Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To develop rat models of oral mucosa ulcer using distinct experimental methodologies,fulfilling research requirements and adhering to the ethical standards for animal care.Methods:96 SD rats were randomly allocated into groups.The rats in control group(n=8)were regularly fed without other treatment.Those in chemical cauterization groups were treated by 20％,40％,60％of glacial acetic acid(GAA)on oral mucosa(n=8);in mechanical damage groups by 30 000 r/min high speed drill induced trauma of 10,20 and 30 mm2 respectively(n=8);in ionizing radiation groups were treated with 10,12,15,20 and 30 Gy on the mucosa respectively(n=8).After the ulcer was appeared,the morphology of the mucosa were observed,the mucosal tissue lesions were examined by HE,Masson and immunofluorescence staining,the expression of TNF-α and IL-1β were detected by qPCR and ELISA respectively,and the body conditions such as diet and body weight of the rats were observed,the pain,dis-tress and discomfor of the rats were evaluated by MORTON&Griffits Guidelines.Results:40％and 60％GAA,20 mm2 and 30 mm2 friction damage and ionizing radiation of 12 Gy or greater may induce oral mucosa ulcer with a diseas coruse of 6-7 d in SD rats.TNF-α and IL-1β mRNA expression in the damaged tissue,the related protein expression in blood serum of the rats were in-creased.MORTON&Griffits Guidelines analysis showed 40％GAA,20 mm2 friction damage and 12 Gy ionizing radiation induced the lowest scores of pain,distress and discomfort of the rats with compatible oral mocosa ulcere induced by the relevat treatment.Conclusion:40％GAA,20 mm2 of friction damage and 12 Gy of ionizing radiation can reliably establish oral mucosa ulcer models and minimize adverse effects on SD rats,and accord with ethical standards of 3R for laboratory animal.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

Objective:To develop rat models of oral mucosa ulcer using distinct experimental methodologies,fulfilling research requirements and adhering to the ethical standards for animal care.Methods:96 SD rats were randomly allocated into groups.The rats in control group(n=8)were regularly fed without other treatment.Those in chemical cauterization groups were treated by 20％,40％,60％of glacial acetic acid(GAA)on oral mucosa(n=8);in mechanical damage groups by 30 000 r/min high speed drill induced trauma of 10,20 and 30 mm2 respectively(n=8);in ionizing radiation groups were treated with 10,12,15,20 and 30 Gy on the mucosa respectively(n=8).After the ulcer was appeared,the morphology of the mucosa were observed,the mucosal tissue lesions were examined by HE,Masson and immunofluorescence staining,the expression of TNF-α and IL-1β were detected by qPCR and ELISA respectively,and the body conditions such as diet and body weight of the rats were observed,the pain,dis-tress and discomfor of the rats were evaluated by MORTON&Griffits Guidelines.Results:40％and 60％GAA,20 mm2 and 30 mm2 friction damage and ionizing radiation of 12 Gy or greater may induce oral mucosa ulcer with a diseas coruse of 6-7 d in SD rats.TNF-α and IL-1β mRNA expression in the damaged tissue,the related protein expression in blood serum of the rats were in-creased.MORTON&Griffits Guidelines analysis showed 40％GAA,20 mm2 friction damage and 12 Gy ionizing radiation induced the lowest scores of pain,distress and discomfort of the rats with compatible oral mocosa ulcere induced by the relevat treatment.Conclusion:40％GAA,20 mm2 of friction damage and 12 Gy of ionizing radiation can reliably establish oral mucosa ulcer models and minimize adverse effects on SD rats,and accord with ethical standards of 3R for laboratory animal.

