OBJECTIVE: To explore mechanisms of acid-sensing ion channel 1 (ASIC1) mediated lumbar nucleus pulposus cell apoptosis through extracellular-signalregulated protein kinase 5 (ERK5) signaling pathway and mitochondrial dysfunction pathway. METHODS: Totally 34 patients with degenerative lumbar disc herniation (LDH) admitted from January 2020 to December 2022 were collected as research objects, including 21 males and 13 females;aged from 29 to 52 years old with an average of (37.43±4.75) years old;22 patients with grade Ⅱ and 12 patients with grade Ⅳ, according to Pfirrmann grading criteria;15 patients with L_4,5 and 19 patients with L₅S₁. The expression of ASIC1 in nucleus pulposus of LDH patients was measured by immunohistochemical staining. Nucleus pulposus cells were cultured by primary culture method, identified by toluidine blue staining and immunohistochemical staining, and the expression of ASIC1 protein was located by immunofluorescence staining. According to the addition of siRNA-ASIC1, ASIC1 overexpression plasmid, and ERK5 inhibitors, the nucleus pulpocyte was divided into three groups, named as SIRNA-silenced group, overexpression group, and inhibitor group, with 3 patients in each group. Cells of each group were collected at 72 h after intervention, expression of ASIC1, ERK5, BCL-xL/BCL-2-associated Death promoter (Bad), B-cell lymphoma-2 associated X (Bax) and B-cell lymphoblast-2 gene (Bcl-2) were detected by reverse transcription-polymerase chain reaction (RT-PCR);intracellular calcium ion levels were detected by calcium ion kit, mitochondrial membrane potential was detected by JC-1 kit, and apoptosis was observed by AV-PI kit. RESULTS: In LDH patients with grade Ⅳ, nucleus pulposus tissue removed during operation revealed poor elasticity, white color and poor ductility, and immunohistochemical results showed increased ASIC1 expression. There was no significant difference in mRNA relative expression of ASIC1 between siRNA silencing group (0.31±0.03) and inhibitor group (0.39±0.05) (P>0.05). The mRNA relative expression level of ERK5 in siRNA silencing group(0.32±0.05) was significantly higher than that in inhibitor group (0.15±0.04)(P<0.05), which suggested ERK5 was the downstream molecule of ASIC1. The mRNA relative expression levels of apoptosis promoting factor Bad and Bax in siRNA silencing group and inhibitor group were lower than those in overexpression group(P<0.05), the relative expression level of anti-apoptosis factor Bcl-2 mRNA was significantly increased (P<0.05). The calcium content in overexpression group was higher than that in siRNA silencing and inhibitor groups (P<0.05), the normal proportion of mitochondrial membrane potential in overexpression group was lower than that in siRNA silencing and inhibitor group (P<0.05), and the apoptosis rate in overexpression group was higher than that in siRNA silencing and inhibitor group (P<0.05). CONCLUSION After the activation of ASIC1 channel protein, calcium ions could enter the cells and act as a second messenger molecule to regulate apoptosis of nucleus pulposus cells by ERK5 signaling pathway and mitochondrial disorder pathway.
Humans ; Acid Sensing Ion Channels/physiology* ; Male ; Female ; Apoptosis ; Middle Aged ; Adult ; Signal Transduction ; Mitogen-Activated Protein Kinase 7/physiology* ; Mitochondrial Diseases/genetics* ; Nucleus Pulposus/metabolism* ; Intervertebral Disc Degeneration/metabolism* ; Mitochondria/metabolism* ; Intervertebral Disc Displacement/genetics*

