Objective Cytotoxic T lymphocytes are the main effector cells of anti-tumor immunity. Active targeting of nanoparticles to T cells and activation of T cells can be achieved by conjugation with specific antibodies. We prepared the biotin-grafted pullulan acetate nanoparticles conjugated with CD3 (Bio-PA-CD3 NPs), and explored their effects on the proliferation, cytokine secretion and uptake of CD8+T cells.Methods We prepared Bio-PA NPs by the dialysis method, conjugated CD3 antibodies to the surface of NPs to make Bio-PA-CD3 NPs, and measured the diameter and Zeta potential of the NPs. We evaluated the effects of the NPs on the proliferation of CD8+T cells and the secretion of cytokines by CCK-8 assay and ELISA, respectively, and quantitatively analyzed the cellular uptakes of the Bio-PA-CD3 NPs by the flow cytometry.Results The Bio-PA-CD3 NPs exhibited regular spherical shapes of even size and with no adhesion. The content of CD3 antibodies on the surface of the NPs decreased with the increased degree of biotin substitution. The CD3 contents of the Bio-PA-CD3 NPs with biotin substitution degrees of 1.6%, 5.4% and 6.3% were (36.1±4.4), (21.4±4.3) and (10.3±4.7) μg/mg, respectively. Compared with Bio-PA NPs, Bio-PA-CD3 NPs at a certain concentration significantly enhanced the proliferation of CD8+T cells in vitro and promoted the secretion of IFN-γ, TNF-β and IL-2 cytokines. The Bio-PA-CD3 NPs manifested a higher cellular uptake with the increased content of CD3 antibodies.Conclusion The Bio-PA-CD3 NPs we prepared could be a promising agent to enhance the immune effect of T cells.

Objective To evaluate the population health for disease prevention and control in Shanghai Minhang District of Shanghai the data of mortality from 1993 to 2015 and communicable diseases from 2002 to 2015.Methods We adopted descriptive epidemiological method to analyze the trends of average life expectancy (ALE),specific death rate and causes of death cis-position from 1993 to 2015,and the incident rates of communicable diseases,incidence trends in Minhang District from 2002 to 2015.Results Overall,the ALE of population in Minhang District increased 11.80 years from 1993 to 2015 (from 71.78 years in 1993 to 83.58 years in 2015),including the ALE of male population increased 14.03 years (from 67.43 years in 1993 to 81.37 years in 2015) and the ALE of female population elevated 9.67 years (from 76.22 years in 1993 to 85.89 years in 2015).In 2015,Crude death rate (CDR) was 755.35/105,which was 21.45％ higher than in 1993 and 2.71％ higher than in 2014,respectively.In the same year,standardized mortality rate (SMR) was 196.07/105,which was 54.17％ lower than in 1993 and 0.51％ lower than in 2014.The top five leading causes of death were circulatory system diseases,tumors,respiratory diseases,endocrine and metabolic diseases,and injury and poisoning,which contributed 91.33％ of the population death.From 2002 to 2015,a total of 23 kinds of notifiable infectious diseases were reported in Minhang District,including 62 845 cumulative cases and 152 cases died.The total reported incidence rate of communicable diseases sharply elevated by 291.98％ during 14 years (Z=10 943.83,P＜0.001),and it increased after standardized.The top five communicable diseases were hand foot and mouth disease (HFMD),scarlet fever,syphilis,tuberculosis and hepatitis B in 2015.Conclusions Over the years,Minhang District of Shanghai comprehensive implemented "health in all policies" by integrating the resources of all levels of regional healthcare institutions.The ALE of the residents was at a high level.The control and prevention of chronic non-communicable diseases and major communicable diseases will continue to be the priority of public health.

