Tolerogenic dendritic cells involve in reconstructing T cell balance in neuroimmune conditions / 中华神经科杂志

Dendritic cells are the most powerful antigen-presenting cells in the human body, which are involved in the occurrence and development of multiple sclerosis, neuromyelitis optica, myasthenia gravis and other neuroimmune conditions. Recently, tolerogenic dendritic cells (tolDCs) are gradually becoming the research focus and therapeutic target of neuroimmune conditions. They can reconstruct the balance of T cells by inducing effector T cell anergy/deletion, and producing antigen-specific regulatory T cells, ultimately achieving the goal of maintaining immune tolerance. In this review, the mechanisms that tolDCs reconstruct T cell balance in neuroimmune conditions are analyzed and the research progress related to tolDC therapy is summarized.

Association of mobile phone use with childhood abuse experiences and sleep quality in medical students / 中国学校卫生

Objective@#To explore the mediating effect and gender difference of mobile phone use in the association between different types of childhood abuse experiences and sleep quality of medical students, so as to provide reference for promoting sleep quality of medical students.@*Methods@#A longitudinal study design method was used to select freshmen and sophomores in two medical colleges in Anhui Province from November to December 2019, follow up data were collected from May to June 2020, and a total of 6 879 students were included in this study. Spearman correlation was used to analyze the association between baseline childhood abuse experiences, baseline mobile phone use and follow up sleep quality. Bootstrap program and Process software were applied to test the mediating effect of mobile phone use in the relationship between childhood abuse and sleep quality.@*Results@#Childhood abuse experiences were positively correlated with mobile phone use and sleep quality score ( r = 0.27 , 0.24, P <0.01), and mobile phone use was positively correlated with sleep quality score ( r =0.31, P <0.01). In the total sample, after adjusting for confounding factors, mobile phone use played a partial mediating role in childhood abuse experiences (including emotional abuse, physical abuse, sexual abuse) and sleep quality, and the mediating effect was 18.08% (18.12%, 17.15%, 24.09%). The mediating effect of mobile phone use on the relationship between childhood emotional abuse, sexual abuse, childhood abuse and sleep quality in girls(18.32%, 28.05%, 18.24%) was higher than in boys(17.81%, 18.94%, 17.63%).@*Conclusion@#Mobile phone use has a mediating effect on the relationship between childhood abuse and sleep quality, controlling mobile phone overuse may contribute to improving the sleep quality for those who have experienced childhood abuse.

Efficacy and safety of baricitinib in the treatment of moderate-to-severe atopic dermatitis: a clinical observation / 中华皮肤科杂志

Objective:To evaluate the efficacy and safety of baricitinib in the treatment of moderate-to-severe atopic dermatitis (AD) .Methods:From June 2020 to June 2021, patients with moderate-to-severe AD who were insensitive or intolerant to topical agents were enrolled from Department of Dermatology, Peking University First Hospital. Before treatment, the patients were evaluated by 4 scales, including the Investigator′s Global Assessment (IGA), Eczema Area and Severity Index (EASI), Itch Numeric Rating Scale (NRS), and Dermatology Life Quality Index (DLQI) ; meanwhile, photos of skin lesions were taken, routine blood test was performed, blood biochemical indices and total IgE levels were measured. After exclusion of contraindications, the patients were treated with oral baricitinib at a dose of 2 mg/d for 16 weeks. Regular follow-up was conducted at weeks 1, 2, 4, 8, 12, 16 and 20 after the start of treatment, clinical evaluation was carried out with the above 4 scales, and adverse events were recorded during the treatment.Results:A total of 24 patients were enrolled in the study, and all completed 16-week oral treatment and 20-week follow-up. All the 4 scale scores showed a continuous downward trend within 20 weeks after the start of treatment. At week 20, the patients′ IGA, EASI, NRS, and DLQI scores significantly decreased from 4.13 ± 0.61, 37.59 ± 14.86, 6.83 ± 2.26 and 18.67 ± 8.64 points respectively at baseline to 1.12 ± 0.49, 4.53 ± 3.78, 0.72 ± 0.58 and 1.39 ± 0.85 points respectively ( t = 22.70, 10.55, 10.69, 8.40, respectively, all P < 0.001). During the follow-up period, no serious adverse reactions were observed; 3 patients experienced gastric discomfort at the start of oral treatment, but the symptoms disappeared after the treatment continued; 3 developed acute allergic manifestations (1 case of allergic conjunctivitis, 2 cases of acute urticaria), which resolved rapidly after the use of antihistamines without recurrence. Conclusion:Baricitinib can provide a safer and more effective treatment option for patients with moderate-to-severe AD, especially those who are insensitive or intolerant to topical agents and need systemic treatments.