Objective:The objective of this research is to study the prevalence and risk factors of psychosocial and behavioral problems in children and adolescents of different ages and genders to provide a scientific foundation for more targeted psychological interventions and social support in the future.Methods:From April 21 to May 31, 2023, a cross-sectional survey was conducted using a stratified random sampling method in five cities (Beijing City, Changchun City, Baicheng City, Shenyang City, Hohhot City) across four provinces in Northern China (Beijing, Jilin, Liaoning, Inner Mongolia). The study was conducted using an online questionnaire among children and adolescents aged 6-16 years. Self-made social and life characteristics questionnaire and Achenbach Child Behavior Check List (CBCL) (for parent) was utilized to investigate the prevalence of psychosocial and behavioral problems and relative influencing factors. Using stepwise regression analysis to screen potential factors affecting the psychosocial and behavioral health of children and adolescents and logistic regression analysis was employed to analyze the risk factors associated while controlling for confounding variables.Results:A total of 10 492 questionnaires were distributed in this study. Among the 8 593 valid questionnaires collected, there were 4 385 males (51.03%) and 4 208 females (48.97%). The sample consisted of 3 348 children aged 6-11 years old and 5 245 children aged 12-16 years old. Out of these participants, 688 individuals (8.01%) were detected positive. In the 6-11 age group, 1 762 boys were assessed, revealing 142 positive cases (8.06%), while 1 586 girls were assessed, with 84 positive cases (5.30%). In the 12-16 age group, 2 623 boys were evaluated, resulting in 237 positive cases (9.04%), and 2 622 girls were evaluated, with 225 positive cases (8.58%). Overall, boys had a higher prevalence rate than girls did, with older age groups showing higher rates compared to younger ones. Logistic regression analysis identified six significant risk factors: parent-child conflict ( OR=4.207, 95% CI: 3.583-4.940), irregular diet patterns( OR=1.862, 95% CI: 1.566-2.213), parental mental illness history( OR=5.381, 95% CI: 2.673-10.83), sleep disorders( OR=4.664, 95% CI: 4.194-5.187), and excessive screen exposure( OR=1.863, 95% CI: 1.577-2.200) were found to be risk factors; whereas having more close friends ( OR=0.510, 95% CI: 0.431-0.603) acted as a protective factor. Conclusions:Psychosocial and behavioral problems in children and adolescents will change with social conditions, with continuous attention required to prevent risk factors. Precise intervention and integral support should be implemented by families, schools and society to provide more accurate protection for children and adolescents.

Background and purpose:Rectal cancer occurs on the inner wall of the rectum,and metastasis-associated in colon cancer 1(MACC1)can promote drug resistance in colon cancer cells.This study aimed to investigate the effect of MACC1 on oxaliplatin resistance in rectal cancer and its mechanism.Methods:Biosignal analysis of MACC1 and TCF7 expressions in rectal cancer tissues and signaling pathways enriched for MACC1 were carried out.The expressions of MACC1 and TCF7 in rectal cancer cells and rectal cancer oxaliplatin-resistant cells were detected by real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),cell viability was detected by cell counting kit-8(CCK-8),and cell proliferation was detected by cell colony formation assay.ECAR values,lactate production and glucose consumption were detected by Seahorse Biosciences XF96.Western blot was used to detect the expressions of glycolysis-related proteins.Dual luciferase reporter gene and ChIP were used to validate the regulatory relationship between MACC1 and TCF7.Normality test and homogeneity of variance analysis was performed on the data of each group by GraphPad Prism 8.0.If it conformed to normal distribution,one-way ANOVA or t-test would be used for inter group comparison,otherwise the comparison between groups would be conducted using Wilcoxon rank sum test.Using a two-sided test,P＜0.05 was considered statistically significant.Results:MACC1 and TCF7 expressions were upregulated in rectal cancer,and knockdown of MACC1 significantly inhibited the viability of rectal cancer drug-resistant cells and the IC50 values of different concentrations of oxaliplatin treatments,as well as reduced the proliferation ability of rectal cancer oxaliplatin-resistant cells.Overexpression of MACC1 was able to promote the proliferation and glycolytic capacity of rectal cancer cells.Further studies revealed that the transcription factor TCF7 existed in the upper reaches of MACC1.Besides,this study analyzed the data from Cancer Genome Atlas Program(TCGA),and the result showed that knockdown of TCF7 was able to attenuate the promotional effect of overexpression of MACC1 on the glycolytic capacity and oxaliplatin resistance of rectal cancer cells.Conclusion:This study demonstrated that the TCF7/MACC1 axis could promote aerobic glycolysis and thus oxaliplatin resistance in rectal cancer cells.The findings suggest that targeting the TCF7/MACC1 axis or inhibiting the aerobic glycolysis pathway may be a novel therapeutic approach to inhibit oxaliplatin resistance in rectal cancer.

