Analysis of influencing factors for clinical efficacy of Perampanel monotherapy in children with focal epilepsy based on machine learning / 中华实用儿科临床杂志

Objective:To analyze influencing factors for the clinical efficacy of Perampanel monotherapy in children with focal epilepsy and promote rational clinical use of Perampanel.Methods:Children who were diagnosed with focal epilepsy and treated with Perampanel monotherapy in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from June 2021 to August 2022 were included in this retrospective study.Efficacy at 3, 6 and 12 months after treatment was taken as the dependent variable.The gender, age at onset, age at initiation of Perampanel monotherapy, course of disease, weight, body mass index (BMI), seizure frequency, epilepsy syndrome, etiology, previous clinical history, developmental retardation, starting and maintenance doses, blood concentration, CYP3A4 and CYP3A5 gene mutations were taken as the independent variables.The effects of these factors on the efficacy of Perampanel monotherapy were analyzed using the Cox proportional hazards regression.The random forest and decision tree models were used to sequence the significance of the influencing factors and find the optimal cut-point for classification. Results:A total of 43 children (31 boys and 12 girls) were enrolled in this study.The average age at onset was (7.6±2.1) years, and the average age at initiation of Perampanel monotherapy was (7.8±2.7) years.The Cox proportional hazards regression analysis indicated that the greater the BMI, the worse the efficacy of Perampanel ( HR=0.74, 95% CI: 0.55-0.99, P=0.045). Through machine learning, the BMI was found to be a significant covariate affecting the efficacy, and when BMI≥21.8 kg/m 2, the negative effect was more significant. Conclusions:The clinical efficacy of Perampanel monotherapy in children with focal epilepsy is related to BMI.The dose of Perampanel for obese children with epilepsy may need to appropriately increase.

Research progress in etiology and pathogenesis of pediatric tic disorder / 中华实用儿科临床杂志

Tic disorder (TD) is one of the typical neurodevelopmental disorders in childhood.More studies have confirmed that the etiology and pathogenesis of TD are related to genetics, environment, immunology, and psychology, etc.Identifying the etiology and pathogenesis helps to guide the treatment of TD.This paper reviews the research progress in the etiology and pathogenesis of pediatric TD in recent years.

Research progress on susceptibility genes in children with tic disorder / 中华实用儿科临床杂志

Tic disorder (TD) is a neurodevelopmental disorder that starts in childhood with tics as its primary clinical manifestation.It is a group of movement disorders with unknown causes.At present, the main pathogenic genes of TD have not been identified.In this paper, TD neurotransmitter-associated susceptibility genes ( DRD2, DRD4, SLC6A4, HDC, ADRA2A), related susceptibility gene variations ( ASH1L, CELSR3, PNKD, NRXN1, CNTN6), and other susceptibility genes ( FLT3, SLITRK1) were reviewed to provide references for the precision treatment based on gene variations.

High-grade cervical lesions diagnosed by JAM3/PAX1 methylation in high-risk human papillomavirus-infected patients / 中南大学学报(医学版)

