Reconstructed Mid-Face Lifting After Tissue Expansion by Suspending the Expander Capsule.

BACKGROUND: An obvious saggy tendency was observed in the expanded flaps from mid-facial reconstruction and resulted in an unsatisfactory postoperative cosmetic outcome. At the time of this writing, the authors introduced a novel technique of mid-face lifting to correct the phenomenon by suspending the expander capsule. METHODS: From September 2018 to August 2023, 11 patients who had undergone our mid-face lifting technique were enrolled in our study. The expanded flap was divided into 2 layers during the surgical procedure. The upper layer, which consists of the skin and the subcutaneous layer, was lifted, and the lower layer, consisting of the expander capsule and SMAS system, was left at the base. Then a capsular flap was lifted from the base and folded upward to lift the reconstructed mid-face. The capsular flap was fixed in the temporal or mastoid region when the saggy tendency was corrected, and the mid-facial contour became symmetric. Finally, the upper layer was trimmed and fixed at the base. Facial movements were restricted after the surgery. RESULTS: The saggy tendency of all the expanded flaps was corrected, and the mid-facial symmetry was rebuilt immediately after the surgery. The effect were long-lasting at 3 months to 2 years of follow-ups. No serious postoperative complications occurred. The patients or their legal guardians were satisfied with the esthetic improvement. CONCLUSION: Reconstructed mid-face lifting with capsular flap was an effective and reliable way to correct the saggy tendency of a mid-facial expanded flap and rebuilt the mid-facial symmetry.

Treatment for benign skin lesion in zygomatic-infraorbital region by the expanded multi-lobe cervicofacial advancement rotation flap in pediatric patients.

PURPOSE: Benign skin lesions in zygomatic-infraorbital regions severely influence pediatric patients' appearance as well as mental health. Treatments are difficult for the high requirements of patients' guardians in both function and aesthetics. The present study aims to introduce a surgical method, Expanded Multi-Lobe Cervicofacial Flap, which combines the advantages of the classical cervicofacial advancement rotation flap and the tissue expansion technique. METHODS: A total of 21 pediatric patients were enrolled. The treatment process included 2 stages: implantation of the skin tissue expander and flap transfer. The excessive skin created by tissue expansion extended the coverage area of the multi-lobe flap. RESULTS: In this retrospective study, follow-up periods were all more than 12 months (20.8 ± 6.7). In the last follow-ups, the flaps were all in good condition, and No facial organ displacement was observed. The patients' guardians were satisfied with the outcomes. CONCLUSIONS: Using the expanded multi-lobe cervicofacial flap for the zygomatic-infraorbital benign skin lesion repair is effective, and this method is especially applicable to the pediatric population.

Outer Fascia of Orbicularis Oculi Muscle (OFOOM)-Orbicularis (OOM)-Aponeurosis Fixation Approach in Double-Eyelid Blepharoplasty Revision.

BACKGROUND: Incisional double-eyelid blepharoplasty is the main surgical technique to obtain an artificial crease. Postoperative complications decrease patients' satisfaction, and patients with prominent depressed groove and persistent pretarsal swelling (sausage phenomenon) usually need revision surgery. To resolve the sausage phenomenon after blepharoplasty, we adopt Outer Fascia of Orbicularis Oculi Muscle (OFOOM)-Orbicularis (OOM)-Aponeurosis Fixation Approach to create natural double eyelids. METHODS: We included 68 patients in the study. The inclusion criteria for revision surgery were as follows: (1) pretarsal OOM remained after primary surgery, (2) prominent depressed surgical scar/groove and persistent pretarsal bulge (sausage phenomenon), (3) postsurgical abnormally wide crease. The surgical procedure involved releasing the pretarsal OOM, forming OFOOM-OOM flap, and OFOOM-OOM flap fixed with aponeurosis. Outcome observations were assessed using the FACE-Q questionnaire, and the follow-up period ranged from 6 to 36 months (mean=18 months). RESULTS: The depressed groove and pretarsal bulge showed significant improvements, and FACE-Q scores of the 68 patients before surgery (mean scores=66) compared with those after surgery (mean scores=90) were significantly different (P<0.01). Four patients with palpebral fold asymmetry and two patients with shallow eyelids received revision surgery, and patients were satisfied with the secondary surgery effects. Six patients presented with unnatural curves of folds and revision surgery alleviated these situations. CONCLUSIONS: Outer Fascia of Orbicularis Oculi Muscle (OFOOM)-Orbicularis (OOM)-Aponeurosis Fixation Approach is an effective way to resolve the sausage phenomenon. The OFOOM-OOM flap is a reliable and flexible structure to create natural double eyelids. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Reconstruction of Large Periorbital Defect With a Pre-expanded Retrograde Postauricular Island Flap: Our 13-Year Experiences.

