Background. Trichosporon asahii (T. asahii) is part of the cutaneous fungal microbiota in humans and can cause lethal opportunistic infection. During infection, microorganisms can adapt to their environment by adjusting gene expression and cellular activities. Objectives. Investigation of the microevolutionary changes in T. asahii during chronic infection. Methods. Two T. asahii strains were isolated from a chronic trichosporonosis patient between a 15-year interval, and the microevolutionary changes were compared by the immune response of dendritic cell (DC), mice survival model, and transcriptome sequencing analysis. Results. Compared with the primary T. asahii strain, the microevolved strain induced much lower expression of TNF-α by mice bone marrow-derived DC and had a much superior survival rate, a total of 2212 significantly differentially expressed genes were identified in the microevolved strain, and functional analysis showed significance in the downregulated transcription and metabolic process, especially the valine, leucine, and isoleucine degradation pathways, which were associated with pathogenicity and virulence; hence, the results were highly consistent with the decreased immunogenicity and virulence of the microevolved strain. Conclusions. These results demonstrated that the microevolution during chronic infection could induce changes in immunogenicity, virulence, and transcriptome, which might lead T. asahii to coexist with the host.

Objective:To investigate the association between ambulatory arterial stiffness index (AASI) and renal poor prognosis in patients with chronic kidney disease (CKD).Methods:A prospective study was conducted to enroll 117 non-dialysis patients with CKD who volunteered for receiving ambulatory blood pressure monitoring test from December 2017 to December 2018 in the Department of Nephropathy of the First Medical Center of Chinese PLA General Hospital. According to the AASI tertiles, patients were divided into low AASI group (≤0.414, n=38), medium AASI group (0.414-0.517, n=40), and high AASI group (≥0.517, n=39). The differences of clinical baseline information among the three groups were compared. The follow-up time was until August 2020. Kaplan-Meier curve and Cox proportional hazard regression model were used to explore the effect of AASI on renal poor prognosis. Results:The median age of 117 patients was 61(49, 65) years old. There were 80 males (68.4%) and patients with hypertension accounted for 77.8%(91 cases). After a median follow-up of 27 months, 34 cases had composite endpoint events [renal replacement therapy (dialysis or kidney transplantation), 40% estimated glomerular filtration rate (eGFR) decline, and death], of which 10 patients were on dialysis, 19 patients had 40% eGFR decline, and 5 patients died. There were significant differences in age, hemoglobin, body mass index, eGFR, 24 h systolic blood pressure (SBP), daytime SBP, nighttime SBP, morning SBP, 24 h mean arterial pressure and 24 h pulse pressure among the three groups (all P<0.05). Kaplan-Meier survival analysis indicated that higher AASI was associated with lower cumulative survival rate in patients (Log-rank test χ2=13.111, P=0.001). Univariate Cox regression analysis showed that high AASI was an influencing factor for renal endpoint events ( P<0.05), and after adjusting for age, gender, mean arterial pressure, eGFR, 24 h urine protein, diabetes and body mass index, high AASI was an independent influencing factor for renal poor prognosis in classification and continuous variable analysis models ( HR=2.88, 95% CI 1.00-8.26, P=0.050; HR=1.50, 95% CI 1.02-2.21, P=0.039). Conclusion:High AASI is an independent influencing factor for renal poor prognosis in CKD patients.

肝纤维化指肝脏细胞外基质弥漫性的过度沉积,是机体对于肝实质损伤的一种修复反应及许多慢性肝病共同的病理过程,也是各种慢性肝病向肝硬化发展的重要步骤.迄今为止,临床尚缺乏特异性有效逆转或阻止肝纤维化进展的药物,尽早对肝纤维化进行诊断具有重要意义.目前肝纤维化的诊断主要靠组织病理学、血清学标志物及影像学手段.肝活检被认为是肝纤维化诊断和分期的金标准,但由于肝活检的风险和局限性,无创肝纤维化评价模式的建立成为临床亟待解决的科学问题和研究热点.本文对近年来肝纤维化血清学无创检测研究进展进行综述,为肝纤维化诊断提供参考.

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.

