Objectives/Goals: Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies. This study explores whether the Niclosamide derivative HJC0152 can act as an immune modulator to reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy efficacy. Methods/Study Population: Niclosamide-derived HJC0152 was developed as a novel cancer therapeutic and immunomodulating agent. Human and murine TNBC cell lines, as well as primary mouse MDSC cells, were treated with HJC0152. PD-L1 expression in TNBC cells and key immunosuppressive markers in MDSCs (Arg1, Arg2, and iNOS) were evaluated. The immunosuppressive function of MDSCs was further assessed using a T cell co-culture assay. In vivo studies are planned to assess the therapeutic efficacy of HJC0152 in combination with anti-PD-1 therapy using syngeneic TNBC mouse models. Results/Anticipated Results: HJC0152 exhibits improved solubility compared to Niclosamide and displays potent anticancer activity both in vitro and in vivo. RNA-Seq analysis of human TNBC cells treated with HJC0152 revealed significant downregulation of PD-L1 gene expression, which was further validated at the protein level by Western blot analysis. In addition, HJC0152 suppressed Arg1 expression in mouse MDSCs, a key mediator of immunosuppressive myeloid cell function. Together, PD-L1 and Arg1 pathways represent critical mechanisms of tumor immune evasion, and our findings highlight HJC0152 as a promising immune modulatory agent capable of enhancing the efficacy of immune checkpoint blockade in TNBC. Discussion/Significance of Impact: This study presents a novel immunotherapy strategy for TNBC using HJC0152, which downregulates tumor-derived PD-L1 and inhibits Arg1 signaling in MDSCs. As the first investigation of HJC0152 combined with anti-PD-1 in TNBC models, it may support future clinical trials and offer a new therapeutic option for TNBC patients.

The presence of diffuse large B-cell lymphoma (DLBCL) cells in bone marrow (BM) smears is recognised as a key morphological basis for diagnosing BM involvement by DLBCL. BM involvement directly affects disease staging, treatment strategies, and prognosis assessment. Nevertheless, traditional manual identification of DLBCL cells in BM smears under a microscope is time-consuming, subject to observer variability, and lacks standardization between hospitals. In this study, we developed an artificial intelligence (AI) detection system (DLBCL-CQnet) based on deep learning, using BM smears from 117 patients with newly diagnosed DLBCL across four centers. DLBCL-CQnet comprises a region of interest (ROI) classification model based on MobileNetV2, and a cell detection and classification model (CDC-MOD) based on YOLOv8. Performance was evaluated using accuracy, precision, recall, F1-score, and mean average precision at an intersection over union threshold of 0.5 (mAP50). MobileNetV2 achieved the best ROI classification performance (accuracy 0.925, precision 0.922, F1-score 0.919), while YOLOv8 yielded a classification accuracy of 0.890 and an mAP50 of 0.934 for DLBCL cell detection. The system achieved an ROI classification accuracy of 0.925, a cell classification accuracy of 0.890, and a mean average precision (mAP50) of 0.934 at an intersection-over-union (IoU) threshold of 0.5. The optimal cutoff for identifying BM infiltration by DLBCL cells was 2.12%, with a specificity of 0.941 and positive predictive value (PPV) of 0.923, demonstrating high diagnostic value. The recognition speed significantly outperforms manual assessment, substantially reducing time consumption. DLBCL-CQnet enables automated, standardized identification of DLBCL cells in BM smears across institutions, serving as a reliable auxiliary diagnostic tool for assessing BM involvement by DLBCL. Its high specificity and operational efficiency streamline diagnostic workflows, especially in resource-constrained environments.

Chimeric antigen receptor (CAR) T cell therapy is a next generation precision immunotherapy that engineers a patient's own T cells to express synthetic CARs, thereby augmenting tumour cell recognition and cytotoxic activity. Despite transformative clinical success in haematologic cancers, nearly half of treated patients relapse or fail to respond, and the translation of CAR-T therapy to solid tumours remains substantially more challenging. Increasing evidence shows that biomechanical forces, including stretch, compression, shear stress, and extracellular matrix (ECM) stiffness, shape immune activation, trafficking, and effector function through mechanotransduction pathways, ultimately modulating immune responses and disease evolution. Biomechanical cues critically influence CAR-T function, governing target recognition, activation dynamics, and cytotoxic engagement. Furthermore, the mechanical landscape of the tumour microenvironment shapes T cell infiltration, persistence, and exhaustion, thereby constraining CAR-T efficacy. These insights have fueled growing interest in biomechanically informed strategies to optimize CAR-T therapies. Here, we review the biomechanical principles governing CAR-T antitumour responses and highlight how ECM rigidity, shear forces, and other mechanical cues shape CAR-T performance. Biomechanics informed strategies that enhance CAR-T cell antitumour immunity offer a novel conceptual framework for advancing precision cancer immunotherapy. Elucidating how CAR-T cells sense and adapt to the mechanical tumour microenvironment will guide the design of next generation products and accelerate their translation into solid tumour indications.

