Objective: To investigate the genotype and phenotype of children with KCNA2 gene related developmental and epileptic encephalopathy (DEE). Methods: Clinical data including the manifestations and electroencephalogram of 8 children with KCNA2 variants treated in the Department of Pediatrics, Peking University First Hospital from March 2017 to June 2019 were collected and analyzed retrospectively. Results: Among the 8 epileptic patients with KCNA2 variants, 5 were males and 3 were females. The age of onset was from 1 day to 11 months. The age at last follow-up ranged from 4 months to 86 months. Two variants including c.1214C>T (loss-of-function) and c.1120A>G (gain-and loss-of-function) were identified. The variant of c.1214C>T was found in six patients (case 1-6). For these patients, the age of onset was from 5 to 11 months and they were characterized by multiple seizure types. All had focal seizures and had normal development before seizure onset with developmental regression after seizure onset. The first electroencephalogram showed epileptic discharges in Rolandic region in two, epileptic discharges in Rolandic region combined with generalized discharge in one, generalized discharge with posterior predominance in two (combined with or transferred to Rolandic region during the course) and epileptic discharges in posterior region combined with generalized discharge in one. And in 5 of them the Rolandic discharges developed into epileptic electrical status (ESES) during sleep. All the six patients were still treated with a combination of multiple antiepileptic drugs. Two of them had seizure controlled at 80 months and 68 months, respectively. The variant of c.1120A>G were identified in two of eight patients (case 7 and 8) and they had seizure onset on the 1st day after birth. Their epileptic seizures were frequent and difficult to control. They had remarkably developmental delay and microcephaly since birth. One case (case 8) had a wide forehead. They had frequent seizures up to the last follow-up. In case 7, the early electroencephalogram showed epileptic discharges in temporal region, and interictal electroencephalogram at 3 months of age showed multifocal discharge with posterior and temporal region predominance. In case 8, the early electroencephalogram was normal and electroencephalogram showed burst suppression at 2 months of age, and it developed epileptiform discharge in posterior region at 1 year of age. Conclusions KCNA2 gene variants can lead to DEE with multiple seizures types. Among them, loss-of-function c.1214C>T is the most common, and these patients have seizure onset at infancy with Rolandic discharges tended to develop into to ESES pattern. The variant of c.1120A>G is a gain-of- and loss-of-function variant, patients with c.1120A>G have seizure onset in neonatal period, the phenotype overlaps with the former but is more severe.

In this paper, Gaussian pixelate Chinese character processing software is designed, and HMD is used to realize the recognition experiment for pixelate Chinese characters based on simulated prosthetic vision. The structure of recognition system, software design and the experiment for determining Gaussian width (sigma) are presented. It is shown that when sigma is 0.235, the recognition program is the best.
Equipment Design ; Image Processing, Computer-Assisted ; Language ; Prostheses and Implants ; Software Design ; Visual Perception

This paper introduces the current development and challenges of vision prosthesis.
Prosthesis Design ; Visual Prosthesis

Objective To explore the therapeutic effects and adverse reaction of high-dose Diazepam (DZP) in patients with electrical status epilepticus during sleep (ESES).Methods Nine patients in the Outpatient of the Department of Pediatrics,Peking University First Hospital from October 2016 to May 2017 with ESES were treated with high-dose DZP.Oral DZP was administered in a dose of 0.75-1.00 mg/kg(maximum:40 mg) during the first night followed by 0.5 mg/(kg · d) (maximum:20 mg) from the second night for 1-3 months and tapered over next 1-3 months.The seizures,electroencephalogram (EEG) changes and adverse reactions were observed before and after DZP treatment.Results Six of 9 patients were male and 3 were female.The age of onset was ranged from 1 year and 6 months to 10 years.Benign childhood epilepsy with central temporal spike was diagnosed in 5 cases,epileptic encephalopathy with continuous spike-and-wave during sleep in 1 case,and ESES related epilepsy in 3 cases.Age of onset DZP treatment ranged from 4 years and 4 months to 12 years,and the duration of DZP treatment was ranged from 1 to 5 months (1 case only for the first night).The follow-up interval was 6-12 months.The efficiency of DZP on seizures:intent effective in 5 patients,effective in 2 patients and ineffective in 2 patients,and the effective rate was 78％ (7/9 cases).The efficiency of DZP on EEG (1 month after DZP treatment):intent effective in 2 patients (EEG normalized),effect in 3 patients and no effect in 2 patients,and the effective rate was 71％ (5/7 cases),while 2 patients did not receive EEG examination.Four of 7 patients (57％) with intent effect and effective of DZP on seizures had seizures relapse during drug reduction and after drug withdrawal,and the EEG deteriorated simultaneously.Adverse reactions of DZP included 3 patients (33％) with adverse reactions,bed-wetting in 2 patients and snoring on the first night in 1 patient who withdrew DZP later.Conclusions The high-dose of DZP has a certain effect on seizures control and ESES suppression in patients with ESES,but also has a certain recurrence rate.The adverse reactions are mild and self-limiting.High-dose DZP treatment could be a choice for refractory patients with ESES to alleviate disease.

