Aberrant activation of glycolysis represents a key metabolic mechanism underlying the initiation and progression of nasal inflammation. Allergic rhinitis, chronic rhinosinusitis, and vasomotor rhinitis exhibit distinct etiologies, yet all are characterized by inflammatory responses, impaired epithelial barrier function, and neurovascular dysregulation, in which glycolytic metabolic reprogramming acts as a central hub connecting immunometabolism and inflammatory regulation.Recent evidence indicates that glycolysis-dependent activation of immune cells provides the essential energy basis for inflammatory onset. In dendritic cells, eosinophils, mast cells, and Th2 cells, the expression of key glycolytic enzymes including HK2, PKM2, and LDHA is upregulated, thereby promoting cellular activation and proinflammatory cytokine release via the mTOR-HIF-1α signaling axis. Notably, the metabolic reprogramming of eosinophils prolongs their survival and enhances the release of cytotoxic granules, while in mast cells, enhanced glycolysis facilitates IgE-mediated degranulation and histamine release. Furthermore, glycolysis also influences the Th17/Treg balance, with enhanced glycolytic flux promoting Th17 differentiation and contributing to the heterogeneous inflammatory profiles observed across different rhinitis subtypes.As a central metabolite, lactate contributes to the formation of a metabolism-inflammation vicious cycle through multiple mechanisms. Lactate acidifies the local microenvironment to activate TRPV1 channels and facilitate neuropeptide release, mediates immune cell chemotaxis through GPR81, and regulates gene expression via histone lactylation, thereby sustaining proinflammatory gene transcription. These lactate-mediated processes collectively amplify local inflammation and contribute to the persistence of nasal symptoms.Glycolytic reprogramming in epithelial cells is modulated by the EGF/EGFR pathway, and its dysregulation may result in disrupted tight junctions, abnormal goblet cell hyperplasia, and subsequent tissue remodeling. Substance P and calcitonin gene-related peptide released from sensory neurons, in conjunction with metabolic products, synergistically maintain persistent inflammatory stimulation by activating mast cells, forming a neuro-immune-metabolic regulatory network that drives disease chronicity.From a therapeutic perspective, glycolytic inhibitors such as 2-deoxyglucose, FX11, and 3-bromopyruvate exert anti-inflammatory effects by targeting key enzymes including HK2 and LDHA, each with distinct mechanisms: 2-DG competitively inhibits hexokinase, FX11 selectively targets LDHA to reduce lactate production, and 3-BrPA modulates multiple glycolytic enzymes. Moreover, traditional Chinese medicine formulas, monomeric active components, and small-molecule compounds have shown promising potential in alleviating nasal inflammation by regulating the mTOR-HIF-1α axis, exerting antioxidant effects, and modulating endoplasmic reticulum stress pathways. The multi-target characteristics of these natural products offer advantages in addressing the complex pathophysiology of nasal inflammatory diseases.Despite these advances, several challenges remain. The non-selective inhibition of glycolysis may interfere with epithelial repair and mucosal regeneration, leading to delayed wound healing. Technical limitations in dynamic metabolic monitoring and sampling precision hinder the accurate assessment of local nasal metabolism. Furthermore, current animal models, which predominantly rely on acute stimulation protocols, inadequately recapitulate the chronic tissue remodeling processes characteristic of human rhinitis.This review systematically summarizes glycolysis as a common metabolic node shared by different rhinitis subtypes, offering a novel theoretical basis for the development of precision therapeutic strategies targeting metabolic reprogramming.

