Long-term clinical effects of intravitreal injections of conbercept for the treatment of choroidal neovascularization in patients with pathological myopia

AIM:To observe the long-term clinical efficacy of intravitreal injections of conbercept,a novel vascular growth factor inhibitor,for the treatment of pathological myopia choroidal neovascularization(PM-CNV).METHODS:A total of 67 eyes(from 67 patients;mean age,54.90±12.7y)with PM-CNV were retrospectively researched.Based on the different schemes used for the administration of the drug,the patients were divided into two groups:group A(n=35;average age,53.31±13.6y;average diopter,9.25±1.72 D),which received only one injection of pro re nata(PRN;1+PRN regimen),and group B(n=32;average age,56.49±11.8y;average diopter,9.63±2.24 D),which received one injection per month for 3mo(3+PRN regimen).Best-corrected visual acuity(BCVA)analysis,intraocular pressure(IOP)examination,slit-lamp microscopy,fundus examination and optical coherence tomography were per formed at each follow-up.The recurrence and treatment times of CNV were recorded.The patients were followed up for at least 12mo.RESULTS:The BCVA was increased in 29 eyes(82.9%)in group A and 30 eyes(93.75%)in group B;no increase or decrease was observed in 6(17.1%)and 2(6.25%)eyes in groups A and B,respectively.The BCVA(log MAR)values before treatment(0.67±0.48 and 0.71±0.56)were significantly higher than those 12mo after treatment(0.31±0.26 and 0.33±0.17)in groups A and B,respectively(P<0.05).The mean central macular thickness(CMT)values had significantly decreased from 346.49±65.99 and 360.10±82.31μm at baseline to 257.29±40.47 and 251.97±48.26μm in groups A and B,respectively,after 12mo of treatment.A total of 21 eyes in group A needed reinjection(60%;average number of injections,2.51±0.98);the corresponding values in group B were 6 eyes(18.75%;average number of injections,3.74±1.22).There were no adverse ocular and systemic complications during the treatment and follow-up.CONCLUSION:Intravitreal injection of conbercept with 1+PRN or 3+PRN improve the visual acuity,reduce macular edema and reduce the level of CMT in patients with PM-CNV.The 3+PRN regimen demonstrates a lower recurrence rate of CNV than the 1+PRN regimen,but requires more treatment.However,both treatment regimens demonstrate long-term safety and efficacy for the treatment of PM-CNV.

Choroidal neovascularization secondary to pathological myopia

Myopic choroidal neovascularization(m CNV), one of the complications of pathological myopia, is also one of the leading causes of visual impairment worldwide. The socioeconomic impact of mC NV in Asian countries is particularly significant due to the rising incidence of pathological myopia. There have been major advances in the treatment of mC NV in the past few years. Previous treatment modalities, such as thermal laser photocoagulation and photodynamic therapy, aimed to prevent vision loss;however, newer modalities such as intravitreal anti-vascular endothelial growth factor(VEGF) agents have been shown to successfully restore vision in many patients. Challenges remain as long term safety and efficacy of anti-VEGF agents are unknown. This article aims to provide a review of the literature of the epidemiology, progression, clinical course and treatment modalities as well as areas of future developments related to myopic CNV.

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.

Factors affecting visual outcome of myopic choroidal neovascularization treated with verteporfin photodynamic therapy

AIM: To evaluate the visual outcomes of choroidal neovascularization (CNV) secondary to pathological myopia and the impact of novel risk factors affecting the final visual outcome. ·METHODS: Interventional case series of 18 consecutive patients with pathological myopia treated with photodynamic therapy (PDT). Inclusion criteria were spherical equivalent -6D or worse or features of pathological myopia on retinal examination. The main outcome measure was final best -corrected visual acuity (BCVA). ·RESULTS: Of 18 eyes, 13 (72.2%) avoided moderate visual loss (≥3 lines of LogMAR BCVA) and 5 eyes (27.8%) improved by at least 1 line after 1 year. Patients with LogMAR BCVA ≤0.3 (Snellen equivalent 20/40) at one year were younger than those with BCVA 】0.3 (mean age 39.0 vs 61.6 years, P =0.001). A higher proportion of eyes with greatest linear dimension (GLD) of ≤1 000μm avoided moderate visual loss (100% vs 50%, P =0.026). Among patients who were treated within 2 weeks of visual symptoms, 88.9% avoided the loss of 3 or more lines compared to 55.6% for those who presented later. The mean improvement in LogMAR BCVA of those with GLD ≤1 000μm was +0.12 compared to a loss of 0.55 LogMAR units for those with GLD 】1 000μm (P =0.02). Visual outcomes were not associated with gender or refractive error.·CONCLUSION: Good visual outcome in myopic CNV is associated with younger age, smaller lesion size and earlier initiation of treatment. These factors are relevant for ophthalmologists considering treatment options for myopic CNV.

