Relationship between Expression of Vascular Endothelial Growth Factor and Cervical Lymph Node Metastasis in Papillary Thyroid Cancer: A Meta-analysis

The aim of the present study was to examine the relationship between the protein expression of vascular endothelial growth factor（VEGF） and lymph node metastasis（LNM） in papillary thyroid cancer（PTC）. VEGF-related articles that had been published until August 2016 were searched from the Pub Med, EMBASE, and MEDLINE to identify the risk factors of LNM in PTC. Rev Man 5.3 software was used for the meta-analysis. Finally, 9 articles met the inclusion criteria and were included in our meta-analysis. LNM was found to be present in 176 of 318 patients（57.8%） with high VEGF expression and in 71 of 159 patients（47.0%） with low VEGF expression. The overall OR was 2.81（95% confidence interval, 1.49–5.29）. LNM occurred more frequently in patients with high VEGF expression than in those with low VEGF expression（P=0.001）. Heterogeneity was markedly decreased in the subgroup analyses of LNM in terms of the patients＇ country of origin and the detection methods. Our meta-analysis concluded that the VEGF protein expression is associated with LNM in PTC.

Meta analysis on the relationship between gene polymorphisms of vascular endothelial growth factorand retinal prognosis risk of prematurity

AIM: To explore the relationship between gene polymorphisms of (VEGF) and retinopathy of prematurity (ROP). METHODS: Literature materials related to gene polymorphisms of VEGF and ROP in PubMed, EMBASE, Cochrane and CBM database were retrieved. These materials were screened according to inclusion and exclusion standards. Patients diagnosed with ROP in clinic were regarded as control group and ROP patients who were in treatment were regarded as observation group. The indexes in two groups were matched except birth weight (BW), gender and gestational weeks. Meta5.1 was used to analyze the relationship between gene polymorphisms of VEGF and ROP. RESULTS: Four random control tests (RCT) were included in this research, including 2611 patients. Met) analysis results showed that VEGF affected ROP, having statistical significance. The combined ratio was 0.44 (95% CI, 0.07, 0.80), 0.42 (95%CI, 0.09, 0.74) and 0.75 (95%CI, 0.02, 1.49), respectively. Carrying +405 allele might increase the premature infants risk of having ROP. CONCLUSION: ROP may be related to its carrying of +405 allele. Large-scale, multi-factor RCT researches are still needed in order to identify the relation between VEGF and ROP.

Hydroxysafflor Yellow A Promotes Vascular Endothelial Cell Proliferation via VEGF/VEGF Receptor

Aim To study the proliferative effeet of hydroxysaftlor yellow A （HSYA） on cultured canine aortic endothelial cell （VEC） in normoxic （21% O2 ） or hypoxic （10% O2 ） culture and the underlying mechanism. Methods The endothelial cells were scratched from trypsined canine aorta endothelium. HSYA was added to the cells at final concentrations of 1 × 10^-3, 1 × 10^-4 and 1 × 10^-5 mol· L^-1, respectively. VEGF （2.6 × 10^-7 mol· L^-1 ）-treated cells were used as the positive control. The proliferative effect of HSYA on VEC was determined at 48, 72, 96, and 120 h in normoxic culture by MTI＂ assay. Similarly, the proliferation of VEC was determined at 12, 24, 48, and 72 h in hypoxic culture by MTF assay. The effects of HSYA on VEC proliferation and VEGF secretion were investigated by MTr and ELISA assays at the presence of the antibodies to VEGF and VEGF receptors. Results Pretreatment with HSYA at concentrations of 1 × 10^-3 and 1 × 10^-4 mol· L^-1 enhanced VEC proliferation in normoxic culture. The most significant enhancing effect of HSYA on VEC proliferation was achieved at 24, 48, and 72 h in hypoxic culture in concentration-dependent and time-dependent manner. HSYA at 1 × 10^-3 mol·L^-1 showed a potency similar to VEGF at 2.6 × 10^-7 mol·L^-1 . Pretreatment with the antibodies of Flt-1, KDR or VEGF blocked the proliferative effect of HSYA with similar potencies. Antibodies of Fit-1 or VEGF antagonized the promoting effect of HSYA on VEGF secretion. Conclusion HSYA promotes VEC proliferation either in normoxic or hypoxic culture, especially in the latter condition. This effect of HSYA is at least partly mediated by VEGF and VEGF receptor.