Clinical efficacy and safety of dupilumab in the treatment of atopic dermatitis / 中华皮肤科杂志

Objective:To evaluate efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) .Methods:A retrospective study was conducted among patients with AD who showed poor response to topical agents and then received standardized injections of dupilumab for 16 weeks in Department of Dermatology, Peking University First Hospital from June 1, 2020 to September 1, 2021. Basic information on the patients was collected, so were the Investigator′s Global Assessment (IGA), Eczema Area and Severity Index (EASI), Itch Numeric Rating Scale (NRS), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM) scores recorded before and at weeks 2, 4, 8, 12, and 16 during treatment. Adverse reactions were recorded during treatment. Wilcoxon rank sum test was used to compare the scores of all patients at the end of follow-up with those before treatment.Results:A total of 57 patients were enrolled in the study, and all completed 16-week injections and follow-up. At week 16, the patients′ IGA, EASI, NRS, DLQI, and POEM scores significantly decreased from 4.0 (4.0, 5.0), 30.0 (17.2, 36.0), 9.0 (7.0, 10.0), 15.0 (11.5, 20.5), and 19.0 (15.5, 23.0) points respectively at baseline to 1.0 (1.0, 1.0), 4.0 (1.6, 7.3), 1.0 (0.0, 1.0), 3.0 (1.0, 4.0), and 4.0 (2.0, 4.0) points respectively ( Z = 6.65, 6.57, 6.59, 6.57, and 6.57 respectively, all P < 0.001). All the 5 scale scores showed a continuous downward trend within 16 weeks after the start of dupilumab treatment. During the follow-up period, no serious adverse reaction was observed, and only two patients developed conjunctivitis. Conclusion:Dupilumab shows marked efficacy in the treatment of AD, with favorable safety.

Superficial fungal infections in psoriatic patients treated with interleukin-17-related biological agents and their management / 中华皮肤科杂志

This review summarizes the contribution of interleukin-17 (IL-17) to the susceptibility to mucocutaneous fungal infections, and superficial fungal infections associated with IL-17-targeting biological agents, such as secukinumab, ixekizumab, brodalumab, bimekizumab and ustekinumab, in the treatment of psoriasis. The superficial fungal infections associated with the treatment with IL-17-related biological agents are usually mild or moderate, and most of them are limited, with a good response to anti-fungal therapy. In addition, this review introduces clinical evaluation, monitoring and treatment of related superficial fungal infections, and provides a basis for safe clinical use of IL-17-targeting biologics.

Invasive candidiasis in the elderly: a single-center, retrospective cohort study / 中华老年医学杂志

