Androgenic alopecia(AGA)is the most common type of clinical alopecia.Androgen receptor(AR)is the most logical candidate gene for regulating the occurrence of AGA.Dermal papilla cells(DPCs)are a special kind of mesen-chymal cells,located in the hair bulb of hair follicles.DPCs play a role in maintaining and inducing the periodic cycling of hair follicles,and are considered as a key cell target of androgen in hair follicles.Tcf4 is a positive regulator of the maintenance of DPC biological features.Previously,we reported that Twist1 can enhance the inductive effect of Tcf4.1 As a transcription factor,AR can bind with Tcf4 to regulate the proliferation in prostate growth and tumori-genesis.2,3 However,whether and how AR interacts with Tcf4 in DPCs remains unknown.

Objective:To analyze clinical characteristics of drug-induced hypersensitivity syndrome (DIHS) , and to compare the European, Japanese and Chinese diagnostic criteria.Methods:A total of 45 patients confirmedly diagnosed with DIHS according to the DIHS criteria originally proposed by Bocquet, were collected from the First Affiliated Hospital (Southwest Hospital) of Army Medical University between January 2009 and January 2019. Clinical data on the 45 patients were retrospectively analyzed, clinical characteristics were summarized and re-evaluated according to the European, Japanese and Chinese diagnostic criteria separately, and differences were analyzed in terms of the latency period, time to rash regression, eosinophil count, liver function indices, etc. One-way analysis of variance was used to compare means among multiple groups, and t test to compare means between two groups. Results:Of the 45 patients, 38 presented with eruptive drug eruptions, and 44 were accompanied by liver damage, 40 by elevated counts of peripheral white blood cells, 38 by eosinophilia, 21 by lymphadenectasis, and 4 by mucosal damage. Common culprit drugs included allopurinol (10 cases) , anti-tuberculosis drugs (7 cases) , cephalosporins (7 cases) , and Chinese medicine (4 cases) . Forty patients were treated with glucocorticoids, and 17 with glucocorticoids and intravenous gamma globulin. After treatment, 44 patients received improvement and 1 died. According to the European diagnostic criteria, there were 29 patients with suspected DIHS and 16 with confirmed DIHS; according to the Japanese diagnostic criteria, 37 patients could be confirmedly diagnosed with DIHS, but 8 could not be confirmedly diagnosed; according to the Chinese diagnostic criteria, 17 patients could be confirmedly diagnosed, but 28 could not be confirmedly diagnosed. According to the Japanese diagnostic criteria, the latency period was significantly longer in the patients with a confirmed diagnosis (36.91 ± 21.73 d) than in those without (20.00 ± 20.82 d, P = 0.04) . Conclusions:Common culprit drugs for DIHS include allopurinol, anti-tuberculosis drugs and cephalosporins. Most patients with DIHS are accompanied by liver damage, and the European diagnostic criteria are preferentially recommended for DIHS.

ObjectiveDuring hair follicle regeneration, hair follicle stem cells (HFSCs) are regulated by signals from dermal papilla cells (DPCs). Previously we found that Tcf4 could promote the proliferation of DPCs. In this study, we focused on whether and how the biological properties of Tcf4-induced DPCs were regulated by Twist1.MethodsTwist1 was overexpressed or knocked down in DPCs following different adenovirus or lentivirus infection. Phase-contrast microscopy was used to observe the agglutinative growth of DPCs. The CCK-8 assay was used to test the proliferation of DPCs. Western blot and qPCR experiments were used to determine the expression of HGF, IGF-1, VEGF, c-myc, survivin, and CyclinD1 in DPCs. ELISAs were used to test the growth factors secreted by DPCs. Conditional medium culture was used to detect the inductive ability of DPCs. Co-immunoprecipitation and immunofluorescence were used to test the binding of Twist1, Tcf4, and β-catenin in DPCs. Immunofluorescence was also used to test the expression of Twist1, Tcf4, and KRT15 in hair follicles.ResultsTwist1 induced DPC agglutinative growth and proliferation. Twist1 upregulated the expression of downstream target genes downstream of Tcf4, c-myc, survivin, in Tcf4-induced DPCs, as well as the expression and secretion of growth factors HGF, IGF-1, VEGF, which had the ability to induce hair follicle growth. The conditional medium from Twist1-treated DPCs increased the expression of KRT40 and MSX2 in HaCaT cells. Twist1 and Tcf4 co-localized in DPCs both in vitro and in vivo. Anti-Twist1 precipitated Tcf4 and β-catenin.ConclusionThese results indicate that Tcf4 and Twist1 play a synergistic role in regulating the hair follicle induction ability of DPCs. Twist1 functions by forming a ternary complex with Tcf4 and β-catenin. Thus, we report new data that elucidate whether and how Twist1 regulates some biological properties of DPCs.

