To assess whether age independently predicts renal function in Takayasu arteritis (TA) patients with abdominal aortic involvemen. This retrospective study included 149 TA patients. Renal function was assessed by estimated glomerular filtration rate (eGFR). Vascular features (severe RAS, aortic plaques) were evaluated via integrated ultrasound and CT angiography. Univariate and multivariate regression analyses identified determinants of eGFR and clinical renal impairment (eGFR < 90 mL/min/1.73m²). Mean age was 33.85 years. Age showed the strongest inverse correlation with eGFR (r = -0.538, p < 0.001). In multivariate analysis, age remained the most robust independent predictor of lower eGFR (standardized β = -0.500, p < 0.001), exceeding the effect of severe RAS (β = -0.143, p = 0.043). The association of aortic plaques with eGFR lost significance after age adjustment. Logistic regression confirmed age as an independent risk factor for renal impairment (adjusted OR = 1.078 per year, 95% CI: 1.036–1.122, p < 0.001). In TA, chronological age is the strongest independent predictor of renal function, surpassing severe RAS. These findings highlight the necessity of incorporating an age-aware perspective into the clinical assessment of renal health in TA, particularly given its typical onset in young adulthood.

Alzheimer's disease(AD),an aging-related disease,is characterized by chronic neuroinflammation and microglial activation,leading to neuronal death.Targeting the NOD-like receptors family pyrin domain containing 3(NLRP3)inflammasome may offer therapeutic benefits.Through extensive screening of a natural herbal library using lipopolysaccharide/nigericin-stimulated BV-2 microglial cells,we discovered that Oenothera biennis,a plant-based functional food,significantly enhanced cell survival and inhibited the NLRP3 inflammasome.This was achieved by downregulating its component proteins and suppressing pyroptosis.Similar protective effects were observed in amyloid β(Aβ)1-42-stimulated BV-2 cells,where O.biennis water extract(OWE)reduced inflammasome activity and modulated microglial phagocytic function.Additionally,OWE protected neuronal PC 12 cells from inflammatory damage,underscoring its neuroprotective potential.Further mechanistic studies revealed that OWE activated autophagy by regulating the AMP-activated protein kinase-phosphoinositide 3-kinase/v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin(AMPK-PI3K/AKT/mTOR)signaling pathway.The effects of OWE on NLRP3 inflammasome inhibition and pyroptosis were reversed by treatment with bafilomycin A1 and compound C,indicating that autophagy plays a key role in these processes.In vivo studies showed that OWE activated autophagy and ameliorated Aβ-induced paralysis and death in Caenorhabditis elegans.Furthermore,OWE demonstrated neuroprotective effects in 3xTg-AD mice by improving cognitive functions and reducing inflammatory markers through autophagy induction.Collectively,our findings suggest that OWE,as a plant-based functional food,inhibits the activation of the NLRP3 inflammasome in microglia via AMPK-PI3K/AKT/mTOR-mediated autophagy,providing a promising therapeutic avenue for AD.

Background The roles of cancer-associated fibroblasts (CAFs) and disulfidptosis in colorectal cancer (CRC) remain unclear. Methods Using single-cell RNA sequencing (scRNA-seq) and disulfidptosis-related genes (DRGs), we analyzed CRC datasets (TCGA-CRC, GSE87211, GSE132257). CAFs were extracted from scRNA-seq for pseudotime analysis. Differentially expressed genes (DEGs) from scRNA-seq (DEGs1), TCGA-CRC (DEGs2), and DRG-associated weighted gene co-expression network analysis (WGCNA) modules were overlapped to obtain intersecting genes. Prognostic genes and a risk model were constructed using Cox regression and least absolute shrinkage and selection operator (LASSO), followed by functional, immune, and drug sensitivity analyses. Results A total of 47 intersecting genes were generated from 127 DEGs1, 5,535 DEGs2, and 3,627 module genes. Machine learning combined with Cox analysis identified two prognostic genes (SRPX and PRELP). Using optimal and median risk scores, CRC patients were stratified into high- and low-risk groups in TCGA-CRC and GSE87211, with significant survival differences observed between the two groups (P < 0.05). M0 macrophages showed positive correlations with risk score (r = 0.36) and PRELP (r = 0.44), while activated CD4 + memory T cells showed negative correlations with risk score (r = -0.27) and PRELP (r = -0.3). Pseudotime analysis revealed CAF subpopulations distributed across three distinct differentiation pathways, with CAF_infa and CAF_PN enriched in early stages, followed by CAF_myo, CAF_AP, and CAF_adi. Conclusions Collectively, both SRPX and PRELP are associated with DRGs and CAFs, offering a new perspective for CRC diagnosis and treatment.

