Objective To study whether intranasally administered transforming growth factor beta1(TGF-?1)can reach central nervous system(CNS)through the trigeminal nerve pathway.Methods Nineteen healthy male SD rats were randomly assigned into control group(n=6)and administration(IN)0.5h group(n=3),1h group(n=4),2h group(n=3)and 6h group(n=3).Rats in IN groups were given 50?l(20?g)recombinant human TGF-?1(rhTGF-?1)intranasally and were sacrificed at 0.5,1,2 or 6h after IN following blood sample collection.The cerebellum,midbrain,pon,medulla and trigeminal nerve were separated quickly and the concentration of TGF-?1 was analyzed by ELISA.Results Compared with the control group(15.01?1.50pg/mg),TGF-?1 was significantly elevated in the trigeminal nerve in all the IN groups(P0.05).TGF-?1 concentrations in plasma and other caudal CNS regions,such as cerebellum,midbrain and cervical spinal cord,were not significantly changed compared with that in control group.Conclusion TGF-?1 is likely to be absorbed by the trigeminal nerve following intranasal administration,and is subsequently delivered to some brain regions through the trigeminal nerve pathway,which may provide a potential treatment strategy for trigeminal nerve and CNS disorders.

Objective To investigate the clinical characteristics and therapy methods of dorsolateral medullary syndrome.Methods The clinical data of 36 cases of dorsolateral medullary syndrome were analyzed retrospectively.Results The palients presented with acute or sub-acute oneset.Vertigo(83.3%),dysarthria(61.1%),dysphagia(52.8%),Horner's syndrome(80.6%),ataxia(72.2%) and crossed sensory disturbance(50%) were the most common symptoms and signs.MRI examination demonstrated dorsolateral medullary infarction in 32 of 36 patients.13 patients received DSA examination and the results showed 6 patients with different degree disease of vertebral arery,2 patients with isolated posterior inferior cerebellar artery occlusion,1 patient with vertebral occlusion and ipsilateral posterior inferior cerebellar artery stenosis.In 33 patients who received anticoagulation,antiplatelet and activating blood circulation to dissipate blood stasis therapies,26 patients improved 7~10 days after treatments and the symptoms almost disappeared during 1～2 months.6 cases remained different degree sensory disturbance and ataxia 1 case died.3 patients were treated with percutaneous transluminal angioplasty and stenting.The symptoms relieved at the day of operation and recovered completely 1 week after operation.Conclusions Dorsolateral medullary syndrome is a clinical syndrome because of insufficient blood-supply in local blood vessel.MRI is sensitive for the diagnosis of dorsolateral medullary syndrome.The location and degree of the disease can be identified by DSA.Intervention treatment is an effective method in the therapy of dorsolateral medullary syndrome.

Endovascular treatment is becoming a novel technique in the treatment of carotid stenosis. Since this technique is in its infancy, there are many controversies on this technique and theory now. This paper briefly reviews the most recent advances in endovascular treatment of carotid stenosis.

Antiplatelet therapy is commonly used for the secondary prevention of embolic stroke of undetermined source (ESUS). However, the embolic source of ESUS is extremely heterogeneous, and the effect of antithrombotic therapy is different. This article describes the etiology and secondary prevention research progress of ESUS, in order to provide reference for clinical diagnosis and treatment.

Aim To evaluate the effects of ferulic acid ( FA ) on lipopolysaccharide ( LPS )-induced neuroin-flammation in microglia cells and its potential mecha-nisms. Methods Microglial activation was induced by stimulation with LPS, and the effects of FA pretreat-ment on microglial activation and production of proin-flammatory mediators, nitric oxide/iNOS were investi-gated. The role of the mitogen-activated protein kinases in the antiinflammatory actions of FA in LPS-stimulated microglia was further elucidated. Results Cell viabil-ity experiments revealed that FA did not produce cyto-toxicity in microglia. FA significantly inhibited LPS-in-duced production of tumour necrosis factor-alpha ( TNF-α) , interleukin-6 ( IL-6 ) , interleukin-1 beta ( IL-1β) , and nitric oxide ( NO ) . Protein and mRNA levels of COX-2 and inducible nitric oxide synthase ( iNOS) were also attenuated by FA. Further experi-ments on intracellular signalling mechanisms showed that inhibition of extracellular regulated kinase ( ERK) contributed to the anti-neuroinflammatory actions of FA. Conclusion The results suggest that FA inhibits LPS-induced microglial inflammation by partial targe-ting of ERK signalling and attenuation of ERK.

