Polymorphisms in the promoter of the CD14 gene and their associations with susceptibility to pulmonary tuberculosis.

Although the role of CD14 in recognizing Mycobacterium tuberculosis is well-understood, the possible role of polymorphisms in susceptibility to develop tuberculosis remains unclear. This study evaluates whether there is an association of polymorphisms within the promoter of the CD14 gene with susceptibility to pulmonary tuberculosis. In a case-control study, we genotyped the eight known single nucleotide polymorphisms SNPs within the promoter of the CD14 gene of 698 Han Chinese subjects. Statistically significant differences between tuberculosis patients and healthy controls were found for G-1619A, T-1359G, A-1145G, and C-159T. The haplotype-GGGT, composed of these four SNPs, exhibited a significant association with the disease. Furthermore, expression levels of soluble CD14 were significantly higher in tuberculosis patients with the GGGT haplotype than with other haplotypes, while IgE expression levels were significantly reduced. Our results suggest that these four SNPs within the promoter of the CD14 gene are associated with susceptibility to pulmonary tuberculosis.

[Study on the characteristics of major birth defects in 1.69 million cases of fetus in Guangxi Zhuang Autonomous Region].

Objective: Tracking the information on 1.69 million fetal cases across Guangxi Zhuang Autonomous Region (Guangxi) so as to study the occurrences of total and major birth defects in order to evaluate the ability on related prevention and control programs in Guangxi. Methods: Using the self-developed "Gui Women's System" to establish a database of 1.69 million fetal cases in Guangxi and to analyze the distribution of time, space and population, as well as the outcomes of pregnancy, using the big data. Results: During the 29 months of observation, the overall live birth rate was 99.25%, with stillbirth rate during pregnancy as 0.44%, stillbirth rate during birth as 0.02%, and the 0-6 days mortality rate as 0.14%. The total detection rate on birth defects was 197.63/10 000; the incidence rate was 103.04/10 000, the birth rate was 102.55/10 000. The overall discovery rate of major birth defects was 48.33/10 000, with the incidence rate as 783 000, the birth rate as 0.58/10 000. The discovery rates of major birth defects in 14 cities were between 35 and 68/10 000, and the birth rate dropped significantly to less than 1.00 in 10 000. Nationalities showed that the number of pregnant women with birth defects more than 50 000 would include Hui (9.68/10 000), Yao (9.57/10 000), and Jing (9.37/10 000). With the increasing age of gestation, number of birth defects, incidence of major birth defects also increased. Ninety-five percent of the major birth defects were found within <28 weeks and with the top 5 kinds of major birth defects as complicated congenital heart disease (9.11/10 000), alpha thalassemia (8.36/10 000), and 21-trisomy syndrome (7.85/10 000), beta thalassemia (5.32/10 000) and fetal edema syndrome (4.92/10 000). The top 5 major birth defects appeared as complicated congenital heart disease (9.11/10 000), alpha thalassemia (8.36/10 000), and 21-trisomy syndrome (7.85/10 000), beta thalassemia (5.32/10 000) and fetal edema syndrome (4.92/10 000). Conclusion: Programs leading to increase the rate on discovery of major birth defects were fundamental in effectively reducing the major birth defects.

MicroRNA-218 alleviates sepsis inflammation by negatively regulating VOPP1 via JAK/STAT pathway.

OBJECTIVE: To investigate the possible role of microRNA-218 in the pathogenesis of sepsis and its underlying mechanism. PATIENTS AND METHODS: MicroRNA-218 expression in peripheral blood mononuclear cells (PBMCs) of 53 sepsis patients and 20 healthy controls was detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). MicroRNA-218 expression in Treg cells of sepsis patients and healthy controls was also detected. The binding condition of microRNA-218 to VOPP1 was confirmed by dual-luciferase reporter gene assay and RNA binding protein immunoprecipitation (RIP) assay, respectively. Furthermore, sepsis mouse model was constructed. MicroRNA-218 mimics or inhibitor was injected into mouse tail vein, respectively. The proportion of Treg cells was compared between sepsis mice injected with microRNA-218 mimics and inhibitor. Expressions of microRNA-218 and VOPP1 in Treg cells extracted from sepsis mouse were detected. ELISA (enzyme-linked immunosorbent assay) assay was conducted to detect serum levels of inflammatory factors (TNF-α, IL-6, TGF-ß, and IL-10) in sepsis mouse. Finally, protein expressions of key genes in JAK/STAT pathway in sepsis mouse spleen were detected by Western blot. RESULTS: MicroRNA-218 expression in sepsis patients was remarkably lower than that of healthy controls, which was gradually decreased with the deteriorating symptoms. Specifically, microRNA-218 expression was the lowest in patients who died of sepsis. Downregulated microRNA-218 was seen in Treg cells extracted from advanced sepsis patients. Both dual-luciferase reporter gene assay and RIP assay suggested that microRNA-218 can bind to VOPP1. VOPP1 expression was negatively regulated by microRNA-218. In advanced sepsis mouse, administration of microRNA-218 mimics increased expressions of TNF-α and IL-6, but decreased expressions of IL-10 and TGF-ß. Western blot results indicated that microRNA-218 can inhibit the JAK/STAT pathway in sepsis mice. CONCLUSIONS: MicroRNA-218 expression in the PBMCs of sepsis patients was remarkably reduced, which inhibited sepsis development via negatively regulating VOPP1 and suppressing JAK/STAT pathway.