ABSTRACT
BACKGROUND: The aetiologies of large-to-giant congenital melanocytic naevi (LGCMN) remain ambiguous. A previous study discovered signatures associated with deficient mismatch repair (dMMR) in patients with LGCMN. However, a screening diagnostic immunohistochemistry (IHC) panel of dMMR in patients with LGCMN has not been performed to date. OBJECTIVES: To identify the MMR status and aetiologies of LGCMN. METHODS: A total of 110 patients with CMN, including 30 giant CMN, 30 large CMN, 30 medium CMN and 20 small CMN, underwent diagnostic IHC (for MSH6, MSH2, PMS2 and MLH1) screening of dMMR. The control group comprised normal skin samples from 20 healthy people. MMR proteins with little effect (MSH3 and PMS1) on the MMR system were stained in all samples. The surgical procedures conducted on each patient were noted because they might alter the behaviour of CMN and confound the results. Binary logistic regression analyses were performed between the phenotypic data and MMR status to identify associations. Whole-exome sequencing was performed on the main naevi, satellite naevi and normal skin tissues of four patients to detect variants. Mutational signature analyses were conducted to explore the aetiologies of LGCMN. RESULTS: dMMR was detected in 37% (11 of 30) of giant, 23% (7 of 30) of large and 7% (2 of 30) of medium CMNs, but were not identified in small CMNs or normal skin tissues. Moreover, multiple LGCMNs had a much higher dMMR rate than did single LGCMNs. The regression analyses showed that MMR status was significantly associated with CMN size and the presence of satellites, but was not correlated with age, sex, location, satellite diversity or tissue expansion. Notably, the pattern of protein loss in LGCMN mainly consisted of PMS2 loss. Mutational signature analyses detected dMMR-related signatures in patients with LGCMN. Additionally, rare deleterious germline mutations in DNA repair genes were detected in LGCMN, mainly in MSH6, ATM, RAD50, BRCA1 and ERCC8. These germline mutations were single-patient variants with unknown significance. CONCLUSIONS: dMMR is one of the aetiologies underlying LGCMN, particularly in patients with giant main lesions and multiple satellite lesions. Further studies are necessary to investigate the role of the DNA repair system, particularly MMR, in LGCMN.
Subject(s)
Nevus, Pigmented , Skin Neoplasms , Humans , DNA Mismatch Repair , Mismatch Repair Endonuclease PMS2/genetics , Mismatch Repair Endonuclease PMS2/metabolism , DNA-Binding Proteins/genetics , Transcription Factors/genetics , DNA Repair Enzymes/genetics , DNA Repair Enzymes/metabolismABSTRACT
BACKGROUND: Soft tissue expansion is a common technique for restoring large skin defects. Fixed-type expanders may be inappropriate for the following reasons: (1) the shapes and sizes of the defects vary in different patients; and (2) the bulged base of the fixed-type expander does not fit the curve of the human body, which may induce complications such as concave deformities or nerve palsy from continuous mechanical compression. The customized expander adjusts better to the shape and the topography of the expansion site compared with the fixed-type expander. It improves expansion efficiency and reduces complications caused by compression. METHODS: Between 2016 and 2022, customized soft tissue expansion was performed in 38 patients with skin lesions, including giant congenital melanocytic nevi and postburn scars. This series of patients included patients with a specific donor site shape that is unsuitable for fixed-type expanders. An expander was customized according to the shape of the donor site and then implanted in the subcutaneous pocket. After the expander reached a sufficient volume, the expander was removed, and the extra expanded skin flap was transferred to resurface the skin lesion. In the follow-up, the outcome and the complications were recorded. RESULTS: All the customized expanders fit not only the dimension but also the topography of the donor site. During expansion, 2 patients experienced leakage of the expander, and 3 patients suffered a skin rupture. In the remaining 33 patients, the expansion was successfully completed, and the expanded flaps restored the skin lesions as designed. The color and texture of the skin flaps remained satisfactory after long-term follow-up. CONCLUSIONS: Unlike fixed-type expanders, our customized expanders make it possible for "accurate" expansion, irrespective of the dimension and topography of the donor area. Customization of the expander helps increase efficiency and reduce complications caused by undue compression.
