[Meta-analysis of the effects of statins on the risk of chronic liver disease and hepatocellular carcinoma].

Objective: To evaluate the relationship between the application of statins and the risk of hepatocellular carcinoma in patients with chronic liver disease. Methods: PubMed, the Cochrane Library, EMBASE, Web of science, WeiPu, Wanfang Med online, and China National Knowledge Infrastructure database were searched. The literatures about statins and the risk of hepatocellular carcinoma in patients with chronic liver disease were collected, with a search deadline of February 2020. Two researchers independently conducted literature screening, data extraction, quality evaluation and proofreading. RevMan5.3 software was used for data analysis. The I2 combined with χ (2) test was used to evaluate the heterogeneity. Funnel plots were used to evaluate the publication bias of the included literature. Results: A total of 12 articles were included. Statins application had significantly reduced the risk of hepatocellular carcinoma in patients with chronic liver disease (OR = 0.50, 95% CI: 0.43~0.58, P < 0.01). Subgroup analysis showed that statins had reduced the incidence rate of hepatocellular carcinoma in patients with chronic hepatitis B (OR = 0.56, 95% CI: 0.47~0.66, P < 0.01) and chronic hepatitis C (OR = 0.56, 95% CI: 0.45~0.71, P < 0.01). Lipophilic statins had significantly reduced the risk of chronic liver disease development to hepatocellular carcinoma (OR = 0.48, 95% CI: 0.39~0.59, P < 0.01), but hydrophilic statins did not reduce the incidence rate of chronic liver disease development to hepatocellular carcinoma, and the difference was not statistically significant (OR = 0.64, 95% CI: 0.36~1.14, P = 0.13). Conclusion: Statins can effectively reduce the risk of hepatocellular carcinoma development in patients with chronic liver disease, including chronic hepatitis B and C. Among them, the lipophilic statins have a significant preventive effect on the development of chronic liver disease to hepatocellular carcinoma, but hydrophilic statins have no obvious effect.

[Analysis of caries experience and the dental treatments under general anesthesia in 103 cases of children with autism spectrum disorders].

Objective: To compare the caries experience and the kinds of dental treatment between children with autism spectrum disorders (ASD) and children without systemic disease who were all treated under general anesthesia. Methods: Totally 103 children with ASD who received dental treatments under general anesthesia in 13 professional dental hospitals around China from April to November 2016 were included in the present study. A group of 97 children without systemic disease, according to the age, gender and application propensity score matching method, were chosen as controls, who received dental treatments under general anesthesia between January 2015 to November 2018 in the same hospitals as the children with ASD. Decay missing filling tooth (DMFT/dmft, DMFT for permanent teeth and dmft for primary teeth) indices of two groups of children and the contents of the dental treatments under general anesthesia were analyzed. Results: No significant difference of DMFT/dmft index ï¼»M (Q 25, Q 75)ï¼½ was found between children with ASD group ï¼»0 (0, 3)/11(8, 14)ï¼½ and control group ï¼»0 (0, 3)/9(7, 13)ï¼½ (P>0.05). The average number of dental treatments under general anesthesia and the average number of endodontic treatment in children with ASD were 13 (11, 15) and 3 (2, 6) teeth respectively, while those in the control group were 12 (9, 14) and 2 (1, 4) teeth respectively, the differences were statistically significant (P<0.01, P<0.05). Conclusions: No significant difference was found between children with ASD and the normal controls who receive dental treatments under general anesthesia in DMFT/dmft index, but the treatment needs of children with ASD is relatively higher, and their tooth decay is relatively severer.

[Effects of ilioinguinal composite tissue flaps in repairing skin and soft tissue defects on hand or foot].

Objective: To explore the effects of ilioinguinal composite tissue flaps in repairing skin and soft tissue defects on hand or foot and reconstructing the flexion and extension functions of wrist, finger, ankle, and toe. Methods: From February 2012 to March 2018, 4, 5, and 3 patients (11 males and 1 female, 23-62 years old) with skin and soft tissue defects on hand or foot were admitted to Traditional Chinese Medicine Hospital of Zhongmu County of Henan Province, Henan Armed Police Corps Hospital, and the Affiliated Jiangyin Hospital of Medical College of Southeast University, respectively. Five patients had hand defects, and 7 patients had foot defects. The areas of skin and soft tissue defects after debridement were 10 cm×8 cm-15 cm×10 cm. The ilioinguinal composite tissue flaps were designed and resected according to the wound area and the length of tendon defects, and the areas of flaps were 10 cm×8 cm-15 cm×12 cm. According to the specific condition of the recipient area, the superficial iliac circumflex artery in the tissue flap was reconstructed by end-to-side anastomosis in 2 patients and end-to-end anastomosis in 1 patient with ulnar artery, end-to-side anastomosis in 4 patients with the dorsal foot artery, end-to-side anastomosis in 2 patients with the posterior tibial artery, and end-to-end anastomosis in 1 patient with the external tarsal foot artery in the recipient area, and the superficial epigastric artery in the tissue flap was reconstructed by end-to-side anastomosis in 1 patient with the radial artery and end-to-end anastomosis in 1 patient with the ulnar artery in the recipient area. The donor sites were sutured directly or repaired with medium split-thickness skin grafts. The survival of tissue flap after the operation and the appearance, texture, and the two-point discrimination distance of the tissue flaps during follow-up were observed. The hand function and foot function were evaluated by the total active movement standard of hand and the Maryland foot score standard, respectively. Results: All the tissue flaps in 12 patients survived. During follow-up of 6-36 months after operation, the tissue flaps were slightly bloated, with linear scars at the junction site in the recipient area, and the two-point discrimination distances of the tissue flaps were 15-22 mm. The hand function was excellent in 3 cases, good in 1 case, and fair in 1 case, and the foot function was excellent in 4 cases, good in 2 cases, and fair in 1 case, and all the patients were satisfied with the function and appearance of hand or foot. Conclusions: The ilioinguinal composite tissue flaps can repair the hand and foot wounds and reconstruct the flexion and extension functions of wrist, finger, ankle, and toe at the same time, which is an effective method to repair this kind of defects.

