Search

Background: Blocking programmed death-1 (PD-1) is considered to be a promising strategy to improve T cell function, and this is being explored in many ongoing clinical trials. In fact, our knowledge about PD-1 is primarily based on the results of short-term experiments or observations, but how long-lasting PD-1 blockade can affect T cell function remains unclear. Methods: We planned to use shRNA-based gene knockdown technology to mimic long-lasting PD-1 blockade. We constructed PD-1 steadily blocked chimeric antigen receptor modified T (CAR-T) cells, and with these cells we can clearly study the effects of PD-1 knockdown on T cell function. The anti-tumor function, proliferation ability and differentiation status of PD-1 silenced CAR-T cells were studied by in vitro and animal experiments. Results: According to short-term in vitro results, it was reconfirmed that the resistance to programmed death-ligand 1 (PD-L1)-mediated immunosuppression could be enhanced by PD-1 blockade. However, better anti-tumor function was not presented by PD-1 blocked CAR-T cells in vitro or in vivo experiments. It was found that PD-1 knockdownmight impair the anti-tumor potential of CAR-T cells because it inhibited T cells' proliferation activity. In addition, we observed that PD-1 blockade would accelerate T cells' early differentiation and prevent effector T cells from differentiating into effect memory T cells, and this might be the reason for the limited proliferation of PD-1 silenced CAR-T cells. Conclusion: These results suggest that PD-1 might play an important role in maintaining the proper proliferation and differentiation of T cells, and PD-1 silencing would impair T cells' anti-tumor function by inhibiting their proliferation activity. [ABSTRACT FROM AUTHOR]

Zoonotic influenza A viruses constantly pose a health threat to humans as novel strains occasionally emerge from the avian population to cause human infections. Many past epidemic as well as pandemic strains have originated from avian species. While most viruses are restricted to their primary hosts, zoonotic strains can sometimes arise from mutations or reassortment, leading them to acquire the capability to escape host species barrier and successfully infect a new host. Phylogenetic analyses and genetic markers are useful in tracing the origins of zoonotic infections, but there are still no effective means to identify high risk strains prior to an outbreak. Here we show that distinct host tropism protein signatures can be used to identify possible zoonotic strains in avian species which have the potential to cause human infections. We have discovered that influenza A viruses can now be classified into avian, human, or zoonotic strains based on their host tropism protein signatures. Analysis of all influenza A viruses with complete proteome using the host tropism prediction system, based on machine learning classifications of avian and human viral proteins has uncovered distinct signatures of zoonotic strains as mosaics of avian and human viral proteins. This is in contrast with typical avian or human strains where they show mostly avian or human viral proteins in their signatures respectively. Moreover, we have found that zoonotic strains from the same influenza outbreaks carry similar host tropism protein signatures characteristic of a common ancestry. Our results demonstrate that the distinct host tropism protein signature in zoonotic strains may prove useful in influenza surveillance to rapidly identify potential high risk strains circulating in avian species, which may grant us the foresight in anticipating an impending influenza outbreak.

With their unique physicochemical properties including excellent stability and biocompatibility, large specific surface area, and easy surface modification, gold nanoparticles (AuNPs) can be used as delivery vectors for drugs, genes, proteins, etc. In addition, AuNPs have excellent photothermal effects and radiosensitization characteristics, and therefore can be widely applied in the photothermal therapy and radiotherapy of cancers. This article reviews the construction, cellular uptake, and drug release of AuNPs drug-delivery systems and their applications in the treatment of tumors.

Purpose: To investigate the temporal and special expressions and functions of perlecan in dental pulp of rats after injury., Methods: Specimens of one side of maxillary molars of 24 male SD rats were collected 1,3,5,7 days after injury, and the other side were used as controls. The specimens were decalcified and embedded in paraffin, sliced by longitudinal section and stained by immunohistochemistry. The staining of perlecan and β1 integrin were examined, and the average optical density (AOD) was compared. The measurement data were analyzed by ANOVA using SPSS 19.0 software package., Results: The staining intensity of perlecan in dental pulp in the experimental group was significantly higher compared with that of the control group. The immunolocalization of perlecan in dental pulp was gradually progressed as the inflamed tissue was progressing after injury, and its AOD was significantly higher than that of control group (F=11.104,P>0.05), especially in the group of 1 d. The staining of β1 integrin was generally enhanced in the pulp 3 d after injury, and its AOD was significantly higher than that of control group (F=124.18,P>0.05)., Conclusions: Perlecan may play an important role in tissue defense mechanism after injury through regulating angiogenesis and inflammatory cell infiltration. Supported by Science and Technology Research Project of Department of Education of Zhejiang Province (20051196) and Wenzhou City (Y20100015).

