Objective: To understand the epidemiological characteristics and disease burden of influenza like illness (ILI) among student populations, so as to provide data support for policy formulation and optimal allocation of health resources. Methods: From January 2024 to February 2025, a questionnaire survey was conducted among parents of kindergarten, primary school, junior and senior high school students in 9 districts of Shenzhen, including Longhua, Futian, Bao an, Longgang, Luohu, Nanshan, Guangming, Pingshan and Yantian. Parents were asked to complete the questionnaire based on whether their children had fever, cough, vomiting, diarrhea, rash and other common symptoms in 2024. A total of 3 537 parents were investigated, and 444 ILI cases were included as study subjects. The epidemiological burden, including incidence rate of influenza, visitation rate, years lived with disability (YLDs) and economic burden (including direct economic burden, indirect economic burden and intangible burden) were analyzed. Results: The incidence rate of influenza among students in Shenzhen in 2024 was 12.55%. The ILI incidence rates in kindergarten, primary school, junior and senior high school were 14.01%, 11.69% and 5.23%, respectively, with a statistically significant difference ( χ 2= 45.20, P <0.01). The ILI consultation rate among students was 85.36%, and the consultation rates in kindergarten (87.36%) and primary school students (84.62%) were higher than those in junior and senior high school students ( 56.52 %) ( χ 2=16.47, P <0.01). A total of 78.88% of cases did not receive etiological detection.The median total economic burden per ILI case was 2 354.62 yuan, including direct medical costs of 300.00 yuan, direct non medical costs of 212.50 yuan, indirect costs of 1 000.00 yuan, and intangible burden of 500.00 yuan. Conclusions Schools are high risk environment for influenza, and younger students are a high risk group for ILI. The disease burden caused by student ILI remains substantial.

OBJECTIVES: Investigating the protective effect of naringenin (NAR) on the osteogenic potential of human periodontal ligament stem cells (hPDLSCs) under oxidative stress and its related mechanisms. METHODS: The oxidative damage model of hPDLSCs was established using hydrogen peroxide (H₂O₂) andthe hPDLSCs were treated with different concentrations of NAR and 0.5 μmol/L forkhead box protein O-1 (FOXO1) inhibitor AS1842856. After that, the cell counting kit-8 (CCK8) was used to determine the optimal concentrations of H₂O₂ and NAR. The alkaline phosphatase (ALP) staining and real time fluorescent quantitative reverse transcription polymerase chain reaction (qRT-PCR) were employed to assess the expression of ALP, runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) in hPDLSCs of each group. The enzyme-linked immunosorbent assay (ELISA) and 2',7'-dichlorofluorescin diacetate (DCFH-DA) staining were utilized to evaluate the expression of reactive oxygen species (ROS), malondialdehyde (MDA) and lactate dehydrogenase (LDH) in hPDLSCs. Meanwhile, qRT-PCR and western blot were used to detect the expression levels of FOXO1 and β-catenin, both are pathway related genes and proteins. RESULTS: H₂O₂ exposure led to an increase in oxidative damage in hPDLSCs, characterized by a rise in intracellular ROS levels and increased expression of MDA and LDH (P<0.05). At the same time, the osteogenic differentiation ability of hPDLSCs decreased, as evidenced by lighter ALP staining and reduced expression levels of osteogenic differentiation-related genes ALP, RUNX2 and OCN (P<0.05). Co-treatment with NAR alleviated the oxidative damage in hPDLSCs, enhanced their antioxidant capacity, and restored their osteogenic ability. The FOXO1 inhibitor AS1842856 downregulated the expression of β-catenin (P<0.05) and significantly diminished both the antioxidant effect of NAR and its ability to restore osteogenesis (P<0.05). CONCLUSIONS NAR can enhance the antioxidant capacity of hPDLSCs by activating the FOXO1/β-catenin signaling pathway within hPDLSCs, thereby mitigating oxidative stress damage and alleviating the loss of osteogenic capacity.
Humans ; Oxidative Stress/drug effects* ; Periodontal Ligament/cytology* ; Hydrogen Peroxide ; Forkhead Box Protein O1/metabolism* ; Stem Cells/cytology* ; Flavanones/pharmacology* ; beta Catenin/metabolism* ; Osteogenesis/drug effects* ; Signal Transduction ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Alkaline Phosphatase/metabolism* ; Osteocalcin/metabolism* ; Cells, Cultured ; Cell Differentiation/drug effects*

