Synchronous supraclavicular vascularized lymph node transfer and liposuction for gynecological cancer-related lower extremity lymphedema: a clinical comparative analysis of three different procedures.

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.

A Carbon-Caged Rhodamine Generating Nitrosoperoxycarbonate for Photoimmunotherapy.

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 (ONOOCO2 -), 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, ONOOCO2 - 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 ONOOCO2 - 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 ONOOCO2 -, and its donor (NPCD565) has broad potential for photo-immunotherapy of cancer.

Mini-Shaped Kiss Flap Design for Palmar and Digital Soft-Tissue Resurfacing.

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.

Vascularized lymph node flaps can survive on venous blood without an arterial inflow: an experimental model describing the dynamics of venous flow using indocyanine green angiography (With video).

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.

Medial Plantar Artery Perforator Kiss Flap for Salvage of Extensive Palmar Skin Defect.

BACKGROUND: Flaps based on the medial plantar artery (MPA) accomplish favorable surgical outcomes in palmar resurfacing due to its outstanding texture, pliability and contour, but primary closure could not be achieved at the donor site when the flap was designed to be relatively large. In this study, the kiss technique was employed 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 our cadaver study. Two or three narrow small skin paddles based on MPA were raised and resembled at the recipient site as a larger flap. S-2PD, hypersensitivity and ROM, QuickDASH, gait and patient satisfaction were evaluated 6 months to 12 months postoperation. RESULTS: From June 2015 to July 2021, 20 cases of reconstruction using the medial plantar artery perforator (MPAP) 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. 12 flaps (60 percent) were double-paddled and 8 flaps (40%) were triple-paddled with a resurfacing area of 27.19cm 2 and 41.1cm 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 characters of the MPAP flap provide excellent reconstruction for extensive palmar defects while minimizing donor site complications. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Using Zhang's supertension-relieving suture technique with slowly-absorbable barbed sutures in the management of pathological scars: a multicenter retrospective study.

Background: An ideal tension-relieving suture should be efficient for >3 months to retrieve normal tensile strength. Most preexisting suturing techniques provided tension elimination followed by relapse and scar proliferation due to absorption and cut-through of the sutures. This study introduces a simple but effective suture technique developed by a senior author (ZYX) to solve this problem. Methods: A total of 120 patients with pathological scar (PS) had intervention treatment with the proposed suturing strategy at three centers from January 2018 to January 2021. A slowly absorbable 2-0 barbed suture was used for subcutaneous tension relieving with a set-back from the wound edge and a horizontal interval between proposed inserting points of 1 cm. The Patient and Observer Scar Assessment Scale (POSAS), scar width, perfusion and eversion of the wound edge were evaluated at 3-, 6- and 12-month follow-up. The time needed to place the tension-relieving suture was recorded and relapse was monitored for 18 months postoperatively. Results: In total, 76 trunks, 32 extremities and 12 cervical PS were included, with an average subcutaneous tension-relieving suture time of 5 min. The Patient and Observer Scar Assessment Scale (POSAS) score decreased from 84.70 ± 7.06 preoperatively to 28.83 ± 3.09, 26.14 ± 1.92 and 24.71 ± 2.00 at 3, 6 and 12 months postoperatively, respectively (p < 0.0001). The scar widths were 0.17 ± 0.08, 0.25 ± 0.09 and 0.33 ± 0.10 cm, respectively, with perfusion significantly decreased from 213.64 ± 14.97 to 112.23 ± 8.18 at 6 months (p < 0.0001). The wound edge flattened out during the first 3 months in most cases with only two scar relapses. Conclusions: Zhang's suture technique provides a rapid and long-lasting tension-relieving effect with ideal scar appearances and lower relapse rates in the surgical management of PS.

Validation and efficacy of 'pure' venous lymph node flap in a rat lymphoedema model.

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.

Cuproptosis-related LncRNAs are correlated with immunity and predict prognosis in HNSC independent of TMB.

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.

Effects and Progress of Photo-Crosslinking Hydrogels in Wound Healing Improvement.

