ABSTRACT Dermatophytosis is a highly prevalent superficial fungal infection, yet antifungal susceptibility testing results remain difficult to interpret because clinical breakpoints are unavailable, and epidemiological cutoff values (ECVs) are still limited for most dermatophyte–drug combinations. We conducted a multicenter study of 305 Trichophyton mentagrophytes and Trichophyton interdigitale isolates collected between 2019 and 2024 at six tertiary hospitals across geographically diverse regions of China. Antifungal susceptibility testing was performed using the CLSI M38 broth microdilution method under standardized quality control, and provisional ECVs were derived following CLSI M57 guidance. For T. mentagrophytes , fluconazole showed a non-unimodal MIC distribution and was not assigned a provisional ECV. The remaining seven agents yielded ECVs of 1 µg/mL for ciclopirox olamine and griseofulvin, 0.5 µg/mL for itraconazole, 0.06 µg/mL for voriconazole, 0.25 µg/mL for posaconazole and amorolfine, and 0.016 µg/mL for terbinafine. For T. interdigitale , fluconazole showed a complex non-unimodal distribution, whereas itraconazole and posaconazole showed unstable low-MIC shoulders precluding ECV estimation. The remaining five agents yielded ECVs of 1 µg/mL for ciclopirox olamine, 0.25 µg/mL for griseofulvin, 0.12 µg/mL for voriconazole and amorolfine, and 0.016 µg/mL for terbinafine. Isolates above the provisional ECVs were uncommon for most combinations (≤2.5%), except for griseofulvin against T. interdigitale (20.5%). Overall, the two species showed distinct MIC distribution profiles, underscoring the value of species-level analysis and continued surveillance. These multicenter CLSI-based data and provisional ECVs provide a contemporary baseline for species-specific interpretation of dermatophyte susceptibility data in China. IMPORTANCE Reliable interpretation of dermatophyte antifungal susceptibility testing remains limited because clinical breakpoints and epidemiological cutoff values (ECVs) are unavailable for most dermatophyte–drug combinations. This is particularly important for the Trichophyton mentagrophytes / Trichophyton interdigitale species complex, which is increasingly implicated in refractory dermatophytosis and may display species-specific susceptibility patterns. In this multicenter study, we established provisional epidemiological cutoff values for most tested species–agent combinations and showed that these two closely related species differ in MIC distribution profiles and in the detection of non-wild-type isolates. These data provide practical laboratory thresholds for recognizing isolates with reduced susceptibility, highlight the limitations of complex-level interpretation, establish a contemporary baseline for dermatophyte susceptibility surveillance in China, and may help support laboratory-informed antifungal decision-making.

BACKGROUND:Tinea capitis is still common in China. The gold standard for treatment is oral antifungal drugs. OBJECTIVE:This study aimed to clarify the current epidemiological characteristics and efficacy of different treatments of tinea capitis in China. METHODS:A multicenter, prospective real-world study involving 20 tertiary hospitals in China was conducted. From August 2020 to December 2021, 819 patients with tinea capitis were enrolled. Data concerning demography, clinical types, fungal tests, treatments and outcomes were analyzed. RESULTS:The most common pathogen was Microsporum canis (69.8%). Itraconazole (45.4%) and terbinafine (33.4%) were commonly used, while griseofulvin (16.0%) and fluconazole (5.3%) were less frequently prescribed. Most patients (81.9%) were clinically cured with the initial systemic antifungal treatment schemes. In treating gray patch tinea capitis, the success rate of oral terbinafine (58.1%) was significantly lower than itraconazole (92.2%) and fluconazole (91.3%). Treatment success rate of terbinafine for M canis tinea capitis was 59.4%. LIMITATIONS:All involved clinical centers are tertiary hospitals. Missing data may introduce bias. CONCLUSION:All 4 antifungal drugs have shown good efficacy and were well tolerated. More attention should be paid to the relatively low success rate of oral terbinafine in treating gray patch and M canis tinea capitis.

