AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.

Objective:To evaluate the efficacy of early bronchoalveolar lavage using electronic bronchoscopy in pediatric drowning cases.Methods:A retrospective analysis of clinical data from 81 pediatric drowning cases treated in the intensive care unit of Hunan Children's Hospital from January 2017 to September 2023 was conducted.Among these,43 cases underwent bronchoalveolar lavage with electronic bronchoscopy within 24 hours of drowning,constituting the treatment group,while 38 cases either did not receive treatment within 24 hours or underwent the procedure after 24 hours,forming the control group.We compared the two groups regarding pre-admission observations,admission observations,and disease progression or prognosis indicators to assess the clinical efficacy of early bronchoalveolar lavage with electronic bronchoscopy in pediatric drowning cases.Results:Compared to the control group,children in the treatment group exhibited a significant reduction in invasive ventilation time [(73.33±13.33) h vs.(94.82±15.77) h] and a significant decrease in pediatric intensive care unit stay [105.00 (94.00,121.00) h vs.123.5 (109.75,149.00) h],with both differences being statistically significant( P<0.05).No significant differences in white blood cell count and neutrophil percentage were observed between the treatment group and control group at admission and on the first day( P>0.05).However,by the third day,there was a significant improvement in white blood cell count in both groups,with statistical significance( P<0.05).There was a significant decrease in C-reactive protein and procalcitonin levels between the treatment group and control group on the 1st and 3rd days,with the differences being significant( P<0.05).Six hours after electronic bronchoalveolar lavage,the P/F ratio in the treatment group was lower than that in the control group (177.09±41.27 vs. 233.50±48.23),but it increased more significantly at 24 hours (286.00±34.32 vs.256.34±44.22),with a significant difference between two groups.The positive rate of lavage fluid culture in the treatment group was significantly higher than that in the control group,and the difference was statistically significant( P<0.05).There was no significant difference in the number of organ function damage between two groups( P>0.05).However,regarding prognosis,the treatment group showed significantly better outcomes than the control group( P<0.05). Conclusion:For pediatric patients with wilderness drowning,early electronic bronchoscopy with alveolar lavage may shorten the duration of invasive mechanical ventilation and pediatric intensive care unit stay,improving prognosis,and is worth promoting.

AIM:This study aims to investigate the regulatory effects of caffeic acid phenethyl ester(CAPE)on metabotropic glutamate receptor 5(mGluR5)and tyrosine kinase Fyn,and to explore its role in alleviating neuroinflam-mation and pathological features of Alzheimer disease(AD).METHODS:In vitro,the murine neuroblastoma N2a cell line was treated with amyloid β-protein 42 oligomers(Aβ42Os;10 nmol/L to 10 μmol/L)for 24 h.Cell viability was as-sessed by MTT assay.Western blot analyzed mGluR5 expression and Fyn phosphorylation(Tyr416).Pharmacological modulators(CHPG/MPEP)were used to evaluate mGluR5-mediated inflammatory cytokine regulation(qPCR)and Fyn ac-tivation.In vivo,wild-type(WT)and 5×FAD mice(WT,WT+CAPE,5×FAD and 5×FAD+CAPE)were analyzed for AD-related proteins,neuroinflammation(ELISA),glial activation(GFAP/Iba-1 immunofluorescence),and β-amyloid deposi-tion(thioflavin S).RESULTS:(1)Treatment with 1 μmol/L Aβ42Os increased mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01)without affecting N2a cell viability.Intracerebral Aβ42Os injection similarly up-regulated hip-pocampal mGluR5 and Fyn(P<0.01).(2)MPEP reduced mGluR5 expression(P<0.01)and Fyn phosphorylation(P<0.01),while suppressing tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)mRNA levels(P<0.01).(3)CAPE decreased mGluR5-Fyn activation in N2a cells,neurons,and 5×FAD mice(P<0.01).(4)CAPE-treated 5×FAD mice exhibited reduced neuroinflammation markers(GFAP,Iba-1,TNF-α,IL-1β,and IL-6),Aβ plaques,and p-APP levels(P<0.01).CONCLUSION:Treatment with CAPE inhibits Aβ42Os-induced mGluR5-Fyn signaling activation,thereby attenuating neuroinflammation and the pathology associated with AD.