Wound healing is a dynamic physiological process, including three stages: inflammation, tissue formation, and remodeling. The quality of wound healing is affected by many topical and systemic factors, while any small factor may affect the process. Therefore, improving the quality of wound healing is a complex and arduous challenge. Photo-crosslinking reaction using visible light irradiation is a novel method for hydrogel preparation. Photo-crosslinking hydrogels can be controlled in time and space, and are not interfered by temperature conditions, which have been widely used in the fields of medicine and engineering. This review aims to summarize the application of photo-crosslinking hydrogels in improving the quality of wound healing, mainly including the material design, application mechanism, and effect of photo-crosslinking hydrogels applied in wound healing, followed by the applicable animal models for experimental research. Finally, this review analyzes the clinical application prospects of photo-crosslinking hydrogels in the field of wound healing.

The Use of Infrared Thermography in Determining Timing for Early Pedicle Division of the Preexpanded Bipedicled Visor Flap after Ischemic Preconditioning.

Background: The preexpanded bipedicled visor flap, supported by the bilateral superficial temporal vessels, stands as an ideal choice for upper and lower lip reconstruction in males. However, the bilateral tissue bridges after flap transfer caused patients significant cosmetic deformity and psychological burden. Early division of bilateral pedicles reduced the length of hospitalization and expenses. In this study, infrared thermography (IRT) was used to guide the early pedicle division after ischemic preconditioning. Methods: This study retrospectively analyzed patients who underwent preexpanded bipedicled visor flap surgery from April 2018 to October 2021. Pedicle division was scheduled at two weeks postflap transfer. Ischemic preconditioning was initiated 3-5 days in advance by repeatedly clamping both pedicles. The temperature alteration of the flap and the temperature difference compared to the normal adjacent tissue were evaluated by IRT. The division surgery was not scheduled until the perfusion assessment indicated adequate. This comprised of subjective examination and indocyanine green angiography. The threshold of temperature difference to determine the pedicle division was analyzed based on the temperature changes between the clamps. Results: A total of 8 male patients successfully conducted the pedicle division without any complications. The delay period after ischemic preconditioning ranged from 14 to 19 days (average 16 days). Through ischemic preconditioning training, the average temperature of the flap gradually increased from 31.85 ± 0.36°C to 33.89 ± 0.50°C, and the temperature difference with the normal surrounding tissues decreased from 2.89 ± 0.30°C to 1.15 ± 0.46°C (95% confidence interval (1.5, 0.8)). The temperature difference stayed unchanged after pedicle division. Conclusion: Ischemic preconditioning shortens the perioperative period to pedicle division. Monitoring the temperature change reflects the revascularization between the flap and the recipient site, thus guiding the pedicle division. The temperature difference less than 1.5°C after clamping both pedicles can be set as the safe threshold for pedicle division.

Microneedle delivery of botulinum toxin type A combined with hyaluronic acid for the synergetic management of multiple sternal keloids with oily skin: A retrospective clinical investigation.

BACKGROUND: For the treatment of sternal keloids, corticosteroid therapy has side effects including abnormal sebum secretion and acne. Relapse of keloids is common after corticosteroid injection in patients with oily skin. To reduce side effects and keloid recurrence, we used a combination of botulinum toxin type A (BTX-A) and hyaluronic acid (HA) as synergetic management for multiple sternal keloids in patients with oily skin. METHODS: In total, 58 patients with multiple sternal keloids who received monthly steroid injections were retrospectively included. Thirty-two patients in the intervention group received an additional injection of BTX-A/HA on the same day as the first injection of the steroid, while the remaining 26 patients were treated as the control group. At baseline and follow-up visits, sebum production and transepidermal water loss (TEWL) were assessed as primary outcomes, and the Vancouver Scar Scale (VSS) score, keloid recurrence, visual analog scale (VAS) score, and patient satisfaction were assessed as secondary outcomes. RESULTS: In the control group, average sebum production and TEWL were increased to 132% and 104% of baseline, respectively, at the 24-week follow-up. In the intervention group, average sebum production and TEWL reached nadir at the 8-week follow-up and then increased to 96% and 91% of baseline, respectively, at the 24-week follow-up. Sternal keloid relapse was observed in 88.5% of the patients in the control group and none of the patients in the intervention group. The total VSS score at 24 weeks was 11.04 ± 0.14 and 8.93 ± 0.26 (p < 0.001) in the control group and intervention group, respectively, and the VAS score was 75 ± 5.10 and 19.14 ± 3.80 (p < 0.001) in the control group and intervention group, respectively. Higher patient satisfaction was reported in the intervention group. CONCLUSIONS: Microneedle delivery of BTX-A/HA decreases sebum production while improving skin barrier function. Thus, this combined therapy can relieve the side effects of corticosteroid therapy and reduce keloid recurrence.

