Case report: Iatrogenic tattoos caused by skin marking pen in a postoperative patient.

In this report, a female patient suffering from pigment retention caused by a skin marking pen was elucidated. The patient underwent blepharoplasty 6 months ago and presented with blue-black linear marks at the upper eyelid incision 2 weeks after surgery. Under dermoscopy, scattered pigments were observed to accumulate in the epidermis of the upper eyelid. The patient was diagnosed with iatrogenic tattoo by a surgical marking pen. We chose surgical excision of the skin with the pigmentation. Previous studies have established that the risk of bacterial contamination, contact dermatitis, and allergies may increase with the surgical marking pens, while pigment retention has not yet been mentioned yet. Here, we present a case with a pigment retention in the incision. The selection of the surgical labelling methods and the management of the pigmentation were also addressed. According to our clinical findings, the risk of pigment retention by marking pens needs to be mentioned in the patient's informed consent. Therefore, the practitioner should ensure that the ink is cleaned by the end of each invasive procedure.

Supraciliary Incision as a Modified Approach for Asian Blepharoptosis Patients.

BACKGROUND: Blepharoptosis may result in an unattractive appearance and vision problems. According to the severity of ptosis, patients may undergo correction surgery using upper eyelid retractors. The conventional incision for surgical procedures was the double-eyelid incision, potentially resulting in an obvious and unnatural scar or long-lasting edema and prolonged recovery time. OBJECTIVES: The aim of this study was to introduce a supraciliary incision as an alternative to the double-eyelid incision for blepharoptosis correction that creates a scarless, natural appearance with a quick recovery time. METHODS: From June 2019 to June 2021, 32 patients (36 eyelids) underwent blepharoptosis correction through a supraciliary incision. MRD1, the height of the eyelid fissure, and the patient's satisfaction with the shape and scar as well as postoperative complications (eyelid insufficiency, conjunctival prolapse, inadequate correction of ptosis, and excessive correction of ptosis). RESULTS: All 32 patients (36 eyelids) were followed up for 6 to 18 months, with an average follow-up of 11.6 months. The postoperative satisfaction rate was 96.43%. There was no overcorrection, but one patient (1 eyelid, 2.8%) was under correction that required secondary correction. One patient (1 eyelid, 2.8%) experienced conjunctival prolapse. Sixteen patients showed lagophthalmos early after surgery, in which one patient experienced early-stage keratitis and completely recovered within two months. CONCLUSION: Blepharoptosis correction via supraciliary incision allows for broader indications and fewer surgical scars without disrupting eyelid integrity, resulting in quick recovery after surgery. 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 .

The application and progress of tissue engineering and biomaterial scaffolds for total auricular reconstruction in microtia.

Microtia is a congenital deformity of the ear with an incidence of about 0.8-4.2 per 10,000 births. Total auricular reconstruction is the preferred treatment of microtia at present, and one of the core technologies is the preparation of cartilage scaffolds. Autologous costal cartilage is recognized as the best material source for constructing scaffold platforms. However, costal cartilage harvest can lead to donor-site injuries such as pneumothorax, postoperative pain, chest wall scar and deformity. Therefore, with the need of alternative to autologous cartilage, in vitro and in vivo studies of biomaterial scaffolds and cartilage tissue engineering have gradually become novel research hot points in auricular reconstruction research. Tissue-engineered cartilage possesses obvious advantages including non-rejection, minimally invasive or non-invasive, the potential of large-scale production to ensure sufficient donors and controllable morphology. Exploration and advancements of tissue-engineered cartilaginous framework are also emerging in aspects including three-dimensional biomaterial scaffolds, acquisition of seed cells and chondrocytes, 3D printing techniques, inducing factors for chondrogenesis and so on, which has greatly promoted the research process of biomaterial substitute. This review discussed the development, current application and research progress of cartilage tissue engineering in auricular reconstruction, particularly the usage and creation of biomaterial scaffolds. The development and selection of various types of seed cells and inducing factors to stimulate chondrogenic differentiation in auricular cartilage were also highlighted. There are still confronted challenges before the clinical application becomes widely available for patients, and its long-term effect remains to be evaluated. We hope to provide guidance for future research directions of biomaterials as an alternative to autologous cartilage in ear reconstruction, and finally benefit the transformation and clinical application of cartilage tissue engineering and biomaterials in microtia treatment.

Mechanisms and applications of adipose-derived stem cell-extracellular vesicles in the inflammation of wound healing.

