OBJETIVE:To explore the clinical and genetic characteristics of two children with Neurodevelopmental disorders (NDDs) due to variants of TANC2 gene. METHODS:Clinical data of two children who were admitted to the Third Affiliated Hospital of Zhengzhou University respectively in April 2020 and April 2021 were retrospectively analyzed. Peripheral blood samples of the children and their parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing. By using "TANC2 gene", "Neurodevelopmental disorders", "Nervous system development disorders", "TANC2" as the key words, similar cases were searched from the CNKI, Wanfang database platform and PubMed database, with the search time set as from the establishment of the database to December 2023. This study was approved by the Third Affiliated Hospital of Zhengzhou University (Ethics No. 2020-57). RESULTS:Case 1 was a 1-year-and-3-month-old girl who had developed convulsions at 1 year old and had three episodes of seizures. Her epilepsy had resolved with the treatment of oxcarbazepine, which was stopped at the age of 2-year-and-7-month. Her language, movement and intelligence development were all normal. Case 2 was a 1-year-and-10-month-old boy, who had developed convulsions at 1 year old. His seizure type was myoclonus, and the frequency was dozens of times a day. His epilepsy had resolved with the treatment of sodium valproate. His language, movement and intelligence development was delayed for about half a year. Genetic analysis showed that both children had harbored novel variants of the TANC2 gene (NM_025185.4), including c.3398G>A (p.Gly1133Glu) and c.2829+1G>A, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the former was rated as likely pathogenic (PS2+PM2_Supporting+PP3) and the latter was rated as pathogenic (PVS1+PS2+PM2_Supporting). Two previous reports were retrieved, which had involved 17 cases and 16 variants. Common features had included autism spectrum disorder (70.6%, 12/17) , intellectual disability (94.1%,16/17) , language and motor retardation (88.2%, 15/17；58.8%, 10/17), facial dysmorphism, epilepsy, ataxia, and thoracic and spinal deformities. CONCLUSION:Variants of the TANC2 gene probably underlay the epilepsy and development delay in these children with NDDs.

目的:观察虚拟现实(VR)技术康复训练在膝骨关节炎康复治疗中的效果.方法:选择 2021 年 10 月至2022 年9 月接受康复治疗的膝骨关节炎患者92 例,分为对照组和试验组,每组 46 例.对照组给予常规康复治疗30 d,试验组在常规康复的基础上给予VR技术康复训练治疗.比较两组患者治疗前后膝关节VAS评分、HSS评分,膝关节积液情况,膝关节积液中IL-1β、IL-6、TNF-α的含量.结果:两组患者治疗前后膝关节VAS评分、HSS评分,膝关节积液中IL-1β、TNF-α含量差值比较差异有统计学意义(P<0.05);治疗后实验组合并膝关节积液占比低于对照组(P =0.031).结论:VR技术康复训练结合适宜康复治疗在膝骨关节炎患者的康复中有积极作用,值得进一步推广应用.

Background Global developmental delay (GDD) is a common neurodevelopmental disorder in childhood whose clinical manifestations are diverse. Currently, there are few large sample analyses of the gender differences of clinical manifestations in GDD children in China. Objective To investigate the gender differences of clinical data in GDD children. Methods Seven hundred and ninety-nine GDD children who received initial inpatient treatment from Department of Child Rehabilitation, Third Affiliated Hospital of Zhengzhou University from January 2020 to February 2022 were recruited. Clinical data including maternal data in pregnancy and the perinatal period, and general data, measurement results of EEG, brain MRI, the Chinese version of Gesell Developmental Scales-Revised of the children and comorbidity rate were retrospectively collected. Gender differences of clinical data of GDD children were analyzed. Results The ratio of male children (n=568) to female children (n=231) was 2.46∶1. The age of first visit in male children〔19.0 (8.8, 33.0) 〕 was older than that of female children〔12.7 (6.8, 27.0) 〕 (P<0.05). The chief complaint was motor retardation (51.1%, 118/231) in female children, and language retardation (41.4%, 235/568) in male children. There were significant differences in chief complaint, birth season, gestational age at birth, gestational age at birth in relation to birth weight, birth weight classification and fine motor classification between male and female children (P<0.05). Male children had lower rates of fetal intrauterine distress, EEG abnormalities and microcephaly and higher rate of autism spectrum disorder than female children (P<0.05) . Conclusion There are gender differences in some clinical data of children with GDD. Male children have higher prevalence of GDD, and females have more clinical symptoms.

