Cognitive impairment caused by ischemic stroke is becoming more and more concerned.It is crucial to explore its pathophysiological mechanism and related clinical predictive indexes for understanding the occurrence,development and treatment of the disease.This article discusses the pathophysiologic mechanism of cognitive impairment after stroke from the aspects of white matter damage,amyloid abnormal deposition,blood-brain barrier damage,and synaptic plasticity injury,and reviews the risk factors,imaging and biological markers that can be used to predict cognitive impairment after stroke.

Cocaine-and amphetamine-regulated transcript (CART), an endogenous neuropeptide, is widely distributed in human organs and tissues, such as brain, gastrointestinal tract and pancreas. It has a variety of important physiological functions, including eating and obesity, stress, mental anxiety, drug addition, and endocrine regulation. Previous studies have suggested that CART is widely distributed in the central nervous system, and it involves in the regulation of a variety of physiological processes and has some central protective effects. It is a potential neuroprotective agent. This article reviews the recent progress in research on the neuroprotective effect of CART on stroke and neurodegenerative disease and its mechanisms, as well as its therapeutic effect in central nervous system diseases.

Objective To investigate the effect of ketamine on the synaptic long-term potentiation(LTP) in the CA1 area of rat hippocampal slices,and to elucidate the mechanisms underlying the effect of ketamine on memory.Methods Hippocampal slices(400 ?m thick) were obtained from the brains of male Sprague-Dawley rats(2 months old) weighing 200-250 g that were decapitated.The slices were incubated in artificial cerebrospinal fluid(ACSF) at room temperature for at least 120 min before use.Forty-nine slices were randomly divided into 7 groups(n=7):control group,ketamine 1,5,10,30,50 and 100 ?mol?L-1 groups.All the slices in each group were perfused with ACSF,ketamine 1,5,10,30,50 or 100 ?mol?L-1,respectively.The slices in each group were performed to record evoked population spikes(PS) using extracellular microelectrode recording technique.Another forty-nine slices were randomly divided into 7 groups(n=7):LTP group,ketamine-LTP 1,5,10,30,50 and 100 ?mol?L-1 groups.All the slices in each group were perfused with ACSF,ketamine 1,5,10,30,50 or 100 ?mol?L-1,respectively.PSs were recorded for at least 30 min before LTP in each group.For LTP induction,high-frequency stimulation(HFS) conditioning pulses(100 Hz?s-1) were applied to the Schaffer collateral-commissural pathway of hippocampus using a bipolar stimulating electrode.The changes in PS amplitude after HFS were analyzed in each group.Results The PS amplitude of the rat hippocampal slices in ketamine 1,5,and 10 ?mol?L-1 groups had no significant difference compared with control group.The PS amplitude in ketamine 30,50 and 100 ?mol?L-1 groups decreased compared with control group(P

Objective Based on detection of the soluble LAIR-1 (sLAIR-1) and sIL-2R in the bile from recipient after liver transplant, the role of sLAIR-1 and sIL-2R in graft acute rejection were analyzed. Methods Bile sLAIR-1 level and sIL-2R were determined by double mAb sandwich enzyme linked immunosorbent assay in 55 cases of liver transplantation. Results In 22 recipients with normal graft function, sLAIR-1 and sIL-2R were detected at low level in the bile. In the 29 cases of liver acute rejection (AR), significant increase of bile sIL-2R level was detected on the lst and 2nd d before final diagnosis. With the effective methylprednisolone pulse therapy, sIL-2R level was decreased significantly on the 3rd d. On the other hand, remarkable increase of bile sLAIR-1 was found on the lst,2nd and 3rd d before final diagnosis. After of methylprednisolone pulse therapy for 3 d, bile sLAIR-1resturned to the control level. Conclusion Both bile sIL-2R and sLAIR-1 are detected at high level in the recipients suffering from liver acute rejection. The level of bile sLAIR-1 changes dramatically and responsively according to liver acute rejection. Therefore, detecting these two markers synergistically may be a promising monitor for rejection after liver transplantation.

