Objective:To explore the diagnostic value of a clinical-radiomics model based on the T 1 mapping and apparent diffusion coefficient (ADC)-based radiomics, and the clinical indicator for renal fibrosis (RF) caused by chronic kidney disease (CKD). Methods:This cross-sectional study prospectively and consecutively enrolled 122 patients with CKD at the Second Affiliated Hospital of Soochow University from September 2021 to December 2023 who were randomly allocated to a training set ( n=85) or a validation set ( n=37) in an approximate 7∶3 ratio using simple random sampling. Patients underwent T 1 mapping and diffusion-weighted imaging scans. Renal biopsy was performed within 3 days after the MRI scans. Patients were categorized into three groups based on the degree of RF: no RF ( n=25), mild RF ( n=55), and moderate to severe RF ( n=42). To differentiate the presence of RF (no RF vs. any RF) and the severity of RF (mild RF vs. moderate to severe RF), univariate and multivariate logistic regression were used to optimize the independent clinical predictor, which constituted the clinical model. Radiomics features were extracted from regions of interest delineated within the renal parenchyma of the right kidney on T 1 mapping and ADC maps. Features were selected using least absolute shrinkage and selection operator regression to build the radiomics model. A clinical-radiomics model was subsequently constructed by integrating the independent clinical predictors with the selected radiomics features. Model diagnostic performance was evaluated using the area under the receiver operating characteristic curve (AUC). Calibration curve was plotted to assess model calibration, and decision curve analysis was performed to evaluate clinical net benefit. Results:Univariate logistic regression analysis revealed that estimated glomerular filtration rate (eGFR), serum creatinine, and blood urea nitrogen exhibited statistically significant differences ( P0.05) in distinguishing both the presence and severity of RF. Multivariate analysis identified eGFR as an independent clinical predictor for both the presence of RF ( OR=0.939, 95% CI 0.898-0.982, P=0.006) and RF severity ( OR=0.956, 95% CI 0.917-0.997, P=0.037). From the MRI images, 7 radiomics features were selected to build the radiomics model for distinguishing the presence of RF, and 8 features were selected for the model assessing RF severity. These radiomics models were then combined with eGFR to construct the clinical-radiomics models. The clinical-radiomics models demonstrated the highest diagnostic performance, with an AUC of 0.935 (95% CI 0.859-0.977) for RF presence and 0.967 (95% CI 0.891-0.995) for RF severity in the training set, and 0.914 (95% CI 0.774-0.981) and 0.908 (95% CI 0.748-0.981) in the validation set. Calibration curves and decision curve analysis confirmed that the clinical-radiomics models exhibited excellent calibration and provided the highest clinical net benefit for assessing RF in CKD patients. Conclusion:The clinical-radiomics model integrating T 1 mapping and ADC-based radiomics and eGFR can effectively improve the diagnostic performance for RF in CKD patients.

Objective:To summarize the clinical characteristics, treatment, and prognosis of children with anti-GT1a antibody-positive Guillain-Barré syndrome (GBS).Methods:A case series study was conducted, including 25 children diagnosed with serum anti-GT1a antibody-positive GBS at Guangzhou Women and Children′s Medical Center from March 2019 to December 2024. Clinical data, treatment protocols, and follow-up outcomes were analyzed. Mann Whitney U test was used to compare the changes in Hughes functional grading scale (HFGS). Results:A total of 25 children included 12 boys and 13 girls, and the age at first onset was (71±8) months. There were 16 children (64%) had preceding infections, and of which 13 children had predominantly respiratory tract infections. At disease peak, neurological manifestations included limb weakness (21 cases (84%)), bulbar palsy (13 cases (52%)), drowsiness (7 cases (28%)), limb pain (9 cases (36%)), ataxia (6 cases (24%)), respiratory muscle paralysis (5 cases (20%)), ophthalmoplegia (5 cases (20%)), and unilateral facial nerve palsy (4 cases (16%)). Cerebrospinal fluid analysis in 23 children revealed albuminocytological dissociation in 18 children. All 25 children underwent whole-spine magnetic resonance imaging (MRI), demonstrated spinal nerve root enhancement in 18 children, with leptomeningeal enhancement combined with spinal nerve root enhancement in 1 child. Electromyography in 16 children showed 15 children abnormality, of which demyelinating lesions in 8 children, mixed demyelinating-axonal changes in 4 children, and pure axonal involvement in 3 children. Intravenous immunoglobulin (IVIG) was administered to 21 cases (84%), of which 3 children required mechanical ventilation and blood purification (plasma exchange in 2 children and immunoadsorption in 1 child) due to disease progression. Four children (16%) received intravenous methylprednisolone (IVMP) instead of IVIG, with 1 child requiring ventilatory support due to respiratory muscle paralysis, and the tracheal tube was removed after continued sequential IVMP treatment. The hospitalization duration of 25 children was (23±3) d. At discharge, HFGS was 1.6 (0.6, 2.7) score. At a follow-up of 12 (4, 18) months, HFGS was 0.1 (0.0, 0.5) score, and higher than that at discharge ( Z=4.38, P<0.05). Two children relapsed but achieved remission after IVIG retreatment with no recurrence during 1-year follow-up. Conclusions:Anti-GT1a antibody-positive GBS in children predominantly presents with limb weakness and bulbar palsy, occasionally complicated by respiratory failure in the acute phase. Demyelinating neuropathy and spinal nerve root enhancement on MRI are characteristic. IVIG therapy yields favorable outcomes, with low residual disability. Relapses are rare but manageable with re-treatment.

