[This corrects the article DOI: 10.1371/journal.pone.0266608.].

Asthma currently affects more than 339 million people worldwide. In the present preliminary study, we examined the efficacy of a new, inhalable soluble epoxide hydrolase inhibitor (sEHI), 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), to attenuate airway inflammation, mucin secretion, and hyper-responsiveness (AHR) in an ovalbumin (OVA)-sensitized murine model. Male BALB/c mice were divided into phosphate-buffered saline (PBS), OVA, and OVA+TPPU (2- or 6-h) exposure groups. On days 0 and 14, the mice were administered PBS or sensitized to OVA in PBS. From days 26–38, seven challenge exposures were performed with 30 min inhalation of filtered air or OVA alone. In the OVA+TPPU groups, a 2- or 6-h TPPU inhalation preceded each 30-min OVA exposure. On day 39, pulmonary function tests (PFTs) were performed, and biological samples were collected. Lung tissues were used to semi-quantitatively evaluate the severity of inflammation and airway constriction and the volume of stored intracellular mucosubstances. Bronchoalveolar lavage (BAL) and blood samples were used to analyze regulatory lipid mediator profiles. Significantly ( p < 0.05) attenuated alveolar, bronchiolar, and pleural inflammation; airway resistance and constriction; mucosubstance volume; and inflammatory lipid mediator levels were observed with OVA+TPPU relative to OVA alone. Cumulative findings indicated TPPU inhalation effectively inhibited inflammation, suppressed AHR, and prevented mucosubstance accumulation in the murine asthmatic model. Future studies should determine the pharmacokinetics (i.e., absorption, distribution, metabolism, and excretion) and pharmacodynamics (i.e., concentration/dose responses) of inhaled TPPU to explore its potential as an asthma-preventative or -rescue treatment.

Background Among the different types of cancer, pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), is the most lethal malignancy, with poor early detection rates and prognosis. The aim of the present study was to investigate the potential genetic effects of the single-nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs3789243, rs4148737), APOB (rs693, rs1042031), CAV1 (rs12672038, rs1997623, rs3807987, rs7804372), and NAMPT (rs9034, rs2505568, rs61330082) on PDAC. Methods A total of 273 patients with PDAC and 263 healthy controls were genotyped using PCR and direct Sanger sequencing. Unconditional logistic regression models were used to evaluate the potential effects of the genotypes, alleles, and haplotypes on the risk of developing PDAC. Results Patients with PDAC possessed a considerably lower frequency of genotypes AG, GG, and allele G at ABCB1 rs4148737 compared with controls. Based on age, sex, smoking status, drinking status, diabetes, and family history of cancer, stratified analyses showed a significant correlation between SNPs at rs4148737 and PDAC. According to specific SNPs, eight haplotypes were constructed along with ABCB1 rs4148737, rs1045642, and rs3789243. Carriers with haplotypes ACC and ATC were more susceptible to developing PDAC, whereas haplotypes GCC and GTC were associated with a reduced likelihood of developing PDAC. The distributions of the other SNPs in each group were not significantly associated with PDAC risk. Conclusions These results suggested that genetic polymorphisms of ABCB1 rs4148737 may influence an individual's risk of developing PDAC.

Gastric cancer is an intractable disease with a poor prognosis and limited treatment options. Its treatment remains a major clinical challenge worldwide. Ephrin-B2 is upregulated and involved in tumor growth in various types of cancer. However, the association between ephrin-B2 and prognosis of gastric cancer, and the potential of ephrin-B2 as a therapeutic target remains unknown. The present study investigated ephrin-B2 as a prognostic factor and a therapeutic target for gastric cancer. Reverse transcription-quantitative polymerase chain reaction was performed to detect the protein expression level of ephrin-B2 in gastric cancer serum samples (n=162) and healthy serum samples (n=165). It was revealed that the protein expression level of ephrin-B2 was significantly upregulated in gastric cancer serum samples compared with the healthy samples. Ephrin-B2 protein expression was associated with tumor size (P<0.001), metastasis (P=0.02) and TNM stage (P=0.03), and was indicated to be an independent prognostic factor for gastric cancer. Furthermore, the Kaplan-Meier survival curve demonstrated that patients with high ephrin-B2 protein expression had shorter overall and progression-free survival rates than those with low ephrin-B2 protein expression. Ephrin-B2 protein expression was induced by small interfering RNA (siRNA) transfection of HGC27 and MKN-45 cells, significantly impeding cell viability and inducing apoptosis of HGC27 and MKN-45 cells compared with the respective negative control (NC) group. Thus, to the best of our knowledge, the present study indicates that ephrin-B2 functions as an oncogene in gastric cancer, and that serum ephrin-B2 level may be a promising non-invasive prognostic indicator, as well as a therapeutic target for gastric cancer.