Advanced Gastric Signet Ring Cell Carcinoma (SRCC) is characterized by aggressive behavior, high metastatic potential, and extremely poor prognosis. There is an urgent need for effective imaging modalities to evaluate systemic metastatic lesions and to dynamically monitor disease progression during treatment. We report a rare case of a 26-year-old female with advanced SRCC presenting with extensive systemic metastases, clinically staged as IV (cT4N3M1). High-frequency and conventional ultrasound imaging revealed metastatic lesions involving the scalp soft tissues, cervical lymph nodes, intercostal soft tissues, pancreatic-splenic hilum region, pelvic cavity, peritoneum and omentum. The ultrasonographic findings were highly consistent with contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) results. The patient received seven cycles of a modified BEMA regimen (oxaliplatin, leucovorin and 5-fluorouracil) combined with nivolumab. Serial ultrasound monitoring indicated continuous disease progression. Due to poor therapeutic response, the patient succumbed to acute obstructive renal failure caused by tumor progression seven months after diagnosis. This report provided a comprehensive ultrasonographic assessment of widespread and rare metastatic sites in advanced SRCC, a scenario seldom documented. The combination of high-frequency ultrasound and Super Microvascular Imaging (SMI) offered precise, radiation-free, and repeatable evaluation of both superficial and deep lesions, proving particularly valuable for real-time monitoring of treatment response in critically ill patients. These findings underscore the unique role of systemic ultrasound in enhancing metastatic detection and therapeutic evaluation for advanced SRCC.

Bone age assessment is a critical tool for evaluating skeletal maturity in children and adolescents, with implications for growth monitoring and clinical decision-making. While traditional radiographic methods such as the Greulich-Pyle and Tanner-Whitehouse systems remain the gold standard, concerns over ionizing radiation exposure have spurred interest in ultrasound-based alternatives. This mini-review synthesizes current evidence on ultrasound bone age assessment, highlighting its advantages as a radiation-free, non-invasive modality with strong correlations to radiographic standards. Key advancements include standardized scoring systems, ossification ratios (e.g., radius/ulna/femur), and acoustic measures (e.g., speed of sound), which enhance reliability and reduce inter-operator variability. However, challenges persist, including protocol standardization, population-specific variability, and operator dependency, particularly in advanced pubertal stages. Future directions emphasize the development of large-scale, longitudinal and multi-ethnic reference databases, consensus guidelines, and AI integration to improve precision. Ultrasound bone age assessment shows promise as a viable clinical tool, but further refinements are needed to address its limitations and ensure equitable applicability across diverse populations.

Takayasu's arteritis (TAK) is a chronic inflammatory disease that often leads to stenosis or occlusion of the common carotid artery (CCA), posing significant risks such as stroke and cognitive impairment. Despite the widespread use of ultrasound in diagnosing and monitoring TAK, the lack of standardized criteria for assessing CCA stenosis has resulted in inconsistent evaluations. This study aims to establish standardized ultrasound diagnostic criteria for CCA stenosis in TAK, focusing on residual inner diameter and wall thickness. A total of 68 TAK patients with 120 CCAs and 120 healthy CCAs controls were included. Ultrasound examinations were performed using the iU22 Philips Healthcare system, with measurements of arterial wall thickness, inner and outer diameters, and carotid blood flow velocity. Head and neck computed tomography angiography (CTA) served as the gold standard for stenosis assessment. Statistical analyses were conducted to evaluate the diagnostic performance of various ultrasound parameters. The study found that the residual inner diameter was the most reliable parameter for assessing CCA stenosis, with high diagnostic accuracy across all stenosis categories (ROC values of 0.901 for ≥ 50

