Autism Spectrum Disorders (ASDs) are reported as a group of neurodevelopmental disorders. The structural changes of brain regions including the hippocampus were widely reported in autistic patients and mouse models with dysfunction of ASD risk genes, but the underlying mechanisms are not fully understood. Here, we report that deletion of Trio, a high-susceptibility gene of ASDs, causes a postnatal dentate gyrus (DG) hypoplasia with a zigzagged suprapyramidal blade, and the Trio-deficient mice display autism-like behaviors. The impaired morphogenesis of DG is mainly caused by disturbing the postnatal distribution of postmitotic granule cells (GCs), which further results in a migration deficit of neural progenitors. Furthermore, we reveal that Trio plays different roles in various excitatory neural cells by spatial transcriptomic sequencing, especially the role of regulating the migration of postmitotic GCs. In summary, our findings provide evidence of cellular mechanisms that Trio is involved in postnatal DG morphogenesis.
Animals ; Dentate Gyrus/metabolism* ; Mice ; Morphogenesis/physiology* ; Neurons/pathology* ; Cell Movement ; Mice, Inbred C57BL ; Autism Spectrum Disorder/pathology* ; Mice, Knockout ; Neural Stem Cells ; Male ; Neurogenesis ; Autistic Disorder/genetics*

Objective To explore the shared potential targets and molecular mechanisms of obesity and type 2 diabetes mellitus(T2DM)using bioinformatics methods,to validate the expression of core targets through animal experiments,and to analyze the intervention potential of active components of traditional Chinese medicine(TCM).Methods The obese population datasets(GSE151839 and GSE162653)were obtained from the Gene Expression Omnibus(GEO)database to screen for differentially expressed genes,which were then intersected with T2DM-related targets from the GeneCards database to identify shared targets.A protein-protein interaction(PPI)network was constructed using the STRING database.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed to identify enriched biological processes and signaling pathways.The expression of core targets in adipose tissue from patients with obesity and T2DM was validated using the GEO database.A total of 12 specific-pathogen-free(SPF)male Sprague-Dawley(SD)rats,aged 8 weeks and weighing between 180 and 200 g,were randomly assigned to a control group and a model group(n=6 each).A T2DM rat model was established,and the mRNA and protein expression levels of core targets in adipose tissue were measured.Molecular docking and molecular dynamics simulations were performed to assess the binding ability of TCM active components to core targets.Results A total of 460 and 796 obesity-related differentially expressed genes were identified in the GSE151839 and GSE162653 datasets,respectively,and 109 shared targets were obtained by intersection with T2DM-related targets.According to PPI network analysis,PTPRC,MMP9,ITGB2,CD86,CCR5,and CCR2 were identified as the core targets.GO and KEGG analysis showed that these targets are mainly enriched in biological processes such as inflammatory response,immune regulation,and cell adhesion.Animal experiments confirmed that the mRNA and protein expression of core targets,including PTPRC,ITGAX,MMP9,ITGB2,CCR2,and CXCL1,were significantly upregulated in the adipose tissue of T2DM rats(P<0.05).Molecular docking and molecular dynamics simulations revealed that berberine and puerarin had good binding ability with PTPRC,MMP9,and ITGB2.Conclusion This study reveals the shared molecular mechanisms between obesity and T2DM and shows that core targets,such as PTPRC and MMP9,may promote disease progression by regulating the inflammation-immune network.These findings provide a theoretical basis for the development of targeted therapeutic strategies based on TCM active ingredients.

Objective:To summarize the best evidence for lower limb rehabilitation robot exercise rehabilitation in stroke patients.Methods:Clinical decisions, best practices, guidelines, evidence summaries, expert consensus, systematic reviews, and randomized controlled trials on lower limb rehabilitation robot exercise rehabilitation in stroke patients were systematically searched in national and international guideline networks, websites of relevant professional societies, and databases. The search period was from database establishment to October 17, 2024. Two researchers independently conducted literature quality evaluation, evidence extraction, and integration.Results:A total of 13 papers were included, including four guidelines, seven systematic reviews, one expert consensus, and one randomized controlled trial. Twenty-six pieces of best evidence were summarized in seven aspects of multidisciplinary teamwork, applicable conditions, rehabilitation management, exercise implementation, evaluation of rehabilitation outcomes, abnormal training responses, and considerations.Conclusions:This study is based on a number of high-quality evidence, standardizing the relevant theories and clinical applications, with a certain degree of scientific and cutting-edge nature, providing practical, reliable and valuable evidence-based references and guidance for medical and nursing staff to use lower limb rehabilitation robots.

