Genetic insight into putative causes of xanthelasma palpebrarum: a Mendelian randomization study.

Xanthelasma palpebrarum (XP) is the most common form of cutaneous xanthoma, with a prevalence of 1.1%~4.4% in the population. However, the cause of XP remains largely unknown. In the present study, we used Mendelian randomization to assess the genetic association between plasma lipids, metabolic traits, and circulating protein with XP, leveraging summary statistics from large genome-wide association studies (GWAS). Genetically predicted plasma cholesterol and LDL-C, but not HDL-C or triglyceride, were significantly associated with XP. Metabolic traits, including BMI, fasting glucose, type 2 diabetes, systolic and diastolic blood pressure, were not significantly associated with XP. Furthermore, we found genetically predicted 12 circulating proteins were associated with XP, including FN1, NTM, FCN2, GOLM1, ICAM5, PDE5A, C5, CLEC11A, CXCL1, CCL2, CCL11, CCL13. In conclusion, this study identified plasma cholesterol, LDL-C, and 12 circulating proteins to be putative causal factors for XP, highlighting the role of plasma cholesterol and inflammatory response in XP development.

Treatment of Discoid Lupus Erythematosus with Upadacitinib: A Case Report.

Cutaneous lupus erythematosus (CLE) is a group of diseases within the spectrum of lupus that primarily manifests with skin lesions. Discoid lupus erythematosus (DLE) is the most common subtype of CLE. Currently, there is no specific medication available for the treatment of CLE. Here, we reported the efficacy and safety of upadacitinib, a JAK1 selective inhibitor, in treating one DLE patient for 28 weeks. Upadacitinib 15mg QD alone improved DLE lesions significantly, while reduction of the drug to 15mg QOD led to a relapse of the skin lesions. Upadacitinib showed favorable safety in this DLE patient in the 28-week period, except for acne, which was controlled by topical application of benzoyl peroxide gel. In this case, we observed rapid and sustained improvement of DLE lesions using upadacitinib with favorable safety, which provided the opportunity to use upadacitinib as an alternative therapy for DLE.

The effectiveness and safety of dupilumab in the management of refractory prurigo nodularis in 45 Chinese patients: A real-life observational study.

Prurigo nodularis (PN) is a chronic, pruritic inflammatory skin disease characterized by severe skin itching and hyperkeratotic nodules. The existing treatment options for PN are limited by severe adverse effects. Dupilumab is an approved biological agent for treating atopic dermatitis and other type 2 inflammatory diseases in adults, showing good efficacy and safety in clinical trials. Recently, dupilumab has shown remarkable effects in patients with PN, but the data on Chinese patients are limited. This study aimed to evaluate the safety and efficacy of dupilumab to treat atopic and nonatopic PN in 45 Chinese patients. To our knowledge, this is the largest cohort to date to evaluate the safety and efficacy of dupilumab to treat atopic and nonatopic PN. To achieve this, 45 patients with PN from the department of dermatology of several Grade A hospitals in Shenzhen, China, were treated with off-label prescription dupilumab. We followed-up the patients on weeks 8 and 16, and the pruritus symptoms, changes in lesion color and area, and the quality of sleep and life were evaluated before and after treatment using the Pruritus Peak Numeric Rating Scale (PP-NRS, 0-10), the Dermatology Life Quality Index/Children's Dermatology Life Quality Index (DLQI/CDLQI, 0-30), and the Investigator's Global Assessment Scales for Stage and Activity (IGA/IGAa, 0-4) at weeks 2, 4, 8, 12, and 16. Total serum immunoglobin E and eosinophilic granulocyte levels were the main laboratory indices for patient evaluation. During treatment, the skin lesions and itching symptoms of these 45 patients were relieved remarkably within 2 weeks. All the PP-NRS, DLQI/CDLQI, and IGA/IGAa scores significantly improved from the baseline to 16-week dupilumab treatment (P < 0.001 for all scores) and no adverse events were reported.

A Case of Giant Perianal Condylomata Acuminata with IgA Nephropathy Treated Successfully by a Topical Chinese Medicine Preparation Paiteling.

