Objective:To investigate the factors affecting phenotypes in the patients of methylmalonic acidemia combined with homocysteinemia cblC type with MMACHC c. 609G>A homologous variant. Methods:A retrospective study on the clinical manifestations, complications, treatment, and outcome in 164patients of cblC type with MMACHC c. 609G>A homologous variant was conducted.The patients were diagnosed by biochemical and genetic analysisfrom January 1998 to December 2020. Results:Among the 164 patients, 2 cases were prenatally diagnosed and began treatment after birth. They are 3 and 12 years old with normal physical and mental development. Twenty-one cases were diagnosed by newborn screening. Among them, 15 cases had with normal development. They were treated fromthe age of two weeks at the asymptomatic period. Six cases began treatment aged 1 to 3 months after onset. Their development was delayed. One hundred and forty-one cases were clinically diagnosed. Their onset age ranges from a few minutes after birth to 6 years old. 110 cases had early-onset (78.0%). 31 cases had late-onset (22.0%). Five of them died. 24 patients lost to follow-up. Of the 141 clinically diagnosed patients, 130 (92.2%) with psychomotor retardation, 69 (48.9%) with epilepsy, 39 (27.7%) with anemia, 30 (21.3%) had visual impairment, 27 (19.1%) had hydrocephalus, 26 (18.4%) had feeding difficulties, 7 (5.0%) with liver damage, and 5 (3.5%) with metabolic syndrome. The frequency of hydrocephalus and seizures was significantly higher in the early-onset group. The urinary methylmalonic acid increased significantly in the patients with epilepsy. During the long-term follow-up, the level of plasma total homocysteine in the seizure-uncontrolled group was significantly higher than that in the seizure-controlled group, the difference had a statistical significance ( P<0.05). Conclusion:Most of the patients with MMACHC c. 609G>A homozygous variant had early-onset disease, with a high mortality and disability rate. If not treated in time, it will lead to neurological damage, resulting in epilepsy, mental retardation, hydrocephalus, and multiple organ damage. Pre-symptomatic diagnosis and treatment are crucial to prevent irreversible neurological damage. Neonatal screening and prenatal diagnosis are important to improve the outcome of the patients.

Objective:The clinical manifestations, types of gene mutations, therapeutic effects and prognostic characteristics of 15 children with cblC type methylmalonic acidemia (MMA) and hydrocephalus were analyzed to improve the clinical understanding of the disease, so as to provide a basis for the treatment of the disease.Methods:From April 2015 to January 2019, 15 patients with MMA and hydrocephalus in Department of Pediatric Surgery, Peking University First Hospital were enrolled, and all gene detection showed clbC type.All the 15 patients underwent ventriculoperitoneal shunt.After surgery, the clinical manifestations and imaging findings were applied as the basis to adjust the pressure of the diverter valve appropriately.Clinical data and gene mutation characteristics of 15 children with cblC type and hydrocephalus were retrospectively analyzed, and the therapeutic effects and prognosis were summarized and analyzed as well.Results:There were 8 males (53.3%) and 7 females (46.7%), aged from 2 to 33 months.All the cases were followed up from 11 to 55 months, without death case and serious postoperative complications of hydroce-phalus.The head circumference of 3 cases (20.0%) was in the normal range, 1 case (6.7%) was greater than the normal range, and 11 cases (73.3%) were less than the normal range.Four patients (26.7%) were transferred to the pediatric intensive care unit after surgery.c.609G>A mutation was the most common in this study, with 7 cases (46.7%) of c. 609G>A homozygous mutation, and 5 cases (33.3%) of c. 609G>A heterozygous mutation.Clinical symptoms of intracranial hypertension were relieved or disappeared.The head circumference progressive enlargement was stopped.The anterior fontanelle tension greatly decreased, all " setting-sun" sign of eyes disappeared, and vision loss and hearing loss were better compared with the pre-operation.Four cases (26.7%) displayed normal intelligence and exercise, and 11 cases (73.3%) were left with mild to severe psychomotor retardation.During the follow-up pe-riod, the head CT showed that the ventricle was remarkably narrowed, and interstitial brain edema obviously improved.Conclusions:Ventriculoperitoneal shunt in the treatment of cblC type MMA with hydrocephalus has positive effects.The head circumference of most cblC type MMA with hydrocephalus is less than the normal range.c.609 G>A is the most common mutation in cblC type MMA with hydrocephalus.Perioperative " metabolic crisis" can result in serious complications.

