Objective To investigate the protective effect of inhibition of adenosine monophosphate activated protein kinase (AMPK) on blood brain barrier (BBB) and its mechanism in hypoxic/ischemic models.Methods Two hundred healthy male SD rats were randomly divided into sham-operated group,model group (ischemia 2 h-reperfusion 0,24 and 72 h [I/R]),and Compound C treated group (giving intraperitoneal injection of 20 mg/kg AMPK specific inhibitor Compound C).Focal cerebral ischemia rat models were established by occluding the middle cerebral artery (MCAO).Neurological deficit was determined by Zea Longa test,infarct size and brain water content were measured by TTC staining,leakage of BBB was determined by Evans blue (EB) staining.Expressions of matrix metalloproteinase (MMP)-2/MMP-9 and nuclear factor (NF)-κB,and release of inflammatory factors were detected by Western blotting.Results As compared with those in the model group,significantly reduced neurological deficit scores in Compound C treated group were noted at I/R 0,24 and 72 h (P＜0.05).After I/R 72 h,Compound C treated group had significantly reduced brain infarct size,brain water content and EB leakage as compared with model group (P＜0.05).The expressions of MMP2/MMP9 in model group (52.58±8.12 and 33.15±6.45) were significantly higher than those in the Compound C treated group (21.20±3.39 and 15.46±4.71,P＜0.05).What is more,as compared with the model group,Compound C treated group had significantly reduced expressions of NF-κB and inflammatory factors (P＜0.05).Conclusions Inhibition of AMPK shows a protective role in BBB after ischemic injury,mainly by inhibiting NF-κB signaling pathway,inhibiting the expression of MMP-2/MMP-9 to reduce the degradation of the base metal film,and maintain the integrity of BBB,thus,improving the ischemic symptoms,reducing the brain water content and reducing infarct size.

OBJECTIVE: To analyze the pathogenic variants of the KIF1A gene and its corresponding protein structure in an autism spectrum disorder (ASD) family trio carrying harmful missense variants in the KIF1A gene. METHODS: The peripheral blood DNA of the patient and his parents was extracted and sequenced using whole exome sequencing (WES) technology and verified by Sanger sequencing. Bioinformatics software SIFT, PolyPhen-2, Mutation Taster, and CADD software were used to analyze the harmfulness and conservation of variants. The Human Brain Transcriptome (HBT) database was used to analyze the expression of the KIF1A gene in the brain. PredictProtein and SWISS-MODEL were further used to predict the secondary structure and tertiary structure of KIF1A wild-type protein and variant protein. PyMOL V2.4 was utilized to investigate the change of hydrogen bond connection after protein variant. RESULTS: The WES sequencing revealed a missense variant c.664A>C (p.Asn222His) in the child's KIF1A gene, and this variant was a de novo variant. The harmfulness prediction results suggest that this variant is harmful. By analyzing expression level of KIF1A gene in the brain. It is found that KIF1A gene widely expressed in various brain regions during embryonic development. By analyzing the variant protein structure, the missense variant of KIF1A will cause many changes in the secondary structure of protein, such as alpha-helix, beta-strand, and protein binding domain. The connection of hydrogen bond and spatial structure will also change, thereby changing the original biological function. CONCLUSION The KIF1A gene may be a risk gene for ASD.
Autism Spectrum Disorder/genetics* ; Child ; Female ; Humans ; Kinesin/genetics* ; Mutation ; Mutation, Missense ; Pregnancy ; Protein Domains ; Whole Exome Sequencing

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 assess the efficacy of parent training (PT) on attention deficit hyperactivity disorder (ADHD) symptoms, behavioral problems, and parenting stress in child with ADHD or ADHD symptoms.Methods:Randomized controlled trials of the effect of PT on ADHD symptoms in Chinese children with ADHD or ADHD symptoms were collected by PsychINFO, PubMed, EMBASE, Web of science, Scopus, China National Knowledge database, WanFang database, the China Science and Technology Journal Database and the China Biology Medicine disc. The quality of the included studies was evaluated by version 2 of the Cochrane tool for assessing risk of bias in randomized trial. Forest plots were drawn using Review Manager 5.4.1, sensitivity analyses of results were performed using Stata 18.0 to assess the stability of the results, and publication bias was assessed using funnel plots and Egger's test.Results:A total of 10 studies containing 571 subjects in the experimental group and 562 subjects in the control group met the inclusion exclusion criteria. Significant differences were observed in various measures, including overall ADHD symptoms (MD=-2.43, 95% CI: -3.95--0.91), inattention (MD=-1.10, 95% CI: -1.94--0.26), hyperactivity/impulsivity (SMD=-0.58, 95% CI: -0.87--0.28), overall conduct problems (SMD=-0.80, 95% CI: -1.05--0.55), conduct problem (SMD=-1.34, 95% CI: -2.31--0.37), learning problem (SMD=-0.81, 95% CI: -1.40--0.23), impulsivity/hyperactivity (SMD=-0.53, 95% CI: -0.78--0.29), hyperactivity index (SMD=-1.27, 95% CI: -1.99--0.55), parenting stress index (SMD=-0.69, 95% CI: -1.12--0.26), difficult child (MD=-1.96, 95% CI: -3.44--0.48), dysfunctional interaction (MD=-3.10, 95% CI: -4.43--1.78), and parenting distress (MD=-3.35, 95% CI: -4.59--2.12)(all P<0.05). However, no significant differences were observed in oppositional-defiant disorder, anxiety, or somatic problem. Conclusions:The initial findings suggested that PT was effective for Chinese children with ADHD or ADHD symptoms.The addition of PT appeared to improve core symptoms of ADHD (inattention and hyperactivity/impulsivity), conduct problems, and parental stress more effectively than routine care alone.

