BACKGROUND: The present study aims to investigate whether mannitol facilitates central nervous system (CNS) entry of vancomycin and alleviates methicillin-resistant Staphylococcus aureus (MRSA) intracranial infection. METHODS: Blood-brain barrier (BBB) permeability was assessed by measuring the concentration of sodium fluorescein (NaF) in the brain tissues of rats and fluorescein isothiocyanate-dextran (FITC-dextran) in a single-cell layer model. Neutrophil infiltration in the brain tissue, inflammatory cytokine levels in the serum, neurological function, and 7-day survival rates were used to evaluate therapeutic effects of mannitol and vancomycin in MRSA-infected rats. Syndecan-1 and filamentous actin (F-actin) levels were measured, and the relationship between F-actin and the endothelial glycocalyx layer (EGL) was explored via the depolymerization agent cytochalasin D and the polymerization agent jasplakinolide. RESULTS: Following mannitol administration, the NaF and vancomycin concentrations in the brain tissue increased rapidly within 5 min and remained stable for 30 min, indicating that mannitol increased BBB permeability for 30 min. In vitro, mannitol treatment led to significantly greater FITC-dextran permeation through a single-cell layer compared to controls. In the MRSA intracranial infection model, rats treated with mannitol and vancomycin simultaneously presented less inflammation, improved neurological function, and increased 7-day survival rate compared to rats treated with vancomycin and mannitol at 10-hour intervals. Further experiments revealed that mannitol decreased the expression of syndecan-1 in brain tissues, which was confirmed by in vitro experiments showing that mannitol significantly decreased syndecan-1 via F-actin depolymerization. CONCLUSION: Mannitol may enhance the therapeutic efficacy of vancomycin against intracranial MRSA infection by decreasing the endothelial glycocalyx of the BBB via F-actin depolymerization.

Asialoglycoprotein receptor(ASGPR),also called galactose receptor,is predominantly expressed on the sinusoidal surface of mammalian hepatocytes and is involved in many physiological functions.For many years ASGPR has been applied for targeting hepatocytes in drug and gene delivery and for functional mapping of the liver,and considerable progress has been made.ASGPR-mediated liver-targeted drug delivery mainly involved anti-tumor drugs and cholesterol-lowering drugs,etc.Liver-targeted gene delivery was often seen in antisense drugs.The research of hepatic imaging mainly involved the evaluation of liver function and identification between hepatocellular carcinoma and hepatic metastasis of tumors.In addition,researchers have also extended its applications to some new fields,such as three-dimension culture of hepatocytes,hepatocytes screening,and hepatocytes transplantation.New achievements in studies of ASGPR-mediated liver targeting are reviewed in this article.

Acute traumatic coagulopathy (ATC) is one of coagulopathy induced by severe trauma in the early phase of trauma.It is always with high morbidity,mortality and multiple organ failure.Early diagnosis and treatment is the main content of trauma surgery in the department of emergency and the key to reduce mortality.Thrombelastography (TEG) can comprehensively assess the different stages of coagulation,early diagnose disturbance of blood coagulation and guide the goal-directed therapy with low complications,mortality and medical costs.TEG has been widely used in the operation of cardiac surgery,liver transplantation and trauma surgery to monitor coagulation and guide therapy.This paper mainly reviews the clinical value of thrombelastography in diagnosis and treatment of acute traumatic coagulopathy.

ObjectiveTo evaluate two "up and down stair" methods used by hemiplegic patients.Methods40 cases with hemiplegia were randomly divided into two groups with 20 cases in each group. Patients in the group A went upstairs with health leg and downstairs with affected leg, while, patients in the group B upstairs with affected leg, downstairs with health leg, and then up and down stairs with health and affected leg alternated. Effects of two training menthods were compared.ResultsEach of two training methods had its advantage and disadvantage, but motor function and mobile ability of patients in the group B were better than patients in the group A (P<0.05).ConclusionHemiplegic patients Should choose different training method of up and down stairs according to his status, and not always choose the method of going upstairs with health leg and downstairs with affected leg.

Objective To investigate the significance of preserving the intercostobrachial nerve (ICBN) during axillary node clearance for breast cancer and share, some technical experiences of this procedure. Methods ICBN was preserved integally or partially in 78 patients of breast cancer (ICBN preserved group) and resected integrally (ICBN resected group) in 18 patients. Sensory disorders and motorial recoveries as well as tumor recurrence were compared between the two groups one week and one year after operation. Results Morbidity of sensory disorders in ICBN preserved group was less than that in ICBN resected group. Motorial recoveries were better in ICBN preserved patients without decreasing the number of axillary nodes resected and without increasing the recurrence of tumor. Conclusion ICBN should be preserved as far as possible during axillary node clearance for breast cancer.