Objective To construct a support system that facilitates the participation of children with special needs(CSN)in physi-cal activity within the context of inclusive education.Methods Based on World Health Organization(WHO)health promoting school(HPS)framework,and integrating WHO International Classification of Functioning,Disability and Health(ICF)as well as the WHO guidelines on physi-cal activity,a systematic and multidimensional support framework was developed.Results In the context of inclusive education,the primary forms of physical activity for CSN included physical educa-tion classes and extracurricular sports activities.A comprehensive support system was developed at macro-,me-so-and micro-levels.At the macro-level,the framework called for the establishment of inclusive physical educa-tion and activity-related policies,accessible and universally designed physical environments,inclusive activity climates,and integrated community resources.At the meso-level,it emphasized creating a supportive profession-al development environment for inclusive physical education teachers,equipping them with skills in inclusive pedagogy,classroom management and extracurricular activity planning.At the micro-level,it focused on the de-sign of physical education curricula tailored to the physical activity and motor development needs of CSN,the es-tablishment of individualized learning support mechanisms,and encouraging active participation in physical edu-cation and physical activities.Conclusion To address the physical activity and educational needs of CSN in inclusive education settings,a three-tiered support system has been constructed.The macro-level involves policy,environment and community;the meso-level focuses on teachers and instructional practices;and the micro-level targets students'learning,motor devel-opment and health.

Objective:To investigate the association between social jetlag and depressive symptoms among college students, as well as its potential influencing factors.Methods:A cross-sectional study was conducted through an online questionnaire platform (Wenjuanxing) from March to April 2023, collecting data on social jetlag, depressive symptoms, and other factors from students at Shantou University. Social jetlag time was defined as the absolute difference between the midpoint of sleep time on weekends and weekdays, with a cutoff at the 75th percentile. The presence of social jetlag was defined as social jetlag time≥1 hour. Depressive symptoms were assessed using the Beck Depression Inventory (BDI), with a score of≥10 indicating the presence of depressive symptoms. Participants were divided into depressive symptom group (BDI≥10) and non-depressive symptom group (BDI<10). Linear regression and logistic regression models were used to analyze the relationship between social jetlag and depressive symptoms, with interaction terms and subgroup analyses to explore potential influencing factors.Results:A total of 1 323 college students were included. The social jetlag time (median 0.71 hour vs. 0.50 hour, Z=-3.36, P<0.001) and prevalence of social jetlag (37.64% vs. 30.57%, χ2=7.03, P=0.008) were both higher in the depressive symptom group than in the non-depressive symptom group. The linear regression model showed that each additional hour of social jetlag was associated with an increase of 0.67 points in BDI score (95% CI=0.16-1.18, β=0.06, P=0.010), after adjusting for age, gender, body mass index, being a medical student, smoking, drinking, caffeine intake, physical exercise, anxiety symptoms, insomnia symptoms, and sleep duration. The logistic regression model indicated that social jetlag was a risk factor for depressive symptoms (O R=1.34, 95% CI=1.02-1.76, P=0.036), which was moderated by physical exercise (interaction P=0.033). Among participants without physical exercise, social jetlag was associated with depressive symptoms ( OR=1.71, 95% CI=1.18-2.48, P=0.005), while no such association was found among those with physical exercise ( OR=0.97, 95% CI=0.64-1.47, P=0.892). Conclusion:Social jetlag may be associated with depressive symptoms in college students. This adverse relationship may be improved by enhancing physical exercise.

