[ ABSTRACT] AIM:To investigate the effects of c-Met on the proliferation and the sensitivity to chemotherapeutic drugs of triple negative breast cancer cells.METHODS: Doxorubicin-resistant cells ( MDA-MB-231/ADR) were estab-lished.The expression of c-Met at mRNA and protein levels in the MDA-MB-231/ADR cells and parental MDA-MB-231 cells was detected by real-time PCR and Western blotting.c-Met siRNA and plasmid or AKT siRNA were transfected into the cancer cells.The cell proliferation and the sensitivity to doxorubicin were determined by MTT assay.RESULTS:The expression of c-Met at mRNA and protein levels in MDA-MB-231/ADR cells was significantly higher than that in parental MDA-MB-231 cells.Transfection with pBABE-puro TPR-MET plasmid into the MDA-MB-231 cells induced cell prolifera-tion and resistance to doxorubicin.Meanwhile, inhibition of c-Met in the MDA-MB-231/ADR cells by siRNA reversed the doxorubicin-resistance.In addition, over-expression of c-Met led to higher phosphorylation level of AKT, which was in-volved in the effects of c-Met on the MDA-MB-231 cell proliferation and doxorubicin-resistance.CONCLUSION: c-Met may have the potential as a therapeutic target in the treatment of triple negative breast cancer.

Objective To investigate the role of nucleotide-binding oligomerization domain 2(NOD2)modified by palmitoyltransferase(ZDHHC5)in brain injury after cardiopulmonary resuscitation(CPR)in mice.Methods Twenty-four male C57BL/6J mice were divided into the blank group,the control group,the ZDHHC5-si group and the NOD2-si group,with 6 mice in each group.Except for the blank group without any treatment,CPR modeling was performed in the other three groups.At 24 h before CPR,mice in the ZDHHC5-si group and the NOD2-si group were injected with ZDHHC5 siRNA and NOD2 siRNA via tail vein,respectively.The modified neurological deficit scale(mNSS)was used to evaluate the neurological function at 24 h,48 h and 72 h in each group.Blood samples and brain tissue were collected 72 h after modeling.Real-time fluorescent quantitative PCR(qPCR)was used to detect ZDHHC5 and NOD2 in brain tissue.The protein expression levels of IL-1β,TNF-α and IL-6 in plasma were detected by enzyme-linked immunosorbent assay(ELISA).Colorimetric method and thiobarbituric acid(TBA)method were used to detect protein expression levels of MDA and MPO in brain tissue,respectively.Western blot assay was used to detect expression levels of Cleaved Caspase-3,ZDHHC5 and NOD2 in brain tissue.HE pathological sections of brain tissue were observed under light microscope.The pathological sections of brain tissue were observed by TUNEL under fluorescence microscope.Results Compared with the blank group,the mNSS score,the expression levels of IL-1β,TNF-α,IL-6,MDA and MPO,and the protein expression levels of Cleaved Caspase-3,ZDHHC5 and NOD2 were significantly increased(P＜0.05),and brain tissue damage and cell apoptosis were aggravated in the other three groups.Compared with the control group,the above indicators were significantly decreased in the ZDHHC5-si group and the NOD2-si group(P＜0.05),and brain tissue damage and cell apoptosis were significantly attenuated.Compared with the NOD2-si group,the above parameters were significantly decreased(P＜0.05),and brain tissue damage and cell apoptosis were further attenuated in the ZDHHC5-si group.Conclusion In the mouse CPR model,NOD2 can produce palmitoylated NOD2 after regulated by ZDHHC5,which further promotes the release of inflammatory factors and causes neuronal apoptosis,ultimately damaging brain tissue and affecting neurological function.

Objective: To analyze the disease burden of stroke and its health loss attributable to passive smoking in people aged 60 years and over in Jiangsu province. Methods: Data were retrieved from the Chronic and Non-communicable Diseases and Risk Factors Surveillance in Jiangsu in 2013 and the death registry system in Jiangsu. Combined with the method in Global Burden of Disease Study 2016 (GBD2016), the indicators, such as population attributable fraction (PAF) and disability-adjusted life years (DALY) for stroke due to passive smoking were calculated. Results: In 2013, the mortality rate, age-standardized mortality rate, DALY and DALY rate of stroke in people aged 60 years and over in Jiangsu were 718.15/100 000, 439.28/100 000, 1 179 602 person years and 9 234.99/100 000, respectively. Year of life lost (YLL) accounted for 87.00% of the total DALY. The DALY and corresponding rate of stroke increased rapidly with age, and were higher in women (612 084 person years and 9 319.71/100 000, respectively) than those in men (567 518 person years and 9 145.33/100 000, respectively). The prevalence of passive smoking was 34.04% in people aged 60 years and over in Jiangsu. The PAF, attributable DALY, attributable DALY rate and its age- standardized rate of stroke due to passive smoking in people aged 60 years and over in Jiangsu were 3.88%, 45 769 person years, 358.12/100 000 and 920.64/100 000, respectively; and were also higher for men (4.35%, 24 687 person years, 397.82/100 000 and 515.30/100 000, respectively) than those for women (3.44%, 21 056 person years, 320.60/100 000, 405.34/100 000, respectively). Conclusions The disease burden of stroke was heavy in the elderly in Jiangsu, and passive smoking might have great influence on the disease burden of stroke. Prevention and control of stroke and passive smoking exposure should be taken actively to improve health for the elderly.