Background Patient-reported outcomes (PROs) are essential for assessing symptomatic adverse events (AEs) from a patient perspective, which significantly impact the quality of life and clinical outcomes in patients with glioma. However, no validated patient-reported outcome measures (PROMs) exist to quantify symptomatic AEs in adult-type diffuse gliomas. Methods The study was conducted in two parts. First, we developed a customised Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) scale for adult-type diffuse gliomas using the Simplified Chinese PRO-CTCAE® item library, informed by initial item screening, patient pilot testing, and a two-round Delphi survey. Delphi experts were recruited through the National Glioma Multidisciplinary Team (MDT) Alliance (NGMA) and invited by email in June 2022 (1st round) and August 2022 (2nd round). We subsequently conducted a multicentre, prospective, observational cohort study (VERONICA) at 13 glioma treatment centres in China between September 2022 and March 2025. Eligible participants were adults aged 18 years or older with a diagnosis of adult-type diffuse glioma, who were able to understand and complete the questionnaires; patients with severe cognitive impairment, severe language dysfunction, or other conditions precluding questionnaire completion were excluded. The primary outcome was the psychometric performance of the customised PRO-CTCAE scale, including test-retest reliability, convergent validity, known-groups validity, and responsiveness, evaluated longitudinally across repeated study visits. VERONICA is registered with ClinicalTrials.gov, NCT05486923. Findings For the Delphi survey, all seven invited experts from six centres participated in 1st round (response rate 100·0%), with moderate agreement in symptom rankings (Kendall's W = 0·415; p < 0·001). In 2nd round, 16 of 20 invited experts from 14 centres participated (response rate 80·0%), with consistent agreement in expert ratings (Kendall's W = 0·351; p < 0·001). The final version of the customised PRO-CTCAE scale comprised 53 items covering 31 symptoms, together with one open-ended free-text item. For VERONICA, 450 participants were enrolled across 13 glioma treatment centres. Mean age was 49·1 years (SD 12·8), and the mean Karnofsky Performance Status (KPS) at baseline (Visit 2) was 72·2 (SD 17·1). 424 provided data eligible for at least one prespecified psychometric analysis. Test-retest reliability was acceptable (intraclass correlation coefficient [ICC] ≥0·70 for 47 of 53 items). Convergent validity was supported by correlations in the expected direction with matched European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) domains, with predominantly moderate-to-strong associations (25 items with r ≥ 0·50). Known-groups validity was supported by discrimination between KPS <70 and ≥70 (Cohen's d ≥ 0·20 for 49 of 53 items; p < 0·05 for 43 of 49 items). In Global Impression of Change (GIC)-anchored responsiveness analyses, 37 items showed standardised response means (SRMs) ≥0·20 among participants reporting worsened overall status. Interpretation The customised PRO-CTCAE scale showed robust psychometric performance for adult-type diffuse gliomas. Remote, longitudinal administration supports low-burden quantification of patient-reported symptomatic AEs in clinical trials and routine neuro-oncology practice. Future work should assess implementation in routine care and clinical trials, and extend translation, cultural adaptation, and validation across different languages. Funding Beijing Medical Award Foundation; Shanghai Municipal Health Commission; Department of Science and Technology of Ningxia Hui Autonomous Region; Huashan Hospital, Fudan University (Clinical Research Project).

OBJECTIVES:WHO grade 4 astrocytomas are associated with poor prognosis, and their prognostic factors remain controversial. This study aimed to identify the prognostic factors and develop a management algorithm for these patients. METHODS:This study retrospectively included 151 CNS5 adult grade 4 astrocytomas from two medical centers. The tumors were classified as histologic grade 2/3 astrocytomas with CDKN2A/B homozygous deletion (molecular grade 4 astrocytoma, MA4), histologic grade 4 astrocytomas with CDKN2A/B homozygous deletion (molecular and histologic grade 4 astrocytoma, MHA4), and histologic grade 4 astrocytomas without CDKN2A/B homozygous deletion (histologic grade 4 astrocytoma, HA4). Prognostic factors were identified and incorporated into recursive partitioning analysis (RPA) for survival risk stratification. RESULTS:Histologic grade 4 astrocytomas with CDKN2A/B homozygous deletion, postoperative tumor volume (TV), and chemoradiotherapy were associated with patient survival. RPA identified three groups with distinct prognoses (p = 0.001). Group 1 had a median overall survival (OS) of 77.8 months, consisting of MA4 and HA4 with postoperative TV on FLAIR ≤ 28.5 mL. Group 2 had a median OS of 32.2 months, including MA4 and HA4 with postoperative TV on FLAIR > 28.5 mL receiving chemoradiotherapy, or MHA4 with postoperative TV on FLAIR ≤ 28.5 mL. Group 3 had a median OS of 14.9 months, including MA4 and HA4 with postoperative TV on FLAIR > 28.5 mL without chemoradiotherapy, or MHA4 with postoperative TV on FLAIR > 28.5 mL receiving chemoradiotherapy. CONCLUSION:Histologic grade 4 astrocytomas with CDKN2A/B homozygous deletion confer the worst survival. Maximal or complete resection, as assessed on FLAIR images, is critical to improving outcomes.

