Objective To employ three dimensional high-resolution vessel wall magnetic resonance imaging(3D hr-VW-MRI)for analyzing the imaging characteristics of posterior circulation non-stenotic intracranial atherosclerotic plaque and to discuss its diagnostic value in identifying culprit plaques.Methods Ninety-three patients(age[62.94±9.70]years old,67 males,26 females)with non-stenotic atherosclerosis in our hospital from Jan.2019 to Jan.2021 were retrospectively recruited.The imaging features of plaques,including luminal area,maximum wall thickness and minimum wall thickness at the most stenotic site,stenosis rate,plaque burden,remodeling index,eccentricity index,enhancement ratio at the most stenotic site,and intraplaque hemorrhage,were measured based on T1-weighted imaging(T1WI)and contrast-enhanced T1WI.The culprit plaque was defined as a lesion arising from the responsible vascular supply area to a fresh infarction on the diffusion weighted imaging(DWI)and T2 fluid attenuated inversion recovery(T2-FLAIR)images with accompanying ischemic stroke/transient ischemic attack(TIA).A plaque was considered to be a nonculprit plaque when it occurred in patients with presumed ischemic stroke/TIA,but without an infarct on DWI and T2-FLAIR.Results Sixty-one culprit plaques and 32 non-culprit plaques were analyzed.The proportions of patients with hyperlipidemia,National Institutes of Health stroke scale(NIHSS)score,narrowest plaque enhancement rate,and incidence of intraplaque hemorrhage in the culprit plaque group were significantly higher than those in the non-culprit plaque group(all P＜0.05).Multivariate logistic regression analyses showed that NIHSS score(odds ratio[OR]=1.799,95％confidence interval[CI]1.303-2.484,P＜0.001),enhancement ratio(OR=1.076,95％CI 1.027-1.128,P=0.002)and intraplaque hemorrhage(OR=30.708,95％CI 2.563-367.925,P=0.007)were associated with plaque type.Conclusion NIHSS score,enhancement ratio at the most stenotic site,and intraplaque hemorrhage are independent risk factors for culprit plaques in patients with posterior circulation non-stenotic intracranial atherosclerotic disease.These indicators may help identify such culprit plaques and could be used to screen individuals with plaques having these characteristics,thereby providing a basis for early preventive interventions.

Objective: To explore the relationship between positive parenting styles and academic emotions in junior high school students, as well as the chain mediation effects of parent-child communication and peer relationships, providing a theoretical basis for family education interventions. Methods: Using stratified cluster random sampling, 1 063 students from four junior high schools in a city in Anhui Province were selected for questionnaire surveys, form March to April, 2025. Core variables were measured using the Short form Parenting Style Scale, Adolescent Parent-Child Communication Scale, Peer Relationship Scale, and Adolescent Academic Emotion Questionnaire. Group comparison was conducted using t-test or analysis of variance, and Pearson correlation analysis was used to examine the correlation between positive parenting styles, peer relationships, parent-child communication and positive academic emotions. Multiple linear regression analysis was used to examine the effects of positive parenting styles, peer relationships and parent-child communication on positive academic emotions. A mediation effect model and Bootstrap method were employed to test the chain mediation effects. Results: Students who were class leaders, had parents with higher education levels, or came from intact families scored significantly higher on positive academic emotions ( t/F =7.23, 13.73, 10.67, 4.45, all P < 0.01 ). Positive parenting styles, peer relationships, and parent-child communication were all positively correlated with positive academic emotions ( r =0.45, 0.41, 0.38), and all three positively predicted positive academic emotions ( β =0.24, 0.23, 0.12) (all P < 0.01 ). Further analysis showed that positive parenting styles directly predicted positive academic emotions ( β =0.40) and also indirectly influenced academic emotions through parent-child communication ( β =0.07), peer relationships ( β =0.05), and the chain mediation path of "parent-child communication → peer relationships" ( β =0.04) (all P <0.05), with the total indirect effect accounting for 40.55%. Conclusion Positive parenting styles enhance junior high school students academic emotions through the chain mediation path of "parent-child communication → peer relationships", providing theoretical support for interventions within the educational ecosystem.