Objective:To analyze the clinical features, genetic characteristics, treatment and follow-up results of patients with hydrocephalus caused by methylmalonic acidemia combined with homocysteinuria, and to discuss the optimal strategies for assessing and treating such patients.Methods:From January 1998 to December 2020, 76 patients with hydrocephalus due to methylmalonic acidemia combined with homocysteinuria in the Department of Pediatrics in 11 hospitals including Peking University First Hospital were diagnosed by biochemical, genetic analysis and brain imaging examination. The patients were divided into operation-group and non-operation-group according to whether they underwent ventriculoperitoneal shunt. The clinical features, laboratory examinations, genotype, and follow-up data were retrospectively analyzed. Data were compared between the two groups using rank sum test, and categorical data were compared using χ 2 test. Results:Among the 76 patients (51 male, 25 female), 5 were detected by newborn screening, while 71 were diagnosed after clinical onset, 68 cases (96%) had early-onset, 3 cases (4%) had late-onset. The most common clinical manifestations of 74 cases with complete data were psychomotor retardation in 74 cases (100%), visual impairment in 74 cases (100%), epilepsy in 44 cases (59%), anemia in 31 cases (42%), hypotonia or hypertonia in 21 cases (28%), feeding difficulties in 19 cases (26%) and disturbance of consciousness in 17 cases (23%). Genetic analysis was performed in 76 cases, all of whom had MMACHC gene variations, including 30 homozygous variations of MMACHC c.609G>A. The most common variations were c.609G>A (94, 62.7%), followed by c.658_660del (18, 12.0%), c.567dupT (9, 6.0%) and c.217C>T (8, 5.3%). Therapy including cobalamin intramuscular injection, L-carnitine and betaine were initiated immediately after diagnosis. A ventriculoperitoneal shunt operation was performed in 41 cases (operation group), and 31 patients improved after metabolic intervention (non-operation group). There was no significant difference in the age of onset, the age of diagnosis, the blood total homocysteine, methionine, and urinary methylmalonic acid concentration between the two groups (all P>0.05). The symptoms of psychomotor development, epilepsy, and visual impairments improved gradually after a long-term follow-up in the operation group. Conclusions:Hydrocephalus is a severe complication of methylmalonic acidemia combined with homocysteinuria. The most common clinical manifestations are psychomotor retardation, visual impairment, and epilepsy. It usually occurs in early-onset patients. Early diagnosis and etiological treatment are very important. Hydrocephalus may improve after metabolic intervention in some patients. For patients with severe ventricular dilatation, prompt surgical intervention can improve the prognosis.

In the past 30 years, with the advancement of functional neurosurgery, neuroelectrophysiology and neuroimaging, deep brain stimulation (DBS), as a new tool for the treatment of dyskinesia, has been considered to have underwent the fastest development in this field.Many patients with dyskinesias have significantly improved their main clinical symptoms after treatment with DBS, some of the improvement are even dramatic.Due to its minimally invasive characteristics, reversibility and adjustability, DBS therapy has been increasingly used in the treatment of dystonia in children.Hereditary dystonia is the most common type of dyskinesia in children, and there is no effective treatment yet.Recently, some dyskinesia at home and abroad centers have carried out DBS treatment for pediatric hereditary dystonia and achieved some encouraging results.Now, the effect of DBS in the treatment of hereditary dystonia in children and the main process of DBS treatment were mainly discussed, and shared the experience based on the clinical practices of Multidisciplinary Collaborative Diagnosis and Treatment Center for Children′s Motor Disorders, Peking University First Hospital.

Objective To summarize the experience of the ventriculoperitoneal shunt in treating children with methylmalonic aciduria combined with hydrocephalus,and to assess the clinical value.Methods From September 2012 to May 2016,a total of 12 patients with methylmalonic aciduria combined with hydrocephalus in Peking University First Hospital were enrolled,including 7 boys and 5 girls.All the 12 patients underwent ventriculoperitoneal shunt.Drug therapy was performed after surgery.The clinical manifestations and imaging findings were used as the basis for adjusting the pressure of the diverter valve appropriately.The clinical condition of patients were evaluated retrospectively.The patients' clinical symptoms,signs,imaging materials,surgical complications and postoperative prognosis were analyzed.Results All the cases were followed up for 3 to 36 months,no death case and no serious postoperative complications of hydrocephalus occurred.Clinical symptoms of intracranial hypertension were relieved or disappeared.The head circumference progressive enlargement stopped.The anterior fontanelle tension decreased significantly.Setting-sun sign of eyes disappeared.One out of 4 cases with convulsion and epilepsy was relieved after the operation.Seven cases of poor vision or vision loss,postoperative visual acuity were improved though not recover to normal eyesight.One case of the children with hearing loss,postoperative hearing recovered.During the follow-up period,the head CT showed that the ventricle was narrowed significantly,interstitial brain edema improved obviously.Conclusion Ventriculoperitoneal shunt is a effective method for treating children with methylmalonic aciduria combined with hydrocephalus,which is beneficial for patients with these diseases.