Anti-vascular endothelial growth factor： the future treatment of choroidal neovascularization in pathologic myopia

-yopia is the most common refractive disorder. High .myopia affects 27%-33% of all myopic eyes inAsia.1,2 ;The pathologic myopia （PM） is the most severe vision-threatening phenotype of high myopia.3 It is also the second most common cause of choroidal neovascularization （CNV） in Asia. Unlike age-related macular degeneration （AMD） which mostly effecting elders, PM causes severe vision loss in young adults, resulting in a significant impairment of their working ability.4 PM has become the second leading cause of low vision and blindness particularly among those aged at 40-49 years in some Asia countries.

Co-existent choroidal neovascular membrane and macular hole in pathologic myopia:a long follow-up clinical outcome and literature review

Choroidal neovascularization(CNV)is an uncommon complication associated with a macular hole.In this case report of a rare condition,we present a pathologic myopia patient with a co-existent macular hole and choroidal neovascular membrane.The patient was treated with photodynamic therapy for CNV,and then vitreous surgery for the retinal detachment and macular hole.At the end of 4 years follow-up,her visual acuity was improved to 0.1 while the macular hole remained open.Optical coherence tomography is a useful inspection method of the diagnosis of CNV and macular hole.

An analysis of vascularity and neovascularization in surgical pathology materials of breast carcinoma and its clinical significance

Breast cancer is one of the most common malignancies among women and its morbidity has recently increased in many parts of the world[1].Numerous factors have been reported to be associated with development of breast cancer including angiogenesis.Angiogenesis or the formation of new blood vessel networks,not only plays a pivotal role in human normal development,but also in pathophysiological conditions such as inflammatory diseases and neoplasms[2]

Effect of endothelial progenitor cells in neovascularization and their application in tumor therapy

Objective To review the effect of endothelial progenitor cells in neovascularization as well as their application to the therapy of tumors.Data sources The data used in this review were mainly from PubMed for relevant English language articles published from 1997 to 2009. The search term was ＂endothelial progenitor cells＂.Study selection Articles regarding the role of endothelial progenitor cells in neovascularization and their application to the therapy of tumors were selected.Results Endothelial progenitor cells isolated from bone marrow, umbilical cord blood and peripheral blood can proliferate, mobilize and differentiate into mature endothelial cells. Experiments suggest endothelial progenitor cells take part in forming the tumor vascular through a variety of mechanisms related to vascular endothelial growth factor, matrix metalloproteinases, chemokine stromal cell-derived factor 1 and its receptor C-X-C receptor-4, erythropoietin, Notchsignal pathway and so on. Evidence demonstrates that the number and function change of endothelial progenitor cells in peripheral blood can be used as a biomarker of the response of cancer patients to anti-tumor therapy and predict the prognosis and recurrence. In addition, irradiation temporarily increased endothelial cells number and decreased the endothelial progenitor cell counts in animal models. Meanwhile, in preclinical experiments, therapeutic gene-modified endothelial progenitor cells have been approved to attenuate tumor growth and offer a novel strategy for cell therapy and gene therapy of cancer.Conclusions Endothelial progenitor cells play a particular role in neovascularization and have attractively potential prognostic and therapeutic applications to malignant tumors. However, a series of problems, such as the definitive biomarkers of endothelial progenitor cells, their interrelationship with radiotherapy and their application in cell therapy and gene therapy of tumors, need further investigation.

