst receptors revealed significant binding with the sst2 and sst5 ligands in 72%, sst3 in 44%, sst1 in 44%, and sst4 in 28% of cases. All insulinomas displaying sst2 binding were also sst5 sensitive. However, the ratio of sst5/sst2 displacement was variable and only equal to that for SRIF(14) in experiments with the sst2/sst5 agonist BIM23244. SRS was performed 10 times in nine patients; it detected 60% of the tumors, including metastases of a malignant insulinoma. All the tumors detected by SRS displayed high levels of (125)I-Tyr(0)DTrp(8)SRIF(14) binding. The mechanisms underlying the loss of expression of sst2/sst5 in a third of insulinomas remains to be determined, but this loss of expression may be involved in beta-cell dysfunction.     

Comparison of micafungin and voriconazole in the treatment of invasive fungal infections in kidney transplant recipients

What is known and Objective: Invasive fungal infections are a major threat to renal transplant recipients. Micafungin and voriconazole are two useful antifungal agents for treating such infections. Our objective is to evaluate the comparative efficacy and safety of micafungin and voriconazole in the initial treatment of such infections. Methods: In this prospective, multicentre, open‐labelled, randomized, controlled trial, renal transplant recipients with invasive fungal infections were assigned to receive either micafungin or voriconazole. The enrolled subjects received a kidney transplant between March 2008 and March 2010 at one of the two transplant centres in Henan Province, China. The efficacy and adverse effects of the two treatments were compared. Results and Discussion: The clinical trial enrolled 65 patients, of whom 31 were treated with micafungin, and 34 with voriconazole. The rates of microbiological evidence of infection in the micafungin and voriconazole groups were 64·5% and 70·5%, respectively, whereas the rates of Candida as the major cultured fungus were 80·0% and 75·0%, respectively. Complicated bacterial infection rates in the two treatment groups were 38·7% and 32·4%, respectively, whereas complicated CMV viral infection occurred at a rate of 19·2% and 23·5%, respectively. Fungal infection within one to 3 months after transplant was 83·6% (26/31) and 85·3% (29/34) in the micafungin and voriconazole groups, respectively. There was no significant difference between the two groups in terms of efficacy, survival beyond 10 days and discontinuation of treatment because of lack of efficacy (P > 0·05). Mortality rates in the micafungin and voriconazole groups were 9·7% (3/31) and 12·1% (4/33), respectively. Rates of adverse effects in the two groups were 41·9% and 51·6% (P > 0·05), respectively. What is new and Conclusions: This is the first comparison of micafungin and voriconazole in renal transplant patients. Our study shows that the effectiveness of micafungin was similar to that of voriconazole in such patients.     

Expression of functional insulin-like growth factor-1 receptor on lymphoid cell subsets of rats.

It has become evident that insulin-like growth factor-1 (IGF-1) acts as a growth factor for immune cells, yet the precise regulatory role of IGF-1 in the immune system is unknown. The aim of this study was to examine the distribution of IGF-1 receptors on rat lymphoid cells. A flow cytometric method was used, with a biotinylated and functionally active IGF-1 analogue, namely des(1-3)IGF-1, which binds well to IGF-1 receptor but poorly to IGF binding proteins, followed by phycoerythrin-conjugated streptavidin (PE-SA) staining. Our results showed that IGF-1 receptors were readily detectable on a wide variety of the immune cells, including T cells, B cells and monocytes, but the binding capacity for IGF-1 was monocytes > B cells > T cells, as determined by titration experiments. Furthermore, the level of expression on resting CD4+ T lymphocytes was greater than on CD8+ cells, and the concentration of biotin-des(1-3)IGF-1 required to demonstrate the binding to IGF-1 receptor on CD8+ cells (68 nmol/l) was 200-fold higher than for CD4+ cells (0.34 nmol/l), indicating that most of the IGF-1 receptor on CD8+ cells represented lower affinity sites. The level of IGF-1 receptor expression was increased several-fold after concanavalin A stimulation on both CD4+ and CD8+ T-cell subsets. Kinetic analysis of the expression of IGF-1 receptor and its association with interleukin-2 receptors (IL-2R) following activation showed a similar pattern, with no significant differences in the ratio of IGF-1 receptor: IL-2R per cell during the 3 days of cell culture. Our studies suggest that biological activities of IGF-1 include direct stimulation of immune cells, and that expression of IGF-1 receptor may have a role in regulation of T-cell function.     

