Coexistence of Malassezia Species and Microsporum canis in the Lesions of Adult with Tinea Capitis.

Tinea capitis, primarily caused by dermatophytes such as Trichophyton and Microsporum species, is a superficial fungal infection affecting the scalp and hair, commonly observed in prepubertal children but rare in adults. Here we report a unique case of an adult female with tinea capitis presenting as diffused alopecia and erythema inflammation on the scalp's apex, mimicking seborrheic dermatitis. Examination of the hair and scalp using fluorescence microscopy and fungal culture identified the presence of hyphae from Malassezia globosa, Malassezia furfur and Microsporum canis. The patient underwent with oral antifungal treatment for 3 months, resulting in the resolution of the rash and subsequent hair regrowth, with no recurrence during 6-month follow-up. In vitro co-culture experiments of Microsporum canis and Malassezia (both Malassezia globose and Malassezia furfur) revealed that Malassezia appears to facilitate Microsporum canis growth, while the reverse was not observed. This data suggests that Malassezia's use of long-chain fatty acids by might reduce its antibacterial effect, potentially aiding adult tinea capitis development caused by Microsporum canis.

Epidemiologic features and therapeutic strategies of kerion: A nationwide multicentre study.

BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.

The effect of subclinical hypothyroidism on hormonal and metabolic profiles and ovarian morphology in patients with polycystic ovary syndrome: a cross-sectional study.

OBJECTIVES: Polycystic ovary syndrome (PCOS) and subclinical hypothyroidism (SCH) are prevalent gynecological conditions. However, the interrelationship between the two remains elusive. This study aims to elucidate the association between these conditions and determine the potential impact of SCH on the physiological and metabolic characteristics of patients with PCOS. METHODS: This cross-sectional study enrolled 133 patients with PCOS from our Hospital. Participants were categorized into two groups: those with PCOS + SCH (n = 58) and those with PCOS (n = 75). Serum hormonal levels, metabolic markers, ovarian volume, and follicle count were compared between the groups. RESULTS: There was a significant difference in BMI between the two groups, with a higher prevalence of obesity in the PCOS + SCH group (p = .014). Compared to the PCOS group, patients with PCOS + SCH had significantly higher levels of TSH (p < .001), triglycerides (p = .025), and HOMA-IR (p < .001), while LH levels were significantly lower (p = .048). However, multivariate linear regression analysis revealed that TSH, triglycerides, LH, and HOMA-IR were not determinants for the occurrence of SCH in patients with PCOS. Additionally, there was a notable reduction in follicle count in the left ovary for the PCOS + SCH group compared to the PCOS group (p = .003), and the overall follicle diameter of the PCOS + SCH group was also smaller (p = .010). CONCLUSION: SCH may exert effects on the physiological and metabolic profiles of patients with PCOS. Further investigation into the relationship between these disorders is warranted to delineate their clinical implications.

Synthesis and evaluation of a 68Ga-labeled spermine derivative for tumor PET imaging.

BACKGROUND: The polyamine transporter system (PTS), which renders it a promising target for tumor therapy and imaging applications, facilitates the transmembrane transport of polyamines. We reported a novel derivative of spermine labeled with gallium-68 ([68Ga]Ga-NOTA-Spermine) for the imaging of the PTS in mouse models of tumor. RESULTS: The radiochemical yield of [68Ga]Ga-NOTA-Spermine was determined to be 64-69 %, demonstrating exceptional stability and radiochemical purity (>98 %). Cellular uptake experiments revealed that A549 cells exhibited peak uptake of [68Ga]Ga-NOTA-Spermine at 90 min (15.4 % ± 0.68 %). Biodistribution analysis demonstrated significant accumulation of [68Ga]Ga-NOTA-Spermine in kidneys and liver, while exhibiting low uptake levels in muscle, brain, and bones. Furthermore, Micro-PET/CT scans conducted on A549 tumor-bearing mouse models indicated substantial uptake of [68Ga]Ga-NOTA-Spermine, with maximum tumor/muscle (T/M) ratios reaching 3.71. CONCLUSION: These results suggest that [68Ga]Ga-NOTA-Spermine holds potential as a PET imaging agent for tumors with high levels of PTS.

Cornuside alleviates psoriasis-like skin lesions in mice by relieving inflammatory effects.

