Characterized by dihydropyrimidinuria, dihydropyrimidinase (DHP) deficiency refers to a rare disorder of pyrimidine degradation, with high phenotypic heterogeneity.The disease-causing gene is DPYS, and less than 40 cases were reported worldwide.Urinary gas chromatography/mass spectrometer (GC/MS) can screen clinically suspected patients, and gene sequencing is the main means of the diagnosis of the disease.This article reviews the pathogenesis, clinical manifestation, genotype and recent research progress of the disease.

Objective To summarize the clinical features of children with viral encephalitis accompa-nied with respiratory failure,and to improve the early diagnosis and treatment. Methods The clinical data of 64 cases with viral encephalitis combined with respiratory failure in our unit from May 2005 to May 2015 were analyzed retrospectively. Results All children were characterized by sudden onset. Among them, 60 cases (93. 7%) had fever,50 cases(78. 1%) had convulsion onset,46 cases(71. 8%) had consciousness disorders, 30 cases(46. 8%) had positive pathological signs. Most of them developed respiratory failure in acute stage. Total 56 cases occurred central respiratory failure,6 cases occurred central respiratory failure with peripheral respiratory failure,2 cases occurred respiratory and circulatory failure. Total 46 cases underwent cerebrospinal fluid examination. Routine biochemical test found 32 abnormal cases,of which 10 cases had intracranial hyper-tension and 19 cases had leukocytosis,and 17 cases had increased protein content. Ten cases were positive in cerebrospinal fluid etiology examination,including herpes simplex virus positive in 8 cases,EB virus positive in 1 case,and coxsackie virus positive in 1 case. There were 6 of 64 cases with abnormal CT scans and 29 of 34 cases with abnormal MRI. The results of EEG examination were abnormal in all patients for the first time. The EEG of 48 cases showed diffuse slow waves-δ activity. EEG examination showed generalized discharges or focal discharges during treatment in 22 cases. Five cases of electrophysiological examination showed cervical spinal cord anterior horn injury. Total 24 cases were complicated with stress ulcer,4 cases with liver damage,6 cases with heart damage,4 cases with renal damage,1 case with lung damage. All cases underwent mechanical ventilation for 2-50 days. Total 33 cases(51. 5%) improved and discharged,14 cases died during hospitaliza-tion,17 cases were given up treatment. Total 25 cases had variety of neurological dysfunctions left. Total 14 cases with epilepsy were followed up for 3 months to 6 years in our department,of which 8 cases were medical-ly intractable epilepsies. Conclusion The children with viral encephalitis complicated with respiratory failure have acute onset,rapid progress,high disability and mortality. Early diagnosis and evaluation,effective mechani-cal ventilation in time,and protecting organ function,help to improve the prognosis.

Objective In this study,we aim to investigate and evaluate the application of peer education on the teaching of medical graduate students and to evaluate the teaching effect,in order to provide the basis for subsequent practice reform.Methods 49 graduate students majoring Internal Medicine-Pulmonology were randomly divided into traditional teaching(24) and peer education groups (25).We chose the primary culture technology of rat distal pulmonary arterial smooth muscle cells to be the teaching contents.For the traditional teaching group,we used the mode of class lecture giving and experimental skills learning under the assistance of the teachers; while in the peer education group,students benefited from the combination of class lecture given by the teacher and the seniors fixed teaching in which seniors help younger students.We selected the experimental operating time,cell purity and the practicing time to reach a standard culture as the evaluation indexes by filling a follow up questionnaire.The SPSS 13.0 was applied to the related data forx2 or t test.Results In the traditional teaching group,the average time to reach three times of standard culture was(3.2 ± 0.5) hour,which was(2.3 ± 0.4) hour in the peer education group.The cell purity was 80.1 ± 3.6％ in the traditional teaching group,while(85.4 ± 5.9)％ in the peer education group.The average practicing time was(6.3 ± 1.0) in the traditional teaching group,while(4.9 ± 0.6) in the peer education group.The peer education group master the teaching content better than the traditional teaching group (P=0.00).95.8％(23/24)of the students in the peer-education group considered the teaching contents simple,which was statistically higher(P=0.00) than traditional group (62.5％,15/24).Meanwhile,95.8％ (23/24)of the students in the peer-education group considered the teaching methods easy to accept,which was also statistically higher(P=0.02) than traditional group(70.8％,17/24).The difference was statistically significant (P=0.02).Conclusion The application effect of peer education is good and there is high degree of acceptance among the students.Besides,peer education accords with the medical postgraduate experiment teaching rules,and can cultivate medical graduate students' spirit of cooperation and communication ability in the process of implementation.

Objective To explore the efficacy of multilevel anterior cervical discectomy and fusion for aged patients with cervical spondylotic myelopathy. Methods 25 aged patients with cervical spondylotic myelopathy were treated by multilevel anterior cervical discectomy and fusion. Japanese Orthopedic Association (JOA) scores were evaluated,clinical results were graded from excellent to poor using Odoms criteria,and the sagittal alignment of fusion segements were measured using Cobb method. Bone fusion and complications was evaluated. Results The final follow up score according to Odoms criteria was excellent in 8 patients ,good in 14 patients,and fair in 3 patients ,with excellent and good rate of 88%. The JOA score at final follow up(7.8) was significantly higher than preoperative(12. 8),with average improvement rate of 54%. At final follow up,bone fusion rate was 100%. Conclusion Multilevel anterior discectomy and fusion for aged patients with cervical spondylotic myelopathy was effective.