OBJECTIVE:Sublobectomy is a modified surgical paradigm based on anatomical lobectomy, incorporating functional boundaries to extend resection safely, particularly for glioblastoma, a highly aggressive brain tumor. This study aimed to evaluate the efficacy and safety of sublobectomy and its prognostic value within the Response Assessment in Neuro-Oncology (RANO) categories for extent of resection. METHODS:Building on their clinical practice, the authors established a sublobectomy standard defined by lobe-specific anatomical boundaries complemented by functional mapping limits and applied it across the frontal, temporal, parietal, and occipital lobes. In this retrospective single-center study, 989 IDH-wildtype glioblastoma cases were analyzed, and 401 met the anatomical criteria for sublobectomy. After excluding cases with residual contrast-enhancing (CE) tumor or incomplete postoperative chemoradiotherapy, 331 cases were included. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize confounding biases. Survival outcomes were assessed using Kaplan-Meier survival analysis and Cox proportional hazards models, while functional outcomes were evaluated using Karnofsky Performance Status, Boston Diagnostic Aphasia Examination, and Eastern Cooperative Oncology Group scores. RESULTS:Sublobectomy significantly improved overall survival (OS) and progression-free survival (PFS) compared to CE tumor resection (median OS: 25.6 vs 18.1 months [p < 0.001], median PFS: 17.0 vs 12.0 months [p < 0.001]). These findings remained consistent after IPTW and PSM analyses. Functional assessments showed no additional risks to quality of life, physical performance, or language function. In RANO class 1 patients, sublobectomy also significantly improved OS and PFS. Subgroup analyses revealed greater survival benefits in patients with TERTp mutations or MGMTp methylation. Maximal safe edema resection emerged as a key factor for improved outcomes. CONCLUSIONS:Sublobectomy is a functionally optimized supramaximal resection strategy with favorable safety and significant survival benefits for glioblastoma patients.

PURPOSE:Glioma progression is often accompanied by language dysfunction, and postoperative recurrence is nearly inevitable, especially in high-grade cases. This study aimed to identify valuable language-based prognostic markers and improve risk management strategies. METHODS:A retrospective longitudinal cohort of 191 glioma patients (2010-2018) was analyzed. Language status was assessed using the Aphasia Battery of Chinese (ABC), adapted from the Western Aphasia Battery. Principal component analysis (PCA) addressed collinearity in language scores, and Cox regression identified predictors for a survival model. Bootstrap validation and SHapley Additive exPlanations (SHAP) were used to confirm model stability and interpretability. Logistic regression was used to test associations between predictors and pathological molecular parameters. RESULTS:Auditory verbal comprehension & writing and repetition emerged as key language predictors in the Cox model, achieving an AUC of 0.834. SHAP analysis confirmed their dominant contribution, defining the model as the Language Tests Combinations (LTC) model. Two-sample t-tests revealed significant differences in language scores between IDH1/2-mutant and wild-type groups. Logistic regression showed strong correlations between language predictors and molecular parameters (MGMT codeletion: AUC = 0.922; 1p/19q: AUC = 0.813; IDH1/2: AUC = 0.748), with tumor locations included as dummy variables. CONCLUSION:Language components were identified as robust predictors of glioma recurrence and were significantly associated with key molecular features. The LTC model represents an internally validated and interpretable exploratory prognostic framework that may complement existing risk-stratification approaches and inform future studies on postoperative glioma management.

