假性血管性水肿：一种新的皮肌炎皮疹

【摘要】 介绍一种新的皮肌炎皮疹类型——假性血管性水肿,其特点为患者面部、口唇、四肢为主出现局限性或弥漫性水肿,非凹陷性,可伴或不伴红斑,皮疹无明显瘙痒。大部分伴假性血管性水肿的皮肌炎患者抗转录中介因子1γ抗体阳性,会出现严重肌肉损伤,肌酶异常增高,以及难治性吞咽困难;少部分患者抗黑素瘤分化相关基因5抗体阳性,此类患者均有肺部累及。因此,皮肌炎患者出现假性血管性水肿时需要高度重视,抗体筛查有助于患者早期诊断和早期差异化治疗,改善患者的症状体征,提高患者的生存率。     

Interaction of Wnt5a with Notch1 is Critical for the Pathogenesis of Psoriasis

BackgroundPsoriasis is characterized by uncontrolled hyperproliferation, aberrant differentiation, and dermal infiltration of immune cells. Recent studies have reported that Wnt5a and Notch1 signaling are altered in psoriatic skin lesions.ObjectiveWe aimed to investigate the interaction of Wnt5a with Notch 1 with respect to inflammation-mediated epidermal hyperproliferation in psoriasis.MethodsExpression of Wnt5a and Notch1 signaling-related proteins were examined in psoriatic skin biopsies. Wnt5a was upregulated in human keratinocytes by treating the cells with its recombinant form (rWnt5a).ResultsIn psoriatic lesions, expression of Wnt5a increased while that of Notch1 decreased when compared to that in non-lesional and normal skin. Treatment with rWnt5a increased the proliferation of keratinocytes and increased their secretion of interleukin (IL)-23, IL-12, and tumor necrosis factor (TNF)-α. Further, exposure of keratinocytes to IL-1α, TNF-α, transforming growth factor-α, and interferon-γ downregulated Notch1 as well as HES 1, which is downstream to Notch1, but increased the Wnt5a levels. The upregulated Wnt5a in keratinocytes downregulated both Notch1 and HES1.ConclusionOur data suggest that Wnt5a and Notch1 signaling exert counteracting influences on each other and are involved, in part, in the pathomechanism of psoriasis.     

Nuclear factor XIIIa staining (clone AC‐1A1 mouse monoclonal) is a sensitive and specific marker to discriminate sebaceous proliferations from other cutaneous clear cell neoplasms

Sebaceous carcinoma is a rare but serious malignancy that may be difficult to diagnose when poorly differentiated. Other epithelial tumors with clear cell change may mimic sebaceous carcinoma. Few useful or specific immunohistochemical markers for sebaceous differentiation are available. Nuclear staining with factor XIIIa (clone AC‐1A1) was recently found to be a highly sensitive marker of sebaceous differentiation. We evaluated nuclear factor XIIIa (AC‐1A1) staining in sebaceous neoplasms vs. other cutaneous clear cell tumors. We stained 27 sebaceous proliferations: sebaceous hyperplasia (7), sebaceous adenoma (8), sebaceoma (5), sebaceous carcinoma (7). We also stained 67 tumors with clear cell change: basal cell carcinoma (8), squamous cell carcinoma (8), hidradenoma (7), desmoplastic trichilemmoma (2), trichilemmoma (10), trichilemmal carcinoma (3), clear cell acanthoma (9), atypical fibroxanthoma (1), syringoma (8), trichoepithelioma (1), metastatic renal cell carcinoma (2), and nevi with balloon cell change (8). Nuclear factor XIIIa (AC‐1A1) staining was present in 100% of sebaceous proliferations; 96% displayed strong staining. Non‐sebaceous clear cell tumors were negative or only weakly positive with factor XIIIa (AC‐1A1) in 95.5%; only 4.5% showed strong staining. This suggests that strong nuclear factor XIIIa (AC‐1A1) staining is a sensitive and specific marker of sebaceous neoplasms vs. other clear cell tumors.     

ki-67和CD—1a的表达对5-ALA光动力治疗尖锐湿疣疗效的影响

目的：评价5-ALA光动力治疗尖锐湿疣（CA）的临床疗效,并探讨疗效与ki-67和CD—1a蛋白表达的相关性。方法：采用5-ALA光动力法对78例CA患者进行治疗,并采用免疫组化法检测ki-67、CD—1a在CA中的表达。结果：5-ALA光动力治疗CA,治愈率78．2％,复发率19．23％;CA皮损中ki-67高表达、CD—1a低表达的患者光动力治疗的临床治愈率低,易复发。结论：5-ALA光动力治疗CA的疗效与ki-67、CD-1a的蛋白表达可能具有一定相关性。     

lncRNA DLX6-AS1通过靶向miR-16-5p/NUCKS1调控皮肤鳞状细胞癌细胞A431增殖、迁移和侵袭

【摘要】 目的 研究长链非编码生长停滞特异性蛋白6反义RNA1（lncRNA DLX6-AS1）对皮肤鳞状细胞癌细胞A431增殖、迁移和侵袭的影响及潜在机制。方法 以双荧光素酶报告系统实验验证lncRNA DLX6-AS1与miR-16-5p、miR-16-5p与核酪蛋白激酶和细胞周期蛋白依赖性激酶底物1（NUCKS1）mRNA的靶向结合。通过单独或联合转染lncRNA DLX6-AS1抑制物（si-DLX6-AS1）、miR-16-5p抑制物（anti-miR-16-5p）、NUCKS1抑制物（si-NUCKS1）和相应对照（DLX6-AS1-NC、anti-miR-NC、NUCKS1-NC）调控A431细胞目的基因的表达,采用qRT-PCR 检测A431细胞lncRNA DLX6-AS1、miR-16-5p、NUCKS1 mRNA的表达;Western印迹检测NUCKS1、细胞周期蛋白D1（Cyclin D1）抗体、基质金属蛋白酶（MMP）2和MMP9蛋白水平;CCK8实验检测细胞存活率;Transwell实验检测细胞迁移和侵袭能力。两组间比较采用独立样本t检验。结果 双荧光素酶报告系统实验显示,lncRNA DLX6-AS1靶向结合miR-16-5p,miR-16-5p靶向结合NUCKS1。si-DLX6-AS1组A431细胞miR-16-5p表达水平（3.01 ± 0.31）高于DLX6-AS1-NC组（1.02 ± 0.10,t = 18.33,P < 0.001）;NUCKS1、Cyclin D1、MMP2和MMP9蛋白相对水平均低于DLX6-AS1-NC组（均P < 0.05）,细胞存活率、迁移和侵袭细胞数亦低于DLX6-AS1-NC组（均P < 0.05）。si-NUCKS1组A431细胞NUCKS1、Cyclin D1、MMP2和MMP9蛋白相对水平均低于NUCKS1-NC组（均P < 0.05）,细胞存活率、迁移和侵袭细胞数亦低于NUCKS1-NC组（均P < 0.05）。低表达lncRNA DLX6-AS1后,anti-miR-16-5p组A431细胞miR-16-5p表达（0.34 ± 0.04）低于anti-miR-NC组（1.00 ± 0.12,t = 15.65,P < 0.05）,Cyclin D1、MMP2和MMP9相对表达水平均高于anti-miR-NC组（均P < 0.05）,细胞存活率、迁移和侵袭细胞数均高于anti-miR-NC组（均P < 0.05）。低表达lncRNA DLX6-AS1、敲减miR-16-5p后,si-NUCKS1组A431细胞NUCKS1、Cyclin D1、MMP2和MMP9蛋白相对水平均低于NUCKS1-NC组（P < 0.05）,细胞存活率、迁移和侵袭细胞数均低于NUCKS1-NC组（P < 0.05）。结论 lncRNA DLX6-AS1可通过靶向miR-16-5p/NUCKS1调控A431细胞增殖、迁移和侵袭,lncRNA DLX6-AS1可能是治疗皮肤鳞状细胞癌的潜在分子靶点。     

Fluorescence urethroscopy following instillation of 5-aminolevulinic acid: A new procedure for detecting clinical and subclinical HPV lesions of the urethra

OBJECTIVE: To report early clinical experience with intraurethral instillation of 5-aminolevulinic acid (ALA) for the detection of clinical lesions (condyloma acuminata) and subclinical human papillomavirus (HPV) lesions of the urethra, not visible by conventional endoscopy. SUBJECTS AND SETTING: Eighty-four men with clinical diagnosis of condyloma acuminata were examined for urethral HPV lesions at the Department of Urology, Ludwig Maximilian University, Munich, Germany. METHODS: The anogenital areas of the patients were thoroughly examined using a magnifying glass before and after application of 5% acetic acid. Conventional as well as fluorescence urethroscopy were performed 1 h after topical application of 0.1% ALA for 15 min. A sensitive colour charge-coupled device camera for fluorescence video inspection was used with spectral analysis. Biopsies were taken for histological examination and HPV detection by polymerase chain reaction (PCR). RESULTS: Forty-three of 84 men attending our clinic for condyloma acuminata had clinical HPV lesions of the urethra. Condylomas of the proximal urethra were found by conventional endoscopy in eight patients. Fluorescence urethroscopy detected additional subclinical lesions in 13 men. All lesions were HPV infections of the urethra confirmed histologically or by PCR. In nine of these subclinical urethra lesions low-risk HPV types (HPV6, 11, 34) were found. Four lesions were associated with high-risk types (HPV18, 31,52,58). CONCLUSIONS: Fluorescence urethroscopy is a promising diagnostic procedure for detecting subtle clinical and subclinical HPV lesions of the urethra, that are normally not visualized by conventional endoscopy. Generally, urethroscopy is recommended in all cases of externally visible condylomas of the urethra after therapy.     

