Nitric oxide synthase(NOS)and its product nitric oxide are involved in learning and memory functions.Increasing evidence shows that NOS plays an important role in the pathogenesis of Alzheimer's disease,influencing β-amyloid protein(Aβ)deposition,neuroinflammation,oxidative stress,abnormal microglia activation,synapse damage,autophagy,abnormal mitochondrial function of nerve cells,and cerebral hypoperfusion or vascular endothelial cell injury.This review summarizes the recent evidence for the role of NOS in the pathogenesis of Alzheimer's disease and provides new feasible targets for the prevention and treatment of Alzheimer's disease.

Nitric oxide synthase(NOS)and its product nitric oxide are involved in learning and memory functions.Increasing evidence shows that NOS plays an important role in the pathogenesis of Alzheimer's disease,influencing β-amyloid protein(Aβ)deposition,neuroinflammation,oxidative stress,abnormal microglia activation,synapse damage,autophagy,abnormal mitochondrial function of nerve cells,and cerebral hypoperfusion or vascular endothelial cell injury.This review summarizes the recent evidence for the role of NOS in the pathogenesis of Alzheimer's disease and provides new feasible targets for the prevention and treatment of Alzheimer's disease.

Background Comorbid attention-deficit/hyperactivity disorder(ADHD)and emotional dysregulation may represent a distinct subtype of ADHD,which is characterized by an increased risk of anxiety or depressive disorder and a poor clinical prognosis,so research is urgently required to explore its unique executive functioning profile and clinical characteristics.However,there is limited research comparing the clinical symptoms and executive function in children with ADHD in terms of the presence or absence of emotional dysregulation.Objective To explore the executive function and clinical characteristics of ADHD children with emotional dysregulation.Methods From June 2020 to December 2023,118 children aged 7 to 12 with ADHD attending the Mental Health Center of West China Hospital,Sichuan University and fulfilling the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)diagnostic criteria were enrolled.Children were classified into emotional dysregulation group(n=68)and non-emotional dysregulation group(n=50)based on the standard T-scores of Achenbach's Child Behavior Checklist(CBCL)-anxious/depressed,aggressive behavior and attention problems subscales.All children were then subjected to complete the Chinese version of Swanson Nolan and Pelham,Version IV Scale-parent form(SNAP-IV),Chinese Wechsler Intelligence Scale for Children(C-WISC),Weiss Functional Impairment Scale-Parent form(WFIRS-P)and 4 tests of the Cambridge Neuropsychological Test Automated Battery(CANTAB):①Stockings of Cambridge(SOC)testing spatial planning.②Intradimensional-extradimensional Set Shifting(IED)testing cognitive/attentional flexibility,adjusting the total errors across the task.③Spatial Working Memory(SWM)testing spatial working memory.④Rapid Visual Information Processing(RVP)testing sustained attention.Results The SNAP-IV Inattention,Hyperactivity/Impulsivity and Oppositional Defiant Disorder domain scores and total score were all higher in emotional dysregulation group compared with non-emotional dysregulation group(t=3.206,5.088,6.316,6.553,P<0.01).The WFIRS-P family,school learning,life skills,self-concept,social activities and risky activities domain scores and total score were all higher in emotional dysregulation group compared with non-emotional dysregulation group(t=6.074,4.406,4.143,3.984,6.575,6.662,8.254,P<0.01).In CANTAB,emotional dysregulation group made more total adjusted errors across the IED task compared with non-emotional dysregulation group(t=2.168,P<0.05).Conclusion Children with ADHD who exhibit emotional dysregulation have been observed to experience more severe core symptoms,impaired social functioning and poorer performance on tests assessing executive function,particularly in the area of cognitive flexibility.

Objective To investigate the mediating effect of social problems in the effect pathway of emotional dysregulation influencing anxiety/depression emotions in children with attention-deficit/hyperactivity disorder(ADHD)and to explore the potential moderating effect of family functionality.Methods A total of 235 children diagnosed with ADHD were enrolled in the study.The paticipants'age ranged from 6 to 12.Emotion Regulation Checklist,Achenbach's Child Behavior Checklist(CBCL)Social Problems Subscale,CBCL Anxious/Depressed Subscale,and Family Assessment Device were used to evaluate the emotional regulation,social problems,anxiety/depression emotions,and family functionality of the participants.A moderated mediation model was employed to analyze whether social problems and family functionality mediate and moderate the relationship between emotional regulation and anxiety/depression emotions.Results Social problems partially mediated the impact of emotional dysregulation on anxiety/depression emotions in ADHD children,with the direct effect being 0.26(95%confidence interval[CI]:[0.17,0.36],P＜0.001),the indirect effect being 0.13(95%CI:[0.07,0.19],P＜0.001),and the mediating effect accounting for 33%of the total effect.Family functionality exhibited a positive moderating effect on the relationship between social problems and anxiety/depression emotions.Conclusion This study contributes to the understanding of complex factors influencing anxiety/depression in children with ADHD,providing reference for the further development of targeted interventions for children with ADHD and the improvement of prognosis.