Wound healing is a sophisticated process consisting of serial phases with overlaps, including hemostasis, inflammation, proliferation, and remodeling. The inflammation response is an early response that plays a crucial role in eliminating microbes and clearing damaged cell debris. However, in some pathological circumstances, such as diabetes mellitus, ischemia, trauma, deep burn, etc., abnormal inflammation can cause impaired wound healing. Adipose-derived stem cells (ADSCs) belong to the mesenchymal stem cell (MSC) family and exhibit prospective applications in tissue regeneration and dermatological repairs. ADSC-secreted extracellular vesicles (ADSC-EVs) mimic the functions of ADSCs without the concerns of cell survival, immune response, or ethical issues. Studies have revealed that ADSC-EVs can inhibit abnormal inflammation responses and accelerate wound healing through various mechanisms. Moreover, some studies explored modifications in the cargo components of ADSC-EVs to enhance their therapeutic efficacy. Given the increasing studies focusing on the potential of ADSC-EVs in wound healing, how they interfere with different phases of this process has been investigated in pieces. In this review, we summarized all up-to-date evidence to map a clearer picture of the underlying mechanisms of ADSC-EVs in inflammation response. The applications of ADSC-EVs aiming at inflammation in the healing process were also reviewed to provide therapeutic strategies for future investigators.

Bioengineered MSC-derived exosomes in skin wound repair and regeneration.

Refractory skin defects such as pressure ulcers, diabetic ulcers, and vascular ulcers represent a challenge for clinicians and researchers in many aspects. The treatment strategies for wound healing have high cost and limited efficacy. To ease the financial and psychological burden on patients, a more effective therapeutic approach is needed to address the chronic wound. MSC-derived exosomes (MSC-exosomes), the main bioactive extracellular vesicles of the paracrine effect of MSCs, have been proposed as a new potential cell-free approach for wound healing and skin regeneration. The benefits of MSC-exosomes include their ability to promote angiogenesis and cell proliferation, increase collagen production, regulate inflammation, and finally improve tissue regenerative capacity. However, poor targeting and easy removability of MSC-exosomes from the wound are major obstacles to their use in clinical therapy. Thus, the concept of bioengineering technology has been introduced to modify exosomes, enabling higher concentrations and construction of particles of greater stability with specific therapeutic capability. The use of biomaterials to load MSC-exosomes may be a promising strategy to concentrate dose, create the desired therapeutic efficacy, and maintain a sustained release effect. The beneficial role of MSC-exosomes in wound healing is been widely accepted; however, the potential of bioengineering-modified MSC-exosomes remains unclear. In this review, we attempt to summarize the therapeutic applications of modified MSC-exosomes in wound healing and skin regeneration. The challenges and prospects of bioengineered MSC-exosomes are also discussed.

In situ photo-crosslinked adhesive hydrogel loaded with mesenchymal stem cell-derived extracellular vesicles promotes diabetic wound healing.

The delayed healing of diabetic wounds is directly affected by the disturbance of wound microenvironment, resulting from persistent inflammation, insufficient angiogenesis, and impaired cell functions. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) showed considerable therapeutic potential in diabetic wound healing. However, the low retention rate of MSC-EVs at wound sites hampers their efficacy. For skin wounds exposed to the outer environment, using a hydrogel with tissue adhesiveness under a moist wound condition is a promising strategy for wound healing. In this study, we modified methacryloyl-modified gelatin (GelMA) hydrogel with catechol motifs of dopamine to fabricate a GelMA-dopamine hydrogel. EVs isolated from MSCs were applied in the synthesized GelMA-dopamine hydrogel to prepare a GelMA-dopamine-EV hydrogel. The results demonstrated that the newly formed GelMA-dopamine hydrogel possessed improved properties of softness, adhesiveness, and absorptive capacity, as well as high biocompatibility in the working concentration (15% w/v). In addition, MSC-EVs were verified to promote cell migration and angiogenesis in vitro. In the skin wound model of diabetic rats, the GelMA-dopamine-EV hydrogel exerted prominent wound healing efficacy estimated by collagen deposition, skin appendage regeneration, and the expression of IL-6, CD31, and TGF-ß. In conclusion, this combination of MSC-EVs and the modified hydrogel not only accelerates wound closure but also promotes skin structure normalization by rescuing the homeostasis of the healing microenvironment of diabetic wounds, which provides a potential approach for the treatment of diabetic wounds.

The Therapeutic Role of ADSC-EVs in Skin Regeneration.

