Background Keloid development following toe syndactyly division is a rare but troublesome condition, which can impose both esthetic and functional burden. Currently, there is no effective treatment for this condition. The present study proposed a new treatment for keloid after syndactyly division by 1470 nm laser and glucocorticoid injection (1470 LAGI). This study aimed to evaluate the efficacy of this treatment modality. Methods A retrospective study was conducted on 12 patients with 36 keloid cases, who underwent treatment with 1470 LAGI. VSS scores were applied for keloid evaluation (pigmentation, vascularity, pliability, and height). VAS was applied for assessing pain and itching, and the recovery rate was recorded. Results This study showed that the 1470 LAGI can improve the pathological status of keloids from toe syndactyly division (p < 0.001), with a recovery rate of 30.56%. Itching and pain also significantly improved (p < 0.001). Conclusion In terms of vascularity, pigmentation, pliability, and height, 1470 LAGI led to keloid regression after toe syndactyly division, with a recovery rate of 30.56%. Besides, the combined treatment significantly decreased the episodes of itching and pain, thereby improving the quality of life. Therefore, it is an effective minimally invasive treatment for keloid following toe syndactyly division in children.

Background:Noxious lifestyle factors including spicy diets and hot baths may lead to scar formation and recurrence. These phenomena are related to the activation of the transient receptor potential vanilloid-1 (TRPV1) cation channel. Our previous study revealed significant upregulation of TRPV1 expression in the dermis of hypertrophic scar (HS), while the exact underlying mechanism of TRPV1 activation in HS remains ill-defined. This study aims to clarify the contribution of TRPV1 activation to HS pathogenesis, particularly in relation to aberrant angiogenesis. Methods:First, this study employs single-cell RNA sequencing technology to analyze the association between vascular endothelial cells and the development of HS. Complementarily, bioinformatics analysis combined with histological validation is utilized to investigate the relationship between TRPV1 channels and aberrant angiogenesis within HS formation. Furthermore, the correlation between TRPV1 activation and HS phenotypes is rigorously validated at the in vivo level. In parallel, in vitro experiments are conducted to elucidate the impact of TRPV1 channel activation on the biological behaviors and functions of vascular endothelial cells. Subsequently, key downstream signaling pathways of TRPV1 are screened, and their molecular mechanisms in regulating vascular endothelial cell-mediated angiogenesis are systematically verified. Finally, a comprehensive analysis is performed to establish the clinical relevance of the TRPV1/nuclear factor kappa-B (NF-κB)/interleukin-6 (IL-6) axis with vascularization severity and adverse prognostic outcomes in hypertrophic scarring. Results:Single-cell RNA sequencing revealed significant cellular heterogeneity in vascular endothelial cells between normal skin and HS, indicating activated angiogenesis and substantial vascular endothelial cell alterations during HS development. Bulk RNA-seq and clinical analyses further confirmed this angiogenesis activation, demonstrating a close association with TRPV1 channel activation. In vivo studies established that capsaicin (CAP)-induced TRPV1 activation exacerbated HS progression through enhanced angiogenesis, whereas TRPV1 ablation or local inhibition markedly attenuated this effect. In vitro experiments demonstrated that TRPV1 activation regulated angiogenesis by promoting pro-angiogenic phenotypes. Transcriptomic analysis and functional validation identified the IL-6/signal transducer and activator of transcription 3 pathway as a downstream NF-κB-dependent pro-angiogenic axis mediated by TRPV1 in HS vascular endothelial cells. Critically, dermal overexpression of the TRPV1/NF-κB/IL-6 axis in HS patients correlated strongly with both disease severity and recurrence. Conclusions:Here, we show that the development of HS is strongly correlated with endothelial angiogenic activity. TRPV1 activation by CAP enhances proangiogenic processes including endothelial proliferation, migration, and tubule formation, while reducing apoptosis through the TRPV1/NF-κB/IL-6 axis. In a rabbit ear HS model, stimulation of TRPV1 contributes to the formation of HS via the TRPV1/NF-κB/IL-6 axis, whereas pharmacological ablation of TRPV1 significantly reversed these phenotypes. These findings shed light on the underlying molecular mechanisms and provide a potential therapeutic target for HS.

