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Chronic hepatitis B (CHB) virus infection is a global health problem. Finding a cure for CHB remains a challenging task.In this study, poly I:C was employed as an adjuvant for HBV therapeutic vaccine (referred to as pHBV-vaccine) and the feasibility and efficiency of pHBV-vaccine in CHB treatment were evaluated in HBV-carrier mice.We found that pHBV-vaccine decreased HBsAg and HBV DNA efficiently and safely in HBV-carrier mice. Further investigation showed that pHBV-vaccine promoted maturation and antigen presentation ability of dendritic cells in vivo and in vitro. This vaccine successfully restored the exhaustion of antigen-specific CD8Findings from this study provide a new basis for the development of therapeutic pHBV-vaccine, which might be a potential candidate for clinical CHB therapy.

The framework of simulating experiment based on a real-time platform has been built by using DDS protocol. To realize the whole process simulation model integration and deduction of target detection, tracking, identification, interception and data communication of ballistic missile defense system, the communication control, system control and human-computer interaction mode based on real time network platform have been implemented in this paper. The simulation framework can effectively integrate all kinds of physical, semi physical and mathematical simulation models, and is compatible and extended.

With the rapid development of higher education, students copying work is becoming increasingly serious.The purpose of this paper is:first, geting the count and frequency of attribute used in program, and second using Chi-square test method to get the similarity between programs. This method has very good results for teachers to detect plagiarism.

This paper used software Solidworks to build 3-D model of a certain Heavy Vehicle Part, then analyzed the model strain state under typical operation condition by ANSYS. The simulation of the part provides the basis for the structural design.

This article addresses design of ROPS model with energy absorption structure based on dimensions of cross section, characteristics of force and deformation pattern of ROPS. Optimum design parameters have been obtained from optimized analysis of multiple-objective structural crashworthiness of thin-walled straight square tube subject to deformation due to pore defect using a combination of finite element analysis, design of experiment, response surface methodology and generic algorithm.

Power control in large wind farm has a big impact on the Grid, especially in low connectivity ratio. Publish subscribe technology is asynchronous loosely coupled, and multi-to-multipoint communication as adapted for large distributed real-time control of network communications needs in the wind farm. This paper presents publish subscribe-based real-time power command-delivery method. It is well used to deliver the control of wind farm, reducing the time-delay in control loops. Simulation results show that the method further improves the quality of the power control of common coupling in large wind farms.

This article addresses the design of ROPS model with energy absorbing structure based on dimensions of cross-section, mechanic properties and deformation pattern of ROPS. Afterwards, optimized buffer and energy-absorbing elements are installed on hexastyle ROPS of certain loader where roll-over accident can be simulated. Results indicate such structure can offer significantly improved protection. Installation of buffer and energy absorbing elements will not only absorb vast amount of motion during roll-over, but also will reduce deformation to ROPS. This has well coordinated the conflict between required rigidity and energy absorbing.

N(3)-o-toluyl-fluorouracil (TFU), the pro-drug of 5-fluorouracil (5-FU), is the metabolite of N(1)-acetyl-N(3)-o-toluyl-fluorouracil (atofluding). We aimed to evaluate the efficacy of TFU as a precursor of 5-FU on the growth inhibition of human gastric carcinoma cell lines SGC-7901 and MKN-45. Growth of SGC-7901 and MKN-45 cells was remarkably suppressed by treatment with TFU in the presence of liver microsomal enzymes in vitro, suggesting that TFU may be converted to 5-FU by the enzymes. Similar treatment of TFU induced apoptosis of the cells, which was deduced from typical apoptotic features such as morphology, the formation of characteristic ladder pattern of DNA migration and the accumulation of sub-G1 phase. Cancer cells xenografts in nude mice were employed to evaluate the efficacy of TFU in vivo. Growth of human gastric carcinoma cells was significantly delayed by oral administration of TFU with low side effects. Apoptosis in xenografts was also observed by means of TUNEL staining method. These results suggest that the treatment of TFU in the presence of liver microsomal enzymes and the oral administration of TFU in mice induced anti-proliferation and apoptosis in gastric carcinoma cells. This suggests that TFU may be a promising pro-drug of 5-FU for cancer treatments.