[Differences in the bone marrow histopathology between pediatric acquired aplastic anemia and refractory cytopenia of childhood].

Objective: To study the differences in the bone marrow histopathology between acquired aplastic anemia (AAA) in children and refractory cytopenia of childhood (RCC) to facilitate their diagnoses and differential diagnosis. Methods: The clinical data and bone marrow biopsies of the RCC and AAA cases diagnosed from January 2008 to December 2018 in Xinhua Hospital, Shanghai Jiaotong University School of Medicine and Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University School of Medicine were analyzed. Results: A total of 71 AAA and 79 RCC cases were analyzed. There were 52 males and 19 females, age ranged 1.0-15.0 years (median, 8.9 years) in the AAA group, and 53 males and 26 females, age ranged 0.5-16.0 years (median, 5.0 years) in the RCC group. All the biopsy specimens of AAA patients had severe hypocellularity; the cellularity of 88.7% (63/71) specimens was under 5.0%, and 11.3%(8/71) was 5%-24%. None of the AAA specimens showed any dysplastic change. All the biopsy specimens of RCC patients had hypocellularity, including 94.9%(75/79) of the specimens with a cellularity of 5%-50%. All of the RCC specimens showed a patchy distribution of hematopoiesis. A dysplastic change of erythroid cells and micromegakaryocytes was found in 40.5% (32/79) and in 60.8% (48/79) of the RCC cases, respectively. Conclusions: The degree of hypocellularity, the distribution pattern of hematopoiesis, the cell composition and localization of erythroid cell clusters and the appearance of micromegaryocytes could help the diagnosis and differential diagnosis of AAA and RCC.

[Clinical phenotypes of epilepsy associated with GABRA1 gene variants].

Objective: To summarize the clinical phenotypes of epilepsy in patients with GABRA1 gene variants. Methods: A total of 11 epileptic patients (4 boys and 7 girls) who were treated in the Department of Pediatrics, Peking University First Hospital from March 2016 to July 2019 and detected with GABRA1 gene heterozygous pathogenic variants by targeted next-generation sequencing were enrolled. The features of clinical manifestations, electroencephalogram (EEG), and neuroimaging were analyzed retrospectively. Results: A total of 11 epileptic patients carried GABRA1 gene pathogenic variants, of whom 10 were de novo variants and the other one was inherited from the patient's mother. Two patients had the same variants. Six variants were novel. Ages at seizure onset ranged from 3 to 14 months, and the median age was 8 months. The seizure was first observed within 1 year in 10 patients and beyond 1 year of age in 1 patient. Multiple seizure types were observed, including focal seizures in 10 patients, generalized tonic clonic seizures (GTCS) in 3 patients, myoclonic seizures in 3 patients, and epileptic spasm in 2 patients. There were 5 patients with multiple seizure types. Sensitivity to fever was observed in 9 patients, among whom 6 patients had a history of status epilepticus. Two patients had photoparoxysmal response. Five patients had abnormal EEG background, and 6 patients had abnormal discharges in EEG during interictal phase. Brain magnetic resonance imaging (MRI) was normal in all patients. Developmental delay in various degrees was present in 9 patients. Among the 11 patients, Dravet syndrome was diagnosed in 5 patients, West syndrome in 2 patients, undiagnosed early-onset epileptic encephalopathy in 1 patient, and focal epilepsy in the other 3 patients. The ages at the last follow-up ranged from 8 months to 12 years. During follow-up, 8 patients were seizure-free for 6 months to 8 years, and 1 patient had discontinuation of medication. Conclusions: In epilepsy associated with GABRA1 gene variants, de novo pathogenic variants are more common than inherited. Most epilepsy caused by GABRA1 gene variants occurs in infancy. Most patients have multiple seizures and focal seizures are common. Most patients have a comparatively favorable prognosis, but they may still have varied degrees of developmental delay.

[Clinical characteristics of PCDH19-female limited epilepsy].

