Effective treatment of corticosteroid-induced facial erythema using fractional radiofrequency microneedling.

OBJECTIVES: To investigate the efficacy of Fractional Radiofrequency Microneedling (FRM) in treating corticosteroid-induced facial erythema. METHODS: A retrospective study was conducted involving eight patients diagnosed as corticosteroid-induced facial erythema. Each patient underwent a single session of FRM. Evaluative measures included Clinician's Erythema Assessment (CEA), Patient's Self-Assessment (PSA), assessment of telangiectasia severity, procedure-associated pain (10-point scale), patient satisfaction (3-point scale) and secondary outcomes. RESULTS: The study found a 75% success rate and 100% effectiveness rate in alleviating erythema symptoms. CEA and PSA scores decreased by 67.7% and 78.1%, respectively. No cases of erythema rebound were recorded during the 3-month follow-up period. CONCLUSIONS: FRM demonstrated effectiveness and safety in treating facial erythema, offering promising advancement in dermatologic therapeutics.

The effect of autophagy on hemoporfin-mediated photodynamic therapy in human umbilical vein endothelial cells.

SIGNIFICANCE: Hemoporfin-mediated photodynamic therapy (HMME-PDT) has been recognized as a safe and effective treatment for port wine stain (PWS). However, some patients show limited improvement even after multiple treatments. Herein, we aim to explore the effect of autophagy on HMME-PDT in human umbilical vein endothelial cells (HUVECs), so as to provide theoretical basis and treatment strategies to enhance clinical effectiveness. METHODS: Establish the in vitro HMME-PDT system by HUVECs. Apoptosis and necrosis were identified by Annexin Ⅴ-FITC/PI flow cytometry, and autophagy flux was detected by monitoring RFP-GFP-LC3 under the fluorescence microscope. Hydroxychloroquine and rapamycin were employed in the mechanism study. Specifically, the certain genes and proteins were qualified by qPCR and Western Blot, respectively. The cytotoxicity was measured by CCK-8, VEGF-A secretion was determined by ELISA, and the tube formation of HUVECs was observed by angiogenesis assay. RESULTS: In vitro experiments revealed that autophagy and apoptosis coexisted in HUVECs treated by HMME-PDT. Apoptosis was dominant in early stage, while autophagy gradually increased in the middle and late stage. AMPK, AKT and mTOR participated in the regulation of autophagy induced by HMME-PDT, in which AMPK was positive regulation, while AKT and mTOR were negative regulation. Hydroxychloroquine could not inhibit HMME-PDT-induced autophagy, but capable of blocking the fusion of autophagosomes with lysosome. Rapamycin might cooperate with HMME-PDT to enhance autophagy in HUVECs, leading to increased cytotoxicity, reduced VEGF-A secretion, and weakened angiogenesis ability. CONCLUSIONS: Both autophagy and apoptosis contribute to HMME-PDT-induced HUVECs death. Pretreatment of HUVECs with rapamycin to induce autophagy might enhance the photodynamic killing effect of HMME-PDT on HUVECs. The combination of Rapamycin and HMME-PDT is expected to further improve the clinical efficacy.

A novel heterozygous frameshift mutation in the KRT6A gene responsible for an uncommon phenotype of pachyonychia congenita: One case report and review of literature.