BACKGROUND: T cell dysfunction, which includes exhaustion, anergy, and senescence, is a distinct T cell differentiation state that occurs after antigen exposure. Although T cell dysfunction has been a cornerstone of cancer immunotherapy, its potential in transplant research, while not yet as extensively explored, is attracting growing interest. Interferon regulatory factor 4 (IRF4) has been shown to play a pivotal role in inducing T cell dysfunction. METHODS: A novel ultra-low-dose combination of Trametinib and Rapamycin, targeting IRF4 inhibition, was employed to investigate T cell proliferation, apoptosis, cytokine secretion, expression of T-cell dysfunction-associated molecules, effects of mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) signaling pathways, and allograft survival in both in vitro and BALB/c to C57BL/6 mouse cardiac transplantation models. RESULTS: In vitro , blockade of IRF4 in T cells effectively inhibited T cell proliferation, increased apoptosis, and significantly upregulated the expression of programmed cell death protein 1 (PD-1), Helios, CD160, and cytotoxic T lymphocyte-associated antigen (CTLA-4), markers of T cell dysfunction. Furthermore, it suppressed the secretion of pro-inflammatory cytokines interferon (IFN)-γ and interleukin (IL)-17. Combining ultra-low-dose Trametinib (0.1 mg·kg -1 ·day -1 ) and Rapamycin (0.1 mg·kg -1 ·day -1 ) demonstrably extended graft survival, with 4 out of 5 mice exceeding 100 days post-transplantation. Moreover, analysis of grafts at day 7 confirmed sustained IFN regulatory factor 4 (IRF4) inhibition, enhanced PD-1 expression, and suppressed IFN-γ secretion, reinforcing the in vivo efficacy of this IRF4-targeting approach. The combination of Trametinib and Rapamycin synergistically inhibited the MAPK and mTOR signaling network, leading to a more pronounced suppression of IRF4 expression. CONCLUSIONS Targeting IRF4, a key regulator of T cell dysfunction, presents a promising avenue for inducing transplant immune tolerance. In this study, we demonstrate that a novel ultra-low-dose combination of Trametinib and Rapamycin synergistically suppresses the MAPK and mTOR signaling network, leading to profound IRF4 inhibition, promoting allograft acceptance, and offering a potential new therapeutic strategy for improved transplant outcomes. However, further research is necessary to elucidate the underlying pharmacological mechanisms and facilitate translation to clinical practice.
Animals ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Interferon Regulatory Factors/metabolism* ; Heart Transplantation/methods* ; T-Lymphocytes/immunology* ; Sirolimus/therapeutic use* ; Pyridones/therapeutic use* ; Graft Survival/drug effects* ; Pyrimidinones/therapeutic use* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Male ; Signal Transduction/drug effects*

Cancer patients often experience worsening pain due to the limitations of traditional pharmacological treatments. This paper explores the innovative application of multi-agent systems in this field. As a key component of artificial intelligence, multi-agent systems assist healthcare providers in making intelligent decisions and interventions based on patients' conditions, and can collaborate with other smart devices to provide personalized care. This review discusses the concept of multi-agent systems, their application in pain management, and the potential challenges and countermeasures, aiming to provide guidance for the intelligent management of cancer patient pain.

Cancer patients often experience worsening pain due to the limitations of traditional pharmacological treatments. This paper explores the innovative application of multi-agent systems in this field. As a key component of artificial intelligence, multi-agent systems assist healthcare providers in making intelligent decisions and interventions based on patients' conditions, and can collaborate with other smart devices to provide personalized care. This review discusses the concept of multi-agent systems, their application in pain management, and the potential challenges and countermeasures, aiming to provide guidance for the intelligent management of cancer patient pain.

Background::Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.Methods::Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation. Results::HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days ( P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4 + and CD8 + T cells in the spleen ( P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes ( CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF) -β pathway-related genes and Treg signature genes ( CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4 + Foxp3 + cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs. Conclusions::HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.

