Objective To construct a hybrid decision-making model that integrates knowledge-driven and data-driven approaches,and to apply it to the etiological diagnosis of ventricular tachycardia(VT).Methods Clinical practice guidelines,expert consensus documents,and medical literature in the field of ar-rhythmia diseases from 2018 to 2023 were retrieved as knowledge sources.Retrospective electronic medical re-cord data of VT patients from Fuwai Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,from 2013 to 2023 were collected as the dataset.A knowledge-driven model was constructed using a knowledge-rule-based approach to establish clinical pathways.A three-class machine learning model for VT eti-ology diagnosis was developed based on real-world data,and the best-performing model was selected as the rep-resentative of the data-driven approach.The machine learning model was embedded into the decision nodes of the clinical pathway in the form of custom operators,forming the hybrid model.The precision,recall,and F1 score of the three models were evaluated.Results Three clinical practice guidelines were included as knowl-edge sources for the knowledge-driven model.A total of 1305 patient records were collected as the dataset,and five machine learning models were constructed,with the XGBoost model performing the best.The hybrid model adopted a knowledge-driven decision-making framework,embedding the XGBoost model into the decision nodes of a two-level classification.The precision,recall,and F1 scores of the three models were as follows:the knowledge-driven model achieved 80.4％,79.1％,and 79.7％;the data-driven model achieved 88.4％,88.5％,and 88.4％;and the hybrid model achieved 90.4％,90.2％,and 90.3％.Conclusions The hybrid model integrating knowledge-driven and data-driven approaches demonstrated higher accuracy,and all its deci-sion outcomes were based on evidence-based practices,aligning more closely with the actual diagnostic reason-ing of clinicians.Further rigorous validation is needed to assess the feasibility of widely applying the hybrid model in the medical field.

Since the outbreak of novel coronavirus pneumonia(COVID-19)in December 2019,SARS-CoV-2,which is constantly mutating,has brought unprecedented challenges to the field of solid organ transplantation.However,kidney transplant recipients(KTRs)are at high risk of developing severe disease after SARS-CoV-2 infection due to years of immunosuppressants and a variety of complications.This article aims to review the latest diagnosis and treatment progress of kidney transplantation under the current new epidemiological background,so as to provide reference for the subsequent management of KTRs under the new epidemiological background.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Electroencephalogram (EEG) is a non-invasive, high temporal-resolution technique for monitoring brain activity. However, affected by the volume conduction effect, EEG has a low spatial resolution and is difficult to locate brain neuronal activity precisely. The surface Laplacian (SL) technique obtains the Laplacian EEG (LEEG) by estimating the second-order spatial derivative of the scalp potential. LEEG can reflect the radial current activity under the scalp, with positive values indicating current flow from the brain to the scalp (“source”) and negative values indicating current flow from the scalp to the brain (“sink”). It attenuates signals from volume conduction, effectively improving the spatial resolution of EEG, and is expected to contribute to breakthroughs in neural engineering. This paper provides a systematic overview of the principles and development of SL technology. Currently, there are two implementation paths for SL technology: current source density algorithms (CSD) and concentric ring electrodes (CRE). CSD performs the Laplace transform of the EEG signals acquired by conventional disc electrodes to indirectly estimate the LEEG. It can be mainly classified into local methods, global methods, and realistic Laplacian methods. The global method is the most commonly used approach in CSD, which can achieve more accurate estimation compared with the local method, and it does not require additional imaging equipment compared with the realistic Laplacian method. CRE employs new concentric ring electrodes instead of the traditional disc electrodes, and measures the LEEG directly by differential acquisition of the multi-ring signals. Depending on the structure, it can be divided into bipolar CRE, quasi-bipolar CRE, tripolar CRE, and multi-pole CRE. The tripolar CRE is widely used due to its optimal detection performance. While ensuring the quality of signal acquisition, the complexity of its preamplifier is relatively acceptable. Here, this paper introduces the study of the SL technique in resting rhythms, visual-related potentials, movement-related potentials, and sensorimotor rhythms. These studies demonstrate that SL technology can improve signal quality and enhance signal characteristics, confirming its potential applications in neuroscientific research, disease diagnosis, visual pathway detection, and brain-computer interfaces. CSD is frequently utilized in applications such as neuroscientific research and disease detection, where high-precision estimation of LEEG is required. And CRE tends to be used in brain-computer interfaces, that have stringent requirements for real-time data processing. Finally, this paper summarizes the strengths and weaknesses of SL technology and envisages its future development. SL technology boasts advantages such as reference independence, high spatial resolution, high temporal resolution, enhanced source connectivity analysis, and noise suppression. However, it also has shortcomings that can be further improved. Theoretically, simulation experiments should be conducted to investigate the theoretical characteristics of SL technology. For CSD methods, the algorithm needs to be optimized to improve the precision of LEEG estimation, reduce dependence on the number of channels, and decrease computational complexity and time consumption. For CRE methods, the electrodes need to be designed with appropriate structures and sizes, and the low-noise, high common-mode rejection ratio preamplifier should be developed. We hope that this paper can promote the in-depth research and wide application of SL technology.