Psoriasis is a chronic inflammatory skin disease substantially affecting the quality of life, with no complete cure owing to its complex pathogenesis. Cornuside, a major bioactive compound present in Cornus officinalis Sieb. et Zucc., which is a well-known traditional Chinese medicine with a variety of biological and pharmacological activities, such as anti-apoptotic, antioxidant, and anti-inflammatory properties. However, its effects on psoriasis remain unclear. Our preliminary analysis of network pharmacology showed that cornuside may be involved in psoriasis by regulating the inflammatory response and IL-17 signaling pathway. Thus, we investigated the protective role and mechanism of cornuside in the pathogenesis of psoriasis in an imiquimod (IMQ)-induced psoriasis mouse model. In-vivo experiments demonstrated that cornuside-treated mice had reduced skin erythema, scales, thickness, and inflammatory infiltration. The Psoriasis Area Severity Index score was significantly lower than that of the IMQ group. Flow cytometry analysis indicated that cornuside effectively inhibited Th1- and Th17-cell infiltration and promoted aggregation of Th2 cells in skin tissues. Cornuside also inhibited the infiltration of macrophages to the skin. Furthermore, in-vitro experiments indicated that cornuside also decreased the polarization of M1 macrophages and reduced the levels of associated cytokines. Western blotting demonstrated that cornuside suppressed the phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular receptor kinase (ERK) in bone marrow-derived macrophages. Our findings indicate that cornuside has a protective effect against IMQ-induced psoriasis by inhibiting M1 macrophage polarization through the ERK and JNK signaling pathways and modulating the infiltration of immune cells as well as the expression of inflammatory factors.

Chinese Chronic Mucocutaneous Candidiasis: A Case Report Series.

Chronic Mucocutaneous Candidiasis (CMC) is a rare immunodeficiency disease characterized by chronic or recurrent superficial Candida infections on the skin, nail, and mucous membranes. Here, we present four Chinese patients with CMC who manifested oral mucosal leukoplakia and nail thickening during early childhood, all displaying fissured tongue lines. The causative pathogens isolated from their oral mucosa and nails were identified as C. albicans and C. parapsilosis through morphology and molecular sequencing. Notably, among the four patients, one presented with vitiligo, while another had hypothyroidism. We have also conducted a review of reported cases of CMC in China and worldwide over the last five years, highlighting potential approaches for diagnosis and treatment. The current molecular evidence in the literature suggests potential for the development of early diagnosis methods, such as screening genetic variables on STAT1 and STAT3. Additionally, potential treatment avenues, including gene-targeted analogues and GM-CSF analogues, could be explored in conjunction with traditional antifungal therapy.

Low toxicity contributes to Sporothrix globosa invade the skin of patients in low-epidemic areas of China.

OBJECTIVE: This study aims to assess the clinical characteristics of sporotrichosis in low-endemic areas of China, including the prevalence geography, genotypic traits of patients, clinical manifestations, and strain virulence and drug sensitivities. The objective is to improve the currently used clinical management strategies for sporotrichosis. METHODS: Retrospective data were collected from patients diagnosed with sporotrichosis through fungal culture identification. The isolates from purified cultures underwent identification using CAL (Calmodulin) gene sequencing. Virulence of each strain was assessed using a Galleria mellonella (G. mellonella) larvae infection model. In vitro susceptibility testing against commonly used clinical antifungal agents for sporotrichosis was conducted following CLSI criteria. RESULTS: In our low-endemic region for sporotrichosis, the majority of cases (23) were observed in middle-aged and elderly women with a history of trauma, with a higher incidence during winter and spring. All clinical isolates were identified as Sporothrix globosa (S. globosa). The G. mellonella larvae infection model indicated independent and dose-dependent virulence among strains, with varying toxicity levels demonstrated by the degree of melanization of the G. mellonella. Surprisingly, lymphocutaneous types caused by S. globosa exhibited lower in vitro virulence but were more common in affected skin. In addition, all S.globosa strains displayed high resistances to fluconazole, while remaining highly susceptible to terbinafine, itraconazole and amphotericin B. CONCLUSION: Given the predominance of elderly women engaged in agricultural labour in our region, which is a low-epidemic areas, they should be considered as crucial targets for sporotrichosis monitoring. S. globosa appears to be the sole causative agent locally. However, varying degrees of melanization in larvae were observed among these isolates, indicating a divergence in their virulence. Itraconazole, terbinafine and amphotericin B remain viable first-line antifungal options for treating S.globosa infection.

Impact of Three Thiazolidinone Compounds with Piperine Skeletons on Trehalase Activity and Development of Spodoptera frugiperda Larvae.