Objective:Currently,traditional cervical cancer screening methods,such as high-risk human papillomavirus testing and liquid based cytology(LBC),still possess limitations.This study aims to identify new diagnostic biomarkers to achieve the goal of"precision screening"via exploring the clinical value of DNA methylation[ΔCtP:paired box gene 1(PAX1)and ΔCtJ:junctional adhesion molecule 3(JAM3)]detection in cervical exfoliated cells for the diagnosis of high-grade cervical lesions. Methods:A total of 136 patients who underwent gynecological examinations in the vaginal room of the Department of Gynecology at the Third Xiangya Hospital of Central South University from June 2021 to June 2022 were retrospectively studied.Among them,122 patients had non-high-grade cervical lesions,and 14 patients had high-grade cervical lesions.The variables included general information(age,body mass index,and menopause status),LBC,high-risk human papillomavirus,cervical tissue pathology,vaginal examination results,and the ΔCt values of JAM3 and PAX1 gene methylation.Logistic regression analysis was used to identify the factors affecting the diagnosis of high-grade cervical lesions,followed by correlation analysis and construction of a conditional inference tree model. Results:Logistic regression analysis showed that the methylation ΔCt values of PAX1 and JAM3 genes and LBC detection results were statistically significant between the high-grade cervical lesions group and the non-high-grade cervical lesions group(all P<0.05).Correlation analysis revealed a negative correlation between cervical pathological changes and ΔCtP(r=-0.36,P<0.001),ΔCtJ(r=-0.448,P<0.001),LBC(r=-0.305,P<0.001),or bacterial diversity(r=-0.183,P=0.037).The conditional inference tree showed that when ΔCtJ>10.13,all of patients had non-high-grade cervical lesions,while ΔCtP>6.22,the number of non-high-grade lesions accounted for 97.5%(117/120),and high-grade lesions accounted for only 2.5%(3/120).When ΔCtJ>8.61 and LBC were atypical squamous cell of undetermined significance or negative for intraepithelial lesions or malignancy(NILM),105(99.1%)patients were non-high-grade cervical lesions,only 1(0.9%)patient was high-grade lesion.When the results of LBC were high-grade lesions,only 9 patients'histopathological examination was the high-grade lesions and 3 non-high-grade lesions.When LBC indicated low-grade lesions,atypical squamous cell of undetermined significance,no intraepithelial lesions,and ΔCtP>6.22,117(97.5%)of patients'histopathological examination was the non-high-grade lesions. Conclusion:The JAM3/PAX1 gene methylation test can be used independently for the stratified diagnosis of high-grade/non-high-grade cervical lesions in women with high-risk human papillomavirus infection,independent of the cytological results of cervical excision.The JAM3/PAX1 gene methylation test can also be used in combination with LBC to make up for the shortcomings of low sensitivity of LBC.In addition,the application of methylation kit in large-scale cervical cancer screening in the future will be good to the detection of more patients with high-grade cervical lesions,and achieve early screening and early treatment for cervical lesions/cancer.

Recommendations for prescription review of commonly used anti-seizure medications in treatment of children with epilepsy / 中华实用儿科临床杂志

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Progress in immunological research on tic disorders in children / 中国医师杂志

Tic disorders is a neurodevelopmental disorder that occurs in childhood. Its etiology and pathogenesis are not yet fully understood, and immune factors are currently a hot and difficult research topic. This article reviews the risk factors, neuroimmune factors, peripheral immune factors, and other related immune pathogenesis and new advances in immunotherapy for Tourette′s syndrome.

Recent advance in perampanel in treating special population with epilepsy / 中华神经医学杂志

Perampanel, one of the third-generation antiseizure drugs, can non-competitively bind a-amino-3- hydroxyl-5-methyl-4-isoxazole-propionate receptor. It has been approved for both monotherapy and adjunctive treatment of patients≥4 years old with focal epilepsy (with or without secondary generalized seizures) in China. Researches on treatment of perampanel in special population such as children, the elderly and women have been constantly updated, but summaries on them are lacked recently. This review summarizes the latest clinical studies on the above-mentioned population, providing reasonable basis for clinicians.

Advances in the levels of neurotransmitters associated with attention deficit hyperactivity disorder in children with tic disorders / 国际儿科学杂志

Tic disorders(TD)including Tourette syndrome are childhood-onset neurodevelopmental disorders characterized by motor and/or vocal tics that commonly affect children′s physical and mental health.More than half of TD patients also have attention deficit hyperactivity disorder(ADHD). The pathogenesis of TD is not clear, and it is believed to be related to the abnormal level of neurotransmitters caused by the dysfunction of the cortical-striatal-thalamic-cortical circuitry, and the disorder of neurotransmitters is also related to the pathogenesis of ADHD, but the current research results on the level of neurotransmitters in TD with comorbid ADHD are controversial, and even some neurotransmitters show completely opposite changes in the two diseases.This paper reviews the research progress of neurotransmitters in children with TD co-suffering from ADHD in recent years, in order to provide ideas for exploring its pathogenesis.

