Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown etiology, primarily characterized by systemic inflammation and hyperactivation of both B and T lymphocytes. Key immunological features include increased consumption of complement components, sustained overproduction of type I interferons (IFN-I), and persistent production of a broad spectrum of autoantibodies, such as anti-dsDNA antibodies. However, the use of autoantibodies as biomarkers for the early detection of SLE is associated with a high false-positive rate, suggesting that antibody characteristics evolve during disease progression.N-glycosylation is a critical post-translational modification of antibodies that significantly influences their structure and receptor-binding properties, thereby modulating biological activities and functions. In particular, glycosylation patterns affect the antibody’s affinity for Fc gamma receptors (FcγRs), subsequently regulating various antibody-mediated immune responses. Numerous studies have investigated the impact of individual monosaccharides—such as sialic acid, fucose, and N-acetylglucosamine, which constitute N-glycans—on the immunological functions of antibodies. This review systematically summarizes the aberrant immunoglobulin G (IgG) N-glycosylation patterns observed in SLE patients, with a focus on correlations between disease progression or complications and quantitative alterations in individual glycan components. We first review how different types of N-glycosylation modifications affect the biological activity and functional properties of IgG, particularly regarding the effects of specific monosaccharides—such as sialic acid, fucose, and galactose—on FcγR binding affinity and the resulting downstream immune functions. We then summarize the differential expression of IgGN-glycans and glycosyltransferase genes between SLE patients and healthy controls, and outline the associations between glycosylation changes and SLE-related pathological responses. In response to the inconsistencies and limitations in current research, we propose potential explanations from the perspectives of study methodologies, participant characteristics, and variations in N-glycan structures, aiming to provide a constructive reference for future studies. Given the close relationship between antibody glycosylation and SLE, this review highlights the potential of IgG N-glycosylation patterns as promising biomarkers for early diagnosis and disease monitoring. In terms of therapy, we discuss how IgG glycosylation can enhance the efficacy of intravenous immunoglobulin (IVIg) treatment and introduce emerging therapeutic strategies that aim to modulate endogenous IgG N-glycans as a novel glycan-based approach for SLE management. In summary, N-glycans are essential structural components of antibodies that regulate immune responses by modulating antibody-receptor interactions. Aberrant glycosylation is closely associated with the pathogenesis of autoimmune diseases, including SLE. However, due to the structural diversity of N-glycans and the complexity of glycosylation processes, the precise roles of IgGN-glycosylation in SLE pathophysiology remain incompletely understood. Moreover, therapeutic strategies targeting IgG glycosylation are still in early development and have not yet reached clinical application. Continued progress in glycan analysis technologies and other biological tools, along with interdisciplinary collaboration, will be essential for advancing this field.

This study aims to comprehensively analyze the material basis of toad visceral oil(hereafter referred to as toad oil), and explore the pharmacological effect of toad oil on atopic dermatitis(AD). Ultra-high performance liquid chromatography-linear ion trap/orbitrap high-resolution mass spectrometry(UHPLC-LTQ-Orbitrap-MS) and gas chromatography-mass spectrometry(GC-MS) were employed to comprehensively identify the chemical components in toad oil. The animal model of AD was prepared by the hapten stimulation method. The modeled animals were respectively administrated with positive drug(0.1% hydrocortisone butyrate cream) and low-and high-doses(1%, 10%) of toad oil by gavage. The effect of toad oil on AD was evaluated with the AD score, ear swelling rate, spleen index, and pathological section results as indicators. A total of 99 components were identified by UHPLC-LTQ-Orbitrap-MS, including 14 bufadienolides, 7 fatty acids, 6 alkaloids, 10 ketones, 18 amides, and other compounds. After methylation of toad oil samples, a total of 20 compounds were identified by GC-MS. Compared with the model group, the low-and high-dose toad oil groups showed declined AD score, ear swelling rate, and spleen index, alleviated skin lesions, and reduced infiltrating mast cells. This study comprehensively analyzes the chemical composition and clarifies the material basis of toad oil. Meanwhile, this study proves that toad oil has a good therapeutic effect on AD and is a reserve resource of traditional Chinese medicine for external use in the treatment of AD.
Animals ; Dermatitis, Atopic/immunology* ; Disease Models, Animal ; Mice ; Male ; Gas Chromatography-Mass Spectrometry ; Humans ; Bufonidae ; Oils/administration & dosage* ; Chromatography, High Pressure Liquid ; Female ; Mice, Inbred BALB C