Objective:To investigate the clinical and mycological characteristics, treatment and prognosis of invasive candidiasis(IC)in the elderly.Methods:This retrospective study included aged patients(≥65 years)admitted to the Peking University First Hospital between January, 2010 and December, 2019, who were diagnosed with IC based on positive culture results.The infecting strains were re-identified and their antifungal drug resistance was tested.The clinical and mycological characteristics, treatment and prognosis information of the elderly patients were collected and compared with those of non-elderly adults.Results:A total of 99 aged patients were included, with a median age of 78(70-83)years and a male-to-female ratio of 2.1∶1.0.The elderly accounted for 62.7%(99/158)of the adult IC patients.Compared with their younger counterparts, elderly patients were more likely to need medium-to long-term hospitalization and intensive care unit(ICU)stay, and to show concurrent heart failure, respiratory failure or renal failure, to require mechanical ventilation, and to show deep-seated bacterial infections and multifocal Candida colonization, especially for those with previous fluconazole exposure( P<0.05). Bloodstream was the most common Candida transmission route(71/99, 71.7%)and Candida albicans was the most prevalent species(47/99, 47.5%). Antifungal resistance was highest for fluconazole(17/117, 14.5%)and voriconazole(15/117, 12.8%). No significant difference was found between elderly patients and non-elderly patients in terms of infected sites, Candida species, and antifungal resistance( P>0.05). A total of 86 patients(86.9%)received systemic antifungal treatment and fluconazole was the most commonly used drug(35/86, 40.7%). The thirty-day all-cause mortality in aged IC patients was 32.6%(29/89), significantly higher than in younger patients( P=0.022). Logistic regression analysis revealed that advanced age( OR=1.12, 95% CI: 1.06-1.20, P<0.001), renal failure( OR=4.81; 95% CI: 1.65-14.03; P=0.004), and a high Candida score( OR=1.81, 95% CI: 1.06-3.11, P=0.031)significantly increased the risk of death. Conclusions:Elderly patients were the main affected population of IC, and the mortality of IC steadily increases with age.Treatment for aged IC patients should be proactive and cautious.

Adverse reactions to interleukin-17A and its receptor antagonists in the treatment of psoriasis / 中华皮肤科杂志

Interleukin (IL) -17A plays a key role in the occurrence and development of psoriasis. To date, several marketed IL-17A and its receptor antagonists have been applied to the treatment of psoriasis, and definite therapeutic effects have been achieved. However, several adverse reactions, including upper respiratory tract infection, Candida infections, neutropenia, inflammatory bowel disease, which can be life-threatening, have been reported in clinical trials and after marketing of these biologics. This review summarizes clinical safety profiles of 3 types of interleukin-17A and its receptor antagonists, i.e., secukinumab, ixekizumab and brodalumab.

Progress of MR imaging markers in the diagnosis of intervertebral disc degeneration and discogenic low back pain / 中华骨科杂志

Low back pain (LBP) is no specific pain in most cases, and 39% to 41% of which is discogenic LBP. Intervertebral disc degeneration (IVD) is basic pathologic change of discogenic LBP. Routine MRI can't quantitatively diagnose IVD and discogenic LBP, but with the application of quantitative MR technology, noninvasive ways to detect components and structure in intervertebral disc become possible. MR imaging markers are various parameter information or images obtained by quantitative MRI, such as T1ρ value, T2 mapping relaxation time, ADC value, FA value, MTR asym value, K sw value, △T1 value, spectral information of metabolic substances, etc. Through the analysis of these information, we can quantitatively measure the content of specific substances in the intervertebral disc and get information about the structure changes in the disc. MR imaging markers can provide accurate and comprehensive information for discogenic LBP and IVD in early stage.

Expert consensus on the diagnosis and treatment of cryptococcal meningitis / 中华内科杂志

Cryptococcal meningitis is a common and refractory central nervous system infection,with high rates of mortality and disability.The experts of the Society of Infectious Diseases of Chinese Medical Association have reached this consensus after a thorough discussion.Based on the current situation of cryptococcal meningitis in China,the management of cryptococcal meningitis includes 6 aspects:introduction,microorganism identification,clinical manifestations and diagnosis,principles of antifungal therapy,treatment of refractory and recurrent meningitis,treatment of intracranial hypertension.There is not a separate consensus on human immunodeficiency virus (HIV) infection in patients with cryptococcal meningitis.This article focuses on different antifungal regimens and reducing intracranial pressure by reference to Infectious Disease Society of America (IDSA) guidelines.The importance of early diagnosis,combined long-term antifungal therapy,control of intracranial hypertension are emphasized.

