OBJECTIVE:To investigate whether MLKL crotonylation is associated with tubular autophagy-lysosome pathway homeostasis in lupus nephritis (LN) and to explore its relationship with RAB1A-mechanistic target of rapamycin (mTOR) signalling. METHODS:Crotonylome proteomics was performed in peripheral blood mononuclear cells from patients with LN, patients with systemic lupus erythematosus without nephritis and healthy controls. Renal biopsy tissues were evaluated for tubulointerstitial fibrosis and autophagy-lysosome pathway-related markers. Mechanistic studies were conducted in lipopolysaccharide-stimulated HK-2 cells. Autophagic flux was assessed using bafilomycin A1. The dependency of mTOR/autophagy changes on RAB1A was tested by siRNA-mediated knockdown. RESULTS:MLKL was identified as a differentially crotonylated protein in LN, with increased crotonylation at K95 and K219. Kidney tissues from patients with LN showed increased fibronectin and collagen III deposition compared with controls, whereas no significant difference was observed between class IV and class V LN. LC3 signal did not differ significantly between groups, whereas LAMP1 expression and LC3-LAMP1 co-localisation were reduced in LN. In HK-2 cells, crotonylation-deficient MLKL mutants were associated with increased LC3-II and reduced p62, whereas K219Q showed the opposite pattern. Autophagic flux assays using bafilomycin A1 showed that K219R-expressing cells had higher LC3-II levels than WT cells both before and after lysosomal inhibition, with comparable BafA1-induced LC3-II accumulation, consistent with increased autophagosome formation rather than impaired lysosomal degradation. HDAC1 knockdown increased MLKL crotonylation and was accompanied by mTOR activation. MLKL crotonylation enhanced RAB1A guanriphosphat osphate (GTP) binding without altering total RAB1A abundance. RAB1A knockdown in MLKL WT-expressing cells attenuated mTOR phosphorylation and partly reversed the autophagy-suppressive marker profile. Sodium crotonate induced an autophagy-suppressive marker profile that was partly reversed by rapamycin. CONCLUSION:MLKL crotonylation is associated with activation of the RAB1A-mTOR axis and altered tubular autophagy-lysosome pathway homeostasis in LN. These findings suggest that tubular injury-related changes in LN may not be fully reflected by glomerulus-based classification alone.

Objective To compare preconception disease-activity indices—systemic lupus erythematosus Disease Activity Score low disease activity (SLE-DAS LDA), lupus low disease activity state (LLDAS) and SLE-DAS remission—with Definitions of Remission in SLE (DORIS) remission in predicting adverse maternal and fetal outcomes among pregnant women with SLE.Methods This retrospective cohort study included 202 pregnancies in 196 women with SLE managed at Shenzhen People’s Hospital between January 2017 and December 2024. Preconception disease activity was categorised using SLE-DAS, LLDAS and DORIS remission criteria. Main outcomes were maternal flares and fetal outcomes, including spontaneous abortion, therapeutic abortion, total fetal loss, preterm delivery and small for gestational age (SGA). Predictive accuracies of indices were compared.Results Preconceptionally, 127 pregnancies (62.8%) met LLDAS, 131 (64.9%) met SLE-DAS LDA and 78 (38.6%) achieved DORIS remission. Compared with higher disease activity, SLE-DAS LDA was associated with fewer maternal flares (22.1% vs 45.1%) and therapeutic abortions (6.4% vs 15.7%). LLDAS was associated with lower rates of flare (21.3% vs 45.3%), therapeutic abortion (7.9% vs 17.3%), total fetal loss (19.7% vs 34.2%) and preterm delivery (22.0% vs 25.3%). SLE-DAS and DORIS remission performed similarly for maternal outcomes, while DORIS remission correlated more strongly with favourable fetal outcomes, including lower total fetal loss (15.4% vs 31.5%), preterm delivery (15.4% vs 28.2%) and SGA (9.0% vs 19.4%). Multivariable analyses confirmed that achieving these disease-activity states preconception independently protected against total fetal loss, maternal flare and therapeutic abortion. LLDAS was the best overall predictor, while SLE-DAS LDA was the most attainable and predictive for maternal complications.Conclusion SLE-DAS LDA effectively predicts maternal complication, while LLDAS better identifies fetal risk. Remission offers similar protection but is less attainable, suggesting LDA suffices for conception planning. Optimising preconception disease control remains essential and warrants multicentre validation.

