Objective:To observe the clinical efficacy of mouse nerve growth factor (mNGF) combined with rehabilitation on children with global developmental delay(GDD).Methods:It was a prospective multicenter clinical randomized controlled trial (RCT) involving 120 children with GDD admitted to 5 hospitals in China from May 2020 to January 2022.They were randomly divided into mNGF group and conventional rehabilitation group using block randomization method.All children were managed by standardized rehabilitation after recruitment, and those in the mNGF group were additionally given mNGF injections.All subjects were surveyed using the Gesell Development Diagnosis Schedules(GDDS) at baseline, 90 days and 120 days after treatment, and their developmental quotient (DQ) was recorded.Clinical efficacy was analyzed by the paired t-test, rank sum test and Chi- squared test. Results:After 90 days of treatment and the continuous follow-up to 120 days, the increases in the DQ of gross motor (7.520±13.900 vs.0.450±11.459), fine motor (7.800±15.346 vs.1.250±11.581), adaptive behavior (7.730±13.428 vs.2.100±12.022) and personal-social behavior (6.780±11.651 vs.1.780±10.120) than baseline were significantly higher in mNGF group than those of conventional rehabilitation group (all P<0.05). Serious adverse events and important drug-related medical events were not reported. Conclusions:mNGF combined with rehabilitation effectively enhances the development levels of gross motor, fine motor, adaptive behavior and personal-social behavior, and continuously improves the condition of GDD in children with a high safety.

Objective:To establish Sprague-Dawley (SD) rat models of cognitive impairment through repeated stimulation of lipopolysaccharide (LPS) in the early brain development, and to inquire into the effect of " multi-hits" mediated by inflammatory response on the histology and behavior of SD rat models and related molecular mechanisms.Methods:This study adopted a group design for experiments.The " multi-hits" SD rat models were established by intraperitoneal injection of LPS.According to the random number table method, 24 pregnant rats were randomly divided into 4 groups: control group, LPS1 group, LPS2 group and LPS3 group, 6 rats in each group.In the control group, saline was intraperitoneally injected into rats with gestational age of 18 days and 20-day-old neonatal rats.Rats with gestational age of 18 days were intraperitoneally injected with saline in the LPS1 group, 0.05 mg/kg LPS in the LPS2 group, and 0.1 mg/kg LPS in the LPS3 group.The pups in LPS1-3 groups were all injected intraperitoneally with 1 mg/kg LPS at the postnatal age of 20 days.The motor and cognitive function of the pups were evaluated overall by behavioral experiments such as forelimb suspension tests, grid tests and water maze tests.The relative expression of glial fibrillary acidic protein (GFAP), Notch1 and Jagged1 in brain tissue of pups was mainly detected by Western blot (WB) and histological experiments.One-way ANOVA analysis of variance and independent samples t- test were used to compare data among groups and between groups, respectively. Results:(1) Behavioral experiments: compared with the control group, LPS1-3 groups showed progressive decrease in forelimb suspension time [(34.81±5.66) s, (22.47±4.35) s, and (13.20±4.25) s vs.(43.88 ± 4.85) s], and the number of missteps in the grid experiment increased progressively (16.13±2.90, 20.75±3.10, 25.13±4.45 vs.9.00±2.72). The differences were statistically significant ( F=69.77, 35.59, all P<0.001). Both the escape latency and total distance in Morri′s water maze test increased progressively ( P<0.05). (2) WB experiment: the relative expression levels of GFAP, Notch1 and Jagged1 proteins in LPS1-3 groups were significantly higher than that in the control group ( P<0.05). (3) Hematoxylin-eosin (HE) staining and electron microscope pathology: compared with the control group, LPS1-3 groups had more loosely arranged frontal cortices and more obvious cell pyknosis.Under the electron microscope, the cytoplasm was swelling to varying degrees, mitochondrial cristae were broken, and part of the nuclear membrane was damaged. Conclusions:In the " multi-hits" cognitive impairment model, the damage to the brain tissue structure and behavioral changes of pups may be related to the up-regulation of Notch1/Jagged1 pathway mediated by repeated exposure to LPS.