Objective:To investigate the association of XPD rs13181 (codon751A/C, Lys751Gln), rs238406 (codon156C/A, Arg156Arg), XPC rs2279017 (i11C/A), and XRCC4 rs3734091 (codon247T/C, Ala247Ser) polymorphisms with colorectal cancer (CRC) susceptibility. Methods:A total of 338 patients with CRC who were treated at the Beijing Cancer Hospital from April 2013 to January 2016 (case group) and 315 healthy controls (control group) were genotyped using TaqMan technology. Results:The genotype GT and G alleles of XPD rs13181 increased the risk of CRC (GT>TT, adjusted OR=1.69, 95%CI=1.15-2.47, P=0.007;G>T, adjusted OR=1.77, 95%CI=1.19-2.64, P=0.005). The genotype GT and T alleles of XRCC4 rs3734091 increased the susceptibility of CRC (GT>GG, adjusted OR=9.02, 95%CI=5.61-14.50, P<0.001;T>G, adjusted OR=4.06, 95%CI=2.49-6.61, P<0.001). Analyses of XPD rs13181 and rs238406 indicated that the haplotype GT significantly decreased the risk of CRC (adjusted OR=0.39, 95%CI=0.18-0.85, P=0.018). Moreover, the combinations of the XPC rs2279017 G allele and the XRCC4 rs3734091 T allele (adjusted OR=28.43, 95%CI=6.85-117.95, P<0.001) and the XPD rs13181 G allele and the XRCC4 rs3734091 T allele (adjusted OR=10.24, 95%CI=4.69-22.35, P<0.001) exhibited significantly increased CRC risk. Conclusion:The polymorphisms of XPD rs13181 and XRCC4 rs3734091 increased the risk of CRC.

Oesophageal squamous cell carcinoma (ESCC) has a generally poor prognosis, due to the lack of effective treatment methods. Immunotherapeutic approaches based on tumour-infiltrating lymphocytes (TILs) have demonstrated that durable responses are produced in some patients with solid tumours, which suggests the potential feasibility of clinical application of immunotherapy for ESCC. However, many of the basic characteristics of TILs in ESCC are poorly understood, including clonality, specificity and spatial heterogeneity of the response of TILs, which depends on the interaction between antigens and T cell receptors (TCRs). We used ultra-deep sequencing of rearranged genes in TCR β-chain (TCRβ) to profile the basic characteristics of T cells in tumour tissues (four to six regions from each tumour) as well as matched adjacent normal tissue and peripheral blood from seven patients diagnosed with primary ESCC. We found that T cell clones within ESCCs were quite different from those of the peripheral blood and even the adjacent normal tissues in general. Although there was a relatively higher degree of overlap of intratumoural TCRβ repertoires than those between the tumour and other tissues, intratumoural TCRβ repertoires were spatially heterogeneous. Due to the restricted sampling, high-throughput TCRβ sequencing could characterize the diversity and composition of a limited (compartment-dependent) fraction of the respective T cell clones in any individual ESCC, expanding our understanding of immune behaviour and immune response and shedding more light on ESCC immunotherapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The case-control study aims to investigate the association of Fas and FasL genetic polymorphisms (Fas-670A/G (rs1800682), Fas-1377G/A (rs2234767) and FasL-844T/C (rs763110)) with esophageal carcinoma susceptibility in a north Chinese population. A total of 204 patients with esophageal carcinoma and 248 healthy controls were enrolled from Henan, China and genotyped by the polymerase chain reaction and restriction fragment length polymorphism method. There were no significant differences in distributions of their genotypes frequencies between patients and controls in Fas-670A/G, Fas-1377G/A and FasL-844T/C polymorphisms (P>0.05). Stratified analysis showed that no significant association was found between esophageal carcinoma and gene polymorphisms of Fas-670 A/G, Fas-1377G/A, and FasL-844T/C (P>0.05). Genetic polymorphisms in the death pathway genes Fas and FasL were not associated with risk of developing esophageal carcinoma in a north Chinese population.

