Cerebral ischemia and the aftermath of reperfusion form a hypoxic/hyperoxic sequence of events that can trigger DNA damage in neurons of central nervous system. Neuronal apoptosis will happen without immediate DNA repair. APE/Ref-1 is a multifunctional protein involoved in DNA base excision repair pathway and in redox reguiation of DNA-binding activity of AP-1 family members, which may play an important role in protection of postischemic neuronal damage.

Objective:The study aims to investigate whether phosphorothioate-modified antisense vascular endothelial growth factor oligodeoxynucleotides(VEGF ASODN)micro-encapsulated in cationic liposome could inhibit angiogenesis and metastasis of lung cancer.Methods:The phosphorothioate-modify VEGF ASODN, VEGF SODN(sense oligodeoxynucleotides) and VEGF MODN(mismatch oligonucleotides)micro-encapsulated in cationic liposome were added into in vitro culture of Lewis lung carcinoma(LLC ) cells,respectively. Expression of VEGF protein was detected by immunohistochemistry staining. And the inhibitory effects on bovine aortic endothelial cell proliferation by conditioned media obtained from LLC cells treated with ODN were observed. 40 mice of Lewis lung cancer models were established and subsequently were randomized into 4 groups: control group, ASODN group, SODN group,and MSODN group. Liposome, ASODN, SODN or MODN were given by twice a week for 4 weeks,respectively.The weights of subcutaneous tumors were measured. The rates of lung metastasis were detected, while the microvessel density(MVD) in tumor mass was detected by imuunohistochemistry staining. Peak systolic flow velocity(PS) and resistance index(RI) were measured with a sonographic scanner.Results:ASODN downregulated the expression of VEGF in LLC cells at the level of protein in vitro. The conditioned media obtained from LLC cells treated with ASODN significantly inhibited the proliferation of bovine aortic endothelial cells. ASODN significantly suppressed the growth of subcutaneous tumors and lung metastasis. MVD, PS and RI of VEGF ASODN group were remarkably different from those of other 3 groups(P

Objective: To investigate whether phosphorothioate-modified antisense vascular endothelial growth factor oligodeoxynucleotides ( VEGF-ASODN) formulated in cationic liposome can inhibit the blood flow of lung cancer. Methods: Lewis lung tumor models were established by subcutaneous injection of Lewis lung carcinoma cells into the right flank of 40 C57BL/6 mice. Twenty-four hours later, mice were randomly assigned into 4 groups; pure liposome, liposome containing ASODN, SODN and MODN. Mice in each group were treated twice a week for 4 weeks. Tumor growth were determined. Peak systolic flow velocity (PS) and resistance index (RI) were measured with a sonographic scanner. Expression of VEGF mRNA were detected by hybridization in situ and RT-PCR. Results: ASODN significantly suppressed the growth of subcutaneous tumors. PS and RI in VEGF-ASODN group were significantly different from those in other 3 groups ( P

Objective To investigate the protective effects of propofol against lung injury following ischemia-reperfusion of hind limbs. Methods Thirty-six Wistar rats weighing 300-350 g were anesthetized with mtraperitoneal 3% pentobarbital 40 mg?kg-1. Bilateral femoral artery and vein were exposed for occlusion of the circulation of the hind limbs. Right internal jugular vein was cannulated for drug administration. The animals were randomly assigned into 3 groups ( n = 12 in each group) : (1) sham-operated group in which bilateral femoral artery and vein were exposed but not occluded; (2) I/R group in which the bilateral femoral artery and vein were occluded for 4h with the atraumatic microclips and the released for 6h reperfusion , and (3) I/R + propofol group received a bolus of 5 mg?kg-1 propofol 10 min before reperfusion followed by propofol infusion at 10 mg?kg-1?h-1. In group 1 and 2 the animals received same amount of normal saline instead of propofol. At the end of 6h reperfusion the animals were sacrificed by bloodletting. The lungs were immediately removed for determination of MDA content, SOD activity, the lung water, iNOS and ICAM-1 expression and microscopic examination. Results I/R significantly increased lung water and MDA content, and expression of iNOS and ICAM-1 and decreased SOD activity, while propofol significantly attenuated these changes induced by I/R of hind limbs. Light microscopic findings in I/R group included alveolar edema, localized pulmonary atelectasis and hemorrhage and large amount of polymorphonuclear infiltration. Electron microscopic examination showed a series of ultrastructural changes such as diffuse irregular thickening of basement membrene, alveolar type Ⅰ cell swelling, alveolar type Ⅱ cell injury associated with emptying of lamella bodies. These changes were significantly less prominent in the rats which received propofol. Conclusion Propofol has protective effects on the lungs against injury induced by I/R of the hind limbs.

