ObjectiveTo establish an educational intervention framework of electronic picture books for children with autism spectrum disorder (ASD) based on Creative Problem Solving (CPS) model, and observe the effect on social function. MethodsElectronic picture books were designed using CPS model, including the program of reading, interactive animation design and associated artistic activities. From March to June, 2023, 24 children with mild to moderate ASD were recruited from Maanshan Institute of Special Education, and randomly assigned into experimental group 1 (CPS-based cognitive picture book interventions, n = 8), experimental group 2 (CPS-based social picture book interventions, n = 8) and control group (Bloom's Taxonomy-based picture book interventions, n = 8), and received the interventions for four weeks, with a total of twelve times. They were assessed with speech, social, perceptual and health behavior using Autism Treatment Evaluation Checklist (ATEC) before and after treatment, and the differences were calculated. ResultsThere was a significant difference among the groups in the social and perceptual scores differences (F > 4.344, P < 0.05) and a near-significant difference in the health behaviour score difference (F = 2.921, P = 0.076). Post Hoc test showed that the differences in social scores were higher in both experimental groups than in the control group (P < 0.05); the difference in perceptual scores was significantly higher in experimental group 1 than in experimental group 2 (P < 0.01), but there was no significant difference with the control group (P > 0.05); the difference in health behavior scores was higher in experimental group 2 than in the control (P < 0.05), and the difference in experimental group 1 was slightly higher than in the control group (P = 0.072). ConclusionElectronic picture book interventions based on the CPS model may be more effective in enhancing social, perceptual and health behavior in children with ASD, but there may be differences among models.

Objective: To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures. Methods: A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test. Results: Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05). Conclusions Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.

Objective:To investigate the relationship between CXCL6 expression and prostate cancer,as well as its effects on the malignant progression of PC-3 cells and the underlying mechanisms.Methods:Multiple databases were used to analyze CXCL6 expression in prostate cancer.And survival analysis,GO,and KEGG enrichment analysis were conducted.According to the concentration of CXCL6,PC-3 cells were divided into 0,100 and 200 ng/ml CXCL6 groups.The effects of up-regulated CXCL6 expression on PC-3 cell proliferation,migration,apoptosis,cycle,and related genes were investigated using CCK-8,EdU assay,scratch test,flow cytometry,and prostate cancer-targeted PCR array.Results:Database analysis revealed that CXCL6 was significantly down-regulated in prostate cancer(P＜0.05),and patients with low CXCL6 expression had a worse prognosis(P＜0.05).In prostate cancer,proteins associated with CXCL6 expression included CXCL1 and CXCL2,and related genes included MIR325 and RASSF6.GO analysis indicated that differentially expressed genes(DEGs)of CXCL6 were primarily enriched in processes such as response to chemokines and the tubular endoplasmic reticulum network(P＜0.05).KEGG analysis showed that DEGs were mainly enriched in signaling pathways such as the Hippo signaling pathway(P＜0.05).CCK-8,EdU assay,scratch test,and flow cytometry results demonstrated that compared with the 0 ng/ml CXCL6 group,the 100 and 200 ng/ml CXCL6 groups exhibited significantly reduced proliferation and migration rates(P＜0.05),significantly increased apoptosis rate(P＜0.05).And the proportion of S-phase cells in the 200 ng/ml CXCL6 group was lower compared to the 0 ng/ml CXCL6 group(P＜0.05).PCR array results showed that compared with the 0 ng/ml CXCL6 group,the expression of genes such as CDH1 and HAL was increased in the 200 ng/ml CXCL6 group,while the expression of genes such as CD5L and EDNRB was decreased.Conclusion:CXCL6 plays a significant role in the malignant progression of PC-3 cells,and its mechanism may be associated with the methylation of promoters of genes such as RASSF1,RARB,and CDH1.

Objective To evaluate the changes of perivascular space(PVS)in patients with subacute ischemic stroke(IS),as well as the relationship between PVS and cognitive dysfunction in IS patients,and to analyze the relationship between PVS indicators and cognitive function in subacute IS patients of different ages.Methods A total of 44 healthy controls(HC)and 39 patients with subacute IS were prospectively included.Automated quantitative analysis of MRI data was conducted to determine pPVS in the white matter and subcortical regions.Differences in pPVS between patients with subacute IS and HC were compared.Correlations between age,pPVS,and cognitive dysfunction were analyzed and modeled.Results Compared with the HC,the white matter pPVS in patients with subacute IS was significantly reduced(t=-2.21,P=0.031).In patients with subacute IS,the white matter pPVS showed a significant positive correlation with lesion volume(r=0.42,P=0.030)and mini-mental state examination(MMSE)scores(r=0.44,P=0.018).Both white matter pPVS(r=-0.42,P=0.010)and MMSE scores(r=-3.82,P=0.000 7)were negatively correlated with age.When age was over 61.35 years,there was a positive correlation between the white matter pPVS and MMSE scores.Conclusion PVS are closely related to cognitive impairment in patients with subacute IS.Age is a significant modulating factor in the relationship between PVS and cognitive dysfunction.Early monitoring of PVS and targeting it for intervention may positively impact the improvement of cognitive dysfunction following IS.