Objective:To develop an efficient and rapid method for the isolation and cultivation of human scalp dermal papilla cells from small specimens.Methods:Hair-bearing skin specimens measuring 0.5 cm × 0.5 cm -0.5 cm × 1 cm in size were obtained from the scalp of 3 patients with pigmented nevus and 6 with sebaceous nevus during surgery in Department of Dermatology, the First Hospital Affiliated to Army Medical University from September 2018 to January 2019. The subcutaneous fat layer containing hair follicles was cut out of the specimens, and hair follicles were sorted with ophthalmic forceps, which were subsequently digested with 0.6% dispase Ⅱ for 30 minutes, then with 0.2% collagenase Ⅳ at 37 ℃ for 30 - 60 minutes, and were centrifuged to obtain hair papillae. Morphological observation was performed on the isolated hair papillae, and dermal papilla cells were cultured, passaged and identified.Results:Under the microscope, the hair papillae isolated by two-step enzyme digestion of small scalp specimens were intact, and showed an inverted pear-like shape, and residual dermal sheaths could be observed around some hair papillae. However, no hair papilla was isolated by one-step enzyme digestion. With the two-step enzyme digestion method, the hair papilla separation rate was 60.8% ± 2.1%, the adherence rate of the dermal papilla cells at 72 hours was 86.6% ± 3.9%, the time for cells to emigrate out of hair papillae was 0.5 - 3.0 days, the total operation duration was 2.0 - 3.0 hours, and the actual operation duration after subtraction of digestion duration was 1.0 - 1.5 hours. The dermal papilla cells isolated by the two-step enzyme digestion method could grow in an aggregative pattern in early stage, but grew in a non-aggregative pattern after 8 passages.Conclusion:The two-step enzyme digestion of small specimens is a simple and efficient method for isolating human scalp dermal papilla cells.

Objective To investigate an efficient rapid method for the isolation and cultivation of human axillary dermal papilla cells.Methods Skin specimens with hair follicles were obtained from the axillary area of patients who received bromhidrosis surgery in the Department of Dermatology of the First Affiliated Hospital to Army Medical University from October 2015 to May 2016.The axillary dermal papilla cells were isolated by two-step enzyme digestion method,one-step digestion method and micro-dissection method separately.Then,axillary dermal papilla cells were cultured and identified.Differences in the operative procedure,separation efficiency and adhesion efficiency of dermal papilla cells,cell emigration duration,total operation duration and actual operation duration were compared among the above 3 methods.Results Compared with the one-step digestion method and micro-dissection method,the two-step enzyme digestion method showed simpler operative procedure,more than 30％ separation rate and 96％ adhesion rate of dermal papilla cells after 1 week.Moreover,the cell emigration duration was shortened by 3-4 days by the two-step enzyme digestion method.The two-step enzyme digestion method also showed longer total operation duration,but shorter actual operation duration compared with the one-step digestion method and micro-dissection method,as well as lower contamination rate compared with the micro-dissection method.Cultured axillary dermal papilla cells grew in an aggregative pattern in the early stage,but grew in a nonaggregative pattern after 6 passages.Immunofluorescence assay showed positive staining for laminin and collagen Ⅳ in axillary dermal papilla cells.Conclusion The modified two-step enzyme digestion method is a kind of simple,efficient and rapid method for the isolation of human axillary dermal papilla cells,and axillary dermal papilla cells can be harvested through this method by using a few specimens.

