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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.
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Antifúngicos , Itraconazol , Microsporum , Tiña del Cuero Cabelludo , Humanos , Preescolar , Antifúngicos/uso terapéutico , Masculino , Femenino , Tiña del Cuero Cabelludo/tratamiento farmacológico , Tiña del Cuero Cabelludo/epidemiología , Tiña del Cuero Cabelludo/microbiología , Itraconazol/uso terapéutico , China/epidemiología , Microsporum/aislamiento & purificación , Niño , Lactante , Glucocorticoides/uso terapéutico , Resultado del Tratamiento , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/epidemiología , Dermatitis Atópica/microbiología , Factores de Riesgo , Adolescente , Adulto , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Background: The Fangji Dihuang formulation (FJDHF) is a widely recognized Traditional Chinese Medicine (TCM) formula that consists of five plant drugs: Stephaniae Tetrandrae Radix, Cinnamomi Ramulus, Rehmanniae Radix, Saposhnikoviae Radix, and Glycyrrhiza Urensis Fisch. This formulation has been known to exhibit clinical therapeutic effects in the treatment of inflammatory skin diseases. However, there is a lack of pharmacological research on its anti-atopic dermatitis (AD) activity. Methods: To investigate the potential anti-AD activity of FJDHF, DNCB was used to induce AD-like skin inflammation in the back of mice. Following successful modeling, the mice were administered FJDHF orally. The extent of the inflammatory skin lesions was recorded at day 4, 7, 14 and 28. UHPLC-Q-Exactive Orbitrap MS was used to identify and match the compounds present in FJDHF with ITCM, TCMIP and TCMSID. In silico predictions of potential target proteins of the identified compounds were obtained from SwishTargetPrediction, ITCM and TargetNet databases. AD-related genes were identified from GSE32924 data set, and FJDHF anti-AD hub genes were identified by MCODE algorithm. ClueGo enrichment analysis was employed to identify the core pathway of FJDHF's anti-AD effect. To further investigate the anti-AD effect of FJDHF, single-cell RNA sequencing data set (GSE148196) from AD patients was analyzed to determine the target cells and signaling pathways of FJDHF in AD. Finally, rt-PCR, flow cytometry, and mouse back skin RNA sequencing were utilized to validate our findings. Results: FJDHF was found to be effective in improving the degree of the AD-like lesions in the mice. Network pharmacological analysis revealed the core pathway of FJDHF to be the IL-17 signaling pathway, which is interactively associated with cytokines. Single-cell RNA sequencing analysis suggested that FJDHF may play an anti-AD role by influencing dendritic cells. Flow cytometry and rt-PCR results showed that FJDHF can reduce the influence of AD sample of IL-4, IFN-γ and the expression of IL-17. The RNA sequencing of mouse back skin also confirmed our conclusion. Conclusion: FJDHF may inhibit DNCB-induced AD-like skin inflammation in mice by inhibiting the IL-17 signaling pathway. Thus, FJDHF can be considered as a potential therapeutic agent for AD.
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Tinea capitis is still common in Wuhan, and there exists significant difference in its pathogen spectrum between this area and other parts of China. In the present study, we aimed to clarify the epidemiological characteristics of tinea capitis and changes of pathogen spectrum in Wuhan and its surrounding areas from 2011 to 2022, and further to present potential risk factors focusing on some major etiological agents. Briefly, a retrospective single-center survey was performed on 778 patients with tinea capitis from 2011 to 2022 in Wuhan, China. The isolated pathogens were identified to species level by morphological examination or by ITS sequencing. The data were collected and statistically analyzed by Fisher's exact test and Bonferroni method. Among all enrolled patients, the most common pathogen was Trichophyton violaceum in both child (310, 46.34%) and adult tinea capitis (71, 65.14%). There existed significant difference in pathogen spectrum between child and adult tinea capitis. Furthermore, black-dot type represented the most common type of tinea capitis for both children (303, 45.29%) and adults (71, 65.14%). Notably, the number of cases caused by Microsporum canis consecutively exceeded that caused by Trichophyton violaceum in children from Jan, 2020 to Jun, 2022. Additionally, we suggested a series of potential factors that might increase the risks of acquiring tinea capitis by focusing on several major agents. Considering the different risk factors related to specific pathogen, it was meaningful to adjust the measures against the spreading of tinea capitis according to the changes of pathogen distribution within recent years.