BACKGROUND:In patients with heart failure with preserved ejection fraction (HFpEF), the impact of type 2 diabetes (T2D) on left ventricular global longitudinal strain (LV GLS) and its prognostic implications remains unclear. We aimed to evaluate LV function using two-dimensional (2D) and three-dimensional (3D) speckle-tracking echocardiography in patients with HFpEF with and without T2D, and to investigate its prognostic significance. METHODS:A total of 335 patients with HFpEF were prospectively enrolled for echocardiographic evaluation. LV GLS was obtained using 2D- and 3D-speckle-tracking echocardiography. Cox proportional hazards regression was used to determine predictors of adverse outcomes. The C-index, Akaike information criterion, integrated discrimination improvement, and net reclassification improvement were used to assess model performance and discriminative ability. RESULTS:LV 2D-GLS and 3D-GLS were impaired in patients with HFpEF and T2D compared with those without T2D. After a median follow-up of 17.6 months, 150 patients experienced adverse outcomes. Both 2D-GLS (hazard ratio, 1.323 [95% CI, 1.225-1.429]; P<0.001) and 3D-GLS (hazard ratio, 1.412 [95% CI, 1.316-1.515]; P<0.001) were independent predictors of adverse outcomes in patients with HFpEF after adjustment for confounders. The predictive accuracy of a model incorporating 3D-GLS (Akaike information criterion=-583.9, C-index=0.775 [95% CI, 0.742-0.808]) was superior to models using 2D-GLS (Akaike information criterion=-533.3, C-index=0.719 [95% CI, 0.678-0.760], ΔC-index=0.056; P=0.034) and LV ejection fraction (Akaike information criterion=-498.9, C-index=0.659 [95% CI, 0.610-0.708], ΔC-index=0.116; P<0.001). The addition of 2D-GLS and 3D-GLS to the base model significantly enhanced its discriminatory and predictive abilities (integrated discrimination improvement=0.225 and 0.280; net reclassification improvement=0.612 and 0.734, respectively, P<0.001 for all). CONCLUSIONS:LV 2D-GLS and 3D-GLS are impaired in patients with HFpEF and T2D, and are independent predictors of adverse outcomes. Moreover, 3D-GLS provides incremental prognostic value over 2D-GLS. REGISTRATION:URL: https://www.chictr.org.cn/; Unique identifier: ChiCTR2100047487.

Valvular heart disease (VHD) leading to inadequate hemodynamic circulation is a major cause of cardiovascular morbidity and mortality worldwide. Right ventricular-pulmonary artery (RV–PA) coupling integrates the ability of RV contractility to adapt to increased pulmonary arterial afterload. If the right ventricle cannot adapt to the elevated afterload by increasing its contractile function, RV-PA uncoupling occurs. RV-PA uncoupling has been shown to be associated with poor outcomes in VHD. This review summarizes the prognostic significance of RV-PA coupling in patients with VHD.

Figure S1. Flowchart of patient selection and enrollment. In total, 50 patients and 195 paired samples (ctDNA and BM DNA) from this population can be analyzed. In the last row, plasma samples from included patients at separate timepoint were depicted. BM, bone marrow; C2D1, Cycle 2 day 1; C3D1, Cycle 3 day 1; C4D1, Cycle 4 day 1

Figure S2. Comparison of CIR stratified by the different timepoint post treatment residual status either of plasma ctDNA (A-C) or mutation in BM (D-F). CIR according to residual status either of plasma ctDNA (A) or mutation in BM (D) at C2D1 post treatment; CIR according to residual status either of plasma ctDNA (B) or mutation in BM (E) at C3D1 post treatment; CIR according to residual status either of plasma ctDNA (C) or mutation in BM (F) at C4D1 post treatment. A higher CIR was associated with patients with ctDNA or BM DNA positive results at any point (all p<0.001). BM, bone marrow; CIR, cumulative incidence of relapse; C2D1, Cycle 2 day 1; C3D1, Cycle 3 day 1; C4D1, Cycle 4 day 1

Figure S5. Comparison of PFS stratified by the different timepoint post-treatment residual status either of plasma ctDNA or MFC at (A) C2D1, (B) C3D1 and (C) C4D1 post-treatment. ctDNA neg-MFC neg was defined as the VAF of mutation being negative for ctDNA and MRD being negative for MFC at each timepoint. ctDNA pos-MFC neg was defined as the VAF of mutation >0.01% for ctDNA and MRD being negative for MFC at each timepoint. ctDNA pos-MFC pos was defined as the VAF of mutation >0.01% for ctDNA and immunophenotype ≥10−4 myeloblasts for MFC at each timepoint. MFC, multiparameter flow cytometry; C2D1, Cycle 2 day 1; C3D1, Cycle 3 day 1; C4D1, Cycle 4 day 1

Figure S3. Kaplan-Meier plot showed the PFS of patients diagnosed as CBF and non-CBF AML underwent dynamic monitoring of mutations by ctDNA from admission to the last cycle of chemotherapy. PFS, progression-free survival. CBF, core binding factor

Table S1. Summary of targeted driver mutations for ctDNA detection

Figure S4. The correlation of the VAFs in the patient-specific tumor mutation site detected in plasma ctDNA and matched MFC based MRD. Scatter plot of the 195 individual mutations detected by both methods (r=0.586, p<0.001).

