早期护理干预对缺血缺氧性脑病患儿智力及行为发育的影响

目的:研究早期护理干预对缺血缺氧性脑病(H IE)患儿智力及行为发育的影响。方法:采用自行设计的早期干预方法,对患儿的视觉、听觉、感觉等给予不同的刺激,加以新生儿抚触、水浴抚触及中医穴位针灸等措施,对干预组患儿进行实施,另设对照组只行一般发育了解。结果:干预组患儿的智力及行为发育指数与对照组相比均有显著性差异。结论:早期护理干预能促进缺血缺氧性脑病患儿的智力及行为的发育,帮助他们尽早康复。     

A catenary model to study transport and conjugation of baicalein, a bioactive flavonoid, in the Caco-2 cell monolayer: demonstration of substrate inhibition

The transport and metabolism of baicalein (Ba) was studied in vitro and in Caco-2 cells. Protein binding of Ba with Caco-2 lysate showed that Ba was bound to two classes of sites: a higher affinity, lower capacity site (K(A1) = 27.6 +/- 4.7 microM(-1), n(1) = 10.6 +/- 0.6 nmol/mg) and lower affinity, higher capacity site (K(A2) = 0.015 +/- 0.0013 microM(-1), n(2) = 413 +/- 21 nmol/mg). Incubation studies of Ba with Caco-2 lysate showed substrate inhibition of both glucuronidation and sulfation, with K(m) values of 0.14 +/- 0.034 and 0.015 +/- 0.0053 microM, and K(I) values of 6.75 +/- 1.70 and 0.37 +/- 0.16 microM, respectively. In the Caco-2 monolayer, Ba (8-47 microM) displayed good apparent permeabilities (P(app)) across the membrane; P(app) was found to be increased with elevated loading concentration in both the absorptive and secretory directions. However, the efflux ratio was less than unity, negating the involvement of apical efflux transporters. The concentration ratios of Ba sulfate (BS) and glucuronide (BG) decreased with increased loading Ba concentration, suggesting that BS and BG are apically excreted via transporters, likely breast cancer resistance protein and multidrug resistance-associated protein 2, respectively. Data fit to the catenary model, composed of basolateral, cellular, and apical compartments, showed a low cellular unbound fraction (0.0019 +/- 0.00018), a high passive diffusion clearance (0.012 +/- 0.00029 ml/min/mg), and substrate inhibition, with sulfation being more readily saturated and inhibited than glucuronidation, as evidenced by smaller K(m) value (0.35 +/- 0.078 versus 1.95 +/- 0.57 microM) and K(I) value (0.58 +/- 0.20 versus 7.90 +/- 1.10 microM); these patterns paralleled those observed in the lysate incubation studies. The results showed that the catenary model aptly predicts substrate inhibition kinetics and offers significant and mechanistic insight into the transport and atypical metabolism of drugs in the Caco-2 monolayer.     

Mechanistic characterization of GS-9190 (Tegobuvir), a novel nonnucleoside inhibitor of hepatitis C virus NS5B polymerase

GS-9190 (Tegobuvir) is a novel imidazopyridine inhibitor of hepatitis C virus (HCV) RNA replication in vitro and has demonstrated potent antiviral activity in patients chronically infected with genotype 1 (GT1) HCV. GS-9190 exhibits reduced activity against GT2a (JFH1) subgenomic replicons and GT2a (J6/JFH1) infectious virus, suggesting that the compound's mechanism of action involves a genotype-specific viral component. To further investigate the GS-9190 mechanism of action, we utilized the susceptibility differences between GT1b and GT2a by constructing a series of replicon chimeras where combinations of 1b and 2a nonstructural proteins were encoded within the same replicon. The antiviral activities of GS-9190 against the chimeric replicons were reduced to levels comparable to that of the wild-type GT2a replicon in chimeras expressing GT2a NS5B. GT1b replicons in which the β-hairpin region (amino acids 435 to 455) was replaced by the corresponding sequence of GT2a were markedly less susceptible to GS-9190, indicating the importance of the thumb subdomain of the polymerase in this effect. Resistance selection in GT1b replicon cells identified several mutations in NS5B (C316Y, Y448H, Y452H, and C445F) that contributed to the drug resistance phenotype. Reintroduction of these mutations into wild-type replicons conferred resistance to GS-9190, with the number of NS5B mutations correlating with the degree of resistance. Analysis of GS-9190 cross-resistance against previously reported NS5B drug-selected mutations showed that the resistance pattern of GS-9190 is different from other nonnucleoside inhibitors. Collectively, these data demonstrate that GS-9190 represents a novel class of nonnucleoside polymerase inhibitors that interact with NS5B likely through involvement of the β-hairpin in the thumb subdomain.     

