A reliable and cost-effective protocol for creating bilirubin cerebral palsy model in rhesus macaque.

BACKGROUND: Cerebral palsy is a severe motor disability in childhood that poses challenges for children, families, and society. Rhesus macaques are the preferred animals for cerebral palsy model, but surgical excision of motor cortex has low success rate and high cost. In this work, we created cerebral palsy rhesus macaque models by intrathecal injection of bilirubin. METHODS: The puncture point for injection was identified as the intervertebral disc space two, located below the intersection of the iliac crest line and the posterior median line. RESULTS: The models showed abnormal posture and increased muscle tension. Diffuse deposits of bilirubin were found in the basal ganglia from the magnetic resonance imaging. Pathological slides also revealed the presence of brain lesions, such as vacuole formation, contraction of neuronal nuclei, and deep staining of nuclei in the histopathological sections of the hippocampus and basal ganglia. CONCLUSION: The model's symptoms closely resemble those observed in humans with spastic cerebral palsy.

Plasma neuron specific enolase (NSE), tumour necrosis factor-alpha (TNF-α) and soluble IL-2 receptor alpha (sIL-2Rα) levels in children with developmental delay (DD): Use of combined ROC curves to increase their diagnostic value.

BACKGROUND: Developmental delay (DD) occurs when children fail to reach developmental milestones in comparison to peers of the same age range. However, there are no valuable biomarkers for the early diagnosis of DD. Since there is no specific marker for screening the disease, we evaluated plasma NSE, TNF-α and sIL2-Rα as potential markers for this purpose. METHODS: In this cross-sectional randomized case-control study, a total of 174 DD patients and 49 matched elderly controls aged between 2 months and 60 months were recruited. A sensitive enzyme-linked immunosorbent assay and an immunoradiometric assay were used to evaluate the levels of plasma IL-1, IL-6, IL-8, IL-10, sIL2-Rα, TNF-α, and NSE. Statistical analyses using t test, χ2, ANOVA, ROC curves and binary logistic regression models were performed. RESULTS: In comparison to the control group, the DD group had greater levels of NSE, TNF-α, and sIL2-Rα(p < 0.05). In the binary logistic regression analysis of DD, NSE had an odds ratio (OR) of 1.783 (95 % CI 1.297 to 2.451, p = 0.000), indicating that NSE was an independent risk factor for DD. The plasma TNF-α level was positively correlated with plasma NSE and sIL2-Rα levels in the DD group (r = 0.366 and 0.433, respectively), and the DQ score and plasma sIL2-Rα level in the DD group were positively correlated. The ROC curve revealed that the respective areas under the NSE, TNF-α, and sIL2-Rα ROC curves were 0.9797, 0.9365, and 0.8533, respectively. Moreover, a significant increase in AUC was observed using combined ROC curve analysis. CONCLUSIONS: Children with DD have significantly altered plasma concentrations of sIL2-Rα, NSE, and TNF-α. NSE, TNF-α and sIL2-Rα can be used as DD blood biomarkers. This information may be helpful in early diagnosis and intervention.

Exome sequencing identified novel variants in three Chinese patients with 5,10-methenyltetrahydrofolate synthetase deficiency.

5,10-methenyltetrahydrofolate synthetase (MTHFS) deficiency is a folate metabolism disorder known as a rare autosomal recessive neurodevelopmental disorder (MIM: #618367). With central nervous system involvements, it is mainly characterized by developmental delay, epilepsy, microcephaly, hypertonia, and cranial nerves involvement. Here, we report three new cases with MTHFS deficiency from two non-consanguineous Chinese families. All patients showed white matter dysplasia and global developmental delay, of which only patient 1 and 2 manifested tonic-clonic seizures. Moreover, patient 2 had severe eczema and patient 3 had recurrent diarrhea. Both phenotypic features are firstly found in MTHFS deficiency. Trio whole-exome sequencing and sanger sequencing were used to identify four novel variants, p.Y169Tfs*17, p.S53F, c.117+1delG, and p.E61G in the MTHFS gene. The identification of four novel pathogenic variants and varied clinical features in three affected patients expands the genotype and phenotype spectrum of MTHFS deficiency. We also reviewed all cases of MTHFS deficiency that had previously been reported. The experience of diagnosis and treatment from these cases provides us a more comprehensive understanding of this rare disease.