BACKGROUND:Glioma, a prevalent cancer in the elderly, is highly malignant, with a poor prognosis and frequent recurrence, causing significant burden on individuals and society. We aimed to develop pre- and postoperative models for predicting short-term recurrence in elderly glioma patients and investigate associated risk factors. METHODS:Based on our largest known sample size, we retrospectively assessed in great detail patients with gliomas who underwent initial surgical resection and were aged over 60 between 2010 and 2018. Finally, two eligible study cohorts comprising 447 and 463 patients were recruited to develop Logistic regression models and Cox models for predicting short and long-term recurrence or death, respectively. Subgroup analyses were performed based on key molecular markers (MGMT promoter methylation and IDH mutation status) and the IDH-wild-type glioblastoma subgroup. RESULTS:Preoperative and postoperative predictive models for short-term recurrence or death achieved an accuracy of 0.70 and 0.82, respectively. By utilizing the preoperative model, we effectively classified patients into high, medium, and low short-term recurrence risk groups, with median progression-free survival (PFS) durations of 125, 224, and 370 days, respectively. Several risk factors for short recurrence were identified, including tumors infiltrating the corpus callosum, preoperative muscle weakness and TP53 mutation. Long-term recurrence risk was associated with symptoms such as drowsiness, numbness or tingling, and diminished enjoyment of life, as determined from the MDASI-BT questionnaire. Subgroup analyses revealed that risk factors for recurrence were highly subtype-specific. CONCLUSION:Both pre- and postoperative models successfully predict short-term recurrence in elderly glioma patients. Key clinical risk factors, such as tumors infiltrating the corpus callosum and various tumor-related symptoms were identified. Additionally, certain common postoperative physical and psychological symptom changes in the MDASI-BT may be predictive markers for long-term relapse. A crucial finding is that the factors associated with recurrence are distinct across molecular subtypes, underscoring the need for subtype-specific risk management.

BACKGROUND: The presence of isocitrate dehydrogenase (IDH) mutations and 1p/19q codeletion significantly influences the diagnosis and prognosis of patients with lower-grade gliomas (LGGs). The ability to predict these molecular signatures preoperatively can inform surgical strategies. This study sought to establish an interpretable imaging feature set for predicting molecular signatures and overall survival in LGGs. METHODS: A cohort of 113 patients with grade 2 or 3 glioma (66 with mutated IDH and 47 with wild-type IDH) was analyzed. The feature set, chief complaints, and onset symptoms were integrated into a logistic regression model to predict IDH mutation and 1p/19q codeletion statuses. Receiver operator characteristic and area under the curve analyses were performed. The predictive model was externally validated using a public database from The Cancer Genome Atlas. RESULTS: Smooth nonenhancing margin and pial invasion were significant predictors of IDH mutation, with odds ratio values of 3.55 (P = 0.03) and 7.89 (P = 1.0 3 10L3), respectively. Using the Visually Accessible Rembrandt Images feature set alone to predict IDH mutation status yielded an area under the curve value of 0.83, which increased to 0.85 and 0.87 when incorporating clinical information and onset symptoms for predicting IDH mutation and 1p/19q codeletion, respectively. CONCLUSIONS: Gliomas with IDH mutations were more likely to exhibit smooth nonenhancing margins and pial invasion. In clinical practice, imaging prediction allows for the assessment of IDH mutation to shift from a postoperative outcome to a preoperative guidance indicator, facilitating more precise treatment for patients with LGGs.

Molecular biomarkers have become an essential part of the diagnosis of adult-type diffuse glioma. Still, complex detection methods and long-term turnaround for these biomarkers hinder integrated diagnosis in clinical practice. We hypothesized that IDH and TERT promoter (TERTp) mutations play similar roles in accurately classifying adult-type diffuse glioma compared to the complicated WHO CNS5-recommended biomarkers, and the detection of IDH and TERTp mutations should be the first layer in clinical practice. We propose a novel layered diagnostic scheme for adult-type diffuse gliomas, with IDH and TERTp mutation detection as the initial layer. We also developed a rapid intraoperative testing technology capable of detecting TERTp and IDH mutations within 35 min. This study involved both a retrospective cohort and a prospective multicenter diagnostic test. The diagnostic accuracy of the layered approach was evaluated using sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC), with a 95