Pachyonychia congenita is an uncommon autosomal dominant skin disorder characterized by hypertrophic nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and cutaneous cysts. And fissured tongue is rarely reported in patients with pachyonychia congenita. The disease is primarily associated with mutations in five keratin genes, namely KRT6A, KRT6B, KRT6C, KRT16 or KRT17. Herein we report a 9-year-old Chinese girl who has thickened nails, keratinized plaques, and fissured tongue since birth. To investigate the underlying genetic cause, whole-exome sequencing and Sanger sequencing were performed in this patient and her family members. We identified a candidate variant c.1460-2_1460del (p.S487Lfs*21) in the KRT6A gene (NM_005554.4) by whole-exome sequencing. Sanger sequencing revealed the absence of the mutation in both parents, indicating that it is a de novo variant. Thus, the novel heterozygous frameshift mutation c.1460-2_1460del (p.S487Lfs*21) within exon 9 of KRT6A was identified as the genetic cause of the patient. Our study identified a rare de novo heterozygous frameshift mutation in the KRT6A gene in a patient with pachyonychia congenita presenting fissured tongue. Our findings expand the KRT6A gene mutation spectrum of Pachyonychia congenita, and will contribute to the future genetic counseling and gene therapy for this disease.

Abrocitinib as a Novel Treatment for Multiple Skin Disorders: 3 Case Reports and a Scoping Review.

Janus kinase (JAK) inhibitors are increasingly being used in dermatology due to their broad potential in managing both local and systemic inflammation. More recently, abrocitinib, an oral JAK 1 inhibitor, has shown promising clinical efficacy in the treatment of various skin disorders beyond moderate to severe atopic dermatitis (AD). We firstly presented three cases, each with diagnosis of pyoderma gangrenosum (PG), livedoid vasculopathy (LV), or hidradenitis suppurativa (HS), and conducted a comprehensive scoping review of the available literature on the use of abrocitinib in the treatment of diverse skin disorders. We summarized a total of 16 skin disorders, including our cases. The results indicated that abrocitinib, whether used as monotherapy or in combination with other treatments, was effective and well-tolerated in these disorders. These findings expanded the range of diseases for which abrocitinib may serve as an alternative therapeutic choice.

Tofacitinib combined with melanocyte protector α-MSH to treat vitiligo through dextran based hydrogel microneedles.

Vitiligo can cause serious damage to the appearance of patients and affect physical and mental health, but there is currently no simple and effective treatment. According to the theory of autoimmune disorder, the separable hydrogel microneedles delivering alpha-melanocyte-stimulating hormone (α-MSH) and tofacitinib were designed to treat vitiligo. This hydrogel microneedles were formed by dextran methacrylate (DexMA) and cyclodextrin-adamantane based host-guest supramolecules (HGSM) through CC double bond polymerization and host-guest assembly. The microneedle tips formed by the double cross-linked hydrogel can pierce the stratum corneum and deliver melanocyte protector α-MSH and JAK inhibitor tofacitinib directly to the epidermis and dermis. Under the treatment of α-MSH/tofacitinib microneedles, massive deposition of melanin in epidermis and hair follicles significantly accelerated skin and hair pigmentation.

Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development.

Background: A keloid is a disease of excessive fibrosis that is characterized by the aberrant proliferation of fibroblasts. However, the molecular mechanisms of fibroblasts during the development of keloids remain unclear. This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts, providing new ideas for the prevention and treatment of keloids. Methods: We utilized bioinformatics tools to analyze data from keloid fibroblasts (KFs) available in the Gene Expression Omnibus (GEO) database to identify the key genes involved in keloid development. Homeobox C6 (HOXC6) emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction, western blot (WB) and immunohistochemistry. Subsequently, the effects of downregulated HOXC6 expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8, flow cytometry, transwell migration and WB assays. Meanwhile, we performed transcriptome sequencing and gene set enrichment analysis (GSEA) to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments. Results: HOXC6 was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs. Downregulation of HOXC6 inhibited proliferation, migration and extracellular matrix (ECM) accumulation and promoted KF apoptosis. GSEA predicted that the hypoxia signaling pathway was associated with HOXC6 in KFs. Transcriptome sequencing suggested that the extracellular regulated protein kinase (ERK) pathway was one of the downstream pathways of HOXC6 in KFs. Our experiments confirmed that hypoxia-inducible factor-1α (HIF-1α) upregulates HOXC6, contributing to KFs proliferation, migration, apoptosis inhibition and collagen accumulation through the ERK signaling pathway. Conclusions: Our findings first revealed that HOXC6 acts as an oncogenic driver in the molecular mechanisms of fibroblasts in keloids. The HIF-1α/HOXC6/ERK axis promotes proliferation, migration and ECM production by KFs, contributing to the progression of keloids. Taken together, HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids.