Objective To study the molecular mechanism of Bel subtype caused by mutation p.R168W of glycosyltransferase B.Methods Serological test,SSP-PCR and direct sequence the Exon6 and Exon 7 of the ABO gene.Construct a 3D molecular model and predict the structural impact of GTB protein mutations.Results A antigen or B antigen can't be detected on the surface of the propositus' RBC,and only anti-A antibodies were detected in her serum.But serological test indicated her daughter's blood type was a normal B type.SSP-PCR test indicated propositus' ABO gene type is O1 B.By gene sequencing the Exon 6 and Exon 7 of the ABO gene,a ABO Bel allel(c.502C＞T,p.R168W)was discoverd in both the propositus and her daughter.Through the propositus' daughter coexisted Bel gene with normal B gene,her blood type was a normal B type.Conclusions ABO gene c.502C＞T mutations cause Bel phenotypes in patients by reducing the stability of GTB.

Objective To observe the clinical efficacy ofTiaozhong YifeiPrescription combined with Western therapy for treatment of cough variant asthma (CVA) remission. Methods Totally 90 patients with CVA remission were randomly divided into TCM group, Western therapy group and TCM and Western therapy group, 30 cases in each group. TCM group was givenTiaozhong YifeiPrescription, 1 dose per day, morning and evening; Western therapy group was given salmeterol xinafoate and fluticasone propionate powder for inhalation, each 1 suction, 2 times a day, inhalation; a mixture ofTiaozhong YifeiPrescription and xinafoate and fluticasone propionate powder for inhalation was given to TCM and Western therapy group, the same as above, continuous treatment for 12 weeks. TCM syndrome score, EOS, IgE, pulmonary function and safety index were observed in the three groups before and after treatment. The recurrence rate and the number of colds after three-month treatment were observed.Results TCM syndrome scores in the three groups decreased after treatment (P<0.05). There was statistical significance between TCM group and TCM and Western therapy group after treatment (P<0.05). The total effective rate of TCM group was 96.67% (29/30), 100.00% (30/30) of Western therapy group, 76.67% (23/30) of TCM and Western therapy group, with statistical significance (P<0.05). After three-month treatment, 1, 0 and 11 cases relapsed in TCM group, TCM and Western therapy group and Western therapy group, respectively, with statistical significance (P<0.001). Compared with the Western therapy group, the number of colds in the TCM group and TCM and Western therapy group significantly decreased (P<0.05). Compared with before treatment, IgE decreased significantly (P<0.05). There was no significant difference in EOS among the three groups before and after treatment (P>0.05). After treatment, the maximum expiratory flow in TCM and Western therapy groupwas higher than that before treatment and lower than that in the Western therapy group (P<0.01), and the other lung function indexes were not statistically significant (P>0.05). 1 mild adverse reaction was found in the TCM and Western therapy, and no obvious adverse reactions were found in other groups (P<0.05).ConclusionTiaozhong Yifei Prescription has good clinical efficacy for CVA.

Objective: To analyze the clinical characteristics and gene mutations of early-onset epileptic encephalopathy(EOEE) caused by ion channel gene mutation, to identify the etiology, to guide the treatment and to provide the basis for genetic counseling. Methods: The clinical data from 17 children with EOEE caused by ion channel gene mutation and the peripheral blood of the children and their parents were collected from June 2014 to May 2018 at the Department of Neurology, Tianjin Children′s Hospital.Epilepsy gene sequencing was performed by using disease gene targeting second generation sequencing technology.The mutation of pathogenic ion channel gene was found.The confirmed mutations were verified by Sanger sequencing and the source of the mutation was identified. Results: Among 17 case with EOEE, 3 cases had genetic mutation, and 14 cases had denovo mutations.Dravet syndrome was found in 8 cases (47.1%), there were SCN1A gene missense mutation in 5 cases, SCN1A gene nonsense mutation in 3 cases, KCNQ2 gene missense mutation in 1 case (5.9%) and non-specific epileptic encephalopathy in 8 cases (47.1%). SCN2A gene missense mutation, SCN4A gene missense mutation, SCN8A gene missense mutation, KCNQ2 gene missense mutation and KCNH gene missense mutation were found in suspected pathogenic mutations.There were 1 missense mutation out of 5 genes, 1 missense mutation of CACNA1A gene, 1 missense mutation of GRIN2A gene and 1 missense mutation of GRIN3A gene.Seventeen patients were treated with 2 or more antiepileptic drugs, 4 with ketogenic diet and 1 with vitamin B₆ supplementation.During 11 to 96 months of follow-up, seizures were completely controlled in 3 cases (17.6%), decreased in 7 cases (41.2%) by more than 50%, and decreased in 7 cases (41.2%) by less than 50%. Conclusions The clinical phenotypes for children with unexplained EOEE are varied, and gene mutations of ion cha-nnel are most common.Some gene sites are denovo mutations which have not been reported such as missense mutation for 3 case SCN1A gene, 1 case SCN2A gene, 1 case CACNA1A gene, 1 case KCNH5 gene, and nonsense mutation for 2 case SCN1A gene, which have enriched the mutation spectrum of EOEE.

