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 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.

Objective The clinical manifestations of cerebral infarction caused by acute basilar arterial occlusion are complex.The purpose of this study is to explore the relationship between lesion location and onset symptoms of cerebral infarction caused by acute basilar arterial occlusion.Methods Fifty three patients diagnosed with cerebral infarction caused by acute artery occlusion were collected from Nanjing Stroke Registry.They were hospitalized in Jinling Hospital from January 2007 to July 2016 and were divided into sudden onset group and progressive onset group.Their clinical and digital subtraction angiography data were analyzed retrospectively.Results Middle and distal segment of the basilar artery occlusions were usually found in sudden onset group.Patients in progressive onset group were more likely to present with proximal segment of the basilar artery occlusions.Significant statistical difference was found between two groups (P<0.05).Logistic regression analysis showed that the symptoms of patients with proximal segment basilar artery occlusion tended to be progressive onset, compared with patients affected by distal segment occlusion (OR=14.77,95%CI:1.57-139.00, P=0.019).Conclusion There was significant relationship between lesion location and onset symptoms of cerebral infarction caused by acute basilar arterial occlusion.Early diagnosis and timely treatment may improve clinical prognosis in patients.

Objective Survivin is overexpressed in gastric cancer. However it not expressed in normal gastric mucosa. The expression of survivin is tightly related to the prognosis of gastric cancer.By gene reconstruction we generated pcDNA3 survivin mutant(Cys84Ala) plasmid, and observed its effect on the gastric carcinoma cell lines. Methods The survivin mRNA and protein expression levels were determined by reverse transcription polymerase chain reaction(RT PCR) analysis,Western blot and immunohistochemical staining respectively . Flowcytometry and acridine orange staning were employed to detect apoptosis. Results Overexpression of survivin mRNA and protein were detected in the gastric cancer cell lines. Inhibition of survivin by survivin mutant cDNA induced apoptosis,activated caspase 3 activity,cleaved PARP and promoted cytochrome C releasing in gastric cancer cells,and effectively sensitized gastric cancer cells to chemotherapeutic agents. Conclusion Inhibition of survivin may induce apoptosis in gastic cancer and sensitize gastric cancer cells to chemotherapeutic agents.Survivin targeted therapeutic protocol may potentially benefit gastric cancer therapy.

Objective Neuroinflammation following traumatic brain injury (TBI) may give rise to neurodisorder.This study aimed to investigate the effect of intranasal delivery of nerve growth factor ( NGF) on neuroinflammation following TBI and its action mechanism in rats. Methods Thirty-six male adult Sprague-Dawley rats were equally divided into a sham , a TBI, and a TBI+NGF group.The rats in the TBI +NGF group were treated with NGF intranasally at 12 and 24 hours after TBI.The levels of IL-1βand TNF-αin the injured cerebral cortex were detected by ELISA , the DNA-binding activity of NF-κB evaluated by EMSA , and the expres-sion of amyloid-β( Aβ42 ) determined by Western blot . Results NGF attenuated the inflammation following TBI .Compared with the TBI group, the level of IL-1βwas obviously decreased in the TBI +NGF group at 12 hours (70.65 ±3.10 vs 37.51 ±1.92) and 24 hours (68.85 ±8.10 vs 36.23 ±2.99, P<0.05), and so was that of TNF-α(47.12 ±7.38 vs 27.63 ±5.77 and 56.15 ±11.20 vs 29.94 ±8.62, P<0.05).The DNA-binding activity of NF-κB was reduced to 111.62 ±0.49 and 131.52 ±0.88, and the expression of Aβ42 to 0.23 ±0.008 and 0.52 ±0.004 at 12 and 24 hours respectively after treatment with NGF , both with statistically significant differences from the TBI group (P<0.05). Conclusion Intranasal administration of NGF attenuates TBI-induced neuroinflamma-tion in rats, which may be associated with its regulatory effect on the Aβ42/NF-κB signaling pathway .

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.