Background:  Several studies have reported HLA-DRB1 may be correlated with PV, but the majority have been based on small sample sizes and the results remain inconsistent and obscure. Objectives:  To investigate the correlation between DRB1 and PV by a meta-analysis of case-control/non-family studies. Methods:  The PubMed, Wiley Online Library, ScienceDirect, Google Scholar, Cochrane Library, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for studies involving:(1) pemphigus; and (2)"human leukocyte antigen","HLA","major histocompatibility complex","MHC", or "DRB1". Eighteen selected studies were used in meta-analyses to evaluate DRB1 alleles and phenotypes by calculating the respective odds ratios (ORs) and 95% confidence intervals (CIs). Stratified meta-analyses and meta-regression analysis were also conducted. Results:  The frequencies of three genotypes (allele and phenotype, respectively) were significantly increased in PV: DRB1*04 (Pc<0.00001, OR=3.61, 95% CI: 2.28-5.71; Pc=0.0002, OR=4.14, 95% CI: 1.98-8.65), DRB1*08 (Pc=0.03, OR=2.25, 95% CI: 1.07-4.70; Pc=0.0003, OR=2.46, 95% CI: 1.51-4.01), and DRB1*14 (Pc<0.00001, OR=6.47, 95% CI: 4.52-9.26; Pc<0.00001, OR=9.68, 95% CI: 4.47-20.98). Three others (allele and phenotype, respectively) were significantly decreased in PV: DRB1*03 (Pc<0.00001, OR=0.28, 95% CI: 0.19-0.41; Pc=0.0001, OR=0.25, 95% CI: 0.12-0.51), DRB1*07 (Pc=0.004, OR=0.45, 95% CI: 0.26-0.78; Pc=0.0002, OR=0.27, 95% CI: 0.14-0.54), and DRB1*15 (Pc=0.001, OR=0.35, 95% CI: 0.18-0.66; Pc=0.002, OR=0.32, 95% CI: 0.16-0.65). Ethnicity partially explained the heterogeneity of DRB1*07, DRB1*08, and DRB1*14 phenotypes. Conclusions:  Our findings suggest that DRB1*04, DRB1*08, and DRB1*14 are statistically significant susceptibility factors for PV. Conversely, DRB1*03, DRB1*07, and DRB1*15 may be negatively associated with PV. Specific HLA-DRB1 may influence the susceptibility or resistance to PV, which needs further investigations.

ABSTRACT: BACKGROUND: Developmental dysplasia of the hip (DDH) is a congenital or acquired deformation or misalignment of the hip joint which affects mainly females. We hypothesized that HOXD9 gene could be regulated in acetabular size or shape and related in DDH developing. METHODS: Two hundred and nine Chinese Han female DDH patients and 173 ethnic, age matched healthy female controls were genotyped for HOXD9 two tag SNPs using sequenom method. RESULTS: One of the two tag SNPs, rs711822, was not shown significantly differences in genotypic or allelic distribution between case and control group. Comparing the genotypic distribution of rs711819, there was significant differences between DDH patients group and control group (chi2 = 7.54, df =2, P =0.023), and the association to DDH developing reached significance (P =0.045, OR =1.79, 95 % CI: 1.01-3.17 by dominant mode). CONCLUSION: In conclusion, the association between one tag SNP of HOXD9 gene and the development of DDH reach significant in our study population, this result indicate the positive correlation between HOXD9 gene and DDH developing. Further study in larger sample size and different population as well as functional studies will help to understand the pathogenesis of DDH.

