Increased regulatory T cells and eosinophils characterize atopic dermatitis-like graft-versus-host disease compared with lichen planus-like graft-versus-host disease.

BACKGROUND: Graft-versus-host disease (GVHD) has various cutaneous manifestations. Little is known about the mechanisms of cutaneous GVHD with different clinical features. OBJECTIVE: To characterize the immunologic features and skin barrier functions of cutaneous GVHD. METHODS: The study included 19 patients with atopic dermatitis (AD)-like GVHD, 8 with lichen planus (LP)-like GVHD, 24 with AD, and 15 healthy controls. The subpopulation of T cells in peripheral blood and skin lesions was measured by flow cytometry and immunofluorescence, respectively. Filaggrin expression in skin lesions was measured by Western blot and immunohistochemistry. Transepidermal water loss was also measured using Tewameter TM 300 (Courage & Khazaka Electronic GmbH, Köln, Germany). RESULTS: The number of peripheral blood eosinophils in AD-like GVHD was significantly higher than that in LP-like GVHD. Type 2 helper T cells in peripheral blood and skin lesions were increased in AD-like GVHD and LP-like GVHD. Regulatory T cells in peripheral blood and skin lesions were increased in AD-like GVHD. Filaggrin expression and transepidermal water loss were increased in skin lesions of AD-like GVHD and LP-like GVHD. LIMITATIONS: The number of patients is limited. CONCLUSION: Although AD-like GVHD and LP-like GVHD both had elevated type 2 helper T cells and impaired skin barrier, increased eosinophils and regulatory T cells were found only in AD-like GVHD.

Alternations in the human skin, gut and vaginal microbiomes in perimenopausal or postmenopausal Vulvar lichen sclerosus.

Vulvar lichen sclerosus (VLS) is a chronic and progressive dermatologic condition that can cause physical dysfunction, disfigurement, and impaired quality of life. However, the etiology of VLS remains unknown. The vulvar skin, intestinal and vaginal microbiomes have been postulated to play important roles in the pathogenesis of this disease. The aim of this study was to compare the compositional characteristics of the vulvar skin, vagina, and gut microbiota between perimenopausal or postmenopausal VLS patients and healthy controls. The study involved six perimenopausal or postmenopausal VLS patients which were based on characteristic clinical manifestations and histologic confirmation and five healthy controls. The pruritus severity of each patient was evaluated using the NRS scale, and the dermatology-specific health-related quality of life was assessed using the Skindex-16. Metagenomic sequencing was performed, and the results were analyzed for alpha and beta diversity. LEfSe analysis were used to investigate the microbial alterations in vulvar skin, gut and vagina. KEGG databases were used to analyze differences in functional abundance. The study found significant differences in alpha diversity between the two groups in stool and vaginal samples (P < 0.05). Patients with VLS had a higher abundance of Enterobacter cloacae, Flavobacterium_branchiophilum, Mediterranea_sp._An20, Parabacteroides_johnsoniiand Streptococcus_bovimastitidis on the vulvar skin, while Corynebacterium_sp._zg-913 was less abundant compared to the control group. The relative abundance of Sphingomonas_sp._SCN_67_18, Sphingobium_sp._Ant17, and Pontibacter_sp_BT213 was significantly higher in the gut samples of patients with VLS.Paenibacillus_popilliae,Gemella_asaccharolytica, and Coriobacteriales_bacterium_DNF00809 compared to the control group. Additionally, the vaginal samples of patients with VLS exhibited a significantly lower relative abundance of Bacteroidales_bacterium_43_8, Bacteroides_sp._CAG:20, Blautia_sp._AM28-10, Fibrobacter_sp._UWB16, Lachnospiraceae_bacterium_AM25-39, Holdemania_filiformis, Lachnospiraceae_bacterium_GAM79, and Tolumonas_sp. Additionally, the butyrate-producing bacterium SS3/4 showed a significant difference compared to the controls. The study found a negative relationship between Sphingobium_sp._Ant17 in stool and Skindex-16 (P < 0.05), while Mediterranea_sp._An20 had a positive correlation with Skindex-16 (P < 0.05) in the skin. Additionally, our functional analysis revealed alterations in Aminoacyl_tRNA_biosynthesis, Glutathione_metabolism, the pentose phosphate pathway, and Alanine__aspartate_and_glutamate_metabolism in the VLS patient group. The study suggests that perimenopausal or postmenopausal patients with VLS have a modified microbiome in the vulvar skin, gut, and vagina. This modification is linked to abnormal energy metabolism, increased oxidative stress, and abnormal amino acid metabolism.

