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Objective:To observe the effect of early goal directed sedation (EGDS) on cerebral oxygen metabolism in patients with acute brain injury.Methods:A prospective cohort study was conducted. A total of 108 patients with acute brain injury admitted to the intensive care unit (ICU) of the Third Medical Center of the PLA General Hospital from January 2015 to December 2019 were enrolled. According to the patient's condition, dexmedetomidine contraindication and tolerance, and combined with the wishes of patients' families, they were divided into EGDS group and on-demand sedation group. Routine treatments such as surgery, mechanical ventilation, dehydration and reduction of intracranial pressure with mannitol, hemostasis or antiplatelets therapy were given according to the patient's condition. All patients were continuously given sufentanil by intravenous infusion for analgesia. Patients in the EGDS group were sedated by continuously intravenous infusion of dexmedetomidine (0.2-0.7 μg·kg -1·min -1) for 72 consecutive hours. Patients in the on-demand sedation group received intravenous bolus of propofol (0.5-1.0 mg/kg) when treatments were interfered due to agitation. Hemodynamic indexes [heart rate (HR), mean arterial pressure (MAP), cerebral perfusion pressure (CPP), intracranial pressure (ICP)], sedation indexes [bispectral index (BIS)], severity indexes [acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, Glasgow coma score (GCS)] and cerebral oxygen metabolism indexes [jugular venous blood lactate (Lac), jugular venous oxygen saturation (SjvO 2), cerebral arterial oxygen content (CaO 2), cerebral extraction rate of oxygen (CERO 2), cerebral arteriovenous blood oxygen content difference (a-vDO 2)] were compared between the two groups before sedation and at 24, 48 and 72 hours of sedation. Results:① Among the 108 patients, 3 patients with cerebral hemorrhage received secondary surgery or had worsening of cerebral hernia were excluded. 105 patients were enrolled in the study, including 54 patients in the EGDS group and 51 patients in the on-demand sedation group. There were no statistically significant differences in gender, age, type of craniocerebral injury, GCS score, proportion of mechanical ventilation and operation ratio between the two groups. ② Compared with before sedation, Lac, CERO 2 and a-vDO 2 of both groups gradually reduced over time of sedation while SjvO 2 and CaO 2 were gradually higher. Those changes were more quickly in the EGDS group, Lac, SjO 2, CERO 2 and a-vDO 2 significantly improved at 24 hours of sedation compared with those before sedation. Above indexes at 72 hours of sedation in the EGDS group were obviously better than those in the on-demand sedation group [Lac (mmol/L): 1.81±0.31 vs. 2.19±0.12, SjvO 2: 0.714±0.125 vs. 0.683±0.132, CaO 2 (mL/L): 201.21±15.25 vs. 179.65±14.07, CERO 2: (27.87±3.66)% vs. (33.00±2.58)%, a-vDO 2 (mL/L): 44.32±5.68 vs. 48.57±8.22, all P < 0.05]. ③ Compared with before sedation, HR, MAP and ICP decreased in the two groups over time while CPP, BIS and GCS score showed increasing trend, especially more quickly in the EGDS group, HR at 24 hours of sedation, MAP, CPP, BIS and GCS score at 48 hours significantly improved as compared with those before sedation. Hemodynamics and sedation related parameters and GCS score at 72 hours of sedation in the EGDS group were significantly better than those in the on-demand sedation group [HR (bpm): 70.69±7.80 vs. 79.85±9.77, MAP (mmHg, 1 mmHg = 0.133 kPa): 84.23±8.76 vs. 89.97±9.48, ICP (mmHg): 14.23±8.76 vs. 15.97±9.48, BIS: 60.56±24.58 vs. 56.86±33.44, GCS score: 8.06±3.63 vs. 7.86±2.98, all P < 0.05]. The APACHE Ⅱ scores were significantly reduced at 72 hours of sedation in both groups as compared with those before sedation, while there was no statistical difference between the two groups. Conclusion:Compared with the on-demand sedation, EGDS could reduce cerebral oxygen metabolism, improve the coma degree, and reduce the severity of the disease in patients with acute brain injury.