Objective: To analyze the clinical characteristics of patients with PCDH19-female limited epilepsy (PCDH19-FE). Methods: The clinical data of 60 female epilepsy patients with PCDH19 gene heterozygous variations at the Department of Pediatrics, Peking University First Hospital from October 2007 to December 2018 were collected and analyzed retrospectively, their clinical manifestations, accessory examination and follow-up treatment were summarized. Results: Data of a total of 60 cases of PCDH19-FE were collected. The seizure onset occurred between 4 and 42 months of age (median: 11 months of age). Focal seizures occurred in 47 patients (78%), generalized tonic-clonic seizures (GTCS) occurred in 30 patients (50%), and other rare types of seizures included atypical absence, myoclonic, clonic, tonic, and atonic seizures. Two or more seizures types existed in 24 patients (40%), and seven patients (12%) had attacks of status epilepticus. Sensitivity to fever was observed in 47 out of them (78%) and clustering of seizures as found in all patients. During the interictal phase, focal discharges were monitored in 22 cases (22/45, 49%), multifocal discharges in 12 cases (12/45, 27%), widely discharging in 2 cases (4%), and both focal and widely discharging in 9 cases (20%). Clinical seizures were detected in 30 patients during the electroencephalogram (EEG) recording, including focal seizures in 22 cases, GTCS seizures in 8 cases, tonic seizure in three cases, myoclonic seizure followed by GTCS in one case, and two types of seizures in four cases. Before seizure onset, 57 patients had normal development and three patients had delayed language development. After seizure onset, varied degrees of intelligence disability were present in 38 cases (63%), language delay in 36 cases (60%), and gait instability in 10 cases (17%). Autistic features occurred in 17 cases (28%); and other behavioral problems like learning difficulties, personality, or emotional disorders existed in 33 cases (55%). Age at last follow-up ranged from one year and 3 months to 22 years and 3 months of age, 17 patients (28%) were seizure-free for more than 2 years (5 to 22 years at the last follow-up). The efficiency of antiepileptic drugs were 65% (33/51) in sodium valproate, 63% (27/43) in levetiracetam and 59% (20/34) in topiramate. Conclusions: The clinical features of PCDH19-FE are characterized by clustering of seizures, focal seizures in most cases, sensitivity to fever mostly, focal discharges principally in EEG, varied degrees of intellectual disability or movement disorder, combined with autism spectrum disorders in partial and high efficiency in sodium valproate or levetiracetam treatment.

[Clinical features of epilepsies associated with GABRB2 variants].

Objective: To analyze the clinical phenotypes of epilepsies in children with GABRB2 variants. Methods: Data of 8 epileptic patients with heterozygous GABRB2 variants were retrospectively collected at the Department of Pediatrics, Peking University First Hospital from April 2016 to December 2018. The clinical, electroencephalographic, neuroimaging characteristics, therapeutic and follow-up were analyzed. Results: Eight patients (4 boys, 4 girls) with heterozygous GABRB2 gene pathogenic variants were enrolled. Eight patients had different GABRB2 variants, among whom 2 patients inherited the variants from either parent, and the other 6 patients had de novo variants. Seven variants were novel. Ages at seizure onset ranged from 1 day to 22 months after birth, and the median age was 6 months. The seizure was first observed within one month of age in 2 patients, 1-6 months in 2 patients, 7-12 months in 2 patients, and beyond 1 year of age in 2 patients. Multiple seizure types were observed, including focal seizures in 6 patients, generalized tonic clonic seizures (GTCS) in 4 patients, myoclonic seizures in 3 patients, and epileptic spasm in 2 patients. Developmental delay was present in 6 patients. In 8 patients, Dravet syndrome was diagnosed in 3 patients, febrile seizures plus and West syndrome in 2 patients, respectively, Ohtahara syndrome in 1 patient. Six patients had epilepsy with fever sensitivity, and status epilepticus developed in all these patients. The ages at the last follow-up ranged from 8 months to 11 years, and the follow-up data showed that 5 patients were seizure-free, and 2 patients still had seizures, and 1 patient died of recurrent status epilepticus complicated with fungal infection. Conclusions: Epilepsies associated with GABRB2 variants were characterized by an onset in infancy, and the clinical features were heterogenous in seizure types and severities. Most patients had multiple seizures with fever sensitivity, and status epilepticus was common. Their seizures were easily induced by fever or infection. Additionally, the majority of the patients had varying degrees of developmental delay.

[Study on correlation between serum 25-hydroxyvitamin D3 level and esophageal variceal bleeding in cirrhotic patients].

