Background:Solar lentigines (SLs), serving as a prevalent characteristic of skin photoaging, present as cutaneous aberrant pigmentation. However, the underlying pathogenesis remains unclear and there is a dearth of reliable diagnostic biomarkers.Objective:The aim of this study was to identify diagnostic biomarkers for SLs and reveal its immunological features.Methods:In this study, gene expression profiling datasets (GSE192564 and GSE192565) of SLs were obtained from the GEO database. The GSE192564 was used as the training group for screening of differentially expressed genes (DEGs) and subsequent depth analysis. Gene set enrichment analysis (GSEA) was employed to explore the biological states associated with SLs. The weighted gene co-expression network analysis (WGCNA) was employed to identify the significant modules and hub genes. Then, the feature genes were further screened by the overlapping of hub genes and up-regulated differential genes. Subsequently, an artificial neural network was constructed for identifying SLs samples. The GSE192565 was used as the test group for validation of feature genes expression level and the model's classification performance. Furthermore, we conducted immune cell infiltration analysis to reveal the immune infiltration landscape of SLs.Results:The 9 feature genes were identified as diagnostic biomarkers for SLs in this study. And an artificial neural network based on diagnostic biomarkers was successfully constructed for identification of SLs. GSEA highlighted potential role of immune system in pathogenesis of SLs. SLs samples had a higher proportion of several immune cells, including activated CD8 T cell, dendritic cell, myeloid-derived suppressor cell and so on. And diagnostic biomarkers exhibited a strong relationship with the infiltration of most immune cells.Conclusion:Our study identified diagnostic biomarkers for SLs and explored its immunological features, enhancing the comprehension of its pathogenesis.

背景 不同剥脱性激光治疗萎缩性痤疮瘢痕的疗效及其影响因素临床资料有限.目的 探讨不同剥脱性激光治疗面部萎缩性痤疮瘢痕的临床疗效和影响因素.方法 回顾性分析 2014年 7月-2022年 8月在解放军医学院第七医学中心皮肤科激光中心采用剥脱性激光治疗面部萎缩性痤疮瘢痕患者的临床资料,包括二氧化碳点阵激光(Deep模式,能量密度12.5～22.5 mJ,光斑密度 5%～10%)、铒像素激光(能量 800～1400 mJ,能量密度 3～6 J/cm2)及等离子体射频(滚动式功率60～70 W,3～4遍/次),间隔 1～12个月治疗 2次.对患者治疗前后照片采用痤疮瘢痕评估量表(Echelle d'Evaluation Clinique des Cicatrices d'acne,ECCA)评分以评估疗效,并根据ECCA评分下降率,分为有效组和无效组,分析影响治疗疗效的影响因素.结果 共纳入 61例患者,治疗前 ECCA评分为(110.16±30.54)分,2次治疗后为(85.98±25.03)分(P＜0.001),临床有效率为 31.15%.Logistic回归提示治疗前ECCA评分是治疗效果的独立影响因素(OR=0.297,95%CI:0.090～0.976,P=0.046),而年龄对治疗效果无显著影响.结论 剥脱性激光治疗面部萎缩性痤疮瘢痕有较好疗效,治疗前ECCA评分是治疗效果的独立影响因素.

敏感性皮肤是一种与皮肤神经系统异常相关的综合征，认知已由先前的单一皮肤屏障受损逐步发展至与基因、皮肤神经系统改变有关的神经源性炎症；这种神经源性炎症可能是系统性神经高反应性的皮肤表现。近年来关于敏感性皮肤的研究日益增多，其中神经相关发病因素是研究热点之一。从病因与发病机制、诊断、治疗方面概述敏感性皮肤的近期研究进展，旨在为相关研究提供信息。

Melanosomes can more effectively absorb energy from a 532 nm laser, destroying the melanosomes. We used a PSNYL pulse width of 240– 400 ps and QSNYL pulse width of 5– 20 ns, both of which are significantly lower than the heat relaxation time (50– 250 ns) of melanosomes and can effectively destroy the melanin particles in the epidermis. In this study, although there was a statistical difference of the lesion clearance rate between QSNYL treatment groups and PSNYL treatment groups, the two groups showed similar visual efficacy. However, shortening the pulse width has a positive effect; for example, for the treatment of nevus of Ota, a shorter pulse width can improve the efficacy of a single treatment significantly, reducing the number of treatments. 5