Based on the α7 nicotinic acetylcholine receptor(α7nAChR), this study examined how tetrahydropalmatine(THP) affected BV2 microglia exposed to lipopolysaccharide(LPS), aiming to clarify the possible mechanism underlying the anti-depression effect of THP from the perspectives of preventing inflammation and regulating polarization. First, after molecular docking and determination of the content of Corydalis saxicola Bunting total alkaloids, THP was initially identified as a possible anti-depression component. The BV2 microglia model of inflammation was established with LPS. BV2 microglia were allocated into a normal group, a model group, low-and high-dose(20 and 40 μmol·L~(-1), respectively) THP groups, and a THP(20 μmol·L~(-1))+α7nAChR-specific antagonist MLA(1 μmol·L~(-1)) group. The CCK-8 assay was used to screen the safe concentration of THP. A light microscope was used to examine the morphology of the cells. Western blot and immunofluorescence were used to determine the expression of α7nAChR. qRT-PCR was performed to determine the mRNA levels of inducible nitric oxide synthase(iNOS), cluster of differentiation 86(CD86), suppressor of cytokine signaling 3(SOCS3), arginase-1(Arg-1), cluster of differentiation 206(CD206), tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. The experimental results showed that THP at concentrations of 40 μmol·L~(-1) and below had no effect on BV2 microglia. THP improved the morphology of BV2 microglia, significantly up-regulated the protein level of α7nAChR, significantly down-regulated the mRNA levels of iNOS, CD86, SOCS3, TNF-α, IL-6, and IL-1β, significantly up-regulated the mRNA levels of Arg-1 and CD206, and dramatically lowered the levels of TNF-α, IL-6, and IL-1β in the cell supernatant. However, the antagonist MLA abolished the above-mentioned ameliorative effects of THP on LPS-treated BV2 microglia. As demonstrated by the aforementioned findings, THP protected LPS-treated BV2 microglia by regulating the M1/M2 polarization and preventing inflammation, which might be connected to the regulation of α7nAChR on BV2 microglia.
Berberine Alkaloids/chemistry* ; alpha7 Nicotinic Acetylcholine Receptor/chemistry* ; Microglia/metabolism* ; Mice ; Animals ; Cell Line ; Corydalis/chemistry* ; Humans ; Molecular Docking Simulation ; Inflammation/drug therapy* ; Nitric Oxide Synthase Type II/immunology* ; Tumor Necrosis Factor-alpha/immunology*

