ObjectiveDiscriminating atypical hepatocellular carcinoma (HCC) from other malignancies in liver nodules classified as Liver Imaging Reporting and Data System category M (LR-M) remains a significant diagnostic challenge on conventional ultrasound examination. The LR-M category, originally intended to capture non-HCC malignancies, paradoxically contains up to 63% of atypical HCCs that deviate from classic enhancement patterns, leading to potential misdiagnosis and suboptimal treatment planning. While deep learning has shown promise in HCC diagnosis, most existing models rely exclusively on single-modality ultrasound, overlooking the diagnostic benefits of integrating complementary information from multiple imaging sources. To address this gap, we propose a novel attention-weighted tri-modal ultrasound network (TUS-Net) that integrates contrast-enhanced ultrasound (CEUS), B-mode ultrasound (BUS), and time-intensity curves (TICs) to improve diagnostic accuracy for these clinically challenging lesions. MethodsOur framework incorporates a three-dimensional convolutional neural network (C3D) backbone to extract spatiotemporal features from CEUS videos, capturing dynamic vascular patterns critical for lesion characterization. To effectively fuse complementary modalities, we introduce a dual-channel feature fusion module (DCFFM) that adaptively combines features from CEUS and BUS through channel-wise attention mechanisms, allowing the model to dynamically weigh the contribution of each modality based on diagnostic relevance. Additionally, we propose a temporal intensity feature fusion module (TIFFM) that leverages quantitative hemodynamic information from TICs to guide the model’s attention toward diagnostically critical temporal phases, such as arterial wash-in and portal venous washout. The model is further enhanced by automated lesion localization using YOLOX and class activation mapping for interpretability, ensuring that predictions align with clinically meaningful imaging features. ResultsEvaluated on a tri-modal ultrasound dataset comprising 161 patients with pathologically confirmed LR-M nodules (131 atypical HCC and 30 non-HCC malignancies), our model achieved an accuracy of 86.83%, a sensitivity of 92.50%, a specificity of 75.50%, and an AUC of 89.32% in screening atypical HCC. Compared to single-modality baselines, TUS-Net demonstrated superior specificity, a clinically critical metric given the higher risk associated with misclassifying non-HCC malignancies. Ablation studies confirmed the contribution of each module, with the full model outperforming both standard C3D and 3D ResNet backbones integrated with attention mechanisms. A reader study involving junior and senior radiologists further validated the clinical utility of AI assistance, showing consistent improvements in specificity and inter-reader consistency, particularly for less experienced clinicians. ConclusionThese results surpass existing benchmark models and demonstrate the potential of our approach to enhance diagnostic precision in clinically specific cases. By intelligently fusing multi-modal ultrasound data with attention-guided mechanisms, TUS-Net offers a reliable and interpretable tool that holds promise for improving the non-invasive diagnosis of atypical HCC in challenging LR-M liver nodules.

ObjectiveDiscriminating atypical hepatocellular carcinoma (HCC) from other malignancies in liver nodules classified as Liver Imaging Reporting and Data System category M (LR-M) remains a significant diagnostic challenge on conventional ultrasound examination. The LR-M category, originally intended to capture non-HCC malignancies, paradoxically contains up to 63% of atypical HCCs that deviate from classic enhancement patterns, leading to potential misdiagnosis and suboptimal treatment planning. While deep learning has shown promise in HCC diagnosis, most existing models rely exclusively on single-modality ultrasound, overlooking the diagnostic benefits of integrating complementary information from multiple imaging sources. To address this gap, we propose a novel attention-weighted tri-modal ultrasound network (TUS-Net) that integrates contrast-enhanced ultrasound (CEUS), B-mode ultrasound (BUS), and time-intensity curves (TICs) to improve diagnostic accuracy for these clinically challenging lesions. MethodsOur framework incorporates a three-dimensional convolutional neural network (C3D) backbone to extract spatiotemporal features from CEUS videos, capturing dynamic vascular patterns critical for lesion characterization. To effectively fuse complementary modalities, we introduce a dual-channel feature fusion module (DCFFM) that adaptively combines features from CEUS and BUS through channel-wise attention mechanisms, allowing the model to dynamically weigh the contribution of each modality based on diagnostic relevance. Additionally, we propose a temporal intensity feature fusion module (TIFFM) that leverages quantitative hemodynamic information from TICs to guide the model’s attention toward diagnostically critical temporal phases, such as arterial wash-in and portal venous washout. The model is further enhanced by automated lesion localization using YOLOX and class activation mapping for interpretability, ensuring that predictions align with clinically meaningful imaging features. ResultsEvaluated on a tri-modal ultrasound dataset comprising 161 patients with pathologically confirmed LR-M nodules (131 atypical HCC and 30 non-HCC malignancies), our model achieved an accuracy of 86.83%, a sensitivity of 92.50%, a specificity of 75.50%, and an AUC of 89.32% in screening atypical HCC. Compared to single-modality baselines, TUS-Net demonstrated superior specificity, a clinically critical metric given the higher risk associated with misclassifying non-HCC malignancies. Ablation studies confirmed the contribution of each module, with the full model outperforming both standard C3D and 3D ResNet backbones integrated with attention mechanisms. A reader study involving junior and senior radiologists further validated the clinical utility of AI assistance, showing consistent improvements in specificity and inter-reader consistency, particularly for less experienced clinicians. ConclusionThese results surpass existing benchmark models and demonstrate the potential of our approach to enhance diagnostic precision in clinically specific cases. By intelligently fusing multi-modal ultrasound data with attention-guided mechanisms, TUS-Net offers a reliable and interpretable tool that holds promise for improving the non-invasive diagnosis of atypical HCC in challenging LR-M liver nodules.