Isocitrate dehydrogenase wildtype (IDHwt) histologic grade 2 adult diffuse gliomas represent a highly heterogeneous entity, and the effects of postoperative adjuvant temozolomide (TMZ) therapy, as well as the predictive value of chemotherapy-related biomarker O6-methylguanine-DNA methyltransferase promoter (MGMT-p) methylation, remain to be further investigated. A Discovery dataset, comprising 108 IDH wt histologic grade 2 gliomas obtained from three public resources, was constructed to investigate the impact of TMZ on patient survival. Furthermore, an independent Validation dataset, consisting of 123 IDH wt grade 2 gliomas, was created to validate the effect of TMZ on patient survival. Kaplan–Meier overall survival (OS) analyses and Cox proportional hazard models were used. Multivariable analysis in the validation dataset demonstrated that temozolomide (TMZ) chemotherapy was an adverse independent prognostic factor for survival in patients with histologic grade 2 IDH -wildtype ( IDH wt) gliomas (HR = 2.19, P = 0.033). Subgroup analyses further revealed that the detrimental effect of TMZ was mainly confined to MGMT -p unmethylated tumors (Discovery cohort: TMZ vs noTMZ, median overall survival [OS]: 37.0 vs 130.0 months, log-rank P = 0.005, HR = 1.89; Validation cohort: TMZ vs noTMZ, median OS: 34.4 vs >120 months, log-rank P = 0.004, HR = 3.39). Moreover, in the validation cohort, TMZ therapy remained associated with significantly poorer survival in the NEC (Not Elsewhere Classified) subgroup (TMZ vs noTMZ, median OS: 73 vs >120 months, P = 0.017), while in molecular GBMs it did not reach statistical significance but still showed a trend toward worse survival (TMZ vs noTMZ, median OS: 20 vs 30 months, P = 0.37). By comparing multi-omics differences between patient groups, we observed that MMR-related genes were specifically downregulated in IDH wt grade 2 gliomas at both the single-cell and bulk transcriptomic levels. The therapeutic benefit of TMZ in IDHwt histologic grade 2 gliomas appears to be limited, with even a potential adverse impact on survival. Therefore, postoperative use of TMZ as a recommended chemotherapy should be approached with caution in these patients, particularly in cases with unmethylated MGMT -p, where alternative treatment strategies are warranted. High MGMT expression and specific downregulation of MMR-related genes may represent key factors underlying the limited efficacy of TMZ in IDH wt, MGMT -p unmethylation grade 2 gliomas. III.

Background:Glioma research has increasingly emphasized quality of life alongside traditional survival metrics, emphasizing functional outcomes, symptom burden, and social reintegration, including the ability to work. While previous studies focused on return-to-work rates, we assessed general work ability as a broader measure of work capacity. We aimed to develop predictive models for general work ability recovery, identify key risk factors, and explore long-term trajectories. Methods:We conducted a retrospective cohort study of 342 patients with glioma (aged 18-64, WHO Grades 2-4) between March 2010 and December 2018. Work ability and symptoms were assessed using the M.D. Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT), which was administered at months 1 and 3 postoperatively, then every three months up to 12 months, and at longer intervals thereafter. Logistic regression predicted 6-month general work ability recovery, and Cox models identified long-term risk factors. Long-term monitoring was conducted to evaluate the stability of work ability recovery across different WHO grades. Results:65.2% (223/342) regaining general work ability within 6 months post-surgery. Brain tumor-specific symptoms were stronger predictors of recovery than general symptoms. Predictive models achieved AUCs of 0.78 (pre-surgery) and 0.82 (post-surgery). Long-term monitoring showed recovery instability, with cumulative recovery rates for WHO Grades 2-4 at 82.1%, 50.8%, and 28.2%, respectively, while peaks at 50.8%, 28.3%, and 7.3%. Conclusions:Brain tumor-specific symptoms significantly impact general work ability recovery. Recovery instability was observed across all patients, underscoring the importance of targeted symptom management, personalized care, and sustained follow-up to improve quality of life.