The clinical application of the retrograde postauricular island flap has been widely restricted because of its limited size and high morbidity of venous congestion. Thus, in this article, we introduced a pre-expanded retrograde postauricular island flap to reconstruct the large periorbital defect. A total of 13 patients with periorbital lesions who had undergone the treatment of our flap were enrolled in the study. The whole series of operations was divided into 3 parts, including expander implantation in the postauricular region, a series of expander inflations, and flap transferring, and special incisions were also designed in the procedure. In the end, all the flaps survived without serious complications. The mean size of the harvested flaps was 2.65 times larger than that of our nonexpanded cases. The reconstructed periorbital region showed a functional and aesthetic repair outcome after a follow-up of 3 to 30 months. To conclude, the pre-expanded retrograde postauricular island flap was a safe way to reconstruct a larger periorbital defect.

Improved Reverse Postauricular Island Flap for Repair of Lower Conjunctival Fornix Retraction.

ABSTRACT: Repair of lower conjunctival fornix retraction is a great challenge for plastic surgeons in the aspects of orbital prosthesis retaining and cosmetic appearance. Hereby, a 25-year-old woman, suffering from lower conjunctival fornix retraction after the removal of retinoblastoma and radiotherapy, was undertaking the treatment with an improved reverse postauricular island flap for expansion of the lower conjunctival fornix, and volume augmentation of the anophthalmic socket in one stage. The flap was based on the parietal branch of the superficial temporal artery and its vascular architecture to the postauricular vascular system, and successfully transferred by passing through a subcutaneous tunnel. The satisfactory result indicated that the mentioned technique may be a good option in surgical rehabilitation of the stable depth of the lower conjunctival fornix, not only from the reliable blood supply and the suitable thickness of the flap but also from the less donor morbidity without an exposed unsightly scar. LEVEL OF EVIDENCE: Level V.

Temporal-fasciae-complex sheet suspension for correction of severe recurrent blepharoptosis.

BACKGROUND: Multiple surgical methods were performed to correct the blepharoptosis. However, the recurrence of blepharoptosis is not uncommon in clinical practice. The Temporal-Fasciae-Complex Sheet (TFC sheet) was an ideal autologous material in correcting the severe blepharoptosis. In the present retrospected study, we introduced our experience in the correction of severe recurrent blepharoptosis with the technique of TFC sheet suspension, and describe the follow-up results to illustrate its effectiveness and practicality. METHODS: A total of 16 patients (23 eyes) with severe recurrent blepharoptosis were enrolled in this study. All the patients were performed with temporal-fasciae-complex sheet suspension surgeries for revision> 12 months after the primary surgeries by the same treatment group. The margin-to-reflex distance 1 (MRD1), correction effect, and eyelid symmetry were used to evaluate clinical outcomes. RESULTS: 19 eyelids (82.6%) showed good correction results, and 5 eyelids (21.7%) showed fair correction results. The average value of preoperative-MRD1(pre-MRD1) was - 0.17 ± 0.97, and the average value of postoperative-MRD1(post-MRD1) was 4.01 ± 1.24. There was a statistically significant difference between pre-MRD1 and post-MRD1 (p < 0.0001). Good symmetry was observed in 13 patients (81.3%). All patients enrolled were satisfied with the surgical results. CONCLUSION: The Temporal-Fasciae-Complex Sheet Suspension is an effective and safe method for correcting the recurrent blepharoptosis.