BackgroundTrichosporon asahii is an opportunistic pathogenic yeast-like fungus. Phospholipase B1 (PLB1) is an important virulence factor of pathogenic fungi such as Candida albicans and Cryptococcus neoformans, and there are few studies on the role of PLB1 in the pathogenicity of T. asahii. ObjectivesTo investigate the role of PLB1 in the pathogenicity of T. asahii. MethodsA strain with low secretion of PLB1 (4848) was screened, a PLB1 overexpression strain (PLB1(OX)) was constructed, and the differences in histopathology, fungal load of organ, survival time of mice, the levels of IL-6, IL-10, TNF-alpha, and GM-GSF in the serum and organs caused by the two strains were compared. ResultsHistopathology showed that spores and hyphae were observed in both groups, and PLB1(OX) led to more fungal invasion. The fungal loads in the kidney, lung, spleen and liver in the PLB1(OX)group were significantly higher than those in the 4848 group, and the survival time of mice was significantly lower than that in the 4848 group. The levels of TNF-alpha in the serum, liver, spleen, lung and kidney of the PLB1(OX) group were lower than those of the 4848 group, while the level of IL-10 in the serum was higher than that of the 4848 group. ConclusionsThese results suggest that PLB1 can enhance the invasive function of T. asahii and affect the secretion of TNF-alpha and IL-10 which may affect the host antifungal immune response, providing evidence that PLB1 plays a role in the pathogenic infection of T. asahii.

Background and objectives: Both artesunate and fractional CO2 laser have been proved effective in the treatment of hypertrophic scars, yet little data are available for the efficacy of artesunate combined with fractional CO2 laser. In order to assess the pre-clinical significance and the underlying mechanism of this combined treatment profile, we attempted to observe the effectiveness of this therapy in rabbit models through determining the expression of BMP-7 and Fas. Materials and methods: Twenty-Four New Zealand white rabbits with established hypertrophic scar samples were randomly divided into control group and three treatment groups. Artesunate (20 mu l/cm(2)) was injected into the rat's scar of artesunate and combination groups, while fractional CO2 laser (Combo mode, deep energy:10 mJ, super energy: 50 mJ) was applied to rats in fractional CO2 laser and combination groups at week 4 after model establishment. All rabbits underwent a total of 3 sessions of treatment once every 2 weeks. Histological and immunohistochemistry study, Western blot assay, cell viability, ELISA and RT-QPCR were performed at week 10 to observe the aspects of hypertrophic scar sample changes and expression of BMP-7 and Fas in the scar tissues. Results: Compared with control group, hypertrophic scars and the collagen fibers were significantly inhibited after treatment, and higher inhibition was seen in the samples in combination group compared to that in artesunate and fractional CO2 laser groups (P < 0.01). Meanwhile, BMP-7 and Fas expressions were both notably increased in all treatment groups, and upregulation of the two proteins was dominant in combination group (P < 0.01). Conclusions: Artesunate combined with fractional CO2 laser is effective in hypertrophic scarring in this rabbit model. Our findings can serve as a potential alternative strategy to treatment of hypertrophic scar in clinical practice. (C) 2021 Published by Elsevier Ltd.

全媒体时代下皮肤病与性病科医学摄影已取得长足发展,应用领域非常广泛,但缺乏完整的理论教育体系和考核标准,仍有较大发展空间.医学摄影中的伦理边界、法律边界、道德建设和人文关怀的培养和教育将直接影响到医务工作者的职业行为,是维护健康和谐的医患关系、提高皮肤病与性病科医疗服务质量的重要支柱.该文结合皮肤病与性病科临床特点,尝试性分析了医学摄影边界性教育的特点,提出增加伦理道德教育和法律法规意识、加强人文关怀等具体实践路径,将医学摄影的边界性教育融入皮肤病与性病科临床带教中去,以期为临床教学提供参考和借鉴.