Decellularized matrix transplantation has emerged as a promising therapeutic approach for repairing tissue defects, with numerous studies assessing its safety and efficacy in both animal models and clinical settings. The host immune response elicited by decellularized matrix grafts of natural biological origin plays a crucial role in determining the success of tissue repair, influenced by matrix heterogeneity and the inflammatory microenvironment of the wound. However, the specific immunologic mechanisms underlying the interaction between decellularized matrix grafts and the host immune system remain elusive. This article reviews the sources of decellularized matrices, available decellularization techniques, and residual immunogenic components. It focuses on the host immune response following decellularized matrix transplantation, with emphasis on the key mechanisms of Toll-like receptor, T-cell receptor, and TGF-β/SMAD signaling in the stages of post-transplantation immunorecognition, immunomodulation, and tissue repair, respectively. Furthermore, it highlights the innovative roles of TLR10 and miR-29a-3p in improving transplantation outcomes. An in-depth understanding of the molecular mechanisms underlying the host immune response after decellularized matrix transplantation provides new directions for the repair of tissue defects.

OBJECTIVE: To carry out genetic testing for a patient with 45,X/46,XY mosaicism and autism spectrum disorder (ASD). METHODS: Peripheral blood samples of the patient and his parents were collected for the extraction of genomic DNA. Trio-based whole exome sequencing and Sanger sequencing were carried out thereafter. RESULTS: The proband and his father were found to harbor a heterozygous c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene. In addition, the proband was also found to harbor a de novo c.268C>T (p.Arg90Trp) missense variant of the MTRR gene. Based on guidelines of the American College of Medical Genetics and Genomics (ACMG), the c.4781G>A (p.Arg1594Gln) variant of the CACNA1I gene was predicted to be pathogenic (PVS1, PM1, PM2, PP3), while the c.268C>T (p.Arg90Trp) variant of the MTRR gene was predicted to be of uncertain significance. CONCLUSION Variants of the CACNA1I and MTRR genes, together with the chromosomal mosaicism, may have predisposed to the susceptibility to the ASD in this patient.
Autism Spectrum Disorder/genetics* ; Genomics ; Heterozygote ; Humans ; Mosaicism ; Whole Exome Sequencing

Objective To establish a finite element model of cell perfusion culture, and study the effect of different perfusion speeds on the movement of suspended cells. Methods The two-dimensional (2D) model of cell and microchannels was established using COMSOL Multiphysics and meshed. Three groups were established according to the perfusion speed, namely, u0=0.196 mm/s, u1=0.117 mm/s, u2=0.04 mm/s. The fluid-structure interaction module was used for calculation. Results The flow field distribution in the microchannel was relatively uniform. During the equal period of time, the ratio of cell suspension perfusion speed was u0∶u1∶u2=5∶3∶1, and the ratio of cell displacement in the microchannel was D0∶D1∶D2=4.1∶ 2.9∶1. When the speed was proportional, the displacement of cells also roughly followed the corresponding proportional change. With the increase of perfusion speed, stress concentration in cells during movement would occur. The stress and fluid shear force (FSS) of cells during movement were within the safe value range, and cell destruction would not occur. Conclusions The suspended cells can enter into the microchannel without injury at a certain perfusion speed. Perfusion techniques can be used in cell implantation of in vitro tissue engineering products.

At present, acellular matrix is an effective replacement material for the treatment of skin damage, but there are few systematic evaluation studies on its performance. The experimental group of this study used two decellularization methods to prepare the matrix: one was the acellular matrix which sterilized with peracetic acid first (0.2% PAA/4% ethanol solution) and then treated with hypertonic saline (group A), the other was 0.05% trypsin/EDTA decellularization after γ irradiation (group B); and the control group was soaked in PBS (Group C). Then physical properties and chemical composition of the three groups were detected. Hematoxylin eosin (HE) staining showed that the acellular effect of group B was good. The porosity of group A and B were both above 84.9%. In group A, the compressive modulus of elasticity was (9.94 ± 3.81) MPa, and the compressive modulus of elasticity was (12.59 ± 5.50) MPa in group B. There was no significant difference between group A or B and group C. The total content of collagen in acellular matrix of group A and B was significantly lower than that of group C (1. 662 ± 0.229) mg/g, but there was no significant difference in the ratio of collagen Ⅰ/Ⅲ between group B and group C. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) showed that there was no significant difference in microstructure. Qualitative detection of fibronectin and elastin in each group was basically consistent with that in group C. Therefore, acellular matrix of group B had better performance as scaffold material. The experimental results show that the acellular matrix prepared by γ-ray sterilization and decellularization of 0.05% Trypsin enzyme/EDTA could be used for the construction of tissue-engineered skin. It could also provide reference for the preparation and mounting of heterogeneous dermal acellular matrix. It was also could be used for electrostatic spinning or three-dimensional printed tissue engineered skin scaffold which could provide physical and chemical parameters for it.
Acellular Dermis ; Cells, Cultured ; Extracellular Matrix ; Porosity ; Tissue Engineering ; Tissue Scaffolds