Research progress of ADPRHL2 gene related stress-induced childhood-onset neurodegeneration with variable ataxia and seizures / 中华实用儿科临床杂志

Stress-induced childhood-onset neurodegeneration with variable ataxia and seizures caused by ADPRHL2 gene mutation is a recently diagnosed hereditary neurodegenerative disease, featured by a small number of reported cases, early age of onset, and high mortality.Therefore, to attract the attention of clinicians, the research progress of ADPRHL2 gene, its protein structure and function, as well as the hereditary mode, pathogenic mechanism, clinical features, and treatment prognosis of stress-induced childhood-onset neurodegeneration with variable ataxia and seizures were reviewed in this paper.

Developmental epileptic encephalopathy associated with the CACNA1E gene mutation / 中华实用儿科临床杂志

One of the important causes of developmental epileptic encephalopathy (DEE) is the mutation of ion channel genes, including the mutation of the CACNA1E gene. CACNA1E-related DEE cases were first reported in 2018.The mutation types include new missense mutations, nonsense mutations and frameshift mutations, but the correlation between mutation sites and types with the phenotype of DEE is not clear.This review aims to summarize the reported CACNA1E-related DEE cases, and explore the correlation between the clinical phenotype of CACNA1E-related DEE and gene mutation sites and mutation types.Meanwhile, possible pathogenesis of CACNA1E-related DEE and the progress of drug intervention were reviewed to provide references for the diagnosis and precise treatment of DEE.

A diabetic foot classification model based on radiomics features of fundus photographs / 中华内分泌代谢杂志

Objective:To construct a diabetic foot classification prediction model based on radiomics features of fundus photographs.Methods:A total of 2 035 fundus photographs of patients with type 2 diabetes diagnosed at Nanfang Hospital between December 2011 and December 2018 were retrospectively collected [282 photographs from patients with diabetic foot(DF), and 1 753 from patients with diabetes mellitus(DM)]. All fundus photographs were randomly divided into a training set(1 424 photos) and a test set(611 photos) using a computer generated random number at 7∶3. After pre-processing the fundus photographs, a total of 4 128 texture features based on the gray matrix were extracted by the Radiomic toolkit, and 11 339 other features were extracted using the ToolboxDESC toolkit. The LASSO algorithm was used to select the 30 features most relevant to DF, and then the Bootstrap + 0.632 self-sampling method was used to further select the 7 best combinations. Logistic regression analysis was used to obtain the regression coefficients and establish the final diabetic foot classification prediction model. ROC curve was drawn, and AUC, sensitivity, specificity, and accuracy of the training and test sets were calculated to verify its prediction performance. Results:We screened 7 fundus radiomics markers for diabetic foot patients, and based on this established a DF/DM classification prediction model. The AUC, sensitivity, specificity, and accuracy of the model were 0.958 6, 0.984 0, 0.920 0, and 0.928 0 in the training set, and 0.927 1, 0.988 9, 0.881 0, and 0.896 9 in the test set, respectively.Conclusion:In this study, seven DF fundus markers were screened using radiomics technology. Based on this, a highly accurate and easy-to-use DF/DM classification model was constructed. This technology has the potential to increase the efficiency of DF screening programs.

Establishment of the normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province / 中华实用儿科临床杂志

Objective:To establish the normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province.Methods:A prospective study was conducted on healthy Han-nationality children aged 3-12 who took physical examination in Wuhan Children′s Hospital, Hubei province from January to August 2021.The children were asked for their medical histories, and those with neurological diseases, psychiatric diseases, infection, trauma, and a drug history in the past 2 weeks were excluded.The plasma of 324 children (262 males, 62 females; 217 cases in the 3-7 years old, 107 cases in the 8-12 years old) and urine of 391 children (302 males, 89 females; 266 cases in the 3-7 years old, 125 cases in the 8-12 years old) were collected.They ultra performance liquid chromatography-mass spectrometry multiple techniques (UPLC-MS/MS) were used to detect 10 kinds of neurotransmitters (e.g., dopamine, epinephrine, glutamic acid, etc.) in plasma and 8 kinds of neurotransmitters (e.g., dopamine, epinephrine, 5-hydroxyindoleacetic acid, etc.) in random urine.The normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province was established.The Kruskal- Wallis H test was made for statistical analysis of the differences in neurotransmitter levels among different age groups and gender groups.The neurotransmitter levels between different groups were compared by the Nemenyi test. Results:There were no significant differences in the levels of various neurotransmitters in children of different genders(all P>0.05). There were significant differences in the levels of dopamine, methoxy-norepinephrine, tryptophan and γ-aminobutyric acid in the plasma of children aged 3-7 years and 8-12 years.There were significant differences in the levels of dopamine, epinephrine, norepinephrine, methoxy-norepinephrine, high vanillic acid and 5-hydroxyindoleacetic acid in the random urine between the 3-7 years old group and the 8-12 years old group. Conclusions:The normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province is established.This study provides reference for clinical practice and lays a foundation for the study of neurotransmitter-related diseases in children.

