ObjectiveTo explore the factors influencing home-based rehabilitation exercise and the needs for digital interventions among patients with spinal muscular atrophy (SMA), based on the behavior change wheel (BCW), and to provide evidence for the development of digital home-based rehabilitation interventions. MethodsA two-phase qualitative study was conducted from December, 2024 to March, 2025. Using convenience sampling, 14 participants were recruited, including patients with SMA, primary caregivers, rehabilitation professionals, clinicians, a patient organization representative and a health policy expert. In phase 1, semi-structured individual interviews were conducted with seven participants, including patients, caregivers and a patient organization representative, to identify factors influencing home-based rehabilitation exercise and unmet needs. In phase 2, a focus group involving 12 stakeholders was conducted, including five participants who had participated in phase 1, to explore requirements for the functions, knowledge content and interface design of a digital intervention, five of them had participated in phase 1. Overall, the two phases involved 14 individual participants, accounting for 19 participant-instances. Thematic analysis was performed using both deductive and inductive approaches, guided by the capability-opportunity-motivation-behavior (COM-B) model. ResultsSix themes were identified. phase 1 showed that patients with SMA experienced inadequate continuity of rehabilitation services and limited access to professional rehabilitation resources, with interruptions in institution-based rehabilitation coexisting with declining adherence to home-based exercise. Home-based rehabilitation exercise was jointly influenced by capability-, opportunity- and motivation-related factors, including limited capabilities of patients and caregivers, constraints in time and supportive conditions and insufficient goals, feedback, and incentives. Individualized rehabilitation plans and professional guidance were the major unmet needs. phase 2 showed that the core functions of a digital intervention should include individualized exercise plans, professional guidance and feedback, reminders and incentives, safety monitoring, remote assessment, and privacy and permission management. Core knowledge content should include stratified exercise guidance, caregiving skills, recognition of abnormal conditions, and information on when and how to seek help. The interface should be simple, impose a low user burden and accommodate different types of users. ConclusionHome-based rehabilitation exercise among patients with SMA is jointly influenced by multiple capability-, opportunity- and motivation-related factors. Digital interventions should prioritize individualized rehabilitation plans, professional guidance and sustained behavioral support. These findings may inform the development of a digital home-based rehabilitation intervention prototype for patients with SMA; its feasibility, safety, clinical effectiveness and economic value require further evaluation.

Mycobacterium tuberculosis ( Mtb) is the causative agent of tuberculosis in humans and animals. Mtb invades the host′s lungs via airborne transmission, infects macrophages and causes tuberculosis. In some cases, the infection can spread to other tissues and organs. Despite the availability of several drugs for the treatment of tuberculosis, the emergence of multi-drug-resistant tuberculosis has led to high morbidity and mortality rates worldwide. Therefore, there is an urgent need for researchers to develop new anti-tuberculosis drugs that can treat tuberculosis more efficiently. Recent studies have shown that the virulence factors of Mtb play a crucial role in its pathogenicity. These factors primarily include secreted proteins, transcription factors, proteases, stress response proteins, metabolism-associated proteins, and cell-surface components. By evading the host′s immune surveillance through mechanisms such as anti-oxidative stress, regulating nutrient synthesis and metabolism, and modulating host cells apoptosis, Mtb is able to achieve long-term survival and spread with in the host. Understanding the mechanisms of Mtb virulence factors can provide new directions for targeted tuberculosis therapy. Therefore, knowledge of these virulence factors is essential for the development of new vaccines and anti-tuberculosis drugs. In this review, we summarize the latest research progress in the virulence factors of Mtb to provide a reference for targeted treatment of tuberculosis.