A study of the regulating gene of femA from methicillin-resistant Staphylococcus aureus clinical isolates

The regulating gene of femA was studied in methicillin-resistant Staphylococcus aureus (MRSA). High-level MRSA, low-level MRSA and methicillin-sensitive S. aureus (MSSA) were identified by agar diffusion. Beta-lactamases were detected by nitrocephin and the presence of the mecA gene was determined by polymerase chain reaction (PCR). Only isolates that were both beta-lactamase-negative and mecA-positive were used. The femA gene and its 250 base pair (bp) upstream sequence were amplified by PCR and expression was determined by real-time fluorescent quantitative PCR. The 250 bp upstream sequence was labelled by BrightStar Psoralen-Biotin and detected by electrophoretic mobility shift assay (EMSA). Expression levels of femA in MSSA, low-level MRSA and high-level MRSA were 3.53 x 10(-3)% - 29.91%, 5.54 x 10(-3)% - 3.1 x 10(2)% and 13.88 - 5.50 x 10(4)%, respectively. EMSA detected a signal shift in 57 high-level MRSA isolates but not in four low-level MRSA and four MSSA strains. Expression of femA in high-level MRSA (non-beta-lactamase-producing) was higher than in low-level MRSA and MSSA. The femA regulating gene probably lies in the 250 bp upstream sequence in MRSA and high-level expression is essential for high-level methicillin resistance.     

Comparative study of different surgical transposition methods for ulnar nerve entrapment at the elbow

This study compared the therapeutic effects of two techniques for surgical decompression treatment for ulnar nerve entrapment at the elbow: subcutaneous transposition and modified submuscular transposition with Z-lengthening of the pronator teres origin. A total of 278 patients with ulnar nerve entrapment (McGowan grades I - III) were randomly assigned to undergo one of these techniques. All patients were followed-up for 2 years. The effects were assessed by preoperative and postoperative cross-sectional area, motor conduction velocity, sensory conduction velocity and nerve action potential. All of these parameters improved after surgery in both groups. For patients with grade I disease, there were no significant differences between the two techniques. For patients with grade II and III disease, modified submuscular transposition was associated with significantly greater improvements compared with subcutaneous transposition. In conclusion, subcutaneous ulnar nerve transposition is recommended for grade I patients and modified submuscular ulnar nerve transposition for grade II and III patients.     

The positive correlation between DJ‐1 and β‐catenin expression shows prognostic value for patients with glioma

The relationship between DJ‐1 and β‐catenin, and its impact on the prognosis for glioma patients has not been fully understood. This study determined the effect of DJ‐1 on β‐catenin and the prognostic significance of this interaction in glioma patients. We collected tumor specimens from 88 glioma patients and determined the expression of DJ‐1, β‐catenin and PTEN by using immunohistochemical staining. The involvement of DJ‐1 and β‐catenin in glioma cell lines was evaluated by immunohistochemistry and Western blotting. High DJ‐1 expression (37.5%) and high β‐catenin expression (34.1%) in glioma specimens were significantly associated with high grade and poor prognosis in glioma patients. However, only high levels of DJ‐1 (P = 0.014) was a strong independent prognostic factor, correlated with a reduced overall survival time. In vitro DJ‐1 expression was positively correlated with the expression levels of β‐catenin and p‐Akt, and negatively correlated with PTEN expression in U87, U251 MG, SWO‐38 and SHG44 human glioma cell lines. After the knockdown of DJ‐1, Akt, p‐Akt or β‐catenin expression levels were not affected in the PTEN‐null cell lines (U87 and U251 MG). However, in the SWO‐38 cell line, which has wild‐type PTEN protein, the level of PTEN increased while Akt/p‐Akt and β‐catenin levels were reduced. Furthermore, β‐catenin staining weakened in SWO‐38 cells after DJ‐1 levels decreased according to immunocytochemical analysis. In conclusion, DJ‐1 and β‐catenin may contribute to the development and recurrence of glioma and are valuable prognostic factors for glioma patients. DJ‐1 may regulate β‐catenin expression via PTEN and p‐Akt.     

蛛网膜下腔出血后不同血液成分与脑血管痉挛及免疫炎症反应的关系

目的：探讨不同血液成分与蛛网膜下腔出血(SAH)后脑血管痉挛(CVS)及血管壁免疫炎症反应之间的关系。方法：分别将全血、孵育全血、富血小板血浆、孵育血浆等分别注入动物蛛网膜下腔，再于不同的时间段处死实验动物观察基底动脉的痉挛情况并测定血管壁中血管细胞粘附分子1(VCAM—1)的表达。结果：富血小板血浆、孵育血浆未引起基底动脉明显痉挛和VCAM—1的上调，全血在第2次注入后第3天出现基底动脉痉挛和VCAM—1表达的上调，孵育全血第1次注入后6小时就引起明显的基底动脉痉挛和VCAM—1的表达上调。结论：血管痉挛程度与血管壁VCAM—1的表达程度相一致；陈旧的红细胞或其裂解产物是引起SAH后血管痉挛和炎症反应主要成分。     

320排动态容积CT诊断脑血管病的价值

目的探讨320排动态容积cT诊断脑血管病的价值。方法对80例怀疑脑血管病患者行320排动态容积cT检查,经两位有经验的神经影像医师读片,评估其诊断价值。结果80例患者发现颅内血管性病变75例,其中60例为颅内动脉瘤,10例脑动脉硬化,3例脑动静脉畸形,2例烟雾病,5例未发现明确原因。结论320排动态容积CT-次扫描16cm容积数据采集,实现脑血管病cT平扫、脑血管造影及脑灌注一站式检查,具有快速、无创、准确性高等优点,对诊断脑血管疾病具有很高临床价值。