血管形成以及VEGF-Nrp1信号通路调控皮肤肿瘤干细胞的形成

肿瘤的发生、转移与组织内血管形成有着极其密切的关联。通过不同途径阻断血管内皮细胞生长因子（VEGF）及其受体的结合,达到抑制肿瘤组织中新生血管形成,并发挥治疗肿瘤的作用是公认的治疗模式。近期的研究发现,皮肤鳞状细胞癌组织中存在一定数量的肿瘤干细胞,VEGF在靠近血管的肿瘤干细胞中高表达。

端粒酶逆转录酶转染内皮祖细胞在缺血性心血管疾病中的应用

动脉硬化所导致的缺血性心脏病严重危害人类健康,临床治疗所面临的最大难题就是如何安全有效的再通阻塞血管和建立侧支循环来改善缺血区的血供。成熟机体内血管形成有两种方式：第一通过机体内存在于外周血、已定向分化的内皮细胞增殖、游走、重塑血管,即血管新生（angiogenesis）。但研究显示,

动静脉内瘘和起搏器同侧所致肿胀手综合征及腔内治疗效果观察

目的观察自体动静脉内瘘(arteriovenous fistula,AVF)和起搏器位于患者手臂同侧时是否容易出现肿胀手综合征以及腔内治疗效果。方法试验组:起搏器同侧建立AVF的患者10例;对照组:起搏器对侧建立AVF的患者10例。观察内容:(1)内瘘侧颈静脉或锁骨下静脉有无透析导管置入史;(2)存在起搏器导线的情况下AVF术后或者存在AVF的情况下同侧安装起搏器术后出现内瘘侧肢体肿胀时间;(3)中心静脉狭窄或者闭塞部位;(4)腔内治疗方法;(5)腔内治疗后复发时间;(6)经皮腔内血管成形术(percutaneous transluminal angioplasty,PTA)对起搏器导线功能有无影响。结果试验组:8例患者内瘘、起搏器同侧共存17.0(2.6,30.0)个月后开始出现肢体肿胀;1例患者内瘘、起搏器同侧共存3.5年后内瘘闭塞,闭塞前内瘘侧肢体仅有轻度肿胀,无需干预;1例患者内瘘、起搏器同侧共存4.5年内瘘侧肢体无肿胀。治疗上,2例患者对侧上肢重新建立内瘘,新的内瘘成熟后关闭患侧内瘘。6例患者行单纯PTA治疗,共10例次,单纯PTA术后至肿胀复发时间为(6.0±4.9)个月,所有患者均未置入支架。PTA术后起搏器功能无异常。对照组:截止到观察终点所有患者均未出现内瘘侧肢体肿胀。结论动静脉内瘘和起搏器位于同侧时相对容易出现肿胀手综合征,中心静脉病变单纯PTA效果相对较差,不建议放置支架。短期观察球囊扩张对起搏器导线功能无明显影响。

急性心肌梗死患者PTCA术后效果评价及预后影响因素分析

目的评价急性心肌梗死(AMI)患者行经皮冠状动脉腔内血管形成术(PTCA)后的治疗效果,探讨影响AMI患者预后的相关影响因素,为预测和改善AMI患者预后提供科学依据。方法回顾性收集2017年9月至2020年3月重庆市巴南区人民医院收治的129例急性心肌梗死患者的相关资料,根据发生不良心血管事件(MACE)情况将其分为MACE组(n=39)和无MACE组(n=90)。分析患者PTCA手术前后心功能指标的改变,比较两组患者相关资料的差异,采用多因素Logistic回归模型分析AMI患者预后的影响因素并绘制风险列线图。结果行PTCA手术治疗后,患者的平均左心室射血分数(LVEF)、左室舒张末期内径(LVEDd)及QT间期离散度(QTd)为(53.60±9.94)%、(53.80±7.43) mm、(45.34±6.80) ms,均较术前[(40.96±6.49)%、(56.93±4.08) mm、(66.88±7.81) ms]显著改善,差异均有统计学意义(P <0.05)。MACE组患者年龄、高血压史、冠心病家族史和吸烟史患者占比、QT间期离散度、血红蛋白和N末端脑钠肽前体(NT-pro BNP)水平均高于无MACE组,Killip分级Ⅰ级患者占比、术后LVEF均低于无MACE组,差异均有统计学意义(P <0.05)。多因素Logistic回归分析结果提示年龄(OR=1.132,95%CI:1.038~1.234)、高血压(OR=4.031,95%CI:1.013~16.029)、Killip分级(OR=3.850,95%CI:1.479~10.023)、术后LVEF(OR=0.938,95%CI:0.811~0.999)和术后QT间期离散度(OR=1.491,95%CI:1.263~1.760)均是患者预后的影响因素。结论 AMI患者行PTCA术后可显著改善患者症状,同时AMI患者的年龄、高血压史、Killip分级情况、术后LVEF水平、QT间期离散度均是患者预后的影响因素。