ObjectiveTo investigate the epidemiological and clinical characteristics of human bocavirus (HBoV) in hospitalized children with acute lower respiratory tract infection (ALRTI) at a single-center children’s hospital in Shanghai, thereby providing evidence for the diagnosis, treatment, and prevention of HBoV infection. MethodsA retrospective study was conducted on 19 537 hospitalized children with ALRTI at Shanghai Children’s Hospital from January 2021 to December 2023. Multiplex polymerase chain reaction (PCR) combined with capillary electrophoresis was used to detect HBoV and 12 other common respiratory viruses /atypical pathogens. The positive detection rate, demographic characteristics (sex, age), temporal distribution (year, season) of HBoV, as well as the clinical characteristics of severe and non-severe pneumonia were analyzed. ResultsThe overall HBoV-positive rate was 2.57% (503/19 537), with 59.44% (299/503) being single infections and 40.56% (204/503) being co-infections. The positive detection rate was significantly higher in boys than that in girls (2.78% vs 2.33%, χ²=3.88, P=0.049). The highest infection rate was observed in toddlers, followed by infants (χ²=379.57, P<0.001). The positive rate peaked in 2021 and reached its lowest point in 2023 (χ²=45.49, P<0.001), with epidemics mainly prevalent in summer and autumn. The main clinical symptoms were cough (90.06%, 453/503), fever (75.94%, 382/503), and wheezing (39.96%, 201/503). Children with severe pneumonia showed a higher incidence of wheezing compared with the non-severe group (P<0.001), while underlying diseases and co-infections had no significant association with disease severity (P>0.05). ConclusionHBoV was an important pathogen of ALRTI in children, predominantly affecting infants and toddlers, with higher susceptibility in boys and seasonal peaks in autumn and summer. The main clinical manifestations included cough, fever, and wheezing, with wheezing being more prevalent in children with severe pneumonia.

Aberrant activation of glycolysis represents a key metabolic mechanism underlying the initiation and progression of nasal inflammation. Allergic rhinitis, chronic rhinosinusitis, and vasomotor rhinitis exhibit distinct etiologies, yet all are characterized by inflammatory responses, impaired epithelial barrier function, and neurovascular dysregulation, in which glycolytic metabolic reprogramming acts as a central hub connecting immunometabolism and inflammatory regulation.Recent evidence indicates that glycolysis-dependent activation of immune cells provides the essential energy basis for inflammatory onset. In dendritic cells, eosinophils, mast cells, and Th2 cells, the expression of key glycolytic enzymes including HK2, PKM2, and LDHA is upregulated, thereby promoting cellular activation and proinflammatory cytokine release via the mTOR-HIF-1α signaling axis. Notably, the metabolic reprogramming of eosinophils prolongs their survival and enhances the release of cytotoxic granules, while in mast cells, enhanced glycolysis facilitates IgE-mediated degranulation and histamine release. Furthermore, glycolysis also influences the Th17/Treg balance, with enhanced glycolytic flux promoting Th17 differentiation and contributing to the heterogeneous inflammatory profiles observed across different rhinitis subtypes.As a central metabolite, lactate contributes to the formation of a metabolism-inflammation vicious cycle through multiple mechanisms. Lactate acidifies the local microenvironment to activate TRPV1 channels and facilitate neuropeptide release, mediates immune cell chemotaxis through GPR81, and regulates gene expression via histone lactylation, thereby sustaining proinflammatory gene transcription. These lactate-mediated processes collectively amplify local inflammation and contribute to the persistence of nasal symptoms.Glycolytic reprogramming in epithelial cells is modulated by the EGF/EGFR pathway, and its dysregulation may result in disrupted tight junctions, abnormal goblet cell hyperplasia, and subsequent tissue remodeling. Substance P and calcitonin gene-related peptide released from sensory neurons, in conjunction with metabolic products, synergistically maintain persistent inflammatory stimulation by activating mast cells, forming a neuro-immune-metabolic regulatory network that drives disease chronicity.From a therapeutic perspective, glycolytic inhibitors such as 2-deoxyglucose, FX11, and 3-bromopyruvate exert anti-inflammatory effects by targeting key enzymes including HK2 and LDHA, each with distinct mechanisms: 2-DG competitively inhibits hexokinase, FX11 selectively targets LDHA to reduce lactate production, and 3-BrPA modulates multiple glycolytic enzymes. Moreover, traditional Chinese medicine formulas, monomeric active components, and small-molecule compounds have shown promising potential in alleviating nasal inflammation by regulating the mTOR-HIF-1α axis, exerting antioxidant effects, and modulating endoplasmic reticulum stress pathways. The multi-target characteristics of these natural products offer advantages in addressing the complex pathophysiology of nasal inflammatory diseases.Despite these advances, several challenges remain. The non-selective inhibition of glycolysis may interfere with epithelial repair and mucosal regeneration, leading to delayed wound healing. Technical limitations in dynamic metabolic monitoring and sampling precision hinder the accurate assessment of local nasal metabolism. Furthermore, current animal models, which predominantly rely on acute stimulation protocols, inadequately recapitulate the chronic tissue remodeling processes characteristic of human rhinitis.This review systematically summarizes glycolysis as a common metabolic node shared by different rhinitis subtypes, offering a novel theoretical basis for the development of precision therapeutic strategies targeting metabolic reprogramming.

OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.

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

This study aims to investigate the optimal ratio of Astragali Radix-Curcumae Rhizoma(AC) for inhibiting the proliferation of 143B osteosarcoma cells, and to investigate the mechanism by which AC inhibits osteosarcoma growth and metastasis through angiogenesis and cell adhesion mediated by the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor-1α(HIF-1α) pathway. A subcutaneous 143B tumor-bearing nude mouse model was successfully established and randomly divided into the model group, and the AC 1∶1, 2∶1, and 4∶1 groups. Body weight, tumor volume, and tumor weight were recorded. Real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of PI3K, Akt, phosphorylated Akt(p-Akt), HIF-1α, vascular endothelial growth factor A(VEGFA), transforming growth factor-β1(TGF-β1), epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, matrix metalloproteinase 2(MMP2), matrix metalloproteinase 9(MMP9), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3 in the hypoxic core region of the tumor tissue. A cell hypoxia model was established, and the effects of AC-medicated serum(model group, AC 1∶1, 2∶1, and 4∶1 groups) on angiogenesis, proliferation, adhesion, invasion, and migration of 143B osteosarcoma cells were examined through CCK-8, flow cytometry, Transwell assay, cell adhesion assay, and HUVEC tube formation assay. The results showed that compared with the model group, the tumor weight and volume were smallest in the 2∶1 group. The expression levels of PI3K, Akt, p-Akt, HIF-1α, VEGFA, and TGF-β1 were significantly decreased, and the protein expression of E-cadherin was significantly increased, while the protein expression of N-cadherin, vimentin, MMP2, and MMP9 was significantly decreased. Additionally, the protein expression of Bax and caspase-3 was significantly increased, and Bcl-2 protein expression was significantly decreased. In vitro experiments showed that after intervention with AC-medicated serum at a 2∶1 ratio, the cell activity, adhesion, invasion, and migration of 143B cells were significantly reduced, apoptosis was significantly increased, and HUVEC tube formation was significantly decreased. In conclusion, the 2∶1 ratio of AC showed the most effective inhibition of 143B cell growth. AC can inhibit the growth and metastasis of osteosarcoma 143B cells by regulating the PI3K/Akt/HIF-1α signaling pathway, inhibiting angiogenesis and reducing cell adhesion, invasion, and migration.
Osteosarcoma/pathology* ; Animals ; Proto-Oncogene Proteins c-akt/genetics* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Humans ; Mice ; Cell Adhesion/drug effects* ; Cell Proliferation/drug effects* ; Neovascularization, Pathologic/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Phosphatidylinositol 3-Kinases/genetics* ; Cell Line, Tumor ; Mice, Nude ; Signal Transduction/drug effects* ; Astragalus Plant/chemistry* ; Bone Neoplasms/physiopathology* ; Male ; Rhizome/chemistry* ; Mice, Inbred BALB C ; Angiogenesis