Objective:To explore and analyze the characteristics and influencing factors of language development in children with attention deficit hyperactivity disorder (ADHD).Methods:A case-control study was used, from May 2021 to August 2023, patients diagnosed with attention deficit hyperactivity disorder (ADHD) were enrolled in the mental health clinic of the Children′s Hospital Affiliated to the Capital Institute of Pediatrics. The language ability of 272 children with ADHD and 117 healthy children who underwent physical examination in children′s health center during the same period were tested by Diagnostic Receptive and Expressive Assessment of Mandarin-Comprehensive (DREAM-C), and the development levels of total language, receptive, expressive, semantics and syntax of the two groups were compared by independent sample t-test. The influential factors of language lag in children with ADHD were analyzed by univariate χ2 analysis and multiple logistic regression. Results:There were 272 children with ADHD, including 206 males and 66 females, with an age range of 6-8 (7.29±1.17) years. While in the control group, there were 117 healthy children, including 91 males and 26 females, with an age range of 6-8 (7.02±0.82) years. The average scores of total language, expressive and syntax of ADHD children were lower than those of healthy children [(92.73±12.47/96.36±11.04), t=-2.857, P<0.05; (84.49±13.24/87.78±15.25), t=-2.029, P<0.05; (87.93±10.26/90.27±11.05), t=2.022, P<0.05]. Univariate χ2 analysis showed that disharmonious family relationship ( χ2=4.183, P<0.05), the main caregivers were non-parents ( χ2=9.121, P<0.05), early screen exposure ( χ2=3.889, P<0.05), ADHD family history ( χ2=5.423, P<0.05) were influential factors of language development lag in ADHD children. The results of multivariate logistic regression model analysis showed that cesarean section ( OR=2.137, 95% CI: 1.078-4.379, P=0.030), disharmonious family relationship ( OR=2.659, 95% CI: 1.178-5.999, P=0.019), early screen exposure ( OR=3.556, 95% CI: 1.127-11.213, P=0.030), ADHD family history ( OR=1.959, 95% CI: 1.058-3.630, P=0.033) were risk factors for comorbidities of language development in children with ADHD. Conclusion:The total language ability, expressive and syntax scores of ADHD children lag behind those of healthy children. The delayed language development of ADHD children is related to delivery mode, family relationship, the main caregivers, early screen exposure, family history of ADHD.

OBJECTIVE To study effects of Jinshui Liujun decoction(JLD) on pulmonary water metabolism and TNF-α/NF-κB signaling pathway in asthmatic mice. METHODS After 1 week of acclimatization, 10 mice were randomly selected by body weight as a blank control group, and the rest of the mice were sensitized by intraperitoneal and subcutaneous injections of ovalbumin sensitizing solution on the 1st, 8th, and 15th day of the experiment. On the 22nd day, they were randomly divided into model control group, positive control group and JLD low, medium and high dose(4.1, 8.2, 16.4 g·kg−1) group, and replicated the asthma mouse model by inhaling nebulized excitation solution(1% ovalbumin) once every other day for 2 consecutive weeks, and at the same time, were given atomized excitation solution(1% ovalbumin) every other day for two weeks to replicate the asthmatic mouse model, and were given the test drug by gavage daily. The effects of JLD on the behavior, lung wet-dry weight ratio, AQP1, AQP5, TNF-α, NF-κB, and NF-κB mRNA expression in asthmatic mice were observed. RESULTS JLD reduced the number of animals with asthma attacks, alleviated asthma symptoms, decreased the lung index and lung wet-to-dry weight ratio, increased the expression level of AQP1 and AQP5 in lung tissues, reduced the content of TNF-α in bronchoalveolar lavage fluid and lung tissues, and down-regulated the expression level of NF-κB and its genes in lung tissues(P<0.05 or P<0.01). CONCLUSION JLD has an anti-asthma effect and its mechanism of action is partially due to its inhibition of the TNF-α/NF-κB signaling pathway, upregulation of AQP1 and AQP5, and improvement of pulmonary water metabolism.

