Objective To investigate the effect on ER expression in MCF-7 cell by siRNA against survivin mediated by adenovirus vector.Methods An adenovirus vector of siRNA against survivin was constructed and used to infect MCF-7 cell.The change of expression of survivin and ER was detected by Western Blot.Results The expression strength of survivin are 0.09 ± 0.04、0.86 ± 0.08、0.82 ± 0.17;expression strength of ER are 1.57 ± 0.09、1.16 ± 0.10、1.23 ± 0.01 respectively in the experimental group,negative control group and blank control group.Statistics analysis shows that the adenovirus vector of siRNA against survivin constructed in the study can suppress the expression of survivin significantly,and suppress the expression of survivin can up-regulate the estrogen receptor (ER) expression.Conclusions The results suggest that there may be a certain regulatory mechanism between survivin and ER signal pathway in MCF-7 cell and siRNA against survivin is of important potential value in the endocrine therapy of hormone receptor positive breast cancer.

Objective To investigate the expression of GRP78 in breast cancer,the relationships among the expression and the clinicopathological characteristics,prognosis were also investigated.Methods The expression of GRP78 was detected in 172 paraffin-embedded breast cancer samples with immunohistochemistry Envision method,the relationships among the expression and the clinicopathological characteristics,prognosis were investigated.Results Positive expression of GRP78 is common in breast cancer.Strong expression of GRP78 was detected in 71 cases (41.28％),and weak expression was detected in 101 cases (58.72％).GRP78 expression wasn't associated with the clinicopathological characterristics except T stage and Her-2 status.Univariate analysis (log-rank test) showed that GRP78 expression correlated with disease free survival and overall survival significantly.Patients with strong GRP78 expression had poorer prognosis compared to those with weak GRP78 expression(P ＜ 0.05).Multivariate analysis utilizing Cox regression analysis showed that GRP78 is an independent biomarker of disease free survival (P ＜ 0.05),but not an independent biomarker of overall survival (P ＞ 0.05).Conclusions Positive expression of GRP78 is common in breast cancer and strong expression is associated with poorer survival.

OBJECTIVE: To investigate the effects of serum containing Scutellaria Barbata extract (ESB) on apoptosis rate and mitochondrial transmembrane potential (MTP) of liver cancer cell line H22 from mice in vitro. METHODS: H22 cells were cultured in vitro and divided into 5 groups: blank control group, low-dose ESB group, medium-dose ESB group, high-dose ESB group and fluorouracil (5-Fu) group. Methyl thiazolyl tetrazolium assay was utilized to determine the proliferation rates of H22 cells. Cellular morphology was observed under a transmission electron microscope (EM). The rhodamine 123 was used as a fluorescence probe to label the H22 cells, and the fluorescence intensities were observed with a laser scanning confocal microscope. The fluorescence intensity of H22 cells indicated the MTP of H22 cells. RESULTS: The inhibition of serum containing ESB on the proliferation of H22 cells in vitro was observed in a time-dependent manner. The typical morphological changes of apoptosis were observed after incubation with ESB-containing serum in high dose for 48h. The apoptosis rates of blank control group, 5-Fu group, low-dose ESB group, medium-dose ESB group and high-dose ESB group were (0.51+/-0.32)%, (11.26+/-2.97)%, (1.07+/-0.46)%, (3.15+/-1.12)%, (7.83+/-2.25)% respectively. ESB could reduce the MTP of H22 cells from mice as compared with the untreated group. The MTPs of the blank control group, 5-Fu group, and low-, medium- and high-dose ESB groups were (245.45+/-67.37), (127.42+/-41.35), (213.68+/-65.52), (186.34+/-56.37) and (142.65+/-39.44) respectively, which were negatively correlated with the apoptosis rates. CONCLUSION: ESB-containing serum effectively induces apoptosis, which may be related to the decrease of MTP in H22 cells.

Objective To explore the progress and prospect of preventive, predictive, personalized and participatory (4P) medicine in China in order to promote the ^“4P^” medicine and provide reference for the government and medical institutions to strengthen health management. Methods An in-depth analysis and review of the ^“4P^” medical service model was conducted through literature review. The prospect of the future development of the ^“4P^” medicine was discussed. Results In recent years, with the advancement of human health concepts and the completion of the genome project, the human healthcare model has been gradually shifting to the ^“4P^” medical service model, namely preventive-predictive-personalized-participatory integrated medicine. It can be seen that modern medical model has been in the process of continuous transformation, which is more human-oriented and emphasizes people^’s initiative. Conclusions With the widespread and understanding of the ^“4P^” medicine among healthcare workers, the value of the “4P” medicine in public health and clinical practice has been continuously proven.

Objective: To observe the changes of extracellular histones and pulmonary microvascular endothelial cells, and study the activating role of extracellular histones to pulmonary microvascular endothelial cells in the pathogenesis of acute respiratory distress syndrome (ARDS) . Methods: The correlation of the severity of acute lung injury with extracellular histones and pulmonary endothelial damage was studied through mice model, and acute lung injury was produced by aspiration of different concentrations of hydrochloric acid (0.01、0.1、0.3 and 0.5 mol/L, 2 ml/kg). Tumor necrosis factor-α (TNF-α), soluble thrombomodulin (sTM) and lung pathological change were measured. The pro-inflammatory role of extracellular histones was tested by injecting calf thymus histones (CTH) or specific anti-H4 antibody through tail vein. The direct activating role of extracellular histones to pulmonary microvascular endothelial cells was studied through pulmonary endothelial model. Results: The extracellular histones in plasma were increased obviously 6h after aspiration of different concentrations of hydrochloric acid in mice. A positive correlation was seen between extracellular histones and concentrations of aspirated hydrochloric acid (r=0.9180, P<0.05). The sTM in plasma also showed a positive correlation with concentrations of aspirated hydrochloric acid (r=0.8701, P<0.05). Merely administering CTH could not only increase TNF-α and sTM in plasma but also cause obvious lung injury, while specific anti-H4 antibody could relieve the inflammation and lung damage caused by CTH. Extracellular histones could directly damage pulmonary endothelial cells to release sTM in pulmonary endothelial model in vitro, while anti-H4 antibody could protect the endothelial cells. Conclusion Extracellular histones are the key endogenic inflammatory mediators during the pathogenesis of ARDS caused by aspiration of hydrochloric acid, which could promote inflammation by directly activating pulmonary endothelial cells.

Hepatotoxicity is a common side effect for patients treated with gefitinib, but the related pathogenesis is unclear and lacks effective predictor and management strategies. A multi-omics approach integrating pharmacometabolomics, pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution. Here, we found that patients with rs4946935 AA, located in Forkhead Box O3 (FOXO3) which is a well-known autophagic regulator, had a higher risk of hepatotoxicity than those with the GA or GG variant (OR = 18.020, 95%CI = 2.473 to 459.1784, P = 0.018) in a gefitinib-concentration dependent pattern. Furthermore, functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity, increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury. In contrast, erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3. This study reveals that FOXO3 mutation, leading to autophagic imbalance, plays important role in gefitinib-induced hepatotoxicity, especially for patients with high concentration of gefitinib. In conclusion, FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.