Evaluation of Rhesus Macaque Models for Cerebral Palsy.

Animal models play a central role in all areas of biomedical research. The similarities in anatomical structure and physiological characteristics shared by non-human primates (NHPs) and humans make NHPs ideal models with which to study human disorders, such as cerebral palsy (CP). However, the methodologies for systematically evaluating NHP models of CP have rarely been assessed, despite the long history of using NHP models to understand CP. Such models should be evaluated using multidisciplinary approaches prior to being used to research the diagnosis and treatment of CP. In this study, we evaluated rhesus macaque CP models established by partial resection of the motor cortex and intrathecal injection of bilirubin. Abnormal posture, motor dysfunction, gross and fine motor behavior, and muscular tension were evaluated, and changes in the cerebral cortex and basal ganglia were observed using 9.4 T magnetic resonance imaging. The results clearly demonstrated the utility of the established evaluation methodology for assessing CP models. This model evaluation methodology may guide researchers through the model building process.

Relationship Between TNF-α and the Risk of Cerebral Palsy: A Systematic Review and Meta-Analysis.

Objective: We performed a meta-analysis to investigate the relationship between blood tumor necrosis factor-alpha (TNF-α) levels and the risk of cerebral palsy (CP) in children. Methods: PubMed, Web of Science, Cochrane Library and Ovid databases were searched from the date of database inception to 26 April 2022. Data were extracted and pooled from observational studies related to TNF-α and the risk of CP in children. Quality was assessed using the Newcastle-Ottawa Scale. We used the inverse variance method with a random-effects model to estimate the odds ratios with 95% confidence intervals (CIs), and stratified analyses and sensitivity analysis were utilized to analyse heterogeneity. Results: Nine studies with 1,117 cases and 3,563 controls were included in our meta-analysis. The quality of the literature was good, and no publication bias was noted. According to the random-effects model, blood TNF-α levels were associated with the risk of CP (OR 1.82; 95% CI, 1.25-2.66) in a heterogeneous set of studies (I 2 = 81.2%, p = 0.000). Conclusion: Our findings indicate that elevated TNF-α levels in the blood are associated with an increased risk of CP. The association of TNF-α with CP requires further investigation.

Rare hypomagnesemia, seizures, and mental retardation in a 4-month-old patient caused by novel CNNM2 mutation Tyr189Cys: Genetic analysis and review.

BACKGROUND: Hypomagnesemia, seizures, and mental retardation (HSMR) syndrome is a rare genetic disease. Presently, only 24 cases have been reported and the clinical features of the disease are yet to be fully described, thereby making diagnosis challenging. METHODS: Trio-whole-exome sequencing was used for the patient and her parents, and the structure of the variant protein was analyzed by molecular dynamics. Finally, the characteristics of HSMR were summarized by reviewing the previous literature. RESULTS: The main disease manifestations in the patient were seizures, liver function damage, hypomagnesemia, atrial septal defect, and sinus arrhythmia. A novel mutation in CNNM2 (c.566A>G/p.Tyr189Cys) was identified by genetic detection. The parents were wild type, and the mutation was rated as pathogenic by American College of Medical Genetics and Genomics guidelines. Ab initio modeling and molecular dynamics simulation show that the mutation destroys the surrounding hydrogen bonds, which may reduce the local stability of the protein structure. In the previous literature, only 24 children with HSMR have been reported, mainly manifested as hypomagnesemia, mental retardation, seizures, and language and motor impairment. CONCLUSION: We have reported the second case of HSMR in the Chinese population, which further expands the phenotypic spectrum of congenital heart disease and the variation spectrum of CNNM2.