Objective:To explore and analyze the characteristics and influencing factors of language development in children with attention deficit hyperactivity disorder (ADHD).Methods:A case-control study was used, from May 2021 to August 2023, patients diagnosed with attention deficit hyperactivity disorder (ADHD) were enrolled in the mental health clinic of the Children′s Hospital Affiliated to the Capital Institute of Pediatrics. The language ability of 272 children with ADHD and 117 healthy children who underwent physical examination in children′s health center during the same period were tested by Diagnostic Receptive and Expressive Assessment of Mandarin-Comprehensive (DREAM-C), and the development levels of total language, receptive, expressive, semantics and syntax of the two groups were compared by independent sample t-test. The influential factors of language lag in children with ADHD were analyzed by univariate χ2 analysis and multiple logistic regression. Results:There were 272 children with ADHD, including 206 males and 66 females, with an age range of 6-8 (7.29±1.17) years. While in the control group, there were 117 healthy children, including 91 males and 26 females, with an age range of 6-8 (7.02±0.82) years. The average scores of total language, expressive and syntax of ADHD children were lower than those of healthy children [(92.73±12.47/96.36±11.04), t=-2.857, P<0.05; (84.49±13.24/87.78±15.25), t=-2.029, P<0.05; (87.93±10.26/90.27±11.05), t=2.022, P<0.05]. Univariate χ2 analysis showed that disharmonious family relationship ( χ2=4.183, P<0.05), the main caregivers were non-parents ( χ2=9.121, P<0.05), early screen exposure ( χ2=3.889, P<0.05), ADHD family history ( χ2=5.423, P<0.05) were influential factors of language development lag in ADHD children. The results of multivariate logistic regression model analysis showed that cesarean section ( OR=2.137, 95% CI: 1.078-4.379, P=0.030), disharmonious family relationship ( OR=2.659, 95% CI: 1.178-5.999, P=0.019), early screen exposure ( OR=3.556, 95% CI: 1.127-11.213, P=0.030), ADHD family history ( OR=1.959, 95% CI: 1.058-3.630, P=0.033) were risk factors for comorbidities of language development in children with ADHD. Conclusion:The total language ability, expressive and syntax scores of ADHD children lag behind those of healthy children. The delayed language development of ADHD children is related to delivery mode, family relationship, the main caregivers, early screen exposure, family history of ADHD.

Objective:The objective of this research is to study the prevalence and risk factors of psychosocial and behavioral problems in children and adolescents of different ages and genders to provide a scientific foundation for more targeted psychological interventions and social support in the future.Methods:From April 21 to May 31, 2023, a cross-sectional survey was conducted using a stratified random sampling method in five cities (Beijing City, Changchun City, Baicheng City, Shenyang City, Hohhot City) across four provinces in Northern China (Beijing, Jilin, Liaoning, Inner Mongolia). The study was conducted using an online questionnaire among children and adolescents aged 6-16 years. Self-made social and life characteristics questionnaire and Achenbach Child Behavior Check List (CBCL) (for parent) was utilized to investigate the prevalence of psychosocial and behavioral problems and relative influencing factors. Using stepwise regression analysis to screen potential factors affecting the psychosocial and behavioral health of children and adolescents and logistic regression analysis was employed to analyze the risk factors associated while controlling for confounding variables.Results:A total of 10 492 questionnaires were distributed in this study. Among the 8 593 valid questionnaires collected, there were 4 385 males (51.03%) and 4 208 females (48.97%). The sample consisted of 3 348 children aged 6-11 years old and 5 245 children aged 12-16 years old. Out of these participants, 688 individuals (8.01%) were detected positive. In the 6-11 age group, 1 762 boys were assessed, revealing 142 positive cases (8.06%), while 1 586 girls were assessed, with 84 positive cases (5.30%). In the 12-16 age group, 2 623 boys were evaluated, resulting in 237 positive cases (9.04%), and 2 622 girls were evaluated, with 225 positive cases (8.58%). Overall, boys had a higher prevalence rate than girls did, with older age groups showing higher rates compared to younger ones. Logistic regression analysis identified six significant risk factors: parent-child conflict ( OR=4.207, 95% CI: 3.583-4.940), irregular diet patterns( OR=1.862, 95% CI: 1.566-2.213), parental mental illness history( OR=5.381, 95% CI: 2.673-10.83), sleep disorders( OR=4.664, 95% CI: 4.194-5.187), and excessive screen exposure( OR=1.863, 95% CI: 1.577-2.200) were found to be risk factors; whereas having more close friends ( OR=0.510, 95% CI: 0.431-0.603) acted as a protective factor. Conclusions:Psychosocial and behavioral problems in children and adolescents will change with social conditions, with continuous attention required to prevent risk factors. Precise intervention and integral support should be implemented by families, schools and society to provide more accurate protection for children and adolescents.