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关键词： Durvalumab plus tremelimumab (DT)   Interleukin (IL)-6   Immune-related adverse events (irAE)  

摘要： Systemic therapy for advanced hepatocellular carcinoma (HCC) has progressed significantly, yet the management of immune-related adverse events (irAEs) remains a challenge, particularly with anti-CTLA-4 and anti-PD-L1 antibodies. We present two cases of severe irAEs during durvalumab plus tremelimumab (DT) therapy, demonstrating successful management and favorable outcomes. In Case 1, a 76-year-old male with metabolic-associated steatotic liver disease-related HCC experienced disease progression after lenvatinib and subsequently initiated DT therapy. He developed Grade 3 immune-related myositis at week 5, which was successfully managed with prednisolone. A partial response (PR) was achieved and maintained, with a 55% tumor reduction at 8 months. In Case 2, a 73-year-old male with alcoholic cirrhosis and a 16-cm HCC received DT therapy. On day 19, he developed Grade 3 immune-related hepatitis and thyroiditis, which were controlled with prednisolone. After steroid tapering, durvalumab was successfully rechallenged, maintaining a 38% tumor reduction at 6 months with a sustained PR. In the case series, lower baseline serum interleukin (IL)-6 levels were associated with the development of Grade >= 3 irAEs. These findings suggest that IL-6 may serve as a predictive biomarker, aiding in risk assessment and the optimization of individualized treatment strategies prior to anti-CTLA-4 therapy.

关键词： Chinese patent medicine   IL-6/JAK2/STAT3 signaling pathway   Nei-Xiao-Pian (NXP)   Thyroid nodules   cell proliferation and apoptosis  

摘要： BACKGROUND:Thyroid nodules (TN) are distinct lesions within the thyroid gland that can cause compression symptoms, disrupt thyroid function, and impact aesthetics and daily life. Nei-Xiao-Pian (NXP), a traditional Chinese patent medicine developed by Suzhou Hospital of Traditional Chinese Medicine, has been effectively used in clinical treatment for TN. Due to the complex nature of traditional Chinese medicine (TCM), limited clinical research exists on NXP, and its precise mechanisms of action remain largely unknown. METHODS:In this study, we investigated the effects of NXP on human tumorous thyroid cells and papillary thyroid carcinoma (PTC) cells. Cells were treated with animal serum containing different concentrations of NXP. Cell viability, cell cycle progression, and apoptosis were assessed using the CCK-8 assay and flow cytometry. A literature review was also conducted to understand the physiological and pathological mechanisms underlying TN. Furthermore, we examined the involvement of the IL6/JAK2/STAT3 signaling pathway in the action of NXP by measuring the protein expression levels of IL-6, JAK2, and STAT3 in PTC cells using western blotting. RESULTS:The present study showed that serum with a specific concentration of NXP reduced the viability of both tumorous thyroid cells and PTC cells, inhibited the proliferation of tumorous thyroid cells, and induced apoptosis. While NXP-containing serum did not significantly affect the cell cycle in PTC cells, it induced apoptosis in a dose-dependent manner. Additionally, NXP-containing serum dose-dependently suppressed the protein expressions of IL-6, JAK2, and STAT3 in PTC cells. CONCLUSION:Our findings suggest that NXP may exert its therapeutic effects on TN by targeting the IL6/JAK2/STAT3 signaling pathway, thereby slowing disease progression. These results highlight a potential mechanism through which NXP could contribute to tumor prevention and treatment, offering a promising direction for future research.

关键词： Needle stick injuries   Infection control   Dental education   Dental students   Saudi Arabia   Sharp injury   Occupational exposure  