The oncolytic virus (OV) therapies against recurrent glioblastoma (rGBM) have been shown the promising clinical outcomes with good safety and extended overall survival. However, the genetic profile of OV therapy in rGBM is not clear yet. Here, we report the phase I clinical trial and genetic profiling results of JL15003, a recombinant poliovirus inChinese patients with rGBM. The primary endpoint was the safety with the determination of MTD and/or RP2D. The secondary endpoint was the efficacy evaluation by iRANO. The dose escalation started from a low dose titration at 1 × 106 CCID50 of single dose JL15003 and then followed the standard “3 + 3” designed dose escalation at doses 5 × 106CCID50, 2 × 107 CCID50, and 8 × 107 CCID50. Total 17 patients were involved in this study and received a single dose administration of JL15003. JL15003 was well tolerated and no dose-limiting toxicities (DLTs) were observed until the highest dose (expansion dose) of 8x107 CCID50. No ≥Grade 3 treatment-related adverse event (TRAE) occurred. The most common TRAE (≥10%) were cerebral edema(11.8%). Median overall survival among the patients who received JL15003 was 19.4 months (as of 27 Mar, 2025). Among the 17 patients, 1 patient was complete response, 2 patient waspartial response and 8 patients were stable disease based on iRANO. Genetic profile demonstrates that JL15003 exhibits in tumor tissue no more than four months, with the therapeutic efficacy strongly associated with glioblastoma cellular states (NPC-like, OPC-like, MES-like, and AC-like). Complementary analyses revealed peritumoral microglia may potentiate anti-tumor immunity through enhanced antigen presentation, indicating a dual role of neural microenvironment components in modulating therapeutic outcomes. The study demonstrates that JL15003 is safe and well tolerated in patients with rGBM and the preliminary efficacy has been shown. In addition, the genetic profiling by single cell seq and RNA Seq provides the data for mechanism analysis and proposes the multi-dose administration of JL15003 and the biomarkers for next trial design in patients with rGBM.

Glioblastoma (GBM) is a highly lethal brain tumor resistant to immunotherapy due to poor brain drug delivery and an immunosuppressive microenvironment. This study introduces a macrophage-based adoptive cell therapy that reprograms the tumor immune landscape to suppress GBM growth. We reveal that macrophage homing to GBM is phenotype-dependent, with anti-inflammatory macrophages more efficiently navigating the brain vasculature and targeting tumors. Based on this observation, we developed engineered M2-like macrophages (eM2-Mφs) capable of programmable polarization. These adoptive cells maintain an anti-inflammatory phenotype during early circulation, allowing deep tumor infiltration, and subsequently switch to a proinflammatory state within the tumor to trigger immune activation. Treatment with eM2-Mφs alone, or combined with low-dose irradiation and/or checkpoint inhibitor, remarkably suppressed tumor growth and extended survival in mouse models. This approach offers a promising strategy to overcome GBM's immunosuppressive barriers and enhance immunotherapy efficacy.

Background The endoplasmic reticulum (ER) stress is a crucial toxic signaling event triggered by chronic exposure to Ultraviolet B radiation (UVB), which significantly exacerbate photodamage responses in the irradiated skin. Therefore, the identification of agents capable of inhibiting ER stress could serve as a promising therapeutic strategy for addressing the unmet clinical needs in the treatment of UVB-induced photodamage. Methods A UVB-irradiated mouse model was used and topical administration of Panax ginseng extract was carried out for a duration of 9 weeks. Vitamin E was used as a positive control. After 9 weeks of administration, the skin appearance, epidermal hyperplasia, infiltration of inflammatory cells, apoptosis, and collagen content were measured. The keratinocytes were irradiated with 6 mJ/cm2 UVB to establish an in vitro model. The levels of ER stress and apoptosis were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence. Results Among the 14 extracts derived from 13 distinct plant species that were screened, Panax ginseng, Prunus mume, and Camellia japonica showed inhibitory effect on UVB-induced ER stress. Notably, Panax ginseng effectively inhibits collagen degradation and apoptosis in both irradiated keratinocytes and Balb/C mice skin. Furthermore, the silencing of VMP1 significantly impeded the cellular protective effect of Panax ginseng extract on UVB-irradiated keratinocytes, indicating that Panax ginseng exerts its protective effects through targeted promotion of VMP1. Conclusion Our data suggest that Panax ginseng extract possess a therapeutical effect on UVB radiation-induced photodamage by promoting VMP1-mediated inhibition of ER stress.

PEGylated interferon-alpha (PEGIFNalpha) demonstrates promising therapeutic outcomes against chronic hepatitis B (CHB), whereas patient response to PEGIFNalpha therapy remains unsatisfied. Shutdown of hepatitis B virus (HBV) antigens by RNA interference (RNAi) could enhance PEGIFNalpha efficacy in CHB patients, whereas the underlying immunological mechanisms remain obscure. We performed studies by utilizing our newly established extracellular humanized IFNAR (IFNAR-hEC) mice. An in-house constructed small interfering RNAs (GalNac-siHBV) was administrated to mice either alone or in combination with PEGIFNalpha. The phenotypic and functional characteristics of peripheral and organ-specific immune cells were assessed by flow cytometry, ELISpot, RNA sequencing (RNA-seq), and single-cell RNA-seq (scRNA-seq) analysis. Our results demonstrated that combined treatment with PEGIFNalpha and RNAi exerted a synergistic and prolonged inhibition of HBsAg (~4log10 IU/mL, vs PBS) and induced a higher incidence of HBsAg seroconversion (~30%), comparing with either monotreatment. Mechanistically, combined therapy improved the functionality of global T and B cells, triggered increased anti-HBs producing B cells, and enhanced IFNgamma-producing T cells. scRNA-seq analysis revealed that the combined therapy reduced inhibitory B cell-B cell interaction, enhanced MHC-I signaling mediated T cell-T cell communication, and improved T cell-B cell crosstalk, thus improving the functionality of T and B cells. Enhanced MHC-II signaling networks across B cells and hepatocytes/Cd8+ T cells further promoted HBsAg seroconversion in the combined treatment groups. These results together provided scientific rationale and lessons for the combination of the two towards better therapeutic efficacy. ### Competing Interest Statement The authors have declared no competing interest.

