Nowadays, tumor is one of the most challenging human health diseases, which oblige human tirelessly to studied for the tumor.Gene therapy is a promising treatment in oncotherapies. Suicide gene therapy is the most widely researched among gene therapies. At the same time, bystander effect take important role in the mechanism of suicide gene therapy. Therefore, more researchers devote themselves to studyinghow enhance the bystander effect in order to improve the effect of suicide gene therapy. This article reviewed in short how to augment bystander effect of suicide gene therapy against cancer.

Objective To investigate the relation between polymorphisms of pulmonary surfactant protein A gene and adaptation to hypobaric hypoxia. Methods The genotype proportions and allel frequencies of 86 Tibetan mountaineers and 90 sea-level Hans were examined with polymerase chain reaction-sequence specific primer(SSP-PCR) reaction for surfactant protein A gene. Results The constituent ratio of A/A,A/G and G/G genotypes in A1-aa62 locus and C/C,A/C and A/A genotypes in A2-aa223 locus showed significant statistic difference between highland group and the sea-level control group(P＜0.05). A1-aa62 G/G and A2-aa223 A/C genotype demonstrated high odds ratio in Tibetan mountaineers. Moreover, the comparisons of genotypes and alleles in A1-219 locus showed no significant difference between the plateau group and the sea-level Han control(P＞0.05). Conclusion The single-nucleotide polymorphisms(SPN) in SP-A1aa62 and SP-A2aa223 may be associated with the adaptation to hypobaric hypoxia.

OBJECTIVETo investigate the dynamic features of angiogenesis in residual tumors after high intensity focused ultrasound (HIFU),and to determine the temporal effect and mechanism of hypoxia inducible factor-2 alpha (HIF-2a) in the angiogenic process of residual tumors.

METHODSXenograft tumors of HepG2 cells were generated by subcutaneously inoculating athymic BALB/c nu/nu mice with the hepatoma cells.About 30 days after inoculation,all mice (except in the control group) were treated by HIFU and assigned randomly to the following 7 groups according to various time intervals post-treatment:1st,3rd,5th day and 1st,2nd,3rd,4th week when the residual tumor tissues were obtained from the experimental groups.Protein levels of HIF-2a and vascular growth factor A (VEGF-A) were quantified by immunohistochemistry and western blotting,and mRNA levels were measured by (real-time quantitative) qPCR. Microvascular density (MVD) was calculated by counting the CD31-positive vascular endothelial cells identified by means of an immunohistochemical staining method.

RESULTSCompared with results from the control group,the protein and mRNA levels of HIF-2a expression reached the highest level in the experimental mice at the 2nd week (P=0.000 and P < 0.01 respectively),and were decreased thereafter(3rd week and 4th week, P=0.000 and P < 0.05).VEGF-A expression in the residual tumor tissues group that received HIFU was significantly decreased,compared with the control group,at all time points uPto 1 week (all P=0.000 and P < 0.01),but the levels increased compared to controls in the 2nd through 4th week (all P=0.000, P < 0.05). Similar results were obtained for MVD.

CONCLUSIONHIFU treatment can inhibit angiogenesis in residual hepatoma tissues in the short-term (1 to 2 weeks post-treatment) in mice with hepatocellular carcinoma,but can promote angiogenesis overtime (2 to 4 weeks post-treatment); the angiogenic process may involve the HIF-2α/VEGFA pathway.

Animals ; Blotting, Western ; Carcinoma, Hepatocellular ; pathology ; Hep G2 Cells ; High-Intensity Focused Ultrasound Ablation ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Immunohistochemistry ; Liver Neoplasms ; pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Neovascularization, Pathologic ; Vascular Endothelial Growth Factor A ; metabolism

Objective To establish experimental vascular dementia rat model and evaluate gait behavior . Methods Vascular dementia rat model induced by bilateral carotid artery ligation methods , 50 days for real-time gait behavioral training and testing after surgery .Results Compared with the sham group , Experimental vascular dementia model rats had 19 gait indicators appeared significantly statistical difference , Animal model gait abnormal behavior is mainly reflected in the forelimb step width increased (P <0.05), each foot walk cycle extension (P <0.05), Each foot stance time increased (P <0.05, P <0.01), and the swing time shortened (P <0.05), Homologous coupling shortened (P<0.05), each foot average footprint area and average intensity increased (P <0.05, P <0.01).Conclusion Experimental rat model of vascular dementia in real time gait abnormal behavior and seen in patients with clinical symptoms similar, can provide a reference model for the establishment and judgment .

