ObjectiveTo explore the molecular mechanism of aerobic exercise to improve hippocampal neuronal degeneration by regulating tryptophan metabolic pathway. Methods60 SPF-grade C57BL/6J male mice were divided into a young group (2 months old, n=30) and a senile group (12 months old, n=30), and each group was further divided into a control group (C/A group, n=15) and an exercise group (CE/AE group, n=15). An aerobic exercise program was used for 8 weeks. Learning memory ability was assessed by Y-maze, and anxiety-depression-like behavior was detected by absent field experiment. Hippocampal Trp levels were measured by GC-MS. Nissl staining was used to observe the number and morphology of hippocampal neurons, and electron microscopy was used to detect synaptic ultrastructure. ELISA was used to detect the levels of hippocampal Trp,5-HT, Kyn, KATs, KYNA, KMO, and QUIN; Western blot was used to analyze the activities of TPH2, IDO1, and TDO enzymes. ResultsGroup A mice showed significant decrease in learning and memory ability (P<0.05) and increase in anxiety and depressive behaviors (P<0.05); all of AE group showed significant improvement (P<0.05). Hippocampal Trp levels decreased in group A (P<0.05) and increased in AE group (P<0.05). Nidus vesicles were reduced and synaptic structures were degraded in group A (P<0.05), and both were significantly improved in group AE (P<0.05). The levels of Trp, 5-HT, KATs, and KYNA were decreased (P<0.05) and the levels of Kyn, KMO, and QUIN were increased (P<0.05) in group A. The activity of TPH2 was decreased (P<0.05), and the activities of IDO1 and TDO were increased (P<0.05). The AE group showed the opposite trend. ConclusionThe aging process significantly reduces the learning memory ability and increases the anxiety-depression-like behavior of mice, and leads to the reduction of the number of nidus vesicles and degenerative changes of synaptic structure in the hippocampus, whereas aerobic exercise not only effectively enhances the spatial learning memory ability and alleviates the anxiety-depression-like behavior of aging mice, but also improves the morphology and structure of neurons in hippocampal area, which may be achieved by the mechanism of regulating the tryptophan metabolic pathway.

Objective To evaluate the effect of donor gender on short-term survival rate of lung transplant recipients. Methods A retrospective analysis was conducted on the data of 1 066 lung transplant recipients. The log-rank test was used to evaluate the differences in short-term fatality among different donor gender groups and donor-recipient gender combination groups. Multivariate Cox regression, propensity score (PS) regression, and propensity score matching (PSM) were employed to control for confounding factors and further assess the differences in fatality. Subgroup analyses were also performed based on donor gender. Results Multivariate Cox regression analysis showed no statistically significant differences in fatality at 30 days, 1 year, 2 years and 3 years postoperatively between male and female donor groups (all P>0.05). After PS regression and PSM, univariate Cox regression analysis indicated that recipients from female donors had a higher fatality at 2 years postoperatively compared to those from male donors, with hazard ratios (95% confidence intervals) of 1.29 (1.01-1.65) and 1.36 (1.03-1.80) respectively. Multivariate Cox regression analysis also revealed no statistically significant differences in fatality at various follow-up time points among different donor-recipient gender combination groups (all P>0.05). Subgroup analyses based on donor sex showed no statistically significant differences in fatality among recipients of different gender within either male or female donor groups (all P>0.05). Conclusions Female donors may reduce the short-term postoperative survival rate of lung transplant recipients, but this negative impact is not sustainable in the long term. At present, there is no evidence to support the inclusion of sex as a factor in lung allocation rules.

ObjectiveTobacco-related diseases remain one of the leading preventable public health challenges worldwide and are among the primary causes of premature death. In recent years, accumulating evidence has supported the classification of nicotine addiction as a chronic brain disease, profoundly affecting both brain structure and function. Despite the urgency, effective diagnostic methods for smoking addiction remain lacking, posing significant challenges for early intervention and treatment. To address this issue and gain deeper insights into the neural mechanisms underlying nicotine dependence, this study proposes a novel graph neural network framework, termed TI-GNN. This model leverages functional magnetic resonance imaging (fMRI) data to identify complex and subtle abnormalities in brain connectivity patterns associated with smoking addiction. MethodsThe study utilizes fMRI data to construct functional connectivity matrices that represent interaction patterns among brain regions. These matrices are interpreted as graphs, where brain regions are nodes and the strength of functional connectivity between them serves as edges. The proposed TI-GNN model integrates a Transformer module to effectively capture global interactions across the entire brain network, enabling a comprehensive understanding of high-level connectivity patterns. Additionally, a spatial attention mechanism is employed to selectively focus on informative inter-regional connections while filtering out irrelevant or noisy features. This design enhances the model’s ability to learn meaningful neural representations crucial for classification tasks. A key innovation of TI-GNN lies in its built-in causal interpretation module, which aims to infer directional and potentially causal relationships among brain regions. This not only improves predictive performance but also enhances model interpretability—an essential attribute for clinical applications. The identification of causal links provides valuable insights into the neuropathological basis of addiction and contributes to the development of biologically plausible and trustworthy diagnostic tools. ResultsExperimental results demonstrate that the TI-GNN model achieves superior classification performance on the smoking addiction dataset, outperforming several state-of-the-art baseline models. Specifically, TI-GNN attains an accuracy of 0.91, an F1-score of 0.91, and a Matthews correlation coefficient (MCC) of 0.83, indicating strong robustness and reliability. Beyond performance metrics, TI-GNN identifies critical abnormal connectivity patterns in several brain regions implicated in addiction. Notably, it highlights dysregulations in the amygdala and the anterior cingulate cortex, consistent with prior clinical and neuroimaging findings. These regions are well known for their roles in emotional regulation, reward processing, and impulse control—functions that are frequently disrupted in nicotine dependence. ConclusionThe TI-GNN framework offers a powerful and interpretable tool for the objective diagnosis of smoking addiction. By integrating advanced graph learning techniques with causal inference capabilities, the model not only achieves high diagnostic accuracy but also elucidates the neurobiological underpinnings of addiction. The identification of specific abnormal brain networks and their causal interactions deepens our understanding of addiction pathophysiology and lays the groundwork for developing targeted intervention strategies and personalized treatment approaches in the future.