Background: Developing and validating a modified parameter, the SYS-G angle (the angle between the lower endplate of the C2 and the upper endplate of C7 vertebrae), as a feasible substitute for the C2–C7 Cobb method in assessing cervical sagittal alignment and exploring its reference range through a large-scale retrospective study. Methods: The visibility of the C6, C7 upper, and C7 lower endplates was graded and compared. Baseline data such as height, weight, body mass index (BMI), age, and sex were analyzed for their impact on the visibility of the C7 lower endplate. Values of C2-6 Cobb angle, SYS-G angle, and C2-7 Cobb angle were measured. The intra- and interobserver reliability, differences, and efficacy of evaluation on cervical lordosis of the parameters were compared, and the correlations among the parameters were analyzed. Furthermore, reference ranges for the SYS-G angle were established based on lateral cervical spine x-rays of 825 asymptomatic Chinese adults across different age groups and sexes. Results: The visibility of the C7 lower endplates was significantly reduced compared to the C6 lower and C7 upper endplates.Age, weight, BMI, and male sex were identified as factors negatively influencing the visibility of the C7 lower endplate. Both intraobserver and interobserver reliability demonstrated excellence for all tested parameters. The linear regression model unveiled a stronger association of the SYS-G angle with the C2-7 Cobb angle compared to the C2-6 Cobb angle. Furthermore, the SYS-G angle exhibited excellent efficacy in evaluating cervical lordosis. Age displayed a positive correlation with the SYS-G angle, and across every age bracket from 20 to 69 years, men exhibited a higher mean SYS-G angle compared to women. Conclusions The visibility of the C7 lower endplate diminishes with increasing age, weight, BMI, and male sex. In cases where the C7 lower endplate is unclear, the SYS-G angle emerges as a reliable method for estimating cervical sagittal morphology. Reference ranges for the SYS-G angle were established across various age groups and sexes among asymptomatic Chinese adults, offering a valuable resource to guide therapeutic interventions for cervical spine disorders and deformities.

Objective:To retrospectively analyze the results of auditory examination,vestibular function examination and laboratory examination of 63 patients diagnosed as vestibular neuritis.Methods:A total of 63 patients diagnosed with vestibular neuritis hospitalized in the Department of Otolaryngology, Head and Neck Surgery of the Third Affiliated Hospital of Sun Yat-sen University, from October 2012 to December 2022 were recruited. All patients met the diagnostic criteria for the 2022 Bárány association vestibular neuritis. Clinical data and the results of pure tone audiometry, electrocochleogram, video electronystagmogram, caloric test, cervical vestibuloevoked myogenic potential（cVEMP）, ocular vestibuloevoked myogenic potential（oVEMP）, video head impulse test（vHIT） was collected.A total of 63 age-and sex-matched healthy subjects in the physical examination center were randomly selected as the control group. The differences of blood indexs and lipid metabolism indexes between the two groups were compared. Results:In patients with vestibular neuritis, 50 out of 63 patients presented normal threshold in pure tone audiometry, 8 out of 63 patients had bilateral high-frequency sensorineural hearing loss and 5 out of 63 patients had unilateral mild high-frequency sensorineural hearing loss, 56 out of 63 cases completed the electrocochleogram, of which 3 cases had a binaural-SP/AP amplitude ratio≥0.4, 5 cases had monaural amplitude ratio ≥0.4. Fifty-five out of 63 patients completed the caloric test with CP values greater than 30% in all. The ratio of patients completed cVEMP, oVEMP and vHIT were 46 cases, 22 cases and 30 cases, respectively. 17 out of 63 cases completed all the four vestibular function tests. According to these tests, 49 patients could determine the extent of injury，including 27 cases with unilateral superior vestibular nerve injury, 21 cases with unilateral superior and inferior vestibular nerve injury and 1 case with unilateral inferior vestibular nerve injury. There were significant differences in neutrophil value（P<0.001）, lymphocyte value（P<0.005）, neutrophil/lymphocyte ratio（P<0.001） and apolipoprotein A1（P<0.001） between patient group and control group. Inflammatory markers were risk factors for patients with vestibular neuritis. The OR values of neutrophil value and blood neutrophil/lymphocyte ratio were 1.81（1.38-2.37, P<0.001） and 2.11（1.41-3.16, P<0.001）, respectively. Apolipoprotein A1 was a protective factor for patients with vestibular neuritis, and the OR value was 0.004（0.001-0.042, P<0.001）. Conclusion:Electrocochleogram could be used in vestibular neuritis patients with normal pure tone threshold to test whether there is hidden hearing loss in these patients. Neutrophil value, lymphocyte value, neutrophil/lymphocyte ratio and apolipoprotein A1 were correlated with vestibular neuritis. The Neutrophil value and neutrophil/lymphocyte ratio were risk factors for morbidity.
Humans ; Vestibular Neuronitis/physiopathology* ; Retrospective Studies ; Female ; Male ; Audiometry, Pure-Tone ; Hearing Loss, Sensorineural/physiopathology* ; Middle Aged ; Adult ; Vestibular Function Tests ; Vestibular Evoked Myogenic Potentials ; Aged