Subject(s)
Plastic Surgery Procedures , Tissue Expansion Devices , Humans , Surgical Flaps , Tissue Expansion/methods , Skin TransplantationABSTRACT
BACKGROUND: Face-lift surgery is the most crucial and constantly evolving technique of facial rejuvenation. Periodic reviews synthesizing the latest face-lift techniques may help surgeons sharpen their surgical procedures. METHODS: A literature search was conducted of the PubMed databases using the search term "face lift" and "rhytidectomy." Articles reporting rhytidectomy of the forehead/brow, midface, lower face, and neck were included. Sixty-nine articles were selected after independent screening by three of the authors. The Oxford Centre for Evidence-based Medicine scale was used for evaluating evidence level. RESULTS: Of the 69 candidate articles, 10 studies (15%) reported techniques of neck lifting; 10 studies (15%) introduced techniques of endoscopic brow lifting; 7 studies (10%) pertained to brow lifting without endoscopic techniques. The most frequently reported locations of rhytidectomy were the brow/forehead (20%), neck (19%), and face-neck (17%). Additionally, articles regarding Asian face-lifts (14%) have been increasing. The evidence level of the articles was generally low, with only 10 articles assessed as level 1-3 with 59 articles as level 4-5. CONCLUSIONS: Face-lift articles with high-level evidence are still lacking. Prominently, forehead lifting and neck lifting have become upward trends of rhytidectomy in recent years, and the techniques of short-scar face-lift have been more valued. LEVEL OF EVIDENCE III: 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 .
Subject(s)
Rhytidoplasty , Humans , Rhytidoplasty/methods , Retrospective Studies , Cicatrix/prevention & control , Endoscopy , Neck , RejuvenationABSTRACT
Cisplatin (CDDP) is the most commonly used chemotherapeutic drug and has an irreplaceable role in cancer treatment. However, CDDP-induced acute kidney injury (AKI) greatly limits its use. Abundant evidence has confirmed that apoptosis contributes to AKI caused by CDDP administration. The nanoparticle form of selenium, also known as Se@SiO2 nanocomposites (NPs), has been proven to be a potential agent to prevent apoptotic cell death. In this article, we established acute kidney injury models in vivo via a single injection of CDDP and used human kidney 2 (HK-2) cells for experiments in vitro. We demonstrated that NPs can improve CDDP-induced renal dysfunction. In addition, therapy with NPs attenuated apoptosis in cells and kidney tissues treated with CDDP. In terms of mechanism, we discovered that Sirt1, a deacetylase with an important role in CDDP-induced acute kidney injury, was remarkedly increased after NPs pretreatment, and the anti-apoptotic effect of the NPs was markedly abrogated after the inhibition of Sirt1. The results linked the protective effect of NPs on nephrotoxicity with Sirt1, suggesting the potential clinical importance of nanomaterials in alleviating the side effects of chemotherapy.
Subject(s)
Acute Kidney Injury/drug therapy , Antineoplastic Agents/adverse effects , Cisplatin/adverse effects , Nanospheres/therapeutic use , Protective Agents/therapeutic use , Selenium/therapeutic use , Silicon Dioxide/therapeutic use , Acute Kidney Injury/chemically induced , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , Animals , Cell Line , Female , Humans , Interleukin-6/metabolism , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Male , Mice, Inbred C57BL , Porosity , Protective Agents/pharmacokinetics , Selenium/pharmacokinetics , Silicon Dioxide/pharmacokinetics , Sirtuin 1/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
SUMMARY: Fat redistribution combined with release of the tear trough ligament in transconjunctival lower blepharoplasty is widely performed to correct lower eyelid bags and tear trough deformities, but suturing the released fat in such a narrow, dissected space remains a challenge. The purpose of this study was to introduce a new surgical technique of internal fixation that advances and sutures the pedicled orbital fat firmly to the midcheek through premaxillary and prezygomatic spaces. Twenty-two patients (age range, 22 to 39 years) with predominant orbital fat prolapse and tear trough deformity without noticeable lower eyelid skin laxity were treated with this method, all of whom had impressive correction of the eyelid bags and tear trough deformities and were pleased with the aesthetic results during an average follow-up of 11.8 months (range, 10 to 14 months). No patient had postoperative hematoma, ectropion, or midface numbness. The maneuver of internal fixation of redistributed orbital fat provides a novel and safe approach to correct eyelid bags and tear trough deformities without additional percutaneous sutures in transconjunctival lower eyelid blepharoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
Subject(s)
Blepharoplasty , Ectropion , Lacerations , Humans , Young Adult , Adult , Blepharoplasty/methods , Eyelids/surgery , Adipose Tissue/transplantation , Orbit/surgery , Lacerations/surgeryABSTRACT
