Recently,increasing cancer researches focus on antibody-drug conjugates(ADCs) which can improve the anti-tumor potency with less adverse effect while benefiting patients in the future. However,safety evaluation of ADCs is a big challenge because of complex components as well as in experience in preclinical studies. In this review,the authors reviewed the mode of action,hazard risks,and toxicity observed in preclinical/clinical studies of ADCs,summarized the preclinical studies of Adcetris(brentuximab vedotin)and Kadcyla(ado-trastuzumab emtansine),and suggested a better strategy of ADCs in preclinical safety evaluation.

Background and purpose:The growth,metastasis,relapse and the prognosis of tumor are correlated with tumor angiogenesis.Therefore,target to angiogenesis and antiangiogenic therapy has become one of the hot points in cancer research field.Some chemotherapeutic drugs can inhibit the growth of new vascular endothelial cell markedly in the way of low-dose and high time administration.This is metronomic chemotherapy or antiangiogenic chemotherapy.Traditional Chinese medicine has an effect on tumor control.In recent years,we discovered that some traditional Chinese medicine have an antiangiogenic effect.This experiment aimed to study the antiangiogenetic ability of oxaliplatin combined with composite radix sophora flavescentis injection(CRSFI) in vitro and in vivo. Methods :We used MTT method to observe the influence of oxaliplatin and composite radix sophora flavescentis injection on human umbilical vein endothelial cells(HUVEC) or LoVo proliferation.The influence of oxaliplatin and composite radix sophora flavescentis injection on HUVEC migration was evaluated by transwell.Chick embryo chorioallantoic membrane(CAM)model was used to check whether the neovascularization of CAM could be suppressed in vivo by them. Results :The survival rate of LoVo within the same doses of oxaliplatin and composite radix sophora flavescentis injection were higher than HUVEC.Oxaliplatin(2 ?g/ml) and composite radix sophora flavescentis Injection(25 ?l/ml) could inhibit the prolifetation of HUVEC;the rate of inhibition were 31.6%,32.1% respectively;the rate of the two drugs combination was 54.4%.So when combined,they had synergistic effect.There was coordinate repression to migration of HUVEC in vitro when we used oxaliplatin(0.5 ?g/ml) and composite radix sophora flavescentis injection(6.25 ?l/ml).They also suppressed angiogenesis of CAM in vivo. Conclusions :This experiment showed that low dose oxaliplatin combined with composite radix sophora flavescentis injection has anti-angiogenic synergetic ability in vivo and the ability of inhibiting the growth of the cells in vitro.

Objective To observe the blocking efficacy of mother to child transmission (MTCT) in pregnant women with positive human immunodeficiency virus(HIV), and explore proper MTCT blocking mode for acquired immunodeficiency syndrome.Methods Clinical data of 23 HIV-positive pregnant women in a hospital from 2005 to 2015 were retrospectively analyzed.Results All 23 HIV-positive pregnant women received highly active antiretroviral therapy (HAART) and comprehensive intervention for blocking MTCT of HIV.Among these women, 12 got pregnant after receiving HAART, 10 were detected positive HIV in early pregnancy (within 28 weeks) and then received HAART, 1 was detected positive HIV 28 weeks after pregnancy and then received HAART.23 HIV-positive pregnant women all delivered normal newborns, follow-up observation of babies found no HIV infection.Conclusion HAART for HIV-positive pregnant women is the key to block MTCT of HIV, combined with preventive medication and artificial feeding of newborns, HAART can effectively prevent MTCT.Mutual blocking mode, such as HAART for HIV-positive pregnant women by specialists, pregnancy check-up, and preventive medicine for infants provided by maternity and child care hospital, is highly efficiency.