Chinese rehabilitation guidelines for cerebral palsy (2022) mainly refers to the international evidence-based medicine and relevant guidelines for rehabilitation of cerebral palsy in recent five years.On the basis of the Chinese rehabilitation guidelines for cerebral palsy (2015), combined with the medical literature and research achievements published at home and abroad before June 2022, the evidence-based practice guidelines are revised by combining the common opinions of pediatric rehabilitation experts in China.The content includes introduction, overview, the assessment and intervention guideline for infants at high risk of cerebral palsy, evaluation of children with cerebral palsy under ICF-CY framework, rehabilitation treatment, Traditional Chinese Medicine rehabilitation therapy, rehabilitation nursing, rehabilitation approaches and management.This article interprets the guide in combination with the hot spots of cerebral palsy prevention and treatment at home and abroad, in order to help pediatric rehabilitation workers deepen their understanding of the guidelines and better guide the clinical rehabilitation practice.

Objective:To analyze the microdeletion and microduplication characteristics of pathogenic copy number variations (pCNVs) and clinical phenotypes in children with neurodevelopmental disorders, and to clarify the genetic pathogenic cause of children with neurodevelopmental disorders.Methods:Children who were identified as neurodevelopment disorders such as global developmental delay and mental disorder, by next generation sequencing-based whole genomic copy number variation testing from January 2017 to November 2019 at the First Affiliated Hospital of Anhui Medical University were enrolled, and the clinical phenotypes and pCNVs were reviewed analyzed.Results:There were 36 pCNVs in total 31 children, consisting of 24 microdeletion segments (66.67%)and 12 microduplication segments (33.33%), with sizes ranging from 320.00 kb to 93.26 Mb (mean 11.33 Mb). pCNVs frequently occurred in chromosome 15 , chromosome 8 and chromosome X, there were 9 children with 9 pCNVs in chromosome 15(25.00%), 3 children with 5 pCNVs in chromosome 8(13.89%)and 3 children with 4 pCNVs in chromosome X(11.11%) .The mainly clinical manifestations were motor disorder (30 children, 96.77%), mental disorder (22 children, 70.97%), speech development delay(22 children, 70.97% )accompanied by the malformation(11 children, 35.48%), abnormal face(11 children, 35.48%) and epilepsy(8 children, 25.81%), multisystem abnormalities generally exist in one individual.Conclusion:This study demonstrates the clinical utility of whole genome CNVs testing in the genetic diagnosis of children with neurodevelopment disorders.Genetic pathogenesis of children with neurodevelopmental disorders can be revealed by the analysis of pCNVs.

Objective: To compare the efficacy of goal-activity-motor environment (GAME) therapy and neurodevelopmental therapy (NDT) in the early intervention of high-risk infants with cerebral palsy (IHRCP), and to provide scientific evidence-based medical basis for early intervention of IHRCP. Methods: A total of 62 cases of IHRCP were enrolled in the Children′s Neurological Rehabilitation Center of the First Affiliated Hospital of Anhui Medi-cal University from June 2017 to December 2018.They were divided into GAME group (32 cases) and NDT group (30 cases) according to the admission order.Gross Motor Function Scale (GMFM), Fine Motor Function Measure (FMFM) and Gesell Development Scale (GDS) were used for detection and comparison.The differences among the gross motor, the fine motor score and the developmental quotient (DQ) between two groups before treatment, 9 months after treatment and 12 months after treatment, and the normalization rate and the incidence of cerebral palsy between the two groups at 12 months of age were compared. Results: (1) Motor function was as follows: at 9 months[GAME: (32.63±15.83) scores, (30.03±15.88) scores], [NDT: (33.37±15.61) scores, (29.67±12.54) scores] and at 12 months[GAME: (40.56±15.79) scores, (36.31±14.98) scores], [NDT: (40.47±15.50) scores, (36.73±14.58) scores] after treatment, and GMFM and FMFM scores in GAME and NDT groups were significantly higher than those before treatment[GAME: (27.56±14.24) scores, (21.75±11.35) scores], [NDT: (26.93±14.96) scores, (21.30±10.67) scores], and the differences were significant (all P<0.01), but there was no significant difference between the 2 groups (all P> 0.05). (2) DQ had no significant difference in DQ between GAME group(63.59±10.83) and NDT group (61.59±7.96) before treatment (P>0.05). The total DQ at 9 months, 12 months, the total DQ of GAME group (73.67±12.00, 81.59±13.03) was significantly higher than that of NDT group (66.05±9.54, 75.17±1.92) (all P<0.05). Among them, the improvement of GAME in speech (79.84±16.56, 83.19±17.05) at 9 months and 12 months, and adaptive ability(78.63±16.37, 85.78±13.60) were significantly higher than that of NDT group(71.63±13.36, 72.53±12.77), (68.20±14.97, 77.43±12.10), and the differences were significant (all P<0.05). (3) Prognosis was as follows: at 12 months after treatment, 25 cases in GAME group and 23 cases in NDT group developed into normal children, there was no significant difference in the normalization rate between the 2 groups (P>0.05); the incidence of cerebral palsy was present in 6 cases in GAME group and 5 cases in NDT group, and there was no significant difference between the 2 groups (P>0.05). Conclusions GAME therapy and NDT had significant effects on both gross and fine exercise of IHRCP, and the efficacy of the two methods is similar.Both GAME therapy and NDT can equally promote IHRCP development into normal infants and reduce the incidence of cerebral palsy.

