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Human leukocyte antigen (HLA)-B27 confers a key role in ankylosing spondylitis (AS) susceptibility. Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms are associated with AS susceptibility in common population. In this study we intended to evaluate the possible association between ERAP1 polymorphisms and AS susceptibility in HLA-27 positive population. Data were collected from Pubmed, Embase, and Cochrane databases. The pooled odds ratios and 95% confidence intervals of the minor allele of each locus were calculated to appraise the associations under ERAP1 polymorphisms and AS in HLA-B27 positive population. Bioinformatics analysis was performed to explore the underlying mechanism. Four studies were included in this meta-analysis. There was a significant association between the minor allele of rs2287987 and reducing the risk of developing AS in HLA-B27 positive population. But there was no significant association between the minor allele of rs30187, rs27044, rs10050860 and rs17482078 and AS susceptibility. According to HaploReg, 5 motifs changed for rs2287987 were found. The eQTL analysis demonstrated that rs2287987 may influence ERAP1 expression. Rs2287987 in ERAP1 may have small influence on AS susceptibility in HLA-B27 positive population. Bioinformatics analysis indicated that the altered motifs and the change of EARP1 expression may influence the AS susceptibility.

BACKGROUND Previous publications indicated that genetic predisposition might play important roles in the onset of osteonecrosis of the femoral head (ONFH) in systemic lupus erythematosus (SLE). Some gene loci such as complement C3d receptor 2 (CR2), nitric oxide synthase 3 (NOS3), collagen type II alpha 1 chain (COL2A1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), and transient receptor potential cation channel subfamily V member 4 (TRPV4) were reported to be involved in this process. AIM To investigate whether the risk of ONFH in SLE is associated with single nucleotide variations (SNVs) in these five genes. METHODS SNVs in the CR2, NOS3, COL2A1, PTPN22, and TRPV4 genes were examined by using FastTarget and Illumina Miseq sequencing technologies in 49 cases of SLE with ONFH. Burrows–wheeler aligner was used to align the sequencing reads to hg19, and GATK and Varscan programs were used to perform SNV calling. PolyPhen-2, SIFT, and MutationTaster were used to assess the functional effects of non-synonymous SNVs. RESULTS Six of the 49 patients were confirmed to have low frequency SNVs, including one patient with SNVs in NOS3 (exon 6: c.814G>A: p.E272K and exon 7: c.814G>A: p.E272K.), four in COL2A1 (rs41263847: exon 29: c.1913C>T: p.T638I, exon 28: c.1706C>T: p.T569I, and rs371445823: exon 8: c.580G>A: p.A194T, exon 7: c.373G>A: p.A125T), and one in CR2 (rs45573035: exon 2: c.200C>G: p.T67S). CONCLUSION The onset of ONFH in SLE might be associated with the identified SNVs in NOS3, COL2A1, and CR2.

Background We report a rare case of secondary acute angle closure attack because of lupus choroidopathy and accompanying polyserositis, as an initial presentation of a novel type of systemic lupus erythematosus in a 44-year-old woman. Case presentation The patient complained of eyelid oedema and chemosis with bilateral severe loss of visual acuity. Systemic lupus erythematosus was diagnosed based on malar rash, polyserositis, proteinuria and positive antibody titers for antinuclear antibodies, anti-DNA, antinucleosome antibodies and ribosomal RNP. Subsequently, secondary bilateral acute angle closure caused by choroidal effusions with lupus choroidopathy was diagnosed. A month after steroid and immunosuppressive drug therapy, the patient’s intraocular pressure and visual acuity returned to normal. During the subsequent year, the secondary acute angle closure did not recur and polyserositis remained under control. Conclusions Bilateral, secondary acute angle closure attack due to SLE choroidopathy can be an initial presentation of SLE, which is often accompanied by polyserositis. Prompt and aggressive high doses of steroids and immunosuppressive therapy are strongly recommended.