Control of fibrosis and hypertrophic scar formation via glycolysis regulation with IR780.

Background: Hypertrophic scars (HS) represent one of the most common clinical challenges due to unsatisfactory therapeutic results. HS formation is associated with the abnormal activation of fibroblasts and their excessive fibrotic behavior. Glycolysis dysregulation has been shown to participate in the incidence and progression of various fibrotic diseases and shows potential as a means of controlling HS formation. This work aimed to discuss the impact of augmented glycolysis on HS and to propose a method for controlling HS formation through glycolysis regulation. Methods: Here, augmented glycolysis was confirmed together with enhanced fibrotic activity in both HS fibroblasts (HFs) and HS tissues, and the suppression of glycolysis also attenuated fibroblast activation. We also introduced IR780, a heptamethine cyanine dye, to regulate glycolysis for the control of HS formation. Results: In vitro, cell studies indicated that IR780 significantly down-regulated glycolysis and suppressed the fibrotic activity of HFs. In vivo, the intralesional injection of IR780 into rabbit HS models led to the downregulation of glycolysis and the control of HS formation. Furthermore, IR780 accumulated preferentially in activated fibroblasts in both in vitro and in vivo studies, and thus specifically downregulated glycolysis and efficiently controlled fibrosis by targeting activated fibroblasts. Conclusions: This work identified a strategy for controlling fibrosis and HS formation from the perspective of glycolysis regulation with IR780 targeting of activated fibroblasts.

Dramatic Effect of Botulinum Toxin Type A on Hypertrophic Scar: A Promising Therapeutic Drug and Its Mechanism Through the SP-NK1R Pathway in Cutaneous Neurogenic Inflammation.

Background: Hypertrophic scar formation may be related to cutaneous neurogenic inflammation (CNI) through the substance P-neurokinin 1 receptor (SP-NK1R) signaling pathway. As a widely used drug in aesthetic clinical work, botulinum toxin type A (BTX-A) has a therapeutic effect on scars, but the actual mechanism remains unclear. This study aimed to clarify the potential mechanism by which BTX-A inhibits CNI in hypertrophic scars both in vitro and in vivo. Methods: Tissue samples were obtained from surgical excisions. Immunohistological analysis was used to locate SP in human hypertrophic scars and normal skin. RT-PCR and western blot analysis were used to evaluate the expression of collagens after SP/BTX-A treatment. A rabbit ear scar model was used to explore the in vivo effect of BTX-A on scar treatment. Results: SP and NK-1R were overexpressed in hypertrophic scars compared to normal skin tissues. Collagen secretion of hypertrophic scar-derived fibroblasts increased with increasing doses of SP. However, BTX-A may downregulate collagen expression through SP-NK1R pathway with or without the presence of SP inducing agent capsaicin. Meanwhile, SP inhibited the expression of NK-1R, and this inhibition was blocked by pretreatment with BTX-A. In vivo, intralesional BTX-A injection can also reduce the volume of scars and inhibit collagen secretion. Capsaicin may cause more severe scar manifestations, while the therapeutic effect of BTX-A remains. Conclusion: Our research confirms that CNI stimulates fibroblasts during scar formation, while BTX-A can reduce collagen secretion by inhibiting the SP-NK1R signaling pathway, thus identifying a novel therapeutic target for this benign solid skin tumor.

An Innovative and Economical Device for Ischemic Preconditioning of the Forehead Flap Prior to Pedicle Division: A Comparative Study.