Squamous Cell Carcinoma of the Nail Unit After Trauma: A Case Report.

Squamous cell carcinoma of the nail unit (SCCNU) is a relatively uncommon tumor with a low rate of metastasis. SCCNU presents with nonspecific symptoms and signs, it is frequently misdiagnosed by dermatologists or surgeons. We report a patient with right-hand ring subungual squamous cell carcinoma who received inappropriate treatment due to a long-term misdiagnosis following trauma. This patient had been treated with acitretin combined with cefaclor, and a certain curative effect was seen, but finally, wide local excision was performed.

Mixed porokeratosis with a novel mevalonate kinase gene mutation: A case report.

BACKGROUND: Porokeratosis is a rare, acquired, or inherited disorder of keratinization. There are numerous clinical types of porokeratosis and they can coexist in one patient and multiple members of an affected family. However, coexistence of disseminated superficial actinic porokeratosis (DSAP) and porokeratosis ptychotropica (Ppt) is rare. CASE SUMMARY: A 45-year-old man presented with long-standing skin lesions. Physical examination identified numerous small, brown 2-mm to 4-mm patches on his face and several hyperkeratotic, verrucous plaques on his trunk and extremities. His father and one of his brothers also had similar lesions for years. Skin biopsies indicated a cornoid lamella in the epidermis. We identified c.155G>A mutation in the mevalonate kinase (MVK) gene, which converted a serine residue to asparagine (p.Ser52Asn) and was causative for porokeratosis in this family. A clinicopathologic diagnosis of DSAP and Ppt with a novel MVK gene mutation was made. The hyperkeratotic plaques on the patient's scrotum were completely removed more than 10 times using a microwave knife. CONCLUSION: An unusual case of DSAP coexisting with Ppt harbored a novel MVK gene mutation also present in the patient's family.

Trichilemmal Carcinoma of the Scalp in a Young Female: A Case Report.

Trichilemmal carcinoma (TC) is a rare malignant cutaneous adnexal neoplasm originating from the outer root sheath of hair follicles, which occurs commonly in sun-exposed areas of the elderly. Here, we introduce a case of a 24-year-old woman with TC on her scalp.

Cutaneous Metastasis from Lung Adenocarcinoma.

Cutaneous metastases are rare and often portend the aggressive malignancy and poor prognosis. We report a case of a 62-year-old man with a rapidly growing nodule on the left back for 2 months. The patient was diagnosed with lung adenocarcinoma shortly before the skin lesion presented. Physical examination showed a dome-shaped purplish red nodule, with ulceration and hemorrhagic crust. Excision of the skin lesion was performed, and the histopathology showed tumor cells infiltrate with immunohistochemistry (TTF-1+CK7+CD20-) favoring primary lung adenocarcinoma.

Secondary Intention Healing of Nasal Ala and Tip Defects: A Simple and Valuable Treatment Option.

Purpose: To investigate the cosmetic outcomes of secondary intention healing of small (<1.5cm) nasal ala and tip defects. Patients and Methods: From August 2017 to October 2020, 42 patients with nasal reconstructions using secondary intention healing were included. Defects after excision ranged from 0.5cm×0.7cm to 1.2cm×1.5cm in size. Foam dressing covering the wounds was changed every 3 to 5 days. Wound esthetic outcomes were graded as excellent, good, acceptable, and poor based on definitions described in the literature. Results: All 42 wounds healed in 3 to 4 weeks, with uniform color, no obvious adverse reactions and high patient satisfaction. Esthetic evaluation: 16 excellent cases (38.1%), 19 good cases (45.2%), 7 acceptable cases (16.7%) and 0 poor cases. Conclusion: Secondary intention healing of small nasal tip and ala defects in Chinese yielded satisfactory esthetic outcomes and should be an integral part of the surgeon's reconstructive algorithm.