Objective: To explore the correlation between serum 25-hydroxyvitamin D3 (25[OH]D(3)) levels and esophageal variceal bleeding (EVB) in cirrhotic patients. Methods: Eighty-three cases with liver cirrhosis hospitalized from November 2016 to January 2017 were collected. The patients were divided into bleeding group (51 cases) and non-bleeding group (32 cases) depending on the presence or absence of bleeding under gastroscopy. Serological tests were performed on both groups, including hemoglobin (Hb), albumin (ALB), alkaline phosphatase (ALP),γ-glutamyltransferase (GGT), interleukin-6 (IL-6), and 25-hydroxyvitamin D3 (25[OH]D(3)). Both groups were analyzed by univariate analysis. The differences between both groups were compared by t-test, after normality test. The other variables were compared by Mann-Whitney U test. The correlation between the relevant variables and EVB were analyzed by Spearman's rank correlation and a multivariate analysis. Cases with primary biliary cirrhosis were relatively low in number (four cases in bleeding group, accounting for 8%, 10 cases in non-bleeding group, accounting for 31%). The effects of ALP and GGT on serum 25(OH)D(3) level were analyzed by stratified analysis. Moreover, ALP and GGT levels were divided into two and three groups: < 140 U/L and >140 U/L and < 30 U/L, > 30 U/L, and ~≤60 U/L. Results: Bleeding group had low levels of hemoglobin (t= -2.827,P= 0.005), alkaline phosphatase (t= -3.097,P= 0.002), gamma-glutamyltransferase (t= -2.292,P= 0.022), and 25(OH)D(3) (t= -3.134,P= 0.002) than non-bleeding group. Both groups (P> 0.05) had similar levels of albumin, interleukin-6, AAR, and FIB-4. Logistic regression analysis showed that 25(OH)D(3), alkaline phosphatase and hemoglobin were independent risk factors for EVB. Spearman's correlation coefficient analysis showed that 25(OH)D(3)was significantly positively and negatively correlated with interleukin-6 (r= 0.306,P= 0.005) and albumin (r= -0.327,P= 0.003). Stratified analysis showed that serum 25(OH)D(3) level was lower in ALP≤140U/L group and the bleeding group, and the difference was statistically significant than non-bleeding group (P= 0.007), while the serum level of 25(OH)D(3)was decreased in both groups for alkaline phosphatase > 140 U/L group, and the difference was not statistically significant (P= 0.051). Furthermore, in the GGT > 60 U/L group, the serum level of 25(OH)D(3)was significantly lower in the bleeding group, and the difference was statistically significant in non-bleeding group (P= 0.003), while the difference between the two groups was not statistically significant (P> 0.05) in GGT≤30 U/ L, > 30 U/L, and ~≤60 U/L group. Conclusion: Serum 25(OH)D(3)level was significantly lower in EVB cirrhotic patients, and it was an independent risk factor for EVB. Serum 25(OH)D(3) low levels was more apparent with ALP normalization or GGT level > 60 U/L.

[Pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy].

Objective: To identify the pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy (PME). Methods: In this cross-sectional study, 26 PME children (11 boys and 15 girls) sent to neurological outpatient clinics and admitted to wards of the Department of Pediatrics, Peking University First Hospital were enrolled prospectively from January 2014 to October 2018. The pathogenic gene variants of PME children and their parents were identified by Sanger sequencing, next generation sequencing panels of epilepsy or trio-based whole exome sequencing and so on. The genotypes and phenotypes of the PME children were anaylzed. Results: The clinical features of 26 children include myoclonus, multiple types of seizures and progressive neurological regression. Their onset ages ranged from 3 months to 15 years. Several pathogenic gene variants were identified in the 15 patients, including TPP1 gene variantions in 3 patients; NEU1, GBA, TBC1D24 and KCNC1 gene variantions in 2 patients respectively; CLN6, MFSD8, ASAH1 and ATN1 gene variantions in 1 patient respectively. Several variants of uncertain significance were identified in 4 patients, including GOSR2 gene compound heterozygous variants in 2 patients, KCTD7 gene compound heterozygous variants in 1 patient, and compound heterozygous variants of an unreported TARS gene in 1 patient. No pathogenic gene variant was identified in 7 patients. In 15 children with the identified pathogenic gene variants, 5 patients were diagnosed with neuronal ceroid lipofuscinoses (NCL), 2 patients with sialidosis, 2 patients with neuronopathic Gaucher disease, 1 patient with dentatorubral-pallidoluysian atrophy (DRPLA), and 1 patient with spinal muscular atrophy-progressive myoclonic epilepsy (SMA-PME). Conclusions: PME include a group of diseases with genetic heterogeneity. Identification of the pathogenic gene variants of PME could help to predict the prognosis and guide the genetic counseling.

[Genotype-phenotype correlation in patients with alternating hemiplegia of childhood].

Objective: To explore the correlation between ATP1A3 genotype and phenotype in children with alternating hemiplegia of childhood (AHC). Methods: This was a retrospective study. The clinical data and peripheral blood DNA of AHC patients were collected in Peking University First Hospital from August 2005 to December 2017. ATP1A3 gene mutations were screened by Sanger sequencing or next generation sequencing (NGS). AHC patients were divided into difference groups according to different hotspot mutations. SPSS 23.0 was used to analyze the correlation between genotype and phenotype. Variance analysis was used to compare the measurement data between groups. Chi square test was used to compare the categorical data between groups. Kruskal-Wallis test was used to compare the unidirectional ordered data between groups. Least-significant difference(LSD) was used to compare the data between two groups. Results: A total of 119 AHC patients were recruited, including 68 males and 51 females. The onset age of 113 (95.0%) patients was within 18 months. There were 119 cases (100.0%) with hemiplegic seizures, 109 cases (91.6%) with abnormal eyeball movements, 104 cases (87.4%) with dystonia, 31 cases (26.1%) with autonomic neurological symptoms, 31 cases (26.1%) with epileptic seizures and 117 cases (98.3%) with long-term developmental delay. In 113 patients (95.0%) with ATP1A3 gene mutations, 111 were de novo mutation and 2 were genetic mutations. A total of 39 mutation types were found, including 37 missense mutations and 2 deletion mutations. Seventeen of them were novel mutations. The three hotspot mutations were D801N (n=34, 30.1%), E815K (n=20, 17.7%) and G947R (n=13, 11.5%). The age of onset of D801N and E815K were earlier than G947R ((3.1±2.1)and (2.3±2.3)vs.(6.4±7.7) months, P=0.004 and 0.003). The age of first hemiplegic events of D801N and E815K were earlier than G947R((6.4±3.1) and (6.8±3.3) vs. (11.4±10.1) months, P=0.004 and 0.016). More patients with E815K mutations presented epilepsy than those with D801N (P=0.003) and G947R (P=0.001). More patients with E815K mutations presented greater motor and intellectual disability than the patients with D801N (P=0.001) and G947R mutations (P=0.001). Conclusions: ATP1A3 gene is the main causative gene of AHC. Three hotspot mutations, D801N, E815K and G947R, were found. Hotspot mutation E815K is associated with the most severe phenotype, which presented an earlier age at the time of the first paroxysmal manifestation and first hemiplegic event, severer developmental delay and a greater proportion of epilepsy.