AIM: To discuss the impacts of pterygium excision combined with low-temperature plasma radiofrequency ablation and autologous conjunctival flap transplantation on tear film function, visual function, and recurrence rate in patients with pterygium.METHODS: A retrospective study was conducted on patients with pterygium who underwent surgery at Jiangyin Hospital of Traditional Chinese Medicine from March 2021 to January 2024. The patients were divided into two groups based on the surgical methods: the excision group with 50 cases(50 eyes)and the combined group with 51 cases(51 eyes). The excision group underwent pterygium excision, while the combined group received low-temperature plasma radiofrequency ablation and autologous conjunctival flap transplantation in addition to the excision. The tear film function [Schirmer's test(SⅠt), tear film break-up time(BUT)], visual quality, therapeutic effect, incidence of complications within 1 a, and recurrence rate were compared between the two groups before and after treatment.RESULTS: The general data of the two groups were comparable(P>0.05). After treatment, the SⅠt and BUT in the combined group were greater than those in the excision group(both P<0.001), while the corneal astigmatism and uncorrected visual acuity were lower than those in the excision group(both P<0.001). The initial treatment efficiency in the combined group(92%)was higher than that in the excision group(76%). Within 1 a, the recurrence rate(8% vs 22%)and complication rate(6% vs 24%)in the combined group were both lower than those in the excision group(both P< 0.05).CONCLUSION: The union of pterygium excision, low-temperature plasma radiofrequency ablation, and autologous conjunctival flap transplantation is beneficial for improving the efficacy, visual acuity, tear film function, and reducing recurrence rate in patients with pterygium.

Aim To investigate the protective effect of Gualou Guizhi granules(GLGZG)on neuronal injury induced by LPS-activated microglia based on Notch signaling pathway.Methods LPS-activated microglia were co-cultured with neurons to construct neuron inju-ry models,and the cells were divided into the control group,model group,Notch inhibitor(DAPT)group,GLGZG(50,100,200 mg·L-1)group,DAPT+100 mg·L-1GLGZG group.After intervention,the activity of HT22 cells was detected by CCK-8 method,and rel-ative mRNA expression was detected by real-time PCR.The relative protein expression was detected by Western blot.Results Compared with the model group,after GLGZG intervention,the cell activity was significantly improved,GLGZG decreased IL-6,IL-12,Bax,Notch 1,caspase-3,Delta-1,NICD,RBPSUH,HES1 expression,and increased Bcl-2 expression(P＜0.05).Compared with the model group,the NICD,RBPSUH and HES1 mRNA and protein expressions significantly decreased after DAPT treatment(P＜0.05),and there was no superposition effect with GLG-ZG.Conclusion GLGZG may play a neuroprotective role by inhibiting inflammatory factors and apoptosis,and inhibiting Notch signaling pathway.

Objective To observe changes of white matter function in adolescent smoker(AS)with resting-state functional MRI(rs-fMRI)fractional amplitude of low-frequency fluctuation(fALFF)technique.Methods Forty-five adolescents(AS group)and 45 control subjects(control group)were prospectively enrolled,and brain rs-fMRI were acquired.Brain regions with fALFF being different between groups were observed,and the correlations with clinical indicators were analyzed.Results Compared with that in control group,fALFF of the right superior longitudinal fasciculus significantly elevated in AS group(FDR correct Q＜0.05),in which the peak of the cluster was positively correlated with score of Fagerstr?m test for nicotine dependence(FTND)(r=0.294,P=0.049).Conclusion White matter function changed in AS,presenting as significantly increased fALFF in right superior longitudinal fasciculus,which was positively correlated with nicotine dependence.