Topical PTH (1-34) is a novel,safe and effective treatment for psoriasis: a randomized self-controlled trial and an open trial

BACKGROUND: There continues to be a need to develop new pharmacological approaches for treating the common skin disease psoriasis. Human skin produces parathyroid hormone related peptide. This peptide is a potent inhibitor of epidermal cell growth. OBJECTIVES: A programme was initiated to determine whether an agonist of this peptide's receptor, PTH (1-34), could be developed as a drug to treat psoriasis. METHODS: PTH (1-34) was formulated in Novasome A cream. Fifteen adult patients with chronic plaque psoriasis who had failed to respond to at least one standard treatment were enrolled in a randomized double-blinded placebo self-controlled trial. The patients topically applied to a 25-cm2 psoriatic lesion 0.1 g of either Novasome A cream or Novasome A cream that contained 20 microg of PTH (1-34) twice a day for 2 months. At the end of the double-blind study, patients were enrolled in an open large area study. Ten patients applied PTH (1-34) (50 microg per 0.1 g) once daily to their psoriatic lesions. The patients were evaluated for their global improvement and calcium metabolism. RESULTS: Novasome A cream enhanced the percutaneous absorption of PTH (1-34) in human skin in comparison with formulations in propylene glycol or normal saline. Psoriatic lesions treated with PTH (1-34) showed marked improvement in scaling, erythema and induration. There was a 67.3% improvement in the global severity score for the lesion treated with PTH (1-34) compared with the placebo-treated lesion, which only showed a 17.8% improvement. Ten patients topically applied PTH (1-34) on all of their lesions in a stepwise manner. A Psoriasis Area and Severity Index score analysis of all the patients revealed improvement of 42.6% (P < 0.02). None of the patients experienced hypercalcaemia or hypercalciuria or developed any side-effect to the medication. CONCLUSIONS: Patients who were resistant to at least one standard therapy for psoriasis had a remarkable improvement in their psoriasis when they applied PTH (1-34) to their lesion(s). No untoward toxicity was observed in any of the subjects. This pilot study suggests that topical PTH (1-34) is a safe and effective novel therapy for psoriasis.     

Topical paricalcitol (19-nor-1 alpha,25-dihydroxyvitamin D2) is a novel, safe and effective treatment for plaque psoriasis: a pilot study

BACKGROUND: There continues to be a need to develop new pharmacological approaches for treating psoriasis. Topical active vitamin D compounds have proven to be both safe and effective for treating psoriasis. Paricalcitol (19-nor-1 alpha,25-dihydroxyvitamin D(2)) is a novel vitamin D analogue which has been developed for the prevention of secondary hyperparathyroidism in patients with chronic renal failure. OBJECTIVES: To investigate the efficacy and safety of 12 weeks' therapy with a once-daily application of paricalcitol ointment (15 microg g(-1)) in comparison with placebo ointment. METHODS: This pilot double-blinded self-controlled study was initiated in 11 patients with moderate plaque psoriasis. To characterize the biological effects further and to evaluate the efficacy of topical paricalcitol treatment in psoriasis, we have analysed immunohistochemically the expression of one of the markers for epidermal differentiation (transglutaminase K) in paricalcitol-treated skin as compared with placebo treatment. RESULTS: Treatment with paricalcitol was superior to placebo treatment beginning at week 1. The global severity score for erythema, plaque elevation and scaling was improved significantly more by paricalcitol ointment than by placebo (P < 0.001). Similar results were obtained for assessments of scaling, erythema and plaque elevation. No symptoms of local skin irritation were noted. Laboratory parameters including serum calcium, phosphorus, parathyroid hormone and urinary calcium/creatinine ratio did not reveal any changes of clinical relevance during treatment. The immunoreactivity of transglutaminase K changed after 12 weeks of paricalcitol treatment almost completely to the pattern characteristic for nonlesional psoriatic skin. CONCLUSIONS: Once-daily application of paricalcitol ointment was safe and effective for the treatment of plaque psoriasis.