Autism spectrum disorder (ASD) is a neurodevelopmental condition with a steadily rising global prevalence, yet effective pharmacological interventions remain notably limited, highlighting an urgent need for safe, accessible, and mechanism-based therapeutic strategies. Physical exercise has emerged as a promising non-pharmacological intervention that ameliorates both core symptoms—social communication deficits and restricted repetitive behaviors—and associated features including cognitive dysfunction and motor impairments, in children and adolescents with ASD. However, the molecular mechanisms mediating these beneficial effects remain incompletely defined, impeding the development of evidence-based exercise prescriptions and biomarker-driven rehabilitation protocols. MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that post-transcriptionally regulate approximately 60% of protein-coding genes. Within the central nervous system, miRNAs orchestrate diverse neurobiological processes including neural progenitor proliferation, neuronal differentiation, dendritic spine morphogenesis, synaptic plasticity, and neuroinflammatory homeostasis. Notably, miRNAs are remarkably stable in biological fluids and can be packaged into extracellular vesicles, rendering them attractive candidates as both mechanistic mediators and non-invasive peripheral biomarkers. Among the hundreds of miRNAs expressed in the brain, three—miR-132, miR-34a, and miR-146a—have emerged as particularly relevant to ASD pathophysiology. This review focuses on these three miRNAs for the following reasons: miR-132 is a master regulator of activity-dependent synaptic plasticity through its modulation of BDNF/MeCP2/PTEN signaling and has been consistently downregulated in ASD prefrontal cortex; miR-34a functions as a pro-apoptotic factor that suppresses Bcl-2-mediated neuronal survival pathways and is upregulated in ASD cerebellum; and miR-146a serves as a key brake on neuroinflammation via TLR7/IRAK1 signaling and shows region-specific dysregulation in ASD temporal lobe. We first summarize evidence from human post-mortem brain tissues and ASD animal models demonstrating the consistent dysregulation of these three miRNAs. Notably, the pathological consequences of these miRNA alterations—impaired synaptic plasticity, excessive neuronal apoptosis, and sustained neuroinflammation—are interconnected and collectively contribute to the heterogeneous symptomatology of ASD. We then present a synthesis of emerging evidence demonstrating that various exercise modalities, including swimming, treadmill running, and voluntary wheel running, can concurrently reverse these ASD-like behavioral phenotypes and normalize the expression of the three key miRNAs. These data provide the first direct experimental evidence linking exercise-induced miRNA modulation to ASD symptom improvement. On the basis of these findings, we propose an integrative “exercise-miRNA-ASD” framework wherein exercise functions as a multi-targeted modulator—simultaneously enhancing synaptic plasticity, promoting neuronal survival, and attenuating neuroinflammation—through coordinated regulation of the three miRNAs. Importantly, this framework is not merely descriptive but offers testable predictions: exercise-induced miRNA changes should be dose-dependent, show temporal correlation with behavioral improvements, and be blunted by miRNA-specific antagonists or CRISPR/Cas9-mediated knockout. Beyond its specific application to ASD, this framework has broader implications. The miR-132/BDNF, miR-34a/Bcl-2, and miR-146a/TLR7 pathways are not ASD-specific but represent fundamental neural stress and repair mechanisms that are dysregulated across Alzheimer’s disease (AD), traumatic brain injury, Parkinson’s disease (PD), and major depressive disorder. Exercise has been shown to modulate these same miRNAs in several of these conditions, suggesting that the “exercise-miRNA-neural function” axis may represent a conserved neuroprotective mechanism that transcends diagnostic boundaries. Thus, we propose that ASD serves as an ideal model disease for elucidating this universal mechanism, with findings potentially generalizable to other neurological disorders. We also critically evaluate current translational barriers: the near-absence of human clinical trials with serial miRNA profiling; the undefined dose-response relationships between exercise parameters and miRNA expression; the unresolved causality issue (current evidence demonstrates association, not causation); and the uncertain correlation between peripheral exosomal miRNA levels and brain miRNA dynamics. We argue that future research must prioritize CRISPR/Cas9-based miRNA manipulation in animal models combined with longitudinal exercise interventions to establish causality, and that cross-disease validation studies are essential to determine whether exercise-induced miRNA changes represent a shared neuroprotective signature or disease-specific responses. Ultimately, we envision a paradigm where a simple blood test measuring exosomal miR-132, miR-34a, and miR-146a levels could guide personalized exercise prescriptions, enabling precision rehabilitation for individuals with ASD and potentially other neurological conditions.

