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关键词： 白血病   淋巴细胞   急性   难愈性创面   负压封闭引流术  

摘要： 目的提高对负压封闭引流术（VSD）治疗急性淋巴细胞白血病（ALL）患儿臀部难愈性创面的认识。方法回顾性分析惠州市中心人民医院2023年3月收治的1例合并臀部巨大创面ALL患儿的临床特点、治疗方案及预后，并复习相关文献。结果患儿为15岁男孩，ALL化疗后发生臀部巨大创面，给予抗感染、创面换药治疗，创面难以愈合，继而行创面清创术、VSD、植皮，并调整化疗方案，最终创面愈合良好。结论VSD治疗可促进肉芽组织增生，为植皮创造条件，缩短住院时间，是儿童白血病难愈性创面有效治疗方式。

关键词： Pulmonary hypertension   Macrophage   IL-33/ST2   IL-6   Lingguizhugan decoction  

摘要： Background: Lingguizhugan decoction (LGZG), a typical Chinese herbal formula, has remarkable clinical effects for treating pulmonary hypertension (PH) with unclear ingredients and mechanisms. This study aimed to evaluate the efficacy of LGZG and the mechanism of its active ingredients in treating PH. Methods: The PH patient phenotype was characterized by transcriptomic assay of peripheral blood mononuclear cells (PBMCs) and multiplex cytokine profiling of serum. The active ingredients of LGZG were identified by UPLC-Q-TOF-MS. The monocrotaline (MCT)-induced PH model was performed to evaluate the effects of LGZG and its active ingredients in vivo. The interleukin-33 (IL-33)-induced RAW264.7 cells and the mouse pulmonary artery smooth muscle cells (mPASMCs) were applied to explored phenotype and mechanism of the active ingredients of LGZG by immunofluorescence, western blotting and RT-qPCR in vitro. Results: Inflammatory receptor activity in PBMCs and serum interleukin-6 (IL-6) levels were elevated in PH patients. Porinic acid B, cinnamic acid, atractylenolide I and glycyrrhizin (PCAG) were characterized and combined to treat the PH, And the IL-33/Growth stimulation expressed gene 2 (ST2) pathway may be the potential mechanism by transcriptomic analysis of lung tissues. Both in vivo and in vitro experiments confirmed that PCAG inhibited the IL-33/ST2 pathway, reduced macrophage polarization, and suppressed IL-6 secretion. Moreover, ST2 overexpression in macrophages attenuated the inhibitory effect of PCAG. Using a co-culture system of macrophages and mPASMCs, we demonstrated that PCAG reduced mPASMCs phenotypic switching by suppressing macrophage-derived IL-6 secretion. Conclusion: The active ingredient of LGZG, PCAG, inhibits the progression of PH by preventing macrophage polarization and IL-6 secretion through the IL-33/ST2 pathway.

摘要： Resistance to CDK4/6 inhibitors (CDK4/6i) is a major challenge in treating hormone receptor-positive, HER2-negative metastatic breast cancer. This study aimed to identify a biomarker predictive of resistance that could also serve as a therapeutic target. Circulating IL-6 levels in 166 patients significantly increased at progression, making IL-6 a non-invasive biomarker to predict CDK4/6i resistance. Knockdown of IL-6 re-sensitized resistant cells to palbociclib and endocrine therapy, underscoring IL-6's critical role in maintaining resistance. Patient-derived xenograft models from patients who progressed within 3 months versus >= 6 months of palbociclib therapy revealed distinct transcriptomic profiles, with later progressors exhibiting IL-6/STAT3 activation, epithelial-to-mesenchymal transition, and immune evasion signatures. Treatment with TTI-101, a STAT3 inhibitor, significantly reduced tumor growth and improved survival in these models, providing preclinical validation for targeting the IL-6/STAT3 axis. These findings support using IL-6 to guide personalized treatment and combining STAT3 inhibitors with CDK4/6i as a transformative strategy to overcome resistance.