Objective To investigate the correlation between blood glucose(BG)control and barrier dysfunction in diabetes mellitus(DM)patients with ulcerative colitis(UC).Methods A total of 120 patients with DM and UC admitted to the Department of Gastroenterology of our hospital between January 2021 and January 2024 were selected and divided into injury group(n=68)and non-injury group(n=52)according to the injury of intestinal barrier function.Pearson correlation analysis was used to analyze the correlation between hemoglobin A1c(HbA1c),fasting plasma glucose(FPG),2 hPG and D-lactic acid(D-LA),diamine oxidase(DAO),lipopolysaccharide(LPS),and Galectin-3.Logistic regression analysis was used to analyze the influencing factors for intestinal barrier dysfunction.Receiver operator characteristic(ROC)curve was drawn to analyze the diagnostic value of BG level for intestinal barrier dysfunction.Results The levels of HbA1c,FPG,2 hPG,D-LA,DAO,and LPS were higher in the injury group than in the non-injury group(P<0.05),and the level of Galectin-3 was lower in the injury group than in the non-injury group(P<0.05).Pearson correlation analysis showed that HbA1c,FPG,and 2 hPG levels were positively correlated with D-LA,DAO,and LPS(P<0.05),and negatively correlated with Galectin-3(P<0.05).Logistic regression analysis showed that HbA1c,FPG and 2 hPG were the influencing factors for intestinal barrier dysfunction.ROC curve analysis showed that the area under the curve of HbA1c,FPG and 2 hPG was 0.968,0.942 and 0.910 for predicting intestinal barrier dysfunction.Conclusions BG level affects the damage of intestinal barrier function,and the risk of intestinal barrier function damage can be reduced by strengthening BG control in clinical practice.

A 20-year-old male patient with T-lymphoblastic lymphoma/leukemia received 9/10 human leukocyte antigen-compatible unrelated peripheral blood stem cell transplantation. He was transplanted with 5.91×10 8 mononuclear cells/kg and 2.88×10 6 CD34 + cells/kg, and neutrophil engraftment was obtained at +11 days and platelet engraftment at +9 days. After transplantation, he presented with repeatedly increased serum creatinine levels, BK virus (BKV) -associated hemorrhagic cystitis, and BKV viremia. BK virus nephropathy was diagnosed based on renal biopsy and metagenomic next-generation sequencing. After adjusting the immunosuppressant, intravenous immunoglobulin, and donor lymphocyte infusion treatment, the patient’s renal function deteriorated progressively, and he eventually died of multiple organ failure at +289 days.

Objective:To investigate the adjunctive diagnostic value of retinal imaging structural parameters combined with apolipoprotein E (ApoE) gene polymorphisms for Alzheimer′s disease (AD).Methods:It was a case-control study, 71 confirmed AD patients who attended the Department of Neurology in Sichuan Provincial People′s Hospital from May 2023 to June 2024 and 156 healthy medical checkups who participated in medical checkups in the Health Management Center were continuously with convenience sampling method; the subjects were included as the AD case group and healthy control group, respectively. Optical coherence tomography (OCT) was used to measure the structural parameters of retinal imaging such as the thickness of the retinal nerve fiber layer (RNFL) and the retinal nerve fiber layer-inner plexiform layer (RNFL-IPL) in the study subjects. Information on demographic characteristics and disease history of the study participants were collected through a questionnaire, and venous blood was collected to test for ApoE gene polymorphisms. The retinal imaging structural parameters, ApoE gene polymorphisms and other related indicators were included in a multifactorial logistic regression model to analyze the main factors affecting the risk of AD. Based on the results of the multifactorial analysis, the receiver operating characteristic (ROC) curves were plotted and the areas under the curve (AUC) were calculated to evaluate the efficacy of different models in the adjunctive diagnosis of AD.Results:Of the 227 study subjects included in the analysis, 153 were females and 74 were males; there were 71 cases in the AD case group with a mean age of (66.73±8.83) years, and there were 156 subjects in the healthy control group with an average age of (61.95±8.21) years. Educational attainment of elementary school and below ( OR=4.683, 95% CI: 2.133-10.282), living visual acuity<0.5 ( OR=2.716, 95% CI: 1.12-6.583), and carrying ≥1 ApoE ε4 genes ( OR=5.331, 95% CI: 2.309-11.891) were positively correlated with the risk of AD. RNFL thickening ( OR=0.923, 95% CI: 0.854-0.998) was negatively associated with the risk of AD (all P<0.05). The AD risk assessment model (Model 4), which included fundus imaging features and ApoE gene polymorphisms, had the highest predictive efficacy (AUC=0.857, P<0.001). Conclusion:Retinal imaging structural parameters differ significantly between AD patients and healthy examinees, and a risk assessment model combining retinal imaging structural parameters and ApoE gene polymorphisms has high predictive value and is expected to serve as an auxiliary diagnostic tool for AD.