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

OBJECTIVE: To explore the clinical features of patients with necrotizing soft tissue infection (NSTI) and the related factors for sepsis, so as to provide a basis for early intervention and improvement of patients' prognosis. METHODS: A retrospective case series study was conducted to analyze the clinical data of NSTI patients admitted to the department of burns and wound repair surgery of Guangdong Provincial People's Hospital from October 2021 to December 2024. Demographic information, underlying diseases, infection characteristics, laboratory test results and etiological findings at admission, treatment status, occurrence of complications (including sepsis) and prognosis were collected. Univariate and multivariate Logistic regression analyses were used to identify the associated factors for sepsis in NSTI patients. Receiver operator characteristic curves (ROC curves) were plotted to evaluate the predictive value of individual and combined factors for sepsis. RESULTS: A total of 159 NSTI patients were enrolled, mainly middle-aged and elderly males. Most patients had comorbidities, including diabetes mellitus (110 cases, 69.2%) and hypertension (67 cases, 42.1%). The main infection site was the lower extremities (104 cases, 65.4%). Common symptoms included redness (96 cases, 60.4%), swelling (129 cases, 81.1%), local heat (60 cases, 37.7%), pain (100 cases, 62.9%), and skin ulceration or necrosis (9 cases, 5.7%). Imaging findings included soft tissue swelling (66 cases, 57.9%), gas accumulation (41 cases, 36.0%), and abnormal signal/density shadows (50 cases, 43.9%). Staphylococcus aureus was the main pathogenic bacterium [12.0% (31/259)], and drug-resistant Escherichia coli had the highest detection rate among drug-resistant bacteria [35.1% (13/37)]. Regarding debridement and repair, most patients (80 cases, 50.3%) underwent debridement ≥ 72 hours after admission, while only 10.1% (16 cases) received debridement within 6 hours. Most patients underwent multiple debridements, with 2 times of debridements being the most common (68 cases, 42.8%), and the maximum times of debridements reached 6. The largest number of patients received secondary suture (44 cases, 27.7%). In terms of complications, sepsis was the most common (66 cases, 41.51%), followed by acute kidney injury, respiratory failure requiring mechanical ventilation, and multiple organ dysfunction syndrome (MODS), while disseminated intravascular coagulation (DIC) was the least common. During the follow-up period, 9 patients (5.66%) were readmitted within 90 days, and 11 patients died, with a mortality rate of 6.92%. Univariate analysis showed that diabetes, coronary heart disease, gout, body temperature, heart rate, C-reactive protein, platelet count, total bilirubin, albumin, creatinine, out-of-hospital treatment, and out-of-hospital use of antimicrobial agents were significantly associated with sepsis in NSTI patients (all P < 0.05). Multivariate Logistic regression analysis showed that coronary heart disease [odds ratio (OR) = 30.085, 95% confidence interval (95%CI) was 2.105-956.935], C-reactive protein (OR = 1.026, 95%CI was 1.009-1.054), and total bilirubin (OR = 1.436, 95%CI was 1.188-1.948) were independent associated factors for sepsis in NSTI patients (all P < 0.05). ROC curve analysis revealed that the combination of the three predictors yielded the highest AUC for predicting sepsis in NSTI patients compared to any individual predictor [area under the curve (AUC) = 0.799 (95%CI was 0.721-0.878)]. CONCLUSIONS The clinical features of NSTI patients show certain regularity. Coronary heart disease, C-reactive protein, and total bilirubin are independent associated factors for sepsis in NSTI patients.
Humans ; Retrospective Studies ; Male ; Sepsis ; Soft Tissue Infections/microbiology* ; Female ; Middle Aged ; Aged ; Adult ; Prognosis ; Risk Factors ; Necrosis ; Logistic Models ; Fasciitis, Necrotizing