Objective:To investigate the targets and mechanisms of cycloastragenol in ameliorating azithromycin-induced drug-induced liver injury(DILI)based on network pharmacology and in vitro experiment validation.Methods:Potential targets of cycloastragenol and DILI were predicted using databases.The common and key targets were screened and subjected to GO and KEGG enrichment analyses,as well as molecular docking validation.Primary hepatocytes from C57BL/6 mice were isolated.The optimal concentration and time for azithromycin-induced DILI in mouse primary hepatocytes were determined using CCK8 and ROS assays.The expression of genes and proteins such as NF-κB p65,p-NF-κB p65,AMPKα,and p-AMPKα was assessed using RT-qPCR and Western blot to evaluate the intervention effect of cycloastragenol(10-50 μmol/L).Results:Network pharmacology analysis identified 10 key genes related to cycloastragenol's improvement of DILI,including heat shock protein 90AA1(HSP90AA1),matrix metalloproteinase 2(MMP2),etc.GO enrichment analysis suggested that cycloastragenol primarily regulates biological processes such as membrane potential and chemical synaptic transmission,and affects cellular components such as neuronal cell bodies and distal axons,and related kinase activities.KEGG enrichment analysis showed that it mainly exerts intervention effects through neuro-signaling pathways and IL-17 signaling pathways.Molecular docking demonstrated strong binding of cycloastragenol to HSP90AA1,MMP2,NF-κB p65,AMPKα,nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1),with a binding energy≤-5.0 kcal/mol for Nrf2.In vitro experiments showed that azithromycin(50 μmol/L,12 h)significantly reduced hepatocyte viability and increased ROS levels(P＜0.01).Different concentrations of cycloastragenol significantly improved the activity of mouse primary hepatocytes,reduced the generation of intracellular ROS,downregulated the phosphorylation level of NF-κB p65,and upregulated the mRNA and protein levels of AMPKα,Nrf2,HO-1,NQO1(P＜0.05).Conclusions:Cycloastragenol may alleviate azithromycin-induced hepatocyte oxidative stress and inflammation by inhibiting NF-κB phosphorylation and activating the AMPK/Nrf2/HO-1/NQO1 pathway,with its mechanism likely closely linked to targeting Nrf2.However,the complex mechanisms of DILI may involve additional unverified pathways.Therefore,further studies are necessary to validate the efficacy and safety of cycloastragenol in animal models.

Encephalomyocarditis virus(EMCV)is a zoonotic pathogen that causes encephalitis and myocarditis as its primary clinical manifestations.To explore effective preventive measures,this study utilized a Bac-to-Bac expression system to insert the EMCV P12A and 3C genes into the pFastBacDual shuttle vector,resulting in the generation of the recombinant baculovirus Ac-P12A-3C.This facilitated the large-scale expression and purification of EMCV virus-like particles(VLPs),which were correctly assembled into particles of approximately 30 nm in diameter,as ob-served by electron microscopy.Immunization and challenge experiments in mice demonstrated that these VLPs could effectively protect against EMCV infection,achieving a protection rate of 100％.Histopathological sections indicated that,compared to the PBS control group,the VLP immuniza-tion group exhibited significantly reduced tissue damage,along with a marked decrease in viral load within the tissues.In piglets,immunization with the VLPs elicited a robust humoral response,with neutralizing antibody titers reaching 1∶320 to 1∶640 after a second immunization,and no signifi-cant adverse reactions were observed throughout the immunization process.This study preliminarily explores the immunogenicity and safety of the VLP vaccine,laying the foundation for the development of a subunit vaccine based on EMCV VLPs and offering a new strategy for the prevention and control of encephalomyocarditis.

Objective:To assess health-related quality of life and disease burden of Chinese Phenylketonuria(PKU)patients and inform optimized management and support strategies.Methods:A cross-sectional survey is conducted to explore questionnaires.The Delphi method was applied to form a standardized questionnaire.Results:A total of 263 valid questionnaires were collected.The average patient age was 7.6 years.Younger patients reported better quality of life.Mean total medical cost per patient was 238 461.9 yuan,exceeding the 2024 national per capita disposable income.Conclusion:PKU patients are facing significant challenges in both quality of life and economic burden.