[Targeting diagnosis and treatment value of chelating anti-IL-1ß mAb-SPIONs in temporal lobe epilepsy model].

Objective: In order to study the diagnosis and treatment value of chelating anti-IL-1ß mAb-SPIONs in temporal lobe epilepsy model induced by lithium chlorid and pilocarpine. Methods: Forty-five temporal lobe epilepsy model rats were randomly and equally divided into saline group, plain-SPIONs group, anti-IL-1ß mAb-SPIONs group. Each group was injected with equal particles at day 3 and day 14 after the onset of seizures. MRI were conducteds before and 4 hours after particles injection and T2 values were measured. The distribution of iron particles in the epileptic tissue was observed and the neuronal loss, astrocyte proliferation and microglia activation were detected. The expressions of IL-1ß and NF-κBp65 in each group were detected meanwhile. Results: At day 14 after seizure, the value of T2 was 84±14 after injecting anti-IL-1ß mAb-SPIONs. Compared with the control group, the value of T2 obviously declined. These phenomena of neuron loss, astrocyte proliferation and microglia activation had been improved obviously. IL-1ßand NF-κBp65 expression also significantly reduced. Conclusion: Anti-IL-1ß mAb-SPIONs can penetrate blood brain barrier and plays an important role in targeting positioning and targeting therapy in temporal lobe epilepsy.

[Clinical phenotypes of TBC1D24 gene related epilepsy].

Objective: To summarize the clinical features of TBC1D24 gene mutations associated with epilepsy. Methods: All the patients with TBC1D24 gene compound heterozygous mutations were retrospectively collected at the Pediatric Department of Peking University First Hospital from March 2015 to July 2017, and the features of clinical manifestations, electroencephalogram, and neuroimaging were analyzed. Results: Eighteen cases with TBC1D24 gene compound heterozygous mutations were included. The age of seizure onset was 1 day to 8 months, and the median age was 90 days. Seizure types included generalized tonic-clonic seizures (GTCS) in 3 cases, focal seizures in 18 cases, myoclonus in 18 cases, and 17 cases had focal myoclonus and myoclonus status. The focal myoclonus involving one or multiple muscle groups, sometimes migrating and alternating, lasting up to minutes to several days, and could be terminated by sleep or sedation drugs. In 11 cases, myoclonus was exacerbated by fever or infections, and 2 cases developed into myoclonic status during infection, in a severe case with the loss of consciousness. The magnetic resonance imaging (MRI) of seven patients was abnormal, including cerebral atrophy or cerebellar atrophy with abnormal signals. Segment myoclonus was captured in 10 patients, but without correlated epileptiform discharges. There were ten cases had varying degrees of developmental delay, 7 were normal, and one patient died of status epilepticus at the age of 4 months. Three cases had hearing disorders. In the 18 patients, the clinical phenotype of 4 cases consisted of epilepsy of infancy with migrating focal seizures, 2 with progressive myoclonus epilepsies, 1 with Dravet syndrome, 1 with DOORS syndrome, and 3 with unclassified epileptic encephalopathy. Conclusions: The clinical feature of TBC1D24 gene mutation related epilepsy was focal myoclonus, and tended to develop into myoclonic status epilepticus, and could be aggravated by infections, and terminated by sleep or sedation drugs. Mental retardation involved or not, neuroimaging could present with cerebral atrophy or cerebellar atrophy with abnormal signals.

[Phenotype study of SCN2A gene related epilepsy].