BACKGROUND: Ischemic preconditioning of the forehead flap prior to pedicle division helps to improve angiogenesis. Clamping the pedicle by a clamped rubber band with vessel forceps is often clinically applied. However, the severe pain and unstable blocking effect influenced the preconditioning process. In this study, we described an innovative device designed for ischemic preconditioning and compared its efficacy with the clamped rubber band. METHODS: The device consists of a self-locking nylon cable tie with a buckle and a rubber tube. The rubber tube is fed over the cable tie to act as a soft outer lining and the cable tie is tightened across the pedicle to block the perfusion for ischemic preconditioning. This device and the standard clamped rubber band were applied respectively before division surgery. The constriction effect, reliability, reproducibility, and the patients' pain tolerance were compared. RESULTS: A total of 20 forehead flaps were included. The cable tie had less incidence of loosening (7.7% vs. 16.6%, p < 0.05) and maintained the pressure more effectively. The pain score for the nylon cable tie was significantly lower than the clamped rubber band (4.25 ± 1.02 vs. 6.75 ± 1.12, p < 0.05), especially for 10 pediatric patients (4.50 ± 0.85 vs. 8.10 ± 1.20, p < 0.01). All 20 pedicles were successfully divided at 19 to 22 days with no surgical complications. CONCLUSION: Compared with the clamped rubber band, the cable tie produces a more reliable and reproducible ischemic preconditioning effect. It is also better tolerated by the patients. Therefore, we recommend using the nylon cable tie as the preferred device for ischemic preconditioning of the forehead flap.

Potential therapeutic effect of NK1R antagonist in diabetic non-healing wound and depression.

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.

IR-808 loaded nanoethosomes for aggregation-enhanced synergistic transdermal photodynamic/photothermal treatment of hypertrophic scars.

Synergistic transdermal photodynamic therapy (PDT)/photothermal therapy (PTT) has emerged as a novel strategy for improving hypertrophic scar (HS) therapeutic outcomes. Herein, a near-infrared heptamethine cyanine dye, named IR-808, has been selected as the desirable photosensitizer owing to its PDT and PTT properties. Benefitting from the transdermal delivery ability of ethosomes (ESs), IR-808 loaded nanoethosomes (IR-808-ES) have been prepared as a novel nanophotosensitizer for the transdermal PDT/PTT of HSs. The special structure of IR-808 aggregate distribution in the ES lipid membrane enhances ROS generation and hyperthermia. The in vitro experiments indicate that the IR-808-ES enhances the PDT/PTT efficacy for inducing the HS fibroblast (HSF) apoptosis via the intrinsic mitochondrial pathway. Furthermore, the in vivo transdermal delivery studies reveal that the IR-808-ES efficiently delivers IR-808 into HSFs in the HS tissue. Systematic assessments in the rabbit ear HS models demonstrate that the enhanced PDT/PTT performance of the IR-808-ES has remarkable therapeutic effects on improving the HS appearance, promoting HSF apoptosis and remodeling collagen fibers. Therefore, the IR-808-ES integrates both the transdermal delivery ability and the aggregation-enhanced PDT/PTT effect, and these features endow the IR-808-ES with significant potential as a novel nanophotosensitizer for the transdermal phototherapy of HSs in the clinical field.

Identification of Therapeutic Targets and Prognostic Biomarkers Among Integrin Subunits in the Skin Cutaneous Melanoma Microenvironment.

The roles of different integrin alpha/beta (ITGA/ITGB) subunits in skin cutaneous melanoma (SKCM) and their underlying mechanisms of action remain unclear. Oncomine, UALCAN, GEPIA, STRING, GeneMANIA, cBioPortal, TIMER, TRRUST, and Webgestalt analysis tools were used. The expression levels of ITGA3, ITGA4, ITGA6, ITGA10, ITGB1, ITGB2, ITGB3, ITGB4, and ITGB7 were significantly increased in SKCM tissues. The expression levels of ITGA1, ITGA4, ITGA5, ITGA8, ITGA9, ITGA10, ITGB1, ITGB2, ITGB3, ITGB5, ITGB6 and ITGB7 were closely associated with SKCM metastasis. The expression levels of ITGA1, ITGA4, ITGB1, ITGB2, ITGB6, and ITGB7 were closely associated with the pathological stage of SKCM. The expression levels of ITGA6 and ITGB7 were closely associated with disease-free survival time in SKCM, and the expression levels of ITGA6, ITGA10, ITGB2, ITGB3, ITGB6, ITGB7, and ITGB8 were markedly associated with overall survival in SKCM. We also found significant correlations between the expression of integrin subunits and the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells). Finally, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed, and protein-protein interaction (PPI) networks were constructed. We have identified abnormally-expressed genes and gene regulatory networks associated with SKCM, improving understanding of the underlying pathogenesis of SKCM.