Objective: To detect the modulation of cytokines production by acute promyelocytic leukemia (APL) cells before or after exposure to all-trans retinoic acid (ATRA). Methods: Diagnoses were performed according to the FAB cytological classification criteria and cytogenetic criteria. Bone marrow or blood samples from APL patients were collected in heparinized microfuge tube. Primary APL cells were separated and purified by traditional Ficoll-Hypaque density centrifugation and enriched after adherence to plastic surfaces. IL-1β, IL-6, IL-8, TNFα and G-CSF levels in the supernatants of cultured leukemia cells were estimated by ELISA method. NBT method was used to detect the differentiation of APL cells at the same time. Results: 96 h after exposure to ATRA at 10−6 M in vitro or 60 mg/day in vivo, APL cells showed a significant increase of IL-1β (P

Objective: To detect the minimal residual diseases (MRD) in acute promyelocytic leukemia (APL) after complete remission (CR) and to analyze its clinical value in prognosis. Methods: Reverse transcription Polymerase chain reaction (RT/PCR) was used to detect MRD of patients with APL. Results: MRD positive rate in patients with APL was 92.8% (39/42) before treatment and 56.7 (21/37) immediately after the ATRA or chemotherapy-induced CR. Furthermore, MRD positive rate was related to the relapse in APL patients and could be considered as a marker to predict the relapse of patients with APL after CR. The MRD detection could also be applied to direct the consolidation therapy to prevent relapses. Conclusion: RT-PCR is valuable to monitor MRD and can be used as a marker to predict relapses.

Lym-2 is a murine monoclonal antibody (MoAb) directed towards a human class II molecule variant reactive with both normal and neoplastic human B lymphocytes. Previous studies have shown that signals transmitted by class II molecules that stimulate normal lymphocytes can be inhibitory for B-cell lymphoma growth by signaling activation-induced cell death. Therefore, we sought to evaluate the effects of nonconjugated murine Lym-2 and a human-mouse chimeric Lym-2 (chCLL-1; with murine variable regions and human constant regions) MoAb on the growth of various human lymphomas by using both in vitro and in vivo assays. Cell lines derived from Burkitt's lymphomas, diffuse large cell B-cell lymphomas, anaplastic large-cell lymphomas, and Epstein-Barr virus–induced B-cell lymphomas were incubated with Lym-2 or chCLL-1 in vitro, and effects on proliferation were determined by [3H]-thymidine incorporation. The effects of Lym-2 in vitro were also compared with those of Lym-1, which is a similar MoAb that has been evaluated clinically. After immobilization, which enhances crosslinking of the MoAbs, both Lym-2 and chCLL-1 were capable of directly inhibiting the growth of various lymphoma lines in vitro. These human lymphomas were then transferred into mice with severe combined immunodeficiency to evaluate the efficacy of these MoAbs in vivo. Treatment with either murine Lym-2 or the chimeric chCLL-1 were significantly effective in improving the survival of tumor-bearing mice. These results indicate that stimulation by nonconjugated chCLL-1 may offer a biological approach to the treatment of various human lymphomas.

Point of common coupling voltage control in large wind farm is a big impact on the Grid, especially under low-connectivity environments. Publish subscribe technology is asynchronous, loosely coupling, and multi-to-multi communication, adapted to large scale distributed real-time control of the communications needs of the wind farm. This paper proposed a publish / subscribe-based real time reactive power control of transmission method. It is well used to supply the control board in the town of wind, reducing the time delay of control loops. Simulation results show that the method further improves the quality of the point of common coupling voltage control in large wind farms.

Worldwide, about 25% of individuals with chronic hepatitis B have fatty liver disease. Lipogenic diets that are completely devoid of methionine and choline induce nonalcoholic fatty liver disease. However, no animal model of nonalcoholic steatohepatitis associated with HBV infection is available, and the influence of viral infection on nutritional hepatic steatosis is unclear.We used HBV surface antigen transgenic mice (HBs-Tg mice), which mimic healthy human carriers with hepatitis B surface antigen. The mice were fed with a high-fat methionine-choline-deficient diet (MCD) to build a reliable rodent nutritional model of nonalcoholic steatohepatitis associated with HBV infection, and the changes in body weight and serum triglycerides were measured. Hepatocyte ballooning changes were determined by hematoxylin and eosin staining. The extent of hepatic fat accumulation was evaluated by oil red O staining. Immunohistochemical assays were performed to detect proliferating cell nuclear antigen as an index of cell proliferation.MCD feeding provoked systemic weight loss and liver injury. MCD feeding caused more macrovesicular fat droplets and fat accumulation in the livers of HBs-Tg mice than in wild-type C57BL/6 mice. In addition, within 30 days of MCD exposure, more PCNA-positive nuclei were found in the livers of HBs-Tg mice.HBs-Tg mice fed with a lipogenic MCD form more macrovesicular fat droplets earlier, coincident with more hepatocyte proliferation, resulting in the appearance of increased susceptibility to experimental steatohepatitis in these mice.

