Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.

Objective To construct a model for predicting ki-67 expression in hepatocellular carcinoma using the intratumoral and peritumoral radiomic features of contrast enhanced magnetic resonance imaging(CEMRI)in the arterial phase as well as clinical imaging features.Methods A total of 120 patients pathologically diagnosed with hepatocellular carcinoma(HCC)from January 2016 to December 2024 in No.910 Hospital of the Joint Logis-tics Support Force of the Chinese People's Liberation Army were retrospectively enrolled and randomly divided into a training set(84 cases)and a test set(36 cases)in a ratio of 7∶3.ITK-SNAP software was used to delineate the global region of interest(ROI)of HCC on the arterial phase MR images.The ROIs of all patients were automatically expanded outward by 2 mm,and then the intratumoral ROI areas were eliminated to obtain the peritumoral ROI.With the help of PyRadiomics software,1 198 intratumoral and peritumoral radiomic features were extracted.Spearman correlation analysis,maximum relevance-minimum redundancy(mRMR),and least absolute shrinkage and selection operator(LASSO)regression were used to reduce the data dimension and select the best features.Then,a radiomics model of the logistic regression(LR)machine learning algorithm was constructed.A combined model including clinical imaging features and radiomics features was established.The area under the curve(AUC),accuracy,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),calibration curve and decision curve analysis(DCA)were used to evaluate the efficacy of the intratumoral and peritumoral radiomics features combined with clinical imaging features model in predicting ki-67 expression in hepatocellular car-cinoma.Results The intratumor model exhibited an efficacy in predicting the expression of ki-67 in hepatocellular carcinoma with AUC values of 0.817 and 0.787 in the training set and test set,respectively.The peritumoral model showed an efficacy with AUC values of 0.805 and 0.633 in the training set and test set,respectively.The intratumoral and peritumoral model demonstrated AUC values of 0.874 and 0.836 in the training set and test set,respectively.The combined model constructed by integrating the intratumoral and peritumoral model with clinical imaging features yielded AUC values of 0.877 and 0.849 in the training set and test set,respectively,indicating clinical imaging features improved the performance of the model.DCA showed that the combined models all had good clinical benefits,with the intratumoral and peritumoral model performing the best.Conclusion The intratumoral and peritumoral radiomics model based on CEMRI arterial phase combined with clinical imaging data can accurately predict the expression of ki-67 in hepatocellular carcinoma.This combined model yields the best clinical benefit.

AIM:To explore the therapeutic effects of Liuwei-Dihuang decoction(LD)on ovarian function in pre-mature ovarian failure(POF)mice,and to uncover the role of the Notch signaling pathway in its mechanism.METHODS:A mouse model of POF was constructed through intraperitoneal injection of cyclophosphamide/busulfan.Subsequently,the mice were randomly divided into six groups(n=12 per group):control,POF model,low-dose LD(LD-L),medium-dose LD(LD-M),high-dose LD(LD-H),and positive drug(0.7 mg/kg diethylstilbestrol)groups.The ovarian histopathologi-cal alterations were assessed by hematoxylin-eosin(HE)staining.Serum levels of follicle-stimulating hormone(FSH),anti-Müllerian hormone(AMH),and estradiol(E2)were quantified via ELISA assays.Immunohistochemistry(IHC)was conducted to compare the expression level of cell proliferation marker Ki-67 in mouse ovarian tissues among the groups.The expression of proteins involved in the Notch pathway components[Notch1,Notch2,Jagged1(JAG-1),and hairy and enhancer of split 1(Hes1)]was determined via IHC and Western blot,while the corresponding mRNA levels of Notch1,Notch2,JAG-1,JAG-2,Hes1,and Hes5 were quantified through the qPCR analysis.RESULTS:Ovarian weight was significantly higher,and the number of atretic follicles was significantly lower in the LD-H and positive drug groups com-pared to the model group(P<0.05).However,serum FSH levels were decreased(P<0.01),whereas those of E2 and AMH were elevated in both treatment groups compared with the model group(P<0.01).In the LD-H group,the expres-sion of key molecules of the Notch pathway components was increased at the protein and mRNA level compared with the model group(P<0.01).CONCLUSION:LD ameliorates ovarian dysfunction in POF mice via activating the Notch sig-naling pathway.

