Potassium iodide enhances the killing effect of methylene blue mediated photodynamic therapy against F. monophora.

BACKGROUND: Chromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated. METHODS: In vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm2) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen (1O2), free iodine (I2), hydrogen peroxide (H2O2), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10 mM KI, 2 mM MB +100 J/cm² and 10 mM KI+2 mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed. RESULTS: KI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I2 and H2O2. CONCLUSION: KI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM.

Successful management of chromoblastomycosis utilizing conventional antifungal agents and imiquimod therapy.

Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host's immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal microscopy manifestations, effectively managed through a combination of itraconazole, terbinafine, and imiquimod, shedding light on novel strategies for managing this challenging condition.

Neutrophil extracellular traps (NETs) and Th-2 dominant immune responses in chronic granulomatous chromobalstomycosis.

Chromoblastomycosis (CBM), a chronic, granulomatous, suppurative mycosis of the skin and subcutaneous tissue, is caused by several dematiaceous fungi. The formation of granulomas, tissue proliferation, and fibrosis in response to these pathogenic fungi is believed to be intricately linked to host immunity. To understand this complex interaction, we conducted a comprehensive analysis of immune cell infiltrates, neutrophil extracellular traps (NETs) formation, and the fibrosis mechanism in 20 CBM lesion biopsies using immunohistochemical and immunofluorescence staining methods. The results revealed a significant infiltration of mixed inflammatory cells in CBM granulomas, prominently featuring a substantial presence of Th2 cells and M2 macrophages. These cells appeared to contribute to the production of collagen I and III in the late fibrosis mechanism, as well as NETs formation. The abundance of Th2 cytokines may act as a factor promoting the bias of macrophage differentiation toward M2, which hinders efficient fungal clearance while accelerates the proliferation of fibrous tissue. Furthermore, the expression of IL-17 was noted to recruit neutrophils, facilitating subsequent NETs formation within CBM granulomas to impede the spread of sclerotic cells. Understanding of these immune mechanisms holds promise for identifying therapeutic targets for managing chronic granulomatous CBM.

Combination therapy with itraconazole and terbinafine for phaeohyphomycosis caused by Exophiala spinifera: A case report and literature review.

Exophiala spinifera is a rare dematiaceous fungus causing cutaneous, subcutaneous and disseminated phaeohyphomycosis (PHM). Standard antifungal therapy for PHM is still uncertain. Here, we report a case of a Chinese male with PHM caused by E. spinifera, who received significant clinical improvement after the treatment with oral itraconazole and terbinafine. With the aim of evaluating the antifungal therapy for PHM caused by E. spinifera, a detailed review was performed.

Fungal Spectrum and Susceptibility Against Nine Antifungal Agents in 525 Deep Fungal Infected Cases.

Background: Deep fungal infection has become an important cause of infection and death in hospitalized patients, and this has worsened with increasing antifungal drug resistance. Objective: A 3-year retrospective study was conducted to investigate the clinical characteristics, pathogen spectrum, and drug resistance of deep fungal infection in a regional hospital of Guangzhou, China. Methods: Non-duplicate fungi isolates recovered from blood and other sterile body fluids of in-patients of the clinical department were identified using biochemical tests of pure culture with the API20C AUX and CHROMagar medium. Antifungal susceptibilities were determined by Sensititre YeastOne® panel trays. Results: In this study, 525 patients (283 female, 242 male) with deep fungal infection were included, half of them were elderly patients (≥60 years) (54.67%, n=286). A total of 605 non-repetitive fungi were finally isolated from sterile samples, of which urine specimens accounted for 66.12% (n=400). Surgery, ICU, and internal medicine were the top three departments that fungi were frequently detected. The mainly isolated fungal species were Candida albicans (43.97%, n=266), Candida glabrata (20.00%, n=121), and Candida tropicalis (17.02%, n=103), which contributed to over 80% of fungal infection. The susceptibility of the Candida spp. to echinocandins, 5-fluorocytosine, and amphotericin B remained above 95%, while C. glabrata and C. tropicalis to itraconazole were about 95%, and the dose-dependent susceptibility of C. glabrata to fluconazole was more than 90%. The echinocandins had no antifungal activity against Trichosporon asahi in vitro (MIC90>8 µg/mL), but azole drugs were good, especially voriconazole and itraconazole (MIC90 = 0.25 µg/mL). Conclusion: The main causative agents of fungal infection were still the genus of Candida. Echinocandins were the first choice for clinical therapy of Candida infection, followed with 5-fluorocytosine and amphotericin B. Azole antifungal agents should be used with caution in Candida glabrata and Candida tropicalis infections.