Objective:To summarize the best evidence for lower limb rehabilitation robot exercise rehabilitation in stroke patients.Methods:Clinical decisions, best practices, guidelines, evidence summaries, expert consensus, systematic reviews, and randomized controlled trials on lower limb rehabilitation robot exercise rehabilitation in stroke patients were systematically searched in national and international guideline networks, websites of relevant professional societies, and databases. The search period was from database establishment to October 17, 2024. Two researchers independently conducted literature quality evaluation, evidence extraction, and integration.Results:A total of 13 papers were included, including four guidelines, seven systematic reviews, one expert consensus, and one randomized controlled trial. Twenty-six pieces of best evidence were summarized in seven aspects of multidisciplinary teamwork, applicable conditions, rehabilitation management, exercise implementation, evaluation of rehabilitation outcomes, abnormal training responses, and considerations.Conclusions:This study is based on a number of high-quality evidence, standardizing the relevant theories and clinical applications, with a certain degree of scientific and cutting-edge nature, providing practical, reliable and valuable evidence-based references and guidance for medical and nursing staff to use lower limb rehabilitation robots.

Objective To investigate the immunotoxicity effect of triphenyl phosphate (TPHP) on thymus tissue of mice, and analyze the related mechanism. Methods Specific pathogen free BALB/c mice were randomly divided into control group, low-, medium- and high-dose groups, with 12 mice per group (equal gender distribution). Mice in these four groups were orally administered doses of 0, 1, 10, and 150 mg/kg body weight of TPHP daily for 60 days. After the exposure, the complete blood count of mice was detected, thymus tissue was collected, coefficient of thymus organs was calculated, and the histopathology changes of thymus were observed. Real-time quantitative polymerase chain reaction was used to assess the expression of genes related to inflammation, oxidative stress, cellular autophagy, and apoptosis in thymic tissues. Results During the exposure period, male mice in the high-dose group had poor fur condition, whisker loss, and increased irritability, while these phenomena were not observed in female mice. At the end of the exposure period, there were no significant changes in mice body weight or thymus organ coefficients among the groups. However, male mice in the high-dose group showed cellular apoptotic changes in the thymic tissue. The amount of white blood cell, lymphocyte, neutrophil granulocyte, red blood cell distribution width, platelet and the plateletcrit of male mice was lower in the high-dose group than that in the control group (all P<0.05). The relative mRNA expression of interleukin (Il)-1β, Il-6, catalase (Cat), P62, as well as the ratio of B-cell lymphoma 2 (Bcl-2) associated X protein (Bax)/Bcl-2 in thymic tissue of male mice were higher in the low-dose group than that in the control group (all P<0.05). The relative mRNA expression of nuclear factor erythroid-2 related factor 2 (Nrf2), superoxide dismutase 1 (Sod1), glutathione peroxidase 1 (Gpx1), P62, as well as the ratio of Bax/Bcl-2 in the thymic tissue of male mice were higher in the medium-dose group than that in the control group (all P<0.05). The relative mRNA expression of Nrf2, Cat, Sod1, Gpx1, P62, cysteinyl aspartate specific proteinase-3, as well as the ratio of Bax/Bcl-2 in the thymic tissue of male mice were higher in the high-dose group than that in the control group (all P<0.05). The relative mRNA expression of Il-1β and the ratio of Bax/Bcl-2 in thymic tissue of female mice were higher in the low- and medium-dose group (all P<0.05), while the relative mRNA expression of interferon-γ, Nrf2, Cat, P62, microtubule-associated protein light chain 3, as well as the ratio of Bax/Bcl-2 in thymic tissue of female mice were higher in the high-dose group than that in the control group (all P<0.05). Conclusion Although TPHP exposure had not significantly affected the body weight, thymus organ coefficient and histopathology of mice, it induced changes in oxidative stress-related indicators in thymic tissue, promoted cellular autophagy, apoptosis, and inflammation in the thymic tissue, with observed gender difference.

The National Disease Control and Prevention Bureau and the National Health Commission jointly issued an announcement on Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement, which presented a method of comprehensive risk assessment method of occupational disease hazards of employers. This method embraces relevant factors at full scale and is simple in operation, but its applicability and accuracy of assessment results need further practical study. Based on the steps of occupational health risk assessment and proven occupational health risk assessment methods available at home and abroad, this paper proposed improvements and discussed the comprehensive risk assessment method of occupational disease hazards of employers, so as to provide a technical basis to implement the occupational disease hazard classification management of employers for relevant government supervision departments.