Podophyllotoxin-combined 5-aminolevulinic acid photodynamic therapy significantly promotes HR-HPV-infected cell death.

BACKGROUND: Human papillomavirus (HPV) infection and related diseases are difficult clinical challenges. The efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating condyloma acuminata is remarkable, with high virus clearance and low recurrence rates. Podophyllotoxin (POD) is the first-line drug with a significant therapeutic effect on condyloma acuminata. However, no studies have determined whether POD-combined ALA-PDT improves high-risk (HR)-HPV-infected cell killing. We aimed to investigate whether POD-combined ALA-PDT could promote HPV-infected cell death more effectively than the single treatment and explore the underlying mechanism. METHODS: In HeLa and SiHa cells, flow cytometry, EdU assay and LDH release test were used to detect apoptosis, cell proliferation change and necrosis, respectively. To investigate whether the combined therapy might activate apoptosis and induce endoplasmic reticulum (ER) stress, flow cytometry was used to determine intracellular levels of ROS and calcium, and Western blotting was used to determine the expression of related proteins. Mitochondrial membrane depolarization was detected by JC-1 assay. Immunofluorescence staining and Western blotting were used to detect the activation of autophagy. RESULTS: Podophyllotoxin -combined ALA-PDT inhibited the proliferation and promoted apoptosis and necrosis more effectively than the single treatment at the same intensity and concentration. The activation of the caspase-dependent apoptosis pathway, ER stress and autophagy was more substantial in POD-combined ALA-PDT than with single treatments. CONCLUSION: Podophyllotoxin -combined ALA-PDT effectively promoted cell death through several pathways in HeLa and SiHa cells. This combination might be a promising therapeutic strategy for the HR-HPV infection.

Safety and effectiveness of 5-aminolevulinic acid photodynamic therapy combined with fractional micro-plasma radio-frequency treatment for verrucous epidermal nevus: A retrospective study with long-term follow-up.

Verrucous epidermal nevus (VEN) is a benign skin disease that seriously affects appearance. Numerous therapeutic methods have been tried with varying results. However, there are few reports on the treatment of VEN by photodynamic therapy (PDT). This study aimed to evaluate the efficacy and adverse effects of 5-aminolevulinic acid (ALA)-PDT in VEN treatment with a long-term follow-up. A total of 16 patients with VEN received ALA-PDT and were followed up for more than 1 year to observe the treatment effects, adverse reactions, and patients' satisfaction. Complete improvement of lesions was observed in 11 patients (three to six sessions of ALA-PDT). Two patients obtained 90-99% improvement (five sessions) and 50-89% improvement in three patients (three to six sessions). They were satisfied with the treatment effects, with an average satisfaction of 4.19/5 (±0.91). Long-term follow-up ranging 14-50 months showed a low recurrence rate (2/16) and no scar left after ALA-PDT. The results demonstrate that ALA-PDT is an effective and safe therapy in treating VEN with mild adverse reactions and a low risk of scar formation.

Circular RNA profiles and the potential involvement of down-expression of hsa_circ_0001360 in cutaneous squamous cell carcinogenesis.