Pediatric vertigo presents with complex etiologies, and its clinical diagnosis and management can be challenging due to children's limited ability to describe their symptoms. Recurrent vertigo episodes in children, who are at a critical stage of development, can readily lead to emotional disorders in both the children themselves and their guardians. This article reports a case of benign paroxysmal vertigo of childhood（BPVC） in a child who sought care from multiple providers. The child was found to have a patent foramen ovale（PFO） and mild emotional disorder. By analyzing challenges encountered during the diagnostic and management process in this case of recurrent pediatric vertigo, this study provides practical guidance for rational selection of diagnostic techniques and the comprehensive assessment of disease status in pediatric vertigo/dizziness.
Child ; Humans ; Affective Symptoms/complications* ; Foramen Ovale, Patent/complications* ; Vertigo/complications*

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

Photodynamic immunotherapy is a promising strategy for cancer treatment. However, the dysfunctional tumor vasculature results in tumor hypoxia and the low efficiency of drug delivery, which in turn restricts the anticancer effect of photodynamic immunotherapy. In this study, we designed photosensitive lipid nanoparticles. The synthesized PFBT@Rox Lip nanoparticles could produce type I/II reactive oxygen species (ROS) by electron or energy transfer through PFBT under light irradiation. Moreover, this nanosystem could alleviate tumor hypoxia and promote vascular normalization through Roxadustat. Upon irradiation with white light, the ROS produced by PFBT@Rox Lip nanoparticles in situ dysregulated calcium homeostasis and triggered endoplasmic reticulum stress, which further promoted the release of damage-associated molecular patterns, enhanced antigen presentation, and stimulated an effective adaptive immune response, ultimately priming the tumor microenvironment (TME) together with the hypoxia alleviation and vessel normalization by Roxadustat. Indeed, in vivo results indicated that PFBT@Rox Lip nanoparticles promoted M1 polarization of tumor-associated macrophages, recruited more natural killer cells, and augmented infiltration of T cells, thereby leading to efficient photodynamic immunotherapy and potentiating the anti-primary and metastatic tumor efficacy of PD-1 antibody. Collectively, photodynamic immunotherapy with PFBT@Rox Lip nanoparticles efficiently program TME through the induction of immunogenicity and oxygenation, and effectively suppress tumor growth through immunogenic cell death and enhanced anti-tumor immunity.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

OBJECTIVES: To investigate the association of serum albumin level after human albumin infusion with 28-day mortality in critically ill patients with acute kidney injury (AKI) and its impact on 90-day outcomes of the patients. METHODS: We conducted a retrospective cohort study based on the MIMIC IV database (2008-2019), including 5918 AKI patients treated with albumin in the ICU. Based on serum albumin levels within 72 h after albumin infusion, the patients were divided into low (<30 g/L), medium (30-35 g/L), and high albumin (>35 g/L) groups. Restricted cubic spline regression and multivariate logistic regression were used to analyze the association of albumin levels with patient mortality, and the results were verified in a external validation cohort consisting of 110 sepsis-induced AKI patients treated in Nanfang Hospital between 2017 and 2022 using survival analysis and multivariate adjustment. RESULTS: In the MIMIC training cohort, multivariate logistic regression showed no significant differences in 28-day mortality of the patients with different albumin levels (P>0.05). However, restricted cubic spline analysis indicated a non-linear dose-response relationship between albumin levels and 28-day mortality (threshold effect: risk increased when albumin levels >3.6 g/dL). Secondary endpoint analysis revealed that the patients with high albumin levels had a shorter duration of mechanical ventilation (P<0.001) but a longer ICU stay (P<0.001). In the validation cohort, albumin levels ≥30 g/L were significantly associated with a reduced 28-day mortality rate (P<0.05). CONCLUSIONS The association between increased serum albumin levels following albumin infusion and 28-day mortality of critically ill patients with AKI exhibits a cohort dependency and can be influenced by multiple factors including disease type and severity, infusion strategies, and statistical methods.
Humans ; Acute Kidney Injury/therapy* ; Critical Illness/mortality* ; Retrospective Studies ; Serum Albumin/analysis* ; Male ; Female ; Intensive Care Units ; Middle Aged ; Logistic Models ; Aged