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@#Abstract: Objective To investigate the clinical types of children's tinea capitis and the distribution of fungal pathogens in Wuhan from 2011 to 2020, and to provide scientific basis for the prevention, diagnosis and treatment of children's tinea capitis. Methods Laboratory data of children with tinea capitis in outpatient and inpatient department of dermatology in Wuhan No.1 Hospital from January 2011 to December 2020 were collected. A total of 542 cases of pediatric tinea capitis were included, with 239 male cases and 303 female cases. Microscopic examination of fungi and culture identification were performed on the affected skin lesions of the children. Chi-square test was used to analyze the differences in pathogen spectrum of children with different age groups and clinical type. Results Among the pediatric tinea capitis patients, the age group with the highest prevalence was preschool children(3 to <7 years old), accounting for 48.52%(263/542). The top three pathogenic fungi were Trichophytes violaceum(49.26%, 267/542), Microsporum canis(31.55%, 171/542) and Trichophyton mentagrophytes (9.96%, 54/542). Trichophyton violaceum was the main pathogen in all ages, followed by Microsporum canis. The infection rate of Microsporum canis in children over 7 years old was lower than that in children under 7 years old, and the infection rate of Trichophyton rubrum in infants was higher than that in other ages. The distribution of Trichophytes violaceum, Trichophyton mentagrophytes, Nannizzia gypseum and Microsporum ferrugineum was uniform in all age groups. Trichophytes violaceum and Trichophyton tousurans mainly caused black-dot ringworm, Microsporum canis mainly caused tinea alba, Trichophyton mentagrophytes,Nannizzia gypseum and Trichophytonrubrum mainly caused kerion. Except for Microsporum ferrugineum, the composition ratios of other fungi species showed statistically significant differences among different clinical types of tinea capitis(P<0.05). Conclusions Preschool children are the most commonly affected age group by pediatric tinea capitis, and black-dot ringworm caused by Trichophytes violaceum is the main clinical type. Analysis of the high-riskage group, pathogenic fungi and clinical types of tinea capitis in children can enhance the understanding of its epidemiological characteristics, which is helpful for early diagnosis and targeted standardized treatment of pediatric tinea capitis.
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Transformation of Fonsecaea pedrosoi into muriform cells enhances the resistance against phagocytosis and elimination by host immune cells, and links to the chronicity of chromoblastomycosis. Here, we aim to determine whether the muriform cells can reproduce in tissue without reverse transformation into hyphal form by using an experimental nu/nu-BALB/c mouse model of chromoblastomycosis due to F. pedrosoi. During the whole 81-day observation period, most of the hyphal inocula had transformed into muriform cells at 75 days postinoculation and maintained as this parasitic morphology till 81 days postinoculation simultaneously with increased fungal loads in tissue and the worsening of footpad lesion. Scanning and transmitting electronic microscope examinations showed that the muriform cells obtained in tissue or induced in vitro can reproduce daughter cells by dividing, and, meanwhile, the daughter cells had the potential to produce buds and grow into hyphae reversely. Furthermore, exoenzyme examination suggested that the profile of exoenzymes constituted by muriform cells was quite different from that constituted by hyphae although the assay showed both of them had obvious metabolic activity. By contrast, most muriform cells in the footpad gradually transformed into the elongated hyphae without obvious infiltration of inflammatory cells during repeated intraperitoneal administration of cyclophosphamide (50 mg/kg, per every other day) from 50 to 80 days postinoculation. Therefore, we infer that F. pedrosoi can reproduce by dividing as muriform cells in mouse tissue, and the morphological transformation between hyphal form and muriform cells is possibly associated with the host immune status.