Objective To investigate the dynamic changes of hippocampal insulin like growth factor-1(IGF-1)/IGF-1 receptor (1GF-1 R) signaling pathway and learning and memory function and to investigate the possible mechanisms of vascular dementia (VaD).Methods A rat chronic cerebral hypoperfusion model was induced by using permanent bilateral common carotid artery ligation.At day 3,1 and 2 weeks,1,2 and 4months after modeling,Morris water maze test was used to evaluate the changes of learning and memory function in rats.HE staining was used to observe the morphological changes of hippocampal neurons.Enzymelinked immunosorbent assay was used to detect the dynamic changes of IGF-1,IGF-1R,Akt and p-Akt in hippocampal tissue.Results One month after modeling,the rats of a model group began to appear significant learning and memory dysfunction.The numbers of crossing the platform were significant lower than those in a sham operation group (1.91 ±0.45 times vs.3.95 ± 1.64 times; t =17.251,P =0.000).With the extension of ischemia time,the degree of injury of pyramidal cells in hippocampal CA1 region aggravated gradually in the model group.The levels of IGF-1 and p-Akt in hippocampal tissue increased early after modeling in the model group,and then they declined gradually to the normal levels.The levels of IGF-1 (0.09 ± 0.05 ng/mg vs.0.20 ±0.03 ng/mg; t =-5.263,P =0.003) and p-Akt (12.50± 1.40 pg/mg vs.17.13 ± 0.87 pg/mg; t =- 5.651,P =0.000) at 1 month were significantly lower than those in the sham operation group and continued to 4 months.There were no significant changes in the levels of IGF-1R and Akt.Conclusions The down-regulation of IGF-1/IGF-1R signaling pathway may be one of the pathogeneses of VaD.

Objective To investigate the relationship between serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) and Suzuki' s grading system in adult moyamoya disease (MMD).Methods Fifty-two adult patients with MMD,who were diagnosed in Jinling hospital between April 2009 and January 2010,were retrieved from the Nanjing Stroke Registry Program (NSRP).Sixteen sex- and age-matched healthy individuals with MMD patients consisted of the control group.Using enzyme-linked immunosorbent assay,serum concentrations of VEGF and MMP-9 were compared between adult MMD patients and healthy individuals.By Suzuki' s six-grading system,patients were divided into different subgroups,and the correlation of serum levels of VEGF and MMP-9 corresponding to different subgroup and Suzuki's grading was respectively analyzed.In addition,the correlation of serum levels of VEGF and MMP-9 was also evaluated.Results Serum VEGF concentrations in ischemic and hemorrhagic MMD patients was respectively ( 289.4 + 69.2 ) pg/ml and ( 324.3 ± 95.6 ) pg/ml and were significantly higher compared to those in healthy controls ( ( 63.5 ± 7.6 ) pg/ml; F =69.43,P ＜ 0.01 ).Similar findings were observed for MMP-9 ( ( 499.4 ± 76.2 ) ng/ml and ( 531.2 + 100.2 ) ng/ml versus (257.1 ±30.7) ng/ml; F =66.023,P ＜0.01 ).With the increase of Suzuki' s grading,serum levels of VEGF and MMP-9 respectively showed a high trend ( r =0.879,P ＜ 0.01:r =0.838,P ＜ 0.01 ).In addition,a positive correlation between serum levels of VEGF and MMP-9 was found in the MMD group( r =0.590,P ＜0.01 ).Conclusion The results show that serum levels of VEGF and MMP-9 in adult MMD are higher than those in healthy controls,which may play a role in neovascularization in MMD,and moreover,serum levels of VEGF and MMP-9 show a high trend with the progression of MMD,which suggest that serum levels of VEGF and MMP-9 can reflect the severity of MMD.

