Objective To explore the effect of pre-hospital nursing intervention in the new regional cooperative rescue model on treatment delay and the therapeutic effect in patients with myocardial infarction.Methods From January 2012 to May 2014,158 patients with acute myocardial infraction (AMI) were selected.Patients were divided into two groups,intervention group and control group,The first medical contact to balloon(FMC-to-B) time,referral time,cardiac function were analysed.Results Mean FMC-to-B time [(94±21)min vs.(102±23) min],referral time in nursing intervention [(5±3) min vs.(9±4) min)] were significantly shorter than those in control group (t=2.14,6.67,P＜0.05).After a month compared with control group,LVEF was increased [(54.8±6.9)％ vs.(48.8±6.9)％],and LVED was deceased [(50.1±8.2) mm vs.(50.5±5.6)mm] in intervention group.Conclusions Pre-hospital nursing intervention can decrease the FMC-to-B time,which could improve the cardiac function.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Colles' Fracture ; therapy ; Exercise Therapy ; Female ; Humans ; Male ; Middle Aged ; Musculoskeletal Manipulations

BACKGROUND: Magnetic resonance diffusion tensor imaging (MRDTI) may non-wounded detect damage of fiber in white matter and becomes an effectively way to evaluate upper motor neuron(UMN) impairments.OBJECTIVE: To investigate the clinical significance of MRDTI on amyotrophic lateral selerosis(ALS).DESIGN: Case contrast observation.SETTING: Department of Neurology, Renmin Hospital of Wuhan University.PARTICIPANTS: Twenty ALS patients were selected from Department of Neurology, Renmin Hospital of Wuhan University from April to December 2005. There were 11 males and 9 females, and their ages ranged from 33 to 73 years with the mean age of (51±10) years. All subjects met the diagnostic criteria of ALS set by World Neurology League.Other 15 healthy subjects were collected as control group. There were 8 males and 7 females, and their ages ranged from 31 to 73 years with mean age of (50±11) years. All subjects provided the confirm consent.METHODS: Based on level of upper and lower motor neuron impairments, ALS patients were divided into UMN impairment group (n =16) and lower motor neuron group (n =4). Functional scores of ALS, illness developing velocity and pyramidal sign scores were performed, respectively. All subjects were scanned with DTI at axial view. Regions of interest [subcortical white matter of precentral gyrul and postcentral gyrul (Pre-CG/Post-CG), centrum semiovale and frontal white matter (CS/FWM), peripheral lateral cerebral ventricle, posterior limb of internal capsule (PIC), cerebral peduncle (CP), genu corpus callosum and splenium corpus callosum (GCC/SCC) and dorsal thalamus (DT)] were selected to measure fractional anisotropy (FA) and apparent diffusion coefficient(ADC).MAIN OUTCOME MEASURES: Correlations among FA, ADC, functional score of ALS, illness developing velocity and pyramidal sign scores.RESULTS: Twenty patients and 15 subjects in the control group were involved in the final analysis. ① FA was reduced and ADC increased in the posterior limb of the internal capsule in patients with UMN signs compared to healthy volunteers (t =3.452, 2.670; P ＜ 0.01, 0.05). Nonparametric tests revealed that there was a trend toward reduced FA in the posterior limb of the internal capsule in B group compared to controls (U =11, P =0.057). ② In UMN impairment group, FA in the posterior limb of the internal capsule was positively correlated with the ALS rating scale (r =0.577, P ＜0.05) and negatively correlated with pyramidalsign scores (r = -0.789, P ＜ 0.01 ),CONCLUSION : The impairment of pyramidal tracts can be noninvasively evaluated by diffusion tensor MR in vivo, thus providing useful information in diagnosing and further understanding MND.

Objective To evaluated the effect of the regional cooperative rescue model implemented on the length of time from first medical contact (FMC) to balloon dilation (B),economic expense and prognosis in patients with acute coronary syndrome (ACS).Methods Patients with ACS (including ST-segment elevation and non-ST-segment elevation) selected from other hospitals within 24 hours after onset were treated with emergency percutaneous coronary intervention.Patients were divided into two groups, regional cooperative rescue group and control group without the regional cooperative rescue model approved.The lengths of FMC-to-B time and Door-to-B time (from arrival at emergency department or OPD to balloon dilation),time required for patients referred to our hospital,cardiac function,averaged hospital costs,average hospital stay,percentage of medication used and a major adverse cardiac event (MACE) were analyzed.Results Mean FMC-to-B time,Door-to-B time,referral time and time consumed to obtain informed consent were significantly shorter [(106±33) min,(31 ±8) min,(62 ±18,8 ±3) min] vs.[(231 ±35) min,(109 ±26) min,(98 ±31) min,(28 ±11) min,respectively] by implementing the regional cooperative rescue compared with control group,and LVEF was increased,and LVED was deceased inregional cooperative rescue group.The mean costs [(44 123.0 ±3 427.0) yuan vs.(51 587.0 ±5 621.0)] yuan,days of hospital stay [(8.7 ±4.1) vs.(13.2 ±6.4)] and percentage of medication used were significantly decreased in the regional cooperative rescue group.The incidence of MACE inregional cooperative rescue group was 6.2％,whereas the incidence in control group was 16.8％.Conclusions The regional cooperative rescue model can improve the prognosis and decrease the FMC-to-B time,the rate of MACE and financial burden in patients with ACS.

Objective: To investigate whether CD137-CD137L signaling could affect the secretion of mouse vascular smooth muscle cells (VSMCs) -derived exosomes through autophagy mediated Rab7 pathway. Methods: Primary thoracic aorta VSMCs from C57BL/6J mouse were obtained by tissue block adherence method. VSMCs between the third to fifth passages were used and VSMCs were divided into 4 groups: control group, CD137 agonist group, lentivirus control group, Rab7 lentiviral interference group. VSMCs in CD137 agonist group were treated with recombinant protein of CD137L (10 μg/ml), VSMCs in lentivirus control group were treated with lentiviral followed by recombinant protein of CD137L (10 μg/ml), VSMCs in Rab7 lentiviral interference group were treated with Rab7 lentiviral intervention followed by recombinant protein of CD137L (10 μg/ml). Western blot was used to detect the protein expression of LC3Ⅱ, p62, Rab7, CD9, CD81 and Hsc70. Fluorescence microscopy was used to track the changes of autophagy in cells infected with mRFP-GFP-LC3. Transmission electron microscope was used to observe the morphology and size of VSMCs-derived exosomes. The nanoparticle tracking analysis(NTA) was used to detect the concentration and size of exosomes in each group. Results: (1) The expressions of Rab7, LC3Ⅱ and p62 protein in VSMCs of CD137 activation group were significantly higher than those in control group (all P<0.05). The expressions of Rab7, LC3Ⅱ and p62 protein in Rab7 lentivirus interference group was lower than in CD137 activation group (all P<0.05), while the expressions were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (2) The total number of fluorescent spots and yellow fluorescent spots in the VSMCs of the CD137 activation group were higher than those in the control group (all P<0.05), and the number of yellow fluorescent spots was higher than that of the red fluorescent spots in the VSMCs of the CD137 activation group ((50.3±0.9) vs. (10.3±1.5)/cell). The total numbers of fluorescent spots and yellow fluorescent spots in VSMCs of Rab7 lentivirus interference group were lower than those of CD137 activation group (both P<0.05), and the number of red fluorescent spots in VSMCs was higher than that of yellow fluorescent spots ((40.7±4.0) and (10.7±1.2)/cell) in the Rab7 lentiviral interference group. The total numbers of fluorescent spots and yellow fluorescent spots in the VSMCs were similar between the lentivirus control group and the CD137 activation group (all P>0.05). (3) Under transmission electron microscopy, the size of the VSMCs-derived exosomes was about 30-150 nm. The exosome markers (CD9, CD81) could be detected in vesicles by Western blot. NTA results showed that the concentration of VSMCs-derived exosomes was significantly higher in the CD137-activated group than in the control group (P<0.05), which was significantly lower in the Rab7 lentiviral interference group than in the CD137-activation group (P<0.05) and was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of Hsc70 protein in exosomes secreted by CD137 activation group was higher than that in the control group (P<0.05). The expression of Hsc70 protein in exosomes was lower in Rab7 lentivirus interference group than in the CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). The expression of LC3Ⅱ protein in exosome was higher in CD137 activation group than in control group (P<0.05), which was lower in Rab7 lentivirus interference group than in CD137 activation group (P<0.05), which was similar between the lentivirus control group and the CD137 activation group (P>0.05). Conclusion The CD137-CD137L signaling may affect the secretion of mouse VSMCs-derived exosomes through modulating the Rab7 pathway mediated autophagy.

Objective: To observe the correlation between Nε-carboxymethyl-Lysine (CML), the main component of advanced glycation end products and the calcification of the anterior tibial artery plaque in patients with diabetic foot post foot amputation. Methods: Sixty patients hospitalized for foot amputation operation due to diabetic foot from June 2012 to June 2016 in the Department of Orthopedics, Affiliated Hospital of Jiangsu University were prospectively recruited.The patients were categorized into mild stenosis (0n=20), moderate stenosis (50%≤stenosis<70%, n=20) and severe stenosis (70%≤stenosis≤100%, n=20) based on the color Doppler ultrasound assessed severity of anterior tibial artery stenosis.The baseline clinical data of patients were collected and anterior tibial artery was isolated.Then, HE staining, O-Cresolphthalein Complexone method, enzymic method and ELASA analysis were then performed to detect the evolution of calcification, arterial calcium content, alkaline phosphatase activity and serum CML concentration, respectively. Results: The results from both color Doppler ultrasound scan before amputation and HE staining after amputation showed that echo intensity as well as spotty blue calcium particles of anterior tibial artery plaque increased significantly in proportion to degree of stenosis and destructed elastic plate of the arterial wall was evidenced in patients with severest stenosis.The content of calcium ((2.3±0.9), (3.9±1.3), (6.6±1.7) μmol/mg, respectively, P<0.001), ALP activity ((102.4±39.4), (202.3±73.4), (483.7±117.9) U/mg, respectively, P<0.001) and serum CML level ((28.9±4.4), (37.9±5.3), (57.3±7.1)μg/L, respectively, P<0.001) increased significantly in proportion to stenosis severity.Pearson correlation analysis showed that serum CML level was positively correlated with the content of calcium (r=0.749, P<0.001) and ALP activity (r=0.923, P<0.001), respectively. Conclusions Serum CML level is positively correlated with the calcification of anterior tibial arterial plaque in patients with diabetic foot and could be used to evaluate the calcification of anterior tibial arterial plaque and stenosis degree of anterior tibial arterial in these patients.

Objective: To investigate whether CD137-CD137L signaling can affect the autophagy of mouse vascular smooth muscle cells(VSMCs) through JNK signal pathway. Methods: Primary culture of C57BL/6J mouse thoracic aorta VSMCs was performed by tissue block adherence method. VSMCs between the third to fifth passages were isolated and cultured. VSMCs were divided into 4 groups: control group, CD137 agonist group, JNK inhibition group, and DMSO group. VSMCs in CD137 agonist group were treated with recombinant protein of CD137L (10 μg/ml), VSMCs in JNK inhibition group were treated with JNK inhibitor SP600125 (10 μmol/L) for 30 minutes followed by recombinant protein of CD137L (10 μg/ml) and DMSO group was treated with the same amount of DMSO in JNK inhibition group for 30 minutes, then added recombinant protein of CD137L (10 μg/ml). Western blot was used to detect the protein expression of p-JNK, LCⅡ and p62 in each group. Fluorescence microscopy was used to track the changes of autophagy in cells which was infected with adenovirus expressing tandem mRFP-GFP-LC3. Transmission electron microscope (TEM) was used to observe intracellular autophagosomes and autolysosomes. Results: (1) Compared with the control group, stimulating CD137-CD137L axis by recombinant protein of CD137L significantly upregulated the expression of p-JNK, LCⅡ and p62 (1.15±0.19 vs. 0.72±0.21, P<0.05;1.03±0.13 vs. 0.59±0.15, P<0.05, and 1.10±0.19 vs. 0.76±0.15, P<0.05). These effects could be reduced by JNK inhibitor (0.61±0.21 vs. 1.15±0.19, P<0.05;0.74±0.11 vs. 1.03±0.13, P<0.05, and 0.21±0.12 vs. 1.10±0.19, P<0.05). The expression of these proteins in DMSO group remained unchanged compared with CD137 agonist group (P>0.05). (2) Changes of autophagy in cells of various group: the number of total fluorescent spots and yellow fluorescent spots in CD137 agonist group was significantly increased compared to control group (total fluorescent spots:(93.00±14.11)/cell vs. (52.33±9.61)/cell, P<0.05, and (64.33±6.81)/cell vs. (25.67±3.51)/cell, P<0.05), moreover, the number of yellow fluorescent spots was higher than the red fluorescent spots fluorescent spots in CD137 agonist group. Compared with CD137 agonist group, pretreatment with JNK inhibitor significantly reduced the number of total fluorescent spots and yellow fluorescent spots ((53.00±3.17)/cell vs. (93.00±14.11)/cell, P<0.05,and (15.33±4.51)/cell vs. (64.33±6.81)/cell, P<0.05). The red fluorescent spots were higher than the yellow fluorescent spots in JNK inhibition group. The number of total fluorescent spots and yellow fluorescent spots in CD137 agonist group was not affected by pretreatment with DMSO (P>0.05). (3) The number of intracellular autophagosomes and autolysosomes was significantly higher in CD137 agonist group than in control group((17.67±6.03)/cell vs. (5.67±2.52)/cell, P<0.05), and the number of autophagosomes was higher than that of autolysosomes in CD137 agonist group((14.00±4.00)/cell vs. (3.67±2.08)/cell, P<0.05). The number of intracellular autophagosomes and autolysosomes was significantly lower in JNK inhibition group compared to CD137 agonist group((5.67±4.04)/cell vs. (17.67±6.03)/cell, P<0.05) and the number of autophagosomes was lower than that of autolysosomes in JNK inhibition group((1.33±1.53)/cell vs. (4.33±2.52)/cell, P<0.05). The number of intracellular autophagosomes and autolysosomes was similar between DMSO group and CD137 agonist group (P>0.05). Conclusion CD137-CD137L signal may influence autophagy of mouse VSMCs via JNK pathway.

Objective: To explore whether CD137-CD137L interaction could induce mouse vascular smooth muscle cells(VSMCs) calcification via P38 MAPK signaling. Methods: (1) Mouse VSMCs obtained from 8-week old male C57 mice were cultured by using method of tissue piece inoculation.The cells from 3 to 8 passage were divided into 4 groups: control group, agonist-CD137 group(recombinant CD137L protein), anti-P38 group(agonist-CD137 group+P38 inhibitor), single anti-P38 group(P38 inhibitor). The calcification was induced by adding a mixture of 10 mmol/L β-glycerophosphate+10^-8 mol/L dexamethasone+10^-7 mol/L insulin in the culture medium.Immunofluorescence was used to observe the changes of VSMCs markers(α-SMA and OPN).Real time-PCR was used to observe the mRNA expression of OPN and RUNX-2. Western blot was used to observe the protein expression of p-P38, OPN and RUNX-2. The level of cell calcification was observed by detecting alkaline phosphatase activity and calcium concentration. (2) The degeree of local calcium deposition was also tested on Von Kossa staining and Alizarin red staining methods in following 5 mouse VSMCs groups: control group, agonist-CD137 group(recombinant CD137L protein), anti-P38 group (agonist-CD137 group+P38 inhibitor), anti-CD137 group (agonist-CD137 group+CD137 inhibitor),agonist-P38 group(anti-CD137 group+P38 agonist). Results: (1) Compared with the control group, the fluorescence intensity of α-SMA was lower in the agonist-CD137 group(2.79±0.25 vs. 5.42±0.47,P<0.05), while the fluorescence intensity of OPN was higher(4.91±0.23 vs. 1.63±0.26, P<0.05). The fluorescence intensity of α-SMA was partly recovered after adding P38 inhibitor(4.48±0.27 vs. 2.79±0.25,P<0.05),but it was still lower than the control group (4.48±0.27 vs. 5.42±0.47, P<0.05),the fluorescence intensity of OPN decreased(2.66±0.15 vs. 4.91±0.23,P<0.05),but it was still higher than that in the control group (2.66±0.15 vs. 1.63±0.26,P<0.05).The fluorescence intensity of α-SMA and OPN(5.32±0.67 vs. 5.42±0.47,1.82±0.30 vs.1.63±0.26,both P>0.05) was similar between the control group and single anti-P38 group.(2) Compared with the control group, the protein level of p-P38(4.15±0.24 vs. 3.48±0.26, P<0.05), OPN(2.43±0.21 vs. 1.53±0.08, P<0.05), RUNX-2(3.20±0.23 vs. 1.13±0.10, P<0.05) was significantly increased in agonist-CD137 group,the above effects were blocked by adding specific P38 inhibitor SB203580(1.16±0.12 vs. 4.15±0.24, 0.50±0.02 vs. 2.43±0.21,and 1.74±0.14 vs. 3.20±0.23,all P<0.05);the protein level of p-P38(2.93±0.60 vs. 3.48±0.26,P>0.05),OPN (1.4±0.64 vs. 1.53±0.08,P>0.05),RUNX-2(1.26±0.26 vs.1.13±0.10, P>0.05) was similar between single anti-P38 group and the control group. (3) Compared with the control group, the mRNA level of OPN (1.51±0.34 vs. 1, P<0.05) and RUNX-2(2.67±0.19 vs. 1, P<0.05) was significantly upregulated in agonist-CD137 group, and these effects were blocked by adding specific P38 inhibitor SB203580(0.33±0.14 vs. 1 and 0.45±0.03 vs. 1,P<0.05);the mRNA level of OPN (1.05±0.09 vs. 1, P>0.05) and RUNX-2(1.18±0.10 vs. 1, P>0.05) was similar between the single anti-P38 group and the control group.(4) Compared with the control group,the ALP activity and calcium concentration(2.40±0.25 vs. 1.40±0.21,5.51±0.33 vs. 3.15±0.31,both P<0.05) were significantly increased in agonist-CD137 group,while the effects could be blocked by adding specific P38 inhibitor SB203580((1.99±0.07) king unit/gprot vs. (2.40±0.25) king unit/gprot, (3.74±0.20) mmol/gprot vs. (5.51±0.33) mmol/gprot, both P<0.05).The ALP activity and calcium concentration was similar between single anti-P38 group and the control group((1.60±0.25) king unit/gprot vs. (1.40±0.21)king unit/gprot, (2.66±0.28) mmol/gprot vs. (3.15±0.31) mmol/gprot, both P>0.05). (5) Compared with the control group,the calcification of VSMCs in the agonist-CD137 group was significantly increased,while the calcification in the anti-P38 group was significantly reduced.Compared with the agonist-CD137 group,the level of calcification in the anti-CD137 group was obviously increased,and the calcification in the agonist-P38 group was significantly higher than that in the anti-CD137 group and the control group. Conclusion These findings suggest that CD137-CD137L signaling may regulate VSMCs calcification via modulating P38 pathway.

Objective: To investigate the feasibility and efficacy of the establishment of regional cooperative acute ST-segment elevation myocardial infarction (STEMI) rescue network among the prefectural-level city hospitals in China. Methods: Based on real-time remote electrocardiogram transmission and "120" emergency systems, we established a regional collaborative STEMI treatment network with our hospital as the network unclears including 8 second-class affiliated hospitals of Jiangsu University in 2013. STEMI treatment time, therapeutic effects and economic indexes were compared before (from January 2010 to December 2012, 180 cases, pre-network) and after (From January 2013 to December 2015, 374 cases, post-network) the establishment of the regional collaborative STEMI treatment network. Results: Post establishment of the rescue network, mean first medical contact (FMC) to balloon (FMC-to-B) time, referral time and obtaining informed consent time were all significantly decreased from (191±41), (94±18), (25±9) minutes to (93±19), (53±18), (7±5) minutes, respectively, in comparison with the pre-network era(all P<0.05). There was a trend of prolonged FMC-to-B time in proportion to aging of STEMI patients(trend P<0.05). Three months post discharge, LVEF was higher (55.3%±10.7% vs. 48.8%±12.1%, P<0.05) and LVEDd was lower ((49.1±10.8)mm vs.(51.8±9.2)mm, P<0.05) in the post-network group compared to pre-network group.In-hospital mortality was also significantly reduced post the establishment of the rescue network (2.14%(8/374) vs. 3.89%(7/180), P<0.05). The results also showed that the total costs (42 017(25 069, 75 148)yuan vs.51 030(28 137, 105 861)yuan), days of hospitalization ((9.1±4.5) days vs. (15.3±4.8)days) and percentage of medicine and consumables were all significantly decreased in the post-network group compared to pre-network group(all P<0.05). Conclusion Establishment of the regional cooperative rescue network is feasible among the prefectural-level city hospitals in China. Establishment of such network can improve the prognosis and decrease the FMC-to-B time, the rate of in-hospital mortality and financial burden of patients with STEMI, and serves as an effective strategy to improve the rescue ability for STEMI patients.

Objective: To investigate whether CD137 induces primary vascular muscle cells (VSMCs) phenotype transformation through activating nuclear factor of activated T-cells 1(NFATc1) signaling. Methods: VSMCs were obtained from aorta of C57BL/6J mice (8 weeks, male) through tissue-piece inoculating. Cells were divided into control group, CD137 agonist group (treated with CD137L recombinant protein) and anti-CD137 group (treated with anti-CD137 antibody). In si-RNA transfection assay, cells were divided into si-control group and si-NFATc1 group which were transfected with control or si-NFATc1 sequence respectively. The levels of NFATc1 and other phenotype related protein such as α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chain (SM-MHC), vimentin were detected by Q-PCR and Western blot. Nuclear protein expression and activity of NFATc1 were detected by immunofluorescence and Western blot. Transwell assay was performed to measure the migration of VSMCs. Results: According to Western blot, the expression of NFATc1 and vimentin was significantly upregulated (5.07±0.36 vs. 1.00±0.00, P<0.05; 3.23±0.27 vs. 1.00±0.00, P<0.05) while α-SMA and SM-MHC expressions was significantly downregulated (0.73±0.15 vs. 1.00±0.00, P<0.05; 0.45±0.05 vs. 1.00±0.00, P<0.05) in CD137 agonist group compare to control group. Compared with CD137 agonist group, the expression of NFATc1 and vimentin was significantly downregulated (1.56±0.27 vs. 5.07±0.36, P<0.05; 1.21±0.17 vs. 3.23±0.27, P<0.05), but the levels of α-SMA and SM-MHC were significantly upregulated (2.01±0.43 vs. 0.73±0.15, P<0.05; 2.85 ±0.32 vs. 0.45±0.05, P<0.05) in anti-CD137 group. Compared with si-con group, the expression of SM-MHC and α-SMA was significantly upregulated while the expression of vimentin was significantly downregulated in si-NFATc1 group. Transwell assay results demonstrated that migration cell numbers was significantly higher in CD137L group compared with control group(3.85±0.31 vs. 1.00±0.00, P<0.05), this effect was significantly attenuated by inhibiting NFATc1. Conclusion CD137 could induce VSMC phenotype transformation through activating NFATc1 signaling.