关键词： Copyrights  

摘要： Osteoarthritis (OA) is a multifactorial disease characterized by joint inflammation and cartilage degeneration, with no disease-modifying drugs available. The vicious cycle between the inflammatory microenvironment (inflamed soil) and dysfunctional chondrocytes (degeneration-related seeds) drives the chronic progressive deterioration of OA. Here, we report a genetically engineered chondrocyte-mimetic nanoplatform (termed HKL-GECM@MPNPs) comprising a honokiol (HKL)-loaded mitochondrion-targeting nanoparticle core coated with an interleukin-1 receptor type 2 (IL-1R2)-overexpressing chondrocyte membrane. HKL-GECM@MPNPs fuse with OA chondrocytes, transferring IL-1R2 onto the plasma membrane and reprogramming the inflamed microenvironment through IL-1 beta blockade. Mitochondrion-targeting cores then directly deliver HKL to restore mitochondrial sirtuin-3 in OA chondrocytes, reprogramming the cells' pathological phenotype. Intra-articular injection of HKL-GECM@MPNPs in OA mice reduces inflammation, alleviates joint pain, and mitigates cartilage damage through a synergistic effect. Moreover, HKL-GECM@MPNPs effectively reverse cartilage degeneration in human OA cartilage explants. This approach highlights the potential of HKL-GECM@MPNPs to combine IL-1 beta blockade and mitochondrial sirtuin-3 restoration as a promising strategy for OA treatment.

关键词： Ulcerative colitis   Sulfasalazine   Biotin   S1PR1   STAT3   IL-23  

摘要： Ulcerative colitis (UC) is a chronic idiopathic mucosal inflammation of colon. The lack of effective remedies urges us to search for new remedies to effectively cure UC. The current study aims to explore the potential therapeutic effect of sulfasalazine (SLZ)/Biotin combination in ameliorating acetic acid (AA)-evoked UC in rats. SLZ (100 mg/kg), Biotin (6 mg/kg) and SLZ plus Biotin were administered orally for 8 days followed by injection of AA (2 mL, 3% v/v) intra-rectally to induce UC on the 8th day. SLZ/Biotin combination therapy attenuated AA-induced UC as proved by mitigation of pathological colonic abnormalities and decrease in disease activity index, colon mass index, colon weight/length ratio, LDH and CRP serum levels. This was associated with a considerable restoration of redox state in colon;MDA, NO and GSH contents. Furthermore, SLZ/Biotin combination therapy reduced colonic inflammation as confirmed by the remarkable decrement of S1P, S1PR1, IL-23, STAT3, and P-STAT3 colonic levels along with downregulation of colonic COX-2 and NF-kappa B protein expressions. Biotin as add-on therapy to SLZ markedly alleviates AA-induced UC via modulating S1P/S1PR1/NF-kB/ IL-23/STAT3 inflammatory signaling pathway with subsequent inhibition of COX-2.

关键词： Emphysema   Chronic Obstructive Pulmonary Disease   Modified Fangji Huangqi decoction   IL-33   Neutrophils  

摘要： Ethnopharmacological relevance: Chronic Obstructive Pulmonary Disease (COPD) is a progressive respiratory disorder with complex pathogenesis and multiple contributing factors. Modified Fangji Huangqi decoction (MFJHQ), a traditional Chinese medicine formula, has demonstrated clinical efficacy in COPD treatment. However, the pharmacological roles and underlying mechanisms of MFJHQ in treating COPD remain unclear. Aim of study: To investigate the therapeutic effects and molecular mechanisms of MFJHQ in the treatment of COPD. Methods: COPD models were established in vitro using alveolar organoid (AOs) and 16 Human Bronchial Epithelial (16HBE) cells separately, induced by porcine pancreatic elastase (PPE) and in vivo in PPE-induced COPD mice. MFJHQ was administered via gavage for three weeks. RNA-sequencing and network pharmacology were employed to elucidate potential mechanisms of action. Results: In vitro, MFJHQ enhanced epithelial barrier integrity by reducing permeability and upregulating zonula occludens-1 (ZO-1) expression. In vivo, MFJHQ effectively improved pulmonary function, alleviated emphysema and airway obstruction, and protected the lung structure from damage. Mechanistically, based on the results of RNA-sequencing and network pharmacology and subsequent experiments MFJHQ inhibited IL-33 and its downstream NF-kappa B signaling and CXCL5 expression, thereby reducing neutrophil recruitment in lung tissues. Conclusion: MFJHQ ameliorates COPD progression by inhibiting neutrophil infiltration through suppression of IL-33 and CXCL5, providing a new therapeutic strategy for COPD.