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Ascomicetos/fisiología , División Celular/fisiología , Cromoblastomicosis , Hifa/fisiología , Animales , Ascomicetos/efectos de los fármacos , Ascomicetos/enzimología , Ascomicetos/ultraestructura , Ciclofosfamida/farmacología , Pie , Hifa/efectos de los fármacos , Hifa/ultraestructura , Inmunosupresores/farmacología , Técnicas In Vitro , Ratones , Ratones Desnudos , Microscopía Electrónica de RastreoRESUMEN
Fonsecaea pedrosoi (F. pedrosoi) is the most common agent of chromoblastomycosis. Transformation of this fungus from its saprophytic phase into pathogenic sclerotic cells in tissue is an essential link to the refractoriness of this infection. Experimental studies in murine models have shown that the absence of CD4+ T cells impairs host defense against F. pedrosoi infection. Clinical research has also suggested that a relatively low level of the Th1 cytokine INF-γ and inefficient T cell proliferation are simultaneously present in patients with severe chromoblastomycosis upon in vitro stimulation with ChromoAg, an antigen prepared from F. pedrosoi. In the present study, we show that in mice intraperitoneally infected with F. pedrosoi-spores, -hyphae or in vitro-induced sclerotic cells respectively, the transformation of this causative agent into sclerotic cells contributes to a compromised Th1 cytokine production in the earlier stage of infection with impaired generation of neutrophil reactive oxygen species (ROS) and pan-inhibition of Th1/Th2/Th17 cytokine production with disseminated infection in the later stage by using a CBA murine Th1/Th2/Th17 cytokine kit. In addition, we have further demonstrated that intraperitoneal administration of recombinant mouse IFN-γ (rmIFN-γ) effectively reduces the fungal load in the infected mouse spleen, and dampens the peritoneal dissemination of F. pedrosoi-sclerotic cells. Meanwhile, exogeneous rmIFN-γ contributes to the formation and maintenance of micro-abscess and restores the decrease in neutrophil ROS generation in the mouse spleen infected with F. pedrosoi-sclerotic cells. Of note, we have once again demonstrated that it is a chitin-like component, but not ß-glucans or mannose moiety, that exclusively accumulates on the outer cell wall of F. pedrosoi-sclerotic cells which were induced in vitro or isolated from the spleens of intraperitoneally infected BALB/c mice. In addition, our results indicate that decreased accumulation of chitin on the surface of live F. pedrosoi-sclerotic cells after chitinase treatment can be self-compensated in a time-dependent manner. Importantly, we have for the first time demonstrated that exclusive accumulation of chitin on the transformed sclerotic cells of F. pedrosoi is involved in an impaired murine Th1 cytokine profile, therefore promoting the refractoriness of experimental murine chromoblastomycosis.
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Ascomicetos/fisiología , Quitina/metabolismo , Cromoblastomicosis/inmunología , Cromoblastomicosis/microbiología , Interferón gamma/biosíntesis , Animales , Ascomicetos/inmunología , Modelos Animales de Enfermedad , Hifa/fisiología , Interferón gamma/inmunología , Lectinas Tipo C/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neutrófilos/inmunología , Células Th17/inmunologíaRESUMEN
PURPOSE: The aim of the study was to evaluate the main sources and epidemiological patterns and speculate on the evolutionary origin of Sporothrix globosa in Asia. METHODOLOGY: Case and case series literature on sporotrichosis in Asia from January 2007 onwards were reviewed using meta-analysis. Phylogenetic analysis of relevant S. globosa was carried out on the basis of concatenated sequences of ITS, TEF3 and CAL. A haplotype network of CAL sequences of 281 Sporothrix isolates was analysed to determine the population structure of S. globosa. RESULTS: Nearly all cases of sporotrichosis caused by S. globosa in Asia were human. In contrast to the remaining pathogenic Sporothrix species, feline transmission was exceptional; nearly all regional cat-associated cases were caused by Sporothrix schenckii. While the latter species was highly variable and showed recombination, S. globosa seemed to be a clonal offshoot, as was Sporothrix brasiliensis. The origin of the segregants was located in an area of high variability in S. schenckii with a relatively high frequency of Asian strains. CONCLUSION: In Asia, S. globosa was the prevalent species. The low diversity of S. globosa suggested a recent divergence with a founder effect of low variability from the variable ancestral species, S. schenckii.
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Sporothrix/genética , Esporotricosis/epidemiología , Esporotricosis/microbiología , Animales , Asia/epidemiología , Proteínas Bacterianas/genética , Calmodulina/genética , Enfermedades de los Gatos , Gatos , Evolución Molecular , Variación Genética , Humanos , Filogenia , Sporothrix/aislamiento & purificación , Sporothrix/patogenicidad , Sporothrix/ultraestructura , Esporotricosis/transmisión , Esporotricosis/veterinariaRESUMEN
Connective tissue nevi represents a kind of hamartoma, and coalescence of the lesions in a cerebriform mode in the lumbar region without Proteus syndrome is rarely seen. Here, we report a 26-year-old woman presenting with nodules and plaques in her left lumbar region of 26 years in duration. Histopathological examination and Masson-trichrome stain showed increased dermal collagen bundles in a haphazard array. The diagnosis of connective tissue nevi was made. This is the first case report on cerebriform connective tissue nevi without Proteus syndrome in the lumbar region.