Trehalases (TREs) are pivotal enzymes involved in insect development and reproduction, making them prime targets for pest control. We investigated the inhibitory effect of three thiazolidinones with piperine skeletons (6a, 7b, and 7e) on TRE activity and assessed their impact on the growth and development of the fall armyworm (FAW), Spodoptera frugiperda. The compounds were injected into FAW larvae, while the control group was treated with 2% DMSO solvent. All three compounds effectively inhibited TRE activity, resulting in a significant extension of the pupal development stage. Moreover, the treated larvae exhibited significantly decreased survival rates and a higher incidence of abnormal phenotypes related to growth and development compared to the control group. These results suggest that these TRE inhibitors affect the molting of larvae by regulating the chitin metabolism pathway, ultimately reducing their survival rates. Consequently, these compounds hold potential as environmentally friendly insecticides.

Skin barrier-inflammatory pathway is a driver of the psoriasis-atopic dermatitis transition.

As chronic inflammatory conditions driven by immune dysregulation are influenced by genetics and environment factors, psoriasis and atopic dermatitis (AD) have traditionally been considered to be distinct diseases characterized by different T cell responses. Psoriasis, associated with type 17 helper T (Th17)-mediated inflammation, presents as well-defined scaly plaques with minimal pruritus. AD, primarily linked to Th2-mediated inflammation, presents with poorly defined erythema, dry skin, and intense itching. However, psoriasis and AD may overlap or transition into one another spontaneously, independent of biological agent usage. Emerging evidence suggests that defects in skin barrier-related molecules interact with the polarization of T cells, which forms a skin barrier-inflammatory loop with them. This loop contributes to the chronicity of the primary disease or the transition between psoriasis and AD. This review aimed to elucidate the mechanisms underlying skin barrier defects in driving the overlap between psoriasis and AD. In this review, the importance of repairing the skin barrier was underscored, and the significance of tailoring biologic treatments based on individual immune status instead of solely adhering to the treatment guidelines for AD or psoriasis was emphasized.

Photodynamic application in diagnostic procedures and treatment of non-melanoma skin cancers.

OPINION STATEMENT: Skin tumors commonly seen in dermatology are involved in all layers of the skin and appendages. While biopsy of affected skin remains an essential method to confirm diagnosis and to predicate tumor prognosis, it has its limitations. Recently, photodynamic diagnosis (PDD) has demonstrated high sensitivity in detecting affected skin and mucosal tissues, providing valuable guidance for precision surgery to resect skin and mucosal tumors. In this review, we summarized the literatures concerning the applications of PDD in diagnostic process and treatment of skin and mucosal conditions such as actinic keratoses (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Bowen's disease (BD) and extramammary Paget's disease (EMPD). The findings suggest that PDD holds substantial promise for expanding clinical applications and deserves further research exploration.

Galleria mellonella in vitro model for chromoblastomycosis shows large differences in virulence between isolates.

BACKGROUND: Chromoblastomycosis is the World Health Organization (WHO)-recognized fungal implantation disease that eventually leads to severe mutilation. Cladophialophora carrionii (C. carrionii) is one of the agents. However, the pathogenesis of C. carrionii is not fully investigated yet. METHODS: We investigated the pathogenic potential of the fungus in a Galleria mellonella (G. mellonella) larvae infection model. Six strains of C. carrionii, and three of its environmental relative C. yegresii were tested. The G. mellonella model was also applied to determine antifungal efficacy of amphotericin B, itraconazole, voriconazole, posaconazole, and terbinafine. RESULTS: All strains were able to infect the larvae, but virulence potentials were strain-specific and showed no correlation with clinical background of the respective isolate. Survival of larvae also varied with infection dose, and with growth speed and melanization of the fungus. Posaconazole and voriconazole exhibited best activity against Cladophialophora, followed by itraconazole and terbinafine, while limited efficacy was seen for amphotericin B. CONCLUSION: Infection behavior deviates significantly between strains. In vitro antifungal susceptibility of tested strains only partly explained the limited treatment efficacy in vivo.

[Genetic analysis of a child with Hypotrichosis simplex].

