The ABCD2 score is validated for evaluating short-term stroke risk after transient ischemic attack (TIA); however, whether it is able to predict the long-term risk of vascular outcome remains uncertain. Recently a new tissue-based definition of TIA has been proposed. The ABCD2 scores of 145 TIA patients admitted to our hospital were retrospectively calculated and stratified into two categories: ≤ 3 points (low risk); 4-7 points (moderate-high risk). At a median follow-up of 81 months, new vascular events were recorded. Follow-up data were available in 107 patients. Seventy one patients had a moderate-high ABCD2 score. Sixty six patients experienced a cerebral ischemic event; 8 a myocardial infarction; 7 died of cerebrovascular or cardiovascular cause. Moderate-high ABCD2 score was significantly associated with the further cerebral ischemic events (hazard ratio [HR], 1.755; 95% confidence interval [CI], 1.019 to 3.024) and with the combined endpoint (HR, 1.818; 95% CI, 1.079 to 3.063). Our study shows that the ABCD2 score may also be used to predict long-term vascular outcome after tissue-based definition of TIA. Moderate-high ABCD2 score is associated with an increased general vascular risk in the long-term follow-up after TIA.
Stroke

Objective To investigate the relationship between cysteine-rich protein 61 ( Cyr61 ) and phosphatidylinositol 3-kinase ( PI3K ) signal pathway on cell proliferation and apoptotic in human ovarian carcinoma cells.Methods Recombinant human Cyr61 (rhCyr61) was pretreated with ovarian carcinoma cells.The expression of Cyr61 protein was detected by confocal spectral microscopy.Then treated the ovarian carcinoma cells with PI3K transduction inhibitors (LY294002) for 24 hours.Cell apoptosis was detected by flow cytometry (FCM).Cell viability was determined by methyl thiazolyl tetrazolium (MTT) method.The mRNA expressions of Cyr61,the protein levels of protein kinase B ( PKB),phospho-PKB and Cyr61 were assaved by real time-PCR and western blot analysis,respectively.Results The Cyr61 and phospho-PKB protein expression in two ovarian carcinoma cells (OV2008 and OVCAR-3 ) were increased in rhCyr61pretreated group.The decreasing of cell apoptosis [ ( 1.4 ±0.9)％,(2.1 ± 1.0)％ ] and increasing of cell proliferation [ ( 124.0 ± 1.8)％,( 133.0 ±2.2)％ ] was detected in the same time,compared with negative control group,there were significant difference ( P ＜ 0.05 ).After exposed to LY294002 for 24 hours,the apoptosis rate of OV2008 and OVCAR-3 in pretreated with rhCyr61 group exposed to LY294002 were (21.1 ± 1.6)％ and (26.4 ± 1.5 )％,respectively.Cells viability [ (59.0 ± 2.3 )％,(51.0 ± 2.0)％ ]was also significantly decreased in OV2008 and OVCAR-3 pretreated with rhCyr61 cells.Meanwhile,the mRNA expressions of Cyr61 (3.2 ± 0.8,6.2 ± 1.1 ) and the protein levels of phospho-PKB and Cyr61 were greatly decreased.Compared with negative control group,there were significant difference in OV2008 and OVCAR-3 cells (all P ＜ 0.0l ).Conclusions The activation of PI3K intracellular signaling pathways may lead to up-regulation of Cyr61 expression.Block PI3K signal pathway could significantly inhibit the expression of Cyr61,and may promote the apoptotic effects and inhibit the cell growth of ovarian carcinoma cells.

OBJECTIVE: To figure out the balance mechanism between brand-name drugs and generic drugs in American drug review. METHODS: This paper reviewed FDA laws and regulations, domestic and foreign literature to retrospect the basis of generic development and explore the brand-name drug companies' action to prevent generic competition. RESULTS AND CONCLUSION: The abbreviate new drug application, patent challenge and market exclusivity in the Hatch-Waxman Act were the basis of generic development. Brand-name drug companies prevented competition by occupying the market, refusing to provide samples, submitting citizen petitions to extend generic drug review time and extending the patent term and market exclusivity of brand-name drugs. The United States legislated and amended relevant laws and regulations, adjusted the generic drug user fee to maintain the stability of the balance, which is worthy of further research.

