Diffuse infiltrating retinoblastoma is an extremely rare form of retinoblastoma which is characterized by its atypical growth pattern. This unusual presentation adds complexity to the diagnostic process. The purpose of this paper is to report a rare presentation of diffuse infiltrating retinoblastoma presenting after an ocular trauma. We described a 7-year-old Filipino boy presenting with total hyphema following an ocular trauma. Comprehensive ophthalmologic clinical and diagnostic evaluations were performed including visual acuity, slitlamp biomicroscopy, ocular ultrasound, neuroimaging, and histopathology post enucleation to determine diagnosis. The misleading, atypical presentation of diffuse infiltrating retinoblastoma may delay diagnosis. While this dilemma is expected in these scenarios, it should be remembered that timing of diagnosis in retinoblastoma is crucial, as this also equates to optimal management. One should remain vigilant for these uncommon presentations especially in the setting of any intraocular inflammation in children.

Human ; Male ; Child: 6-12 Yrs Old ; Wounds And Injuries ; Visual Acuity ; Retinoblastoma ; Research Report ; Neuroimaging ; Inflammation ; Hyphema ; Contusions

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major chronic respiratory condition with high morbidity and mortality, imposing a serious economic and public health burden. The World Health Organization ranks COPD among the top 4 chronic diseases worldwide. Zangsiwei Qingfei Mixture (ZSWQF), a novel Tibetan herbal formulation independently developed by our research team, has shown therapeutic potential for chronic respiratory diseases. This study aims to evaluate the effects of aerosolized ZSWQF on cigarette smoke-induced COPD in mice and explore its underlying mechanisms. METHODS: Thirty C57 mice were randomly divided into a Control group, a COPD group, and a ZSWQF group. The Control group received saline aerosol inhalation without cigarette smoke exposure; both the COPD group and the ZSWQF group were exposed to cigarette smoke, with the former receiving saline inhalation and the latter treated with ZSWQF aerosol. White blood cell (WBC) count was performed using a fully automatic blood cell analyzer. Serum, alanine transaminase (ALT), and serum creatinine (SCr), as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). BALF cell classification was determined using a hematology analyzer. Lung function was assessed with a small animal pulmonary function system, including airway resistance (RI) and cyclic dynamic compliance (CyDN). Lung tissues were stained with hematoxylin and eosin (HE), and mean linear intercept (MLI) and destruction index (DI) were calculated to evaluate morphological changes. Network pharmacology was applied to identify disease-related and ZSWQF-related targets, followed by intersection and protein-protein interaction (PPI) network analysis, and enrichment analysis of biological functions and pathways. Primary type II alveolar epithelial cell (AEC II) from SD rats were isolated and divided into a Control group, a lipopolysaccharide (LPS) group, a normal serum group, a water extract of ZSWQF (W-ZSWQF) group, a ZSWQF containing serum group, and a MLN-4760 [angiotensin-converting enzyme (ACE) 2 inhibitor]. Western blotting was performed to assess protein expression of ACE, p38 [a mitogen-activated protein kinase (MAPK)], phospho (p)-p38, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, inhibitor of nuclear factor-kappa B alpha (IκBα), p-IκBα, and p-p65 subunit of nuclear factor-kappa B (NF-κBp65). RESULTS: WBC counts were significantly higher in the COPD group than in controls (P<0.01) and decreased following ZSWQF treatment (P<0.05). No significant intergroup differences were found in organ weights, ALT, or SCr (all P>0.05). Serum and BALF levels of IL-6, IL-8, and TNF-α, as well as total BALF cells, neutrophils, and macrophages, were elevated in the COPD group compared with controls and reduced by ZSWQF treatment (P<0.05). COPD mice exhibited increased RI, decreased CyDN, marked alveolar congestion, inflammatory infiltration, thickened septa, and higher MLI and DI values versus controls (P<0.05); ZSWQF treatment significantly reduced MLI and DI (P<0.05). Network pharmacology identified 151 potential therapeutic targets for ZSWQF against COPD, with key nodes including TNF, IL-6, protein kinase B (Akt) 1, albumin (ALB), tumor protein p53 (TP53), non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT) 3, matrix metalloproteinase (MMP)-9, and beta-catenin (CTNNB1). Enrichment analysis indicates involvement of cancer-related, phosphatidylinositol 3-kinase (PI3K)/Akt, hypoxia-inducible factor (HIF)-1, calcium, and MAPK signaling pathways. Western blotting results showed that compared with the LPS group, AEC II treated with ZSWQF-containing serum exhibited decreased expression of ACE, p-p38/p38, p-ERK1/2/ERK1/2, p-JNK/JNK, p-IκBα/IκBα, and p-NF-κBp65, while ACE2 expression was upregulated, consistent with the MAPK/nuclear factor-kappa B (NF-κB) pathway regulation predicted by network pharmacology. CONCLUSIONS Aerosolized ZSWQF provides protective effects in COPD mice by reducing airway inflammation and remodeling.
Animals ; Pulmonary Disease, Chronic Obstructive/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Mice, Inbred C57BL ; Male ; Network Pharmacology ; Smoke/adverse effects* ; Bronchoalveolar Lavage Fluid ; Administration, Inhalation ; Inflammation/drug therapy* ; Tumor Necrosis Factor-alpha ; Lung/drug effects* ; Interleukin-6/blood*

