Infantile hemangiomas (IHs) can lead to significant complications during the proliferative phase, particularly in thick lesions that are not adequately controlled by topical timolol due to its limited skin penetration. Oral propranolol is effective but limited by systemic side effects and resistance. To overcome these challenges, we developed a novel barbed microneedle (MN) system for depth-specific dual-drug delivery. Bleomycin (BLM) is loaded in the needle tips for deep ablation, while timolol (TM) is incorporated in the base hydrogel for superficial vasoconstriction, enabling synergistic therapy (TM-BLM@MN). The barbed structure secured prolonged retention in vivo. In vitro, the TM-BLM@MN significantly inhibited hemangioma stem cell proliferation, migration, and tube formation. In vivo, treatment of TM-BLM@MN achieved a 1.93-fold greater reduction in tumor volume compared to controls and markedly suppressed pathological angiogenesis by histology. TM-BLM@MN as a minimally invasive platform demonstrates high efficacy for thick IH and holds strong potential for clinical translation and home-based therapy.

Facial port-wine stains (PWS) are often complicated by subcutaneous adipose hyperplasia, yet the underlying cellular and molecular mechanisms remain unclear. Here, using single-cell RNA sequencing of facial adipose tissues, we identified a distinct subpopulation of adipose stem and progenitor cells that expressed high levels of SPSB1 in hypertrophic PWS. SPSB1 expression was transcriptionally upregulated by FOSL1. Functional assays revealed that SPSB1 potently promoted adipogenesis both in vitro and in vivo. Mechanistically, SPSB1, acting as an adapter for the Cullin-RING E3 ligase complex, directly interacted with HDAC1. It specifically mediated K48- and K29-linked polyubiquitination of HDAC1 at lysine residues 89 and 361, respectively, thereby targeting HDAC1 for degradation via both the ubiquitin-proteasome and autophagy-lysosome pathways. The degradation of HDAC1 increased chromatin accessibility of key adipogenic genes and promoted their expression. Furthermore, HDAC1 downregulation relieved its transcriptional repression on the SPSB1 promoter, establishing a positive feedback loop that perpetuated the pro-adipogenic signal. Collectively, our findings delineated a novel SPSB1-HDAC1 regulatory axis that drove pathological adipose hyperplasia in facial PWS, highlighting SPSB1 and HDAC1 as potential therapeutic targets for this condition.

Background Large unilateral facial hemangiomas, particularly those involving the parotid gland, are significant due to their potential to cause severe facial asymmetry. No universally accepted classification exists for assessing the severity or determining appropriate surgical interventions. This study proposes an algorithm for managing involuting or involuted hemangiomas with facial asymmetry, based on magnetic resonance imaging (MRI) findings. Methods Sixteen patients presenting with facial asymmetry who underwent surgical procedures for involuting or involuted hemangiomas were included in this study. Patients were categorized into four types based on the association between MRI findings of hemangiomas and surgical procedures. Those without facial asymmetry who did not require surgery were classified as Type I and were therefore excluded from analysis. Results Ten patients who received liposuction were classified as Type II, three patients who underwent lipectomy with a minimal access cranial suspension lift were classified as Type III, and three patients who underwent lipectomy with formal facial nerve dissection were classified as Type IV. All 16 patients showed improvement in facial asymmetry and deformity. The mean postoperative follow-up period was 7.8 months. No major complications were observed in any of the types. Conclusion Surgical interventions of hemangiomas associated with facial asymmetry are typically performed during the involuting or involuted phase, offering a less invasive approach with lower morbidity. Preoperative MRI findings can effectively delineate the extent and depth of fibrofatty tissue, assisting surgeons in selecting the optimal therapeutic strategy. Our classification system may serve as a practical guide for surgical planning.

Background: Vascular anomalies (VAs), including hemangiomas and vascular malformations, present a significant diagnostic challenge due to their high prevalence, complex classification (nearly 100 subtypes), and visual mimicry. Current Multimodal Large Language Models (MLLMs) struggle in this specialized domain, often failing to capture fine-grained visual features or lacking evidence-based reasoning. To address these limitations, we introduce HevaDx, an agentic diagnostic system that explicitly decouples visual perception from clinical reasoning. Methods: Leveraging a newly constructed large-scale dataset of VA patients, HevaDx employs a lightweight visual specialist for precise feature extraction and a reasoning specialist equipped with Retrieval-Augmented Generation (RAG) for therapeutic planning. This cooperative architecture mitigates the “reasoning gap” observed in end-to-end models by grounding decisions in up-to-date clinical guidelines. Results: Experimental results demonstrate that HevaDx achieves high performance with a top-3 diagnostic accuracy of 94.8% and a treatment recommendation accuracy of 83.3%. Conclusions: By bridging visual precision with transparent, verifiable logic, HevaDx offers a reliable framework for AI-assisted management of vascular anomalies.