Objective:To explore the depressive emotion among students in an international high school as the micro-environment of intercultural context,focusing on the relationships among depression,interpersonal compe-tence and intercultural sensitivity.Methods:Ninety-four tenth-grade students from an international school were se-lected for assessment during their high school stage,encompassing a duration of three years and six semesters(iden-tified as T1 to T6).The severity of depression was assessed with the Self-rating Depression Scale(SDS)six times(T1-T6).The level of interpersonal competence and intercultural sensitivity were measured twice(T1,T5)with the Interpersonal Competence Questionnaire(ICQ)and Intercultural Sensitivity Scale(ISS).Results:The scores of SDS exhibited a discernible pattern from stages T1 to T6,characterized by an initial incline followed by a subse-quent decline(P＜0.01).The SDS scores were negatively correlated with the ICQ scores at T1 and T5(r=-0.48,-0.47,Ps＜0.01)and ISS(r=-0.62,-0.59,Ps＜0.01),but the scores of ICQ(β=-0.20,P=0.057)and ISS(β=-0.02,P=0.897)at T1 were unable to predict SDS scores at T5.Notably,the mediating effects from scores of ISS in the relationship between scores of ICQ and SDS were statistically significant in both the hori-zontal(T1 95％CI:-0.41--0.12;T5 95％CI:-0.53--0.13)and longitudinal contexts(95％CI:-0.42--0.15).Conclusion:The interpersonal competence and intercultural sensitivity in international high school students have a positive significance in alleviating their depression during the adaptation in micro-environment of in-tercultural context.

Objective Network pharmacology and molecular docking techniques were used to predict the potential mechanisms by which the active components of Piper nigrum(PN)regulate depressive-like behaviors in chronic restraint stress(CRS)mice.Methods The major chemical components and targets of PN were screened using the Traditional Chinese Medicine Systems Pharmacology database.Targets related to ferroptosis and depression were obtained from the Online Mendelian Inheritance in Man,GeneCards,and FerrDB databases.The intersecting targets were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway enrichment analyses,and molecular docking was performed to validate the binding capacities between the core targets and their corresponding active components.Finally,we established a CRS mouse model.Mice were treated with PN 75,150,and 300 mg/kg for 4 weeks,followed by behavioral assessments and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)to verify the expression of core genes.Results Nine active components were screened from PN,corresponding to 27 targets,and 8377 targets related to depression and 547 targets associated with ferroptosis were screened from the databases.The intersection of these three sets resulted in 25 target genes.KEGG enrichment analysis revealed that these core targets were predominantly enriched in signaling pathways,including cholinergic synapses,serotonergic synapses,and neuroactive ligand-receptor interactions.Molecular docking result showed that the main active components of PN had strong binding affinities for the targets CHRM2,SLC6A4,PTGS2,and SLC6A2.Behavioral assessments demonstrated that PN significantly increased the sucrose preference index(P＜0.01,P＜0.001),reduced immobility time in the tail suspension and forced swimming tests(P＜0.01,P＜0.001),and enhanced exploratory behavior in the open field test(P＜0.05.P＜0.01,P＜0.001).PN significantly reduced the serum levels of inflammation markers(P＜0.05.P＜0.01,P＜0.001),as shown by enzyme-linked immunosorbent assay,and neurotransmitter analysis revealed that PN significantly increased the levels of serotonin and acetylcholine in the mouse hippocampus(P＜0.05).RT-qPCR showed that PN demonstrated the mRNA expression of SLC6A4(P＜0.05.P＜0.01,P＜0.001).Conclusions PN may improve depressive-like behavior in mice by modulating serotonin and acetylcholine levels,inhibiting inflammatory responses,participating in immune regulation,and exerting neuroprotective effects.

Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.