This study employed bioinformatics to screen the feature genes related to efferocytosis in diabetic kidney disease(DKD) and explores traditional Chinese medicine(TCM) regulating these feature genes. The GSE96804 and GSE30528 datasets were integrated as the training set, and the intersection of differentially expressed genes and efferocytosis-related genes(ERGs) was identified as DKD-ERGs. Subsequently, correlation analysis, protein-protein interaction(PPI) network construction, enrichment analysis, and immune infiltration analysis were performed. Consensus clustering was conducted on DKD patients based on the expression levels of DKD-ERGs, and the expression levels, immune infiltration characteristics, and gene set variations between different subtypes were explored. Eight machine learning models were constructed and their prediction performance was evaluated. The best-performing model was evaluated by nomograms, calibration curves, and external datasets, followed by the identification of efferocytosis-related feature genes associated with DKD. Finally, potential TCMs that can regulate these feature genes were predicted. The results showed that the training set contained 640 differentially expressed genes, and after intersecting with ERGs, 12 DKD-ERGs were obtained, which demonstrated mutual regulation and immune modulation effects. Consensus clustering divided DKD into two subtypes, C1 and C2. The support vector machine(SVM) model had the best performance, predicting that growth arrest-specific protein 6(GAS6), S100 calcium-binding protein A9(S100A9), C-X3-C motif chemokine ligand 1(CX3CL1), 5'-nucleotidase(NT5E), and interleukin 33(IL33) were the feature genes of DKD. Potential TCMs with therapeutic effects included Astragali Radix, Trionycis Carapax, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma, which mainly function to clear heat, replenish deficiency, activate blood, resolve stasis, and promote urination and drain dampness. Molecular docking revealed that the key components of these TCMs, including β-sitosterol, quercetin, and sitosterol, exhibited good binding activity with the five target genes. These results indicated that efferocytosis played a crucial role in the development and progression of DKD. The feature genes closely related to both DKD and efferocytosis, such as GAS6, S100A9, CX3CL1, NT5E, and IL33, were identified. TCMs such as Astragali Radix, Trionycis Carapa, Sargassum, Rhei Radix et Rhizoma, Curcumae Radix, and Alismatis Rhizoma may provide a new therapeutic strategy for DKD by regulating efferocytosis.
Humans ; Computational Biology ; Diabetic Nephropathies/physiopathology* ; Protein Interaction Maps ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; Phagocytosis/genetics* ; Efferocytosis

This study developed a core outcome set(COS) for traditional Chinese medicine(TCM) interventions in diabetic peripheral neuropathy(DPN), standardizing evaluation metrics for TCM efficacy and providing a new framework for DPN treatment and management. A systematic search was conducted across databases, including CNKI, Wanfang, and PubMed, targeting clinical trial literature published between January 1, 2013, and January 1, 2023. The search focused on extracting outcome indicators and measurement tools used in TCM treatments for DPN. Retrospective data collection was performed from January 2018 to June 2023, involving 200 DPN patients hospitalized at the Department of Endocrinology of the First Affiliated Hospital of Anhui University of Chinese Medicine. Additionally, semi-structured interviews were conducted with inpatients, outpatients, their families, and nursing staff to further refine and enhance the list of outcome indicators. After two rounds of Delphi questionnaire survey and consensus meeting, a consensus was reached. The study initially retrieved 3 421 publications, of which 170 met the inclusion criteria after review. These publications, combined with retrospective analysis and semi-structured interviews, supplemented the list of indicators. After two rounds of Delphi surveys, experts agreed on 24 indicators and 6 measurement tools. The final COS determined by expert consensus meeting included 5 domains and 13 outcome indicators: neurological function signs, quality of life, TCM syndrome score, nerve conduction velocity, current perception threshold test, fasting blood glucose, 2 h postprandial blood glucose, glycated hemoglobin, complete blood count, urinalysis, liver function test, kidney function test, and electrocardiogram.
Humans ; Diabetic Neuropathies/drug therapy* ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Male ; Female