Using Modified Skin-Stretching Technique as an Alternative Solution for the Closure of Moderate and Extensive Skin Defects.

External skin-stretching devices have been developed and used for wound closure since 1970s. Devices such as Miami STAR®, SureClosure®, TopClosure®, and WiseBand® have their own advantages and disadvantages. The modified external skin-stretching technique of this case series study has the advantage to improve tension distribution and simplified the application. Between January 2014 and June 2017, 20 patients were treated with the modified external skin-stretching device for the closure of the skin defects of the trunk (n = 6) and extremities (n = 14). Skin defects ranged from 8 × 5 to 19 × 16 cm achieved primary closure with the utilization of the modified skin-stretching device without major complications. Subsequent minor revisions were performed under local anesthesia between 6 and 12 months postoperatively. The modified skin-stretching device utilized biomechanical properties and mechanical creep of skin tissue to achieve a reliable and effective primary closure for moderate to extensive skin defects. Therefore, this modified external skin-stretching technique provided, in the appropriate setting, an effective alternative to skin grafts or free flaps.

Infrared thermography-guided designing and harvesting of pre-expanded pedicled flap for head and neck reconstruction.

BACKGROUND: Pre-expanded pedicled flaps possess a more flexible transfer pattern and higher tissue utilization than random flaps, but the perfusion is fully dependent on the chosen axial vessels. A precise mapping of the vessels would assist the surgical design and increase the likelihood of success. The application of Infrared thermography (IRT) has been previously reported for perforator location. The aim of this study is to report the use of IRT in mapping the course and distribution of axial vessels in the pre-expanded flap to guide the designing and harvesting. METHODS: Patients who underwent head and neck reconstruction using pre-expanded flaps were included. After tissue expansion, IRT was used to mark the vessel distribution along the expanded flap. The results were compared with color Doppler ultrasound (CDU) and/or computed tomographic angiography (CTA). The flap was designed and raised based on the pre-operative marking by IRT. The mark was verified intraoperatively. RESULTS: A total of 26 expanded flaps were performed, including 20 pedicled flaps and 6 free flaps. IRT succeeded to map the vessel distribution in all cases. All marked results were verified by CDU, CTA, and intraoperative dissection (26/26, 100%). IRT showed more comprehensive distribution of vascular branches than CDU or CTA, and could be utilized intraoperatively to identify the arteries. CONCLUSION: IRT provides accurate and comprehensive mapping of the axial vessel distribution in the pre-expanded flaps, assisting with flap design and harvest. It is easy to use and non-invasive as an important tool pre- or intraoperatively to ensure the safe elevation.

Single-Cell and Bulk Transcriptome Data Integration Reveals Dysfunctional Cell Types and Aberrantly Expressed Genes in Hypertrophic Scar.

Hypertrophic scar (HS) is a common skin disorder characterized by excessive extracellular matrix (ECM) deposition. However, it is still unclear how the cellular composition, cell-cell communications, and crucial transcriptionally regulatory network were changed in HS. In the present study, we found that FB-1, which was identified a major type of fibroblast and had the characteristics of myofibroblast, was significantly expanded in HS by integrative analysis of the single-cell and bulk RNA sequencing (RNA-seq) data. Moreover, the proportion of KC-2, which might be a differentiated type of keratinocyte (KC), was reduced in HS. To decipher the intercellular signaling, we conducted the cell-cell communication analysis between the cell types, and found the autocrine signaling of HB-1 through COL1A1/2-CD44 and CD99-CD99 and the intercellular contacts between FB-1/FB-5 and KC-2 through COL1A1/COL1A2/COL6A1/COL6A2-SDC4. Almost all the ligands and receptors involved in the autocrine signaling of HB-1 were upregulated in HS by both scRNA-seq and bulk RNA-seq data. In contrast, the receptor of KC-2, SDC4, which could bind to multiple ligands, was downregulated in HS, suggesting that the reduced proportion of KC-2 and apoptotic phenotype of KC-2 might be associated with the downregulation of SDC4. Furthermore, we also investigated the transcriptionally regulatory network involved in HS formation. The integrative analysis of the scRNA-seq and bulk RNA-seq data identified CREB3L1 and TWIST2 as the critical TFs involved in the myofibroblast of HS. In summary, the integrative analysis of the single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data greatly improved our understanding of the biological characteristics during the HS formation.