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PURPOSE: We investigated the role of tumor-associated macrophages (TAMs) on the epithelial to mesenchymal transition (EMT) of colorectal cancer cells and determined the potential mechanism involved in the metastatic process. MATERIALS AND METHODS: In this study, flow cytometry was used to detect the expression of target proteins. We used transwell assay to evaluate the migration of cancer cells under specific conditions. Using real-time polymerase chain reaction, we examined the expressions of cytokines and EMT-related markers in mRNA level. Animal assay was performed for analysis in vivo and hematoxylin and eosin was used to visualize the effect of TAMs on tumor metastasis. We also used immunohistochemistry and Western blotting to detect the expression of target proteins. RESULTS: Here, we observed enrichment of TAMs in colorectal tumor tissues, resulting in high metastasis in clinical therapy. Moreover, those TAMs could facilitate the EMT progression of colorectal cancer cells, which is induced by the transforming growth factor-β (TGF-β) derived from TAMs, leading to the invasion and migration of cancer cells. CONCLUSION: Our results demonstrated that TAMs contributed the EMT progression through a TGF-β/Smad2,3-4/Snail signaling pathway, and disrupting this pathway with TGF-β receptor inhibitor could suppress metastasis, readjusting our focus to the connection of TAMs and cancer metastasis.
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Animals , Blotting, Western , Colorectal Neoplasms , Cytokines , Eosine Yellowish-(YS) , Flow Cytometry , Hematoxylin , Immunohistochemistry , Macrophages , Neoplasm Metastasis , Real-Time Polymerase Chain Reaction , RNA, MessengerABSTRACT
Objective@#To investigate the influence of different discontinuation time of aspirin and clopidogrel before off-pump coronary artery bypass grafting (OPCABG) on postoperative bleeding and blood products transfusion requirement.@*Methods@#Three hundred and fifty-three coronary artery disease patients who underwent OPCABG from January 2017 to January 2018 at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University were retrospectively analysed. There were 268 males and 85 females, aged (66.0±9.1)years. All patients were divided into three groups: (1) guideline-recommended group: patients who discontinued clopidogrel for >5 days without discontinuing aspirin before surgery; (2) without discontinuing group: patients who discontinued clopidogrel for ≤5 days without discontinuing aspirin before surgery; (3) discontinuing group: patients who discontinued clopidogrel for >5 days with discontinuing aspirin before surgery. Postoperative bleeding recorded as chest tube drainage (CTD) volume and blood products transfusion requirement and perioperative complications were recorded. CTD volumes within 12 hours after surgery between groups were compared by Mann-Whitney U tests, CTD volumes after 12 hours postoperatively were compared by repeated measures analysis of variance and blood products transfusion and complications incidence were compared by χ2 test or Fisher′s precise test.@*Results@#The 12 hours CTD volumes of guideline-recommended group, without discontinuing group, discontinuing group after surgery were 280(153) ml (M(QR)), 291(229) ml, 225(161) ml, respectively. There were no significant differences in postoperative 12 hours CTD volumes (P=0.865), red blood cells transfusion incidence (χ2=2.626, P=0.149) and fresh frozen plasma (FFP) transfusion incidence (χ2=1.258, P=0.324) between guideline-recommended group and without discontinuing group. However, the 12 hours CTD volumes were significantly higher in guideline-recommended group patients compared with disconutinuing group patients (U=5 247, P=0.002). No significant differences were observed in red blood cells (χ2=0.182, P=0.757) and FFP (χ2=0.083, P=0.839) transfusion rate between these two groups. Repeated measures analysis of variance indicated that when patients began to take antiplatelet drugs (aspirin and clopidogrel) after 12 hours postoperatively, the change of CTD volumes beyond 12 hours after surgery didn′t differ either between guideline-recommended group and without discontinuing group (F=0.019, P=0.941) or between guideline-recommended group and discontinuing group (F=2.447,P=0.113). Besides, the incidence of perioperative arrhythmia was significantly higher in guideline-recommended group patients compared with without discontinuing group patients (4.8% vs. 0, χ2=5.073, P=0.038).@*Conclusions@#OPCABG patients who discontinued aspirin before surgery had lower postoperative 12 hours CTD volumes but similar blood products transfusion rate and CTD volumes beyond 12 hours postoperatively compared with patients adhering to the current guideline-recommended protocol. And for patients who discontinued clopidogrel for ≤5 days, postoperative CTD volumes and blood products transfusion requirement were similar but the incidence of perioperative arrhythmia was significantly lower compared with guideline-treated patients.