Identification and antimicrobial susceptibility of 52 pathogenic fungi causing candidemia in Nanchang City of Jiangxi Province / 中国感染控制杂志

Objective To explore the constitute and antimicrobial susceptibility of pathogenic fungi causing candidemia in Nanchang City of Jiangxi Province.Methods Candida spp.isolated from blood specimens of patients at a hospital in Nanchang in March-October 2015 were collected, fungal strains were identified by amplifying the internal transcribed spacer (ITS) and large ribosomal subunit (D1/D2 region of 26rRNA), antifungal susceptibility of fungi was detected.Results A total of 1 332 positive blood culture specimens were collected, including 74 fungal positive specimens, accounting for 5.56％, 52 strains of Candida spp.were obtained, most were Candida tropicalis (n=17,32.69％),followed by Candida albicans(n=16, 30.77％) and Candida parapsilosis complex (n=16, 30.77％).Identification results of ITS and D1/D2 region were identical.52 strains of Candida spp.were sensitive to both micafungin and caspofungin, epidemiological cutoff value(ECV) of amphotericin B showed that 52 strains were all wild type.Resistance rates of Candida tropicalis to fluconazole and voriconazole were 29.41％ and 17.64％ respectively, ECV of itraconazole and posaconazole showed that wild type accounted for 82.35％ and 94.12％ respectively;resistance rates of Candida albicans to fluconazol and voriconazole were 93.75％ and 81.25％ respectively, ECV of itraconazole and posaconazole showed that wild type accounted for 75.00％ and 81.25％ respectively;Candida parapsilosis complex strains were sensitive to both fluconazole and voriconazole, ECV of itraconazole and posaconazole showed that all were wild type;all Candida glabrata strains had intermediate resistance rates to fluconazole, ECV of voriconazole, itraconazole, and posaconazole showed that wild type accounted for 66.67％, 100.00％, and 100.00％ respectively.Conclusion Candida tropicalis is the most common pathogenic fungus causing candidemia in Nanchang of Jiangxi, followed by Candida albicans and Candida parapsilosis complex.Azole, echinocandin, and amphotericin B are still first-line antifungal agents.

Rhizopus arrihizus swollen spores induce mice dendritic cells to Th1 and Th17 differentiation / 中华微生物学和免疫学杂志

Objective To study the mechanism of adaptive immunity against Rhizopus arrihizus (R. arrihizus) infections. Methods Bone marrow derived dendritic cells (BMDCs) were separated from C57BL/6 mice and Card9-/- mice and then were cultured in vitro. Resting spores and swollen spores of R. arrihizus were in vitro co-cultured with BMDCs with or without Syk inhibition. Secretion of cytokines ( IL-23, IL-1βand IL-12) was analyzed by ELISA after 24 hours of culture. Na?ve T cells derived from C57BL/6 mice were in vitro co-cultured with spore-stimulated BMDCs for four days. Levels of IL-17A and IFN-γ in supernatants of cell culture were analyzed by ELISA. Flow cytometry was performed to analyze T cell differ-entiation. Confocal microscopy was used to observe the images of stained β-glucan on the surface of resting and swollen spores. Swollen spores were co-cultured with Dectin-1, Dectin-2, TLR2 and mannose receptor ( MMR) , and the binding results were analyzed by flow cytometry. Results Swollen spores but resting spores could induce the maturation of BMDCs and promote the secretion of cytokines (IL-23, IL-1βand IL-12). Co-culturing T cells with swollen spore-stimulated BMDCs enhanced their differentiation to Th17 and Th1. In addition, swollen spores promoted the secretion of Th1-related cytokine ( IFN-γ) and Th17-related cytokine (IL-17A). Adding Syk inhibitor to Card9-/-BMDCs or wild type BMDCs significantly inhibited the secretion of cytokines and T cell differentiation, especially in the Card9-/- group. β-glucan was overserved on the surface of swollen spores, but not on resting spores. On the surface of swollen spores existed pathogen associated molecular patterns ( PAMPs) that could bind with Dectin-1 and TLR2. Conclusion Swollen spores of R. arrihizus could active BMDCs to secrete cytokines of IL-23, IL-1β and IL-12 and trigger T cell responses in vitro. The possible mechanism might be associated with β-glucan exposed on the surface of swollen spores that binds with Dectin-1. The responses between BMDCs and R. arrihizus are Syk-Card9-dependent.