Aim To study inhibitory effect of 5-fluorouracil encapsulated by galactosylceramide liposomes (5-Fu-GCL)on 5-Fu-resistent HepG_2 cells and its mechanisms. Methods Inhibitory effect of 5-Fu-GCL on established model of 5-Fu-resistant HepG_2 cells was assessed with MTT assay in vitro. The concentration-time course of 5-Fu-GCL in intracellular fluid was detected with high performance liquid chromatography (HPLC). Thymidylic acid synthase (TS) expression was observed with immunohistochemical method,and NO content was determined with chemical method. Results Obvious inhibitory effects of 5-Fu-GCL (75,150,300,600,1200?mol?L-1) on 5-Fu-resistant HepG_2 cells were observed with IC_ 50 of 158.6 ?mol?L-1,far lower than that of free 5-Fu (400.9 ?mol?L-1). 5-Fu-GCL (300 ?mol?L-1) inhibited 5-Fu-resistant HepG_2 cells in a time-dependent manner,and the inhibitory effect of 5-Fu-GCL was stronger than that of free 5-Fu during 12～48 h. Compared with free 5-Fu,5-Fu-GCL (300 ?mol?L-1) increased the content of intracellular fluid in 5-Fu-resistant HepG_2 cells. 5-Fu-GCL(62.5,300,1200 ?mol?L-1) not only inhibited the expression of TS,but also increased the production of NO in 5-Fu-resistant HepG_2 cells,and these effects of 5-Fu-GCL(300,1200 ?mol?L-1) were stronger than those of free 5-Fu. Conclusion 5-Fu-GCL has inhibitory effect on 5-Fu-resistant HepG_2 cells. The effect may be related to the increased concentration of 5-Fu-GCL in intracellular fluid,inhibited expression of TS and increased production of NO.

BACKGROUND:Recombinant fusion protein is cascaded by staphylokinase and hirudin according to the thrombin cognition sequence, and has double functions and a molecular weight of 23 ku. The recombinant fusion protein can be highly expressed in the engineering bacteria at high-density fermentation. OBJECTIVE:To construct and purify recombinant staphylokinase-hirudin fusion protein in the engineering bacteria after high-density fermentation, and to explore the feasibility of construction and the expression value. METHODS:The engineering bacteria were cultured at high density and staphylokinase-hirudin fusion protein was induced to express. The bacteria were centrifuged and ultrafiltrated after repeated freezing and thawing. The supernatant was colected with ion exchange chromatography method. The staphylokinase-hirudin fusion protein was isolated and purified, then the fibrinolytic activity and expression in bacteria were observed. RESULTS AND CONCLUSION: The engineering bacteria were cultured and the fusion protein was induced at 17 hours. The results showed that, staphylokinase-hirudin fusion protein expression was detected at 0.5 hours after induction, and the expression levels were increased as the fermentation time; at 20 hours, the expression level reached the peak. The dried weight of the bacteria was 32.20 g/L and the expression level of target proteins was 1.48 g/L. After purification, the purity of recombinant staphylokinase-hirudin fusion protein was as high as 98%, fibrinolytic activity was about 2.6×104 IU/mg, the probability of activity recovery was 56%. The purification process of recombinant staphylokinase-hirudin fusion protein is convenient, less time, repeatable and alows large-scale production.

Objective To investigate the protective effects of recombinant human erythropoietin (rHuEPO) on caecal ligation and puncture (CLP)-induced acute liver injury.Methods Ninety-six healthy male Sprague-Dawley rats weighing 250-300 g were randomly divided into 3 groups:normal control group (sham group,n =32),CLP model group (sepsis group,n =32) and rHuEPO treatment group (n =32).The rat model of sepsis was established by caecal ligation and puncture.In treatment group,rats were treated with rHuEPO 5000 U/kg administered through caudalis vein after CLP procedure.Continuous observation was carried out until 24 h after modeling.Of each group,8 rats were sacrificed at 2 h,6 h,12 h and 24 h,respectively,and then the liver tissue samples and blood samples were collected.Blood samples were assayed for determining the levels of serum cytokines [tumor necrosis factor-alpha (TNF-α)],and inducible nitric oxide synthase (iNOS) by using the enzyme-linked immunoadsorbentassay (ELISA) method.The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also detected.Histopathological changes of liver tissues were observed under optical and transmission electron microscopy.Results (①)The levels of ALT,AST,TNF-a,iNOS in serum of rats in control group were lower than those in model group and rHuEPO group (P ＜0.01).The levels of TNF-α,IL-6 and iNOS in serum of rats in rHuEPO group were decreased significantly compared with model group (P ＜ 0.01).(②) The optical microscopy and the transmission electron microscopy showed hepatocyte edema,liver focal necrosis,inflammatory cell infiltration in portal area and severe congestion of interlobular veins,hepatocyte karyopyknosis,mitochondrial and endoplasmic reticulum (ER) obviously decreased in sepsis group at 24 h.Hepatic injury was attenuated after employment of rHuEPO.Conclusions Recombinant human erythropoietin can inhibit the levels of ALT,AST,TNF-a,iNOS in serum,thus modifying the inflammatory response and providing protective effects against acute liver injury in the wake of infection.