目的 探索皮肤病学专业学位硕士研究生亚专业特色培养方案的关键要素,为我国皮肤病学专业学位研究生的教育方案的制订提供思路和依据.方法 运用德尔菲法,调研10家医院皮肤病学主要亚专业领域专家共55名,初步拟定包含亚专业培养体系的各级指标及权重.结果 共45名专家参与了函询,函询专家的权威系数为0.82,肯德尔协调系数(Kendall′W)χ2检验的P值小于0.01,最终得到皮肤病学专业学位硕士研究生相关培养方案的要素细则.结论 该研究所形成的皮肤病学专业学位硕士研究生培养方案关键要素构建具体可操作,可为其培养方案的制订提供参考与借鉴.

Dermal papilla cells (DPCs) are important components of hair follicles and play a critical role in hair follicle development. However, the mechanisms by which DPCs induce hair follicle development remain unclear. In the present study, we identified the mitotic arrest deficient protein MAD2B as a modifier of DPCs. Overexpression of MAD2B inhibited DPC aggregative growth and proliferation induced by the Wnt signaling activator T cell factor 4 (TCF4), and decreased TCF4-induced expression and the release of hair growth-related cytokines, including hepatocyte growth factor, insulin-like growth factor-1, and vascular endothelial growth factor in DPCs. In contrast, knockdown of MAD2B promoted TCF4-induced DPC proliferation, but did not affect the expression and secretion of cytokines by TCF4-induced DPCs. These results suggest a functional antagonism between MAD2B and TCF4 in DPC-induced hair follicle development. Mechanistically, MAD2B physically interacted with TCF4 to repress TCF4 transcriptional activity via β-catenin mediation, leading to reduced β-catenin/TCF4-dependent transactivation and Wnt signaling activity. These results demonstrate, for the first time, that MAD2B plays a negative role in TCF4-induced DPC growth and proliferation.

目的 探讨组蛋白去甲基化酶JMJD2B(Jumonji domain-containing protein 2B)小干扰RNA(siRNA)对人皮肤鳞状细胞癌A431细胞株生物学行为的影响.方法 采用免疫组化和细胞免疫荧光的方法检测JMJD2B在人皮肤鳞状细胞癌组织和A431细胞中的表达,转染JMJD2B siRNA至A431细胞株,分别采用CCK-8、克隆形成实验、流式细胞仪、Transwell法检测细胞增殖、克隆、周期分布、凋亡、迁移及侵袭情况.结果 JMJD2B在肿瘤组织中的表达高于正常皮肤.与未转染组和转染对照组比较,JMJD2B siRNA转染组增殖、克隆、迁移及侵袭能力显著受抑,肿瘤细胞发生G1期阻滞,细胞凋亡比例增加(P＜0.05).结论 JMJD2B在人皮肤鳞状细胞癌中呈高表达,JMJD2B siRNA能促进A431细胞的凋亡,同时也抑制了肿瘤细胞的增殖、克隆、迁移以及侵袭的能力.

OBJECTIVE:The aim of the present study was to provide more information on the role of illness perception in patients with androgenetic alopecia (AGA) and those with alopecia areata (AA), and to further investigate the relationship of illness perception with psychological disorders and dermatological QoL. METHODS:The study included 342 patients who were diagnosed with AGA (n=212) or AA (n=130) for the first time at our institution between October 2013 and December 2014. All patients were surveyed before clinical examination by several questionnaires including the Brief Illness Perception, Self-rating Depression Scale, Self-rating Anxiety Scale, and Dermatology Life Quality Index (DLQI). RESULTS:In the AGA patients, the illness perception and QoL were low, whereas the prevalence of clinical depression and anxiety was higher compared to the AA patients. Illness perception was associated with psychological distress and low QoL in both groups, and some illness perception dimensions were found to be significant predictors of the DLQI scores. CONCLUSION:Illness perception plays an important role in AGA and AA patients, and is associated with psychological distress and low QoL. The identification of critical components of illness perception in alopecia patients could help to understand alopecia specificities, to design consultations and interventions according to the perception, and to improve physical and mental outcomes as well as QoL in alopecia patients.

