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BACKGROUND: China has low seasonal influenza vaccination rates among priority populations. In this study, we aimed to evaluate a pay-it-forward strategy to increase influenza vaccine uptake in rural, suburban, and urban settings in China. METHODS: We performed a quasi-experimental pragmatic trial to examine the effectiveness of a pay-it-forward intervention (a free influenza vaccine and an opportunity to donate financially to support vaccination of other individuals) to increase influenza vaccine uptake compared with standard-of-care user-paid vaccination among children (aged between 6 months and 8 years) and older people (≥60 years) in China. Recruitment took place in the standard-of-care group until the expected sample size was reached and then in the pay-it-forward group in primary care clinics from a rural site (Yangshan), a suburban site (Zengcheng), and an urban site (Tianhe). Participants were introduced to the influenza vaccine by project staff using a pamphlet about influenza vaccination and were either asked to pay out-of-pocket at the standard market price (US$8·5-23·2; standard-of-care group) or to donate any amount anonymously (pay-it-forward group). Participants had to be eligible to receive an influenza vaccine and to have not received an influenza vaccine in the past year. The primary outcome was vaccine uptake. Secondary outcomes were vaccine confidence and costs (from the health-care provider perspective). Regression methods compared influenza vaccine uptake and vaccine confidence between the two groups. This trial is registered with ChiCTR, ChiCTR2000040048. FINDINGS: From Sept 21, 2020, to March 3, 2021, 300 enrolees were recruited from patients visiting three primary care clinics. 55 (37%) of 150 people in the standard-of-care group (40 [53%] of 75 children and 15 [20%] of 75 older adults) and 111 (74%) of 150 in the pay-it-forward group (66 [88%] of 75 children and 45 [60%] of 75 older adults) received an influenza vaccine. People in the pay-it-forward group were more likely to receive an influenza vaccine compared with those in the standard-of-care group (adjusted odds ratio [aOR] 6·7 [95% CI 2·7-16·6] among children and 5·0 [2·3-10·8] among older adults). People in the pay-it-forward group had greater confidence in vaccine safety (aOR 2·2 [95% CI 1·2-3·9]), importance (3·1 [1·6-5·9]), and effectiveness (3·1 [1·7-5·7]). In the pay-it-forward group, 107 (96%) of 111 participants donated money for subsequent vaccinations. The pay-it-forward group had a lower economic cost (calculated as the cost without subtraction of donations) per person vaccinated (US$45·60) than did the standard-of-care group ($64·67). INTERPRETATION: The pay-it-forward intervention seemed to be effective in improving influenza vaccine uptake and community engagement. Our data have implications for prosocial interventions to enhance influenza vaccine uptake in countries where influenza vaccines are available for a fee. FUNDING: Bill & Melinda Gates Foundation and the UK National Institute for Health Research. ispartof: LANCET INFECTIOUS DISEASES vol:22 issue:10 pages:1484-1492 ispartof: location:United States status: published

© Copyright 2018, Mary Ann Liebert, Inc. Lung cancer, caused mainly by smoking, is one of the most prevalent diseases in China, resulting in high mortality rates. The increasing incidence of chronic disease due to lung cancer places a huge burden on the welfare and cost to the Chinese society. Amplification of the fibroblast growth factor receptor 1 (FGFR1) is associated with high incidence and mortality in lung cancer patients. FGFR1 signaling is implicated in oncogenic traits such as proliferation, cell survival, angiogenesis, and migration. Targeting FGFR1 and its ligand basic FGF (bFGF) is a key step forward in developing new therapies for this crippling disease. Lung adenocarcinoma is the most common subtype of non-small-cell lung cancer. In this study, A549, a lung adenocarcinoma cell line widely used in vitro as a model for drug metabolism and as a transfection host, was used to study FGFR1. A stable lentiviral FGFR1 over-expression system in lung cancer cells is described for the study of anti-lung cancer drug candidates targeting FGFR1. Ligand binding to FGFR1 activates the PI3K/Akt/mTOR signaling pathway and increases adhesion, invasion, and migration in this model. Using a unique FGF monoclonal antibody developed in the laboratory, the overactive PI3K pathway was effectively blocked, abrogating the negative metastatic signaling pathways in lung cancer cells. Importantly, this model provides an effective and simple screening kit for anti-FGF1 drug compounds for lung cancer treatment and a tool for understanding the molecular mechanisms of the FGFR1 signaling pathway in lung cancer. Furthermore, this toolkit based on a FGFR1 lentiviral construct model is transferrable to study FGFR1 signaling in any type of cancer cell.