Large skin defects caused by burns, unhealing chronic wounds, and trauma, are still an intractable problem for clinicians and researchers. Ideal skin regeneration includes several intricate and dynamic stages of wound repair and regeneration of skin physiological function. Adipose-derived stem cells (ADSCs), a type of mesenchymal stem cells (MSCs) with abundant resources and micro-invasive extraction protocols, have been reported to participate in each stage of promoting skin regeneration via paracrine effects. As essential products secreted by ADSCs, extracellular vesicles (EVs) derived from ADSCs (ADSC-EVs) inherit such therapeutic potential. However, ADSC-EVs showed much more clinical superiorities than parental cells. ADSC-EVs carry various mRNAs, non-coding RNAs, proteins, and lipids to regulate the activities of recipient cells and eventually accelerate skin regeneration. The beneficial role of ADSCs in wound repair has been widely accepted, while a deep comprehension of the mechanisms of ADSC-EVs in skin regeneration remains unclear. In this review, we provided a basic profile of ADSC-EVs. Moreover, we summarized the latest mechanisms of ADSC-EVs on skin regeneration from the aspects of inflammation, angiogenesis, cell proliferation, extracellular matrix (ECM) remodeling, autophagy, and oxidative stress. Hair follicle regeneration and skin barrier repair stimulated by ADSC-EVs were also reviewed. The challenges and prospects of ADSC-EVs-based therapies were discussed at the end of this review.

A LCMS-based untargeted lipidomics analysis of cleft palate in mouse.

BACKGROUND: Recent studies have shown that lipid metabolism was abnormal during the formation of cleft palate. However, the composition of these lipid species remains unclear. OBJECTIVE: Aims of this study were to identify the lipid species components and reveal the key lipid metabolic disorders in cleft palate formation. METHODS: The pregnant mice were divided into experimental group exposed to all-trans retinoic acid (RA-treated group) (n = 12) and control group (n = 12) at embryonic gestation day 10.5 (E0.5). The component of the palatal tissue metabolome was analyzed using a LCMS-based nontargeted lipidomics approach. Multivariate statistical analysis was then carried out to assess the differences between the RA-treated group and the control group. RESULTS: Twenty-nine lipid species were found to discriminate between RA-treated and control embryos. Among them, 28 lipid species increased and 1 lipid species decreased in the RA-treated group. Among these lipids, 13 were triglycerides, 9 were PEs, 3 were PCs, 2 were PSs, 2 were DGs. Further analysis of the number of carbons and unsaturated bond of triglycerides showed that TGs with high unsaturated bonds constituted a higher fraction in the RA-treated group. A higher amount of triglycerides containing 52, 54, 56, 58, 60 carbons, and 1 to 8 unsaturated bonds. Of note, under RA treatment, TG 50:1, 52:2, 56:6and 60:8 became the most prominent. CONCLUSION: Lipid metabolism is significantly different in the formation of cleft palate induced by RA, and the unsaturated triglycerides increased in the RA-treated group may play an important role in the formation of cleft palate.

Mining database for the expression and gene regulation network of JAK2 in skin cutaneous melanoma.

BACKGROUND: Skin cutaneous melanoma (SKCM) is the most common subtype of skin malignancy, with ever-increasing incidence, mortality, and disease burden. Dysregulation of JAK-STATs signaling pathway is involved in the pathogenesis and progression of cancers, thus affecting the prognosis of cancer patients. The function of JAKs in SKCM is still not clarified. METHODS: A total of five online portal (GEPIA, TIMER, GeneMANIA, LinkedOmics, and GSCALite) is used to mine the expression and gene regulation network JAK2 in SKCM. RESULTS: JAK2 expression was downregulated in SKCM and significantly associated with pathological stage and the prognosis of patients. The functions of JAK2 and associated genes were primarily involved in the DNA recombination, cell cycle checkpoint, metabolic process, NOD-like receptor signaling pathways, p53 signaling pathway and apoptosis. JAK2 level was significantly correlated with the abundance of immune cells and the level of immune biomarkers. Low expression of JAK2 were resistant to QL-VIII-58, TL-1-85, Ruxolitinib, TG101348 and Sunitinib. CONCLUSIONS: Our results reveal the expression and gene regulation network of JAK2 in skin cutaneous melanoma, providing more evidences about the role of JAK2 in carcinogenesis.

MiR-106a-5p modulates apoptosis and metabonomics changes by TGF-ß/Smad signaling pathway in cleft palate.