The coronavirus disease 2019 (COVID-19) pandemic profoundly disrupted the global epidemiology of respiratory syncytial virus (RSV), leading to atypical off-season surges and altering infection dynamics across different climatic zones. This review synthesizes evidence on the landscape of pediatric RSV co-infections in this transformed post-pandemic context. RSV co-infection is frequent, with human rhinovirus (HRV) being the most common viral co-pathogen and Streptococcus pneumoniae (Spn) and Haemophilus influenzae (Hi) predominating as bacterial co-infections. Critically, these co-infections are significantly associated with heightened disease severity, including more intense clinical presentations, prolonged hospitalizations, increased intensive care unit (ICU) admission rates, and greater therapeutic complexity. The relaxation of non-pharmaceutical interventions has been linked to a rebound in co-infection rates. While advances in molecular diagnostics have improved detection, and new prophylactics like nirsevimab offer promise, significant challenges remain. These include gaps in understanding pathogenic synergies, inequities in access to novel interventions, and the need for strategies to manage the ongoing evolution of RSV epidemiology. This underscores the necessity for enhanced surveillance, equitable prevention, and targeted research to mitigate the substantial burden of pediatric RSV co-infections.

Artificial intelligence (AI) is transforming anti-tumor drug discovery by addressing key challenges across the development pipeline. It enables multimodal data integration (genomics, proteomics, and imaging) through advanced frameworks like integrated graph convolutional network (IGCN) and CrossAttOmics, enhancing target identification and biomarker discovery. Generative drug design using generative adversarial networks (GANs), diffusion models, and variational autoencoders accelerates the creation of novel molecules with optimized properties, such as human carboxylesterase 2A (hCES2A) inhibitors to mitigate irinotecan toxicity. AI-driven prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) leverages graph neural networks and organ-on-chip technologies to improve pharmacokinetic profiling and safety assessment. An emerging area is the integration of traditional Chinese medicine (TCM) with AI. Network pharmacology and machine learning (ML) elucidate multi-target mechanisms of TCM compounds (e.g., β-elemene inducing ferroptosis via ferritin heavy chain 1/glutathione peroxidase 4 (FTH1/GPX4) axis). Bayesian optimization and nanoformulations enhance TCM bioavailability. In clinical translation, AI optimizes trials through radiomics for programmed cell death protein 1 (PD-1) response prediction, circulating tumor DNA (ctDNA) analysis for relapse monitoring, and digital pathology. It also addresses drug resistance via single-cell RNA sequencing (scRNA-seq) to identify resistant subclones and TCM agents. Challenges include data heterogeneity, model interpretability, and clinical validation. Future directions focus on interdisciplinary strategies combining quantum computing for molecular simulations, federated learning for data privacy, and AI-personalized TCM formulations. A 2030 roadmap prioritizes building unified TCM-AI databases and target-specific generative algorithms to bridge empirical knowledge with precision oncology.

Virus-associated hematological malignancies have become a key focus in oncology research due to their complex pathological mechanisms and unique immune escape capabilities. In recent years, research in this area has increased with a deeper understanding of the role of viruses in tumorigenesis. However, the immune escape mechanisms in virus-associated hematological malignancies remain incompletely elucidated, posing challenges for the development and optimization of treatment strategies. This review summarizes the roles of various known viruses-particularly Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), human T-cell leukemia virus type 1 (HTLV-1), Kaposi's sarcoma-associated herpesvirus (KSHV), hepatitis B virus (HBV), and hepatitis C virus (HCV) in the pathogenesis of hematological malignancies. It focuses on elucidating how tumor cells utilize multiple immune escape mechanisms to evade host immune surveillance. Simultaneously, incorporating the latest research advances, it delves into cutting-edge therapeutic approaches, including targeting viral proteins, immune checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy, oncolytic viruses, virus-specific T-cell therapy (VST), and therapeutic vaccines. By integrating the molecular mechanisms of virus-associated hematological malignancies with clinical applications, this article aims to provide a theoretical basis and future research directions for precision therapy in this field.