A prospective randomized controlled study on mouse nerve growth factor in the treatment of global developmental delay in children. / é¼ ç¥žç»ç”Ÿé•¿å› å­æ²»ç–—å ¨é¢æ€§å‘è‚²è¿Ÿç¼“çš„å‰çž»æ€§éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To study the clinical effect of mouse nerve growth factor (mNGF) in the treatment of children with global developmental delay (GDD). METHODS: A prospective clinical trial was conducted in 60 children with GDD who were treated in the First Affiliated Hospital of Anhui Medical University between July 2016 and July 2017. These children were randomly divided into two groups: conventional rehabilitation treatment and mNGF treatment group (n=30 each). The children in the conventional rehabilitation treatment group were given neurodevelopmental therapy, and those in the mNGF treatment group were given mNGF treatment in addition to the treatment in the control group. The evaluation results of the Gesell Developmental Scale were compared between the two groups before and after treatment. RESULTS: Before treatment and after 1.5 months of treatment, there was no significant difference in the developmental quotient (DQ) of each functional area of the Gesell Developmental Scale between the mNGF treatment and conventional rehabilitation treatment groups (P>0.05). After 3 months of treatment, the mNGF treatment group had significantly higher DQs of gross motor, fine motor, and personal-social interaction than the conventional rehabilitation treatment group (P˂0.05). The incidence rate of transient injection site pain after injection of mNGF was 7% (2/30), and there was no epilepsy or other serious adverse reactions. CONCLUSIONS: In children with GDD, routine rehabilitation training combined with mNGF therapy can significantly improve their cognitive, motor, and social abilities.

[Clinical phenotypes and genetic features of families with Duchenne muscular dystrophy].

OBJECTIVE: To study the phenotypes and genetic features of families with Duchenne muscular dystrophy (DMD). METHODS: Seven children from six families with DMD diagnosed by gene testing were enrolled. The clinical and genetic features of the families were analyzed. RESULTS: There were two new mutations and four maternal inheritance mutations in the six families. The proband of family 1 had one point de novo mutation and one insertion de novo mutation of the DMD gene. Three families had point mutation, one family had fragment deletion of exon, and one family had fragment duplication of exon. The youngest age of onset of the probands was 6 months. All probands had skeletal muscle dyskinesia and significant changes in muscle enzymes, with different severities of clinical phenotypes. Three probands had mild mental retardation. The results of echocardiography were normal for all probands. The mother of the proband in family 6 had mild clinical phenotype. CONCLUSIONS: Gene testing can be used for the confirmed diagnosis of DMD. Mental retardation is a frequent clinical phenotype of DMD. The symptoms of myocardial involvement are not obvious in the early stage. Female carriers may have mild clinical symptoms.

The effects of hyperbilirubinaemia on synaptic plasticity in the dentate gyrus region of the rat hippocampus in vivo.

INTRODUCTION: The aim of our study is to investigate the effect of hyperbilirubinaemia on synaptic plasticity in the dentate gyrus (DG) region of the rat hippocampus. MATERIAL AND METHODS: Seven-day-old healthy Sprague Dawley (SD) rats were randomly divided into a control group and an experiment group (n = 20 in each group). The input/output (I/O) functions, paired-pulse reactions (PPR), excitatory postsynaptic potential (EPSP), and population spike (PS) amplitude were measured in the DG area of both groups of rats in response to stimulation applied to the lateral perforant path. RESULTS: Compared with that in the control rats, the current-voltage curves of both EPSP slope and PS amplitude in the experimental rats were significantly depressed. The average peak facilitation was 187 ±16% in the control and 164 ±18% in the experiment group (F = 21.054, p < 0.01). The facilitation period duration of PS was 155 ms in the experimental rats, which was less than that of the controls (235 ms). In the control group, the long-term potentiation (LTP) amplitudes were 140 ±3.5% and 242 ±6%, when estimated from the EPSP slope and PS amplitude, respectively, which were significantly depressed to 124 ±3.4% (EPSP slope, F = 70.489, p < 0.01) and 138 ±8.6% (PS amplitude, F = 253.46, p < 0.01), respectively, in the experiment group. CONCLUSIONS: These findings suggest that hyperbilirubinaemia could induce impairment of synaptic plasticity in the rat DG area in vivo, including I/O function, paired-pulse ratio (PPR), and LTP, which may be closely related to cognitive impairment.

The expression of Th9 and Th22 cells in rats with cerebral palsy after hUC-MSC transplantation.