Ankylosing spondylitis (AS) is an immune-mediated spondyloarthropathy with unmet clinical needs. We conducted a superiority, phase 3, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of XKH004, a humanized monoclonal antibody targeting interleukin-17A/F in active AS. Of 489 screened patients with inadequate response to conventional therapy, 166 were excluded based on predefined criteria. The remaining 323 eligible patients were randomized 1:1 via a centralized interactive web-response system to receive subcutaneous XKH004 160 mg every 4 weeks or placebo until week 16. All patients completed a 52-week follow-up period, comprising 44 weeks of open-label XKH004 treatment followed by an 8-week safety follow-up. Participants and investigators were blinded to treatment allocation. Efficacy analyses utilized the Cochran–Mantel–Haenszel test. The primary endpoint was Assessment of SpondyloArthritis international Society 40 (ASAS40) response at week 16; secondary endpoints included ASAS20/50, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Ankylosing Spondylitis Quality of Life, and Ankylosing Spondylitis Disease Activity Score. At week 16, ASAS40 response was achieved by 45.4% with XKH004 (n = 161) vs 19.4% with placebo (n = 162; absolute difference, 95% confidence interval, 15.47–35.02; P < 0.001), with efficacy in the XKH004 group sustaining and further improving to 66.2% by week 52. Serious adverse events occurred in 1.2% and 2.5% of patients in the XKH004 and placebo groups, respectively. Overall, XKH004 was well tolerated and induced rapid, sustained improvements, supporting its potential as a novel therapeutic option for active AS. The trial was registered in the China Drug Experiment database (CTR20232310) and ClinicalTrials.gov (NCT07498634) and supported by the National Natural Science Foundation of China, National Key Research and Development Project, Shanghai Municipal Key Clinical Specialty, and Shanghai Science and Technology Development Funds.

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by immune cell dysfunction. The endomembrane system, consisting of the endoplasmic reticulum (ER) and Golgi apparatus (GA), plays a central role in protein synthesis and trafficking. However, the regulatory architecture of the ER-Golgi axis in RA immune cells remains incompletely understood.MethodsWe performed an integrative multi-omics analysis of peripheral blood mononuclear cells (PBMCs) from 96 RA patients and 90 healthy controls (HCs). Proteomic data were obtained from a previously published study from our research group, and transcriptomic data were retrieved from the GEO database (GSE17755). Protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape. Kinase activity and related signaling molecules were identified based on the functional annotations of differentially expressed proteins and phosphoproteins. Upstream transcription factor (TF) regulatory networks were built through integration with hTFtarget. Drug candidates were screened using the DSigDB database.ResultsRA immune cells exhibited coordinated dysregulation of the ER-Golgi axis. Proteomics revealed downregulation of vesicular transport components (RAB1A, SEC16A) and upregulation of ER stress-related proteins (DNAJC3, SERPINH1). Phosphoproteomics identified 122 differentially phosphorylated sites, including novel hypophosphorylation of SEC16A (S1305/S1356) and decreased phosphorylation of PRKCD at T507, T295, and S664, suggesting altered PRKCD-related signaling in RA immune cells. PPI network analysis highlighted RPS3 as a dual hub linking translation and inflammatory signaling. Upstream regulatory analysis identified PML, STAT1, CBFB, and RAD21 as potential TFs, while AKT1-CK2-PRKD and TBK1-IKBKB constituted major kinase hubs. These findings indicate coordinated alterations in vesicular transport, ER stress-related processes, and inflammatory signaling in RA immune cells.ConclusionsThis integrative multi-omics analysis characterizes coordinated alterations of the ER-Golgi axis in RA immune cells and highlights candidate regulatory nodes, including SEC16A phosphorylation sites, RPS3, and major kinase hubs. As a hypothesis-generating study, these findings provide a systems-level framework for understanding how endomembrane dysregulation may be associated with sustained immune activation in RA.

