The link between glutaminolysis and osteoarthritis (OA) has only recently begun to be elucidated. Here, we report the association of obesity- and injury-induced cartilage damage with impaired glutaminolysis in chondrocytes. Defective glutaminolysis triggered the onset and progression of OA, with enhanced catabolism and decreased anabolism. Supplementation of α-ketoglutarate (αKG), a key component in glutaminolysis and an epigenetic factor, effectively protected cartilage against degradation in vivo via a TCA cycle- and HIF-1α-independent manner. Mechanistically, OA pathogenic factors increased H3K27me3 deposition on promoters of key glutaminolysis genes, including Slc1a5 and Gls1, leading to impaired glutaminolysis. Conversely, αKG facilitated Kdm6b-dependent H3K27me3 demethylation of not only glutaminolysis genes to rescue Gln metabolism but also Ube2o to reverse OA. Elevated Ube2o expression led to TRAF6 ubiquitination and subsequent inhibition of NF-κB signaling, thereby reversing the pathological reprogramming of glycolysis and oxidative phosphorylation and protecting against cartilage destruction. Collectively, these results demonstrated that OA pathogenic factors impair glutaminolysis through epigenetic regulation, which further exacerbate OA. Moreover, αKG restores metabolic homeostasis and alleviates OA through H3K27me3 demethylation.

Thin endometrium(TE) has been widely recognized as a critical factor contributing to reduced success rates of assisted reproductive technology (ART). In recent years, platelet-rich plasma (PRP) has been extensively employed in the treatment of thin endometrium; however, its underlying mechanisms remain poorly understood, and its clinical efficacy remains controversial. Given the superior therapeutic outcomes demonstrated by platelet concentrates (PCs) in regenerative medicine, the present study aimed to investigate the therapeutic potential and mechanistic basis of injectable platelet-rich fibrin (i-PRF) in an ethanol‑induced rat model of thin endometrium. i-PRF was prepared from human blood and characterized for growth factor release and microstructure. Rats were divided into control, Model, Ethanol + NS, and Ethanol+i-PRF groups.Endometrial morphology was assessed by H E and immunohistochemistry. Receptivity was evaluated by LIF/VEGF expression and embryo implantation counts. In vitro, endometrial stromal cells (ESCs) were co-cultured with platelets, and mitochondrial transfer was tracked using MitoTracker®. Platelet mitochondrial respiration was inhibited with oligomycin/FCCP to assess functional contribution. i-PRF released VEGF-A, TGF-β1, and PDGF-AB for up to 15 days (peak at 7 days), with a dense fibrin network entrapping abundant platelets. Ethanol injection significantly reduced endometrial thickness from 409.27 ± 55.86 μm to 104.48 ± 57.03 μm and decreased gland number from 22.4 ± 4.34 to 9.2 ± 3.77 (both p < 0.05).Administration of i-PRF reversed these pathological changes, restoring endometrial thickness to 464.11 ± 27.1 μm and gland count to 29.0 ± 9.41 (*p* < 0.05 vs. model). Immunohistochemical analysis revealed that i-PRF treatment increased the abundance of vimentin⁺,cytokeratin 18⁺ (CK-18⁺) and ki-67+ cells and enhanced the expression of leukemia inhibitory factor (LIF) and vascular endothelial growth factor (VEGF). Compared with the model group, the Ethanol + i‑PRF group exhibited a markedly higher embryo number (3.88 ± 3.91, P < 0.001); although this value was lower than that of the control group (5.00 ± 3.46), the difference did not reach statistical significance (P > 0.05). In vitro co-culture of endometrial stromal cells (ESCs) with platelets promoted ESC proliferation and VEGF secretion. Confocal microscopy confirmed the direct transfer of platelet mitochondria to ESCs. Inhibition of platelet mitochondrial respiration did not block ESC proliferation but significantly suppressed VEGF and vimentin expression (p < 0.05). i-PRF effectively repairs thin endometrium in a rat model, and mitochondrial transfer from platelets to ESCs plays a key role in promoting endometrial regeneration. These findings support i-PRF as a promising therapy for TE.