Bullous Pilomatricoma After Influenza Vaccination.

Pilomatricoma, also known as "benign calcifying epithelioma", is an uncommon slow-growing benign adnexal skin tumor, which originates from primitive cells of the hair matrix and usually appears as a solitary, firm, and asymptomatic nodule beneath the skin. Bullous pilomatricoma is a rare form of pilomatricoma, always presenting with firm subcutaneous nodules with a bullous appearance. In this study, we report a 9-year-old Chinese presenting girl with bullous pilomatricoma after influenza vaccination.

Autosomal recessive monilethrix: Novel variants of the DSG4 gene in three Chinese families.

BACKGROUND: Monilethrix is a rare hereditary hair loss disorder characterized by hair fragility and beaded hair shaft alterations. Monilethrix is classically inherited in an autosomal dominant (AD) fashion caused by variants in the hair keratin genes KRT81, KRT83, or KRT86. Interestingly, an autosomal recessive (AR) form of monilethrix with variants in DSG4 gene has also been reported in recent years. OBJECTIVE: To identify causative variants in Chinese patients with autosomal recessive (AR) form of monilethrix. METHODS: Three families with AR form of monilethrix were observed and sequence variant analysis of DSG4 was performed by polymerase chain reaction (PCR), quantitative real-time PCR, and DNA sequencing. RESULTS: All the patients had sparse, fragile hair involving the scalp, eyebrows, and eyelashes with keratotic follicular papules and pruritus since birth. Atypical-beaded hairs and broken hair shaft fragments were identified in all the patients under dermoscopy. Heterozygous variants c.837del and c. 2389C > T, a homozygous splice site variant c.2355 + 1G > A, and a homozygous 48,644 bp large deletion variant g.31381440_31430084del in the DSG4 gene were identified and verified in the families. CONCLUSION: This report provided further evidence for the phenotypic spectrum and clinical features of, and the expanded variant database of AR form of monilethrix.

LncRNA UCA1 negatively regulates NF-kB activity in psoriatic keratinocytes through the miR125a-A20 axis.

Psoriasis is one of the most common chronic inflammatory skin diseases that affects approximately 3% of the world's population. Hyper proliferation, infiltration of inflammatory cells and aberrant differentiation of keratinocytes are the three most important characteristics of psoriasis. Previous reports showed that NF-κBis the crucial mediator linking psoriatic keratinocytes and immune cell states through its effects on chemokine and cytokine production. To identify the role of NF-κB in psoriasis, we conducted ELISA assay to detect the activity of NF-κB in lesional skin and nonlesional skin of patients with psoriasis. Mounting evidence suggests that the interaction between long noncoding RNAs (lncRNAs) and microRNAs plays important role in the regulation of the initiation and development of various diseases. In this article, we identified that lncRNA UCA1 was down-regulated in lesional skin of patients with psoriasis. Further studies showed that lncRNA UCA1 could promote the expression of A20 by inhibitingmiR125a, and up-regulated A20 decreased the activity of NF-κB through its ubiquitin editing function. Taken together, we identified and demonstrated that lncRNA UCA1 negatively regulated NF-κB activity in psoriasis through the miR125a-A20 axis.

Highly efficient treatment of textile dyeing sludge by CO2 thermal plasma gasification.

Textile dyeing sludge is complex hazardous material with increasing amount year by year, and the conventional treatment techniques are limited by many drawbacks such as water/soil contamination, incomplete degradation of hazardous organics or inefficient fixation of toxic heavy metals. This work reported the first example of thermal plasma gasification treatment of textile dyeing sludge in a homemade rotating arc plasma reactor, which not only significantly reduced the volume and eliminated the safety risk of textile dyeing sludge, but also produced valuable syngas that can be used for chemical industry. At a feed rate of 36 g/min and a CO2 flow rate of 0.43 Nm3/h (14.08 g/min), the carbon conversion efficiency of gasification was 99.9%; and the energy conversion efficiency could reach 71.8%; and the lower heating value of syngas-rich produced gas was 8.91 MJ/Nm3. At the same time, the volume reduction ratio of sludge was 41.19% and the fixing efficiency of the heavy metals in solid products reached above 99%. Toxicity characteristic leaching procedure confirmed the solid products were harmless in a wide environmental pH range. The proposed method exhibits its great potential of simultaneously realizing harmless, minimization and reclamation of textile dyeing sludge and even other hazardous solid waste.