OBJECTIVES:Lung ultrasound (LUS) assesses lung lesion severity in systemic autoimmune rheumatic disease-associated interstitial lung disease (SARD-ILD). The ultrasound manifestations of SARD-ILD include pleural line (PL) abnormalities and heterogeneous B-line (BL) distribution. We aimed to investigate the feasibility of a modified ultrasound scoring system based on refined grading of BL and PL features in patients with SARD-ILD, to determine whether BLs and PLs can effectively reflect ILD patterns across different lung compartments. METHODS:One hundred and ninety-five patients with nine SARD-ILDs underwent LUS-chest high-resolution computed tomography (HRCT) pairing was used to determine BLs and PLs diagnostic performance for ILD patterns characterization. BL and PL scores for both were refined to obtain the modified LUS score. Correlations with the Warrick score, ILD-GAP, and severity based on forced vital capacity (FVC) were analysed, and receiver operating characteristic (ROC) were calculated. RESULTS:Using HRCT as a criterion, BLs and PLs showed high concordance for diagnosing ground-glass opacity (kappa = 0.606) and reticular opacity (kappa = 0.743), respectively. Modified LUS scores were positively correlated with the Warrick score (r = 0.863; P < 0.001) and ILD-GAP (r = 0.613; P < 0.005). ROC analysis revealed optimal modified LUS score thresholds of 11.5 for identifying cases with high fibrosis burden (Warrick score >8), 18.5 for high mortality risk (ILD-GAP ≥2), and 9.5 for severe functional impairment (FVC% predicted <60%). CONCLUSION:BLs and PLs have different diagnostic significances for different ILD patterns. The modified LUS scoring system reliably assesses lesion severity and suggesting poor prognosis in SARD-ILD compared with computed tomography scan.

What is already known about this topic?:Human papillomavirus (HPV) is a globally prevalent sexually transmitted infection, with multiple genotypes strongly associated with cancers and other diseases. While extensive epidemiological data exist for HPV in females, studies on HPV genotype distribution in males, particularly those with confirmed HPV exposure, remain limited. What is added by this report?:This study provides a comprehensive analysis of HPV genotype distribution and its association with clinical outcomes in males with confirmed HPV exposure. The results demonstrate that low-risk HPV genotypes predominate in this population, with certain diseases showing unique HPV genotype associations. Additionally, older males exhibited a greater tendency toward multiple genotype co-infections. What are the implications for public health practice?:This study underscores the importance of including males in HPV vaccination programs. Expanding vaccination coverage to males, combined with early screening and targeted public health education, can effectively reduce HPV transmission between sexes and decrease the overall burden of HPV-related diseases.

Inflammatory cytokine overproduction is critically involved in immune dysregulation and tissue damage, but the role of interleukin-18 (IL-18), a cytokine associated with inflammasome activation, in modulating the T-cell response and autoimmune pathogenesis remains largely unclear. In this study, we detected high expression levels of the IL-18 receptor α chain (IL-18Rα) in murine and human Th17 cells. In culture, IL-18 markedly promoted Th17 cell differentiation with increased GM-CSF production, a phenotype of pathogenic Th17 (pTh17) cells. Transcriptomic profiling via RNA sequencing revealed that IL-18-induced pTh17 cells presented increased glycolytic flux and proinflammatory signatures. Mechanistically, IL-18 promoted Stat3 phosphorylation, which stabilized Bhlhe40 mRNA to potentiate Bhlhe40-dependent glycolysis and cytokine production. In patients with primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE), IL-18 levels in plasma and inflamed tissues were significantly increased and positively correlated with disease activity. Moreover, the expression levels of IL-18 were markedly increased in the salivary glands of experimental Sjögren’s syndrome (ESS) model mice and the renal tissues of lupus model mice. Furthermore, adoptive transfer of IL-18-induced pTh17 cells profoundly exacerbated disease severity and tissue damage in recipient IL-17-deficient mice, whereas IL-18 neutralization with a monoclonal antibody effectively suppressed the pTh17 cell response and ameliorated tissue pathology in both ESS and lupus mice. Together, our findings reveal a novel function of IL-18 in driving the pTh17 cell response during autoimmune development, indicating that IL-18 blockade may serve as a promising therapeutic strategy for the treatment of autoimmune diseases.

