SNPs rs644242 and rs662702 had marginal significance (P = 0.063), and further analyses showed that these SNPs were associated with extreme myopia (≤ -11 D). The OR for extreme myopia was 2.1 (empiric P = 0.007) for the CC genotype at SNP rs662702 at the 3'UTR. The functional assay for SNP rs662702 demonstrated that the C allele had a significantly lower expression level than did the T allele (P = 0.0001). SNP rs662702 was predicted to be located in the microRNA-328 binding site, which may explain the differential allelic effect on gene expression. CONCLUSIONS; In this study, a functional SNP was identified at the 3'UTR that influences the risk for extreme myopia. The functional assay suggested that the risk allele can reduce PAX6 protein levels which significantly increases the risk for myopia.

No abstract

Genetic factors are important in the development of glioma. Interleukin-12 (IL-12) is a multifunctional cytokine that induces Interferon (IFN)-gamma secretion and plays an important role in antitumor immunity. Interleukin-27 (IL-27) is a novel IL-12 family member, and the present studies demonstrate that IL-27 mediates a potent antitumor activity. The aim of this study was to investigate whether IL-12 and IL-27 gene polymorphisms and their serum levels are associated with glioma. We analyzed IL-12 gene 16974 A/C and IL-27 gene -964 A/G, 2905 T/G, and 4730 T/C polymorphisms in 210 patients with glioma and 220 matched controls, using polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing methods, while serum IL-12p40 and IL-27p28 levels were measured by enzyme-linked immunosorbent assay. Serum IL-12p40 and IL-27p28 levels were decreased in patients with glioma compared with controls (p < 0.01). There were significant differences in the genotype and allele frequencies of the IL-12 gene 16974 A/C polymorphism between the group of patients with glioma and the control group (p < 0.05). Moreover, genotypes carrying the IL-12 16974 C variant allele were associated with decreased serum IL-12p40 and IL-27p28 levels compared to the homozygous wild-type genotype in patients with glioma. The IL-12 gene 16974 A/C polymorphism may regulate expression of the serum IL-12p40 and IL-27p28, and associate with increased risk of glioma. Thus, genotypes carrying the IL-12 16974 C variant allele had a decreased ability to produce IL-12 and IL-27, which may contribute to glioma susceptibility.

MSX1 is a favorable candidate gene for susceptibility to non-syndromic orofacial clefts (NSOCs). However, the roles of MSX1 genetic variants in the development of NSOC are controversial and vary among human populations. In the present study, the roles of 4 potentially functional single-nucleotide polymorphisms (SNPs) of MSX1 (rs12532 in 3'-untranslated region [UTR], and rs3821947, rs3821949, and rs4464513 in 5' upstream) were investigated in a case-control study of 602 NSOC cases and 605 healthy controls. The findings showed that rs12532 located within 3'-UTR of MSX1 could influence the risk of developing NSOC. Individuals who carried the variant genotype (rs12532AA genotype) showed a decreased possibility of developing NSOC (AA vs. GG: OR = 0.69, 95% CI = [0.49, 0.98]). Interestingly, similar effects were also observed on cleft lip with palate (CLP), in a stratified analysis (allelic comparison-12532A allele vs. 12532G allele, OR = 0.80, 95% CI = [0.66, 0.99]; genotypic comparison-AA vs. GG, OR = 0.58 95% CI = [0.37, 0.91]). Sequence analysis indicated that this SNP might alter the binding ability of miR-3649, confirmed by luciferase activity assay showing a lower expression level of rs12532 A allele compared with that of the G allele (p < .001 for 293A and COS7 cell lines). Furthermore, an in vivo study showed that MSX1 expression among individuals carrying the AA genotype of rs12532 was markedly lower than that in those with the GG genotype, while the inverse correlation was observed for miR-3649, thus providing a possible interaction between MSX1 and miR-3649 in the etiology of NSOC. Taken together, these findings indicate that SNPs in the miRNA-binding sites might play an important role in the development of NSOCs. Furthermore, if confirmed in subsequent studies, the polymorphisms may be considered as additional markers for the evaluation of infants' risk of NSOCs.

The early postnatal period is the most dynamic and vulnerable stage in the assembly of intestinal microbiota. Antibiotics are commonly prescribed to newborn preterm babies and are frequently used for a prolonged duration in China. We hypothesized that the prolonged antibiotic therapy would affect the early development of intestinal microbiota and their metabolites. To test this hypothesis, we analyzed the stool microbiota and metabolites in 36 preterm babies with or without antibiotic treatment. These babies were divided into three groups, including two groups treated with the combination of penicillin and moxalactam or piperacillin-tazobactam for 7 days, and the other group was free of antibiotics. Compared to the antibiotic-free group, both antibiotic-treated groups had distinct gut microbial communities and metabolites, including a reduction of bacterial diversity and an enrichment of harmful bacteria such as Streptococcus and Pseudomonas. In addition, there was a significant difference in the composition of gut microbiota and their metabolites between the two antibiotic-treated groups, where the piperacillin-tazobactam treatment group showed an overgrowth of Enterococcus. These findings suggest that prolonged antibiotic therapy affects the early development of gut microbiota in preterm infants, which should be considered when prescribing antibiotics for this population.

Tumours treated with TTT have significant recurrence rates. Although tumour control may ultimately be achieved with TTT, close monitoring of these tumours is necessary, since repeat TTT or alternative therapies may be required.

To gain insight into the epidemiology of childhood drug resistant tuberculosis (DR-TB) in China that has the second largest burden of TB and the largest number of multidrug resistant (MDR) TB cases in the world, we performed the cross-sectional study to investigate drug resistance of four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol) using Mycobacterium tuberculosis isolates from 196 culture-confirmed pediatric TB cases diagnosed in the Children’s Hospital of Chongqing Medical University, China during 2008–2013. Univariate and multivariate logistic regression analyses were performed to assess the associations between patient demographic and clinical characteristics and DR-and MDR-TB, respectively. Twenty-eight percent (56/196) of the study patients exhibited resistance to at least one of the four first-line anti-TB drugs tested. MDR was found in 4.6% (9/196) of the study patients. More than half (5/9, 55.6%) of the MDR cases were from a single county of Chongqing. A significant association was found between being acid-fast bacilli-smear negative and DR-TB (adjusted OR, 2.33; 95% CI, 1.13–4.80) and between having concurrent thoracic-extrathoracic involvement and MDR-TB (adjusted OR, 9.49; 95% CI, 1.05–85.92), respectively. The findings of this study indicate that the rate of DR is high among pediatric TB patients in Chongqing and suggest an urgent need for studies to identify MDR transmission hotspots in Chongqing, thereby contributing to the control DR- and MDR-TB epidemics in China. The study also generates new insight into the pathogenesis of DR and MDR M. tuberculosis strains and highlights the importance of studying childhood TB to the goal of global TB control.

Although anti-TNF agents are expected to impede autoimmune-related processes such as alopecia areata, these drugs have been found to be causally related to the development of alopecia areata. Ophthalmologists who are increasing involved in using these biologic agents should be aware of possible side effects.