Clinical features and genetic analysis of the early-onset epileptic encephalopathy caused by sodium channel mutations / 中华实用儿科临床杂志

Objective:To explore the clinical phenotype characteristics of early-onset epileptic encephalopathy (EOEE) caused by sodium channel mutations.Methods:A retrospective study was used.A total of 52 EOEE patients treated in the Department of Neurology, Children′s Hospital of Fudan University and Department of Neurology, Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from June 2016 to June 2019 were recruited.Peripheral blood samples of 52 patients and their parents were collected for analyzing pathogenic mutations by the next generation sequencing and copy number variations of whole exons in family. Chi- square test was used to compare seizure control data among different voltage-gated sodium channel α1 subunit ( SCN1A) mutation types. Results:A total of 35/52 cases (67.3%) were diagnosed as Dravet syndrome, 3/52 cases (5.8%) were West syndrome, and 14/52 cases (26.9%) were non-symptomatic EOEE.The electroencephalogram (EEG) findings showed a large number of multifocal spikes, spike-slow waves, sharp waves, and sharp-slow waves.A total of 45/52 cases (86.5%) showed normal brain magnetic resonance imaging(MRI), 1 case had slightly widened bilateral frontal sulcus, 1 case had widened bilateral temporal pole and frontal top subarachnoid space, and the remaining 5 cases had widened extracerebral space and slightly larger ventricles.Thirteen cases were re-examined with brain MRI, and 3 cases had mild brain atrophy.A total of 43/52 cases (82.7%) were examined with SCN1A gene mutations, of which 28/52 cases (53.8%) were missense mutations, 5/52 cases (9.6%) were nonsense mutations, 7/52 cases (13.5%) were frameshift mutations and 3/52 cases (5.8%) were splice site mutations.A total of 3/52 cases (5.8%) had SCN2A mutations, of which 2/52 cases (3.8%) were missense mutations, and 1/52 case (1.9%) was a frameshift mutation, 1/52 cases (1.9%) carrying the missense mutation of the SCN3A gene.A total of 5/52 cases (9.6%) had missense mutations of the SCN8A gene.After an average of 1-year follow-up, a total of 13/52 cases (25.0%) had more than 1-year control of seizure, of which 6/52 cases (11.5%) with seizure control for more than 2 years, and 4/52 cases (7.7%) with more than 3-year control.Children carrying SCN1A missense mutations were relatively easier to be controlled for seizures than those carrying SCN1A truncation mutations (nonsense mutations+ frameshift mutations) ( P<0.05). In 5 children carrying SCN8A mutations, 2 cases of them had seizures control for more than 1 year after adding Oxcarbazepine, but the improvement of mental motor function was not obvious. Conclusions:In children with EOEE associated with sodium channel gene mutations, SCN1A, SCN2A, SCN3A, and SCN8A mutations were pathogenic factors.Among them, SCN1A was the most common pathogenic gene for EOEE, with the mutation rate of 82.7%.Dravet syndrome was the most common clinical phenotype of EOEE associated with sodium channel gene mutations.Epileptic seizures in children carrying SCN1A missense mutations were easier to be controlled than those with truncated mutation (nonsense mutations + frameshift mutations), suggesting that the gene mutation type was related to the degree of seizures control.Oxcarbazepine was effective in the treatment of EOEE with SCN8A gene mutations, indicating that the combination therapy using anti-epilepsy drugs can be applied to EOEE patients according to the type of gene function.