Objective:To evaluate the efficacy of early bronchoalveolar lavage using electronic bronchoscopy in pediatric drowning cases.Methods:A retrospective analysis of clinical data from 81 pediatric drowning cases treated in the intensive care unit of Hunan Children's Hospital from January 2017 to September 2023 was conducted.Among these,43 cases underwent bronchoalveolar lavage with electronic bronchoscopy within 24 hours of drowning,constituting the treatment group,while 38 cases either did not receive treatment within 24 hours or underwent the procedure after 24 hours,forming the control group.We compared the two groups regarding pre-admission observations,admission observations,and disease progression or prognosis indicators to assess the clinical efficacy of early bronchoalveolar lavage with electronic bronchoscopy in pediatric drowning cases.Results:Compared to the control group,children in the treatment group exhibited a significant reduction in invasive ventilation time [(73.33±13.33) h vs.(94.82±15.77) h] and a significant decrease in pediatric intensive care unit stay [105.00 (94.00,121.00) h vs.123.5 (109.75,149.00) h],with both differences being statistically significant( P<0.05).No significant differences in white blood cell count and neutrophil percentage were observed between the treatment group and control group at admission and on the first day( P>0.05).However,by the third day,there was a significant improvement in white blood cell count in both groups,with statistical significance( P<0.05).There was a significant decrease in C-reactive protein and procalcitonin levels between the treatment group and control group on the 1st and 3rd days,with the differences being significant( P<0.05).Six hours after electronic bronchoalveolar lavage,the P/F ratio in the treatment group was lower than that in the control group (177.09±41.27 vs. 233.50±48.23),but it increased more significantly at 24 hours (286.00±34.32 vs.256.34±44.22),with a significant difference between two groups.The positive rate of lavage fluid culture in the treatment group was significantly higher than that in the control group,and the difference was statistically significant( P<0.05).There was no significant difference in the number of organ function damage between two groups( P>0.05).However,regarding prognosis,the treatment group showed significantly better outcomes than the control group( P<0.05). Conclusion:For pediatric patients with wilderness drowning,early electronic bronchoscopy with alveolar lavage may shorten the duration of invasive mechanical ventilation and pediatric intensive care unit stay,improving prognosis,and is worth promoting.

Objective:To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE). Methods:Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children′s Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed. Results:Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c. 677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group ( P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures. Conclusion:The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.

Objective:To explore the immune infiltration cells in rheumatoid arthritis (RA) synovial lesions, and to provide new research directions and therapeutic targets for the pathogenesis and treatment of RA.Methods:The three gene expression data sets GSE77298, GSE55457 and GSE1919 were downloaded from gene expression omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo), and the data were merged with Perl. The "limma" package was used to adjust batch differences. In R, "CIBERSORT" software was used to obtain the expression matrix of 22 kinds of immune cells corresponding to RA synovial tissue samples and normal synovial tissue samples were analyzed with the three packages of "e1071", "parallel" and "preprocessCore". Perl was used to screen samples with P<0.05 in the immune cell matrix. R's "barplot" function was analyzed by the percentage of 22 immune cells in samples with P<0.05. The "pheatmap" package of R was used to visualize heatmaps, and "corrplot" package was used to draw correlation heatmaps. The "vioplot" package of R was used to draw violin plots of differences via the wilcox test. Results:The results of immune cell infiltration analysis showed that in RA synovial tissue samples and normal synovial tissue samples at P<0.05, B cells naive and natural killer cells resting were under-expressed in RA synovial tissue, and plasma cells, mast cells resting, macrophages M1, B cells memory and T cells regulatory were highly expressed in RA synovial tissue. This study also found that in the same sample, the correlation coefficient between natural killer cells resting and neutrophils ( r=0.91) was the highest, indicating synergistic effect between the two. In the same sample, the correlation coefficient between macrophages M0 and plasma cells ( r=-0.88) was the lowest, indicating antagonistic effect between the two. Conclusion:The immune infiltrating cells in RA synovial lesions discovered in this study provide a certain theoretical basis and research direction for the research on the disease mechanism and treatment of RA.

Objective: To understand the relationships of social exclusion, personality trait and emotion regulation with willingness to seek help after being bullied, and to provide reference for rationalized intervention of campus bullying among middle school students. Methods: A tatal of 2 040 middle school students from a middle school in Jiangxi Province were selected as the research objects, and surveyed by general situation questionnaire, Olweus Bullying Questionnaire, Willingness to Seek Help Scale, social exclusion scale, personality scale and Emotion Regulation Scale. Among them, a further survey of 381 bullies was conducted and SPSS 26.0 was used for statistical processing of data. Results: About 55.88% (133/238) and 58.74% (84/143) reported willingness to seek help after being bullied among middle and high school students, respectively( χ 2=0.30, P >0.05). There were no significant differences in gender and residency( P >0.05). In junior middle school students, compared with the non help willingness group( 3.83± 0.78，3.35±1.03，3.33±1.03，29.81±7.77), the rejected scores of the help willingness group were lower(3.57±0.75), scores of affinity and openness in personality traits were higher(3.69±0.88，3.72±0.79), the cognitive reappraisal scores were higher( 32.42 ±8.25). Among senior middle school students, the rejected and expression suppression scores of the help willingness group were lower(3.51±0.67，26.96±7.47), while extroversion personality traits were higher(3.61±0.95). Multivariate unconditional Log binomial regression analysis showed that high score of expression suppression was associated with less willingness to seek help( OR=0.94, P =0.02). Conclusion Social exclusion, personality trait and emotional regulation may have certain influences on willingness to seek help after being bullied among junior and senior middle school students, effects varies by grade level.

