Newly identified nuocytes or group 2 innate lymphoid cells (ILC2s) play an important role in Th2 cell mediated immunity such as protective immune responses to helminth parasites, allergic asthma, and chronic rhinosinusitis. However, the contributions of ILC2s in the occurrence and development of cancer remain unknown. Our previous study found that there was a predominant Th2 phenotype in patients with gastric cancer. In this study, the ILC2s related genes or molecules in PBMC from patients with gastric cancer were measured, and the potential correlation between them was analyzed. The expression levels of RORα, GATA3, T1/ST2, IL-17RB, CRTH2, IL-33, IL-5, and IL-4 mRNA were significantly increased in patients, but no significant changes were found in ICOS, CD45, and IL-13 expression, and there was a positive correlation between RORα or IL-13 and other related factors, such as ICOS and CD45. The increased frequency of ILC2s was also found in PBMC of patients by flow cytometry. In addition, the mRNA of Arg1 and iNOS were also significantly increased in patients. These results suggested that there are polarized ILC2s in gastric cancer patients which might contribute to immunosuppressive microenvironment and closely related to the upregulation of MDSCs and M2 macrophages.

T helper 17(Th17) cell is a new subset of CD4+ T cells that produce a proinflammatory cytokine interleukin‐17 (IL‐17). Th17 cells have recently been shown to play a critical role in many autoimmune diseases that had previously been thought to be Th1 dominant. Although Hashimoto’s thyroiditis (HT) was thought to be a Th1‐type disease, the contributions of Th17 cells to the pathogenesis remain unclear. In this study, we investigated the expression levels of Th1/Th17 cell‐associated factors in peripheral blood mononuclear cells (PBMC) and plasma from patients with HT by quantitative real‐time polymerase chain reaction (RT‐qPCR) and enzyme‐linked immunosorbent assay (ELISA). Our results showed that the expression levels of Th1 cells‐related T‐bet and interferon‐γ (IFN‐γ) mRNA in PBMC from HT significantly decreased. However, the mRNA of Th17 coherent retinoic acid‐related orphan nuclear receptor gamma t (RORγt) and IL‐17 in patients with HT increased. In addition, a negative correlation between T‐bet and RORγt mRNA expression was found in patients with HT, and the similar phenomena also appeared on the levels of mRNA and plasma concentration between IFN‐γ and IL‐17. It suggested that Th17 cells rather than Th1 cells predominated among patients suffering from HT, and Th17 cells might be involved in the pathogenesis of HT.

BackgroundThe prognoses of young breast cancer patients are poor. The purpose of this study is to evaluate the different characteristics and prognoses among different subtypes of young breast cancer patients.MethodsThe study included 1360 patients <40 years-old (y) and 3110 patients 40-50y with operable breast cancer in Shanghai Cancer Center, Fudan University. The characteristics, overall survival (OS) and disease-free survival (DFS) were compared.ResultsThe median follow-up was 54.1 months. More grade III tumors and more lymph-vascular invasions (P < 0.01) were presented in <40y group when compared with 40-50y group. More patients <40y presented with Luminal B (25.3% vs. 17.5%, P < 0.01) and triple negative (16.7% vs. 13.4%, P < 0.05) breast cancer while fewer had Luminal A tumor (48.5% vs. 59.2%, P < 0.01). Younger patients with tumors of both Luminal A and Luminal B types were at increased risk for worse DFS (P = 0.03, HR = 1.69, 95% CI = 1.05-2.72; P < 0.01, HR = 3.61, 95% CI = 2.50-5.22) when compared with the older patients. Patients <40y with Luminal B tumor had a two point five fold higher risk of death compared with older counterparts (P < 0.01, HR = 2.54, 95% CI = 1.35-4.79), however, a worse overall survival rate was not observed in the younger women with Luminal A breast cancer (P > 0.05). In multivariate analysis, Luminal B subtype was also a strong predictor of disease relapse (HR = 1.09, 95% CI = 1.01 to 1.19, P < 0.01) in younger patients with Luminal subtype tumors.ConclusionCharacteristics of breast cancer suggested a more aggressive biology in Chinese patients with breast cancer diagnosed at young age. Luminal B subtype may have a negative effect on the prognosis of young patients in China which should be validated further.

This paper describes preliminary findings on the influence of 60-Hz (2-mT) magnetic fields on tumor promotion and co-promotion in the skins of mice. The effect of magnetic fields on natural killer (NK) cell activity in spleen and blood was also examined. Groups of 32 juvenile female mice were exposed to the magnetic field as described in part I. The dorsal skin of all animals was treated with a subthreshold dose of the carcinogen 7,12-dimethyl-benz(a)anthracene (DMBA). One week after the treatment, two groups were sham exposed (group A) or field exposed at 2 mT (group B) 6 h/day for 21 weeks, to test whether the field would act as a tumor promoter. No tumors developed in these two groups of mice. To test whether the magnetic field would modify tumor development by directly affecting tumor growth or by suppressing immune surveillance, two additional groups of mice were treated weekly with the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) and then either sham exposed (group C) or field exposed (group D). The time to appearance of tumors was shorter (but not statistically so) in the group exposed to magnetic fields and TPA. Some differences in NK cell activity and spleen size were observed between the sham- and field-exposed groups.