Interpretation to the European clinical guidelines of psychological interventions for Tourette syndrome and other tic disorders in 2021 / 中华实用儿科临床杂志

Tic disorders are one of the common neurodevelopmental disorders in children, which are mainly managed by pharmacological and non-pharmacological treatment.Psychological interventions belong to the non-pharmacological treatment, which, however, have not yet been fully recognized and understood in China.The analyses on clinical effectiveness and availability to pediatric patients are limited.This study aims to interpret the clinical guidelines of psychological interventions for Tourette syndrome and other tic disorders by European Society for the Study of Tourette syndrome in the journal of European Child and Adolescent Psychiatry in 2021, aiming to provide reference for the psychological interventions of tic disorders in China.

Research progress of refractory tic disorders / 中华实用儿科临床杂志

Refractory tic disorders (RTD) are a recently emerging concept gradually formed in pediatric neurology/psychiatry.Currently, the concept and diagnostic criteria of RTD remain unclarified, and it is extremely difficult to treat RTD.In this article, the definition, clinical features, influence factors, diagnosis, differential diagnosis, pharmacological treatment and non-pharmacological treatment of RTD in children were reviewed.

Influencing factors of image cleanliness scores of magnetically-controlled capsule endoscopy / 中华消化内镜杂志

Objective:To explore the influencing factors of the image cleanliness scores of magnetically-controlled capsule endoscopy (MCE) and the methods to improve cleanliness scores.Methods:Data of patients undergoing MCE from October 2017 to August 2020 in Peking University First Hospital were analyzed retrospectively. The cleanliness scores at six regions of the stomach (cardia, fundus, body, angularis, antrum, and pylorus) were recorded (1-4 points), and the sum of the scores from these six regions was also calculated. Clinical features [gender, age, body mass index, indication, use of esophagus cap, and medication of proton pump inhibitors(PPI)], and gastric preparation regimens (one dose of pronase: simethicone 5 mL + pronase 20 000 U + sodium bicarbonate 1 g; or two doses of pronase: simethicone 5 mL + pronase 40 000 U + sodium bicarbonate 2 g) were collected. Cleanliness scores were defined as poor (group P, total cleanliness scores≤18) and as good (group G, total cleanliness scores>18). Clinical features, indication, use of esophagus cap and PPI, and preparation regimes were compared. Factors influencing cleanliness scores were analyzed.Results:A total of 238 consecutive patients with median age of 61.5 (54.0, 76.3) years were recruited according to inclusion criteria, among whom 68(28.6%) were female. There were 35 patients (14.7%) in group P with median age of 67.0 (56.0, 83.0) years. There were 203 patients(85.3%)in group G with median age of 61.0 (53.0, 75.0) years. No significant differences were found in age, sex, body mass index or esophagus cap use( P>0.05). Indications of abdominal symptoms or digestive system diseases( OR= 2.899, 95% CI: 1.258-6.681, P=0.012) and PPI use ( OR=3.168, 95% CI: 1.261-7.959, P=0.014) were more likely to yield a low cleanliness score. Gastric preparation regimen with two doses of pronase ( OR=0.201, 95% CI: 0.067~0.603, P=0.004)was more likely to avoid a low cleanliness score. Conclusions:Indications of digestive system diseases or abdominal symptoms and PPI use may decrease the cleanliness scores of MCE, while gastric preparation with double doses of pronase may improve it.

Interpretation of expert consensus for diagnosis and treatment of tic disorders in China / 中华实用儿科临床杂志

Tic disorders (TD) is a kind of neuropsychiatric disorders developing during childhood and cha-racterized by tics.In August 2020, the TD Consortium Neurology Group of Chinese Pediatric Society, Chinese Medical Association has developed an English version of Expert Consensus on Diagnosis and Treatment of Tic disorders in children to help improve the diagnosis, treatment and long-term management of TD, as well as international communication.Now the consensus is interpreted as follows, including its pathophysiology, clinical characteristics, diagnosis, comorbidity, treatment and prognosis.