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 effect of ultrasound-guided stellate ganglion block(SGB)on intraoperative fentanyl dosage in the patients undergoing open thyroidectomy.Methods A total of 70 patients with elective open thyroidectomy under general anesthesia in the Affiliated Hospital of North Sichuan Medical College from November 2021 to April 2022 were selected as the study subjects and divided into the SGB group(group S,n=35)and the control group(group C,n=33).The group S conducted ultrasound-guided SGB at 15 min before anesthetic induction(injection of 0.25％marcaine 6-8 mL),and group C conducted the stellate ganglion recognition under the ultrasound guidance in 15 min before anesthetic induction without conducting other operations.All patients all received the anesthesia induction and maintenance under the same BIS moni-toring.The fentanyl dosage,recovery time,anesthetic drugs dosage,fluid infusion amounts,bleeding volume,use rate of atropine and ephedrine,operation time and postoperative complications as well as the VAS scores in PACU 30 min,at postoperative 3,6,12,24 h were recorded.Results Compared with group C,the intraopera-tive amount of fentanyl in group S was significantly decreased[(247.9±65.4)μg vs.(295.7±61.5)μg,P=0.003].The propofol dosage,cisatracurium dosage,fluid infusion amounts,bleeding amounts,use rate of atro-pine and ephedrine,recovery time and incidence rate of complications had no statistical differences between the two groups(P＞0.05).The VAS scores at various time points in group S all were lower than those in group C(P＜0.05).Conclusion Ultrasound-guided SGB could reduce the fentanyl use amounts during operation in the patients with open thyroidectomy.

Objective:This study aimed to compare the efficacy and safety of cladribine, smustine, etoposide, cyclophosphamide, and cytarabine (C+SCAV) and smustine, etoposide, cytarabine, and melphalan (SEAM) conditioning regimens in autologous stem cell transplantation (auto-HSCT) for non-Hodgkin’s lymphoma (NHL) .Methods:A retrospective analysis was conducted on 61 NHL patients who received auto-HSCT in the Department of Hematology, the First Affiliated Hospital of Suzhou University, from March 2018 to May 2021. The C + SCAV group and SEAM group had 19 and 42 patients, respectively.Results:① Among the 61 patients with NHL, 37 were male and 24 were female. The median age was 48 (21-66) years old. There were 19 cases in the C+SCAV group and 42 cases in the SEAM group. There was no significant difference in the baseline characteristics between the two groups ( P>0.05) . ② The median time to neutrophil and platelet engraftment in the C+SCAV cohort were 10 (8-15) days and 13 (9-22) days, respectively, which does not differ from the SEAM group ( P=0.103, P=0.403) . ③ No differences existed between the two groups in terms of survival. The 1-year progression-free survival (PFS) was (76.5±10.3) % for patients receiving C+SCAV and (78.4±6.8) % for those who received SEAM ( P=0.841) . The 1-year overall survival was 100.0% for the C+SCAV group and 95.2±3.3% for the SEAM group ( P=0.339) . ④The 1-year PFS of patients with complete remission in the C+SCAV group was similar to those who in the SEAM group [ (92.3±7.4) % vs (82.5±7.2) %, P=0.406]. ⑤ The incidence of non-hematological serious adverse events (≥ grade 3) in the C+SCAV group and SEAM group were 10.5% (2/19) and 40.5% (17/42) ( P=0.013) , the incidence of severe mucositis was 5.3% (1/19) and 31.0% (13/42) ( P=0.015) , and the incidence of severe infection (≥ grade 3) was 10.5% (2/19) and 19.0% (8/42) ( P=0.389) , respectively. Conclusion:C + SCAV conditioning regimen appeared to be no different from the SEAM regimen in terms of survival. It can lower the incidence of SAE and does not increase the risk of severe infection. As a result, it can be used as an alternative conditioning regimen for lymphoma patients undergoing auto-HSCT.