BACKGROUND: Caspase-3 exists in normal cell in form of zymogen and is capable of stimulating cell apoptosis after activated by apoptosis inducing factors.OBJECTIVE: To observe the activity of caspase-3 in hippocampal cytosolic S-100 and neuronal apoptosis in hippocampal regions, so as to discuss the relationship between hippocampal neuronal apoptosis and caspase3 activity during the whole brain ishcemic-reperfuasional injury.DESIGN: Randomized controlled experiment.SETTING: Emergency Department of Southwest Hospital Affiliated to the Third Military Medical University of Chinese PLA.MATERIALS: This experiment was carried out at Southwest Hospital Affiliated to the Third Military Medical University of Chinese PLA from January to April 1999. Totally 182 male Wistar rats were randomly divided into 3 groups: namely sham operation group of 14 rats, cerebral IR group of 84, rats acetyl-asp-glu-val-asp-aldehyde (AC-DEVD-CHO) treatment group of 84 rats, rats in the latter two groups were then subdivided into IR 8, 24, 48, 72, 120 and 168 hours time points subgroups with 14 rats in each.METHODS: The whole brain ischemia 20 minutes and reperfusional model was established on rats in brain IR group and Ac-DEVD-CHO treatment group, and rats were executed separately at post-reperfusional 8, 24,48, 72, 120 and 168 hours for obtaining hippocampal specimen; rats in sham operation group were only underwent anesthesia and operation without common carotid arterial occlusion and burns of vertebral artery, they were executed at 72 hours after operation and hippocampal specimen was obtained. The quantity of amino-methylcoumarin that was produced from the same mass of specimen within same decomposition time was used to reflect the activity of caspase-3. Brain slices that were obtained from different time points were stained and embedded for observing the hippocampal cell apoptosis under fluorescence microscope at 330-350 nm.MAIN OUTCOME MEASURS: ① The caspase-3 activity in hippocampal S-100 in different post-IR time point groups. ② The hippocampal cell apoptosis in different post-IR time point groups. ③ relationship between caspase-3 activity and neuronal apoptosis in hippocampal regions.RESULTS: Totally 182 rats were enrolled in this experiment, 14 rats got lost, thereby date of 168 rats was entered the result analysis. ① The changes of caspase-3 activity in hippocampal S-100 in different post-IR time point groups: There was no change in sham operation group at postoperative 72 hours. In contrast with cerebral IR group, there were obvious reduction in Ac-DEVD-CHO treatment group at post-reperfusional 24, 48,72, 120 and 168 hours [(1.71±0.03, 1.22±0.03; 2.77±0.09, 1.59±0.7;5.54±0.51, 2.3±0.19, 6.28±1.71, 3.43±0.46; 3.11±1.21, 1.73±0.14) nkat/kg;P ＜ 0.05 or 0.01]. ② The hippocampal cell apoptosis in different post-IR time point groups: Under 400× field of vision, the number of apoptotic cells in sham operation group was 1.2±0.4 cells at postoperative 72 hours.It was lower in Ac-DEVD-CHO treatment group at post-reperfusional 24,48, 72, 120 and 168 hours than cerebral IR group [(6.4±1.7, 2.8±0.8;11.8±1.3, 5.8±1.9; 19.8±3.1, 10.0±1.9; 31.2±5.9, 16.4±2.4; 19.8±2.3, 9.0±2.3)cells/400× field of vision; P ＜ 0.01]. ③ Relationship between caspase-3activity and neuronal apoptosis in hippocampal regions: It was proved of linear correlation in cerebral IR group and Ac-DEVD-CHO treatment group,displaying significantly positive correlation r= 0.935 6 or 0.980 0, P ＜ 0.01).CONCLUSION: Caspase-3 activation is one of the major inducer for hippocampal neuronal apoptosis, playing important role in hippocampus neuronal apoptosis in rats during IR injury.

