ObjectiveThis study aims to develop and validate a novel multimodal predictive model， termed criss-cross network（CCNet）-directed graph neural network（DGNN）（CGN）， for accurate assessment of pulmonary nodule progression in high-risk individuals for lung cancer， by integrating longitudinal chest computed tomography（CT） imaging with both traditional Chinese and western clinical evaluation data. MethodsA cohort of 4 432 patients with pulmonary nodules was retrospectively analyzed. A twin CCNet was employed to extract spatiotemporal representations from paired sequential CT scans. Structured clinical assessment and imaging-derived features were encoded via a multilayer perceptron， and a similarity-based alignment strategy was adopted to harmonize multimodal imaging features across temporal dimensions. Subsequently， a DGNN was constructed to integrate heterogeneous features， where nodes represented modality-specific embeddings and edges denoted inter-modal information flow. Finally， model optimization was performed using a joint loss function combining cross-entropy and cosine similarity loss， facilitating robust classification of nodule progression status. ResultsThe proposed CGN model demonstrated superior predictive performance on the held-out test set， achieving an area under the receiver operating characteristic curve（AUC） of 0.830， accuracy of 0.843， sensitivity of 0.657， specificity of 0.712， Cohen's Kappa of 0.417， and F₁ score of 0.544. Compared with unimodal baselines， the CGN model yielded a 36%-48% relative improvement in AUC. Ablation studies revealed a 2%-22% increase in AUC when compared to simplified architectures lacking key components， substantiating the efficacy of the proposed multimodal fusion strategy and modular design. Incorporation of traditional Chinese medicine （TCM）-specific symptomatology led to an additional 5% improvement in AUC， underscoring the complementary value of integrating TCM and western clinical data. Through gradient-weighted activation mapping visualization analysis， it was found that the model's attention predominantly focused on nodule regions and effectively captured dynamic associations between clinical data and imaging-derived features. ConclusionThe CGN model， by synergistically combining cross-attention encoding with directed graph-based feature integration， enables effective alignment and fusion of heterogeneous multimodal data. The incorporation of both TCM and western clinical information facilitates complementary feature enrichment， thereby enhancing predictive accuracy for pulmonary nodule progression. This approach holds significant potential for supporting intelligent risk stratification and personalized surveillance strategies in lung cancer prevention.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

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The symptoms of allergic diseases are complex and changeable, and the pathogenesis is complex and difficult to distinguish, and the prevalence of allergic diseases has gradually increased in recent years. Due to the relative limitations of Western medical treatment, in order to further meet the clinical treatment goals, the "lung being responsible for regulating visceral activities" is now used as the theoretical basis, combined with modern medicine, to explore the pathogenesis and etiological mechanism of this disease. Based on the classics, it is proposed that allergic diseases have four characteristics: "onset of allergies, seasonality of disease onset, diversity of symptoms, and recurrence of recovery", and summarized the etiology and pathogenesis as "stagnation of incubative pathogenic factors and disharmony between the nutritive and defensive levels, imbalance of waterways and obstruction of phlegm and dampness, a dysfunction in the pivotal qi flow leading to malnourishment of the skin and hair, the intermingling of cold and heat leads to the dysfunction of the orifices, a disorder of the blood-governing organs leads to extravasation of blood", and advocated that the treatment should take into account the symptoms, syndromes, viscera, and seasons, and clarify the syndromes, which would provide a new research idea for the exploration of the TCM connotation of this disease.

Currently,there are practical and technical difficulties in the construction of clinical ques-tions in the development of clinical practice guidelines.Clinicians or guideline developers seldom construct clin-ical questions based the actual case scenario,leading to some information loss between structured and actual clinical connotation.To overcome this challenge,we proposed a case-guided questions construction approach,and carried out case research and verification in the formulation of the guideline.We found that this method could more efficiently and scientifically assist the formulation of clinical questions,and provide reference for clinicians or guideline developers.

