Abdominal aortic aneurysm (AAA) is a deadly condition of the aorta, carrying a significant risk of death upon rupture. Currently, there is a dearth of efficacious pharmaceutical interventions to impede the advancement of AAA and avert it from rupturing. Here, we investigated dihydromyricetin (DHM), one of the predominant bioactive flavonoids in Ampelopsis grossedentata (A. grossedentata), as a potential agent for inhibiting AAA. DHM effectively blocked the formation of AAA in angiotensin II-infused apolipoprotein E-deficient (ApoE^-/-) mice. A combination of network pharmacology and whole transcriptome sequencing analysis revealed that DHM's anti-AAA action is linked to heme oxygenase (HO)-1 (Hmox-1 for the rodent gene) and hypoxia-inducible factor (HIF)-1α in vascular smooth muscle cells (VSMCs). Remarkably, DHM caused a robust rise (∼10-fold) of HO-1 protein expression in VSMCs, thereby suppressing VSMC inflammation and oxidative stress and preserving the VSMC contractile phenotype. Intriguingly, the therapeutic effect of DHM on AAA was largely abrogated by VSMC-specific Hmox1 knockdown in mice. Mechanistically, on one hand, DHM increased the transcription of Hmox-1 by triggering the nuclear translocation and activation of HIF-1α, but not nuclear factor erythroid 2-related factor 2 (NRF2). On the other hand, molecular docking, combined with cellular thermal shift assay (CETSA), isothermal titration calorimetry (ITC), drug affinity responsive target stability (DARTS), co-immunoprecipitation (Co-IP), and site mutant experiments revealed that DHM bonded to HO-1 at Lys243 and prevented its degradation, thereby resulting in considerable HO-1 buildup. In summary, our findings suggest that naturally derived DHM has the capacity to markedly enhance HO-1 expression in VSMCs, which may hold promise as a therapeutic strategy for AAA.

Gelsemium elegans (G. elegans) is an extremely poisonous plant that is widely distributed in southern China and southeastern Asia. G. elegans poisoning events occur frequently in southern China, and are therefore an urgent public health problem requiring multidisciplinary action. However, the toxic components and toxicological mechanisms remain unclear. Here, we describe a systematic investigation on the toxic components of G. elegans, resulting in the isolation and identification of 120 alkaloids. Based on acute toxicity screening, the structure-toxicity relationship of Gelsemium alkaloids was proposed for the first time. Moreover, gelsedine- and humantenine-type alkaloids were detected in the clinical blood sample, and were confirmed to be causative in the poisoning. The most toxic compound, gelsenicine (1), had selective inhibitory effects toward ventral respiratory group (VRG) neurons in the medulla, which is the main brain region controlling respiration in the central nervous system. Gelsenicine (1) strongly inhibited the firing of action potentials in VRG neurons through its ability to stimulate GABA_A receptors, the main receptors involved in inhibitory neurotransmission. Application of GABA_A receptor antagonists successively reversed action potential firing in gelsenicine (1)-treated VRG neurons. Importantly, the GABA_A receptor antagonists securinine and flumazenil significantly increased the survival of poisoned animals. Our findings provide insight into the components and mechanisms of G. elegans toxicity, and should assist the development of effective emergency treatments for G. elegans poisoning.

Objective:To investigate the clinicopathological and molecular genetic characteristics of intracranial mesenchymal tumors with FET::CREB fusion transcript.Methods:The clinical and imaging data of 6 cases of intracranial mesenchymal tumors with FET::CREB fusion from December 2018 to December 2023 were collected at the First Affiliated Hospital of Zhengzhou University. Their histological features, immunophenotype and molecular characteristics were analyzed.Results:Among the 6 patients, 4 were males and 2 were females, and the median age was 20 years. The clinical symptoms were increased intracranial pressure in 5 cases and epilepsy in 1 case. The lesion sites were cerebellum (2 cases), frontal lobe (2 cases), parietal lobe (1 case), and cranioorbital communication (1 case). The radiological features mainly showed solid or cystic components, with obvious annular enhancement on MRI. The histopathological features showed a wide spectrum of morphology, clear boundaries and fibrous pseudocapsule. The tumor cells were arranged in a lamellar or nodular pattern, and some in cord or loose network. The tumor cells were spindle, oval, epithelioid or stellate. The stroma was collagenous or mucin-rich, and accompanied by abundant lymphocytes and plasma cells infiltration. By immunohistochemical staining, desmin, CD99 and EMA were expressed in 6 cases, CD68 in 1 case, MUC4 in 1 case, synaptophysin in 2 cases, and ALK in 1 case. The Ki-67 proliferation index was between 1%-15%. Molecular analysis showed EWSR1::ATF1 fusion in 3 cases, EWSR1::CREB1 fusion in 2 cases, and EWSR1::CREM fusion in 1 case.Conclusions:Intracranial mesenchymal tumors with FET::CREB fusion are relatively rare and typically occur in children and younger adults. These tumors have a broad morphological spectrum and often express desmin, CD99 and EMA. The molecular characteristics are the gene fusions of FET family (mainly EWSR1, FUS) with CREB family transcription factors (ATF1, CREB1 or CREM). It is necessary to distinguish these tumors from meningiomas and solitary fibrous tumors, and the combination of immunohistochemical staining and molecular genetic testing can effectively help identify these tumors.