Objective To investigate the effect of JNK signal pathway in acute necrotizing pancreatitis (ANP) associated lung injury.Methods A total of 24 SD rats were randomly divided into sham group and ANP group,ANP rats were induced by retrograde injection of 5％ sodium taurocholate into common bile duct.The rats were sacrificed 12 and 24h later,and the pancreas and lung tissue were resected and underwent routine pathologic examination,ELISA method was used to detect the level of TNF-α and IL-1β in lung tissue.Expression of JNK mRNA was detected by real time PCR,and the expression of JNK protein were evaluated by Western blotting.Results There was bleeding,necrosis,large amount of inflammatory cells infiltration in pancreatic tissue; and there was edema,pulmonary consolidation,interstitial edema,inflammatory cells infihration in lung tissue in ANP group.The levels of TNF-α and IL-1β,JNK mRNA,JNK protein,phosphorylation JNK were ( 374.3 ± 124.0) pg/ml,(649.0 ± 114.9) pg/ml,2.57 ± 0.76,1.40 ± 0.81,0.81 ± 0.20 in ANP group,which were significantly higher than those in with sham group[( 218.2 ± 68.4)pg/ml,(524.3±58.4)pg/ml,1.03±0.11,0.32±0.11,0.32±0.11,P＜0.05].Conclusions JNK signal pathway plays an important role in experimental ANP associated lung injury in rats.

Objective To investigate the effects of hyperbaric oxygen (HBO) on the systemic inflammation response in patients with severe traumatic brain injury (TBI), and to explore HBO therapy mechanisms. Methods Seventy patients with severe TBI were randomly divided into a routine treatment group ( RT group, n = 35 ) and an HBO group (n=35). All patients received conventional treatment, but the HBO group received additional early HBO therapy. Twenty age-and sex-matched normal subjects were recruited and served as normal controls. Serum interleukin-6 (IL-6) was measured by ELISA, and C reactive protein (CRP) was also measured on days 1, 7, 14 and 21 after injury. Sequential organ failure assessments (SOFAs) and Glasgow coma scale (GCS) scores were evaluated at the same time points. Systemic inflammatory response syndrome (SIRS) was assessed daily. Results The concentrations of serum IL-6 and CRP increased obviously following TBI, but patients in the HBO group exhibited significantly lower levels at each time point than those in the RT group. In the HBO group fewer cases of SIRS developed,and they had a significantly shorter average duration than those in the RT group. The average SOFA score in the HBO group was significantly lower than that of the RT group at days 14 and 21 after injury, and the GCS scores had improved significantly more by day 21. Compared with the patients who were free of SIRS, the patients with SIRS showed higher levels of IL-6 and CRP, higher SOFA scores as well as lower GCS scores ( all differences statistically significant). Conclusions HBO therapy can attenuate systemic inflammation after TBI, protect the functions of important organs and improve clinical outcomes. Decreasing the level of IL-6 may contribute to the effectiveness of HBO.

Objective: To determine the inhibitory effects of maltitol-gum on Streptococcus mutans, Lactobacilli and Actinomyces viscosus in dental plaque. Methods: Thirty 13-15 years old children with DMFS>4 were divided into three groups, maltitol chewing gums group(A group), xylitol chewing gum group(B group) and blank gum base group (C group). The plaque samples were collected and colony forming units were counted. Results: The levels of three-species cariogenic pathogens in three groups were statistically down-regulated when compared with the baseline(P<0.001).Moreover, A group and B group resulted in a higher decrease of Streptococcus mutans levels compare with C group(P<0.05). The levels of Lactobacilli and Actinomyces viscosus were not statistically different between groups(P>0.05). Conclusion: Maltitol-gum can lead to a significant suppression on Streptococcus mutans levels in dental plaque,while the inhibitory effect of the maltitol-gum on Lactobacilli, Actinomyces viscosus is not obvious.

Objective To investigate the relationship between carotid stiffness and coronary angiography in elderly patients with coronary heart disease(CHD). Methods Thirty-five elderly patients with CHD who underwent coronary angiography were enrolled in the study. The carotid stiffness was measured by ultrasound, the results were compared with those in hypertension group,hyperlipemia group and healthy elderly group. Results There were significant differences in carotid tensity (8.15 ± 1.54), arteriectasis ( 0.34 ± 0.07 ) and carotid stiffness ( 640.51 ± 150.98 ) of elderly patients with CHD compared to other groups (all P＜0.05 or P ＜ 0. 01 ). There was significant correlation between coronary angiography score and carotid stiffness in elderly patients of CHD(P＜0.05 or P＜0.01). Conclusions There is close relationship between carotid atherosclerosis and coronary atherosclerosis in elderly patients with CHD.