Objective:The clinical symptoms of children with global developmental delay (GDD) were analyzed to provide the scientific basis for the intervention of children with GDD.Methods:The results of the neuro-psychobehavioral scale were collected from 32 511 children with GDD from June 2020 to November 2023. Inclusion criteria: Children diagnosed with GDD according to the Diagnostic and Statistical Manual of Mental Disorders-V, ages 0.0 to 4.9 years. Exclusion criteria: children with common hearing impairment and visual impairment. The Chi-square tests were used for statistical analysis.Results:There were more boys than girls with GDD in outpatient clinics (68.2% vs. 31.8%). Among the children, the proportion of developmental delay in 5, 4, 3, and 2 domains was 31.1%, 23.4%, 22.9% and 22.6% respectively. The rate of delay in 2-3 domains was lower in boys (41.9%) than in girls (53.1%). The rate of delay in 4-5 domains was higher in boys (58.1%) than in girls (46.9%) ( χ2=352.11, P<0.001). Overall, outpatient GDD decreased with age. From 1.0-1.9 to 4.0-4.9 years of age, the proportion of children with developmental delay in 5 domains increased with age (18.2%, 36.4%, 43.9%, 52.4%). Among children aged 0.0-0.9 years, the proportion of 2 domains of developmental delay was higher (33.4%).Among children aged 1.0-1.9 years, the proportion of 2-3 domains of developmental delay was higher (30.7%). Among children aged 2.0-, 3.0-, 4.0-4.9 years, the proportion of developmental delay in 5 domains was higher (36.4%, 43.9%, 52.4%). In children with GDD, the fine motor delay occurred most frequently (85.1%), followed by social self-care (83.9%), language (79.0%), adaptation (62.3%), and gross motor (52.8%). The frequency of developmental delays in fine motor, adaptability, language, and social self-care in boys was higher than that in girls ( χ2=161.37, χ2=41.10, χ2=320.90, χ2=238.54, all P<0.001). The age groups with the highest delay incidence of gross motor, fine motor, adaptability, language, and social self-care were: 4.0-4.9 years (70.6%), 3.0-3.9 years (97.4%), 4.0-4.9 years (81.2%), 2.0-2.9 years (90.9%),2.0-2.9 years (95.4%). The proportions of fine motor delay in GDD children aged 0.0-0.9, 3.0-3.9 and 4.0-4.9 years were (74.5%, 97.4%, 96.8%) and the proportions of social self-care delay in GDD children aged 1.0- and 2.0-2.9 years were (92.1%, 95.4%). Peripheral and mild developmental delays were predominant in children with GDD. The proportion of severe language delay (6.4%) was higher than that in other fields. Conclusions:The proportion of GDD children with developmental delay in 4-5 domains was 54.5%. The most frequent domain of delay was fine motor. The frequencies of developmental delays in fine motor skills, adaptability, language, and social self-care in boys were higher than in girls. Most of the developmental delays in GDD children were marginal and mild. The rate of severe developmental delay in language was higher than in other domains.