The first patient, a 10-year-old girl, presented with pancytopenia and recurrent epistaxis, along with a history of repeated upper respiratory infections, café-au-lait spots, and microcephaly. Genetic testing revealed compound heterozygous mutations in the DNA ligase IV (LIG4) gene, leading to a diagnosis of LIG4 syndrome. The second patient, a 6-year-old girl, was seen for persistent thrombocytopenia lasting over two years and was noted to have short stature, hyperpigmented skin, and hand malformations. She had a positive result from chromosome breakage test. She was diagnosed with Fanconi anemia complementation group A. Despite similar clinical presentations, the two children were diagnosed with different disorders, suggesting that children with hemocytopenia and malformations should not only be evaluated for hematological diseases but also be screened for other potential underlying conditions such as immune system disorders.

GJB2 encodes connexin 26 (Cx26), the most commonly mutated gene causing hereditary non-syndromic hearing loss. Cx26 is mainly expressed in supporting cells (SCs) and fibrocytes in the mammalian cochlea. Gene therapy is currently considered the most promising strategy for eradicating genetic diseases. However, there have been no significant effects of gene therapy for GJB2 gene mutation-associated deafness because deficiency of Cx26 leads to expanded sensory epithelial damage. In this study, the AAV2.7m8 serotype combined with the gfaABC1D promoter targeted infection of SCs is identified. It is found that Gjb2 gene replacement therapy in wild-type mice results in sensory hair cells (HCs) deficits, excessive inflammatory responses, and hearing loss. This may be one of the key factors contributing to the hardship of GJB2 gene replacement therapy. Dexamethasone (DEX) shows promising results in inhibiting macrophage recruitment, with a protective effect against HC damage. Further, the combination of AAV2.7m8-Gjb2 with DEX shows a synergistic effect and enhances the gene therapy effect in a conditional Cx26 null mice model. These results indicate that the combination of gene therapy and medication will provide a new strategy for the treatment of hereditary deafness associated with GJB2 defects.

Table S2. Representativeness of Study Participants

BACKGROUND:This study aimed at exploring the correlation between T-cadherin and programmed death-ligand 1 (PD-L1), as well as their prognostic value in patients with human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC).METHODS:Immunohistochemical staining was used to identify the protein expression of T-cadherin and PD-L1. Spearman linear correlation analysis was used to determine their association. Kaplan-Meier analysis was utilized to plot overall survival (OS) and disease-free survival (DFS) curves. Cox proportional hazards regression was used to conduct univariate and multivariate analysis.RESULTS:The results showed a negative association between protein expression of T-cadherin and PD-L1 (r = -0.760, p < 0.001), positive expression of T-cadherin was associated with a better OS (p < 0.001) and DFS (p < 0.001), while positive PD-L1 expression was associated with a worse OS (p = 0.002) and DFS (p < 0.001). The expression of T-cadherin and PD-L1 were independent prognostic predictors for OS and DFS.CONCLUSIONS:In conclusion, expression of T-cadherin and PD-L1 were largely inversely correlated and independent prognostic factors for patients with HPV-negative HNSCC.

The modular multilevel inverter circuit structure is introduced, three traditional multi-carrier PWM modulation strategies for modular multilevel inverter circuits are studied and analyzed, and the inverter-side output voltage spectrum is analyzed by simulation. Based on the traditional multi-carrier PWM modulation strategy, this paper uses the PWM technology combining multi-reference wave and multi-carrier to analyze and simulate, and builds a modulation model and a circuit model of the modular multilevel inverter circuit in the Matlab/Simulink environment. Compared with the simulation results of the traditional multi-carrier PWM strategy, the multi-carrier modulation algorithm of the multi-reference wave can slightly reduce the total harmonic distortion rate. At the same time, the multi-carrier modulation algorithm of multiple reference waves can ensure that the capacitor voltage values of each submodule of the modular multilevel inverter circuit are equal so that there is no circulation phenomenon between each phase. Finally, a physical platform is built to verify the authenticity of the simulation experiment.