Objective: To summarize the phenotype of epileptic children with SCN2A mutations. Methods: Epileptic patients who were treated in the Pediatric Department of Peking University First Hospital from September 2006 to October 2017 and detected with SCN2A mutations by targeted next-generation sequencing were enrolled. Clinical manifestations of all patients were analyzed retrospectively. Results: A total of 21 patients (16 boys and 5 girls) with SCN2A mutations were collected. Twenty-one SCN2A mutations were identified. Ten patients had mutations inherited from one of their parents and 11 patients had de novo mutations. The age of epilepsy onset was from 2 days to 2 years and 6 months: six patients with seizure onset in neonates (29%) , six patients with seizure onset between 1 month and 3 months of age (29%), three patients with seizure onset between 4 months and 6 months of age, two patients with seizure onset between 7 months and one year of age, and four patients with seizure onset beyond one year of age. Multiple seizure types were observed. The focal seizure was the most common seizure type which was observed in 18 patients (86%) . Spasm seizure was observed in 6 patients (29%) . Other seizure types were rare. In 19 patients, seizures manifested in clusters (90%) . In 3 patients, seizures manifested fever-sensitive. Nine of ten patients with inherited SCN2A mutations had normal development. However, all patients with de novo SCN2A mutations had mild or severer development delay. In 21 patients with SCN2A mutations, five were diagnosed with benign familial infantile epilepsy, 3 with benign familial neonatal-infantile epilepsy, 3 with Ohtahara syndrome, 3 with West syndrome, 2 with encephalopathy with early infantile onset epilepsy, one with febrile seizures plus, one with Dravet syndrome, one with encephalopathy with childhood-onset epilepsy, one with autism with epilepsy and one with intellectual disability with epilepsy. Conclusions: The clinical features of patients with SCN2A mutations include that main seizure onset is the neonate and early infancy, and the main seizure type is the focal seizure, manifested in clusters. The large spectrum of SCN2A-related epilepsy, which not only includes epilepsy with a comparatively favorable prognosis, but also epileptic encephalopathy. De novo mutations often lead to severe phenotype with development delay.

[Spectrum of mutations in benign familial neonatal-infantile epilepsy].

Objective: To investigate the spectrum of mutations in families with benign familial neonatal-infantile epilepsy (BFNIE) . Methods: Clinical data and peripheral blood DNA samples of all BFNIE probands and their family members were collected from Peking University First Hospital between December 2012 and April 2016. Clinical phenotypes of affected members were analyzed. Genomic DNA was extracted from peripheral blood samples with standard protoco1. Mutations in PRRT2 were screened using Sanger sequencing. For families that PRRT2 mutations were not detected by Sanger sequencing, candidate gene mutations were further screened by next-generation sequencing for epilepsy. Results: A total of 7 families were collected. Of the 30 affected members, 15 were male and 15 were female. The age of epilepsy onset was from 2 days to 6 months. Genetic testing led to the identification of gene mutations in all families. One family had the PRRT2 hotspot mutation (c.649dupC). Three families had missense SCN2A mutations (c.2674G>A/p.V892I, c.2872A>G/p.M958V, and c.2627A>G/p.N876S) . Both c.2872A>G/p.M958V and c.2627A>G/p.N876S were novel SCN2A mutations. Three families had KCNQ2 mutations. Two of them had missense mutations (c.958G>A/p.V320I and c.998G>A/p.R333Q) . The KCNQ2 mutation c.958G>A/p.V320I was novel. One family had a gene deletion of KCNQ2, which also extended to the adjacent gene, CHRNA4; and the deletion involved all the exons of KCNQ2 and CHRNA4. Conclusions: Mutations in KCNQ2, SCN2A, and PRRT2 are genetic causes of BFNIE in Chinese families. The detection rate for gene mutations is high in BFNIE families. KCNQ2 and SCN2A mutations are common in BFNIE families. SCN2A mutations (c.2872A>G/p.M958V and c.2627A>G/p.N876S) and KCNQ2 mutation (c.958G>A/p.V320I) are novel mutations.

[Study on mosaicism of SCN1A gene mutation in parents of children with Dravet syndrome].

Objective: To investigate the clinical phenotypes and the mutant allele proportion of parents with SCN1A gene mutation mosaicism of Dravet syndrome (DS) children, thus to provide guidance for family reproduction and prenatal diagnosis. Method: The clinical data and peripheral blood DNA samples of DS patients with a SCN1A gene mutation proved by Sanger sequencing were collected prospectively from February 2005 to November 2016 in Department of Pediatrics, Peking University First Hospital. The same mutation was searched in parents and other available relatives. Parental somatic mosaicism was confirmed and quantified by Ion Torrent Personal Genome Machine (PGM) and Raindrop droplet digital PCR (ddPCR). The families were followed up and prenatal diagnosis was provided. Result: Mosaicisms of SCN1A gene mutation in parents were identified in 5.2% (30 out of 575) DS families. Seventeen were fathers and thirteen were mothers. The mutant allele proportion ranged from 1.7% to 32.9% by PGM and from 0.82% to 34.51% by ddPCR, respectively. In 30 parents with somatic mosaicism, thirteen were asymptomatic, ten had a history of febrile seizures (FS), five with epilepsy, one with febrile seizure plus and one had a history of afebrile seizure. Four families had two children with DS. Three siblings of the probands were confirmed genetically with the same pathogenic mutation. One deceased sister of the proband was assumed to have the same pathogenic mutation because she matched DS diagnosis after medical history review despite no blood sample. Two families received prenatal diagnosis. One second pregnancy was terminated because the fetus inherited the mutation as the mother's wish. Conclusion: Sanger sequencing detects parents of some children with DS are SCN1A mutation mosaics. PGM and ddPCR can be used for accurate quantification of mutant mosaics, which can provide accurate guidance for family genetic counseling.

[Clinical and neuroimaging features of acute encephalopathy after status epilepticus in Dravet syndrome].

