Yifeng Guo

Mutations in the filaggrin gene in Han Chinese patients with atopic dermatitis

To cite this article: Zhang H, Guo Y, Wang W, Shi M, Chen X, Yao Z. Mutations in the filaggrin gene in Han Chinese patients with atopic dermatitis. Allergy 2011; 66: 420–427.

Polymorphisms in cytotoxic T lymphocyte associated antigen-4 influence the rate of acute rejection after renal transplantation in 167 Chinese recipients.

Gene polymorphisms of cytotoxic T lymphocyte associated antigen 4 (CTLA4) play an influential role in the graft rejection and long-term clinical outcome of organ transplantation. We investigated the associations of five CTLA4 single nucleotide polymorphisms (SNPs) (rs733618T/C, rs4553808A/G, rs5742909C/T, rs231775G/A, rs3087243G/A) on the early acute rejection (AR) of Chinese deceased donor renal transplantation recipients. Genotyping of the CTLA4 SNPs was performed in 167 deceased donor renal transplantation recipients. Each patient underwent a 6-month follow-up observation for AR. The incidence of AR during the 6 months post-transplantation was 26.9% (45 out of 167 patients). Patients experiencing AR were found to have a higher frequency of the rs733618TT genotype and T allele (p=0.000 and p=0.002, respectively). While the haplotype CACAG was merely observed in non-AR group (corrected p=0.000), the frequency of haplotype TACGG was significantly higher in AR group than in non-AR group even after 50,000 permutation tests (corrected p=0.018). In conclusion, these polymorphisms statistically significantly associated with acute renal allograft rejection may be considered as a risk factor of AR in Chinese renal transplantation recipients except for haplotype CACAG as a protective one.

A novel recombinant lineage’s contribution to the outbreak of coxsackievirus A6-associated hand, foot and mouth disease in Shanghai, China, 2012-2013

Since late 2012, coxsackievirus A6 (CVA6) has gradually become the predominant pathogen responsible for hand-foot-mouth disease (HFMD) in several provinces of China. A total of 626 patients diagnosed with HFMD in Shanghai, China from January 2012 to September 2013 were enrolled in this study. Of these, 292 CVA6 infected cases were subjected to clinical analyses. Whole-genome sequencing, recombination and phylogenetic analyses were also performed. A recombinant CVA6 monophyletic lineage was found during an outbreak of CVA6-associated HFMDs in Shanghai, China in November 2012, and accounted for 21.9% (64/292) of the CVA6 strains during the study period. Recombination analyses showed that the 2C gene of the novel CVA6 virus was probably derived from a coxsackievirus A4 (CVA4) strain circulating in the population. Clinical observation showed that this recombinant CVA6 virus led to a more generalized rash than did the non-recombinant CVA6 virus. This newly emerged CVA6 lineage was associated with a considerable proportion of HFMD cases from 2012 to 2013 in Shanghai, and poses a potential threat to public health.

Associations of FLG mutations between ichthyosis vulgaris and atopic dermatitis in Han Chinese

r = 0.303, P = 0.031, respectively). Although allergic rhinitis is regarded as a local disease within the nasal cavity, serum YKL-40 levels in patients with allergic rhinitis were significantly elevated compared to controls and lower than those of asthmatics. This finding might be explained by the extent of the area involved in disease or tissue remodeling. Then serum YKL-40 levels are positively correlated to the severity of allergic rhinitis and the degree of itching, which is caused by the hypersensitivity of the peripheral nervous system to mucosa. Although exact function and biologic characteristics of YKL-40 are not elucidated, this study suggests that serum YKL-40 may play a potential role in the pathogenesis of allergic rhinitis. The further studies are needed to understand the pathophysiologic mechanisms of YKL-40.

Prevalence of Atopic Dermatitis in Chinese Children aged 1–7 ys

Prevalence of atopic dermatitis (AD) is increasing worldwide. Up to date, there has been no face-to-face nation-wide study in China. We aim to explore the prevalence of clinical diagnosed AD in children aged 1–7 ys in China. Twelve metropolises were chosen from different areas of China. In each region, we selected 4–10 kindergartens and 2–5 vaccination clinics randomly. A complete history-taking and skin examination were performed by dermatologists. The definite diagnosis of AD and the severity were determined by two or three dermatologists. All criteria concerned in UK diagnosis criteria, characteristic presentation of AD and atypical manifestations were recorded in detail. A total of 13998 children from 84 kindergartens and 40 vaccination clinics were included. The prevalence of AD was 12.94% by clinical diagnosis of dermatologists overall, with 74.6% of mild AD. Comparatively, prevalence of AD based on UK diagnostic criteria was 4.76%. This is the first face-to-face nation-wide study in Chinese children aged 1–7 ys, revealing that the prevalence of AD in children is closer to that of wealthier nations.

