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The development of single Chinese materia medica is an important direction of technological innovation in the field of Chinese materia medica at present， and the study of its comprehensive intellectual property protection system is of great significance to the intellectual property protection of the whole chain of innovative enterprises of single Chinese materia medica. Based on this， this paper takes the comprehensive protection system of intellectual property of Callicarpa nudiflora constructed by Jiuzhitang Pharmaceutical as a model to conduct empirical research， analyzes the protection forms applicable to intellectual property of Chinese materia medica， such as patents， administrative protection， trademarks， designs and intangible cultural heritages， and discusses the valuable and insufficient aspects of the protection system currently constructed by Jiuzhitang Pharmaceutical and puts forward the following suggestions：①paying attention to patent applications for planting/processing methods of raw medicinal materials， ②emphasizing the protection of geographical indications， authentic medicinal herbs， and new plant varieties， ③actively promoting product and technology upgrades， ④applying for data protection during product iteration， ⑤emphasizing the layout timing of patent and administrative protection， ⑥focusing on improving goodwill， ⑦enhancing awareness of intellectual property protection and promoting deep integration of industry， academia， and research. We hope that innovative enterprises engaged in the development of single Chinese materia medica can learn from the experience of the case， and optimize the strategy to better protect related products.
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Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
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Objective:To investigate the prognostic factors of oligometastatic (OM) non-small cell lung cancer (NSCLC) patients and the safety and effectiveness of early radiotherapy intervention.Methods:A retrospective analysis was conducted, including 159 OM NSCLC cases (metastatic sites≤5, metastasis organs≤3) admitted to Department of Radiation Oncology in First Affiliated Hospital of Soochow University from January 2015 to December 2018. Among 159 cases, there were 107 males and 52 females, with the median age of 63 years. 137 cases were administrated via early radiotherapy intervention, and 22 cases via delayed radiotherapy intervention. The receiver operating characteristic curve (ROC) was used to determine the progression-free survival time (PFS)/overall survival time (OS) to ascertain the best cut-off value for local control and prognosis. Survival analysis was calculated by Kaplan-Meier curves, and Log rank test was used for comparison of these curves. Cox proportional hazards regression model was used for multivariate survival analysis.Results:The median follow-up time of 159 cases was 28.2 months. During the follow-up period, there were 16 cases with complete remission (10.1%), 53 cases with partial remission (33.3%), 27 cases with stable disease (17.0%), and 63 cases with progressed disease(39.6%). The local control rates at 3, 6 and 12 months were 83.9%, 59.7% and 41.0%, respectively. The median progression-free survival (PFS) of 159 patients was 8.0 months, the median survival time (OS) was 35.0 months, and 1, 2, and 3-year survival rates were 77.3%, 63.0% and 45.1%, respectively. Adverse reactions related to radiotherapy were relatively mild, mostly grade 1 and 2. PFS/OS= 0.3 is the best cut-off value for determining the patient′s local control and prognosis. The result of univariate analysis showed that gender, number of OM organs, T staging, radiotherapy intervention mode, tumor target volume absorbed dose (DT-GTVnx), PFS/OS were significantly related to median PFS ( χ2=4.175, 16.508, 4.408, 10.300, 6.842, 38.175, P<0.05); gender, pathological type, number of OM organs, initial diagnosis stage, T stage, N stage, lobectomy, radiotherapy intervention mode, tumor target volume (V-GTVnx), tumor load, local control status were significantly related to median OS ( χ2=6.672, 8.330, 21.299, 5.398, 6.874, 6.893, 5.611, 115.206, 4.017, 5.110, 21.299, P< 0.05). The result of multivariate analysis showed that delayed radiotherapy intervention ( HR=3.728, 95% CI 2.099-6.622, P<0.001) was an independent risk factor for PFS in patients with OM NSCLC, and PFS/OS>0.3 ( HR=0.123, 95% CI 0.062-0.246, P<0.001) was an independent protective factor for PFS in patients with OM NSCLC; male ( HR=1.665, 95% CI 1.024-3.043, P=0.033), high tumor burden ( HR=2.113, 95% CI 1.088-4.107, P=0.027), delayed radiotherapy interventions ( HR=15.076, 95% CI 7.925-28.680, P<0.001) were independent risk factors for OS in patients with OM NSCLC. Conclusions:OS of patients with OM NSCLC is significantly prolonged in female, low tumor burden and early radiotherapy intervention. Early radiotherapy intervention significantly improved the prognosis, and radiotherapy-related adverse reactions could be tolerated. These might suggest that local radiotherapy is safe and effective in the treatment of OM NSCLC patients.
