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关键词： chronic hepatitis B   serum ferritin   HBsAg   PEG IFN-alpha 2b   ALT  

摘要： Background: Chronic hepatitis B (CHB) caused by HBV infection leads to persistent liver inflammation. PEG IFN alpha-2b shows higher functional cure rates than oral antivirals, but identifying optimal candidates remains challenging. This study evaluates serum ferritin as a predictive biomarker for PEG IFN alpha-2b efficacy. Methods: Serum ferritin, HBsAg and transaminase were monitored in CHB patients treated with PEG IFN alpha-2b at baseline (0w), 12w and 24w. Patients were divided into the effective group (HBsAg reduction >= 1 log10 IU/mL or clearance) and the ineffective group (HBsAg reduction <1 log10 IU/mL) at 24 weeks. Similarly, for the results at 48 weeks, the patients were divided into the clearance group (achieving HBsAg clearance) and the non-clearance group (not achieving HBsAg clearance). To analyze the correlation between serum ferritin and the decrease of HBsAg, a multivariate logistic regression model was constructed. Potential confounding factors such as age, gender, HBeAg and HBV DNA status, ALT, AST, and iron metabolism indicators (FE, TIBC, TS) were included to evaluate the independent predictive effect of ferritin levels on the therapeutic effectiveness, calculate the corrected OR value and 95% CI. The predictive effect was evaluated by the ROC curve. Results: Among patients with chronic hepatitis B (CHB) who completed the PEG IFN alpha-2b course of treatment, the serum ferritin levels of all patients showed an increasing trend at baseline and during the treatment process, and the serum ferritin level in the effective treatment group (HBsAg reduction >= 1 log10 IU/mL or clearance) was significantly higher than that in the ineffective treatment group. It was confirmed by Spearman's rank correlation analysis that the serum ferritin level was positively correlated with the decrease in HBsAg. Further analysis through the multivariate logistic regression model revealed that serum ferritin remained an independent predictor of the antiviral efficacy of

摘要： INTRODUCTION:The residual risk of chronic kidney disease (CKD) progression remains high in clinical trials of kidney protective drugs in patients with diabetic kidney disease (DKD). METHODS:In a prospective study, we assessed whether 16 plasma and 10 urine cytokine levels can inform the residual risk of CKD progression in 93 incident patients with DKD treated by Nephrology according to clinical guidelines. RESULTS:Plasma and urine levels of 12 plasma and 7 urinary cytokines differed between patients with DKD and from healthy controls. Participants were categorized into CKD G1-G2 (preserved GFR) and CKD G3-G5 (GFR <60 ml/min/1.73 m2). After a median of 7.27 years (IQR; 5.34-9.56), 13/40 (32.5%) patients with CKD G1-G2 at baseline had progressed to CKD G3-G5. Progressors had higher plasma IL-22 and TNF-α levels than non-progressors. Plasma IL-22 and TNF-α levels in progressors were similar to those in patients already in CKD G3-G5 at baseline, suggesting that cytokine dysregulation precedes CKD progression. In patients with CKD G1-G2, cut-off points for plasma IL-22 and TNF-α predicted progression with an AUC of 0.76 and 0.77, respectively. Additionally, patients with CKD G1-G2 and plasma TNF-α or IL-22 levels equal to or above the cut-off value had significantly lower eGFR values at the end of follow-up and had more frequently progressed to a very high risk KDIGO category. In cluster analysis, clusters displaying the highest urinary or plasma cytokine levels were associated with worse GFR outcomes. CONCLUSION:Plasma IL-22 and TNF-α may help to identify patients with early DKD with a high residual risk of CKD progression despite treatment.