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Nevo/patología , Neoplasias Cutáneas/patología , Adulto , Femenino , Humanos , Región LumbosacraRESUMEN
Fonsecaea pedrosoi (F. pedrosoi), a major agent of chromoblastomycosis, has been shown to be recognized primarily by C-type lectin receptors (CLRs) in a murine model of chromoblastomycosis. Specifically, the ß-glucan receptor, Dectin-1, mediates Th17 development and consequent recruitment of neutrophils, and is evidenced to have the capacity to bind to saprophytic hyphae of F. pedrosoi in vitro. However, when embedded in tissue, most etiological agents of chromoblastomycosis including F. pedrosoi will transform into the sclerotic cells, which are linked to the greatest survival of melanized fungi in tissue. In this study, using immunocompetent and athymic (nu/nu) murine models infected subcutaneously or intraperitoneally with F. pedrosoi, we demonstrated that T lymphocytes play an active role in the resolution of localized footpad infection, and there existed a significantly decreased expression of Th17-defining transcription factor Rorγt and inefficient recruitment of neutrophils in chronically infected spleen where the inoculated mycelium of F. pedrosoi transformed into the sclerotic cells. We also found that Dectin-1-expressing histocytes and neutrophils participated in the enclosure of transformed sclerotic cells in the infectious foci. Furthermore, we induced the formation of sclerotic cells in vitro, and evidenced a significantly decreased binding capacity of human or murine-derived Dectin-1 to the induced sclerotic cells in comparison with the saprophytic mycelial forms. Our analysis of ß-glucans-masking components revealed that it is a chitin-like component, but not the mannose moiety on the sclerotic cells, that interferes with the binding of ß-glucans by human or murine Dectin-1. Notably, we demonstrated that although Dectin-1 contributed to the development of IL-17A-producing CD3+CD4+ murine splenocytes upon in vitro-stimulation by saprophytic F. pedrosoi, the masking effect of chitin components partly inhibited Dectin-1-mediated Th17 development upon in vitro-stimulation by induced sclerotic cells. Therefore, these findings extend our understanding of the chronicity of chromoblastomycosis.
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Ascomicetos/citología , Quitina/farmacología , Lectinas Tipo C/metabolismo , Células Th17/efectos de los fármacos , Células Th17/metabolismo , beta-Glucanos/metabolismo , Animales , Ascomicetos/efectos de los fármacos , Ascomicetos/metabolismo , Ascomicetos/fisiología , Antígeno CD11c/metabolismo , Pared Celular/efectos de los fármacos , Quitina/química , Cromoblastomicosis/genética , Cromoblastomicosis/inmunología , Cromoblastomicosis/metabolismo , Enfermedad Crónica , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Humanos , Peróxido de Hidrógeno/farmacología , Inmunocompetencia , Masculino , Ratones , Ratones Endogámicos BALB C , Infiltración Neutrófila/efectos de los fármacos , Bazo/inmunología , Células Th17/inmunologíaRESUMEN
In most female patients, the symptoms of genital infection due to Neisseria gonorrhoeae tend to be slight or even absent. Our previous studies suggested that progesterone might play a role in female asymptomatic gonococcal infection. In this study, we demonstrated that progesterone induced the expression of thymic stromal lymphopoietin (TSLP) and regulatory T cells (Treg)-related transcription factor Foxp3, and inhibited the expression of Th17 related transcription factor RORγt, and reduced the influx of neutrophils in murine vaginal gonococcal infection. Blockade of TSLP with antibody partially reversed the effects of progesterone on the murine model of gonococcal vaginal infection. In in vitro experiments, progesterone induced a rapid up-regulation of TSLP in vaginal epithelial cells stimulated with N. gonorrhoeae. Blocking thymic stromal lymphopoietin receptor (TSLPR) with a TSLPR monoclonal antibody partially prevented progesterone suppression of IL-17-producing T cells differentiation, and progesterone promotion of CD4âºCD25âºFoxp3⺠regulatory T cells differentiation. Altogether, our results indicate that the progesterone suppresses Th17 cell responses, and enhances the development of Treg cells, through TSLP-dependent mechanisms, and play a role in female asymptomatic gonococcal infections.