Objective To explore the relationship between WT1 and prognosis of patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), and to evaluate the possibility of WT1 as a potential marker for monitoring the minimal residual disease (MRD). Methods Bone marrow mononuclear cells from 58 patients with primary AML, 32 patients with primary ALL, 40 patients with AML-complete remission (CR), 28 patients with ALL-CR and 31 patients with trilineage hyperplasia (control group) were collected. Real-time fluorescent quantitative PCR method was used to detect the expression of WT1 in all patients. The expression threshold of WT1 in each group was established. WT1 copy number/ABL copy number ratio×100%denotes the relative expression level of WT1 gene. Results Median relative expression level of WT1 in the control patients was much lower than that in primary AML patients [0.026%(0-0.240%) vs. 20.880 % (3.550 %-48.500 %), Z=-7.74, P<0.000 1]. Relative expression level of WT1 between AML-CR patients [0.102%(0-5.380%)] and primary AML patients had significant difference (Z=-8.34, P<0.000 1). Moreover, the relative expression level rate of the first course in AML patients with higher WT1 expression level (>20.880 %) was 60.7 % (17/28), while the CR rate was 76.7 % (23/30) in those with lower WT1 expression. WT1 expression was increased dramatically in recurrent AML patients. Relative expression level of WT1 was significantly higher in primary ALL patients [0.350 % (0.021 %-10.780 %)] compared with that in the control group Z=-2.58, P<0.05. There was no significant difference in relative expression level of WT1 between ALL and ALL-CR patients [0.038 % (0-2.800 %), P=0.065]. Conclusion WT1 expression level in AML patients is relatively high, which could be used as an effective index of prognosis evaluation and MRD monitoring for AML patients, but not for ALL patients.

Objective To explore the regulation mechanism of X box binding protein 1 (XBP1)signal transduction pathway for TNF-α and effective approach in ischemia/reperfusion (I/R) injury of liver transplantation for short hairpin RNA (shRNA) interference used to gene therapy in liver graft.Methods Male Sprague-Dawley rats were divided into three groups: the cold ischemia transfection group (CIT), the in vivo transfection group (IVT) and the control group. Experiments of orthotopic liver transplantation were performed by two cuff method. The rats in CIT were perfused with XBP1-shRNA plasmid (pSIXBP1) during cold ischemia phase, those in IVT received the equivalent volume (2 ml) of pSIIRAK 4 after portal vein inoculation, and those in the control group were not subjected to any treatment. Rats were killed at 60 or 180 min after restoring reperfusion of hepatic portal vein.Histopathological damage degree of graft liver was observed by light microscope. The expression levels of XBP1 gene and protein were detected by RT-PCR and Western blotting. The activities of NF-κB and the serum TNF-α level were detected by ELISA. Results All the indexes including the degree of histopathological damage, the expression levels of XBP1 mRNA and protein and the TNF-α level were significantly decreased in CIT as compared with IVT and control group (P＜0. 05). However,there was no significant difference in NF-κB activity among the three groups (P＞0. 05). Conclusion The role of XBP1 pathway in TNF-α gene regulation and that of NF-κB pathway in rat liver I/R injury are two relatively independent aspects, and the depression of XBP1 expression with XBP1 shRNA through portal vein perfusion during cold ischemia phase could effectively alleviate graft hepatic I/R