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a child with Hypotrichosis 14. METHODS: A child who had presented at the Henan Provincial People's Hospital on May 4, 2020 due to hair thinning was selected as the study subject. Clinical data of the child was collected. Peripheral venous blood samples were collected from the child and her parents. Genomic DNA was extracted and subjected to whole exome sequencing. Candidate variants were validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 5-year-old female, had presented with thin, soft lanugo-like hair which was easy to fall off. The child was found to harbor compound heterozygous missense variants of the LSS gene, namely c.1609G>A (p.V537M) in exon 17 and c.802T>G (p.F268V) in exon 8, which were respectively inherited from her father and mother. Both variant sites were highly conserved, though based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as variants of unknown significance (PM2_Supporting+PP3+PP4). CONCLUSION: The c.1609G>A (p.V537M) and c.802T>G (p.F268V) compound heterozygous variants of the LSS gene probably underlay the clinical phenotype in this patient.

Carbonic Anhydrase 3 is required for cardiac repair post myocardial infarction via Smad7-Smad2/3 signaling pathway.

Appropriate fibrosis is required to prevent subsequent adverse remodeling and heart failure post myocardial infarction (MI), and cardiac fibroblasts (CFs) play a critical role during the process. Carbonic anhydrase 3 (CAR3) is an important mediator in multiple biological processes besides its CO2 hydration activity; however, the role and underlying mechanism of CAR3 on cardiac repair post MI injury remains unknown. Here, we found that CAR3 expression was up-regulated in cardiac tissue in infarct area at the reparative phase of MI, with a peak at 7 days post MI. The upregulation was detected mainly on fibroblast instead of cardiomyocyte, and primary cardiac fibroblasts treated with TGF-ß1 recaptured our observation. While CAR3 deficiency leads to weakened collagen density, enlarged infarct size and aggravated cardiac dysfunction post-MI. In fibroblast, we observed that CAR3 deficiency restrains collagen synthesis, cell migration and gel contraction of cardiac fibroblasts, whereas overexpression of CAR3 in CFs improves wound healing and cardiac fibroblast activation. Mechanistically, CAR3 stabilizes Smad7 protein via modulating its acetylation, which dampens phosphorylation of Smad2 and Smad3, thus inhibiting fibroblast transformation. In contrast, inhibition of Smad7 acetylation with C646 blunts CAR3 deficiency induced suppression of fibroblast activation and impaired cardiac healing. Our data demonstrate a protective role of CAR3 in cardiac wound repair post MI via promoting fibroblasts activation through Smad7-TGF-ß/Smad2/3 signaling pathway.

Effects of secukinumab and ixekizumab on major adverse cardiovascular events in patients with psoriasis: a meta-analysis of randomized controlled trials.

Introduction: The aims of this study is to analyze the risk of major adverse cardiovascular events (MACEs) in patients with psoriasis treated with secukinumab and ixekizumab. Methodology: We systematically identified randomized controlled trials (RCTs) that focused on the treatment of psoriasis with secukinumab and ixekizumab by conducting computerized searches of PubMed, Embase, and the Cochrane Library databases, spanning from their inception to October 31st, 2022. The search terms used included psoriasis, secukinumab, ixekizumab, and randomized controlled trial. Two independent evaluators conducted literature screening, data extraction, and assessed the quality of included studies based on predetermined inclusion and exclusion criteria. The gather data was subjected to meta-analysis using the statistical software RevMan 5.4. Results: A total of 20 articles, encompassing 23 randomized controlled trials involving 10,746 psoriasis patients were included in the analysis. During the double-blind treatment period, the meta-analysis results indicated the following: There was no significant difference in the incidence of MACEs between the secukinumab and placebo groups [RR = 0.61, 95% CI (0.26, 1.44), p = 0.26]. Similarly, there was no significant difference in the incidence of MACEs with ixekizumab compared to the placebo group [RR = 0.47, 95% CI (0.15, 1.47), p = 0.20]. Furthermore, no significant difference in the incidence of MACEs was observed between secukinumab 300 mg and secukinumab 150 mg treatment groups [RR = 1.00, 95% CI (0.23, 4.35), p = 1.00]. Likewise, there was no significant difference in the incidence of MACEs between the ixekizumab Q4W (every 4 weeks) and ixekizumab Q2W (every 2 weeks) administration groups [RR = 4.01, 95% CI (0.45, 35.89), p = 0.21]. Conclusion: The findings of this study suggest that neither secukinumab nor ixekizumab is significantly associated with the risk of MACEs in patients with psoriasis during double-blind treatment.Systematic review registration: Unique Identifier: CRD42022373756 https://www.crd.york.ac.uk/.

Rheumatoid Arthritis Patient With Neurofibromatosis Type 1: Case Report and Review of the Literature.