Retinoschisis and intravitreal ranibizumab treatment for myopic choroidal neovascularization

Background Intravitreal ranibizumab injection is effecitve on treating myopic CNVs,but it could be a risk factor for developing more severe retinoschisis in eyes with preexisted retinoschisis and epiretinal membrane.This study aimed to explore the incidence and features of retinoschisis after intravitreal ranibizumab injection for myopic choroidal neovascularization.Methods Eighty-three eyes of 81 patients with choroidal neovascularization secondary to pathologic myopia were treated with intravitreal ranibizumab injection.The best corrected visual acuity and optical coherence tomography （OCT） images were recorded at baseline and every month thereafter.Central retina thickness and maximal retina thickness were measured.The subjects were divided into three groups.Eleven eyes that had retinoschisis and epiretinal membrane were in group 1,six eyes that had simple epiretinal membrane were in group 2,and 66 eyes that had neither retinoschisis nor epiretinal membrane were in group 3.Six contralateral eyes in group 1 which had retinoschisis and epiretinal membrane but were not treated with intravitreal ranibizumab injection were set as the control group.Results Seven of the 11 eyes in group 1 developed more severe retinoschisis,the mean maximal retinal thickness increased from （380.28±90.13） to （467.00±70.20） μm （P 〈0.05）.The retinoschisis of all 6 eyes of the control group did not aggravate.Compared with the control group,the aggravation ratio of retinoschisis increased significantly （P 〈0.05）.No new onset of retinoschisis took place in group 2 and group 3.Conclusion Intravitreal ranibizumab injection may be a risk factor for aggravation of retinoschisis in eyes with preexisted retinoschisis and epiretinal membrane.

Evaluation of a novel deep learning based screening system for pathologic myopia

AIM:To evaluate the clinical application value of the artificial intelligence assisted pathologic myopia(PM-AI)diagnosis model based on deep learning.METHODS:A total of 1156 readable color fundus photographs were collected and annotated based on the diagnostic criteria of Meta-pathologic myopia(PM)(2015).The PM-AI system and four eye doctors(retinal specialists 1 and 2,and ophthalmologists 1 and 2)independently evaluated the color fundus photographs to determine whether they were indicative of PM or not and the presence of myopic choroidal neovascularization(mCNV).The performance of identification for PM and mCNV by the PMAI system and the eye doctors was compared and evaluated via the relevant statistical analysis.RESULTS:For PM identification,the sensitivity of the PM-AI system was 98.17%,which was comparable to specialist 1(P=0.307),but was higher than specialist 2 and ophthalmologists 1 and 2(P<0.001).The specificity of the PM-AI system was 93.06%,which was lower than specialists 1 and 2,but was higher than ophthalmologists 1 and 2.The PM-AI system showed the Kappa value of 0.904,while the Kappa values of specialists 1,2 and ophthalmologists 1,2 were 0.968,0.916,0.772 and 0.730,respectively.For mCNV identification,the AI system showed the sensitivity of 84.06%,which was comparable to specialists 1,2 and ophthalmologist 2(P>0.05),and was higher than ophthalmologist 1.The specificity of the PM-AI system was 95.31%,which was lower than specialists 1 and 2,but higher than ophthalmologists 1 and 2.The PM-AI system gave the Kappa value of 0.624,while the Kappa values of specialists 1,2 and ophthalmologists 1 and 2 were 0.864,0.732,0.304 and 0.238,respectively.CONCLUSION:In comparison to the senior ophthalmologists,the PM-AI system based on deep learning exhibits excellent performance in PM and mCNV identification.The effectiveness of PM-AI system is an auxiliary diagnosis tool for clinical screening of PM and mCNV.