Aspergillus lentulus (A. lentulus) is an emerging pathogenic fungus with intrinsic resistance to multiple antifungal agents. Understanding its pathogenic mechanisms and the host’s responses is essential for the development of effective therapeutic strategies. The Galleria mellonella (G. mellonella) larvae model offers a convenient and physiologically relevant in vivo system to investigate fungal virulence and host–pathogen interactions, including the dynamics of oxidative stress. In this study, G. mellonella larvae were infected with A. lentulus to assess its virulence. Larval survival rates and intestinal histopathology were evaluated post-infection. Oxidative stress responses were characterized by quantifying intracellular reactive oxygen species (ROS) levels and measuring the activity of key antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST). Additionally, malondialdehyde (MDA) levels were measured as an indicator of lipid peroxidation. At 24h post-infection, A. lentulus significantly reduced larval survival and caused notable intestinal tissue damage, although its virulence was lower compared to Aspergillus fumigatus (A. fumigatus). The infection induced a marked increase in oxidative stress, as indicated by elevated ROS levels (p < 0.01), reduced activities of the antioxidant enzymes SOD, CAT, and GST, and a 57

Background:The emerging pathogenic species Aspergillus lentulus, within the Aspergillus fumigatus complex, poses a significant threat to patient health owing to its high rates of drug resistance and mortality. The aim of this study was to characterize the intraspecies morphology, virulence, and in vitro antifungal susceptibility of A. lentulus. Methods:We cultured A. lentulus isolates from different sources (three clinical isolates and one environmental isolate), along with A. fumigatus (n=1) and Aspergillus fumigatiaffinis (n=1), to observe colony color, diameter, sporulation timing, and spore production. Virulence was assessed using a Galleria mellonella infection model, and survival curves were generated to evaluate strain pathogenicity. Antifungal susceptibility was determined using the colorimetric microdilution method with Sensititre YeastOne® panels. Results:Compared to A. fumigatus and A. fumigatiaffinis, A. lentulus exhibited whitish colonies with pale green overtones, delayed sporulation initiation, and reduced spore yield. The four A. lentulus isolates showed intrastrain variability in the timing of colony color transition, growth rates, sporulation onset, and spore quantification. Virulence experiments demonstrated that all A. lentulus isolates successfully infected G. mellonella larvae and exhibited concentration- and time-dependent survival patterns. Clinical isolates consistently showed significantly lower larval survival rates than the environmental isolates at all infection concentrations. Antifungal susceptibility testing revealed the following minimum inhibitory concentration (MIC) ranges for A. lentulus: posaconazole 0.5-2 μg/mL, itraconazole 1-2 μg/mL, and voriconazole 2-8 μg/mL. Specifically, the clinical isolate A. lentulus-10199 and environmental isolate A. lentulus-10201 exhibited elevated voriconazole MICs (8 μg/mL). All strains demonstrated high MICs for amphotericin B (≥4 μg/mL) and caspofungin (≥8 μg/mL). Conclusion:Aspergillus lentulus exhibited both interstrain and intrastrain variations in growth rate and sporulation characteristics. Clinical isolates demonstrated greater virulence potential than environmental isolates. Aspergillus lentulus displayed favorable susceptibility to posaconazole but reduced susceptibility to voriconazole, amphotericin B, and caspofungin.