Induction of Regulatory B-Cells by Mesenchymal Stem Cells is Affected by SDF-1α-CXCR7

Background/Aims: Mesenchymal stem cells (MSCs) possess immunomodulatory properties on a diverse array of immune cell lineages, including regulatory T and B cells (Tregs and Bregs, respectively). However, their specific effects and mechanisms underlying induction of Bregs remain unclear. The immune regulatory function of MSCs is exerted through both cell-cell contact and the release of soluble factors. The main objective of this study was to examine the role of the SDF-1-CXCR4/CXCR7 axis in the secretory action of MSCs, and potential effects on the immunoregulatory function of these cells. Methods: MSCs were isolated from mouse bone marrow and characterized according to their multilineage differentiation potential and their surface antigen expression. CD19+ B cells purified from mice splenocytes were co-cultured with MSCs at various ratios in the presence of LPS and αCD40. After 4 days, intracellular IL-10 production and cell surface CD1d and CD5 expression by CD19+ B cells were determined using flow cytometry, and the secretion of IL-10, IL-6, IgM, and IgG were assessed with ELISA. MSCs were treated with different concentrations of stromal derived factor-1α (SDF-1α) stimuli or transiently overexpressed with CXCR7. and their cell viability and immune regulatory effects of MSCs on Bregs were assessed. Results: MSCs induced IL-10-producing regulatory B cells and primarily stimulated the CD1d+CD5+B cell subset of IL-10+Breg cells to express IL-10. IL-10, IL-6, and IgM secretion were additionally induced by MSCs. The CXCR7 pathway was required for MSC viability and the production of paracrine factors under SDF-1α culture condition. Low concentrations of SDF-1α promoted the immunomodulatory effect of MSCs, leading to a further increase in IL-10-producing regulatory B cells and IL-10 secretion. In contrast, high concentrations of SDF-1α inhibited MSCs induction of IL-10+Breg cells. Notably, CXCR7 overexpression in MSCs reversed the inhibitory effect of high concentrations of SDF-1α and promoted the immunomodulatory effect of these cells. Conclusion: MSCs induce IL-10+Breg cells, which contribute to the generation of an immunosuppressive environment. SDF-1α and its receptor, CXCR7 play important roles in the immunomodulatory function of MSCs by regulating their paracrine actions.

Clinical features of atopic dermatitis in a hospital‐based setting in China

Background  Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. There have been few detailed reports of the clinical evaluation of Chinese patients with AD.

Knockdown of Regulator of Cullins-1 (ROC1) Expression Induces Bladder Cancer Cell Cycle Arrest at the G2 Phase and Senescence

Regulator of Cullins-1 (ROC1) is a key subunit in the Cullin-RING ligase (CRL) protein complex. Overexpression of ROC1 protein is associated with tumor progression and poor prognosis of non-muscle invasive bladder transitional cell carcinoma (NMIBC). This study was designed to assess the effects of ROC1 knockdown in bladder cancer cells and to determine the potential mechanisms involved. A total of 112 bladder cancer tissue specimens were recruited for immunohistochemical analyses of ROC1 overexpression. Bladder cancer cell lines were used to knockdown ROC1 expression using ROC1 siRNA. Our data showed that ROC1 knockdown remarkably inhibited bladder cancer cell growth, arrested cells at the G2 phase of the cell cycle, and induced the p53-dependent cell senescence. Molecularly, G2 arrest was associated with upregulation of p21, p27, cyclin B1, and Cdc2 proteins. ROC1 knockdown induced-senescence functioned through p53/p21 pathway. Knockdown of p21 expression partially rescued ROC1 knockdown-induced growth inhibition in cancer cells. Furthermore, nude mouse xenograft analyses confirmed these in vitro data. In conclusion, data from the current study indicate that ROC1 plays an essential role in bladder cancer progression and could serve as a novel anticancer target for bladder transitional cell carcinoma (BTCC).