Clinical analysis of cutaneous manifestations and related factors in patients with ulcerative colitis / 中华内科杂志

Objective To investigate the cutaneous manifestations in patients with ulcerative colitis (UC) and related factors.Methods Patients admitted to Department of Gastroenterology Peking University First Hospital from January 1994 to December 2014 and diagnosed as UC were retrospectively enrolled in this study.Skin disorders were confirmed by the dermatologists.Clinical data were collected and compared between patients with and without cutaneous manifestations.Results Among the total 373 UC patients,there were 34 cases (9.1％) with cutaneous manifestations,including 11 pyoderma gangrenosum,8 erythema nodosum,6 eczema,3 psoriasis,2 pemphigus,1 granulomatous cheilitis,1 ichthyosis,1 acne rosacea,and 1 impetigo.The skin manifestations may occur after the diagnosis,simultaneously or even before the diagnosis of UC,which were 24,7 and 3 patients respectively.The mean age in patients with skin lesions was (47.2 ± 12.1) years,male to female ratio 0.79∶ 1.More patients with skin manifestations had severe activity of UC compared with non-skin group [50.0％ (17/34) vs 25.1％ (85/339),P =0.01].In addition,the proportion of extensive colitis in skin lesion group was significantly higher than that in non-skin group [76.5％ (26/34) vs 54.6％ (185/339),P =0.04].Conclusions The cutaneous manifestations associated with UC are polymorphic,erythema nodosums and pyoderma gangrenosums are the most common skin lesions seen in UC patients.Skin lesions occur concurrently,pre or post the diagnosis of UC.Skin lesions in UC patients suggest more severe disease activity.Clinicians need to pay more attention to this group.

Th and Treg response induced by Aspergillus fumigatus pulsed dendritic cells in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dendritic cells (DCs) can recognize the pathogen-associated molecular patterns (PAMP) of Aspergillus fumigatus (A. fumigatus), activating the immune response. During A. fumigatus infection, a Th and Treg response induced in the fungi-pulsed DCs is not yet well understood.</p><p><b>METHODS</b>In this study, bone marrow-derived dendritic cells (BMDCs) were separated and proliferated from C57BL/6 mice. A. fumigatus pulsed DCs were generated and cultured with CD4(+) T cells derived from the spleen of C57BL/6 mice in vitro. CD4(+) T cells differentiation after co-culture were analyzed by flow cytometry, ELISA, and real-time PCR analysis.</p><p><b>RESULTS</b>The A. fumigatus pulsed DCs exhibited increased Th1 and Treg frequency, Th1-related cytokines (IFN-γ and IL-12), Treg-related cytokines (TGF-β) and T-bet, and Foxp3 mRNA levels compared with the control group. There was no significant difference between A. fumigatus pulsed DCs group and the control group about Th17 and Th2 frequency.</p><p><b>CONCLUSIONS</b>The inactivated conidia of A. fumigatus were able to activate BMDCs and made them capable of triggering T cell responses in vitro. A. fumigatus loaded DCs was a weak inducer of Th17 and Th2, but induced a strong Th1 and Treg response.</p>