Aims: Aspergillus lentulus is an important newly recorded species in the A. fumigatus complex and its resistance to azole drugs and the high mortality rate of infected individuals have emerged as problems. Comprehensive understanding of the A. lentulus is limited due to lack of genome-wide fine mapping data. The aim of this study was to investigate the A. lentulus signature at the molecular level, analyze the genome-wide profile of this strain, and predict its possible genes that execute azole resistance. Methods: In this study, a whole-genome sequencing of a clinically isolated A. lentulus strain (named A. lentulus PWCAL1) was studied by PacBio Sequel sequencing platform. Azole resistance genes were predicted based on whole-genome sequencing data analysis, gene function annotation, comparative genomic analysis, and BLASTP alignment using the Mycology Antifungal Resistance Database to comprehensively understanding the genome-wide features, pathogenicity, and resistance mechanisms of A. lentulus. Results: The results of whole-genome sequencing demonstrated that the total length of A. lentulus PWCAL1 genome was 31255105 bp, the GC content was 49.24%, and 6883 coding genes were predicted. A total of 4565, 1824, and 6405 genes were annotated in the Gene Ontology, Clusters of Orthologous Groups, and Kyoto Encyclopedia of Genes and Genomes databases, respectively. In the Pathogen Host Interactions Database and the Database of Fungal Virulence Factors, 949 and 259 interacting virulence factors were identified, respectively, with the main virulence factor-mutant virulence phenotype, being enriched in reduced virulence. Comparative genomic analysis showed that there were 5456 consensus core genes in this strain and four closely related strains of A. fumigatus complex, which were mainly involved in human diseases, metabolism, organismal systems, etc. Among the three aligned A. lentulus strains, the number of unique genes of this bacterium was the highest with a number of 171, and these genes were mainly associated with carbohydrate metabolism and cell growth and death. Resistance gene prediction demonstrated that the A5653 gene of this bacterium had F46Y/N248T double point mutations on the CYP51A gene, but no tandem repeat mutations in the promoter region were detected. Furthermore, 12 genes belonging to the fungal multidrug resistance ATP-binding cassette (ABC) transporters were identified based on the complete genome sequence and phylogenetic analysis of A. lentulus, which belonged to the ALDp subfamily, the PDR subfamily (AtrB, CDR1, and CDR2), and the MDR subfamily (MDR1), respectively, and there were four genes that are annotated to the major facilitator superfamily multidrug transporter. Further phylogenetic tree classification of the ABC transporter subfamilies predicted in the nine selected A. fumigatus complex strains showed that these putative ABC proteins were divided into two main clusters, which belonged to the PDR (CDR1, CDR2, AtrB, and AtrF) and MDR subfamilies (MDR1, MDR2, and MDR3). The distribution of these ABC proteins varies among different species of the A. fumigatus complex. Conclusions: The main result obtained from this study for the whole genome of A. lentulus provide new insights into better understanding the biological characteristics, pathogenicity, and resistance mechanisms of this bacterium. In this study, two resistance mechanisms, which include CYP51A gene mutation and multidrug-resistant ABC transporter, were predicted in a single isolate. Based on the predicted CYP51A-F46Y/N248T site mutation combination, we speculate that the CYP51A gene of A. lentulus may be partially responsible for azole resistance. Based on the predicted ABC transporter family genes, we hypothesize that resistance to multiple azoles in A. lentulus is mediated, at least in part, by these ABC transporters with resistance.

Antifungal-resistant dermatophytes (ARD) infection is a hotspot issue in clinical microbiology and the dermatology field. Trichophyton indotineae as the dominant species of dermatophyte with terbinafine-resistance or multidrug resistance, is easy to be missed detection clinically, which brings severe challenges to diagnosis and treatment. ARD infection cases have emerged in China, and it predicts a risk of transmission among human. Based on the existing medical evidence and research data, the Mycology Group of Combination of Traditional and Western Medicine Dermatology and Chinese Antifungal-Resistant Dermatophytoses Expert Consensus Group organized experts to make consensus on the management of the infection. Here, the consensus formulated diagnosis and treatment recommendations, to raise attention to dermatophytes drug resistance problem, and expect to provide reference information for the clinical diagnosis, treatment, prevention and control.

Objective To assess the efficacy of combination therapy of clindamycin and rifampicin in recurrent furunculosis. Methods This study was conducted at the outpatient Department of Dermatology (Khalifa Gul Nawaz teaching hospital MTI, Bannu, Bannu Medical College) from December 2019 to December 2020. A total of 150 patients aged between 18 and 65 years of recurrent furunculosis were enrolled. Mupirocin 2 percent was applied on the lesions involving the nostrils, and anal region twice daily, and took oral 400mg tablet of metronidazole three times daily for 10 days. They were prescribed Clindamycin 300 mg twice daily and Rifampicin 600 mg OD for 10 days. The drug was considered efficacious if the patient had no episode of furuncles during a 2-3 month follow‐up period. Results There were 74 patients in Group A and 76 in Group B. Patients in Groups A and B had 30 (40.54%) and 46 (60.52%) male patients and 44 (59.45%) and 30 (39.47%) female patients, respectively. Patients had five major sites of disease recurrence; face 31 (20.6%), neck 30 (20%), axilla 32 (21.3%), buttock 36 (24%) and groin in 21 (14%) patients. Conclusion Combination therapy of clindamycin, rifampicin, metronidazole and mupirocin can be considered a promising therapy for treating recurrent furunculosis.