Research on regularity of traditional Chinese medicine in treatment of Alzheimer's disease based on data mining / 中国中药杂志

To explore prescription medication regularity in the treatment of Alzheimer's disease with traditional Chinese medicine(TCM). With Alzheimer's disease or senile dementia as the subject, collecting and sorting out the journal papers in CNKI were collected as the data source to establish the literature research database of Alzheimer's disease prescriptions, and then the association rule analysis, factor analysis and systematic cluster analysis on the included TCM were conducted. Among the 113 prescriptions included in the standard, the single herb Acori Tatarinowii Rhizoma was the most common. The herbs were mainly warm and flat among four pro-perties, mainly sweet, bitter and spicy among five flavors. The drugs were mainly distributed in five internal organs, and the most commonly used drugs were deficiency tonifying drugs as well as blood activating and stasis removing drugs. In the association rule analysis, it was found that there were 6 drug pairs with the highest association strength. Eight common factors were extracted from the factor analysis, and they were classified into 6 categories in the systematic cluster analysis. The results have shown that the overall principles in treating Alzheimer's disease with modern Chinese medicine are tonifying deficiency, invigorating circulation, activating blood and dispelling phlegm.

Clinical value of TDI combined with 2D-STI on evaluating the microcirculation dysfunction and left ventricular dysfunction in patients with non-obstructive coronary angina / 中华心血管病杂志

Objective: To explore the value of tissue Doppler imaging (TDI) combined with two-dimensional speckle tracking imaging (2D-STI) at rest on evaluating microcirculation dysfunction and left ventricular dysfunction in patients with angina and no obstructive coronary artery disease(ANOCA). Methods: This retrospective study recruited 78 ANOCA patients, who hospitalized in the People's Hospital of Liaoning Province from August 2019 to July 2021. These patients underwent conventional echocardiography examination, including TDI and 2D-STI, to evaluate the left ventricular dysfunction, and adenosine stress echocardiography (SE) to evaluate the coronary flow velocity reserve (CFVR). ANOCA patients were divided into coronary microcirculation dysfunction CMD group (CFVR<2) and control group (CFVR≥2) according to CFVR. Clinical data, routine echocardiographic parameters, TDI parameters including isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT), ejection time (ET), and STI parameters including global longitudinal peak strain (GLS), time to peak (TTP); peak strain dispersion (PSD) were compared between the two groups. Binary logistic regression was used to analyze the risk factors of CMD and the predictive value of each parameter to construct a joint prediction model for the diagnosis of CMD in this patient cohort. Results: The mean age was (55.5±11.2) years, 43 (55%) patients were females in this patient cohort, 38 (49%) patienst were didvided into the CMD group and 40 (51%) into the control group. Age, prevalence of hypertension, diabetes, dyslipidemia, and smokers were significantly higher in the CMD group than in the control group (all P<0.05). Tei index was higher, IVCT and TTP were longer, PSD was higher, ET was shorter, and absolute GLS was lower in the CMD group than in the control group (all P<0.05). The results of logistic regression analysis showed that longer IVCT, higher Tei index, higher time to PSD and lower absolute GLS were the independent risk factors of CMD. The ROC curve revealed that the predicting efficacy on CMD was satisfactiory with the combined predictors: AUC=0.884, sensitivity of 82% and specificity of 80%. Conclusions: TDI combined with 2D-STI is associated with a good diagnostic value on the diagnosis of CMD and left ventricular dysfunction in patients with ANOCA, which provides a feasible non-invasive tool for the diagnosis of CMD and risk stratification of patients with ANOCA.

Progress in applying surfactants to lignocellulose hydrolysis for sugar production / 生物工程学报

Lignocellulose is a major biomass resource for the production of biofuel ethanol. Due to its abundance, environmental friendliness and renewability, the utilization of lignocellulose is promising to solve energy shortage. Surfactant can effectively promote the enzymatic hydrolysis of lignocellulose. By discussing the influence and mechanism of different surfactants on the enzymatic hydrolysis, we provide references for finding appropriate surfactants in enzymatic hydrolysis process.