Over the past three decades, more and more antisense drugs have been approved for marketing or clinical trails. Antisense technology has become the focus of pharmaceutical research due to its unique advantages in treating diseases and strong clinical development potential. There is a big difference from traditional small molecule chemical drugs, and macromolecular protein biological drugs. Antisense drugs are a very independent drug form. Antisense drugs were initially used to treat diseases with single gene mutations, but recently they have gradually begun to be used for the treatment of common diseases. Rational antisense drug design is crucial for disease treatment based on genetics. This paper reviews the latest progress in the field of action mechanism, chemical modification and delivery strategy of antisense drugs, and analyzes the current intractable problems. It is believed that with the resolution of these problems, the research of antisense drugs can reach a new level.

OBJECTIVETo study the genotype frequencies of peroxisome proliferators-activated -receptors-gamma C161-->T gene and its possible association with the metabolic syndrome and dietary intakes.

METHODSThe PCR-PFLP method was used to detect the polymorphism of PPARgammaC161-->T gene of 224 adults with metabolic syndrome and 224 normal adults in Shanghai. Their physical examinations, dietary investigation and the serum biochemistry were analyzed.

RESULTS(1) The genotype frequencies of PPARgamma C161-->T CC, CT and TT were 32.4%, 49.6% and 18.0% respectively, which were in agreement with Hardy-Weinberg equilibrium. There was no significant difference in the distribution of genotypes or allele between the metabolic syndrome group and the control group, and the result was the same between male and female subjects. (2) The levels of body mass index,waist width and hip width were significantly different among three genotypes groups. Subjects of the CT genotype had the highest levels. (3) There was significant difference in the negative correlation with the intake of protein and serum TG levels in the metabolic syndrome group.

CONCLUSIONThe results suggested PPARgamma gene C161-->T should be associated with body mass index, waist width and hip width. It might contribute to the heterogeneity in diet response to TG.

Adolescent ; Adult ; Aged ; Alleles ; Causality ; China ; Diabetes Mellitus, Type 2 ; genetics ; Diet ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Metabolic Syndrome ; genetics ; Middle Aged ; Obesity ; genetics ; PPAR gamma ; genetics ; Polymorphism, Genetic

AIMTo observe expressions and changes of Tau protein, pSer202 and Tau protein's contents during the differentiation process of bone-marrow mesenchymal stem cells (MSCs) into neural cells, and discuss Tau's effects on it.

METHODSEGF and bFGF were combined for the induction of 4th, 8th, and 12th-MSCs into neural cells. Expressions of Tau protein and pSer202 were tested by immunocytochemistry. ELISA assay was applied for testing Tau protein's contents during differentiation process.

RESULTSPositive rates of Tau protein in uninduced MSCs of 4th, 8th, and 12th-MSCs were under < 6%; After 14-day induction, the cellular morphologic characteristics in different passages were very similar to neurons, positive rates of Tau protein had no significant differences between passages (P > 0.05), but had differences with their uninduced groups (P < 0.05). There hadn't had expression of pSer202 in uninduced and induced groups of passages. ELISA assay indicated that there was an upward tendency in Tau protein's contents during the 14-day induction process, those in the 14th day had no significant differences between passages too (P > 0.05).

CONCLUSIONThe increase in Tau protein's expressions and its non-phosphorylated state may make for MSCs differentiating into normal neural cells and formation of neuronal processes.

Animals ; Bone Marrow Cells ; cytology ; Cell Differentiation ; Cells, Cultured ; Guinea Pigs ; Mesenchymal Stromal Cells ; cytology ; Neurons ; cytology ; tau Proteins ; metabolism