BACKGROUND:Standardized salvage treatments for refractory/relapse Langerhans cell histiocytosis (LCH) remain to be established. Trametinib (TRA) has shown marked efficacy in LCH, but cohort studies regarding efficacy and safety of TRA monotherapy in refractory/relapse LCH were scarce. METHODS/RESULTS:We retrospectively analyzed 22 patients with refractory/relapse LCH treated with TRA monotherapy. Patients were treated for a median of 21.4 months (3.0-51.6 months). Nineteen (86.4%) of 22 of patients remained progression-free during TRA treatment. Sixteen patients stopped TRA (not due to progression or toxicity), of which 10 remained progression free, with median follow-up time of 28.7 months (1.5-44.6 months) after TRA withdrawal, and 6 patients experienced relapse, with median time to relapse from post-TRA withdrawal of 3.7 months (2.7-16.5 months). Two patients continued on TRA at last follow-up and one switched to chemotherapy due to toxicity. Three-year event-free survival was 50.7% (95% CI: 27.7-69.8), with a median follow-up time of 36.4 months (3.0-67.6 months). From TRA initiation to 12 months of treatment, cell-free BRAF/MAP2K1 mutation status in blood presented as negative to negative or positive to negative was correlated with superior event-free survival rate (EFS) rate. Toxicity was tolerable, and adverse events were predominantly skin rash (77.3%), paronychia (22.7%), and diarrhea (13.6%). CONCLUSION:Overall, TRA was effective and safe in the treatment of patients with refractory/relapse LCH, offering a convenient therapeutic alternative.

Chronic active Epstein-Barr virus disease (CAEBV), an Epstein-Barr virus (EBV)+ T/Natural Killer (NK)-cell lymphoproliferative disorder, remains critically undefined in treatment and prognostic stratification due to its rarity. We analysed 149 paediatric systemic CAEBV patients, of whom 134 received LDEP (liposomal doxorubicin, etoposide, pegylated asparaginase and methylprednisolone) chemotherapy as a bridge to haematopoietic stem cell transplantation (HSCT). Diagnostic delay was common (median 6.0 months), with 41.6% presenting atypically with localized symptoms at onset. Haemophagocytic lymphohistiocytosis developed in 50.3%. EBV infection involved pan-lymphoid lineages in 85.2%, with NK-cell predominance (44.3%) enriched in the hydroa vacciniforme/severe mosquito bite allergy subtype. LDEP induced favourable response in 59.0%, significantly improving HSCT rates (98.7% vs. 69.1%). Overall, 127 patients (85.2%) underwent HSCT, with 3-year post-transplant survival of 84.5% ± 3.5%. Inferior post-HSCT survival was independently associated with active disease at transplantation (hazard ratio [HR] = 6.17, p < 0.001) and also linked to longer chemotherapy-to-HSCT interval (>3.5 months) and poor LDEP response. Non-transplanted patient had 90.9% mortality. The entire cohort had a 3-year overall survival of 72.6% from diagnosis, with poor LDEP response, hepatic dysfunction and leucopenia as independent risk factors. This large paediatric cohort defines the clinical spectrum of CAEBV, establishes LDEP as an effective bridging regimen to HSCT-particularly in early-stage disease-and highlights the need for early disease activity control and timely transplantation.