目的 评估青蒿素及其衍生物单药及联合常用抗真菌药对阿萨希毛孢子菌(T.asahii)浮游状态及生物膜状态下的体外抑菌效果.方法 以15株T.asahii临床株为研究对象,采用微量肉汤稀释法测定青蒿素、双氢青蒿素、青蒿琥酯对T.asahii浮游菌的最低抑菌浓度(MIC),并测定最敏感青蒿素类药物联合5种抗真菌药(氟康唑、咪康唑、伊曲康唑、两性霉素B、卡泊芬净)对T.asahii浮游菌及生物膜的体外抑制作用,计算部分抑菌浓度指数(FICI).结果 相比于青蒿素、双氢青蒿素,T.asahii对青蒿琥酯的敏感性最高.青蒿琥酯与卡泊芬净、青蒿琥酯与咪康唑、青蒿琥酯与氟康唑联用对T.asahii浮游菌均具有协同作用,比例分别为73.3％、33.3％、33.3％;青蒿琥酯与卡泊芬净、青蒿琥酯与咪康唑、青蒿琥酯与两性霉素、青蒿琥酯与氟康唑联用对T.asahii生物膜也具有不同程度的协同作用,比例分别为66.7％、53.3％、33.3％、26.7％.结论 青蒿琥酯单药对T.asahii的体外抑制作用最强,青蒿琥酯与卡泊芬净、咪康唑联用对T.asahii有明显的抗真菌增效剂潜力.

目的 观察医用冷敷贴缓解海姆泊芬光动力治疗鲜红斑痣术后灼痛及修复皮肤稳态的疗效.方法 收集2019年11月至2021年4月解放军总医院第七医学中心皮肤科符合纳排标准的面中部鲜红斑痣患者40例,随机分为试验组和对照组,每组20例.接受海姆泊芬光动力治疗后,试验组术后即刻治疗部位使用医用冷敷贴1 h,之后每日敷贴1 h,连续使用3 d;对照组无特殊处理,自然恢复.分别于术后即刻与0.5、1、12h进行疼痛指数(NRS)评分.于术前10 min,术后即刻与30min、1 h检测皮肤表面温度.于术前10min,术后即刻与24、48、72 h检测经皮水分丢失(TEWL)和角质层含水量(WCSC).统计两组术后1、2、3周结痂率.治疗前后不同时间点观察指标的比较采用两因素重复测量方差分析,组间和组内比较采用Bonferroni或Sidak's检验.结果 术前试验组与对照组年龄、性别构成及TEWL、WCSC差异均无统计学意义(P＞0.05).术后即刻,试验组与对照组NRS评分差异无统计学意义(8.00±1.17、8.20±1.06,F=0.30,P=0.592);术后0.5、1 h时试验组NRS评分(6.25±1.29、4.80±0.77)均低于对照组(7.15±0.99、6.50±0.69,均P＜0.05).术后即刻试验组与对照组皮肤表面温度分别升高至(35.211±1.333)℃和(35.637±0.832)℃,两组差异无统计学意义(P=0.062);术后30、60 min时试验组分别为(29.11±1.59)℃、(32.46±1.07)℃,均低于对照组[(35.01±0.91)、(34.86±0.74)℃,F=212.63、100.20,P＜0.001].术后 48、72h 时试验组TEWL 分别为(12.44±0.67)、(10.85±0.81)g·h-1·m-2,均低于对照组[(14.61±0.34)、(14.93±0.24)g-h-1·m-2,F=195.87、520.54,P＜0.001],而WCSC分别为(57.83±9.29)、(52.64±8.09)AU,均高于对照组[(43.87±4.82)、(38.68±5.33)AU,F=24.41、49.22,P＜0.001].试验组术后 1 周有3例结痂,对照组为6例,两组结痂率差异无统计学意义(P=0.451).结论 海姆泊芬光动力治疗鲜红斑痣术后应用医用冷敷贴可降低表皮温度,发挥镇痛作用,缩短术后疼痛时间,同时促进皮肤通透屏障功能的恢复.