The information commons concept-based stereoscopic resources support system for academic library with brand-new connotations and its application were proposed according to the increasing development and expansion of informationization, networking and digitization in different social fields, the significant change in disseminating methods of information resources, and the need of readers for library service.

SUMMARY Hemophilia A is aninherited bleeding disorder, lack of coagulation factorⅧ( FⅧ) , and if combined with intracranial malignant tumor, the operation risk is very high. Department of Pediatric Sur-gery in Peking University First Hospital used coagulation factor replacement therapy, succeeded in the operation of 2 cases of intracranial malignant tumor with hemophilia A in children, with no abnormal bleeding events. The establishment of the multi subject cooperation group before operation, good preoper-ative preparation, enough alternative factors, and close postoperative monitoring, are the key to the suc-cessful treatment.

A method to assess library-holding journals according to their weighted citations was proposed in light of the actual needs of users for core journals, the use of library-holding journals and references by authors in different orders of precedence.The Western journal of rheumatology, highly cited by authors of Second Military Medical U-niversity, were assessed using this method, showing that this method is better than the citation analysis-based tra-ditional method in assessment of journals.

Objective To analyze the categories of co-existed nervous system anomalies in children with meningomyelocele in order to consummate the treating strategy for meningomyelocele.Methods Sixty-nine children who had complete clinical data diagnosed as meningomyelocele in Department of Pediatric Surgery,Peking University First Hospital from Jan.2005 to Jun.2013,were retrospectively analyzed.Preoperative spinal MRI was routinely performed.Ultrasonagraphy,CT,MRI or combination of the 2 measures were adopted to evaluate the brain.Microscopically excision of the sac,exploration of the spinal canal,brisement of the tethered cord and meningomyelocele repair were routine operation procedures.Other lesions detected during operation were treated accordingly.MRI findings and intraoperative findings were also compared.Results Preoperative spinal MRI found 59 cases of cone bit,24 cases of syringomyelia,20 cases of mild syringomyelus,14 cases of diastematomyelia,6 cases of intraspinal cyst,6 cases of intraspinal lipoma.Nineteen cases of hydrocephalus were diagnosed by iconography,among which 5 cases complicated with caudal herniation of cerebellar tonsils.Seventeen cases of diastematomyelia,8 cases of intraspinal lipoma,6 cases of intraspinal cyst were detected and treated during operation.Three cases of intraspinal lipoma and 3 cases of osseous diastematomyelia were ignored by preoperative MRI reports.Two cases of intraspinal epidermoid cyst were misdiagnosed as general cyst.One case of teratoma who was not found on MRI was detected by operation and resected.Syringomyelus or syringomyelia was found in all the children complicated with hydrocephalus.Sixty-one cases(88.4％) among the 69 cases complicated with other nervous system anomalies.All of patients were followed up for 4-71 months,averaged 23.8 months.All of patients had no new symptom.Conclusions Children with meningomyelocele often complicate with multiple nervous system anomalies.Preoperative brain and entire spinal iconography,together with thorough intraoperative exploration,are very important so as to avoid omission the co-existed lesions during operation.

Aim To investigate whether Ca~(2+)/calmodulin-dependent kinase Ⅱ(CaMKⅡ)contribute to tumor necrosis factor α(TNF-α)-induced cardiomyocyte hypertrophy.Methods The protein content was assayed with Lowry's method.The cardiomyocytes volumes were measured by computer photograph analysis system.The protein synthesis was assayed with[~3H]-lencine incorporation method.[Ca~(2+)]_i transient was measured by Till image system by cell-loading Fura-2/AM.The expression of CaMKⅡδ_B was determined by Western blot.Results ① TNF-α significantly induced the increase of protein content, [~3H]-leucine incorporation and cell size;These responses were significantly suppressed by KN93, a selective CaMKⅡ inhibitor.② TNF-α increased the amplitude of the spontaneous Ca~(2+) transients in cultured ventricular myocytes from the neonatal rat;CaMKⅡ inhibitor KN93 can suppress the elevation induced by TNF-α.③ TNF-α significantly increased the expression of CaMKⅡδ_B.Concluslon CaMKⅡ signal pathway are involved in TNF-α-induced cardiomyocyte hypertrophy in rats.