Chromosomal structural variations (CSVs) that comprise multiple gene mutations are important determinants for multiple diseases. However, the relationship between CSVs, rheumatoid arthritis (RA), and lung cancer is not well understood. In this study, we analyzed CSV associations and differences between RA and RA with lung cancer (RA LC) using genome sequencing, with RA-associated interstitial lung disease (RA ILD) as a disease control. First, we analyzed the CSVs of each individual. Then, we identified common CSVs within each disease group and finally analyzed specific CSVs between different diseases. Gene Ontology/KEGG terms, canonical pathways, and feature gene sets were used for the functional annotation and analysis of CSV-related pathways. Cell size regulation and axon guidance were mutated in all disease groups. Protein deubiquitination was mutated in RA LC, while the negative regulation of extractable stroma and protein catabolism was mutated in RA ILD. Characterization of clinical data also revealed correlations with these specific pathways. This study identifies common and specific CSVs and associated pathways for RA, LC, and ILD, uncovering key genetic factors that provide new insights into their diagnosis and treatment.

Systemic lupus erythematosus (SLE) has been associated with gut microbiota in some studies. There is no clear evidence that cytokines act as mediators. We first assessed the differences in gut microbiota between SLE patients and healthy controls using 16S rDNA sequencing. Subsequently, we used the summary statistics of gut microbiota, cytokines, and SLE from large genome-wide association studies. To explore the causal relationships between gut microbiota and SLE and identify potential mediating cytokines, we performed bidirectional Mendelian randomization analyses. Finally, the levels of potentially mediating cytokines were determined by ELISA. Fecal 16S rDNA sequencing showed that there was gut microbiota disorder in SLE patients. Based on two-sample analysis, seven gut microbiota taxa were causally associated with SLE. SLE influenced the relative abundance of two gut microbiota taxa in our large-scale MR study. Mediation analyses revealed that the causal relationship between genus Lachnospiraceae UCG001 and SLE was exclusively mediated by fibroblast growth factor 19 (FGF19) levels and the causal relationship between order Lactobacillales and SLE was exclusively mediated by tumor necrosis factor receptor superfamily member 9 (TNFRSF9) levels. Elevated levels of FGF19 affected the association between the reduced relative abundance of the genus Coprobacter and SLE, mediating by a proportion of 10.64

Objective Our study aimed toconstruct a web-based calculator to predict high risk patients of interstitial lung disease (ILD) in systemic lupus erythematosus (SLE). Methods This retrospective study comprised training and test cohorts, including 581 and 86 patients, respectively. Univariate, least absolute shrinkage and selection operator (LASSO), random forest (RF), eXtreme Gradient Boosting (XGBoost), and logistic regression (LR) analyses were performed. A Venn diagram was used to investigate critical features. Receiver operating characteristic (ROC) analysis and decision curve analysis were used to evaluate the model’s performance. Risk stratification was performed using the best ROC cut-off value. The web-based calculator was established using Streamlit software. Results Characteristics such as Raynaud’s phenomenon, pulmonary artery systolic pressure, serositis, anti-U1RNP antibodies, anti-Ro52 antibodies, C-reactive protein, age, and disease course were associated with SLE complicated by ILD (SLE-ILD). LR-Venn, RF-Venn, XGBoost-Venn, LASSO-logic, RF, and XGBoost models were constructed. In training cohort, the XGBoost model demonstrated the highest area under the ROC curve (AUC, 0.890; cut-off value, 0.197; sensitivity, 0.793; specificity, 0.836) and provideda netbenefitin decision curve analysis (odds ratio [OR] for SLE-ILD [high- vs. low-risk], 19.6). The model was validated in the test cohort (AUC, 0.866; sensitivity, 0.722; specificity, 0.897; OR, 22.7). Furthermore, an XGBoost model-based web calculator was developed. Conclusion Our web calculator (https://st-xgboost-app-kcv9qm.streamlit.app/) greatly improved risk prediction for SLE-ILD and was implemented effectively.