To evaluate the therapeutic effect of subcutaneous tunnel hepaticoplasty on the treatment of hepatolithiasis.The early complications and clinical effects of 99 hepatolithiasis cases who underwent subcutaneous tunnel hepaticoplasty from January 1993 to August 2006 were analyzed retrospectively. The stones of 28 (28.3%) patients were in the left lobe, 24.2% (24/99) in the right, and 47.5% (47/99) in bilateral lobe. Sixty-six patients (66.7%) had both stones and biliary strictures. During the procedure, a portion of the liver habouring stone was resected if necessary. The hepatic duct and strictures were opened, the stones were removed, and the porta hepatis was repaired by one end of a segment of jejunum. The other end of the jejunum was set subcutaneously. The gall bladders of 27 patients (27.3%) were used as subcutaneous tunnel instead.Ninety-five out of ninety-nine cases were followed up with an average of 4.2 years (1 month to 13.5 years). The rates of residual stone, recurrent stone and cholangitis were 23.2% (23/99), 20.0% (19/95) and 14.7% (14/95) respectively. Postoperatively, 34 cases who had residual or recurrent stones were underwent lithotomy by choledochoscope through the subcutaneous blind loop and the achievement ratio was 91.2% (31/34).Subcutaneous tunnel hepatocholangioplasty decreases the relapsing cholangitis effectively, and makes an easy way to take out residual or recurrent stones.

Lymphocyte function associated antigen-1 (CD11a/CD18, LFA-1) plays an important role in the structure of the immunological synapse and is required for efficient lysis of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. To study the activation mode of LFA-1 on the NK cell surface, optical tweezers were used in the work. As an emerging technology, optical tweezers are widely used to manipulate microscopic objects and measure the forces of molecular interactions in the field of biological research. In our study, a new platform was constructed to study the single molecular behavior of receptor on cell surface using optical tweezers. Based on the platform, the interaction between an NK cell and a polystyrene microsphere coated with anti-LFA-1 antibody was observed. The result confirmed that the adhesion forces between an NK cell and a polystyrene bead were time-dependent. According to our findings, we propose that anti-LFA-1 antibody may cause the clustering of LFA-1 on NK cell surface.

To study the anti-melanoma immunity efficacy of Ag85B antigen gene therapy in vivo.C57BL/6 mice were inoculated s.c. with B16 cells, and 8 days later the mice were inoculated s.c. again with B16 cells (control group 1), B16/pcDNA3 cells (control group 2) or B16/pcDNA3-Ag85B cells (experimental group), respectively. Tumor volume, survival time, serum IFN-gamma level and IL-4 level of 3 groups mice were observed. Antitumor activity of Ag85B was studied.From 12 to 23 day, the mean tumor volume of mice increased from 1.1058 cm(3) and 0.9123 cm(3) to 7.5983 cm(3) and 5.8746 cm(3) in the control group 1 and 2, respectively. But it increased from 0.5158 cm(3) to 1.5080 cm(3) in the experimental group. The mean survival time of mice was 24.1 days and 24.7 days in the control group 1 and 2, respectively. That was 27.8 days in the experimental group. Within 13 days after the last inoculation, the serum IFN-gamma level of all groups experienced increased (That increased to 26.3 ng/L, 23.0 ng/L and 25.2 ng/L in the control group 1, 2 and the experimental group, respectively). Subsequently, the serum IFN-gamma level in the two control groups decreased (That decreased to 19.3 ng/L and 18.3 ng/L in the control group 1 and 2) while it still augmented in the experimental group (That increased to 46.5 ng/L). IL-4 level was slightly but not significantly enhanced and then declined in all mice.Ag85B induced the increase of serum IFN-gamma level in the animals experiments, inhibited the tumor growth and prolonged the survival of the tumor-bearing mice.

Interleukin 12 (IL-12) and/or interleukin 18 (IL-18) gene ablated mice were applied for the investigation of the tissue expression of interferon gamma (IFN-gamma). For IL-12(-/-), IL-18(-/-), IL-12(-/-)/18(-/-) and wt mice, reproductive performance were recorded and IFN-gamma concentrations in heart, lung, liver, spleen, kidney and serum were quantified by ELISA. There were no significant differences of IFN-gamma in heart, lung and kidney between 4 strains although control group was higher. It was observed that for IL-12(-/-) mice, compared with other 3 groups, IFN-gamma in liver and spleen were decreased (p0.05) and reproductive performance appeared to be impaired. Serum IFN-gamma level of IL-12(-/-)/18(-/-) mice was significantly higher (p0.05). It was showed that IFN-gamma productions under the normal condition were independent upon IL-12 and IL-18, its expressions in various tissues were different, and optimal IFN-gamma is necessary for the normal growth and development of mammals. This study is helpful for clinical cytokines therapy.