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Objective:To investigate the value and feasibility of early goal directed sedation (EGDS) in patients with acute brain injury.Methods:A total of 110 patients with acute brain injury who were admitted to intensive care unit (ICU) of the Third Medical Center of the Chinese People's Liberation Army General Hospital from January 2015 to March 2019 were included and randomly divided into EGDS group and standard sedation group (STD) using the random number table. Patients in the EGDS group were sedated by continuous intravenous infusion of dexmedetomidine (initial dose of 0.2 μg·kg -1·min -1) for 72 consecutive hours. Patients in the STD group received intravenous bolus of propofol as appropriate clinically. Richmond agitation-sedation score (RASS) and electroencephalogram bispectral index (BIS) were used to continuously monitor the level of sedation. All patients were given sufentanil for analgesia. Routine treatments such as dehydration and reduction of intracranial pressure with mannitol, hemostasis or antiplatelet therapy were given according to the patients' condition. Vital signs, acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, Glasgow coma scale (GCS) score, BIS value, artery blood gas analysis, duration of mechanical ventilation, analgesic dosage and adverse events were recorded in two groups before and 24, 48, and 72 hours after sedation. Results:① Among the 110 patients, patients who received the second surgery due to cerebral hemorrhage, had worsening of cerebral hernia, withdrew during the course of the study, or whose family members abandoned treatment were excluded from the study. Finally, 105 patients were enrolled in the study, including 56 patients in the EGDS group and 49 in the STD group. There was no significant difference in gender, age, types of brain injury, baseline APACHEⅡ or GCS score or rate of mechanical ventilation between the two groups. ② Compared with before sedation, heart rate (HR) significantly decreased till 72 hours after sedation in both groups, and the decrease in the EGDS groups was more obvious as compared with the STD group (bpm: 70.49±7.53 vs. 79.83±9.48, P < 0.05). Besides HR, significant improvement was found in the APACHEⅡ and GCS scores in the STD group at 72 hours of sedation as compared with before sedation, and no significant difference was found in other indicators. Compared with before sedation, arterial partial pressure of carbon dioxide (PaCO 2) was significantly increased from the 24th hour of sedation, mean artery pressure (MAP) was decreased significantly and GCS score, BIS value were increased significantly from the 48th hour of sedation, till 72 hours, which were all improved significantly as compared with the STD group [72-hour PaCO 2 (mmHg, 1 mmHg = 0.133 kPa): 40.30±5.98 vs. 31.57±8.20, 72-hour MAP (mmHg): 85.01±8.26 vs. 89.54±9.41, 72-hour GCS score: 8.62±3.34 vs. 7.89±2.74, 72-hour BIS: 60.87±24.79 vs. 56.68±33.43, all P < 0.05]. APACHEⅡ score was significantly lower only at the 72nd hour of sedation as compared with before sedation in the EGDS group, and no significant difference was found as compared with the STD group (17.10±7.05 vs. 18.90±3.32, P > 0.05). Oxygenation index (PaO 2/FiO 2) was significantly increased only at the 24th hour of sedation in the EGDS group as compared with the STD group (mmHg: 261.05±118.45 vs. 226.45±96.54, P < 0.05). ③ The duration of mechanical ventilation was significantly shorter in the EGDS group than that in the STD group (hours: 20.56±9.03 vs. 27.75±11.23, P < 0.05), and the total administered dose of sufentanil was significantly lower in the EGDS group than that in the STD group (μg: 79.16±26.76 vs. 102.46±35.48, P < 0.05). ④ Compared with the STD group, the incidence of bradycardia in the EGDS group was increased significantly [10.71% (6/56) vs. 6.12% (3/49), P < 0.05], while the incidence of tachycardia was decreased significantly [14.29% (8/56) vs. 38.78% (19/49), P < 0.05], but no significant difference was found in the incidence of hypotension [5.36% (3/56) vs. 4.08% (2/49), P > 0.05]. The incidence of unexpected extubation in the STD group was 4.08% (2/49), which did not occurre in the EGDS group. Conclusion:EGDS can improve the GCS score and BIS value of patients with acute brain injury, suggesting that the EGDS is safe and feasible, which can help improve neurological function in patients with acute brain injury.
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Objective@#To explore the regulatory mechanism of E2F1 transcription factor on M2 macrophages in full-thickness skin defect wounds of mice.@*Methods@#E2F1 gene knockout heterozygotes C57BL/6 mice and wild-type C57BL/6 mice were introduced and self-reproduced. Two weeks after birth, E2F1 gene knockout homozygotes mice and wild-type mice were identified by polymerase chain reaction (PCR). Twelve identified 6-8 weeks old male E2F1 gene knockout homozygotes C57BL/6 mice and wild-type C57BL/6 mice were selected respectively according to the random number table and set as E2F1 gene knockout group and wild-type group. A full-thickness skin defect wound was made on the back of each mouse. On post injury day (PID) 2 and 7, 6 mice in each group were selected according to the random number table and sacrificed, and the wound tissue was excised. The expression of CD68 and CD206 double positive M2 macrophages was observed by immunofluorescence method, and the percentage of CD206 positive cells was calculated. The protein expression of CD206 was detected by Western blotting. The mRNA expression of arginase 1 was detected by real-time fluorescent quantitative reverse transcription PCR (RT-PCR). Wound tissue specimens of the two groups on PID 7 were obtained, and the protein and mRNA expressions of peroxisome proliferator-activated receptor gamma (PPAR-γ) were detected by Western blotting and real-time fluorescent quantitative RT-PCR respectively. The above-mentioned experiments were repeated four times. Three specimens of wound tissue of mice in wild-type group on PID 7 were obtained to detect the relationship between E2F1 and PPAR-γ by co-immunoprecipitation and Western blotting, and this experiment was repeated two times. Data were processed with unpaired t test.@*Results@#The size of PCR products of E2F1 gene knockout homozygotes C57BL/6 mice and wild-type C57BL/6 mice were 227 and 172 bp respectively, which were the same as those of the designed DNA fragments. On PID 2 and 7, the number of CD68 and CD206 double positive M2 macrophages in the wound tissue of mice in E2F1 gene knockout group was more than that of wild-type group, and the percentages of CD206 positive cells in the wound tissue of mice in E2F1 gene knockout group were (0.234±0.032)% and (0.584±0.023)% respectively, which were significantly higher than (0.129±0.017)% and (0.282±0.071)% of wild-type group (t=3.29, 3.54, P<0.05). On PID 2 and 7, the protein expression of CD206 in the wound tissue of mice in E2F1 gene knockout group were 1.00±0.23 and 1.63±0.26 respectively, which were significantly higher than 0.43±0.06 and 0.97±0.08 of wild-type group (t=2.41, 2.45, P<0.05). On PID 2 and 7, the mRNA expressions of arginase 1 in the wound tissue of mice in E2F1 gene knockout group were 0.482±0.105 and 0.195±0.031 respectively, which were significantly higher than 0.163±0.026 and 0.108±0.017 of wild-type group (t=3.04, 2.86, P<0.05). On PID 7, the protein and mRNA expressions of PPAR-γ in the wound tissue of mice in E2F1 gene knockout group were 0.61±0.12 and 0.51±0.13 respectively, which were significantly higher than 0.20±0.04 and 0.20±0.04 of wild-type group (t=3.36, 2.86, P<0.05). On PID 7, detection of the wound tissue of mice in wild-type group showed that PPAR-γ had unidirectional effect on E2F1.@*Conclusions@#E2F1 transcription factor affects the polarization of M2 macrophages by inhibiting the expression of PPAR-γ, thereby inhibiting the healing process of full-thickness skin defect wounds in mice.