BACKGROUND: The molecular mechanisms of abnormal palatogenesis were investigated in this study. A key regulator, miR-106a-5p, and its target pathway were analyzed. OBJECTIVES: This research is trying to clarify the underlying mechanism of the modulation of miRNA transcription during the formation of cleft palate by 7T and 9.4T NMR metabolomic platforms. METHOD: Differentially expressed miRNAs and mRNAs were analyzed by microarray analysis and verified by qRT-PCR. The protein expression in TGFß signaling pathways were analyzed by Western Blotting. The relationship between miR-106a-5p and TGFß were analyzed by luciferase reporter assay. Cell apoptosis were analyzed by flow cytometer. And finally, the metabonomics were analyzed by NMR and multivariate data analysis models (MVDA). RESULTS: The expression of miR-106a-5p increased in cleft palatal tissue and negatively correlated with the protein level of Tgfbr2. The luciferase assay further proved that the tgfbr2 was a direct target of miR-106a-5p. In another aspect, miR-106a-5p increased apoptosis level in palatal mesenchymal cells, possibly because its inhibition of TGFß signaling pathway. Moreover, low cholesterol and choline levels with high citric acid and lipid levels were observed by 7T and 9.4T NMR metabonomic analysis, which inferred the disorder of cell membrane synthesis in cleft palate formation. Furthermore, transformation from choline to phosphatidylcholine regulated by miR-106a-5p was also disrupted, resulting in phosphatidic choline synthesis disorder and reduced cell membrane synthesis. CONCLUSIONS: The regulatory mechanism of cleft palate was studied at transcriptional and metabolomics levels, which may provide important information in understanding the primary cause of this abnormality.

Multi­organ assessment via a 9.4­Tesla MRS evaluation of metabolites during the embryonic development of cleft palate induced by dexamethasone.

The aim of the present study was to determine the association between maternal metabolism and development of the fetal palate, and to suggest a potential non­invasive prenatal diagnostic method for fetal cleft palate (CP). Dexamethasone (DXM) was used to create a CP mouse model. A 9.4­Tesla (T) magnetic resonance spectroscopy (MRS) imager was used to measure an array of metabolites in the maternal serum, placental tissue, amniotic fluid and fetal palates. Multivariate statistical analysis was performed using SIMCA­P 14.1 software. Following DXM treatment, variations were detected in multiple metabolites in the female mice and their fetuses based on 9.4T MRS. It was indicated that in the experimental group during CP formation, leucine, valine, creatine, acetate and citrate levels in the palatal tissue were lower, whereas lactate, alanine, proline/inositol and glutamate­containing metabolite levels were higher, compared with the levels in the control group. In placental tissue and amniotic fluid, succinate and choline levels were lower in the experimental group. The relative concentrations of cholesterol and lipids in palatal tissues from mice treated with DXM were higher compared with the concentrations in tissues from mice in the control group, with the exception of (CH2)n lipids. In the placental tissue, the alteration in cholesterol level exhibited the opposite trend. Lipid levels for the different lipid forms varied and most of them were unsaturated lipids.

Association Between an Interferon Regulatory Factor 6 Gene Polymorphism and Nonsyndromic Cleft Palate Risk.

Background: Involvement of interferon regulatory factor 6 (IRF6) gene polymorphisms in nonsyndromic cleft palate (NSCP) risk remains controversial. This investigation was performed to evaluate the relationship between IRF6 gene polymorphisms and NSCP risk. Materials and Methods: Two hundred forty-one patients with NSCP (including 103 complete trio families) were recruited, and 242 unaffected individuals were included as controls. Polymorphisms for the IRF6 rs2235371, rs801619, rs642961, rs44844880, and rs8049367 loci were characterized in both groups. Furthermore, eligible studies were identified from the databases through June 1, 2017, and were included in a meta-analysis to enhance the robustness of our conclusions. Results: The IRF6 rs2235371 A allele and AA genotype in the case group were found at higher frequencies than in the control group (A allele: p < 0.0016; AA genotype: p < 0.0049). The IRF6 rs801619 AA genotype and G allele were associated with NSCP risk (G allele: p < 0.0061; AA genotype: p < 0.0195). At the IRF6 rs642961, rs44844880, and rs8049367 loci genotype and allele frequencies were not statistically different between the NSCP group and normal controls. In the meta-analysis, the IRF6 A/G gene polymorphism (rs2235371) and IRF6 A/G gene polymorphism (rs642961) were associated with NSCP risk in the general population, whereas the IRF6 A/C gene polymorphism (rs2013162) was not. Conclusion: The IRF6 A/G gene polymorphisms at rs2235371 and rs642961, but not the IRF6 A/C gene polymorphism rs2013162, were associated with NSCP risk.

Association between SATB2 gene polymorphism and cleft palate only risk in eastern Guangdong population and a meta-analysis.

To characterize the associations between the cleft palate (CPO) and single nucleotide polymorphisms (SNPs) of special AT-rich sequence-binding protein 2 (SATB2). We recruited 241 CPO and performed a case-control study with 242 controls. Concurrently, 103 of the patients and their normal parents were recruited to perform a case-parent trio study. Sixteen selected SNPs were genotyped. Furthermore, A meta-analysis was used to enhance the robustness of our conclusions. The case-control study provided no support for the hypothesis that any of the 16 selected SNPs played a significant role in CPO. In the meta-analysis, we also did not find that the SATB2 was associated with nonsyndromic cleft palate risk, in Asians or in Caucasians. The 16 selected SNPs do not contribute to the development of CPO.