Hepatocellular carcinoma (HCC) is the fifth most common malignancy caused by environmental and genetic factors. MicroRNAs (miRNAs) are a class of short non-coding RNAs with posttranscriptional regulatory functions. They participate in diverse biological pathways and function as gene regulators. Genetic polymorphisms in 3' untranslated regions (3' UTRs) targeted by miRNAs alter the strength of miRNA binding, with consequences on regulation of target genes thereby affecting the individual's cancer risk. We have previously predicted polymorphisms falling in miRNA-binding regions of cancer genes. We selected an insertion/deletion (Indel) polymorphism (rs3783553) in the 3' UTR of interleukin (IL)-1alpha (IL1A) for a case-control study in a Chinese population. With samples from 403 HCC patients and 434 healthy control individuals, strong evidence of association was observed for the variant homozygote. This association was validated in a second independent case-control study with 1074 HCC patients and 1239 healthy control individuals (odds ratio = 0.62; 95% confidence interval = 0.49-0.78). We further show that the 'TTCA' insertion allele for rs3783553 disrupts a binding site for miR-122 and miR-378, thereby increasing transcription of IL-1alpha in vitro and in vivo. These findings suggest that functional polymorphism rs3783553 in IL1A could contribute to HCC susceptibility. Considering IL-1alpha affects not only various phases of the malignant process, such as carcinogenesis, tumor growth and invasiveness, but also patterns of interactions between malignant cells and the host's immune system, our results indicated that IL-1alpha may be a promising target for immunotherapy, early diagnosis and intervention of HCC.

To establish the prognostic value of B7-H4 expression by tumor cells in gastric cancer patients, we evaluated the association of B7-H4 expression with clinicopathologic factors and overall survival of gastric cancer patients. A retrospective cohort study including 156 gastric cancer patients was performed in the present report. Immunohistochemical assay was used to evaluate the expression of B7-H4 in the surgical specimens of gastric cancer tissues. Multi-univariate COX model was then used to evaluate the association of B7-H4 expression with the patients' survival and clinicopathological parameters. B7-H4 expression in the gastric cancer cells was observed in about 44.9% gastric cancer specimens. Univariate analysis demonstrated that there was no correlation between B7-H4 expression and sex, age, histological type, pathological grade or tumor size. In contrast, B7-H4 expression correlated positively with cancer invasiveness and lymph node metastasis. In addition, the median overall survival time of patients with lower B7-H4 expression was 13 months longer than that of patients with higher expression (chi(2) = 12.38, P < 0.0001), and the median disease-free survival time of patients with lower B7-H4 expression was significantly longer than that of patients with higher expression (33 vs. 16 months, chi(2) = 14.977, P < 0.0001). After adjustment for other confounding factors, the COX model analysis indicated that the death risk was significantly higher in patients with higher B7-H4 expression than those with lower expression (RR = 1.85, 95% CI = 1.15-2.96). The present study demonstrated that higher B7-H4 expression in cancer cells was associated with poor prognosis of gastric cancer patients. This is consistent with the idea that B7-H4 promotes cancer progression, likely via inhibition of anti-tumor immune responses.

BackgroundThe residents’ knowledge, attitudes and practices related to ambient air pollution and health will help to improve the understanding of environmental protection and make environmental health policies more targeted and effective. This study aimed at knowing the attitudes and behaviors towards ambient air pollution and health.MethodsA cross-sectional survey was conducted in Ningbo, China in January 2015. Personal information and questions pertaining to the knowledge, attitudes and practices towards ambient air pollution and health were collected through questionnaire investigations. Descriptive statistics, chi-square tests and multiple unconditional logistic regression analysis were used.ResultsThe questionnaire was completed by 1604 respondents (59.41 % women). The awareness rate was 64.59 % and varied significantly with age, levels of education, and occupation (all p < 0.05). Only 5.80 % of the total participants were satisfied with the air quality in Ningbo in 2014. Most respondents (78.80 %) expressed concern about the possible aggravation of the haze. More than 80 % of participants believed that it will take at least 3-5 years or longer before the air quality is improved. Television and internet resources have replaced books and newspapers as the primary sources for obtaining knowledge about haze and related protective measures. 85.22 % of respondents were concerned about air quality index (AQI). Most of the residents have taken protective measures indoors during haze weather. 48.50 % have worn face masks when going outside, the most frequently type of face masks selected were cotton (39.85 %) or gauze face masks (36.24 %). Age and occupation were the main factors associated with the level of knowledge about air pollution (p < 0.05).ConclusionsThere were a relatively high knowledge awareness rate, strong health protection consciousness and high enthusiasm for air pollution control among Ningbo residents. The elderly people and less-educated residents are the targetable population for improving environment.