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关键词： TNF-alpha   PCOS   Polymorphism   Insulin resistance   Kashmir  

摘要： Background Polycystic ovary syndrome (PCOS) is a chronic inflammatory disease characterized by a hyperandrogenic state, irregular menses, and polycystic ovaries (PCO). Tumor necrosis factor-alpha (TNF-alpha), a key pro-inflammatory cytokine, plays a significant role in this process of inflammation. Studying TNF-alpha polymorphisms is important as genetic variations may influence TNF-alpha expression, potentially affecting individual susceptibility to disease and its severity. The -1031 (T > C) single-nucleotide polymorphism (SNP) in the TNF-alpha has been linked to inflammatory and metabolic disorders, but its association with PCOS, particularly in Kashmiri population, is not well explored. Objectives The objective of the study was to assess the impact of -1031 (T > C) SNP in the TNF-alpha on the vulnerability of PCOS in women from Kashmir and to find out its correlation with clinical, hormonal, and metabolic parameters. Methods This study enrolled 210 PCOS patients and 203 age and body mass index (BMI) matched healthy controls. Genotyping of -1031 (T > C) SNP was performed using the restriction fragment length polymorphism (RFLP) method. Biochemical, hormonal, and metabolic profiles were investigated. The study primarily employed Chi-square tests, t tests, and ANOVA. Results TC genotype was significantly more frequent in PCOS cases (43.8%) vs. controls (21.6%) [odds ratio (OR) = 2.81;95% confidence interval (CI) 1.83-4.33;p = 0.001)]. The C allele frequency was higher in cases (21.9%) vs. controls (10.83%) (OR = 2.30;95% CI 1.56-3.40;p = 0.001). TC genotype carriers showed higher fasting insulin, homeostasis model assessment insulin resistance index (HOMA-IR), triglyceride levels, and reduced quantitative insulin sensitivity check index (QUICKI), indicating insulin resistance (IR) (p < 0.05). Conclusion The -1031 (T > C) SNP in the TNF-alpha gene is significantly associated with increased susceptibility to PCOS in Kashmiri women, with the TC genotype linked to high

关键词： guselkumab   IL-23   psoriasis   psoriatic arthritis  

摘要： Background: Psoriasis is a chronic inflammatory condition that may develop into psoriatic arthritis (PsA) in a significant number of patients. Clinical signs such as enthesitis and nail involvement have been suggested as early indicators of this progression. IL-23 inhibitors have demonstrated effectiveness in psoriasis and, more recently, in PsA. This article aims to evaluate the effect of IL-23 inhibitors on clinical outcomes and progression of PsA in patients with moderate-to-severe psoriasis and early musculoskeletal involvement. Methods: This was a retrospective, multicentre observational study conducted in Italy. Data were collected from 207 adult patients who had already started treatment with guselkumab, risankizumab or tildrakizumab prior to inclusion. All clinical data, including baseline characteristics and follow-up outcomes, were retrieved retrospectively from medical records across eight dermatology centres. Results: Enthesitis was observed in 44.8% of patients with joint involvement. Guselkumab was the most commonly used treatment (57%) and demonstrated sustained improvements in Psoriasis Area and Severity Index, Visual Analogue Scale pain and Dermatology Life Quality Index scores. Importantly, no patients with enthesitis treated with guselkumab progressed to overt PsA. At 52 weeks, the average Psoriasis Area and Severity Index score was 0.61, Visual Analogue Scale pain score was 0.59 and Dermatology Life Quality Index score was 0.91. Conclusion: IL-23 inhibitors have proven effective in managing both skin and joint symptoms in patients with psoriasis at risk for PsA. Whilst the findings suggest that IL-23 inhibitors may help control early musculoskeletal symptoms in patients with psoriasis at risk of PsA, the absence of systematic rheumatological evaluation and the retrospective design preclude definitive conclusions about their disease-modifying potential. These results suggest a potential disease-modifying role that warrants further prospective vali

摘要： Glaucoma, age-related macular degeneration, and diabetic retinopathy are complex eye diseases that involve inflammation. Several cellular models are developed to study inflammation mechanisms in the posterior segment of the eye. These models, are composed of cells of various origins (human or animal), derived from different tissues (retina, choroid, skin, and umbilical cord) and belonging to different cell types (epithelial, endothelial, vascular, and neuronal). Multiple culture techniques are employed to analyze specific inflammatory responses. Various experimental approaches are used to induce inflammation in these cellular models and identify underlying molecular mechanisms. This review highlights the diversity of cell models used to study posterior ocular inflammation. It emphasizes the use of primary cell cultures, established cell lines, and different co-culture approaches. The goal is to further increase our understanding of these diseases which affect millions of people worldwide.