AbstractMolecular features are incorporated into the integrated diagnostic system for adult diffuse gliomas. Of these, copy number variation (CNV) markers, including both arm‐level (1p/19q codeletion, +7/−10 signature) and gene‐level (EGFR gene amplification, CDKN2A/B homozygous deletion) changes, have revolutionized the diagnostic paradigm by updating the subtyping and grading schemes. Shallow whole genome sequencing (sWGS) has been widely used for CNV detection due to its cost‐effectiveness and versatility. However, the parallel detection of glioma‐associated CNV markers using sWGS has not been optimized in a clinical setting. Herein, we established a model‐based approach to classify the CNV status of glioma‐associated diagnostic markers with a single test. To enhance its clinical utility, we carried out hypothesis testing model‐based analysis through the estimation of copy ratio fluctuation level, which was implemented individually and independently and, thus, avoided the necessity for normal controls. Besides, the customization of required minimal tumor fraction (TF) was evaluated and recommended for each glioma‐associated marker to ensure robust classification. As a result, with 1× sequencing depth and 0.05 TF, arm‐level CNVs could be reliably detected with at least 99.5% sensitivity and specificity. For EGFR gene amplification and CDKN2A/B homozygous deletion, the corresponding TF limits were 0.15 and 0.45 to ensure the evaluation metrics were both higher than 97%. Furthermore, we applied the algorithm to an independent glioma cohort and observed the expected sample distribution and prognostic stratification patterns. In conclusion, we provide a clinically applicable algorithm to classify the CNV status of glioma‐associated markers in parallel.

BackgroundSystemic lupus erythematosus (SLE) is a multi-system autoimmune disease that affects multiple organs and cause a wide range of severe clinical manifestations, including lupus nephritis (LN), which is a major risk factor for morbidity and mortality in individual with SLE. Ursolic acid (UA) is a natural compound with favorable anti-inflammatory properties and has been employed to treat multiple disease, including inflammatory diseases, diabetes, and Parkinson's disease. However, its therapeutic potential on LN and the underlying mechanisms remains unclear.PurposeThis aim of this study was to investigate the impact of UA on LN and its underlying mechanism.MethodsMRL/lpr lupus-prone mouse model was used and UA was administered orally for 8 weeks. Dexamethasone was used as a positive control. After 8 weeks of administration, the spleen-to-body-weight ratio, renal function, urine albumin excretion, cytokines levels, and the deposition of immune complex were measured. The primary mouse glomerular mesangial cells (GMCs) and SV40-MES-13 were stimulated by lipopolysaccharide (LPS), either alone or in combination with nigericin, to establish an in vitro model. The activation of NLRP3 inflammasome were investigated both in vivo and in vitro using qRT-PCR, immunoblotting, and immunofluorescence.ResultsOur results revealed that UA prominently alleviated LN in MRL/lpr lupus-prone mice, leading to a significant reduction in proteinuria production, infiltration of immune cells infiltration, and histopathological damage in the renal tissue. In addition, UA exerted inhibitory effects on the secretion of IL-1β, IL-18, and caspase-1, pyroptosis, and ASC speck formation in primary mouse GMCs and SV40-MES-13 cells. Furthermore, UA facilitated the degradation of NLRP3 by suppressing SUMO1-mediated SUMOylation of NLRP3.ConclusionUA possess a therapeutical effect on LN in MRL/lpr mice by enhancing the degradation of NLRP3 through inhibition of SUMO1-mediated SUMOylation of NLRP3. Our findings provide a basis for proposing UA as a potential candidate for the treatment of LN.