To study the cytotoxic activity of NK-92 cells irradiated against human ovarian cancer.NK-92 cells were exposed to different doses of radiation and assayed for proliferation by a standard (3)H-thymidine incorporation assay and cell count by using trypan blue exclusion. The cytotoxic activity of NK-92 cells against targets was measured in a standard (51)Cr-release assay in vitro. The effectiveness of irradiated NK-92 cells on ovarian cancer was compared with the control group of cancers (without injection of irradiated NK-92 cells).(1) In vitro:The proliferation of NK-92 cells was inhibited by radiation of 4, 8 and 16 Gy, respectively. From the (3)H-thymidine incorporation data, irradiation by 4 Gy reduced cell proliferation to 29% of control, while 8 Gy reduced proliferation to 6%. The cytotoxicity of NK-92 cells at 4 Gy 2 days following irradiation was approximately 42%-62% for ovarian cancer cell HO-8910, while it was 33%-58% at 8 Gy. (2) In vivo: Tumor size in treatment group was (0.047 +/- 0.019) cm(3) on day 30 after inoculation, and (0.167 +/- 0.021) cm(3) on day 40 and (0.343 +/- 0.022) cm(3) on day 50, while the sizes were smaller in treatment group (P0.01). In addition, the tumor group animals died between 74-82 days after injection of HO-8910 cells, while the treatment group animals were alive over 120 days (P0.01).Our study indicates that injection of irradiated NK-92 cells may be a potentially effective treatment for human ovarian carcinoma.

To investigate the regulatory effect of IFN-gamma on recognition of target cells by human natural killer (NK) cells.The cytotoxic activity of human NK cell lines (NK92, NKL) was detected by MTT method. Expression of NK cell receptors (NKG2D, NKG2A/B, KIR2DL1 and KIR2DS1) and MICA on target cells (the ligand of NKG2D) was measured by RT-PCR.Both NK92 and NKL cells exerted higher cytotoxicity to tumor cells with MICA expression, while tumors without MICA expression could resist NK cell lysis. IFN-gamma (1000 U/ml) inhibited NK lysis of tumor cells with MICA expression through down-regulating the expression of NKG2D, but up-regulating the expression of NKG2A/B and KIR2DL1.IFN-gamma has a negative effect on activation and cytotoxicity of human NK cells by altering the balance between the expression of activating and inhibitory receptors on NK cells in favor of inhibition. This may serve to limit NK cell over-activation in vivo.

In this research, the regulatory effects of T-lymphocytes on the expansion of hematopoietic cells in human bone marrow were studied. Anti-CD3 McAb and anti-CD8 McAb were used to eliminate the T-lymphocytes in bone marrow MNCs. Cell surface antigens were analysed by flow cytometry. Hematopoietic cells expanded with hematopoietic growth factors (HGFs) in a liquid culture system and the number of CD34(+) cell, CFU-GM and CFU-GEMM were determined. After cultured with HGFs for 20 days the total number of cells expanded by 75.8, 79.6, 77.4 and 67.0 folds respectively in three experimental groups (anti-CD3 McAb, anti-CD8 McAb and anti-CD3 + anti-CD8 McAb) and control group (MNC of bone marrow). The number of CFU-GM in the four groups were 173.67 +/- 18.90, 165.33 +/- 26.58, 170.33 +/- 21.50 and 79.67 +/- 8.33 respectively. The number of CFU-GEMM in the four groups were 431.33 +/- 34.56, 370.33 +/- 42.10, 386.67 +/- 10.02 and 177.67 +/- 26.86 respectively. There were significant differences in the number of CFU-GM and CFU-GEMM between experimental groups and control group. The results showed that the T-lymphocytes in bone marrow could inhibit the expansion of hematopoietic cells in vitro and the formation of CFU-GM and CFU-GEMM. The regulatory mechanism was to be explored.

A survey of the previous literature and the data shown here indicate that neuroendocrine hormones such as growth hormone and prolactin may be of potential clinical use after bone marrow transplantation (BMT) to promote hematopoietic and immune recovery. The amounts of hormones used in our model do not promote weight gain suggesting that their lymphohematopoietic actions were independent of their anabolic effects. While the hormones may not produce the same extent of immune/hematopoietic effects when compared to conventional hematopoietic and immune stimulating cytokines (i.e. IL-2 or G-CSF), their pleiotropic effects and limited toxicity after systemic administration makes them attractive to test in the post-BMT setting. However, more work needs to be performed to understand the mechanism(s) of their action, particularly with regard to T-cell function and development.