The lymphatic system serves many more functions than simply maintaining tissue fluid homeostasis, and its structural and functional changes indicate the occurrence of disease. Current clinical methods for the assessment of the lymphatic system, however, are severely limited because of their nontargeting ability, invasiveness, high cost, and radiation risk. Herein, we propose a simple and painless method for visualizing and quantifying the lymphatic system. This method is based on the noninvasive administration of a novel lymphatic tracer via dissolvable microneedles, followed by the application of a portable detection device for near-infrared (NIR) imaging. The tracer is prepared by incorporating the clinically approved NIR fluorescent dye methylene blue (ME) into the nanomaterial monomethoxyl poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-PCL@ME). This novel tracer displays superior fluorescence properties, stability, biocompatibility, and targeting features in comparison with ME solution alone. Lymphography with MPEG-PCL@ME in vivo clearly revealed the lymphatic vessel morphology. Notably, compared with ME and indocyanine green, MPEG-PCL@ME can easily identify the dominant lymphatic vessels and nodes in rats with higher imaging quality. Furthermore, a series of segmental contracting sections are detected with MPEG-PCL@ME, allowing straightforward identification of the lymphatic pump, which provides direct evidence for exquisitely evaluating lymphatic functions.

Noxious lifestyle factors including spicy diets and hot baths may lead to scar formation and recurrence. These phenomena are related to the activation of the transient receptor potential vanilloid (TRPV1) cation channel. Our previous study revealed significant upregulation of TRPV1 expression in the dermis of hypertrophic scar (HS), while the exact underlying mechanism of TRPV1 activation in HS remains ill-defined. Firstly, this study employs single-cell RNA sequencing technology to analyze the association between vascular endothelial cells and the development of HS. Complementarily, bioinformatics analysis combined with histological validation is utilized to investigate the relationship between TRPV1 channels and aberrant angiogenesis within HS formation. Furthermore, the correlation between TRPV1 activation and HS phenotypes is rigorously validated at the in vivo level. In parallel, in vitro experiments are conducted to elucidate the impact of TRPV1 channel activation on the biological behaviors and functions of vascular endothelial cells. Subsequently, key downstream signaling pathways of TRPV1 are screened, and their molecular mechanisms in regulating vascular endothelial cell-mediated angiogenesis are systematically verified. Finally, a comprehensive analysis is performed to establish the clinical relevance of the TRPV1/nuclear factor kappa-B (NF-κB)/interleukin-6 (IL-6) axis with vascularization severity and adverse prognostic outcomes in hypertrophic scarring. Single-cell RNA sequencing revealed significant cellular heterogeneity in vascular endothelial cells between normal skin (NS) and HS, indicating activated angiogenesis and substantial vascular endothelial cell alterations during HS development. Bulk RNA-seq and clinical analyses further confirmed this angiogenesis activation, demonstrating a close association with TRPV1 channel activation. In vivo studies established that capsaicin (CAP)-induced TRPV1 activation exacerbated HS progression through enhanced angiogenesis, whereas TRPV1 ablation or local inhibition markedly attenuated this effect. In vitro experiments demonstrated TRPV1 activation regulated angiogenesis by promoting pro-angiogenic phenotypes. Transcriptomic analysis and functional validation identified the IL-6/Signal Transducer and Activator of Transcription 3 (STAT3) pathway as a downstream NF-κB-dependent pro-angiogenic axis mediated by TRPV1 in HS vascular endothelial cells. Critically, dermal overexpression of the TRPV1/NF-κB/IL-6 axis in HS patients correlated strongly with both disease severity and recurrence. Here, we show that the development of HS is strongly correlated with endothelial angiogenic activity. TRPV1 activation by CAP enhances proangiogenic processes including endothelial proliferation, migration and tubule formation, while reducing apoptosis through the TRPV1/ NF-κB/ IL-6 axis. In a rabbit ear HS model, stimulation of TRPV1 contributes to the formation of HS via the TRPV1/NF-κB/IL-6 axis, whereas pharmacological ablation of TRPV1 significantly reversed these phenotypes. These findings shed light on the underlying molecular mechanisms and provide a potential therapeutic target for HS.