2019年12月以来,我国武汉地区乃至全国发生新型冠状病毒肺炎(novel coronavirus disease, COVID-19)疫 情.虽 然 新 型 冠 状 病 毒(novel coronavirus,2019-nCoV)感染很少发生特征性皮损,但就感染、免疫和变态反应而言,与皮肤科等其他学科有异曲同工、相互借鉴之处.不同学科的科研工作者,从整合医学的角度去思考和探讨2019-nCoV感染,可能会有助于深化对这种新发感染的认识和理解,拓宽研究思路.

BACKGROUND:Lung cancer is a common leading cause of cancer-related death worldwide. Ailanthone, a natural compound isolated from Chinese herb Ailanthus altissima, has been reported to exert antiproliferative effects on various cancer cells.METHODS:The present study aimed to investigate the role of ailanthone in the lung cancer cells and the correlation between the ailanthone and microRNA (miR)-195. The cell viability, proliferation, and apoptosis were determined by cell counting kit-8 assay, bromodeoxyuridine incorporation method, annexin V-fluorescein isothiocyanate/propidium iodide assay, respectively. Apoptosis- and autophagy-related proteins, as well as regulatory factors in the signaling pathways, were analyzed by Western blot method. The expression of miR-195 was quantified by quantitative reverse transcription-polymerase chain reaction.RESULTS:The results confirmed that ailanthone was involved in the lung cancer cell progress by inhibiting cell viability and proliferation, but promoted cell apoptosis and autophagy. We also found that ailanthone upregulated the expression of miR-195. Further, the downregulated miR-195 inhibited the apoptosis and autophagy induced by ailanthone. Moreover, our studies revealed that miR-195 inhibitor promoted the phosphorylation of PI3K, AKT, JAK, and STAT3, which was inhibited by ailanthone.CONCLUSION:All these findings suggest that ailanthone plays key roles in lung cancer progress and is closely correlated with miR-195 expression.

例1:男,33岁.面颈部弥漫性暗红斑10年.双侧面颊、耳前、下颌和颈侧红棕色斑片,可见毛细血管扩张、灰黑色色素沉着、毛囊角化性丘疹及角栓,皮肤触之有颗粒感.例2:男,49岁.面颈部红斑2年.耳周皮肤、颈前区、项部红斑,其上可见少许毛细血管扩张及散在毛囊性丘疹.结合典型的临床表现,诊断为面颈部毛囊性红斑黑变病.

A 22-years-old male patient, was suffering from Ewing's sarcoma in right leg with multiple lung and bone metastases, and metastatic tumor of 11th thoracic vertebrae with paraplegia. During the period of hospitalization and chemotherapy the patient developed symptoms of abdominal skin pain and blisters, and the lesions spread rapidly to the whole body in one week. The diagnosis of varicella-zoster virus infection was confirmed by histopathology and virus detection. The infection was cured after antiviral, neurotrophic and supportive treatment.

The Spitzenkörper is a dynamic and specialized multicomponent cell complex present in the tips of hyphal cells. The amphiphilic styryl dye FM4-64 was found to be ideal for imaging the dynamic changes of the apical vesicle cluster within growing hyphal tips. It is widely used as a marker of endocytosis and to visualize vacuolar membranes. Here we performed uptake experiments using FM4-64 to study the dynamic of the Spitzenkörper in Trichosporon asahii. We observed that Spitzenkörpers were present at the tip of the budding site of the spore, blastospore, and the germ tube of T. asahii. We also found that Spitzenkörpers were present at the tip of the hyphae as well as the subapical regions. Cytochalasin D, an inhibitor of actin polymerization, leads to abnormal Spitzenkörper formation and loss of cell polarity.

Syringocystadenoma papilliferum is a rare benign hamartomatous adnexal tumor of the apocrine or eccrine sweat glands. We present a case of syringocystadenoma papilliferum of an adult female with papulonodular lesion located on the mammary. This case illustrates the atypical location of this rare disease and presents a brief review of the natural history of syringocystadenoma papilliferum, as well as its pathogenesis and differential diagnosis.