Interpretation of The International Statistical Classification of Diseases and Related Health Problems-11 published by World Health Organization(WHO) and The Diagnostic and Statistical Manual of Mental Disorders of Fifth published by American Psychological Association(APA), and reference of literature in recent 10 years.In order to be in agreement with international standards which used to classify the diagnosis of neurodevelopmental disorders in children and to provide a reference for clinical diagnosis.

Cerebral palsy or high risk of cerebral palsy can be diagnosed accurately and early using the clinical signs and symptoms of cerebral palsy,involves neuroimaging,standardized neurological and standardized motor assess-ments before 6 months' corrected age. When the clinical diagnosis is suspected but cannot be made with certainty,re-commend using the interim clinical diagnosis of high risk of cerebral palsy until a diagnosis is confirmed,because infant with cerebral palsy require and benefit from different early interventions. Before 5 months' corrected age,the most pre-dictive tools for detecting risk are term - age magnetic resonance imaging(MRI),the Prechtl Qualitative Assessment of General Movements(GMs),and the Hammersmith Infant Neurological Examination(HINE). After 5 months' corrected age,the most predictive tools for detecting risk are MRI,HINE and the Developmental Assessment of Young Children. Early diagnosis and early intervention can optimize infant motor and cognitive plasticity,prevent secondary complica-tions. Cerebral palsy - specific early intervention maximizes neuroplasticity and minimizes deleterious modifications to muscle and bone growth and development. Early interventions included Goals - Activity - Motor Enrichment,neurode-velopmental treatment(Bobath,Vojta),Conductive Education and Environmental enrichment. Infants with of cerebral palsy who receive early CIMT have better hand function,and infants with any type and topography of cerebral palsy who receive GAME have better motor and cognitive skills than those who receive usual care.

The U. K.' National Institute for Health and Care Excellence (NICE)published the guideline:Cerebral palsy in under 25s:assessment and management in 2017,which emphasizes prenatal and maternity respiratory tract or genito - urinary infection and neonatal sepsis (particularly with a birth weight below 1. 5 kg)are two independent risk factors for cerebral palsy which are worthy of clinical attention. The brain magnetic resonance imaging (MRI)may assess and classify the etiology of cerebral palsy. Of all the children with congenital cerebral palsy,45％are long to cerebral white matter damaged,13％ basal ganglia or deep grey matter damaged,10％ congenital malforma-tion,and 7％ focal infarcts. The early symptoms of cerebral palsy,early identification of dangerous signals are described. The multidisciplinary optimized management is established to deal with difficulties in eating,drinking and swallowing,saliva control,speech,language and communication,pain,discomfort,depression,sleep disturbance,registe-ring and processing sensory information,mental health,nutritional status,comorbidities,medicare and adulthood transi-tion. Its core objective is to improve the social participation and individual function development of children with cere-bral palsy,and to provide information and multidisciplinary support systems for them.