Objective:To investigate the dynamic changes of cytokine levels in patients with sepsis and to identify potential biomarkers for evaluating the prognosis of the disease.Methods:A total of 195 patients with sepsis hospitalized at the Department of Infectious Diseases and the Department of Critical Care Medicine of the First Affiliated Hospital of Soochow University from August 2022 to October 2024 were recruited, and 70 healthy individuals undergoing physical examinations were recruited as the healthy control group. The levels of 11 cytokines, including interferon γ (IFN-γ), interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) were compared between the sepsis patients and the healthy controls. Spearman correlation analysis was used to assess the correlation between cytokine levels and sequential organ failure assessment (SOFA) scores in sepsis patients. Receiver operating characteristic curves were plotted and the area under the curve (AUC) was calculated to evaluate the diagnostic value of cytokines for sepsis. Delong test was used to compare AUC. Based on the 28-day survival outcomes, the sepsis patients were categorized into non-survival group and survival group. The levels of the 11 cytokines in patients on the 1st, 3rd, 7th, 14th, 21st and 28th days after confirmed sepsis were dynamically monitored, and their change characteristics were analyzed. Mann-Whitney U test was used for statistical comparison. Results:The age of the 195 patients with sepsis was 68.0 (55.0, 76.0) years old, including 124 males (63.6%), 64 died and 131 survived.The levels of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, TNF-α, CRP in the sepsis group were all higher than those in the healthy control group ( Z=-2.99, -5.42, -4.95, -4.09, -5.05, -11.30, -8.66, -8.23, -5.64, -4.75, -2.12 and -10.75, respectively, all P<0.05). The differences were statistical significance. The levels of IL-2 ( r=0.149, P=0.037), IL-6 ( r=0.223, P=0.002), IL-8 ( r=0.159, P=0.026), and IL-10 ( r=0.188, P=0.009) in patients with sepsis were positively correlated with SOFA scores. The AUC of CRP in diagnosing sepsis was 0.989 with the sensitivity of 97.4% and the specificity of 100.0%. The AUC of IL-6 in diagnosing sepsis was 0.953, with the sensitivity of 93.3% and the specificity of 97.1%, and the AUC of IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-8, IL-10, IL-12P70, IL-17A, and TNF-α were 0.620, 0.718, 0.699, 0.665, 0.703, 0.850, 0.836, 0.727, 0.691, and 0.574, respectively.The AUC of the 11 cytokines were all lower than that of CRP, and the differences were all statistically significant ( Z=2.34, 10.24, 8.03, 8.08, 10.64, 8.70, 5.91, 5.17, 8.91, 9.25 and 4.10, respectively, all P<0.05).During the dynamic monitoring, the IFN-γ and IL-1β levels in the non-survival group increased gradually. The IFN-γ levels on the 14th and 21st day in the non-survival group were higher than those in the survival group ( Z=0.53 and 0.08, respectively, both P<0.05), and IL-1β levels on the 14th, 21st, and 28th days were also higher than those in the survival group ( Z=0.03, 0.26 and 0.31, respectively, all P<0.05). IL-6 and IL-8 levels reached their peaks on the 14th day, which were significantly higher than those in the survival group ( Z=0.01 and 0.02, respectively, both P<0.05), and then decreased, and the differences were all statistically significant. Conclusions:The levels of IFN-γ and IL-1β in the non-survival sepsis patients show a gradually increasing trend. The dynamic changes of IL-6 have certain significance for the prediction of disease severity and prognosis evaluation in sepsis.

Objective To investigate the relationship between different interleukins (ILs) and gynecological tumors, including cervical cancer, endometrial cancer, and uterine leiomyoma using two-sample Mendelian randomization (MR) analysis. Methods IL and gynecological tumor data were obtained from European populations by using the IEU OpenGWAS open database. Two-sample MR analysis was applied, different interleukins were used as exposure factors, significant SNP in GWAS data were selected as instrumental variables, and the instrumental variables were independent of each other. The risk of three kinds of gynecological tumors was analyzed separately to explore the causal relationship between ILs predicted by genes and outcome indicators. The TwoSampleMR package in R language (4.3.1) software was used for statistical analysis. MR analysis was performed using inverse variance weighted, MR Egger regression, weighted median, simple mode, and weighted mode methods. Results IL-18 receptor 1 (P=0.039) and IL-24 (P=0.025) were negatively correlated with the risk of cervical cancer. IL-4 (P=0.040), IL-21 (P=0.026), and IL-37 (P=0.027) were positively correlated with the risk of endometrial cancer. IL-15 receptor subunit alpha (P=0.005) was negatively correlated with the risk of endometrial cancer. IL-17A (P=0.005) and IL-37 (P=0.018) were negatively correlated with the risk of uterine leiomyoma. IL-21 (P=0.035) was positively correlated with the risk of uterine leiomyoma. Conclusion Genetically predicted IL-4, IL-15Rα, IL-17A, IL-18R1, IL-21, IL-24, and IL-37 are causally associated with the risk of three gynecological tumors. Further exploration of the molecular mechanism of ILs in gynecological tumors may provide potential therapeutic targets for the treatment of gynecological tumors.

Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals