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Recent studies have demonstrated that superfamily of transforming growth factor-β (TGF-β) plays vital roles in the development of nervous system and neurological diseases.Growth differentiation factor l 0 (GDF 10) is one of the most prominent members of this superfamily.GDF 10 has been shown to participate in tissue formation during cerebellar development and be closely related to the outcomes of neuralgia,ischemic stroke and other neurological diseases.These findings provide novel ideas for research into pathogenesis of nervous system diseases and targets for development of new therapeutic approaches.This article reviews biochemical structure of GDFI0,its downstream signaling pathways,and its roles in cerebellar development,neuralgia and ischemic stroke.Also the possible neurological diseases that may be treated by GDF10 are listed.
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Objective To investigate the role of Src signaling pathway in neurogenesis promoted by choline acetyltransferase (CHAT) + neurons in the subventricular zone (SVZ) after ischemic stroke.Methods The eighty-four mice were randomly assigned into four groups:sham-operated mice treated with vehicle (Sham+vehicle,n=18),middle cerebral artery occlusion (MCAO)-operated mice treated with vehicle (MCAO+vehicle,n=22),MCAO mice treated with donepezil (MCAO+donepezil,n=21),MCAO mice treated with donepezil and Src inhibitor KX2-391 (MCAO+donepezil+KX2-391,n=23).Mice were subjected to the temporary MCAO model of ischemic stroke.Modified neurological severity score (mNSS) was used to assess neurologic function of the mice.Proliferative cells were labeled with Ki67,and neuroblasts with doublecortin (DCX).The expression of Ki67+/DCX+ in the SVZ was detected by immunofluorescence.The expression of Ki67,phospho-epidermal growth factor receptor (p-EGFR),p-Raf,Src and p-Akt in the SVZ were quantified by Western blot.Results MCAO+donepezil+KX2-391 group showed worse performance in the mNSS test than MCAO+donepezil group (P＜0.05).Ten days after MCAO,the number of Ki67+/DCX+ cells in the SVZ of MCAO+donepezil group was 125.33± 13.71/area,which was 71.67± 18.35/area in MCAO+ donepezil+KX2-391 group (P＜0.05).What's more,the expression of proteins Ki67,p-EGFR,p-Raf,Src and p-Akt in mice of MCAO+donepezil group was markedly increased,which was (1.39±0.23),(1.42±0.19),(0.88±0.13),(1.14±0.19),(1.04±0.18) and it was decreased in MCAO+donepezil+KX2-391 group,which was 0.84±0.26,0.94±0.26,0.73±0.15,0.71±0.18,0.81±0.19(P＜0.05).Conclusion CHAT+ neurons in SVZ may promote neurogenesis after stroke via Src-epidermal growth factor receptor (EGFR) signaling pathway.
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Objective To investigate the predictive value of neutrophil and lymphocyte ratios (NLR)for the prognosis in patients with acute cerebral infarction. Methods From January 2014 to December 2015,307 consecutive patients with acute cerebral infarction admitted to the Department of Neurology,the Fifth Affiliated Hospital of Zhengzhou University were enrolled retrospectively,including 80 females and 227 males. They were divided into ether a good prognosis group (n = 195)or a poor prognosis group (n = 112)according to the scoring criteria of the modified Rankin scale (mRS). The age,gender, past medical history,National Institutes of Health stroke scale (NIHSS)score were documented on admission. The NLR values were calculated according to the neutrophil and lymphocyte counts on admission. Logistic regression analysis was used to analyze the influencing factors of poor prognosis of acute cerebral infarction. The receiver operating characteristic curve (ROC)was used to evaluate the predictive effect of the NLR level on patients with acute cerebral infarction on admission. Results (1)Compared with the good prognosis group,the age,incidence of recurrent cerebral infarction,NIHSS score on admission, NLR levels on admission in the poor prognosis group were higher. There were significant differences between groups (69 ± 12 years vs. 62 ± 14 years,25. 0% [28 / 112]vs. 14. 4% [28 / 195],5. 00 [3. 00, 9. 00]vs. 3. 00 [1. 75,5. 00],and 3. 66 [2. 62,7. 91]vs. 2. 47 [1. 94,3. 40];all P 0. 05). (2)Multivariate logistic regression analysis showed that the increase of the age,NLR level on admission,and increased NIHSS score on admission,were independent risk factor for poor prognosis (OR 1. 030,1. 148,and 1. 427,respectively,95% CI were 1. 007 -1. 053,1. 059 -1. 246,and 1. 247 -1. 634, respectively;all P < 0. 05). (3)The diagnostic cut-off value of the NLR level on admission for the poor prognosis in patients with acute cerebral infarction was 2. 84. Its sensitivity was 69. 6% and specificity was 64. 6% . Conclusion The increase of the NLR level on admission had certain reference function on the poor prognosis in patients with acute ischemic stroke.