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Objective@#To evaluate the impacts of an on-pump beating-heart versus an off-pump coronary artery bypass grafting (CABG) technique for surgical revascularization on the early clinical outcomes in patients with a left ventricular ejection fraction (EF) of 35% or less.@*Methods@#A total of 216 consecutive patients with an echocardiographic estimated EF of 35% or less who underwent non-emergency, primary, isolated CABG from January 2010 to December 2014 at Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University were included in this study and were divided into either an OBCAB group (patients who received on-pump beating-heart CABG surgery, n=88) or an OPCAB group (patients who received off-pump CABG surgery, n=128). The early clinical outcomes were investigated and compared. The outcomes were compared between groups by t-test, χ2 test or Fisher′s exact test, when appropriate.@*Results@#No significant differences emerged between the two groups in baseline characteristics of the entire cohort except for more patients with diabetes and a larger left ventricular endo-diastolic diameter in the OBCAB group. Patients in the OBCAB group compared to the OPCAB group had a similar in-hospital mortality (3.4% vs. 4.7%, P= 0.741). Mean EF, as measured preoperatively and early postoperatively (before discharge), significantly improved from (31.0±2.8)% to (35.6±2.9)% (t=10.61, P=0.000) in the OBCAB group and from (31.0±2.9)% to (34.8±3.3)% (t=9.68, P=0.000) in the OPCAB group, respectively. The improvement of mean LVEF in the OBCAB group was significantly higher than that in the OPCAB group ((4.7±0.2)% vs. (3.6±0.3)%, t=29.53, P=0.000). Patients in the OBCAB group compared to the OPCAB group had a significant higher early postoperative EF ((35.6±2.9)% vs.(34.8±3.3)%, t=1.892, P=0.034) but shared a similar baseline EF ((31.0±2.8)% vs. (31.0±2.9)%, t=0.012, P=0.930). Patients in the OBCAB group compared to the OPCAB group received a greater number of grafts and an increased amount of drainage during the first 24 h (3.7±0.8 vs. 2.8±0.6, t=9.442, P=0.000; (715±187) ml vs. (520±148) ml, t=8.544, P=0.000, respectively), without evidence of worse in-hospital mortality or major postoperative morbidity.@*Conclusion@#The on-pump beating-heart technique may be an acceptable alternative to the off-pump technique for surgical revascularization in patients with an estimated EF of 35% or less.
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Objective To investigate the clinical characteristics,surgical experience and mid-term outcome of coronary artery bypass graft surgery in patients aged ≤ 40 years.Methods From Jan.,2009 to Dec.,2015,12 patients with median age of (37.9 ± 2.5) years (range 32-40 years,10 males) were diagnosed with coronary artery disease and underwent coronary artery bypass graft surgery at Zhongshan Hospital,Fudan University.The clinical characteristics included five cases with hypertension,three cases with diabetes mellitus,four cases with hyperlipemia,eight cases with smoking history,seven cases with myocardial infarction.Six cases had at least one branch totally occluded.Two cases once underwent percutaneous coronary intervention surgery and implanted with five and three stents respectively.The perioperative data and follow-up results were retrospectively analysed.Results There was no in-hospital death and no death during follow-up period.Surgical techniques included bilateral internal mammary arteries combined with radial artery were operated in six cases,bilateral internal mammary arteries combined with great saphenous vein in two cases,left internal mammary arteries combined with great saphenous vein in four cases,off-pump in nine cases and on-pump in three cases.The mean follow-up time was (47.8 ± 24.3) months.During the follow-up one case suffered with saphenous vein graft restenosis 5 years after the surgery and underwent percutaneous coronary intervention.Other cases were all alive and assessed New York Heart Association's function class Ⅰ-Ⅱ.Conclusions Younger patients usually suffer with severe coronary artery disease when diagnosed because they often have excellent compensative capacity and the pathogenesis is concealed.The mid-term results of coronary artery bypass graft surgery in patients aged ≤40 years are satisfactory.
