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Li K.,Shanghai Skin Disease Hospital | Li K.,University of California at San Francisco | Wang C.,Shanghai Skin Disease Hospital | Lu H.,Shanghai Skin Disease Hospital | And 3 more authors.
PLoS Neglected Tropical Diseases | Year: 2013

Background:Syphilis, a sexually transmitted disease caused by spirochetal bacterium Treponema pallidum, can progress to affect the central nervous system, causing neurosyphilis. Accumulating evidence suggest that regulatory T cells (Tregs) may play an important role in the pathogenesis of syphilis. However, little is known about Treg response in neurosyphilis.Methodology/Principal Findings:We analyzed Treg frequencies and Transforming Growth Factor-β (TGF-β) levels in the blood and CSF of 431 syphilis patients without neurological involvement, 100 neurosyphilis patients and 100 healthy donors. Suppressive function of Tregs in peripheral blood was also assessed. Among syphilis patients without neurological involvement, we found that secondary and serofast patients had increased Treg percentages, suppressive function and TGF-β levels in peripheral blood compared to healthy donors. Serum Rapid Plasma Reagin (RPR) titers were positively correlated with Treg numbers in these patients. Compared to these syphilis patients without neurological involvement, neurosyphilis patients had higher Treg frequency in peripheral blood. In the central nervous system, neurosyphilis patients had higher numbers of leukocytes in CSF compared to syphilis patients without neurological involvement. CD4+ T cells were the predominant cell type in the inflammatory infiltrates in CSF of neurosyphilis patients. Interestingly, among these neurosyphilis patients, a significant decrease in CSF CD4+ CD25high Treg percentage and number was observed in symptomatic neurosyphilis patients compared to those of asymptomatic neurosyphilis patients, which may be associated with low CSF TGF-β levels.Conclusions:Our findings suggest that Tregs might play an important role in both bacterial persistence and neurologic compromise in the pathogenesis of syphilis. © 2013 Li et al.


Dai T.,Peking Union Medical College | Dai T.,Shanghai Xuhui Central Hospital | Li K.,Shanghai Skin Disease Hospital | Lu H.,Shanghai Skin Disease Hospital | And 3 more authors.
Journal of Clinical Microbiology | Year: 2012

Previously, a small study showed that 14f was the predominant subtype of Treponema pallidum in Shanghai, China. The result was quite different from the genotype distribution in other areas of China. This study aimed to identify the strain types of Treponema pallidum in samples collected over a 5-year period in Shanghai. From 2007 to 2011, genital swabs were collected from patients with syphilis from the Shanghai Skin Disease Hospital. Positive specimens were typed by the enhanced typing method by adding a tp0548 gene to the existing arp and tpr genotype system. In total, 304 of the 372 enrolled patients yielded fully typeable DNA. Ten arp types (4, 6, 8, 9, 11, 12, 13, 14, 15, and 19), 3 tpr types (a, d, and o), and 5 tp0548 types (a, c, f, g, and i) were identified. In total, 12 subtypes were identified with a combination of the arp and tpr genes. Subtype 14d was found in 270 samples (88.8%). When the combination included the tp0548 gene, the 12 CDC subtypes identified were divided into 14 strain types. The predominant type was 14d/f (88.8%), followed by 15d/f (3.6%), 13d/f (1.3%), and 19d/c (1.3%). Two of the 44 14d/f-infected patients and both of the 19d/c-infected patients who underwent a lumbar puncture were diagnosed with neurosyphilis. This study showed that the predominant type in Shanghai was 14d/f. While this is in keeping with data from other areas in China, it is different from an earlier report showing that 14f is the most common genotype in Shanghai. Further studies are needed to better understand the association between strain types and neurosyphilis. Copyright © 2012, American Society for Microbiology. All Rights Reserved.


