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.

Disseminated malignancy is the main cause of cancer-related death.The spontaneous circulation of tumor cells is responsible for distant metastasis;therefore it is of potential importance to specifically and sensitively detect the circulating tumor cells,which not only allows for more accurate prediction of cancer prognosis,but also helps to tailor individualized anticancer treatment.This paper reviews the enrichment,detection and analyzing methods of circulating tumor cells.

[Objective]To introduce a new technique of ankle arthrodesis with trephine by lateral approach and evaluate its clinical effects.[Method]Ankle arthrodesis with trephine was performed in 20 patients with serious lesions.Lateral incision was adopted and osteotomy of fibula facilitated the exposure of the fusion site.A trephine of appropriate diameter was used for bi-osteotomy,thus inside the trephine gaining two bone blocks were then rotated 90? and replanted in situ.The pruned fibula was fixed with screws as on-lay!grafting.Proper cast was utilized postoperatively to maintain a functional position.[Result]The average follow-up period was 26 months(ranged from 6 months to 4 years).All the wounds healed well at 2 weeks and the callus appeared 4 weeks postoperatively.Sufficient pain relief was obtained in all patients at 12 weeks and appearance improved greatly.A solid union was achieved in all cases through the radiograph.[Conclusion]The use of trephine in ankle fusion by lateral approach is proved to be a simple technique with high union rate.The main advantages of the technique over other methods of arthrodesis include: excellent exposure by regular incision;less disturbance of the original joint,thereby preserving normal height of the joint and length of the extremity;no need for extra graft through in-situ grafting of the bone blocks and rigid on-lay grafting of lateral malleolus for high primary stability.

Objective To study the repair of great vessels injured by firearm in extremities. Methods From May 2002 to Sep. 2005, 15 cryopreserved homologous arteries were transplanted to repair the defects of great vessels of extremities in 14 patients, including 5 cases of defect of brachial arteries, 1 case of defect of axillary artery, 1 case of popliteal artery damage and 7 cases of defect of femoral arteries. The average length of homologous arterial transplants was 9.5 cm. After operation, all the 14 patients were monitored and treated according to principles of microsurgery. Result No early reject reaction was found in all the 14 cases, and all the wounds healed after Ⅱ stage treatment. With Doppler ultrasonic examination 2-3 weeks after healing, it was proved that 100% of the vessels were patent. In 4 to 8 month follow up, the function of the extremities recovered well, and no delayed reject reaction was observed. Conclusion The vessels after cryopreservation is a suitable biomaterial in homologous transplantation for repairing the defect of great vessels of the extremities as a result of firearm injury.

Objective To investigate changes in NF ?B signal pathway in PAM stimulated by lipopolysaccharide(LPS) in vitro , and to explore the molecular pathological mechanism of acute lung injury(ALI). Methods After PAM were stimulated by LPS, the changes in expression of IKK mRNA, activation of NF ?B, degradation of I?B, and secretion of TNF ? in PAM were measured at 0, 15min, 30min, 1h, 2h, and 4h by in situ hybridization, electrophoretic mobility shift assay (EMSA), and enzyme linked immune absorbing analysis (ELISA), respectively. Results The expression of IKK ? mRNA was increased 15min after LPS stimulation and reached the peak at 30 min, then returned to the base line after 1 hour. The changes in I?B ? mRNA were opposite. The activity of NF ?B was increased 15min after LPS stimulation, peaking at 1 hours, and returned to the pre stimulation level after 2 hours. The content of TNF ? was increased initially at 30min, reached the peak at 1 hour, and gradually returned to the pre stimulation level in 2～4 hour. Conclusion The transduction pathway of activation of IKK ? degradation of I?B/activation of NF ?B/synthesization of TNF ? might play a critical role in the molecular pathological mechanism of LPS induced ALI.

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.

This study was aimed to carry out pharmacological research on the hemostatic activity and mechanism of Yi medicine Ma-Bu (Paris polyphylla Smith var stenophylla Franch.). One kind of C27 steroidal saponin from P. polyphylla Smith var stenophylla Franch. was isolated and identified as Paris saponin H (PSH). The effect of PSH on the index of bleeding time (BT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) of mice were measured. The results showed that PSH have significant hemostatic activity by shortening BT. The effect of PSH on shortening PT and APTT of mouse was not significant. However, the FIB was enhanced significantly after treatment with PSH. It was concluded that PSH had no significant promoting effect on the extrinsic coagulation pathway (ECP) or the intrinsic coagulation pathway (ICP). The enhancement of FIB may be a pathway for the effect of hemostatic activity by PSH.