Objective To investigate the mechanism of Wenhe Decoction in the treatment of febrile seizures through network pharmacology based on NLRP3/Caspase-1/GSDMD signaling pathway;To conduct experimental verification.Methods The active components and targets of Wenhe Decoction were retrieved and screened through TCMSP,BATMAN-TCM,PubChem databases and SwissADME platform.The disease targets of febrile seizures were found in GenCards,OMIM and DisGeNET databases.The intersection targets of Wenhe Decoction and the disease and the active components corresponding to the intersection targets were imported into Cytoscape 3.7.2 software to construct the Chinese materia medica-active components-targets network.The intersection targets were submitted to the STRING database to construct a protein-protein interaction network,and then the intersection targets were imported into the Metascape database for GO and KEGG pathway enrichment analysis.The febrile seizures rat model was established,and Wenhe Decoction of 4.05,8.1 and 16.2 g/kg were given respectively by gavage for 21 days.The rats were placed in batches in(45±0.5)℃constant temperature water bath to induce convulsive seizures,and the convulsive latency time and convulsive duration of rats were recorded.The behavioral differences of mice were observed.The morphology of hippocampal tissue were observed by HE and Nissl staining.The ROS content of hippocampal tissue was detected by DHE fluorescent probe technology.The serum ATP,GABA,Glu,Caspase-1,GSDMD,IL-1β and IL-18 contents were detected by ELISA,and the expression of NLRP3 inflammasome-related protein in hippocampal tissue was detected by Western blot.Results Network pharmacology analysis obtained 98 active components of Wenhe Decoction and 1 838 targets.162 targets were obtained by intersecting with disease targets,the core components for the treatment of febrile seizures were β-sitosterol,quercetin,luteolin,trans-squalene,sitosterol,saponin,etc.,and the core targets were EGFR,TNF,JUN,MTOR,etc.,and mainly through the regulation of inflammatory response,apoptosis,mitochondrial function and energy metabolism,mediating anti-inflammatory pathways such as PI3K-Akt signaling pathway and calcium signaling pathway to exert anticonvulsant effects.The experimental results showed that Wenhe Decoction could prolong the convulsive latency and shorten the duration of convulsions in febrile seizures model rats,decrease the level of convulsions,and the pathological damage of hippocampal tissue was improved and damaged neurons were repaired.The serum contents of ROS,Glu,Caspase-1,GSDMD,IL-1β and IL-18 were significantly reduced,and ATP and GABA contents significantly increased.The protein expressions of NLRP3,ASC,pro-Caspase-1,pro-IL-1β and pro-IL-18 in hippocampal tissue significantly decreased.Conclusion Wenhe Decoction may intervene in febrile seizures rats through NLRP3/Caspase-1/GSDMD signaling pathway,inhibit pyroptosis to reduce the occurrence of neuroinflammation,and then affect the balance of neurotransmitters Glu and GABA to play a role in anti-febrile seizures and prevent brain tissue damage.

Objective To investigate the mechanism of Wenhe Decoction in the treatment of febrile seizures through network pharmacology based on NLRP3/Caspase-1/GSDMD signaling pathway;To conduct experimental verification.Methods The active components and targets of Wenhe Decoction were retrieved and screened through TCMSP,BATMAN-TCM,PubChem databases and SwissADME platform.The disease targets of febrile seizures were found in GenCards,OMIM and DisGeNET databases.The intersection targets of Wenhe Decoction and the disease and the active components corresponding to the intersection targets were imported into Cytoscape 3.7.2 software to construct the Chinese materia medica-active components-targets network.The intersection targets were submitted to the STRING database to construct a protein-protein interaction network,and then the intersection targets were imported into the Metascape database for GO and KEGG pathway enrichment analysis.The febrile seizures rat model was established,and Wenhe Decoction of 4.05,8.1 and 16.2 g/kg were given respectively by gavage for 21 days.The rats were placed in batches in(45±0.5)℃constant temperature water bath to induce convulsive seizures,and the convulsive latency time and convulsive duration of rats were recorded.The