A 66-year-old neurofibromatosis type 1 (NF1) patient with polyarticular pain for nine years, aggravated for two days, was transferred from the Emergency Intensive Care Unit (EICU) to our rheumatology department. She was diagnosed with NF1 nine years ago by a gene mutation detection and coronary heart disease (CHD) three months ago. The patient was diagnosed with rheumatoid arthritis (RA) this time. After 24 days of treatment with appropriate medication, the patient was discharged with relieved joint pain. However, about four months later, the patient died of circulatory failure caused by myocardial infarction. We analyzed the possible reasons for her outcome and made a review of the literature. There are few clinical reports of NF1 complicated with RA. We found five cases reported in the literature up to date during our search and included them in our communication to compare with our case. NF1 combined with RA mainly affects adult women and usually starts with NF1 and is followed by RA after at least six years of NF1 symptom onset. Although the summarized characteristics of clinical and potential pathogenesis of NF1 combined with RA were limited with these six cases, we hope that this will help clinicians to increase their understanding of this rare complication, thus helping to guide clinical medication.

Two Cases of Superficial Fungal Infection Caused by Non-Albicans Candida Species Manifest Greenish-black Discoloration.

The clinical manifestation of superficial candidiasis varies depending on the infectious sites and causative Candida species that brings a great challenge to diagnose or treat without mycological or pathological evidence in clinical settings. Oral mucosal candidiasis and onychomycosis are most common types of superficial candidiasis. Typically, oral mucosal candidiasis manifests as white or erythematous thrush coated on the tongue and other interior oral cavity; and onychomycosis caused by Candida spp. presents with thick, fragile, or cracked fingernails or toenails in yellow or white discoloration. Here, we report one case of patient with a black hairy tongue caused by Candida tropicalis and one case of greenish discolored onychomycosis caused by Candida parapsilosis. The cases of superficial candidiasis with the same discolored lesions were searched in literature and compared with our cases in clinical manifestation, causative pathogen and treatment. These cases highlight the importance of mycological diagnosis for identifying non-Candida albicans Candida species (NCAC) in superficial infections to guide an effective therapy.

Novel Butenolide Derivatives as Dual-Chitinase Inhibitors to Arrest the Growth and Development of the Asian Corn Borer.

OfChtI and OfChi-h are considered potential targets for the control of Asian corn borer (Ostrinia furnacalis). In this work, the previously reported OfChtI inhibitor 5f was found to show certain inhibitory activity against OfChi-h (Ki = 5.81 µM). Two series of novel butenolide derivatives based on lead compound 5f were designed with the conjugate skeleton, contributing to the π-binding interaction to chitinase, and then synthesized. Compounds 4a-l and 7a-p displayed excellent inhibitory activities against OfChtI and OfChi-h, respectively, at a concentration of 10 µM. Compound 4h was found to be a good dual-Chitinase inhibitor, with Ki values of 1.82 and 2.00 µM against OfChtI and OfChi-h, respectively. The inhibitory mechanism studies by molecular docking suggested that π-π stacking interactions were crucial to the inhibitory activity of novel butenolide derivatives against two different chitinases. A preliminary bioassay indicated that 4h exhibited certain growth inhibition effects against O. furnacalis. Butenolide-like analogues should be further studied as promising novel dual-chitinase inhibitor candidates for the control of O. furnacalis.

Practice guideline on ovarian tissue cryopreservation and transplantation in the prevention and treatment of iatrogenic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) refers to the decline of ovarian function before the age of 40. POI causes a reduction in or loss of female fertility, accompanied by different degrees of menopausal symptoms, which increases the risk of chronic diseases related to early menopause and seriously affects patients' quality of life and health. It is conservatively estimated that at least one million prepubertal girls and women of reproductive age in China are at risk of iatrogenic POI caused by radiotherapy and chemotherapy every year. With the development of medical technology and the breakthrough of scientific and technological advances, preventing and treating iatrogenic POI have become possible. International and national guidelines consider cryopreserved ovarian tissue transplantation to be the most promising method of preserving the ovarian function and fertility of prepubertal girls and women of reproductive age who cannot delay radiotherapy and chemotherapy. In order to guide the clinical application of ovarian tissue cryopreservation and transplantation technology in China, the Guideline Working Group finally included 14 scientific questions and 18 recommendations through a questionnaire survey, field investigation, and consultation of a large number of Chinese and English literature databases in order to provide a reference for colleagues in clinical practice.