BACKGROUND: Health literacy is a public health goal which can be used as an independent factor of health outcomes. This study aimed to assess the association between health literacy and health status, as well as the two mediating factors of behavior and self-efficacy among residents aged 15-69 years in Qingdao. METHODS: A cross-sectional survey was implemented among residents aged 15-69 years (N = 3793) in Qingdao, China. A combination of stratified cluster random and proportional probability sampling methods was used to select subjects for this study. Data were collected using "The Chinese Citizen Health Literacy Questionnaire (2019)". We proposed a hypothetical model for the relationship between sociodemographic characteristics, health literacy, self-efficacy, health behavior, and health status, and used path analysis to validate the hypothesis. RESULTS: The path analysis showed that higher education (β = 0.293) and income (β = 0.135) are positively and directly associated with greater health literacy, which was positively associated with health status (β = 0.057). Health literacy is a direct influencing factor of health behavior (β = 0.070) and self-efficacy (β = 0.099). Health behavior (β = 0.041) and self-efficacy (β = 0.173) exerted a positive direct effect on health status. The model explained 14.1% of variance for health literacy, 3.8% for self-efficacy, 5.7% for health behavior, and 15.0% for health status. CONCLUSIONS Health literacy was identified to be a critical factor in health status. The results emphasized that the dissemination of health knowledge, development of healthy behavior, and cultivation of self-efficacy should be jointly promoted to reinforce the level of health status among residents in future work.
Adolescent ; Adult ; Aged ; China ; Cross-Sectional Studies ; Female ; Health Behavior ; Health Knowledge, Attitudes, Practice ; Health Literacy/statistics & numerical data* ; Health Status ; Humans ; Male ; Middle Aged ; Young Adult

Objective:To explore the potential Hub genes, key miRNAs, biological processes and related signaling pathways in the pathogenesis of osteoarthritis (OA), and provide bioinformatics basis for the pathogenesis and treatment of OA.Methods:The expression profiling chip of OA synovial tissue sample from Gene Expression Omnibus (GEO) were downloaded, differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction network (PPI) was constructed. STRING and Cytoscape was used for module analysis, and the Hub gene was further identified, and further miRNAs mining of the Hub gene was carried out.Results:Finally, 9 Hub genes (SOCS3, BTRC, FBXO32, KLHL22, UBE3A, HUWE1, UBR4, ANAPC5, TRIM50) and 2 key miRNAs (hsa-miR-103a-3P, hsa-miR-107) related to the progression of OA were identified .They might be potential biomarkers for the pathogenesis of OA. We also found that signal transduction, the transcriptional positive regulation of RNA polymerase Ⅱ promoter, and protein serine/threoninase activity had a certain correlation with the pathogenesis of OA. In addition, our analysis results showed that cAMP signaling pathway and Rap1 signaling pathway were also involved in the progression of OA.Conclusion:The potential biological molecules, biological processes and related pathways identified in this study may guide us for the further research on the etiology and treatment of OA.

Type 1 diabetes is a autoimmune disease that occurs under the influence of both genetic predisposition and environmental factors,mediated mainly by T lymphocytes with various kinds of other involved immune cells.The autoimmune attacks eventually lead to the islet beta cell destruction and insulin insufficiency.Multiple fundamental studies and clinical trials have revealed that umbilical cord blood pluripotent stem cells have the potential to help restore immune balance,induce immune tolerance,stop the autoimmune attacks against beta cells,and promote beta cell regeneration in type 1 diabetes mellitus (T1DM),by means of cell to cell contact and soluble cytokine secretion.For the past few years,the National Clinical Research Center for Metabolic Diseases of Second Xiangya Hospital has been leading the research on stem cell education therapy and has performed the therapy for 35 juvenile type 1 diabetes patients from China and foreign countries,introducing a novel treatment for T1DM.