Zhang S.,Fudan University | Liu S.,Taizhou Municipal Hospital | Yu N.,Shanghai Skin Disease Hospital | Xiang L.,Fudan University
Archives of Dermatological Research | Year: 2011

Intercellular adhesion molecule-1 (ICAM-1) expression has been detected in melanocytes around active vitiligo patches as well as in surgically transplanted melanocytes. However, it is unclear whether and how skin injury induces the inappropriate expression of ICAM-1 and other proinflammatory genes in melanocytes. We previously reported that human melanocytes expressed TLR3. We hypothesized that the TLR3 expressed in melanocytes may recognize skin injury by binding to the endogenous ligands secreted by the damaged keratinocytes. Here we showed that RNA released from necrotic keratinocytes induced the upregulation of ICAM-1 protein and mRNA, as shown by FACS and real-time RT-PCR. Use of NF-κB inhibitor prevents upregulation of ICAM-1 in melanocytes indicating a direct role of NF-κB in necrotic keratinocyte-mediated upregulation of ICAM-1. Using a shRNA-expressing lentivirus, we demonstrated that in human melanocytes, TLR3 seems to be necessary for the upregulation of ICAM-1. Using oligonucleotide microarray, we demonstrated a dramatic increase in proinflammatory cytokine and chemokine transcripts (CXCL10, CXCL11, TNFSF10, CCL5, CCL4, CCL2, IFNB1, CCL20, IL-8, and CCL11). These observations suggested that RNA released from necrotic keratinocytes might act as an endogenous TLR3 ligand for the stimulation of ICAM-1 and other proinflammatory gene expression in human melanocytes, which might be involved in the pathogenesis of vitiligo following skin physical trauma. © 2011 Springer-Verlag.


Gu W.,Shanghai Skin Disease Hospital | Yang Y.,Shanghai Skin Disease Hospital | Wu L.,Shanghai Skin Disease Hospital | Yang S.,Shanghai Skin Disease Hospital | Ng L.-K.,Public Health Agency of Canada
BMJ Open | Year: 2013

Objective: In this study, we aimed to determine the performance characteristics of toluidine red unheated serum test on cerebrospinal fluids (CSF-TRUST) as compared to venereal disease research laboratory test on cerebrospinal fluids (CSF-VDRL) for laboratory the diagnosis of neurosyphilis. Design: A cross-sectional study. Setting: Sexually transmitted infections (STIs) clinics. Participants and methods: CSF and serum samples were collected from 824 individual STD clinic patients who have syphilis and are suspected to progress to neurosyphilis within a 9-month period. CSF-VDRL and CSF-TRUST were performed parallelly on the same day when collected. Treponema pallidum particle agglutination (TPPA) tests were also performed on the CSF and the serum samples, and biochemical analysis of the CSF samples was also performed. Results: The overall agreement between CSF-TRUST and CSF-VDRL was 97.3%. The reactive ratios of the CSF samples were 22.1% by CSF-TRUST and 24.8% by CSF-VDRL, respectively. All CSF-TRUST-reactive cases were reactive in the CSF-VDRL. Twenty-two samples with CSF-TRUST-negative were tested CSFVDRL- reactive with low titres (1 : 1 to 1 : 4). Over 97% of the double-reactive CSF samples (CSF-VDRL and CSF-TRUST) had an identical titre or a titre within a two-fold difference. The agreement of CSF-TPPA and CSF-VDRL was 71.9%. Similarly, the agreement of CSF-TPPA and CSF-TRUST was 69.2%. Conclusions: Our results revealed that CSF-TRUST could be used as an option for CSF examination in settings without CSF-VDRL in place.


Zhang S.,Fudan University | Yu N.,Shanghai Skin Disease Hospital | Zhang R.,Fudan University | Wu J.,Fudan University
Investigative Ophthalmology and Visual Science | Year: 2016

PURPOSE. Inflammasome activation and IL-1β production have been proposed to have an important role in age-related macular degeneration (AMD). Growing evidence is emerging for involvement of interleukin-17A (IL-17A) in AMD pathogenesis. We investigated the effects of IL-17A on the activation of inflammasome and production of IL-1β in primary human RPE cells. METHODS. Primary human RPE cells were isolated and cultured for the following experiments. Expression patterns of IL-17 receptor A (IL-17RA), IL-17 receptor C (IL-17RC), and ACT1 were analyzed by RT-PCR, flow cytometry, and immunofluorescence. IL-17A was added to the cell cultures, and cytokine expression, signaling pathways, and inflammasome machinery were investigated using real-time RT-PCR, ELISA, Western blot, flow cytometry, and small interfering RNA. RESULTS. Retinal pigment epithelial cells constitutively expressed IL-17RA, IL-17RC, and ACT1. IL-17A upregulated the mRNA levels of pro-IL-1β, IL-8, CCL2, and CCL20, as well as the protein level of IL-1β. IL-17A induced the phosphorylation of Akt, Erk1/2, p38 MAPK, and NFjB p65 in RPE cells. Blocking NF-jB attenuated IL-17A–induced expression of pro-IL-1β mRNA. IL-17A enhanced pro-caspase-1 and NLRP3 mRNA expression. Inhibiting caspase-1 activity and silencing NLRP3 decreased IL-1b secretion, confirming NLRP3 as the IL-17A– responsive inflammasome on the posttranscriptional level. The mechanism of IL-17A– triggered NLRP3 activation and subsequent IL-1β secretion was found to involve the generation of reactive oxygen species. CONCLUSIONS. Our results suggest that IL-17A triggers a key inflammatory mediator, IL-1β, from RPE cells, via NLRP3 inflammasome activation, holding therapeutic potential for AMD. © 2016. Sci all right reserved.


Yuan C.,Shanghai Skin Disease Hospital | Wang X.-M.,Shanghai Skin Disease Hospital | Yang L.-J.,Shanghai Skin Disease Hospital | Wu P.-L.,Shanghai Skin Disease Hospital
International Journal of Dermatology | Year: 2014

Background: Tranexamic acid (TA) is a traditional plasmin inhibitor, and its role in the renovation of damaged skin has become the topic of a lot of research. The aim of this study is to determine whether TA could repair the skin barrier by means of tight intercellular junctions. Methods: Two kinds of damaged skin models were set up and subjected to repeated application of sodium lauryl sulfate and irradiation of ultraviolet B. Through bioengineering technology and immunohistochemistry tests, TA-induced changes in skin were detected. Results: After 1, 3, 7, and 14 days of application, TA can significantly accelerate barrier recovery and decrease the melanin index values of ultraviolet B irritation skin. The mean optic density of occludin from TA treatment is higher than from self-repair. Conclusion: These experiments suggest that TA can accelerate skin barrier recovery and upregulate occludin induced by physicochemical damages of human skin, but it is advisable to perform more research on the upregulation of occludin in molecular mechanism in the future. © 2013 The International Society of Dermatology.


Liu N.,Shanghai Skin Disease Hospital | Wang X.,Shanghai Skin Disease Hospital | Odio M.,Procter and Gamble
Pediatric Dermatology | Year: 2011

Chinese cloth diapers differ from disposable diapers in several respects that are central to our understanding of the etiology of diaper dermatitis (DD), yet there are no published reports on the dermatological correlates of this manner of infant care, which is prevalent among the world's second-largest pediatric population. The objective was to determine the prevalence and severity of DD in exclusive users of Chinese cloth diapers. This observational study was conducted during a single home visit to 694 Chinese children who were exclusive users of cloth diapers in five inland cities of China. During each home visit, study nurses documented the presence and severity of DD using a visual dermatological scale and conducted transepidermal water loss (TEWL) and pH measurements. Diaper dermatitis was rare in the buttocks and genital area of the children (<20%) but was common in the perianal and intertriginous regions (50-70%). TEWL and pH were mildly higher in babies with DD than in those without DD in the genital and buttocks area. Diaper dermatitis is common in children who use traditional Chinese cloth diapers, especially in the perianal and intertriginous regions. © 2011 Wiley Periodicals, Inc.


