Objective:To evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans ; Drug Resistance, Neoplasm/drug effects* ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Mutation/genetics* ; Neoplasms/genetics* ; Antineoplastic Agents/therapeutic use*

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 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 evaluate the efficacy of corticosteroids in male children with Duchenne muscular dystrophy (DMD), and provide evidence for the rational clinical use of medication.Methods:This was a multicenter medical record series study which conducted from January 15 th to March 14 th, 2025. A total of 53 male children with DMD admitted to the Department of Rehabilitation of Children′s Hospital, Zhejiang University School of Medicine, Children′s Hospital of Chongqing Medical University and Affiliated Children′s Hospital of Soochow University from 2020 to 2024 were enrolled. Clinical data, corticosteroid usage, and the follow-up data were collected. The North star ambulatory assessment (NSAA) was used as the primary efficacy indicator. Generalized estimating equations (GEE) exchangeable working matrices were used for longitudinal analysis, and the least squares mean were used to compare the change trend of the efficacy evaluation index across different medication durations. Results:The age at the initiation of corticosteroid treatment was (6.3±1.9) years. The follow-up duration was 1.2 (0.9, 2.2) years. After treatment, the raw scores and linear scores of NSAA were both significantly higher than those before treatment ((22±7) vs. (19±5) points, (60±16) vs. (53±8) points; t=3.98, 3.69; both P<0.001). The 10 meter running time and time rising from floor were both shorter than those before treatment (6 (4, 8) vs. 7 (6, 9) s, 5 (3, 6) vs. 6 (5, 9) s; Z=2.62, 3.47; both P<0.01). GEE model analysis revealed all nonlinear correlation between motor function (NSAA linear score, 10-meter running velocity, and rising from floor velocity) and the duration of corticosteroid treatment (all P<0.05). Least squares mean comparison all showed that the medication effect first increased and then decreased with duration, reaching the peak at 1.1-2.0 years after treatment (all P<0.05). Conclusions:Corticosteroids can improve the motor function in male children with DMD, with the maximum treatment effect occurring 1 to 2 years after the initiation of treatment. It is necessary to comprehensively leverage time-varying efficacy of corticosteroids to optimize individualized treatment regimens for maximal motor function benefits in children with DMD.

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 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.

Proteasome activator PA28γ,also known as Ki antigen,REGγ or PSME3,is first found as Ki antigen in the serum of a patient with systemic lupus erythematosus,which belongs to 11S proteasome activator family together with PA28α and PA28β.In the amino acid sequence,PA28γ has 25%homology with PA28α and PA28β and its seven-subunit homomer is a 20S proteasome acti-vator,which mainly exists in the nucleus and participates in ubiquitin and ATP-dependent or independent protein degradation.More and more studies have reported the role of PA28γ in human immune-related diseases.This article reviews the function of PA28γ as a proteasome activator and its role in immune-related diseases including cancer,inflammation and virus infection-related diseases and other diseases in recent years,so as to reveal the role of PA28γ in the occurrence and development of immune-related diseases and its potential as a target for immunotherapy.

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.