OBJECTIVE: To explore the genetic basis for a child with dihydropyrimidase (DHP) deficiency. METHODS: High-throughput sequencing was carried out for the child. Suspected variants were verified by using Sanger sequencing. RESULTS: The proband was found to carry compound heterozygous variants of the DPYS gene, namely c.1468C>T (a missense variant) and c.1339-1363del (a frameshifting variant). CONCLUSION The compound heterozygous variants of the DPYS gene probably underlie the DHP in this child. Above result has enabled genetic counseling and prenatal diagnosis for his parents.

OBJECTIVETo analyze the incidence trends and characteristics of lymphoma in Beijing, 1998-2010.

METHODSTotal of 9 763 new cases diagnosed as lymphoma in 1998-2010 were extracted from the population-based database of Beijing Cancer Registry, covering population of 151 601 066 person-years. Incidence, age-adjusted incidence, cumulative incidence, truncated incidence and annual percentage change (APC) were calculated. The gender-specific, age-specific and pathology-specific incidence trends were analyzed.

RESULTThe incidence rate of lymphoma was 6.48/100 000 (9 763/150 720 187) during the period of 1998-2010, increased from 3.78/100 000 (410/10 850 626) in 1998 to 8.88/100 000 (1 111/12 518 114) in 2010 with an increasing rate of 136.17% (APC = 5.21%, P < 0.05). The incidence rate of Hodgkin lymphoma increased from 0.25/100 000 (27/10 850 626) in 1998 to 0.47/100 000 (59/12 518 114) in 2010 with an increasing rate of 88.00% (APC = 4.33%, P < 0.05). The incidence rate of non-Hodgkin lymphoma was increased from 2.89/100 000 (314/10 850 626) in 1998 to 5.93/100 000 (742/12 518 114) in 2010 with an increasing rate of 105.19% (APC = 4.19%, P < 0.05) . During the period of 1998-2010, the incidence of lymphoma was 7.78/100 000 (7 125/91 621 898) in urban areas and 4.47/100 000 (2 638/59 098 289) in rural areas, 7.40/100 000 (5 632/76 121 672) in males and 5.54/100 000 (4 131/74 598 518) in females.

CONCLUSIONThe incidence of lymphoma keeps increasing in 1998-2010, and the incidence was higher in males than females, urban areas than rural areas. The incidence patterns of Hodgkin lymphoma and non-Hodgkin lymphoma were different.

Aged ; China ; epidemiology ; Female ; Humans ; Incidence ; Lymphoma ; Male ; Rural Population ; Urban Population

Objective:To explore the clinical characteristics of pediatric glucose transporter type 1 deficiency syndrome (GLUT1 DS), evaluate the efficacy and safety of ketogenic diet therapy (KDT).Methods:Clinical data of 19 children with GLUT1 DS admitted to Children′s Hospital of Fudan University, Tianjin Children′s Hospital, Shenzhen Children′s Hospital, Children′s Hospital of Nanjing Medical University and Jiangxi Provincial Children′s Hospital between 2015 and 2019 were collected retrospectively. The first onset symptom, main clinical manifestations, cerebrospinal fluid features and genetic testing results of patients were summarized, the efficacy and safety of ketogenic diet treatment were analyzed. Results:Among the 19 cases, 13 were males and 6 females. The age of onset was 11.0 (1.5-45.0) months,the age of diagnosis was 54.0 (2.8-132.0) months. Epilepsy was the first onset symptom of 13 cases. Different forms of tonic-clonic seizures were the most common types of epilepsy (7 cases with generalized tonic-clonic seizures, 5 cases with focal tonic or clonic seizures, 4 cases with generalized tonic seizures). Antiepileptic drugs were effective in 4 cases. Paroxysmal motor dysfunction was present in 12 cases and ataxia was the most common one. All patients had different degrees of psychomotor retardation. Among 17 patients received cerebrospinal fluid examination, cerebrospinal fluid (CSF) glucose level was lower than 2.2 mmol/L and CSF glucose/glycemic index was<0.45 in 16 cases, only 1 case presented normal CSF glucose level (2.3 mmol/L) and normal CSF glucose/glycemic index(0.47). SLC2A1 gene mutations were found in 16 patients, missense, frameshift and nonsense mutations were the common types with 5 cases, 5 cases and 3 cases respectively. All 19 patients were treated with ketogenic diet, which was effective in 18 cases in seizure control, 11 cases in dyskinesia improvement and 18 cases in cognitive function improvement. No serious side effects were reported in any stage of KDT.Conclusions:The diagnosis of GLUT1 DS is often late. It is necessary to improve the early recognition of the disease and perform CSF glucose detection and genetic testing as early as possible. The KDT is an effective and safe treatment for GLUT1 DS, but a small number of patients have not response to diet therapy.