Cartilage exhibits remarkable subtype diversity—hyaline, fibrocartilage, and elastic—each with unique extracellular matrix architecture and mechanical function. Despite the clinical promise of adipose-derived mesenchymal stem cells (ADMSCs) for cartilage regeneration, whether distinct in vivo cartilage microenvironments can instruct ADMSC differentiation toward corresponding subtypes remains poorly defined. Green fluorescent protein-labeled human ADMSCs were encapsulated in a fibrin hydrogel and implanted into three representative cartilage sites—auricular (elastic), articular (hyaline), and meniscal (fibrocartilage)—in an immunodeficient rat model. Regenerated tissues were harvested at 4 weeks for histology (H E), immunofluorescence analysis of hyaline (COL II, aggrecan), fibrocartilage (COL I, tenomodulin), and elastic (fibrillin-1, elastin) markers, and RT-PCR quantification of lineage-associated gene expression. ADMSCs survived and engrafted within all three microenvironments. Articular cartilage implants exhibited strong hyaline-like differentiation, characterized by intense COL II and aggrecan expression and upregulation of SOX9, COL2A1, and ACAN. Meniscal implants instead displayed a fibrocartilage-like profile with robust COL I and tenomodulin expression and elevated COL1A1, TNMD, and SCX transcripts. In contrast, auricular cartilage implants showed negligible expression of hyaline, fibrocartilage, or elastic markers, accompanied by global downregulation of chondrogenic and elastogenic genes. These results demonstrate that local cartilage niches exert distinct instructive effects on ADMSC fate: articular and meniscal environments effectively guide hyaline- and fibrocartilage-like differentiation, whereas the auricular niche under the tested conditions fails to support elastic or hyaline lineage commitment. Our findings highlight the decisive role of the tissue microenvironment in modulating ADMSC differentiation and underscore the need for bioengineered, niche-mimetic scaffolds to achieve subtype-specific cartilage regeneration—particularly for complex elastic tissues such as the auricle.

Background:Extensive postburn facial scarring cannot achieve aesthetic resurfacing with skin graft or mismatched flaps. Although adjacent flap donor sites, such as the neck or deltopectoral area, provide ideal skin characteristics, flap transfer may be highly limited due to the absence of proper axial vessels. Here, we demonstrate an innovative reconstructive alternative in terms of prefabrication and tissue expansion for extensive facial resurfacing. Methods:A serratus anterior fascia flap within the serratus branch of the thoracodorsal artery was harvested and microsurgically transferred as the pedicle of a prefabricated cervicothoracic flap. The flap, with the fascia located in a subcutaneous pocket over a tissue expander, was raised, islanded, and rotated to reconstruct the facial defect after reliable expansion and maturation. Flap size, donor/recipient site, surgical outcomes, and donor-site morbidity were all evaluated. Results:The flap sizes ranged from 13 × 10 to 27 × 21 cm. All 15 patients with extensive postburn facial scars, aged 15-40 years (mean 30.73 y), achieved successful reconstruction without major complications after 6-12 months of follow-up. Conclusions:The prefabricated, expanded cervicothoracic flap with the serratus branch of the thoracodorsal artery demonstrated a favorable color and texture match with the recipient site. The donor site can be primarily closed with minimized aesthetic and functional compromise.

