ZBTB24 regulates the apoptosis of human T cells via CDCA7/TRAIL-receptor axis.

Mutations in ZBTB24 and CDCA7 cause the Immunodeficiency, Centromeric Instability and Facial Anomalies syndrome type 2 and 3 (ICF2/3), respectively. Most ICF2 patients carry ZBTB24 nonsense mutations and are thus ZBTB24-deficient. Although the immune deficiency in ICF2 patients is primarily regarded as a B-cell defect due to the greatly reduced serum antibodies and circulating memory B cells, the reduced expansions of PBMCs stimulated by mitogens or recall antigens suggest a T-cell defect in these patients as well. However, the molecular mechanisms behind this T-cell dysfunction remain unknown. In the present study, we demonstrated that ZBTB24-deficiency significantly represses the proliferation of human T cells by promoting TRAIL-induced cell death. Downregulation of ZBTB24 in both Jurkat and human primary T cells upregulates the expression of TRAIL and/or its death receptors (TRAIL-R1/2), and induces significant amount of cells to undergo apoptosis. The profound survival defects of ZBTB24-deficient cells are largely reversed by blocking TRAIL/TRAIL-R interactions with exogenous recombinant TRAIL-R2. Moreover, ZBTB24-downregulation reduces the expression of CDCA7, and knockdown of the latter in human T cells results in a phenotype resembling that caused by ZBTB24-depletion. Functionally, overexpression of CDCA7 abrogates the increased apoptosis in ZBTB24-depleted Jurkat T cells. Together, these data indicated that ZBTB24 regulates human T-cell apoptosis via CDCA7/TRAIL-R axis. Our study thus not only provides a molecular explanation for the T-cell defects in ZBTB24-deficient ICF2 patients, but also highlights a convergence between ZBTB24 and CDCA7, the two ICF genes, in modulating the functions of T cells.

[Establishment of early warning control charts based on the syndromic surveillance data of outpatient diarrhea in Beijing].

OBJECTIVE: To establish the control charts for early warning of diarrhea based on the syndromic surveillance data from enteric clinic in Beijing. METHODS: The outpatient data from enteric clinic of a Grade Three General hospital in Haidian district, Beijing from April 1 to Oct. 31, 2009 and from May 1 to Nov.10, 2010 were collected, according to the moving average method, the baseline calculated, the value of probability α and µα, the early warning value based on the formula "w=Xj+µαSj" calculated and the early warning control charts drew at last. RESULTS: According to the harmfulness, the severity and controllability of diarrheal diseases, the value of probability α was determined as 0.01, then µα (unilateral) as 2, based on the early warning value, the control charts of diarrheal diseases, bacillary dysentery and other infectious diarrhea were established. CONCLUSION: The enteric clinic requires to further collect baseline data to evaluate and continuously adjust the established control charts for the best early warning model in accordance with the enteric clinic.

Clinical predictors for diagnosing pandemic (H1N1) 2009 and seasonal influenza (H3N2) in fever clinics in Beijing, China.

OBJECTIVE: Symptomatic predictors of influenza could assess risks and improve decisions about isolation and outpatient treatment. To develop such predictors, we undertook a prospective analysis of pandemic (H1N1) 2009 and seasonal influenza (H3N2) in patients attending fever clinics. METHODS: From 1 May 2009 to 1 January 2010, all adult patients admitted to fever clinics for suspected influenza, confirmed by real time RT-PCR, were enrolled. Predictors of influenza virus infection were selected with logistic regression models. Measures of sensitivity, specificity, positive and negative likelihood ratios (LRs) were calculated to identify the best predictors. RESULTS: The clinical features and routine blood test results of influenza (H1N1) 2009 and seasonal influenza were similar. The positive and negative LRs of current US CDC influenza-like illness (ILI) criteria were modest in predicting influenza infection. Our modified clinic predictors improved the ability of the positive and negative LRs to recognize pandemic (H1N1) 2009 and seasonal influenza. The revised criteria are: fever >38 °C accompanied by at least one of the following-cough, arthralgia or relative lymphopenia. CONCLUSION: Patients with symptoms and signs that meet the new criteria are likely to have influenza and timely antiviral therapy may be appropriate. In addition, physicians should ascertain if influenza is circulating within the community or if there is a contact history of influenza and combine this information with the newly developed criteria to clinically diagnose influenza.

Membrane Bound CRT Fragment Accelerates Tumor Growth of Melanoma B16 Cell In Vivo through Promoting M2 Polarization via TLR4.