Objective To develop a competency framework for teachers in inclusive education settings based on World Health Orga-nization rehabilitation competency framework(RCF).Methods Based on the five core competency domains of RCF,along with its core values and beliefs,this study analyzed the specific competency requirements for teachers in inclusive education settings,and summarized the specific competencies,behavioral requirements,and core values and beliefs within these five domains.Additionally,Inter-national Classification of Functioning,Disability and Health(ICF)was used to supply the competency frame-work from a functional perspective.Results RCF-based teacher competency framework for inclusive education settings encompassed five core domains and two foundational components.In the practice domain,the framework emphasized a student-and family-centered approach,requiring flexible teaching strategies to meet individualized needs.In the professionalism domain,it highlighted educational equity,ethical responsibility and rights of students with special needs.In the learning and development domain,it underscored continuous learning and professional growth for teachers to enhance adapt-ability and innovation in inclusive education.In the management and leadership domain,it stressed teamwork and resource integration to improve the quality of inclusive education services.In the research domain,it encour-aged teachers to integrate evidence-based practices into their teaching to ensure scientific and empirical educa-tional decision-making.Additionally,the core values emphasized respect,equity and inclusion,while the beliefs reflected confidence in each student's potential and a commitment to individualized support.Based on ICF,the specialized competencies for teachers in inclusive education primarily involved five aspects:integrating educa-tion and rehabilitation,functional assessment and individualized education planning,assistive technology,acces-sible learning environments,and digital empowerment technologies.Conclusion Based on RCF and ICF,a multidimensional and composite competency framework has been developed for teachers in inclusive education settings,which providing a systematic theoretical foundation for competency de-velopment,assessment and training,upholding a individual-centered approach,and emphasizing educational eq-uity and holistic student development.

Objective To construct a support system that facilitates the participation of children with special needs(CSN)in physi-cal activity within the context of inclusive education.Methods Based on World Health Organization(WHO)health promoting school(HPS)framework,and integrating WHO International Classification of Functioning,Disability and Health(ICF)as well as the WHO guidelines on physi-cal activity,a systematic and multidimensional support framework was developed.Results In the context of inclusive education,the primary forms of physical activity for CSN included physical educa-tion classes and extracurricular sports activities.A comprehensive support system was developed at macro-,me-so-and micro-levels.At the macro-level,the framework called for the establishment of inclusive physical educa-tion and activity-related policies,accessible and universally designed physical environments,inclusive activity climates,and integrated community resources.At the meso-level,it emphasized creating a supportive profession-al development environment for inclusive physical education teachers,equipping them with skills in inclusive pedagogy,classroom management and extracurricular activity planning.At the micro-level,it focused on the de-sign of physical education curricula tailored to the physical activity and motor development needs of CSN,the es-tablishment of individualized learning support mechanisms,and encouraging active participation in physical edu-cation and physical activities.Conclusion To address the physical activity and educational needs of CSN in inclusive education settings,a three-tiered support system has been constructed.The macro-level involves policy,environment and community;the meso-level focuses on teachers and instructional practices;and the micro-level targets students'learning,motor devel-opment and health.

Objective To develop a competency framework for teachers in inclusive education settings based on World Health Orga-nization rehabilitation competency framework(RCF).Methods Based on the five core competency domains of RCF,along with its core values and beliefs,this study analyzed the specific competency requirements for teachers in inclusive education settings,and summarized the specific competencies,behavioral requirements,and core values and beliefs within these five domains.Additionally,Inter-national Classification of Functioning,Disability and Health(ICF)was used to supply the competency frame-work from a functional perspective.Results RCF-based teacher competency framework for inclusive education settings encompassed five core domains and two foundational components.In the practice domain,the framework emphasized a student-and family-centered approach,requiring flexible teaching strategies to meet individualized needs.In the professionalism domain,it highlighted educational equity,ethical responsibility and rights of students with special needs.In the learning and development domain,it underscored continuous learning and professional growth for teachers to enhance adapt-ability and innovation in inclusive education.In the management and leadership domain,it stressed teamwork and resource integration to improve the quality of inclusive education services.In the research domain,it encour-aged teachers to integrate evidence-based practices into their teaching to ensure scientific and empirical educa-tional decision-making.Additionally,the core values emphasized respect,equity and inclusion,while the beliefs reflected confidence in each student's potential and a commitment to individualized support.Based on ICF,the specialized competencies for teachers in inclusive education primarily involved five aspects:integrating educa-tion and rehabilitation,functional assessment and individualized education planning,assistive technology,acces-sible learning environments,and digital empowerment technologies.Conclusion Based on RCF and ICF,a multidimensional and composite competency framework has been developed for teachers in inclusive education settings,which providing a systematic theoretical foundation for competency de-velopment,assessment and training,upholding a individual-centered approach,and emphasizing educational eq-uity and holistic student development.