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Objective Functional mitral regurgitation (FMR) refers to the systolic regurgitation of mitral valve secondary to compromised cardiac function or geometry abnormity with non-organic change of leaflets and ancillary parts of the valve.Severe aortic insufficiency (AI) with left ventricular dilation and dysfunction is clinically a complex heart disease and its postoperative complications and mortality are higher than usual valvular surgery.And such patients are often accompanied by FMR.It is generally acknowledged that FMR may improve after aortic valve replacement(AVR).This study follow up AI patients with left ventricular dilation and dysfunction and preoperative 2 + ＜ FMR≤3 + to evaluate the outcome of FMR after AVR.Preoperative clinical data is assessed by regression analysis.Methods From January 2000 to April 2011 our hospital treated 74 cases of patients with severe aortic regurgitation combined with left ventricular dilation (LVEDds ≥70 mm) and dysfunction (left ventricle ejection fraction,LVEF≤0.35) accompanied by 2 + ＜ FMR≤3 +.Postoperative follow-up was performed.Results The perioperative mortality rate was 8.1％.Average follow-up time was (14.9 ± 7.7) months and follow-up rate of 83.6％.5 patients died during follow-up.6 months after surgery,the average of FMR was (2.64 ± 1.17) (+),compared with preoperative data.LVEDd,LAD,CPMA,all P ＞ 0.05 compared with the preoperative data.LVEF,PAH,both P ＜ 0.05 compared with preoperative data.3.Multiple regression analysis:FMR pre/FMR post ratio is not correlated with age,gender,weight,LVEDd ≥ 75 mm,LVEF≤0.30,hypertension,ventricular arrhythmia and FMR postoperative improvement.However,PAH ≥ 50 mm Hg(1 mm Hg =0.133 kPa),LAD ≥ 50 mm,PAH≥50 mm Hg,CPMA ≥ 15mm,preoperative atrial fibrillation was negatively correlated with FMR postoperative improvement.Conclusion Severe AI with left ventricular dilation and dysfunction is a critical clinical heart disease and its postoperative complications and mortality are high.PAH ≥ 50 mm Hg,LAD ≥ 50 mm,PAH ≥ 50 nun Hg,CPMA ≥ 15mm,preoperative atrial fibrillation was negatively correlated with FMR postoperative improvement.Since patients with 2 + ＜ FMR ≤3 + usually do not improve or even worsen after AVR,those who have these above conditions preoperatively,should be treated on FMR during AVR.
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Objective Functional mitral regurgitation (FMR) refers to the systolic regurgitation of mitral valve secondary to compromised cardiac function or geometry abnormity with non-organic change of leaflets and ancillary parts of the valve.Severe aortic insufficiency (AI) with left ventricular dilation and dysfunction is clinically a complex heart disease and its postoperative complications and mortality are higher than usual valvular surgery.And such patients are often accompanied by FMR.It is generally acknowledged that FMR may improve after aortic valve replacement (AVR).This study follow up AI patients with left ventricular dilation and dysfunction and preoperative 2 + ＜ FMR ≤3 + to evaluate the outcome of FMR after AVR.Preoperative clinical data is assessed by regression analysis.Methods From January 2000 to April 2011,74 cases of patients were treated,who with severe aortic regurgitation combined with left ventricular dilation (left ventricle,LVEDD ≥ 70 mm) and dysfunction (left ventricle ejection fraction,LVEF ≤ 0.35) accompanied by 2 + ＜ FMR ≤3 +.Postoperative follow-up was performed.Calculation FMR preoperative/FMR postoperative ratio,the age,sex,weight,high blood pressure,ventricular arrhythmia,atrium fibrillation,LVEDD,LVEF,left atrium diameter(LAD),pulmonary artery pressure (PAH),mitral leaflet coaptation point and the mitral annular(CPMA).All factors for logistic multiple faotors regression analysis.Results The perioperative mortality rate was 8.1％.Average follow-up time was (14.9 ± 7.7) months and follow-up rate of 83.6％.5 patients died during follow-up.6 months after surgery,the average of FMR was 2.64 ± 1.17 (+),P ＞0.05 compared with preoperative data.LVEDD,LAD,CPMA,P ＞0.05 compared with the preoperative data.LVEF,PAH,both P ＜0.05 compared with preoperative data.3.Multiple regression analysis:FMR preoperative/FMR postoperative ratio is not correlated with age,gender,weight,LVEDD ≥75 mm,LVEF≤0.30,hypertension,ventricular arrhythmia and FMR postoperative improvement.However,PAH ≥50 mm Hg,LAD ≥50 mm,PAH ≥50 mm Hg,CPMA ≥ 15 mm,preoperative atrial fibrillation was negatively correlated with FMR postoperative improvement.Conclusion Severe AI with left ventricular dilation and dysfunction is a critical clinical heart disease and its postoperative complications and mortality were high.PAH ≥50 mm Hg,LAD ≥50 mm,PAH ≥50 mm Hg,CPMA ≥15 mm,preoperative atrial fibrillation was negatively correlated with FMR postoperative improvement.Since patients with 2 + ＜ FMR≤3 + usually do not improve or even worsen after AVR,those who have these above conditions preoperatively,should be treated on FMR during AVR.