猴痘是由猴痘病毒感染引起的人畜共患传染病,临床症状与天花类似,但严重程度较天花轻.猴痘主要在非洲地区传播和流行,但自 2022 年 5 月以来,猴痘在多个非流行国家及地区出现大规模流行和暴发,并出现人际传播.因其具有一定的传染性和病死率,世界卫生组织建议所有国家均应警惕猴痘疫情的发生.该文主要从流行病学、临床诊疗等方面阐述猴痘的特点,旨在为预防猴痘疫情在我国发生及传播提供理论参考.

目的 研究微进化对阿萨希毛孢子菌(Trichosporon asahii,T.asahii)感染宿主情况及感染后机体免疫反应等方面的影响.方法 用微进化株(TEVO)与阿萨希毛孢子菌原代株(TO)感染Balb/c小鼠,比较两株菌感染小鼠脏器组织中真菌的相对载量、髓过氧化物酶(myeloperoxidase,MPO)、血清β-葡聚糖水平以及脾脏T细胞分化差异.结果 TEVO菌株以孢子状态为主,TO菌株以菌丝生长状态为主;TEVO组小鼠各组织相对载量、血浆(1,3)-β-D-葡聚糖水平及MPO浓度均明显低于TO组;TEVO组小鼠脾脏中CD4+T细胞和CD8+T细胞的比例均高于TO组.结论 微进化后的TEVO菌株对宿主的感染能力以及感染前期宿主对TEVO菌株的防御和杀伤能力均低于TO菌株,这可能与TEVO菌株表型变化密切相关.

Objective:To evaluate the effect of microevolution on phenotypes and drug resistance of the Trichosporon asahii biofilm. Methods:The standard strain of Trichosporon asahii was obtained from the Fungal Biodiversity Institute of the Royal Netherlands Academy of Arts and Sciences, the fluconazole-sensitive primary strain (TO) of Trichosporon asahii was isolated from a case of trichosporonosis diagnosed in the Department of Dermatology, the Seventh Medical Center of Chinese People′s Liberation Army General Hospital in 2000, and the fluconazole-resistant evolved strain (TEVO) of Trichosporon asahii was isolated from the above patient in 2014. Biofilms of the above-mentioned strains were formed in vitro, and tetrazolium salt XTT reduction assay was performed to evaluate growth kinetics of the Trichosporon asahii biofilm, and laser scanning confocal microscopy to determine the thickness of the biofilm; the sessile minimum inhibitory concentrations (SMICs) of fluconazole, itraconazole and voriconazole against the biofilms at different growth stages were determined in vitro for the evaluation of the resistance of the biofilms. One-way analysis of variance was used for comparisons among multiple groups, and Hartley test for testing homogeneity of variance. If the variance was homogeneous, least significant difference test was used for multiple comparisons; if the variance was heterogeneous, Tamhane′ T2 test was used for multiple comparisons. Results:In the adhesion (0 h) and formation stages (4- 24 hours) of the Trichosporon asahii biofilm, the metabolic activity of the evolved strain TEVO was the weakest (adhesion stage: F = 35.705, P < 0.001; formation stage: F = 15.042, P < 0.001) . At 48 hours after adhesion, the biofilms matured, and the TO strain showed the weakest metabolic activity ( F = 10.985, P < 0.001) . In the maturation stage, the biofilm thickness of the TEVO strain (26.1 ± 1.18 μm) was significantly higher than that of the TO strain (22.8 ± 1.73 μm, P = 0.001) , but significantly lower than that of the standard strain (29.5 ± 1.28 μm, P = 0.001) . As drug susceptibility testing showed, the SMICs of azole antifungal agents against the TEVO strain were higher than those against the TO strain in the adhesion and formation stages of the Trichosporon asahii biofilm, and the SMICs of azole antifungal agents against the biofilms of the 3 strains of Trichosporon asahii were all over 1 024 mg/L in the maturation stage of the biofilm. Conclusion:Under the dual pressure of host environment and antifungal drugs, adaptive changes took place in the phenotypes of the Trichosporon asahii biofilm with an increase in the resistance to azole antifungal drugs.