Objective:To investigate the association between social jetlag and depressive symptoms among college students, as well as its potential influencing factors.Methods:A cross-sectional study was conducted through an online questionnaire platform (Wenjuanxing) from March to April 2023, collecting data on social jetlag, depressive symptoms, and other factors from students at Shantou University. Social jetlag time was defined as the absolute difference between the midpoint of sleep time on weekends and weekdays, with a cutoff at the 75th percentile. The presence of social jetlag was defined as social jetlag time≥1 hour. Depressive symptoms were assessed using the Beck Depression Inventory (BDI), with a score of≥10 indicating the presence of depressive symptoms. Participants were divided into depressive symptom group (BDI≥10) and non-depressive symptom group (BDI<10). Linear regression and logistic regression models were used to analyze the relationship between social jetlag and depressive symptoms, with interaction terms and subgroup analyses to explore potential influencing factors.Results:A total of 1 323 college students were included. The social jetlag time (median 0.71 hour vs. 0.50 hour, Z=-3.36, P<0.001) and prevalence of social jetlag (37.64% vs. 30.57%, χ2=7.03, P=0.008) were both higher in the depressive symptom group than in the non-depressive symptom group. The linear regression model showed that each additional hour of social jetlag was associated with an increase of 0.67 points in BDI score (95% CI=0.16-1.18, β=0.06, P=0.010), after adjusting for age, gender, body mass index, being a medical student, smoking, drinking, caffeine intake, physical exercise, anxiety symptoms, insomnia symptoms, and sleep duration. The logistic regression model indicated that social jetlag was a risk factor for depressive symptoms (O R=1.34, 95% CI=1.02-1.76, P=0.036), which was moderated by physical exercise (interaction P=0.033). Among participants without physical exercise, social jetlag was associated with depressive symptoms ( OR=1.71, 95% CI=1.18-2.48, P=0.005), while no such association was found among those with physical exercise ( OR=0.97, 95% CI=0.64-1.47, P=0.892). Conclusion:Social jetlag may be associated with depressive symptoms in college students. This adverse relationship may be improved by enhancing physical exercise.

Objective:To summarize the clinical phenotypes and genetic variations of children with epilepsy related to CLCN4 gene mutations. Methods:A retrospective analysis was conducted on 9 children with epilepsy who were diagnosed with CLCN4 gene mutations through whole-exome sequencing of family members. These children were treated at the Department of Pediatrics, Peking University First Hospital from December 2016 to March 2024. Their clinical manifestations, electroencephalogram, cranial imaging characteristics, and treatment follow-up were reviewed. Results:Among the 9 children, 6 were male and 3 were female. All cases involved de novo mutations. Three cases carried the c.823G>A/p.V275M variant, 2 cases carried the c.2152C>T/ p.R718W variant, 1 case carried the c.1630G>A/pG544R variant, and 1 case carried the c.2167C>T/ p.R723W variant. Two cases carried the unreported new variant c.848G>T/p.S283I and c.818G>A/ p.G273E. The onset age of epilepsy ranged from 55 days to 10 years, with a median onset age of 14 months. Seven out of 9 children had epilepsy onset before the age of 2 years. The types of seizures varied: 8 had focal seizures, 1 had generalized tonic-clonic seizures, 2 had myoclonic seizures, 1 had epileptic spasms, and 1 had atypical absence seizures. Three children experienced multiple types of seizures. All 9 children exhibited developmental delays to varying degrees: 8 had global developmental delay and 1 had cognitive developmental delay. Developmental delays were observed in 7 children before the onset of epilepsy. Clinically, 1 child was diagnosed with infantile epileptic spasms syndrome, 7 with unclassified developmental and epileptic encephalopathy, and 1 with focal epilepsy with developmental delay. At the last follow-up, the age of the children ranged from 2 years and 5 months to 13 years and 9 months. Seizures had been controlled in 3 children for a duration of 4 to 12 months. Conclusions:De novo variants are common in CLCN4 variants. Most seizures onset in infancy, seizure types are various, and focal seizures are common. Most of them have developmental delay and drug-resistant epilepsy, and some of them have developmental delay before seizure onset, which is consistent with the characteristics of developmental and epileptic encephalopathy.