NLRP3 inflammasome activation contributes to fungal clearance and lung injury during Talaromyces marneffei infection.

The increased levels of IL-1ß and IL-18 cytokines have been associated with the severity of sepsis and outcomes of patients infected with Talaromyces marneffei. Previous studies have suggested that NLRP3 plays an important role in caspase-1 activated secretion of IL-1ß and IL-18 in fungal-infected macrophages. In the present study, the role of the NLRP3 inflammasome in talaromycosis is investigated in an in vitro assay and in vivo with a mice systemic infection model. We found that the NLRP3 inflammasome pathway in infected mice is activated along with increased production of IL-1ß. Such an activation of the NLRP3 inflammasome is also observed in either mice or human macrophages challenged with T. marneffei conidia. Our results indicate that IL-1ß release by infected macrophages is NLRP3 inflammasome-dependent and NLRP3 contributes to death of mice at the early stage of pulmonary infection. Moreover, a greater number of MPO-positive cells are found in the lungs of infected Nlrp3-/- mice and WT mice with reduced LDH levels, especially at the last stage of infection. Therefore, we conclude that the NLRP3 Inflammasome activation is important for fungal clearance, neutrophil recruitment and lung injury during T. marneffei Infection.

Autophagy benefits the in vitro and in vivo clearance of Talaromyces marneffei.

Talaromycosis, namely Talaromyces marneffei infection, is increasing gradually and has a high mortality rate even under antifungal therapy. Although autophagy acts differently on different pathogens, it is a promising therapeutic strategy. However, information on autophagy in macrophages and animals upon infection by T. marneffei is still limited. Therefore, several models were employed here to investigate the role of autophagy in host defense against T. marneffei, including RAW264.7 macrophages as in vitro models, different types of Caenorhabditis elegans and BALB/c mice as in vivo models. We applied the clinical T. marneffei isolate SUMS0152 in this study. T. marneffei-infected macrophages exhibit increased formation of autophagosomes. Further, macrophage autophagy promoted by rapamycin or Earle's balanced salt solution (EBSS) inhibited the viability of intracellular T. marneffei. In vivo, compared with uninfected Caenorhabditis elegans, the wild-type nematodes upregulated the expression of the autophagy-related gene lgg-1 and atg-18, and nematodes carrying GFP reporter were induced to form autophagosomes (GFP::LGG-1) after T. marneffei infection. Furthermore, the knockdown of lgg-1 significantly reduced the survival rate of T. marneffei-infected nematodes. Likewise, the autophagy activator rapamycin reduced the fungal burden and suppressed lung inflammation in a mouse model of infection. In conclusion, autophagy is essential for host defense against T. marneffei in vitro and in vivo. Therefore, autophagy may be an attractive target for developing new therapeutics to treat talaromycosis.

Epidemiology and Clinical Findings of Tinea Capitis: A 23-Year Retrospective, Single-Center Study in Guangzhou, China.

BACKGROUND: Tinea capitis (TC) is one of the most common public health concerns due to its high incidence in preadolescent children. The epidemiological and clinical characteristics of TC vary depending on geographical regions and have changed over the past decades. OBJECTIVES: This study aimed to identify epidemiological changes in recent decades, including the prevalence and clinical and mycological characteristics of TC in southern China. METHODS: We conducted a retrospective study at the Department of Dermatology of Sun Yat-sen Memorial Hospital, Sun Yat-sen University from June 1997 to August 2020. RESULTS: We retrospectively evaluated 401 TC patients. Of these, 157 patients (39.2%) were preschool children aged 3-7 years and the majority were males. However, the prevalence in children under 3 years old is on the rise (from 19.67% during 1997-2010 to 32.49% during 2011-2020). Grey patches were the most common clinical pattern and mostly occurred in children (71.3%), while the proportion of grey patches and black dots was almost the same in adults. Although Microsporum canis (76%) was the most common causative organism, the number of the T. mentagrophytes complex, as a zoophilic fungus, has increased more than that of the anthropophilic fungi T. violaceum in the recent decade. There was a significant difference in the portion of sex among different age groups, and the gender difference was more notable in the adult group, which showed that the TC prevalence in females was 9 times that in males. In males, M. canis and the T. mentagrophytes complex were the two most common causative fungi, while M. canis and T. violaceum were the two most common causative fungi in females. Additionally, approximately 61.7% of black dot TCs occurred in females. For treatment, oral antifungal therapeutics were widely used in most patients with different treatment durations, although without a significant difference in efficacy (P = 0.106). CONCLUSIONS: In the last decade, the prevalence of TC in children under 3 years old increased, and boys dramatically outnumbered girls. In adults, the TC prevalence in females is nine times that in males, and most TCs occurring in females are presented as black dots. Moreover, the zoophilic T. mentagrophytes complex has replaced T. violaceum and is now the second most prevalent organism, followed by M. canis of TC.