Objective:To explore the characteristics of potential categories of chronic disease co-morbid patients' learned helplessness, and to analyze the differential characteristics of different categories of chronic disease co-morbid patients.Methods:Convenience sampling method was used to select patients with chronic disease co-morbidities who attended The NO.1 People's Hospital of Xiangyang, Hubei University of Medicine, from June to December 2023 as survey respondents. General information questionnaire, Learned Helplessness Scale, Health Questionnaire Somatic Symptom Cluster Scale, Kessler Psychological Distress Scale, and Comprehension Social Support Scale were used for the cross-sectional survey. The potential profile of learned helplessness, and the influencing factors of potential categories of learned helplessness was analyzed.Results:A total of 810 patients with chronic co-morbidities were investigated. There were 453 males and 357 females, aged (65.03±10.89) years old. The learned helplessness of these patients was categorized into three different potential categories, which were named as low-level learned helplessness group, medium-level learned helplessness group, high-level learned helplessness, accounting for 17.5% (142/810), 23.5% (190/810), and 59.0% (478/810), respectively. Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with more severe physical symptoms ( OR=1.456, 1.391, both P<0.01). Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with more severe the psychological distress ( OR=1.359, 1.917, both P<0.01). Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with lower levels of social support ( OR=0.928, 0.874, both P<0.01). Compared with the low-level learned helplessness group, patients with a duration of illness >5 years were used as controls, patients with a duration of illness 2-5 years were more likely to belong to the medium-level learned helplessness group and high-level learned helplessness group ( OR=74.586, 62.620, both P<0.01). Compared with the low-level learned helplessness group, patients with neutral personalities were compared, patients with extroverted personalities had a lower probability of belonging to the medium-level learned helplessness group ( OR=0.105, P<0.05), while patients with introverted personalities had a lower probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group ( OR=0.052, 0.046, both P<0.01). Conclusions:Patients with chronic disease co-morbidities have higher levels of learned helplessness during disease treatment and have more distinctive categorical characteristics. Healthcare professionals should adopt targeted nursing interventions according to different categories of chronic disease co-morbid patients to reduce the level of learned helplessness.

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.

Objective:Exploring the role and mechanism of CHMP4C in regulating necroptosis during gastric can-cer development and progression.Method:The expression of CHMP4C in pan-cancer was analyzed by bioinformatics methods,and the expression of CHMP4C was detected in human normal gastric epithelial cells and GC cell lines by RT-qPCR and Western blot.Overexpression or knockdown of CHMP4C was performed in GC cell lines,and the effects of CHMP4C on the growth and proliferation of GC cells were detected using CCK-8 and clone formation assays.The CCK-8 experiment and Hoechst/PI double staining experiment were used to detect the changes in GC cell mortality and PI positive cell ratio after treatment with the necroptsis inducer TSZ or inhibitor necrostatin-1(Nec-1).Western blot assay was used to detect the protein and phosphorylation levels of RIPK1,RIPK3,and MLKL in GC cells.Result:CHMP4C was upregulated in GC tissues and cells.The CCK-8 and clone formation experiments showed that overex-pression of CHMP4C significantly improved the proliferation ability and colony formation efficiency of GC cells,while knockdown of CHMP4C significantly weakened GC cells.Moreover,the results of CCK-8 and Hoechst 33342/PI double staining experiments showed that upregulated CHMP4C could inhibit TSZ induced GC cell death;Nec-1 can reverse the decrease in GC cell viability caused by CHMP4C knockdown.Western blot experiment showed that the levels of p-RIPK1,p-RIPK3,and p-MLKL were significantly decreased in overexpressing cells,while they were increased in knockdown cells.After treatment with Nec-1,the expression levels of these three proteins decreased in knockdown cells.Conclusion:CHMP4C may promote GC progression by negatively regulating necroptosis through inhibiting the phosphorylation of the RIPK1/RIPK3/MLKL signaling pathway,suggesting that it is expected to be a potential target for GC therapy.