BACKGROUND microRNAs (miRNAs) are involved in the regulation of various cellular processes, such as differentiation, proliferation, metabolism, and apoptosis, and they have been implicated in several diseases, including cancers. METHODS To assess the role of miRNA in the progression of breast cancer, we performed TaqMan-based miRNA profiling for plasma from patients with breast cancer (n = 53), unrelated diseases (n = 40), or matched healthy controls (n = 40), and for breast tumors or adjacent non-tumors (n = 41). RESULTS We selected 18 miRNAs with predicted roles in breast cancer and demonstrated that let-7i (p = 0.019), let-7a (p = 0.02), and miR-650 (p = 0.008) were significantly up-regulated in plasma; miR-21 (p < 0.001) is up-regulated in breast cancer tissue, and miR-30e was down-regulated in both plasma (p < 0.001) and breast cancer tissues (p = 0.004). Plasma miR-30e expression was shown to be statistically associated with age (p = 0.0402) and clinical stage (p = 0.007). However, receiver-operating characteristic curve analyses suggested that miR-30e expression cannot significantly differentiate breast cancer from healthy tissue or plasma. Consistent with a potential role for miR-30e in breast cancer, three predicted targets of miR-30e (RAB11A, BNIP3L, and RAB32) are up-regulated in breast cancer tissue. CONCLUSIONS These findings suggest that reduced miR-30e correlates with the clinical stage of breast cancer. It is worthwhile to further explore that the potential role of miR-30e as a tumor suppressor in breast cancer, as well as its potential therapeutic utility.

Background E2F-1 is a transcription factor that stimulates cellular proliferation and cell cycle progression. E2F-1 alone is sufficient to stimulate cells to initiate DNA synthesis, and this unscheduled entry into S phase is a potent trigger of apoptosis. Gemcitabine, a novel pyrimidine analogue with structural and metabolic similarities to cytarabine, also can efficiently induce apoptosis, especially for cancer cells that are already in S phase. Gemcitabine has established antitumor activity against solid tumors, including head and neck, ovarian, and non-small cell lung cancers. Therefore, we hypothesized that exogenous E2F-1 expression could accumulate cells in the S phase and thus sensitize them to gemcitabine. Methods We constructed an adenoviral vector (AdCMVE2F-1) to transduce the exogenous E2F-1 gene into human cancer cells. Infection of human colon cancer cells with AdCMVE2F-1 resulted in the overexpression of E2F-1 mRNA and protein in a dose-dependent manner and consequently induced accumulation in S phase as measured by FACS analysis. To assess the synergistic antitumor effect of AdCMVE2F-1 and gemcitabine, the human colon cancer cel lines SW620, DLD-1, and LoVo were infected with AdCMVE2F-1 at various multiplicities of infection and then exposed to various concentrations of gemcitabine 24 hours after infection. Result Isobologram analysis showed that E2F-1-transduced cancer cells exhibited higher sensitivity to gemcitabine treatment compared to control virus-infected cells. Treatment with AdCMVE2F-1 plus gemcitabine enhanced endogenous p53 expression in LoVo cells, which contain wild-type p53; however, the finding that the synergistic effect can also be observed in mutant p53-expressing SW620 and DLD-1 cells suggests that wild-type p53 function may not be necessary for the therapeutic effects of this drug combination. Conclusions: Our data demonstrate that overexpression of ectopic E2F-1 protein may render cels more sensitive to gemcitabine-mediated apoptosis, an outcome that has important general implications for the treatment of human cancer.

BACKGROUND MicroRNAs (miRNAs) exist stably and reproducibly in plasma and may be used as biomarkers for various diseases. Little is known about circulating miRNAs in the peripheral blood of juvenile patients with asthma. METHODS In this study, we used hybridization arrays to compare the miRNA expression profiles among 6 juvenile patients with or without asthma. Using quantitative PCR (qPCR), we verified the expression levels of these miRNAs in plasma from patients with asthma (n = 40) and healthy subjects (n = 14). RESULTS Our results showed that the levels of plasma miR-Let7C, miR-486, and miR-1260a in childhood asthma patients were significantly higher than in healthy controls (p < 0.01). Additionally, miR-1260a is correlated with the treatment schedule of these patients and patients with long treatment times had higher expression of miR-1260a than short treatment times; miR494 was significantly associated with challenge, and miR-3162-3p was significantly associated with MEF25 in asthma patients suggesting a potential correlation of miRNA levels with clinical disease parameters. Receiver operator characteristic analysis confirmed that the levels of miR-3162-3p could be used to discriminate childhood asthma patients from healthy subjects (area under the curve of 0.821), suggesting it may be a potential diagnostic biomarker. CONCLUSIONS These results indicate that circulating miR-3162-3p and miR-1260a should be further evaluated as potential non-invasive biomarkers in diagnosis and treatment for childhood asthma.