BACKGROUND:Systemic sclerosis (SSc) is the most severe connective tissue disorder. Recent studies have demonstrated that genetic factors may play a role in the development of SSc. The aim of this study was to investigate the association of signal transducer and activator of transcription 4 (STAT4) rs7574865 and interferon regulatory factor 5 (IRF5) rs2004640 polymorphisms with risk of SSc.METHODS:Case-control studies were obtained from the electronic database of PubMed, Medline, Embase, and CNKI (China National Knowledge Infrastructure) up to December 2013. The association between STAT4 and IRF5 polymorphisms and SSc susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (CI).RESULTS:Six related studies, including 4746 SSc cases and 7399 healthy controls, were pooled in this meta-analysis. For STAT4 polymorphism, we observed a statistically significant positive association between risk factor T allele carriers and SSc susceptibility (OR = 1.37, 95% CI = 1.27-1.48, P < 0.00001) in the overall population. The presence of limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) scleroderma also showed a significant association with each of the genetic models (P < 0.00001). For IRF5 polymorphism, the T allele was shown to be strongly associated with increased SSc risk (OR = 1.27, 95% CI = 1.17-1.39, P < 0.00001). No significant heterogeneity between studies was found.CONCLUSIONS:The results demonstrated that STAT4 rs7574865 and IRF5 rs2004640G/T substitution are associated with a susceptibility to SSc, and they may serve as the SSc genetic susceptibility factor. These data confirmed that genetic polymorphisms may play a role in the development of SSc and have provided new insight into the pathogenesis of SSc.

临床资料<br>　　患者，男，44岁。主因双足、双手皲裂、溃疡、挛缩伴疼痛40余年、加重2年，于2015年1月13日就诊。患者2岁时，无明显诱因双手出现红斑、鳞屑伴瘙痒，随后双足出现类似症状，于当地医院按“鹅掌风”给予相关治疗（具体不详），症状无缓解且进行性加重。双手指、双足趾逐渐挛缩，双手指关节僵硬，屈曲状固定，不能抓握，足趾、足跖角化增厚；近2年，双足症状进一步加重，且右足跖溃烂，影响行走。1年前，于当地医院诊断为双下肢坏死，建议截肢治疗，患者拒绝。患者父母非近亲结婚，家族中无类似症状。患者自发病来听力、读说能力正常，无明显脱发、口腔溃疡及智力障碍，其余皮肤正常，发汗功能良好。皮肤科情况：双手掌、手背、指背见弥漫性蜡黄色或黑褐色角化斑块，境界不清，其上凹凸不平，双手指挛缩畸形，仅残存第一指节，呈屈曲状，指甲增厚、浑浊（图1a）。左足跖弥漫性角化增厚，表面可见蜡黄色、黑褐色角化斑块，未见破溃、渗出及出血，足趾末端挛缩畸形（图1b），右足跖溃烂，有恶臭味，可见较多渗出、痂皮及新生肉芽组织，痂皮剥脱后出血明显，足趾末端趾节缩短，踝部皮肤呈黑褐色（图1c）。身体其他部位正常，未见类似损害。右足跖皮损组织病理示：角化过度，表皮增生，可见片状表皮均质改变、坏死及细胞间海绵水肿，真皮乳头水肿，真皮见小血管扩张，内皮细胞呈钉突样改变（图2）。因患者拒绝，未行X线检查。双下肢及踝关节CT平扫提示：双踝关节及足部感染，以右侧为甚；双下肢血管超声检查提示双下肢动脉硬化样改变。根据患者病史及各项检查结果，诊断为残毁性掌跖角皮症。给予患者换药并建议截肢治疗，患者拒绝，后失访。

The aim of the current study was to observe the effects of suppressor of cytokine signaling 1 (SOCS1) silencing in human melanoma cells on cell biological behavior and interferon- (IFN-) sensitivity, and to investigate the use of SOCS1 as a therapeutic target in the treatment of melanoma. Western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to verify that SOCS1 interference effectively silenced the expression of SOCS1 in the Mel526 human melanoma cell line. For IFN- stimulation, western blot analysis was used to observe changes in expression levels of signal transduction and transcription activator (STAT) 1 and phosphorylated STAT (pSTAT) 1. Changes in the expression levels of IFN- regulatory factor 1 (IRF-1) were measured with RT-qPCR. Changes in the sensitivity of melanoma cells to IFN- were detected using an MTT assay. The cell proliferation rate was observed by cell counting and changes in the cell cycle were detected with flow cytometry. The results revealed that SOCS1 interference effectively silences SOCS1 expression in Mel526 cells. However, the S stage of the cell cycle was markedly extended. Following the inhibition of SOCS1 expression, the proliferation experiment demonstrated that the proliferation ability of Mel526 cells was decreased. Following IFN- stimulation, the expression levels of pSTAT and IRF-1 increased significantly compared with those in the controls. The MTT experiment showed that SOCS1 interference caused the median inhibitory concentration (IC50) of oxaliplatin in Mel526 cells to decrease significantly. In conclusion, SOCS1 interference reduced the proliferation ability of Mel526 human melanoma cells and increased their sensitivity to IFN-.