Based on serum metabolomics and gut microbiota technology, this study explores the effects and mechanisms of the water extract of Ziziphi Spinosae Semen(SZRW) and the petroleum ether extract of Ziziphi Spinosae Semen(SZRO) in improving depressive-like behaviors induced by sleep deprivation. A modified multi-platform water environment method was employed to establish a rat model of sleep deprivation. Depressive-like behaviors in rats were assessed through the sucrose preference test and forced swim test. The expression of barrier proteins, such as Occludin, in the colon was determined by immunofluorescence. UPLC-Q-Orbitrap MS was utilized to analyze the serum metabolic profiles of sleep-deprived rats, screen for differential metabolites, and analyze metabolic pathways. The diversity of the gut microbiota was detected using 16S rRNA gene sequencing. Spearman correlation coefficient analysis was conducted to assess the correlation between differential metabolites and gut microbiota. The results indicated that SZRO significantly increased the sucrose preference index and decreased the immobility time in the forced swim test in rats. A total of 34 differential metabolites were identified through serum metabolomics. SZRW and SZRO shared five metabolic pathways, including phenylalanine metabolism. SZRW uniquely featured taurine and hypotaurine metabolism, while SZRO uniquely featured linoleic acid metabolism and tyrosine metabolism. Correlation analysis revealed that SZRW could upregulate the abundance of Bilophila, promoting the production of indole-3-propionic acid and subsequently upregulating the expression levels of intestinal tight junction proteins such as ZO-1, Occludin, and Claudin-1. SZRO could indirectly influence metabolic pathways such as arginine metabolism and linoleic acid metabolism by upregulating the abundance of gut microbiota such as Coprococcus and Eubacterium species. Both SZRW and SZRO can regulate endogenous metabolism, including amino acids, energy, and lipids, alter the gut microbiota microecology, and improve depressive-like behaviors. SZRO demonstrated superior effects in regulating metabolic pathways and gut microbiota structure compared to SZRW. The findings of this study provide a scientific basis for elucidating the pharmacodynamic material basis of Ziziphi Spinosae Semen.
Animals ; Rats ; Gastrointestinal Microbiome/drug effects* ; Male ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Depression/blood* ; Rats, Sprague-Dawley ; Sleep Deprivation/complications* ; Ziziphus/chemistry* ; Antidepressive Agents/administration & dosage* ; Behavior, Animal/drug effects* ; Humans

Objective:Exploring the role and mechanism of CHMP4C in regulating necroptosis during gastric can-cer development and progression.Method:The expression of CHMP4C in pan-cancer was analyzed by bioinformatics methods,and the expression of CHMP4C was detected in human normal gastric epithelial cells and GC cell lines by RT-qPCR and Western blot.Overexpression or knockdown of CHMP4C was performed in GC cell lines,and the effects of CHMP4C on the growth and proliferation of GC cells were detected using CCK-8 and clone formation assays.The CCK-8 experiment and Hoechst/PI double staining experiment were used to detect the changes in GC cell mortality and PI positive cell ratio after treatment with the necroptsis inducer TSZ or inhibitor necrostatin-1(Nec-1).Western blot assay was used to detect the protein and phosphorylation levels of RIPK1,RIPK3,and MLKL in GC cells.Result:CHMP4C was upregulated in GC tissues and cells.The CCK-8 and clone formation experiments showed that overex-pression of CHMP4C significantly improved the proliferation ability and colony formation efficiency of GC cells,while knockdown of CHMP4C significantly weakened GC cells.Moreover,the results of CCK-8 and Hoechst 33342/PI double staining experiments showed that upregulated CHMP4C could inhibit TSZ induced GC cell death;Nec-1 can reverse the decrease in GC cell viability caused by CHMP4C knockdown.Western blot experiment showed that the levels of p-RIPK1,p-RIPK3,and p-MLKL were significantly decreased in overexpressing cells,while they were increased in knockdown cells.After treatment with Nec-1,the expression levels of these three proteins decreased in knockdown cells.Conclusion:CHMP4C may promote GC progression by negatively regulating necroptosis through inhibiting the phosphorylation of the RIPK1/RIPK3/MLKL signaling pathway,suggesting that it is expected to be a potential target for GC therapy.

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.