Objective:To investigate the recognition advantage of metaphorical micro-counseling dialogue texts in mental health contexts,and to explore a potential explanatory role of insight.Methods:A total of 104 col-lege students,recruited through a network announcement,were randomly assigned to three groups.In the learning phase,participants read negative cognitions paired with metaphorical or literal solutions and rated the insightfulness of each solution.In the recognition phase,previously unseen solutions were intermixed,and participants judged whether each item had been presented before and rated their confidence.Recognition was assessed after 15 minutes(n=37),1 day(n=33),or 7 days(n=34).Reaction time was recorded,and recognition sensitivity and criterion was calculated using signal detection theory.Results:At three intervals,the scores of insightfulness,recognition sen-sitivity,recognition criterion,and recognition confidence of metaphorical solutions were both higher than those of literal solutions(Ps＜0.001),and the recognition reaction time of metaphorical solutions were all shorter than those of literal solutions(P＜0.001).The insightfulness scores of the solutions were positively correlated with the scores of recognition sensitivity,recognition criterion,recognition confidence,and recognition reaction time(β=0.67,0.13,0.18,-0.39).Conclusion:This study suggests that the use of metaphors in mental health contexts may en-hance long-term memory,with insight playing a significant mediating role in this process.

Objective:To develop CNN-Dinov2, a deep learning-based automatic classification model for Gram-stained images, enabling rapid diagnosis of three prevalent Gram-negative bacilli in bloodstream infections: Escherichia coli ( E.coli), Klebsiella pneumoniae ( K.pneumoniae), and Pseudomonas aeruginosa ( P.aeruginosa). Methods:This evaluation study analyzed 1 425 Gram-stained microscopic images from patients with bloodstream infections at Houjie Hospital, in Dongguan City, collected between January 2023 and January 2024. The images, all positive for blood culture and identified as target strains, were categorized into Escherichia coli (419 images), Klebsiella pneumoniae (411 images), Pseudomonas aeruginosa (413 images), and other Gram-negative bacilli (182 images). They were randomly split into a training set (1 141 images), a validation set (141 images), and a test set (143 images) in an 8∶1∶1 ratio. A hybrid CNN-Dinov2 model was developed by integrating ResNet′s local feature extraction with Dinov2′s global pre-trained features, followed by a fully connected layer. The model was optimized by inputting the preprocessed images and adjusting parameters through loss calculation and backpropagation. AlexNet, Dinov2, and ResNet18 served as control models. The models′ classification performance was assessed using accuracy, precision, weighted F1 score, and recall rate, derived from the confusion matrix. The PR curve and AP value further evaluated each model′s classification capability across the four image categories. Results:The CNN-Dinov2 model achieved a training accuracy of 99.74%, a validation accuracy of 98.12%, and a validation loss of 0.070 6, demonstrating robust generalization without overfitting. Validation metrics revealed superior performance with an accuracy of 98.60%, precision of 98.65%, a weighted F1 score of 98.60%, and a recall rate of 98.60%, outperforming other models. The confusion matrix confirmed its strong classification capability, with the highest sum of diagonal values for identifying four types of bacteria. The macro average precision (AP) values under the precision-recall (PR) curves were all 1, indicating excellent discrimination across all categories. Overall, the CNN-Dinov2 model exhibited the best performance among the four models evaluated.Conclusion:This study successfully developed CNN-Dinov2, an automated classification model for Gram staining images. It offers valuable support for the rapid diagnosis of bloodstream infections caused by Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, demonstrating practical utility.

