Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Electroencephalography (EEG) is a non-invasive neurophysiological monitoring technique. It records the electrical activity of the cerebral cortex using electrodes placed on the scalp surface. Owing to its high safety, portability, and millisecond-level temporal resolution, EEG has been widely utilized in a variety of fields, including clinical diagnosis, brain-computer interfaces (BCIs), and cognitive neuroscience research. However, due to its microvolt-level amplitude, EEG is highly susceptible to various artifacts, including electrooculographic (EOG), electrocardiographic (ECG), electromyographic (EMG), and power line interference (PLI). These artifacts can obscure genuine neural activity and introduce spurious electrophysiological features. Consequently, they may compromise EEG signal quality, thereby reducing the reliability of downstream analyses. To address this issue, numerous EEG artifact removal methods have been developed, including both traditional denoising techniques and deep learning-based approaches. Traditional EEG denoising methods have long served as the primary solutions for artifact removal. Representative approaches include filtering, regression, and blind source separation. Although these methods have demonstrated effectiveness in specific scenarios, they suffer from several inherent limitations. Filtering assumes that artifacts and EEG signals can be separated in the frequency domain, but many artifacts, such as EOG and EMG, overlap with EEG spectra, which may lead to the loss of valuable neural information. Regression methods require high-quality artifact references to estimate and subtract contaminations, limiting their effectiveness in reference-free scenarios. Blind source separation can remove artifacts without external references, but it typically requires the number of EEG channels to exceed the number of sources, restricting its application in single- or low-channel EEG recordings. Deep learning-based EEG denoising methods address these limitations effectively. First, they learn the nonlinear mapping between contaminated and clean EEG directly from data in an end-to-end manner. This approach does not rely on assumptions about spectral separability, thereby preserving neural activity more completely. Second, the reference information is incorporated during the training phase, allowing the trained model to perform artifact removal independently without external references. Third, deep learning models can be flexibly designed to accommodate various recording setups, achieving robust denoising for both high-density and single-channel EEG. Collectively, these advantages enable deep learning-based methods to overcome the main challenges of traditional approaches, providing more accurate and reliable EEG signal recovery. The superior denoising performance of deep learning-based EEG denoising methods has attracted increasing attention in EEG artifact removal research. As a result, many deep learning-based denoising methods have been developed and successfully applied in neural engineering areas. However, a systematic review of the techniques and applications in this field is still lacking. To address this gap, this paper reviews recent advances in deep learning-based EEG denoising from four perspectives: technical principle, benchmark dataset, denoising model, and evaluation method. Representative applications in neural signal analysis and BCI decoding are also summarized. Furthermore, the advantage, existing challenge, and future research direction of deep learning-based EEG denoising are discussed. This review aims to provide valuable theoretical insights and technical guidance for researchers. It is also expected to promote further advances and broader applications of deep learning-based EEG denoising techniques.

ObjectiveTo explore the effect of a novel initiation model on initiating behavioral requests in children with autism spectrum disorder (ASD). MethodsFrom November to December, 2022, 44 children with ASD were selected from Jiaxing Sunlight Rehabilitation Kindergarten, and divided into prelinguistic group (n = 23) and linguistic group (n = 21) according to the language function. The initiation-requested skills, and types and frequency of initiation-requested behaviors were observed under the novel initiation model and the conventional initiation model. ResultsBoth the groups scored higher in the novel initiation model than in the conventional initiation model for initiation-requested skills (|t| > 2.794, P < 0.05) and types of initiation-requested behaviors (|t| > 3.697, P < 0.01), and it increased for the frequency of the use of two- and three-behavioral initiation of requests (χ² > 7.986, P < 0.05). ConclusionThe novel initiation model can improve initiation request skills in children with ASD.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Objective:To assess the safety and efficacy of Blinatumomab in treating children with acute B-lymphoblastic leukemia（B-ALL）.Methods:The clinical data of 10 B-ALL children who were admitted to the Department of Pediatrics，the First Affiliated Hospital of Xi’an Jiaotong University from May 2022 to April 2024 and treated with Blinatumomab were analyzed retrospectively.Results:All the 10 cases had a complete remission of bone marrow and all minimal residual disease（MRD）were negative. Serious adverse events were reported after chemotherapy，including intracranial venous sinus thrombosis with acute cerebral infarction，acute pancreatitis，paralytic ileus，syndrome of abnormal secretion of antidiuretic hormone，severe pneumonia，liver injury，sepsis（β-lactamase resistant Escherichia coli，Pseudomonas aeruginosa），oral mucositis，persistent agranulocytosis with bloodstream infection. All patients interrupted chemotherapy and received Blinatumomab injections for 14 days. During treatment，there was hematological toxicity，which resulted in grade 3-4 neutropenia in 5 cases within the first 7 days. Transient low-grade fever was observed in 4 cases of non-hematological toxicity during days 1-3 of treatment. One patient experienced a headache on the 7th day of treatment，which worsened on the 14th day，but it improved with mannitol treatment. Mild liver injury was present in 3 cases. Interleukin-6 reached a peak of 71.86 pg/mL on the second day of treatment in one case，whereas it was normal in others. All patients were found to be free of cytokine release syndrome. T lymphocyte count increased in 5 patients after 14 days of Blinatumomab treatment，but B lymphocyte count and serum immunoglobulin levels declined in 10 patients. Hypogammaglobulinemia was observed in 3 of these patients. The median follow-up time was 7.8（3.0-24.0）months. All patients achieved MRD-negative complete remission and 6-month overall survival rate and progression-free survival were both 100%.Conclusion:Children with B-ALL can benefit from using Blinatumomab，which is safer than conventional chemotherapy，as a new treatment strategy for those who cannot tolerate traditional chemotherapy.