Circular RNAs (circRNAs) act as sponges of noncoding RNAs and have been implicated in many pathophysiological processes, including tumor development and progression. However, their roles in cutaneous squamous cell carcinoma (cSCC) are not yet well understood. This study aimed to identify differentially expressed circRNAs and their potential functions in cutaneous squamous cell carcinogenesis. The expression profiles of circRNAs in three paired cSCC and adjacent nontumorous tissues were detected with RNA sequencing and bioinformatics analysis. The candidate circRNAs were validated by PCR, Sanger sequencing and quantitative RT-PCR in another five matched samples. The biological functions of circRNAs in SCL-1 cells were assessed using circRNA silencing and overexpression, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS), flow cytometry, transwell and colony formation assays. In addition, the circRNA-miRNA-mRNA interaction networks were predicted by bioinformatics. In summary, 1115 circRNAs, including 457 up-regulated and 658 down-regulated circRNAs (fold change ≥ 2 and P < 0.05), were differentially expressed in cSCC compared with adjacent nontumorous tissues. Of four selected circRNAs, two circRNAs (hsa_circ_0000932 and hsa_circ_0001360) were confirmed to be significantly decreased in cSCC using PCR, Sanger sequencing and quantitative RT-PCR. Furthermore, hsa_circ_0001360 silencing was found to result in a significant increase of the proliferation, migration and invasion but a significant decrease of apoptosis in SCL-1 cells in vitro, whereas hsa_circ_0001360 overexpression showed the opposite regulatory effects. hsa_circ_0001360 was predicted to interact with five miRNAs and their corresponding genes. In conclusion, circRNA dysregulation may play a critical role in carcinogenesis of cSCC, and hsa_circ_0001360 may have potential as a biomarker for cSCC.

The clinical efficacy of treatment using the autologous non-cultured epidermal cell suspension technique for stable vitiligo in 41 patients.

Background: Vitiligo is an acquired depigmentation skin disorder mainly caused by the destruction of melanocytes. There are many therapeutic options available for vitiligo, but the options are not uniformly effective.Objectives: This study aimed to explore the clinical effect of the autologous non-cultured epidermal cell suspension (NCES) technique in the treatment of patients with stable vitiligo.Methods: A retrospective study of before-after comparisons was undertaken with 41 patients with stable vitiligo who received treatment with the NCES technique. The percentage of repigmentation area was evaluated using image analysis of the appearance before and 6-9 months after operation.Results: A total of 41 patients (18 males and 23 females) with a duration of clinical stability for ranging from 1 to 10 years (mean 1.6 ± 1.9) were included. The mean age was 20.2 years (range, 8-50) and 4 (9.8%) were children under the age of 14 years. After 6-9 months of follow-up, 80.5% (33/41) of the patients showed good response; among these patients, 17.1% (7/41) showed complete or almost complete repigmentation. Interestingly, all 4 children showed very good response (more than 76% repigmentation). There were no significant differences in the efficacy of treatment between the different transplantation areas of the facial neck, trunk, and distal limbs and there were no adverse effects such as infection or scar formation.Limitation: This study included only a single center with a small sample size.Conclusions: Our study shows that the NCES technique has a high therapeutic effect, is safe for patients with stable vitiligo, and may be a very promising potential option for treating children.

A novel GNAS mutation inherited from probable maternal mosaicism causes two siblings with pseudohypoparathyroidism type 1A.

Objectives Objectives Pseudohypoparathyroidism type 1A (PHP1A) is caused by maternal inheritance of GNAS mutations. It is characterized by the resistance to several hormones, primarily the parathyroid hormone (PTH), and the features of Albright's hereditary osteodystrophy. Case presentation Here, we present a family comprised two affected brothers with PHP1A and identify a novel mutation (c.277C>T) in the GNAS gene. The siblings developed a slightly different presentation in the same clinical condition. Although both patients presented with PTH resistance, which is the hallmark of PHP, the proband showed the thyroid-stimulating hormone resistance with the progression of heterotopic ossification from skin and subcutaneous tissue into deep connective tissue, while the younger brother with normocalcemia did not show the resistance to other hormones. The patients may inherit the mutation from their mother who presumably carries the mutation as a mosaicism. Conclusions Our case highlights the significance of considering mosaicism as an explanation for apparent de novo cases of pseudohypoparathyroidism.