关键词： Acute acquired concomitant esotropia   Dry eye   Tear film biomarkers   Random forest models   Risk factors  

摘要： Background Acute acquired concomitant esotropia (AACE) causes diplopia and asthenopia, severely affecting quality of life. This study aimed to explore the association between dry eye (DE) tear film biomarkers and Type III AACE. Methods We enrolled 52 patients (52 eyes) with Type III AACE and 50 controls (50 eyes). Assessments included tear meniscus height (TMH), tear film non-invasive break-up time (NIBUT), corneal fluorescein staining (CFS), Schirmer's test (ST), and the Dry Eye-Related Quality of Life Score (DEQS). Tear samples were analyzed for cytokine levels using a multiplex immunoassay. Logistic regression analyses identified risk factors, and a random forest classifier evaluated predictive performance. Results Patients with Type III AACE without DE showed significantly reduced NIBUT and elevated levels of cytokines (e.g., MMP-2, MMP-13, and IFN-gamma) compared to normal controls (all P < 0.05). Near-distance work duration showed a moderate positive correlation with Galectin-3 (r = 0.64, P < 0.05). MMP-2, MMP-13, and IFN-gamma were identified as independent risk factors (arear under the curve (AUC): 0.91, 0.91, 0.94). The random forest model achieved an AUC of 1.00. Conclusion Elevated tear levels of MMP-2, MMP-13, and IFN-gamma were strongly associated with Type III AACE, highlighting their potential as predictive biomarkers.

关键词： IL-33/ST2 pathway   M2 macrophage   fibrosis   innate lymphoid cell   kidney disease  

摘要： Group 2 innate lymphoid cells (ILC2s) are tissue-resident immune cells that respond rapidly to epithelial-derived cytokines such as interleukin (IL)-33, producing type 2 cytokines including IL-5 and IL-13. While ILC2s are well recognized for their roles in regulating inflammation and tissue remodeling in barrier organs, their functions in the kidney have only recently gained attention. In this review, we summarize the localization, activation, and effector functions of ILC2s in the kidney and explore their immunoregulatory interactions with macrophages, particularly in promoting M2 polarization. We further provide an overview of the therapeutic relevance of the IL-33/ST2/ILC2 axis in renal pathology, organizing current findings across models of acute kidney injury (AKI), chronic kidney disease (CKD), and glomerulonephritis (GN). ILC2s are primarily distributed in the perivascular tubulointerstitial regions of both the renal cortex and outer medulla, where they exert anti-inflammatory and antifibrotic effects through cytokine-mediated mechanisms. Importantly, recent studies suggest that the outcomes of IL-33-mediated interventions are highly context-dependent, influenced by factors such as dosage, disease phase, and temporal dynamics. A comprehensive understanding of the IL-33/ST2/ILC2 axis may offer new insights into immune modulation and tissue protection strategies for kidney diseases.

关键词： SARS-CoV-2   cytokines   immunoglobulins   immunophenotyping   immunosenescence   inflammaging  

摘要： BACKGROUND:Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. OBJECTIVE:We aimed to investigate the impact of IFNλ polymorphism ( gene-rs12979860) on the immune/inflammatory response to vaccination with CoronaVac for COVID-19 in older adults who were CMV-seropositive. METHODS:Blood samples from 42 CMV-seropositive older adults (73.7 ± 4.5 years) were collected before and 30 days after immunization with a second dose of the CoronaVac vaccine to evaluate the immune/inflammatory response. RESULTS:At genotyping, 20 subjects were homozygous for the C/C alleles (Allele-1 group), 5 were homozygous for the T/T Alleles (Allele-2 group), and 17 were heterozygous (C/T, Alleles-1/2 group). The Allele-1 group showed higher IgG levels for COVID-19 ( = 0.0269) and intermediate monocyte percentage ( = 0.017), in contrast to a lower non-classical monocyte percentage ( = 0.0141) post-vaccination than pre-vaccination. Also, this group showed that IgG levels for CMV were positively associated with a systemic pro-inflammatory state and senescent T cells (CD4+ and CD8+). The Allele-2 group presented higher IFN-β levels at pre- ( = 0.0248) and post-vaccination ( = 0.0206) than the values in the Allele-1 and Alleles-1/2 groups, respectively. In addition, the Allele-2 and Alleles-1/2 groups showed that IgG levels for COVID-19 were positively associated with a balanced systemic inflammatory state. CONCLUSION:CMV-seropositivity in older adults who had Allele-1 could lead to an unbalanced systemic inflammatory state, which may impair their antibody response to COVID-19 vaccination compared to other volunteer groups.