The application of Real-time PCR in invasive aspergillosis diagnosis / 中华检验医学杂志

Objective To investigate the value of Real-time PCR in the diagnosis of invasive aspergillosis(IA) and to compare it with galactomannan antigen assays.Methods A retrospective study was performed on 110 episodes of hospitalization of 88 patients who were at risk of invasive aspergillosis at Peking University First and Renmin Hospital from May 2008 to December 2010.23 cases with diagnosis and clinical diagnosis IA were classified as infection group and 87 cases with suspected diagnosis and non-IA were classified as non-infeciton group according to the international criterion.Real-time PCR and gaiactomannan antigen detections were performed on 257 serum samples.A receiver operating characteristic curve (ROC)was developed based on the quantitative cycle numbers and an optimal cut off value of quantification cycle (Cq) was determined.The sensitivity (Se),specificity (Sp),positive predictive value (PPV) and negative predictive value (NPV) were calculated under different considerations among which McNemar chi-square tests were used for statistical analyze.Results The area under ROC curve of Real-time PCR for the diagnosis of IA was 0.91 (95％ CI:0.825-0.995) and the optimal cut off value of Cq was 39.45.The Se and Sp of one positive PCR,two positive PCR,one positive GM and two positive GM were 87.0％,79.3％ ; 58.3％,97.8％ ; 78.3％,63.2％ ; and 58.3％,82.6％,respectively.When one positive PCR was considered as the diagnostic criterion of IA,Real-time PCR was able to diagnose 100％ and 84.2％ of proven and probable IA cases,respectively.The Sp of one/two positive PCR were statistically higher than one/two positive GM (P ＜ 0.05),respectively.The Sp of two positive PCR was statistically higher than one positive PCR (P ＜0.05).The Se and Sp were 65.2％,89.7％ and 100％,52.3％ for one positive PCR combined one positive GM and one PCR or GM positive,respectively.Conclusions Real-time PCR assays have better sensitivities and specificities than GM in the diagnosis of invasive aspergillosis.When two PCR positive were considered,better specificity and positive predictive value were achieved.

Identification of Peudallescheria boydii/Scedosporium apiospermum dinical isolates by sequence differences of ITS and TUB / 中华检验医学杂志

ObjectiveTore-identifyfifteenclinical Pseudallescheriaboydii/Scedosporium apiospermum isolates by the sequence difference of ITS rDNA and partial β-tubulin gene (TUB) and thus understand thepathogenicstrain typesfor guiding theclinicaltreatment.MethodsMorphological appearances,D-ribose assimilation and sequencing of ITS and TUB were used to re-identify the fifteen clinical strains of Pseudallescheria boydii/Scedosporium apiospermum.The sequences of ITS and TUB were analyzed with Clustal X and MEGA 4 software.Results No difference of morphological appearances was found in the fifteen strains.Cleistothecium was observed in one isolate.All the strains were D-ribose assimilation positive.The clinical strains were re-identified as P.boydii species complex by the CBS database (http://www.cbs.knaw.nl).ElevenstrainswereP.boydiiandfourstrainswereS.apiospermum respectively.Conclusions P.boydii and S.apiospermum cannot be identified correcdy by the time-consuming conventional morphological method and biochemical characteristics.The study recommend that the clinical isolates of P.boydii and S.apiospermum should be identified utilizing a combination of traditional phenotype method and molecular biotechnology.

A case of cutaneous leishmaniasis misdiagnosed as cutaneous aspergillosis and successfully treated with terbinafine / 中华皮肤科杂志

A 5-year-old Mongolian girl from Inner Mongolia presented with a painless,round skin lesion on the left cheek for 10 months.Several weeks prior to the development of lesions,her left cheek was seratched by a dog.Subsequently small asymptomatic erythematous papules developed at the scratched site and gradually enlarged.Direct microscopy of scales from the lesions revealed septate,branching hyphae and fungal culture grew Eurotiom amstelodami(perfect stage of aspergillus).She was initially diagnosed as cutaneous aspergillosis and treated with itraconazole 200 mg per day for 2 months,but limited improvement was achieved.Histopathological examination with Wright-Giemsa staining of skin biopsies revealed abundant leishman Donovani hodies intracellulatry and extracellularly in the dermis and subcutaneous tissue; PAS staining of tissue specimens showed no fungal element and fungal culture was negative.She was finally diagnosed with cutaneous leishmaniasis.After treatment with terbinafine 125 mg per day for 2 months,the lesion subsided.