ObjectiveTo investigate and analyze a measles outbreak in an elementary school in Henan province, thereby providing a basis for the prevention and control of measles outbreaks. MethodsOn-site epidemiological investigation and outbreak disposition were carried out for the suspected cases related to this outbreak reported by the China Disease Control and Prevention Information System. Blood and pharyngeal swab specimens were collected from suspected cases and close contacts. Laboratory tests included serological testing, nucleic acid testing, and genotyping for measles virus, and data were analyzed in Excel 2019 software. ResultsAn outbreak of measles in an elementary school was reported in May 2024 in Henan province, with three confirmed cases, two of which were sequenced to be of the B3 genotype. The cases showed typical symptoms such as fever and rash. Among the students in the grades where the cases were located, 75.41% (276/366) had a history of immunization with ≥2 doses of measles component-containing vaccine (MCV) and 8.47% (31/366) had no history of immunization with MCV. The outbreak was effectively controlled after taking emergency vaccination, catch-up vaccination after checking for missed cases, and other measures. ConclusionsThe outbreak is caused by a measles virus strain of B3 genotype, and the dense school population and weak immunization barriers are main factors for this outbreak. In the future, efforts should be made to improve the system of school enrollment vaccination certificate verification and catch-up vaccination, increase the coverage of MCV, and build a strong immunization barrier.

Objectives: To identify factors influencing influenza vaccination willingness and uptake among adults aged ≥60 years in Henan Province and to evaluate the effect of a brief educational intervention on vaccination willingness and behavior. Methods: In September 2024, a cross-sectional survey based on the Behavioral and Social Drivers (BeSD) framework was conducted among adults aged ≥60 years across five counties in Henan. For participants without baseline willingness, a 3 min one-on-one educational intervention was delivered. In May 2025, following the end of the 2024–2025 influenza vaccination season (which runs from 1 October to 31 March in Henan Province), we retrieved vaccination records for all participants from the Henan Provincial Immunization Information System. This system captures all influenza vaccinations administered at designated vaccination clinics across the province. To ensure completeness for doses administered outside the provincial system (e.g., in other provinces or at private healthcare facilities), we conducted telephone follow-up interviews with all participants whose baseline vaccination intention was inconsistent with their actual vaccination behavior (i.e., willing but unvaccinated or unwilling but vaccinated). During these interviews, for those who reported receiving the vaccine outside Henan Province or at private facilities, we inquired about the specific date and location of vaccination to supplement the registry data. We also explored the reasons behind the intention–behavior discrepancy. For these participants, we requested vaccination certificates or other supporting documentation to confirm their vaccination status. Results: Baseline vaccination willingness was 68.20% (1630/2390), whereas the actual vaccination rate was only 6.95% (166/2390), yielding a willingness-to-behavior conversion rate of 9.51% (155/1630) among those with baseline willingness. Of the 760 participants without baseline willingness, 543 (71.45%) completed the 3 min one-on-one instant educational intervention and the follow-up assessment; the remaining 217 were excluded due to refusal or loss to follow-up. Among these 543 completers, 46 (8.47%) became willing to vaccinate, and eight (1.47%) were subsequently vaccinated. Multivariate analysis identified the social processes dimension as the strongest correlate of both willingness (OR = 1.38 per 1-point increase, 95% CI: 1.33–1.44) and uptake (OR = 1.12, 95% CI: 1.03–1.22). Urban residence was associated with higher willingness (OR = 1.41, 95% CI: 1.12–1.78) and higher uptake (OR = 1.64, 95% CI: 1.11–2.42). Current smokers had a significantly lower uptake than never smokers (OR = 0.43, 95% CI: 0.22–0.85). Among the 11 participants without baseline willingness who were eventually vaccinated (eight from the intervention group and three from the non-intervention group), family/friend influence (63.64%, 7/11) and physician recommendation (36.36%, 4/11) were the primary drivers. For those with willingness but no action (n = 1475), the main barriers were perceived good health (33.29%), high vaccine cost (27.12%), and lack of time (26.31%). Conclusions: Influenza vaccination among older adults in Henan exhibits a “high willingness, low conversion” pattern, with social processes as the strongest driver bridging the intention–behavior gap. A brief educational intervention improved willingness but failed to translate into meaningful uptake, underscoring that knowledge transfer alone is insufficient. We recommend a multi-component strategy that (1) mobilizes family members and community doctors as trusted vaccine advocates; (2) leverages family and village doctor networks to reduce urban–rural disparities; (3) counters the “perceived good health” barrier with age-specific risk communication; and (4) integrates vaccine recommendations into routine care for high-risk groups, particularly frequent outpatient attendees and smokers.