Neuroprotective effect of ischemic preconditioning in focal cerebral infarction: relationship with upregulation of vascular endothelial growth factor

Neuroprotection by ischemic preconditioning has been confirmed by many studies, but the precise mechanism remains unclear. In the present study, we performed cerebral ischemic pre- conditioning in rats by simulating a transient ischemic attack twice （each a 20-minute occlusion of the middle cerebral artery） before inducing focal cerebral infarction （2 hour occlusion-reper- fusion in the same artery）. We also explored the mechanism underlying the neuroprotective effect of ischemic preconditioning. Seven days after ocdusion-reperfusion, tetrazolium chloride staining and immunohistochemistry revealed that the infarct volume was significantly smaller in the group that underwent preconditioning than in the model group. Furthermore, vascular endothelial growth factor immunoreactivity was considerably greater in the hippocampal CA3 region of preconditioned rats than model rats. Our results suggest that the protective effects of ischemic preconditioning on focal cerebral infarction are associated with upregulation of vascu- lar endothelial growth factor.

Functions of Müller cell-derived vascular endothelial growth factor in diabetic retinopathy

Müller cells are macroglia and play many essential roles as supporting cells in the retina.To respond to pathological changes in diabetic retinopathy(DR),a major complication in the eye of diabetic patients,retinal Müller glia produce a high level of vascular endothelial growth factor(VEGF or VEGF-A).As VEGF is expressed by multiple retinal cell-types and Müller glia comprise only a small portion of cells in the retina,it has been a great challenge to reveal the function of VEGF or other globally expressed proteins produced by Müller cells.With the development of conditional gene targeting tools,it is now possible to dissect the function of Müller cell-derived VEGF in vivo.By using conditional gene targeting approach,we demonstrate that Müller glia are a major source of retinal VEGF in diabetic mice and Müller cell-derived VEGF plays a significant role in the alteration of protein expression and peroxynitration,which leads to retinal inflammation,neovascularization,vascular leakage,and vascular lesion,key pathological changes in DR.Therefore,Müller glia are a potential cellular target for the treatment of DR,a leading cause of blindness.

Expression and Clinical Significance of Vascular Endothelial Growth Factor in Benign and Malignant Tissues of Breast

Objective： To detect the expression of vascular endothelial growth factor （VEGF） and microvessel density （MVD） count in breast benign affection, breast atypical hyperplasia and breast carcinoma in situ, and to clarify the relationship between VEGF expression, MVD and the clinicopathological features of these diseases. Methods： The expression of VEGF and MVD count in 115 cases breast benign diseases （including 40 breast fibroid tumor, 40 breast cystic hyperplasia and 35 intraductal papilloma, 19 breast atypical hyperplasias and 32 breast carcinomas in situ were examined by immunohistochemistry staining （SP-method）. Results： The positive rate of VEGF in breast benign diseases, breast atypical hyperplasia and breast carcinoma in situ were 21.74%（25/115）, 31.58.% （6/19）and 53.13%（17/32） respectively. It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The expression of VEGF increased gradually in the three groups （P〈0.05）. The MVD count of the three groups were 14.41 ± 2.59, 18.89± 4.47 and 21.13 ± 4.12 respectively, It was the lowest in breast benign affection group, and was the highest breast carcinoma in situ group. The MVD count of the three groups increased gradually （P〈0.05）. In VEGF positive group, MVD count was 19.41 ±4.78; In VEGF negative group, MVD count was 14.91±3.15. The MVD count was higher in VEGF positive group than that in VEGF negative group （P〈0.05）. Conclusion： The results of this study suggested that VEGF could promote microvessel growth in breast tumors. The occurrence and progression of breast cancer might be related with the expression of VEGF.

Expression of vascular endothelial growth factor and its role in oncogenesis of human gastric carcinoma

AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated. RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P【0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P【0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P【0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P【0.05 vs control SGC-7901 group). CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.