Cancer-related lymphedema (CRL), the most common type of secondary lymphedema, seriously reduces the life quality of cancer patients. In-depth studies on the pathogenesis of CRL are limited, impeding the development of therapeutic approaches. In this study, an analysis of intercellular heterogeneity reveals a trend towards fibrosis in skin cell subpopulations and identifies the phenomenon of T-cell mesenchymal transition (TcMT). T cells with a mesenchymal phenotype-fibroblast-like (Fib-like) T cells and myofibroblast-like (Myofibro-like) T cells-exhibit a unique fibrotic phenotype and impaired immune function. Furthermore, PDGFRB expression by Fib-like T cells in the affected skin is likely to influence disease severity by regulating TcMT. Additionally, we observe the manifestation of the fibrotic phenotype of T cells in single-cell data from the stromal vascular fraction (SVF) of CRL patients, suggesting that TcMT may be a pathological feature and potential therapeutic target of CRL and providing deep insights into disease pathophysiology.

Background: Despite being considered the golden standard for nasal reconstruction for decades, there has been a lack of detailed investigation into the hemodynamic differences between bilateral supratrochlear vessels during forehead flap procedures. In this study, the authors utilized infrared thermography (IRT) to identify the dominant supratrochlear vessel as the nourished pedicle, aiming to achieve optimal surgical outcomes. Methods: A total of 24 regular and 40 pre-expanded forehead flaps, consecutively included from October 2017 to February 2023, were retrospectively divided into two groups for analysis. In group A (11 regular and 23 pre-expanded flaps), bilateral supratrochlear arteries were identified using infrared thermography (IRT) and color Doppler ultrasound (CDU), with the flap designed based on the dominant side. In group B (13 regular and 17 pre-expanded flaps), the flap was designed directly at the ipsilateral side. Vascular disparities and surgical outcomes were compared. Results: Among the 34 flaps in group A, bilateral hemodynamic disparities were observed in 13 flaps (38.2 %), comprising of 3 regular flaps (27.2 %) and 10 pre-expanded flaps (43.5 %). The complication incidences for group A is lower than that for group B (5/34 VS 9/30, p < 0.05). The complication rate between regular and pre-expanded flaps was 3/24 versus 11/40, p <0.05. All complications resulted in a delayed pedicle division. Conclusion: The potential asymmetry of supratrochlear arteries could significantly impact the prognosis of nasal reconstruction with forehead flaps, especially within tissue expansion technique. It is essential to identify the dominant side to achieve optimized surgical outcomes. (c) 2025 Asian Surgical Association and Taiwan Society of Coloproctology. Publishing services by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and huntington's disease, pose significant threats to human health, with current treatment options remaining limited. Piezoelectric materials, known for their ability to convert mechanical energy into electrical signals at the nanoscale, hold great promise in the diagnosis and treatment of neurodegenerative diseases due to their excellent electromechanical properties, environmental stability, and sensitivity. This review systematically outlines the working principles and classifications of piezoelectric materials. Subsequently, the recent advances in piezoelectric materials and their applications in the diagnosis and treatment of neurodegenerative diseases are highlighted. Finally, the challenges and perspectives regarding the development of future piezoelectric materials are discussed. This review aims to provide a comprehensive reference for the further application of piezoelectric materials in neurodegenerative diseases.