BACKGROUND:In recent years, the number of invasive aspergillus infection cases caused by Aspergillus lentulus (A. lentulus) has gradually increased and this fungus is usually difficult to distinguish from Aspergillus fumigatus in morphology. All of these presents a great challenge to the treatment of invasive fungal infections caused by A. lentulus. The present study aims to discuss the antifungal resistance, virulence and inflammatory factors' changes after the infection of larvae of A. lentulus separated from patients with chronic obstructive pulmonary disease (COPD) to reflect the host immune response. METHODS:A. lentulus isolated from COPD patients was identified by morphology and molecular biology, and its drug sensitivity was determined in vitro. Then the virulence factors and inflammatory response related factors of A. lentulus were determined by the model of A. lentulus infecting larvae. These were divided into three groups: A. lentulus standard strain, A. lentulus strain isolated from patients; PBS control. The infection model was formed by injecting the suspension of A. lentulus at a concentration of 1×106 CFU into larvae, in order to determine the (1,3)-β-D-glucan and galactomannan levels, and determine the caspase-1 and TNF-α concentration in Galleria mellonella larvae by RT-PCR. RESULTS:The results revealed that A. lentulus had good sensitivity to itraconazole, voriconazole and micafungin, while (1,3)-β-D-glucan was negative in the two groups. The level of galactomannan in the two groups was higher than that in the control group, and the difference was statistically significant (P<0.05). However, there was no statistical difference between the standard strain group and patient strain group (P>0.05). After the infection of larvae, caspase-1 and TNF-α in the Galleria mellonella larvae increased in the two groups, and these elevated levels were statistically significant in both groups (P<0.05). However, there was no significant difference between the two groups (P>0.05). CONCLUSIONS:There is no significant difference in virulence factor and host inflammatory response between A. lentulus isolated from COPD patients and standard strains. Galactomannan has more advantages in the early detection of A. lentulus invasive infection. Furthermore, the caspase-1-mediated inflammasome pathway may be involved in the host immune response to A. lentulus.

Background: Invasive fungal infection received more and more attention because of its high mortality, Candida albicans and Aspergillus fumigatus is the most common pathogenic fungus for systematic fungal infection, A. lentulus was isolated and identified recently and named as a sister of A. fumigatus. Objectives: The current study aimed to explore the concentration and time-dependent relationships of the virulence of fungi due to the change in the Interleukin-1 beta (IL-1β) level. Methods: Candida albicans, A. fumigatus, and A. lentulus suspensions with a multiplicity of infection = 0, 1, 5, 10, and 20 units were used to treat mouse dendritic cells. The IL-β level was measured by enzyme-linked immunosorbent assay (ELISA) at 2, 6, 12, 24, and 48 hours after the treatment was administered. Results: The main effects and interactions between the multiplicity of infection, intervention duration, and the dependent variable of IL-1β were significant. Besides, there were statistically significant differences. Only C. albicans and A. lentulus could induce IL-1β 48 hours after administration. Furthermore, the production of IL-1β induced by A. fumigatus was higher than that induced by A. lentulus and C. albicans. Conclusions: This study demonstrated concentration- and time-dependent relationships in IL-1β production by dendritic cells induced by three types of fungi. Candida albicans and A. lentulus exhibited a slow phase-in in vitro inflammation induction. The inflammatory response induced by A. fumigatusin vitro has the characteristics of a short action time and a strong toxic effect. Finally, A. lentulus is less virulent than A. fumigatus, and its inflammation-inducing time is relatively longer.