山姜素调节VEGF/SphK1/S1P信号通路对膝骨关节炎大鼠血管生成的影响

目的探讨山姜素(APT)调节血管内皮生长因子/鞘氨醇激酶1/1磷酸鞘氨醇(VEGF/SphK1/S1P)信号通路对膝骨关节炎(KOA)大鼠血管生成的影响。方法采用改良的Videman法构建KOA大鼠模型,将90只大鼠分为对照组(Control组)、模型组(Model组)、山姜素低剂量组(L-APT组)、山姜素高剂量组(H-APT组)、山姜素高剂量组+慢病毒阴性对照组(APT+NC组)、山姜素高剂量组+过表达SphK1慢病毒组(APT+SphK1组),每组15只。HE染色观察大鼠软骨组织病理变化;酶联免疫吸附试验测定软骨组织白细胞介素(IL)-1β、肿瘤坏死因子α(TNF-α)、IL-6、基质金属蛋白酶-13(MMP-13)水平;TUNEL检测软骨组织细胞凋亡情况;免疫组化检测血管内皮生长因子(VEGF)、CD31蛋白表达情况;Western blot检测血管内皮生长因子受体2(VEGFR2)、磷酸化VEGFR2(p-VEGFR2)、SphK1、S1P蛋白水平。结果与Control组比较,Model组大鼠出现病理损伤,细胞凋亡率、IL-1β、TNF-α、IL-6、MMP-13、VEGF阳性表达、CD31阳性表达和p-VEGFR2、SphK1、S1P蛋白表达水平增加(P<0.05);与Model组比较,L-APT组、H-APT组病理损伤明显减轻,细胞凋亡率、IL-1β、TNF-α、IL-6、MMP-13、VEGF阳性表达、CD31阳性表达和pVEGFR2、SphK1、S1P蛋白表达水平降低(P<0.05);与APT+NC组比较,APT+SphK1组软骨组织病理损伤加重,细胞凋亡率、IL-1β、TNF-α、IL-6、MMP-13、VEGF阳性表达、CD31阳性表达和p-VEGFR2、SphK1、S1P蛋白表达水平增加(P<0.05)。结论APT通过抑制VEGF/SphK1/S1P信号通路抑制KOA大鼠血管生成。

舌鳞癌组织中性粒细胞对血管生成的作用及其意义

目的探讨口腔舌鳞癌(OSCC)组织内微血管密度(MVD)与中性粒细胞浸润的相关性,及其与临床病理参数及病人术后生存的关系。方法采用免疫组织双染方法检测OSCC组织中肿瘤MVD及中性粒细胞浸润的情况,分析MVD与病人临床病理特征的关系;Kaplan-Meier生存曲线分析OSCC组织MVD高低对病人生存预后的影响;Cox回归模型分析影响OSCC病人生存的独立危险因素;成管实验观察中性粒细胞对血管生成的影响。结果OSCC组织内高MVD与较高TNM分期、淋巴结转移、较大肿瘤和肿瘤复发有关(χ^(2)=8.161~26.312,P<0.001)。生存分析显示,OSCC组织高MVD组的总体生存时间及无病生存时间均短于低MVD组(χ^(2)=7.860、15.270,P<0.05);Cox回归分析显示,肿瘤MVD、肿瘤大小和肿瘤复发是影响OSCC病人术后生存的独立预后因素(β=-1.426~1.468,P<0.05)。Spearman相关分析显示,OSCC组织中肿瘤MVD与中性粒细胞密度呈正相关(r=0.352,P<0.05)。成管实验结果显示,与中性粒细胞共培养后,内皮细胞的血管生成作用增强(t=2.744~4.372,P<0.05)。结论OSCC组织内高MVD提示病人预后不良,可能作为判断OSCC病人预后的潜在指标。OSCC组织内MVD与中性粒细胞浸润有关,中性粒细胞的丰富浸润可促进肿瘤血管生成。