Vascular cognitive impairment is a group of disorders characterized by cognitive dysfunction caused by vascular factors. Disruption of the blood-brain barrier is an early pathophysiological mechanism of vascular cognitive impairment. Dynamic contrast-enhanced magnetic resonance imaging and arterial spin labeling-based blood-brain barrier imaging techniques can quantitatively assess the integrity of the blood-brain barrier. In recent years, these techniques have gradually been applied to detect the extent of blood-brain barrier dysfunction. This article provides a comprehensive review of the basic principles of relevant magnetic resonance techniques and the progress made in their application to the assessment of the blood-brain barrier in vascular cognitive impairment.

Objective:To investigate the changes in symptoms of inflammatory bowel disease (IBD) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic, as well as the situation of IBD treatment medication use.Methods:A cross-sectional survey study method was used. A questionnaire survey was conducted on a voluntary sampling basis for IBD patients of multiple centers nationwide from December 1st to 31st 2022, collecting clinical data of patients diagnosed with COVID-19 through nucleic acid/antigen testing. Patients were divided into symptomatic exacerbation group and asymptomatic exacerbation group based on whether they felt an exacerbation of IBD symptoms including abdominal discomfort, increased bloody stool or the appearance of purulent bloody stool, increased frequency of diarrhea, etc. And the differences in age, gender, body mass index (BMI) , underlying disease conditions, SARS-CoV-2 vaccination status, IBD type, disease activity, COVID-19 symptoms, and treatment medication between the two groups were compared.Results:A total of 497 patients were included, 317 males and 180 females; age (35.27±11.54) years; 355 CD patients and 142 UC patients; more than 50% of patients exhibited respiratory system symptoms such as fever, muscle soreness, fatigue, cough, expectoration, nasal congestion, and some IBD patients exhibited digestive system symptoms and nervous system symptoms. The symptomatic exacerbation group consisted of 104 patients (20.93%) , and the asymptomatic exacerbation group consisted of 393 (79.07%) . There were no statistically significant differences in gender, age, BMI, underlying diseases, IBD type, and SARS-CoV-2 vaccine doses between the two groups (all P>0.05) . Compared with the asymptomatic exacerbation group, the proportion of patients in the disease active phase was higher [47.12% (49/104) vs. 24.68% (97/393) , P<0.001], and the proportion of patients using mesalazine/sulfasalazine was higher (35.58% vs. 23.41%, P = 0.012) , and the proportions of COVID-19 symptoms such as diarrhea, headache, and dizziness were all higher (all P<0.05) in the symptomatic exacerbation group. Among the 237 IBD patients using biologics, there was a statistically significant difference in the types of biologics used between the symptomatic and asymptomatic exacerbation groups (χ 2 = 9.351, P = 0.031) . Among the 240 patients using biologics, the proportion of delaying or interrupting the use of biologics was higher in symptomatic exacerbation group than that of the asymptomatic exacerbation group, and the difference was statistically significant [45.45% (20/44) vs. 23.98% (47/196) , χ 2 = 8.235, P = 0.004]. Among the 47 patients using immunosuppressants, there was no statistically significant difference in the proportion of stopping immunosuppressants between the symptomatic and asymptomatic exacerbation groups ( P = 0.263) . Conclusion:The main symptoms of IBD patients infected with COVID-19 are respiratory and systemic symptoms, and those in the active phase of the disease or those delaying or withdrawing biologics are more likely to experience an exacerbation of IBD symptoms during the infection.