Objective To investigate the value of high-resolution magnetic resonance imaging (HR-MRI) of arterial walls in the diagnosis of cerebral artery dissection (CAD).Methods The patients diagnosed as CAD and completed computed tomography angiography (CTA),magnetic resonance angiography (MRA),digital subtraction angiography (DSA),and HR-MRI were enrolled retrospectively.The detection rate and diagnostic value of the 4 imaging techniques were compared and analyzed.Results A total of 15 patients were enrolled,5 had internal carotid artery dissection,7 had vertebral artery dissection,2 had middle cerebral artery dissection,and 1 had basilar artery dissection.HR-MRI revealed 11 intramural hematoma,9 intimal flap,3 double lumen sign,and 2 pseudoaneurysm.A total of 18 CADs were detected in 15 patients,17 (94.44％),14 (77.78％),5 (27.78％) and 6 (33.33％) were detected with HR-MRI,DSA,CTA and MRA,respectively.There were significant difference in CAD detection rates of HR-MRI,DSA,CTA and MRA (x2 =24.939,P ＜ 0.001).The CAD detection rate of HR-MRI and DSA were significantly higher than those of CTA and MRA (all P ＜ 0.01 for HR-MRI,all P ＜ 0.05 for DSA),but there was no significant difference in CAD detection rate between HR-MRI and DSA.Conclusion HR-MRI is a diagnostic method for CAD with higher sensitivity.

Liver fibrosis is a common chronic liver disease, which is a stress response process of liver cells affected by one or more pathogenies for long term or repeatedly. During the fibrosis process, massive accumulated extracellular matrix can form scar tissue, which results in liver dysfunction or failure and seriously endangers the health of people. According to many independent reports, stem cell therapy can facilitate the alleviation of liver fibrosis. During the stem cell therapy, stem cells migrate to the injury site of liver and alleviate the liver fibrosis by improving the microenvironment of the scar area via paracrine way. This article reviews the formation, treatment, and stem cell therapy of liver fibrosis.

Objective To systematically review the effectiveness and safety of transcutaneous electricalnerve stimulation (TENS) on symptomatic diabetic neuropathy (DNP). Methods Electronic databases such asPUBMED, EMBASE, Cochrane Central Register of Controlled Trials, and Chinese Biomedical Database weresearched by using such mesh and text keywords as "TENS" and "diabetic neuropathy". Randomized controlled trials(RCTs) on the effect of TENS on symptomatic diabetic neuropathy were included. Studies were selected and availa-ble data was extracted independently by two reviewers. Meta-analysis was performed using RevMan 4.2.8 software.Results Three RCTs involving 78 patients were included in this study. Compared with sham-stimulation, TENStherapy significantly reduced the score in pain (SMD -2.35, 95% CI [-4.24, -0.46 ] ) and the score in numb-ness (WMD -0.18, 95% CI [-0.32, -0.05 ] ). Subgroup analysis shows that TENS therapy was associated with a significant reduction in the score of pain in both 4-week treatment duration ( SMD - 5.37, 95% CI [ - 6.97,- 3.77 ] ) and 6-week treatment duration ( SMD - 1.01, 95% CI [ - 2.01, - 0.01 ] ), but not 12-week treatmentduration (SMD - 1.65, 95% CI [ -4.02, 0.73 ] ). Conclusion TENS therapy is a promising and safe strategyfor treatment of symptomatic diabetic neuropathy. More studies are still warranted to accumulate the evidence of theeffect of TENS therapy on DNP.