Aicardi-Goutières 综合征(Aicardi-Goutières syndrome,AGS)是一种罕见的以神经系统及皮肤受累为主的早发性遗传性疾病,1984年被Aicardi等[1]首次描述,其主要临床表现为严重的发育迟缓、智力障碍或倒退、癫痫、小头畸形;影像学检查可见颅内钙化、白质异常及脑萎缩;病理表现为体内干扰素水平增多,脑脊液淋巴细胞增多[2].日本报道AGS发病率约为1/900万[3],国内尚无AGS患病率的相关报道[2].目前已发现的致病基因有TREX1,RNASEH2 B,RNASEH2 C,RNASEH2A,SAMHD1,ADAR1 和 IFH1,分别对应 AGS 的 1-7型[2,4].最新研究表明,PNPT1基因突变也可能导致AGS[5].TREX1所致的AGS属AGS1型,也是最经典的AGS类型,占所有AGS患儿的17％[6]o本文回顾性分析1例携带TREX1基因复合杂合变异(其中C.352C＞G为新发现的变异)所致的AGS患儿的临床资料,并总结近5年国内外报道的相关文献,以提高临床对AGS的认识.

Objective:To observe the effect of mirror visual feedback training on upper limb function and muscle tension in children with spastic hemiplegia resulting from cerebral palsy (SHCP).Methods:Seventy-six children aged 2-5 with SHCP were randomly divided into a control group of 33 and a treatment group 34. All were given routine occupational therapy, physical therapy, massage and physical agents. Each therapy session lasted 30 minutes daily, 5 times a week over 3 weeks as a course of treatment. There was a one week interval after each of 6 courses, so the total treatment lasted 6 months. The treatment group was additionally trained with mirror visual feedback with the same schedule. Before, as well as after 3 and 6 months of treatment, each patient′s upper limb motor function, fine motor function and muscle tone were evaluated using the Fugl-Meyer motor function assessment scale (FMA), the Peabody fine motor development scales (PDMS-FM), the modified Ashworth scale (MAS) and integrated electromyograms (iEMGs).Results:There were no significant differences between the two groups before treatment. After both 3 and 6 months significant improvement was observed in both groups′ average FMA score, PDMS-FM total score, grip, and visual motor integration. At both points the treatment group′s averages were significantly better than those of the control group. The average MAS and iEMG results, however, were not significantly different at either time point.Conclusions:For children with spastic hemiplegia caused by cerebral palsy, mirror visual feedback training can effectively improve upper limb functioning, but it cannot reduce their muscle tone.

目的 了解全面性发育迟缓（GDD）患儿的危险因素、临床特点的性别差异。方法 回顾性收集从2020年1月到2022年2月在我院首次住院治疗的GDD患儿危险因素、临床特点等资料；将具有完整病例资料的患儿纳入研究，分析GDD患儿的危险因素、临床特点的性别差异。结果 共纳入799例GDD患儿，其中男568例，女231例，男女比例为2.46:1。与女性患儿［12.7（6.8，27.0）］相比，男性患儿首次就诊月龄［19.0（8.8，33.0）］较晚，P＜0.001；女性患儿以运动发育迟缓（51.1%）为主要就诊原因，男性患儿以语言发育迟缓（41.4%）为主要就诊原因，P＜0.001。男性患儿秋季出生比例（30.6%）高于女性患儿（22.1%）；P＜0.05。危险因素及临床特征方面，男性患儿宫内窘迫、脑电图异常、小头畸形、过期产、小于胎龄儿、超低体重儿、精细动作重度发育迟缓比例分为4.9%、11.1%、0.9%、0.7%、9.2%、0.5%和6.7%，均低于女性（分别为10.0%、17.7%、4.8%、3.0%、15.6%、3.0%和10.2%）；男性患儿ASD、巨大儿比例分别为17.4%、11.8%，高于女性患儿（8.2%和5.2%）；均P＜0.05。结论 GDD患儿在部分危险因素及临床特点上存在性别差异，GDD患儿中女性比例低，但临床症状相对重。