The glucagon receptor (GCGR) is a critical target for the treatment of metabolic disorders such as Type 2 Diabetes Mellitus (T2DM) and obesity. Activation of GCGR enhances systemic insulin sensitivity through paracrine stimulation of insulin secretion, presenting a promising avenue for treatment. However, the discovery of effective GCGR agonists remains a challenging and resource-intensive process, often requiring time-consuming wet-lab experiments to synthesize and screen potential compounds. Recent advances in artificial intelligence technologies have demonstrated great potential in accelerating drug discovery by streamlining screening and efficiently predicting bioactivity. In the present work, we propose DeepGCGR, a two-layer deep learning model that leverages graph convolutional networks (GCN) integrated with a multiple attention mechanism to expedite the identification of GCGR agonists. In the first layer, the model predicts the bioactivity of various compounds against GCGR, efficiently filtering large chemical libraries to identify promising candidates. In the second layer, DeepGCGR classifies high bioactive compounds based on their functional effects on GCGR signaling, identifying those with potential agonistic or antagonistic effects. Moreover, DeepGCGR was specifically applied to identify novel GCGR-regulating compounds for the treatment of T2DM from natural products derived from traditional Chinese medicine (TCM). The proposed method will not only offer an effective strategy for discovering GCGR-targeting compounds with functional activation properties but also provide new insights into the development of T2DM therapeutics.
Deep Learning ; Drug Discovery/methods* ; Humans ; Diabetes Mellitus, Type 2/metabolism* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To investigate the association between plasma homocysteine(Hcy)level and coronary artery calcification(CAC)and its clinical predictive efficacy.Methods A total of 172 patients who underwent coronary CT angiography North China University of Science and Technology Affiliated Hospital from April 2019 to May 2021 and CAC score(CACS)＞0 were enrolled.According to the CACS value,the subjects were divided into mild calcification group(n=136)and severe calcification group(n=36),and the clinical characteristics of two groups were compared and analyzed.Multivariate Logistic regression model was used to screen the independent influencing factors of CAC severity,and a prediction model was constructed based on the Hcy detection value.The clinical diagnostic value was evaluated by the receiver operating characteristic(ROC)curve.Results There were significant differences in Hcy,white blood cell count,triglyceride and magnesium ion levels between two groups(P＜0.05).Multivariate Logistic regression analysis showed that Hcy,white blood cell count and magnesium ion level were independent risk factors for the progression of CAC.Furthermore,a regression model based on Hcy was constructed and ROC curve was fitted to evaluate its predictive efficacy.The results suggested that the predictive model had the best performance when the critical value of Hcy was set at 27.4μmol/L:the sensitivity was 55.6％,the specificity was 97.1％,and the area under the curve was 0.765.Conclusion Hcy serves as an independent risk factor for the severity of CAC and can effectively predict the progression of CAC with high accuracy.

Objective:To explore the clinical value of computed tomography-three-dimensional(CT-3D)imaging technique in assessing small airway disease(SAD)in children with asthma.Methods:A total of 104 pediatric patients with suspected SAD,who admitted to our hospital from September 2021 to August 2024,were selected,and they were divided into lesion group(48 cases,with obstruction in small airway)and control group(56 cases,lung function without abnormality)according to the results of test for pulmonary function.Both two groups underwent test for lung function and respiratory biphasic CT scan,and the manifestations of high resolution CT(HRCT)image were observed.The correlation between the SAD and the relative indicators of determining ventilation function of lung,which included maximum mid-expiratory flow(MMEF25-75%),forced expiratory flow at 75%vital capacity(FEF75%),forced expiratory flow at 50%vital capacity(FEF 50%),forced expiratory flow at 25%vital capacity(FEF25%)and forced expiratory volume at the first second(FEV1),was analyzed.Results:The MMEF25-75%,FEF75%,FEF50%,FEF25%and FEV1 in the lesion group were significantly lower than those of the control group(t=8.735,12.757,9.724,13.928,10.303,P＜0.05).The incidences of bronchial wall thickening,air retention,Mosaic sign and bronchiole obstruction of HRCT signs of the lesion group were significantly higher than those of the control group(x2=10.715,6.119,6.330,6.587,P＜0.05).Bronchial wall thickening significantly correlated with MMEF25-75%,FEF75%,FEF50%,FEF25%and FEV1(r=-0.360,-0.379,-0.374,-0.367,-0.268,P＜0.001),respectively,and the correlation between it and FEF75%was extremely strong.Air retention significantly correlated with FEF75%and FEV1(r=-0.249,-0.240,P＜0.05),respectively.The Mosaic sign significantly correlated with MMEF25-75%,FEF75%and FEV1(r=-0.236,-0.245,0.257,P＜0.05),respectively.Bronchial obstruction significantly correlated with MMEF25-75%,FEF75%,FEF50%and FEV1(r=-0.248,-0.271,-0.253,-0.275,P＜0.05),respectively.The incidence of asthma in the lesion group was significantly higher than that in the control group(x2=36.783,P＜0.05).Conclusion:The incidence of bronchiolar wall thickening,air retention,Mosaic sign and bronchiolar obstruction of HRCT signs significantly increase in SAD children.They highly correlated with the indicators of ventilation function of lung,especially FEF75%and FEV1,which can reflect the function of small airway at a certain extent.They have great value for identifying early SAD.The application of CT-3D imaging technique in SAD children has a certain of predictive value for the occurrence of asthma.

