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.
Diabetic macular edema (DME) is the most threatening complication of diabetic retinopathy that affects visual function, which is characterized by intractability and recurrent attacks. Currently, the clinical routine treatments for DME mainly include intravitreal injection, grid laser photocoagulation in the macular area, subthreshold micropulse laser, periocular corticosteroid injection, and vitrectomy. Although conventional treatments are effective for some patients, persistent, refractory, and recurrent DME remains a clinical challenge that needs to be urgently addressed. In recent years, clinical studies have found that certain combination therapies are superior to monotherapy, which can not only restore the anatomical structure of the macular area and effectively reduce macular edema but also improve visual function to some extent while reducing the number of treatments and the overall cost. This makes up for the shortcomings of single treatment modalities and is highly anticipated in the clinical setting. However, the application of combination therapy in clinical practice is relatively short, and its safety and long-term effectiveness need further exploration. Currently, new drugs, new formulations, and new therapeutic targets are still under research and development to address different mechanisms of DME occurrence and development, such as anti-vascular endothelial growth factor agents designed to anchor repetitive sequence proteins with stronger inhibition of vascular leakage, multiple growth factor inhibitors, anti-inflammatory agents, and stem cell therapy. With the continuous improvement of the combination application of existing drugs and treatments and the development of new drugs and treatment technologies, personalized treatment for DME will become possible.
Objective To observe and evaluate the safety and efficacy of anti-vascular endothelial growth factor (VEGF) in the treatment of eyes with macular edema (ME) secondary to branch retinal vein occlusion (BRVO) in Lhasa, Tibet. MethodsA retrospective case series. From September 2018 to January 2022, a total of 41 patients (41 eyes) with BRVO-ME, who were diagnosed in Department of Ophthalmology of Tibet Autonomous Region People’s Hospital, were included in this study. There were 21 eyes in 21 males and 20 eyes in 20 females. The median age was 53 (31,75) years. There were 24 patients with hypertension (58.8%, 24/41). Best corrected visual acuity (BCVA), ocular pressure, fundus color photography and optical coherence tomography (OCT) were performed in all eyes. The BCVA was performed using the international standard logarithmic visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The foveal macular thickness (CMT) was measured by OCT. All eyes were treated with intravitreous injection of anti-VEGF drugs, once a month, among which 23 eyes (56.1%, 23/41) received intravitreous injection of ranibizumab (IVR), and 18 eyes (43.9%, 18/41) received intravitreous injection of conbercept (IVC), and were grouped accordingly. There was no significant difference in age (Z=－0.447), gender composition (Z=－0.485), logMAR BCVA (t=－1.591), intraocular pressure (t=－0.167) and CMT (t=－1.290) between two groups (P＞0.05). During the follow-up, the same devices and methods were used at baseline to perform relevant examinations, and the changes of BCVA, intraocular pressure, CMT and new cardiovascular and cerebrovascular events were compared between baseline and the last follow-up. logMAR BCVA, intraocular pressure and CMT were compared between baseline and last follow-up using Student t test. The comparison of injection times and follow-up time between IVR group and IVC group was conducted by Mann-Whitney U test. ResultsAt baseline, logMAR BCVA, intraocular pressure, and CMT were 0.852±0.431, (12.5±2.5) mm Hg (1 mm Hg= 0.133 kPa), and (578.1±191.1) μm, respectively. At the last follow-up, the number of anti-VEGF drug treatments was (2.7±1.2) times; logMAR BCVA and CMT were 0.488±0.366 and (207.4±108.7) μm, respectively, with CMT > 250 μm in 14 eyes (34.1%, 14/41). Compared with baseline, BCVA (t=4.129) and CMT (t=－0.713) were significantly improved, with statistical significance (P＜0.001). The injection times of IVR group and IVC group were (2.6±0.9) and (3.0±1.5) times, respectively. There were no significant differences in the number of injection times (t=－1.275), logMAR BCVA (t=－0.492), intraocular pressure (t=0.351) and CMT (t=－1.783) between the two groups (P＞0.05). No new hypertension, cardiovascular and cerebrovascular events occurred in all patients during follow-up. At the last follow-up, there were no eye complications related to treatment modalities and drugs. ConclusionShort-term anti-VEGF treatment can improve the visual acuity of BRVO secondary ME patients and alleviate ME in Lhasa, Tibet. The safety and efficacy of ranibizumab and conbercept were similar.