Objective: To investigate the electroclinical findings in epilepsy children with epileptic negative myoclonus (ENM) restricted to the lower limb as the first seizure type. Methods: Each retrieved electroencephalogram record performed between March 2011 and March 2018 at the Department of Pediatrics of Peking University First Hospital was searched with "midline" . There were 302 records of 175 patients with "benign" or "functional" midline spikes. A retrospective review of each patient′s hospital record was performed. Thirteen patients had ENM restricted to the lower limb as the first seizure type. The clinical and electroencephalogram characteristics of them were analyzed. Results: Thirteen patients manifested ENM restricted to the lower limb as the first seizure type, diagnosed as benign childhood focal epilepsy with vertex spikes (BEVS). Six patients had ENM as the first and only seizure type during the short-time follow-up. Among them, there were 1 male and 5 females. The age at seizure onset was (2.5±0.7) years. One of them had electrical status epilepticus during sleep (ESES) identified on electroencephalogram at theage of 4 years and 8 months. The last follow-up age was (3.8±1.5) years. The remaining 7 patients developed nocturnal focal motor seizures. Among them, there were 4 males and 3 females. The age at seizure onset was (3.5±0.7) years. Two of them were diagnosed as BEVS evolving into benign childhood epilepsy with centrotemporal spikes (BECTS) and 5 were diagnosed as BEVS concurring with BECTS. The age at focal seizures was (4.1±0.6) years. The interval ranged from 1 month to 1 years. Six of 7 patients had electrical ESES with the age of (5.2±1.0) years. All had developmental regression, further diagnosed as atypical benign partial epilepsy (ABPE). The median age at last follow-up was 5.9 years. Five of 13 patients had repeated electroencephalogram records at our apartment, showing that epileptiform discharges in midline regions were significantly reduced either in frequency or amplitude with the improvement of ENM restricted to the lower limb and that independent epileptiform discharges in Rolandic regions from midline regions were noticed with the onset of nocturnal focal seizures. Conclusions ENM restricted to the lower limb has a close association with vertex (midline) epileptiform discharges. ENM restricted to the lower limb as the first seizure type is a peculiar phenomenon of BEVS. Some patients could evolve into BECTS or overlap with BECTS, and further into ABPE. The age of seizure onset in BEVS with ENM restricted to the lower limb as the first symptom is a little earlier than in BECTS. Ignorance of the close association between midline spikes and ENM restricted to the lower limb may lead to misdiagnosis of these patients.

OBJECTIVETo investigate clinical and molecule genetics features of four Ph-positive leukemia patients characterized by pericentric inv(9)(p22q34) with the der(9)t(9;22)(q34;q11).

METHODSCytogenetic analysis was carried out on bone marrow directly or after short-period culture. R banding was used for karyotype analysis. BCR/ABL fusion gene was detected with interphase fluorescence in situ hybridization (FISH), and chromosome painting was carried out using specific probes. RT-PCR was used to detect BCR/ABL chimeric transcripts.

RESULTSOne patient with acute myeloid leukemia (AML) presented three clones, which included one with a normal karyotype, one with t(9;22)(q34;q11), and one with inv(9)(p22q34) involving the der(9)t(9;22) and additional t(8;12)(q12;p11). The inv(9)(p22q34) has always co-occurred with der(9)t(9;22)(q34;q11) accompanied by der(22)t(9;22)(q34;q11) in all metaphases from the three patients with chronic myeloid leukemia (CML). B3a2 transcript was detected in all patients by RT-PCR. Inv(9)(p22q34) was found in both CML and AML, and was associated with poor prognosis.

CONCLUSIONInv(9)(p22q34) is a novel, rare, but recurrent secondary chromosomal abnormality for Ph-positive leukemia. Leukemia with der(9)t(9;22) and inv(9)(p22q34) has unique clinical and laboratory characteristics.

Adult ; Chromosome Inversion ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 9 ; Female ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; Leukemia, Myeloid, Acute ; genetics ; Male ; Middle Aged ; Translocation, Genetic

OBJECTIVE: To explore the genetic basis for a child with mental and motor retardation, language impairment, facial dysmorphism and epilepsy. METHODS: Whole exome sequencing was carried out to detect pathogenic variant in the proband, and candidate variant was selected based on his phenotype. Sanger sequencing was used to verify the variant in the proband, his parents and other family members. RESULTS: The proband was found to carry a frameshifting mutation of MBD5 gene, namely c.2217delT (p.F739Lfs*6), which was inherited from his mother and unreported previously. Sanger sequencing confirmed that his brother carried the same mutation with a similar phenotype. His mother also had poor language expression when she was young, in addition with poor academic performance, though she could do some housework and had no history of convulsion. CONCLUSION A novel pathogenic variant of the MBD5 gene was discovered, which has enriched the mutational spectrum of the MBD5 gene. Above discovery has enabled genetic counseling and prenatal diagnosis for the family.
Child ; DNA-Binding Proteins/genetics* ; Female ; Humans ; Intellectual Disability/genetics* ; Male ; Mutation ; Pedigree ; Phenotype ; Pregnancy ; Whole Exome Sequencing