BACKGROUND: This study aimed to investigate the expression of Th9 and Th22 cells in rats with cerebral palsy (CP) after human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation. METHODS: First, hUC-MSCs were isolated from fresh umbilical cords and identified. Rats were divided into the normal group, CP group, and hUC-MSC transplantation group. The Morris water maze and balance beam tests were performed to evaluate the neurobehavioral ability of the rats. The levels of TNF-α, IL-6, IL-9, and IL-22 in rat brain tissues were detected by ELISA. Th9 and Th22 proportions in brain tissues were detected by flow cytometric analysis. The mRNA levels of IL-9, IL-22, PU.1, and AHR in brain tissues were determined by qRT-PCR. RESULTS: hUC-MSC transplantation enhanced the neurobehavioral ability of CP rats. Furthermore, Th9 and Th22 proportions were decreased in brain tissues from CP rats after hUC-MSC transplantation. The levels of proinflammatory cytokines (TNF-α and IL-6), Th9-related IL-9 and PU.1, and Th22-related IL-22 and AHR were markedly higher in brain tissues from CP rats than in brain tissues from control rats, but their levels were significantly decreased after hUC-MSC transplantation. CONCLUSION: Our data indicate that Th9 and Th22 proportions are decreased in CP rats after hUC-MSC transplantation.

Biallelic INTS1 Mutations Cause a Rare Neurodevelopmental Disorder in Two Chinese Siblings.

This study presents two Chinese siblings with a rare neurodevelopmental disorder (NDD) caused by biallelic INTS1 mutations and investigates the clinical features of this disease by means of in silico analysis. Two siblings, an 11-year-old brother and a 5-year-old sister, visited our hospital due to physical retardation and profound intellectual disability. Whole-exome sequencing (WES) was performed for the girl, and Sanger sequencing was used to validate the identified variants. Phenotype correlation analysis and in silico genetic interaction network analysis were performed to investigate genes that could lead to diseases similar to the rare disease in the patients. Growth retardation, distinct intellectual disability, hypertelorism, mild cataract, uneven teeth, abnormal palmar and plantar creases, and dubious genitalia were noted in the sister. No neurological features related to neuropathy were found. The brother showed features and growth delay similar to his sister. Heterozygous novel variants of c.1645A>G,p.Met549Val and c.5881C>T,p.Gln1961* in INTS1 were considered a candidate etiology. Sanger sequencing demonstrated that the variants were inherited from the grandfather and (maternal) grandmother. Phenotype correlation analysis revealed that CTDP1 mutation-induced congenital cataracts-facial dysmorphism-neuropathy (CCFDN) mostly overlapped with the performance of our patients. In silico analysis of the genetic interaction network showed that INTS1 is highly associated with INTS8 and CTDP1. Our study further validated that biallelic INTS1 mutations could bring about the onset of a novel neurodevelopmental disorder.

Inhibition of the PI3K/Akt signaling pathway impedes the restoration of neurological function following hypoxic-ischemic brain damage in a neonatal rabbit model.

OBJECTIVE: Hypoxic-ischemic brain damage (HIBD), frequently occurring in infancy and childhood, is a major cause of mortality and severe neurologic impairment. This study was performed to examine the effect of the PI3K/Akt signaling pathway on HIBD in a neonatal rabbit model. MATERIALS AND METHODS: Uterine artery occlusion was used to establish HIBD models in neonatal rabbits, which were then subjected to sham operation, dimethyl sulfoxide (2 mL) or LY294002 (inhibitor of PI3K/Akt signaling pathway, 6.4 µg/kg). Behavioral neurological assessment was performed in neonatal rabbits delivered by cesarean section, after which serum neuron-specific enolase (NSE) level and cerebral water content were determined. The level of cleaved caspase-3 level and apoptosis of neurons were observed by immunohistochemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. Furthermore, the expression of PI3K/Akt signaling pathway- and apoptosis-related factors was examined. RESULTS: In neonatal rabbits, HIBD increased the fetal death rate; reduced neurological scores of posture, righting reflex, and deglutition reflex; elevated serum NSE levels, cerebral water content, cleaved caspase-3-positive expression in hippocampal CA1 region and apoptotic neurons; inactivated PI3K/Akt signaling pathway as well as reduced Bcl-2 expression and increased BAD and Bax expression. Notably, the treatment of LY294002 further aggravated neurological impairment in neonatal rabbits in response to HIBD. CONCLUSION: Following the HIBD caused by intrauterine asphyxia, the LY294002 administered through auricular vein infusion into pregnant rabbits exacerbates neurological impairment of neonatal rabbits, suggesting that inhibition of PI3K/Akt signaling pathway may serve as a candidate therapeutic target for neurological recovery.