Conventional treatments for Raynaud’s phenomenon (RP) often show limited effectiveness due to their inability to address both vascular and inflammatory aspects. This study evaluates the combination of high-density fat grafting (HDFG) with botulinum toxin A (BTX-A) for treating RP. Eleven patients with 20 affected hands diagnosed with RP were recruited and randomly assigned to receive either HDFG combined with BTX-A (intervention group, n = 11) or HDFG alone (control group, n = 9). Efficacy was assessed using Visual Analog Scale (VAS) pain scores and McCabe Cold Sensitivity Scores, along with finger ulcer healing time and infrared thermal imaging to evaluate blood perfusion improvements. The HDFG-BTX group showed significant improvements in hand symptoms. VAS pain scores decreased from a pre-treatment mean of 5.33 to 0.84 post-treatment (mean reduction of 4.49, p = 0.018), indicating effective pain relief. McCabe scores improved from 272.73 to 75.00 (mean reduction of 197.73, p = 0.001), demonstrating reduced cold sensitivity. Ulcer healing time was shorter in the HDFG-BTX group (14.25 days) compared to HDFG alone (25.6 days, p < 0.001), highlighting faster recovery. Infrared imaging indicated significant enhancements in blood perfusion. HDFG combined with BTX-A is a reliable and beneficial intervention for RP, leading to high patient satisfaction. • Combining high-density fat grafting with botulinum toxin A significantly improves symptoms in Raynaud’s phenomenon. • This novel therapy enhances pain relief, blood flow, and ulcer healing, demonstrating strong patient satisfaction.

Lymphedema, a severe and complex inflammatory disease caused by lymphatic system insufficiency and impeded lymphatic drainage that causes an enormous physical and psychological burden on patients and may even lead to death, has long been a challenging issue in the medical field. Clinically, conventional approaches including surgical treatment and conservative treatment have been employed for lymphedema therapy, but their curative effect is still unsatisfactory because of high operational difficulty, high cost, and long-term reliance. In this study, a novel kind of piezoelectric microneedle driven by ultrasound (US) is proposed to regulate macrophage polarization and remodel the pathological inflammatory microenvironment in a noninvasive manner, thereby promoting lymphatic regeneration and improving lymphedema. US-mediated piezoelectric microneedles can significantly enhance the anti-inflammatory M2-type polarization of macrophages while suppressing pro-inflammatory M1-type polarization in vitro. Enhancements in macrophage M2 polarization can trigger increased secretion of anti-inflammatory factors (e.g., IL-4, IL-10, and Arg-1) that promote inflammatory microenvironment remodeling and immune rebalancing. In a mouse-tail lymphedema model, a higher proportion of M2 macrophage polarization marker CD206 is observed accompanied by normal lymphangiogenesis and lymphedema subsiding following piezoelectric microneedles with US stimulation treatment. Additionally, based on RNA sequencing and mechanistic investigation, it was revealed that US-mediated piezoelectric microneedles can activate signaling pathways related to M2 macrophage polarization that regulate inflammatory responses and improve lymphatic function, consequently alleviating lymphedema. Collectively, this study provides a new strategy for lymphedema therapy in a noninvasive and drug-free manner as well as a potent tool to manipulate macrophages for other immunological diseases.

Photoimmunotherapy is a promising cancer treatment modality. While potent 1-e − oxidative species are known to induce immunogenic cell death (ICD), they are also associated with unspecific oxidation and collateral tissue damage. This difficulty may be addressed by post-generation radical reinforcement. Namely, non-oxidative radicals are first generated and subsequently activated into powerful oxidative radicals to induce ICD. Here, we developed a photo-triggered molecular donor ( NPCD565 ) of nitrosoperoxycarbonate (ONOOCO 2 − ), the first of its class to our knowledge, and further evaluated its feasibility for immunotherapy. Upon irradiation of NPCD565 by light within a broad spectral region from ultraviolet to red, ONOOCO 2 − is released along with a bright rhodamine dye ( RD565 ), whose fluorescence is a reliable and convenient build-in reporter for the localization, kinetics, and dose of ONOOCO 2 − generation. Upon photolysis of NPCD565 in 4T1 cells, damage-associated molecular patterns (DAMPs) indicative of ICD were observed and confirmed to exhibit immunogenicity by induced maturation of dendritic cells. In vivo studies with a bilateral tumor-bearing mouse model showcased the potent tumor-killing capability of NPCD565 of the primary tumors and growth suppression of the distant tumors. This work unveils the potent immunogenicity of ONOOCO 2 − , and its donor ( NPCD565 ) has broad potential for photo-immunotherapy of cancer.