Objective:To explore the clinical value of computed tomography-three-dimensional(CT-3D)imaging technique in assessing small airway disease(SAD)in children with asthma.Methods:A total of 104 pediatric patients with suspected SAD,who admitted to our hospital from September 2021 to August 2024,were selected,and they were divided into lesion group(48 cases,with obstruction in small airway)and control group(56 cases,lung function without abnormality)according to the results of test for pulmonary function.Both two groups underwent test for lung function and respiratory biphasic CT scan,and the manifestations of high resolution CT(HRCT)image were observed.The correlation between the SAD and the relative indicators of determining ventilation function of lung,which included maximum mid-expiratory flow(MMEF25-75%),forced expiratory flow at 75%vital capacity(FEF75%),forced expiratory flow at 50%vital capacity(FEF 50%),forced expiratory flow at 25%vital capacity(FEF25%)and forced expiratory volume at the first second(FEV1),was analyzed.Results:The MMEF25-75%,FEF75%,FEF50%,FEF25%and FEV1 in the lesion group were significantly lower than those of the control group(t=8.735,12.757,9.724,13.928,10.303,P＜0.05).The incidences of bronchial wall thickening,air retention,Mosaic sign and bronchiole obstruction of HRCT signs of the lesion group were significantly higher than those of the control group(x2=10.715,6.119,6.330,6.587,P＜0.05).Bronchial wall thickening significantly correlated with MMEF25-75%,FEF75%,FEF50%,FEF25%and FEV1(r=-0.360,-0.379,-0.374,-0.367,-0.268,P＜0.001),respectively,and the correlation between it and FEF75%was extremely strong.Air retention significantly correlated with FEF75%and FEV1(r=-0.249,-0.240,P＜0.05),respectively.The Mosaic sign significantly correlated with MMEF25-75%,FEF75%and FEV1(r=-0.236,-0.245,0.257,P＜0.05),respectively.Bronchial obstruction significantly correlated with MMEF25-75%,FEF75%,FEF50%and FEV1(r=-0.248,-0.271,-0.253,-0.275,P＜0.05),respectively.The incidence of asthma in the lesion group was significantly higher than that in the control group(x2=36.783,P＜0.05).Conclusion:The incidence of bronchiolar wall thickening,air retention,Mosaic sign and bronchiolar obstruction of HRCT signs significantly increase in SAD children.They highly correlated with the indicators of ventilation function of lung,especially FEF75%and FEV1,which can reflect the function of small airway at a certain extent.They have great value for identifying early SAD.The application of CT-3D imaging technique in SAD children has a certain of predictive value for the occurrence of asthma.

Objective To investigate the association between plasma homocysteine(Hcy)level and coronary artery calcification(CAC)and its clinical predictive efficacy.Methods A total of 172 patients who underwent coronary CT angiography North China University of Science and Technology Affiliated Hospital from April 2019 to May 2021 and CAC score(CACS)＞0 were enrolled.According to the CACS value,the subjects were divided into mild calcification group(n=136)and severe calcification group(n=36),and the clinical characteristics of two groups were compared and analyzed.Multivariate Logistic regression model was used to screen the independent influencing factors of CAC severity,and a prediction model was constructed based on the Hcy detection value.The clinical diagnostic value was evaluated by the receiver operating characteristic(ROC)curve.Results There were significant differences in Hcy,white blood cell count,triglyceride and magnesium ion levels between two groups(P＜0.05).Multivariate Logistic regression analysis showed that Hcy,white blood cell count and magnesium ion level were independent risk factors for the progression of CAC.Furthermore,a regression model based on Hcy was constructed and ROC curve was fitted to evaluate its predictive efficacy.The results suggested that the predictive model had the best performance when the critical value of Hcy was set at 27.4μmol/L:the sensitivity was 55.6％,the specificity was 97.1％,and the area under the curve was 0.765.Conclusion Hcy serves as an independent risk factor for the severity of CAC and can effectively predict the progression of CAC with high accuracy.