MiR-181c-5p对卵巢癌干细胞样细胞肿瘤血管生成拟态的作用及其机制

目的探讨miR-181c-5p对卵巢癌干细胞样细胞(OCS-LCs)肿瘤血管生成拟态(VM)的作用及其机制。方法采用无血清悬浮培养法将人卵巢癌细胞系OVCAR3细胞诱导形成OCS-LCs。将OVCAR3细胞分为A~C组,各组分别转染NC-miR-181c-5p、siRNA-miR-181c-5p和pRNA-miR-181c-5p。通过成球实验评估A~C组细胞成球能力。采用实时荧光定量PCR(RT-qPCR)方法检测A~C组细胞miR-181c-5p的相对表达量,采用Western blot实验检测A~C组细胞Oct-4、Nanog、HIF-1α和VEGF蛋白相对表达量。采用CCK-8实验检测A~C组细胞的活性,采用三维立体培养实验检测A~C组的血管形成率。结果OVCAR3细胞成功被诱导形成OCS-LCs。RT-qPCR实验结果显示,B组细胞的miR-181c-5p相对表达量显著低于A组,C组高于A组(t=2.25、8.68,P<0.05)。成球实验结果显示,B组与A组、A组与C组相比,细胞的成球周期显著缩短,最大的细胞球直径显著增大,成球率显著增加(t=5.56~33.66,P<0.05)。Western blot实验结果表明,B组与A组、A组与C组相比,Oct-4、Nanog、HIF-1α和VEGF蛋白相对表达量显著升高(t=4.51~56.15,P<0.05)。CCK-8实验结果显示,B组的细胞活性高于A组,C组低于A组(F=97.70~281.80,P<0.05)。三维立体培养实验结果显示,B组与A组、A组与C组相比较,血管形成率显著性提高(t=3.70、18.67,P<0.05)。结论miR-181c-5p可能通过降低细胞中HIF-1α和VEGF蛋白的表达,从而抑制OCS-LCs的VM形成。

oxLDL/β2GPⅠ/aβ2GPⅠ复合物通过TLR4/MyD88/NF-κB途径促进血管内皮细胞血管生成

目的探讨氧化型低密度脂蛋白(oxLDL)/β2糖蛋白Ⅰ(β2GPⅠ)/抗β2糖蛋白Ⅰ抗体(aβ2GPⅠ)复合物对血管内皮细胞增殖、迁移及血管生成的影响及其机制。方法将人脐静脉内皮细胞(HUVEC)培养至对数生长期,分为对照组(正常培养)、oxLDL组(50 mg/L oxLDL)、oxLDL/β2GPⅠ/aβ2GPⅠ组(50 mg/L oxLDL/100 mg/Lβ2GPⅠ/100 mg/L aβ2GPⅠ)和血管内皮生长因子(VEGF)组(100μg/L VEGF)。实时荧光定量PCR(qPCR)法检测血管生成相关因子VEGF、血管内皮钙黏蛋白(VE-cadherin)、基质金属蛋白酶(MMP)-2及MMP-9的基因表达;CCK-8检测细胞增殖;划痕愈合实验和Transwell实验检测细胞的迁移和侵袭能力;基质胶管腔形成实验检测HUVEC的血管生成能力;Western blot法检测Toll样受体4(TLR4)、髓样分化因子88(MyD88)和核因子κB(NF-κB)的蛋白表达。结果与对照组相比,oxLDL/β2GPⅠ/aβ2GPⅠ组细胞增殖活力在处理48 h时增加;此外,与对照组相比,oxLDL/β2GPⅠ/aβ2GPⅠ组细胞迁移及血管生成能力增强,VEGF、VE-cadherin、MMP-2及MMP-9的mRNA水平升高(P<0.05),TLR4和MyD88蛋白水平及p-NF-κB p65/NF-κB p65比值升高(P<0.05)。结论oxLDL/β2GPⅠ/aβ2GPⅠ复合物可能通过TLR4/MyD88/NF-κB通路诱导血管内皮细胞增殖、迁移及血管生成。

康柏西普不同给药方案治疗病理性近视脉络膜新生血管

目的:比较康柏西普不同给药方案治疗病理性近视脉络膜新生血管(PM-CNV)的疗效。方法:前瞻性临床研究。选取2019-01/2022-01在我院确诊为PM-CNV的患者42例42眼,根据初始治疗方案分为1+PRN组和3+PRN组,其中1+PRN组患者20例20眼初始1 mo玻璃体腔注射给药1次后按需给药(PRN);3+PRN组患者22例22眼初始3 mo每月玻璃体腔注射给药1次后PRN。初始治疗后随访12 mo,比较两组患者最佳矫正视力(BCVA)、中心凹视网膜厚度(CMT)、CNV面积及注药次数。结果:与治疗前相比,治疗后1、3、6、12 mo,两组患者视力均改善,CMT均降低,CNV面积均减小(P<0.01),但两组患者BCVA、CMT、CNV面积均无组间差异(P>0.05)。1+PRN组患者平均注药次数明显少于3+PRN组[2(1,3)次vs 3(3,4)次,P<0.05],但初始治疗后再注药次数多于3+PRN组[1(0,2)次vs 0(0,1)次,P<0.05]。结论:康柏西普两种方案均可安全有效治疗PM-CNV,改善BCVA,降低CMT,减小CNV面积,1+PRN治疗方案总注药次数更少,而3+PRN治疗方案再注药次数更少。