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Objective:To investigate the clinical characteristics and gene variation of asparagine synthase deficiency that is caused by ASNS gene variation. Methods:In Department of Neuroendocrine Pediatrics, Affiliated Hospital of Qingdao University from October 2018 to February 2020, the clinical data of a family of asparagine synthase deficiency were analyzed retrospectively.The pathogenic mutation of the proband was screened by the full exon analysis technique.The pathogenic sites of candidate genes were determined by combining the phenotype of the proband.In the heterotopic spot of the proband, his parents and other family members were verified by Sanger sequencing.Meanwhile, the relevant literature database was consulted, and the reported ASNS mutation related cases were collected and reviewed. Results:The female with proband visited the hospital at the age of 4 months, and she had recurrent convulsions at the age of about 3 months.Physical examination showed that the child suffered from microcephaly, and mental and motor retardation.Meanwhile, video electroencephalogram examination displayed extensive moderate high amplitude spiny slow wave and sharp slow wave.Exon sequencing illustrated that the compound heterozygous variants of ASNS gene were c. 1211G>A (p.R404H) and c. 1643C>T (p.S548F), respectively.c.1211G>A was a known pathogenic variant, and c. 1643C>T was a new variant.The proband′s younger brother visited the hospital at the age of 2 months, developed convulsions at the age of 1 month, and developed mental and motor retardation.Electroencephalogram displayed that bilateral posterior head was dominant, multiple foci and extensive spike wave, and spike slow wave and fast wave were distributed.Sanger sequencing revealed the same ASNS compound heterozygous variants as the proband.Both of them died of status convulsion at the age of 7 months and 6 months, respectively. Conclusions:This study is helpful to further understand the clinical features of the disease and reveal a new pathogenic mutation of ASNS gene, so as to enrich the mutation spectrum of ASNS gene, thus providing important basis for clinical treatment and genetic counseling.
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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.
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Child , Female , Humans , Male , Pregnancy , DNA-Binding Proteins/genetics , Intellectual Disability/genetics , Mutation , Pedigree , Phenotype , Exome SequencingABSTRACT
For effective resistance to virus attack and infection, reducing virus transmission chance, it is extremely important for the medical staff and related workers to have their own safe protection. This paper summarizes the development causes, common locations, and prevention ways about the device related pressure injuries on the face resulted from wearing medical-grade protective equipment for a long working time. The paper proposes the nursing strategy for device related pressure injuries and other nursing strategy is proposed to take care efficiently the device related pressure injuries. Meantime, a corresponding nursing strategy is also suggested to deal with the correlative skin diseases during the application of medical-grade protective equipment. These paper aims to provide reference for the prevention of device related pressure injuries and the care of skin-related diseases for clinical working staff, especially to the respectable personnel in front line of fighting against Corona virus disease 2019.
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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.