BACKGROUND: Hypertrophic scars and keloid treatment is a major problem in plastic surgery. While small keloids can be treated with resection followed by radiotherapy, large keloids require treatment with a tissue expander. Conventional methods increase the need for auxiliary incisions, causing new scar hyperplasia. AIM: To introduce a new method for the treatment of keloids with an expander. METHODS: Between 2018 and 2021, we performed surgeries to treat large keloids in nine patients with a two-stage approach. In the first stage, an intrascar incision was made in the keloid, and a customized expander was implanted under the keloid and the surrounding normal skin. A period of 3-6 mo was allowed for skin expansion. In the second stage, after the initial incision healed, a follow-up surgery was performed to remove the expander, resect the keloid, and repair the expanded skin flap. To accomplish this, an incision was made along the scar boundary to avoid making a new surgical incision and creating new scars. Superficial radiotherapy was then performed postoperatively. RESULTS: Two patients had anterior chest keloids. After treatment, the anterior chest incision was broken repeatedly and then sutured again after debridement. It healed smoothly without scar hyperplasia. Keloids were successfully removed in 7 patients without recurrence. CONCLUSION: This method was performed through a keloid incision and with a custom expander embedded. After full expansion, the keloid was directly resected using a linear suture, which avoids new surgical incisions and scars and can successfully remove large-area keloids. The treatment is effective, providing new insights and strategies for the treatment of similar large-area keloid and hypertrophic scar cases in the future.
ABSTRACT
The nevogenesis of large/giant congenital melanocytic nevus (lgCMN) is a complex biological process including several integral prenatal stages. Limited by ethical concerns, the debate of whether lgCMN develops from the epidermis to the dermis or in the opposite direction remains controversial. With the present study of the accompanying satellite nevi, we tend to support that lgCMN develops from epidermis to dermis. The satellite nevi were divided into 3 groups: big (diameter >10 mm), medium (>5 mm but ≤10 mm), and small (≤5 mm). Hematoxylin and eosin and immunohistochemical staining (SOX10, Ki67, and p16) were performed to compare the nevocyte infiltration depth as well as the positively stained rates among these satellite nevi. Compared to big satellite nevi, less deeply the nevocytes infiltrated the dermis, as well as more cells expressed SOX10 and Ki67 in the epidermis and fewer cells expressed p16 in the dermis of small satellite nevi. Additionally, two specimens were obtained from each of 4 patients who underwent serial resections of lgCMN at an average interval of 1.75 years to examine the histopathological changes. In the present study, satellite nevi of different sizes represent different stages of lgCMN from early to late, deepening our comprehension of the sequential stages of lgCMN nevogenesis. Initially, abnormal nevocytes seeded, proliferated, and spread along the epidermis. At rete ridges that protrude from the papillary dermis within the epidermis, some nevocytes formed nests and gradually penetrated into the dermis. Eventually, the nevocytes infiltrated the dermis and entered a homeostatic state. This study provides new evidence supporting the theory of epidermal-to-dermal nevogenesis in lgCMN.
Subject(s)
Nevus, Pigmented , Nevus , Skin Neoplasms , Pregnancy , Female , Humans , Ki-67 Antigen , Nevus, Pigmented/congenital , Nevus, Pigmented/pathology , Skin Neoplasms/pathologyABSTRACT
Objective.Interictal epileptiform discharges (IEDs) are an important and widely accepted biomarker used in the diagnosis of epilepsy based on scalp electroencephalography (EEG). Because the visual detection of IEDs has various limitations, including high time consumption and high subjectivity, a faster, more robust, and automated IED detector is strongly in demand.Approach.Based on deep learning, we proposed an end-to-end framework with multi-scale morphologic features in the time domain and correlation in sensor space to recognize IEDs from raw scalp EEG.Main Results.Based on a balanced dataset of 30 patients with epilepsy, the results of the five-fold (leave-6-patients-out) cross-validation shows that our model achieved state-of-the-art detection performance (accuracy: 0.951, precision: 0.973, sensitivity: 0.938, specificity: 0.968, F1 score: 0.954, AUC: 0.973). Furthermore, our model maintained excellent IED detection rates in an independent test on three datasets.Significance.The proposed model could be used to assist neurologists in clinical EEG interpretation of patients with epilepsy. Additionally, this approach combines multi-level output and correlation among EEG sensors and provides new ideas for epileptic biomarker detection in scalp EEG.