目的 探讨佩利措伊斯-梅茨巴赫病(PMD)的临床及分子遗传学特征.方法 回归性分析2015年6月至2020年10月郑州大学第三附属医院确诊的12个家系共14例PMD患儿的临床表现和基因突变特点.结果 14例均为男性,就诊年龄5 d至10岁,起病年龄1 d至7个月.首发症状表现为眼球震颤9例,大运动发育迟缓3例,呻吟样呼吸、哭声弱1例,异常姿势2例.临床表现:14例均存在发育迟缓,其中10例以运动发育迟缓更为明显;肌张力低下10例,肌张力增高3例;12例存在眼球震颤.临床分型经典型8例,先天型2例,中间型4例.14例患儿头颅磁共振成像(MRI)均表现为脑白质髓鞘化障碍,脑干听觉诱发电位检测异常7例.14例先证者中,7例蛋白脂蛋白1(PLP1)基因为2～8号外显子重复变异;1例为X染色体Xq22.2处重复0.33Mb区域,覆盖了PLP1基因100％的区域;1例c.83G>A变异,1例c.226G>C变异,2例c.259delC变异,2例c.157dupA变异.12例先证者为遗传性突变,均为母源遗传,母亲为无临床症状的携带者.c.83G>A、c.226G>C、c.259delC、c.157dupA均为国际上未报道的新突变.结论 PMD的首发症状以眼球震颤最为常见;发育迟缓、肌张力异常、眼球震颤为其最常见的临床症状;头颅MRI提示脑白质髓鞘化障碍.PLP1基因突变中重复变异最多,其次为点突变,c.83G>A、c.226G>C、c.259delC、c.157dupA变异为尚未报道的新突变.

[Abstract] Objective To understand the gender differences in risk factors and clinical characteristics of children with global developmental delay (GDD). Methods The data of risk factors and clinical characteristics of children with GDD who were hospitalized for the first time in our hospital from January 2020 to February 2022 were collected retrospectively, and the children with complete case data were included in the study to analyze the gender differences in risk factors and clinical characteristics of children with GDD. Results A total of 799 children with GDD were included, including 568 males and 231 females, the male-to-female ratio is

目的 了解脑瘫患儿高危因素、临床特点及其与癫痫发生的关系,探讨脑瘫患儿共患癫痫的危险因素.方法 回顾性收集从2019年1月-2022年2月在郑州大学第三附属医院住院治疗的脑瘫患儿的病例资料,将患儿分为脑瘫共患癫痫组和未共患癫痫组,采用x2检验分析两组间高危因素、临床特点等资料,应用多因素Logistic回归对共患癫痫的危险因素进行分析.结果 共纳入630例脑瘫患儿,其中男421例,女209例;脑瘫共患癫痫组患儿155例,未共患癫痫组患儿475例,癫痫发生率24.6％.脑瘫共患癫痫组患儿在宫内窘迫、窒息、多胎及新生儿先天性畸形史方面的发生率高于未共患癫痫组患儿(x2=4.788、9.368、5.255、12.111,P＜0.05),两组患儿在脑瘫分型、头颅MRI分类、粗大运动功能分级方面差异有统计学意义(x2=213.686、14.640、481.531,P＜0.05).多因素Logistic回归结果显示,痉挛型四肢瘫(OR=14.090,95％CI:1.950～101.813)、新生儿先天性畸形史(OR=1.891,95％CI:1.155～3.095)、围生期窒息史(OR=1.527,95％CI:1.034～2.255)可能是脑瘫患儿共患癫痫的危险因素(P＜0.05).结论 脑瘫患儿共患癫痫的发病率较高,病情重,识别危险因素可以为针对性的临床治疗提供依据.

目的 探讨佩梅病的临床、影像及遗传学特征.方法 回顾分析及随访1个核心家系中兄弟两人同患佩梅病的临床资料.结果 先证者男性,7岁,弟弟5岁,均表现为自幼运动发育迟缓,不能独站、独走,而智力发育基本不受影响.T 2加权像头颅磁共振成像表现为脑白质弥漫性高信号.先证者及弟弟均存在蛋白脂蛋白1(PLP 1)基因c.259 delC半合子变异;母亲为携带者.兄弟两人均确诊为中间型佩梅病.随访3年,运动功能异常加重,先证者仅能短暂扶站,四肢肌力Ⅲ级;先证者弟弟足踝变形,明显足内翻,无法扶站;智力均无明显倒退.结论 发现国内未见报道的PLP 1基因c.259 delC半合子变异所致佩梅病.