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Objective:Based on the hyperlipidemia rat model and network pharmacology technology, the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia was analyzed. Method:The levels of blood lipids and inflammatory factors were measured through prophylactic administration of low, medium and high-dose Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs in hyperlipidemia rats. The active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs were screened out through Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP) and text mining. The targets of active ingredients screened through the Swiss Target Prediction, Similarity ensemble approach (SEA), DrugBank database. The disease targets were collected through Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), DrugBank, DisGeNET database. The targets of active ingredients and disease target were integrated, and screened through topological parameters to gain the main candidate targets of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the gene ontology (GO) functional enrichment analysis were conducted through ClueGO and Database for Annotation, Visualization and Integrated Discovery (DAVID), respectively. The traditional Chinese medicine-chemical ingredient-target network model, and the target-pathway network model were constructed through Cytoscape, and their crosstalk target and signal pathway were analyzed. Result:Animal experiments showed that the prophylactic administration of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs significantly reduced the levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) in serum of rats with hyperlipidemia, increased high-density lipoprotein (HDL-C) levels, and inhibited the expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). According to the findings, 27 active ingredients, such as mandenol, diosmetin and α-spinasterol, might be the main active ingredients of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs, 16 crosstalk targets and 10 signal pathways might be the main therapeutic targets and pathways, main targeting apolipoprotein A1 (APOA1), apolipoprotein A2 (APOA2), apolipoprotein C3 (APOC3), lipoprotein lipase (LPL), low-density lipoprotein receptor (LDLR) and other crosstalk targets affected cholesterol metabolism, bile secretion, peroxisome proliferator activated receptor (PPAR) signaling pathway in regulating the lipid level, targeting tumor necrosis factor (TNF), IL-6, interleukin-1β (IL-1β), mitogen-activated protein kinase 1 (MAPK1), C-C motif chemokine 2 (CCL2) and other crosstalk targets affected tumor necrosis factor (TNF) signaling pathway, Toll-like receptor signaling pathway, interleukin-17 (IL-17) signaling pathway, and hypoxia inducible factor (HIF) signaling pathway in regulating the inflammatory factor level. The DAVID database for GO enrichment analysis showed that the hyperlipidemia was treated mainly through biological processes, such as inflammation, lipid localization, storage and lipid metabolism. Conclusion:These findings can predict the mechanism of action of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs against hyperlipidemia, and provide a theoretical basis for the material basis and clinical application of Trichosanthis Fructus-Allii Macrostemonis Bulbus herb pairs.
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For effective resistance to virus attack and infection, reducing virus transmission chance, it is extremely important for the medical staff and related workers to have their own safe protection. This paper summarizes the development causes, common locations, and prevention ways about the device related pressure injuries on the face resulted from wearing medical-grade protective equipment for a long working time. The paper proposes the nursing strategy for device related pressure injuries and other nursing strategy is proposed to take care efficiently the device related pressure injuries. Meantime, a corresponding nursing strategy is also suggested to deal with the correlative skin diseases during the application of medical-grade protective equipment. These paper aims to provide reference for the prevention of device related pressure injuries and the care of skin-related diseases for clinical working staff, especially to the respectable personnel in front line of fighting against Corona virus disease 2019.
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Objective@#To investigate the clinical and electroencephalogram (EEG) characteristics and treatment of ring chromosome 14 syndrome, and to improve its early recognition and accurate diagnosis.@*Methods@#The cli-nical and EEG characteristics of 4 patients with ring chromosome 14 syndrome confirmed by genetic diagnosis were analyzed in the neurology outpatient department and ward of pediatrics in Peking University First Hospital from August 2012 to August 2018.The treatment and prognosis of the 4 patients were followed up.@*Results@#Of the 4 patients, there were 2 males and 2 females.All the patients had developmental delay, abnormal facial features such as wide eye spacing, low nasal bridge and microcephaly.Seizures occurred in all the patients with varying onset ages from 8 months to 1 year.Seizure types included focal seizure, tonic seizure and generalized tonic-clonic seizure.EEG monitoring ages varied from 9 months to 4 years and 4 months.The characteristic EEG pattern manifested as slow activity of background, unilateral or bilateral anterior, posterior or diffuse slow activity, with or without interposed multifocal epileptiform discharges.Cranial magnetic resonance imaging (MRI) showed non-specific abnormality in 1 patient and normal in 3 patients.The ages at the last follow-up ranged from 1 year and 8 months to 7 years and 1 month with intervals from 9 months to 6 years and 5 months.Valproic acid combined with other antiepileptic drugs was used to treat seizures.Seizure reduction instead of control was observed in all the 4 cases.At the last follow-up, the development of movement and language were all delayed in the 4 patients.One case could walk independently, three could walk unsteadily alone; two could speak 2-3 simple words, one could call only " baba, mama" , and one had no language development.@*Conclusions@#The ring chromosome 14 syndrome is a rare disease caused by chromosome abnormality.Its main clinical manifestations included facial abnormalities, microcephaly, epilepsy, developmental delay especially for language and cognitive disability.The types of seizures included both focal and generalized.EEG showed non-specific features with slow background activity, with the migratory slow waves mixing multi-focal discharges as the main common pattern.The epilepsy of this disease was often drug resistant.Valproic acid combined with other antiepileptic drugs could reduce seizures.Seizures without control could further affect development outcome.