Human leukocyte antigen (HLA)-B27 plays a crucial role in the pathogenesis of AS. TNF polymorphisms have been reported to be associated with AS susceptibility, but the results of these previous studies have been inconsistent. The aim of this study was to explore whether TNF polymorphism is associated with AS susceptibility in HLA-27-positive population. Our search was done in the Pubmed, Embase, and Cochrane databases (up to March 2020). The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) of the minor allele of each locus were presented to assess the associations between TNF polymorphisms and AS in HLA-B27-positive population. Ten studies from 8 articles were included in this meta-analysis. In the population of HLA-B27-positive patients and random healthy controls, there were statistical significance in the evaluation of association between the minor allele of TNF-238, -308, -857, -1031 and -863 and AS susceptibility, respectively. In the population of HLA-B27-positive patients and HLA-B27-positive healthy controls, there were no statistical differences in the comparison of minor allele of with their respective major allele in the fixed model. There was no association of the TNF polymorphisms with AS in the HLA-B27-positive AS group and HLA-B27-positive control group. Polymorphisms of TNF-238, -308, -857, -1031, -863 were associated with AS susceptibility in the HLA-B27-positive AS patients and random control population. Other gene SNPs except TNF may play an important role in AS susceptibility in HLA-B27-positive population.

Studies investigating the association between the polymorphisms in TNF and ankylosing spondylitis have been reported the conflicting results. Here we performed a meta-analysis based on the evidence available from the literature up-to-date to further clarify this relationship. Our systematic search was done in the PubMed, Embase and Cochrane databases (up to March 2020). The pooled and individual odds ratios (ORs) with 95% confidence intervals (CIs) of the minor allele of each locus were presented to assess the associations between TNF polymorphisms and AS in different ethnicities in common population. Seventeen studies, consisting of seven European studies, eight East Asian studies and two Latin-American studies, were included in this meta-analysis. In the total population, the A allele in TNF-238 (OR = 0.702, 95%CI = 0.506–0.973, p = 0.034) and TNF-308 (OR = 0.638, 95%CI = 0.507–0.804, p = 0.000), the C allele in TNF-1031 (OR = 0.594, 95%CI = 0.446–0.791, p = 0.000), the T allele in TNF-850 (OR = 3.462, 95%CI = 1.764–6.798, p = 0.000) and rs769178 (OR = 2.593, 95%CI = 2.175–3.091, p = 0.000) were significantly associated with AS susceptibility. There were no significant association between the minor alleles of TNF-376, TNF-857, TNF-863 and AS susceptibility. There are inconsistent results in the Latin-American population and East Asian population with those in the total population. Our meta-analysis suggests that TNF-α polymorphisms at positions − 238, − 308, − 850, − 1031 and rs769178 could have an influence on ankylosing spondylitis susceptibility in the total population. But there is no association of the TNF-376, TNF-857, TNF-863 polymorphisms with ankylosing spondylitis. Some results in the subgroups are not consistent with those in the total population.

The aim of this study is to investigate the association of the polymorphisms in tumor necrosis factor (TNF) and granulin (GRN) with ankylosing spondylitis (AS) in a Chinese Han population. Five single nucleotide polymorphisms (SNPs) covering TNF and six SNPs covering GRN were investigated in 861 Chinese Han AS patients and 864 healthy controls. For rs1799964, the C allele was linked to reduced risk of AS (p 0.0001, OR = 0.60, 95% CI = 0.50-0.71). The carriers of the C/C homozygote showed a significantly lower risk of AS compared with the TT homozygote and the C/T heterozygote under the recessive model (p 0.0001, OR = 0.23, 95% CI = 0.12-0.45). For rs1800629, the A allele was also linked to reduced risk of AS (p 0.0001, OR = 0.54, 95% CI = 0.39-0.74). For rs1800630, the A allele was also linked to reduced risk of AS (p 0.0001, OR = 0.59, 95% CI = 0.48-0.72). The carriers of the A/A homozygote showed a significantly lower risk of AS compared with the C/C homozygote and the A/C heterozygote under the recessive model (p 0.0001, OR = 0.18, 95% CI = 0.07-0.47). For rs769178, the T allele was linked to increased risk of AS (p 0.0001, OR = 2.59, 95% CI = 2.18-3.09). The carriers of the T/T homozygote showed a significantly higher risk of AS compared with the GG homozygote and the G/T heterozygote under the recessive model (p 0.0001, OR = 3.34, 95 %CI = 1.95-5.72). There was no significant difference between the AS patients and the controls in the genotype or allele frequencies of rs361525. For GRN, there was no significant difference between the AS patients and the controls in the genotype or allele frequencies of rs25646, rs3760365, rs3785817, rs4792939, rs5848, rs850713 (p 0.05). This study indicates that polymorphisms in TNF are related to AS, but polymorphisms in GRN are not related to AS susceptibility in a Chinese Han population.