5-aminolevulinic acid photodynamic therapy and excision surgery for nevoid basal cell carcinoma syndrome with multiple basal cell carcinomas and PTCH1 mutation.

This report describes a PTCH1 c.1804C > T (p.Arg602*) mutation causing a Chinese nevoid basal cell carcinoma syndrome (NBCCS) with multiple basal cell carcinoma (BCC) phenotype. Multiple modalities including microwave ablation, photodynamic therapy, and excision surgery have a good respond to the NBCCS. The current results broaden the spectrum of PTCH1 mutations responsible for NBCCS.

Successful clearance of extensive/recalcitrant cutaneous warts by acitretin monotherapy: A case series study.

Most available options for the treatment of warts are limited by the potential for scarring, pain, lack of response, or recurrences, and the patients are often unable to tolerate and accept those experiences. The aim of this study was to evaluate the clinical efficacy and safety of oral systemic acitretin monotherapy in patients with extensive/recalcitrant cutaneous warts. The patients were given a dose of acitretin of 0.8 mg kg-1 day-1 , and the clinical efficacy and safety of acitretin was assessed every 2 weeks for 2 months. A total of 14 patients (12 males and 2 females) were included, with an age of 14-60 years (mean 33 ± 14.7 years) and a course of 4-48 months (mean 21.6 ± 13.4 months). After 2 months of acitretin treatment, 42.9% (6/14) of patients (including warts of the feet, legs, and hands) exhibited complete response, 28.6% (4/14) excellent response, and 28.6% (4/14) good response. All patients demonstrated significant improvement, and the drug was well tolerated, with no patients discontinuing therapy due to side effects. Common mild side effects included dry skin and cheilitis. There were no recurrences during a follow-up period of 6 months. Acitretin monotherapy is an effective, safe, and well-tolerated treatment for patients with extensive/recalcitrant cutaneous warts who are unsuitable for or unwilling to accept traditional treatment methods.

Yes-Associated Protein Promotes the Development of Condyloma Acuminatum through EGFR Pathway Activation.

OBJECTIVE: Investigate the role of Yes-associated protein (YAP1) in the development of condyloma acuminatum (CA). METHODS: We enrolled 30 male patients with CA and 20 healthy individuals as a control group, to compare the YAP1 expression in their tissue samples. Following this, we overexpressed and downregulated YAP1 expression in HaCaT cells to examine the migratory, proliferative, and apoptotic potential of HaCaT cells expressing different levels of YAP1. RESULTS: In the CA patient tissue samples, an increase in YAP1 expression can be observed. In vitro,the overexpression of YAP1 was shown to promote the growth and migration of HaCaT cells and to activate epidermal growth factor receptor (EGFR) pathway-associated proteins, while the downregulation of YAP1 inhibited cell growth and migration of these cells. CONCLUSIONS: YAP1 promotes the growth of keratinocytes in CA through the activation of the EGFR pathway, and it may mediate the development of human papilloma virus-associated diseases.

Photodynamic therapy in a patient with facial angiofibromas due to tuberous sclerosis complex.

The facial angiofbromas due to tuberous sclerosis complex produced significant social and emotional distress for affected individuals, but there is no specific therapeutic strategy up to now. Herein, we report a case of facial angiofibromas successfully treated by 5-aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) with no recurrence for 6 years, thus providing a promising therapeutic option.

Exome sequencing identifies a KRT9 pathogenic variant in a Chinese pedigree with epidermolytic palmoplantar keratoderma.