To investigate the adjuvant effect of plasmid DNA encoding superantigen SEA (D227A) (pmSEA) on immune responses induced by HBV DNA vaccine containing HBV preS2 and S antigen in BABL/c (H-2d). BALB/c mice were immunized intramuscular injection with HBV DNA vaccine (pHBVS2S) mixed with or without pmSEA plasmid. Antibodies againat HBV PreS2 and S antigen in the sera were accessed by Anti-HBs ELISA, and the HBsAg specific cytotoxic T lymphocytes (CTLs) activity was determined by 5 Chromium Release Assay. The HBs peptide-specific IFN-gamma secreting T cells were detected by ELISPOT. Anti-HBs antibody titers and CTLs activity in mice immunized with pmSEA + pHBVS2S group were significant higher (P < 0.05) than pHBVS2S DNA vaccine group. The ratio of IgG1/IgG2a (0.282) was apparently different from the group immunized with peptide (10). Mice immunized with HBV DNA vaccine plus adjuvant produce higher titer of IgG1 and IgG2a antibodies against HBV S antigen 1.36 and 1.73 time higher than that without adjuvant respectively. HBs peptide--specific IFN-gamma secreting T cells increased 2 - 3 times by the pmSEA adjuvant, compared to DNA vaccine group. HBV DNA vaccine (pHBVS2S) induces humoral and cellular immuno-responses in BALB/c mice, and the responses could be significantly boasted by the plasmid encoding mSEA. Therefore the pmSEA was a potential adjuvant for DNA vaccines.
Adjuvants, Immunologic ; Animals ; Enterotoxins ; immunology ; Hepatitis B ; immunology ; prevention & control ; therapy ; Hepatitis B Antibodies ; blood ; Hepatitis B Vaccines ; immunology ; Interferon-gamma ; secretion ; Mice ; Mice, Inbred BALB C ; Staphylococcus aureus ; immunology ; Superantigens ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Vaccination ; Vaccines, DNA ; immunology

OBJECTIVETo evaluate the basic procedure of endovascular stent-graft repair in the treatment of aortic arch aneurysm.

METHODS>From March 2000-February 2002, a total of 46 patients with aortic arch aneurysms were treated with the custom-made endovascular stent-graft. Of them, twenty-three patients (50%) had aneurysms at the middle of the arch, 22 patients (48%) had aneurysms at the arch-descending aorta, and 1 patient (2%) had aneurysm at the descending thoracic aorta. The diameter of all stents was 0.15 - 0.25 times larger than that of the aorta proximal to the entry tear of dissection or the opening of aneurysm. The diameter of the proximal end of the stents was ranged from 34 - 38 mm. The length of stents ranged from 90 - 120 mm. The stent was made of shape memory nitinol.

RESULTSThe stent was delivered successfully in 45 patients (98%). None of the patients had any access-related complications. Either the primary entry tear of aortic dissection or the inlet of aneurysm was occluded in 43 patients (96%), with an early endoleak in 2 patients (4%). All truth lumen of the dissection recovered to normal. Of the patients in acute period, 1 was referred to surgical repair and 2 died. Follow-up for 1 month to 23 months, showed late endoleak in 3 patients (7%). Forty-three patients restored normal life.

CONCLUSIONSEndovascular stent-graft could be applied in the repair of aortic arch aneurysm. Further studies are needed to to assess the long-term efficacy of this method.

Adult ; Aged ; Aortic Aneurysm, Thoracic ; diagnostic imaging ; surgery ; Blood Vessel Prosthesis Implantation ; methods ; Female ; Humans ; Male ; Middle Aged ; Stents ; Tomography, X-Ray Computed

In recent years,the CTLA-4 immunoglobulin biologics,a negative regulator in the immune system,have been obtained due attention in autoimmune diseases,transplantation rejection,and antineoplastic agents.CTLA-4 can inhibit T cell activation,reduce the expression of RANKL and other cytokines through regulating immune response,and effectively alleviate the process of bone resorption.According to previous study,CTLA-4 was involved in osteoclast-induced bone destruction and bone remodeling.In this review,the effect of CTLA-4 on the autoimmune diseases,on the osteoclast formation,and on the alveolar bone remodeling in the periodontal tissue was involved,and the related research were also evaluated to look forward to possible future basic research and clinical application direction.