We investigate a water-filled bottle rolling down an incline and ask the following question: is a rolling bottle better described by a model ignoring all internal motion where the bottle is approximated by a material point sliding down an incline, or is it better described by a rigid solid cylinder rolling down the incline without skidding? The measurements presented here represent a special case of similar experiments described by K.A. Jackson et al. (see Ref. 1 and references within). There exists also a report by Kagan describing the motion of soda cans rolling on an incline. In our case we investigate motion of the fully filled bottle. We demonstrate that within accuracy of our experiment the motion of the bottle can be described by a simple “frictionless water” model. The analysis of the dynamics of the bodies sliding and rolling on a ramp is a standard component of introductory physics classes, and a required component of the Advanced Placement (AP) Physics curriculum.

With the rapid development of China train control system (CTCS-3), stability and safety of the CTCS-3 have become the focus of the train industry. According to the CTCS-3 functional requirement specification issued by the Ministry of Railways, this paper implements the following three aspects: Firstly, some representative functional scenarios of Radio Block Centre (RBC) are selected to build the models by Colored Petri Net (CPN) and to generate the RBC test cases of XML format. Secondly, the sequence sets of test cases may be optimized based on the improved ant colony algorithm and ideological maze. What is the optimization idea is that not only can be the shortest pathes found but also the redundant phenomenon of test sequence generation can be reduced according to the natural law of ants foraging. Finally, the RBC test platform may automatically generate test cases and test sequences for the simulation. The result shows that the proposed method can achieve optimization of test sequences successfully and reduce the test time greatly.

Background Killer cell immunoglobulin-like receptors (KIR) contribute to the pathogenesis of multiple auto-immune diseases via the modulation of NK-, NKT- and T-cells. Thus, we want to know whether the expression pattern of KIR is associated with systemic lupus erythematosus (SLE) susceptibility. Methods Here, real-time quantitative PCR and fluorescence-activated cell sorting (FACS) were used to measure the stimulatory KIR (sKIR) and inhibitory KIR (iKIR) mRAN and protein levels on NK-, NKT- and T-cells in both SLE patients and healthy controls. Results In SLE patients, CD158a/h (KIR2DL1/S1) was highly expressed while CD158b/i/j (KIR2DL2/L3/S2, iKIR/iKIR/sKIR) was lowly expressed in NK- and NKT-cells in patients. The expression levels of KIR2DL1 and KIR2DL2 (iKIRs) were decreased while the expression levels of KIR2DS1 (sKIR) were increased in NK- and NKT-cells in the patients. Conclusions We found that SLE patients represent aberrant expression of stimulatory and inhibitory KIRs in NK- and NKT-cells. Consequently, these different expression levels of KIRs may contribute to the abnormal function of these cells, which lead to the risk of SLE.

With the rapid development of China train operation and control system, validity and safety of behavioral functions of the system have attracted much attention in the railway domain. In this paper, an automated test sequence optimization method was presented from the system functional requirement specification of the high-speed railway. To overcome the local optimum of traditional ant colony algorithm, the maze algorithm is integrated with the ant colony algorithm to achieve the dynamical learning capacity and improve the adaptation capacity to the complex and changeable environment, and therefore, this algorithm can produce the optimal searching results. Several key railway operation scenarios are selected as the representative functional scenarios and Colored Petri Nets (CPN) is used to model the scenarios. After the CPN model is transformed into the extensible markup language (XML) model, the improved ant colony algorithm is employed to generate the optimal sequences. The shortest searching paths are found and the redundant test sequences are reduced based on the natural law of ants foraging. Finally, the Radio Blocking Center (RBC) test platform is designed and used to validate the optimal sequence. Testing results show that the proposed method is able to optimize the test sequences and improve the test efficiency successfully.