BACKGROUND:Individuals with rheumatoid arthritis (RA) are at a significantly increased risk of developing lung cancer (LC), with a 30%-40% higher incidence compared to the general population. Although a link between the two conditions has been established, the molecular mechanisms and genetic factors remain not fully elucidated. This study aims to uncover the potential associations between LC and RA through an integrative approach of transcriptomics and genomics analysis. METHODS:We collected whole-genome expression data from patients with LC, RA, and healthy controls. Next-generation sequencing (NGS) was applied to analyze genomic variations in blood samples from RA patients, including those with comorbid LC and interstitial lung disease (ILD). Using bioinformatics tools, we identified differentially expressed genes (DEGs) and conducted an integrative analysis of pathways shared and specific to LC and RA. RESULTS:The transcriptome analysis identified 1,051 DEGs common to both LC and RA, with distinct regulatory patterns. Among these, 441 genes were commonly upregulated, 345 were downregulated, and 265 exhibited opposite regulation between the two diseases. After integrating significant genomic mutation data, an additional 92 upregulated, 90 downregulated, and 41 oppositely regulated key genes were identified. Functional and enrichment analyses of these key genes revealed shared alterations in immune-related pathways, particularly the upregulation of viral response and immune signaling pathways, and the downregulation of T-cell receptor (TCR) signaling, T cell activation, and non-coding RNA metabolism. Furthermore, lymphocyte and leukocyte migration, as well as the positive regulation of programmed cell death, showed opposite regulation patterns between the two diseases. Laboratory tests also revealed changes in lymphocytes. CONCLUSION:This study delineates potential common mechanisms between LC and RA, suggesting that an enhanced viral response, attenuated TCR signaling, and reduced T cell activation in the peripheral system may represent shared pathological mechanisms, potentially contributing to the increased LC risk in RA patients. Conversely regulated DEGs may serve as novel biomarkers for pulmonary diseases. The changes in immune-related pathways and their potential association with lymphocyte activity provide new perspectives for understanding the relationship between LC and RA.

BACKGROUND:To explore the therapeutic and preventive effect of dendritic cells injection combined with radical prostatectomy on prostate cancer in mice. METHODS:We extracted antigens from mouse prostate cancer cells RM-1 and cocultured them with dendritic cells to induce maturation. We constructed in situ carcinoma and subcutaneous tumor models of the mouse prostate. The efficacy of dendritic cell injection combined with radical prostatectomy was evaluated in the carcinoma in situ model, and the ability of dendritic cells to prevent prostate cancer was evaluated in the subcutaneous tumor model. Means of assessment included ultrasonography, flow cytometry analysis, and Elisa. RESULTS:Dendritic cell injection combined with radical prostatectomy effectively inhibited the growth of prostate carcinoma in situ in mice, as well as the growth of subcutaneous tumors of prostate cancer in mice. After dendritic cell injection, the levels of CD4 + T cells and Treg cells in the spleens of mice were significantly increased, and the levels of IL-2 and TNF-γ in the peripheral serum were significantly increased. CONCLUSIONS:Injection of mature dendritic cells induced by mouse prostate cancer cell RM-1 antigen can inhibit the growth of prostate cancer. Radical prostatectomy combined with dendritic cell injection might be a potential treatment strategy for prostate cancer.

Background and objectives: Interstitial lung disease (ILD) is the main cause of morbidity and mortality in patients with connective tissue disease (CTD). Therefore, effective biomarkers for diagnosis and predicting progression of CTD-ILD could be significant. Galectin-9 (Gal-9) has been reported to be associated with autoimmune diseases. Here, this study aims to investigate the role of circulating Gal-9 in the diagnosis and progression monitoring in patients with CTD-ILD. Methods: A total of 128 patients with CTD-ILD, 101 patients with CTD and 52 healthy controls were enrolled in this study. Serum Gal-9 levels were measured by enzyme-linked immunosorbent assay, and its correlation with clinical indices in patients with CTD-ILD were assessed using Spearman’s analysis. Receiver operating characteristic (ROC) analysis was applied to measure the diagnostic accuracy of Gal-9 in patients with CTD-ILD. Kaplan-Meier analysis was performed to assess the progression of ILD in patients with CTD-ILD with high and low baseline levels of serum Gal-9. Results: Serum Gal-9 levels were significantly higher in CTD-ILD patients than either CTD patients or healthy controls (median 18.3 ng/mL vs. 9.3 ng/mL vs. 7.6 ng/mL). Serum Gal-9 levels showed a significantly positive correlation with serum inflammatory indexes and Krebs von den Lungen-6 (KL-6), as well as lung computed tomography scores and reduced pulmonary function in patients with CTD-ILD (all p < 0.05). Additionally, serum Gal-9 exhibited moderate diagnostic ability to identify the presence of ILD in patients with CTD. Intriguingly, longitudinal study revealed a significant reduction in serum Gal-9 levels after treatment in patients with CTD-ILD (35.0 ng/mL vs. 17.3 ng/mL, p = 0.0012). Furthermore, patients with CTD-ILD with a baseline serum Gal-9 level of ≥ 10.45 ng/mL experienced a higher percentage of ILD progression than those with a level of < 10.45 ng/mL over a two-year follow-up (36.4% vs. 0.0%). Conclusions: Serum Gal-9 could serve as a potential circulating indicator for both the presence and severity of ILD, and it may also have prognostic significance in predicting ILD progression in patients with CTD.