Objective To construct a model for predicting ki-67 expression in hepatocellular carcinoma using the intratumoral and peritumoral radiomic features of contrast enhanced magnetic resonance imaging(CEMRI)in the arterial phase as well as clinical imaging features.Methods A total of 120 patients pathologically diagnosed with hepatocellular carcinoma(HCC)from January 2016 to December 2024 in No.910 Hospital of the Joint Logis-tics Support Force of the Chinese People's Liberation Army were retrospectively enrolled and randomly divided into a training set(84 cases)and a test set(36 cases)in a ratio of 7∶3.ITK-SNAP software was used to delineate the global region of interest(ROI)of HCC on the arterial phase MR images.The ROIs of all patients were automatically expanded outward by 2 mm,and then the intratumoral ROI areas were eliminated to obtain the peritumoral ROI.With the help of PyRadiomics software,1 198 intratumoral and peritumoral radiomic features were extracted.Spearman correlation analysis,maximum relevance-minimum redundancy(mRMR),and least absolute shrinkage and selection operator(LASSO)regression were used to reduce the data dimension and select the best features.Then,a radiomics model of the logistic regression(LR)machine learning algorithm was constructed.A combined model including clinical imaging features and radiomics features was established.The area under the curve(AUC),accuracy,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),calibration curve and decision curve analysis(DCA)were used to evaluate the efficacy of the intratumoral and peritumoral radiomics features combined with clinical imaging features model in predicting ki-67 expression in hepatocellular car-cinoma.Results The intratumor model exhibited an efficacy in predicting the expression of ki-67 in hepatocellular carcinoma with AUC values of 0.817 and 0.787 in the training set and test set,respectively.The peritumoral model showed an efficacy with AUC values of 0.805 and 0.633 in the training set and test set,respectively.The intratumoral and peritumoral model demonstrated AUC values of 0.874 and 0.836 in the training set and test set,respectively.The combined model constructed by integrating the intratumoral and peritumoral model with clinical imaging features yielded AUC values of 0.877 and 0.849 in the training set and test set,respectively,indicating clinical imaging features improved the performance of the model.DCA showed that the combined models all had good clinical benefits,with the intratumoral and peritumoral model performing the best.Conclusion The intratumoral and peritumoral radiomics model based on CEMRI arterial phase combined with clinical imaging data can accurately predict the expression of ki-67 in hepatocellular carcinoma.This combined model yields the best clinical benefit.

AIM:To explore the therapeutic effects of Liuwei-Dihuang decoction(LD)on ovarian function in pre-mature ovarian failure(POF)mice,and to uncover the role of the Notch signaling pathway in its mechanism.METHODS:A mouse model of POF was constructed through intraperitoneal injection of cyclophosphamide/busulfan.Subsequently,the mice were randomly divided into six groups(n=12 per group):control,POF model,low-dose LD(LD-L),medium-dose LD(LD-M),high-dose LD(LD-H),and positive drug(0.7 mg/kg diethylstilbestrol)groups.The ovarian histopathologi-cal alterations were assessed by hematoxylin-eosin(HE)staining.Serum levels of follicle-stimulating hormone(FSH),anti-Müllerian hormone(AMH),and estradiol(E2)were quantified via ELISA assays.Immunohistochemistry(IHC)was conducted to compare the expression level of cell proliferation marker Ki-67 in mouse ovarian tissues among the groups.The expression of proteins involved in the Notch pathway components[Notch1,Notch2,Jagged1(JAG-1),and hairy and enhancer of split 1(Hes1)]was determined via IHC and Western blot,while the corresponding mRNA levels of Notch1,Notch2,JAG-1,JAG-2,Hes1,and Hes5 were quantified through the qPCR analysis.RESULTS:Ovarian weight was significantly higher,and the number of atretic follicles was significantly lower in the LD-H and positive drug groups com-pared to the model group(P<0.05).However,serum FSH levels were decreased(P<0.01),whereas those of E2 and AMH were elevated in both treatment groups compared with the model group(P<0.01).In the LD-H group,the expres-sion of key molecules of the Notch pathway components was increased at the protein and mRNA level compared with the model group(P<0.01).CONCLUSION:LD ameliorates ovarian dysfunction in POF mice via activating the Notch sig-naling pathway.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with biallelic loss-of-function variants in the RBM42 gene. The patient is a 2-year-old female with severe central nervous system (CNS) abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing (WES) reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family. The p.A438T variant is in the RRM domain which impairs RBM42 protein stability in vivo. Additionally, p.A438T disrupts the interaction of RBM42 with hnRNP K, which is the causative gene for Au-Kline syndrome with overlapping disease characteristics seen in the index patient. The human R102* or A438T mutant protein failed to fully rescue the growth defects of RBM42 ortholog knockout ΔFgRbp1 in Fusarium while it was rescued by the wild-type (WT) human RBM42. A mouse model carrying Rbm42 compound heterozygous variants, c.280C>T (p.Q94*) and c.1306_1308delinsACA (p.A436T), demonstrated gross fetal developmental defects and most of the double mutant animals died by E13.5. RNA-seq data confirmed that Rbm42 was involved in neurological and myocardial functions with an essential role in alternative splicing (AS). Overall, we present clinical, genetic, and functional data to demonstrate that defects in RBM42 constitute the underlying etiology of a new neurodevelopmental disease which links the dysregulation of global AS to abnormal embryonic development.
Female ; Animals ; Mice ; Humans ; Child, Preschool ; Intellectual Disability/genetics* ; Heart Defects, Congenital/genetics* ; Facies ; Cleft Palate ; Muscle Hypotonia