Objective To investigate the protective effect and mechanism of the antioxidant Lutein in a mouse model of dry age-related macular degeneration(AMD)induced by hydroquinone.Methods Twenty-four specific pathogen-free(SPF)grade male C57BL/6 mice,aged 6-8 weeks,were randomly divided into 3 groups(n=8 per group).The control group was fed a standard diet and water for 3 months.The model group and the drug intervention group received 8 g·L-1 hydroquinone in drinking water combined with a high-fat diet for 2 months to establish the dry AMD mouse model.After modeling,the model group resumed a standard diet and water for 1 month.The drug group received oral gavage daily at 8:00 AM,administered Lutein at 0.1 g per kg body weight(dissolved in distilled water),for 1 month.At the experimental endpoint,all mice were euthanized,and samples were collected for analysis.The ultrastructure of retinal pigment epithelial(RPE)cells was observed by electron microscopy.Serum activities of superoxide dismutase(SOD),catalase(CAT),and glutathione peroxidase(GSH-Px)were measured using a microplate reader.mRNA expression levels of nuclear factor ery-throid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and glutamate-cysteine ligase(GCL)in retinal tissue were de-tected by real-time quantitative PCR.Protein expression levels of Nrf2,HO-1,and GCL in retinal tissue were determined by Western blot.Results In the model group,mitochondria and intracellular organelles in RPE cells exhibited vacuolar de-generation,with compromised structural integrity;simultaneously,microvilli were disorganized and significantly reduced in number.In the drug group,the mitochondrial structure of RPE cells was relatively well-preserved,with morphology largely normal;microvilli structure was clear,and density showed some recovery compared to the model group.Compared to the control group,serum activities of SOD,CAT,and GSH-Px were significantly decreased in the model group(all P＜0.01).Compared to the model group,serum activities of SOD,CAT,and GSH-Px were significantly increased in the drug group(all P＜0.05).Compared to the control group,retinal mRNA expression levels of Nrf2,HO-1,and GCL were significantly decreased in the model group(all P＜0.01).Compared to the model group,retinal mRNA expression levels of Nrf2,HO-1,and GCL were significantly increased in the drug group(all P＜0.01).Compared to the control group,retinal protein ex-pression levels of Nrf2,HO-1,and GCL were decreased in the model group(all P＜0.05).Compared to the model group,retinal protein expression levels of Nrf2,HO-1,and GCL were increased in the drug group(all P＜0.05).Conclusion The antioxidant Lutein promotes the expression of downstream target genes HO-1 and GCL by activating the Nrf2 signaling pathway,which not only enhances the biosynthesis levels of antioxidant enzymes(SOD,CAT,GSH Px),but also effec-tively inhibits oxidative stress response by enhancing autophagic activity.

Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of patients with adrenal diffuse large B-cell lymphoma(DLBCL).Methods·From March 2002 to December 2022,a total of 105 patients with adrenal DLBCL admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival outcomes,and prognostic factors.Patients'gene mutation profiles were evaluated by targeted sequencing of 152 lymphoma-related genes.Results·The median age of the patients was 62(15?82)years and the male-to-female ratio was 2.3∶1.Among them,63 patients(60.0%)were over 60 years old,22 patients(21.0%)had an Eastern Cooperative Oncology Group(ECOG)performance status of two or higher,87 patients(82.9%)were staged Ann Arbor Ⅲ?Ⅳ,92 patients(87.6%)had elevated serum lactate dehydrogenase(LDH)levels(above the upper limit of reference),84 patients(80.0%)had extranodal invasion in at least two organs,67 patients(63.8%)were of non-germinal center B-cell(non-GCB)origin,and 95 patients(90.5%)had an international prognosis index(IPI)scored over 2.With a median follow-up of 28.3(0.7?191.9)months,the estimated 2-year overall survival(OS)rate and progression-free survival(PFS)rate were 68.3%and 53.1%,respectively.The estimated 5-year OS rate and PFS rate were 52.6%and 44.0%,respectively.Among 93 patients who could be evaluated for clinical outcomes,62(66.7%)got a complete response(CR).Univariate analysis and multivariate Cox analysis revealed that age over 60 years was an adverse prognostic factor for PFS,and ECOG performance status of two or higher was an adverse prognostic factor for both OS and PFS.Targeted gene sequencing in 46 adrenal diffuse DLBCL patients showed high mutation frequencies in lysine methyltransferase 2D(KMT2D;n=17,37%),Pim-1 proto-oncogene,serine/threonine kinase(PIM1;n=17,37%),MYD88 innate immune signal transduction adaptor(MYD88;n=15,33%),CD79b molecule(CD79B;n=13,28%),and BTG anti-proliferation factor 2(BTG2;n=10,22%).Conclusion·Age over 60 years is an adverse prognostic factor for PFS,and ECOG performance status of two or higher is an adverse prognostic factor for both OS and PFS in patients with adrenal DLBCL.Patients exhibited high frequencies of KMT2D,PIM1,MYD88,CD79B,and BTG2 mutations,as well as an increased proportion of the MCD-like subtype.