VEGF Pathway-targeted Therapy for Advanced Renal Cell Carcinoma: A Meta-analysis of Randomized Controlled Trials

Immunotherapy which has been in practice for more than 20 years proves effective for the treatment of metastatic renal cell carcinoma （mRCC）. Anti-angiogenesis-targeted therapy has recently been identified as a promising therapeutic strategy for mRCC. This study was aimed to evaluate the effectiveness of vascular endothelial growth factor （VEGF） pathway-targeted therapy for mRCC by comparing its effectiveness with that of immunotherapy. The electronic databases were searched. Randomized controlled trials （RCTs） on comparison of VEGF inhibiting drugs （sorafenib, sunitinib and bevacizumab） with interferon （IFN） or placebo for mRCC treatment were included. Data were pooled to meta-analyze. A total of 7 RCTs with 3451 patients were involved. The results showed that anti-VEGF agents improved progression-free survival （PFS） and offered substantial clinical benefits to patients with mRCC. Among them, sunitinib had a higher overall response rate （ORR） than IFN （47% versus 12%, P〈0.000001）. Bevacizumab plus IFN produced a superior PFS [risk ratio （RR）： 0.86, 95% confidence interval （CI）： 0.76-0.97; P=0.01] and ORR （RR： 2.19; 95% CI： 1.72-2.78; P〈0.00001） in patients with mRCC over IFN, but it yielded an increase by 31% in the risk of serious toxic effects （RR： 1.31; 95% CI 1.20-1.43; P〈0.00001） as compared with IFN. The overall survival （OS） was extended by sorafenib （17.8 months） and sunitinib （26.4 months） as compared with IFN （13 months）. It was concluded that compared with IFN therapy, VEGF pathway-targeted therapies improved PFS and achieved significant therapeutic benefits in mRCC. However, the risk to benefit ratio of these agents needs to be further evaluated.

Efficiency and safety of laser photocoagulation with or without intravitreal ranibizumab for treatment of diabetic macular edema: a systematic review and Meta-analysis

AIM： To compare the therapeutic effect and safety of laser photocoagulation along with intravitreal ranibizumab（IVR） versus laser therapy in treatment of diabetic macular edema（DME）.METHODS： Pertinent publications were identified through comprehensive searches of Pub Med, EMBASE, Web of Science, Cochrane Library, and Clinical Trials.gov to identify randomized clinical trials（RCTs） comparing IVR＋laser to laser monotherapy in patients with DME. Therapeutic effect estimates were determined by weighted mean differences（WMD） of change from baseline in best corrected visual acuity（BCVA） and central retinal thickness（CRT） at 6, 12, or 24 mo after initial treatment, and the risk ratios（RR） for the proportions of patients with at least 10 letters of improvement or reduction at 12 mo. Data regarding major ocular and nonocular adverse events（AEs） were collected and analyzed. The Review Manager 5.3.5 was used.RESULTS： Six RCTs involving 2069 patients with DME were selected for this Meta-analysis. The results showed that IVR＋laser significantly improved BCVA compared with laser at 6mo（WMD： 6.57; 95% CI： 4.37-8.77; P〈0.00001）, 12mo（WMD： 5.46; 95% CI： 4.35-6.58; P〈0.00001）, and 24mo（WMD： 3.42; 95% CI： 0.84-5.99; P=0.009） in patients with DME. IVR＋laser was superior to laser in reducing CRT at 12 mo from baseline with statistical significance（WMD：-63.46; 95% CI：-101.19 to-25.73; P=0.001）. The pooled RR results showed that the proportions of patients with at least 10 letters of improvement or reduction were in favor of IVR＋laser arms compared with laser（RR： 2.13; 95% CI： 1.77-2.57; P〈0.00001 and RR： 0.37; 95% CI： 0.22-0.62; P=0.0002, respectively）. As for AEs, the pooled results showed that a significantly higher proportion ofpatients suffering from conjunctival hemorrhage（study eye） and diabetic retinal edema（fellow eye） in IVR＋laser group compared to laser group（RR： 3.29; 95% CI： 1.53-7.09; P=0.002 and RR： 3.02; 95% CI： 1.24-7.32; P=0.01, respectively）. The incidence of other ocular and nonocular AEs considered in this Meta-analysis had no statistical difference between IVR＋laser and laser alone.CONCLUSION： The results of our analysis show that IVR＋laser has better availability in functional（improving BCVA） and anatomic（reducing CRT） outcomes than laser monotherapy for the treatment of DME. However, the patients who received the treatment of IVR＋laser may get a higher risk of suffering from conjunctival hemorrhage（study eye） and diabetic retinal edema（fellow eye）.

Evaluation of tumor response to antiangiogenic therapy in patients with recurrent gliomas using contrast-enhanced perfusion-weighted magnetic resonance imaging techniques:A meta-analysis

BACKGROUND It is of vital importance to find radiologic biomarkers that can accurately predict treatment response. Usually, the initiation of antiangiogenic therapy causes a rapid decrease in the contrast enhancing tumor. However, the treatment response is observed only in a fraction of patients due to the partial radiological response secondary to stabilization of abnormal vessels which does not essentially indicate a true antitumor effect. Perfusion-weighted magnetic resonance imaging(PWMRI) techniques have shown implicitness as a strong imaging biomarker for gliomas since they give hemodynamic information of blood vessels. Hence, there is a rapid expansion of PW-MRI related studies and clinical applications.AIM To determine the diagnostic performance of PW-MRI techniques including:(A)dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI); and(B)dynamic susceptibility contrast magnetic resonance imaging(DSC-MRI) for evaluating response to antiangiogenic therapy in patients with recurrent gliomas.METHODS Databases such as PubMed(MEDLINE included), EMBASE, and Google Scholar were searched for relevant original articles. The included studies were assessed for methodological quality with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Medical imaging follow-up or histopathological analysis was used as the reference standard. The data were extracted by two reviewers independently, and then the sensitivity, specificity, summary receiver operating characteristic curve, area under the curve(AUC), and heterogeneity were calculated using Meta-Disc 1.4 software.RESULTS This study analyzed a total of six articles. The overall sensitivity for DCE-MRI and DSC-MRI was 0.69 [95% confidence interval(CI): 0.53-0.82], and the specificity was 0.99(95%CI: 0.93-1) by a random effects model(DerSimonianeeLaird model). The likelihood ratio(LR) +, LR-, and diagnostic odds ratio(DOR)were 12.84(4.54-36.28), 0.35(0.22-0.53), and 24.44(7.19-83.06), respectively. The AUC(± SE) was 0.9921(± 0.0120), and the Q* index(± SE) was 0.9640(± 0.0323).For DSC-MRI, the sensitivity was 0.73, the specificity was 0.98, the LR+ was 7.82,the LR-was 0.32, the DOR was 31.65, the AUC(± SE) was 0.9925(± 0.0132), and the Q* index was 0.9649(± 0.0363). For DCE-MRI, the sensitivity was 0.41, the specificity was 0.97, the LR+ was 5.34, the LR-was 0.71, the DOR was 8.76, the AUC(± SE) was 0.9922(± 0.2218), and the Q* index was 0.8935(± 0.3037).CONCLUSION This meta-analysis demonstrated a beneficial value of PW-MRI(DSC-MRI and DCE-MRI) in monitoring the response of recurrent gliomas to antiangiogenic therapy, with reasonable sensitivity, specificity, +LR, and-LR.

Safety and efficacy of EFGR and VEGF signaling pathway inhibition therapy in patients with colorectal cancer: a meta-analysis