Background: This study evaluated vaccine prescription conversion and identified associated factors in Henan Province, China, during 2025. Methods: The study was conducted in Lingbao City, Henan Province. All vaccine prescriptions issued in 2025 were collected, and vaccination status was linked through the Henan Provincial Immunization Information Management System. Subgroup analyses were stratified by vaccine type (NIP vs. non-NIP). Univariate analyses used χ2, Mann–Whitney U, and Kruskal–Wallis H tests. Multivariable analyses employed Firth-corrected logistic regression for conversion behavior, and mixed-effects models with random intercepts for patient ID for conversion timeliness, analyzed using a two-part model. All analyses were performed using R software (version 4.5.3). Results: Among 50,887 prescriptions, the overall conversion rate was 13.8%. NIP vaccines had a higher conversion rate than non-NIP vaccines (76.8% vs. 12.5%, p < 0.001) and a higher same-day conversion rate (13.9% vs. 7.4%; χ2 = 59.585, p < 0.001), but longer delays among non-same-day conversions (23 vs. 4 days). Manual prescriptions were associated with significantly higher conversion in both NIP (OR = 3.913) and non-NIP (OR = 37.720) subgroups. Vaccination clinics were associated with a nearly 20-fold higher odds (OR = 19.386). Interaction analyses showed manual prescriptions were more strongly associated with conversion and shorter delays in older adults, and had stronger associations with conversion for non-NIP vaccines (χ2 = 22.275, p < 0.001). Vaccination clinics were most strongly associated with conversion in children (ΔP = 0.130); however, the improvement in same-day conversion among older adults was relatively smaller, suggesting additional barriers beyond clinic availability may exist in this population. Conclusions: Manual prescriptions and vaccination clinics were associated with higher vaccine prescription conversion, with particularly pronounced effects on non-NIP vaccines. Older adults exhibited the lowest conversion rates. In parallel with promoting electronic prescriptions, co-issuing paper prescriptions is recommended, particularly for non-NIP vaccines and older adults.

Background:Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma and often carries a poor prognosis. Current prognostic systems such as the International Prognostic Index (IPI) and National Comprehensive Cancer Network (NCCN)-IPI do not incorporate patients' nutritional, immune, or inflammatory status, which may affect outcomes. Methods:We retrospectively analyzed 423 newly diagnosed DLBCL patients and collected 12 clinical indicators reflecting nutritional, immune, and inflammatory status. Patients were randomly divided into training and validation sets in a 7:3 ratio. A LASSO-Cox regression model was applied to identify variables for constructing the Nutritional and Immune-Inflammatory Scoring System (NII). The independent prognostic value of NII was evaluated using univariable and multivariable Cox regression analyses. Its added prognostic value was further assessed in combination with the IPI and NCCN-IPI. Results:We developed the NII, including Nutritional Risk Screening 2002 (NRS2002), Geriatric Nutritional Risk Index (GNRI), systemic immune-inflammation index (SII), lactic dehydrogenase to albumin ratio (LAR), β2-microglobulin (β2-MG), and CD8+ T cells. A high NII (≥ 6) effectively identifies high-risk DLBCL patients and serves as an independent prognostic factor beyond other clinical characteristic, IPI, and NCCN-IPI. DLBCL patients with a high NII (≥ 6) exhibit significantly adverse clinical features, including older age, lower frequency of the non-GCB subtype, advanced Ann Arbor stage (III/IV), poor performance status (ECOG PS ≥ 2), involvement of ≥ 2 extranodal sites, presence of B symptoms, elevated lactate dehydrogenase (LDH) levels, and classification into higher-risk groups according to IPI and NCCN-IPI. Combining NII with IPI or NCCN-IPI significantly improves the assessment of patient prognosis compared to using IPI or NCCN-IPI alone. Conclusion:The NII score, integrating readily available nutritional, immune, and inflammatory markers, enhances prognostic accuracy in DLBCL and complements conventional scoring systems. This simple tool may aid in early identification of high-risk patients and guide personalized treatment.

Haematological malignancies are one of the most common tumors, with a rising incidence noted over recent decades. Viral infections play significant roles in the pathogenesis of these malignancies globally. This review delves into the contributions of various known viruses—specifically Epstein-Barr virus (EBV), human immunodeficiency virus (HIV), human T-cell leukemia virus type 1 (HTLV-1), Kaposi’s sarcoma-associated herpesvirus (KSHV), human cytomegalovirus (HCMV), hepatitis B virus (HBV), hepatitis C virus (HCV), and human papillomavirus (HPV)—in the development of haematological malignancies. These viruses are shown to drive tumorigenesis through mechanisms, such as metabolic reprogramming, epigenetic modifications, and remodeling of the immune microenvironment. By directly disrupting fundamental cellular functions and altering metabolic and epigenetic pathways, these viruses foster an immune milieu that supports both viral persistence and tumor growth. A thorough understanding of these viral oncogenic processes is crucial not only for etiological discovery but also for developing targeted interventions. This review emphasizes the need for continued research into the specific ways these viruses manipulate the host cell’s metabolic and epigenetic environments, aiming to provide insights that could guide future advancements in treatment modalities.