The absent in melanoma 2 (AIM2), a cytosolic dsDNA inflammasome, can be activated by viral DNA to trigger caspase-1. Its role in immunopathology of chronic hepatitis B and C virus (HBV, HCV) infection is still largely unclear. In this study, the expression AIM2, and its downstream cytokines, caspase-1, IL-18 and IL-1β, in liver tissue of patients with chronic hepatitis B and C (CHB, CHC) were investigated.

BACKGROUND:Nicotinamide phosphoribosyl transferase (Nampt) plays a crucial role in tumorigenesis. The present study examines whether genetic polymorphisms of NAMPT are related to the risk of developing esophageal squamous cell carcinoma (ESCC).METHODS:A total of 810 subjects were enrolled in this study, including 405 ESCC patients and 405 healthy controls. Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), genotypes at rs61330082, rs2505568 and rs9034 of NAMPT were identified. Haplotypes were constructed using PHASE software. Multivariate logistic regression models were used to evaluate the potentiating effects of the genotypes, alleles and haplotypes on the development of ESCC.RESULTS:The presence of genotypes CT and TT and allele T at rs61330082 was less frequent in ESCC cases than in controls (48.89% vs. 53.33%, P < 0.01, 95% CI: 0.33-0.68; 18.52% vs. 30.37%, P < 0.01, 95% CI: 0.22-0.50; 42.96% vs. 57.04%, P < 0.01, 95% CI: 0.38-0.61; respectively). No statistically significant differences existed in the distributions of genotypes or alleles at rs2505568 or rs9034 between ESCC cases and controls. Of five haplotypes constructed, haplotypes CTC, CTT and CAC were higher in ESCC cases (P < 0.01, OR = 1.57, 95% CI: 1.16-2.12; P = 0.04, OR = 1.72, 95% CI: 1.03-2.85; P < 0.01, OR = 3.39, 95% CI: 1.99-5.75; respectively) than in controls.CONCLUSION:Genetic polymorphisms of NAMPT, specifically genotype CC and allele C at rs61330082 as well as haplotypes CTC, CTT and CAC, were significantly correlated with ESCC susceptibility.

Objective: To investigate the association of caveolin-1 (CAV1) genetic variants (C239A (rs1997623), G14713A (rs3807987), G21985A (rs12672038), T29107A (rs7804372)) with esophageal squamous cell carcinoma (ESCC) susceptibility.Methods: A total of 427 patients with ESCC and 427 healthy controls were genotyped using the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method.Results: There were significant differences between patients and controls in distributions of their genotypes and allelic frequencies in G14713A and T29107A polymorphisms. Furthermore, haplotype analysis revealed that haplotypes CAAT and CAGT were associated with high risk for ESCC, while haplotype CGGA was protective against ESCC. Stratified analysis showed the associations between the SNPs (G14713A and T29107A) and ESCC risk were noteworthy among female patients and patients who never smoke or drank alcohol.Conclusions: Genetic polymorphisms of CAV1 G14713A and T29107A might affect an individual's susceptibility in developing ESCC, making them efficient potential genetic biomarkers for early detection of ESCC.

Genetic variations in MDM2, PTEN and P53 might be involved in cancer susceptibility. To assess the contribution of polymorphisms in these three genes to the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population, we genotyped MDM2 T309G, Del1518, PTEN rs701848, rs2735343 and P53 Arg72Pro polymorphisms using PCR-restriction fragment length polymorphism analysis in 226 ESCC cases and 226 cancer-free controls. Here we showed that the risk of ESCC was elevated in subjects with any of the variant genotypes of PTEN rs2735343 and P53 Arg72Pro polymorphisms, but not any genotype of MDM2 or PTEN rs701848. Moreover, multiplicative interactions were observed between PTEN rs2735343 and P53 Arg72Pro or smoking status on risk of ESCC. Our study firstly indicated that PTEN rs2735343 might be a susceptibility factor for ESCC and reaffirmed the role of P53 Arg72Pro in ESCC in this Chinese population, but did not replicate the positive association between MDM2 T309G and ESCC found previously.