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Objective Analysis the clinical data of high-EuroSCORE 114 patients due to ronary surgery to elucidatethe surgical advantages between on-pump and off-pump CABG.Methods From September 2008 to March 2011,114 highEuroSCORE patients due to coronary surgery were randomly divided into off-pump group 48,and on-pump gronp 66 cases.Preoperative,intra-operative and peri-operative clinical data of all the patients were collected.All patients were followed up for 1 month postoperatively.Results The baseline of the two groups had no significant difference.Application of internal mammary artery,positive inotropic drugs and IABP assistance between the two groups were similar,P ＞0.05,Compared with the offpump group,patients in on-pump gnup had longer operation time,hut more graft counts and a higher rate of revascularization [ (3.71±0.55)gnifis vs.(2.82±0.39)grafts ],P ＜ 0.05.There were no significant differences of peri-operative mortality and post-operative complications between the two groups,P ＞0.05.The patients in on-pump group had more post-operative chest drainage in the first 24 hours[ (875.0±134.2)ml vs.(589.4±102.5)ml] and blood transfusion[ (656.3±84.4)ml vs.(433.3±62.9) ml ] compared with the off-pump group,P ＜ 0.05.The data of l-month follow up denonstrated that echocardiographic data,NYHA and symptoms of angina of the two groups had no significant difference,P ＞ 0.05.Conclusion Compared with OPCAB,CCAB did not increase postoperative renal failure,neurological complications and lung injury in highrisk patients,but had more complete revascularization.The disadvantage of CCAB was postoperative bleeding,blood productsuse.
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Objective Stanford type A acute aortic dissection is a life-threatening medical condition with high rates of morbidity and mortality that requires surgical repair, on an emergency basis. The extent of aortic arch repair that should be carried out during emergency surgery of this type is controversial. This study was conducted to report clinical experience on aortic arch repair and determine surgical indication, optimal operative procedures and strategy for Stanford type A acute aortic dissection. Methods 210 consecutive patients with acute Stanford A aortic dissection who underwent aortic arch replacement combined with implantation of stented elephant trunk into the descending aorta between August 2005 and August 2010. Surgical procedures included hemi-aortic arch replacement in 92 patients, subtotal aortic arch replacement in 50 patients and total aortic arch replacement in 68 patients. All operations were performed with the aid of deep hypothermic circulatory arrest and selective antegrade cerebral perfusion (SACP). Enhanced computed tomography scanning was performed to evaluate the postoperative outcomes, particularly the fate of the false lumen remaining in the descending thoracic aorta by aortic arch replacement combined with implantation of stented elephant trunk during follow up. Results Average cardiopulmonary bypass time was (146 ±52) min. The average cross clamp time was(93 ±25)min and average selective cerebral perfusion and circulatory arrest time was(35 ±14)min. The overall in-hospital mortality was 4. 8% (10/210) and morbidity was 8. 6% ( 18/210). Postoperative complications included acute renal failure, stroke, mediastinitis and respiratory insufficiency. During the follow-up period [mean (27 ± 18) months, ranged 2 to 60 months], 1 patient underwent reoperation due to the descending thoracic and abdominal aortic aneurysm. There was no late death. Follow-up enhanced CT scanning showed about 74% false lumens obliterated at the level of the distal border of the stent graft post operation. Conclusion Open aortic arch replacement is an effective approach and provides acceptable outcomes for type A acute aortic dissection. Optimal treatment strategy is the key factor to success in emergency surgical intervention.