In recent years, pyroptosis, an inflammatory form of programmed cell death, has gained increasing attention in the field of metabolic disease research. Pyroptosis is closely associated with inflammatory responses. A growing body of evidence suggests that pyroptosis not only plays a critical role in regulating inflammation but can also influence metabolic status, cellular function, and tissue damage through multiple pathways, thereby either exacerbating or alleviating the progression of metabolic diseases. However, the precise molecular mechanisms of pyroptosis and its roles across different metabolic diseases remain unclear, and investigations into related therapeutic targets are still in early stages. Systematically elucidating the mechanisms by which pyroptosis contributes to metabolic diseases and exploring its potential roles in inflammation and pathophysiology may provide new insights and strategies for the prevention and treatment of metabolic disorders, and further promote advances in this research field.
Pyroptosis/physiology* ; Humans ; Metabolic Diseases/metabolism* ; Inflammation/physiopathology* ; Animals ; Inflammasomes

Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

Objective:Inflammation has been confirmed to play an important role in the occurrence and development of sudden sensorineural hearing loss（SSNHL）, and the neutrophil-to-lymphocyte ratio（NLR） is a biomarker positively correlated with the degree of inflammation. This study aims to identify the difference in serum NLR between patients with SSNHL and normal population, and to evaluate the predictive efficacy of NLR for the occurrence and prognosis of SSNHL, thereby guiding the clinical diagnosis and treatment of SSNHL. Methods:In this study, 96 patients diagnosed with SSNHL admitted to our department from January 2023 to March 2024 and 96 patients diagnosed with vocal cord polyps admitted to our department during the same period were recruited as a control group. Multivariate Logistic regression was used to evaluate independent related factors, and a nomogram was constructed to predict the probability of SSNHL. The receiver operating characteristic（ROC） curve and calibration curve were used to evaluate the accuracy of prediction. Results:Multivariate logistic regression analysis showed that a high level NLR（OR2.215; 95%CI1.597-3.073; P<0.001） were independently associated with the presence of SSNHL. High age（OR1.036; 95%CI1.009-1.067; P=0.012）, high FIB（OR2.35; 95%CI1.176-4.960; P=0.019） were the risk factor for SSNHL. Incorporating these 3 factors, a forest plot and a nomogram were generated. The ROC curve, nomogram and calibration curve showed that the model had good clinical practicability. A low NLR（OR0.598; 95%CI0.439-0.816; P<0.001） was significantly associated with a favorable prognosis of SSNHL. Conclusion:Elevated NLR can serve as an promising biomarker for assessing the risk of SSNHL. The nomograms calculation model may be utilized as a tool to estimate the probability of SSNHL. Low level NLR is significantly associated with a good prognosis of SSNHL.
Humans ; Neutrophils ; Female ; Male ; Lymphocytes ; Hearing Loss, Sensorineural/blood* ; Hearing Loss, Sudden/diagnosis* ; Middle Aged ; Prognosis ; Nomograms ; ROC Curve ; Adult ; Logistic Models ; Biomarkers/blood* ; Lymphocyte Count ; Inflammation/blood* ; Clinical Relevance