Objective To evaluate in vitro anti tumor effect of host lymphocyte primed by CalmetteGuerin bacillus (CGB) activated dendritic cells (DC) based PANC1 lysate. Methods DCs were obtained from peripheral blood mononuclear cells of healthy volunteer and cuitured by rhGM CSF and rhIL 4. DC vaccines for pancreatic cancer were loaded with PANC1 tumor lysate (TL) and were further maturated by CGB.CD1a, CD83, CD86 and HLA-DR phenotype was characterized by flow cytometer, and IL-12p70 and TNF-α concentration in DC culture supernatant were measured by ELISA. Autologous mixed lymphocyte proliferation and the cytotoxicity of cytotoxic T lymphocytes primed by activated DCs to PANC1, PaTu8988 and SCG7901 tumor cells was measured by CCK 8 test. Results When DCs based PANC1 lysate were activated by CGB,the expression rates of CD83 and CD86 were increased from (3.7±0.3)% and (38.6±5.0)% to (16.5±0.6)% and (76.6±2.5)% (P ＜0.05 ). The concentrations of cytokines ILpl2p70 and TNF-α were increased from (20.18±2.06 ) pg/mland (61.38±1.19) pg/mlto (62.48±3.80) pg/mland (592.53±17.96)pg/ml (P＜0. 01 ). When co-cultured with CGB activated DCs based PANC1 lysate in proportion of 0.40)% , (3.39±1.05)% , (2.82±0.39)% significantly increased to (55.38±3.58)% , (75.0±2.54) % , (77.07±3.4)% , (99.07±2.4)% (P＜0.01) , respectively. The killing effects of lymphocytes 2.77)%, (19.03±3.04) %; but the killing effects on PaTu8988 and SCG7901 were significantly decreased.Conclusions DC vaccines for pancreatic cancer could be more maturated when activated by CGB, and could show a high capability of anti-tumor in vitro.

High-level researchers,who can efficiently enhance the research strength of the college,are often brought in at high cost.Therefore there is often the need to scientifically evaluate these researchers when introduce them.We here discuss the main indicators for the evaluation of High-level researchers.Taking into consideration of their age,research span,et al.,we propose a model for the quantitative evaluation of research capability based on research achievement and prediction of future achievement,

Objective To investigate the effect of mild therapeutic hypothermia for different lengths of time on cerebral edema and hypoxia-inducible factor 1 α (HIF-1α),vascular endothelial growth factor (VEGF) expressions following intracerebral hemorrhage (ICH) so as to explore possible mechanism for better application of mild hypothermia.Methods ICH models were made in rats by stereotaxically injecting autologous artery blood into right caudate nucleus.Forty male Sprague-Dawley (SD) rats were randomly (random number) divided into 5 groups (n =8 each):sham-operated (sham),normothermic (NT),hypothermic-1 hour (MH1),hypothermic-2 hours (MH2),hypothermic-4 hours (MH3).Normothermic and sham-operated animals were kept at (37.0-± 0.2) ℃ of body temperature.Animals in the hypothermic groups received immediately and rapid cooling after ICH and kept at (33.0 ± 0.5) ℃ of body temperature for 1,2 and 4 hours respectively.Rats were sacrificed at 48 hours after cerebral hemorrhage.Then brain water content and BBB permeability were determined.Quantitative real-time PCR and Western blot were used to analyze the expression of HIF-1α and VEGF.Results The content of brain water,Evans blue concentration in brain,and the mRNA expression and protein levels of HIF-1α and VEGF were noticeably higher in NT group than those in sham group (P ＜0.01).There were statistically significant difference in the expression of HIF-lα mRNA and protein but little difference in other indicators between MH1 group and NT group.Compared with NT group,MH2 group and MH3 group brought about an improvement in BBB permeability and remarkable down-regulation of protein levels and expression of HIF-1 α and VEGF mRNA,whereas there were no statistically significant difference in expression of indicators between the two groups.Conclusions Mild therapeutic hypothermia induced rapidly and immediately after ICH could limit the development of brain edema in rats by down-regulating expression and protein levels of HIF-1 α mRNA,and in turn suppressing the evaluation of VEGF mRNA and protein expression.The brain edema was effectively reduced in animals treated with hypothermia for 2 hours' or 4 hours ' duration with little difference in magnitude of reduction in brain edema between these two modalities of hypothermia.