Clinical and genetic variation analysis of 97 patients with Duchenne muscular dystrophy / 中国实用儿科杂志

OBJECTIVE:(DMD),summarize the gene mutation hotspots in 97 cases and to explore the correlation between clinical manifestations and genotype. METHODS: Totally 97 patients with DMD diagnosed by genetic examination from January 2014 to 2018 were collected and analyzed. The clinical manifestations,serum analyses and gene mutation results were analyzed. RESULTS: The main clinical manifestations of 97 patients(96 boys)were feeding difficulties,increased muscle enzyme and limb weakness.Creatine kinase(CK),lactate dehydrogenase(LDH)and aspartate aminotransferase(AST)muscle enzymes were significantly increased. By combining deep-sequencing technologies,the large deletions of DMD gene mutation was in 62 cases(63.92%);there were 11 cases(11.34%)of large duplication mutation,and 24 cases(24.74%)of point mutation. All of the mutations could occur in any position in the DMD gene,but there were two hot spots;45 cases were located in the central region gene exon 45～55(72.58%);12 cases of deletion mutation were located in 5'exon end exon 2～19 area(19.35%). CONCLUSION: The main clinical manifestations of the DMD children are feeding difficulty,increased muscle enzyme and limb weakness.The patients with significantly increased muscle enzyme should receive a timely defection of DMD gene.

Influence of ketogenic diet on the clinical effects and electroencephalogram features in 31 children with pharmacoresistant epileptic encephalopathy / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of ketogenic diet (KD) on the clinical and electroencephalogram features in children with pharmacoresistant epileptic encephalopathy.</p><p><b>METHOD</b>Thirty-one children (19 boys, 12 girls) aged 7 months to 7 years (mean 2 years 5 month) with epilepsy refractory to conventional antiepileptic drugs (AEDs) were included in this study. In addition to their original AED treatment, the children were assigned to different ketogenic diets based on their age. The prospective electro-clinical assessment was performed prior to the KD and then one week, one month and again 3 months after the initiation of therapy, respectively.</p><p><b>RESULT</b>The reduction of seizure frequency in 52%, 68% and 71% of all patients exceeded 50% one week, one month and three months after KD treatment respectively. KD is particularly effective in myoclonic astatic epilepsy (MAE; Doose Syndrome) and West syndrome with 100% and 81.25% of the patients having a greater than 50% seizure reduction, respectively. After 3 months of KD treatment, more than 2/3 patients experienced a reduction in interictal epileptiform discharges (IEDs) and improvement in EEG background.</p><p><b>CONCLUSION</b>The clinical and electroencephalographic improvement confirms that KD is beneficial in children with refractory epilepsy.</p>

Morphological and behavioral consequences of recurrent seizures in neonatal rats are associated with glucocorticoid levels / 神经科学通报·英文版

<p><b>OBJECTIVE</b>It is well documented that epilepsy can increase neurogenesis in certain brain regions and cause behavioral alternations in patients and different epileptic animal models. A series of experimental studies have demonstrated that neurogenesis is regulated by various factors including glucocorticoid (CORT), which can reduce neurogenesis. Most of studies in animal have been focused on adulthood stage, while the effect of recurrent seizures to immature brain in neonatal period has not been well established. This study was designed to investigate how the recurrent seizures occurred in the neonatal period affected the immature brain and how CORT regulated neurogenesis in immature animals.</p><p><b>METHODS</b>Neonatal rats were subjected to 3 pilocarpine-induced seizures from postnatal day 1 to day 7. Then neurogenesis at different postnatal ages (i.e. P8, P12, P22, P50) was observed. Behavioral performance was tested when the rats were mature (P40), and plasma CORT levels following recurrent seizures were simultaneously monitored.</p><p><b>RESULTS</b>Rats with neonatal seizures had a significant reduction in the number of Bromodeoxyuridine (BrdU) labeled cells in the dentate gyrus compared with the control groups when the animals were euthanized on P8 or P12 (P<0.05); whereas there was no difference between the two groups on P22. Until P50, rats with neonatal seizures had increased number of BrdU-labeled cells compared with the control group (P<0.05). In Morris water maze task, pilocarpine-treated rats were significantly slower than the control rats at the first and second day, and there were no differences at other days. In probe trial, there was no significant difference in time spent in the goal quadrant between the two groups. Endocrine studies showed a correlation between the number of BrdU positive cells and the CORT level. Sustained increase in circulating CORT levels was observed following neonatal seizures on P8 and P12.</p><p><b>CONCLUSION</b>Neonatal recurrent seizures can biphasely modulate neurogenesis over different time windows with a down-regulation at early time and up-regulation afterwards, cause persistent deficits in cognitive functions of adults, and increase the circulating CORT levels. CORT levels are related with the morphological and behavioral consequences of recurrent seizures.</p>

Application of Botulinum Toxin in Spastic Cerebral Palsy / 中国康复理论与实践

@#This aticle introduced the process of Botulinum toxin from toxin to drug, as well as the application in Spastic Cerebral Palsy such as dose, therapeutic estimation and side-effect etc.

