Objective:To report the clinical features of KCNQ2-associated epilepsy and the novel mutations and unreported clinical phenotype of KCNQ2 gene, so as to provide help for treatment selection and prognosis evaluation.Methods:Among 979 patients with epilepsy and developmental delay who were admitted to the Department of Neurology,Children′s Hospital Affiliated to Capital Institute of Pediatrics from July 2015 to October 2019, a total of 13 patients were selected from 12 families with KCNQ2 gene mutation by whole exome sequencing technology. Suspected mutations were verified by Sanger sequencing on the probands and their parents to identify the source. The clinical phenotype and genotype were analyzed according to these results.Results:Among the 13 patients with epilepsy, the onset age of four cases were older than six months [two cases in infancy (epilepsy encephalopathy), one case in early childhood (epilepsy encephalopathy) and one case in adolescence (benign epilepsy)]. Eight cases were treated with oxcarbazepine, of whom five cases were seizure free, and two cases showed partial response (>50%). Two cases treated with topiramate were seizure free. Five novel mutations were found in this research, including c.379T>G(p.Y127D), c.1A>C(initial codon mutation), c.708G>C(p.W236C), c.1027G>T(p.A343S) and c.1649T>G(p.V550G).Conclusions:Although it was rare in clinical work, the variation of KCNQ2 gene existed in patients with childhood-onset epilepsy and adolescent-onset epilepsy. Meanwhile, five novel mutations of KCNQ2 gene were reported, which further expanded its gene spectrum. This research supported that oxcarbazepine was the efficient medicine for the KCNQ2-associated epilepsy. Genetic testing showed great help to the treatment of epilepsy.

Objective To explore the effects of aerobic exercise and resistance training on center arterial blood pressure.Methods Fifteen healthy men who had not practiced aerobic exercise or resistance training within the previous 6 months were enrolled in this study.A self-matched pairs design was adopted.All of the subjects performed moderate intensity aerobic exercise,for 30 min initially,and after 2 weeks,performed resistance training at 60％ of their l-repeat maximum effort (1-RM).Their central aortic systolic blood pressure (CSBP) before and after aerobic exercise and resistance training were measured and compared,respectively.The changes in CSBP and an augmentation index (AI) of radial artery and relative blood pressure were compared between the two interventions.Results CSBP decreased significantly after both sorts of training.The two types of training showed no significant difference in their effects on CSBP.However,after a 20 min recovery,systolic blood pressure and pulse pressure were significantly lower after aerobic exercise than after resistance training.The significant difference persisted after 20 min and 40 min of re-covery.The AI of the radial artery was also significantly lower 5 min after aerobic exercise than after resistance train-ing.Conclusions After moderate aerobic exercise and resistance training,CBSP,AI and systolic pressure all display favorable changes.However,moderate intensity aerobic exercise provides the better effect in improving blood pressure.

Objective To investigate the effect of EMG-triggered stimulation on drop foot for poststroke hemiplegia. Methods 36 hemiplegic patients were randomized into routine group (n=18) and EMG-triggered stimulation group (triggered group, n=18). 2 groups were assessed by Fugl-Meyer Assessment (FMA), range of motion (ROM) of ankle dorsiflexion and iEMG values before and after treatment. Results The scores of FMA, degrees of ROM, iEMG values of the tibialis anterior, and co-contraction ratio improved in 2 groups after treatment (P<0.05), and the triggered group had better effect than the routine group (P<0.05). Conclusion EMG-triggered stimulation can improve muscle strength, and decrease co-contraction ratio.