In order to obtain the lead compound for treatment of rheumatoid arthritis (RA), in this study, therapeutic efficacy of three bispecific antibodies (BsAB-1, BsAB-2 and BsAB-3) against both hIL-1beta and hIL-17 were compared on CIA model mice. First, by ELISA method we compared the binding capacity of the three bispecific antibodies to the two antigens. The results showed that all three antibodies could simultaneously bind both antigens, among these antibodies, BsAB-1 was superior over BsAB-2 and BsAB-3. CIA model was established with chicken type II collagen (CII) and developed RA-like symptoms such as ankle swelling, skin tight, hind foot skin hyperemia. The CIA mice were treated with three antibodies once every two days for total of 29 days. Compared with the CIA model mice, the RA-like symptoms of the antibody treated-mice significantly relieved, while the BsAB-1 treated-mice were almost recovered. CII antibody level in the serum and cytokines (IL-2, IL-1beta, IL-17A and TNF-alpha) expression in the spleen were examined. Compared with the CIA model mice, all three antibodies could significantly reduce CII antibody and cytokine expression levels. BsAB-1 antibody was more potent than BsAB-2 and BsAB-3. In summary, BsAB-1 is superior over BsAB-2 and BsAB-3 in amelioration of RA symptoms and regulation of CII antibody production and pro-inflammatory cytokine expression, therefore, BsAB-1 can be chosen as a lead compound for further development of drug candidate for treatment of RA.
Animals ; Antibodies ; metabolism ; Antibodies, Bispecific ; immunology ; therapeutic use ; Antigen-Antibody Reactions ; Arthritis, Experimental ; chemically induced ; metabolism ; therapy ; Arthritis, Rheumatoid ; chemically induced ; metabolism ; therapy ; Collagen Type II ; immunology ; Interleukin-17 ; metabolism ; Interleukin-1beta ; metabolism ; Interleukin-2 ; metabolism ; Male ; Mice ; Spleen ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

Objective To construct luciferase reporter vector containing full-length high-mobility group box 1 ( HMGB1, GenBank NM-010439) promoter for the screening of medicine. Methods The full-length HMGB1 promoter was amplified by polymerase chain reaction ( PCR) , and then was inserted into GV238 vector to construct plasmid GV238-HMGB1-P-Luc. GV238-HMGB1-P-Luc combined with internal reference plasmid pRL was co-transfected into Hela cells ( GV238-HMGB1-P-Luc group, which served as positive control group) . Plasmid pGL3-basic combined with pRL was co-transfected into Hela cells (pGL3-basic group, which served as negative control group) . Additionally, lipopolysaccharides ( LPS, 0.2 μg/mL) was used as the activator for the positive control group (LPS group), and then sodium butyrate (SB, 10 mmol/L) was used as the inhibitor for LPS group ( SB group) . At the end of experiment hour 24, luciferase activity was detected. Results The results of digestion, amplification, sequencing and identification showed that the full length of HMGB1 promoter was 2 140 bp, and the DNA sequence was correct, without mutation. Luciferase activity in GV238-HMGB1-P-Luc group was increased as compared with that of the pGL3-basic group ( P<0.05) . Luciferase activity in the LPS group was increased ( P<0.01, compared with that of GV238-HMGB1-P-Luc group) , and then was decreased after the administration of SB ( P<0.01, compared with that of the LPS group) . Conclusion A model of luciferase reporter vector containing HMGB1 promoter has been successfully constructed. Its activity can be increased by LPS, and then is in hibited by SB. The model can be used for further screening of medicine with the activities of regulating HMGB1 promoter.

OBJECTIVETo evaluate the efficacy and safety of entecavir maleate (ETV) versus ETV in Chinese patients with hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB).

METHODSThe patient population of this previously published randomized, double-blind, double-dummy, controlled, multicenter study was expanded by patients in the 0.5 mg/day ETV maleate group (total n = 110) and patients in the 0.5 mg/day ETV group (total n = 108). At treatment weeks 12, 24 and 48, hepatitis B virus (HBV) DNA levels were measured by the Roche Cobas Ampliprep/Cobas Taqman PCR assay. Adverse events (AE) were recorded.

RESULTSAs in the original analysis, the two treatment groups showed similar characteristics at baseline. In addition, the results for the all therapeutic effects showed identical trends to the results obtained in the original analysis, including the statistically similar effects of ETV and ETV maleate treatment-induced decreases in mean HBV DNA level at weeks 12, 24, and 48 (ETV: by 4.28, 5.00, and 5.53 log10 IU/ml vs. ETV maleate: by 4.46, 4.99, and 5.51 log10 IU/ml, respectively; all vs. baseline P more than 0.05), achievement of undetectable levels of serum HBV DNA ( less than 20 IU/ml) at week 48 (ETV: 38.18% vs. ETV maleate: 35.19%; P more than 0.05), HBeAg loss rates at week 48 (ETV: 10.91% vs. ETV maleate: 12.96%; P more than 0.05), HBeAg seroconversion rates at week 48 (ETV: 7.77% vs. ETV maleate: 10.38%; P more than 0.05), normalization of alanine aminotransferase at week 48 (ETV: 75.47% vs. ETV maleate: 82.86%; P more than 0.05), and overall incidence of AE (ETV: 18.02% vs. ETV maleate: 17.43%; P more than 0.05).