Objective To investigate the effect of statin pretreatment on collateral circulation and prognoses of patients with cardiac large artery occlusive stroke.MethodsFifty-three patients with cardiac large artery occlusive stroke admitted to our hospital from January 2016 to July 2019 were selected. All patients had unilateral middle cerebral artery occlusion. DSA was used to evaluate the collateral flows, and the differences of collateral flows and prognoses in patients took statins before onset were compared with those did not take statins.ResultsAs compared with patients did not take statins, patients took statins had higher incidences of diabetes and coronary heart disease, lower content of low density cholesterol, higher proportion of patients with good collateral circulation (grading 3 to 4), and lower modified Rankin scale scores 3 months after surgery, with statistically significant differences (P< 0.05). Multivariate Logistic regression analysis showed that percentage of patients took statins was independent factors affecting collateral flow in patients with cardiac arterial occlusive stroke(OR=5.000, 95％CI: 1.136-22.006,P=0.033).ConclusionIn patients with cardiac large artery occlusive stroke, statin pretreatment could improve collateral flow and clinical prognoses.

Objective To compare biomechanical performance of four-part proximal humeral fractures fixed by novel locking plate or by AO-PHILOS plate. Methods The finite element fixation models of both the novel locking plate and AO-PHILOS plate for four-part proximal humeral fractures were established, respectively. The maximum Von Mises stress and displacement under 4 different functional positions of shoulder abduction in the two fixation models were compared by finite element analysis. Results The maximum displacement in shoulder abduction of 0°,30°,60°,90° were 6.644, 7.079, 5.850, 3.005 mm, respectively, in novel locking plate fixation model, and 6.293, 6.826, 5.774, 3.023 mm, respectively, in AO-PHILOS plate fixation model. Since the maximum displacements in both fracture fixation models were similar, it indicated that there was no significant difference in the stability for fixing proximal humeral fracture. The maximum Von Mises stress in shoulder abduction of 0°,30°,60°,90°were 1 033.0, 904.1, 888.1, 1 062.0 MPa in novel locking plate fixation model, while in AO-PHILOS plate fixation model, it showed 743.1, 692.4,486.4,393.5 MPa, respectively. During the process of shoulder abduction, the total stress in both fracture fixation models gradually decreased, but the new locking plate decreased in a larger range, showing an obvious stress dispersion. Conclusions Both the novel locking plate and AO-PHILOS plate can be used as internal fixation treatment for complex four-part proximal humeral fractures with no significant difference in stress distribution, and both showing a stable fixation effect. For fixing proximal humeral fractures with osteoporosis combined with the great and less tuberosity, the novel locking plate has an advantage over AO-PHILOS plate due to its unique anatomical wings and better fixing effect.

OBJECTIVETo examine the incidence and clinical significance of NPM1 mutations in childhood acute myeloid leukemia (AML) patients.

METHODSNPM1 mutations of 70 newly diagnosed childhood AML were detected by high resolution melting (HRM) analysis on the LightCycler 480. The incidence and clinical significance were analyzed.

RESULTSNPM1 mutations were identified in 32 (45.7%) of the 70 AML children. There was no significant difference in clinical characteristics between patients with or without NPM1 mutation, but patients with NPM1 mutation had a higher platelet count (P = 0.013). There was also no significant difference in NPM1 mutation between normal and abnormal karyotype groups. In AML-ETO or PML-RARα positive groups, the incidence of NPM1 mutations was significant lower (P = 0.048). There was no significant difference in response rates after induction therapy (P = 0.217), but the complete remission (CR) rate was higher in the NPM1-mutated group (81.3%). There was a trend toward higher event-free survival (EFS) and overall survival (OS) rates in the NPM1 mutated patients than that in wild NPM1 patients (EFS = 53.8% vs 41.4%, OS = 52.7% vs 39.2%), but the difference was not statistically significant (P = 0.374 and 0.380).

CONCLUSIONNPM1 mutations were relatively common in our cohort of AML patients. There was no significant difference in clinical characteristics between patients with and without NPM1 mutation. The NPM1 mutation patients group seemed to have better therapy response, but the difference was not statistically significant.

Child ; Disease-Free Survival ; Humans ; Leukemia, Myeloid, Acute ; genetics ; Mutation ; Nuclear Proteins ; genetics ; Prognosis