Objective: To systematically evaluate the correlation between selenium in the body and the risk of chronic kidney disease (CKD), so as to provide insights into CKD prevention and control. Methods: Publications pertaining to the correlation between selenium level and CKD were retrieved from electronic databases, including CNKI, WanFang Data, PubMed and Web of Science from inception until July 28, 2022. Meta-analysis was performed using the software Stata 16.0, and all measures were expressed with standardized mean difference (SMD) and its 95%CI. The source of heterogeneity was analyzed using subgroup analysis and meta-regression, and sensitivity analysis was performed using the leave-one-out method. In addition, the publication bias was evaluated with d funnel plot, Egger's test and Begg's test, and the robustness of the result was evaluated using the trim and filling method. Results: A total of 2 990 publications were screened, and 63 eligible publications were included in the final analysis, including 18 cross-sectional studies, 40 case-control studies, 2 cohort studies and 3 randomized controlled trials (RCTs), which covered 5 099 CKD patients and 6 334 controls. Meta-analysis showed lower selenium levels in CKD patients than in controls (SMD=-1.828, 95%CI: -2.132 to -1.523, P<0.001). Subgroup analysis showed lower selenium levels among CKD patients than among controls from Asia, Europe and multiple continents (P<0.05), and lower selenium levels were detected in patients undergoing conservative treatment, hemodialysis and peritoneal dialysis than in controls (P<0.05), while the selenium levels were significantly lower in CKD patients than in controls in cross-sectional studies, case-control studies and RCTs (P<0.05). The selenium level was significantly lower among CKD patients than among controls regardless of the study year, sample size and score for quality of publications (P<0.05). Sensitivity analysis showed robustness of this meta-analysis. Publication bias was identified by funnel plot, Begg's test and Egger's test, and the robustness of the result was found using the trim-and-fill method. Conclusion There may be a possible correlation between selenium and the risk of CKD.

Objective:To investigate thyroid function, physical growth, and psychological and behavioral development in children with congenital hypothyroidism.Methods:Thirty-two children with congenital hypothyroidism who were born in Yuyao People's Hospital from January 2014 to December 2018 were included in the observation group. Thirty healthy neonates who were born in the same period were included in the control group. Thyroid function index changes at the age of 1 year relative to at birth, physical, intellectual, and neuropsychological development and bone age at the age of 1 year were compared between the observation and control groups.Results:Thyroid-stimulating hormone level at birth was significantly higher in the observation group than in the control group [(18.23 ± 2.71) mU/L vs. (2.85 ± 0.34) mU/L, t = 30.84, P < 0.001]. Free thyroxine level at birth was significantly lower in the observation group than in the control group [(6.76 ± 1.54) pmol/L vs. (17.91 ± 2.04) pmol/L, t = 24.39, P < 0.001]. In the observation group, thyroid-stimulating hormone and free thyroxine levels at the age of 1 year were (2.68 ± 0.78) mU/L and (17.26 ± 2.11) pmol/L, respectively, which were not significantly different from those in the control group [(2.77 ± 0.63) mU/L and (17.54 ± 2.20) pmol/L, t = 0.50, 0.51, both P > 0.05]. Body weight, body length, head circumference, and bone age at the age of 1 year were (9.21 ± 1.20) kg, (79.84 ± 3.05) cm, (43.73 ± 1.42) cm, (1.01 ± 0.15) years old, respectively in the observation group, which were significantly lower than those in the control group [(10.12 ± 1.32) kg, (84.54 ± 3.41) cm, (45.85 ± 2.04) cm, (1.14 ± 0.28) years old, t = 2.84, 5.73, 4.77, 2.30, P < 0.05]. The proportion of children patients with bone age lag was significantly higher in the observation group than in the control group [21.88% (7/32) vs. 3.33% (1/30), χ2 = 4.74, P < 0.05]. There was a significant difference in intellectual development at the age of 1 year between the two groups ( χ2 = 7.05, P < 0.05). Gross movement, fine movement, adaptability, language ability, and social ability in the observation group were scored (90.43 ± 6.96) points, (92.03 ± 6.03) points, (88.45 ± 4.85) points, (84.04 ± 5.71) points, and (85.05 ± 6.17) points, respectively, which were significantly lower than those in the control group [(99.47 ± 5.40) points, (104.12 ± 5.71) points, (98.47 ± 5.22) points, (94.16 ± 4.98) points, and (104.34 ± 5.70) points ( t = 5.69, 8.09, 7.84, 7.42, 12.76, all P < 0.001]. Conclusion:Neonate patients with congenital hypothyroidism have obvious physical growth and psychological and behavioral development disorders. Early screening and treatment of neonatal congenital hypothyroidism should be strengthened to improve the prognosis.