Objective:To explore the effect of nursing scheme based on efficacy theory combined with nutritional intervention on patients with multiple myeloma (MM) complicated with renal failure. Methods:Ninety-two patients with MM complicated with renal failure in our hospital from April 2022 to April 2024 were randomly divided into control group (46 cases, using conventional nursing) and observation group (46 cases, using nursing scheme based on efficacy theory combined with nutritional intervention). The CDSES score of self-efficacy, CD-RISC score of resilience, CFS score of cancer-related fatigue, nutrition related indicators (ALB, Hb, PA) and FLIC score of quality of life were compared between the two groups. Results:After the intervention, both groups showed increased CDSES and CD-RISC scores, with the observation group significantly higher than controls. And the levels of ALB, Hb and PA in the observation group were significantly higher than those in the control group. Cancer fatigue scale (CFS) scores at T1, T2, and T3 were reduced from baseline (T0) in both groups; and the observation group was significantly lower than the control group. After the intervention, the scores of the four dimensions of good body and ability, good psychology, difficulties caused by cancer and good society of the two groups were significantly improved, and the scores of the observation group were higher than those of the control group; The scores of nausea dimension in the two groups were significantly lower than those before the intervention, and the control group decreased more than the observation group (p < 0.05). Conclusion:The efficacy theory-based nursing plan combined with nutritional intervention benefits MM patients with renal failure. It improves self-efficacy and psychological resilience, reduces cancer-related fatigue, and enhances nutritional status and overall quality of life.

Acute respiratory infections (ARIs) in children present complex interactions between respiratory pathogens and host, contributing to high morbidity, hospitalization, and mortality. In this cross-sectional study, 2,044 pediatric in-patient samples were tested for 198 pathogens using targeted next-generation sequencing (tNGS). Pathogen spectrum and co-infection pattern were analyzed alongside blood-test results and clinical data. Pediatric ARIs presented staggered viral epidemics and age-specific infection patterns from 2022 to 2023. Viral infections were predominant in children under 3 years (67.5%). Specific viral-bacterial co-infections were associated with disease severity, including human metapneumovirus (HMPV)-Streptococcus pneumoniae (OR = 3.172, 95% CI: 1.257-8.009), human parainfluenza virus (HPIV)-Fusobacterium nucleatum (3.016, 1.051-8.653), and HPIV-S. pneumoniae (2.825, 1.007-7.927). Subnormal levels of prealbumin and creatinine served as biomarkers for homeostasis disruption in viral-bacterial co-infections. From June to December 2023, Mycoplasma pneumoniae (MP) became the dominant pathogen in preschool (31.3%) and school-age (45.3%) children. High MP loads were correlated with elevated eosinophil, IL-4, and IL-6 and decreased IgG and IL-2, linking to airway hyperreactivity and inflammation. At low MP loads, patients co-detected with human herpesvirus (HHV) (50.0%), or Haemophilus influenzae (40.0%) had a high proportion of severe cases. This study delineated the complex pathogen landscape of pediatric ARIs and highlighted the major role of viral-bacterial and MP-bacterial co-infections. Monitoring these pathogens through tNGS can aid in precise diagnosis and targeted treatment to improve clinical outcomes in children.IMPORTANCEMoving beyond the outdated "one germ, one disease" model, this study characterizes the etiological and epidemiological landscape and highlights co-infection patterns of virus-bacterium or MP-bacterium in 2044 pediatric respiratory in-patient children across three epidemic phases. Specific pathogen combinations are associated with clinical severity, as well as host immune and metabolic profiles. Our findings underscore the necessity of detecting pathogen-pathogen and host-pathogen dynamics, rather than individual pathogens, thereby informing precision diagnostics and targeted intervention strategies.