Over the years many guidelines have been offered as to how to achieve good quality designs. We would like to be able to determine to what degree these guidelines actually help. To do that, we need to be able to determine when the guidelines have been followed. This is often difficult as the guidelines are often presented as heuristics or otherwise not completely specified. Nevertheless, we believe it is important to gather quantitative data on the effectiveness of design guidelines wherever possible.In this paper, we examine the use of "Dependency Injection", which is a design principle that is claimed to increase software design quality attributes such as extensibility, modifiability, testability, and reusability. We develop operational definitions for it and analysis techniques for detecting its use. We demonstrate these techniques by applying them to 34 open source Java applications.

Abstract. Solamargine (SM), a steroidal alkaloid glycoside extracted from the traditional Chinese herb Solanum incanum, has been evidenced to inhibit the growth and induce apoptosis in a number of human cancer cell lines. In the present study, the anticancer effect of SM and underlying molecular mechanism of SM-induced apoptosis were investigated on the human hepatocellular carcinoma cells, SMMC7721 and HepG2. The proliferation effects of SM on the SMMC7721 and HepG2 cell lines were evaluated using MTT and colony formation assays. In addition, the percentage of apoptosis was measured using an Annexin V/propidium iodide staining method and the cell cycle distribution mediated by SM was analyzed using flow cytometry. The expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, caspase-9, proliferating cell nuclear antigen (pcna) and Ki67 proteins were examined to further demonstrate the proliferate and apoptosis effects of SM on the hepatoma cells. The results indicated that SM effectively inhibited hepatoma cell proliferation and promoted apoptosis. SM resulted in cell cycle arrest at the G 2 /M phase in the two cell lines. In addition, SM downregulated the levels of proliferation-associated (Ki67 and pcna) and anti-apoptotic (Bcl-2) proteins, and promoted the activity of apoptosis-associated proteins (Bax, caspase-3 and caspase-9). Therefore, the activation of the Bcl-2/Bax and caspase signaling pathways may be involved in the SM-induced apoptosis of hepatoma cells.

In recent years, T helper (Th) 9 cells have been demonstrated to be key mediators in immune responses in asthmatic lungs, and innate lymphoid cells 2 (ILC2s) have been described as a novel type of innate immunocyte with the ability to enhance immunoglobulin E (IgE) production. However, the interaction between ILC2s and Th9 cells in the pulmonary system of a mouse model of asthma remains to be elucidated. In the present study, the response state of lung tissue with regards to Th9 and ILC2s in a mouse model of asthma was investigated by detecting Th9‑ and ILC2‑associated cytokine receptors. The present study also investigated the association between the expression levels of the cytokine receptors in lung tissue samples and the IgE levels in sera samples from mouse models of asthma. Results from the present study demonstrated that the frequency of ILC2s and Th9 cells was significantly increased in the lung tissue samples, indicating that a Th2-type immune response had occurred. In addition, high mRNA expression levels of RAR‑related orphan receptor α, interleukin 1 receptor‑like 1, transcription factor PU.1 and interleukin (IL)‑9 were observed. Furthermore, IL‑5Rα, IL‑13Rα2 and high‑affinity IgE receptor were increased in mouse models of asthma, and a positive association was observed between the expression levels of ILC2‑ or Th9‑associated receptors in tissue samples and IgE levels in the sera. This indicated that ILC2s and Th9 were in a state of polarization and may promote each other in the lung tissue of mouse models of asthma, and that the lung tissue was responding to the two types of cells via increased expression of receptors.

BackgroundWe aimed to evaluate the prognostic value of the lymph node ratio (LNR) in patients with axillary lymph node-positive triple-negative breast cancer (TNBC).MethodsThe prognostic efficacy was investigated in the first cohort from the Surveillance, Epidemiology, and End Results (SEER) dataset (n=4114) and was further validated in an independent cohort from Fudan University Shanghai Cancer Center (n=417). Patients were classified into low-, medium- and high-risk LNR groups.ResultsMultivariate analysis revealed that the LNR was an independent predictor of overall survival (hazard ratio (HR) for high-risk LNR: 3.24; 95% confidence interval (CI): 2.56 to 4.09) and breast cancer-specific survival (HR for high-risk LNR: 3.57; 95% CI: 2.76 to 4.62) in the SEER population and also for disease-free survival (HR for high-risk LNR: 4.29; 95% CI: 2.24-8.21) in the validation population. Subgroup analysis revealed that patient classification according to the LNR could discriminate among groups of patients with different survival rates based on pathological nodal (pN) staging.ConclusionThe LNR shows potential for use as an additional prognostic factor for TNBC patients with positive lymph node involvement. Considering the heterogeneity of TNBC, use of the LNR might allow for optimization of the pN staging system and should be considered when making treatment decisions.