Objective To explore the application of heteroscedastic time series model to the analysis of data of infectious diseases.Methods ARIMA and AR-GARCH models were used to fit the incidence of gonorrhea.Results The time series in this study,which was heteroscedastic significantly,finally was well fitted by AR(1)-GARCH(0,1) model through model selecting.Conclusions AR-GARCH model is suitable for analyzing heteroscedastic time-series data of infectious diseases.

Glioblastoma multiforme (GBM) is the most malignant form of glioma, and its treatment through traditional surgery combined with chemotherapy and radiotherapy has limited efficacy. Chimericantigen receptor T-cells (CAR-T) are recombinant receptors for antigen, which, in a single molecule, redirect and mediateantigen recognition, T-cell activation, and, in the case of second-generation chimeric antigen receptors (CARs) costimulation (CD28 or 4-BB), augment T-cell functionality and persistence. CARs are the focus of attention in emerging treatment options for GBM. This article mainly introduces the development process of CAR-T therapy and the recent success of adoptive transfer of CAR-T cells. Effective targets of the treatment of GBM with CAR-T according to this research are discussed as well. Some of the most extensively studied targets on GBM, especially interleukin-13 receptor α chain variant 2, epidermal growth factor receptor-Ⅷ(EGFRⅧ), human epidermal growth factor receptor 2 (ErbB2), and ephrinA2 receptor (ErbA2), and the different characteristics of each kind of alloantigen-specific CAR-T cells, are the basis for CAR-T therapy and indicate their different characteristics or utilities and the prospect of further clinical research. The discovery of selective expression of interleukin-13 receptor alpha 2 in glioma cells more than 20 years ago prompted the clinical trial of CAR-T therapy in stage I GBM tumors, and the therapy was proven safe and effective. EGFRⅧ is a neoantigen presenting only in cancer cells and glioblastoma stem cells. Its presence is correlated with poor prognosis, and a phase Ⅰ/Ⅱ trial is ongoing at different institutes. ErbB2-specific CARs were also expressed in human Tcells.Adoptive transfer of EphA2 (or ErbB2)-specific T cells resulted in the regression of glioma xenografts. Thus, target-specific CAR-T immunotherapy may be a promising approach for the treatment of different target-positive GBM. Finally, we summarize the application value and challenge of CAR-T cell therapy in the treatment of GBM.

BACKGROUND:The biopsy material induced by foreign body is autologous tissue, which, in theory, avoids the role of immune rejection and destruction faced by non-autologous implants. This biology advantage has no way to comparison by synthetic and de-cel ular materials.
OBJECTIVE:To explore a biotube consisting of autologous cel s and extracel ular matrix and to evaluate its structure and mechanical features.
METHODS:The biotubes were prepared by embedding silicon rods as a mold intraperitoneal y. Specimens were analyzed by mechanical tests, histological observation and superficial study.
RESULTS AND CONCLUSION:It was easy to excite the biotubes prepared by embedding silicon tube
intraperitoneal y. The biotube mainly included col agen-rich extracel ular matrices and myofibroblasts appearing as elongated cel s with circumferential or longitudinal orientations. At 1 month of embedding, the wal was 70-250μm in thickness and had burst strength of (1 100±187) mm Hg (1 mm Hg=0.133 kPa), with perfect sewability. The biotubes, which possess the ability for wide adjustments in their shapes, are composed of autologous cel s and extracel ular matrices, and are an ideal graft for tissue engineering because they avoid immunological rejection and have sufficient mechanical strength.