Objective:To translate and culturally adjust Decisional Fatigue Scale (DFS) , and test its reliability and validity.Methods:The Chinese version of DFS was formed through the method of double translation, back translation and expert consultation. Using the convenient sampling method, 247 medical staffs from 16 departments in 76 wards of Xiangyang No.1 People's Hospital Affiliated to Hubei University of Medicine were selected as the research objects. Content validity, criterion validity and structure validity were used for validity evaluation, and internal consistency reliability, split half reliability and retest reliability were used for reliability evaluation. A total of 247 questionnaires were sent out in this study and 247 were effectively received, with effective recovery of 100.00%.Results:The total Cronbach's α coefficient of Chinese DFS was 0.933, the half-reliability coefficient was 0.849 and the retest reliability coefficient was 0.838 ( P<0.01) . Both the item content validity index and scale content validity index were 1.00, and the correlation coefficient with the total score of SRF-S was 0.729 ( P<0.01) . One common factor was extracted by exploratory factor analysis and 65.64% of the variation was explained cumulatively, which was consistent with the dimensions of the original scale. Confirmatory factor analysis showed that all fitting indexes were up to standard and the fitting degree was good. Conclusions:The reliability and validity of the Chinese version of DFS in medical staffs is good, which can be used to evaluate the degree of decision-making fatigue of Chinese medical staffs.

Objective:To understand the identification value of pointing gestures in children with autism spectrum disorder(ASD) and its relationship with functional development.Methods:From December 2020 to November 2021, 1 099 children from Children’s Health Care Center of Beijing Children’s Hospital were tested by pointing gestures test, including 942 ASD children and 157 typical developed children.And the data of children's neuropsychological development scale from 800 children aged 1.0-5.9 were collected.SPSS 20.0 was used for statistical analysis. Trend test was used to analyze the distribution of pointing gestures test sensitivity in autistic children, and ANOVA was used to analyze the relationship between pointing gestures test scores and functional development fields.Results:The sensitivity of pointing gestures was 83.5% in children aged 1.0-10.0 years, 76.3%-93.1% in children aged 1.0-4.9 years, and 93.1%-95.1% in children aged 1.0-2.9.With the increase of age, the sensitivity of pointing gestures in autistic children (linear-by-linear association =164.889, P<0.001) and the Yoden index had a decreasing trend. The positive predictive value (91.53%-100.00%) and negative predictive value (75.36%-91.84%) were found in the children aged 1.0-10.0 years.The sensitivity of pointing gestures test was 44.9% in children with mild autism aged 1.0-10.0 years and 46.5%-65.9% in children with mild autism aged from 1.0-3.9 years. The sensitivity of pointing gestures test was 81.5% in children with moderate autism aged from 1.0-10.0 years and 87.3%-97.8% in children with moderate autism aged 1.0-3.9 years. The sensitivity of the pointing gestures test was 97.2% in children with severe autism aged 1.0-10.0 years, and 100.0% in children with severe autism aged 1.0-3.9 years. The sensitivity of the pointing gestures in mild, moderate and severe autism children decreased with age (linear-by-linear association values were 16.725, 64.232, 66.732 respectively, all P<0.001). The children with severe autism mainly scored 2 points (80.3%, 419/522) on the pointing gestures test , and children with moderate autism mainly scored 1 point(64.2%, 170/265) on the pointing gestures test. There were significant differences in functional development among different pointing gestures test groups.Functional development score in the autism children with 0 score of pointing gestures test was significantly higher than those with 1 score and 2 scores of pointing gestures test (all P<0.05). Conclusion:Pointing gestures has good sensitivity in children with autism (especially 1.0-4.9 years of age), and may serve as an objectively observable screening method. The better children with autism score on the pointing gestures, the better their functional development.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.