p75 neurotrophin receptor (p75 NTR) is a member of the tumor necrosis factor receptor superfamily, which interacts with tropomyosin receptor kinase (Trk) receptor or binds neurotrophic factors. It mediates a variety of complex signal transduction pathways, induces synaptic growth and affects cell survival. After acute cerebral ischemia, p75 NTR binds effector factors such as pro-nerve growth factor (proNGF) and sortilin, activating downstream apoptotic signal molecules and leading to neuronal death. Therefore, elucidating the pathways and molecular mechanisms of p75 NTR that mediate neuronal apoptosis in acute cerebral ischemia is of great significance for the development of new therapeutic drugs for acute cerebral ischemia.

Objective To study the radiosensitizing effect of caffic acid phenethyl ester(CAPE)on human cervical cancer HeLa cells.Methods MTT assay was used to measure the relation between the inhibition effect and CAPE concentrations by CAPE with different concentrations on HeLa cells for 24 hours.HeLa cells were divided into the control and experimental groups,both of which were given 0,2,4,6 and 8 Gy of 60Co γ-irradiation,respectively.The cell clones were counted.Meanwhile HeLa cells were divided into the control,CAPE,irradiation and combination groups.Flow cytometric analysis was adopted to detect the changes of cell cycle distribution induced by CAPE.Results The inhibition rate of CAPE acting on Hela cells increased with concentrations(F=126.49～3654.88,P＜0.01).HeLa cells cloning survival decreased with the increase of radiation dose(F=174.42～9422.81,P＜0.01).At the game radiation dose,HeLa cells cloning survival was less in experimental group than conlrol group(F=120.14～251.91,P＜0.01).The mean lethal dose(D0)(1.45 and 1.82 Gy)and the quasi-threshold dose(Dq)(1.89 and 3.21 Gy)of HeLa cells in experimental group decreased comparing with control group,SER was 1.26.Compared with the sole irradiation group,cells in G2/M phase of the CAPE group and the sole irradiation group increased(P＜0.01)while the combination group decreased(P＜0.01).Conclusions CAPE could increase the radiation sensitivity of HeLa cells by G2/M arrest and may be related to the inhibition of the sub-lethal damage repair.

Objective To investigate the radiosensitizing effects of artesunate on human HeLa cells of cervical cancer in vitro.Methods Hela cells were irradiated with 60Co γ-rays.The dose rate was 0.635 Gy/min and the radiation dose was 0,1,2,4,6 Gy,respectively.The anti-proliferation activities of artesunate on HeLa cells were evaluated with MTT assay,to determine the most appropriate drug concentration.The effect of radiosensitivity was observed by using clonogenic assay.The single-hit multitarget model was used to plot the HeLa cell's dose-survival curve,to calculate mean lethal dose,quasithreshold dose and sensitization enhancement rate,and to evaluate its radiosensitization effect.The apoptosis was analyzed with flow cytometry (FCM) to further test the radiation senseitization of artesunate on HeLa cells.Results The inhibition of artesunate on HeLa cells increased with concentration.In radiation group,the cell cloning efficiency were 91.67% ,82.02% ,58.60% ,25.01%,respectively,and in artesunate (2.0 μ mol/L) + radiation group,the cell cloning efficiency were 74.93% ,60.53% ,22.38% ,5.05%.In radiation group and artesunate (2.0 μmol/L) + radiation group,the mean lethal dose(D0) was 2.95 and 2.07 Gy,respectively,while the qusai-threshold dose (Dq) were 2.01 and 1.24 Gy,respectively,and SER was 1.43.Compared with 2 and 6 Gy radiation group,the apoptosis rate of drug + radiation group increased from 12.26% ,40.08% to 22.71% ,59.92%.Conclusions The inhibiting effect of artesunate on HeLa cells is concentration-dependent.Artesunate has radiosensitizing effect on HeLa cells in vitro.

Objective To evaluate the effect of artemether on the cell cycle and the radiosensitivity in human nasopharyngeal carcinoma cell line CNE-1.Methods Cell growth inhibition was assessed with MTT.The method of colony-forming was used to detect the radiation sensitivity.Cell cycle distribution was analyzed by using flow cytometry.The protein expressions of clyclin B1 and Weei were detected by using Western blot.Results The growth of CNE-1 cells was inhibited in a dose-dependent manner.The concentration of 20 μmol/L artemether had radiosensitive effect on CNE-1 cells at 24 h after administration,and SER was 1.481.When CNE-1 cell was irradiated,the G2/M cells increased (t =4.59,P ＜ 0.05).After exposure to combination of artemether and irradiation,the G2/M cells were decreased (t= 10.60,P ＜ 0.05).Western blot showed that artemether increased the level of cyclin B1 expression and inhibited the level of Weel expression.Conclusions The noncytotoxic concentration of artemether could enhance radiosensitization of CNE-1 cells.The radiosensitivity enhancement of artemether might depend on the exposure time.The effect is most obvious when radiation is delivered 24 h after expose to artemetherr.The radiosensitizing effect could be related to apoptosis.

Objective To explore the appropriate target ranges of blood glucose in intensive insulin therapy (ⅡT) for acute hyperglycemia following traumatic brain injury (TBI).Methods A randomized,open-label and controlled clinical trial was performed on 208 patients,admitted to our hospitals from Junuary 2014 to Sepember 2016.They were divided into ⅡT group (n=156),who were subdivided into slight (10.1-13.0 mmol/L),moderate (7.1-10.0 mmol/L),and strict (4.4-7.0 mmol/L) control blood glucose groups (n=52),and non-ⅡT group (n=52).Survival analysis 6 months after treatment was performed by Kaplan-Meier method.Modified Rankin scale (mRS) scores and Barthel index (BI),Glasgow Outcome scale (GOS) scores,concentrations of lactic acid in cerebrospinal fluid (CSF) and glycosylated hemoglobin,Glasgow coma scale (GCS) scores,Acute Physiology and Chronic Health Evaluation (APACHE Ⅱ) scores,Length of staying in intensive care unit (ICU) and incidence of adverse events were compared between the patients from different groups at different treatment times.Results Blood glucose level within 7 d of admission in patients ofⅡT group was in target ranges.The survival rate of patients from slight and moderate control blood glucose groups was significantly higher than that in the non-ⅡT group and strict control blood glucose group 6 months after treatment (x2=4.237,P=0.040;x2=5.621,P=0.018).As compared with those in the non-ⅡT group and strict control blood glucose group,the mRS scores 3 months after treatment were significantly decreased,and GOS scores and BI one,3 and 6 months after treatment were significantly increased in patients from slight and moderate control blood glucose groups (P＜0.05).As compared with that in the non-ⅡT group,and slight and moderate control blood glucose groups,the glycosylated hemoglobin level 7 d after treatment was significantly decreased in strict control blood glucose group (P＜0.05).As compared with those in the non-ⅡT group and strict control blood glucose group,the concentration of lactic acid in CSF 7 d after treatment,APACHE Ⅱ scores 7 and 14 d after treatment,length of staying in ICU and incidence of adverse events were significantly decreased in patients from slight and moderate control blood glucose groups (P＜0.05).The mean value of blood glucose in slight and moderate control blood glucose groups was (8.40±0.39) mmol/L.Conclusion Proper ⅡT improves the outcomes of TBI patients and (8.40±0.39) mmol/L are established as the target ranges in ⅡT for TBI.