Some special types of malignant melanoma easily misdiagnosed for their atypical clinical manifestation and histopathologic changes. Five cases of uncommon malignant melanoma were presented there, including amelanotic type, local metastasis of limb type, malignant change of Innate nevus in shape of cutaneous tag, desmoplastic and neurotropic type.

目的 探讨皮肤结外鼻型血管内NK/T细胞淋巴瘤的临床病理特征、诊断和鉴别诊断、治疗及预后.方法 回顾性分析1例皮肤结外鼻型血管内NK/T细胞淋巴瘤患者的临床资料、组织病理形态、免疫组化染色及原位杂交染色.结果 光镜下皮肤附属器周围、血管周围和血管内可见中等大小的异型淋巴样细胞,肿瘤细胞胞质比较丰富、淡染,细胞核圆形、卵圆形或不规则,染色质深染,部分血管内可见纤维素样渗出物.免疫组化显示肿瘤细胞CD3和粒酶B(+),CD56部分(+),CD5和CD8散在(+),CD4、CD20和MPO(-);CD31显示大部分肿瘤细胞位于血管内;Ki-67阳性率＞50％.EBER分子原位杂交(+).结论 皮肤结外鼻型血管内NK/T细胞淋巴瘤是一种罕见的血管内淋巴瘤,临床和病理均易与皮肤血管炎性病变混淆,因此掌握其临床病理特征对该病的诊断和鉴别诊断具有重要意义.

Objective To investigate the relationships between inhibititing lipid raft formation and pathogencity of (Trichosporon asahii, T. asahii) in murine model. Methods Fifty mice were immunosuppressed and divided into 5 groups randomly on the basis of the different suspensions. The experimental groups were inoculated suspensions dealing with amphotericin B which concentrations were 0.2 μg/ml, 0.5μg/ml, 1.0μg/ml, 2.0μg/ml respectively, and the control group was not processed. The death of each group were written down within three weeks, and then the main viscera of the mice were examined by mycologic culture and histopathology. Finally the infection rate were counted. Results The fatality rate and infection rate of countrol group were 80%and 90%respectively. While the number of two groups dealing with amphotericin B which density were 1.0μg/ml, 2.0μg/ml was 37.5%to 20%and 50%to 40%respectively, and was signiifcantly less than the control group(P<0.05). In spite of the number of the other two groups which density were 0.2μg/ml, 0.5μg/ml was decreased, there was no remarkably difference compared with the control group(P>0.05). Histopathology showed acute pyogenous inlfammation and granuloma with arthrospores and mycelia in the tissues. Conclusion Inhibited the lipid raft formation by amphotericin B, the pathogencity of T. asahii decreased apparently. With the increasing of density of amphotericin B, the fatality rate and infection rate of mice decreased gradiently. It was indicated that inhibititing the lipid raft of T. asahii can result in lowering the pathogencity. This discovery provide a clue for a new target of anti-fungal drug.

目的 探讨抑制阿萨希毛孢子菌(Trichosporon asahii,Zasahii)顶体(Spitzenkorper)形成后对其细胞增殖及致病性的影响.方法 经不同浓度细胞松弛素D(0.5、1.0及2.0 μmol/L)处理阿萨希毛孢子菌,以抑制其顶体形成,体外测定生长曲线及生长菌落变化;小鼠体内接种上述菌悬液后,统计小鼠3周内的死亡率,并取内脏进行组织培养和病理检查,统计感染率.结果 经细胞松弛素D处理抑制顶体形成后,Z asahii细胞生长明显延迟8～16 h,生长菌落直径明显变小;小鼠死亡率及感染率亦出现不同程度降低,并随着药物浓度的升高,其致病性明显降低.结论 抑制阿萨希毛孢子菌顶体形成后,细胞增殖明显受到抑制,且致病性也随细胞松弛素D浓度的增加而降低.提示顶体可以作为研制新型抗真菌药物的新靶点.