Background:Patients with functional gastrointestinal disorders(FGIDs)often experience stigma related to symptom attribution and psychological interventions.Treatment as usual,including the use of neuromodulators,has shown limited effectiveness.Therefore,there is an urgent need for a comprehensive and individualized psychosomatic approach to effectively manage FGIDs in clinical practice.Aims:To evaluate whether the psychosomatic model of gastroenterology provide superior outcomes in FGIDs management compared with treatment as usual.Methods:A total of 165 FGIDs patients who attended the Department of Gastroenterology at the Third Affiliated Hospital of Soochow University from May 2024 to July 2024 were enrolled and randomly assigned to the treatment as usual group and the psychosomatic gastroenterology treatment group.Patients in treatment as usual group received lifestyle modifications and pharmacotherapy,including neuromodulators,while those in psychosomatic gastroenterology group received the symptom-oriented stepped reattribution model in addition to treatment as usual.After a 4-week intervention,treatment efficacy was assessed based on patient-reported outcomes.Neuromodulators adherence and overall clinical efficacy were compared between the two groups.Results:After 4 weeks of intervention,the effectiveness rates were 51.2％in the treatment as usual group and 85.0％in the psychosomatic gastroenterology group(P＜0.001).Neuromodulators adherence rates were 38.5％in the treatment as usual group and 85.4％in the psychosomatic gastroenterology group(P＜0.001).Patients in the psychosomatic gastroenterology group showed significantly lower scores on the GAD-7,PHQ-9,PHQ-15,and GCBI scales and higher scores on the GIQLI scale compared to the treatment as usual group(all P＜0.05).Conclusions:The psychosomatic model of gastroenterology significantly improves the neuromodulators adherence and the overall clinical efficacy in FGIDs patients compared with treatment as usual.

Background:Patients with functional gastrointestinal disorders(FGIDs)often experience stigma related to symptom attribution and psychological interventions.Treatment as usual,including the use of neuromodulators,has shown limited effectiveness.Therefore,there is an urgent need for a comprehensive and individualized psychosomatic approach to effectively manage FGIDs in clinical practice.Aims:To evaluate whether the psychosomatic model of gastroenterology provide superior outcomes in FGIDs management compared with treatment as usual.Methods:A total of 165 FGIDs patients who attended the Department of Gastroenterology at the Third Affiliated Hospital of Soochow University from May 2024 to July 2024 were enrolled and randomly assigned to the treatment as usual group and the psychosomatic gastroenterology treatment group.Patients in treatment as usual group received lifestyle modifications and pharmacotherapy,including neuromodulators,while those in psychosomatic gastroenterology group received the symptom-oriented stepped reattribution model in addition to treatment as usual.After a 4-week intervention,treatment efficacy was assessed based on patient-reported outcomes.Neuromodulators adherence and overall clinical efficacy were compared between the two groups.Results:After 4 weeks of intervention,the effectiveness rates were 51.2％in the treatment as usual group and 85.0％in the psychosomatic gastroenterology group(P＜0.001).Neuromodulators adherence rates were 38.5％in the treatment as usual group and 85.4％in the psychosomatic gastroenterology group(P＜0.001).Patients in the psychosomatic gastroenterology group showed significantly lower scores on the GAD-7,PHQ-9,PHQ-15,and GCBI scales and higher scores on the GIQLI scale compared to the treatment as usual group(all P＜0.05).Conclusions:The psychosomatic model of gastroenterology significantly improves the neuromodulators adherence and the overall clinical efficacy in FGIDs patients compared with treatment as usual.