The opportunistic fungal pathogen Trichosporon asahii (T. asahii) is an important causal agent of mortality in immunocompromised patients and associated with frequent relapses, even with sufficient antifungal treatment. Investigating the proteomes of initial and recurrent isolates may help to identify within-host adaptive changes. In this study, using tandem mass tag (TMT)-labeling combined with liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) technology, we analyzed the proteomes of two T. asahii strains that were isolated 15 years apart from the same patient who suffered initial and recurrent episodes of systemic disseminated trichosporonosis. A total of 597 differentially expressed proteins were identified. Functional analysis showed that the increased proteins were primarily concentrated on peptide/protein/energy/drug metabolism and translation. Most of the results were determined to be consistent with the findings of phenotypic assays, such as tests for drug susceptibility, temperature growth, biofilm formation, melanization and paromomycin assays. Moreover, we performed multiple reaction monitoring (MRM) mass spectrometry to verify 27 candidate proteins, and the results of this experiment were also highly consistent with the results of the TMT analysis. Therefore, to the best of our knowledge, these data provide the first molecular evidence of how the T. asahii proteome changes related to host-specific adaptation during human infection. Significance: Systemic infection with Trichosporon asahii (T. asahii) has recently been recognized as an important causal agent of mortality in immunocompromised patients. Although triazole treatment usually works efficiently in the early phase of infection, many patients relapse. Hence, comparative analyses of the proteomics of initial and recurrent isolates may reveal evidence of adaptive changes within the host. Our study demonstrates that the recurrent strain has undergone proteomic changes using tandem mass tag (TMT)-labeling combined with liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). Moreover, the results of phenotypic assays, including drug susceptibility, temperature growth, biofilm formation, melanization and paromomycin assays, were highly consistent with the proteomic changes, and multiple reaction monitoring (MRM) verification also showed similar trends to the TMT results. In summary, our study is the first to investigate the adaptation of T. asahii under pressure from antifungal chemotherapy and host immune responses.

全球真菌感染率、耐药率升高,给人类健康带来严重威胁,需研发全新的抗真菌药以及挖掘现有药物的潜在抗真菌作用.青蒿素及其衍生物不仅具有抗疟疾等作用,新近发现其对多种病原真菌也具有抑制作用或增效抗真菌药的作用.该文将青蒿素及其衍生物对常见致病真菌的作用研究进行综述,为新型抗真菌药物的发现或研发提供参考.

雄激素性秃发(androgenetic alopecia,AGA)是非瘢痕性秃发的常见原因.男性多于女性,20 ～30岁开始发生,初期表现为发际线后移,后期头皮中央的毛发变薄;女性患者多表现为头顶部头发稀疏,额部发际线通常保留.有研究报告显示AGA患者的生活质量下降,秃发对患者的心理产生重大影响,易导致焦虑和抑郁[1].国外已出版关于男性和女性 AGA诊治共识, 2014年国内专家发表了 AGA诊疗指南[2].北京中西医结合学会医学美容专业委员会、国家皮肤与免疫疾病临床医学研究中心在近年国内外雄激素性秃发的诊疗指南及研究进展基础上制定本共识,充分发挥中西医结合的优势,重点增加了中医中药、灸法及微针治疗内容,为雄激素性秃发的临床诊疗提供参考依据.

目的 研究微进化对阿萨希毛孢子菌(T.asahii)与巨噬细胞RAW264.7相互作用的影响.方法 将微进化前后的T.asahii与RAW264.7细胞共培养,检测RAW264.7对两株菌的吞噬和杀伤能力以及两株菌对RAW264.7产生的细胞毒性的差异,同时分析RAW264.7自身细胞因子分泌情况的变化.结果 巨噬细胞对原代菌株(TO)的吞噬能力以及杀伤率均明显高于微进化株(TEVO);TO菌株对巨噬细胞的细胞毒性要强于TEVO;当巨噬细胞与菌株按1:3或1:6共培养24 h时,与TO共培养的巨噬细胞TNF-α和IL-6的分泌量要高于TEVO组,而按1:9共培养时TEVO组细胞因子的分泌量却高于TO组.结论 微进化后的TEVO菌株与巨噬细胞的相互作用明显弱于原代株TO,这也为TEVO菌株在宿主体内长期共存提供了良好的基础.