Objective To investigate the effects of different doses of ulinastatin on severe thermal injuryinduced myocardial damage in rats. Methods One hundred and eighty female SD rats weighing 180-220 g were usedin this study. Thirty percent of the total body surface (TBS) was shaved chemically with 20% sodium sulphate and then exposed to 92 ℃ water for 18 s. The animals with third degree thermal injury involving 30% of the TBS were randomly divided into 3 groups (n = 60 each): group Ⅰ thermal injury (group TI); group Ⅱ and Ⅲ received intraperitoneal ulinastatin 40 000 and 80 000 U/kg respectively immediately after thermal injury (group U1 , U2). The TI group received equal volume of normal saline IP instead of ulinastatin. Blood samples were taken from abdominal aorta before (baseline) and at 1, 3, 6, 12 h after thermal injury for determination of serum concentrations of cTnI, IL-1β, IL-6, IL-10 and TNF-α (10 samples at each time points). Ten animals were sacrificed at each time point after blood sampling. The myocardial specimens were obtained for microscopic examination and measurement of MDA content and SOD activity. Results Compared with group TI, the serum concentrations of cTnI, IL-1β, IL-6 and TNF-α and MDA content in myocardium were significantly decreased and the myocardial SOD activity was significantly increased in group U1 , while in group U2 the senum concentrations of cTnI, IL-Iβ, IL-6 and TNF-α and myocardial MDA content were significantly increased and the myocardial SOD activity was significantly decreased. There was no siginificant difference in the serum concentrations of IL-10 among the three groups. Microscopic examination showed that myocardial damage was accentuated in group U2 as compared with group U1. Conclusion Ulinastatin 40 000 U/kg can ameliorate severe thermal injury-induced myocardial injury through inhibition of inflammatory response and lipid peroxidation response, whereas ulinastatin 80 000 U/kg accentuates myocardial damage.

OBJECTIVEThe aim of this study is to investigate the effect and complication of immediate implantation of particulate hydroxylapatite artificial bone after teeth extraction.

METHODSParticulate hydroxylapatite artificial bone was implanted into 65 extraction sockets after teeth extraction. All patients were followed up until 3 months after the operation. They are examined with clinical examination and X-ray examination to observe the effect and complication of the implantation operation.

RESULTSThe wound healed well in all cases without any complication. Compared to the alveolar ridge before teeth extraction, and the height of the alveolar ridge after teeth extraction didn't decrease.

CONCLUSIONImplantation of particulate hydroxylapatite artificial bone after teeth extraction could maintain the height of the alveolar ridge and reduce the complication of teeth extraction. It would be helpful for the following prosthetic restoration. The immediate implantation of artificial bone is therefore needed further study.

Adult ; Aged ; Alveolar Bone Loss ; prevention & control ; Alveolar Ridge Augmentation ; methods ; Biocompatible Materials ; Bone Substitutes ; Dental Implantation, Endosseous ; Dental Implants, Single-Tooth ; Denture, Partial, Temporary ; Female ; Humans ; Hydroxyapatites ; Male ; Middle Aged ; Tooth Extraction ; adverse effects

OBJECTIVETo investigate the expression change of integrin alpha 5 during mandibular fracture healing.

METHODSUsing rabbit mandibular fracture model, the fractured bone tissues were obtained and paraffin slices were made on the days of 1, 3, 5, 7, 14, 30, 60 and 90 after surgery, respectively. Non-fractured mandibles were used as normal control. LsAB immunohistochemical method was used to detect the expression of integrin alpha 5 in bone tissue, especially on osteoblasts and osteoclasts.

RESULTSIntegrin alpha 5 was widely expressed in fractured bone and surrounding soft tissues. The expression of integrin alpha 5 increased 7 days after fracture, peaked in 14 to 30 days and returned to nearly normal in 60-90 days.

CONCLUSIONDuring mandibular fracture healing, the expression of integrin alpha 5 in bone tissue increased clearly. It is estimated that integrin alpha 5 players an important role in fracture healing.

Animals ; Female ; Fracture Healing ; Immunohistochemistry ; In Situ Hybridization ; Integrin beta1 ; biosynthesis ; genetics ; Male ; Mandibular Fractures ; metabolism ; Osteoblasts ; physiology ; RNA, Messenger ; biosynthesis ; genetics ; Rabbits

Objective To explore the interaction of streptococcus suis serotype 2 recombinant suilysin ( SLY ) with platelets, and provide the theoretical basis for clinic treatment of patients infected with S.suis.Methods The nickel column affinity chromatography was used to purify the recombinant SLY.The hemolytic acivity was identified by optical density before the platelets aggregation induced by a SLY was detected by a platelet aggregometer or electron microscope and the effect of aspirin on platelets aggregation was analyzed.The impact of wild type 05ZYH33 and sly-deficient mutant strainΔSLY on platelets of mice was compared to predict the interaction of the SLY with platelets in vivo.Results and Conclusion Hemolytic activity of recombinant SLY was 2000 hemolytic units( HU) and platelets aggregation was induced at 1 μg/ml.The aggregation can be inhibited by aspirin in 5 mmol/L.SLY can also increase the volume and reduce the amount of platelets in mice.