CONCLUSIONPerforming analysis of the therapeutic efficacies of entecavir maleate versus entecavir with a larger study population confirmed our original findings of similar efficacy and safety profiles for these two drugs in patients with HBeAg-positive CHB.

Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Double-Blind Method ; Female ; Guanine ; adverse effects ; analogs & derivatives ; therapeutic use ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Male ; Treatment Outcome ; Young Adult

BACKGROUNDIn-stent restenosis (ISR) has become one of the most challenging problems in patients with coronary heart disease. At present, using non-invasive methods to assess ISR is a hot topic. In this investigation we attempted to explore the potential of magnetocardiography (MCG) in diagnosis of in-stent restenosis.

METHODSMCG was analyzed in 52 patients with coronary artery disease for three times: before stenting, one month and 7 months after successful intracoronary stenting.

RESULTSThe average classification of total maps (ACTM) and the ratio of abnormal maps (RAM) were lower in 1 month after intracoronary stenting compared with that obtained before stent planting (2.91 vs 2.52, 65.74% vs 42.80%, P < 0.01), while complex ventricular excitation index (CVEI) increased from -42.63 to -20.05 (P < 0.01). In ISR subgroup (n = 16), RAM decreased in 1 month after intracoronary stenting compared to it before stenting (68.99% vs 45.26%, P < 0.05). ACTM increased in 7 months compared to that obtained in 1 month after stenting (3.15 vs 2.51, P < 0.05). According to the ROC curve, ACTM showed its unique diagnostic value in restenosis patients. The sensitivity and specificity of ACTM were 80.0%, 69.40%, respectively. Its positive predictive value and negative predictive value were 54.6% and 88.5%, respectively.

CONCLUSIONSAfter successful intracoronary stenting, most parameters of MCG were improved. ACTM was of prognostic value in diagnosing ISR.

Adult ; Aged ; Angioplasty, Balloon, Coronary ; Coronary Artery Disease ; diagnosis ; Coronary Restenosis ; diagnosis ; Female ; Humans ; Magnetocardiography ; methods ; Male ; Middle Aged ; Stents ; adverse effects

OBJECTIVETo explore the impacts of denervation on the morphology and the expression of neuronal nitric oxide synthase (nNOS) of prostate of the adolescent rats.

METHODSAdolescent male SD rats were randomly divided into group A and group B. The right pelvic ganglion denervation was performed in group B with the help of surgical microscope, and group A received a sham operation. Five weeks later, the ventral prostates were obtained for morphologic observation, apoptosis detection and the evaluation of nNOS expression.

RESULTSA 30.8% reduction of right ventral prostate (RVP) fresh weight was found in group B. After denervation, histological features showed an overall decrease in the numbers of cells and cell height, and apoptosis indexes (AI) was significantly higher than that in group A (P <0.01), while the expression of nNOS decreased apparently (P < 0.01).

CONCLUSIONThe study indicates that denervation can cause apoptosis of the prostatic, and affect the prostate growth of the adolescent rat. During this process, nNOS plays an important role in the regulation of apoptosis.

Animals ; Apoptosis ; Denervation ; In Situ Nick-End Labeling ; Male ; Nitric Oxide Synthase Type I ; biosynthesis ; Prostate ; cytology ; innervation ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sexual Maturation

OBJECTIVETo investigate the magnetocardiography (MCG) changes in coronary artery disease (CAD) patients with normal or unspecific changes in resting electrocardiogram (ECG).

METHODSMCG mapping was performed by MCG-7 (MaGIC, Magiscan GmbH) installed in an unshielded room. All patients underwent ECG and coronary angiogram examinations and patients with normal or unspecified ECG changes and coronary artery narrowing > or = 70% in at least 1-vessel were defined as CAD group (n = 120). Patients with normal coronary angiogram served as control (n = 82). Four parameters: ACTM (average classification of total maps), RAM (ratio of abnormal maps), CVEI (complex ventricular excitation index) and R-max/T-max ratio, were analyzed in CAD and control groups.