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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.
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Objective@#To explore the effects of application of Plato analysis combined with plan-do-check-action (PDCA) cycle in scientific research management of nurses with primary position title.@*Methods@#Twenty-six nurses with primary position title were recruited in this self pre- and post-control study. From January 2012 to December 2013, they were guided by normal scientific research management. In January 2014, the factors which hinder these nurses from writing papers were investigated by the questionnaire titled " the impediments that hinder nurses with primary position title from writing papers" . Based on " twenty-eighty percent laws" of Plato analysis method, the main influencing factors which hinder nurses with primary position title from writing papers were " had no idea" and " did not know how to write although with ideas" . From January 2014 to December 2015, based on the results of the survey and combined with PDCA cycle method, interventions were planned, carried out, analyzed by stage, and then improved continuously. Impediments which hinder writing papers of 26 nurses in January 2014 and December 2015, specific scientific research achievement, total scientific research achievement, and average scientific research achievement of these 26 nurses before intervention (from January 2012 to December 2013) and after intervention (from January 2014 to December 2015) were analyzed. Data were processed with McNemar exact probability test, Wilcoxon signed rank sum test.@*Results@#(1) The cumulative percentages of main impediments " had no idea" and " did not know how to write although with ideas" were decreased from 76.93% in January 2014 to 23.07% in December 2015. The number of nurses who " had no idea" was significantly reduced from 14 in January 2014 to 4 in December 2015 (P<0.01). The total number of nurses who had impediments which hinder writing papers was significantly reduced from 26 in January 2014 to 10 in December 2015 (P<0.01). (2) The total scientific research achievement and average scientific research achievement of the 26 nurses were significantly increased from 5 before intervention to 32 after intervention and 0.19 before intervention to 1.23 after intervention, respectively (Z=-4.838, -3.703, P<0.01). Among which, numbers of specific scientific research achievement of papers published in Journals of Statistic Source, papers published in other journals, science and technology awards, fund projects, national utility model patents, and patents for invention after intervention were all increased than those before intervention (P<0.05 or P<0.01).@*Conclusions@#Plato analysis can accurately analyze the main impediments that hinder nurses with primary position title from writing papers. Plato analysis combined with PDCA cycle can improve the overall ability of scientific research of nurses with primary position title and affect the achievements in nursing scientific research, which is worthy of promotion.
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Objective To investigate the clinical and electroencephalogram (EEG) characteristics and treatment of ring chromosome 14 syndrome,and to improve its early recognition and accurate diagnosis.Methods The clinical and EEG characteristics of 4 patients with ring chromosome 14 syndrome confirmed by genetic diagnosis were analyzed in the neurology outpatient department and ward of pediatrics in Peking University First Hospital from August 2012 to August 2018.The treatment and prognosis of the 4 patients were followed up.Results Of the 4 patients,there were 2 males and 2 females.All the patients had developmental delay,abnormal facial features such as wide eye spacing,low nasal bridge and microcephaly.Seizures occurred in all the patients with varying onset ages from 8 months to 1 year.Seizure types included focal seizure,tonic seizure and generalized tonic-clonic seizure.EEG monitoring ages varied from 9 months to 4 years and 4 months.The characteristic EEG pattern manifested as slow activity of background,unilateral or bilateral anterior,posterior or diffuse slow activity,with or without interposed multifocal epileptiform discharges.Cranial magnetic resonance imaging (MRI) showed non-specific abnormality in 1 patient and normal in 3 patients.The ages at the last follow-up ranged from 1 year and 8 months to 7 years and 1 month with intervals from 9 months to 6 years and 5 months.Valproic acid combined with other antiepileptic drugs was used to treat seizures.Seizure reduction instead of control was observed in all the 4 cases.At the last follow-up,the development of movement and language were all delayed in the 4 patients.One case could walk independently,three could walk unsteadily alone;two could speak 2-3 simple words,one could call only " baba,mama",and one had no language development.Conclusions The ring chromosome 14 syndrome is a rare disease caused by chromosome abnormality.Its main clinical manifestations included facial abnormalities,microcephaly,epilepsy,developmental delay especially for language and cognitive disability.The types of seizures included both focal and generalized.EEG showed non-specific features with slow background activity,with the migratory slow waves mixing multi-focal discharges as the main common pattern.The epilepsy of this disease was often drug resistant.Valproic acid combined with other antiepileptic drugs could reduce seizures.Seizures without control could further affect development outcome.