Objective: To investigate the efficacy of PEG-interferon alpha (PEG-IFN alpha) treatment of HBeAg-positive chronic hepatitis B and HBV genotypes and liver tissues effect of HBeAg seroconversion., Methods: 54 cases confirmed by liver biopsy, genotype clear HBeAg positive chronic hepatitis B (CHB) patients according to body weight, respectively, subcutaneous injection of PEG-IFN-alpha2a 135 microg or 180 microg, or PEG-IFN-alpha2b 50 microg, 80 microg or 100 microg once weekly treatment for 48 weeks and followed for 24 weeks after discontinuation. Statistics of HBeAg seroconvertion, HBV genoty pes and liver histology e antigen seroconversion after the end of treatment., Results: 54 patients were followed up at the end of HBeAg seroconversion rate was 29.63% (16/54). Genotype B patients with HBeAg seroconversion rate was 35.29%, 27.03% higher than the C-type patients, but the difference was not statistically significant (chi2 = 0.382, P = 0.537). Inflammation of the liver activity highter ( > G2) , the degree of fibrosis heavier ( > S1) HBeAg seroconversion rate (50.00% vs. 25.00%, 40.90% vs. 21.88%), but were not statistically significant (chi2 = 1.391, 1.444, P = 0.238, 0.229). Activity of HBV genotype, liver inflammation, liver fibrosis and other factors by multivariate Logistic regression analysis, only liver inflammation activity of the important factors of HBeAg seroconversion., Conclusion: Important factors, liver inflammation activity of PEG-interferon alpha treatment of HBeAg-position chronic hepatitis B patients and HBV genotypes and liver fibrosis may be of little significance.

Objective: To explore the histopathological features of chronic hepatitis B virus (HBV) carriers and chronic hepatitis B (CHB) patients with mildly elevated serum alanine aminotransferase (ALT)., Methods: 105 patients were divided into three groups according to serum ALT levels: Group A [ALT level < or = 0.5 x upper limits of normal (ULN)], Group B (0.5 x ULN < ALT level < or = 1 x ULN) and Group C(1 x ULN < ALT level < 2 x ULN). Grade of liver inflammation and stage of liver fibrosis in the three groups were compared. The changes in clinical parameters were then observed in patients who had liver histopathological changes., Results: Among 40.95% of the patients, hepatitis degree went to G2 or even worse; and among 30.43% of the patients whose ALT level were normal, the hepatitis degree reached G2 or even worse. In 26.67% of the patients, degree of fibrosis went to S2 or even worse, and for the 17.39% patients whose ALT level were normal, degree of fibrosis went to S2 or even worse. The aggravation of liver inflammation and fibrosis was correlated with ALT and hyaluronic acid increasing (all P < 0.05)., Conclusions: Frequent monitoring of serum ALT and hyaluronic acid may help to understand histopathological changes in the liver. Liver biopsy applied to CHB should be regarded as a main basis if antiviral therapy should be conducted.

Objective: To investigate the relationship between serum HBV DNA loads and liver histology damage in the patients with HBeAg-negative chronic hepatitis B., Methods: The retrospective study was performed. The 514 patients were divided into two groups according to the HBeAg status and the HBeAg positive group was as control. The relationship among HBV DNA loads, live histological inflammation grades and fibrosis stages was analyzed., Results: The HBV DNA loads in HBeAg-negative group and HBeAg-positive group were (5.38 +/- 1.27) log10 copies/ml and (6.80 +/- 1.18) log10 copies/ml respectively (P < 0.001). The inflammation grades and fibrosis stages of liver tissues in HBeAg-negative group were all significantly higher than those in HBeAg-positive group (P < 0.001). In HBeAg-negative group, HBV DNA loads displayed a positive correlation with the inflammation grades and fibrosis stages of liver tissues (P < 0.001)., Conclusion: In the patients with HBeAg-negative chronic hepatitis B, HBV viral loads are lower than those with HBeAg-positive chronic hepatitis B, and HBV viral loads display a positive correlation with liver the inflammation grades and fibrosis stages of liver tissues.