PIK3CA mutations drive benign adipose overgrowth in facial infiltrating lipomatosis (FIL), but the downstream molecular mechanisms remain incompletely understood. This study investigated the role of palmitoyl-protein thioesterase 1 (PPT1)-mediated depalmitoylation in regulating aberrant adipogenesis induced by mutant PIK3CA. Using single-cell RNA-seq, molecular dynamics simulations, and functional assays in primary human FIL adipose-derived stem and progenitor cells (ASPCs), immortalized cell lines, and mouse models, we dissected the signaling pathway linking PIK3CA mutation to adipogenesis. Techniques included ChIP-qPCR, acyl-biotin exchange assays, luciferase reporter assays, and RNA/ATAC sequencing. PIK3CA mutations transcriptionally repressed PPT1 via PI3K-AKT-c-JUN signaling. Downregulated PPT1 enhanced palmitoylation of the transcriptional coactivator P300 at C1176. This modification stabilized P300 by impairing its interaction with HSC70 and subsequent chaperone-mediated lysosomal degradation. Furthermore, C1176 palmitoylation inhibited P300 phase separation, thereby preserving its histone acetyltransferase activity. Sustained P300 activity promoted chromatin accessibility and expression of adipogenic genes, driving excessive adipogenesis in FIL. These findings established a novel "palmitoylation-phase separation-epigenetic regulation" axis in cellular fate determination and revealed PPT1 and P300 as potential therapeutic targets for FIL.

The regeneration and repair of complex tissues in plastic and reconstructive surgery are fundamentally limited by the inability to rapidly form functional hierarchical vascular networks. This challenge is central to issues ranging from graft failure to the treatment of vascular anomalies. However, traditional experimental systems have long presented bottlenecks. Conventional two-dimensional cell cultures fail to replicate three-dimensional vascular microenvironments, whereas animal models are hampered by significant interspecies discrepancies. Although vascular organoids are a promising human-relevant model, they are limited by diffusion-limited necrosis, structural immaturity, and poor reproducibility. Microfluidic organoids-on-chips (OoCs) have emerged to overcome these hurdles by providing precise control of the cellular microenvironment and enabling the development of robust, perfusable, and mature vascular structures. This review describes how vascular organoids-on-chips (VOoCs) serve as a transformative platform with direct clinical implications for plastic and reconstructive surgeries. We highlight their unique utility in modeling vascular anomalies such as infantile hemangiomas, providing a human-specific system for deciphering disease mechanisms and screening therapeutics such as propranolol. Furthermore, we explore their role in engineering pre-vascularized tissues, where VOoCs could be leveraged to fabricate skin flaps and composite grafts with an embedded perfusable microvasculature designed for rapid anastomosis upon transplantation, thereby addressing the critical bottleneck of ischemia. Finally, we discuss the potential of VOoCs to enable personalized medical strategies through patient-specific disease modeling and drug testing. By bridging the long-standing gap between in vitro models and human physiology, VOoCs offer surgeons and tissue engineers powerful tools to refine disease models, enhance graft survival, and accelerate the development of novel regenerative therapies.

Infantile hemangiomas (IH) are a common pediatric condition that, if not diagnosed and treated early, can lead to functional impairments or permanent disfigurement. However, accurate diagnosis and timely treatment recommendations often depend on the expertise of clinicians and expensive medical imaging, which presents significant challenges in resource-limited settings, especially in low- and middle-income countries. While existing computer-aided diagnosis (CAD) methods have been developed for IH, they mainly assist clinicians rather than offering direct decision-making support, which limits their impact on patient care. To address these challenges, we propose DeepIH, the first near-patient system designed for treatment recommendation of IH based on deep learning. DeepIH is methodologically innovative in two key ways: (1) it accepts camera-shot images as input, enabling patients to conveniently access treatment recommendations through accessible edge devices like smartphones or laptops; (2) it directly generates treatment recommendations, reducing reliance on clinician oversight and enabling faster, more accessible care. Through evaluation on our established dataset, DeepIH achieves an impressive 95.8% accuracy in detecting lesion regions and 84.9% top-3 accuracy in recommending treatments, which even surpasses a fine-tuned foundation model by 1.7%. These findings, for the first time, validate the viability of near-patient diagnosis for IH, highlighting its potential significance in clinical applications as it allows patients to receive treatment recommendations through everyday devices like smartphones or laptops.