目的:探讨斑秃(AA)对患者生活质量的影响,分析皮肤病生活质量指数(DLQI)在评估患者生活质量时的信度及因子结构.方法:采用DLQI量表评估AA患者的生活质量,并用信度分析及因子分析评估DLQI的信度及因子结构.结果:共调查了168例AA患者,DLQI得分为0～26分,平均为(6.82±5.85)分.DLQI评分与患者的病程、脱发面积、斑秃类型、拉发试验、甲改变及应激事件等6个因素有关.DLQI量表信度分析显示,整体量表的Cronbach系数α=0.876(＞0.7),删除问题l,α达最大值0.886.因子分析显示,DLQI量表用于测评AA时,特征值＞1的因子有2个,累计贡献率达59.58％.结论:AA对患者的生活质量有中等程度的影响.DLQI可以用来评估AA患者的生活质量,且具有较好的信度和效度.

No study has tested the reliability and validity of the revised Symptom Checklist 90 (SCL‐90‐R) for patients with alopecia areata (AA), and few have used it to evaluate the mental health of AA patients. To assess the psychological status in Chinese AA patients using the SCL‐90‐R, and to evaluate its reliability and validity, the psychological status of 168 patients and 100 controls was evaluated with the Chinese‐version SCL‐90‐R. From this study, we found that The Global Severity Index and nine subscale scores on the SCL‐90‐R were significantly higher in AA patients than that in the controls. Moreover, The Global Severity Index and nine subscale scores on the SCL‐90‐R were associated with disease duration, age of onset, sex and type of AA. In addition, the SCL‐90‐R presented good internal consistency (whole scale α = 0.98 and split‐half coefficient = 0.95). The intercorrelations between the nine subscales and their correlations with the total scale were 0.58–0.93. Factor analysis produced 22 factors with eigenvalues more than 1.0; the first factor explained 33.88% of the variance. Only hostility and paranoid ideation merged into one factor. Taken together, our data indicated that Chinese AA patients demonstrate greater psychopathology than healthy controls. The SCL‐90‐R can be used to assess global psychological distress in AA patients with good reliability and validity.

Objective To investigate the cognitive degree about the disease in patients with alopecia areata and to analyze the related factors of illness perceptions about alopecia areata. Methods Choose the first diagnosed patients with alopecia areata to complete the brief illness perception questionnaire (BIPQ) at the department of dermatology clinic of Southwest Hospital of Third Military Medical University, from October 2013 to October 2014. Results The patients’ average age: 31.82±10.28; male/female ratio: 0.71; the overall BIPQ score: 40.15±9.12. The highest item-related scores were found for concern (8.42±2.20), consequences ( 5.72±2.88) and emotional response (5.68±2.85), and the lowest for treatment control (3.35±2.63) and identity (3.09±2.36 ). The difference of BIPQ is relevant to sex. Other factors such as age, marriage, education, family history, job category and duration and so on, make no difference. Conclusions The BIPQ reveals gender difference in alopecia areata. Doctors should pay more attention to the cognition about the disease in patients with alopecia areata, correct patients’ excessive perceptions of their illness and heavier mental stress, establish scientiifc perception of disease, so as to promote disease recovery.

临床资料<br>　　患者，男，35岁。主因右侧胸肩部、背部出现肤色囊肿并逐渐增多4年余，于2013年7月15日就诊。4年前患者右侧肩部出现3颗玉米粒大小皮损，表面皮肤正常，无痛痒，未予诊治，皮损数量渐增多，呈带状分布于右侧胸肩部、背部。患者平素体健，否认局部外伤史，家族中无类似疾病者。体格检查：一般情况好，营养中等，各系统检查未见明显异常，全身浅表淋巴结无增大。皮肤科情况：患者右胸肩部、背部肩胛区分别可见呈带状分布的隆起性肤色或淡黄色囊肿，大小不一，直径2 mm～1 cm，稍高出皮面，表面光滑（图1），移动度可，有囊性感，无明显压痛，未扪及血管搏动感；余皮肤、指、趾甲无异常。分别取肩部及背部皮损行组织病理检查，组织病理表现基本一致：真皮浅层毛细血管周围有稀疏的淋巴细胞及组织细胞浸润；真皮内可见囊腔，囊壁由复层鳞状细胞组成，无颗粒层，囊壁上可见皮脂腺小叶，囊腔内少量红染物质，周围见稀疏的淋巴细胞及组织细胞浸润（图2）。诊断：脂囊瘤。本例患者无明显不适，了解详细病情后，不接受任何治疗，故嘱其注意观察并随诊。