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OBJECTIVE@#To investigate whether the tonic-clonic seizure (TCS) induced by intermittent photic stimulation (IPS)was generalized tonic-clonic seizure (GTCS)or partial secondarily tonic-clonic seizure (PGTCS),and to analyze the relationship between them.@*METHODS@#Video-electroencephalogram (VEEG)database of Peking University First Hospital from March 2010 to October 2018 were reviewed. Fifteen cases with idiopathic epilepsy who had TCS induced by IPS were included in this study, and their clinical and electroencephalogram (EEG)characteristics were retrospectively analyzed.@*RESULTS@#In this study, 4 of the 15 cases were boys and 11 were girls. The age of seizure onset ranged from 1 to 13 years. According to the medical records: 12 cases were considered as GTCS,while the remaining 3 cases were considered as PGTCS. The age at VEEG monitoring ranged from 2.5 to 16.0 years. All backgrounds of the VEEG were normal. Interictal discharges:generalized discharges in 11 cases, of which 4 cases coexisted with posterior discharges, 2 cases coexisted with Rolandic discharges, the other 5 cases merely had generalized discharges; merely focal discharges in two cases, one in the Rolandic area and the other in the posterior area; no interictal discharge in the remaining 2 cases. IPS induced photoparoxysmal response (PPR)results: 2 cases without PPR,the remaining 13 cases with PPR of generalized discharges, and 6 of the 13 cases coexisted with posterior discharges. IPS induced photoconvulsive response (PCR)results: GTCS in one case (contradictory to medical history),PGTCS in 11 cases (consistent with medical history),and GTCS and PGTCS hardly to distinguish in the remaining 3 cases. Of the three conditions above, there were generalized myoclonic seizures induced by IPS before TCS in 7 cases.@*CONCLUSION@#The medical history was unreliable in determining whether TCS was generalized or focal. Myoclonic seizures can coexist with PGTCS, and sometimes GTCS was indistinguishable from PGTCS, indicating that the dichotomy of seizure types need to be improved. Photosensitive TCS should be regarded as a continuum between focal and generalized seizures.
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Female , Humans , Male , Electroencephalography , Epilepsy, Generalized , Epilepsy, Tonic-Clonic , Retrospective Studies , SeizuresABSTRACT
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.
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Objective To investigate the clinical and genetic features of a Chinese child with spinal muscular atrophy with progressive myoclonic epilepsy(SMA-PME)and review the related literatures.Methods The clinical and genetic data of 1 patient with SMA-PME,who had visited the Department of Pediatrics,Peking University First Hospital in August 2016,were analyzed.The clinical and genetic features of 10 reported ASAH1-related cases and this case were reviewed.Results The patient was a girl aged 4 years.At the age of 1 year and 2 months,she was able to walk independently and then started to show slowly progressive difficulty in walking.At age 3 years and 9 months,she developed frequent myoclonic jerks of trunk or even falls,and had occasional staring.The patient was revealed to have compound heterozygous mutations in ASAH1 gene,c.256_c.257insA(p.T86Nfs*14)inherited from her father and c.125C>T(p.T42M)inherited from her mother.The mutation p.T86Nfs*14 was not reported before.Since the onset of the disease,her motor skills were progressive impaired but intelligence was basically normal.A total of 10 ASAH1-related cases were reported until October 2016.By analyzing the data of the 10 foreign cases and this case,muscular weakness and seizures were presented in all cases.Onset usually with muscular weakness,other symptoms including tremor,dysphagia and recurrent pneumonia etc.The total 8 mutations were found and the most frequent mutation was c.125C>T.The mode of inheritance all conformed to autosomal recessive.In all cases,early developmental milestones were normal,and no obvious cognitive impairment were found during the course of the disease in some of them.Four ca-ses were dead at the age of 13 to 19 years in the literatures.Conclusion SMA-PME is a rare autosomal recessive disease associated with mutations of ASAH1 gene.The patient is the first Chinese case of SMA -PME confirmed by ASAH1 gene mutations that including a common mutation and a novel frame shift mutation.