Establishment and validation of a nomogram to predict the neck contracture after skin grafting in burn patients: A multicentre cohort study.

Cervical burn contracture is one of the burn contractures with the highest incidence and severity, and there is no effective method to predict the risk of neck contracture. This study aimed to investigate the effect of combined cervicothoracic skin grafting on the risk of neck contracture in burn patients and to develop a nomogram to predict the risk of neck contracture after skin grafting in burn patients. Data from 212 patients with burns who underwent neck skin grafting were collected from three hospitals, and the patients were randomly divided into training and validation sets. Independent predictors were identified through univariate and multivariate logistic regression analyses and incorporated into a prognostic nomogram. Its performance was assessed using the receiver operating characteristic area under the curve, calibration curve, and decision curve analysis. Burn depth, combined cervicothoracic skin grafting, graft thickness, and neck graft size were significantly associated with neck contractures. In the training cohort, the nomogram had an area under the curve of 0.894. The calibration curve and decision curve analysis indicated good clinical applicability of the nomogram. The results were tested using a validation dataset. Combined cervicothoracic skin grafting is an independent risk factor for neck contracture. Our nomogram demonstrated excellent performance in predicting neck contracture risk.

Epidemiology and Predictors for Cervical Burn Scar Contractures: A Multicenter Cohort Study.

Cervical burn scar contracture (BSC) affects many important neck functions and the patients' quality of life. However, it remains unclear which patients have a higher risk of neck BSCs. This study aimed to describe the epidemiology and identify the independent risks of cervical BSC formation and severity. Clinical and demographic data of 106 patients with burn scars were retrospectively collated and analyzed from 3 different Chinese hospitals between December 2016 and December 2020. Both univariate and multivariate logistic regression analyses were performed to identify the independent risks for BSC formation and severity at 12 months postburn. Lateral flexion was the most common plane of motion (POM) limited by contractures (29.4%), whereas the POM most commonly limited by severe contractures was the extension (24.6%). Most patients with contractures had those in 3 to 4 POMs (72.1%). Neck skin grafting was an independent risk factor for BSC formation, and cervical and cervicothoracic skin grafting were independent risk factors for BSC severity. These results may help to identify high-risk patients with contractures in the early stages of burns to carry out individualized early prevention and treatment.

Identification and functional analyses of a novel FOXL2 pathogenic variant causing blepharophimosis, ptosis, and epicanthus inversus syndrome.

AIM: To discover the molecular pathogenic basis of the blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES), and to predict the clinical subtype according to in vitro experiments, which is significant to the prognosis. METHODS: A 3-year-old sporadic female patient with typical clinical manifestations of BPES was enrolled. The coding region of forkhead box L2 (FOXL2) gene was sequenced, and the functional assays were performed in vitro by Western blotting, subcellular localization experiment, luciferase reporter assay, and quantitative real-time polymerase chain reaction. RESULTS: A novel FOXL2 point pathogenic variant (c.274G>T) was detected, resulting in a truncated protein (p.E92*). Functional studies demonstrated that the FOXL2 pathogenic variant induced the subcellular mislocalization and the abnormal transcriptional activity on promoters of the steroidogenic acute regulatory protein (StAR or STARD1) gene and the odd-skipped related 2 transcription factor (OSR2) gene. CONCLUSION: A novel pathogenic variant is identified to expand the spectrum of the known FOXL2 mutations. The in vitro experiments provide reference data and more insights to the molecular pathogenesis of BPES. The predicted high risk of ovarian insufficiency makes it significant for the patient enrolled to have further follow-up and therapy concerning female endocrinology.

PTB Regulates the Metabolic Pathways and Cell Function of Keloid Fibroblasts through Alternative Splicing of PKM.

Keloids, benign fibroproliferative cutaneous lesions, are characterized by abnormal growth and reprogramming of the metabolism of keloid fibroblasts (KFb). However, the underlying mechanisms of this kind of metabolic abnormality have not been identified. Our study aimed to investigate the molecules involved in aerobic glycolysis and its exact regulatory mechanisms in KFb. We discovered that polypyrimidine tract binding (PTB) was significantly upregulated in keloid tissues. siRNA silencing of PTB decreased the mRNA levels and protein expression levels of key glycolytic enzymes and corrected the dysregulation of glucose uptake and lactate production. In addition, mechanistic studies demonstrated that PTB promoted a change from pyruvate kinase muscle 1 (PKM1) to PKM2, and silencing PKM2 substantially reduced the PTB-induced increase in the flow of glycolysis. Moreover, PTB and PKM2 could also regulate the key enzymes in the tricarboxylic acid (TCA) cycle. Assays of cell function demonstrated that PTB promoted the proliferation and migration of KFb in vitro, and this phenomenon could be interrupted by PKM2 silencing. In conclusion, our findings indicate that PTB regulates aerobic glycolysis and the cell functions of KFb via alternative splicing of PKM.

Extracellular Vesicles Derived from Auricular Chondrocytes Facilitate Cartilage Differentiation of Adipose-Derived Mesenchymal Stem Cells.

PURPOSE: Adipose-derived mesenchymal stem cell (ADSC)-based therapies have been utilized for cartilage regeneration because of their multi-lineage differentiation ability. However, commonly used cartilage inducers such as the transforming growth factor beta-3 (TGF-ß3) may be prone to cartilage dedifferentiation and hypertrophy. The directional differentiation of elastic cartilage is limited nowadays. Extracellular vesicles (EVs) have been reported to influence the specific differentiation of mesenchymal stem cells (MSCs) by reflecting the composition of the parental cells. However, the role of auricular chondrogenic-derived EVs (AC-EVs) in elastic chondrogenic differentiation of ADSCs has not yet been reported. RESULTS: AC-EVs isolated from the external ears of swine exhibited a positive effect on cell proliferation and migration. Furthermore, AC-EVs efficiently promoted chondrogenic differentiation of ADSCs in pellet culture, as shown by the elevated levels of COL2A1, ACAN, and SOX-9 expression. Moreover, there was a significantly higher expression of elastin and a lower expression of the fibrotic marker COL1A1 in comparison with that achieved with TGF-ß3. The staining results demonstrated that AC-EVs promoted the deposition of cartilage-specific matrix, which is in good concordance with the real-time polymerase chain reaction (RT-PCR) results. CONCLUSIONS: Auricular chondrogenic-derived EVs are a crucial component in elastic chondrogenic differentiation and other biological behaviors of ADSCs, which may be a useful ingredient for cartilage tissue engineering and external ear reconstruction. NO LEVEL ASSIGNED: This journal requires that authors 42 assign a level of evidence to each submission to which 43 Evidence-Based Medicine rankings are applicable. This 44 excludes Review Articles, Book Reviews, and manuscripts 45 that concern Basic Science, Animal Studies, Cadaver 46 Studies, and Experimental Studies. For a full description of 47 these Evidence-Based Medicine ratings, please refer to the 48 Table oôf Contents or the online Instructions to Authors 49 www.springer.com/00266 .

Aesthetic Sideburn Reconstruction Using an Expanded Hair Bearing Skin Flap With Natural Hairline.

BACKGROUND: Hairline is the marginal line of hair growth on the scalp. Patients with sideburn defects, caused by tumor resection, severe infection, or burns, might have low self-esteem and mental stress. The purpose of this article was to explore a surgical method of applying the expanded scalp flap with natural hairline for cosmetic reconstruction of hairline, so as to provide reference for future clinical work. METHODS: In this study, a retrospective analysis was conducted on 23 patients in the plastic surgery ward of the Plastic Surgery Hospital of the Chinese Academy of Medical Sciences from January 2015 to December 2018, who underwent expanded scalp flap cosmetic reconstruction of the sideburns with natural hairline (14 males and 9 females; average age, 18.7 ± 13.7 years). The follow-up time was 8 to 44 months. RESULTS: Patient satisfaction rate (scored 4 or more) was 95.7%, with an average score of 4.59. A total of 16 patients were very satisfied, and 6 were satisfied. There were 21 patients who had good flap survival, and 2 patients who had venous congestion at the distal end of the flap. One case relieved voluntarily 3 days postsurgery, and the other case had partial skin necrosis at the distal end, healing phase II. These 2 cases were classified as grade I according to the Clavien-Dindo classification. In 9 of the patients, the reconstructed sideburn presented a natural look with good hair angle and great size and shape, with average scores of 4.61, 4.52, and 4.48. The scars at the donor site were inconspicuous, and there were no complaints (average score, 4.61). The rest of the patients received satisfactory appearances after surgery. CONCLUSION: In conclusion, the technique described above presented a fine method for sideburn reconstruction. Based on the achieved aesthetic scores of our study, as well as the high patient satisfaction rate (95.7%), the aforementioned technique is acceptable for both surgeons and patients.

The Transfer of Expanded Forehead Superthin Flap Without Frontalis and Less Hair Follicles Pedicled by Superficial Temporal Vessels.

BACKGROUND: The expanded forehead flap pedicled with superficial temporal vessel(s) is a common method to treat facial scar deformity. However, local bulkiness and hair retention have limited the use of this flap. METHODS: Five cadavers were used for anatomy to confirm the forehead "safety zone." A retrospective study was performed on 15 patients with facial scar deformity who were undergoing the expanded forehead superthin flap (without the expanded capsule, frontalis muscle, and with less hair follicles) pedicled with superficial temporal vessel(s) to transfer and repair the deformity. RESULTS: Through cadaver anatomy, the range where the subdermal vascular network laid superficial to the hair follicle level was named the "safety zone," whose average distance between the bilateral penetrating points was 10.2 cm (8.7-11.6 cm). Fifteen patients with facial scar deformity were treated with the superthin flap technique. The trimming size of the safety zone flap was (6-10) × (12-20) cm. The median time of thinning the safety zone was 35 minutes (range, 25-40 minutes). All flaps healed well. The median residual ratio of the hair follicle was 39.8% (29.9%-50.5%). All patients were satisfied with the contour of the flap. CONCLUSION: We firstly proposed a concept of forehead safety zone and used the superthin flap without the frontalis muscle and less hair follicles to treat facial scar deformity, and obtained an improved therapeutic effect. We think this is an appealing technique that can manifest facial concave and convex in the fine part, improve compliance of the flap, and reduce the times of laser hair removal.

A New Technique for Chondrolaryngoplasty in Patients Assigned Female at Birth.

BACKGROUND: Chondrolaryngoplasty is a classical facial feminization surgery for transgender women. In recent years, however, an increasing number of patients assigned female at birth are seeking chondrolaryngoplasty for esthetic purposes. Traditional chondrolaryngoplasty can no longer cope with problems of the growing group whose leading cause of laryngeal prominence differs from the transgender population. METHODS: A modified technique is designed as a supplement to the classical procedure. After the cartilage reduction process, paired platysma flaps are raised and advanced successively, resulting in an overlapped area over the thyroid notch, to further camouflage the thyroid prominence. To evaluate the efficiency of the new technique, a retrospective survey of 34 patients (5 men and 29 women) who underwent the surgery from 2016 to 2021 was performed, via a 5-point Likert scale including 7 questions. Physician assessment was also accomplished to provide an extra estimation. Complications were followed up and analyzed to evaluate the safety of modified surgery as well. RESULTS: Although only half of the patients graded prominence changes more than "moderately changed," as many as 75.0% of them still expressed "completely satisfied" or "satisfied very much" with the outcome. Similarly, physician assessment indicated a satisfactory result in appearance improvement. No severe and irreversible complications occurred after surgery, but lasting scar-related issues were reported by 4 patients and should be paid more attention to. CONCLUSIONS: Generally speaking, the new technique is both safe, efficient, and satisfying for most patients, especially ones assigned females at birth with esthetic demand.

Medial gastrocnemius resection for calf reduction by using a popliteal mini-incisional approach in Asians.

BACKGROUND: To create a new approach of resecting medial gastrocnemius for calf reduction and to meet the increasing requirement of the beauty standard of calf sliming in Asian. METHODS: Twenty patients with 39 calves underwent gastrocnemius resection for calf reduction. Under general anesthesia, a 5 cm incision, along the popliteal crease, was made down to the sub-popliteal deep fascia on a prone position. The medial belly of the gastrocnemius muscle was then dissected, in a blunt way, from the popliteal fossa down to the Achilles tendon around the muscular belly when its neurovascular bundle was ligated and cut off. Thereafter, the medial gastrocnemius was pulled out of the wound and incised transversely off at the level of the popliteal fossa while the attachment to the Achilles was transected with a long rectangular scissors. The incisional wound was finally closed in layers. RESULTS: Twenty patients with 39 calves were treated using the above-mentioned technique without severe complications. The harvested gastrocnemius muscle weighed 192.1 g in mean (from 104.5 g to 307.6 g). The calf circumference was significantly decreased from 36.3 cm in mean to 32.8 cm in mean before and after the operation (p <0.05). CONCLUSIONS: The above-mentioned technique may be a safer, simpler, and more efficient method for calf reduction with less morbidity of the potential complications, in comparison with the traditional techniques.

Tear Trough Ligament Release and Autologous Fat Injection as a New Method for Tear Trough Deformity Correction.

BACKGROUND: Even though the tear trough (TT) deformity is only 2 cm in length, it can give a worn, even haggard appearance on the face. The authors developed a novel approach and presented findings from the clinical effect. METHODS: Between February 2018 and January 2021, the medical records of patients treated with autologous fat injection for TT deformity were researched. The fat was placed under the orbicularis oculi muscle with a sharp cannula. During that period, the TT ligament was also released with the cannula. After the fat was injected entirely, we still needed to repeatedly puncture this ligament to release it until there was no puncture resistance. Improvement was evaluated by measuring patients' and investigators' global aesthetic improvement scale. RESULTS: 152 of 173 patients completed the follow-up plan and were enrolled in this study. The most common complications reported were temporary swelling and lumpiness. At 1 month, 3 months, 6 months, 12 months, and 24 months, the satisfaction rate of patient self-assessment was 93.4%, 89.5%, 86.8%, 84.3%, and 82.4%, respectively. The Investigator Global Aesthetic Improvement Scale showed 94.1% of patients' improvement after one month, 83.6% after three months, 78.3% after six months, 75% after 12 months, and 71.8% after 24 months. CONCLUSION: Fat injection based on TT ligament release to correct TT deformity is a novel, easy and effective treatment that deserves to be further used. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Three-Dimensional Z-Epicanthoplasty Retains the Depth of the Medial Canthus With Scars That Are Less Visible.

BACKGROUND: Traditional coronal Z-epicanthoplasty usually generates visible scars, and V-Y advancement or skin redraping can damage the normal shape of the lower eyelid. In addition, these methods usually lead to loss of the medial canthus depth, which is important for the natural appearance of East Asians. This report aims to describe a 3-dimensional Z-epicanthoplasty that can maintain the depth of the medial canthus with fewer visible scars. METHODS: Patients who underwent 3-dimensional Z-epicanthoplasty from January 2016 to December 2019 were included. In our method, excess skin in the horizontal direction was first rotated to the vertical position and then turned inward from a coronal to a sagittal orientation to supplement the skin deficiency of the medial canthus in the sagittal orientation. The skin flap turned in the sagittal orientation and maintained the depth of the medial canthus and the natural appearance of the eye. RESULTS: In total, 138 patients were included, and the follow-up interval ranged from 6 to 36 months. After the surgery, the epicanthi were removed, and the shapes of the patients' eyes were significantly improved and appeared natural. The surgical scars were hidden in the sagittal orientation rather than in the coronal orientation, which cannot be seen easily. The depth of the medial canthus was well preserved without any lower eyelid destruction. Patients were satisfied with the natural appearance of the medial canthus. CONCLUSIONS: This method could not only correct the epicanthal fold effectively with scars that are less visible but also maintain the depth of the medial canthus and make the appearance of the eye look more natural.