The relationship between the preference of mating type (MAT) and source in the opportunistic pathogen Talaromyces marneffei.

Genome-wide comparisons have shown Talaromyces marneffei possessed a stable mating type locus in its meiosis genes. But the function of the mating type locus in T. marneffei is not clear. The potential sex recombination might lead to problems in clinical, such as the evolution of increased resistance to antifungal drugs and virulence. To determine the mating type in a sample of 107 T. marneffei isolates and to explore the possible relationship between fungus virulence and mating type or source. We used PCR analysis to determine the distribution of mating type genes and also analyzed the relationship between mating type and isolated sources (including HIV-positive patients, HIV-negative patients, bamboo rats, and the environment). Further, the Drosophila melanogaster model of infection was used to compare the differences of virulence in mating type and sources. Our results showed the entire sample population of T. marneffei with an overabundance of MAT1-2 alleles, but with a higher ratio of MAT1-1 in the isolates from HIV-negative patients. However, no significant differences in the survival of the D. melanogaster infected neither with MAT1-1 (6.5 days) nor MAT1-2 (4 days) isolates. Similar results were also observed in virulence analysis tested with different sources of isolates. So, we found that all isolates bore single mating type idiomorphs and unequal distribution. The distribution of the MAT genes seems related to different sources. And the virulence differences are independent of mating type genotype and source.

Our work shows the entire sample population of 107 Talaromyces marneffei isolates with an overabundance of MAT1-2 alleles, but with a higher ratio of MAT1-1 in the isolates from HIV-negative patients. And fungus virulence is independent of mating type genotype and source in the Drosophila melanogaster model.

Deletion C-terminal thioesterase abolishes melanin biosynthesis, affects metabolism and reduces the pathogenesis of Fonsecaea monophora.

Dematiaceous Fonsecaea monophora is one of the major pathogens of chromoblastomycosis. It has been well established that melanization is catalyzed by the type I polyketide synthase (PKS) in F. monophora. Multidomain protein Type I PKS is encoded by six genes, in which the last enzyme thioesterase (TE) catalyzes the cyclization and releases polyketide. Two PKS genes AYO21_03016 (pks1) and AYO21_10638 have been found in F. monophora and both PKS loci have the same gene arrangement but the TE domain in AYO21_10638 is truncated at 3'- end. TE may be the key enzyme to maintain the function of pks1. To test this hypothesis, we constructed a 3'-end 500 bp deletion mutant of AYO21_03016 (Δpks1-TE-C500) and its complemented strain. We profiled metabolome of this mutant and analyzed the consequences of impaired metabolism in this mutant by fungal growth in vitro and by pathogenesis in vivo. Compared with wild-type strain, we found that the mutant repressed pks1 expression and other 5 genes expression levels were reduced by more than 50%, perhaps leading to a corresponding melanin loss. The mutant also reduced sporulation and delayed germination, became vulnerable to various environmental stresses and was less resistance to macrophage or neutrophil killings in vitro, and less virulence in mice footpad model. Metabolomic analysis indicated that many metabolites were remarkably affected in Δpks1-TE-C500, in particular, an increased nicotinamide and antioxidant glutathione. In conclusion, we confirmed the crucial role of C-terminal TE in maintaining fully function of pks1 in F. monophora. Deletion of TE negatively impacts on the synthesis of melanin and metabolites that eventually affect growth and virulence of F. monophora. Any potential inhibitor of TE then could be a novel antifungal target for drug development.