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OBJECTIVE@#To investigate the clinical significance of high-frequency oscillations (HFOs) on scalp electroencephalography (EEG) in patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS).@*METHODS@#Twenty-one CSWS patients treated for epilepsy from January 2006 to December 2016 in Pediatric Department of Peking University First Hospital were enrolled into the study. Selected clinical variables including gender, age parameters, seizure frequencies and antiepileptic drugs were compared between (a). HFO-positive group and HFO-negative group before methylprednisolone treatment and (b). excellent seizure outcome group and not-excellent seizure outcome group after methylprednisolone treatment. Interictal HFOs and spikes in pre- and post-methylprednisolone scalp EEG were measured and analyzed.@*RESULTS@#Before methylprednisolone treatment, there were 12 of 21 (57%) CSWS patients had HFOs, with a mean value 43.17 per 60 s per patient. The 12 patients with HFOs tended to have more frequent epileptic negative myoclonus/atonic/myoclonus/atypical absences than those without HFOs in a month before methylprednisolone treatment. A total of 518 HFOs and 22 592 spikes were found in the pre-methylprednisolone EEG data of 21 patients, and 441 HFOs (86%) were associated with spikes. The highest amplitudes of HFOs were significantly positively correlated with that of spikes (r=0.279, P<0.001). Rates reduced by methylprednisolone treatment were statistically significant for both HFOs (P=0.002) and spikes (P=0.006). The percentage of reduction was 91% (473/518) and 39% (8 905/22 592) for spikes and HFOs, respectively. The percentage of spike and HFOs changes was respectively 100% decrease and 47% decrease in the excellent seizure outcome group, and they were 79% decrease and 18% increase in the not-excellent seizure outcome group.@*CONCLUSION@#Prevalence of HFOs might reflect some aspect of epileptic activity. HFOs were more sensitive to methylprednisolone treatment than spikes and had a good correlation with the prognosis of seizures, and HFOs could be applied to assess epilepsy severity and antiepileptic therapy.
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Child , Humans , Anticonvulsants/therapeutic use , Electroencephalography/methods , Epilepsy/physiopathology , Epilepsy, Absence , Methylprednisolone , Scalp , Seizures , SleepABSTRACT
Objective To identify the Y-chromosomal genetic types for the soldier's remains from Huaihai Campaign,and to offer a clue for search of their paternal relatives.Methods DNA of the remains were extracted by the ancient DNA extraction method.Yfiler kit was used for the multiplex amplification of 17 Y-STR loci.The haplogroups of the samples were speculated.Detailed genotyping of the selected Y-SNP was performed based on the latest Y-chromosome phylogenetic tree.Haplotype-sharing analysis was done based on the data of Y-SNP and Y-STR,the closest modern individual information to the genetic relationship of remains was gained.Results A total of 8 Y-STR haplotypes were observed on 17 Y-STR loci of 8 male individuals.Furthermore,6 Y-SNP haplogroups were identified,which were O2a1-M95+,O1a1-P203+,O3*-M122+/M234-,D1-M15+,C3*-ST and R1a1-M17+.Conclusion Identification of Y-chromosomal genetic types for the soldier's remains from Huaihai Campaign shows a reference value on inferring the geographical origins of old materials.