With the rapid changes in lifestyle,the prevalence of nonalcoholic fatty liver disease(NAFLD)has become increasingly severe in China,and it has become a major public health concern.With a deeper understanding of this disease,the latest consensus statement has changed the name from NAFLD to MAFLD,and this updated definition transitions from an exclusion-based approach to an inclusive framework,which not only improves clinical diagnostic accuracy,but also highlights the key role of metabolic disorders in the progression of NAFLD.In recent years,the in-depth studies on the mechanism of carcinoembryonic antigen-associated cell adhesion molecule 1-mediated insulin clearance have highlighted the importance of insulin clearance in the development and progression of NAFLD.This article reviews the research advances in the role of insulin clearance in MAFLD.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

Objective:To investigate the clinicopathological characteristics and prognostic influencing factors in young breast cancer patients.Methods:A retrospective case series study was conducted. The clinical data of 408 young patients with breast cancer in the Fifth Medical Center of Chinese PLA General Hospital from January 2005 to December 2020 were retrospectively analyzed. The clinical characteristics and prognostic influencing factors of patients were observed. The Kaplan-Meier method was used to analyze overall survival (OS) and disease-free survival (DFS) of patients. Univariate analysis of prognostic factors was conducted by using the log-rank test, and multivariate analysis was performed by using Cox proportional risk model.Results:The median age [ M ( Q1, Q3)] of 408 young female patients with breast cancer was 36 (33, 39) years; the 5-year OS and 5-year DFS rates were 89.9%, 84.0% of 387 breast cancer patients in early and middle stage (except for stage Ⅳ). There were statistically significant differences in the 5-year OS and 5-year DFS rates (excluding stage Ⅳ of DFS) of patients with different clinical staging and molecular subtypes (all P < 0.05). The differences were statistically significant in the 5-year DFS rate of patients with different pathological types and histological grades (all P < 0.05). There were no statistically significant differences in the 5-year OS and DFS rates between the patients receiving breast-conserving surgery or mastectomy (all P > 0.05). The results of multivariate Cox regression analysis indicated that clinical staging ( HR = 3.121, 95% CI: 2.301-4.233, P < 0.001) and molecular classification ( HR = 1.441, 95% CI: 1.126-1.845, P = 0.004) were independent prognostic factors for OS. Additionally, clinical staging ( HR = 3.001, 95% CI: 2.174-4.141, P < 0.001) was identified as an independent prognostic factor for DFS. Conclusions:The prognosis of young breast cancer patients is closely related to clinical staging and molecular subtype. The later the clinical stage is, the poorer prognosis is. Luminal-type breast cancer has a better prognosis than other subtypes. For early-stage breast cancer patients who meet the criteria for breast-conserving surgery, breast-conserving surgery is the first-choice alternative.

Background/Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) is a chronic liver disease characterized by hepatic steatosis. Ubiquitin-specific protease 29 (USP29) plays pivotal roles in hepatic ischemiareperfusion injury and hepatocellular carcinoma, but its role in MASLD remains unexplored. Therefore, the aim of this study was to reveal the effects and underlying mechanisms of USP29 in MASLD progression. Methods: USP29 expression was assessed in liver samples from MASLD patients and mice. The role and molecular mechanism of USP29 in MASLD were assessed in high-fat diet-fed and high-fat/high-cholesterol diet-fed mice and palmitic acid and oleic acid treated hepatocytes. Results: USP29 protein levels were significantly reduced in mice and humans with MASLD. Hepatic steatosis, inflammation and fibrosis were significantly exacerbated by USP29 deletion and relieved by USP29 overexpression. Mechanistically, USP29 significantly activated the expression of genes related to fatty acid β-oxidation (FAO) under metabolic stimulation, directly interacted with long-chain acyl-CoA synthase 5 (ACSL5) and repressed ACSL5 degradation by increasing ACSL5 K48-linked deubiquitination. Moreover, the effect of USP29 on hepatocyte lipid accumulation and MASLD was dependent on ACSL5. Conclusions USP29 functions as a novel negative regulator of MASLD by stabilizing ACSL5 to promote FAO. The activation of the USP29-ACSL5 axis may represent a potential therapeutic strategy for MASLD.

OBJECTIVES: To investigate the association between methylation levels of tumor suppressing subtransferable candidate 1 (TSSC1) and melanophilin (MLPH) genes in peripheral blood and coronary heart disease (CHD) in Chinese population. METHODS: This case-control study was conducted in 86 CHD patients and 95 healthy individuals, whose methylation levels of TSSC1 and MLPH genes in peripheral blood were determined using mass spectrometry. Mann-Whitney U test was used to compare the methylation levels in different subgroups. The correlation of TSSC1 and MLPH gene methylation levels with age and gender were evaluated using Spearman correlation coefficient and contingency coefficient, respectively. RESULTS: Compared with the healthy individuals, the CHD patients showed a significant correlation between MLPH hypermethylation and myocardial infarction (MI) (MLPH_CpG_2.7: P=0.045; MLPH_CpG_3/cg06639874: P=0.049; MLPH_CpG_5: P=0.019), and this correlation was even stronger in individuals below 65 years of age (MLPH_CpG_2.7: P=0.014; MLPH_CpG_4: P=0.001) and in male subjects (MLPH_CpG_2.7: P=0.004; MLPH_CpG_3/cg06639874: P=0.044). The methylation level of TSSC1 gene in peripheral blood was not found to correlate with CHD or its subtypes. CONCLUSIONS Our findings suggest a correlation of MLPH hypermethylation in peripheral blood with CHD and MI in Chinese population, especially in individuals below 65 years and in male individuals.
Humans ; DNA Methylation ; Male ; Female ; Middle Aged ; Case-Control Studies ; Aged ; Coronary Disease/blood* ; Adult ; CpG Islands

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL