Hair follicle stem cells promote epidermal regeneration under expanded condition.

Skin soft tissue expansion is the process of obtaining excess skin mixed with skin development, wound healing, and mechanical stretching. Previous studies have reported that tissue expansion significantly induces epidermal proliferation throughout the skin. However, the mechanisms underlying epidermal regeneration during skin soft tissue expansion are yet to be clarified. Hair follicle stem cells (HFSCs) have been recognized as a promising approach for epidermal regeneration. This study examines HFSC-related epidermal regeneration mechanisms under expanded condition and proposes a potential method for its cellular and molecular regulation.

Patient-specific factors for deformity after upper blepharoplasty in an Asian population.

BACKGROUND: The success of upper blepharoplasty depends on both surgeon experience and skill as well as patient factors. Therefore, we aimed to identify patient-specific characteristics that may contribute to poor prognoses by analyzing data derived from patients with various deformities after undergoing upper blepharoplasty. METHODS: This study included 202 patients who underwent revision surgery for upper blepharoplasty. We explored relationships between types of deformities before revisions and relevant patient factors before initial surgery using statistical analyses. RESULTS: Age > 30 years, thick upper lid skin, medial epicanthus, and other patient factors were significantly associated with the deformities. Asymmetrical, disappeared, shallow, and low creases were the most prevalent deformities. For these four most prevalent deformities, the concordance indices and 95% confidence limits of the risk prediction models were 0.654 (0.575-0.734), 0.724 (0.637-0.810), 0.783 (0.702-0.863), and 0.750 (0.655-0.844), respectively. CONCLUSIONS: Among the four most prevalent prognostic deformities, significant patient factors included medial epicanthus, thick upper eyelid skin, weak levator palpebrae superioris, age > 30 y, and a short gap between eyes and brows. We also attempted to clarify the clinical importance of these patient factors. Our findings provide a guide and reference for future investigations into upper blepharoplasty.

Machine learning prediction models for in-hospital postoperative functional outcome after moderate-to-severe traumatic brain injury.

AIM: This study aims to utilize machine learning (ML) and logistic regression (LR) models to predict surgical outcomes among patients with traumatic brain injury (TBI) based on admission examination, assisting in making optimal surgical treatment decision for these patients. METHOD: We conducted a retrospective review of patients hospitalized in our department for moderate-to-severe TBI. Patients admitted between October 2011 and October 2022 were assigned to the training set, while patients admitted between November 2022 and May 2023 were designated as the external validation set. Five ML algorithms and LR model were employed to predict the postoperative Glasgow Outcome Scale (GOS) status at discharge using clinical and routine blood data collected upon admission. The Shapley (SHAP) plot was utilized for interpreting the models. RESULTS: A total of 416 patients were included in this study, and they were divided into the training set (n = 396) and the external validation set (n = 47). The ML models, using both clinical and routine blood data, were able to predict postoperative GOS outcomes with area under the curve (AUC) values ranging from 0.860 to 0.900 during the internal cross-validation and from 0.801 to 0.890 during the external validation. In contrast, the LR model had the lowest AUC values during the internal and external validation (0.844 and 0.567, respectively). When blood data was not available, the ML models achieved AUCs of 0.849 to 0.870 during the internal cross-validation and 0.714 to 0.861 during the external validation. Similarly, the LR model had the lowest AUC values (0.821 and 0.638, respectively). Through repeated cross-validation analysis, we found that routine blood data had a significant association with higher mean AUC values in all ML and LR models. The SHAP plot was used to visualize the contributions of all predictors and highlighted the significance of blood data in the lightGBM model. CONCLUSION: The study concluded that ML models could provide rapid and accurate predictions for postoperative GOS outcomes at discharge following moderate-to-severe TBI. The study also highlighted the crucial role of routine blood tests in improving such predictions, and may contribute to the optimization of surgical treatment decision-making for patients with TBI.

Prospective comparative clinical study: Efficacy evaluation of collagen combined with hyaluronic acid injections for tear trough deformity.

BACKGROUND: Tear trough filling is a popular facial rejuvenation procedure, and hyaluronic acid is typically used as the filler of choice. However, Tyndall's phenomenon, a common complication following hyaluronic acid injection, can occur, leading to skin discoloration of the lower eyelid. AIMS: This single-center, prospective, comparative clinical study aimed to evaluate the efficacy of collagen and hyaluronic acid injections in treating tear trough deformity. METHODS: Sixty patients were enrolled between June 2022 and January 2023. Patients were randomly allocated into three groups: Group A received hyaluronic acid, Group B received hyaluronic acid combined with collagen, and Group C received collagen alone. Baseline characteristics, including age, sex, and tear trough deformity grade were considered before therapy. Changes in tear trough deformity scores, Global Aesthetic Improvement Scores, and the presence of the Tyndall effect were analyzed at 1 and 3 months postinjection to determine differences among the three groups. RESULTS: Baseline profiles of the three groups were similar. In the first month postinjection, there was no difference in the Global Aesthetic Improvement Scores and tear trough deformity between the three groups. However, in the third-month postinjection, there was a significant difference in scores between patients in Group C and those in Groups A or B. The Tyndall effect manifested in three patients in Group A, which was significantly different from that in Groups B and C. CONCLUSION: The combined use of hyaluronic acid with collagen in injectable fillers corrected tear trough deformities and reduced the occurrence of the Tyndall phenomenon, which can be problematic with hyaluronic acid alone. Additionally, this combination may help overcome the disadvantage of a shorter retention period when using collagen alone.

Machine learning models for predicting in-hospital outcomes after non-surgical treatment among patients with moderate-to-severe traumatic brain injury.

AIM: This study aims to develop prediction models for in-hospital outcomes after non-surgical treatment among patients with moderate-to-severe traumatic brain injury (TBI). METHOD: We conducted a retrospective review of patients hospitalized for moderate-to-severe TBI in our department from 2011 to 2020. Five machine learning (ML) algorithms and the conventional logistic regression (LR) model were employed to predict in-hospital mortality and the Glasgow Outcome Scale (GOS) functional outcomes. These models utilized clinical and routine blood data collected upon admission. RESULTS: This study included a total of 196 patients who received only non-surgical treatment after moderate-to-severe TBI. When predicting mortality, ML models achieved area under the curve (AUC) values of 0.921 to 0.994 using clinical and routine blood data, and 0.877 to 0.982 using only clinical data. In comparison, LR models yielded AUCs of 0.762 and 0.730 respectively. When predicting the GOS outcome, ML models achieved AUCs of 0.870 to 0.915 using clinical and routine blood data, and 0.858 to 0.927 using only clinical data. In comparison, the LR model yielded AUCs of 0.798 and 0.787 respectively. Repeated internal validation showed that the contributions of routine blood data for prediction models may depend on different prediction algorithms and different outcome measurements. CONCLUSION: The study reported ML-based prediction models that provided rapid and accurate predictions on short-term outcomes after non-surgical treatment among patients with moderate-to-severe TBI. The study also highlighted the superiority of ML models over conventional LR models and proposed the complex contributions of routine blood data in such predictions.

Key Roles of Conjunctiva Fornix-Bulbar Conjunctiva-Tenon Capsule in Conjoint Fascial Sheath Suspension.

BACKGROUND: Bulbar conjunctival prolapse is one of the complications of conjoint fascial sheath (CFS) suspension and has a negative impact on surgical results. To explore the prevention methods of this complication, the authors compared the incidence of it between the below-conjunctiva fornix-bulbar conjunctiva-Tenon capsule (CBT) approach and the above-CBT approach to dissecting CFS in CFS suspension and shared their experience in the treatment of bulbar conjunctival prolapse. METHODS: From January of 2020 to August of 2021, 81 patients with severe congenital ptosis who underwent CFS suspension were enrolled and divided into two groups. Forty-five patients' (group A) CFS was dissected by means of the below-CBT approach and 36 patients' (group B) CFS was dissected by means of the above-CBT approach. Data regarding the incidence and outcomes of bulbar conjunctival prolapse and the postoperative condition were collected and analyzed. RESULTS: The incidence of bulbar conjunctival prolapse was 24.44% in group A and 2.78% in group B. Of the 12 bulbar conjunctival prolapse patients, seven patients' conditions improved after conservative treatment, and five did not. All of them underwent bulbar conjunctiva resection within 1 year and were cured. No recurrent prolapse was observed within 3 months postoperatively. At the last follow-up, the mean marginal reflex distance 1 and palpebral fissure height were 4.09 ± 0.19 mm and 9.85 ± 0.62 mm, respectively. There were no complications except lagophthalmos (16 eyelids), asymmetric eyelid contour (one patient), and trichiasis (two eyelids). CONCLUSIONS: The incidence of bulbar conjunctival prolapse decreased significantly by dissecting CFS by means of the above-CBT approach. For patients with bulbar conjunctival prolapse after CFS suspension, bulbar conjunctiva resection could provide satisfactory results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The Optimal Layer for Breast Augmentation in an Autologous Fat Grafting Murine Model.

BACKGROUND: Fat grafting is an effective procedure for breast augmentation, but the variations in this technique result in unpredictable fat retention. Therefore, animal models are needed to simulate the operation and the optimal layer for fat retention. OBJECTIVES: An autologous fat grafting murine model for breast augmentation was built to detect a new layer for fat grafting in the chest. METHODS: The left side of the female rat inguinal fat flap was harvested, dissected into small pieces, and autotransplanted into 3 different layers of the breast. Retention rate and hematoxylin and eosin (H&E) staining were measured at 1, 4, 8 12, and 16 weeks. Immunofluorescence staining was utilized to detect adipocytes and endothelial cells, and immunohistochemistry was conducted to evaluate the expression of integrins ß1 and α6. RESULTS: The volume of fat grafts slightly grew in the intramuscular and submuscular layers at Week 4. Retention rates in the subcutaneous layer and submuscular layer were significantly higher than the intramuscular layer at Week 16. H&E staining showed that oil cysts existed in the subcutaneous layer throughout the 16 weeks. At the terminal time point, well-vascularized mature adipose structures were observed in intramuscular and submuscular layers, with smaller adipocytes in intramuscular layers. Immunohistochemistry analysis showed that integrin ß1 was identically expressed in every adipocyte in all the layers, whereas integrin α6 selectively expressed in bigger adipocytes in the intramuscular layer. The expression intensities of integrin ß1 and α6 were significantly higher in the intramuscular layer than in the subcutaneous and submuscular layers. CONCLUSIONS: The angiogenic and moderate mechanical environment makes the submuscular layer the optimal layer for fat retention.

Transcription factor c-Maf drives macrophages to promote hypertrophic scar formation.

BACKGROUND: Hypertrophic scar (HS) is caused by the abnormal proliferation of fibroblasts and excessive deposition of extracellular matrix (ECM). Emerging evidence demonstrates that c-Maf positive M2 macrophages were mainly located in the hypertrophic scar tissues of proliferative phase. But whether c-Maf positive M2 macrophages can promote hypertrophic scar formation through modulating hypertrophic scar fibroblasts remains elusive. AIMS: The aim of this study is to investigate the effects of c-Maf positive M2 macrophages on the biological behaviors and functions of hypertrophic scar fibroblasts and the potential mechanism. METHODS: HE and Masson trichrome staining were used to examine the histological features of human hypertrophic scar. Immunofluorescence staining was employed to label and quantify the c-Maf+ /CD68+ M2 macrophages. CCK8, wound healing, and transwell assays were utilized to test the effects of c-Maf overexpressed M2 macrophages or the cell culture supernatants on the proliferation and migration of hypertrophic scar derived fibroblasts (HFBs) and normal skin derived fibroblasts (NFBs). Western blot and qPCR were harnessed to test the expressions of COL1, COL3, and α-SMA in the co-cultivated fibroblasts and TGF-ß1 in the c-Maf overexpressed M2 macrophages. RESULTS: Increased number of c-Maf+ /CD68+ M2 macrophages were found in HS in contrast to the normal skin (NS). Elevated proliferation and migration were observed in the HFBs or NFBs co-cultured with c-Maf overexpressed macrophages or the cell culture supernatants. A higher mRNA and protein expressions of COL1, COL3, and α-SMA were recorded in the HFBs co-cultured with c-Maf overexpressed macrophages or treated with its culture supernatants. In addition, augmented mRNA and protein expressions of TGF-ß1 were also investigated in the c-Maf overexpressed macrophages. CONCLUSION: c-Maf positive macrophages promote hypertrophic scar formation through regulating HFBs proliferation, migration, and ECM deposition via the secreted TGF-ß1.

Photobiomodulation Facilitates Rat Cutaneous Wound Healing by Promoting Epidermal Stem Cells and Hair Follicle Stem Cells Proliferation.

BACKGROUND: Cutaneous wound healing represents a common fundamental phenomenon requiring the participation of cells of distinct types and a major concern for the public. Evidence has confirmed that photobiomodulation (PBM) using near-infrared (NIR) can promote wound healing, but the  cells involved and the precise molecular mechanisms remain elusive. METHODS: Full-thickness skin defects with a diameter of 1.0 cm were made on the back of rats and randomly divided into the control group, 10 J, 15 J, and 30 J groups. The wound healing rate at days 4, 8, and 12 postoperatively was measured. HE and Masson staining was conducted to reveal the histological characteristics. Immunofluorescence staining was performed to label the epidermal stem cells (ESCs) and hair follicle stem cells (HFSCs). Western blot was performed to detect the expressions of proteins associated with ESCs and HFSCs. Cutaneous wound tissues were collected for RNA sequencing. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes analysis was performed, and the hub genes were identified using CytoHubba and validated by qRT-PCR. RESULTS: PBM can promote reepithelialization, extracellular matrix deposition, and wound healing, increase the number of KRT14+/PCNA+ ESCs and KRT15+/PCNA+ HFSCs, and upregulate the protein expression of P63, Krt14, and PCNA. Three hundred and sixty-six differentially expressed genes (DEGs) and 7 hub genes including Sox9, Krt5, Epcam, Cdh1, Cdh3, Dsp, and Pkp3 were identified. These DEGs are enriched in skin development, cell junction, and cadherin binding involved in cell-cell adhesion etc., while these hub genes are related to skin derived stem cells and cell adhesion. CONCLUSION: PBM accelerates wound healing by enhancing reepithelialization through promoting ESCs and HFSCs proliferation and elevating the expression of genes associated with stem cells and cell adhesion. This may provide a valuable alternative strategy to promote wound healing and reepithelialization by modulating the proliferation of skin derived stem cells and regulating genes related to cell adhesion.

Tape Tarsorrhaphy in the Management of Lagophthalmos Caused by Severe Congenital Blepharoptosis Procedures.

BACKGROUND: Lagophthalmos, a common complication after blepharoptosis correction, has plagued oculoplastic surgeons. The goal of this study was to investigate the effect of tape eyelid closure on reducing the occurrence of lagophthalmos after blepharoptosis correction. METHODS: From April 2020 to June 2021, a total of 112 patients with severe congenital ptosis received corrective surgery at the Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University. Of these, 48 underwent frontalis muscle advancement technique and 64 underwent conjoint fascial sheath suspension. Preoperative data collected included demographics, levator function, Bell's phenomenon, and marginal reflex distance 1 (MRD1). Postoperative data included surgery type, MRD1, eyelid closure function, aesthetic outcomes (including eyelid contour, eyelid symmetry, and eyelid crease), keratitis, and other complications. RESULTS: Frontalis muscle advancement technique group: the median of safe eye closure time was 7.3 months (positive Bell's phenomenon; interquartile range [IQR], 3.8-10.8 months) and 13.9 months (poor Bell's phenomenon; IQR, 11.6-16.1 months). There was a significant improvement between the preoperative and postoperative MRD1 (-1.52 ± 0.82 vs 3.85 ± 0.58 mm, P < 0.05). Conjoint fascial sheath suspension group: the median of safe eye closure time was 5.7 months (positive Bell's phenomenon; IQR, 2.9-8.5 months) and 12.4 months (poor Bell's phenomenon; IQR, 8.1-16.7 months). There was a significant improvement between the preoperative and postoperative MRD1 (-1.02 ± 0.91 vs 4.15 ± 1.03 mm, P < 0.05). All patients/guardians were satisfied with the aesthetic outcomes. CONCLUSIONS: Tape tarsorrhaphy is a safe, easy-to-learn method for treating lagophthalmos with a good aesthetic outcome.

The Aesthetic Evaluation of the Brow-Eye Continuum After Correction of Severe Congenital Ptosis in Children With Extended Frontalis Muscle Advancement Technique.

BACKGROUND: Severe congenital ptosis is a common ocular deformity in pediatric patients that can significantly impact visual development and aesthetic appearance, leading to negative psychosocial outcomes. The frontalis muscle advancement technique is a well-established surgical treatment for severe congenital ptosis. Aesthetic changes of the brow-eye continuum often plays an important role in ptosis surgery. METHODS: We conducted a single-center retrospective case series study of patients with severe congenital ptosis who underwent the frontalis muscle advancement technique at the Department of Plastic and Reconstructive Surgery, Xijing Hospital, Fourth Military Medical University between April 2020 and June 2021. The study aimed to evaluate the aesthetic changes of the eyebrow-eyelid continuum after surgery. The main outcome measurements included marginal reflex distance 1, palpebral fissure height, eyebrow position, upper eyelid to lower eyebrow distance, lower eyelid to upper eyebrow distance, and nasal base to lower eyelid distance. RESULTS: The study included 48 patients (66 eyelids), with 30 unilateral and 18 bilateral patients. Our analysis found that eyebrow height decreased by an average of 4.8% postoperatively relative to preoperatively in all patients. CONCLUSIONS: The frontalis muscle advancement technique has demonstrated effectiveness in achieving aesthetically pleasing outcomes in children with severe ptosis. It is crucial to pay careful attention to the brow-eye continuum during the correction process, as its harmony can greatly impact the final result.

Integrative lactylation and tumor microenvironment signature as prognostic and therapeutic biomarkers in skin cutaneous melanoma.

BACKGROUND: The incidence of skin cutaneous melanoma (SKCM), one of the most aggressive and lethal skin tumors, is increasing worldwide. However, for advanced SKCM, we still lack an accurate and valid way to predict its prognosis, as well as novel theories to guide the planning of treatment options for SKCM patients. Lactylation (LAC), a novel post-translational modification of histones, has been shown to promote tumor growth and inhibit the antitumor response of the tumor microenvironment (TME) in a variety of ways. We hope that this study will provide new ideas for treatment options for SKCM patients, as well as research on the molecular mechanisms of SKCM pathogenesis and development. METHODS: At the level of the RNA sequencing set (TCGA, GTEx), we used differential expression analysis, LASSO regression analysis, and multifactor Cox regression analysis to screen for prognosis-related genes and calculate the corresponding LAC scores. The content of TME cells in the tumor tissue was calculated using the CIBERSORT algorithm, and the TME score was calculated based on its results. Finally, the LAC-TME classifier was established and further analyzed based on the two scores, including the construction of a prognostic model, analysis of clinicopathological characteristics, and correlation analysis of tumor mutation burden (TMB) and immunotherapy. Based on single-cell RNA sequencing data, this study analyzed the cellular composition in SKCM tissues and explored the role of LAC scores in intercellular communication. To validate the functionality of the pivotal gene CLPB in the model, cellular experiments were ultimately executed. RESULTS: We screened a total of six prognosis-related genes (NDUFA10, NDUFA13, CLPB, RRM2B, HPDL, NARS2) and 7 TME cells with good prognosis. According to Kaplan-Meier survival analysis, we found that the LAClow/TMEhigh group had the highest overall survival (OS) and the LAChigh/TMElow group had the lowest OS (p value < 0.05). In further analysis of immune infiltration, tumor microenvironment (TME), functional enrichment, tumor mutational load and immunotherapy, we found that immunotherapy was more appropriate in the LAClow/TMEhigh group. Moreover, the cellular assays exhibited substantial reductions in proliferation, migration, and invasive potentials of melanoma cells in both A375 and A2058 cell lines upon CLPB knockdown. CONCLUSIONS: The prognostic model using the combined LAC score and TME score was able to predict the prognosis of SKCM patients more consistently, and the LAC-TME classifier was able to significantly differentiate the prognosis of SKCM patients across multiple clinicopathological features. The LAC-TME classifier has an important role in the development of immunotherapy regimens for SKCM patients.

Machine learning and single-cell transcriptome profiling reveal regulation of fibroblast activation through THBS2/TGFß1/P-Smad2/3 signalling pathway in hypertrophic scar.

Hypertrophic scar (HS) is a chronic inflammatory skin disorder characterized by excessive deposition of extracellular matrix, and the mechanisms underlying their formation remain poorly understood. We analysed scRNA-seq data from samples of normal skin and HS. Using the hdWGCNA method, key gene modules of fibroblasts in HS were identified. Non-negative matrix factorization was employed to perform subtype analysis of HS patients using these gene modules. Multiple machine learning algorithms were applied to screen and validate accurate gene signatures for identifying and predicting HS, and a convolutional neural network (CNN) based on deep learning was established and validated. Quantitative reverse transcription-polymerase chain reaction and western blotting were performed to measure mRNA and protein expression. Immunofluorescence was used for gene localization analysis, and biological features were assessed through CCK8 and wound healing assay. Single-cell sequencing revealed distinct subpopulations of fibroblasts in HS. HdWGCNA identified key gene characteristics of this population, and pseudotime analysis was conducted to investigate gene variation during fibroblast differentiation. By employing various machine learning algorithms, the gene range was narrowed down to three key genes. A CNN was trained using the expression of these key genes and immune cell infiltration, enabling diagnosis and prediction of HS. Functional experiments demonstrated that THBS2 is associated with fibroblast proliferation and migration in HS and affects the formation and development of HS through the TGFß1/P-Smad2/3 pathway. Our study identifies unique fibroblast subpopulations closely associated with HS and provides biomarkers for the diagnosis and treatment of HS.

Combined signature of G protein-coupled receptors and tumor microenvironment provides a prognostic and therapeutic biomarker for skin cutaneous melanoma.

BACKGROUND: G protein-coupled receptors (GPCRs) have been shown to have an important role in tumor development and metastasis, and abnormal expression of GPCRs is significantly associated with poor prognosis of tumor patients. In this study, we analyzed the GPCRs-related gene (GPRGs) and tumor microenvironment (TME) in skin cutaneous melanoma (SKCM) to construct a prognostic model to help SKCM patients obtain accurate clinical treatment strategies. METHODS: SKCM expression data and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential expression analysis, LASSO algorithm, and univariate and multivariate cox regression analysis were used to screen prognosis-related genes (GPR19, GPR146, S1PR2, PTH1R, ADGRE5, CXCR3, GPR143, and OR2I1P) and multiple prognosis-good immune cells; the data set was analyzed according to above results and build up a GPR-TME classifier. The model was further subjected to immune infiltration, functional enrichment, tumor mutational load, immunotherapy prediction, and scRNA-seq data analysis. Finally, cellular experiments were conducted to validate the functionality of the key gene GPR19 in the model. RESULTS: The findings indicate that high expression of GPRGs is associated with a poor prognosis in patients with SKCM, highlighting the significant role of GPRGs and the tumor microenvironment (TME) in SKCM development. Notably, the group characterized by low GPR expression and a high TME exhibited the most favorable prognosis and immunotherapeutic efficacy. Furthermore, cellular assays demonstrated that knockdown of GPR19 significantly reduced the proliferation, migration, and invasive capabilities of melanoma cells in A375 and A2058 cell lines. CONCLUSION: This study provides novel insights for the prognosis evaluation and treatment of melanoma, along with the identification of a new biomarker, GPR19.

Complications of Injected Exogenous Growth Factor for Cosmetic Facial Rejuvenation: A Case Series and Sequential Therapy.

BACKGROUND: Exogenous growth factor presents promising soft tissue regeneration, but the complications from injectable exogenous growth factor seem to be growing. However, there is no detailed summary of complications and sequential treatment protocols. It is noted that the injection of exogenous growth factor into the soft tissue is an unreasonable or even illegal procedure, which could cause uncontrollable tissue growth and some other complications. METHODS: A total of 65 patients underwent analysis retrospectively for complications related to the injection of exogenous growth factor from 2017to 2022 at Xijing Hospital in China. Initially the symptoms mainly consisted of redness, skin temperature arisen, itching, tissue hypertrophy, localized swelling, mass, and lump, with later manifestations including ulcerations and purulent discharge. A comprehensive treatment scheme was formulated based on the location and size of the lumps as well as the type of complication. Post-treatment satisfaction was evaluated over a mean 16-month follow-up (range 6-39 months). RESULTS: A total of 65 patients participated in the treatment. Drug injection therapy was initially performed on all patients. If injections were not effective, surgical treatment (debridement/excision/liposuction) was performed. Twenty-eight patients were managed with intralesional injections alone. Patients reported improved satisfaction in 23 cases (82.14%), full symptom resolution in 3 cases (10.72%), and no improvement in 2 cases (7.14%). Surgery was required for 37 patients. Postoperative improved satisfaction was reported in 30 cases (81.08%), full symptom resolution was recorded in 4 cases (10.82%), and no improvement was seen in 3 cases (8.10%). CONCLUSIONS: This study highlights the management of complications arising from exogenous growth factor injections through the implementation of a sequential therapy approach. Specifically, this approach involves the initial administration of drug injection therapy, and if drug injection therapy proves ineffective, then surgical treatment is pursued. In conclusion, the injection of exogenous growth factors into soft tissues should be forbidden. 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 .

Tape Eyelid Closure: An Effective Solution for Nocturnal Lagophthalmos in Patients with Ptosis and Poor Bell's Phenomenon.

BACKGROUND: Poor Bell's phenomenon is often considered a relative contraindication for ptosis surgery, as it increases the risk of corneal exposure and dry eye symptoms after surgery. However, the Bell's phenomenon may vary in different individuals and sleep stages, making it inaccurate to predict the position of the eye during sleep based on awake examination. This study aimed to investigate the role of Bell's phenomenon in ptosis surgery and the management of nocturnal lagophthalmos. METHODS: We conducted a retrospective case series of 23 patients with ptosis and poor Bell's phenomenon who underwent different surgical techniques at Xijing Hospital from April 2020 to June 2021. We assessed Bell's phenomenon at different stages of sleep and collected data on ptosis degree, surgical approach, lagophthalmos, complications, and outcomes. RESULTS: Of the total 23 patients originally considered for study, 9 with frontalis muscle advancement technique, 8 with conjoint fascial sheath suspension, 4 with levator resection technique, and 2 with levator aponeurosis plication technique. All patients achieved satisfactory correction of ptosis. One patient had prolonged lagophthalmos and underwent reoperation to lower the eyelid height. Other complications were minor and resolved with conservative treatment. CONCLUSION: We conclude that poor Bell's phenomenon is not a relative contraindication for ptosis surgery. Nocturnal lagophthalmos should be monitored after ptosis surgery regardless of the Bell's phenomenon results. Tape eyelid closure can be an effective solution to protect the corneal surface during nocturnal lagophthalmos. 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 Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Role of single-cell ferroptosis regulation in intercellular communication and skin cutaneous melanoma progression and immunotherapy.

BACKGROUND: The involvement of ferroptosis in the pathogenesis and progression of various cancers has been well established. However, limited studies have investigated the role of ferroptosis-mediated tumor microenvironment (TME) in skin cutaneous melanoma (SKCM). METHODS: By leveraging single-cell RNA sequencing data, the nonnegative matrix factorization (NMF) approach was employed to comprehensively characterize and identify distinct gene signatures within ferroptosis-associated TME cell clusters. Prognostic and treatment response analyses were conducted using both bulk datasets and external cancer cohort to evaluate the clinical implications of TME clusters. RESULTS: This NMF-based analysis successfully delineated fibroblasts, macrophages, T cells, and B cells into multiple clusters, enabling the identification of unique gene expression patterns and the annotation of distinct TME clusters. Furthermore, pseudotime trajectories, enrichment analysis, cellular communication analysis, and gene regulatory network analysis collectively demonstrated significant intercellular communication between key TME cell clusters, thereby influencing tumor cell development through diverse mechanisms. Importantly, our bulk RNA-seq analysis revealed the prognostic significance of ferroptosis-mediated TME cell clusters in SKCM patients. Moreover, our analysis of immune checkpoint blockade highlighted the crucial role of TME cell clusters in tumor immunotherapy, facilitating the discovery of potential immunotherapeutic targets. CONCLUSIONS: In conclusion, this pioneering study employing NMF-based analysis unravels the intricate cellular communication mediated by ferroptosis within the TME and its profound implications for the pathogenesis and progression of SKCM. We provide compelling evidence for the prognostic value of ferroptosis-regulated TME cell clusters in SKCM, as well as their potential as targets for immunotherapy.