[Primary culture and identification of adult dermal fibroblasts].

Objective To establish a method for primary culture of adult dermal fibroblasts. Methods Fresh skin tissues were digested with dispase II to separate the epidermis from dermis. Then fibroblasts were isolated from the dermis by tissue-adhesive and type I collagenase digestion method respectively. The growth of cells was observed under an inverted phase contrast microscope. the expression of vimentin in cultured cells was detected by immunofluorescence cytochemical staining to identify cell type and assess the purity of fibroblasts. The proliferation activity of fibroblasts was analyzed by MTT assay and drew growth curve. Cell cycle distribution was detected by flow cytometry. Results The fibroblasts were cultured for 48 hours, and more than 95% adherent cells were obtained by collagen protease separation. At the same time, the cells began to grow from the adherent wall at the edge of the tissue block. A large number of fibroblasts adherently grew on day 5. The cells grew rapidly, and on day 7, the layers of proliferating cells were covered in petri dishes. A small number of epithelial cells were mixed in fibroblasts obtained from the tissue-adhesive method, while the vimentin positive rate of cells isolated by collagenase digestion method was nearly 100%, almost all of which were fibroblasts. Conclusion Both collagenase digestion and tissue-adhesive method are rapid, economical and effective methods for obtaining dermal fibroblasts. Collagenase digestion method can prevent epithelial cell contamination more effectively, and the isolated dermal fibroblasts have good proliferative capacity.

Author Correction: Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis.

This corrects the article DOI: 10.1038/ncomms7793.

Atopic Dermatitis-like Graft-versus-host Disease and Lichen Planus-like Graft-versus-host Disease: Alterations in Skin Barrier Function and Related Molecules.

BACKGROUND: Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Skin barrier disruption could induce thymic stromal lymphopoietin (TSLP) expression, and the expression of TSLP was increased in lesions of atopic dermatitis (AD)-like GVHD and lichen planus (LP)-like GVHD. This study attempted to investigate the skin barrier function of AD-like GVHD and LP-like GVHD and possible mechanisms. METHODS: Eighteen AD-like GVHD patients, 12 LP-like GVHD patients, and 14 healthy volunteers were enrolled in this study. Skin biopsy was done in five AD-like GVHD patients, eight LP-like GVHD patients, and eight healthy volunteers. The intensity of pruritus was assessed by visual analog scale itch score and detailed pruritus score. Transepidermal water loss (TEWL) was measured using Tewameter® TM 300. Immunohistochemistry was used to observe the expression of loricrin, involucrin, LL37, and human ß-defensins 2 (hBD2) in skin lesions. Western blot analysis was used for analyzing the protein levels of loricrin and involucrin in skin lesions. Real-time polymerase chain reaction was performed to assess the mRNA levels of LL37 and hBD2 in skin lesions. RESULTS: Pruritus score was higher in patients with AD-like GVHD (11.33 ± 5.35) than that of patients with LP-like GVHD (2.58 ± 3.09, P< 0.001). Compared with healthy controls (HCs, 4.52 ± 1.24 g·m-2·h-1), TEWL was increased in AD-like GVHD (26.72 ± 9.02 g·m-2·h-1, P < 0.001) and LP-like GVHD patients (18.78 ± 4.57 g·m-2·h-1, P< 0.001), and expressions of loricrin and involucrin were also increased in skin lesions of AD-like GVHD and LP-like GVHD patients (all P< 0.05). LL37 mRNA expression was decreased in lesions of AD-like GVHD and LP-like GVHD patients (P = 0.005 and P = 0.008, vs. HCs, respectively). hBD2 mRNA expression was increased in skin lesions of AD-like GVHD and LP-like GVHD patients (P = 0.002 and P< 0.001, vs. HCs, respectively). CONCLUSIONS: Skin barrier dysfunction is present in AD-like GVHD and LP-like GVHD. The immunoreactions, but not the congenital defect, are considered to be the primary cause of skin barrier impairment in AD-like GVHD and LP-like GVHD.