Subject(s)
Deep Learning , Epilepsy , Electroencephalography , Epilepsy/diagnosis , Humans , ScalpABSTRACT
Large to giant congenital melanocytic nevus (lgCMN) is a benign cutaneous tumor that develops during embryogenesis. A large number of lgCMN patients are ineligible for surgical treatment; hence, there is an urgent need to develop pharmacological treatments. Clinically, tumorigenesis and progression essentially halt after birth, resulting in the homeostasis of growth arrest and survival. Numerous studies have employed whole-genome or whole-exome sequencing to clarify the etiology of lgCMN; however, transcriptome sequencing of lgCMN is still lacking. Through comprehensive transcriptome analysis, this study elucidated the ongoing regulation and homeostasis of lgCMN and identified potential targets for treatment. Transcriptome sequencing, identification of differentially expressed genes and hub genes, protein-protein network construction, functional enrichment, pathway analysis, and gene annotations were performed in this study. Immunohistochemistry, real-time quantitative PCR, immunocytofluorescence, and cell cycle assays were employed for further validation. The results revealed several intriguing phenomena in lgCMN, including P16-induced cell cycle arrest, antiapoptotic activity, and immune evasion caused by malfunction of tumor antigen processing. The arrested cell cycle in lgCMN is consistent with its phenotype and rare malignant transformation. Antiapoptotic activity and immune evasion might explain how such heterogeneous cells have avoided elimination. Major histocompatibility complex (MHC) class I-mediated tumor antigen processing was the hub pathway that was significantly downregulated in lgCMN, and ITCH, FBXW7, HECW2, and WWP1 were identified as candidate hub genes. In conclusion, our research provides new perspectives for immunotherapy and targeted therapy.
Subject(s)
Biomarkers, Tumor/genetics , Cell Cycle Checkpoints/genetics , Nevus, Pigmented/genetics , Skin Neoplasms/genetics , Tumor Escape/genetics , Adolescent , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/analysis , Biomarkers, Tumor/antagonists & inhibitors , Carcinogenesis/genetics , Carcinogenesis/immunology , Child , Child, Preschool , Female , Gene Expression Profiling , Humans , Immunohistochemistry , Immunotherapy/methods , Infant , Male , Melanocytes , Molecular Targeted Therapy/methods , Nevus, Pigmented/immunology , Nevus, Pigmented/surgery , Nevus, Pigmented/therapy , Primary Cell Culture , Protein Interaction Maps/genetics , Protein Interaction Maps/immunology , Skin/pathology , Skin Neoplasms/immunology , Skin Neoplasms/surgery , Skin Neoplasms/therapy , Young AdultABSTRACT
AIMS: To improve the Magnetoencephalography (MEG) spatial localization precision of focal epileptic. METHODS: 306-channel simulated or real clinical MEG is estimated as a lower-dimensional tensor by Tucker decomposition based on Higher-order orthogonal iteration (HOOI) before the inverse problem using linearly constraint minimum variance (LCMV). For simulated MEG data, the proposed method is compared with dynamic imaging of coherent sources (DICS), multiple signal classification (MUSIC), and LCMV. For clinical real MEG of 31 epileptic patients, the ripples (80-250 Hz) were detected to compare the source location precision with spikes using the proposed method or the dipole-fitting method. RESULTS: The experimental results showed that the positional accuracy of the proposed method was higher than that of LCMV, DICS, and MUSIC for simulation data. For clinical real MEG data, the positional accuracy of the proposed method was higher than that of dipole-fitting regardless of whether the time window was ripple window or spike window. Also, the positional accuracy of the ripple window was higher than that of the spike window regardless of whether the source location method was the proposed method or the dipole-fitting method. For both shallow and deep sources, the proposed method provided effective performance. CONCLUSION: Tucker estimation of MEG for source imaging by ripple window is a promising approach toward the presurgical evaluation of epileptics.