Objective To investigate the feasibility of the upper- arm electronic sphygmomanometer for evaluating the blood pressure in patients with atrial fibrillation. Methods Consecutive hospitalized patients with atrial fibrillation for coronary angiography were selected, and the application of upper- arm electronic sphygmomanometer and mercury sphygmomanometer of blood pressure were applied and in the process of coronary angiography, the radial artery invasive blood pressure was recorded and the correlation was analyzed. Results Mercury sphygmomanometer and radial artery invasive blood pressure measurement had a good consistency on systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure in atrial fibrillation patients, the differences were not statistically significant (P>0.05). Upper- arm electronic sphygmomanometer and radial artery invasive blood pressure measurement had some consistency (pulse rate range, pulse rate of 70-90 beats / min) on systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure in atrial fibrillation patients, the differences were not statistically significant (P>0.05). Upper-arm electronic sphygmomanometer and mercury sphygmomanometer had some consistency (pulse rate range, pulse rate of 70-90 beats / min) on systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure in atrial fibrillation patients, the differences were not statistically significant (P>0.05). The correlation between mercury sphygmomanometer and radial artery invasive blood pressure measurement were found on systolic blood pressure, diastolic blood pressure, pulse pressure, mean arterial pressure in atrial fibrillation patients (r=0.71-0.78, P<0.05),which were better than those of upper- arm electronic sphygmomanometer and radial artery invasive blood pressure measurement (r=0.53-0.70, P <0.05). Conclusions The upper- arm electronic sphygmomanometer can be used for the assessment of blood pressure in patients with atrial fibrillation.

Objective:To investigate the clinical characteristics of children with high-risk acute lymphoblastic leukemia (ALL) receiving lasting remission after severe infection.Methods:The data of 3 children with high-risk ALL who were treated in Children's Hospital Affiliated of Zhengzhou University in 2014, 2015 and 2017 were analyzed retrospectively. The clinical and laboratory characteristics of all patients were also analyzed, and the relevant literatures were reviewed.Results:All 3 children were clinically classified as high-risk ALL with severe infection. A variety of anti-infective drugs and blood products were used in the treatment, and all achieved lasting remission.Conclusions:Children with high-risk ALL after severe infection can acquire lasting remission, which may be related with the production of infection stimulating inflammatory factors and cytokines to activate certain immune pathways, or various kinds of antibiotics, blood products participating in the immune regulation to make the body regain the immune surveillance function of the tumor cells.

Objective To investigate the effect of metformin on the growth of human anaplastic thyroid cancer cell HTh74Rdox which is doxorubicin resistant. Methods The HTh74Rdox was treated with different concentrations of metformin for 48 h. Cell morphology was observed by microscope, cell viability was tested by methylthiazoletetrazolium (MTT), cell apoptosis by annexin Ⅴ and propidium iodide double staining, the anti-oncogenic miRNA was assayed by realtime fluorescence quantitative PCR (RT-PCR), and the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway tested by western blot. Furthermore, the anti-oncogenic miRNAs were knockdown by miRNA inhibitors (miR-34a, miR-101, miR-125b, and miR-138 inhibitors) and the cells were treated by metformin for 48 h, after that, cell apoptosis was detected by annexin Ⅴ and propidium iodide double staining, the expression of protein related to AMPK/mTOR signaling pathway was detected by western blot. Results Metformin inhibited the growth of human anaplastic thyroid cancer cell HTh74Rdox in a concentration-dependent manner, the cell apoptosis was induced by metformin, and there was a significantly lower expression of miR-34a, miR-101, miR-125b, and miR-138 in the HTh74Rdox. However, the four above miRNAs were upregulated by metformin, and AMPK/mTOR pathway was also activated by metformin. When these miRNAs were suppressed by miR-inhibitors (miR-34a, miR-101, miR-125b, miR-138 inhibitors), the stimulating effect of apoptosis and AMPK/mTOR pathway by metformin were reversed. Conclusion Metformin significantly suppresses cell viability of human anaplastic thyroid cancer cell HTh74Rdox, and stimulates AMPK/mTOR pathway and apoptosis by upregulating the expressions of miR-34a, miR-101, miR-125b, miR-138 in HTh74Rdox cell.