Objective: To investigate the clinical and neuroimaging characteristics of acute encephalopathy (AE) after status epilepticus (SE) of patients with Dravet syndrome (DS). Method: The clinical data of DS patients who had AE (coma ≥24 h) after SE were retrospectively collected from February 2005 to August 2016 in Peking University First Hospital and SCN1A gene tests were performed.The clinical and neuroimaging features were summarized. Result: Twenty-two patients (9 males and 13 females) with AE were collected among 412 DS patients during follow-up.Of which 18 patients had SCN1A gene mutations while the remaining 4 patients had no SCN1A gene mutations.The onset age of AE was between 6 months and 10 years.The duration of SE varied between 40 minutes and 9 hours.Prior to the onset of SE, twenty-one patients had high fever, and one patient had normal temperature.Coma lasted from 2 days to 20 days.Nine patients died after the AE, and 13 patients survived with massive neurological regression.From AE to the last visit, the median time of follow-up was 2 years and 3 months (from 7 months to 4 years and 4 months). Nine of 13 survivors had varied improvement in motor, language and cognition, while the remaining 4 patients had no significant improvement.After AE, there were 6 patients with seizure-free, 4 patients with reduced seizures, and 3 patients with no change in seizure frequency, moreover, spasm occurred in 2 patients.Six patients had brain magnetic resonance imaging (MRI) in acute phase and showed bilateral (2 patients) or unilateral (4 patients) hemisphere edema, accompanied by subcortical white matter hyperintense signal in T1 and T2 weighted images in two patients.The neuroimaging of 13 survivors demonstrated diverse cortical atrophy during recovery phase, among which 4 patients showed cerebellar atrophy, one patient had right pontine atrophy, 4 patients accompanied by signal abnormalities in subcortical and periventricular white matter, 2 patients showed right hippocampal sclerosis, and one patient showed signal abnormalities in bilateral basal ganglia. Conclusion: SE is more prone to occur in Dravet patients who have high fever.It may result in AE or even death in severe cases.Survivors will leave severe neurological sequelae.The neuroimaging shows brain edema in acute phase.In recovery phase the neuroimaging shows diverse brain atrophy, moreover, a few patients may be associated with cerebellar or pontine atrophy, hippocampal sclerosis or abnormal signals in white matter or basal ganglia.

[Changes in peripheral blood 25 - hydroxyvitamin D3, Th17 cells, and CD4+ regulatory T cells and their clinical significance in patients with primary biliary cirrhosis].

Objective: To investigate the changes in peripheral blood 25-hydroxyvitamin D3[25-(OH)D3], CD4+regulatory T (Treg) cells, and Th17 cells in patients with primary biliary cirrhosis (PBC) and their mechanism of action in PBC. Methods: A total of 22 patients with PBC were enrolled and the male/female ratio was 1:21, with a mean age of 61±12 years. There were 7 healthy volunteers matched for age in the normal control group. Electrochemiluminescence immunoassay was used to measure the peripheral blood 25-(OH)D3level in the PBC group and normal control group, and flow cytometry was used to analyze the changes in Th17 cells and CD4+Treg cells. The t-test, rank sum test, Pearson correlation analysis, or Spearman's rank correlation analysis was used for statistical analysis according to the type of the data. Results: The PBC group had a significantly lower serum 25-(OH)D3level than the normal control group (9.49±3.65 vs 27.35±2.35 ng/ml,P< 0.01). Compared with the normal control group, the PBC group had a significantly higher percentage of Th17 cells (2.05%±1.17% vs 0.99%±0.12%,P< 0.01) and a significantly lower percentage of CD4+Treg cells (2.54%±1.14% vs 3.78%±0.51%,P< 0.05); there was a significant difference in Th17/Treg ratio between the PBC group and the normal control group (1.00±0.63 vs 0.26±0.02,P< 0.01). In the PBC group, peripheral blood 25-(OH)D3 was not correlated with Th17 cells or Th17/Treg ratio (r= -0.062 and -0.328,P> 0.05), while it was positively correlated with the percentage of CD4+Treg cells (r= 0.468,P< 0.05). Conclusion: Patients with PBC have significant reductions in peripheral blood 25-(OH)D3and percentage of CD4+Treg cells, a significant increase in the percentage of Th17 cells, and immune unbalance of Th17 cells and CD4+Treg cells. 25-(OH)D3can upregulate the percentage of CD4+Treg cells and thus affect the development and progression of PBC, and exogenous vitamin D may improve immune function in PBC patients.

[Clinical features and gene mutations in epilepsy of infancy with migrating focal seizures].