Objective Epidermal growth factor receptor(EGFR) and vascular endothelial growth factor(VEGF) inhibitors are two targeted therapies for metastatic colorectal cancer(mCRC). However, few studies have focused on the safety and efficacy of combined targeted therapy against those of a single inhibition therapy of EFGR or VEGF. This meta-analysis aimed to compare the anti-tumor activity of the combined inhibition therapy and single inhibition therapy in patients with mCRC. Methods We searched PubMed, Medline, the Cochrane library, Embase, and annual meeting proceedings for relevant clinical trials. Objective response rate(ORR), progression-free survival(PFS), overall survival(OS), and adverse events were extracted and calculated.Results Nine trials comprising 3977 patients were selected for the analysis. The combined inhibition therapy showed a 3.7% improvement in ORR compared with single inhibition, and this difference was statistically significant [hazard ratio(HR) = 1.33; 95% confidence interval(CI), 1.01–1.74; P = 0.04]. Subgroup analysis showed that the combined EGFR and VEGF inhibitor therapy had an 11.65% improvement in ORR compared with VEGF inhibitor therapy(OR = 2.14; 95% CI, 1.34–3.40; P = 0.001). EGFR and VEGF inhibitor therapy and chemotherapy had an 18.08% improvement in ORR compared with chemotherapy(OR = 2.21; 95% CI, 1.05–4.64; P = 0.04). Moreover, EGFR and VEGF inhibitor therapy significantly improved PFS compared with VEGF inhibitor therapy(OR = 0.82; 95% CI, 0.69–0.97; P = 0.02). VEGF inhibitor therapy and chemotherapy significantly improved PFS compared with EGFR and VEGF inhibitor therapy and chemotherapy(OR = 1.20; 95% CI, 1.11–1.30; P = 0.00). In addition, EGFR and VEGF inhibitor therapy showed improved OS compared with VEGF inhibitor therapy(HR = 0.78, 95% CI: 0.65–0.94; P = 0.008). Finally, the combined inhibition therapy showed an obviously increased risk of cutaneous and mucosal effects(RR = 6.45; 95% CI: 2.71–15.36; P < 0.01), diarrhea/abdominal pain(RR = 1.97; 95% CI: 1.45–2.68; P < 0.01), fatigue/asthenia(RR = 1.60; 95% CI: 1.10–2.32; P = 0.01), dehydration or electrolyte disturbance(RR = 2.78; 95% CI: 1.48–5.21; P < 0.01), nail disorder(RR = 8.23; 95% CI: 1.52–44.57; P = 0.01), and dizziness/headache(RR = 3.43; 95% CI: 1.89–6.23; P < 0.01) compared with single inhibition therapy.Conclusion Compared with single inhibition therapy, the combined inhibition therapy significantly improved ORR, PFS, and OS in the treatment of mCRC patients. Compared with a single-targeted agent, the combined therapy of anti-EGFR and anti-VEGF drug provided an efficacy advantage, although it led to greater toxicity.

血管生成素样蛋白4通过调节成纤维细胞和内皮细胞功能影响糖尿病足进程

背景:研究表明,血管因素对糖尿病足的发生具有重要影响。目的:探讨血管生成素样蛋白4在糖尿病足形成中的重要作用。方法:①对糖尿病足患者的基因表达谱数据进行生物信息学分析,找到关键基因。收集糖尿病足患者以及无糖尿病健康人的皮肤标本进行苏木精-伊红染色、免疫组化染色以及qRT-PCR实验,检测血管生成素样蛋白4表达情况。②培养人永生化皮肤成纤维细胞系和原代人脐静脉内皮细胞,将2种细胞分别分为对照组和外源性补充血管生成素样蛋白4组,通过划痕实验以及CCK-8实验分别检测成纤维细胞的迁移能力和增殖能力,通过Ki67实验检测内皮细胞的增殖能力。结果与结论:①生信分析发现,血管生成素样蛋白4基因的下调可能是导致糖尿病足形成的关键基因。②苏木精-伊红染色结果显示,与正常皮肤相比,血管生成素样蛋白在糖尿病足皮肤内弱表达,且其mRNA水平相对表达量降低(P<0.01)。③划痕实验结果显示,与对照组相比,血管生成素样蛋白4组成纤维细胞迁移能力明显增强;CCK-8细胞增殖实验显示,血管生成素样蛋白4组成纤维细胞的吸光度值在24,48 h均高于对照组(P<0.01,P<0.001);提示血管生成素样蛋白4可增强高糖处理的成纤维细胞迁移及增殖能力。④Ki67实验结果显示,与对照组相比,血管生成素样蛋白4组内皮细胞Ki67阳性细胞数目明显多于对照组;CCK-8细胞增殖实验显示,血管生成素样蛋白4组内皮细胞的吸光度值在24,48 h均高于对照组(P<0.05,P<0.001)。(5)以上结果均提示血管生成素样蛋白4可增强高糖处理内皮细胞的增殖能力。

