In the American Heart Association’s Scientific Sessions 2021, the results of six clinical trials related to cardiovascular surgery were revealed. The PALACS trial demonstrated that posterior left pericardiotomy during open heart surgery was associated with a significant reduction in postoperative atrial fibrillation; the EPICCURE study found that injection of mRNA encoding vascular endothelial growth factor (VEGF-A mRNA) directly into the myocardium of patients undergoing elective coronary artery bypass grafting (CABG) improved patients’ heart function; the VEST trial once again proved the safety and potential value of external stent for vein graft. This article will interpret the above-mentioned three studies.
Retinopathy of prematurity (ROP) is a retinal vascular disease in preterm or low birth weight infants and a leading cause of childhood blindness. Anti-vascular endothelial growth factor (VEGF) therapy offers advantages such as minimal invasiveness and convenient intervention; however, it carries a relatively high risk of disease reactivation, necessitating long-term follow-up due to the potential for severe outcomes. Studies indicate that post-anti-VEGF reactivation rates vary regionally and are related with birth status, ROP severity, and the specific anti-VEGF agent used. Most reactivations occur 6-16 weeks after initial treatment, at a postmenstrual age of 37-60 weeks. Reactivated lesions often develop at the original ridge or the junction of vascularized and avascular retina, and may present with dilation and tortuosity of the posterior retinal vessels, peripheral vascular leakage, neovascularization, or retinal detachment. Fundus fluorescein angiography may reveal Plus disease, posterior arterial tortuosity, abnormal nondichotomous retinal vessel branching at the junction of vascularized and avascular retina, irregular circumferential vessels, vasoobliteration with capillary nonperfusion, neovascularization, and fluorescein leakage. The choice of retreatment (such as retinal laser photocoagulation, intravitreal anti-VEGF injection, or vitrectomy) should be decided by the timing and severity of reactivation, along with prognostic considerations. It is recommended to establish a standardized management protocol for reactivation after anti-VEGF treatment in ROP to enable early detection and intervention, thereby preventing severe visual impairment. Future studies should focus on the mechanisms underlying ROP reactivation, differences in reactivation rates and timing among various anti-VEGF agents, predictive models for reactivation risk, and long-term management of reactivated disease.
ObjectiveTo observe the efficacy and safety of vitrectomy combined with subretinal injection of alteplase (tPA) and intravitreal injection of Conbercept in the treatment of large area submacular hemorrhage (SMH) secondary to polypoidal choroidal vasculopathy (PCV). MethodsA retrospective clinical study. From January to September 2021, 32 eyes of 32 patients with massive SMH secondary to PCV diagnosed in the Affiliated Eye Hospital of Nanchang University were included in the study. Large SMH was defined as hemorrhage diameter ≥4 optic disc diameter (DD). There were 32 patients (32 eyes), 20 males and 12 females. The mean age was (72.36±8.62) years. All patients had unilateral disease.The duration from onset of symptoms to treatment was (7.21±3.36) days. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examination. BCVA examination was performed using the international standard visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The central macular thickness (CMT) was measured by spectral domain-OCT. The average size of SMH was (6.82±1.53) DD. The logMAR BCVA 1.73±0.44; CMT was (727.96±236.40) μm. All patients were treated with 23G pars plana vitrectomy combined with subretinal injection of tPA and intravitreal injection of Conbercept. At 1, 3, 6 and 12 months after treatment, the same equipment and methods were used for relevant examinations before treatment. The changes of BCVA and CMT, the clearance rate of macular hemorrhage, and the complications during and after surgery were observed. BCVA and CMT before and after treatment were compared by repeated measures analysis of variance. ResultsCompared with before treatment, BCVA gradually increased at 1, 3, 6 and 12 months after treatment, and the differences were statistically significant (F=77.402, P＜0.001). There was no significant difference in BCVA between any two groups at different time points after treatment (P＞0.05). Correlation analysis showed that BCVA at 12 months after treatment was negatively correlated with the course of disease (r=－0.053, P=0.774). One week after treatment, macular hemorrhage was completely cleared in 30 eyes (93.75%, 30/32). The CMT was (458.56±246.21), (356.18±261.46), (345.82±212.38) and (334.64±165.54) μm at 1, 3, 6 and 12 months after treatment, respectively. Compared with before treatment, CMT decreased gradually after treatment, and the difference was statistically significant (F=112.480, P＜0.001). There were statistically significant differences in different follow-up time before and after treatment (P＜0.001). The number of treatments combined with Conbercept during and after surgery was (4.2±1.8) times. At the last follow-up, there was no recurrence of SMH, retinal interlamellar effusion and other complications. Conclusion Subretinal injection of tPA combined with intravitreal injection of Conbercept is safe and effective in the treatment of large SMH secondary to PCV, and it can significantly improve the visual acuity of patients.