Objective: To evaluate the parabiotic tissue protection concept in the repairment of acute radiation-induced skin injury. Methods: Seven patients(3 males and 4 females) with acute radiation injury treated in the Department of Plastic Surgery of the Second Affiliated Hospital of Soochow University from February 2014 to January 2018. The ages of patients ranged from 45 to 76 years. The wound areas include perineum and buttock (n=3), chest(n=2), and thigh(n=2). In the early stage, subregional " sandwich" surgical dressing was used to protect the probiotic tissue. Two months later, the necrotic tissue was clearly demarcated, the debridement was underwent, and the parabiotic tissue was preserved as far as possible. Vacuum sealing drainage(VSD)was applied to cover and soak wound with normal saline to moisturize the wound and promote the benign transformation of ecological tissue. Ten days later, the granulation grown well, and the skin flaps and myocutaneous flaps with good blood supply were designed to repair the wounds. The VSD device was continued to be used, to drain effusion under flap and promote the growth of cystic cavity granulation, with the purpose to promote blood supply of the skin flap, perform the final biological cleaning effect on the parabiotic tissue of the wound surface, promote the benign transformation of parabiotic tissue, and reduce the further necrosis. Results: Seven patients with Ⅳ degree acute radiation-induced injury wounds were treated 6-10 weeks for surgery preparation, and 2-4 weeks for VSD-application after debridement. Except for part of flap was necrotized on 10th day after the first operation in one patient, all the other patients achieved satisfied outcome in a surgery. There was no further radiation-induced ulcer occurred during the 0.5-3 years of follow-up. Conclusions The concept of parabiotic tissue protection during preoperative, intraoperative and postoperative recovery phase can promote parabiotic tissue transformed to a good result after acute radiation injury, and reduce the size and depth of soft tissue necrosis, which can provide a good foundation for the secondary repair with flap and reduce complications.

Objective:To investigate the genetic association of single nucleotide polymorphisms (SNPs) in gamma-aminobutyric acid type A (GABAA) receptor genes cluster on chromosome 15q12 with autism in Chinese Han population.Methods:Totally 502 autism trios of Chinese Han ethnicity (including 502 autism individuals and 1004 healthy biological parents) were selected.All children met the autism diagnosis of Diagnostic and Statistical Manual of Mental Disorders,Fourth edition (DSM-Ⅳ).Genotyping for 15 selected tag SNPs in three GABAA receptor genes (GABRB3,GABRA5,and GABRG3) was performed using Agena Bioscience MassARRAY platform.The family-based association test for 15 tag SNPs was performed to compare the transmitted frequency of al leles of heterozygous genotypes from parents to offspring in autism trios.Results:The C allele of rs7180500 in GABRG3 and the A allele of rs4906902 in GABRB3 exhibited the preferential transmission from parents to affected offspring (Z =3.573,P ＜0.001;Z =3.141,P =0.002),and the association was significant after Bonferroni correction.Conclusion:It suggests that GABRG3 and GABRB3 which located in chromosome 15q12 might be susceptibility genes in Chinese Han population.

Objective:To investigate the association of AKT1 gene polymorphism with risperidone in the treatment of first-episode and untreated schizophrenia for 8 weeks.Methods:A total of 150 patients with Chinese schizophrenia who met DSM-Ⅳ,including 128 cases of risperidone (treatment dose 4-6 mg/d) for 8 weeks were treated with risperidone (treatment dose 4-6 mg/d).The Positive and Negative Symptom Scale (PANSS) reduction rate was used to evaluate the curative effect of drugs after 8 weeks.Using DNA sequencing,four single nucleotide polymorphisms (SNP) loci (rs1130214,rs10149779,rs1130233,rs2494732) genotype were detected in 128 Han patients with schizophrenia,and quantitative trait locus analysis (QTL) was used to explore the association between AKT1 gene polymorphisms and the efficacy of risperidone in the treatment of schizophrenia.Results:AKT1 gene rs1130233 (G ＞ A) and rs2494732(C ＞ T) were significantly associated with the increase in PANSS after 8-week risperidone treatment of schizophrenia (P ＜ 0.05).After repeated testing Bonferroni correction was still statistically significant.The correlation between rs1130214and rs10149779 in this sample was not statistically significant (P ＞0.05).Conclusion:This study suggests that polymorphisms of the AKT1 gene may be associated with the efficacy of risperidone in the treatment of schizophrenia in the Chinese Han population and is expected to provide a basis for the prediction of individual drug efficacy.