Objective:To discuss the clinical efficacy of low-temperature radiofrequency ablation assisted by endoscopy combined with resection and drainage of cervical abscess for the treatment of congenital pyriform sinus fistula （CPSF） in the acute inflammatory period of children. Methods:Clinical data of 30 patients with CPSF in the acute inflammatory period who received low-temperature radiofrequency ablation assisted by endoscopy under laryngoscope, combined with resection and drainage of cervical abscess, from January 2018 to December 2023 were reviewed. After the operation, patients were followed up closely at different stages. All patients underwent color Doppler ultrasound and electronic laryngoscopy, and the results were analyzed. Results:All 30 children successfully completed the surgery without pharyngeal fistula, dysphagia, perifistula, or distal fistula infection, and the incision in the neck healed well. The follow-up survey ranged from 6 months to 2 years, and no recurrences were observed. Conclusion:Low-temperature radiofrequency ablation assisted by endoscopy combined with resection and drainage of cervical abscess is a promising method for treating CPSF in the acute inflammatory period. It is less traumatic, simple, safe, has a significant curative effect, and a low recurrence rate. This approach can be used as a supplementary operation for CPSF in children and provides a new way for clinical treatment.
Humans ; Pyriform Sinus/abnormalities* ; Abscess/surgery* ; Drainage ; Fistula/congenital* ; Female ; Male ; Child ; Radiofrequency Ablation ; Treatment Outcome ; Postoperative Period ; Endoscopy ; Laryngoscopy ; Inflammation ; Child, Preschool

One of the main pathological features of airway inflammatory diseases is hypersecretion of airway mucus, which is manifested by goblet cell hyperplasia and mucociliary clearance dysfunction. In recent years, it has been found that the molecular structure of calcium activated chloride ion channels, transmenbrane protein 16A（TMEM16A）, is closely related to airway mucus hypersecretion.TMEM16A not only mediates ion transepithelial transport and hydration, but also participates in the regulation of mucin secretion. TMEM16A is highly expressed in airway epithelium of a variety of inflammatory diseases of upper and lower airway, such as asthma, cystic fibrosis, allergic rhinitis, chronic sinusitis and so on. Understanding the expression level and regulation mechanism of TMEM16A in different airway diseases and revealing its physiological function and pathological mechanism is critical for targeted disease treatment. This paper summarizes the research status of the discovery process, structural characteristics and regulatory mechanism of TMEM16A, and then summarizes the expression level of TMEM16A in asthma, cystic fibrosis, allergic rhinitis and chronic sinusitis ant related pathological mechanisms, clarifies the potential value of TMEM16A as a therapeutic target for the above four diseases, in order to guide treatment of airway inflammatory diseases.
Humans ; Asthma/metabolism* ; Anoctamin-1 ; Cystic Fibrosis/metabolism* ; Neoplasm Proteins/metabolism* ; Sinusitis/metabolism* ; Chloride Channels/metabolism* ; Rhinitis, Allergic/metabolism* ; Inflammation