ObjectiveTo observe and analyze the influencing factors for the prognosis of anti-vascular endothelial growth factor (VEGF) drug treatment in patients with macular neovascularization (MNV) under 45 years old. MethodsA retrospective clinical case study. A total of 89 MNV patients with 96 eyes who were diagnosed and treated with anti-VEGF drugs in Department of Ophthalmology of The Second Hospital of Lanzhou University from January 2020 to January 2024 were included in the study. The ages of all patients were ＜45 years old. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations; 49 eyes underwent OCT angiography (OCTA) examination. The BCVA examination was carried out using the international standard visual acuity chart and was converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity for statistics. The macular foveal thickness (CMT) was measured using an OCT instrument. The size of the MNV lesion was measured using the software of the OCTA self-contained device. The affected eyes were given intravitreal injection of anti-VEGF drugs once, and then the drugs were administered as needed after evaluation. The follow-up time after treatment was ≥6 months. During the follow-up, relevant examinations were performed using the same equipment and methods as before treatment. The last follow-up was taken as the time point for efficacy evaluation. According to the OCT image characteristics of the MNV lesions, the affected eyes were divided into the fibrous scar group and the non-fibrous scar group, with 52 (54.16%, 52/96) and 44 (45.83%, 44/96) eyes respectively. Comparing the CMT and BCVA at the last follow-up with those at the baseline, the affected eyes were divided into the CMT reduction group, the CMT increase group, the BCVA improvement group and the BCVA reduction group, with 66 (68.75%, 66/96), 30 (31.25%, 30/96) eyes and 74 (77.08%, 74/96), 22 (22.92%, 22/96) eyes respectively. The Mann-Whitney U test was used for the comparison of non-normally distributed measurement data between groups. Logistic regression analysis was used to analyze the independent factors affecting the prognosis of MNV patients. ResultsThere were no statistically significant differences in the age (Z=?0.928) and gender composition ratio (χ2= 0.123) between the fibrous scar group and the non-fibrous scar group (P＞0.05); there were statistically significant differences in the number of eyes with a follow-up time of ≥36 months and ＜36 months (χ2= 3.906, P=0.048); there were statistically significant differences in the size of the MNV lesions (Z=?2.385, P=0.017); there were statistically significant differences in the number of eyes with different vascular network morphologies (χ2=12.936, P=0.001). Before treatment and at the last follow-up, the CMT of the affected eyes was 267.50 (237.25, 311.75) μm and 242.00 (217.25, 275.75) μm respectively; logMAR BCVA was 0.20 (0.10, 0.50) and 0.35 (0.16, 0.60) logMAR respectively. There were statistically significant differences in the CMT and logMAR BCVA before treatment and at the last follow-up (Z=?3.311,?1.984; P=0.001, 0.047). There were statistically significant differences in different ages (Z=?2.284), myopic diopter (χ2=7.437), etiology (χ2=6.956), and disease course (Z=?1.687) between the CMT reduction group and the CMT increase group (P＜0.05). There were statistically significant differences in the number of eyes with different subjective feelings between the BCVA improvement group and the BCVA reduction group (χ2=10.133, P＜0.05). The results of logistic regression analysis showed that the etiology was an independent risk factor for CMT thickening. ConclusionsAge, etiology, myopic diopter, disease course, follow-up time, lesion size and the morphology of the neovascular network are the influencing factors for the prognosis of anti-VEGF drug treatment in MNV patients under 45 years old. The etiology is an independent risk factor for CMT increase.
ObjectiveTo detect expressions of E-cadherin (E-cad) and vascular endothelial growth factor (VEGF) in gastrointestinal stromal tumor (GIST) tissues and analyze their relationships with clinicopathologic features of patients with GIST.MethodsForty paraffin-embeded specimens of surgical resected GIST from January 2015 to March 2018 in the Pathology Department of Yuhuangding Hospital Affilicated to Qingdao University were retrieved. The expressions of E-cad and VEGF proteins were detected by the immunohistochemical method.ResultsThe positive expression rates of E-cad and VEGF proteins in the GIST tissues were 10.0% (4/40) and 50.0% (20/40), respectively. The positive expression rates of E-cad and VEGF proteins were associated with the tumor diameter, mitotic counts, and risk classification (P<0.05). The positive expression rate of the E-cad was negatively related to that of the VEGF in the GIST tissues (rs=–0.55, P=0.001).ConclusionFrom results of this study, VEGF and E-cad might be related with malignancy of GIST, which might be potential facators in predicting prognosis of GIST.