miR-484通过调控HIF-1α/VEGF信号通路对胃癌血管生成的影响

【目的】探讨miR-484是否通过调控HIF-1α/VEGF信号通路参与胃癌血管的生成。【方法】分别在阴性对照(miR-NC组)、miR-484模拟物(miR-484 mimics组)和miR-484抑制剂(miR-484 inhibitors组)3种条件下转染SCG-7901胃癌细胞。检测不同组SCG-7901细胞中缺氧诱导因子-1α(HIF-1α)、血管内皮生长因子(VEGF)的mRNA和蛋白表达情况及胃癌细胞的增殖情况。将转染成功的SCG-7901细胞与血管内皮细胞分别在缺氧条件下共培养,采用ELISA法检测培养基中HIF-1α和VEGF的表达情况,CCK8检测血管内皮细胞的增殖情况。【结果】miR-484 mimics处理后,SCG-7901细胞的增殖能力显著降低,而miR-484 inhibitor处理组的细胞增殖能力则显著提高。与miR-NC组比较,miR-484 mimics组SCG-7901细胞的HIF-1α、VEGF mRNA和蛋白表达下调(均P<0.01),miR-484 inhibitor组的结果与之相反。在缺氧条件下,与miR-NC组相比,miR-484 mimics显著降低了培养基中HIF-1α和VEGF水平(均P<0.05),血管内皮细胞增殖能力降低(P<0.05),而miR-484 inhibitor组的结果与之相反。【结论】miR-484可能通过下调HIF-1α/VEGF通路抑制胃癌细胞增殖和肿瘤血管形成。

甲状腺实性结节超声造影与免疫组织化学分析

目的探讨甲状腺良恶性实性结节CEUS增强模式与CD34、VEGF、CK19和Ki-67免疫组织化学表达的相关性。方法采用低机械指数实时灰阶谐波CEUS技术,对80例甲状腺患者的82个实性结节进行CEUS,包括甲状腺乳头状癌结节38个、髓样癌3个,结节性甲状腺肿31个、腺瘤7个、桥本病结节3个。术后行CD34、VEGF、CK19和Ki-67免疫组织化学染色。比较良恶性结节CEUS增强模式和免疫组织化学表达水平差异,分析其相关性。结果甲状腺良恶性结节的增强模式存在差别(P<0.01),良性结节78.05%(32/41)表现为环状增强,恶性结节92.68%(38/41)表现为不均匀增强。恶性结节的CD34、VEGF、CK19和Ki-67表达显著高于良性结节(P<0.01)。非均匀增强与CD34、VEGF、CK19呈正相关(r=0.39,P<0.001;r=0.26,P=0.04;r=0.54,P<0.001);环状增强与CD34、CK19、Ki-67呈负相关(r=-0.38,P<0.001;r=-0.59,P<0.001;r=-0.25,P=0.03)。结论 CEUS和CD34、VEGF、CK19和Ki-67免疫组织化学染色有助于鉴别甲状腺良恶性结节。

瘦素在结肠癌的表达及意义

目的观察血清瘦素(leptin)在结肠癌患者中的变化及其意义。方法研究分结肠癌组(40例)、溃疡性结肠炎组(30例)及正常对照组(40例),采用全自动生化分析仪检测各组血清总胆固醇(TC)、甘油三酯(TG)等生化指标并应用放射免疫分析法及ELISA法检测血清瘦素、癌胚抗原(CEA)及血管内皮生长因子(VEGF)。结果与正常对照组比,结肠癌组血清TC、TG、瘦素、CEA、VEGF含量升高(P<0.05),溃疡性结肠炎组血清TG、瘦素含量升高(P<0.05);与结肠癌组比,溃疡性结肠炎组血清瘦素、CEA、VEGF含量降低(P<0.05),TC、TG含量无明显改变。血清瘦素与TC、TG、VEGF呈正相关,而与CEA无相关性。结论血清瘦素可能通过VEGF发挥其对结肠癌的促进作用。