Inducing an anti-inflammatory response before neurogenesis is crucial in effectively addressing peripheral nerve damage. Herein, we developed shell-core-structured nanofilms (Cur/PLCL@BDNF/CNT) using poly-(l-Lactide)-Caprolactone (PLCL) and curcumin (Cur, an anti-inflammatory agent) as the shell layer, and carbon nanotubes (CNT) and brain-derived neurotrophic factor (BDNF, a neurogenic factor) as the core via coaxial electrospinning technology. The resulting Cur/PLCL@BDNF/CNT film exhibited a characteristic fibrous structure with remarkable shell-core architecture, demonstrating unweakened mechanical properties. Notably, it displayed sustained release kinetics with distinct stages: prioritized Cur release within the initial 12 days and delayed BDNF release between 10 to 30 days. Additionally, the Cur/PLCL@BDNF/CNT film demonstrated high biocompatibility with Schwann cells. Subsequent in vitro analysis revealed the potent anti-inflammatory capabilities of the released Cur from the shell layer, while the BDNF released from the core layer effectively induced neurogenic differentiation of Schwann cells. The Cur/PLCL@BDNF/CNT film was rolled into a nerve conduit and then utilized for nerve regeneration in a 10 mm rat sciatic nerve defect model. The staged release of Cur and BDNF facilitated by the Cur/PLCL@BDNF/CNT film established an anti-inflammatory microenvironment before initiating nerve regeneration, resulting in better nerve restoration. This study emphasizes the significance of shell-core-structured nanofilms in temporally regulating anti-inflammation and neurogenesis.

BACKGROUND:Although palmar and digital soft-tissue resurfacing with intrinsic flaps may provide functional and aesthetic reconstruction, the donor site may result in a tight closure or need for a skin graft once the flap is raised. In this series, the "mini-shaped kiss flap" was used to increase the resurfacing efficiency and preserve hand function.METHODS:The mini-shaped kiss flaps, based on common palmar digital arteries (eg, princeps pollicis artery and ulnar palmar digital artery), were developed for the resurfacing of distal or proximal finger areas. The tiny skin paddles were "kissed" together and transferred as pedicled in proposed dimensions and shape. The flap size, donor/recipient site, perforator source, whether free or pedicled, surgical outcome, and donor-site morbidity were evaluated.RESULTS:Twenty mini-shaped kiss flaps were harvested for the purpose of palmar and digital resurfacing. The flap sizes varied from 3 × 1.2 cm to 5 × 2 cm. All 19 patients, aged 6 to 52 years (mean, 35 years), achieved successful reconstruction without major complications after 6- to 12-month follow-up.CONCLUSIONS:The mini-shaped kiss flap technique exhibited favorable surgical outcomes with excellent color and texture match to the recipient sites. The reverse midpalm, thenar, and hypothenar island flap can be raised at the cost of an unnoticeable linear scar with minimized functional compromise in the donor area.CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, IV.

Objective: Gynecological cancer-related lower extremity lymphedema (GC-LEL), a chronic, progressive condition, lacks a standardized treatment. Currently, supraclavicular vascularized lymph node transfer (SC-VLNT) is a favored approach in the treatment of lymphedema, and there is a trend toward combination technology. This study conducts a comparative analysis of three techniques for treating GC-LEL with simultaneous SC-VLNT and liposuction. Methods: A cohort of 35 patients with GC-LEL was examined, comprising 13 patients who underwent single lymph nodes flap with a skin paddle (SLNF+P), 12 who received single lymph nodes flap without a skin paddle (SLNF), and 10 who accepted dual lymph nodes flap without a skin paddle (DLNF). Patient demographics and outcomes were meticulously documented, covering intra- and postoperative variables. Results: The median limb volume reduction were 56.4% (SLNF+P), 60.8% (SLNF), and 50.5% (DLNF) in stage II, and 54.0% (SLNF+P), 59.8% (SLNF), and 54.4% (DLNF) in stage III. DLNF group procedures entailed longer flap harvesting and transplantation times. The SLNF+P group, on average, had an 8-day postoperative hospitalization, longer than others. All patients noted subjective improvements in Lymphedema Quality of Life scores, with lymphoscintigraphy revealing enhanced lymphatic flow in 29 of the 35 cases. A notable decrease in cellulitis incidence was observed. Additionally, the occurrence of cellulitis decreased significantly, except for DLNF (Stage II). The median follow-up time was 16 months (range, 12-36 months), with no reported severe postoperative complications. Conclusions: For advanced GC-LEL, SLNF combined with liposuction is a preferred treatment, offering fewer complications, shorter operative time, and hospitalization. (J Vasc Surg Venous Lymphat Disord 2024;12:101905.)