Objective: To evaluate the association of smoking with the risk of ankylosing spondylitis (AS) using a Mendelian randomization (MR) approach. Methods: A total of 16 383 186 AS-associated single nucleotide polymorphisms (SNPs), 378 smoking initiation associated SNPs and 126 lifetime smoking score-associated SNPs were collected from three large-scale genome-wide association studies (GWAS). The association of smoking phenotypes with the risk of AS was examined using inverse-variance weighted (IVW) with AS as a outcome variable, smoking initiation and lifetime smoking score as exposure factors and SNPs with strong associations with smoking as instrumental variables, and sensitivity analyses were performed with maximum likelihood-based method, MR pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression analysis. Results: A 33.5% increased risk of AS was found among genetically predicted smokers relative to non-smokers (OR=1.335, 95%CI: 1.059-1.682), and an increase in predicted lifetime smoking by per standard deviation resulted in a 101.4% increased risk of AS (OR=2.014, 95%CI: 1.341-3.024). The maximum likelihood-based method and MR-PRESSO test showed consistent correlated effect estimations and MR-Egger regression analysis identified no evidence of pleiotropy. Conclusion It is genetically predicted that smoking is associated with an increased risk of AS.

Objective: To investigate the causal relationship between gut microbiota and polycystic ovary syndrome (PCOS) using a Mendelian randomization (MR) study, so as to provide insights into the pathogenesis of PCOS and the formulation of prevention and treatment strategies. Methods: The genetic data on gut microbiota was derived from a meta-analysis of genome-wide association studies (GWAS) involving 18 340 participants. The genetic data on PCOS was sourced from two GWAS meta-analyses in European populations, serving as the discovery set and the validation set, respectively. A two-sample MR analysis was conducted using the discovery set, with the inverse variance weighted (IVW) method as the primary approach. Sensitivity analyses employed the weighted median method, MR-Egger regression, and the MR-PRESSO test. The validation set was utilized for verification, and a meta-analysis was performed to combine the results from the two datasets. Results: Forward MR analysis results showed that nine types of gut microbiota were statistically associated with PCOS (all P<0.05). Specifically, the association of family Streptococcaceae (OR=1.442, 95%CI: 1.097-1.895), genus Actinomyces (OR=1.359, 95%CI: 1.036-1.784), genus Ruminococcaceae UCG 011 (OR=0.755, 95%CI: 0.619-0.921), genus Sellimonas (OR=0.766, 95%CI: 0.657-0.893) and genus Streptococcus with PCOS (OR=1.496, 95%CI: 1.136-1.972) remained consistent in the sensitivity analysis. Reverse MR analysis showed no evidence for the causal association between PCOS and the aforementioned five types of gut microbiota (all P>0.05). The MR analysis results of the validation set showed that there was no statistical association between the aforementioned five types of gut microbiota and PCOS (all P>0.05). However, the associations remained significant for genus Actinomyces (OR=1.226,95%CI：1.010-1.503) and genus Streptococcus (OR=1.266,95%CI：1.042-1.452) in the meta-analysis (both P<0.05). Conclusion This study provides the evidence that genus Actinomyces and genus Streptococcus are causally associated with PCOS.