Effects and consequence of recurrent seizures of neonatal rat on the hippocampal neurogenesis / 中华儿科杂志

<p><b>OBJECTIVE</b>Seizures occur more frequently in the neonatal period than at any other time in life. A controversy which has been debated for the recent years is whether recurrent neonatal seizures can lead to long-term adverse consequences or are simply a reflection of underlying brain dysfunction and are not intrinsically harmful. Despite numerous clinical observations showed that seizures may be detrimental to the developing brain, the pathological mechanism has not yet been completely understood. The goal of this study was to investigate what effect was induced by recurrent seizures in neonatal rats on dentate granule cell neurogenesis.</p><p><b>METHODS</b>Sixty-four neonatal Wistar rats were randomly divided into seizure group (n = 40) and control group (n = 24). The rats of seizure group were subjected to three times of pilocarpine injections intraperitonealy at postnatal day 1 (P1), 4 (P4) and 7 (P7). Neonatal rats of the control group were given saline injection (i.p.) at the same time points. The rat were sacrificed separately at the next four time points: immediately after the third seizure (P7), the fourth day after the seizure (P11), the fourteenth day (P21) and the forty fifth day (P52), corresponding control group rats were killed accordingly. The rats in both seizure and control groups were given bromodeoxyuridine (BrdU) injection 36 hours before sacrifice to indicate newly generated cells. Brain tissue sections were prepared and subjected to Nissl staining for neuronal loss, by BrdU labeling for cell proliferation and by BrdU + NF200 (neurofilament 200) double labeling for the identification of the newly formed cells.</p><p><b>RESULTS</b>The numbers of BrdU-labeled cells were age-dependent in the control group, decreased with age, and their morphorlogy and distribution changed (P < 0.01). BrdU-labeled cells decreased significantly in the seizure group compared with the matched controls at P7 and P11 (P < 0.01), while at P21 there was no significant difficence between the two groups. On the contrary, BrdU-labeled cells increased significantly in the seizure group compared with the matched controls at P52 (P < 0.01). Most BrdU-labeled cells in granular cell layer (GCL) of both seizure group and control group coexpressed NF200.</p><p><b>CONCLUSION</b>Recurrent seizures during neonatal period lead to decreased neurogenesis at the early stage after the third seizure, and at later time points increase of neurogenesis. Most of newly generated cells can differentiate into neurons.</p>

Neurogenesis of dentate granule cells following kainic acid induced seizures in immature rats / 中华儿科杂志

<p><b>OBJECTIVE</b>Data accumulated over the past years have led to widespread recognition that neurogenesis, the emergence of new neurons, persists in the hippocampal dentate gyrus of the adult mammalian brain, and can be increased by seizures in multiple models. Also, aberrant reorganization of dentate granule cell axons, the mossy fiber sprouting, occurs in human temporal lobe epilepsy and rodent epilepsy models. However a number of studies suggest that the immature brain is less vulnerable to the morphologic alteration of hippocampus after seizures. The goal of this study was to determine whether the seizures can induce dentate granule cell neurogenesis and mossy fiber sprouting in the immature rat.</p><p><b>METHODS</b>Seizures was elicited by unilateral microinfusion of kainic acid (KA, 1 micro g) into the amygdula at postnatal day 15 (P15). Rat pups were given bromodeoxyuridine (BrdU) intraperitoneally on day 5 after KA administration and killed 7 d or 21 d later. The brains were processed for BrdU mitotic labeling combined with double-label immunohistochemistry using neuron-specific, early differentiation marker TuJ1 (betaIII tubulin) or granule-specific marker CaBP (calcium-binding protein calbindin D28k) as well as glia-specific marker GFAP (glial fibrillary acidic protein). Mossy fiber sprouting in intermolecular layer and CA3 subfield was assessed in Timm-stained sections both 1 month and 3 months after KA administration by using a rating scale and density measurement.</p><p><b>RESULTS</b>The dentate BrdU-immunoreactive cells of the KA-treated rats increased significantly compared with those of control rats on day 7 and 21 after BrdU administration (7 d: 244 +/- 15 vs. 190 +/- 10; 21 d: 218 +/- 19 vs. 133 +/- 12, P < 0.05). Approximately 80.2% and 78.7% of BrdU-labeled cells coexpressed TuJ1 in KA-treated rats and control rats on day 7 after BrdU respectively (P > 0.05). On 21 d after BrdU, 60.2% and 58.2% of dentate BrdU-labeled cells coexpressed GaBP in KA-treated rats and control rats respectively (P > 0.05). GFAP colocalized with 3%-5% dentate BrdU-labeled cells in the rats of both groups on day 7 and 21 after BrdU. It was also demonstrated that status epilepticus at P15 did not result in any detectable mossy fiber sprouting within the hippocampus both 1 month and 3 months after KA administration.</p><p><b>CONCLUSIONS</b>KA induced seizures can increase granule cell neurogenesis in the immature rat. Most of newly appeared cells migrate from subgranular proliferation zone (SGZ) into granule cell layer, the hilus as well as the molecular layer, and there they can differentiate into granule neurons. These observations also indicate that there is an early developmental resistance to seizure-induced mossy fiber sprouting in the immature brain.</p>