Background Several surgeons have described studies of free-tissue transfers using veins instead of arteries. These innovative microsurgical techniques can offer several advantages, such as an easier dissection during flap harvesting, and represent an alternative during an accidental surgical mistake or development of new surgical procedures. The purpose of this study was to describe and explore different constructs of vascularized lymph node transfer (VLNT) only based on venous blood flow in a mouse model, evaluate their blood flow microcirculation through indocyanine green (ICG) angiography and investigate the lymphatic drainage function and the lymph nodes' structures. Methods Five types of venous lymph node flaps (LNF) were created and investigated: Types IA, IB, IC, IIA and IIB were developed by ICG intraoperatively (with videos in the article). Seven weeks later, by applying methylene blue, the recanalization of the lymphatic vessels between the LNF and the recipient site was detected. Lymph nodes were collected at the same time and their structures were analyzed by hematoxylin and eosin staining analysis. Results All of the venous LNFs developed except Type IC. Seven weeks later, methylene blue flowed into Types IA, IB, IIA and IIB from recipient sites. When comparing with arteriovenous lymph node, the medullary sinus was diffusely distributed in venous lymph nodes. The proportion of cells was significantly reduced (p < 0.05). The artery diameters were significantly smaller (p < 0.05). The veins diameters and lymphatic vessels output in Types IA, IB, IIA and IIB were more dilated (p < 0.05). Conclusions This research demonstrated that Type IA, IB, IIA and IIB venous LNFs can retrogradely receive venous blood supply; they can survive, produce a lymphatic recanalization and integrate with the surrounding tissue, despite lymph node structural changes. Our results will improve the understanding of the survival mechanism of venous LNFs and will help researchers to design new studies or lymphatic models and eventually find an alternative procedure for the surgical treatment of lymphedema.