Methylation-mediated silencing of Dlg5 facilitates bladder cancer metastasis.

UNLABELLED Dlg5 (Discs large homolog 5), a member of the membrane-associated guanylate kinase adaptor family of scaffolding proteins, has been shown to participate in cancer progression. However, little is known about whether abnormal expression of Dlg5 facilitates bladder cancer metastasis. In the current study we initiated a study analyzing Dlg5 expression and its roles in human bladder cancer metastasis. The expression of Dlg5 is decreased in most bladder cancer tissues compared with adjacent normal tissues, and Dlg5 expression is further downregulated in patients with muscle-invasive tumors. DNA methylation analysis showed a methylation of Dlg5 gene in bladder cancer cell lines and in bladder cancer tumors, especially in muscle-invasive tumors. Hypermethylation of Dlg5 in bladder tumors is tightly correlated with silencing of Dlg5 expression, which is further functionally validated by demethylation analysis in bladder cancer cell lines. Knockdown of Dlg5 increases cancer cell invasion in vitro and promotes cancer metastasis in vivo. Of clinical significance, Kaplan-Meier analysis showed that downregulation of Dlg5 is significantly associated with reduced overall survival in patients with bladder cancer. CONCLUSION These data suggest that inhibition of Dlg5 by DNA hypermethylation contributes to provoke invasive phenotypes in bladder tumor.

Successful Treatment of Neurological Malignant Atrophic Papulosis in Child by Corticosteroid Combined with Intravenous Immunoglobulin

Malignant atrophic papulosis (MAP) is a rare thrombo-obliterative vasculopathy of unknown origin [1]. The skin, gastrointestinal tract, and central nervous system (CNS) are most frequently affected [2]. MAP occurs most commonly in young to middle-aged adults [3], while a few of cases with MAP in newborns and children have been described. Treatment of MAP is difficult and no consistently effective therapy has been found. Herein, we describe a child with neurological MAP who responded well to combination therapy with corticosteroid and intravenous immunoglobulin (IVIG) infusion. A 9-year-old boy was admitted to hospital in November 2010 with a 4-year history of asymptomatic papules and right eyelid ptosis for 1 year. The patient is the first-born male of nonconsanguineous parents. There was no family history of note. In 2006, several erythematous papules appeared on his legs and later scarred spontaneously leaving central white atrophy. Afterward, similar skin rashes presented gradually over the years. Two successive biopsies of lesions on the left leg and trunk showed epidermal atrophy with hyperkeratosis, liquefaction degeneration of the basal cell layer, and zones of mucin deposition in dermis. Thus, the diagnosis of MAP was made. Aspirin and Salvia Miltiorrhiza therapy was initiated from August 2009, but stopped in August 2010 due to stomach upset and thrombocytopenia. In November 2009, the patient developed right eyelid ptosis with mild visual impairment. In September 2010, the patient presented to the emergency department with a sudden dizziness, several episodes of nausea and vomiting, as well as malaise and difficulty to walk. Magnetic resonance imaging (MRI) of the brain disclosed bilateral subdural fluid collection in the fronto-temporo-parietal regions. Cerebrospinal fluid (CSF) analysis revealed a high protein concentration and white cell count. The symptoms disappeared after emergency treatment with mannitol and antibiotics. The patient was transferred in November 2010 to our hospital because of progression of skin rash and aggravation of right eyelid ptosis. Dermatologic examination revealed multiple papules ranging from 3 to 6 mm in diameter with an atrophic, porcelain-white central zone and a surrounding erythematous border over the neck, trunk and limbs (Figure 1B). Ophthalmological examination showed right eyelid ptosis and pupil partially obstructed (Figure 1A). A neurological examination revealed no abnormalities. Laboratory investigations including full blood count, coagulation function, biochemistry profile, antinuclear antibody, antineutrophil cytoplasmic antibody, anticardiolipin antibody, serum immunoglobulin, and T lymphocyte subsets were unremarkable. Brain MRI still showed bilateral subdural fluid collection in the frontotemporo-parietal regions (Figure 2A). Magnetic resonance angiography (MRA) revealed occlusion of the left middle cerebral artery in the medial section with distal collateral circulation formation (Figure 1D). CSF analysis showed significantly elevated protein at 2272 mg/L (normal 150–450), high IgG synthesis rate,