中医情志护理在老年患者行急诊PTCA术护理中的效果探讨

目的谈论中医情志护理在老年患者行急诊经皮冠状动脉腔内血管形成术(PTCA)护理中的效果。方法对45例老年急性心肌梗死行PTCA术患者采用中医情志护理,观察护理效果。结果 45例患者均能较好的配合临床手术治疗,临床术后较好,无并发症的发生。结论采用中医情志护理对老年患者行急诊PTCA术护理中的效果较好。

Effects of endostatin on expression of vascular endothelial growth factor and its receptors and neovascularization in colonic carcinoma implanted in nude mice

AIM:To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS:Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups.Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested,the tumor volumes were determined,and the expressions of CD34,VEGF and FIk-1 were examined by immunohistochemical method. RESULTS:Tumor volume was significantly inhibited in the endostatin group(84.17%)and tumor weight was significantly inhibited in the endostatin group(0.197±0.049) compared to the control group(1.198±0.105)(F=22.56, P=0.001),microvessel density(MVD)was significantly decreased in the treated group(31.857±3.515)compared to the control group(100.143±4.290)(F=151.62,P<0.001). Furthermore,the expression of FIk-1 was significantly inhibited in the treated group(34.29%) ompared to the control group(8.57%)(X^2=13.745,P=0.001).However no significant decrease was observed in the expression of vascular endothelial growth factor(VEGF)between these two groups(X^2=0.119,P=0.730). CONCLUSION:Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/FIk-1 pathway.This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.

A fusion protein containing murine vascular endothelial growth factor and tissue factor induces thrombogenesis and suppression of tumor growth in a colon carcinoma model

Induction of tumor vasculature occlusion by targeting a thrombogen to newly formed blood vessels in tumor tissues represents an intriguing approach to the eradication of primary solid tumors. In the current study, we construct and express a fusion protein containing vascular endothelial growth factor (VEGF) and tissue factor (TF) to explore whether this fusion protein has the capability of inhibiting tumor growth in a colon carcinoma model. The murine cDNA of VEGF A and TF were amplified by reverse transcriptase polymerase chain reaction (RT-PCR), and then cloned into prokaryotic expression plasmid pQE30 with a linker. The expression product recombinant VEGF-TF (rVEGF-TF) was purified and proved to have comparable enzyme activity to a commercial TF and the capability of specific binding to tumor vessels. Significant decrease of tumor growth was found in the mice administered with rVEGF-TF on Day 6 after initiated rVEGF-TF treatment (P<0.05), and the tumor masses in 2 of 10 mice were almost disappeared on Day 14 after the first treatment. In addition, valid thrombogenesis and tumor necrosis were observed in the tumor tissues injected with rVEGF-TF. Our results demonstrate that occlusion of tumor vasculature with rVEGF-TF is potentially an effective approach for cancer therapy.

Risk factors of thrombosis in abdominal veins

AIM: To estimate the prevalence of inherited and acquired thrombophilic risk factors in patients with abdominal venous thrombosis and to compare the risk factor profiles between Budd-Chiari syndromes (BCS) and splanchnic vein thrombosis (SVT). METHODS: In this retrospective study, 36 patients with abdominal venous thrombosis were studied. The patients were divided into Budd-Chiari group (hepatic vein, IVC thrombosis) and splanchnic venous thrombosis group (portal, splenic, superior mesenteric veins) based on the veins involved. Hereditary and acquired thrombophilic risk factors were evaluated in all patients. RESULTS: Twenty patients had SVT, 14 had BCS, and 2 had mixed venous thrombosis. Ten patients (28%) had hereditary and 10 patients (28%) acquired thrombophilic risk factors. The acquired risk factors were significantly more common in the SVT group (SVT vs BCS: 45% vs 7%, χ2 = 5.7, P = 0.02) while hereditary risk factors did not show significant differences between the two groups (SVT vs BCS: 25% vs 36%, χ2 = 0.46, P = 0.7). Multiple risk factors were present in one (7%) patient with BCS and in 3 patients (15%) with SVT. No risk factors were identified in 57% of patients with BCS and in 45% of patients with SVT. CONCLUSION: Hereditary and acquired risk factors play an important role in the etiopathogenesis of abdominal venous thrombosis. Acquired risk factorsare significantly more common in SVT patients while hereditary factors are similar in both groups.

INTERVENTIONAL OR SEMI-INTERVENTIONAL TREATMENT FOR BUDD-CHIARI SYNDROME

Objective. Report the results of interventional or semi-interventional techniques for 173 patients with Budd-Chiari syndrome.Method. This group included 120 males and 53 females. The pathologic lesions composed of localized complete occlusion of inferior vena cava (IVC) (78), IVC stenosis (49), IVC membrane with a hole (37), membrane of hepatic vein (HV) (3), IVC thrombosis (4), IVC membrane with thrombosis (2) and IVC lesion with occlusion of HV (32). Treatment methods included that I: Percutaneous transinferior vena cava angioplasty (PTA) (76); II: IVC PTA with stent (59); III: Percutaneous transhepatic vein recanalization (3); IV: IVC thrombolysis through a catheter (4); V; Combined transcardiac and trans-femoral venous membranotomy and balloon dilation (22); VI: V and stent (17); VII; Stenting during radical surgery (3); VIII: Additional operation after intervention (23).Results. The immediate technique success rate for intervention was 90.1%, for the semi-intervention was 100%. The IVC pressure was reduced from 3 to 29 cmH20. Complications occurred in 8 cases. The death rate was 2.9%. A follow-up study showed the recurrence rates were 14.5% in IVC PTA group, 1.7% in IVC PTA with stent, 18.2% in combined technique without stent and no recurrence was found in other groups.Conclusion. The PTA is the first choice for localized lesions. When elastic recoil occurs, immediate stenting is suggested. The semi-interventional approach is advised for PTA failure and more complicated cases. For those with both IVC lesion and occlusion of HV, the additional operation is needed after IVC intervention.

COMBINED INTRAOPERATIVE ILIAC ARTERY STENTS AND FEMORO- POPLITEAL BYPASS FOR MULTILEVEL ATHEROSCLEROTIC OCCLUSIVE DISEASE

Objective. To review our preliminary experience and evaluate our early results of a combined intraoperative iliac angioplasty and stenting with infrainguinal revascularization in multilevel atherosclerotic occlusive disease. Methods. From July 1999 to April 2000, intraoperative iliac angioplasty and stenting combined with simultaneous femoro- popliteal bypass were performed on 12 lower extremities of 10 patients suffering from multilevel atherosclerotic occlusive disease. There were 8 men and 2 women, average 72 years. The indications for procedures included disabling claudication in 3 and rest pain in 7 patients. Results. Eleven iliac angioplasty and stent procedures combined with simultaneous 9 femoro- popliteal bypass and 3 femoro- femoral- popliteal bypass were performed in 12 limbs of 10 patients. Angioplasty and stent placement was technically successful in all patients. One contralateral femoral- popliteal bypass was failure after femorofemoral- popliteal bypass. There were no additional instances of procedural or postoperative morbidity or mortali- ty. Mean follow- up was 5 months (range 1～ 10 months). During the follow- up period, one femoro- infrapopliteal graft became occluded after 7 months and above- knee amputation was required. The cumulative primary patency rate of stented iliac arteries, femoro- femoral bypass grafts and femoro- popliteal bypass grafts were 100％ (11/11), 100％ (3/3) and 90.9％ (10/11) in the follow- up period, respectively. The amputation rate was 8.3％ (1/12). Conclusions. Intraoperative iliac artery PTA and stent placement can be safely and effectively performed simultaneously with infrainguinal revascularization for multilevel atherosclerotic occlusive disease by skilled vascular surgeon, using a portable C arm fluoroscopy in the operating room. Furthermore, iliac artery PTA and stenting was valuable adjunct to distal bypass either to improve inflow and outflow, or to reduce the extent of traditional surgical intervention, and also, any angioplasty and stenting- related complications can be immediately corrected as well.