<正>病历摘要患者女,46岁,因"反复肝功异常2年,乏力、皮肤瘙痒7个月余"于2010年8月9日入院。患者于2年前查体发现肝功异常,谷丙转氨酶(ALT)92 U/L,谷草转氨酶(AST)60U/L,谷氨酰转肽酶(GGT)112 U/L。

Background/Aims: To study the effect of cytotoxic T-lymphocyte antigen 4 gene haplotypes to susceptibility of esophageal squamous cell carcinoma.Methodology: A gender- and age-matched case-control design was used in this study. PCR-RFLP method was used to detect the genotype of CTLA4 in 205 patients and 205 control individuals in the Anyang area. Furthermore, haplotypes were calculated by PHASE2.1 software. Finally, the conditional logistic regression analysis was carried out to analyze the relevance between the risk of ESCC and the genotypes or haplotypes of CTLA4 gene.Results: The CTLA4 rs231775 and rs4553808 genotypes in patients with ESCC were significantly different from controls (p=0.004, p=0.023, respectively). The AG and AA genotypes of rs231775 were highly correlated with the risk of ESCC (Adjusted OR=2.280, 95%CI=1.433-3.629, p=0.001; Adjusted OR=2.192, 95%CI=1.229-3.911, p=0.008, respectively), and AG genotype of rs4553808 also increased the susceptibility of ESCC (Adjusted OR=1.848, 95%CI=1.220-2.800, p=0.004). Further study suggested that AAG haplotype may enhance the risk of ESCC (Adjusted OR=5.035, 95%CI=1.599-15.860, p=0.005), but GAA haplotype played a protective role (Adjusted OR=0.413, 95%CI=0.251-0.680, p=0.001).Conclusions: Our research confirmed that CTLA4 genetic variation was related to ESCC in the Anyang area and GAA haplotype was the protective factor of ESCC.

BACKGROUND AND AIMS:Low molecular mass protein-2 (LMP2) and low molecular mass protein-7 (LMP7) genes play a critical role in foreign antigen processing on the major histocompatibility complex-I CD8(+) cytotoxic T-lymphocyte pathway. This study was designed to investigate whether the sequence variants in the LMP2/LMP7 coding region were associated with intestinal Mycobacterium tuberculosis (M. tuberculosis) infection or with the co-infection of pulmonary tuberculosis. METHODS:A total of 168 patients with intestinal tuberculosis and 235 normal controls were recruited for this study. Two polymorphisms of LMP2 (Arg60-His) and LMP7 (Gln145-Lys) were identified by polymerase chain reaction-restriction fragment length polymorphism method. The associations of the LMP2/LMP7 genotype and haplotype with intestinal M. tuberculosis infection were assessed by using logistic regression analysis. RESULTS:The results revealed that LMP7 position codon 145 Lys/Lys and Gln/Lys alleles in the coding region were associated with the infection of intestinal M. tuberculosis (P=0.003, odds ratio [OR]= 3.86 and P < 0.001, OR = 2.28, respectively). Meanwhile, the Arg-Lys and Cys-Lys haplotypes exhibited significant relation to the intestinal M. tuberculosis infection (P= 0.006, OR=1.87; P=0.021, OR=1.83, respectively). No significant associations were observed for any of the single-nucleotide polymorphism genotypes or haplotypes with the co-infection of pulmonary tuberculosis (P > 0.05). CONCLUSIONS:The results indicated that the genetic variant within the LMP2/LMP7 gene would increase the risk of intestinal M. tuberculosis infection.

Objective An HPV 16 E7 monoclonal antibody was prepared.This antibody will be useful for diagnosing early cancers and developing therapeutic vaccines.Method A plasmid constructed with PGEX4T-1-HPV16 E7 was transformed into E.coli BL21,and expression of the fusion protein was induced by IPTG.Spleen cells from immunized Balb/c mice were fused with SP2/0 cells by a routine method,and the valence of the antibody was evaluated using ELISA.Expansion,isolation and freezing of clones were carried out,and finally an ascitic fluid which contained monoclonal antibodies was produced.Result The HPV16 E7 monoclonal antibody was found specifically in the nuclei of a variety of cancers tissues.Conclusion The HPV16 E7 protein antibody is a specific McAb.