联合多期增强CT纹理分析及血液学指标术前预测胃癌VEGFR2表达状态

目的探讨多期动态增强CT纹理分析参数联合血液学指标术前预测胃癌血管内皮生长因子受体2(vascu‐lar endothelial growth factor receptor2,VEGFR2)表达状态的价值。方法选取本院148例胃癌患者资料,获得术前血液学指标和三期增强CT纹理分析参数。基于组内相关系数和差异性检验对参数进行特征筛选。基于二元Logistic回归构建血液学模型、CT纹理分析模型及综合模型来预测VEGFR2表达状态。通过受试者工作特征曲线评估三个模型的诊断效能,并通过列线图来可视化地预测胃癌患者VEGFR2的表达状态。结果基于血液学指标构建的血液学模型曲线下面积(area under the curve,AUC)为0.687。由静脉期纹理分析参数构建的CT纹理分析模型的AUC值为0.624。联合血液学模型和CT纹理分析模型构建的综合模型AUC值为0.723。结论联合多期动态增强CT纹理分析参数及血液学指标有助于术前预测胃癌VEGFR2表达状态。

血清TIMP-1、VEGF水平对自然分娩初产妇产后压力性尿失禁严重程度的预测价值

目的探讨自然分娩初产妇血清基质金属蛋白酶组织抑制因子-1(tissue inhibitor of metall oproteinase-1,TIMP-1)、血管内皮生长因子(vascular endothelial growth factor,VEGF)水平对产后压力性尿失禁(post partum stress urinary incontinence,PSUI)严重程度的预测价值。方法选取2019年12月至2023年7月220例PSUI自然分娩初产妇为病例组,根据尿垫试验结果分为轻度组158例和中重度组62例。另纳入同期220例无PSUI的自然分娩初产妇作为对照组。采用ELISA法检测入组者血清TIMP-1、VEGF水平;采用Pearson法分析PSUI患者血清TIMP-1与VEGF的相关性;采用多因素Logistic回归分析PSUI患者疾病严重程度的影响因素;采用受试者工作特征曲线分析血清TIMP-1、VEGF对PSUI患者疾病严重程度的预测价值。结果病例组血清TIMP-1水平显著低于对照组,血清VEGF水平显著高于对照组(P<0.01)。中重度组血清TIMP-1水平显著低于轻度组,血清VEGF水平、年龄≥35岁比例、新生儿体质量显著高于轻度组(P<0.05,P<0.01)。PSUI患者血清TIMP-1与VEGF呈负相关(r=-0.671,P<0.05)。TIMP-1是PSUI患者疾病程度加重的保护因素(P<0.01),VEGF是PSUI患者疾病程度加重的危险因素(P<0.01)。TIMP-1、VEGF单独及联合预测PSUI患者疾病严重程度的曲线下面积(area under curve,AUC)分别为0.857、0.808、0.901,其中联合预测的AUC高于二者单独预测(P<0.01)。结论PSUI患者血清TIMP-1低表达,VEGF高表达,且TIMP-1、VEGF与病情程度密切相关,二者联合在预测PSUI患者疾病严重程度方面有较高的价值。

服用非那雄胺的前列腺增生患者前列腺转录组景观特征分析

目的通过转录组分析从基因表达方面探讨非那雄胺对良性前列腺增生(BPH)患者的影响。方法收集2020年10月—2021年10月于北京大学第三医院接受前列腺电切术的患者,根据患者术前是否长期(>6个月)服用非那雄胺分为用药组和非用药组,两组各8例。对两组患者的前列腺组织标本进行转录组测序分析,定量聚合酶链式反应(qPCR)及免疫组化分析验证其结果。结果用药组与非用药组相比,上调基因857个,下调基因806个。通路富集分析显示,非那雄胺导致焦点粘附通路中血管内皮生长因子D型(VEGFD)表达下调;组间网络分析提示钙信号通路为整个过程的关键通路;进一步对其进行基因集富集分析(GSEA)发现分化簇38(CD38)基因表达上调。qPCR及免疫组化验证支持上述转录组结果,同时发现雄激素受体表达升高。结论非那雄胺通过下调焦点粘附通路中VEGFD的表达减少前列腺微血管生成,进而降低BPH手术出血的风险,长期服用非那雄胺导致钙信号通路中CD38表达上调,可能与非那雄胺抵抗有关。