Malnutrition increases hippocampal neurogenesis in the immature rat after status epilepticus / 中华儿科杂志

<p><b>OBJECTIVE</b>Neurogenesis in the dentate gyrus of hippocampus persists in brain of the immature and adult mammalian including human and it can be regulated by physiological and pathological events including nutritional status and seizures. The present study was designed to investigate the potential effects of malnutrition followed by status epileptics on hippocampal neurogenesis in the immature rat.</p><p><b>METHODS</b>Rat pups were divided into 4 groups: malnourished (M), nourished (N), malnourished plus seizures (MS) and nourished plus seizures (NS). The rat pups of group M and group MS were maintained on a starvation regimen from postnatal day 2 (P2) to P18. The status epilepticus of the rat pups in group MS and group NS was elicited by unilateral microinfusion of kainic acid (KA) into the amygdula at P15. Rat pups of the 4 groups were given bromodeoxyuridine (BrdU) intraperitoneally twice daily for 2 days beginning at P17. At P19, the rat pups were killed and the brains were processed for BrdU mitotic labeling combined with double-label immunohistochemistry using early neuron- or glia-specific markers TuJ1 (beta III tubulin) or GFAP (glial fibrillary acidic protein).</p><p><b>RESULTS</b>There were no significant differences in the latent time of seizure between group M and group N [(12.4 +/- 2.6) min vs. (12.1 +/- 2.9) min, P < 0.05]. Histological assessment did not reveal any evidence of hippocampal cell loss after status epilepticus in either group. BrdU-labeled cells were significantly higher in the rats of group MS (374 +/- 18) than group M (303 +/- 20), group NS (312 +/- 24) than group N (269 +/- 18), respectively (P < 0.01). There was also significant difference between group M and group N, group MS and group NS, respectively (P < 0.01). No significant difference was seen between the rats of group NS and group M (P > 0.05). Approximately 60% of BrdU-labeled cells coexpressed TuJ1, and 5% approximately 10% of those co-expressed GFAP.</p><p><b>CONCLUSION</b>Early malnutrition do not alter KA seizure susceptibility and the behavioral manifestations of seizures at P15. Although malnutrition and status epilepticus can increase the proliferation of newly developed cells in the immature rat respectively, malnutrition followed by status epilepticus further increases this proliferation. Furthermore, most of newly developed cells differentiate into early neurons.</p>

Localization assessment of kidney with ectopic ureter:analysis of 58 girls / 中华泌尿外科杂志

Objective To present the means of localizing the kidney with ectopic ureter in order to provide the reliable ground for surgical strategy. Methods Clinical manifestation study,IVU,SPECT imaging and cystoscopy were conducted.All the 58 patints are female with a mean age of 3.4 years.According to the creteria presented in reference,5 were type Ⅰ,42 type Ⅲ,1 type Ⅳ,8 type Ⅴ and 2 type Ⅵ. Results Operative finding revealed the accurate localization and diagnosis rate of IVU has been 95%(40/42) in type Ⅲ ectopic ureter,B-ultrasonograph 27%(12/53),SPECT 37%(6/16).With the combined consideration of imaging procedures and cystoscopy,the accurate localization and diagnosis rate has been 98%(57/58). Conclusions Combined use of imaging procedures and cystoscopy would improve the localization and diagnosis rate.Cystoscopy is the most reliable except in type Ⅲ ectopic ureter.

Study Progress of Infantile Spasms in Molecular Genetics / 实用儿科临床杂志

Infantile spasms is a type of refractory epilepsy syndrome.This epilepsy syndrome is characterized by special tonic spasms,a peculiar set of electroencephalographic findings termed hypsarrhythmia,and arrest of psychomotor development in most patients.The etiology is not clearly understood.Recently,mutations of the arista less related homeobox gene(ARX),cyclin-dependent kinase-like 5(CDKL5)/se-rine/threonine kinase 9 gene(STK9),membrane associated guanylate kinase 2 gene(MAGI2),et al,and abnormal chromosome had been found to be responsible for infantile spasms.In this review,progress of infantile spasms in molecular genetics are discussed.