The influence of massage on neonatal hyperbilirubinemia: a meta-analysis of randomized controlled trials.

Introduction: The efficacy of massage to treat neonatal hyperbilirubinemia remains controversial. We conducted a systematic review and meta-analysis to explore the influence of massage on the neonatal hyperbilirubinemia. Methods: We search PubMed, Embase, Web of science, EBSCO, and Cochrane Library databases through November 2017 for randomized controlled trials (RCTs) assessing the effect of massage on neonatal hyperbilirubinemia. This meta-analysis is performed using the random-effect model. Results: Six RCTs involving 357 patients are included in the meta-analysis. Overall, compared with the control group in neonatal hyperbilirubinemia, massage therapy is associated with substantially reduced serum bilirubin level within 4 d (mean difference (MD) = -2.31; 95% CI = -2.92 to -1.70; p < .00001) and transcutaneous bilirubin level within 4 d for neonatal hyperbilirubinemia (MD = -1.97; 95% CI = -2.55 to -1.39; p < .00001), but results no remarkable impact on serum bilirubin level on 2 d (MD = -0.82; 95% CI = -2.16-0.52; p = .23), transcutaneous bilirubin level on 2 d (MD = -0.17; 95% CI = -1.34 to 1.00; p = .77), frequency of defecation daily on 2 d (MD = 0.57; 95% CI = -0.03 to 1.16; p = .06), and frequency of defecation daily within 4 d (MD = 0.83; 95% CI = -0.11 to 1.76; p = .08). Conclusions: Massage therapy can significantly reduce serum bilirubin level and transcutaneous bilirubin level within 4 d, but demonstrates no influence on serum bilirubin level and transcutaneous bilirubin level on 2 d, frequency of defecation daily on 2 and 4 d for neonatal hyperbilirubinemia.

Infantile neuroaxonal dystrophy caused by PLA2G6 gene mutation in a Chinese patient: A case report.

Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disorder. Phospholipase A2 group VI (PLA2G6) gene mutations have been identified in the majority of individuals with INAD. The present case report is on a Chinese female pediatric patient (age, 18 months) diagnosed with INAD with deafness. To date, only four cases of INAD with hearing loss have been reported, PLA2G6-association has not been investigated. Next-generation DNA sequencing technology was used to identify disease-associated genes and Sanger sequencing was applied to verify the mutation in the patient's pedigree. Two mutations were identified in the PLA2G6 gene: c.1T>C (E2) and c.497 (E4) to c.496 (E4): Insert C. The distribution frequency of those mutations in the Single Nucleotide Polymorphism, HapMap, 1000 Genomes and Exome Aggregation Consortium databases was 0. However, cases of INAD appear to be underreported, particularly those from China. The identification of two mutations in the present study suggests unique PLA2G6 mutations in Chinese patients, and greatly expands on the spectrum of known mutations in INAD patients.

The influence of zinc sulfate on neonatal jaundice: a systematic review and meta-analysis.

INTRODUCTION: Zinc sulfate may be a promising approach to treat neonatal jaundice. However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of zinc sulfate on hyperbilirubinemia among neonates. METHODS: PubMed, EMbase, Web of science, EBSCO, Cochrane library databases, Ovid, BMJ database, and CINAHL were systematically searched. Randomized controlled trials (RCTs) assessing the effect of zinc sulfate versus placebo on the prevention of jaundice in neonates were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcomes were total serum bilirubin (TSB) on three days and seven days, the incidence of hyperbilirubinemia. Meta-analysis was performed using random- or fixed-effect models. RESULTS: Five RCTs involving 645 patients were included in the meta-analysis. Overall, compared with placebo, zinc sulfate supplementation failed to significantly reduce TSB on three days (mean difference (MD) = 0.09 mg/dL; 95% confidence interval (CI) = -0.49 to 0.67; p = .77), TSB on seven days (MD = -0.37 mg/dL; 95% CI = -98 to 0.25; p = .25) as well as the incidence of hyperbilirubinemia (OR = 1.14; 95% CI = 0.74 to 1.76; p = .56). Zinc sulfate showed no influence on phototherapy requirement (OR = 0.90; 95% CI = 0.41 to 1.98; p = .79), but resulted in significantly decreased duration of phototherapy (MD = -16.69 h; 95% CI = -25.09 to -8.3 h; p < .0001). CONCLUSIONS: Zinc sulfate could not reduce the TSB on three days and seven days, the incidence of hyperbilirubinemia and phototherapy requirement, but lead to significantly decreased duration of phototherapy.

