UGT1A1 promoter polymorphism increases risk of nilotinib-induced hyperbilirubinemia.

Nilotinib is a novel BCR-ABL inhibitor with significantly improved potency and selectivity over imatinib. In Phase I and Phase II clinical studies of nilotinib in patients with a variety of leukemias, infrequent instances of reversible, benign elevation of bilirubin were observed. Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) glucuronidates bilirubin in humans, and a polymorphism in the promoter of the gene that encodes it has been associated with hyperbilirubinemia during treatment with a number of drugs. Pharmacogenetic analysis of that TA-repeat polymorphism found an association between the (TA)7/(TA)7 genotype and risk of hyperbilirubinemia in Phase I patients with imatinib-resistant/intolerant chronic myeloid leukemia (CML) or relapsed/refractory Ph+ acute lymphoblastic leukemia (ALL); this result was replicated in two separate analyses of the chronic phase (CP) and accelerated phase (AP) CML arms of a Phase II study. As nilotinib is not known to be glucuronidated by UGT1A1, the combined impact of inhibition of UGT1A1 activity by nilotinib and genetic polymorphism is the most likely cause of the increased rate of hyperbilirubinemia.     

盐酸托莫西汀旋光异构体的手性拆分研究

目的:建立盐酸托莫西汀旋光异构体的手性拆分方法。方法:Waters 高效液相色谱仪,Chiralcel OD(250 mm×4.6 mm,5μm)手性柱,正己烷-异丙醇-二乙胺(80:20:0.2)为流动相,流速为1.0 mL·min~(-1),紫外检测波长为271 nm。结果:左旋盐酸托莫西汀峰和右旋盐酸托莫西汀峰能很好地分开,分离度为5.5,拖尾因子小于1.2,理论塔板数大于5000,该方法可以用来测定盐酸托莫西汀中的右旋异构体,最低检出限为4 ng。供试品右旋盐酸托莫西汀溶液在4 h 内基本稳定(RSD=2.4%),3批样品中右旋盐酸托莫西汀含量均低于0.5%。结论:本方法快捷、简便,灵敏度高,可以用于原料药中右旋盐酸托莫西汀含量的测定,结果满意。     

糖尿病视网膜病变黄斑囊样水肿与诱导型一氧化氮合成酶G-954C基因多态性

目的:分析中国人诱导型一氧化氮合成酶G-954C等位基因位点的基因表型在糖尿病视网膜病变黄斑囊样水肿患者与正常对照的差异。方法:病例对照,89例糖尿病视网膜病变黄斑囊样水肿的患者与年龄及性别匹配的90例健康对照纳入该项研究。研究采用了巢式聚合酶链式反应、限制性核酸内切酶技术、基因片段的序列测定。主要检测指标为诱导型一氧化氮合成酶G-954C位点的基因表型。结果:89例患者和90例健康对照的诱导型一氧化氮合成酶G-954C位点的基因表型全部检测结果为GG型。结论:诱导型一氧化氮合成酶G-954C位点的基因多态性可能在中国人为较低的变异频率,而且可能与糖尿病视网膜病变黄斑囊样水肿的易感性关系不大。     

椎板复合结构瓣回植治疗腰椎间盘突出症长期随访报告

目的探讨椎板复合结构瓣回植术式治疗腰椎间盘突出症的远期临床疗效。方法应用椎板复合结构瓣回植术式治疗腰椎间盘突出症176例,男117例,女59例,年龄18～79岁。合并中央椎管狭窄者32例,侧隐窝狭窄者57例。结果随访5～10年,平均7年。优143例,良27例,可6例。结论本术式显露范围广、椎管减压彻底,使椎管重新成形,有效的预防术后脊柱不稳、顽固性腰痛等并发症。     

Overexpression of CDC25B and LAMC2 mRNA and protein in esophageal squamous cell carcinomas and premalignant lesions in subjects from a high-risk population in China.

Molecular events associated with the initiation and progression of esophageal squamous cell carcinoma (ESCC) remain poorly understood but likely hold the key to effective early detection approaches for this almost invariably fatal cancer. CDC25B and LAMC2 are two promising early detection candidates emerging from new molecular studies of ESCC. To further elucidate the role of these two genes in esophageal carcinogenesis, we did a series of studies to (a) confirm RNA overexpression, (b) establish the prevalence of protein overexpression, (c) relate protein overexpression to survival, and (d) explore their potential as early detection biomarkers. Results of these studies indicated that CDC25B mRNA was overexpressed (>/=2-fold overexpression in tumor compared with normal) in 64% of the 73 ESCC cases evaluated, whereas LAMC2 mRNA was overexpressed in 89% of cases. CDC25B protein expression was categorized as positive in 59% (144 of 243) of ESCC cases on a tumor tissue microarray, and nonnegative LAMC2 patterns of protein expression were observed in 82% (225 of 275) of cases. Multivariate-adjusted proportional hazard regression models showed no association between CDC25B protein expression score and risk of death [hazard ratio (HR) for each unit increase in expression score, 1.00; P = 0.90]; however, several of the LAMC2 protein expression patterns strongly predicted survival. Using the cytoplasmic pattern as the reference (the pattern with the lowest mortality), cases with a diffuse pattern had a 254% increased risk of death (HR, 3.52; P = 0.007), cases with no LAMC2 expression had a 169% increased risk of death (HR, 2.69; P = 0.009), and cases with a peripheral pattern had a 130% greater risk of death (HR, 2.30; P = 0.02). CDC25B protein expression scores in subjects with esophageal biopsies diagnosed as normal (n = 35), dysplastic (n = 23), or ESCC (n = 32) increased significantly with morphologic progression. For LAMC2, all normal and dysplastic patients had a continuous pattern of protein expression, whereas all ESCCs showed alternative, noncontinuous patterns. This series of studies showed that both CDC25B and LAMC2 overexpress RNA and protein in a significant majority of ESCC cases. The strong relation of LAMC2 pattern of protein expression to survival suggests a role in prognosis, whereas the association of CDC25B with morphologic progression indicates a potential role as an early detection marker.     

粘附分子CD29和VEGF在胃癌组织中的表达及临床意义

目的：探讨胃癌组织中粘附分子CD29的表达水平及其与血管内皮生长因子（vascular endothelial grouth factor,VEGF）的关系。方法：选择胃癌患者84例和浅表性胃炎患者48例对CD29和VEGF抗体SP法免疫组化染色。结果：84例胃癌标本中CD29有68例阳性,阳性率为80.9%,48例浅表性胃炎组织中有12例阳性表达,阳性率为25%（P〈0.05）。胃癌中70例（83.3%）VEGF阳性表达。其中有63例VEGF与CD29共同表达。具显著正相关（P〈0.05）。CD29的表达与患者的年龄、性别和肿瘤的大小、组织学类型及浸润深度无关。但与肿瘤的淋巴结转移具有显著的相关性（P〈0.05）。结论：CD29可通过介导VEGF的表达促进肿瘤新生血管的形成,从而进一步促进肿瘤的生长和转移。     

非经典抗精神病药对双相情感障碍患者代谢的影响

目的 探讨非经典抗精神病药对双相情感障碍患者代谢的影响.方法 评估125例至少治疗3个月的双相情感障碍患者的代谢综合征（MS）发生情况.入组患者曾接受药物治疗,包括非经典抗精神病药物（利培酮、奥氮平和奎硫平）或情感稳定剂（碳酸锂、丙戊酸盐和卡马西平）.根据患者使用药物不同,将其分成3组：单用非经典抗精神病药物（A组）、合用非经典抗精神病药和情感稳定剂（B组）及单用情感稳定剂（C组）.结果 125例患者,40例（32.0%）检出MS;A组患者MS检出率与B、C组比较,差别有统计学意义（P＜0.05）;但在非经典抗精神病药奥氮平组、奎硫平组和利培酮组3组间MS检出率差别无统计学意义（P＞0.05）.结论 服用非经典抗精神病药的双相情感障碍患者易发生MS.使用抗精神病药治疗者,均应定期检测BMI、腰围、血压、血糖和血脂水平.     

心音图运动试验中的信噪比分析

为了验明ＰＣＧＥＴ方法的可信度,作者进行了该心音图运动试验中的信噪比分析。对３０个志原者进行了ＰＣＧＥＴ,运动后基带幅值的平均值与运动前基带幅值平均值的比值为１．１５０;各受试者运动后ＳＩ幅值对运动前ＳＩ幅值的倍数的平均值为１０．５７,这表明,ＰＣＧＥＴ提高了信／噪比,心内噪声、心胸系统传播过程中产生的噪声、呼吸噪声、肌肉噪声和环境噪声没有防碍ＰＣＧＥＴ的应用。ＰＣＧＥＴ可作为心力储备的无伤性、简     

The receptive fields of cat retinal ganglion cells in physiological and pathological states: where we are after half a century of research

Studies on the receptive field properties of cat retinal ganglion cells over the past half-century are reviewed within the context of the role played by the receptive field in visual information processing. Emphasis is placed on the work conducted within the past 20 years, but a summary of key contributions from the 1950s to 1970s is provided. We have sought to review aspects of the ganglion cell receptive field that have not been featured prominently in previous review articles. Our review of the receptive field properties of X- and Y-cells focuses on quantitative studies and includes consideration of the function of the receptive field in visual signal processing. We discuss the non-classical as well as the classical receptive field. Attention is also given to the receptive field properties of the less well-studied cat ganglion cells-the W-cells-and the effect of pathology on cat ganglion cell properties. Although work from our laboratories is highlighted, we hope that we have given a reasonably balanced view of the current state of the field.     

The inhibitory effects of jujuboside A on rat hippocampus in vivo and in vitro

Jujuboside A (JuA) is a glycoside extracted from the seed of Ziziphus jujuba Mill var. spinosa (Bunge) Hu ex H F Chou, a Chinese herbal medicine, which has long been known as a sedative-hypnotic drug. The present study used the method of intracerebroventricular (i.c.v.) JuA in vivo to detect the effect of JuA on paired-pulse responses of dentate gyrus granule cells in urethane-anaesthetized rats, and the method of hippocampal slice bathing in JuA in vitro to detect the effects of JuA on the responses of CA1 pyramidal cells. The results showed that JuA significantly decreased the slopes of excitatory postsynaptic potential (EPSP) and the amplitudes of population spike (PS) in the first responses of granule cells and significantly decreased EPSP and PS in the responses of CA1 pyramidal cells. The good quantitative correspondence between in vitro and in vivo results indicates that studies using hippocampal formation allow research on the inhibitory effects of JuA in the rat central nervous system (CNS). In conclusion, our study accessed the inhibitory effects of JuA on hippocampal formation in vivo and in vitro, which contributed to the further research on the mechanism of its effects on CNS.