Background In this study, we preconditioned human adipose-derived stem cells (ADSCs) with acetoacetate (AcAc) and explored whether it could improve cell survival and enhance the tissue regeneration of chemical burns in mice. Methods To evaluate the therapeutic efficacy of AcAc, human ADSCs were preconditioned with 10 mM AcAc (AcAc-hADSCs). Cell proliferation, migration, paracrine release of growth factors, and proangiogenic effects of AcAc-hADSCs were subsequently assessed. Subsequently, HCl acid burns were induced on the dorsal skin of ICR mice, and wound healing progression was monitored through macroscopic examination. The wounds were harvested for histological assessment via staining. Angiogenesis in wounds was detected via immunohistochemical staining. hADSCs were prelabeled with DiO, and their wound survival was detected via an in vivo bioluminescence imaging system. Results Pretreatment with AcAc enhanced the migration of ADSCs and the paracrine release of proangiogenic cytokines, including HIF-1α, VEGFA, HGF, FGF-2 and TGF-β, and increased the expression of SOD1. Compared with those treated with control hADSCs, the wounds that received AcAc-hADSCs presented accelerated re-epithelialization, increased extracellular matrix (ECM) deposition, and improved the microvessel density by HIF-1α-VEGFA pathway. Moreover, the DiO-labelled AcAc-hADSCs could be observed even after 72 h; while ADSCs could be only detected at 24 h. In addition, wounds treated with AcAc-hADSCs presented more Ki67 + cells. qRTPCR analysis revealed a significant increase in the expression of proangiogenic factors and a decrease in the levels of IL-1, IL-6 and iNOs in wounds that received AcAc-hADSCs. Conclusion These findings demonstrate that AcAc preconditioning enhances hADSC persistence in wounds, consequently promoting both re-epithelialization and angiogenesis.

Langerhans cell histiocytosis (LCH) is an inflammatory and neoplastic disorder. The levels of metabolites in the plasma of children with LCH have not been studied and may be related to disease progression. We committed to find novel pre-diagnostic metabolites in the plasma of LCH children with posterior pituitary involvement (PI). Non-targeted metabolomics sequencing was used to detect specific and pre-diagnostic metabolites in the plasma of children with LCH. Plasma samples from 56 children with LCH and 27 healthy volunteers were enrolled. Plasma samples of children with LCH were divided into three groups: children have no PI or central nervous system-risk (CNS-risk) bone lesions (NPC group), children with CNS-risk bone lesions but without PI (CNS-risk group), and children with PI (PI group). The N-acetylneuraminic acid, lipoamide, L-Glutathione oxidized and indole-3-propionic acids were potential pre-diagnostic metabolites for LCH children with PI in comparison with the healthy volunteers. Metabolites in the plasma of LCH children with PI enriched specific signaling pathways including arachidonic acid metabolism, ferroptosis, etc. Through targeted metabolomics sequencing, we verified that specific metabolites were existed in the stratified involvements of patients with LCH, such as N-acetylneuraminic acid and Vitamin A, which may be related with alteration of blood-brain barrier permeability and LCH disease progression. Through the joint multi-omics analyses, we discovered that the peripheral dendritic cells may have ferroptosis phenomena, which was regulated by osteopontin secreted in the plasma of patients with LCH. Analyses and identification the differential metabolites in the plasma of children with LCH may significantly improve the early diagnosis and stratified treatment of children with pituitary invovlement.

Background: A portion of children with Langerhans cell histiocytosis (LCH) exhibit recurrent or persistent disease-related fever at their first visit. We aimed to clarify the clinical characteristics, laboratory indicators, prognostic differences, and optimal regimens for these children with fever. Methods: A cross-sectional design (single-center, retrospective, and observational) was adopted for this study. A total of 448 pediatric patients diagnosed with LCH in our hospital from January 2016 to December 2019 were retrospectively enrolled and divided into two groups: children with fever (n=52) and children without fever (n=396). The clinical characteristics, laboratory indicators, and outcomes of regimens for these children were analyzed with SPSS 16.0 software. Results: Children with initial fever had distinct clinical characteristics and laboratory indicators, including an age younger than two years, risk-organ involvement, accompanying hemophagocytic syndrome, and higher levels of cell-free DNA BRAF(V600E) mutation, among others. Patients in the fever group also had a significantly lower treatment efficacy from first-line treatment and a lower 3-year progression-free survival (PFS) rate (approximately 5.22% and 64.23%, respectively; P<0.001). Multivariate Cox regression analysis indicated that fever, risk-organ involvement, skin involvement, ferritin level, and dynamic erythrocyte sedimentation rate were independently prognostic factors for outcomes of first-line treatment. However, the 3-year PFS rates did not differ significantly between patients with fever and without fever after the administration of second-line or target regimens. Conclusions: Among pediatric patients with LCH, those with initial fever exhibit more severe clinical symptoms and worse prognoses after first-line chemotherapy. Alternative strategies may mitigate fever-associated risk, and this possibility should be confirmed through prospective research.