Sepsis is the leading cause of mortality in critically ill patients.Studies indicate that immune suppression in sepsis is more often associated with poor outcome.Dendritic cells may contribute largely to the development of immune suppression during sepsis.This article reviews the emerging data indicating the key role of dendritic cells in sepsis induced immune suppression.A deeper insight into the dendritic cell changes during sepsis may provide a powerful weapon against sepsis.

Objective To explore the impact of blockade of SDF-1/CXCR4 signaling pathway by T140 on degradation of typeⅡ collagen in human articular cartilage and to define the mechanism of action of T140. Methods 144 pieces of cartilage (Mankin score of 0 or 1) were obtained from osteoarthritis patients undergoing total knee replacement ( OA cartilage group) and 144 pieces of cartilage (Mankin score of 0 or 1) were obtained from patients receiving traumatic amputation (normal cartilage group). Each group was treated with SDF-1 of 100 ng/mL, then divided into three subgroups A, B, and C. The cartilage tissue in each group was cultured in the nutrient solution containing of T140, MAB310, or SDF-1 (1 000 nmol/L) for 48 or 96 hours. RT-PCR was used to detect expression of typeⅡcollagen mRNA in the cartilage tissue. Results Level of type Ⅱcollagen mRNA was markedly higher in subgroup A than in subgroup B and subgroup C at the same group and the same time (P <0.05). The expression level of type Ⅱcollagen mRNA at the same time and in the same subgroup of OA cartilage group were lower than that in normal cartilage group (P < 0.05). Conclusions SDF-1 induces degradation of typeⅡcollagen in human articular cartilage thruogh the SDF-1/CXCR4 signaling pathway. T140 can block the SDF-1/CXCR4 signaling pathway and reduce the degradation of type II collagen.

Objective: To evaluate mid-term outcomes for the application of homograft valve conduits in right ventricular outlfow reconstruction in patients with congenital heart disease. Methods: We retrospectively studied 122 patients who received right ventricular outlfow reconstruction by homograft valve conduits application in our hospital from 2007-10 to 2014-07. The patients were divided into different sets of groups, by surgical procedure: Ross group,n=38 and Non-Ross group,n=84; by median age: ≤6 years group,n=61 and >6 years group, n=61; by the type of valve conduits: Aortic homograft group,n=21 and Pulmonary homograft group,n=101; by the diameter of conduits: ≤19 mm group,n=31 and >19 mm group,n=91. The relationships between pre-operative conditions, different types of conduits and diameters to the prognosis were analyzed; the post-operative death, re-operation, free homograft valve conduits failure rates were followed-up in all patients. Results: The average follow-up time was (35.4 ± 22.2) months and 2/122 (1.6%) patients died during that period, the overall free conduits failure rates at 1, 5 and 7 years post-operation were 94.2%, 81.2% and 75.4% respectively. The free conduits failure rates in Pulmonary homograft group at 1, 5, 7 years post-operation were 96.2%, 86.1%,79.9% and in Aortic homograft group were 80.0%, 59.7%, 59.7% respectively,P=0.011; in Ross group were 96.4%, 89.0%, 89.0% and in Non-Ross group were 91.3%, 78.3%, 67.1% respectively,P=0.045. While the age, conduits diameter, cyanosis and re-operation had no statistical meaning to free conduits failure rates, allP>0.05. Conclusion: Application of homograft valve conduits had good mid-term outcomes in right ventricular outflow reconstruction in patients with congenital heart disease, while the long-term effects should be further emphasized in clinical practice.