恩替卡韦与拉米夫定治疗HBeAg阴性慢性乙型肝炎的对照研究

Ⅱ期临床试验已经证实恩替卡韦是一种治疗HBeAg阴性慢性乙型肝炎有效和可选择的抗病毒药物。采用双盲法将648例未曾接受过核苷类药物治疗的HBeAg阴性慢性乙型肝炎随机分配进入恩替卡韦（0．5mg／d）治疗组或拉米夫定（100mg／d）治疗组，疗程至少52wk。     

The access and processing of familiar idioms by brain-damaged and normally aging adults.

Idiom interpretation tasks are routinely used in the clinical evaluation of adults with brain damage, and idiom processing has received increasing attention in the psycholinguistic literature. Clinical evidence suggests that adults with unilateral right-hemisphere damage (RHD) are insensitive to nonliteral meanings conveyed by idiomatic expressions and other figurative forms. However, this portrayal is derived from their terminal responses to tasks that reflect multiple aspects of mental operations (off-line measures), obscuring the source of poor performance. This study used an on-line word-monitoring task to assess RHD, left-hemisphere-damaged, and normally aging adults' implicit knowledge of familiar idiomatic expressions. Brain-damaged subjects performed similarly to normal controls on this task, even though the clinical subjects fared poorly by comparison on an off-line idiom definition measure. These results suggest that adults with unilateral brain damage can activate and retrieve familiar idiomatic forms, and that their idiom-interpretation deficits most likely reflect impairment at some later stage of information processing. Further, error analysis of idiom-definition performance did not support the customary characterization of RHD adults as excessively literal responders. The paper discusses clinical implications of the nature and use of idiom interpretation tasks.     

Skilled forelimb reaching for pasta guided by tactile input in the rat as measured by accuracy, spatial adjustments, and force

Rats are capable of reaching for food with a single forelimb, but since they locate the target of their reach using olfaction, it is unclear how they adjust their limb movement to compensate for errors. Although it is thought that their reaching movement is ballistic and can only be adjusted by trial and error, whether they can use haptic cues to aid in locating and identifying a target has not been examined. The present study addressed this question by allowing rats to reach through a slot for rigidly held pieces of uncooked pasta of varying thickness, which could be oriented vertically or horizontally from different points around the slot and which were attached to a force transducer. The tasks required that animals not only adjust their reach and grasp to the target's location but also identify the target based on its texture. Acquisition curves were made of head orientation, limb transport trajectories, number of attempts per success, paw orientation, breaking direction and force of the grasp. A haptic discrimination test used pasta and similar sized metal rods with different tactile properties as discriminanda. The results indicated that whereas postural orientation and limb transport trajectory were not modified as a function of target orientation, paw orientation and grasp force did vary as a function of the sensory qualities of the target object, and the rats could make a haptic discriminative choice of a target object. The results show that the rat is capable of adjusting paw movements using haptic information, suggesting that somatosensory features of sensorimotor control of limb and paw movements in carnivores and primates are shared by rodents. This commonality points to a conservation of motor control in mammals, explains some of the idiosyncratic features of rat reaching behavior, and confirms that rodents provide a good model for investigating sensorimotor functions.     

Identification of the key amino acids of gliai cell line-derived neurotrophic factor family receptor alpha 1 involved in its biological function

Glial cell line-derived neurotrophic factor （GDNF） plays a critical role in neurodevelopment and survival of midbrain dopaminergic and spinal motor neurons in vitro and in vivo. The biological actions of GDNF are mediated by a two-receptor complex consisting of a glycosylphosphatidylinositol-linked cell surface molecule, the GDNF family receptor alpha 1 （GFR alpha 1）, and receptor protein tyrosine kinase Ret. Although structural analysis of GDNF has been extensively examined, less is known about the structural basis of GFR alpha 1 function. In this study, based on evolutionary trace method and relative solvent accessibility prediction of residues, a set of trace residues that are solvent-accessible was selected for site-directed mutagenesis. A series of GFR alpha 1 mutations was made, and PC12 cell lines stably expressing different GFR alpha 1 mutants were generated. According to the survival and differentiation responses of these stable PC12 cells upon GDNF stimulation and the GDNF- GFR alpha 1-Ret interaction assay, residues 152NN153, Arg259, and 316SNS318 in the GFR alpha 1 central region were found to be critical for GFR alpha 1 binding to GDNF and eliciting downstream signal transduction. The single mutation R259A in the GFR alpha 1 molecule simultaneously lost its binding ability to GDNF and Ret. However N152A/N153A or S316A/N317A/ S318A mutation in the GFR alpha 1 molecule still retained the ability to bind with Ret. These findings suggest that distinct structural elements in GFR alpha 1 may be involved in binding to GDNF and Ret.     

Reversible findings of restricted diffusion in 5‐flourouracil neurotoxicity

A 35‐year‐old woman presented with neurotoxicity correlated to an i.v. regimen of 5‐fluorouracil as episodes of acute confusional state and abnormalities of symmetrically restricted diffusion in the periventricular white matter and corpus callosum. On discontinuing the medication, the areas of severely restricted diffusion had entirely resolved, with minimal residual T2 signal abnormality. In this case, immediate discontinuation of the chemotherapeutic agent apparently reversed the patient's symptoms and findings on MRI. The scant information available in the published literature regarding this phenomenon is reviewed with regard to 5‐fluorouracil.