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Objective To investigate changes in the number of endothelial progenitor cells (EPC) from peripheral blood and pathological feature in the development of transplant arteriosclerosis in mouse abdominal aortic allografts, and discuss their correlations. Methods A segment of abdominal aorta was transplanted orthotopically from C57BL/6 to Balb/c mice. The grafts were harvested at 3rd day, 2nd week, 4th week and 6th week after the operation and studied by light and electronic microscopy. Regional changes in the lumen and intima were measured with computer imaging analysis system. EPC from peripheral blood were quantified by flow cytometry. Results Endothelium injury and inflammatory cells infiltration were seen in the aortic allografts at 3rd day after transplantation.Neointimal lesions and acute rejection were observed as early as 2nd week after surgery. The lumen of allografts was significantly narrowed due to neointima hyperplasia and had progressed at 4th and 6th week postoperatively. The number of circulation EPC was increased from 1 st day after operation and reached the peak at 3rd day. Thereafter the number of EPC was decreased rapidly and significantly less at 14th and 28th day postoperation than that pre-operation. Conclusion Abdominal aortic transplantation from C57BL/6 to Balb/c mice presents typical pathological feature of transplant arteriosclerosis. The number of EPC from peripheral blood is related to the process of injured endothelial repair and neointima formation of aortic grafts. EPC count may be considered a novel biological marker and therapeutic intervention for transplant arteriosclerosis.
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Objective To evaluate the clinical application and midterm result of mitral valve repair with multiple techniques for patients with complex mitral valve regurgitation. Methods From January, 2000 to July, 2006, 34 patients with complex mitral regurgitation, including 24 males and 10 females, aged 23 - 65 years [ average (42.8 ± 11.7) years ], comprised the study group. The data of the cardiac function (NYHA/EF), the diameter of left ventricular, left atria and the degree of mitral regurgitation were analyzed before and after operation. Results There was no mortality or major morbidity or reoporatien. Patients were followed up from 1 to 54 months [ average (31.2 ± 19.4) months]. The degree of mitral valve regurgitation decreased significantly after operation. The mean degree of pre-operatien mitral regurgitation was 3.62 ± 0.49, and follow-up degree was 1.18 ± 0.99 ( P ＜ 0.05) respectively.The diameters of left ventricular and left atria reduced. The postoperative cardiac function improved apparently. EF increased from 0.55 ± 0.11 preoperatively to 0.57 ± 0.10 postoperatively ( P = 0.06). Conclusion The comprehensive application of multiple techniques in repairing complex mitral valve regurgitation may be effective, and with a satisfying midterm results.
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Objective To summarize the mid-term outcomes of minimally invasive direct coronary artery bypass (MIDCAB). Methods A series of 33 patients underwent MIDCAB from November 2000 to April 2003: 29 of them received MIDCAB only and 4 received the hybrid approach operation (combining MIDCAB of the left anterior descending artery with percutaneous coronary intervention of the remaining diseased coronary arteries). Out of the 33 cases, conventional MIDCAB was carried out in 25 cases, 4 underwent thoracoscopy-assisted operation and 4 received the surgery with the assistance of the AESOP robot system. Results No operation-related deaths or complications were seen in the study. The extubation time was (7.5?1.9) hours, the chest drainage volume was (274?197) ml, the blood transfusion rate 9.1% (3/33) and the postoperative hospital stay (6.9?1.7) days. Follow-up in all the 33 cases for (24.3?5.7) months revealed no long-term deaths and the recurrence rate of angina was 9.1% (3/33). Postoperative coronary angiography in 4 cases found 1 case of 50% stricture of anastomosis and 3 cases of anastomotic patency between the anterior descending artery and left internal mammary artery. Postoperative catheter revascularization was required in 2 cases (6%). Conclusions The mid-term outcomes of MIDCAB is satisfactory.