Giant condylomata acuminata (a sexually transmitted disease caused by HPV infection) currently is treated in many methods. Surgery, the mainstay treatment of giant condylomata acuminata, may cause a high cost or scar formation. It is important to explore effective and safe treatment options. Although the external treatment of traditional Chinese medicine treatment of condyloma acuminatum has not been widely used, in our case, the use of traditional Chinese medicine successfully treated a perianal giant condyloma acuminatum patient who also suffered from mixed hemorrhoid and IgA nephropathy meanwhile. The treatment process was simple and the effect obvious. There was no recurrence more than 10 months after treatment finished, and the patients felt safe, comfortable and highly coordinated. The outcome of this case suggests that the traditional Chinese medicine might be considered as a mild and effective option for the treatment of giant condyloma acuminatum.

Novel nanofibrous membrane-supporting stem cell sheets for plasmid delivery and cell activation to accelerate wound healing.

The integration of biomaterials with cells for high overall performances is vitally important in tissue engineering, as scaffold-free cell sheet lacks enough mechanical performance and cell viability while cell-free scaffold possesses limited biological functions. In this study, we propose a new strategy to strengthen cell sheets and enhance cell activity for accelerating wound healing based on a novel sandwich structure of cell sheet-plasmid@membrane-cell sheet (CpMC). Specifically, the CpMC contains two adipose-derived stem cell (ADSC) sheets on outer surfaces and an electrospun gelatin/chitosan nanofibrous membrane (NFM) encapsulating vascular endothelial growth factor (VEGF) plasmids in between. The physicochemical properties of NFM including swelling, stiffness, strength, elasticity, and biodegradation can be tailored by simply adjusting the ratio between gelatin and chitosan to be 7:3 which is optimal for most effectively supporting ADSCs adhesion and proliferation. The swelling/biodegradation of NFM mediates the sustained release of encapsulated VEGF plasmids into adjacent ADSCs, and NFM assists VEGF plasmids to promote the differentiation of ADSCs into endothelial, epidermal, and fibroblast cells, in support of the neoangiogenesis and regeneration of cutaneous tissues within 2 weeks. The proposed membrane-supporting cell sheet strategy provides a new route to tissue engineering, and the developed CpMC demonstrates a high potential for clinical translation.

Risk Information Seeking Behavior in Disaster Resettlement: A Case Study of Ankang City, China.

In 2011, the Chinese government launched a disaster mitigation and preparedness program called the Resettlement of South Shaanxi (RSS). Due to the wide geographical scope and complex interests, the possibility of conflicts was increased during and after resettlement. Efficient risk communication improves the supply of information about risks and meets the risk-related information needs of individuals. Using the risk information seeking and processing (RISP) model, this research applied a structural equation model and survey with a structured questionnaire to study ways to improve risk communication in disaster resettlement. A total of 616 valid questionnaires were provided by study respondents in resettlement sites in Ziyang County, Ankang City, Shaanxi Province. The results indicated the following: (1) the public's information seeking behavior relies more on village committees and village officials than other channels. Emerging information channels, such as Weibo and WeChat (social media applications in China), do not play leading roles in disseminating risk information. (2) There are differences between the information channels used by residents and the channels that residents believe the most. (3) Relevant channel beliefs, information sufficiency, perceived hazard characteristics, and self-efficacy directly influence risk information seeking behavior. However, the capacity to gather information has non-significant direct influences on information seeking behavior. (4) Perceived hazard characteristics and self-efficacy drive risk information seeking behavior in both direct and indirect ways through information sufficiency.

MicroRNA-429 inhibits cancer cell proliferation and migration by targeting the AKT1 in melanoma.

MicroRNAs (miRNAs; miR) have been proven to act as both oncogenes and tumor suppressors. However, the mechanism of action of miR429 in melanoma cells remains to be elusive. The present study aims to explain the functional role and mechanism of miR429 in the pathogenesis of melanoma. In our study, we have demonstrated that has-miRNA429 (miR429) is a tumor suppressor in melanoma cells. Luciferase reporter assays demonstrated that the overexpression of miR429 reduced the transcriptional activity of AKT serine/threonine kinase 1 (AKT1). Furthermore, the results showed that the mRNA and protein expression levels of AKT1 were downregulated in the melanoma cell lines when miR429 was overexpressed according to qRT-PCR and western bolt, indicating MicroRNA-429 may directly target AKT1 in melanoma. In vivo, overexpression miR-429 could obviously enhance the inhibition effect of tumor size and weight in the nude mice. Taken together, our findings suggest that novel miR429-regulated pathway may serve as new insights into melanoma oncogenesis and metastasis.