In this study, a cascade of anoxic and oxic fluidized bed biofilm reactors system was carried out to treat synthetic municipal wastewater. The parameters of the influent flow rates and C/N ratios were discussed. System performance was acceptable for chemical oxygen demand (COD), ammonia, and total nitrogen removal. A decrease of ammonia and total nitrogen removal efficiencies, however, was observed when the influent flow rates increased to 5.04 and 6.12 1 h(-1). Total nitrogen removal decreased at the influent C/N ratio of 3:1. The measured ratios of COD reduction in the anoxic column to nitrogen removal through nitrification-denitrification were 3.7, 3.5, 3.3, and 3.1 g COD/g(-1) N on average when the influent C/N ratios changed from 6:1 to 3:1. The observed sludge yield (Yobs) was 0.169 g VSS g COD(-1) because of perfect denitrification in the anoxic column and the relatively long solids retention time.

The involvement of microglial activation in metal neurotoxicity is becoming increasingly recognized. Some metal ions, such as zinc (II) and manganese (II), have been recently reported as microglial activators to induce the release of inflammatory mediators including cytokines, chemokines and nitric oxide (NO) which are involved in the pathogenesis of neurological diseases. Cobalt is essential for human life. However, excessive cobalt is cytotoxic and neurotoxic. In the present study, we determined cobalt-induced production of NO and cytokines/chemokines in N9 cells, a murine microglial cell line. High levels of cobalt significantly up-regulated iNOS mRNA and protein expression, which resulted in the release of NO. Cobalt induced the production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in a concentration- and time-dependent manner in both N9 cells and primary mouse microglia and increased lipopolysaccharides (LPS)-induced cytokine production. Further study showed that cobalt induced cytokine production by a mechanism involving both nuclear factor kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. The involvement of reactive oxygen species (ROS) in microglial activation was also confirmed. These findings suggested that cobalt neurotoxicity should be attributed not only directly to neuronal damage but also indirectly to microglial activation which might potentiate neuronal injury via elevation of proinflammatory mediator levels.

More than one-third of Alzheimer's disease (AD) patients show nigrostriatal pathway disturbances, resulting in akinesia (inability to initiate movement) and akathisia (inability to remain motionless). The high prevalence of this dysfunction of dopaminergic neuron in the nigrostriatal pathway in AD suggests that AD is a significant risk factor for substantia nigra pars compacta (SNpc) lesions. Previously, we have demonstrated that allopregnanolone (APα) promotes neurogenesis and improves the cognitive function in a triple transgenic mouse model of AD (3xTgAD). In this study, we sought to exam 1) the SNpc lesions in 3xTgAD mice and 2) the impact of APα on promoting the regeneration of new dopaminergic neurons in SNpc of 3xTgAD mice. The number of Nissl-stained total neurons, tyrosine hydroxylase (TH) positive neurons, and BrdU/TH double positive newly formed neurons were analyzed with unbiased stereology. In the SNpc of 3xTgAD mice, TH positive neurons was 47 ± 18 %(p = 0.007), total neurons was 62 ± 11.6 %(p = 0.016), of those in the SNpc of non-Tg mice, respectively. APα treatment increased the TH positive neurons in the SNpc of 3xtgAD mice to 93.2 ± 18.5 %(p = 0.021 vs. 3xTgAD vehicle) and the total neurons to 84.9 ± 6.6 (p = 0.046 vs. 3xTgAD vehicle) of non-Tg mice. These findings indicate that there is a loss of neurons, specifically the TH positive neurons in SNpc of 3xTgAD mice, and that APα reverses the lesion in SNpc of 3xTgAD by increasing the formation of new TH neurons.

SUMMARY:Intracranial meningeal hemangiopericytomas in children and adolescents are prone to bleeding during surgery. CT and MR imaging may serve a role in preoperative diagnosis. The purpose of this report was to describe the radiologic findings in 9 pathologically proved cases of intracranial meningeal hemangiopericytomas in children and adolescents. The average duration of symptoms was short (mean, 4.0 months; median, 1.5 months). The intraoperative blood loss was large (mean, 3561 mL; median, 1000 mL). Tumors were extra-axial, irregularly multilobular, and hypervascular. Radiologically, they showed mixed attenuation on precontrast CT images, heterogeneous signal intensity on precontrast MR imaging, and marked and heterogeneous enhancement on postcontrast MR imaging. Bone erosion was sometimes present, but hyperostosis was not present. On MR imaging, multiple signal intensity voids of vessels were observed in 100%(8/8) of tumors with AVM-like signal intensity flow voids in 25%(2/8) of tumors. These results suggest that CT and MR imaging findings may be helpful for preoperative diagnosis.