Facial infiltrating lipomatosis (FIL) is a rare congenital disorder characterized by excessive adipose tissue accumulation and infiltration, leading to severe functional and aesthetic impairments. Current surgical interventions face high recurrence rates and complications, necessitating exploration of molecular mechanisms driving FIL. N6-methyladenosine (m6A) RNA modification plays an essential role in modulating RNA stability and contribute to the regulation of adipogenesis. However, the detailed mechanism by which m6A regulator regulates the pathogenesis of FIL remains unclear. We focused on FTO-mediated m6A demethylation and evaluated FTO expression in FIL adipose tissues and adipose stem and progenitor cells (ASPCs) using Western blotting, qPCR, immunohistochemistry, and single-cell RNA sequencing. The regulatory mechanism of FTO on SLC7A11 was explored via MeRIP-seq, RIP-qPCR, and luciferase reporter assays. In vivo effects were evaluated using xenograft, NAC gavage, and AAV8-mediated SLC7A11 overexpression models. The mechanisms by which SLC7A11 influenced adipogenesis were investigated through ATAC-seq, ChIP-qPCR, and enzyme activity assays. FTO was upregulated in FIL tissues and ASPCs, correlating with reduced m6A levels, enhanced adipogenesis, and disease severity. Mechanistically, FTO decreased m6A modification of SLC7A11, impairing IGF2BP1-mediated stabilization and reducing SLC7A11 expression. This lowered cystine uptake and GSH/GSSG ratio, inhibiting SIRT6 activity and elevating H3K9ac at promoters of adipogenic genes (PPARG, CEBPA, FABP4), thereby enhancing chromatin openness and transcriptional activation. In vivo, SLC7A11 overexpression impaired adipogenic effects. Modulating GSH/GSSG ratios via NAC or BSO validated the redox-epigenetic axis in regulating adipogenesis. Our findings collectively demonstrate that FTO drives FIL progression by m6A-dependent suppression of SLC7A11, disrupting redox balance and regulating SIRT6-H3K9ac-mediated epigenetic reprogramming to promote adipogenesis. Targeting the FTO/SLC7A11/GSH/SIRT6 axis offers a promising therapeutic strategy for FIL.

CASE PRESENTATION:A 7-year-old girl was referred to our vascular anomaly center for further evaluation of multiple lung nodules. These nodules were incidentally detected on a CT scan during hospitalization for treatment of mycoplasma pneumonia at another hospital. The biopsy results suggested the possibility of vascular tumors. Physical examination revealed clear breath sounds without rales. Furthermore, no skin lesions or other positive signs were observed. The patient was not receiving supplemental oxygen. Before she came to our center, the patient had received antibiotic treatment for mycoplasma pneumonia. The CT scan after recovery revealed that the multiple nodules in both lungs persisted despite the resolution of the infection.

Diabetes-associated skin defects represent a significant global health challenge. While flap grafts have been a preferred treatment for soft-tissue injuries in diabetic patients, their survival is often compromised by impaired vascularization, infection, and the adverse diabetic pathological microenvironment. To address these limitations, a hybrid photo-crosslinkable hydrogel (HPC) integrated hemangioma stem cell-derived nanovesicle (HemV)-loaded dual-metal-polyphenol network (dMPN) (HemV@dMPN/HPC) is developed. HemVs, derived from highly vascularized infantile hemangioma tissues, play a key role in promoting cell proliferation and angiogenesis. The dMPN facilitates the gradual release of copper (Cu2+) and magnesium ions (Mg2+), stimulating angiogenesis and mitigating inflammation. The HPC further sustains ion release while preserving the therapeutic efficacy of HemVs. Moreover, both HPC and Cu2+ act to confer antibacterial properties, further accelerating wound healing. This multifunctional HemV@dMPN/HPC platform offers a promising therapeutic strategy for treating large diabetic skin defects and can potentially improve flap graft survival.

Infantile hemangiomas (IHs) are the most common benign vascular tumors observed in children. Owing to mechanical compression during the critical visual development period, periorbital IHs carry a high risk of irreversible ocular sequelae, such as strabismus, anisometropia, and amblyopia. Early multidisciplinary intervention is pivotal in preventing long-term impairment. However, evidence of infancy-to-adulthood outcomes remains limited. The first case describes a 24-year-old woman with right periorbital IH diagnosed in infancy. Despite the complete regression of the lesion in adulthood, the patient developed severe strabismus and monocular amblyopia. The second is a similar case of a 19-year-old woman with regressed IH yet evident strabismus. Despite lesion regression with residual scarring after electrochemical therapy, steroid injections, and surgical resection, significant strabismus persisted. These two long-term follow-up cases provide compelling evidence that periorbital IH may entail irreversible oculomotor dysfunction and refractive errors, highlighting the importance of early multidisciplinary intervention during the critical period of visual development.