behavioral differences of mice were observed.The morphology of hippocampal tissue were observed by HE and Nissl staining.The ROS content of hippocampal tissue was detected by DHE fluorescent probe technology.The serum ATP,GABA,Glu,Caspase-1,GSDMD,IL-1β and IL-18 contents were detected by ELISA,and the expression of NLRP3 inflammasome-related protein in hippocampal tissue was detected by Western blot.Results Network pharmacology analysis obtained 98 active components of Wenhe Decoction and 1 838 targets.162 targets were obtained by intersecting with disease targets,the core components for the treatment of febrile seizures were β-sitosterol,quercetin,luteolin,trans-squalene,sitosterol,saponin,etc.,and the core targets were EGFR,TNF,JUN,MTOR,etc.,and mainly through the regulation of inflammatory response,apoptosis,mitochondrial function and energy metabolism,mediating anti-inflammatory pathways such as PI3K-Akt signaling pathway and calcium signaling pathway to exert anticonvulsant effects.The experimental results showed that Wenhe Decoction could prolong the convulsive latency and shorten the duration of convulsions in febrile seizures model rats,decrease the level of convulsions,and the pathological damage of hippocampal tissue was improved and damaged neurons were repaired.The serum contents of ROS,Glu,Caspase-1,GSDMD,IL-1β and IL-18 were significantly reduced,and ATP and GABA contents significantly increased.The protein expressions of NLRP3,ASC,pro-Caspase-1,pro-IL-1β and pro-IL-18 in hippocampal tissue significantly decreased.Conclusion Wenhe Decoction may intervene in febrile seizures rats through NLRP3/Caspase-1/GSDMD signaling pathway,inhibit pyroptosis to reduce the occurrence of neuroinflammation,and then affect the balance of neurotransmitters Glu and GABA to play a role in anti-febrile seizures and prevent brain tissue damage.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective This study aimed to investigate the effects of silencing Ras homolog family member C(RhoC)on the proliferation,apoptosis,invasion,migration,and epithelial-mesenchymal transition(EMT)of salivary adenoid cystic carcinoma(SACC)and its molecular mechanisms.Methods A total of 27 SACC lesions and normal salivary gland tissues that were surgically resected at Qingdao Municipal Hospital from January 1,2019 to March 1,2024 were selected,and the expression levels of RhoC were detected by Western blot and immunohistochemistry.Three small interfering RNA(siRNAs)were designed to target the RhoC gene sequence,transfected into SACC-LM and SACC-83 cell lines,and evaluated for transfection efficiency.The protein expression levels of RhoC,Rho-asso-ciated protein kinase-1(ROCK1),p38 mitogen-activated protein kinase(p38MAPK),phosphorylated-p38MAPK(p-p38MAPK),twist family bHLH transcription factor 1(TWIST1),E-cadherin,N-cadherin,and Vimentin were com-pared using Western blot.CCK-8 assay,flow cytometry,transwell invasion assay,and wound healing assay were conducted to assess the differences in cell proliferation,apoptosis,invasion,and migration abilities among the groups.Bioinformatics methods were also used to predict possible upstream micro RNAs(miRNAs)of RhoC and their expression levels in SACC.Moreover,dual-luciferase reporter gene experiments were performed to verify the binding sites of miR-138-5p and RhoC.Results RhoC was highly expressed in SACC(P＜0.05).After silencing RhoC,the test group showed a significant decrease in the expression level of ROCK1,p-p38MAPK,TWIST1,N-cadherin,and Vimentin,as well as a significant increase in the expression level of E-cadherin(P＜0.05).No signifi-cant difference in the expression level of p38MAPK was observed(P＞0.05).The cell proliferation,invasion,and mi-gration ability decreased in the test group,whereas the apoptosis rates significantly increased(P＜0.05).miR-138-5p was lowly expressed in SACC,and miR-138-5p mimic can significantly downregulated the luciferase activity of 293T cells after transfection with a RhoC wild-type plasmid(P＜0.05).Conclusion RhoC is highly expressed in SACC,and RhoC silencing may target the downstream ROCK1/p38MAPK/TWISTl signaling pathway,thereby in-hibiting the proliferation,invasion,migration,and EMT of SACC while promoting its apoptosis.On the contrary,miR-138-5p is lowly expressed in SACC and is a potential upstream gene of RhoC,and there may be binding sites between the two genes.