Prenatal exposure to TAK242 affects the childhood autism in offspring in animal models of autism spectrum disorder.

OBJECTIVES: To evaluate whether prenatal exposure to TAK242 affects childhood autism in the offspring in animal models of autism spectrum disorder (ASD). MATERIALS AND METHODS: The pregnant rats were pseudo-randomly divided into three groups, the ASD model group, the TAK242 treatment group, and the control group. The ASD model was constructed by injecting IP with LPS. The blood samples from 1-month-old offspring were collected for cytokine evaluation and the social interaction test was used in the offspring of ASD rats. Rats were killed and the hippocampus, cerebral cortex, and cerebellum were used for the immunohistochemical study. RESULTS: As compared to the control, the levels of IFN-γ, IL-1ß, IL-2, and IL-6 were significantly increased (P<0.05), and the levels of IL-4, IL-10, and TGF-ß were significantly decreased (P <0.05) in the offspring of ASD rats; whereas those cytokines were significantly reversed after prenatal exposure to TAK242 (P<0.05). The hesitation time and none-social interaction time were significantly increased as compared to the control (P<0.05); whereas they were both decreased after prenatal exposure to TAK242 (P<0.05). This was contrary to the social interaction time (P<0.05). The expression of GFAP and IBA1 in the cortex, hippocampus, and cerebellum were stronger in the LPS group as compared to control group, and this effect was reversed after prenatal exposure to TAK242. CONCLUSION: Prenatal exposure to TAK242 affects serum cytokines levels and the social interaction time in rat offspring in animal models of ASD.

Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder.

Autistic spectrum disorder (ASD) is a neurodevelopmental disorder and has a high prevalence in children. Recently, mitochondrial oxidative stress has been proposed to be associated with ASD. Besides, SIRT1/PGC-1α signaling plays an important role in combating oxidative stress. In this study, we sought to determine the role of SIRT1/PGC-1α signaling in the ASD lymphoblastoid cell lines (LCLs). In this study, the mRNA and protein expressions of SIRT1/PGC-1α axis genes were assessed in 35 children with ASD and 35 healthy controls (matched for age, gender, and IQ). An immortalized LCL was established by transforming lymphocytes with Epstein-Barr virus. Next, we used ASD LCLs and control LCLs to detect SIRT1/PGC-1α axis genes expression and oxidative damage. Finally, the effect of overexpression of PGC-1α on oxidative injury in the ASD LCLs was determined. SIRT1/PGC-1α axis genes expression was downregulated at RNA and protein levels in ASD patients and LCLs. Besides, the translocation of cytochrome c and DIABLO from mitochondria to the cytosol was found in the ASD LCLs. Moreover, the intracellular reactive oxygen species (ROS) and mitochondrial ROS and cell apoptosis were increased in the ASD LCLs. However, overexpression of PGC-1α upregulated the SIRT1/PGC-1α axis genes expression and reduced cytochrome c and DIABLO release in the ASD LCLs. Also, overexpression of PGC-1α reduced the ROS generation and cell apoptosis in the ASD LCLs. Overexpression of PGC-1α could reduce the oxidative injury in the ASD LCLs, and PGC-1α may act as a target for treatment.

NMDA receptor subunit and CaMKII changes in rat hippocampus by congenital HCMV infection: a mechanism for learning and memory impairment.