Calreticulin (CRT) is a major calcium-binding luminal resident protein on the endoplasmic reticulum that can also be released extracellular as well as anchored on surface of cells. Previously, we demonstrated that soluble recombinant CRT fragment 39-272 (CRT/39-272) exhibited potent immunostimulatory effects as well as immunoregulation effects on immune cells. Here, we constructed stable B16 melanoma cell lines expressing recombinant CRT/39-272 on the membrane (B16-tmCRT/39-272) to investigate the roles of cell surface CRT on tumor progression. We found that B16-tmCRT/39-272 cells subcutaneously inoculated into C57BL/6 mice exhibited stronger tumorigenicity than the B16-EGFP control cells. The tumor associated macrophages infiltrated in tumors were mainly M2 phenotype. Regulatory T cells (Tregs) were also expanded more in bearing mice. Consistent with the in vivo results, B16-tmCRT/39-272 promoted macrophage polarization toward F4/80+CD206+ M2 macrophages and promoted transforming growth factor beta (TGF-ß) secretion in vitro, which could promote naïve CD4+ T cell differentiation into Tregs. These results imply that the tmCRT/39-272 could accelerate tumor development by enhancing M2 macrophage polarization to induce TGF-ß secretion, and then promoted Treg differentiation in the tumor microenvironment. Our data may provide useful clues for better understanding of the potentiating roles of CRT in tumorigenesis.

[Analysis of syndromic surveillance of 63 325 outpatients in Fever Clinic in Beijing].

OBJECTIVE: To describe findings from syndromic surveillance of Fever Clinic visits and to determine the utility of monitoring Fever Clinic admissions as an indictor of respiratory infectious disease activity in Beijing. METHODS: A census on outpatients in Fever Clinics was conducted in two grade 3 general hospitals in Beijing from April 1, 2009 to March 31, 2010 based on a typical survey, the epidemiological characteristics of outpatients were analyzed and correlation among Fever Clinic visits, acute febrile respiratory illness (ARI) visits, influenza-like illness (ILI) visits and influenza visits determined. RESULTS: The seasonal patterns for Fever Clinic visits, ARI visits and ILI visits were quite similar, but that for influenza visits peaked later than those for ARI and ILI visits. There were high positive relationships between ARI visits, ILI visits or influenza visits and Fever Clinic visits, with a pearson's correlation coefficient of 0.99, 0.99 and 0.48, respectively (P<0.001). CONCLUSION: Syndromic surveillance of Fever Clinic visits is valuable for early warning of respiratory infectious disease outbreaks. The Fever Clinic provides a platform for early diagnosis and treatment of respiratory infectious disease.

[Analysis of disease types of outpatients with intestinal diseases from two grade-three general hospitals in Beijing].

OBJECTIVE: To understand the spectrum of diseases and epidemiological characteristics of outpatients at Entric Disease Clinic, with a focus on analysis of the distribution of infectious diarrheal diseases in different populations and to explore disease control strategies on Enteric Infectious Diseases for focal groups. METHODS: A census on outpatients at Entric Disease Clinics was conducted in two class Three comprehensive hospitals in Beijing from April 1 to October 31, 2009 based on a descriptive study using diarrhea-syndrome surveillance system set in the two clinics, thus to depict the spectrum of diseases and epidemiological characteristics of outpatients, and analyze the proportion of infectious diarrhea in diarrheal diseases specifically and the rate changes of infectious diarrhea in different months, age groups and occupational groups. RESULTS: Diseases are varied at the two enteric diseases clinics among the patients and there are mainly 10 kinds of diseases, "non-infectious diarrhea" accounted for the highest percentage (77.4%), followed by "unspecified diarrhea" (11.7%), and infectious diarrhea accounted for the least proportion(8.7%)."Gastroenteritis and enteritis" are the most frequently diagnosed cases among all the diseases, was a total of 7 565 cases, accounting for 70.2%. The volume of visits reached its top during summer and autumn(July to September), and the mean volume of visits in this period is (60.78+/-16.85) cases/day. The volume of visits has an obvious seasonal trend, and visits during July and August are the most frequent (41.82% altogether). Patients with "infectious diarrhea" had a highest ratio(5.3%) in May and lowest (1.1%) in October while patients with "bacillary dysentery" accounted for a highest ratio(8.2%) in September and lowest(3.8%) in April. Outpatients are mainly from Beijing city(61.9%), in which young and middle-aged people accounted for 73.9% in total, and student is the main occupation (28.8%). The distributions of diarrheal diseases are the same in different age groups but differ from different occupational groups. Infectious diarrhea accounted for a highest proportion(9.2%) in 18-to-44-year-old age group when using age grouping, and a highest proportion(15.2%) in restaurant service personnel when using occupation grouping. CONCLUSION: The volume of outpatients attended at general hospitals is overwhelming especially in July and August, and the major type is "non-infectious diseases", which indicates an arduous task on prevention and control of Enteric Infectious Diseases. Infectious diarrhea took up a certain amount, but the rate is not that high, which indicates possible missing diagnosis of patients with infectious diseases.Our focal groups would be young and middle-aged people and students in the city. Therefore, the need to extend the consultation hours is urgent. Meanwhile, for the main goal of surveillance and early warning on Enteric Infectious Diseases, all aspects of construction of Enteric Disease Clinic should be strengthened, such as enhance laboratory tests on pathogens, improve diagnosis level of physicians and etc.