Objective To explore the characteristics of blood lipid metabolism indicators and risk factors of prognosis in children with systemic lupus erythematosus (SLE). Methods A total of 54 children who were diagnosed with SLE and hospitalized in Chengdu Women and Children’ s Central Hospital from January 2013 to August 2022 were selected. Clinical data of all children were collected and blood lipid metabolism indicators and biochemical indicators were detected , and binary logistic regression was used to analyze the prognosis risk factors in children with SLE. Results Among the 47 cases (87.04%) had abnormal blood lipid metabolism at admission, and is mainly manifested as elevated levels of LDL-C, TG and TC and decreased level of HDL-C. The proportion of cardiovascular system damage, hematological system damage, urinary protein positivity, and SLEDAI-2000 score in the group with good prognosis were lower than those in the group with poor prognosis, while the proportion of dsDNA positivity was higher in the group with poor prognosis. Binary Logistic regression analysis showed that the cardiovascular system damage and positive urinary protein were risk factors for poor prognosis, with statistically significant differences (P<0.05). Conclusion Abnormal blood lipid metabolism is common in children with SLE, and cardiovascular system damage and positive urinary protein may increase the risk of poor prognosis in young children.

AIM:To investigate the impact of aquaporin 4(AQP4)expression inhibition on autophagy and apoptosis in a mouse model of cerebral ischemia-reperfusion(I/R)injury,and to elucidate its underlying mechanism.METHODS:Cerebral I/R injury was induced in mice via transient middle cerebral artery occlusion(tMCAO).Totally 60 mice were randomly divided into sham group,I/R group,AQP4 inhibition group,and 3-methyladenine(3-MA)group,with 15 mice in each group.Among them,the mice in sham and I/R groups received intraperitoneal injections of normal saline,while those in AQP4 inhibition group and 3-MA group received intraperitoneal injections of AER-271(2 mg·kg-1·d-1)and AER-271+3-MA(2 mg·kg-1·d-1)for 3 d,respectively,once per day.Longa score was adopted to assess the neu-rological function,and to record changes in body weight.Cerebral infarction volume and histopathological alterations were evaluated using hematoxylin-eosin staining.Western blot analysis was performed to determine the levels of AQP4,LC3-Ⅱ,P62 and cleaved caspase-3,while the LC3-Ⅱ,P62,cleaved caspase-3 and NeuN(neuronal marker)colocalization and expression assessment were conducted with immunofluorescence.RESULTS:The mice in I/R and AQP4 inhibition groups exhibited extensive cerebral infarction,cerebral edema,and elevated Longa scores.However,in comparision to I/R group,the mice in AQP4 inhibition group showed significantly reduced cerebral infarct volume,cerebral edema vol-ume,and Longa score(P<0.05).Additionally,in contrast to sham group,the mice in I/R group displayed increased ex-pression of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.01),accompanied by decreased body weight and P62 expression(P<0.05 or P<0.01).Furthermore,compared with I/R group,the mice in both AQP4 inhibition group and 3-MA group demonstrated a decrease in the expression levels of AQP4,LC3-Ⅱ and cleaved caspase-3(P<0.05 or P<0.01),along with increased body weight and P62 expression(P<0.05 or P<0.01).Nonetheless,no significant differences were ob-served between AQP4 inhibition group and 3-MA group regarding Longa score,cerebral infarct volume,body weight,and the expression of AQP4,LC3-Ⅱ,cleaved caspase-3 and P62.CONCLUSION:Inhibition of AQP4 expression signifi-cantly reduces cerebral infarction area and nerve injury severity in tMCAO mice.Moreover,AQP4 expression inhibition decelerates autophagy and apoptosis after cerebral infarction,with the additional autophagy inhibitor showing no notable impact on the protective effect of AQP4 inhibition.