Retrospective analysis of percutaneous transluminal coronary angioplasty and coronary stenting

Objective To examine long term efficacy of percutaneous transluminal coronary angioplasty (PTCA),coronary stenting and to assess the factors affecting its efficacy Methods A total of 790 patients who underwent successful PTCA and PTCA+stent in this hospital were followed by direct interview or letter The rate of follow up was 84 2% and the period of follow up was 0 9-12 7 (3 5±2 4) years Results During follow up, 4 (0 5%) patients died, 22 (2 8%) had nonfatal acute myocardial infarction, 10 (1 3%) had coronary artery bypass surgery, and 98 (12 4%) had repeat PTCA The rate of recurrent angina pectoris was 31 1% The cardiac event free survival rate calculated by the Kaplan Meier method was 88 2% at 1 year and 80 6% at 12 7 years Cox regression analysis showed that there was a positive correlation between AMI history, stent implantation and the risk of cardiac events, and there was a negative correlation between the number of diseased arteries and the risk of cardiac events Compared to the PTCA group, patients with PTCA+stent had significantly lower rates of total cardiac events Conclusion The long term efficacy of PTCA, especially PTCA + stent in Chinese patients was very satisfactory, suggesting that PTCA+stent therapy should be the major treatment for revascularization in patients with coronary heart disease

Recombinant human Flt3 ligand exerts both direct and indirect effects on hematopoiesis

OBJECTIVE: To investigate the direct effects of the Flt3 ligand (FL) on hematopoiesis, such as the stimulation of the formation of hematopoietic colonies and the proliferation of dendritic cells, as well as the indirect stimulation of hematopoiesis, especially via the proliferation of endothelial cells. METHODS: Mononuclear cells from human cord blood were plated in methylcellulose medium containing different cytokines to induce hematopoietic colony formation. Dendritic cells (DCs) were induced from the mononuclear cells with a cytokine cocktail with or without recombinant human soluble FL (rhFL; 100 ng/ml). The Flt3 receptors on the surface of a human microvascular endothelial cell line (ECV) were analyzed by flow cytometry. The proliferation of ECV stimulated by rhFL was measured with the microculture tetrazolium assay. The levels of FL, IL-6, IL-8, G-CSF and GM-CSF in the supernatant of ECV cultures were measured by enzyme linked immunoabsorbent assay (ELISA). RESULTS: rhFL stimulates colony formation from cord blood when used as a sole stimulant. FL in combination with other cytokines increased colony formation significantly. The number of DCs was approximately 2.5 times higher when rhFL was used. rhFL stimulates the proliferation of ECV on which Flt3 receptors are expressed. Furthermore, ECV secretes FL, IL-6, IL-8, G-CSF and GM-CSF, which were augmented by tumor necrosis factor-alpha and rhFL. CONCLUSIONS: rhFL enhances hematopoietic colony formation and DC proliferation from human cord blood cells. FL not only stimulates the proliferation of ECV, but is also secreted by ECV. FL may exert direct and indirect effects on hematopoiesis.

ADAMTS-7 promotes vascular smooth muscle cells proliferation in vitro and in vivo

Vascular smooth muscle cell(VSMC) proliferation and migration are pivotal for the pathogenesis of atherosclerosis and post-angioplasty restenosis. We have recently reported that a disintegrin and metalloproteinase with thrombospondin motifs-7(ADAMTS-7), a novel metalloproteinase, contributes directly to neointima formation by mediating VSMC migration. However, whether ADAMTS-7 affects VSMC proliferation remains unclear. In this study, we found that luminal adenoviral delivery of ADAMTS-7 aggravated intimal hyperplasia 7 d after injury, paralleled by an increased percentage of PCNA-positive cells in both intima and media. In contrast, perivascular administration of ADAMTS-7 si RNA, but not scrambled si RNA to injured arteries attenuated intimal thickening at day 7, paralleled with reduced intimal VSMC replication, without alteration of VSMC proliferation in the media. In accordance, [3H]-thymidine incorporation assay in primary cultured rat VSMCs revealed an enhanced replication rate(by 61%) upon ADAMTS-7 overexpression and retarded proliferation(by 23%) upon ADAMTS-7 si RNA administration. Our data demonstrates that ADAMTS-7 promotes VSMC proliferation both in vitro and in vivo. ADAMTS-7 may therefore serve as a novel therapeutic target for atherosclerosis and post-angioplasty restenosis.