BACKGROUND Adipose-derived stem cells (ADSCs) hold significant therapeutic potential for regenerative medicine, particularly in wound healing, owing to their multipotency, paracrine activity, and relative abundance. However, the clinical application of ADSC-based therapies is substantially limited by the harsh microenvironment of acute wounds, characterized by hypoxia, nutrient deprivation, and oxidative stress, which leads to massive apoptotic cell death post-transplantation. Preconditioning strategies to enhance cellular resilience have thus gained considerable interest. Recent insights from cancer biology highlight the crucial role of metabolic reprogramming, orchestrated by hypoxia-inducible factor-1α (HIF-1α), in promoting survival under stress. Our previous work demonstrated that preconditioning with α-ketoglutarate (α-KG) enhances ADSC survival and accelerates wound healing, purportedly through HIF-1α upregulation. Nevertheless, the precise metabolic mechanisms by which α-KG preconditioning confers cytoprotection remain incompletely elucidated. AIM To investigate the mechanistic role of HIF-1α in mediating the enhanced survival and regenerative capacity of α-KG-preconditioned ADSCs in an acid burn wound model. Specifically, we sought to determine whether HIF-1α activation drives complementary adaptations in glutamine and glycogen metabolism to maintain redox and energy homeostasis, respectively, under the multifactorial stress conditions of a wound. METHODS Human ADSCs were isolated from lipoaspirates and preconditioned with dimethyl-α-KG. In vitro , cells were subjected to single or combined stressors (hypoxia, glucose deprivation, H2O2-induced oxidative stress). Genetic modulation was performed using lentiviral shRNAs targeting HIF-1α, GLS1, and PYGL, or an overexpression vector for GLS1. Metabolic profiling included assessments of glycolytic flux, glucose oxidation, fatty acid β-oxidation, oxygen consumption, and glycogen content. Redox status was evaluated via glutathione (GSH) (GSH/GSH disulfide) ratios and reactive oxygen species (ROS) levels. In vivo , a murine acid burn wound model was established, and pre-labeled ADSCs were implanted. Cell survival was tracked via flow cytometry (Annexin V-PI) and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Wound healing was assessed histologically. RESULTS α-KG preconditioning significantly enhanced the survival of ADSCs both in vitro under stress and in vivo in burn wounds. This was concomitant with HIF-1α stabilization. Mechanistically, HIF-1α orchestrated a dual metabolic adaptation: (1) It promoted glutaminolysis via GLS1, increasing glutamate and GSH synthesis, which enhanced antioxidant capacity and reduced ROS levels; and (2) It simultaneously stimulated glycogen storage (Gys1 upregulation) and mobilization (Pygl upregulation), preserving energy (ATP:AMP ratio) during glucose deprivation. Genetic inhibition of GLS1 abrogated the ROS detoxification benefit, while PYGL knockdown abolished the energy maintenance advantage, both reducing survival. Crucially, combined inhibition of both pathways completely negated the prosurvival effect of α-KG, confirming their synergistic role. In vivo , α-KG-preconditioned ADSCs accelerated wound closure, improved re-epithelialization, and enhanced angiogenesis compared to controls, effects that were HIF-1α-dependent. CONCLUSION This study demonstrates that α-KG preconditioning significantly enhances ADSC survival and therapeutic efficacy in burn wound healing through HIF-1α-mediated metabolic reprogramming. HIF-1α activation coordinately upregulates glutamine-driven GSH synthesis for redox homeostasis and glycogen storage for bioenergetic resilience, providing a dual mechanism of cytoprotection. These findings establish metabolic preconditioning as a potent, translatable strategy to improve the efficacy of stem cell-based therapies not only in wound healing but potentially in other ischemic and inflammatory conditions characterized by poor cell survival.