Objective To investigate the distribution of the three polymorphisms of cytotoxic T lymphocyte-associated antigen 4 (CTLA4) gene and their association with susceptibility of esophageal cancer (EC). Methods Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP)method was used to detect the genotype of CTLA4 three polymorphism sites in 205 patients ( 113 males and 92 females) and 205 gender-age-matched control individuals. The associations of genetic polymorphisms and haplotypes of them with susceptibility of EC were analyzed by conditional logistic regression model. Results The AA and AG genotypes of + 49A/G increased the risk of EC ( P ＜ 0. 01, OR = 2. 192; P ＜0. 01, OR =2. 280, respectively). The AG genotype of -1661A/G was also more in EC group than in control group (P ＜0. 01, OR = 1. 848). The distribution of GG genotype had no difference between the two groups ( P ＞ 0. 05). - 1772 site was also not associated with ESCC susceptibility (P ＞ 0. 05). Haplotype AAG increased the risk of EC ( P ＜ 0. 01, OR = 5. 035 ), but haplotype GAA played a protective role ( P ＜0. 01, OR = 0. 413 ). Conclusion The polymorphisms of CTLA4 exon 1 + 49A/G and promoter -1661A/G are associated with susceptibility of EC. Further association study confirmed that haplotype AAG is the risk factor of EC, but GAA played a protective role.

目的 FASL-844基因多态性与多种肿瘤易感性相关.本研究旨在探讨FASL-844基因多态性与食管癌易感性的关联.方法 提取204例食管癌患者及248例健康查体者外周血基因组DNA,用聚合酶链反应-限制性片段长度多态性法(PCR-RFLP)确定FASL-844基因型.结果 FASL-844 TT、TC、CC基因型在病例组和对照组中的分布频率分别为3.9%、45.6%、50.5%和4.4%、39.1%、56.5%,差异无统计学意义(P>0.05).Logistic回归分析表明,FASL-844基因多态性与食管癌发生风险无关.进一步分层分析显示,FASL-844基因多态性与食管癌发生风险仍无关联.结论 FASL-844基因多态性与河南安阳地区食管癌发生风险无相关性.

Objective To investigate the relationship of the expression of insulin growth factor-Ⅰreceptor(IGF-ⅠR),Insulin-like growth factor-Ⅱ receptor(IGF-ⅡR) and the histological type,stage,infiltration and metastasis of gastric carcinoma(GC).Methods The expressions of IGF-ⅠR and IGF-ⅡR were tested by S-P immunohistochemistry in 67 cases of GC,16 cases of chronic atrophic gastritis(CAG) and 13 cases of chronic atrophic gastritis dysplasia(CAGD),and with the biological behaviour of GC correlation analysis.Results The positive expression rate of IGF-ⅠR in GC group was 64.2%.The positive expression rates of IGF-ⅠR in GC groups and in CAGD groups were much higher than that in CAG groups(P0.01 or 0.05).The positive expression rate of IGF-ⅡR in GC group was 59.7%,which expressed more than that in CAG group(P0.01).The expression of IGF-ⅠR closely correlated with the tumor differentiation,depth of infiltration,tumor size,lymph node metastasis and TNM stage(P0.05)respectively.The expression of IGF-ⅡR also correlated with the tumor differentiation(P0.05),but no correlation with depth of infiltration,tumor size,lymph node metastasis and TNM stage.Conclusions The excessive expression of IGF-ⅠR and IGF-ⅡR may be synergist in the carcinogenesis and development of GC,but IGF-ⅡR may have more influence on its biological behavior.The combination of IGF-ⅠR and IGF-ⅡR may be a reference marker in the surgical treatment and the prognosis of GC.

目的探讨Fas-1377基因多态性与胃癌易感性的关系。方法提取234例胃癌患者(观察组)及321例健康献血者(对照组)的外周血基因组DNA,用聚合酶链反应—限制性片段长度多态性法确定Fas-1377基因型。结果 Fas-1377AA、GA、GG基因型在观察组和对照组中的分布频率分别为13.25%、44.44%、42.31%和12.15%、47.04%、40.81%,组间比较无统计学差异(P>0.05)。Logistic回归分析表明,Fas-1377基因多态性与胃癌发生风险无关。结论 Fas-1377基因多态性与华北地区胃癌发生风险无明显相关性。