孕中晚期胎儿血细胞各项参数变化的研究

目的探讨孕中晚期胎儿血细胞各项参数变化规律,了解胎儿血细胞的生成情况,为产前胎儿宫内疾病诊断提供依据。方法采用Bayer ADVIA120全自动五分类血细胞分析仪对249例孕18～39周胎儿脐血血细胞进行以下各项参数的检测:白细胞计数(WBC)、中性粒细胞百分比(NEU%)、淋巴细胞百分比(LYM%)、单核细胞百分比(MON%)、嗜酸性粒细胞百分比(EOS%)、嗜碱性粒细胞百分比(BASO%)、红细胞计数(RBC)、血红蛋白含量(HGB)、红细胞比容(HCT)、红细胞平均体积(MCV)、红细胞平均血红蛋白量(MCH)、平均红细胞血红蛋白浓度(MCHC)、红细胞体积分布宽度(RDW)、血小板PLT等。结果孕中晚期胎儿脐血细胞各项参数中有5项(WBC、NEU%、RBC、HGB、HCT)随着孕周增加而逐渐增大;有2项(MCV、LYM%)随着孕周增加而逐渐减小;还有7项(EOS%、MON%、BASO%、MCH、MCHC、RDW、PLT)在各孕周中变化不大。脐血血细胞各项参数与出生后水平存在显著差异。结论胎儿脐血血细胞成分处在一个动态变化的过程中,不同妊娠阶段胎血中各系血细胞的构成比有较大的差异。因此探讨孕中晚期胎儿血细胞各项参数变化规律有重要意义,在诊断胎儿期贫血,炎症等宫内疾病有重要参考价值。     

椎基底动脉狭窄血管内支架成形术效果分析

目的 探讨症状性椎基底动脉血管内支架成形术的远期效果.方法 选取症状性椎动脉狭窄接受血管内支架治疗的33例患者,对临床症状和支架内再狭窄情况进行随访观察分析.结果 33例患者支架成形术后临床症状均明显改善,术前平均狭窄率为（92.36±3.23）％,术后即刻平均残余狭窄率为（9.13±2.57）％.术后23例临床症状完全消失,10例明显改善.1例基底动脉重度狭窄患者术后出现一侧肢体麻木的并发症,1例术后出现脑栓塞表现,3d后恢复正常.随访6～24个月,9例出现头晕、头昏等不适症状,其中29例获得数字减影血管造影检查,残余狭窄率为（19.27±5.62）％,3例椎动脉开口支架内再狭窄＞50％,再次给予支架内成形术,症状消失.结论 症状性椎基底动脉狭窄血管内支架成形术能够明显缓解脑缺血症状,提高患者生存质量,同时有一定的再狭窄率.     

Activation of phosphatidylinositol 3-kinase/Akt-mammalian target of Rapamycin signaling pathway in the hippocampus is essential for the acquisition of morphine-induced place preference in rats

Hippocampus is a critical structure for the acquisition of morphine-induced conditioned place preference (CPP), which is a usual learning paradigm for assessing drug reward. However, the precise mechanisms remain largely unknown. Phosphatidylinositol 3-kinase (PI3K) and its downstream targets, including Akt, mammalian target of Rapamycin (mTOR) and 70-kDa ribosomal S6 kinase (p70S6K), are critical molecules implicated in learning and memory. Here, we tested the role of PI3K/Akt-mTOR-p70S6K signaling pathway in morphine-induced CPP in the hippocampus. Our results showed that the acquisition of morphine CPP increased phosphorylation of Akt in the hippocampal CA3, but not in the nucleus accumbens (NAc), the ventral tegmental area (VTA) or the CA1. Moreover, the phosphorylated Akt exclusively expressed in the CA3 neurons. Likewise, levels of phosphorylated mTOR and p70S6K were significantly enhanced in the CA3 following morphine CPP. The alterations of these phosphorylated proteins are positively correlated with the acquisition of morphine CPP. More importantly, microinjection of PI3K inhibitor (LY294002) or mTOR inhibitor (Rapamycin) into the CA3 prevented the acquisition of CPP and inhibited the activation of PI3K-Akt signaling pathway. In addition, pre-infusion of β-FNA (β-funaltrexamine hydrochloride), a selective irreversible μ opioid receptor antagonist, into CA3 significantly prevented the acquisition of CPP and impaired Akt phosphorylation. All these results strongly implied that the PI3K-Akt signaling pathway activated by μ opioid receptor in hippocampal CA3 plays an important role in acquisition of morphine-induced CPP.