Objective To study the changes of transcriptome levels in a Bama minipig model of hypertrophic scar during wound healing and pressure therapy by using RNA sequencing (RNA-seq) technique. Methods The Bama minipig model was established by skin wounds from the back and pressure (3.4 kPa) was initiated at 60 days after skin injury. Total RNA was extracted from scar tissues at 0, 14, 30, 60, and 90 days after skin injury and then sequenced. The resulting sequences were mapped to porcine reference genomes and transcriptomes were reconstructed to search for differentially expressed genes (DEGs). The DEGs were further subjected to GO and KEGG analysis using bioinformatics method, while part of the genes were selected for verification using qRT-PCR. Results After preprocessing, more than 78% reads in each group were accurately aligned to the reference sequence. The DEGs identification result showed that 568 genes were differentially expressed after pressure treatment, with 289 up-regulated and 279 down-regulated. GO enrichment analysis revealed that DEGs in each group were mainly associated with extracellular matrix, tissue development and skin development. KEGG analysis showed that the DEGs in each group during wound healing were mainly enriched in extracellular matrix-receptor interactions, focal adhesion and apoptosis pathways; while the DEGs after pressure treatment were mainly enriched in PI3K-Akt and MAPK signaling pathway except the pathways mentioned. qRT-PCR showed that the expression patterns of 6 DEGs were consistent with RNA-seq analysis, confirming the reliability of RNA-seq result. Conclusions RNA-Seq analysis identified differentially expressed genes in animal model of scars during wound healing and pressure therapy, which provided experimental evidence for clinical scar treatment.

Objective: To explore the risk factors of pancreatic fistula after pancreatoduodenectomy and its relationship with pancreatic fibrosis. Methods: Retrospective analysis was made including 408 patients who underwent pancreaticoduodenectomy from January 2013 to December 2015 in Department of Hepatobiliary Surgery of the First Affiliated Hospital of Third Military Medical University. There were 274 males and females, aging from 14 to 82 years with an average age of 54.6 years. Postoperative pathological diagnosis: 285 cases with pancreatic ductal adenocarcinoma, 81 cases with gastrointestinal tumors, 13 cases with neuroendocrine tumors, 16 cases with inflammatory changes, 8 cases with pancreatic papillary tumors, 4 cases with serous cystadenoma, 1 case with retroperitoneal liposarcoma.Univariate analysis using pearson′s χ² test, multivariate analysis using binary Logistic regression analysis, correlation analysis using Spearman rank correlation analysis and the predictive value of pancreatic fibrosis in pancreatic fistula after pancreaticoduodenectomy was assessed using the area under the receiver operating characteristic(ROC) curve. Results: There were 123 cases (30.1%) with postoperative pancreatic fistula among 408 patients. Univariate analysis showed that body mass index(BMI)(P=0.005), preoperative gamma-glutamyltranspeptidase content(P=0.046), pancreatic duct diameter(P=0.001), CT value of pancreatic tissue(P=0.049), operation time(P=0.037), pancreatic stiffness (intraoperative judgment)(P=0.001) and percentage of pancreatic fibrosis(P=0.034) were the prognostic factors of pancreatic fistula. Multivariate analysis showed that BMI≥25 kg/m², pancreatic duct diameter ≤3 mm, pancreatic tissue CT value <40 Hu, pancreatic hardness (intraoperative judgments) for the soft and pancreatic lobular fibrosis percentage ≤25% of postoperative pancreatic fistula occurrence of high-risk factor(P<0.05). Pancreatic fistula′s CT value and percentage of pancreatic fibrosis were significantly lower than non-pancreatic fistula group, the difference was statistically significant(P<0.05). There were significant differences in CT value and pancreatic lobular fibrosis among different grades of pancreatic fistulae(P<0.05). Pancreatic fistula severity was negatively correlated with the CT value of pancreatic body and the percentage of fibrosis of the pancreas(P=0.005, 0.019), and there was a significant correlation between CT value of pancreatic body and the percentage of fibrosis of the pancreas(r=0.699, P=0.028). The areas under the ROC curve of percentage of pancreatic fibrosis and CT value of the pancreatic body were 0.745 and 0.714, respectively. Both of them were moderate predictive value for pancreatic fistula after pancreaticoduodenectomy. Conclusions The degree of pancreatic fibrosis is a prognostic factor for pancreatic texture and pancreatic fistula after pancreaticoduodenectomy. CT value of pancreatic body can be used as a quantitative index of pancreatic fibrosis, and predict the prognostic of pancreatic fistula after pancreaticoduodenectomy.