Novel Mutations in PSENEN Gene in Two Chinese Acne Inversa Families Manifested as Familial Multiple Comedones and Dowling-Degos Disease.

BACKGROUND: Acne inversa (AI), also called hidradenitis suppurativa, is a chronic, inflammatory, recurrent skin disease of the hair follicle. Familial AI shows autosomal-dominant inheritance caused by mutations in the γ-secretase genes. This study was aimed to identify the specific mutations in the γ-secretase genes in two Chinese families with AI. METHODS: In this study, two Chinese families with AI were investigated. All the affected individuals in the two families mainly manifested with multiple comedones, pitted scars, and a few inflammatory nodules on their face, neck, trunk, axilla, buttocks, upper arms, and thighs. Reticulate pigmentation in the flexures areas resembled Dowling-Degos disease clinically and pathologically. In addition, one of the affected individuals developed anal canal squamous cell carcinoma. Molecular mutation analysis of γ-secretase genes including PSENEN, PSEN1, and NCSTN was performed by polymerase chain reaction and direct DNA sequencing. RESULTS: Two novel mutations of PSENEN gene were identified, including a heterozygous missense mutation c.194T>G (p.L65R) and a splice site mutation c.167-2A>G. CONCLUSIONS: The identification of the two mutations could expand the spectrum of mutations in the γ-secretase genes underlying AI and provide valuable information for further study of genotype-phenotype correlations.

Whole-exome SNP array identifies 15 new susceptibility loci for psoriasis.

Genome-wide association studies (GWASs) have reproducibly associated ∼40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P<5.00 × 10(-08)). In addition, we also replicate four known susceptibility loci TNIP1, NFKBIA, IL12B and LCE3D-LCE3E. These susceptibility variants identified in the current study collectively account for 1.9% of the psoriasis heritability. The variant within AIM2 is predicted to impact protein structure. Our findings increase the number of genetic risk factors for psoriasis and highlight new and plausible biological pathways in psoriasis.

Preparation of natural alpha-tocopherol from non-alpha-tocopherols.

Non-alpha-tocopherols are hydroxymethylated and hydrogenated to produce alpha-tocopherol in one pot process by simultaneously reacting with paraformaldehyde and hydrogen in the presence of catalysts of benzenesulfonic acid and 5% Pd/C in an autoclave. Effects of various operation conditions have been studied. The preferable reaction conditions are: temperature 180 degrees C to 200 degrees C, pressure 5.0 MPa, acid concentration 0.5 g/100 ml ethanol, mass ratio of Pd/C to tocopherols 7.1 g/100 g, and reaction time 5.0 h. A product with alpha-tocopherol content of 80% was obtained by using a raw material with a total tocopherols content of 80.54%. The conversion of non-alpha-tocopherols is almost 100%, and the mole yield of alpha-tocopherol is more than 90%.

A large-scale screen for coding variants predisposing to psoriasis.

To explore the contribution of functional coding variants to psoriasis, we analyzed nonsynonymous single-nucleotide variants (SNVs) across the genome by exome sequencing in 781 psoriasis cases and 676 controls and through follow-up validation in 1,326 candidate genes by targeted sequencing in 9,946 psoriasis cases and 9,906 controls from the Chinese population. We discovered two independent missense SNVs in IL23R and GJB2 of low frequency and five common missense SNVs in LCE3D, ERAP1, CARD14 and ZNF816A associated with psoriasis at genome-wide significance. Rare missense SNVs in FUT2 and TARBP1 were also observed with suggestive evidence of association. Single-variant and gene-based association analyses of nonsynonymous SNVs did not identify newly associated genes for psoriasis in the regions subjected to targeted resequencing. This suggests that coding variants in the 1,326 targeted genes contribute only a limited fraction of the overall genetic risk for psoriasis.