Aim To investigate the effect of sanguina-rine on regulating the pathway of cell apoptosis by in-ducing reactive oxygen species (ROS) in HepG2 cells. Methods MTT method was used to detect the cell viability of HepG2 cell after the treatment of san-guinarine. The changes of ROS were observed by indi-cator DCFH-DA and DHE staining. The apoptosis was detected by Hoechst 33342 and Annexin V/PI stai-ning;Rhodamine 123 staining was used to detect mito-chondrial membrane potential. Western blot was used to detect expressions of key cell-apoptotic protein. Re-sults The cell viability of HepG2 cells showed a de-creasing trend with the increasing concentration of san-guinarine. Sanguinarine could significantly increase cellular ROS,decrease mitochondrial membrane poten-tial in HepG2 cell, and promote apoptosis of HepG2 cells. The expression of Bax, cleaved-caspase-3 and cytoplasmic Cyt-C significantly increased after the treatment of sanguinarine, however, the expression of Bcl-2 was inhibited. Conclusion Sanguinarine could activate mitochondrial pathway of apoptosis mediated by cellular uncontrolled ROS and promote apoptosis of HepG2 cells.

Objective To investigate the application and advantage of graded management of nurses in clinic work. Methods This subject introduced the method of graded management of nurses in general surgery department, in order to improve methods of nursing personnel, scheduling, training and allocation. Then, the clinical basic nursing of quality and the patients' degree of satisfaction were compared and analyzed after and before application to graded management. Results Nurses' responsibility was strengthened obviously, patients' rate of satisfaction reached 99% and the quality of nursing improved, which was higher than before, and there was statistical difference (P < 0.05 ). Conclusions The mode of graded management makes nursing human resource more reasonably, and meets the need of clinical nursing work, so it is better than common management mode.

Objective To investigate the protection mechanism of dexmedetomidine against retinal ischemia-reperfusion injury (RIRI) in mice.Methods Forty-eight male C57BL/6 mice born 8 weeks were randomly into sham group,model group and experimental group.Each group had 16 mice.Mice model of RIRI were prepared.Before modeling 15 min,dexmedetomidine 25 μg · L-1 was injected into the abdominal cavity in experimental group,and the same dose of 0.9％ normal saline was injected into the abdominal cavity in sham group and model group.The RIRI model was established successfully then these mice were killed after reperfusion 24 h.The superoxide dismutase (SOD) was detected by WST-1 method,the malondialdehyde (MDA) was detected by TBA method,and the glutathione peroxidase (GSH-PX) was determined by colorimetry.The tumor necrosis factor alpha (TNF-α),interleukin-6 (IL-6),1-methylcyclopropene (MCP-1) and interleukin-10 (IL-10) were detected by ELISA.Results Compared with the sham group,the levels of SOD (45.47 ± 8.16) U · mg-1 and GSH-PX (264.64 ± 27.31) U · mg-1 in the retinal tissue of the model group were decreased significantly (P ＜ 0.05).While MDA (1.56±0.41) nmol · mg-1,TNF-α (2.67±0.23) ng · mL-1,IL-6 (2.84±0.34) ng · mL-1,MCP-1 (0.68 ±0.06) ng · mL-1 and IL-10 (0.21 ±0.02) ng · mL-1 in the retinal tissue of the model group were decreased significantly (P ＜ 0.05).Compared with the model group,the levels of SOD (71.05 ± 9.34) U · mg-1,GSH-PX (382.20 ±31.56) U · mg-1 and IL-10 (0.44 ±0.07) ng · mL-1 in the retina tissue of the experimental group were decreased significantly (P ＜ 0.05).while MDA (1.02 ± 0.23) nmol · mg-1,TNF-α (1.53 ± 0.20)ng· mL-1,IL-6 (1.6 ±0.07) ng · mL-1 and MCP-1 (0.41 ±0.07) ng · mL-1 of the experimental group experimental group were decreased significantly (P ＜ 0.05).Conclusion Dexmedetomidine can significantly reduce RIRI,the mechanism may be related to inhibit oxygen free radical-induced lipid peroxidation injury and inhibit the secretion of inflammatory cytokines.