BACKGROUND:The burden of interstitial lung disease (ILD)-associated heart failure (HF) poses a significant challenge to the prognosis of ILD patients. This study aimed to characterize the disease burden and analyse future trends of ILD-associated HF, offering valuable insights to inform targeted prevention and control strategies. METHODS:Data on the prevalence and years lived with disability (YLDs) of ILD-associated HF were retrieved from the Global Burden of Disease (GBD) database for the period 1990-2021. Trends in ILD-associated HF were evaluated using average annual percentage change (AAPC) and percentage change analyses. Future prevalence data were projected up to 2050 using predictive modelling. RESULTS:Globally, the number of patients with ILD-associated HF increased from 20,229 in 1990 to 104,059 in 2021, with the prevalence rising from 0.53 to 1.41 per 100,000 population. Prevalence rates were disproportionately higher in older populations, with individuals over 95 years experiencing a 17.78-fold increase over the study period. Additionally, a positive correlation was observed between higher socioeconomic development index (SDI) levels and ILD-associated HF prevalence. Among 204 countries, 71.1% exhibited an increasing trend in prevalence. However, Bayesian age-period-cohort (BAPC) modelling predicts a declining trend over the next 28 years. CONCLUSION:Over the past three decades, the global burden of ILD-associated HF has escalated, particularly among individuals aged over 65 and in regions with high SDI levels. These findings underscore the need for region-specific, personalized intervention strategies to mitigate disease progression and enhance the quality of life for ILD patients.

Regulatory B cells (Bregs) play a pivotal role in the immune modulation of rheumatoid arthritis (RA). The levels of CD19+CD24hiCD38hi Bregs in peripheral blood and their association with clinical indicators in RA patients have not been extensively studied. The aim of this study was to investigate the alterations in peripheral blood CD19+CD24hiCD38hi Breg levels in RA patients and their association with clinical indicators. Additionally, we explored the variations in Breg levels before and after treatment. Overall, 90 patients with newly diagnosed RA and 32 healthy controls were prospectively enrolled. Symptoms and laboratory findings were collected. Flow cytometry and three-color fluorescence antibody labeling were employed to detect CD19+CD24hiCD38hi Breg levels in peripheral blood mononuclear cells (PBMCs). The proportion of CD19+CD24hiCD38hi Bregs among mature B lymphocytes was analyzed, and correlations with clinical indicators were examined. A follow-up study of 26 RA patients was conducted to compare changes in Breg levels before and after six months of treatment. The levels of CD19+CD24hiCD38hi Bregs in RA patients were 89.63

This study aims to evaluate the effects of warm acupuncture combined with conventional functional rehabilitation training (FRT) on the recovery of breast cancer (BC) patients following radical mastectomy, focusing on immune function, pain management, and quality of life (QoL). This retrospective study involved 118 BC patients who underwent radical surgery at the Second People's Hospital Affiliated to Fujian University of Chinese Medicine between January 2022 and May 2024. The included patient were assigned into an experimental group (EG, n=62, warm acupuncture in conjunction with conventional FRT) and a control group (CG; n=56; conventional FRT only). Postoperative outcomes, including surgery duration, intraoperative blood loss (IOBL), drainage volume (DV), length of hospital stay, upper limb mobility, immune function indicators, and pain scores, were compared between the two groups. Multivariate logistic regression was employed to identify factors affecting treatment outcomes. The EG demonstrated significantly lower visual analog scale (VAS) scores at post-operative 2, 4, and 8 weeks compared to the CG (all P < 0.05). The incidence of upper limb lymphedema in the EG was 9.26%, notably lower than the 24.07% observed in the CG (P < 0.05). Immune function indicators, including CD3+, CD4+, CD8+, and the CD4+/CD8+ ratio, were significantly higher in the EG postoperatively (P < 0.05). Furthermore, the EG reported significantly improved scores in role physical, general health, vitality, social functioning, role emotional, mental health, and physiological functioning, alongside significantly lower scores in bodily pain compared to the CG (all P < 0.05). Multivariate logistic regression analysis revealed CD3+ and CD4+/CD8+ ratio as independent factors affecting patient treatment efficacy (both P < 0.05). In conclusion, the combination of warm acupuncture and conventional FRT significantly enhances immune function, pain management, and overall QoL in BC patients after surgery, with CD3+ and CD4+/CD8+ ratios being crucial factors influencing recovery.

