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Talaromyces (Penicillium) marneffei is an AIDS-defining infection in Southeast Asia and is associated with high mortality. It is rare in non-immunosuppressed individuals, especially children. Little is known about host immune response and genetic susceptibility to this endemic fungus. Genetic defects in the interferon-gamma (IFN-γ)/STAT1 signaling pathway, CD40/CD40 ligand- and IL12/IL12-receptor-mediated crosstalk between phagocytes and T-cells, and STAT3-mediated Th17 differentiation have been reported in HIV-negative children with talaromycosis and other endemic mycoses such as histoplasmosis, coccidioidomycosis, and paracoccidioidomycosis. There is a need to design a diagnostic algorithm to evaluate such patients. In this article, we review a cohort of pediatric patients with disseminated talaromycosis referred to the Asian Primary Immunodeficiency Network for genetic diagnosis of PID. Using these illustrative cases, we propose a diagnostics pipeline that begins with immunoglobulin pattern (IgG, IgA, IgM, and IgE) and enumeration of lymphocyte subpopulations (T-, B-, and NK-cells). The former could provide clues for hyper-IgM syndrome and hyper-IgE syndrome. Flow cytometric evaluation of CD40L expression should be performed for patients suspected to have X-linked hyper-IgM syndrome. Defects in interferon-mediated JAK-STAT signaling are evaluated by STAT1 phosphorylation studies by flow cytometry. STAT1 hyperphosphorylation in response to IFN-α or IFN-γ and delayed dephosphorylation is diagnostic for gain-of-function STAT1 disorder, while absent STAT1 phosphorylation in response to IFN-γ but normal response to IFN-α is suggestive of IFN-γ receptor deficiency. This simple and rapid diagnostic algorithm will be useful in guiding genetic studies for patients with disseminated talaromycosis requiring immunological investigations., (Copyright © 2019 Lee, Lao-araya, Yang, Chan, Ma, Pei, Kui, Mao, Yang, Zhao, Trakultivakorn and Lau.)

Due to the increase in the prevalence and incidence of allergic diseases, improving the sensitivity and specificity of screening indexes is critical. Total immunoglobulin E (IgE) is a traditional index for judging allergic diseases, while its specificity is relatively poor. Serum-specific IgE (sIgE) is an objective index with high specificity in the diagnosis of allergic diseases. In the present research, the total IgE and sIgE of 3,721 patients with allergic diseases were analyzed to further illuminate the association between them. The data were derived from 3,721 patients. The serum-sIgE to 14 types of common allergens and total IgE were detected. A total of 2,419 cases (65.0%) of 3,721 patients exhibited increasing total IgE and 1,215 patients (32.7%) exhibited positive sIgE. The consistency rate of the two indexes was 60.4%, and the κ-value was 0.28. In 135 patients with normal total IgE, 82.2% exhibited one sIgE positive and 17.8% exhibited two or more sIgE positive. While the number of positive sIgE increased and the detecting level enhanced, the number of positive total IgE markedly increased. Patients (84.1%) with increasing total IgE were associated with positive sIgE, but the increase of total IgE could not be completely explained by the total accumulation of sIgE. Total IgE may play an important role on screening allergic disease while sIgE could be used as crucial evidence for allergy diagnosis. Although the consistency of the two methods was poor, neither total IgE nor sIgE could replace each other. Combining the two indexes with clinical manifestations together will improve the method.