Objective To investigate the roles of Caspase 3 in neuron apoptosis following cerebral ischemia/reperfusion in the rat hippocampus. Methods A model of rats with global ischemia induced by occlusion of the four vessels according to the method by Pulsinelli et al was used in this study. A total of 182 Wistar rats [(220?20) g] were divided randomly into three groups: control group ( n =14), cerebral ischemia group ( n =84), and cerebral ischemia group treated with acetyl asp glu val asp aldehyde (Ac DEVD CHO, n =84). Time points for observation included 8, 24, 48, 72, 120, and 168 h in the latter two groups. Caspase 3 activity in cytosolic extracts (S 100) of hippocampus and apoptotic neurons in hippocampus following cerebral ischemia/reperfusion were observed at the above mentioned time points, respectively. Results (1) No caspase 3 activity was detected in S 100 from the control group. In S 100 from the ischemia group, weak caspase 3 activity was detected at 8 h, but it increased gradually and peaked at 120 h, and then decreased apparently at 168 h after reperfusion. After treatment with Ac DEVD CHO following cerebral ischemia/ reperfusion, caspase 3 activity was inhibited to some extent at each time point. (2) Apoptotic cells were occasionally observed in hippocampus in the control group, but the apoptotic cells increased apparently at 24 h, peaked at 120 h, and decreased a few at 168 h after reperfusion in ischemia group. After treatment with Ac DEVD CHO following cerebral ischemia/reperfusion, apoptosis decreased to some extent at each time point (except 8 h following cerebral ischemia/ reperfusion). (3) Caspase 3 activity in S 100 from hippocampus was positively correlated with apoptotic neurons in hippocampus following cerebral ischemia/reperfusion at each time point ( r =0.9356 in ischemia group, r =0.980 0 in treatment group). Conclusion Caspase 3 may be one of the key causes resulting in neuron apoptosis in rat hippocampus after cerebral ischemia/reperfusion. It may play an important role in ischemia reperfusion brain injury.

Inheirted metabolic disodrers(IMD)involves in multiple substance dysbolism,which usually results in irreversible neurological lesions because of various categories and complicated clinical manifestations.In resent years,IMD became one of the hot spots in medical domain around the world,original diagnostic technique and management progressed unceasingly.This paper provides an overview of the traditio-nal detection and treatment about IMD,and reviews the new techniques such as gene analysis,gene chip,organ transplantation and enzyme replacement therapy at the same time.

Objective To research pacemaker cells outside conductive system of rat and mouse heart. Methods Paraffin and frozen serial sections (stained with HE, Masson, cholinesterase technique), and ultrastructural sections, from atrial tissue of 10 rats and 15 mice were observed by light and electron microscopy to find latent pacemaker-like cells. Results Some round or elliptical cells were scattered and irregularly detected in right and left atrial tissue of rat and mouse. Their nuclei were larger, plasma was clearer and cellular organelles were fewer than those of working myocyte. These cells were similar to pacemaker cells in sinoatrial node.Conclusion There are some pacemaker-like cells in right and left atrial tissue of rat and mouse. The finding can provide a morphological basis for ectopic beat of atrium.

Objective To explore the characteristics and regulations of CD28 and CTLA-4 expressions in the process of mice' T-cell inefficiency induced by staphylococcal enterotoxin A(SEA).Methods Twelve mice were averagely divided into three groups(4 each).The mice in group 1 received single injection of SEA,and the mice in group 2 and 3 received SEA injection twice and three times,respectively,with a 3 days interval.Mice were sacrificed at day 1,3,7 and 14 after the last injection,and then the splenic lymphocytes were isolated.The expressions of CD28 and CTLA-4 in cellular membrane and the intracellular expressions of CTLA-4 and IL-2 were detected with flow cytometry.Results In group 1,the CD28 expression in cellular membrane and the intracellular expression of IL-2 were significantly up-regulated,while the CTLA-4 expressions both in cellular membrane and intracellular expression were lower with no obvious changes.In group 2,the expressions of both CD28 and IL-2 were up-regulated slightly,the expressions of CTLA-4 increased significantly both in cellular membrane and intracellular expression,even more increase was the intracellular CTLA-4 expression.In group 3,the expressions of CD28 and CTAL-4 in cellular membrane and the intracellular CTLA-4 expression declined,and at day 7 the intracellular IL-2 expression was undetectable.Conclusions SEA may obviously promote the activation of naive T-cells when initially used to induce the splenic lymphocytes,while multiple stimulations(e.g.3 times) of SEA may lead T-cells to anergy.On the process of inefficiency,the declined IL-2 production may be closely related to the down-regulation of CD28 expression;the up-regulation of CTLA-4 expression may profit inducing inefficiency,but is not on the maintenance of inefficiency.