Background: Dairy safety has caused widespread concern in society. Unsafe dairy products have threatened people's health and lives. In order to improve the safety of dairy products and effectively prevent the occurrence of dairy insecurity, countries have established different prevention and control measures and safety warnings. Objective: The purpose of this study is to establish a dairy safety prediction model based on machine learning to determine whether the dairy products are qualified. Methods: The 34 common items in the dairy sampling inspection were used as features in this study. Feature selection was performed on the data to obtain a better subset of features, and different algorithms were applied to construct the classification model. Results: The results show that the prediction model constructed by using a subset of features including "total plate", "water" and "nitrate" is superior. The SN, SP and ACC of the model were 62.50%, 91.67% and 72.22%, respectively. It was found that the accuracy of the model established by the integrated algorithm is higher than that by the non-integrated algorithm. Conclusion: This study provides a new method for assessing dairy safety. It helps to improve the quality of dairy products, ensure the safety of dairy products, and reduce the risk of dairy safety.

Alzheimer's disease (AD) is a chronic neurodegenerative disease that 4 widespread in the elderly. The etiology of AD is complicated, and its pathogenesis is still unclear. Although there are many researches on anti-AD drugs, they are limited to reverse relief symptoms and cannot treat diseases. Therefore, the development of high-efficiency anti-AD drugs with no side effects has become an urgent need. Based on the published literature, this paper summarizes the main targets of AD and their drugs, and focuses on the research and development progress of these drugs in recent years.

BACKGROUND:Nilatinib is an irreversible tyrosine kinase inhibitor, which is used in the treatment of some kinds of cancer. To study the interaction between Neratinib and MAD2L1, a potential tumor target, is of guiding significance for enriching the medicinal value of Neratinib.METHOD:The binding mechanism between Mitotic arrest deficient 2-like protein 1 (MAD2L1) and Neratinib under simulative physiological conditions was investigated by molecule simulation and multi-spectroscopy approaches.RESULTS:Molecular docking showed the most possible binding mode of Neratinib-MAD2L1 and the potential binding sites and interaction forces of the interaction between MAD2L1 and Neratinib. Fluorescence spectroscopy experiments manifested that Neratinib could interact with MAD2L1 and form a complex by hydrogen bond and van der Waals interaction. These results were consistent with the conclusions obtained from molecular docking. In addition, according to Synchronous fluorescence and three-dimensional fluorescence results, Neratinib might lead to the conformational change of MAD2L1, which may affect the biological functions of MAD2L1.CONCLUSION:This study indicated that Neratinib could interact with MAD2L1 and lead to the conformational change of MAD2L1. These works provide helpful insights for the further study of biological function of MAD2L1 and novel pharmacological utility of Neratinib.

In recent years, the successful implementation of human genome project has made people realize that genetic, environmental and lifestyle factors should be combined together to study cancer due to the complexity and various forms of the disease. The increasing availability and growth rate of 'big data' derived from various omics, opens a new window for study and therapy of cancer. In this paper, we will introduce the application of machine learning methods in handling cancer big data including the use of artificial neural networks, support vector machines, ensemble learning and naive Bayes classifiers.

The hippocampus is critical for memory and emotion and both N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid (AMPA) receptors are known to contribute for those processes. However, the underlying molecular mechanisms remain poorly understood. We have previously found that mice undergo memory decline upon dcf1 deletion through ES gene knockout. In the present study, a nervous system-specific dcf1 knockout (NKO) mouse was constructed, which was found to present severely damaged neuronal morphology. The damaged neurons caused structural abnormalities in dendritic spines and decreased synaptic density. Decreases in hippocampal NMDA and AMPA receptors of NKO mice lead to abnormal long term potentiation (LTP) at DG, with significantly decreased performance in the water maze, elevated- plus maze, open field and light and dark test. Investigation into the underlying molecular mechanisms revealed that dendritic cell factor 1 (Dcf1) contributes for memory and emotion by regulating NMDA and AMPA receptors. Our results broaden the understanding of synaptic plasticity's role in cognitive function, thereby expanding its known list of functions.