Objective To investigate the risk factors and clinical significance of layered plaques that were detected by optical coherence tomography(OCT)in patients with angiographically intermediate coronary lesions,and relationship with prognosis.Methods This was a signal-center retrospective study focusing on patients whom underwent coronary angiography and OCT.The layered plaque group and non-layered plaque group were divided according to the presence or absence of stratified plaque.Clinical data,laboratory indicators,angiography,and OCT results were collected and compared between the two groups.Using logistic regression to analyze the relationship between stratified plaques and clinical features;Cox regression analysis was used to investigate the influencing factors of cardiovascular adverse events in patients with critical coronary artery disease.Results A total of 172 patients were enrolled,including 96 patients in non-layered plaque group and 76 patients in layered plaque group.Male(OR 2.415,95％CI 1.162-5.020,P=0.018),diabetes(OR 2.505,95％CI 1.137-5.525,P=0.023)and history of hyperlipidemia(OR 3.590,95％CI 1.478-6.333,P=0.003)were independent risk factors for stratified plaque.In OCT analysis,the proportion of thin-cap fibroatheroma(TCFA)plaque,macrophage infiltration,microvascularization,thrombosis,plaque rupture,and intimal dissection,as well as lipid plaque length,lipid plaque arc,and lipid plaque index were higher in the layered plaque group.After adjusting for other risk factors,macrophage infiltration is independently associated with stratified plaques(OR 2.106,95％CI 1.019-4.353,P=0.044).Kaplan-Meier survival analysis showed that the target lesion revascularization rate in the layered plaque group was higher than that in the non-layered plaque group(Log-rank P=0.030).Cox regression analysis shows that it has both stratified plaque and thin fibrous membrane plaque characteristics was an independent predictor of cardiovascular adverse events(HR 5.165,95％CI 1.696-15.727,P=0.004).Conclusions In patients with angiographically intermediate coronary lesions,OCT detection of stratified lesions is often accompanied by other unstable plaque features,indicating an increased risk of adverse cardiovascular events.Simultaneously possessing features of stratified plaques and TCFA is an independent predictor of adverse cardiovascular events in patients with critical coronary artery disease.

Objective:To investigate the role of Gasdermin E (GSDME) -mediated keratinocyte pyroptosis induced by Cutibacterium acnes ( C.acnes) in the pathogenesis of acne. Methods:The human immortalized keratinocyte HaCaT cells were stimulated with heat-inactived C.acnes for 15 minutes to 24 hours, and Western blot analysis was performed to determine the expression of cleaved GSDME (GSDME-NT) in HaCaT cells at different time points. Skin tissue samples were collected from 5 acne patients and 4 healthy controls, who visited the Hospital for Skin Diseases, Chinese Academy of Medical Sciences from January 2 to December 1, 2024; additionally, 3 samples of acne cyst contents and 3 samples of normal follicle contents were collected. Immunohistochemical study and Western blot analysis were conducted to determine GSDME-NT expression in the epidermis. Enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin (IL) -1β and tumor necrosis factor (TNF) -α in acne cyst or normal follicle contents. GSDME-knockdown HaCaT cells were constructed by transfection with lentivirus carrying GSDME-shRNA, and HaCaT cells transfected with lentivirus carrying the nonsense sequence control (NC) served as controls; ELISA was performed to detect the levels of IL-1β and TNF-α in GSDME-knockdown HaCaT cells after C. acnes stimulation ( C. acnes + GSDME knockdown group) , as well as in the phosphate-buffered saline (PBS) + NC group, C. acnes + NC group, and PBS + GSDME knockdown group. Western blot analysis was conducted to determine the GSDME-NT expression in HaCaT cells pretreated with or without retinol after C. acnes stimulation. Results:The cleavage of GSDME in HaCaT cells began at 1 hour after in vitro C. acnes stimulation, and GSDME-NT could be detected at this time. Compared with the control epidermis, the proportion of GSDME-NT-positive HaCaT cells (9.34% ± 2.92% vs. 3.05% ± 1.14%, t = -3.47, P = 0.026) and GSDME-NT protein expression levels ( t = -3.51, P = 0.025) significantly increased in the lesional epidermis of acne patients. The levels of IL-1β and TNF-α were significantly higher in the acne cyst contents than in the normal follicle contents (IL-1β: 1 337.24 [1 182.32, 2 230.61] pg/ml vs. 0.00 [0.00, 108.21] pg/ml, Z = 1.99, P = 0.046; TNF-α: 811.31 [438.26, 817.73] pg/ml vs. 46.67 [12.41, 53.21] pg/ml, Z = 1.96, P = 0.049) . ELISA showed that the levels of IL-1β and TNF-α were significantly higher in the C. acnes + NC group (12.12 ± 3.07 pg/ml, 26.06 ± 1.57 pg/ml, respectively) than in the PBS + NC group (3.73 ± 2.24 pg/ml, 10.14 ± 0.79 pg/ml, P = 0.003, < 0.001, respectively) ; compared with the C. acnes + NC group, the levels of IL-1β and TNF-α significantly decreased in the C. acnes + GSDME knockdown group (3.38 ± 0.93 pg/ml, 12.67 ± 2.10 pg/ml, P = 0.003, < 0.001, respectively) . The GSDME-NT expression was significantly lower in the retinol + C. acnes group than in the C. acnes group ( P = 0.029) . Conclusion:C. acnes may induce GSDME-mediated pyroptosis in keratinocytes, thereby promoting the release of inflammatory factors and aggravating the inflammatory response in acne, while retinol may be able to inhibit this process.