人工神经元网络用于复方氯丙嗪的含量测定

将误差反向传播(BP)的人工神经元网络(ANN)模型，用于复方氯丙嗪紫外重叠光谱分 析。对ANN模型的参数进行了优化。采用f(x)二1/(1+e^-x)作为网络节点的输入输出转换函数的三 层神经网络具有较佳性能，当取隐含节点数为15时，该网络预测结果的最小平均相对误差为1.22％， 将研制的ANN模型用于复方氯丙嗪含量测定，其结果与药品标准法和偏最小二乘法(PLs)一致。     

雪灵芝对二乙基亚硝胺诱导大鼠肝癌组织细胞的抑制作用

目的：验证雪灵芝是否具有抑制大鼠肝癌的功效。方法：实验于2003—09/2004—08在广西疾病预防控制中心SPF级动物实验室完成。选用健康成年SD大鼠160只。按体质量分层随机分为5组：空白对照组、模型组、雪灵芝高剂量组、雪灵芝中剂量组和雪灵芝低剂量组，每组32只。雪灵芝高、中、低剂量组大鼠分别灌胃2．500，1．250，0．625mL/kg雪灵芝溶液，阴性对照组和模型组灌胃等量蒸馏水，1次／d，连续60d。第61天开始雪灵芝高、中、低剂量组和模型组灌胃二乙基亚硝胺溶液，对照组灌胃等量的生理盐水。于停止灌胃90d后各组处死一半受试大鼠（雌雄各半），检测血常规及血清主要生化指标，观察各脏器大体形态改变、脏器的癌变程度。1周后给剩余大鼠灌胃雪灵芝溶液（不含二乙基亚硝胺）。7周后处死余下的一半雄性大鼠，进行相同操作。8周后处死余下的全部大鼠，操作及检测方法同前。结果：纳入的160只SD大鼠，145只进入结果分析，15只脱落。①病理切片检查结果：除阴性对照组，其他各组大鼠肝组织均发生癌变或癌前病变。雪灵芝高、中、低剂量组的癌前病变发生率与模型组相近（P〉0．05）；癌变的发生率均低于模型组，差异有显著性意义（P〈0．05，0．01）。②大体标本检查结果：阴性对照组大鼠肝脏的大体标本均无异常改变，其他各组大鼠的肝脏有些可见表面粗糙等病理改变。模型组大体标本病理改变的阳性率高于雪灵芝高、中、低剂量组，差异有显著性意义（P〈0．05）。肉眼观模型组癌变发生率高于其他各组。③其他脏器检查结果：模型组2只大鼠有肝癌肺转移。结论：以较大剂量的二乙基亚硝胺连续灌胃30d可以复制大鼠肝癌模型；雪灵芝对二乙基亚硝胺诱导的大鼠肝癌具有预防和抑制的作用。     

Exploratory analysis of four polymorphisms in human GGH and FPGS genes and their effect in methotrexate-treated rheumatoid arthritis patients

The enzyme folylpoly-gamma-glutamase synthethase (FPGS) plays an important role in the intracellular polyglutamation of the disease-modifying antirheumatic drug methotrexate (MTX) and the length of the polyglutamated MTX product correlates with the time that MTX resides in the cell. The glutamates are released from MTX by activity of the enzyme gamma-glutamyl-hydrolase (GGH), thereby allowing the efflux of MTX. GGH 452C>T has been associated with decreased catalytic activity and higher accumulation of long-chain MTX-polyglutamate. However, single nucleotide polymorphisms (SNPs) in FPGS and GGH genes have not yet been explored for association with MTX efficacy or toxicity. We selected for SNPs with frequencies higher than 10% or, in case of FPGS 114G>A, causing an amino acid change with no known frequencies. In this study, frequencies of two SNPs in FPGS (1994A>G and 114G>A, rs10106 and rs10760502, respectively) and GGH genes (452C>T and 16T>C, rs11545078 and rs1800909, respectively), were determined using a newly developed method in rheumatoid arthritis patients (n = 352) and in a group of healthy controls (n = 360). Next, the SNPs were associated with response to MTX in rheumatoid arthritis patients treated with MTX monotherapy. In rheumatoid arthritis patients, allele frequencies of FPGS 1994A>G were 0.534 (A) and 0.466 (G), and for FPGS 114G>A 0.714 (G) and 0.286 (A). Allele frequencies of GGH 16T>C were 0.737 (T) and 0.263 (C) and for GGH 452C>T 0.912 (C) and 0.088 (T). No significant differences in allele frequencies between rheumatoid arthritis patients and healthy controls were found. In addition, the SNPs were not associated with good clinical response to MTX. Only patients with the GGH 16C-allele and one or no copies of the GGH 452C-16T haplotype were associated with good clinical improvement at 3 months upon treatment with MTX. No associations with efficacy at 6 months and MTX-induced toxicity were found. Therefore we conclude that despite the positive association of the GGH 16C-allele and one or no copies of the GGH 452C-16T haplotype with good clinical improvement at 3 months upon treatment with MTX, the tested SNPs in GGH and FPGS genes are suggested not to be clinically important for MTX treatment outcome.     

Isolated Segond fracture in a pediatric patient

Physicians diagnosing and managing knee injuries have become familiar with the lateral capsule sign, or Segond fracture on radiography. The Segond fracture is considered highly suggestive of an anterior cruciate ligament (ACL) tear in the adult population. This conclusion is not as well described in the pediatric patient. Recent anatomic studies have confirmed the presence of the anterolateral ligament (ALL), a structure described by Dr. Segond, and hypothesized to be the etiology of the lateral capsular avulsion. Although case reports of Segond fractures with an intact ACL in pediatric patients have been presented, there is usually a concomitant rotatory instability, tendinous injury, physeal fracture or posterolateral disruption. It is not currently clear the role that the ALL plays in the setting of Segond fracture with an intact ACL. We present a case of an isolated Segond fracture and briefly review the literature relating to this diagnosis. The literature suggests that a Segond fracture without an ACL tear is more common in the pediatric age group compared to adults. Our unique case is the presence of an isolated Segond fracture in a pediatric athlete.     

A Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of Armodafinil for Excessive Sleepiness Associated With Jet Lag Disorder

OBJECTIVE: To assess the effect of armodafinil, the longer-lasting isomer of modafinil, on jet lag disorder.PARTICIPANTS AND METHODS: This double-blind, randomized, parallel-group, multicenter study was conducted between September 18, 2008, and February 9, 2009. Adults with a history of jet lag symptoms on previous flights through multiple time zones flew from the United States to France (a 6-hour time zone change) for a 3-day laboratory-based study period. Participants received armodafinil (50 or 150 mg/d) or placebo each morning. Wakefulness was assessed by the coprimary outcomes, mean sleep latency on the Multiple Sleep Latency Test (MSLT) (average of all MSLT sessions across days 1 and 2) and Patient Global Impression of Severity in relation to jet lag symptoms (averaged across days 1 and 2).RESULTS: A total of 427 participants received armodafinil at 50 mg/d (n=142), armodafinil at 150 mg/d (n=143), or placebo (n=142). Armodafinil at 150 mg/d provided a significant benefit in sleep latency on the MSLT (days 1-2: mean, 11.7 minutes vs 4.8 minutes for placebo; P<.001) and participants'' perception of their overall condition in relation to jet lag symptoms (Patient Global Impression of Severity, days 1-2: mean, 1.6 vs 1.9 for placebo; P<.05). The most frequently reported adverse events for armodafinil at 150 mg/d were headache (27%), nausea (13%), diarrhea (5%), circadian rhythm sleep disorder (5%), and palpitations (5%).CONCLUSION: Armodafinil increased wakefulness after eastward travel through 6 time zones.Trial Registration: clinicaltrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00758498","term_id":"NCT00758498"}}NCT00758498ANCOVA = analysis of covariance; KSS = Karolinska Sleepiness Scale; MSLT = Multiple Sleep Latency Test; NPSG = nocturnal polysomnography; PGI-S = Patient Global Impression of Severity; STAI = State and Trait Anxiety Inventory; SWD = shift work disorderJet lag disorder is a circadian rhythm sleep disorder that occurs as a consequence of rapid travel through multiple time zones.¹ The traveler may experience excessive sleepiness, fatigue, insomnia, irritability, gastrointestinal disturbance, or other symptoms after arrival at the destination.^2-4 Jet lag symptoms arise from the desynchronization between the body''s circadian rhythm, which is synchronous with the location of departure, and the new sleep/wake cycle required at the destination.^1-4 Effects tend to be more severe when a greater number of time zones are traversed, and following eastbound travel.^2,5,6 Although the percentage of people flying across multiple time zones who develop jet lag disorder is unclear, it is estimated that possibly up to two-thirds of all travelers experience jet lag and may experience symptoms such as excessive sleepiness during the day or insomnia.² A treatment for excessive sleepiness that promotes daytime wakefulness may be especially beneficial to travelers who have a limited amount of time at their destination, precluding a circadian readjustment.Armodafinil, the longer-lasting R-isomer of racemic modafinil,⁷ is a wakefulness-promoting medication. The terminal half-life of the R-isomer is approximately 15 hours, compared with 3 to 4 hours for the S-isomer.^8,9 In a study of patients with shift work disorder (SWD), another circadian rhythm disorder, armodafinil 150 mg/d significantly improved wakefulness and clinicians'' perception of patients'' overall condition, compared with placebo.¹⁰ The primary objective of this study was to evaluate armodafinil (50 mg/d and 150 mg/d) for treatment of excessive sleepiness associated with jet lag disorder due to eastbound travel in a population of travelers with a history of jet lag symptoms.