酒精性肝病大鼠模型的建立

目的为深入研究酒精性肝病的发病机制,提供一个简单可行的动物模型,并利用此模型检测血浆PDGF含量在酒精性肝病发生发展中的变化。方法本研究在平衡饮食的条件下,以400mL·L^(-1)乙醇,8g·kg^(-1)·d^(-1),日3次灌胃至4wk末,自5wk,以500 mL·L^(-1)乙醇,9g·kg^(-1)·d^(-1),日3次灌胃至8 wk末,自9 wk,以500mL·L^(-1)乙醇,10g·kg^(-1)·d^(-1)日3次灌胃至12wk末,诱导酒精性肝病大鼠动物模型,分别于4wk末、8wk末、12wk末观察肝脏病理学改变,并用生物活性法测定了对照组及实验组不同病理阶段血浆中血小板源性生长因子(PDGF)的含量。结果光镜显示对照组肝细胞以中央静脉为中心呈放射状排列,酒精摄入4wk末,肝细胞中重度脂肪变性,8wk末肝细胞变性坏死,炎性细胞浸润,Mallory染色可见胶原于中央静脉沉积增加,12wk末变性坏死及炎性细胞浸润明显,Mallory染色可见胶原自中央静脉向窦周隙伸展,呈现轻度肝纤维化改变,PDGF含量结果可见与同时期对照组相比,实验组PDGF含量(kU·L^(-1))均有显著增高,4,8,12wk分别为67±15 vs 31±18(P<0.05),130±30vs33±19(P<0.001),202±20 vs 36±6(P<0.001);实验组不同时期差异明显,随病程进展病变加重,8wk与4wk相比,P<0.01,12wk与8wk相比,P<0.001。结论灌胃为一种简单可行的造模方法;PDGF可能在酒精性肝纤维化的发生发展中起重要作用,但详细机制有待进一步探讨。

靶向肿瘤新生血管的顺磁性纳米脂质体在MRI诊断肺癌中的研究

目的：构建以肿瘤新生血管为靶向的顺磁性纳米脂质体，通过对荷瘤裸鼠模型行MRI以观察其在探查微小肿瘤病灶方面的应用价值。方法：靶向多肽-脂肪酸接枝物采用9-芴甲氧羰基（fiuorenylmethoxy carbony，Fmoc）固相合成法获得，薄膜超声法制备靶向纳米脂质体，超滤离心法测定钆双胺（Gd—DPTA—BMA）包封率；激光粒度分析仪测定平均粒径；偶氮氯膦Ⅲ比色法测定钆含量；对肺腺癌A549裸鼠移植瘤模型行MRI，评价靶向纳米脂质体对肿瘤特异性MRI信号增强作用。结果：分别制备获得以整合素αVβ3、血管内皮生长因子受体（vascular endothdial growth factor receptor，VEGFR）-1、VEGFR-2为靶点的及不同连接方式的靶向纳米脂质体，包封率为55．5％-60．1％；平均粒径为109～128nm，其中以整合素受体αVβ3和VEGFR-2为靶点分子的顺磁性纳米脂质体在裸鼠移植瘤模型中显示出良好的肿瘤特异性MRI成像信号增强作用，尤以整合素受体为佳；其中连接臂又以采用疏水性连接臂6-氨基己酸效果最好。MRI T1加权像上肿瘤信号强度明显增强，可达对照的1.8—2．8倍，并清晰显示直径为2—5mm的微小肿瘤病灶；体内生物分布测定表明，肿瘤部位Gd^3＋浓度高于心脏、肺、肝脏、肌肉等器官，也略高于脾脏和肾脏。结论：构建的靶向顺磁性纳米脂质体具有肿瘤特异性，肿瘤部位持续时间长，MRI信号强度高。可清晰显示直径2—5mm微小肿瘤病灶，有可能发展成为新的肿瘤特异性磁共振对比剂。