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Objective@#To investigate the clinical and genetic features of a Chinese child with hyperekplexia and review the related literature.@*Method@#The clinical and genetic data of one patient with hyperekplexia, who had visited the department of Pediatrics, Peking University First Hospital in July 2012, were analyzed. "Hyperekplexia" "startle disease" "GLRB" were used as key words to search at CNKI, Wanfang and PubMed from the database from creation to August 2016.@*Result@#The one-year-old female patient showed exaggerated startle reflexes and generalized stiffness in response to external sudden, unexpected stimuli at 2 hours after birth, which existed every day. Her younger twin sister died of severe apnea due to a continuous generalized stiffness at the age of 7 months. Physical examination exhibited the positive nose-tapping reflex. There were no obvious abnormalities in laboratory tests, electroencephalogram (EEG) and neuroimaging tests. The patient was revealed to have compound heterozygous mutations in GLRB gene, c. 298-1G>A (or IVS4-1G>A) inherited from the father and c. 347T>C (p. L116P) inherited from the mother. The mutation L116P in GLRB gene was not reported before. During the follow-up until 5 years old, the girl′s symptoms of startle reflexes and generalized stiffness were controlled with clonazepam treatment. Her mental development was normal, but she walked very carefully as wide-based gait to avoid of external sudden stimuli. Literature retrieval obtained 8 reports (all in English) with 39 GLRB-related cases. Combined analysis of the data of the 39 foreign cases and our case showed that the onset age of all 40 cases was in neonatal or in utero, and all presented exaggerated startle reflexes and generalized stiffness in response to external stimuli. Other symptoms included neonatal apneas (83%, 20/24), falls (56%, 15/27) and squint (42%, 10/24) etc. EEG (13/13) and brain imaging (90%, 28/31) were normal, or unrelated/nonspecific to hyperekplexia. In the total 17 mutations of GLRB gene found in 28 cases, the most frequent mutations were GLRB gene M177R (9 cases) and IVS5+ 5G>A (5 cases). Most cases (82%, 32/39) had received the treatment of clonazepam. The symptoms of hyperekplexia all could be improved in different degree after treatment, and 84% (32/38) of the cases were completely controlled or only existed exaggerated startle reflexes. The psychomotor development could be normal (13 cases) or retarded (25 cases).@*Conclusion@#The patient presented typical clinical manifestations of hyperekplexia and had a good response to clonazepam. The patient carried GLRB gene mutations found by genetic analysis, and was finally diagnosed with hyperekplexia. The younger twin sister died due to lack of timely diagnosis and treatment, suggesting the significance of early detection and proper treatment for this disease.
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Objective To analyze the clinical characteristics and pyridox (am)ine-5'-phosphate oxidase(PNPO) gene mutations in 2 patients with PNPO deficiency.Methods The identical twin brothers were diagnosed at the Department of Pediatrics of Peking University First Hospital in February 2016.The clinical presentations,course of treatment,blood biochemistry,metabolic screening,EEG,brain magnetic resonance imaging (MRI) and epilepsy-related genes detection (including PNPO gene) of them were analyzed.Results These 2 patients were born at 35 +5weeks gestation and had asphyxia after birth.The seizures started within the first day,which was uncontrolled by various antiepileptic drugs.EEG showed atypical hypsarrhythmia or multifocal epileptiform discharges.MRI showed nonspecific abnormality.Pyridoxine was used as monotherapy or combination with various antiepileptic drugs during the treatment.Seizures had ever been controlled by pyridoxine alone for up to 1 month.Antiepileptic drugs were withdrawn gradually under the circumstances of seizures persisting when they became 5 years old.During the past year,pyridoxine was used alone.They still had seizures at their age of 6 years and 4 months.Blood metabolic screening showed that the level of arginine,asparaginic acid and methionine decreased.Urinary metabolic screening showed vanillic acid elevating prominently in both patients,49.78 and 36.60 times beyond normal,respectively.Genetic analysis showed compound heterozygous variants ofPNPO gene in both patients:c.445_448del (p.P150RfsX27) and c.481C ＞T (p.R161C).These 2variants were not reported previously.After definite diagnosis was made,pyridoxine was replaced by pyridoxal-5'-phosphate (PLP) immediately.Seizures increased slightly at the initial treating with PLP,then reduced gradually and were controlled eventually.Psychomotor development was severely delayed in 2 patients.Conclusions Infantile onset intractable seizures in these 2 patients responded to pyridoxine.The results of blood and urinary metabolic screening suggest the possibility of PNPO deficiency.This is the first time to report patients with PNPO deficiency diagnosed by PNPO gene mutations in China.Seizures could be controlled by PLP monotherapy eventually.