Malfunctioned gap junctional intercellular communication (GJIC) has been thought associated with malignant transformation of normal cells. However, the role of GJIC related proteins such as connexins for sustaining the malignant behavior of cancer stem cells (CSCs) remains unclear. In this study, we obtained tumorspheres formed by glioma stem cells (GSCs) and adherent GSCs, and then examined their GJIC. All GSCs showed reduced GJIC, and differentiated glioma cells had more gap junction-like structures than GSCs. GSCs expressed very low level of connexins, Cx43 in particular, which are key components of gap junction. We observed hypermethylation in the promoter of gap junction protein α1 (GJA1), which encodes Cx43 in GSCs. Reconstitution of Cx43 in GSCs inhibited their capacity of self-renewal, invasiveness and tumorigenicity via influencing E-cadherin and its coding protein, which leads to changes of the expression of Wnt/β-catenin targeting genes. Our results suggest that GSCs require the low expression of Cx43 for maintaining their malignant phenotype, and up-regulation of Cx43 might be a potential strategy for treatment of malignant glioma.

Chromosome 3p21-22 harbors two clusters of chemokine receptor genes, several of which serve as major or minor coreceptors of HIV-1. Although the genetic association of CCR5 and CCR2 variants with HIV-1 pathogenesis is well known, the role of variation in other nearby chemokine receptor genes remain unresolved. We genotyped exonic single nucleotide polymorphisms (SNPs) in chemokine receptor genes: CCR3, CCRL2, and CXCR6 (at 3p21) and CCR8 and CX3CR1 (at 3p22), the majority of which were non-synonymous. The individual SNPs were tested for their effects on disease progression and outcomes in five treatment-naïve HIV-1/AIDS natural history cohorts. In addition to the known CCR5 and CCR2 associations, significant associations were identified for CCR3, CCR8, and CCRL2 on progression to AIDS. A multivariate survival analysis pointed to a previously undetected association of a non-conservative amino acid change F167Y in CCRL2 with AIDS progression: 167F is associated with accelerated progression to AIDS (RH = 1.90, P = 0.002, corrected). Further analysis indicated that CCRL2-167F was specifically associated with more rapid development of pneumocystis pneumonia (PCP)(RH = 2.84, 95% CI 1.28-6.31) among four major AIDS-defining conditions. Considering the newly defined role of CCRL2 in lung dendritic cell trafficking, this atypical chemokine receptor may affect PCP through immune regulation and inducing inflammation.

Malignant tumors are thought to be initiated by a small population of cells that display stem cell properties, including the capacity of self-renewal, multipotent differentiation, initiation of tumor tissues and resistance to therapy. Cancer stem cells (CSCs) have also been identified in gliomas in which they are named as glioma stem-like cells (GSLCs), or glioma stem cells. In xenograft transplantation models, GSLCs propagate tumor and promote tumor progression. The tumorigenesis of GSLCs depends not only on their autonomous proliferation but also on interaction with microenvironment components. Among these components, G protein coupled chemoattractant receptors (GPCRs) and their agonists have attracted much attention for their capacity to mediate leukocyte infiltration, angiogenesis, tumor invasion and metastasis. Chemoattractant GPCRs are widely expressed by tumor cells and stromal cells and recognize agonists present in the tumor microenvironment. Such GPCRs have been found to be expressed also by CSCs including GSLCs. In this brief review, we will summarize the recent development in the studies of the function, regulation and signal transduction of chemoattractant GPCRs in GSLCs in hope to promote a better understanding of the mechanistic basis of the progression of gliomas and the identification of molecular targets for the novel anti-glioma therapy.