Susceptibility testing of Aspergillus biofilms against common antifungal drugs and a preliminary study on molecular mechanisms of antifungal drug resistance in Aspergillus biofilms / 中华皮肤科杂志

Objective To explore the susceptibility of Aspergillus biofilms to common antifungal drugs and molecular mechanisms of antifungal drug resistance of Aspergillus biofilms. Methods The susceptibility of planktonic spores of 22 clinical isolates of Aspergillus spp. to amphotericin B, caspofungin and voriconazole was evaluated by a standard broth microdilution method. Meanwhile, in vitro model of Aspergillus spp. biofilm was established for the 22 isolates, then the susceptibility of Aspergillus spp. biofilm to amphotericin B, caspofungin and voriconazole was evaluated by a method for antifungal susceptibility testing combined with colonmetric XTT-reduction assay. In addition, real-time reverse transcription (RT)-PCR was performed to determine the relative expressions of drug efflux pump genes and azole target enzyme genes during the formation of Aspergillus spp. biofilms. Results In terms of planktonic spores of Aspergillus spp., the- minimal inhibitory concentration (MIC) range was 0.5 to 2 mg/L for amphotericin B, 0.5 to 1 mg/L for voriconazole, and the minimal effective concentration (MEC) range was 0.125 to 0.25 mg/L for caspofungin. As far as Aspergillus spp.biofilms was concerned, the sessile minimum concentration required to inhibit the growth of 50% organisms (SMIC50) and 80% organisms (SMIC80) ranged from 2 to > 32 mg/L and from 8 to > 32 mg/L, respectively, for amphotericin B, from 32 to > 256 mg/L and from 256 to >256 mg/L respectively for caspofungin, from 4 to >256 mg/L and from 32 to > 256 mg/L, respectively for voriconazole. During the formation of Aspergillus spp.biofilms, no change was observed for the expression of any of the 7 tested drug efflux pump genes or azole target enzyme genes at 4 hours, while a significant increase was noted in the expression of AfuMDRl, CYP51B and CYP51A genes at 8 hours, as well as in the expression of AfuMDRl, AfuMDR2, AfuMDR4, CYP51A,CYP51B at 12, 16 and 24 hours. Of these genes, CYP51A showed the strongest increase in expression at the above 4 time points. The expression of AfuMDR3 and atrF experienced no significant change during the formation of Aspergillus spp. biofilms. Conclusions Compared to planktonic spores, Aspergillus spp. biofilms exhibit a decreased susceptibility to amphotericin B, caspofungin and voriconazole. After the formation of biofilms, the expression of drug efflux pump genes and azole target enzyme genes is elevated in Aspergillus spp.

Molecular mechanisms of cross-resistance to azole antifungal agents in a clinical isolate of Aspergillus fumigatus: a preliminary study / 中华皮肤科杂志