Background Malignant melanoma derives from the neuroectodermal mucosa. Melanoma accounts for 1-3 percent of malignancies in children and adults. The incidence and clinical properties of the disease are multifactorial and have biological and environmental variables. Tumor thickness was correlated to age, blood supply, site and nerve supply separately. Objective This study was made to determine the clinical and histopathological correlation of malignant melanoma. Material and Methods A retrospective observational study was conducted at a tertiary care hospital, Urumqi in China to study the clinical and histopathological correlation of malignant melanoma. A detailed history and thorough physical examination of patients, lab tests including primary or secondary tumor biopsies, complete blood count and PET scans help in diagnosis. Clinical staging was done on the basis of regional lymph node involvement and distant metastasis. Results The highest no. of patients (28.20%) was recorded for 60-69 years age group followed by (25.64%) in 70-79 years age group. The largest no. (30.76%) of cases comprised of acral lentiginous melanoma as well as nodular melanoma followed by lentigo maligna melanoma (20.51%) and superficial spreading melanoma (17.95%). The highest no. of patients (35.90%) had tumor thickness of 1-2 mm followed by (20.51%) cases had 2-4 mm, (17.95%) cases had 4 mm in our study. Conclusion This study investigated histopathological and clinical results. The main result we found was that the trunk was involved to major extent than the periphery. Frequently involved subtypes were nodular melanoma and acral melanoma. Female are more commonly affected in this study then male 2:1.

目的 本研究旨在观察分离于新疆的球形孢子丝菌临床株刺激小鼠树突状细胞(Dendritic cells,DCs)后不同炎症因子分泌表达的特征,初步预测这些炎症因子的功能.方法 菌株来源于淋巴管型孢子丝菌病患者.将该菌配置成不同浓度的菌悬液(1×104个/mL～1×107个/mL),刺激小鼠DC(细胞悬浮液浓度1×106细胞/mL),分别收集6 h、24 h、48 h、72 h时细胞培养上清液,采用酶免法检测IL-1β、IL-6、IL-4、TNF-α、IFN-γ的含量表达.结果 以最低浓度菌液(1×104个/mL)刺激DC,被刺激后的DC分泌了IL-1β、IL-6和TNF-α,不同时间点分泌量分别为:IL-1β(6 h:21.26±3.03;24 h:24.04±4.25;48 h:24.90±4.31;72 h:27.29±6.09)、IL-6(6 h:44.38±3.73;24 h:101.72±12.28;48 h:133.10±8.67;72 h:180.38±13.84)、TNF-α(6 h:860.36±20.64;24 h:356.03±11.46;48 h:457.43±17.39;72 h:1454.53±19.46),但是IFN-γ和IL-4未见分泌表达.IL-1β和IL-6分泌水平有随时间和剂量依赖而逐渐增高,但是TNF-α释放量呈现不规律表达.结论 DC参与了球形孢子丝菌感染的天然免疫应答,分泌的关键炎症因子是IL-1β、IL-6、和TNF-α,表达量为TNF-α>IL-6>IL-1β.其中IL-1β和IL-6分泌表达量具有时间和剂量依赖性.

Aspergillus takadae is characterized by its heterothallic reproduction, pale yellow cleistothecia, broadly lenticular ascospores with two short equatorial crests and smooth convex surfaces, and broadly ellipsoidal to ovate conidia with a smooth wall. The validation of these novel species is supported further by the analyses of the beta-tubulin, calmodulin, actin, and RPB2 sequences. In addition, the phylogenetic tree and DDBJ accession numbers of all the species of Aspergillus section Fumigati are presented. We report on the crossing of A. takadae species and the result of crossing A. takadae with a closely related species, A. spathulatus. (C) 2019 Published by Elsevier B.V. on behalf of the Mycological Society of Japan.

Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Metastatic disease have a grave prognosis in comparison to early stage metastatic cancer where surgical treatment can benefit the patients thus traditional chemotherapy regimens have been found to offer relatively little survival benefit. Treatment of advanced or metastatic melanoma includes involvement of biological modalities such as immunotherapeutic approaches, targeted therapies and epigenetic modification therapies. The goal of immunotherapy for cancer is to provide an effective anticancer immune response. These biological therapies restore or increase the activities of specific immune-system components and counteract immunosuppressive signals produced by cancer cells. Monoclonal antibodies, are laboratory-produced antibodies that bind to specific antigens expressed by cells, such as a protein that is present on the surface of cancer cells but is absent from normal cells. They interfere with the action of proteins that are necessary for tumor growth. When bound to bevacizumab, VEGF cannot interact with its cellular receptor, preventing the signaling that leads to the growth of new blood vessels. MAb’s that bind to cell surface growth factor receptors prevent the targeted receptors from sending their normal growth-promoting signals. The targeted therapeutic agents modulate specific pro-oncogenic mutations such as v-Raf murine sarcoma viral oncogene homolog B (BRAF), MEK inhibitors and CDK4/CDK6, PTEN and GNAQ/GNA11 genes. This review summarizes the biological agents and newer modalities of treatments, and their recent advancements and contributions in the treatment of patients with metastatic melanoma.

In the past ten years, the occurrence of basal cell carcinoma (BCC) has amplified manifold. There are many treatment procedures to cure BCC, which includes micrographic surgery by means of surgical margins of 3-5mm based on size of tumor, intrusion and location. The normally used method for treatment of basal cell carcinoma is excision by surgery. The most commonly used advanced method of excision in the treatment of bcc is Mohs’ micrographic surgery (MMS). There is no proper guideline, which mentions surgery as the treatment of choice as there are no controlled randomized studies matching surgery with nonsurgical treatment options in BCC. Excision is a competent and meticulous technique as there is a low recurrence of tumor following the histological examination of tumor margins.

Systemic lupus erythematosus (SLE) is an autoimmune syndrome associated with severe organ damage resulting from the activation of immune cells. Recently, a role for caspase-1 in murine lupus was described, indicating an involvement of inflammasomes in the development of SLE. Among multiple inflammasomes identified, the NLRP3 inflammasome was connected to diverse diseases, including autoimmune encephalomyelitis. However, the function of NLRP3 in SLE development remains elusive. In this study, we explored the role of NLRP3 in the development of SLE using the pristane-induced experimental lupus model. It was discovered that more severe lupus-like syndrome developed in Nlrp3(-R258W) mice carrying the gain-of function mutation. Nlrp3(-R258W) mutant mice exhibited significantly higher mortality upon pristane challenge. Moreover, prominent hypercellularity and interstitial nephritis were evident in the glomeruli of Nlrp3(-R258W) mice. In addition, hyper activation of the NLRP3 inflammasome in this mouse line resulted in proteinuria and mesangial destruction. Importantly, all of these phenotypes were largely attributed to the Nlrp3(-R258w) mutation expressed in myeloid cells, because Cre recombinase mediated depletion of this mutant from such cells rescued mice from experimental lupus. Taken together, our study demonstrates a critical role for NLRP3 in the development of SLE and suggests that modulating the inflammasome signal may help to control the inflammatory damage in autoimmune diseases, including lupus.

The paper is intended to analyze and evaluate the specific curative effect and safety of 2% liranaftate ointment in treating patients with tinea pedis and tinea cruris. 1,100 cases of patients with tinea pedis and tinea corporis & cruris were selected as research objects and were divided into two groups according to the random number table method. They were treated with different methods: 550 cases of patients were treated with 2% liranaftate ointment for external use in the observation group and the rest 550 cases of patients were treated with 1% bifonazole cream in the control group. The treatment time was two weeks for patients with tinea corporis & cruris and four weeks for those with tinea pedis respectively. Meanwhile, the one-month follow-up visit was conducted among the patients to compare the curative effects of two groups. After the medication, the curative effectiveness rate was 87.65% (482/550) in the observation group, while that was 84.91% (467/550) in the control group. After the average follow-up visits of (15.5±2.4), the curative effectiveness rate 96.55% (531/550) in the observation group, while that was 91.45% (503/550) in the control group. Two groups of patients recovered well with a low incidence of adverse reactions in the treatment, and the overall curative effect was good with the inter-group difference at P>0.05, so it was without statistical significance. The curative effect of 2% liranaftate ointment is safe and obvious in treating tinea pedis and tinea corporis & cruris, so it is valuable for clinical popularization and application.