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Objective To observe the activities of ChAT + neurons in subventricular zone (SVZ) after ischemic stroke and their effects on angiogenesis in peri-infarction region and related signaling pathways. Methods C57BL/6 mice were randomly assigned into sham group,middle cerebral artery occlusion (MCAO) group and atropine group. Ischemic models were made by permanent coagulation of the distal middle cerebral artery. The expression of ChAT,AChE in SVZ and VEGF,VEGFR2,pERK in peripheral regions of ischemic injury was evaluated by Western blotting and immunofluorescence. 5-bromodeoxyuridine(BrdU)/CD31 double-labeled cells were also tested by immunofluorescence. Results At 14 d after the surgery,the ratio of ChAT/AChE in SVZ increased after stroke(P < 0.05). Compared with those in Sham group,the levels of VEGF,VEGFR2 and pERK were higher in MCAO group(P<0.05)and VEGFR2-positive and BrdU/CD31-positive cells increased significantly. However,lower expression of VEGF,VEGFR2 and pERK and less VEGFR2-positive and BrdU/CD31-positive cells were found in atropine group when compared with that in MCAO group. Conclusions The activities of ChAT +neurons in SVZ are enhanced after ischemic injury and they can promote angiogenesis in peripheral region of ischemic injury via upregulating VEGF-VEGFR2 signaling pathway and improving the brain function restoration.
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Objective To investigate the dynamic changes of microglial polarization at the perihe-matoma area and provide timepoint evidence for interventing microglial polarization as well as studying the polarization mechanism after intracerebral hemorrhage ( ICH ) . Methods Healthy male Sprague Dawley (SD) rats were randomly divided into sham group,ICH-4 h,1 d,3 d,7 d and 14 d groups with 6 in each group. The rats in ICH groups were injected collagenase VII-s into the caudate nucleus to establish the in-tracerebral hematoma model and rats in sham operated group were treated with the same amount of saline. The brains were taken at 4 h,1 d,3 d,7 d,14 d in the ICH group,1 d in sham group. Microglia typeⅠ( M1, CD11b++CD86+) and microglia typeⅡ( M2,CD11b++Arg-1+) were examined by immunofluorescence and the number of M1 and M2 around hematoma were analyzed. Results ( 1) The M1 and M2 were both ob-served at 4 h after ICH and a small quantity of branches were still presented on M1. ( 2) M1 took the main position in acute stage (1~3 d),early subacute stage(3~7 d) and chronic stage (>14 d) after ICH.The number of M2 was elevated transiently in superacute (<24 h) and late subacute stage (7 d).The number of M2 (31.40±1.69) was more than M1 (21.43±1.81) at 4 h after ICH ( t=- 4.085, P=0.002),and the number of M2 (116.25±5.06) significantly exceeded M1 (85.75±7.32) again on day 7 ( t=-0.690, P=0.001). Conclusion M1 is in a dominant position in acute,early subacute and chronic stages after ICH;M2 is dominant in superacute and late subacute stages. Investigating the mechanism of M2 formation at acute period ( such as 4 h) or late subacute stage ( such as 7 d) ,and inhibiting M1 formation in the early subacute stage ( 1~3 d) have important significance for clinical treatment of ICH.
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Objective To identify the effects of intracerebroventricular treatment of Norrin on vascular density in peri-infarct area and blood brain barrier (BBB),and explore the mechanisms underlying these changes.Methods (1) Twenty-four mice were randomly divided into sham-operated group,ischemia for 6,24 and 72 h groups (n=6);middle cerebral artery occlusion (MCAO) models in the later 3 groups were induced by suture-occluded method;Western blotting was employed to detect the Norrin expression in the brain tissues.(2) Male C57BL/6 mice were randomly divided into sham-operated group,vehicle group and Norrin treatment group (n=30);MCAO models in the later two groups were induced by suture-occluded method;intracerebroventricular (i.c.v) injection of 250 ng Norrin was performed immediately after MCAO;the changes of neurological function were assessed by modified neurological deficits scale (mNSS);infarct volume was examined by triphenyl tetrazolium chloride (TTC) staining;the changes of brain water content were identified by dry-wet method;immunofluorescence staining was performed to detect the vascular density;Evens blue (EB) extravasation was assessed by means of EB fluorescent quantitation;Western blotting was used to detect the expressions of angiopoietin-2 (Ang-2),zonula occludens protein-1 (ZO-1) and nucleus β-catenin.Results (1)Western blotting results demonstrated that as compared with that in the sham-operated group,the Norrin expression in the ischemia for 6 h group was significantly increased (P＜0.05);further increased trend was noted in the ischemia for 24 and 72 h groups.(2) One and 3 d after MCAO,the mNSS scores in the Norrin treatment group was significantly decreased as compared with those in the vehicle group (P＜0.05);3 d after MCAO,Norrin treatment group had significantly reduced infarct volume,dramatically increased vascular density in peri-infarct area,significantly decreased water edema and EB extravasation,and remarkably up-regualted expressions of Ang-2 and Zo-1 and accumulation of β-catenin in nucleus as compared with the vehicle group,with significant differences (P＜0.05).Conclusion Ischemic stroke induces the up-regulation of Norrin;exogenous Norrin enhances angiogenesis and promotes BBB repair,the underlying mechanism involves in the up-regulation of Ang-2 and Zo-1 mediating by Norrin/β-catenin signaling.
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Objective Recent researches indicate that Eph/ephrin signaling pathway is possibly related to adult neurogenesis after cerebral injury..With brief introduction of their structures and interactions,the review focus on their possible mechanism in adult neurogenesis.Methods The literatures between 2010 and 2015 were retrieved following online databases:PUBMED,ScienceDirect,Wanfang and CNKI database.The key words used in the reasearch were Eph,ephrin,cerebral injury,adult neurogenesisand so on.Results Totally 42 related articles were enrolled.And these papers discribed how researchers performed their experiments and further explained Eph/ephrin 's vital roles in adult neurogenesis.Conclusion Eph/ephrin signaling can influence adult neurogenesis after cerebral injury.positively or negatively.And Akt may be a downstream signaling molecule of Eph/ephrin that change the progress of adult neurogenesis.However,the detailed mechanisms remain to be further study.
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Objective To explore the effects of tumor necrosis factor-α stimulated gene-6 (TSG-6) on early inflammation and blood brain barrier (BBB) in mice after ischemic stroke (IS).Methods A total of 90 healthy male C57BL/6j mice were randomly divided into sham-operated group (n=30),vehicle group (n=30) and TSG-6 treatment group (n=30);the middle cerebral artery occlusion models (IS) in the later two groups were established with suture emboli method;50 μg TSG-6 or PBS was immediately injected into mice via tail vein after IS.Neurological function deficits were assessed by modified neurological severity scale (mNSS) one and three days after IS;infraction volume was examined by triphenyl tetrazolium chloride (TTC) staining,the changes of brain water content were examined by wet and dry weight method,evans blue (EB) extravasation was assessed by means of EB fluorescent quantitation,myeloperoxidase (MPO) activity was tested by ultraviolet specterphotometry,and Western blotting was used to detect the expressions of matrix metalloproteinase-9 (MMP-9),high-mobility group protein box 1 (HMGB1) and toll-like receptor 4 (TLR4) three days after IS.Results Three days after IS,the mNSS scores (5.253±1.712),infraction volume ([26.100±5.640]％),EB extravasation ([7.233± 3.434] μg/g),brainwater content ([71.667±6.518]％),MPO activity ([70.383±17.558] mU/g) and HMGB1,TLR4 and MMP-9 expressions (0.503±0.230,0.482±0.159 and 0.611±0.170) in the TSG-6 treatment group were significantly lower or smaller than those in the vehicle group ([7.923±2.138],([36.883±8.553]％),([11.867±4.135] μg/g),([80.467±7.045]％),([112.617±26.782] mU/g),[0.861± 0.137],[0.833 ±0.193] and [0.910 ±0.156]) three days after IS (P＜0.05);the expressions of MMP-9 (0.611±0.170),HMGB1 (0.503±0.230) and TLR4 (0.482±0.159) in mice of TSG-6 treatment group were significantly down-regulated as compared with those in vehicle group those days after IS (P＜0.05).Conclusion TSG-6 can exert neuroprotective effect by protecting BBB from damage and reducing brain edema by reduction of MMP-9 after stroke,which is mediated by downregulation of HMGB 1 and its receptor TLR4 and the infiltration ofneutrophile granulocytes.