Molecular Characteristics of Regional Chromoblastomycosis in Guangdong, China: Epidemiological, Clinical, Antifungal Susceptibility, and Serum Cytokine Profiles of 45 Cases.

Chromoblastomycosis (CBM) is a chronic disease caused by several species of dematiaceous fungi. In this study, a regional collection of 45 CBM cases was conducted in Guangdong, China, a hyper-endemic area of CBM. Epidemiology findings indicated that the mean age of cases was 61.38 ± 11.20 years, long duration ranged from 3 months to 30 years, and the gender ratio of male to female was 4.6:1. Thirteen cases (29%) declared underlying diseases. Verrucous form was the most common clinical manifestation (n = 19, 42%). Forty-five corresponding clinical strains were isolated, and 28 of them (62%) were identified as F. monophora; the remaining 17 (38%) were identified as F. nubica through ITS rDNA sequence analysis. Antifungal susceptibility tests in vitro showed low MICs in azoles (PCZ 0.015-0.25 µg/ml, VCZ 0.015-0.5 µg/ml, and ITZ 0.03-0.5 µg/ml) and TRB (0.015-1 µg/ml). Itraconazole combined with terbinafine was the main therapeutic strategy used for 31 of 45 cases, and 68% (n = 21) of them improved or were cured. Cytokine profile assays indicated upregulation of IL-4, IL-7, IL-15, IL-11, and IL-17, while downregulation of IL-1RA, MIP-1ß, IL-8, and IL-16 compared to healthy donors (p < 0.05). The abnormal cytokine profiles indicated impaired immune response to eliminate fungus in CBM cases, which probably contributed to the chronic duration of this disease. In conclusion, we investigated the molecular epidemiological, clinical, and laboratory characteristics of CBM in Guangdong, China, which may assist further clinical therapy, as well as fundamental pathogenesis studies of CBM.

Deep learning-based diagnosis models for onychomycosis in dermoscopy.

BACKGROUND: Onychomycosis is a common disease. Emerging noninvasive, real-time techniques such as dermoscopy and deep convolutional neural networks have been proposed for the diagnosis of onychomycosis. However, deep learning application in dermoscopic images has not been reported. OBJECTIVES: To explore the establishment of deep learning-based diagnostic models for onychomycosis in dermoscopy to improve the diagnostic efficiency and accuracy. METHODS: We evaluated the dermoscopic patterns of onychomycosis diagnosed at Sun Yat-sen Memorial Hospital, Guangzhou, China, from May 2019 to February 2021 and included nail psoriasis and traumatic onychodystrophy as control groups. Based on the dermoscopic images and the characteristic dermoscopic patterns of onychomycosis, we gain the faster region-based convolutional neural networks to distinguish between nail disorder and normal nail, onychomycosis and non-mycological nail disorder (nail psoriasis and traumatic onychodystrophy). The diagnostic performance is compared between deep learning-based diagnosis models and dermatologists. RESULTS: All of 1,155 dermoscopic images were collected, including onychomycosis (603 images), nail psoriasis (221 images), traumatic onychodystrophy (104 images) and normal cases (227 images). Statistical analyses revealed subungual keratosis, distal irregular termination, longitudinal striae, jagged edge, and marble-like turbid area, and cone-shaped keratosis were of high specificity (>82%) for onychomycosis diagnosis. The deep learning-based diagnosis models (ensemble model) showed test accuracy /specificity/ sensitivity /Youden index of (95.7%/98.8%/82.1%/0.809) and (87.5%/93.0%/78.5%/0.715) for nail disorder and onychomycosis. The diagnostic performance for onychomycosis using ensemble model was superior to 54 dermatologists. CONCLUSIONS: Our study demonstrated that onychomycosis had distinctive dermoscopic patterns, compared with nail psoriasis and traumatic onychodystrophy. The deep learning-based diagnosis models showed a diagnostic accuracy of onychomycosis, superior to dermatologists.