Vascular Endothelial Growth Factor and Cluster of Differentiation 34 for Assessment of Perioperative Bleeding Risk in Gastric Cancer Patients

Background： Angiogenesis is the formation of new blood vessels to supply nutrients to tumors. Vascular endothelial growth factor （VEGF） and cluster of differentiation 34 （CD34） are important signaling proteins involved in angiogenesis. Many studies have demonstrated that VEGF and CD34 are related to tumor progression. This study focused on the relationship between VEGF, CD34, and perioperative hemorrhage in patients with gastric cancer. Methods： To observe the relationship between VEGF and CD34, we tracked 112 patients with advanced gastric cancer for 5 years to assess factors related to hemorrhage, using immunohistochemistry. The results were subjected to statistical analysis using a 2 × 2 contingency table, logistic regression, and receiver operating characteristic （ROC） test. Results： The concentrations of VEGF and CD34 were critically correlated with perioperative hemorrhage and neural invasion in patients with gastric cancer （P 〈 0.05）. Expression of VEGF and CD34 was related （P 〈 0.05, χ2 = 6.834）. VEGF and CD34 co-expression strongly increased the risk of preoperative bleeding （area under the ROC curve 〉0.7, P 〈 0.05）. Conclusions： Expression of VEGF and CD34 was critically correlated with perioperative hemorrhage in gastric cancer patients. Co-expression of VEGF and CD34 could be an effective indicator for evaluating the risk ofperioperative bleeding in gastric cancer patients.

筛选GDM孕妇子代罹患心血管疾病的可能基因及信号通路

目的:寻找妊娠期糖尿病(GDM)孕妇子代罹患心血管疾病的相关基因及信号通路。方法:通过生物信息学方法,利用GEO数据库中GDM孕妇胎儿脐带来源的人脐静脉血管内皮细胞(HUVECs)基因芯片数据,结合R(R3.6.4)平台,筛选出GDM孕妇和对照组新生儿脐带来源的HUVECs中差异表达的基因。利用GO及KEGG工具对表达显著相关基因进行基因本体和KEGG通路分析并构建蛋白质互作网络。结果:共筛选出2091个差异表达基因(正相关1146个,负相关945个)。GO分析和KEGG富集分析发现,差异基因主要参与血管系统发育的调节、血管生成、上皮细胞增殖等生物学功能,差异表达基因主要通过PI3K-Akt等信号通路发挥作用。结论:GDM孕妇子代PDGFRB等可能的关键差异基因可能通过PI3K-Akt信号通路参与了心血管疾病等的发生发展。提示关注GDM高危孕妇,从源头降低GDM子代罹患心血管疾病风险。

脐血血管内皮生长因子水平及血气分析与新生儿视网膜出血相关性研究

目的:探讨脐血血管内皮生长因子(VEGF)水平及血气分析与新生儿视网膜出血(RH)的相关性。方法:选取产科分娩并且行新生儿眼底筛查的596例新生儿。统计新生儿眼底检查结果,根据是否伴有眼底出血分为RH组(230例)和正常对照组(366例),分析VEGF水平及血气分析与新生儿RH的关系。结果:596例新生儿中,RH发生率为38.59%(230/596)。两组患者在产妇年龄、产次、多胎、分娩方式、窒息、产钳助产、胎龄、VEGF、pH值、二氧化碳分压(PaCO_(2))、氧分压(PaO_(2))、碱剩余(BE)值比较,差异有统计学意义(均P<0.05);而在妊娠期糖尿病、妊娠期高血压、贫血、性别、出生体重比较,差异无统计学意义(均P>0.05)。阴道分娩、窒息、产钳助产、VEGF≥251.67pg/ml、pH值<7.32、PaCO_(2)≥52.53mmHg、PaO_(2)<24.37mmHg、BE值<-3.49mmol/L是影响新生儿RH的独立危险因素(均P<0.05)。结论:脐血VEGF水平及血气分析均与KH密切相关。