Background: Accurate assessment of Rheumatoid Arthritis (RA) activity remains a challenge. Multimodal photoacoustic/ultrasound (PA/US) joint imaging emerges as a novel imaging modality capable of depicting microvascularization and oxygenation levels in inflamed joints associated with RA. However, the scarcity of large-scale studies limits the exploration of correlating joint oxygenation status with disease activity. Objective: This study aimed to explore the correlation between multimodal PA/US imaging scores and RA disease activity, assessing its clinical applicability in managing RA. Methods: In this study, we recruited 111 patients diagnosed with RA and conducted examinations of seven small joints on their clinically dominant side using a PA/US imaging system. The PA and power Doppler ultrasound (PDUS) signals were semi-quantitatively assessed using a 0-3 grading system. The cumulative scores for PA and PDUS across these seven joints (PA-sum and PDUS-sum) were calculated. Relative oxygen saturation (So(2)) values of inflamed joints on the clinically dominant side were measured, and categorized into four distinct PA+So(2) patterns. The correlation between PA/US imaging scores and disease activity indices was systematically evaluated. Results: Analysis of 777 small joints in 111 patients revealed that the PA-sum scores exhibited a strong positive correlation with standard clinical scores for RA, including DAS28 [ESR] (rho = 0.682), DAS28 [CRP] (rho = 0.683), CDAI (rho = 0.738), and SDAI (rho = 0.739), all with p < 0.001. These correlations were superior to those of the PDUS-sum scores (DAS28 [ESR] rho = 0.559, DAS28 [CRP] rho = 0.555, CDAI rho = 0.575, SDAI rho = 0.581, p < 0.001). Significantly, in patients with higher PA-sum scores, notable differences were observed in the erythrocyte sedimentation rate (ESR) (p < 0.01) and swollen joint count 28 (SJC28) (p < 0.01) between hypoxia and intermediate groups. Notably, RA patients in the hypoxia group exhibited higher clinical scores in certain clinical indices. Conclusion: Multi-modal PA/US imaging introduces potential advancements in RA assessment, especially regarding So(2) evaluations in synovial tissues and associated PA scores. However, further studies are warranted, particularly with more substantial sample sizes and in multi-center settings.

OBJECTIVE:RA is characterized by hypoxia in the synovial tissue. While photoacoustic (PA) imaging offers a method for evaluating tissue oxygenation in RA patients, studies exploring the link between the oxygenation status of extrasynovial tissue in the wrist and disease activity remain scarce. We aimed to assess synovial oxygenation in RA patients using a multimodal photoacoustic-US (PA/US) imaging system and establish its correlation with disease activity. METHODS:A retrospective study was conducted on 111 patients with RA and 72 healthy controls from 2022 to 2023. Dual-wavelength PA imaging quantified oxygen saturation (So2) levels in the synovial membrane and peri-wrist region. Oxygenation states were categorized as hyperoxia, intermediate oxygenation, and hypoxia based on So2 values. The association between oxygenation levels and the clinical disease activity index was evaluated using a one-way analysis of variance, complemented by the Kruskal-Wallis test with Bonferroni adjustment. RESULTS:Of the patients with RA, 39 exhibited hyperoxia, 24 had intermediate oxygenation, and 48 had hypoxia in the wrist extrasynovial tissue. All of the control participants exhibited the hyperoxia status. Oxygenation levels in patients with RA correlated with clinical metrics. Patients with intermediate oxygenation had a lower disease activity index compared with those with hypoxia and hyperoxia. CONCLUSION:A significant correlation was found to exist between wrist extrasynovial tissue oxygenation and disease activity in patients with RA.