The generation and functional characterization of induced pluripotent stem cells from human intervertebral disc nucleus pulposus cells.

Disc degenerative disease (DDD) is believed to originate in the nucleus pulposus (NP) region therefore, it is important to obtain a greater number of active NP cells for the study and therapy of DDD. Human induced pluripotent stem cells (iPSCs) are a powerful tool for modeling the development of DDD in humans, and have the potential to be applied in regenerative medicine. NP cells were isolated from DDD patients following our improved method, and then the primary NP cells were reprogramed into iPSCs with Sendai virus vectors encoding 4 factors. Successful reprogramming of iPSCs was verified by the expression of surface markers and presence of teratoma. Differentiation of iPSCs into NP-like cells was performed in a culture plate or in hydrogel, whereby skin fibroblast derived-iPSCs were used as a control. Results demonstrated that iPSCs derived from NP cells displayed a normal karyotype, expressed pluripotency markers, and formed teratoma in nude mice. NP induction of iPSCs resulted in the expression of NP cell specific matrix proteins and related genes. Non-induced NP derived-iPSCs also showed some NP-like phenotype. Furthermore, NP-derived iPSCs differentiate much better in hydrogel than that in a culture plate. This is a novel method for the generation of iPSCs from NP cells of DDD patients, and we have successfully differentiated these iPSCs into NP-like cells in hydrogel. This method provides a novel treatment of DDD by using patient-specific NP cells in a relatively simple and straightforward manner.

Langerhans cell histiocytosis in adults: a case report and review of the literature.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a proliferative disease of histiocyte-like cells that generally affects children. Immunohistochemistry is essential to obtain the correct diagnosis, and treatment protocols are controversial. OBJECTIVE: Langerhans cell histiocytosis (LCH) is easy to be misdiagnosed because of its various clinic features and laboratory results. This research focused on the clinicopathological, histopathological, immunohistochemical and other features of LCH and aimed to analyze LCH clinical features for improving diagnosis and decreasing misdiagnosis rate. CASE REPORT: A case of rare adult LCH was reported and the clinicopathological features were summarized by literature review. The multifocal form of this case includes diabetes insipidus, exophthalmos and mucocutaneous lesions in axillae and anogenital regions, such as infiltrated nodules, extensive coalescing, scaling, crusted papules and ulcerated plaques. The Langerhans cells diffusely infiltrated in the dermis and the tumor cells were positive for CD1a and S-100 expression. The diagnosis was Langerhans cell histiocytosis based on the pathological and immunohistochemical changes. CONCLUSION: LCH has high rate of misdiagnosis and definitive diagnosis depends on pathological biopsy and X-ray examination. The prognosis is related to the onset age and the quantity of affected organs. Although specific therapeutic approach hasn't been well established, combined chemotherapy for multisystem lesions and surgical operation or radiotherapy for unifocal lesions may improve the therapy.

Characterization of Sporothrix schenckii by random amplification of polymorphic DNA assay.

OBJECTIVES: To investigate the DNA polymorphism of Sporothrix schenckii (S. schenckii) and to find the relationship between DNA patterns and geographic areas and clinical manifestations. METHOD: The total DNA was extracted with hexadecyltrimethyl-ammonium bromide. Random Amplification of Polymorphic DNA (RAPD) assay was used to study DNA typing of 24 strains of S. schenckii collected from different areas and isolated from different clinical types. RESULTS: Of seven random primers used, three primers (OPAA11, OPD18 and OPB07) gave good reactions, the sequences of which were 5'-ACCCGACCTG-3', 5'-GAGAGCCAAC-3', 5'-GGTGAC~GCAG-3' respectively. The RAPD patterns of the 24 isolates were not completely identical, showing certain degrees of hereditary variability. Different isolates showed a common conserved DNA band with the same primer. Different clinical types showed different genotypes. CONCLUSION: RAPD analysis is useful in DNA typing of S. schenckii, the DNA band type of which is related to geographic origin and Clinical manifestation.