伊伐布雷定对冠心病患者血管内皮功能影响的Meta分析

目的评价伊伐布雷定对冠心病患者血管内皮功能的影响。方法检索PubMed、Embase、Cochrane图书馆、Web of Science、中国知网、万方数据、维普网、中国生物医学文献数据库,收集伊伐布雷定(干预组)对比安慰剂或β受体阻滞剂(对照组)的随机对照试验(RCT),检索时限为各数据库建库起至2023年3月20日。筛选文献、提取数据和评价质量后,采用RevMan5.4软件进行Meta分析。结果共纳入12项RCT,共计1206例患者。Meta分析结果显示,干预组患者的内皮依赖性血管舒张功能(FMD)[MD=1.71,95%CI(0.96,2.46),P<0.00001]、一氧化氮(NO)[MD=5.80,95%CI(5.02,6.59),P<0.00001]水平均显著高于对照组,内皮素1(ET-1)水平显著低于对照组[MD=-7.45,95%CI(-8.42,-6.47),P<0.00001]。两组患者的非内皮依赖性血管舒张功能(NMD)比较,差异无统计学意义[MD=0.13,95%CI(-0.74,1.00),P=0.77]。按照对照组用药和干预时间的不同进行的亚组分析结果显示,与安慰剂比较,使用伊伐布雷定患者的FMD水平显著升高(P<0.05);与安慰剂、β受体阻滞剂比较,使用伊伐布雷定患者的NO水平均显著升高(P<0.05)、ET-1水平均显著降低(P<0.05)。无论干预时间长短,干预组患者的FMD、NO、ET-1水平均较对照组显著改善(P<0.01),NMD比较差异无统计学意义(P>0.05)。结论伊伐布雷定能显著改善冠心病患者的血管内皮功能。

康柏西普对高糖环境下的人脐静脉内皮细胞中金属蛋白酶-2、-9和基质金属蛋白酶抑制剂-1、-2表达水平的影响

目的 研究康柏西普对高糖环境下的人脐静脉内皮细胞(Human Umbilical Vein Endothelial Cells,HUVECs)金属蛋白酶-2、-9 (Matrix metalloproteinase-2、-9,MMP-2、MMP-9)和基质金属蛋白酶抑制剂-1、-2 (Tissue inhibitor of metalloproteinase-1、-2,TIMP-1、TIMP-2)表达水平的影响。方法 采用传代细胞系培养方法培养人脐静脉血管内皮细胞,细胞分组如下:(1)正常对照组(葡萄糖浓度:5.56mmol/l);(2)高渗对照组(5.56mmol/l葡萄糖+24.44mmol/l甘露醇);(3)高糖组(葡萄糖浓度:30mmol/l);(4)低康柏西普组(30mmol/l葡萄糖+1ug/ml康柏西普);(5)中康柏西普组(30mmol/l葡萄糖+10ug/ml康柏西普);(6)高康柏西普组(30mmol/l葡萄糖+100ug/ml康柏西普)。采用酶联免疫吸附测定法检测HUVECs分泌至培养基中的VEGF、MMP-2、MMP-9、TIMP-1和TIMP-2水平。结果 与正常对照组相比,高糖组HUVECs中的VEGF (124.63±5.32pg/ml vs 169.05±24.18pg/ml)和MMP-9 (1018.06±75.61pg/ml vs 1287.50±38.19pg/ml)表达显著升高(P<0.05),MMP-2、TIMP-1及TIMP-2的表达没有明显变化(P>0.05)。与高糖组相比,低、中、高康柏西普组HUVECs中VEGF(117.68±17.98pg/ml、97.62±6.24pg/ml、93.53±8.24pg/ml)的表达均显著降低(P<0.05),中、高康柏西普组HUVECs中MMP-9 (1084.72±37.58pg/ml、893.06±41.93pg/ml)的表达显著降低(P<0.05),低、中、高康柏西普组MMP-2以及TIMP-1和TIMP-2的表达水平无均显著改变(P>0.05)。结论 康柏西普可显著降低高糖环境下人脐静脉内皮细胞中MMP-9的表达水平,对MMP-2、TIMP-1和TIMP-2无明显影响。