Community Health Committee (CHC), an innovative public participation mechanism of grassroots health service management, established a bottom-up communication channel between the public and government to communicate health related problems and opinions, and set up a grassroots community health services supervision system. The rural residents were endowed with opportunities to take part in grassroots health care decision making and management by CHC. CHC changed the top-down model of traditional health management, improved the grassroots medical services, and increased governance capability of local government We introduced the CHC practice in Zhejiang project counties, exhibited the primary effects and experience of this pilot program, and explored new mechanism and model for rural community residents to participate in grassroots health service management

Objective To investigate the value of hyperintense vessel signs (HVS) on fluidattenuated inversion recovery (FLAIR) sequence for assessing the patterns of collateral blood flow in adult moyamoya disease (MMD).Methods Forty-one adult patients with non-hemorrhagic MMD retrieved from Nanjing Stroke Registry Program between August 2008 and January 2011 were identified by digital cerebral angiography and performed the examination of FLAIR sequence in Jinling hospital.According to the different sites of HVS located in the territory of the middle cerebral artery,the patterns of HVS were classified into grades 0-3: Grade 0,absence of HVS ; Grade 1,HVS limited in the cerebral sulci of temporal lobe and Sylvian fissure ; Grade 2,HVS in the cerebral sulci of frontal and parietal lobe regions and Sylvian fissure;and Grade 3,HVS in the combined territories of Grade 1 and Grade 2.According to the intracerebral collateral blood flow,steno-occlusions of the arteries were classified into three types: Type 1,residual antegrade flow across steno-occlusive lesions; Type 2,retrograde flow via leptomeningeal vessels; Type 3,the combined collateral blood flow of Type 1 and Type 2.The relationship between the patterns of intracerebral collateral blood flow and the location of HVS was analyzed.Results Of 41 adult patients with non-hemorrhagic MMD,there were 3 patients presented with unilateral vascular lesions and 38 with bilateral vascular lesions,so the total number of vascular lesions of the cerebral hemispheres was 79.Because three patients showed the absence of HVS in bilateral hemispheres,the total number of the presence of HVS of the cerebral hemispheres was 73.Therefore,the percentage of the presence of HVS was 92.4％ (73/79) in vascular lesions of the cerebral hemispheres.Importantly,the patterns of slow collateral blood flow corresponding to Grade 1 HVS were all antegrade (7/7) ; the collateral patterns corresponding to Grade 2 HVS were mainly retrograde leptomeningeal flow (95.0％,19/20) ; and the patterns corresponding to Grade 3 HVS were mainly slow combined collateral blood flow(84.8％,39/46).Furthermore,with the changing sites of HVS from the cerebral sulci of temporal lobe to the cerebral sulci of frontal and parietal lobe regions,the directions of collateral flow changed with a shift from antegrade to retrograde,which was statistically significant.Conclusion The different locations of HVS can reflect the different patterns of collateral blood flow,and the locations of HVS may predict the directions of intracerebral collateral blood flow in adult MMD patients.

ObjectiveTo develop doxorubicine-loaded nanomicelles based on a type of novel starshaped 4-arm PLGA-PEG-NH2 amphiphilic block copolymers.Methods 4s-(PLGA-PEG-NH2) synthesized by 4s-PLGA and (H2N-PEG-NH2) according to N,N'-dicyclohexylcarbodiimide(DCC) condensation reaction was demonstrated by 1H NMR spectroscopy and gel permeation chromatography(GPC); DOX-loaded 4s-(PLGA-PEG-NH2) nanomicelles were self-assembled by doxorubicin(DOX) and 4s-(PLGA-PEG-NH2) via emulsion-solvent evaporation method and characterized in terms of morphology,particle size and size distribution,drug loading,encapsulation efficacy,cell uptake and cytotoxicity studies.Results4s-(PLGA-PEG-NH2) were capable of selfassembling intocore-shell nanomicelles structure and encapsulating DOX into their hydrophobic cores.The mean size of DOX-loaded 4s-(PLGA-PEG-NH2) was nanometer size; drug loading and encapsulation efficacy were around 7.5％ and 75.2％,respectively.Mean surface charge of the micelles was around -17.6 mV.In vitro cell uptake and cytotoxicity studies indicated that comparing to the DOX-loaded linear-(PLGA-PEG-PLGA)nanomicelles,DOX-loaded 4s-(PLGA-PEG-NH2) nanomicelles showed better performance in uptaking by HeLa cells and higher cytotoxicity to cancer cells.Conclusion4s-(PLGA-PEG-NH2) amphiphilic block copolymers can be successfully used in encapsulating DOX,self-assemblingcore-shell nanomicelles in aqueous solvent.Therefore,4s-(PLGA-PEG-NH2) copolymers can be considered as a promising drug carrier in effectively carrying hydrophobic drug,improving the efficacy while reducing the side effect.