Background: Flaps based on the medial plantar artery (MPA) accomplish favorable surgical outcomes in palmar resurfacing because of their outstanding texture, pliability, and contour, but primary closure cannot be achieved at the donor site when the flap is designed to be relatively large. In this study, the kiss technique was used for the reconstruction of extensive palmar defects, which minimized donor-site morbidity. Methods: A modified flap surgical strategy was systemically developed based on the perforator distribution of the MPA through a cadaver study. Two or three narrow, small skin paddles based on the MPA were raised and resembled at the recipient site as a larger flap. Static two-point discrimination, hypersensitivity and range of motion, QuickDASH, gait, and patient satisfaction were evaluated 6 months to 12 months after the operation. Results: From June of 2015 to July of 2021, 20 cases of reconstruction using the MPA perforator kiss flap were performed for the resurfacing of palmar skin defects. All flaps survived uneventfully, with coverage matching the texture and color of the recipients, except one flap that exhibited venous congestion and recovered after revision. Twelve flaps (60%) were double-paddled, and eight flaps (40%) were triple-paddled, with a resurfacing area of 27.19 cm 2 and 41.1 cm 2 , respectively. All donor sites achieved primary closure without major complications. Conclusions: Versatile kiss flap combinations were developed based on further understanding of the MPA system. Durable and pliable characteristics of the MPA perforator flap provide excellent reconstruction for extensive palmar defects while minimizing donor-site complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The venous lymph node flap (vLNF) is regarded as an arterialized or ‘pure’ venous flap, subject to which type of vessel provides blood supply to the flap. However, whether the vLNF drainage function is maintainable or sufficient for the treatment of lymphoedema is yet to be elucidated. In this study, the venous flow‐through lymph node flaps or ‘pure’ vLNF was investigated in a rat's tail (lymphoedema model), and the therapeutic effect was analysed to clarify its potential value for the treatment of lymphoedema. The subjects (rats) were divided into three groups, the experimental group (‘pure’ vLNF group), the control group (lymphoedema group), and the baseline group. The tail circumference and diameter were recorded for 5 weeks after the operation. Five weeks after surgery, the lymphatic drainage function was evaluated using indocyanine green (ICG) lymphography, while the skin thickness and collagen layer were assessed by histological analysis. The average diameter and circumference of the experimental group were significantly shorter than the control group (p < 0.01). When comparing ICG lymphography within the three groups, the baseline group showed that the ICG entered the inguinal lymph node and appeared in the liver while the ICG still accumulated in the oedematous tail with no fluorescence emerging in other parts of the rat's body, in the control group. In the experimental group, the ICG entered the vLNF via the flap junction with the rat's tail and fluorescence emerging in the rat's liver. When comparing the three groups above with the control group, the experimental group's skin and collagen layer thickness were significantly improved (p < 0.01). Lymphatic recanalization was shown to appear between ‘pure’ vLNF and the recipient area. Moreover, vLNF was shown to drain lymph fluid via the venous system, thus relieved swelling and fibrosis of the lymphoedematous tissue. Consequently, this could represent a new potential surgical approach for the treatment of lymphoedema.

Aims: Cuproptosis is a novel cell death pathway, and the regulatory mechanism in head and neck squamous cell carcinoma (HNSC) remains to be explored. We determined whether cuproptosis-related lncRNAs (CRLs) could predict prognosis in HNSC.Methods and Results: First, we identified 10 prognostic CRLs by Pearson correlation and univariate Cox regression analyses. Next, we constructed the CRLs prognostic model based on 5 CRLs screened by the least absolute shrinkage and selection operator (LASSO) Cox analysis. Following this, we calculated the risk score for HNSC patients and divided patients into high- and low-risk groups. In our prognostic model, HNSC patients with higher risk scores had poorer outcomes. Based on several prognostic features, a predictive nomogram was established. Furthermore, we investigated principal component analysis to distinguish two groups, and functional enrichment analysis of 176 differentially expressed genes (DEGs) between risk groups was performed. Finally, we analyzed relationships between tumor mutation burden (TMB) and risk scores.Conclusion: Cuproptosis-related lncRNAs can be applied to predict HNSC prognosis independent of TMB, which is closely correlated with tumor immunity.

Diabetes is a global disease with huge impacts on patients due to its complications, among which non-healing wounds and depression are common and challenging. The neurokinin 1 receptor (NK1R) inhibitor, aprepitant has been broadly applied for an antidepressant effect in depressive patients. Recent literature has indicated a therapeutic effect of downregulation in NK1R to diabetes-related fracture, cardiomyopathy, gastroparesis, and ocular surface disorders. In this study, differential expression genes in diabetes and depression were analyzed based on several RNA sequencing datasets from the GEO database to confirm NK1R in the overlapping set. Interaction network and gene set enrichment analysis were subsequently conducted. As a result, NK1R-related genes took part in angiogenesis, epithelial-mesenchymal transition (EMT), collagen deposition, and inflammation in diabetes and depression. In vivo, the downregulation of NK1R was proved to promote vascular proliferation and enhance diabetic wound healing, which provides a potential therapeutic target for the management of diabetic non-healing wounds and depression.