Objective To investigate the mechanism by which Senegenin(SEN)alleviates microglial inflammatory response through the nuclear factor erythroid 2-related factor 2(Nrf2)/NOD-like receptor protein 3(NLRP3)pathway.Methods BV2 mouse microglia cells were randomly divided into control group,model group,SEN group and MCC950 group.Cells in control group were not treated,and cells in model group were added with 1 μg/ml lipopolysaccharide(LPS);Cells in SEN group were added with 1 μg/ml LPS+4 μmol/L SEN,and cells in MCC950 group were added with 1 μg/ml LPS+10 μmol/L MCC950 for 24 hours.CCK-8 method was used to detect the effect of different concentrations of SEN on the viability of BV2 cells.Griess method was used to determine the release amount of nitric oxide(NO)in the supernatant.Real-time fluorescent quantitative PCR was used to determine the mRNA expression levels of NLRP3,lymphocyte apoptosis-associated spect-like protein containing a CARD(ASC),caspase-1,interleukin(IL)-1β and IL-18 mRNA.Immunofluorescence staining was used to detect the expression levels of ASC,IL-1β,Nrf2 and heme oxygenase-1(HO-1).Western blotting was used to detect the expression levels of NLRP3,caspase-1,ASC,IL-1β,IL-18,Nrf2,HO-1,nuclear factor kappa B(NF-κB)and inducible nitric oxide synthase(iNOS).Results The results of CCK-8 method showed that there was no significant difference in the viability of BV2 cells treated with 2～20 μmol/L SEN compared with control group(P>0.05).Compared with control group,the viability of BV2 cells in model group decreased significantly(P<0.05).Compared with model group,the viability of BV2 cells in 4 μmol/L SEN group was significantly restored(P<0.05).Compared with control group,the results of Griess method showed that the release amount of NO in cells of model group increased significantly(P<0.05);the results of real-time PCR showed that the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA in cells of model group increased significantly(P<0.05);the results of Western blotting showed that the protein expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 proteins in cells of model group increased significantly(P<0.05),and the immunofluorescence staining results showed that the expression levels of iNOS and NF-κB protein in cells of model group increased,and the expression levels of Nrf2 and HO-1 decreased,with statistically significant differences(P<0.05).Compared with model group,the release amount of NO in cells of SEN group and MCC950 group decreased,and the expression levels of NLRP3,ASC,caspase-1,IL-1β and IL-18 mRNA and proteins decreased,with statistically significant differences(P<0.05);in the SEN group,the expression levels of iNOS and NF-κB decreased,and immunofluorescence staining showed that Nrf2 was translocated into the nucleus,and the expression levels of Nrf2 and HO-1 proteins increased significantly,with statistically significant differences(P<0.05).Conclusions SEN could alleviate the inflammatory response of mouse microglia cells induced by LPS and inhibit the activation and expression of NLRP3 inflammasome,with an effect comparable to that of the inflammasome inhibitor MCC950.The mechanism may be related to the regulation of the expression of upstream factors Nrf2 and HO-1.

Breast cancer is the leading cause of cancer-related mortality among women worldwide and has drawn extensive research attention.Owing to its molecular heterogeneity,drug resistance,and low therapeutic response,single-modality treatments often fail to achieve satisfactory efficacy or broad applicability.Combination therapy,designed based on the pathophysiological characteristics,related signaling pathways,and biomarkers of breast cancer,has emerged as a promising approach for improving therapeutic outcomes.With the advancement of research on combination strategies,the understanding of their molecular mechanisms—particularly key signaling pathways and biomarkers—has become increasingly important.However,comprehensive reviews addressing these molecular mechanisms and synergistic strategies remain scarce.This article summarizes recent advances in combination therapy for breast cancer,providing a comprehensive review of recent combination therapies for breast cancer and their underlying molecular mechanisms,and focusing on key signaling pathways involved in combination therapy and synergistic strategies,thereby providing theoretical insights and reference for researchers,graduate students,and clinicians engaged in the development of novel combination therapeutic strategies for breast cancer and related malignancies.