Chitosan is a promising biomaterial for tissue engineering, but its functionality is limited by a lack of bioactive sites. This study develops chitosan/amniotic membrane microcarriers to enhance vascularization and tissue regeneration for subcutaneous adipose tissue. The incorporation of decellularized amniotic membrane enhances the bioactivities of chitosan in promoting cell differentiation and angiogenesis. Optimized preparation yielded porous microcarriers with a particle size of 261.2 +/- 28 mu m and an average pore size of 19.0 +/- 4 mu m. In vitro degradation analysis showed accelerated degradation with higher amniotic membrane content. Cytocompatibility and adipogenic capacity assessments indicated that the microcarriers supported cell adhesion and proliferation over 7 days, with amniotic membrane facilitating adipogenic differentiation of adipose-derived stem cells. When injected subcutaneously into nude mice, these microcarriers formed neoplastic adipose tissues, which were harvested 8 weeks later. Fluorescence staining, oil-red O staining and CD31 labeling demonstrated that amniotic membrane incorporation significantly enhanced in vivo adipose tissue formation and angiogenesis.

Stimulator of interferon genes (STING) agonists have been developed and tested in clinical trials for their antitumor activity. However, the specific cell population(s) responsible for such STING activation-induced antitumor immunity have not been completely understood. In this study, we demonstrated that endothelial STING expression was critical for STING agonist-induced antitumor activity. STING activation in endothelium promoted vessel normalization and CD8+ T cell infiltration - which required type I IFN (IFN-I) signaling- but not IFN-γ or CD4+ T cells. Rather than an upstream adaptor for inducing IFN-I signaling, STING acted downstream of interferon-α/β receptor (IFNAR) in endothelium for the JAK1-STAT signaling activation. Mechanistically, IFN-I stimulation induced JAK1-STING interaction and promoted JAK1 phosphorylation, which involved STING palmitoylation at the Cysteine 91 site but not its C-terminal tail (CTT) domain. Endothelial STING and JAK1 expression was significantly associated with immune cell infiltration in patients with cancer, and STING palmitoylation level correlated positively with CD8+ T cell infiltration around STING-positive blood vessels in tumor tissues from patients with melanoma. In summary, our findings uncover a previously unrecognized function of STING in regulating JAK1/STAT activation downstream of IFN-I stimulation and provide a new insight for future design and clinical application of STING agonists for cancer therapy.

CONTEXT.—:Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. OBJECTIVE.—:To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. DESIGN.—:We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. RESULTS.—:A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. CONCLUSIONS.—:Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.

The demand for insulating materials with superior dielectric properties has increased. Among these materials, polymers containing cyclic structure including cyclic olefin copolymer (COC) and cyclic olefin polymer (COP) stand out because of their excellent dielectric properties originating from the pure hydrocarbon structure. Introducing fluorine into polymers is one efficient strategy for optimizing the dielectric and the related important properties. Here, three fluorinated norbornene derivatives with high fluorine content are synthesized and copolymerized via coordination-insertion polymerization (CIP) and ring-opening metathesis polymerization (ROMP). The obtained fluorinated COCs and COPs have high fluorine contents (up to 48.2 wt.%) and exhibit excellent dielectric properties with dielectric constant (Dk) of 2.11-2.24 and dielectric loss (Df) of 0.0021-0.0031 at 10 GHz. Moreover, these fluoropolymers show good solvent tolerance, high toughness (elongation at break up to 779%), enhanced thermal stability (Td,5% of 427-440 °C), low hydrophilicity (water uptake <0.01%), and excellent gas separation properties. These results imply that these fluoropolymers are suitable as a potential candidate for substrate material utilized in the application of insulating materials.