Objective To investigate the molecular mechanisms of cross-resistance to azoles in a clinical isolate of Aspergillus fumigatus. Methods A. fumigatus was isolated from a patient with invasive aspergillosis.Clinical Laboratory Standard Institute M38-A2 broth microdilution method and E-test method were used to determine the minimum inhibitory concentrations (MICs) or minimum effective concentration (MEC) of itraconazole, voriconazole, amphotericin B, posaconazole and caspofungin for the A. fumigatus isolate. DNA was extracted from the isolate and subjected to the amplification of cyp51A gene encoding the target enzyme of azole antifungal agents followed by sequence analysis. Results The broth microdilution test showed that the MEC of caspofungin was 0.5 mg/L, and MICs of itraconazole, voriconazole and amphotericin B were ≥ 16 mg/L,8 mg/L and 1 mg/L, respectively, for this isolate; while E-test assay revealed that the MICs of caspofungin,itraconazole, voriconazole, amphotericin B and posaconazole were 0.047 mg/L, ≥32 mg/L,≥32 mg/L, 12 mg/L and ≥32 mg/L, respectively. Sequence analysis showed an insertion of a 34-bp tandem sequence in the promoter region of the cyp51A gene as well as a T364A point mutation causing the substitution of leucine 98 (L98H). In addition, there were some other mutations in the cyp51A gene of this isolate, such as A137T,G585A, C814A, G836C, T991C and A1350G, which could result in corresponding amino acid substitutions.Conclusions An A. fumigatus strain with cross-resistance to azole antifungal agents is isolated. There is an insertion of a 34-bp tandem sequence into the promoter region as well as a T364A point mutation in the cyp51A gene, which contribute to the cross resistance to azole antifungal agents including itraconazole, voriconazole,and posaconazole. In addition, other mutations causing amino acid substitutions have also been detected in the cyp51 A gene of this isolate.

Two cases of tinea caused by Microsporum gyeum and their pathogenic analysis / 中华皮肤科杂志

Two patients were admitted to the hospital for 2-month history of pruritic eruptions on the forehead and 2-week history of pruritie eruptions on the leg, respectively. Both patients had a history of pet contact. Topical application of glucocorticoids did not work well. Dermatological examination revealed a patch measuring 5 cm ×6 cm on the forehead of one patient and a patch measuring 2 cm × 3 cm on the leg of the other patient. Both patches were surrounded by red papules and scaling. Microscopic examination of skin scales revealed hyphae and chain-like spores, and culture of skin scales grew Microsporum gyeum. Both the isolates of Microsporum gyeum were sensitive to ketoconazole, miconazole, bifonazole, terbinafine, and voriconazole. Both patients were healed after treatment with oral terbinafine and topical ciclopirox olamine.

In vitro susceptibility testing of 16 strains of Exophiala dermatitidis to 6 commonly used antifungal agents / 中华皮肤科杂志

Objective To investigate the in vitro susceptibility of 16 strains of Exophiala dermatitidis to 6 commonly used antifungal agents. Methods The Glinical and Laboratory Standards Institute (CLSI)M27-A2 protocol was carried out to determine the MIGs of terbinafine (TRB), itraconazole (ITC), amphotericin B (AMB), fluconazole (FLC), voriconazole (VRC), and caspofungin (GAS) to 16 strains of E. dermatitidis, and E-test was performed to determine those of VRG, ITC and AMB. Besides, the minimal fungicidal concentrations (MFGs) of the above antifungal agents to the 16 strains of E. dermatitidis were further assessed.The activity of TRB in combination with ITC and VRG against E. dermatitidis was also estimated. Results The MIC ranges of TRB, VRC, ITC, AMB, FLC, and CAS were 0.125 - 0.25 mg/L, 0.25 - 0.5 mg/L, 2.0 mg/L,2.0 mg/L, 16 - 32 mg/L and 16 - 64 mg/L respectively as shown by M27-A2 microdilution assay, while the MIC ranges of VRG, ITG and AMB, as determined by E-test, were 0.032 - 0.094 mg/L, 0.047 - 0.5 mg/L and 0.125 - 3.0 mg/L, respectively. The MFC ranges of TRB, VRC, ITG, AMB and FLG were 0.125 - 0.5 mg/L,0.25 - 0.5 mg/L, 2.0 - 4.0 mg/L, 2.0 - 4.0 mg/L and 16 - 64 mg/L, respectively. No synergism in the acitivity against E. dermatitidis was observed for the combination of TBR with ITC or VRC. Conclusion E. dermatitidis is susceptible to TRB, ITC, AMB, and VRC, but less sensitive to both FLC and GAS.