Objective To systematically evaluate expression of vascular endothelial growth factor (VEGF) protein in triple negative breast cancer (TNBC) and analyze its correlation between positive expression of VEGF protein and clinicopathologic features of patient with TNBC. Methods The published literatures relevant VEGF protein expression in TNBC and its relation to clinicopathologic features of patient with TNBC in China were retrieved by means of CNKI, Wanfang, VIP, China Biomedical, Chaoxing Medalink, PubMed databases, and other search tools. The literatures were independently filtered, extracted, and assessed by two reviewers according to the inclusion criteria and exclusion criteria. The meta-analysis was conducted by using RevMan 5.3 software. Results A total of 11 literatures were included and involved 1 838 patients (750 patients in the TNBC group and 1 088 patients in the non-TNBC group). The results of meta-nalysis showed that the positive expression of VEGF protein in the TNBC group was significantly higher than that in the non-TNBC group 〔OR=2.64, 95%CI (2.14, 3.26), P<0.000 01〕 , which was significantly increased in the TNBC patients with positive lymph node or stage Ⅲ–Ⅳ as compared with the negative lymph node or stage Ⅰ–Ⅱ 〔OR=0.30, 95% CI (0.14, 0.46), P=0.000 2; OR=0.43, 95% CI (0.29, 0.62), P<0.000 01〕 . However, the positive expression of VEGF protein was no associated with the age of patients with TNBC or tumor size (P>0.05). Conclusions VEGF highly expresses in TNBC and it is expected to be a new therapeutic target. Positive expression of VEGF protein is related to positive lymph node and late TNM stage, and it might be associated with prognosis of patient with TNBC.
ObjectiveTo investigate the mechanism of G protein coupled receptor kinase interacting protein 1 (GIT1) affecting angiogenesis by comparing the differentiation of bone marrow mesenchymal stem cells (BMSCs) differentiated into endothelial cells between GIT1 wild type mice and GIT1 gene knockout mice.MethodsMale and female GIT1 heterozygous mice were paired breeding, and the genotypic identification of newborn mice were detected by PCR. The 2nd generation BMSCs isolated from GIT1 wild type mice or GIT1 gene knockout mice were divided into 4 groups, including wild type control group (group A), wild type experimental group (group A1), GIT1 knockout control group (group B), and GIT1 knockout experimental group (group B1). The cells of groups A1 and B1 were cultured with the endothelial induction medium and the cells of groups A and B with normal cluture medium. The expressions of vascular endothelial growth factor receptor 2 (VEGFR-2), VEGFR-3, and phospho-VEGFR-2 (pVEGFR-2), and pVEGFR-3 proteins were detected by Western blot. The endothelial cell markers [von Willebrand factor (vWF), platelet-endothelial cell adhesion molecule 1 (PECAM-1), and vascular endothelial cadherin (VE-Cadherin)] were detected by flow cytometry. The 2nd generation BMSCs of GIT1 wild type mice were divided into 4 groups according to the different culture media: group Ⅰ, primary cell culture medium; group Ⅱ, cell culture medium containing SAR131675 (VEGFR-3 blocker); group Ⅲ, endothelial induction medium; group Ⅳ, endothelial induction medium containing SAR131675. The endothelial cell markers (vWF, PECAM-1, and VE-Cadherin) in 4 groups were also detected by flow cytometry.ResultsWestern blot results showed that there was no obviously difference in protein expressions of VEGFR-2 and pVEGFR-2 between groups; and the expressions of VEGFR-3 and pVEGFR-3 proteins in group A1 were obviously higher than those in groups A, B, and B1. The flow cytometry results showed that the expressions of vWF, PECAM-1, and VE-Cadherin were significantly higher in group A1 than in groups A, B, and B1 (P<0.05), and in group B1 than in groups A and B (P<0.05); but no significant difference was found between groups A and B (P>0.05). In the VEGFR-3 blocked experiment, the flow cytometry results showed that the expressions of vWF, PECAM-1, and VE-Cadherin were significantly higher in group Ⅲ than in groupsⅠ, Ⅱ, and Ⅳ, and in group Ⅳ than in groups Ⅰ and Ⅱ (P<0.05); but no significant difference was found between groups Ⅰ and Ⅱ (P>0.05).ConclusionGIT1 mediates BMSCs of mice differentiation into endothelial cells via VEGFR-3, thereby affecting the angiogenesis.