Inhibiting Warburg Effect Can Suppress the Biological Activity and Secretion Function of Keloid Fibroblasts.

BACKGROUND: Keloids have always been a difficult problem in the clinic. In our previous study, we demonstrated a Warburg effect in keloid fibroblasts (KFs), like tumors. In this study, we aimed to investigate the effects of the suppression of the Warburg effect on the biological activity and function of KFs. METHODS: KFs were isolated and cultured with different concentrations of oxamate, a classical competitive lactate dehydrogenase A (LDHA) inhibitor. First, the suppression effect of oxamate on the Warburg effect in KFs was verified. After treatment with oxamate, a scratch wound assay, real-time PCR, flow cytometry, CCK8 kit, and western blotting were used to detect the migration ability, collagen production, apoptosis, cell proliferation, cell cycle distribution, and related molecular mechanisms in KFs. RESULTS: As expected, oxamate inhibited the Warburg effect in KFs in a dose-dependent manner. After the inhibition of the Warburg effect in KFs, the cell migration rate decreased significantly, the mRNA transcription levels of type I collagen and α-SMA were significantly lower, the cell apoptosis rate increased significantly, the cell proliferation activity decreased significantly, and G0/G1 phase cells in KFs increased significantly. The expression of cyclin D1 and its upstream regulatory factors, Akt protein and GSK3 ß (phospho S9), decreased significantly. CONCLUSION: Inhibiting the Warburg effect in KFs significantly suppressed cell proliferation, enhanced cell apoptosis, inhibited cell migration ability, reduced collagen secretion, and induced G0/G1 arrest through the Akt-GSK3ß-Cyclin D1 pathway. Therefore, inhibiting the Warburg effect in KFs may provide a new option for the prevention and treatment of keloids. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Warburg effect in keloids: A unique feature different from other types of scars.

Keloid fibroblasts (KFs) undergo reprogramming of the metabolic phenotype from oxidative phosphorylation to the Warburg effect. However, more studies are needed to demonstrate whether there is a Warburg effect in KFs and to determine whether there is a similar phenomenon in other types of scars or in the proliferative stage of scars. In our study, the mRNA and protein expression of key glycolytic enzymes, glucose consumption and lactate production in KFs, normal skin fibroblasts (NFs), atrophic scar fibroblasts (ASFs), proliferative stage scar fibroblasts (PSSFs), and hypertrophic scar fibroblasts (HSFs) were detected. In addition, the effects of 2-deoxy-d-glucose (2-DG, a glycolysis inhibitor) on cell proliferation in KFs and NFs were studied. We found that the mRNA and protein expression of key glycolytic enzymes in KFs were significantly upregulated compared with those in NFs. Glucose consumption and lactate production in KFs were also higher than that in NFs. However, we found no similar phenomenon in ASFs, PSSFs, or HSFs. When treated with 2mmol/l 2-DG, the cell viability of KFs decreased more than that of NFs. What's more, treatment with increasing concentrations of 2-DG could inhibit cell viability and migration of KFs in a dose-dependent manner. In conclusion, the Warburg effect in KFs is a feature different from ASFs, PSSFs, or HSFs. Keloids are essentially different from other types of scars in terms of energy metabolism. This characteristic of KFs could provide new hope for the early diagnosis and treatment of keloids.