Objective:To investigate the effect of microRNA-363-5p targeted binding to THBS3 on angiotensin Ⅱ-induced apoptosis in cardiomyocytes and its molecular mechanism.Methods:A human-derived cardiomyocyte cell line(AC16)was used to establish an in vitro cardiomyocyte apoptosis model with angiotensin Ⅱ(AngⅡ),and a dual luciferase reporter assay was performed to detect the relationship between miR-363-5p and THBS3;apoptosis rate was detected by flow cytometry,and real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was performed to detect the relative expression of microR-363-5p,ATF-6mRNA,THBS3mRNA expression;Western Blot to detect the relative expression of caspase-12,caspase-3,GRP78,Bax,Bcl-2.Results:(1)Compared with the control group,the relative expression level of miR-363-5p in AngⅡ group was significantly decreased.(2)Compared with Mir-inhibitor-NC and Mir-mimics-NC groups,the apoptosis rate of miR-inhibitor and miR-mimics groups was significantly increased and decreased,the relative expression level of Bax protein was significantly increased and decreased,and the relative expression level of Bcl-2 was decreased and increased.(3)miR-363-5p targeted binding to THBS3.(4)Compared with the THBS3-OENC group,the relative expression of Bax and caspase-3 proteins was significantly higher,the relative expression of Bcl-2 protein was significantly lower,and the apoptosis rate was higher in the THBS3-OE group.(5)Compared with the negative control group,the relative expression of Bax and caspase-3 proteins in the miR-mimcs+THBS3-OE group was significantly higher,the relative expression of Bcl-2 protein was significantly lower,the apoptosis rate was significantly higher,and the cell viability was significantly lower.(6)Compared with the miR-inhibitor group,the relative expression of GRP78 and caspase-12 was decreased in the miR-inhibitor-4-PBA group,and the apoptosis rate was significantly reduced.(7)Compared with the negative control group,the apoptosis rate was elevated in the ATF-6-OE group,and the relative expression of caspase-12 was significantly increased.(8)Compared with the negative control group,miR-inhibitor+ATF-6 siRNA group showed decreased apoptosis rate and decreased relative expression of caspase-12.Conclusions:MicroRNA-363-5p is able to target binding to THBS3 to regulate myocardial apoptosis,a process that may be mediated through the endoplasmic reticulum stress ATF-6 pathway.

Folate receptor α(FRα),encoded by the FOLR1 gene,is overexpressed in various solid tumors but minimally expressed in normal cells,making it a prime target for anti-tumor therapy.Antibod-y-drug conjugates(ADCs)can accurately deliver cytotoxic agents to tumor cells,enhancing treatment specificity and efficacy.Recent years have seen remarkable progress in the development of FRα-targeted ADCs,with multiple drugs entering clinical trials and demonstrating promising anti-tumor activity and safety.This review covers the latest clinical advances in FRα-targeted ADCs.It provides a detailed in-troduction to the structure and function of FRα,its expression in solid tumors,and the clinical progress of FRα-targeted ADCs.It particularly focuses on the clinical trials of drugs like Mirvetuximab Sor-avtansine,Luveltamab Tazevibulin,and Farletuzumab Ecteribulin.These drugs have shown significant anti-tumor effects in different cancer types,and Mirvetuximab Soravtansine has received FDA accelerated approval.Despite their potential,FRα ADCs face challenges in clinical applications,such as toxicity management,biomarker definition,and clinical translation.Future research should optimize FRα ADC design,including antibody selection,linker stability,and drug load efficiency,and explore their combi-nation with other therapies to enhance efficacy and broaden the therapeutic window.Additionally,in-depth studies on the role of FRα in the tumor microenvironment and its interaction with other signaling pathways will strengthen the theoretical basis for FRα ADC drug development.In summary,the develop-ment of FRα ADC drugs is rapidly advancing and is expected to offer new treatment options for FRα-posi-tive cancer patients.

Aim To study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P＜0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P＜0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.

Objective To investigate the dynamic functional connectivity differences between insomnia patients and healthy controls in triple brain networks[the significant network(SN),the default mode network(DMN),and the executive control network(ECN)]using functional magnetic resonance imaging,and uncover their associations with cognitive ability.Methods Dynamic functional connectivity analysis was performed on functional magnetic resonance imaging data from 40 insomnia patients and 40 healthy controls.The changes in dynamic functional connectivity values were studied for SN,DMN,ECN[including the left executive control network(LECN)and the right executive control network(RECN)];the similarities and differences in time characteristic indicators such as time score,average dwell time,and conversion rate were explored;and their associations with clinical information were analyzed.Results The SN-LECN and DMN-RECN dynamic functional connectivity was significantly higher in insomnia patients than in healthy controls(P=0.013,0.047),while the RECN-LECN and RECN internal functional connectivity strength was lower in insomnia patients than in healthy controls(P<0.001).Additionally,the fractional time in state 2 in insomnia group was significantly higher than that in healthy controls(P<0.001),and it was positively correlated with the Pittsburgh sleep quality index(r=0.524,P=0.001).Conclusion Insomnia patients exhibit significant abnormalities in triple brain network dynamic functional connectivity,which may be related to abnormalities in cognitive control and sensory processing in insomnia patients.These findings provide a new perspective for further research on the neural mechanisms and potential intervention strategies for insomnia.