OBJECTIVES: To investigate the epidemiological characteristics of human metapneumovirus (hMPV) and the risk factors for severe pneumonia in hospitalized children. METHODS: The epidemiological characteristics of hMPV in hospitalized children at Hebei Children's Hospital from January 2019 to December 2023 were retrospectively analyzed. The clinical data of hospitalized children with hMPV infection from April to December 2023 were included, and independent risk factors for severe pneumonia were identified through logistic regression. RESULTS: A total of 44 092 children were tested, with an hMPV positive rate of 7.30% (3 220/44 092). Children aged 3-6 years constituted the largest proportion (40.93%, 1 318/3 220) among hMPV-positive cases. The detection rate varied significantly by year (P<0.001), peaking in 2022 (12.35%, 978/7 919). The peak season of the epidemic was winter and spring from 2019 to 2021, but shifted to spring and summer from 2022 to 2023. The proportion of co-infection was 38.70% (1 246/3 220), primarily with rhinovirus (600/1 246, 48.15%), Mycoplasma pneumoniae (217/1 246, 17.42%), and respiratory syncytial virus (182/1 246, 14.61%). The main manifestations of hMPV pneumonia were cough, expectoration, and fever. Children with severe pneumonia were significantly younger (P<0.05). Wheezing, underlying diseases, co-infection, and younger age were identified as independent risk factors for severe pneumonia (P<0.05). CONCLUSIONS There are significant annual and seasonal differences in the epidemiological characteristics of hMPV in hospitalized children. Young age, underlying diseases, wheezing, and co-infection are independent risk factors for severe pneumonia.
Humans ; Risk Factors ; Metapneumovirus ; Child, Preschool ; Child ; Male ; Female ; Paramyxoviridae Infections/complications* ; Pneumonia/epidemiology* ; Retrospective Studies ; Child, Hospitalized ; Infant ; Logistic Models ; Seasons ; Hospitalization

Objective:To explore the characteristics of potential categories of chronic disease co-morbid patients' learned helplessness, and to analyze the differential characteristics of different categories of chronic disease co-morbid patients.Methods:Convenience sampling method was used to select patients with chronic disease co-morbidities who attended The NO.1 People's Hospital of Xiangyang, Hubei University of Medicine, from June to December 2023 as survey respondents. General information questionnaire, Learned Helplessness Scale, Health Questionnaire Somatic Symptom Cluster Scale, Kessler Psychological Distress Scale, and Comprehension Social Support Scale were used for the cross-sectional survey. The potential profile of learned helplessness, and the influencing factors of potential categories of learned helplessness was analyzed.Results:A total of 810 patients with chronic co-morbidities were investigated. There were 453 males and 357 females, aged (65.03±10.89) years old. The learned helplessness of these patients was categorized into three different potential categories, which were named as low-level learned helplessness group, medium-level learned helplessness group, high-level learned helplessness, accounting for 17.5% (142/810), 23.5% (190/810), and 59.0% (478/810), respectively. Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with more severe physical symptoms ( OR=1.456, 1.391, both P<0.01). Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with more severe the psychological distress ( OR=1.359, 1.917, both P<0.01). Compared with the low-level learned helplessness group, the probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group was higher for patients with chronic co-morbidities with lower levels of social support ( OR=0.928, 0.874, both P<0.01). Compared with the low-level learned helplessness group, patients with a duration of illness >5 years were used as controls, patients with a duration of illness 2-5 years were more likely to belong to the medium-level learned helplessness group and high-level learned helplessness group ( OR=74.586, 62.620, both P<0.01). Compared with the low-level learned helplessness group, patients with neutral personalities were compared, patients with extroverted personalities had a lower probability of belonging to the medium-level learned helplessness group ( OR=0.105, P<0.05), while patients with introverted personalities had a lower probability of belonging to the medium-level learned helplessness group and high-level learned helplessness group ( OR=0.052, 0.046, both P<0.01). Conclusions:Patients with chronic disease co-morbidities have higher levels of learned helplessness during disease treatment and have more distinctive categorical characteristics. Healthcare professionals should adopt targeted nursing interventions according to different categories of chronic disease co-morbid patients to reduce the level of learned helplessness.

Objective:To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease.Methods:A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c. 556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+ PM2_Supporting+ PM3). Conclusion:The c. 556_559dupGTTC (p.L187Rfs*5) and c. 919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.