Background: Human immunodeficiency virus (HIV)-associated lymphomas (HAL), mainly aggressive B-cell lymphomas, pose a significant challenge in cancer research due to their multifaceted pathogenesis and aggressive clinical course. Despite the clinical importance, the genomic and immune characteristics of these lymphomas remain poorly elucidated. Methods: We employed single-cell RNA sequencing (scRNA-seq) on lymph node samples from aggressive B-cell lymphomas, mainly including 6 cases of diffuse large B-cell lymphoma (DLBCL) and 5 cases of Burkitt lymphoma (BL) from people living with HIV (PLWH), along with 3 DLBCL cases from individuals without HIV for comparison. Results: Malignant B cells in HAL consistently exhibited high proliferative and oxidative phosphorylation (OXPHOS)-type metabolic signatures. Moreover, these cells demonstrated loss expression of major histocompatibility complex class I (MHC-I), strategically reducing tumor immunogenicity. HAL harbors special populations of naive and atypical memory B cells that exhibited high metabolic and immune-activated transcriptional profiles. Additionally, HAL exhibited senescence-like dysfunction in T cells, characterized by the reductions in regulatory activity of Treg and cytotoxic activity of CD8+ T cells, as well as decreases expression of IL7R genes and increases expression of FOS and FOSB genes. Our immunofluorescence results showed that the cytotoxic CD8+ T cells in HAL may have a dysfunction of lytic granule polarization. Furthermore, macrophages from HAL exhibited stronger immunosuppressive transcriptional characteristics, and a robust immunosuppressive SPP1-CD44 interaction was predicted between C1QA+ macrophages and T cells. Conclusions: Our findings clearly indicate that HAL differs significantly from non-HAL, ranging from malignant B cells to the immune microenvironment. This study provides a comprehensive single-cell atlas of HIV-associated aggressive B-cell lymphomas, offering new insights into aggressiveness and immune evasion observed in HAL.

Objective To explore the clinical characteristics, treatment, and prognosis of patients with newly diagnosed plasmablastic lymphoma (PBL). Methods The clinical data of 13 newly diagnosed PBL patients admitted to Chongqing University Cancer Hospital from January 2013 to June 2024 were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier survival curve and Log-rank test. Univariate and multivariate Cox regression model analyses were used for analyzing prognostic factors. Results ①The number of male and female cases was 10:3. The median age was 52.15 (26-78) years old. Six cases (46.1%) had extranodal organ involvement as the initial symptom, including 3 cases (23.1%) of oral and maxillofacial region. There were 7 cases (53.9%) in Ann-Arbor stage Ⅰ~Ⅱ and 6 cases (46.1%) in stage Ⅳ. Six cases (46.1%) had B symptoms. Two cases (15.3%) had an IPI score ≥3. Nine cases (69.2%) had elevated peripheral blood EB-DNA detection. One case had bone marrow invasion (7.7%), and one case had central nervous system invasion. ②All patients expressed CD38, CD138, and MUM-1. B-cell markers such as PAX-5 and Bcl-6 were occasionally seen. Six cases (46.2%) had positive EBER detection. ③All 13 patients received chemotherapy, and 3 cases received combined radiotherapy. The median follow-up was 48.31 (16-141) months. The median OS was 33.08 (11-79) months, and the median PFS was 25.62 (2-79) months. ④Seven cases received the EPOCH regimen, 6 cases received the CHOP or CHOP-like regimen. Five cases received new drugs in the first-line treatment (3 cases combined with bortezomib, 1 case combined with lenalidomide, and 1 case combined with a PD-1 inhibitor). Three cases received combined local radiotherapy. After first-line treatment, 5 cases had a CR evaluation, 6 cases had a PR evaluation, 1 case had SD, and 1 case had NA. ⑤The best efficacy evaluation: 5 cases had CR, 7 cases had PR, and 1 case had NA. The combination of new drugs and autologous stem cell transplantation (ASCT) in the first-line treatment had obvious benefits, but the use of new drugs such as Lenalidomide and Selinexor in the third-line and above had poor effects. ⑥Kaplan-Meier analysis showed that the overall survival of PBL was significantly related to IPI score 3-5, B symptoms, and male gender (P<0.05). According to univariate COX regression analysis, for newly diagnosed PBL, anemia (≤120g/L) and IPI score 3-5 were factors for poor prognosis of PFS. IPI score 3-5 was a factor for poor prognosis of OS. Combined HIV infection had no significant impact on prognosis. Conclusions For PBL treated through standardized treatment, the impact of HIV infection on prognosis can be overcome. At initial diagnosis, anemia (≤120g/L) and IPI score 3-5 are factors for poor prognosis of PFS in PBL. IPI score 3-5 is a factor for poor prognosis of OS. The first-line treatment choice of combining new drugs (Bortezomib, Lenalidomide, PD-1 inhibitor) and ASCT is expected to improve the prognosis of PBL.