BACKGROUND: Epidermolytic palmoplantar keratoderma (EPPK) is a rare skin disorder and its pathogenesis and inheritability are unknown. OBJECTIVE: To investigate the inheritance and pathogenesis of EPPK. METHODS: Two EPPK cases occurred in a three-generation Chinese family. Patient-parents trio EPPK was carried out and the identified candidate variants were confirmed by Sanger sequencing. RESULTS: A heterozygous missense pathogenic variant, c.488G > A (p.Arg163Gln), in the keratin (KRT) 9 gene was detected in the proband and his son via targeted exome sequencing, and then validated by Sanger sequencing. This pathogenic variant cosegregated with the EPPK in extended family members, and was predicted to be pathogenic by SIFT, PolyPhen2, PROVEAN, and Mutation Taster. This heterozygous variation was not evident in 100 healthy controls. CONCLUSION: This report describes a KRT9 c.488G > A (p.Arg163Gln) variant causing a diffuse phenotype of Chinese EPPK. The current results broaden the spectrum of KRT9 pathogenic variants responsible for EPPK and have important implications for molecular diagnosis, treatment, and genetic counseling for this family.

Two de novo GJA1 mutation in two sporadic patients with erythrokeratodermia variabilis et progressiva.

BACKGROUND: Erythrokeratodermia variabilis et progressiva (EKVP, OMIM 133200) is a rare hereditary disorder characterized by varies from transient, fast moving erythema to persistent brown hyperkeratotic plaques. Recently, mutations in the genes gap junction alpha 1 gene (GJA1), GJB3, and GJB4 have been reported to cause EKVP. Here, we report the identification of two de novo missense mutations in the GJA1 gene in two unrelated individuals with EKVP. METHODS: The patients and his family members were subjected to mutation detection in the candidate gene GJA1, GJB3, and GJB4 by Sanger sequencing. The expression of connexin (Cx) 43 was detected by immunohistochemistry and immunofluorescence (IF) studies in the lesions. RESULTS: A 12-year-old boy presented with multiple hyperkeratotic plaques on the face, neck, elbows, wrists, limbs, knees, inguinal region, hands, and feet. A 7-year-old girl presented with symmetrical erythematous, plaques on the hands, feet, wrists, and ankles. A novel heterozygous missense mutation c.848C > T (p.P283L) in exon 2 of the GJA1 gene was identified in both patients. A novel heterozygous missense mutation c.869C > A (p.T290N) in exon 2 of the GJA1 gene was also identified in the boy. These mutations were not found in the unaffected family members and 100 normal controls. In the patients' lesions, Cx43 protein was located to the cytomembrane and cytoplasm in the stratum corneum, and granular layer. Compound heterozygous mutations in the boy showed a more severe clinical phenotype and cytoplasmic mislocalization. CONCLUSIONS: The novel mutations c.848C > T (p.P283L) and c.869C > A(p.T290N) arose de novo and were considered as the cause of two Chinese EKVP. GJA1 P283L and T290N mutations lead to Cx43 protein cytoplasmic mislocalization. Our finding expands the mutant spectrum of GJA1 gene and adds new understanding of the genotype-phenotype correlation.

Study on the psychological health and related risk factors in 245 patients with psoriasis in Inner Mongolia.

To investigate the psychological health and related risk factors in patients suffering from psoriasis. A total of 245 inpatients and outpatients with psoriasis were selected from January 2014 to December 2015. Patients with psoriasis were assessed a homemade questionnaire as well as the Psoriasis Area and Severity Index (PASI), Selfrating Anxiety Scale, Self-rating Depression Scale, Trait Coping Style Questionnaire and Social Avoidance and Distress Scale.Differences in sex, age, marital status, type of medical payment, occupation, economic situation, disease severity, and type of psychological state of psoriasis patients were significant, there was no significant difference in psychological health between psoriasis patients with different levels of educational attainment. Scores for anxiety, depression, social avoidance, and social distress were positively correlated with disease severity and negative-coping scores, but a significant negative correlation was observed with scores for social support and positive coping. Stepwise regression analysis of factors influencing psychological health showed that total social support and negative-coping scores could explain 65.2% of the variation. Patients with psoriasis can suffer from anxiety, depression, social distress, and social avoidance. Physicians should pay greater attention to deterioration in mental health of psoriasis patients.