In the present study, we studied the expression of T-bet, a key marker for type 1 immune responses, within the tumor microenvironment of gastric cancer, and analyzed its association with clinicopathological parameters. One hundred and fifty-two archival paraffin-embedded gastric tumor tissues were collected, and the expression of T-bet in these cancer tissue specimens was examined by immunohistochemistry. T-bet(+) tumor-infiltrating lymphocytes (TILs) in some gastric cancer tissues were further characterized by flow cytometric analysis. The density of T-bet(+) TILs in gastric cancer tissues in relation to patient's clinicopathological parameters and postoperative prognosis has been analyzed. Herein, we have found significant increases in T-bet(+) lymphocytes in tumor tissues as compared with normal stomach tissues, gastritis tissues or gastric polyp specimens. T-bet(+) cells mainly consisted of CD4(+), CD8(+) and CD56(+) TILs. In addition, lower numbers of T-bet(+) TILs were associated with poor clinicopathological parameters such as invasion to muscular layer, larger tumor size and advanced cancer stages. Moreover, patients with higher numbers of T-bet(+) TILs have longer disease-free survival and overall survival. Thus, our study supports the idea that tumor growth elicits spontaneous type 1 cellular immune responses and tumor progression is associated with suppression of antitumor immunity. T-bet expression within tumor can serve as a prognostic indicator for gastric cancer and a potential biomarker for immunotherapy.

Estrogen-metabolizing gene and estrogen receptor (ER) genes are the possible risk factors implicated in the initiation and development of breast through estrogen tumorigenesis pathway. We examined whether CYP1A1 MspI, ERa PvuII, and ERa XbaI genetic polymorphisms could increase the risk of breast cancer among Chinese women and gene-gene joint effect on the breast cancer risk in a subset from a population-based case-control study conducted in urban Shanghai from January 1, 1998 and November 31, 2001. PCR-RFLP method based on buccal cells was used to examine the three candidate polymorphisms in 282 breast cancer cases and 298 controls. Compared with CYP1A1 MspI m1/m1, the risk of breast cancer was doubled for genotypes CYP1A1 MspI m1/m2 [odds ratio (OR), 1.83; 95% confidence interval (95% CI), 1.24-2.69] and CYP1A1 MspI m2/m2 (OR, 2.22; 95% CI, 1.26-3.85). The association seemed to be stronger among cases diagnosed older than 45 years and women without a family history of breast cancer. ERa PvuII pp and ERa XbaI xx polymorphisms, which are in possible linkage disequilibrium, were both associated with a nonsignificantly elevated risk in all subjects; the associations seemed to be stronger among women with a family history of breast cancer. There seems to be a joint effect on the breast cancer risk between CYP1A1 MspI and ERa XbaI genotypes (m2/m2 and xx; OR, 5.87; 95% CI,

Regulatory T cells (Tregs), a key mediator in regulating anti-tumor immune suppression, tumor immune escape, metastasis and relapse, are considered an important therapeutic target in immunotherapy of human cancers. In the present investigation, elevated CD19+ CD24+ CD38+ regulatory B cells (Bregs) were observed in PBMCs of invasive carcinoma of breast (IBCa) patients compared with that in patients with fibroadenoma (FIBma) or healthy individuals, and the positive correlation existed between Bregs and CD4+ CD25+ CD127− Tregs (r = 0.316, P = 0.001). We found that PD-L1 expression was higher on Bregs in IBCa patients compared with patients with FIBma or healthy individuals (P < 0.05, respectively), and that a tight correlation exists between CD19+ CD24+ CD38+ PD-L1+ Bregs and CD19+ CD24+ CD38+ Bregs (r = 0.267, P = 0.007), poor TNM phases and up-regulated expression of PD-L1 on Bregs. The pattern of PD-1 expression on CD4+ T cells indicated that high level of PD-1hi expressed on CD4+ CD25+ CD127+ effector T cells (P < 0.001). More importantly, the presence of PD-L1 on Bregs was positively correlated with Tregs (r = 0.299, P = 0.003), but negatively correlated with PD-1hi effector T cells (r = −0.22, P = 0.031). Together, results of the present study indicated that PD-L1 is an important molecule on Bregs, mediated the generation of Tregs in IBCa.

Supplementary data are available at Bioinformatics online.

To determine the prevalence and risk factors of IBS in children 8–13 years of age in Suzhou city, a cross-sectional study was conducted on children in grades 1 through 6 in public elementary schools in three districts of Suzhou. A multistage stratified random-sampling survey was conducted in a primary investigation using standardized questionnaires. Rome II criteria were used to confirm IBS and their risk factors were analyzed. Of 8,000 questionnaires 7,472 responded satisfactorily for a response rate of 93.4%. IBS was diagnosed in 10.81%. A decrease in the prevalence of IBS was significantly associated with advancing age and grade in school (trend test, P < 0.05). The prevalence of IBS in females was higher but not significantly different than males. The significant risk factors for IBS included young age (OR = 0.94), food allergy (OR = 1.53), gastroenteritis during childhood (OR = 1.29), eating fried food (OR = 1.62), anxiety (OR = 1.49), psychological insults in early childhood (OR = 1.47), and parental history of constipation (OR = 1.81; all P < 0.05). IBS prevalence of 10.81% in study population warrants preventive measures such as encouraging dietary changes, preventing gastroenteritis and childhood psychological insults.