Gene targeted mutagenesis and replacement can be used to modify gene sequence in genomic background without position effect or insertion inactivation in transgenic plants. Targeted mutagenesis organism has little biosafety concerns free of transgenes or marker genes. Gene targeted mutagenesis and replacement in high plants now appears to be a potential tool for gene functional analysis in situ, crops genetic improvement and molecular design. Zinc finger nuclease(ZFN)is most important and would be widely used in gene targeted mutagenesis and replacement through introducing double-strand breaks in genome. Strategies for gene targeted mutagenesis and replacement in plants is discussed. ZFN is described in detail from its structure, operation model and application in plants. Developmental prospect of ZFN in plant gene targeted mutagenesis and replacement is also discussed.

Objective: To assess fluid-attenuated inversion recovery (FLAIR) vascular hyper-intensity (FVH) and explore its relationship with CT perfusion (CTP) penumbral/infarct core mismatch ratio and diffusion weighted imaging (DWI) final infarct volume in acute ischemic stroke (AIS) patients with middle cerebral artery occlusion (MCAO). Methods: The CTP and MRI images of 38 AIS patients with MCAO were reviewed. The FVH score (longitudinal direction) [FVH score (L)] and FVH score (transverse direction) [FVH score (T)] were quantified on the FLAIR images. The FVH score (L) (range, 0-16) was based on a rostrocaudal extension of FVH and the FVH score (T) (range, 0-3) was based on FVH supply of the occluded MCA territory. The mismatch ratio was calculated from the ratio of the [mean transit time - cerebral blood volume (CBV)] lesion/CBV lesion on the CTP images. The DWI infarct volume was measured on the DWI images. Results: The mismatch ratio was larger for the group of FVH score (L)=7~8 than those of FVH score (L)=5~6 and FVH score (L)=3~4 (p=0.03), whereas the DWI infarct volume was smaller (p=0.04). Similarly, the mismatch ratio of FVH score (T)=2~3 group was larger than FVH score (T)=1 group (p=0.01), whereas the DWI infarct volume was smaller (p=0.02). Both FVH score (L) and FVH score (T) correlated positively with mismatch ratio (P=0.02, P=0.001, respectively), but negatively with DWI infarct volume (P=0.03, P=0.004, respectively). Conclusions: Higher FVH score is associated with larger mismatch ratio and smaller DWI infarct volume in AIS patients with MCAO. FLAIR vascular hyperintensity may represent collateral arterial circulation, and may play a role in protecting the ischemic penumbra.
Infarction, Middle Cerebral Artery

Objective: To observe the clinical effects of Shu-acupuncture method in Nei Jing (Classic of Internal Medicine) in the treatment of shoulder and arm pain. Methods: A total of 90 patients with shoulder and arm pain were randomly divided into an observation group and a control group, 45 cases in each group. The treatment of Shu-acupuncture method in Nei Jing (Classic of Internal Medicine) was adopted in the observation group, routine acupuncture was used in the control group. The two groups were treated once every day, with 5 treatments as one course, and a 2-day rest between two courses. After 3 courses, pain was assessed by visual analog scale (VAS), and the clinical effects were compared between the two groups. Results: After the treatment, VAS scores were significantly changed in both groups (both P<0.01). The VAS score was lower in the observation group than that in the control group, with a statistical difference between the two groups (P<0.05). The total effective rate was 100% in the observation group, versus 91.1% in the control group, the difference was statistically significant (P<0.05). Conclusion: The therapeutic effect of Shu-acupuncture method in Nei Jing (Classic of Internal Medicine) is better than that of routine acupuncture in treating shoulder and arm pain.

OBJECTIVETo explore the underwater decompression schedule for 100 m Trimix conventional diving operations and evaluate its safety through a simulated rabbits Trimix conventional diving.