Objective Through modelling autism spectrum disorder(ASD) in condition of Poly-IC,to analyze the development,nervous pathological changes and behavior of rats in experiments,and to define whether the Sprague-Dawley(SD) rats are suitable for the study of ASD.Methods Ten SD rats were randomly divided in 2 groups with 5 rats in each group.The experimental group rats were injected intraperitoneally with 5 mg/kg Poly-IC at gestational day 12,while the rats in control group were injected intraperitoneally with 9 g/L normal saline at the gestational day 12.The body weight,eye-opening time,swimming performance,and conduct parallel water maze test,social communication ability test of each offspring were recorded,and the developmental state of rats and the existence of autism-like social behavior were evaluated.The alterations in hippocampus morphology of offspring rats were indirectly observed with immunofluorescence double standard dyeing.Results Compared with the control group,the weights of the experimental rats were lighter,opening-eye time was delayed,swimming score was lower,in each measurement point.The differences above all were significant(all P ＜0.05).The near-escape scores of experiment rats in social communication ability test were lower than those of rats in control group.The rats in the experimental group needed more time to get the Morris water maze platform,and the times of rightly run through the Morris water maze decreased significantly,and the differences were significant (all P ＜ 0.05).Pathological results revealed that the mineralocorticoid receptor (MR) average optical density value (0.061 3 ± 0.028 8) and the glucocorticoid receptor (GR) mean optical density value (0.041 9 ± 0.040 3) in hippocampal CA1 area of experiment rats were lower than those of the control group (MR:0.081 3 ±0.053 9;GR:0.061 2 ±0.043 6) (t =10.319,10.241;all P ＜0.05).There was no significant difference between MR/GR ratio(the ratio of MR and GR optical density value in the same vision area) in experimental group and in the control group.Conclusions The Poly-IC during early pregnancy can cause lag behind in motor development,harm the social communication ability,lose memory ability to learn,and develop ASD symptoms of SD rat,and these symptoms may be associated with abnormal expression of MR and GR on the hippo-camp cells surface.AS a consequence,early pregnant SD rats exposed to Poly-IC can be used for the establishment of the model of ASD which can provide a platform for the research of ASD.

Objective To establish spastic cerebral palsy model of macaque by partial resection of motor cortex and explore its evaluation method.Methods Four individuals of 3-month-old macaques were divided into healthy control group and operation model group according to random number table.Partial resection of the motor cortex was carried out in operation model group,in which precentral gyrus cortex from above the right lateral cerebral fissure to the inter-hemicerebral fissure,together with the posterior-superior frontal gyrus (about 0.3 to 0.5 cm in front of the anterior median sulcus) cortex were removed with the depth of about 0.5 to 0.6 cm.After the operation,the continuous camera shooting was used to record whether left limb motor dysfunction and abnormal posture existed or not.Muscle tension was assessed by manual examination of muscle tone with reference to the modified Ashworth scale.The quantitative indexes of the two groups were detected by using the gross motor and fine motor assessment scale.9.4T magnetic resonance imaging (MRI) was used to detect the brain imaging changes.Results After operation,the macaque in the operation model group immediately showed left hemiparesis,left upper limb abnormal lifting,left lower limb paralysis,left limb claudication,and eating mainly relied on the right side of the body.After 6 weeks of operation,left limb activity of the operation model group was significantly lower than that of the healthy control group,and the gross motor scores and fine motor scores were significantly lower than those of the healthy control group(Friedman test:χ2=33.939,P<0.05;χ2=37.526,P<0.05).The macaque in the operation model group showed some symptoms that abnormal posture mainly tilted to the left for the rest,sitting in a corner of the monkey cage,left arm was put on the cage to maintain postural balance,and movement was left slightly inclined,which had simulated the typical clinical manifestations of human spastic hemiplegic cerebral palsy.Muscle tension was checked by hand,and the left limb paralysis and muscle tension decreased after operation in the model group,and the left muscle tension increased gradually after 5 weeks,and gradually increased to score 4 points and the score remained 3 after 10 weeks.Brain MRI of 3 weeks postoperatively suggested scar tissue formation after right motor cortex resection,which supported the pathological changes of the hemiplegic cerebral palsy models.Conclusions Through the partial resection of the motor cortex,the model of spastic cerebral palsy was established successfully.The results of behavioral evaluation and MRI showed that the model was consis-tent with spastic hemiplegia.