Fan G.-B.,Shanghai Skin Disease Hospital | Wu P.-L.,Shanghai Skin Disease Hospital | Wang X.-M.,Shanghai Skin Disease Hospital
Skin Research and Technology | Year: 2012

Background/purpose: Cigarette smoking not only causes systemic health problems, but may also be an underlying cause of premature skin aging. Cigarette smokers frequently have morphological changes in facial skin that may be attributed to reduced oxygen in this region. The purpose of this study was to measure the oxygen content in facial skin before and after smoking. Methods: Twenty-five volunteers participated in this study. Changes in oxygen content of the facial skin were measured before and after 30 min of cigarette smoking. Skin temperature and oxygen content were evaluated in the periorbital and periolar regions. Results: There was a significant increase in temperature after smoking. The oxy hemoglobin and partial pressure of oxygen decreased in both the periocular and perioral areas after smoking. There were no changes in deoxy hemoglobin and partial pressure of carbon dioxide at these areas. Conclusion: Significant changes were seen in temperature and oxygen content after only 30 min of smoking. The results from this study suggest that alterations in the skin temperature and oxygen content in facial skin after smoking may be an underlying cause of premature skin aging. © 2011 John Wiley & Sons A/S.


Zhou P.,Shanghai Skin Disease Hospital | Gu X.,Shanghai Skin Disease Hospital | Lu H.,Shanghai Skin Disease Hospital | Guan Z.,Shanghai Skin Disease Hospital | Qian Y.,Shanghai Skin Disease Hospital
Sexually Transmitted Infections | Year: 2012

Objectives: To study 17 cases of secondary syphilis that progressed to neurosyphilis despite appropriate treatments and whose rapid plasma reagin (RPR) titres showed a fourfold decrease within 6 months but did not revert to negative. Methods: Secondary syphilis patients with the following criteria were analysed: (1) RPR titres declined fourfold within 3 months after therapy, (2) patients denied high-risk sexual behaviours following treatment, (3) RPR titre remained serofast 24 months after treatment, (4) reactive cerebrospinal fluid (CSF) - venereal disease research laboratory (VDRL) and CSF - Treponema pallidum Particle Agglutination Test (TPPA) and (5) HIV antibody negative. Results: 14 male and three female patients met the criteria. 13 patients were asymptomatic. The CSF leucocyte count was elevated in 10 patients of whom nine also had elevated CSF - proteins. The RPR titres following secondary syphilis treatments were ≥1:32 in five cases, 1:16 in four cases, 1:8 in six cases and 1:4 in two cases. Following treatments for neurosyphilis, four cases with neurological or psychiatric manifestations resolved or improved, nine cases with raised CSF - white blood cells returned to normal and nine of 12 cases with raised CSF - protein declined to normal. Conclusions: Neurosyphilis may be detected in immunocompetent patients despite appropriate therapy for early-stage syphilis and appropriate serological responses. Clinicians should consider a CSF examination in any treated patient with evidence of disease progression irrespective of prior treatment history and serological response.


Ding Y.,Shanghai Skin Disease Hospital | Yi X.,Shanghai Skin Disease Hospital | Yu N.,Shanghai Skin Disease Hospital
Clinical and Experimental Dermatology | Year: 2013

Psoriasis is characterized by a T-helper (Th)1/Th17 immune response, and an increase in IgE levels is a prototypical marker of Th2 immunity. The aim of this retrospective case-control study was to analyse serum total IgE levels in generalized pustular psoriasis (GPP), a rare and severe variant of psoriasis. The levels of IgE in patients with GPP and patients with psoriasis vulgaris (PV) were compared with those of healthy controls. IgE levels were also compared with the levels of C-reactive protein (CRP), an indicator of systemic inflammation. The percentage of patients with GPP who had increased IgE levels was significantly higher than that of patients with PV and of healthy controls. The mean levels of IgE were also higher in the GPP group. The IgE levels in patients with GPP had a significant positive correlation with CRP levels. We hypothesize that serum IgE level is a general indicator for increased inflammation in GPP and PV. Click here for the corresponding questions to this CME article. © 2013 British Association of Dermatologists.

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