Objective: To summarize the clinical features and gene mutations of epilepsy of infancy with migrating focal seizures (EIMFS). Method: Clinical features and electroencephalograms(EEG)of 9 patients with EIMFS of Peking University First Hospital from May 2015 to January 2016 were analyzed. Candidate gene mutations were screened by next generation sequencing. Result: Among the 9 patients, 3 were males and 6 were females. Two patients had family history. Seizure onset age was 2 days to 3 months after birth (median age 35 days). Migrating focal seizure was presented. Seizures manifested as eyes and(or)head deviation, involuntary blinking, swallowing, trembling or stiffness of limbs, hand clenching, flushing and cyanosis of lips, etc. Four patients had a history of status epilepticus. All 9 patients had psychomotor delay. EEG of all patients presented relatively slow background; during interictal phase, there were multi-focal epileptic discharges, which dominated one hemisphere or brain region; seizures were recorded in all 9 cases, which manifested eyes or(and)head deviation, stiffening or trembling of limbs, lip smacking, etc. Corresponding EEG showed low-medium-amplitude fast waves that originated from some brain regions and migrated to other regions. Cranial magnetic resonance imaging (MRI) was abnormal in 4 cases, which predominantly showed white matter dysplasia and enlargement of subarachnoid spaces. Two cases carried heterozygous missense mutations of SCN1A gene, while 3 cases carried heterozygous missense mutations of KCNT1 gene, all of which were de novo. One case carried compound heterozygous mutation of TBC1D24 gene(p.Gln207*, p. Ala289Va). Gene mutation was not found in 3 cases. All patients used multiple antiepileptic drugs (AED) and their seizures were not controlled. Follow-up ranged from 2 months to 5 years and 8 months, during which 4 were found dead. Two were lost to follow-up. Conclusion: EIMFS is clinically characterized by early onset, which is usually within 3 months after birth, migrating focal seizures, psychomotor delay, bad response to AED and high death rate. The interictal EEG showed multi-focal discharges, while ictal EEG shows migrating multifocal discharges. Genetic analysis can assist in diagnosis and genetic counseling.

[Genotype and phenotype of female Dravet syndrome with PCDH19 mutations].

OBJECTIVE: To explore the genotype and phenotype of female Dravet syndrome (DS) patients with PCDH19 mutations. METHOD: Clinical data of all DS patients seen at Pediatric Department of Peking University First Hospital from February 2005 to May 2015 were prospectively collected. Genomic DNAs were extracted from the patients and their family members. Female DS patients without SCN1A mutation were enrolled. PCR and Sanger sequencing were performed to identify PCDH19 mutations. Clinical data of DS patients with PCDH19 mutations were summarized. RESULT: Five different heterozygous PCDH19 mutations were identified in six unrelated patients of 75 SCN1A-negative female DS patients (8%), among whom five patients had de novo mutations and one patient's mutation was inherited from her affected mother. Three missense mutations and two insertion mutations were all located in exon 1. Mean age of onset of the six patients with PCDH19 mutations was 6.8 months (range 5-9 months). Onset of seizures were triggered by fever in four patients, after vaccination in one and without fever in one. Generalized tonic clonic seizure (GTCS) was the first seizure type in four patients and focal seizure with secondary generalized tonic clonic seizures in the remaining two. During the course, all patients presented multiple seizure types including generalized tonic clonic seizures and focal seizures in all six patients, myoclonic seizures in three, absence seizures and atonic seizures in one respectively. In all patients, seizures manifested fever-sensitive and in clusters. Seizures were always in brief duration, in most less than 5 minutes, except one experienced twice status epilepticus triggered by fever. Six patients had development delay after the seizure onset, two with autism spectrum disorder, three with ataxia. CONCLUSION: PCDH19 is another important gene of DS after SCN1A, mutations mainly occurred de novo. PCDH19 gene mutation should be routinely screened in female DS patients without SCN1A mutation. The clinical features of female DS patients with PCDH19 mutations include that the main seizures types are generalized tonic clonic seizures and focal seizures, seizures occurr in clusters and fever-sensitive, short seizure duration, rare status epilepticus, common development delay and some may manifest autism spectrum disorders.

Association between high visceral fat area and postoperative complications in patients with Crohn's disease following primary surgery.

AIM: The aim of this study was to determine the association between visceral fat area (VFA) on CT and postoperative complications after primary surgery in patients with Crohn's disease (CD). METHOD: Inclusion criteria were patients with a confirmed diagnosis of CD who had preoperative abdominal CT scan. The areas of total fat, subcutaneous fat and visceral fat were measured using an established image-analysis method at the lumbar 3 (L3) level on CT cross-sectional images. Visceral obesity was defined as a visceral fat area (VFA) of ≥ 130 cm(2) . Clinical variables, intra-operative outcomes and postoperative courses within 30 days were analysed. RESULTS: A total of 164 patients met the inclusion criteria. Sixty-three (38.4%) patients had postoperative complications. The mean age of the patients with complications (the study group) was 40.4 ± 15.4 years and of those without complications (the control group) was 35.8 ± 12.9 years (P = 0.049). There were no differences in disease location and behaviour between patients with or without complications (P > 0.05). In multivariable analysis, VFA [odds ratio (OR) = 2.69; 95% confidence interval (CI): 1.09-6.62; P = 0.032] and corticosteroid use (OR = 2.86; 95% CI: 1.32-6.21; P = 0.008) were found to be associated with postoperative complications. Patients with visceral obesity had a significantly longer operative time (P = 0.012), more blood loss (P = 0.019), longer bowel resection length (P = 0.003), postoperative ileus (P = 0.039) and a greater number of complications overall (P < 0.001). CONCLUSION: High VFA was found to be associated with an increased risk for 30-day postoperative complications in patients with CD undergoing primary surgery.