Objective:To explore the effect, postoperative mucosal pathological changes and molecular biological changes of reboot operation for type 2 inflammation chronic rhinosinusitis with nasal polyps（CRSwNP） patients, and to provide theoretical basis for the clinical application of this kind of operation. Methods:We collected 29 patients who were diagnosed with CRSwNP with type 2 inflammatino response and underwent Reboot surgery from June 2022 to August 2023, and 27 patients who were diagnosed with deviated septum and underwent simple submucosal resection of the septum as the control group. We conducted nasal symptom scoring, endoscopic sinusitis scoring, and CT scanning of the sinuses before and after surgery, as well as HE staining, immunohistochemical staining, and detection of inflammatory factors using Elisa kits at the time of surgery, 1, 3, and 6 months postoperatively. We also observed the ultrastructural changes using transmission electron microscopy and scanning electron microscopy, and performed proteomic analysis of the mucosa in the ethmoid sinus area of the sinusitis patients at the time of surgery and 6 months postoperatively. Results:After 6 months of postoperative follow-up, CT scores of the nasal cavity and sinuses had gradually decreased compared with the preoperative period. The VAS score of main symptoms, SNOT-22 score and Lund-Kennedy endoscopic score were decreased after 12 months follow-up. The histological morphology of the mucosa in the area of the screen was significantly improved compared with the preoperative period, with a reduction in the number of eosinophils. The levels of inflammatory factors such as IL-4 and IL-5 et al. in the mucosa of the area of the screen were gradually reduced compared with the preoperative period. The histological morphology, ultrastructure, and cilia structure of the mucosa in the area of the screen were gradually improved compared with the preoperative period, though not recovered completely. The number of CD4⁺T and CD8⁺T cells not changed significantly before and after the surgery yet. By conducting proteomic analysis of the ethmoidal sinus mucosa before and after surgery, differential proteins were selected, and bioinformatics analysis was conducted on the differentially expressed proteins. By using cytoHubba to identify hub genes and intersecting them with the genes related to chronic sinusitis, we found that MMP9 expression increased in non-type 2 CRS and type 2 CRS in sequence, while ACTC1 expression decreased in non-tpye 2 CRS and type 2 CRS in sequence. Conclusion:Reboot surgery can improve the postoperative symptoms and signs of patients, improve the pathological morphology of the mucosa, and influence the expression of protein after surgery. However, the surgery may not have a significant impact on the distribution of T cell subpopulations and inflammation signal pathway in the nasal mucosa.
Humans ; Sinusitis/metabolism* ; Nasal Polyps/metabolism* ; Nasal Mucosa/ultrastructure* ; Chronic Disease ; Rhinitis/complications* ; Inflammation ; Male ; Female ; Postoperative Period ; Adult ; Interleukin-5/metabolism* ; Interleukin-4/metabolism* ; Middle Aged ; Proteomics ; Rhinosinusitis

OBJECTIVES: To investigate the effect of high glucose on macrophage polarization and the role of immune-responsive gene 1 (IRG1) in mediating its effect. METHODS: RAW264.7 cells were transfected with IRG1-overexpressing plasmid or IRG1 siRNA via electroporation and cultured in either normal or high glucose for 72 h to observe the changes in cell viability and morphology using CCK-8 assay and phase contrast microscopy. The protein levels of IRG1, iNOS, Arg-1, IL-1β and IL-10 in the treated cells were detected with Western blotting, and the fluorescence intensities of iNOS and Arg-1 were detected using immunofluorescence assay. The protein levels of IL-1β and IL-10 in the culture medium were determined with ELISA. RESULTS: High glucose exposure significantly reduced IRG1 and Arg-1 expressions, increased iNOS and IL-1β expressions and IL-1β secretion, and decreased IL-10 level in RAW264.7 cells. Transfection with the IRG1-overexpressing plasmid provided the cells with obvious resistance to high glucose-induced changes in iNOS, Arg-1, IL-1β and IL-10, whereas IRG1 knockdown further enhanced the effects of high glucose exposure on Arg-1 expression and the expression and secretion of IL-10. CONCLUSIONS High glucose promotes M1 polarization of the macrophages possibly through a mechanism to inhibit the expression of IRG1 protein, thus leading to chronic inflammatory response.
Animals ; Mice ; Macrophages/drug effects* ; Glucose/pharmacology* ; Interleukin-10/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; RAW 264.7 Cells ; Interleukin-1beta/metabolism* ; Arginase/metabolism* ; RNA, Small Interfering/genetics* ; Transfection ; Inflammation

OBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors. METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing. RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats. CONCLUSIONS JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Depression/drug therapy* ; Neurotransmitter Agents/metabolism* ; Rats ; Inflammation ; Male ; Hippocampus ; Behavior, Animal/drug effects*