An Open-label, Self-control, Prospective Study on Cognitive Function, Academic Performance, and Tolerability of Osmotic-release Oral System Methylphenidate in Children with Attention-deficit Hyperactivity Disorder / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Attention-deficit hyperactivity disorder (ADHD) is the most common mental and behavioral disorder in school-aged children. This study evaluated the effect of osmotic-release oral system (OROS) methylphenidate (MPH) on cognitive function and academic performance of Chinese school-aged children with ADHD.</p><p><b>METHODS</b>This 12-week, prospective, multicenter, open-label, self-controlled study enrolled 153 Chinese school-aged children with ADHD and 41 non-ADHD children. Children with ADHD were treated with once-daily OROS-MPH (18 mg, 36 mg, or 54 mg). The primary endpoints were Inattention/Overactivity (I/O) with Aggression Conners Behavior Rating Scale (IOWA) and Digit Span Test at week 12 compared with baseline. Secondary endpoints included opposition/defiant (O/D) subscale of IOWA, Clinical Global Impression (CGI), Coding Test, Stroop Color-word Test, Wisconsin Card Sorting Test (WCST), academic performance on teacher-rated school examinations, and safety at week 12 compared with baseline. Both non-ADHD and ADHD children received the same frequency of cognitive operational test to avoid the possible bias caused by training.</p><p><b>RESULTS</b>A total of 128 patients were evaluated with cognitive assessments. The OROS-MPH treatment significantly improved IOWA Conners I/O subscale scores at week 12 (3.8 ± 2.3) versus baseline (10.0 ± 2.4; P < 0.0001). Digit Span Test scores improved significantly (P < 0.0001) with a high remission rate (81.1%) at week 12 versus baseline. A significant (P < 0.0001) improvement was observed in O/D subscale of IOWA, CGI, Coding Test, Stroop Color-word Test, WCST, and academic performance at week 12 versus baseline. Very few practice-related improvements were noticed in the non-ADHD group at week 12 compared with baseline. No serious adverse events and deaths were reported during the study.</p><p><b>CONCLUSIONS</b>The OROS-MPH treatment effectively controlled symptoms of ADHD and significantly improved academic performance and cognitive function of Chinese school-aged children with ADHD. The treatment was found to be safe and generally well-tolerated over 12 weeks.</p><p><b>TRIAL REGISTRATION</b>ClinicalTrials.gov, NCT01933880; http://clinicaltrials.gov/ct2/show/NCT01933880?term=CONCERTAATT4099&rank=1.</p>

Research on genes susceptible to childhood absence epilepsy / 中华医学遗传学杂志

Despite a few genes that do not encode ion channels have been identified as implicating some kinds of human idiopathic epilepsies(IE) in recent years, but genetic discoveries have shown the ion channels to play a central role in genetic pathomechanism of IE. The gene mutations of ion channels are a common cause of some rare monogenic IE which could be so-called as channelopathies, and able to be applied to account for the questioned epileptic syndrome to minority of families and sporadic cases. However, more frustrating has been from the genetic research on more common IE with complex inheritance due to the unknown mode of inheritance, the phenotypic heterogeneity and the uncertainty of genetic overlap among syndrome subtypes, which have limited gene mapping. Absence epilepsy is a kind of common IE subtype and shows a complex way to inherit. Evidences from heredity investigation indicate that eleven genes are correlated with absence epilepsy, of which four encode the neuronal calcium channel subunits. Therefore, calcium channel genes may be considered as important candidates for involving in absence epilepsy. To focus the genetics research on calcium channel genes of absence epilepsy may be opening an optimal gate to the pathogenetic study of more common IE with complex inheritance, and benefit to elucidate the molecular mechanisms of absence epilepsy finally, one of the more common IE subtypes with complex inheritance.

The effect of CACNA1H gene G773D mutation on calcium channel function / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the effect of CACNA1H gene mutation G773D on calcium channel function.</p><p><b>METHODS</b>By the overlap extension PCR we introduced G773D mutation into a human Cav3.2acDNA for constructing the mutant. And then using whole cell clamp technique, we studied the alterations of channel behavior in transfected HEK-293 cells.</p><p><b>RESULTS</b>There were no difference in kinetics of activation and inactivation of calcium channel between wild type and mutant. However comparing with the wild-type Cav3.2 channel, G773D mutant could increase the calcium current density significantly.</p><p><b>CONCLUSION</b>CACNA1H gene G773D mutation is able to increase calcium current and neuronal excitability.</p>