Objective To explore the influence on the expressions of vascular endothelial growth factor (VEGF) gene and matrix metalloproteinase-2 (MMP-2) gene in hepatocellular carcinoma of SMMC-7721 cells with RNA interference (RNAi) silencing the expression of hypoxia inducible factor-1α (HIF-1α) gene. Methods Firstly, constructed short hairpin RNA (shRNA) targeting for HIF-1α gene, and then transfected it to SMMC-7721 cells after combining with plasmid. The SMMC-7721 cells were divided into three groups, silencing group, negative control group, and blank control group, which were transfected with HIF-1α-shRNA-pGenesil-1 recombinant vector, shRNA-HK-pGenesil-1 recombinant vector, and pGenesil-1 vector respectively. Transfection cells were screened by the concentration of 500 μg/mL G418, and then positive and negative cell clones with transfection recombination carrier were obtained. Detected the expressions of HIF-1α mRNA, VEGF mRNA, and MMP-2 mRNA in the 3 groups with real time PCR (RT-PCR) technology, under the condition of hypoxic training 6 h, 12 h, and 24 h, as well as conventional oxygen training. Results There was no expression of HIF-1α mRNA at conventional oxygen condition in the 3 groups, and there was no significant difference in expressions of VEGF mRNA and MMP-2 mRNA among the 3 groups (P>0.05) at the condition of conventional oxygen training. The expressions of HIF-1α mRNA, VEGF mRNA, and MMP-2 mRNA in the silencing group, compared with the the negative control group and the blank control group, were obviously decreased (P<0.05) under the condition of hypoxic training (6, 12, and 24 h), while there was no significant difference between the negative control group and the blank control group at each time point (P>0.05), but the expressions of HIF-1α mRNA, VEGF mRNA, and MMP-2 mRNA in the 3 groups under every condition of hypoxic training were all higher than those of conventional oxygen condition (P<0.05). Under the condition of hypoxic training, the expressions of HIF-1α mRNA, VEGF mRNA, and MMP-2 mRNA in the 3 groups decreased over time, and there was significant difference between any 2 time points in each group (P<0.05). Conclusion RNAi technique can effectively silence the expression of HIF-1α mRNA of SMMC-7721 cells, and then silence the expressions of VEGF and MMP-2 mRNA, to inhibit the invasion and metastasis of hepatocellular carcinoma.
Anti-vascular endothelial growth factor (VEGF) drugs have been widely used in clinic by inhibiting angiogenesis to treat ocular diseases such as malignant tumors and diabetic retinopathy. However, recent studies have shown that intravitreal injection of anti-VEGF drugs may have significant systemic absorption, leading to a series of renal damages such as worsening hypertension, proteinuria, new glomerular disease, and thrombotic microangiopathy. This article reviews the renal toxicity of intravitreal injection of anti-VEGF drugs in the treatment of diabetic retinopathy and other ocular diseases, aiming to provide recommendations for clinicians.
Retinal vein occlusion (RVO) is a closely related disease of ophthalmology and systemic diseases. The Expert consensus on clinical diagnosis and treatment path of retinal vein occlusion in China (consensus) emphasizes that etiological diagnosis and treatment should be paid primary attention to, and etiological exploration should be placed in an important position in the diagnosis and treatment path. In addition to etiological treatment, the consensus emphasizes that clinical attention should be paid to the management of anterior segment neovascularization, neovascular glaucoma and macular edema. Especially for patients with short course of central retinal vein occlusion, the occurrence of 100-day glaucoma should be vigilant, and active anti-vascular endothelial growth factor (VEGF) drugs, laser photocoagulation and intraocular pressure treatment should be taken. For the treatment of macular edema, the consensus points out that anti-VEGF drugs and intraocular glucocorticoid sustained-release agents are effective, but the latter should be used cautiously to avoid problems such as high intraocular pressure glaucoma and accelerated cataract formation. For deficient RVO, the consensus defines its concept, defines the time point of treatment when combined with macular edema, and clarifies the applicable conditions of laser therapy.