摘要： BackgroundNeedle stick injuries (NSIs) pose a significant occupational hazard to healthcare professionals, including dental students. Despite the availability of guidelines and preventive strategies, knowledge, training, and compliance remain inadequate among dental students. Therefore, this study aimed to evaluate the Prospective gain of an educational pack in reducing NSIs and improving knowledge of attitudes towards, and compliance with NSI prevention and management guidelines among dental *** prospective audit design was employed over four weeks, involving fourth-, fifth-, and sixth-year dental students. The study consisted of three phases: pre-assessment, educational intervention, and post-assessment. Baseline knowledge, attitudes, and practices were evaluated using a structured questionnaire. Self-reported compliance with safe sharps handling practices has been designated as the primary outcome. The educational pack, comprising presentations, comparative data, interactive scenarios, and guidelines, was delivered during the intervention phase. Post-intervention assessments used the same questionnaire to measure changes in outcomes. Data were analysed using SPSS, and statistical significance was set at p <= ***-intervention, the incidence of NSIs significantly decreased, with self-reported cases reducing from 17.2% to 4.3%. Knowledge scores improved markedly, with the percentage of correct answers to key questions rising from 34.5% to 93.1% among sixth-year students (p = 0.032). Gender-based analysis revealed statistically significant improvements in scores for both male and female students, with female students achieving higher post-assessment scores for key questions (e.g. 93.8% vs 75.6%, p = 0.014). Students with lower GPAs demonstrated the greatest improvement, with scores increasing from 14.3% to 100% in some areas (p = 0.022).ConclusionThe findings underscore the change following the intervention of structured infection control t

关键词： eosinophilic granulomatosis with polyangiitis   eosinophilia   refractory peripheral neuropathy   TNF-alpha blockade   etanercept  

摘要： Eosinophilic granulomatosis with polyangiitis (EGPA) is characterized by abnormal eosinophilia and extravascular eosinophilic granuloma formation. Conventional treatments combining glucocorticoids and immunosuppressants can alleviate the condition in most patients with EGPA. However, the efficacy of blocking tumor necrosis factor (TNF)-alpha-mediated inflammatory reactions in managing EGPA remains controversial. Here, we report a case of refractory EGPA that did not respond to glucocorticoid pulse therapy and adequate cyclophosphamide. The disease was ultimately controlled through the coadministration of etanercept.

关键词： Copyrights  

摘要： Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal cytokine storm syndrome. Its high mortality rate reflects limited therapeutic options and a poor understanding of disease-causing signaling. We show that the NLRP3 inflammasome is responsible for increased mortality in a model of secondary HLH (sHLH). Unexpectedly, neither deletion of the NLRP3-activated pyroptotic effector GSDMD nor combined deletion of the inflammasome-activated cytokines interleukin-1 beta (IL-1 beta) and IL-18 conferred strong protection from sHLH. Instead, co-deletion of GSDMD and caspase-8-activated GSDME limited sHLH-driven lethality, demonstrating redundancy in the pyroptotic machinery required to induce sHLH. We also found that bromodomain and extraterminal domain (BET) inhibitors prevent NLRP3-driven pyroptosis, which acted by blocking inflammasome priming. BET inhibitors prevented increased NLRP3 levels in diseased tissue, limited the production of sHLH-associated IL-1 beta, interferon-gamma, and tumor necrosis factor, and protected from sHLH pathogenesis. These findings suggest that targeting NLRP3 could limit sHLH and identify clinically relevant bromodomain-selective BET inhibitors capable of eliminating NLRP3-driven pyroptosis and the sHLH cytokine storm.

关键词： endophthalmitis   proteomic profiler   inflammation   cell death   retina   IL-33  

摘要： Bacterial and fungal pathogens are major causes of infectious endophthalmitis following eye surgery or trauma, often leading to vision impairment or blindness. The distinct clinical outcomes observed in bacterial and fungal endophthalmitis suggest differences in host immune responses. To investigate these differences, we utilized cytokine arrays and murine models of bacterial (Staphylococcus aureus) and fungal (Aspergillus fumigatus) endophthalmitis. Our analysis revealed that cytokine responses peaked in bacterial infections at 12-24 h, whereas fungal infections exhibited a delayed peak at 48 h. Several inflammatory mediators, including MMP9, MMP3, CD14, LIX, LCN2, retinol-binding protein 4, ICAM1, and VCAM1, were differentially elevated. Notably, interleukin-33 (IL-33) levels peaked early in bacterial infections but continued to rise throughout all time points in fungal endophthalmitis. Analysis of patient vitreous samples further confirmed higher levels of IL-33 in bacterial (n=40) and fungal (n=20) endophthalmitis cases. Functional studies in IL-33-deficient mice revealed an increased fungal burden and elevated TNF-alpha and IL-6 levels, but bacterial endophthalmitis severity remains largely unaffected. Additionally, bone marrow-derived macrophages from IL-33-/- mice exhibited increased cell death in response to fungal and bacterial infection. Our findings reveal divergent innate immune responses between bacterial and fungal endophthalmitis and emphasize the immunomodulatory function of IL-33 in ocular infections.