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Objective To explore the relation between plasmocytoid dentritic cells (pDCs) and cerebral immune-inflammation reaction following ischemic stroke. Methods Circulating pDCs were measured by flow cytometry in 62 patients with acute ischaemic stroke (AIS), 26 healthy controls, 12 patients with asymptomatic cerebral infarction stenosis (ACI-S), and 14 patients with transient ischaemic attack (TIA). The sizes of infarct lesions were assessed by DWI scanning. AIS group was further divided into lacunar infarction group, small infarction group,and large infarction group according to the infarction area. The correlation between the number of pDCs and NHISS score and CRP level was also analyzed in AIS group. Results The labsolute number of pDCs and the percentage of pDCPs to circulating blood white cells were significantly lower in AIS group than in the healthy control group (P<0.001). As compared with lacunar infarction group, the number of pDCPs decreased significantly in large infarction group. The number of pDCPs was negatively correlated with the levels of CRP and the NIHSS score. Conclutions Patients with AIS has a decreased level of circulating pDCs, which may be involved in the gathering of circulating pDCs in the infarcted brain to trigger cerebral immune reaction.
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OBJECTIVE@#To evaluate the therapeutic effect of remaining integrated mediastinal pleura upon the aortic arch and performing the anastomosis at the left cervix in radical operation for esophageal carcinoma.@*METHODS@#Ninety-eight patients with esophageal carcinoma were treated with the operation mentioned above. Among them, 56 patients had cancer in the middle, 12 in the upper-middle, 24 in the lower-middle segments, and 6 had double-primary tumors, with carcinoma length of (5.2+/- 2.4) cm. The TNM stages were 6 of Stage I and 92 of Stages II-III. All cases were squamous cell carcinomas.@*RESULTS@#All patients had satisfactory operation processes, without perioperative death, chylothorax, dyspnea, gastric retention, incision infection, and severe gastro-esophageal reflux. The life quality of the patients was improved.@*CONCLUSION@#The radical operation with remaining integrated mediastimal pleura upon the aortic arch and anastomosis at the cervix for treating esophageal carcinomas is of minimal invasion with fewer complications, and may be used in clinical practice.
الموضوعات
Aged , Female , Humans , Male , Middle Aged , Anastomosis, Surgical , Methods , Aorta, Thoracic , General Surgery , Carcinoma, Squamous Cell , General Surgery , Esophageal Neoplasms , General Surgery , Pleura , General Surgery , Thoracic Surgical Procedures , Methodsالملخص
Objective The experimental study on the lift-up speed of a new kind of compliant aerodynamic foil thrust bearings was performed on the multifunctional test rig established for testing the performances of foil gas bearings. Methods The lift-up speed of foil gas thrust bearing under given axial load was analyzed through the spectrum of axial displacement response in frequency domain. Results The test results indicated that the difference in the spectrum of axial displacement responses before and after lifting up of the rotor was obvious. After lifting up of the rotor, there were only larger components of rotation frequency and lower harmanic frequencies. If the rotor wasn't lift-up, there were also larger components of other frequencies in the spectrum. Conclusion So by analyzing the spectrum of axial displacement response, the results showed that the lift-up speed was about 1 860 rpm when the axial load was 31N.
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<p><b>OBJECTIVE</b>To study the effect of changing source-sink ratio on dry matter accumulation yield, distribution and interrelated physiological index of Cynanchum bungei.</p><p><b>METHOD</b>Bud, fruit or side tress of C. bungei were picked artificially in the development stage. LAI, chlorophyll content, photosynthesis of single leaf, accumulation and distribution of dry matter at different and treatments were measured. The untreated plant was used as the control.</p><p><b>RESULT</b>Although leaf decrease can be compensated by the increasing photosynthesis rate of single leaf, the LAI was small, chlorophyll decomposes quickly and these leaves showed the signs of early ageing. The matter accumulation was lower than that of control. Picking bud and fruit made photosynthesis rate of single leaf descend, chlorophyll decomposes slowly and its content keeps high, that inhibited ageing of the plant obviously. The LAI keeps larger, photosynthate was abundant. Dry matter accumulation and distribution to the root were higher than that of control and that of side tress picked. So, the yield with this treatment increased.</p><p><b>CONCLUSION</b>Picking bud can increase LAI, postpone the decomposition of chlorophyll, and protract the functional leaves. Consequently, picking bud can add the accumulation of dry matter, increase proportion to radix and improve the yield and economy benefit.</p>