摘要： Le fonti storico-cliniche del periodo bizantino suggeriscono che differenti forme di gozzo tiroideo erano presenti nella popolazione dei territori dell’Impero. In particolare, Ezio di Amida (VI d.C.), vissuto al tempo dell’Imperatore Giustiniano I, fornisce una classificazione del gozzo che trova numerosi riscontri nelle varianti patologiche che conosciamo oggi e permette di supporre che abbia potuto osservare questi differenti tipi direttamente nella sua pratica clinica. Effettivamente, l’analisi retrospettiva dell’iconografia delle rappresentazioni figurative bizantine mediante Visual Thinking Strategy permette di concludere che il gozzo tiroideo era una patologia diffusa nella popolazione dell’Impero Romano d’Oriente, configurando una possibile epidemiologia indicativa di gozzo endemico.

关键词： HLA-II   esophageal squamous cell carcinoma   neoantigen   immunohistochemistry   transcriptomics   immune microenvironment   prognosis  

摘要： Ectopic expression of human leukocyte antigen class II (HLA-II) on tumor cells correlates with anti-tumor immunity and prognosis in various cancers, but its role in esophageal squamous cell carcinoma (ESCC) remains unclear. Methods: HLA-II expression was evaluated in 34 ESCC tissue sections and a 102-sample tissue microarray (TMA) using immunohistochemistry (IHC) and in 10 ESCC cell lines via flow cytometry. Transcriptome sequencing of KYSE270, KYSE180, KYSE450, and KYSE510 was performed to investigate HLA-II regulatory mechanisms, while tumor samples from 104 ESCC patients were analyzed for neoantigen load. The prognostic significance of neoantigen burden was assessed using Cox regression. Results: HLA-II was ectopically expressed in ESCC, with positivity rates of 20.59% (34 tissues) and 25.49% (TMA). Among 10 ESCC cell lines, only KYSE270 exhibited spontaneous HLA-II expression. Transcriptome analysis revealed 1278 KYSE270-specific genes enriched in immune-related pathways (e.g., "Cytokine-cytokine receptor interaction"), suggesting immune-mediated HLA-II regulation. IFN-gamma stimulation induced HLA-II expression in KYSE180, KYSE450, and KYSE510, indicating broader inducible HLA-II potential. In 104 patients, MHC-II-restricted neoantigen burden varied widely (0-75) and lacked direct correlation with HLA-II expression. Additionally, MHC-II-restricted neoantigen load was not significantly associated with overall survival (p > 0.05). Conclusion: Ectopic HLA-II expression in ESCC may influence the tumor immune microenvironment, while the prognostic value of MHC-II-restricted neoantigen burden in ESCC remains unclear, providing potential implications for immunotherapy strategies.

关键词： extracellular vesicles   mesenchymal stem/stromal cells   epidermal growth factor(EGF)   tumor necrosis factor-alpha (TNF-alpha)   hypoxia  

摘要： Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC-EVs) are promising therapeutic agents for various diseases. However, current methods to improve MSC-EV production are insufficient to meet the clinical demands. Although various strategies have been investigated to enhance MSC-EV production, they are often hampered by limited scalability, loss of stemness, or suboptimal therapeutic outcomes. Our study identified three key stimulators that significantly boosted MSC-EV production: epidermal growth factor (EGF), tumor necrosis factor-alpha (TNF-alpha), and hypoxia. Employing an orthogonal design, we developed an optimized cell culture condition, subsequently referred to as ETH (EGF 10 ng/mL, TNF-alpha 50 ng/mL, and a hypoxic environment of 1% O2) preconditioning. This approach led to a remarkable 4- to 5-fold increase in MSC-EV yield while preserving the stemness of MSCs. Through proteomic analysis, we elucidated the underlying mechanisms of ETH preconditioning, providing insight into the complex processes driving enhanced MSC-EV production. Notably, MSC-EVs generated through ETH preconditioning demonstrated enhanced therapeutic potential including superior angiogenesis, collagen deposition, and regulation of inflammation. These findings present a scalable and effective strategy for elevating MSC-EV production, paving the way for its broader clinical application in regenerative medicine.