Purpose To investigate the clinicopathological and molecular genetic characteristics of Warthin-like mucoepidermoid carcinoma(WLMEC).Methods Eight cases of WLMEC were collected.HE staining,immunohisto-chemistry,and fluorescence in situ hybridization were performed to observe their histological morphology,immunophe-notype,and molecular genetic characteristics.Clinical information was analyzed,and follow-up was conducted.Re-sults Among the eight cases of WLMEC,three were male and five were female,aged from 28 to 65 years(median age:47 years),all occurring in the parotid gland.All eight cases had clear boundaries and appeared as polycystic structures.Besides the homogeneously eosinophilic material,blue-stained mucoid material was visible in the cyst cavi-ty.The epithelium was arranged in various ways,including single-layer,double-layer,or multi-layer.The cells had a bland-looking morphology with round or oval nuclei.Compared to Warthin tumor,the cytoplasm was significantly less eosinophilic and flatter.Mitotic figures were rare.A prominent lymphoid stroma with abundant plasma cell infiltration was observed,especially in areas adjacent to the epithelium.The tumor cells expressed CK(AE1/AE3),CK5/6,p63,and CK7.The epithelial arrangement was disordered,unlike the typical double-layered structure seen in Warthin tumor.The Ki67 index ranged from 1％to 5％.MAML2 gene rearrangement was detected in all eight cases.No recur-rence was observed during the follow-up period of 1 to 54 months after surgical resection.Conclusion WLMEC is a rare low-grade malignant tumor originating from salivary glands.Compared with Warthin tumor,patients with WLMEC are younger and more commonly female.The presence of epithelial cells that are not typically arranged in a regular double layer with strong eosinophilia,as well as the abundance of plasma cells beneath the epithelium,serve as impor-tant diagnostic clues.Performing MAML2 gene testing on suspicious cases can aid in the accurate diagnosis of this dis-ease.

Objective:To investigate the effect of metaphorical acceptance-based intervention on alleviating negative emotions in college students.Methods:Totally 112 college students were assigned to the metaphorical in-tervention group(n=40),the non-metaphorical intervention group(n=36),and the control group(n=36).Both intervention groups received online group intervention once a week for 2 weeks,while the control group received no intervention.The Generalized Anxiety Disorder-7(GAD-7),Patient Health Questionnaire-9(PHQ-9),Acceptance and Action Questionnaire-2nd Edition(AAQ-Ⅱ),and a self-report acceptance item were used to assess participants'anxiety,depression,experiential avoidance,and acceptance at baseline,2-week post-intervention,1-week follow-up,and 3-week follow-up.Results:After 2-week interventions,the scores of GAD-7,PHQ-9,and AAQ-Ⅱ in the meta-phorical group were lower than that at baseline,and the scores of self-report acceptance were higher than that at baseline(Ps＜0.01).In the non-metaphorical group,the scores of GAD-7 at 1-week follow-up,the scores of PHQ-9 at 2-week post-intervention and 1-week follow-up,and the scores of AAQ-Ⅱ after 2-week post-intervention were all lower than that at baseline(Ps＜0.05).The scores of self-report acceptance after 2 weeks post-intervention were all higher than baseline(Ps＜0.001).The decrease of scores of AAQ-Ⅱ only mediated the reduction of scores of GAD-7(95％CI=-2.39--0.38)and PHQ-9(95％CI=-2.65--0.44)caused by metaphorical acceptance-based intervention.Conclusion:Online metaphorical acceptance-based intervention may have larger efficacy than non-metaphorical intervention in continuously alleviating anxiety,and the reduction of experiential avoidance plays an important role in alleviating anxiety and depression in metaphorical acceptance-based intervention.