595-nm pulsed dye laser and fractional CO2 laser have been demonstrated effective to treat hypertrophic scar. The underlying mechanism may involve transforming growth factor-beta1 (TGFβ1) and proliferating cell nuclear antigen (PCNA), but remains to be clarified. Our study was performed to investigate how 595-nm pulsed dye laser combined with fractional CO2 laser treats hypertrophic scars in a rabbit model through regulating the expression of TGFβ1 and PCNA. Twenty-four New Zealand white rabbits were randomly divided into control group, pulsed dye laser group, fractional CO2 laser group, and pulsed dye laser + fractional CO2 laser (combination) group. Surgical wounds were made and allowed to grow into hypertrophic scars at day 28. Next, 595-nm pulsed dye laser (fluence: 15 J/cm2; square: 7 mm; pulse duration: 10 ms) was used in pulsed dye laser and combination group, while fractional CO2 laser (combo mode, deep energy: 12.5 mJ; super energy: 90 mJ) in fractional CO2 laser and combination groups, once every 4 weeks for 3 times. The appearance and thickness of hypertrophic scar samples were measured with hematoxylin-eosin and Van Gieson's straining. The expressions of TGFβ1 and PCNA were evaluated by immunohistochemical and western blot analysis. A significant improvement was noted in the thickness, size, hardness, and histopathology of hypertrophic scar samples after laser treatment, especially in combination group. Scar Elevation Index (SEI), fiber density (NA), and collagen fiber content (AA) decreased most significantly in combination group (2.10 ± 0.14; 2506 ± 383.00; 22.98 ± 2.80%) compared to 595-nm pulsed dye laser group (3.35 ± 0.28; 4857 ± 209.40; 42.83 ± 1.71%) and fractional CO2 laser group (2.60 ± 0.25; 3995 ± 224.20; 38.33 ± 3.01%) (P < 0.001). Furthermore, TGFβ1 and PCNA expressions were more suppressed in combination group (8.78 ± 1.03; 7.81 ± 1.51) than in 595-nm pulsed dye laser (14.91 ± 1.68; 15.73 ± 2.53) and fractional CO2 laser alone group (15.96 ± 1.56; 16.13 ± 1.72) (P < 0.001). The combination of 595-nm pulsed dye laser with fractional CO2 laser can improve the morphology and histology of hypertrophic scars in a rabbit model through inhibiting the expression of TGFβ1 and PCNA protein. Our findings can pave the way for new clinical treatment strategies for hypertrophic scars.

报告1例小棘状毛壅病.患者女,26岁.胸、背部毛囊性黑色丘疹5年.患者同卵双生姐姐有类似病史,症状较轻微,家族中其他成员无类似疾病.皮肤科检查:背部、腋前区、胸部及腹部可见毛囊性黑色小丘疹,触之稍有粗糙感,呈弥漫和对称性分布.皮肤镜及显微镜检查示角栓中均可见成簇状毳毛.背部皮损组织病理检查:可见围绕毛囊开口的表皮呈乳头瘤样增生.诊断:小棘状毛壅病.

皮肤转移癌多为单发或多发坚实结节.该文报道2例少见的源于乳腺癌和肺癌皮肤转移,表现为丹毒样癌(carcinoma erysipeloides)的患者.结合文献报道对丹毒样皮肤转移癌的原发肿瘤进行了归纳分析,提示丹毒样癌与其他皮肤转移癌一样,腺癌可能是其主要来源,腺癌细胞与真皮淋巴管可能存在某种特殊粘附机制,淋巴管阻塞为癌细胞免疫逃逸提供了机会.