Random-pattern skin flaps are widely employed in tissue reconstruction, however, their survival is frequently hindered by ischemia, leading to necrosis. Metabolic alterations have been implicated in playing critical roles in angiogenesis during tissue repair. Using RNA sequencing analysis in a mouse model, we identified significant disruptions in glutamine metabolism, which substantially impaired angiogenesis within random-pattern skin flaps. Although local glutamine repletion failed to alleviate ischemia, administering α-ketoglutarate (α-KG) markedly promoted angiogenesis, as evidenced at both gene and protein levels. In human umbilical vein endothelial cells,α-KG enhanced the stability of hypoxia-inducible factor (HIF-1) alpha through activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Notably, α-KG treatment improved flap viability by augmenting blood perfusion, an effect correlated with upregulation of vascular endothelial growth factor expression. Together, these results reveal a novel mechanism by which α-KG enhances random-pattern skin flap viability via promoting angiogenesis through the PI3K/Akt/HIF-1α pathway, offering promising therapeutic insights for improving flap survival.

Iatrogenic injury-induced ureteral stricture often occurs during the treatment of ureteral disorders, and can lead to serious consequences requiring further medical care. The stricture prevention requires effective strategies to inhibit fibrosis, reduce oxidative stress and inflammatory responses during the insertion of ureteral stents. Here, we explore the anti-stricture effects of commercial ureteral stents modified with hydrogel coatings, which contain functionalized poly (lactic-co-glycolic acid) (fPLGA) nanoparticles (NPs) loaded with the drug of pirfenidone (PFD). The polyacrylamide (PAM) hydrogel coatings are robustly grafted onto the polyurethane (PU) stent using the surface initiated radical polymerization, while PFD-fPLGA NPs decorated with acryloyl functional groups were securely anchored in PAM networks during the reaction. This NPs-hydrogel coating possesses multiple advantages, such as high hydrophilicity and low elastic modulus, which can reduce frictional force and alleviate irritation during stent insertion. The hydrogel coating exhibits excellent stability, with only 45 % mass loss after being immersed in an artificial urine environment for 3 months, and also demonstrates good biocompatibility and antifouling performance. More importantly, the slow degradation of fPLGA leads to sustained delivery of antifibrotic PFD, with a cumulative drug release rate of approximately 82 % within 12 weeks. These combined benefits contribute to the prevention of ureteral strictures after iatrogenic injury, as evidenced by inhibited fibrosis, alleviated oxidative stress, and suppressed inflammatory response in both vitro and in vivo studies.

OBJECTIVE:Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm in which the inflammatory microenvironment plays a crucial role in the development and progression of disease. The prognostic value of circulating lymphocyte subsets and cytokines remains uncertain. METHODS:The authors retrospectively analyzed baseline peripheral lymphocyte subsets and serum cytokines in 330 consecutive pediatric patients. Immune profiles were compared across disease extent, clinical events, and biological features. Prognostic associations with progression-free survival (PFS) were tested using univariable and multivariable models. RESULTS:Peripheral immune profiles varied with disease extent. Patients with multisystem risk-organ involvement (MS RO+) had fewer total T and Th1 cells, more CD4⁺ T and B cells, and higher IL-6, IL-10, and IFN-γ. Patients who progressed or relapsed showed a similar pattern, and non-survivors had particularly high IL-10. In the first-line cohort, the proportions of T, B, CD4⁺ T, CD8⁺ T, and Th1 cells, ratios of CD4/CD8 and Th1/Th2, and levels of IL-6, IL-10 predicted progression/relapse, and Youden-derived cut-offs dichotomized with distinct PFS. On multivariable Cox, IL-6, IL-10, Th1/Th2 ratio, RO status, and week-6 responses were independent predictors, and a nomogram model with good predictive capability was formed. IL-10 remained independently prognostic in multisystem LCH; the immune indices were not prognostic in single-system LCH. External validation in 103 patients confirmed risk stratification and model performance with well-calibrated PFS estimates. CONCLUSION:Baseline peripheral lymphocyte subsets and cytokines carried prognostic information in pediatric LCH. The IL-6, IL-10, and Th1/Th2 profile supported risk stratification and may inform treatment planning.