This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Objective To identify disulfidptosis-related gene(DRG)in acute myocardial infarction(AMI)by bioinformatics,analyze the molecular pattern of DRGs in AMI,and construct a DRGs-related prediction model.Methods AMI-related datasets were downloaded from the Gene Expression Omnibus database,and DRGs with differential expression were screened in AMI.CIBERSORT method was used to analyze the immune infiltration.Based on the differentially expressed DRGs,the AMI patients were classified into distinct subtypes via consensus clustering,followed by immune infiltration analysis,differential expression analysis,gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis,and gene set variation analysis.Weighted gene co-expression network analysis(WGCNA)was then performed to construct subtype-associated modules and identify hub genes.Finally,least absolute shrinkage and selection operator,random forest,and support vector machine-recursive feature elimination were used to screen feature genes to construct a DRGs-related prediction model.The model's diagnostic efficacy was evaluated by nomogram and receiver operating characteristic(ROC)curve analysis,followed by external validation.Results Nine differentially expressed DRGs were identified between AMI patients and controls.Based on the expression levels of these nine DRGs,AMI patients were divided into two DRGs subtypes,C1 and C2.Increased infiltration of monocytes,M0 macrophages,and neutrophils was observed in AMI patients and C1 subtype(all P<0.05),indicating a close correlation between DRGs and immune cells.There were 257 differentially expressed genes between the C1 and C2 subtypes,which were related to biological processes such as myeloid leukocyte activation and positive regulation of cytokines.Fcγ receptor-mediated phagocytosis and NOD-like receptor signaling pathway activity were enhanced in C1 subtype.WGCNA analysis suggested that the brown module exhibited the strongest correlation with DRG subtypes(r=0.67),from which 23 differentially expressed genes were identified.The feature genes screened by three machine learning methods were interpolated to obtain a DRGs-related prediction model consisting of three genes(AQP9,F5 and PYGL).Nomogram and ROC curves(AUC_train=0.891,AUC_test=0.840)showed good diagnostic efficacy.Conclusions DRGs were closely related to the occurrence and progression of AMI.The DRGs-related prediction model consisting of AQP9,F5 and PYGL may provide targets for the diagnosis and personalized treatment of AMI.
Humans ; Myocardial Infarction/diagnosis* ; Transcriptome ; Computational Biology ; Gene Expression Profiling ; ROC Curve ; Gene Regulatory Networks ; Nomograms ; Disulfidptosis

With the continuous development of informatization, digitalization and artificial intelligence technology, the working mode of the pathology department has gradually changed from the traditional manual check, paper circulation and physical carrier storage to the informatization process and digital storage. The traditional pathology discipline has ushered in unprecedented opportunities and challenges. Digital pathology department also emerge as the times require. Simultaneously, with the full integration of artificial intelligence technology in pathology department, the concept of "department of digital and intelligentialized pathology" was proposed. Based on information and digital technology, the digital intelligent pathology department integrates intelligent management system, optimizes the previous cumbersome management and workflow of the pathology department, develops advanced technologies such as intelligent material extraction, unmanned organization processing, artificial intelligence quality control, artificial intelligence diagnosis, and promotes the intelligent construction of the pathology department.

Objective To understand the application of skin disinfectant in neonatal intensive care units(NICUs)nationwide.Methods From April to May 2023,application of skin disinfectant in 93 NICUs nationwide was sur-veyed with convenience sampling method by a self-designed questionnaire.Questionnaire contents included types of disinfectant,disinfection tools,cleaning and disinfection frequency,disinfectant drying status,removal of disinfec-tant,and adverse reactions caused by disinfectant.Results A total of 93 nursing units in 71 medical institutions from 25 provinces/municipalities were included in this study.In NICUs,three most commonly used disinfectants were ethanol(79.57％),iodophor(74.19％),and anerdian(62.37％).In nursing units for neonates＜2 months of age,chlorhexidine was prohibited in 28 units(30.11％),used with caution in 23 units(24.73％),allowed in 9 units(9.68％),and there was no unified requirement in 33 units(35.48％).When using ethanol,staff only wiped once in 13(17.57％)nursing units.In some nursing units,there was no unified requirements on the wiping fre-quency of disinfectant.As for the removal of residual iodine,saline was used in 29(42.03％)nursing units,ethanol in 8(11.59％),and 19(27.54％)did not have unified requirements.The adverse reactions of disinfectant mainly included rash and contact dermatitis.Disinfectants that caused adverse reactions included ethanol,iodophor,aner-dian,and chlorhexidine.Conclusion In clinical practice,unified standards for the use of neonatal skin disinfectant remain absent.Selection and use of neonatal skin disinfectant vary considerably.Neonatal skin disinfectants have common adverse reactions.It is necessary to strengthen the training of health care workers on the standardized use of disinfectant,as well as carry out large-scale and rigorous randomized controlled trial designs to provide scientific basis for the correct selection of disinfectant.