Objective:To investigate the recognition advantage of metaphorical micro-counseling dialogue texts in mental health contexts,and to explore a potential explanatory role of insight.Methods:A total of 104 col-lege students,recruited through a network announcement,were randomly assigned to three groups.In the learning phase,participants read negative cognitions paired with metaphorical or literal solutions and rated the insightfulness of each solution.In the recognition phase,previously unseen solutions were intermixed,and participants judged whether each item had been presented before and rated their confidence.Recognition was assessed after 15 minutes(n=37),1 day(n=33),or 7 days(n=34).Reaction time was recorded,and recognition sensitivity and criterion was calculated using signal detection theory.Results:At three intervals,the scores of insightfulness,recognition sen-sitivity,recognition criterion,and recognition confidence of metaphorical solutions were both higher than those of literal solutions(Ps＜0.001),and the recognition reaction time of metaphorical solutions were all shorter than those of literal solutions(P＜0.001).The insightfulness scores of the solutions were positively correlated with the scores of recognition sensitivity,recognition criterion,recognition confidence,and recognition reaction time(β=0.67,0.13,0.18,-0.39).Conclusion:This study suggests that the use of metaphors in mental health contexts may en-hance long-term memory,with insight playing a significant mediating role in this process.

Objective:To investigate the effect of metaphorical acceptance-based intervention on alleviating negative emotions in college students.Methods:Totally 112 college students were assigned to the metaphorical in-tervention group(n=40),the non-metaphorical intervention group(n=36),and the control group(n=36).Both intervention groups received online group intervention once a week for 2 weeks,while the control group received no intervention.The Generalized Anxiety Disorder-7(GAD-7),Patient Health Questionnaire-9(PHQ-9),Acceptance and Action Questionnaire-2nd Edition(AAQ-Ⅱ),and a self-report acceptance item were used to assess participants'anxiety,depression,experiential avoidance,and acceptance at baseline,2-week post-intervention,1-week follow-up,and 3-week follow-up.Results:After 2-week interventions,the scores of GAD-7,PHQ-9,and AAQ-Ⅱ in the meta-phorical group were lower than that at baseline,and the scores of self-report acceptance were higher than that at baseline(Ps＜0.01).In the non-metaphorical group,the scores of GAD-7 at 1-week follow-up,the scores of PHQ-9 at 2-week post-intervention and 1-week follow-up,and the scores of AAQ-Ⅱ after 2-week post-intervention were all lower than that at baseline(Ps＜0.05).The scores of self-report acceptance after 2 weeks post-intervention were all higher than baseline(Ps＜0.001).The decrease of scores of AAQ-Ⅱ only mediated the reduction of scores of GAD-7(95％CI=-2.39--0.38)and PHQ-9(95％CI=-2.65--0.44)caused by metaphorical acceptance-based intervention.Conclusion:Online metaphorical acceptance-based intervention may have larger efficacy than non-metaphorical intervention in continuously alleviating anxiety,and the reduction of experiential avoidance plays an important role in alleviating anxiety and depression in metaphorical acceptance-based intervention.

Purpose To investigate the clinicopathological and molecular genetic characteristics of Warthin-like mucoepidermoid carcinoma(WLMEC).Methods Eight cases of WLMEC were collected.HE staining,immunohisto-chemistry,and fluorescence in situ hybridization were performed to observe their histological morphology,immunophe-notype,and molecular genetic characteristics.Clinical information was analyzed,and follow-up was conducted.Re-sults Among the eight cases of WLMEC,three were male and five were female,aged from 28 to 65 years(median age:47 years),all occurring in the parotid gland.All eight cases had clear boundaries and appeared as polycystic structures.Besides the homogeneously eosinophilic material,blue-stained mucoid material was visible in the cyst cavi-ty.The epithelium was arranged in various ways,including single-layer,double-layer,or multi-layer.The cells had a bland-looking morphology with round or oval nuclei.Compared to Warthin tumor,the cytoplasm was significantly less eosinophilic and flatter.Mitotic figures were rare.A prominent lymphoid stroma with abundant plasma cell infiltration was observed,especially in areas adjacent to the epithelium.The tumor cells expressed CK(AE1/AE3),CK5/6,p63,and CK7.The epithelial arrangement was disordered,unlike the typical double-layered structure seen in Warthin tumor.The Ki67 index ranged from 1％to 5％.MAML2 gene rearrangement was detected in all eight cases.No recur-rence was observed during the follow-up period of 1 to 54 months after surgical resection.Conclusion WLMEC is a rare low-grade malignant tumor originating from salivary glands.Compared with Warthin tumor,patients with WLMEC are younger and more commonly female.The presence of epithelial cells that are not typically arranged in a regular double layer with strong eosinophilia,as well as the abundance of plasma cells beneath the epithelium,serve as impor-tant diagnostic clues.Performing MAML2 gene testing on suspicious cases can aid in the accurate diagnosis of this dis-ease.