Risk prediction model for high frequency noise-induced hearing loss in young male workers exposed to noise / 中国职业医学

@#Abstract: Objective - - （ ） To investigate the influencing factors of high frequency noise induced hearing loss NIHL in young ， Methods maleworkersexposedtonoise andtoestablishariskpredictionmodelforNIHL. Theyoungmaleswhowerenewly recruitedandwithnormalhearinginnoiseoperationsinanautomobilemanufacturingenterprisefrom 2016to2018wasselected - asresearchsubjectusingaretrospectivecohortstudy.Afollow upsurveywasconducted.MultivariateCoxproportionalhazards， regressionmodelwasusedtoanalyzetheinfluencingfactorsofNIHL andthepartialregressioncoefficientwasusedtoconstruct （PI） PI ， - （PI< ） - theprognosticindex model.Accordingtothe value thesubjectsweredividedintolow riskgroup 0.00 andhigh （PI ） - Results ， risk group ≥0.00 .Kaplan Meiermethod wasused toanalyzetherisk ofNIHL. By 2020 theincidenceofNIHL （ ）， - ， was 33.4% 167/500 which was pure high frequency NIHL and no speech frequency NIHL was detected. Cox proportional - hazard regression model analysis showed that the risk of high frequency NIHL was 2.03 times higher than those with （P< ）， occupational noise exposure level exceeding the standard 0.01 1.62 times higher in those with drinking than in those （P< ）， （P< without drinking 0.05 and 1.69 times higher in those with noisy living environment than in those without drinking ） PI 0.05 . The model constructed according to the partial regression coefficients of the above three influencing factors is PI x x x - （ ， =−0.44+0.71 occupational intensity + 0.49 drinking + 0.52 The probability of high frequency NIHL 3.9% ， ， ， ） - ， ， ， ， 12.3% 19.4% 30.4% 51.1% in the high risk group at 12 24 36 48 and 52 months after taking office was higher than - （ ， ， ， ， ）， that in the low risk group 2.3% 8.3% 10.7% 15.3% and 27.5% especially in the third year after taking office.

Talaromyces marneffei infection in non-HIV-infected patients in mainland China.

BACKGROUND: Talaromyces marneffei, formerly known as Penicillium marneffei, is a significant emerging pathogenic fungus in Southeast Asia which can generate life-threatening systemic infections. Human immunodeficiency virus (HIV) infection is considered as the most underlying disease among systemic infections. However, infections due to T. marneffei without HIV are increasing in recent years. OBJECTIVES: Research the characteristics of T. marneffei infection in non-HIV individuals in mainland China. METHODS: In this study, we searched Pubmed, China National Knowledge Infrastructure (CNKI) and WanFang from inception to 31 December 2019 for studies reporting T. marneffei infection. Our research concentrates on non-HIV-infected cases and their epidemiology, clinical manifestations, laboratory findings, treatment methods and prognosis. RESULTS: T. marneffei infections in non-HIV individuals are increasing. Due to frequent present with atypical symptoms, these non-HIV-infected cases were usually misdiagnosed as other diseases, containing tuberculosis (80.7%), bacterial pneumonia (20.5%), lung cancer (5.1%) or other diseases (5.1%). CONCLUSIONS: T. marneffei infection in non-HIV individuals should be taken seriously. Their symptoms and signs are not typical. Accurate diagnosis and timely antifungal agent treatment is the key to the treatment for the disease.

Antifungal Susceptibility Profiles of Olorofim (Formerly F901318) and Currently Available Systemic Antifungals against Mold and Yeast Phases of Talaromyces marneffei.

In vitro antifungal susceptibility profiling of 32 clinical and environmental Talaromyces marneffei isolates recovered from southern China was performed against olorofim and 7 other systemic antifungals, including amphotericin B, 5-flucytosine, posaconazole, voriconazole, caspofungin, and terbinafine, using CLSI methodology. In comparison, olorofim was the most active antifungal agent against both mold and yeast phases of all tested Talaromyces marneffei isolates, exhibiting an MIC range, MIC50, and MIC90 of 0.0005 to 0.002 µg/ml, 0.0005 µg/ml, and 0.0005 µg/ml, respectively.

Deletion of pksA attenuates the melanogenesis, growth and sporulation ability and causes increased sensitivity to stress response and antifungal drugs in the human pathogenic fungus Fonsecaea monophora.