RESULTSRAM (62% vs. 35%) and ACTM (2.62 +/- 0.98 vs. 2.29 +/- 0.90, P < 0.05) were significantly higher in CAD group than in control group. CVEI was found in abnormal zone (-100 - 0) in CAD group while in normal zone (0 - 100) in control group. The ratio of Rmax/Tmax in CAD group was also significantly higher in CAD group than in control group (6.41 +/- 3.29 vs. 4.10 +/- 2.00, P < 0.01). ROC curve analysis indicates that RAM, CVEI and Rmax/Tmax ratio were helpful parameters for CAD diagnosis and the diagnostic sensitivity was 67.1%, 65.9% and 64.3%; the specificity was 65.1%, 68.3% and 68.3% respectively.

CONCLUSIONMCG was a useful tool for diagnosing chronic myocardium ischemia in CAD patients with normal or unspecific changes resting ECG.

Adult ; Aged ; Aged, 80 and over ; Coronary Angiography ; Coronary Artery Disease ; diagnosis ; Electrocardiography ; Female ; Humans ; Magnetocardiography ; Male ; Middle Aged ; Sensitivity and Specificity

OBJECTIVETo investigate the effect of gene Af116609 on gastric cancer multi-drug resistance (MDR) by introducing it into gastric cancer multi-drug resistant (MDR) cell line SGC7901/VCR.

METHODSGene Af116609 was cloned from SGC7901/VCR by RT-PCR and its differential expression between gastric cancer MDR cells and its parental cells was displayed by Northern blot. The gene was introduced to gastric cancer cells by transfection of recombinant eukaryotic expression vector by electroporation. MTT assay in vitro was applied to investigate its effect on multi-drug resistance phenotype of gastric cancer cells.

RESULTSThe full length CDS of gene Af116609, as long as 327 bp, was cloned from gastric cancer MDR cell line SGC7901/VCR and its sequence was coincident with the hypothetical gene Af116609 in GenBank. It was overexpressed in MDR cells than its parental cells at mRNA level. In the MTT assay in vitro, the drug sensitive cells transfected with sense eukaryotic expression vector showed upregulated targeted gene, with increased resistance to vincristine, 5-fliorouracil and arabinoside, and decreased resistance to adriamycin, but no influence on resistance to methotrexate. However, the drug resistant cells transfected with anti-sense eukaryotic expression vector, showed down regulated targeted gene, with less resistance to all the five anticancer drugs to different degrees.

CONCLUSIONGene Af116609 is related to MDR phenotype of gastric cancer cells and may become a candidate molecular target to reverse the MDR of gastric cancer.

Antineoplastic Agents, Phytogenic ; pharmacology ; Autoantigens ; genetics ; Cell Line, Tumor ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Humans ; RNA, Small Cytoplasmic ; genetics ; Ribonucleoproteins ; genetics ; Stomach Neoplasms ; genetics ; pathology ; Vascular Endothelial Growth Factor A ; biosynthesis ; Vincristine ; pharmacology

OBJECTIVETo explore the role of macrophage colony-stimulating factor (MCSF) in the pathogenesis of preeclampsia.

METHODSBy ELISA method, MCSF concentrations were determined in serum samples obtained from 39 patients with preeclampsia and 40 normal pregnant women as controls. The concentrations of serum MCSF were compared between preeclampsia and normal pregnancy, and between early-onset and late-onset preeclampsia.

RESULTSerum MCSF concentrations were significantly higher in preeclamptic women than those in controls (431.0 kIU compared with 179.1 kIU, P<0.001). There were no significant differences in serum MCSF levels between early-onset and late-onset preeclampsia (P>0.05). Serum MCSF was not correlated with maternal age, gestational age, and placenta weight (P>0.05 for all).

CONCLUSIONIncreased level of serum MCSF is an important indicator of preeclampsia and it may play a role in the pathogenesis of the disease.

Adult ; Female ; Humans ; Macrophage Colony-Stimulating Factor ; blood ; Pre-Eclampsia ; blood ; etiology ; Pregnancy