The aim of this study was to investigate the effects of congenital human cytomegalovirus infection on the expression levels of N-methyl-D-aspartate receptors (NRs) and Ca/calmodulin-dependent protein kinase II (CaMKII) in the hippocampal neurons of neonatal Sprague-Dawley (SD) rats. Pregnant SD rats were divided into an experimental group and a control group (n=10 in each group). Spatial learning and memory of the offspring of SD rats were evaluated using the Morris water-maze test. Pathological studies of hippocampus sections were carried out. The concentration of [Ca] was measured using a dual-wavelength spectrophotometer method. The expression levels of NRs were detected by an immunohistochemical study. Western blot was performed to detect the expression level of CaMKII. In the Morris water-maze test, the rats in the experimental group showed significantly increased escape latency and distance traveled than the control group. Damaged and structural disorders of the dentate granule in the hippocampus were found in the experimental rats. Immunohistochemistry results showed that the expression levels of NR subunits in the hippocampus of the experimental group were significantly decreased. The concentration of [Ca] in the experimental group was significantly increased. In contrast, the level of CaMKII in the experimental group was significantly decreased. The expressions of the NR subunit and CaMKII were decreased in rat hippocampus by human cytomegalovirus congenital infection, which may be associated with the mechanism underlying the impairment of learning and memory function.

Effects of pomegranate extract in supplementing gonadotropin-releasing hormone therapy on idiopathic central precocious puberty in Chinese girls: a randomized, placebo-controlled, double-blind clinical trial.

Central precocious puberty (CPP) without organic abnormality is called idiopathic CPP (ICPP). The objective of this trial was to evaluate the effects of pomegranate extract in supplementing gonadotropin-releasing hormone (GnRH) analog therapy on ICPP-affected girls in the Chinese population. 286 girls, diagnosed with ICPP were initially enrolled into this trial, and among them 225 eligible patients were randomized to receive a combinational GnRH analog treatment supplemented with either a placebo or pomegranate extract on a daily basis for a period of 3 months. Their demographics, secondary sexual characteristics and hormone profiles were analyzed at baseline and end of trial. After 3 months of treatment, demographic profiles including bone age, growth velocity and height standard deviation score for bone age, and secondary sexual characteristics including uterus and ovary volume, as well as serum hormone profiles including estradiol, peak luteinizing hormone and insulin-like growth factor 1 were all significantly improved in girls receiving a combinational treatment of both GnRH analog and pomegranate extract. Daily consumption of pomegranate extract was able to supplement and improve the treatment outcomes of the GnRH analog therapy for ICPP in Chinese girls.

Psychometric properties of the Autism-Spectrum Quotient in both clinical and non-clinical samples: Chinese version for mainland China.

BACKGROUND: The Autism-Spectrum Quotient (AQ) is widely used to quantify autistic traits, which have been evaluated in the parents of individuals with autism spectrum disorders (ASD) and in the general population. This paper's objective was to investigate the AQ's psychometric properties of the Chinese version for mainland China and to establish whether the pattern of sex differences in the quantity of autistic traits exists. We also examined the usefulness of the AQ in differentiating between individuals with ASD, schizophrenia (SCH), obsessive-compulsive disorder (OCD) and healthy controls (HC). METHODS: In this study, the psychometric properties of the AQ were assessed in 1037 parents of children with ASD and in 1040 parents of typically developing children (TDC). Additionally, 32 participants with ASD, 37 patients with SCH, 38 OCD patients and 38 healthy controls (matched for age, gender and IQ) were assessed with the AQ. RESULTS: The internal consistency and test-retest reliability of the AQ and AQ subscales were within an acceptable range. Parents of ASD children scored higher than TDC parents on total AQ and AQ subscales, and TDC parents scored more than parents of ASD children on 2 items of 50. Fathers scored higher than did mothers on total AQ and four subscales, with the sole exception being the subscale attention to detail. The total AQ score of the ASD group was higher than that of the SCH, OCD and HC groups, and the total AQ score of the HC group was significantly lower than that of the SCH and OCD groups, with no differences being observed between the SCH and OCD groups. CONCLUSIONS: The Mandarin AQ demonstrated promising psychometric properties and was a reliable instrument for quantifying autistic traits in both clinical and non-clinical samples in mainland China.