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Objective To investigate the relationship between serum prealbumin (PA) and inflammation in acute myocardial infarction (AMI) patients. Methods A prospective observational study was conducted. AMI patients hospitalized in the cardiovascular department of the General Hospital of Chinese People's Armed Police Forces from June 2014 to June 2016 were enrolled in the study. At the same time, healthy cases were enrolled as control. Venous blood was taken from patients at admission. Serum PA was detected by immune projection turbidimetry method and high-sensitivity C-reactive protein (hs-CRP) was measured by latex enhanced immune turbidimetry. High-sensitivity cardiac troponin T (hs-cTnT), and interleukin (IL-6, IL-8) was measured by electrochemical luminescence method. Creatine kinase-MB isoenzyme (CK-MB) was detected by rate method. PA, inflammatory factor and myocardial enzyme were compared between two groups. The correlation between PA and inflammatory factors was analyzed by Pearson linear correlation; The diagnostic value of PA was analyzed by receiver operating characteristic (ROC) curve. Results 173 AMI patients and 86 healthy controls were enrolled in the study. There were no significant differences in gender, age, history of smoking, hypertension and diabetes. Compared with the control, the levels of serum PA in AMI patients was lower [PA (g/L): 0.215±0.056 vs. 0.280±0.057], hs-CRP, IL-6, IL-8, hs-cTnT and CK-MB were higher [hs-CRP (mg/L): 6.63±3.52 vs. 2.25±1.45, IL-6 (ng/L): 38.03±22.43 vs. 6.13±3.38, IL-8 (ng/L): 295.61±98.70 vs. 17.24±7.31, hs-cTnT (μg/L): 4.789±2.874 vs. 0.009±0.008, CK-MB (U/L): 244.48±165.54 vs. 12.20±5.24], the difference was statistical significant (all P 0.05). It was shown by ROC curve analysis that area under ROC curve (AUC) of PA for diagnosis of AMI was 0.783±0.039, and the 95% confidence interval (95%CI) was 0.706-0.860 (P < 0.05). When the cut-off value was 0.190 g/L, the sensitivity was 29.63%, and the specificity was 62.22%. Conclusion PA may be involved in the inflammatory process of AMI and had a diagnostic value for AMI.
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Objective To explore the necessity and function of the sustentaculum tali screw placement for the treatment of Sanders type Ⅱ calcaneal fracture.Methods The data of Dicom that CT scan with bone was input into Mimics 12.0 software and Ansys 13.0 software for construction of calcaneus three-dimensional finite element model.Then,this model was imported into Solidworks 2010 software.Type Ⅱ calcaneal fracture model was established according to Sanders type cutting of calcaneus.Geometric parameters of AO calcaneal plate and screws were imported to the Solidworks 2010 software.Two internal fixation simulations were established based on the calcaneal model.In one model,the steel was placed on the outside with bone and the cancellous' bone screws were infiltrated respectively into the vertical bone since two screw holes which under the articular surface behind the steel plate,two screw holes which rear of the steel plate,a screw hole of the below calcaneus,two screw holes which in front of steel plate.In another model,a cortical bone screw was infiltrated into the sustentaculum tali through the bottom screw hole of articular surface of the steel plate.The two internal fixation models were loaded under the same condition,and non linear finite element analysis was carried out.The stress distribution in the two internal fixation models was calculated respectively.Results The maximum principal stress focused on the cortical bone of sustentaculum tali in both of the models under the same condition of loading.Bone joint displacement,maximum principal stress of calcaneal and internal fixation system in the model with sustentaculum screw fixation were smaller than that in the model without sustentaculum screw fixation.The stress in the model with sustentaculum screw fixation was more dispersed.Conclusion The placement of sustentaculum tali screw is essential for fixation of type Ⅱ calcaneal fracture to achieve the biomechanical stability and can be used in clinical.
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<p><b>OBJECTIVE</b>To explore the expression of inducible nitric oxide synthase (iNOS) in restenosis rats and function of Astragalus membranaceus and Angelica sinensis.</p><p><b>METHOD</b>The restenosis model was established by denuding aorta endothelium, rats were randomly divided into control group, model group, A. membranaceus treatment group, A. sinensis treatment group, combined A. membranaceus with A. sinensis treatment group. After intramuscular injection of drugs for 21 dayss, the changes of iNOS in restenosis rats were observed by histomorphology and immunohistochemisty, the effects of A. membranaceus and A. sinensis on iNOS in restenosis rats was also investigated.</p><p><b>RESULT</b>A small quantity of iNOS were detected in the intima and media of normal aorta, the expression of iNOS was increased on 3 day after denuding aorta endothelium, the expression of iNOS increasd and the color darken along with injury damage and intima thickening. Compared with model group, the expression of iNOS decreasd in A. membranaceus, A. sinensis treated group, A. membranaceus and A. sinensis treated group changed more significantly.</p><p><b>CONCLUSION</b>iNOS was involved in blood vessel restenosis by denuding aorta endothelium, A. membranaceus, A. sinensis could inhibit intimal proliferation through iNOS.</p>
Subject(s)
Animals , Male , Rats , Angelica sinensis , Chemistry , Astragalus Plant , Chemistry , Constriction, Pathologic , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Gene Expression Regulation, Neoplastic , Nitric Oxide Synthase Type II , Metabolism , Rats, Sprague-DawleyABSTRACT
ObjectiveTo observe the effects of human IL-10 gene transfection on the mRNA and protein expressions of IL-1β and TNF-α in the penumbra area following focal cerebral ischemia-reperfusion injury in rats and to investigate its neuroprotective mechanism. MethodsRats were divided into four groups: normal control group, ischemic control group, empty plasmid group and human IL-10 gene transfected group. The mRNA and protein expressions of IL-1β and TNF-α in the penumbra area were detected by fluorescence real-time quantitative PCR and ELISA respectively. ResultsIn normal control group, ischemic control group, empty plasmid group and human IL-10 gene transfected group, the levels of protein expression of TNF-α in penumbra area were(0.66±0. 04) ,(1.16±0.26),(1. 155±0. 26)ng/g and(0. 84±0. 05)ng/g, and the levels of protein expression of IL-1βin penumbra area were(0.37±0.05), (1.25±0.39), (1.21±0.57) ng/g and(0.62+0.05)ng/g, respectively. Compared with normal control group, the levels of protein expression of TNF-α and 1L-1β were significantly higher in other three groups(all P＜0. 01), and lower in human IL-10 gene transfected group than in ischemic control group and empty plasmid group(all P＜0. 01). In normal control group, ischemic control group, empty plasmid group and human IL-10 gene transfectedgroup, the levels of mRNA expression of TNF-α in penumbra area were 1.00 ±0.53,9.42±1.83,9.69±1.96 and 3.53±1.09, and the levels of mRNA expression of IL-1β in penumbra area were 1.00 ±0.51,27. 81±4.84,23.96 ± 4.90 and 13.55± 4.45, respectively. Compared with normal control group, the levels of mRNA expression of TNF-α and IL-1β were significantly higher in other three groups(all P＜0. 01), and lower in human IL-10 gene transfected group than in ischemic control group and empty plasmid group(all P＜0. 01). ConclusionsThe human IL-10 gene transfection may play an protective effect on cerebral ischemia through inhibiting mRNA and protein expression of IL-1β and TNF-α in the penumbra area following focal cerebral ischemia-reperfusion in rats.
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BACKGROUND: Plasminogen activator inhibitor 1 is the main regulator of the fibrinolytic system in vivo. The increase of plasminogen activator inhibitor 1 is closely related to thrombotic disease and it is also an independent risk factor for development of thrombotic disease.OBJECTIVE: To investigate the effect of huangqi(Astragalus), danggui (Angelica) and ligustrazine as medicines activating blood and eliminating stasis on the expression of plasminogen activator inhibitor 1 in HepG2 hepatocarcinoma cell strain.DESIGN: A randomized controlled study.SETTING: First Cadre Department of General Hospital of Chinese People' s Armed Police Force.MATERIALS: The experiment was completed in Academy of Military Medical Sciences of PLA from August to December 2004. HepG2 hepatocarcinoma cell strain was cultured. According to different drugs in culture medium, they were divided into six groups: control group, huangqi group,danggui group, huangqi + danggui group, compound danshen group and ligustrazine group.METHODS: Huangqi, danggui, huangqi + danggui, compound danshen and ligustrazine were added in HepG2 culture medium respectively. MTS assay was used to detect the effect of medicines activating blood and eliminating stasis on proliferation of HepG2 cells, plasminogen activator inhibitor 1 was assayed by specific enzyme-linked immunosorbent assays(ELISA),plasminogen activator inhibitor 1 activity was measured by amidolytical assay. 0.5 μg/mL of transforming growth factor β1 cells was added in HepG2 culture medium to stimulated production of plasminogen activator inhibitor 1. Control group was treated under the same conditions but without Chinese herbs.RESULTS: The inhibitory rates of cellular proliferation in huangqi and danggui groups werc(6.51 ±2. 66)% and (4.42 ±2. 19)%, but those in huangqi + danggui, compound danshen and ligustrazine groups were (12. 06 ±4. 98)%, (16. 38 ±4.06)% and(32. 83 ±9.8)% respectively,t = 2. 447 - 3. 707, P ＜ 0.05. Compared with the control group, huangqi,danggui, compound danshen and ligustrazine significantly inhibited plasminogen activator inhibitor 1 expression(22.68 ± 2.20, 11.11 ± 1.23,19.66±1.53, 15.45±1.27, 16.90±0.33, 14.01±0.74, t=2.447-3.707, P ＜ 0.05) and activity(2.16±0.014, 2.01 ±0.006, 1.95±0.014, 1.79±0. 104, 1.53±0.045, 1.48±0.012, t =2.447-3. 707,P ＜ 0.05) in HepG2 cells. The evident inhibitory effects were observed in the group of huangqi + danggui, especially in compound danshen and ligustrazine.CONCLUSION: The plasminogen activator inhibitor 1 expression and activity were inhibited effectively by huangqi, danggui, compound danshen and ligustrazine.
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Objective To investigate the effect of Astragalus Membranaceus( Ast) and Angelica Sinensis( Ang) on antithrombosis and explore the molecular mechanism. Methods Plasminogen activator inhibitor-1 ( PAI-1) expression and activity were selected to observe the antithrombosis effect of Ast and Ang ( 3 and 6 mg/ml) on 0. 5 ng/ml TGF-?1 treated endothelial cells. PAI-1mRNA expression was detected by RT-PCR,PAI-1 antigen assay was detected by specific enzyme-linked immunosorbent assays( ELISA) ,and PAI-1 activity was measured by amidolytical assay. Results Ast and Ang significantly inhibited PAI-1 mRNA expreesion,antigen and activity in endothelial cells. The more powerful effects could be observed when treated by Ast and Ang together. Conclusion The PAI-1 mRNA expression,antigen and activity is inhibited effectively by Ast and Ang,which may be the mechanism of their treatment for antithrombosis.
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Objective To investigate the effects of Astragalus membranaceus and Angelica sinensis on the hemodynamics and pathological features of arterial wall in restenosis of blood vessel in rats in order to find the potential mechanism of the effect of Astragalus membranaceus and Angelica sinensis in preventing restenosis after ablation of intima. Method Thirty SD rats were randomly divided into 5 groups (6 each):control group (C),model group (M),Astragalus membranaceus treatment group (H),Angelica sinensis treatment group (D),and combined Astragalus membranaceus with Angelica sinensis treatment group (HD). The restenosis model was reproduced by denuding rat's aorta endothelium with balloon catheter in all the groups except group C. After intramuscular injection of Astragalus membranaceus 0.42ml/(kg?d) in group H,Angelica sinensis 0.21ml/(kg?d) in group D,and Astragalus membranaceus 0.42ml/(kg?d) together with Angelica sinensis 0.21ml/(kg?d) in group HD for 21 days,the changes in hemodynamics and the pathological features of arterial wall were observed in all the groups. Result Compared with rats of group C,in which the intima was smooth and the smooth muscle cells (VSMCs) in media were orderly arranged,the intimal thickness of aorta,pulsatile index (PI) and resistance index (RI) increased,while the diameter of lumen,blood velocity decreased remarkably in group M. Compared with the rats in group M,the extent of hyperplasia and thickness was notably reduced,RI and PI were lower while blood velocity was lowered in group H,D and HD after being treated for 21 days. Conclusion Hyperplasia induced by remaval of endothelial cells may be reduced and blood circulation may be improved to different extents by individually or simultaneously use of Astragalus membranaceus and Angelica sinensis,thus preventing restenosis of the aorta after removal of its intima.
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AIM: To investigate whether the expression of integrin ?_3 and the activation of focal adhesion kinase(FAK) are involved in neointima formation after de-endothelium.METHODS: The model of intima hyperplasia was prepared by balloon injury.The levels of osteopontin(OPN),integrin ?_3 and FAK in vascular tissue were detected by Western blotting and immunohistochemistry.RESULTS: There were similar expression patterns in OPN,integrin ?_3 and FAK following balloon injury.The levels of three proteins were markedly increased 3 days after operation and reached the peak at 7th day.The increased FAK was mainly the phosphorylated form.The migration and proliferation of vascular smooth muscle cells was associated with the increase in the expression of integrin ?_3 and FAK,and was parallel with rapid turnover of extracellular matrix(ECM).CONCLUSION: The interaction of cells with ECM mediated by OPN and integrin ?_3 is essential for migration.The integrin ?_3-FAK pathway is involved in neointima formation.