Although teniposide(VM26)is widely used in the treatment of lymphoma,its poor water sol-ubility,low bioavailability and systemic toxicities still limit its clinical application.Nano-delivery systems are effective in increasing the bioavailability and reducing the toxicity of VM26,but there is an urgent need to overcome the problem of its non-specific targeting.Therefore,in this paper,we designed and constructed a hyaluronic acid-modified teniposide-targeted nano-delivery system(VM26-TNDS),and characterised its drug encapsulation rate,particle size and zeta potential.We also investigated the effects of VM26-TNDS on B-cell lymphoma cells with different expression of CD44 receptor,in terms of cellular targeting,inhibitory effect of proliferation,and induction of apoptosis and necrosis.The results showed that the drug encapsulation efficiency of VM26-TNDS exceeded 85％,and its liquid formulation could be stably stored at 4 ℃ for more than 6 months without precipitation.Based on CD44 receptor expression,Granta-519(high expression),Raji(medium-low expression)and SU-DHL-4(almost no expression)were screened for cellular experiments.Compared with VM26-NDS,the targeted modification could effec-tively reduce the uptake of VM26-TNDS by RAW264.7 and increase the uptake of VM26-TNDS by CD44 receptor-expressing lymphoma cells.The inhibitory proliferative effect and apoptotic necrosis-inducing a-bility of VM26-TNDS were stronger than those of VM26-NDS for Granta-519 and Raji cells,whereas there was no significant difference in the inhibitory effect on proliferation and ability to induce apoptosis and necrosis between VM26-NDS and VM26-TNDS in SU-DHL-4 cells,reflecting the targeting advantage for VM26-TNDS,as expected.However,its toxic effect on B-cell lymphoma cells only reflected the targeting advantage at some concentrations(0.25 μmol/L and 0.5 μmol/L),which met the expectation.The a-bove results indicate that a teniposide-targeted nano-delivery system,VM26-TNDS,has been successfully prepared in this study.VM26-TNDS improves the delivery efficiency of VM26 by targeting human B-cell lymphoma cells expressing the CD44 receptor,thus killing human B-cell lymphoma cells more effectively and overcoming the problem of non-specific targeting in drug delivery to improve the therapeutic effect.Its biological therapeutic effects and mechanisms still need to be proved by more in vitro and in vivo ex-perimental evidence.

Objective:To explore the impulsivity characteristics of patients with attention deficit hyperactivity disorder(ADHD)comorbid with borderline personality disorder(BPD)and the mediating role of emotion regula-tion strategies.Methods:A total of 96 patients with ADHD meeting the diagnostic criteria of the American Diagnos-tic and Statistical Manual of Mental Disorders,Fourth Edition(DSM-Ⅳ)were enrolled,48 of whom had comorbid BPD.Impulsivity was assessed with the Barratt Impulse Scale(BIS)and the impulse control difficulty dimensions of Emotional Regulation Difficulty Scale(DERS).Emotion regulation strategies were evaluated with the Emotion Regulation Questionnaire(ERQ).Results:No significant differences were found between the ADHD with and with-out BPD group in cognitive impulsivity,motor impulsivity,or non-planning impulsivity as assessed with the BIS(Ps＞0.05).However,the ADHD with BPD group showed higher scores on the DERS impulse control difficulty subscale(P＜0.001)and less frequent use of cognitive reappraisal strategies(P＜0.001).Cognitive reappraisal partially mediated the relationship between ADHD with BPD and impulse control difficulties,with an effect size of 25.9％.Conclusion:ADHD patients comorbid with BPD exhibit heightened emotional impulsivity,which might be partially mediated by reduced use of cognitive reappraisal.

The scaphoid bone is one of the important bone of hand,which is frequently injured and difficult to treat in clinical practice.Therefore,it is very important to deeply study the microstructure and biomechanical characteristics of the scaphoid bone for understanding its injury mechanism and optimizing treatment scheme.Microcomputed tomography(micro-CT)provides high-resolution imaging of bone tissue,while finite element analysis can help to simulate the stress distribution and behavioral patterns of the scaphoid bone under various physiological and pathological states.The high-resolution three-dimensional image of the scaphoid bone obtained by micro-CT technology can be used to construct finite element models of real anatomical structure of the scaphoid bone,thus achieving accurate simulation of the mechanical properties of the scaphoid bone.The fusion of these two advanced technologies provides a new perspective for revealing the structural and functional relationships and injury mechanism of the scaphoid bone.Therefore,this paper reviews the anatomical characteristics of the scaphoid bone and its biomechanical behavior in different states,emphasizing the specific applications and advantages of micro-CT and finite element analysis techniques in the study of the scaphoid bone.By summarizing the research findings in recent years,this paper provides novel scientific basis and methods for the diagnosis,treatment,and prevention of scaphoid bone-related disorders.