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ObjectiveTo summarize the short-term effects o f Symmetry aortic co nnector in off-pump coronary artery bypass grafting (OPCAB) operation. MethodsTwo hundreds and four patients suffering from coronary artery d isease underwent OPCAB from September 2002 to June 2003. Among the 204 patients, saphenous vein grafts were used in 167 patients and Symmetry aortic connectors were adopted in 100 of them.ResultsOf 142 connectors used, 2 connectors fai led and manual r epairs were required in 3 cases because of anastomotic leakage, the success rate being 96 5% (137 of 142). The number of proximal anastomosis was (1 4?0 5) per case and the number of distal anastomosis (3 5?0 8) per case. The proximal a na stomotic blood flow was (46 5?22 3) ml/min. The fitting time for connectors w as (4 0?1 1) min, and anastomoses were all accomplished within 10 seconds. The op eration time was (3 2?0 4) hours. The operative death rate was 1% (1 of 100). R e-operation of thoracotomy was required in 1 case because of bleeding but not an astomotic bleeding. No myocardial infarction or stroke occurred in the peri-oper ative period. The postoperative drainage amount was (547?247) ml. The blood tra nsfusion rate was 36 0% (36 of 100). The postoperative hospital stay was (7 8 ?1 6) days.ConclusionsSymmetry aortic connector can be saf ely and effectively used in coronary artery bypass grafting operations, with satisfactory short-term clinical effects. The procedure may shorten operation time, avoid aortic clampi ng, and lower the incidence of stroke.
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Objective To summarize clinical results of 29 cases of multi-vessel coronary disease treated by hybrid revascularization.Methods A total of 29 consecutive patients(all male,aged 62.8?9.7 years) with coronary artery disease(two-vessel,n=10;three-vessel,n=19) were treated with minimally invasive direct coronary artery bypass(MIDCAB)(left internal mammary artery to left anterior descending artery,LIMA-to-LAD) and percutaneous coronary intervention(PCI) between January 2000 and April 2005.The left ventricular ejection fraction(LVEF) was 0.576?0.108.Concomitant diseases included hypertension in 23 patients,insulin-dependent diabetes mellitus in 5 patients,chronic obstructive pulmonary disease in 2 patients,and old myocardial infarction in 14 patients.Results The 29 patients received 33 grafts(LIMA: 27 grafts;great saphenous vein: 6 grafts).Balloon angioplasty was carried out in 41 coronary lesions,usually following surgery.The mean number of revascularization was 2.5 per patient.There was no surgery-related complications and mortality.The blood flow in the LIMA was 45?14 ml/min.The chest drainage volume was 274?197 ml.Blood transfusion was required in 2 patients(6.9%).The length of ICU stay was 1.9?0.1 d and the length of hospital stay was 4~11 d(mean,7.5 d).Follow-up for 2.2?0.9 years showed no late death and myocardial infarction.Postoperative New York Heart Association(NYHA) Classification showed Class Ⅰ in 25 patients and Class Ⅱ in 4 patients.Repeated angiography was conducted in 4 patients,which found great saphenous vein graft occluded in 1 patient and stent re-stenosis in 2 patients.Conclusions The midterm results of hybrid techniques for coronary artery disease are satisfactory.Hybrid procedure is beneficial to high-risk patients.The long-term results need further investigation.
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Objective:To study if L-arginine cardioplegia can protect myocardium from ischemia/reperfusion injury. Method:Fourteen patients undergoing valve replacement were randomly divided into two groups:control group (crystal cardioplegia,C group),and test group(crystal cardioplegia+L-arginine,E group). Before aortic-clamping and after aortic unclamping,blood samples were taken to measure the concentrations of NO_2~-/NO_3~-, lactic acid (LA), malonylaldehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD). Immediately after aortic clamping and before aortic-unclamping, tissues were taken from the left atrial and examed with electron microscopy. Result: In C group NO_2~-/NO_3~- level decreased at aortic unclamping, 30 minutes later decreased significantly compared with that before aortic-clamping(P