Objective:To investigate the changes in symptoms of inflammatory bowel disease (IBD) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus disease 2019 (COVID-19) pandemic, as well as the situation of IBD treatment medication use.Methods:A cross-sectional survey study method was used. A questionnaire survey was conducted on a voluntary sampling basis for IBD patients of multiple centers nationwide from December 1st to 31st 2022, collecting clinical data of patients diagnosed with COVID-19 through nucleic acid/antigen testing. Patients were divided into symptomatic exacerbation group and asymptomatic exacerbation group based on whether they felt an exacerbation of IBD symptoms including abdominal discomfort, increased bloody stool or the appearance of purulent bloody stool, increased frequency of diarrhea, etc. And the differences in age, gender, body mass index (BMI) , underlying disease conditions, SARS-CoV-2 vaccination status, IBD type, disease activity, COVID-19 symptoms, and treatment medication between the two groups were compared.Results:A total of 497 patients were included, 317 males and 180 females; age (35.27±11.54) years; 355 CD patients and 142 UC patients; more than 50% of patients exhibited respiratory system symptoms such as fever, muscle soreness, fatigue, cough, expectoration, nasal congestion, and some IBD patients exhibited digestive system symptoms and nervous system symptoms. The symptomatic exacerbation group consisted of 104 patients (20.93%) , and the asymptomatic exacerbation group consisted of 393 (79.07%) . There were no statistically significant differences in gender, age, BMI, underlying diseases, IBD type, and SARS-CoV-2 vaccine doses between the two groups (all P>0.05) . Compared with the asymptomatic exacerbation group, the proportion of patients in the disease active phase was higher [47.12% (49/104) vs. 24.68% (97/393) , P<0.001], and the proportion of patients using mesalazine/sulfasalazine was higher (35.58% vs. 23.41%, P = 0.012) , and the proportions of COVID-19 symptoms such as diarrhea, headache, and dizziness were all higher (all P<0.05) in the symptomatic exacerbation group. Among the 237 IBD patients using biologics, there was a statistically significant difference in the types of biologics used between the symptomatic and asymptomatic exacerbation groups (χ 2 = 9.351, P = 0.031) . Among the 240 patients using biologics, the proportion of delaying or interrupting the use of biologics was higher in symptomatic exacerbation group than that of the asymptomatic exacerbation group, and the difference was statistically significant [45.45% (20/44) vs. 23.98% (47/196) , χ 2 = 8.235, P = 0.004]. Among the 47 patients using immunosuppressants, there was no statistically significant difference in the proportion of stopping immunosuppressants between the symptomatic and asymptomatic exacerbation groups ( P = 0.263) . Conclusion:The main symptoms of IBD patients infected with COVID-19 are respiratory and systemic symptoms, and those in the active phase of the disease or those delaying or withdrawing biologics are more likely to experience an exacerbation of IBD symptoms during the infection.

Objective:To use the spatiotemporal distribution model and INLA algorithm to study the spatiotemporal characteristics and influencing factors of tuberculosis in Shanghai and to provide a theoretical basis for formulating regional tuberculosis epidemic prevention and control measures.Methods:Based on the data of registered pulmonary tuberculosis cases in Shanghai during 2013-2020 derived from the tuberculosis management information system of China Disease Control and Prevention Information System, the hierarchical Bayesian model was adopted to fit the tuberculosis case data, identify the spatiotemporal variation characteristics of tuberculosis, and explore the potential socioeconomic characteristics and other factors related to health services and spatiotemporal characteristics.Results:From 2013 to 2020, 29 281 registered tuberculosis cases were reported in Shanghai, with an average annual incidence of 25.224/100 000. From 2013 to 2020, the incidence trend increased first and then decreased, the highest incidence was reported in 2014 (27.991/100 000). The incidence of tuberculosis in Shanghai is characterized by spatial clustering. Through the spatial characteristics and risk analysis of the reported incidence of tuberculosis, it is found that the high-risk area of tuberculosis in Shanghai is the suburban communities, whereas downtown communities are the low-risk areas. The incidence risk of pulmonary tuberculosis is associated with the gross domestic product per capita ( RR=0.48), the number of beds per 10 000 persons ( RR=0.56), the normalized vegetation index ( RR=0.50), and the night light index ( RR=0.80). Conclusions:With the steady progress of tuberculosis prevention and control in the central urban area of Shanghai, special attention should be paid to the prevention and control in the suburbs further to improve the social and economic level in the suburbs and increase the coverage rate of urban green space, to reduce the incidence of tuberculosis and reduce the disease burden of tuberculosis in Shanghai.