Backgrounds Our previous study revealed that HIV+ DLBCL patients exhibit senescent-like dysfunction in CD8+ T cells. While it is known that fatty acid metabolism regulates cellular senescence through pathways such as oxidative stress and inflammation, whether fatty acid metabolism is dysregulated in CD8+ T cells of HIV+ DLBCL patients and its potential role in modulating cellular senescence remains unexplored. Methods Gene expression profiling of GSE17372 (13 HIV+ DLBCL tumor) and GSE10846 (414 HIV- DLBCL tumor) from the Gene Expression Omnibus (GEO) database was analyzed to get differentially expressed fatty acid metabolism-related genes (DEFAMRGs). The enrichment analysis and protein-protein interaction (PPI) networks of DEFAMRGs were established. The relative fractions of 22 immune cell types were detected using the “CIBERSORT”. The correlation analysis between DEFAMRGs and immune cells was constructed to discover the potential DEFAMRGs associated with immune cells. Oil red O staining and Nile red staining were used to assess lipid droplets in CD8+ T cells from HIV⁺ DLBCL and HIV⁻ DLBCL patients. Multiplex fluorescence immunohistochemistry (mIHC) and flow cytometry were employed to evaluate CD8⁺ T cell senescence and cytotoxic granule secretion. Cytometric bead array (CBA) was performed to measure senescence-associated secretory phenotype (SASP) in plasma. Correlation analysis was conducted to determine the relationship between lipid droplet accumulation and cellular senescence in CD8⁺ T cells. Results We identified 66 differentially expressed fatty acid metabolism-related genes (DEFAMRGs) between HIV+ DLBCL and HIV- DLBCL tissues, including 27 upregulated and 39 downregulated genes. GO analysis revealed that DEFAMRGs were primarily enriched in pathways related to fatty acid metabolic processes, long-chain fatty acid metabolism and fatty acid biosynthetic processes. KEGG analysis indicated significant enrichment of DEFAMRGs in the PPAR signaling pathway, Rap1 signaling pathway, and fatty acid degradation pathway. Additionally, we identified ten hub FAMRGs in HIV+ DLBCL, including PTGS2, AKT1, APOE, VEGFA, ALOX5, IL-18, PPARa, SPP1, PPIG, and ABCB1. We also observed a decrease in follicular helper T cells, monocytes, naive B cells, resting dendritic cells, eosinophils, and Tregs in the HIV+ DLBCL microenvironment. In contrast, activated memory CD4+ T cells, resting macrophages, plasma cells, and resting NK cells were increased. Correlation analysis demonstrated that the expression of ABCB1 and IL-18 was associated with the proportion of CD8+ T cells, while APOE correlated with CD4+ T cell proportions in HIV+ DLBCL. Meanwhile, lipid accumulation was significantly elevated in CD8+ T cells of HIV+ DLBCL patients. The surface expression of senescence-associated markers CD27 and CD28 decreased, whereas CD57 expression markedly increased. Additionally, the secretion of perforin and granzyme B was significantly reduced. Plasma levels of senescence-associated secretory phenotype (SASP) (IL-8, IL-33) were also notably elevated in HIV+ DLBCL patients. Further correlation analysis revealed that lipid content in CD8+ T cells was positively associated with surface CD27 and CD28 expression but negatively correlated with CD57. Conclusions In this study, we identified ten types of significantly altered immune cells and ten hub DEFAMRGs in HIV+ DLBCL tissues. These DEFAMRGs may contribute to changes in immune cell populations in the tumor microenvironment of HIV+ DLBCL. Additionally, we observed lipid metabolic dysregulation and senescence-associated phenotypes in CD8+ T cells from HIV+ DLBCL patients. The intracellular lipid content was correlated with CD8+ T cell senescence, suggesting that dysregulated lipid metabolism may play a role in promoting CD8+ T cell senescence in HIV+ DLBCL.