Osteoarthritis (OA) is a prevalent age-related degenerative joint disorder characterized by dysregulation of metabolism. While several studies have examined the metabolic changes in OA, there exists a lack of a comprehensive retrospective analysis of its current development, research hotspots, and future trends. In this study, we employed bibliometric approaches to retrospectively review the development, mechanisms, and future trends of metabolic changes in OA. We utilized VOSviewer software to quantitatively and visually depict: (a) annual temporal trends in literature and citation counts; (b) national/regional publications and collaborations; (c) institutional and author contributions; (d) journal contributions and relevance; (e) analysis of research hotspots and directions through keywords. By analyzing keywords and research hotspots, we systematically illustrated the influential factors of metabolic changes in OA, including inflammation, apoptosis, oxidative stress, and autophagy. Conclusively, the research field of metabolic changes in OA is rapidly expanding, and we aim to provide a more comprehensive and insightful perspective for targeting metabolic disorders in OA.

BACKGROUND AND OBJECTIVE:Arteriovenous malformations (AVMs) in soft tissues are uncommon congenital vascular malformations, which are challenging to treat due to the high flow, risk of uncontrollable bleeding, and infiltrative growth. Surgical resection and interventional embolization are the main treatment for AVMs. The authors aim to summarize an individualized treatment strategy for treating AVMs in soft tissues to achieve the optimal outcome. METHODS:The medical records of patients with soft tissue AVMs who were treated in our center from January of 2006 to December of 2023 were reviewed retrospectively. Treatment included surgical resection, interventional embolization, combinational therapy, bleomycin A5 injection, and copper wire retention. The treatment option for each patient was based on the Schobinger classification, the location, depth, and size of the lesion. The patients were followed up for 3 months to 5 years. The indications, precautions, complications, and outcomes of above treatment were analyzed, and the treatment strategy was hence summarized. RESULTS:A total of 68 patients were included in the study, including 37 male patients and 31 female patients with a mean age of 24.7 years (range: 3-62). Patients were followed up for 3 months to 5 years. Nine Schobinger stage I, 43 stage II, 14 stage III, and 2 stage IV case were included. Lesions consisted of 5 Yakes type I, 33 type II, 11 type III, and 16 type IV. Three patients could not be identified with Yakes classification due to lack of arteriographic data. Surgery alone was performed in 35 cases, including simple surgical resection with primary closure/local flap transfer (n=18), surgical resection with expanded flap reconstruction (n=7), and surgical resection followed by skin grafting (n=10). Interventional embolization alone was performed in 11 cases, including 7 cases through an intra-arterial approach and 4 cases through a direct puncture of the nidus. Ten cases underwent combinational treatment which consisted of a preoperative embolization and a subsequent surgery within 48 hours. Five cases underwent bleomycin A5 injection and 7 cases underwent copper wire retention therapy. Control (42, 61.8%) and improvement (13, 19.1%) was achieved in 68 patients (55, 80.9%). During the follow-up, 6 patients reported recurrence and received another surgery. Complications of surgical treatment included partial flap necrosis (n=5) and incision dehiscence (n=3) which healed after dress changing. No skin necrosis or ectopic embolism occurred after embolization. Sixty-six patients were very satisfied with the appearance and 2 patients were basically satisfied with the appearance. CONCLUSIONS:The individualized therapy considering Schobinger classification, site, depth, and size of AVMs can achieve satisfactory results. Surgery and embolization are still the mainstay treatment methods for arteriovenous malformations.

OBJECTIVE:Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS:Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS:The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION:Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.