Objective: The objective of this study is to investigate the influence of mechanical properties and sintering performance by adding 5% weight percentage aids to nano-compound zirconia toughened alumina (ZTA) ceramics., Methods: Micrometer Al2O3 and nanometer ZrO2 (quality ratio 4:1) were used to get 55% volume percentage slurry. Magnesium oxide and titanium oxide were taken as aids which were 5% weight percentage of the Al2O3 and ZrO2 powder. Five groups (number 0, 1, 2, 3, 4 group) were divided according to different proportion of aids. After gel-casting, the porcelain pieces were sintered at 1150, 1200, 1300, 1400, 1450, 1500, 1600 degrees C for 2 hours. Static three-point flexure strength, line shrinkage, relative density were measured and scanning electron microscopy (SEM) was used to observe section., Results: Number 1 (MgO 1%, TiO2 4%) group had the highest bending strength. It was (401.78+/-19.50) MPa after sintering at 1600 degrees C for 2 hours and was higher than 0 group (380.64+/-44.50) MPa. Bending strength became lower than 0 group when MgO was more than 2% or more than that weight percentage of ZTA powder. When MgO content was higher than 2% or more than that weight percentage, there was no difference in relative density raising rate between each sintering assistants groups. When the sintering temperature was higher than 1200 degrees C, all groups showed obvious line-shrinkage and the groups which contained sintering assistants were all was higher than 0 group., Conclusion: Adding MgO and TiO2 aids from 1% to 4% weight percentage of ZTA will promote fritting and increase ZTA nano-compound ceramics mechanical properties. Adding 2% MgO aids or more than that weight percent will has no obvious help to increase the relative density raising rate of ZTA nano-compound ceramics and will degrade the mechanical properties of ZTA nano-compound ceramics.

Purpose: The aim of the present investigation is to evaluate the effects of fluid shear stress on the cells of osteoblasts and to determine the mechanisms involved., Methods: The fluid shear stress with a magnitude of 0 (control group), 0.6, 1.0, 2.0, 3.0, 4.0, 5.0 Pa was exerted on the third passage of osteoblasts for 1 hour,and incubation in static condition for 24 hours. The cell apoptotic index was tested by the terminal transferase dUTP nick end-labeling(TUNEL) method. The expression of bcl-2 ,Bax and caspase-3 were detected by immunohistochemical method. Statistical analysis was performed using SPSS11.5 software package for one-way ANOVA., Results: The apoptosis of osteoblasts and the expression of bcl-2, Caspase-3 were not affected significantly by the fluid shear stress with a magnitude from 0 to 2.0 Pa(P>0.05) . But in the 3.0,4.0 and 5.0 Pa groups, the number of apoptotic cells and the expression of caspase-3 increased while the expression of bcl-2 decreased(P<0.05).There was no significant difference in expression of Bax in all groups., Conclusions: The physiological fluid shear stress does not affect apoptosis of osteoblasts. However,the fluid shear stress of over-magnitude may lead to the decrease the expression of bcl-2,which results in activation of caspase-3 and apoptosis of osteoblasts. Supported by Research Grant from Zhejiang Provincial Education Committee(Grant No.20061823).

Objective: To compare therapeutic effects of auricular point sticking combined with Tongshiji treatment and simple Tongshiji treatment on child ametropic amblyopia., Methods: Three hundred children of ametropic amblyopia were classified as mild, moderate and severe groups, 100 cases in each group. The each group was again randomly divided into a simple Tongshiji treatment (control group) and a auricular point sticking combined with Tongshiji treatment group (observation group). Their therapeutic effects were compared., Results: The total effective rate in the observation group were 100.0%, 79.8% and 71.0%, and in the control group were 100.0%, 54.3% and 48.2% respectivety for mild, moderate and severe groups. For the mild amblyopia children, there was no significant difference between the two groups in the therapeutic effect; for the moderate and severe ametropic amblyopia children, the therapeutic effect in the observation group was better than that in the control group (P<0.05)., Conclusion: Auricular point sticking combined with Tongshiji treatment for child ametropic amblyopia is of characteristics of convenient manipulation, obvious and rapid therapeutic effect.