Objective:This study aimed to investigate the duration of hepatitis B surface antibody (HBsAb) level maintenance and characterize the corresponding IgG-H CDR3 repertoire in volunteers exhibiting either ultra-high or extremely low HBsAb levels following hepatitis B virus (HBV) vaccination. Methods:This study was designed to monitor the longitudinal changes in HBsAb levels at multiple time points post-vaccination in healthy volunteers exhibiting either ultra-high or extremely low antibody responses following HBV vaccination. Furthermore, we employed high-throughput sequencing technology to conduct a comprehensive analysis of the compositional differences in the IgG-H CDR3 repertoire. Peripheral blood samples were collected at four distinct phases: pre-vaccination, post-second vaccination, post-third vaccination, and during the follow-up period, to characterize the dynamic changes in the antibody repertoire. Results:The longitudinal analysis revealed distinct patterns in antibody response kinetics between the two groups. In the ultra-high responder cohort, a peak HBsAb level (25,354 ± 17,993 mIU/mL) was observed following the second vaccine dose. This was followed by a gradual decline, with mean levels stabilizing at 11,356 ± 9,098 mIU/mL post-third dose and 4,229 ± 2,694 mIU/mL at the 4-year follow-up. The ultra-high hepatitis B surface antibody level group (Group H) exhibited a decrease in IgG-H CDR3 diversity after the second vaccination, followed by an increase after the third vaccination. Compared to the extremely low hepatitis B surface antibody level group (Group L), Group H showed higher characteristic immunoglobulin heavy chain variable region V gene (IGHV) usage frequencies in the CDR3 repertoire after both vaccinations than before vaccination. Additionally, the average mutation rate of the IgG-H CDR3 repertoire in Group H was slightly higher than that in Group L after the third vaccination. Notably, multiple samples from Group H revealed common conserved CDR3 region motifs associated with HBV, as reported in the literature: "YGLDV", "DAFD", "YGSGS", "GAFDI", and "NWFDP". Conclusion:The prolonged maintenance of ultra-high antibody levels induced by recombinant HBV vaccines in individuals may be closely related to the characteristic IGHV usage and mutation frequency in individual responses. These findings could provide novel insights into the complex mechanisms of HBV vaccines and HBV infection.

Human respiratory syncytial virus (HRSV), a leading cause of paediatric respiratory infections, is a major contributor to global childhood morbidity. The primary objective of this study was to investigate the epidemiology and phylogenetic characterization of HRSV in paediatric severe acute respiratory infection (SARI) cases in Hangzhou. A total of 2,277 paediatric SARI samples were screened for HRSV. Epidemiological trends, including age- specific positivity rates, were analysed. Whole- genome sequencing was performed on 113 HRSV- positive samples (subgroup A n=60, subgroup B n=53) to characterize genetic evolution. Phylogenetic analysis identified viral lineages and evolutionary rates. In silico binding free energy calculations assessed the impact of antigenic site mutations on monoclonal antibody (mAb) binding. In this study, disruptions in transmission patterns and age- specific positivity rates were observed in 2021 and 2023, coinciding with strict COVID- 19 non- pharmaceutical interventions. A novel A.D.3.X lineage, circulating during 2021-2023 and defined by five unique AA substitutions in the G gene, was identified. The emergence of this lineage may have contributed to the observed epidemiological disruptions. In silico binding free energy calculations predicted that antigenic site mutations (N276S and I206M) in local strains reduce binding affinities for mAbs motavizumab and nirsevimab. These results emphasize HRSV's genetic diversification in Eastern China and underscore the necessity for continuous genomic surveillance to track antigenic evolution and refine prevention strategies for high- risk paediatric populations.

Knowledge gaps exist on whether SARS-CoV-2 co-infection alters recombination frequency or induces phylogenetic incongruities in endemic β-coronaviruses (HCoV-OC43, HCoV-HKU1), limiting our understanding of cross-species evolution. Among 7213 COVID-19 and 1590 non-COVID-19 acute respiratory cases (2021–2022) screened via multiplex PCR, β-coronavirus co-infections (SARS-CoV-2 + HCoV-OC43/HKU1) and single HCoV-OC43/HKU1 infections were identified. Whole-genome sequencing (Illumina NovaSeq) was performed. Phylogenies were reconstructed using Bayesian inference (MrBayes). Recombination was assessed via Bootscan analysis (SimPlot). Co-infection prevalence was low (0.51%, mainly HCoV-HKU1: 0.28%, HCoV-OC43: 0.11%). HCoV-OC43 diverged into lineage 1 (genotype K) and a novel recombinant lineage 2 (genotypes F/J/G/I segments), exhibiting accelerated evolution. HCoV-HKU1 remained genetically stable (genotype B). Co-infection status did not influence evolutionary outcomes. While SARS-CoV-2 co-infection may favor transmission of endemic HCoVs, their evolution appears driven by population-level selection, not co-infection. HCoV-OC43 underwent recombination-driven diversification, contrasting sharply with HCoV-HKU1’s stasis, highlighting distinct evolutionary strategies. Integrated genomic and clinical surveillance is critical for tracking coronavirus adaptation.

The coronavirus pandemic in China ended in 2022, and stringent control measures were lifted in 2023. This study investigated the pathogen and endemic characteristics of enteroviruses (EVs) in patients with influenza-like illness (ILI) in Hangzhou, China, in 2023, providing a foundation for the prevention and control of EV infections. Throughout 2023, 3,480 throat swab samples were collected from hospitals across Hangzhou. Among these, 130 were positive for EVs, with a positivity rate of 3.74