Fonsecaea monophora, which is very similar to Fonsecaea pedrosoi in morphological features, has been commonly misdiagnosed as F. pedrosoi. Like F. pedrosoi, F. monophora has been also identified as a predominant pathogen of Chromoblastomycosis (CBM). Melanin has been recognized as a virulence factor in several fungi, however, it is still largely unknown about the biological role of melanin and how melanin is synthesized in F. monophora. In this study, we identified two putative polyketide synthase genes (pks), AYO21_03016 (pksA) and AYO21_10638, by searching against the genome of F. monophora. AYO21_03016 and AYO21_10638 were further targeted disrupted by Agrobacterium tumefaciens-mediated transformation (ATMT). We discovered that pksA gene was the major polyketide synthase required for melanin synthesis in F. monophora, rather than AYO21_10638. Phenotypic analysis showed that, knocking out of the pksA gene attenuated melanogenesis, growth rate, sporulation ability and virulence of F. monophora, as compared with wild-type and complementation strain (pksA-C). Furthermore, the ΔpksA mutant was confirmed to be more sensitive to the oxidative stress, extreme pH environment, and antifungal drugs including itraconazole (ITC), terbinafine (TER), and amphotericin B (AMB). Taken together, these findings enabled us to comprehend the role of pksA in regulating DHN-melanin pathway and its effect on the biological function of F. monophora.

Comparison of a fractional 2940-nm Er:YAG laser and 5% amorolfine lacquer combination therapy versus a 5% amorolfine lacquer monotherapy for the treatment of onychomycosis: a randomized controlled trial.

Onychomycosis is a fungal infection of the nail. The aim of this randomized controlled clinical trial was to compare the efficacy of 2940-nm Er:YAG laser treatment combined with a 5% amorolfine lacquer versus amorolfine monotherapy for treating onychomycosis. In this study, patients with onychomycosis of the great toenail were randomly assigned to a combination therapy group and a monotherapy group. In the combination therapy group, the included toenails were treated with a fractional 2940-nm Er:YAG laser at weeks 1, 2, 3, 4, 8, and 12, combined with a 5% amorolfine lacquer twice a week for 12 weeks, while in the monotherapy group, the included toenails were treated with only a 5% amorolfine lacquer twice a week for 12 weeks. The onychomycosis severity index (OSI) score and the mycological clearance rate (MCR) of the included toenails were assessed at baseline, week 12, and week 24. At weeks 12 and 24, the great toenails with mild and moderate onychomycosis in the combination therapy group showed obvious improvement and a greater decrease in OSI than those in the monotherapy group. At week 24, the toenails with mild and moderate onychomycosis in the combination therapy group also showed a better MCR. For the toenails with severe onychomycosis, little improvement was observed in either group at week 12 or week 24. In conclusion, fractional 2940-nm Er:YAG laser treatment combined with a 5% amorolfine lacquer is more effective than amorolfine monotherapy in short-term improvement of onychomycosis.

Murine Macrophage Requires CD11b to Recognize Talaromyces marneffei.

INTRODUCTION: Talaromyces marneffei (T. marneffei) is an emerging pathogenic fungus. Macrophage-1 antigen (Mac-1, CR3, CD11b/CD18) is an important receptor on innate immune cells and can recognize pathogens. However, the importance of CR3 in phagocytosis of T. marneffei by macrophages and their responses to T. marneffei have not been clarified. METHODS: We show that interaction of mouse peritoneal macrophages (pMacs) or RAW264.7 macrophages with T. marneffei of its conidia spores and yeast cells enhances CR3 expression on macrophages. The phagocytosis rate was determined using flow cytometry, RT-PCR and Western blotting were used to detect CD11b expression, and the levels of IFN-γ, TNF-α, IL-2, IL-4, IL-6 and IL-10 in the co-culture supernatants were determined by ELISA. RESULTS: Incubation of mouse macrophages with T. marneffei promoted phagocytosis of T. marneffei, which was dramatically mitigated by pretreatment with anti-CD11b antibody or knockdown of CR3 expression on macrophages. Then, interferon γ, tumor necrosis factor α, IL-4, IL-10 and IL-12 production in macrophages incubation with heat-killed T. marneffei was detected. CD11b expression on mouse macrophages was upregulated by T. marneffei. Incubation of T. marneffei promoted phagocytosis of T. marneffei by macrophages and high levels of pro-inflammatory and anti-inflammatory cytokine production by macrophages, which were mitigated and abrogated by pre-treatment with anti-CD11b or knockdown of CD11b expression. CONCLUSION: These data indicated that murine macrophage requires CD11b to recognize Talaromyces marneffei and their cytokine responses to heat-killed T. marneffei in vitro.