Objective: To analyze the allergic status to common inhalant allergens and food allergens in clinical patients in Harbin in northeastern China and provide evidence to develop the prevention strategy of allergic disease., Methods: The data were collected from 5 473 patients with clinical suspected allergic diseases seeking medical care in the Second Affiliated Hospital of Harbin Medical University. Among these patients, 2 530 (46.2%) were males aged 0-86 years, the youngest was only 1 month old and 2 579 (47.1%) were young children and teenagers. The serum specific Immunoglobulin E (sIgE) to 14 kinds of common allergens and serum total IgE were detected by using AllergyScreen test (Mediwiss Analytic GmbH, Moers, Germany)., Results: In 5 473 subjects the positive rate of sIgE was 33.1% (n=1 813). Cow milk (6.9%) and wheat (3.1%) were the most common food allergens, followed by house dust mite mix (12.5%) and mould mix (9.4%) and the age and gender specific differences in the positive rate were significant. For the children aged <7 years the positive rates to cow milk, beef-mutton, and egg white/egg yolk were high, but the positive rates to house dust mite mix, ragweed estragon, and mould mix were low (P<0.05). For the adults the positive rates to aeroallergens were high while the rates to food allergens were low., Conclusion: The results from this study showed that the food allergens in Harbin had geographic characteristics, which support the viewpoint that the environment factors play an important role in the incidence of allergic diseases. Also, the detection of sIgE and total IgE are essential to identify relevant allergens for the purpose of early diagnosis, management and prevention of allergic disease., (Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)

Osteoporosis (OP) is associated with cardiovascular disease. Moreover, osteoporosis has been shown to be an independent predictor of cardiovascular mortality. Recent studies revealed that altered blood rheology plays a critical role in atherosclerosis. A study confirmed that whole blood viscosity (WBV) is a predictor of cardiovascular events. However, little research has been conducted to investigate the relationship between blood viscosity and osteoporosis. In this cross-sectional study, we investigated the relationship between the rheological parameters and bone mineral density (BMD) in 481 subjects in the International Physical Examination and Healthy Center of the Second Affiliated Hospital, Harbin, China. Different biochemical stress and physical activity are correlated to lumbar spine BMD. Stepwise multivariate linear regression analysis revealed that WBV was a significant factor for decreased BMD (β=-0.513; P<0.001 for lumbar spine L2-4 BMD; β=-0.157; P=0.003 for femoral neck BMD). In conclusion, The findings show that WBV is elevated in osteoporosis and negatively correlated with BMD. Further studies are warranted to investigate whether antiosteoporosis medication could normalize whole blood viscosity in postmenopausal women with osteoporosis., (© 2013.)

The clinical side-effects of increased cyclooxygenase (COX) activity induced by pathologic conditions have raised concerns recently. However, a better understanding of the mechanisms underlying the subsequent neurotoxicity requires knowledge of pathways downstream of COX, especially prostaglandin E2 (PGE2) and its receptors. Therefore, this study was performed to investigate the effects of PGE2 receptor 1 (EP1) activity on neuronal cell death resulting from hypoxia/reoxygenation (Hyp). As cyclinD1 activity has been shown to regulate neuronal apoptosis as well, the role of cyclinD1 was investigated, as well. Cortical neural cells isolated from fetal Wistar rats were cultured for 12 d and exposed to Hyp conditions to establish an in vitro Hyp model. To determine the effects of EP1 activity on Hyp-induced neurotoxicity, cells were treated with 17-phenyl trinor-PGE2 (17-pt), a synthetic EP1 agonist, or sc-51089, an EP1 antagonist, then exposed to hypoxic conditions for 3h and reoxygenated for 21 h. Following Hyp, cell viability was quantified by MTT assays, and apoptosis was assessed by flow cytometry. Protein expression levels of caspase-3 and cyclinD1 were examined by Western blot analysis. Treatment of cultured cortical neurons with 17-pt significantly decreased the survival rate of Hyp-treated neurons (p<0.05), while treatment with sc-51089 increased the survival rate. Treatment with 17-pt also led to increased expression levels of caspase-3, further supporting a role for EP1 in the observed neurotoxicity. However, cyclinD1 expression levels were unchanged following treatment with either 17-pt or sc-51089. Therefore, EP1 may play an important role in Hyp-induced neuronal apoptosis, but this neurotoxic activity is unlikely to involve cyclinD1., (Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.)