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Citocinas/metabolismo , Gonorrea/inmunología , Neisseria gonorrhoeae/inmunología , Progesterona/metabolismo , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Animales , Modelos Animales de Enfermedad , Femenino , Factores de Transcripción Forkhead/metabolismo , Gonorrea/microbiología , Tolerancia Inmunológica , Ratones , Ratones Endogámicos BALB C , Linfocitos T Reguladores/efectos de los fármacos , Células Th17/efectos de los fármacos , Linfopoyetina del Estroma TímicoRESUMEN
We report a case of subcutaneous phaeohyphomycosis due to Phialophora verrucosa in a 64-year-old Chinese farmer suffering from CD4+ lymphopenia. He presented with diffuse and infiltrated plaques involving the entire face including the eyes, neck, occiput, and extending to the dorsal regions of his torso. The patient is notable for the discrete multifocal nature of the illness in the absence of disseminated infection and rarity of P. verrucosa as a cause of subcutaneous phaeohyphomycosis.
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Feohifomicosis/diagnóstico , Feohifomicosis/patología , Phialophora/aislamiento & purificación , Agricultura , Antifúngicos/administración & dosificación , Pueblo Asiatico , ADN de Hongos/química , ADN de Hongos/genética , Histocitoquímica , Humanos , Itraconazol/administración & dosificación , Linfopenia/complicaciones , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Naftalenos/administración & dosificación , Feohifomicosis/microbiología , Análisis de Secuencia de ADN , Terbinafina , Resultado del TratamientoRESUMEN
Mannan-binding lectin (MBL), a lectin homologous to C1q, greatly facilitates C3/C4-mediated opsonophagocytosis of Candida albicans (C. albicans) by human neutrophils, and has the capacity to bind to CR1 (CD35) expressed on circulating neutrophils. The intracellular pool of neutrophil Dectin-1 plays a critical role in stimulating the reactive oxygen species (ROS) generation through recognition of ß-1,3-glucan component of phagocytized zymosan or yeasts. However, little is known about whether MBL can mediate the opsonophagocytosis of Candida albicans by neutrophils independent of complement activation, and whether MBL-mediated opsonophagocytosis influence the intracellular expression of Dectin-1 and ROS production. Here we showed that the inhibited phagocytic efficiency of neutrophils as a result of blockage of Dectin-1 was compensated by exogenous MBL alone in a dose-dependent manner. Furthermore, the expressions of Dectin-1 at mRNA and intracellular protein levels were significantly up-regulated in neutrophils stimulated by MBL-pre-incubated C. albicans, while the expression of surface Dectin-1 remained almost unchanged. Nevertheless, the stimulated ROS production in neutrophils was partly and irreversibly inhibited by blockage of Dectin-1 in the presence of exogenous MBL. Confocal microscopy examination showed that intracellular Dectin-1 was recruited and co-distributed with ROS on the surface of some phagocytized yeasts. The ß-1,3-glucanase digestion test further suggested that the specific recognition and binding site of human Dectin-1 is just the ß-1,3-glucan moiety on the cell wall of C. albicans. These data demonstrate that MBL has an ability to mediate the opsonophagocytosis of Candida albicans by human neutrophils independent of complement activation, which is coupled with intracellular Dectin-1-triggered ROS production.
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Lectinas Tipo C , Lectina de Unión a Manosa/administración & dosificación , Fagocitosis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Candida albicans/inmunología , Candida albicans/patogenicidad , Pared Celular/inmunología , Pared Celular/metabolismo , Activación de Complemento/inmunología , Humanos , Lectinas Tipo C/antagonistas & inhibidores , Lectinas Tipo C/inmunología , Lectinas Tipo C/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Receptores de Complemento 3b/inmunología , Receptores de Complemento 3b/metabolismo , Zimosan/metabolismo , beta-Glucanos/farmacologíaRESUMEN
In the present study, we aim to evaluate the application potential of a combined assay of human telomerase reverse transcriptase (hTERT) and E6 oncoprotein in screening the virus-infected keratinocytes with higher telomerase activity in human papillomaviruses (HPV) 16- and 18-related bowenoid papulosis (BP). HPV16/18 DNA in BP (n = 123) was identified by in situ hybridization, the expression of hTERT and E6 in HPV16/18-related BP (n = 68) was determined by immunohistochemistry. We demonstrated that the expression of hTERT correlated well with that of E6 oncoprotein in HPV16/18-related BP lesions (Spearman rho = 0.868, P < 0.01). Furthermore, the majority of keratinocytes with positive nuclear staining for hTERT or E6 in the consecutive sections of each HPV16/18-related BP lesion showed nuclear paleomorphism or nuclear mitosis. In conclusion, we suggested that a combined assay of hTERT and E6 oncoprotein can be used to screen the HPV-infected keratinocytes with higher telomerase activity in HPV16-related and HPV18-related BP lesions.