METHODSAccording to the Haldane theory, the assumed time units, the classification of tissue compartments, the nitrogen super-saturation safety coefficient and the selection of methods used for the calculation of the simulated 100 m Trimix conventional diving schedule were properly selected, and the calculating method for the dive decompression schedule was thus firmly established. In our experiments, five tissue compartments were selected during the calculation of decompression schedule: 5 min, 10 min, 20 min, 40 min and 75 min, and the nitrogen super-saturation safety coefficient was calculated by 1.6. Eight New Zealand rabbits were performed a simulated 100 m Trimix dive program which was established according to the Haldane theory, and eight rabbits for intact group. The tissues wet/dry ratio and ethology were detected and observed before and after the simulated diving to evaluate the safety of decompression schedule.

RESULTSBy using the developed underwater decompression schedule, abnormal ethology changes in rabbits could not be observed after compression and decompression to the surface; and the tissues wet/dry ratio of simulated diving rabbits had no significant changes compared with the intact group (P > 0.05).

CONCLUSIONThe decompression schedule calculated by Haldane theory seemed to be safe and reliable, the diving breathing gas concentration did not cause oxygen toxicity and nitrogen narcosis among the dive rabbits, and dive efficiency was greatly improved by using enriched oxygen gas in UPTD safety range during decompression.

Objective:To explore the effects of LncRNA HCG18 on endoplasmic reticulum stress and autophagy via regulating miR-185-5p/AGER axis in diabetic nephropathy (DN) .Methods:The kidney tissues of patients with DN were collected and the podocyte injury model induced by high glucose (HG) was established. The expression of HCG18 in renal tissue in DN patients and cell model was detected. The localization and expression of HCG18 in cells were determined. The regulatory relationship between HCG18 and miR-185-5p, miR-185-5p and AGER was testified. QRT-PCR and western blot were used to detect the expression of endoplasmic reticulum stress related factors (CHOP, XBP1) and autophagy related factors (Beclin-1, p62) .Results:Compared with non-DN patients, HCG18 was overexpressed in renal tissue of DN patients ( P<0.05) . Compared with normal glucose (NG) group, mRNA and protein expression of endoplasmic reticulum stress related factors (CHOP, XBP1) were overexpressed but mRNA and protein expression of autophagy related factors Beclin-1 were inhibited, p62 mRNA and protein expression were increased (all P<0.05) . HCG18 regulated the miR-185-5p/AGER axis and played a biological role. Knocking down of HCG18 reduced endoplasmic reticulum stress, activated autophagy and reduced podocyte injury, but this effect can be partially reversed by miR-185-5p inhibitors. Conclusion:HCG18 regulates the miR-185-5p/AGER signal axis and promotes DN progression through regulating endoplasmic reticulum stress and autophagy.

Objective To investigate the role of nuclear factor-kappa B(NF-?B)/inhibitor protein-kappa B(I?B) signal pathway in viral transactivation of transcription in steroid responsive simple nephrotic syndrome(SRSNS).Methods Children with SRSNS(inclu-ding active stage and remissive stage) were examined,and were compared to children with nephritic nephrosis,secondary glomerular di-seases,bronchiolitis and healthy children.Electro-mobility shift assays,reverse transcription-polymerase chain reaction(RT-PCR) and enzyme-linked immunosorbent assay(ELISA) were used to detect the activity of NF-?B,the gene expression of respiratory tract viruses (including respiratory syncytial virus and influenza virus) in peripheral blood mononuclear cells(PBMCs) and the levels of viral antibody in plasma,respectively.The protein levels of I?B? and IL-8 were measured through Western blot and ELISA in SRSNS at active stage and healthy children.Results Compared with SRSNS at remissive stage and other groups,the activity of NF?B in SRSNS at active stage was much higher.And there was a positive linear correlation trend between the activity of NF-?B and the gene expression of respiratory tract viruses in SRSNS at active stage.With healthy children,the level of IL-8 in plasma from SRSNS at active stage was significantly increased.There was a positive correlation between the activity of NF?B and the level of IL-8(r=0.88 P