Objective To evaluate the correlation of vascular endothelial growth factor (VEGF) and vascular endothelial cadherin (VE-Cadherin) in serum with the severity of obstructive sleep apnea (OSA) and explore their clinical value in OSA. Methods A total of 90 patients with OSA admitted to the Sleep Monitoring Center of the Affiliated Hospital of Xuzhou Medical University from April 2023 to June 2024 were prospectively selected. Based on the apnea-hypopnea index (AHI), the patients were divided into a mild group (5 - 15 times/hour, n=30), a moderate group (>15 - 30 times/hour, n=28), and a severe group (>30 times/hour, n=32). Thirty healthy individuals who underwent physical examinations during the same period were included as a control group. The levels of serum VEGF and soluble VE-Cadherin (sVE) in all subjects were detected by enzyme-linked immunosorbent assay. The differences in serum VEGF and sVE levels among the groups were compared, and the correlations between serum VEGF and sVE levels and sleep parameters were explored. The moderate and severe OSA patients were given 3 months of continuous positive airway pressure (CPAP) treatment, and the changes in sleep parameters and serum VEGF and sVE levels before and after treatment were compared. Results The levels of serum VEGF and sVE in the OSA patients increased with the severity of the disease; the levels of serum VEGF and sVE in the moderate and severe OSA groups were significantly higher than those in the healthy control group and the mild OSA group (P<0.05). The levels of serum VEGF and sVE in the severe OSA group were significantly higher than those in the moderate OSA group (P<0.05). There was no significant difference in the expression levels of serum VEGF or sVE between the mild OSA group and the healthy control group (P>0.05). The sensitivity and specificity of serum VEGF in diagnosing OSA were 65.6% and 93.3%, respectively, with an area under curve (AUC) value of 0.845. The sensitivity and specificity of serum VE-Cadherin in diagnosing OSA were 64.4% and 96.7%, respectively, with an AUC value of 0.835. After 3 months of CPAP treatment, AHI, longest apnea time, serum VEGF and sVE levels in the moderate and severe OSA groups decreased significantly, mean arterial oxygen saturation and lowest arterial oxygen saturation increased significantly (P<0.05). Conclusions The levels of VEGF and VE-Cadherin in serum of OSA patients are significantly elevated and positively correlated with the severity of OSA. Monitoring the changes in the levels of VEGF and VE-Cadherin in serum of OSA patients is helpful for evaluating the therapeutic effect of CPAP.
Objective To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV). MethodsA prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance. ResultsEighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA (F=50.298) gradually increased, CRT (F=25.220), PED height (F=144.16), SFCT (F=69.77), LVCT (F=136.69), CVI (F=72.70) gradually decreased after treatment. The differences were statistically significant (P＜0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. ConclusionSubretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.
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.
Objective To analyze the diagnostic value of shear wave elastography (SWE) combined with vascular endothelial growth factor B (VEGF-B) and hemoglobin A1c (HbA1c) in early diabetic peripheral neuropathy (DPN). Methods A total of 100 patients with type 2 diabetes mellitus (T2DM) admitted to Mianyang Central Hospital between October 2020 and October 2023 were selected and divided into a T2DM with DPN group (n=31) and a T2DM without DPN group (n=69) based on the presence or absence of DPN. Additionally, 50 healthy individuals from the same hospital’s health examination center were included as a healthy control group. The basic clinical characteristics, mean elasticity (Emean) values of the left and right median and tibial nerves, serum VEGF-B, and HbA1c levels were compared among the three groups. The diagnostic efficacy of SWE, VEGF-B, and HbA1c for DPN was evaluated using receiver operating characteristic (ROC) curves, and Pearson correlation analysis was performed to assess the relationships between median/tibial nerve Emean and VEGF-B/HbA1c. Results The Emean values of the left and right median nerves, Emean values of the left and right tibial nerves, serum VEGF-B, and HbA1c levels in the T2DM with DPN group were significantly higher than those in the T2DM without DPN group and the healthy control group (P<0.05). The Emean values of the left and right median and tibial nerves, Emean values of the left and right tibial nerves, and HbA1c level in the T2DM without DPN group were significantly higher than those in the healthy control group (P<0.05), while no significant difference was observed in serum VEGF-B level between the T2DM without DPN group and the healthy control group (P>0.05). The area under the ROC curve for the combined diagnosis of DPN using SWE, VEGF-B, and HbA1c was 0.859 [95% confidence interval (0.828, 0.955)]. The sensitivity of the combined diagnosis (93.72%) was significantly higher than that of individual diagnoses (78.82%, 75.39%, and 71.05%, respectively; P<0.05), while the specificity (88.64%) showed no significant difference compared to individual diagnoses (80.18%, 78.96%, and 82.88%, respectively; P>0.05). Positive correlations were observed between median/tibial nerve Emean and VEGF-B/HbA1c levels (r=0.428, 0.395, 0.416, and 0.416, respectively; P<0.05). Conclusions Elevated median/tibial nerve Emean, serum VEGF-B, and HbA1c levels are closely associated with DPN. The combination of SWE, VEGF-B, and HbA1c improves diagnostic sensitivity for DPN, demonstrating significant clinical value.
ObjectiveTo observe the long-term effects of anti-vascular endothelial growth factor (VEGF) drug initiation combined with dexamethasone intravitreal implant (DEX) on the structural integrity of the outer macular region of the eye in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). MethodsA retrospective clinical study. From February 2018 to August 2022, 54 patients diagnosed with CRVO combined with ME (CRVO-ME) in Department of Ophthalmology of Central Theater Command General Hospital were included in the study. Among them, there were 30 males and 24 females, all with monocular disease. According to different treatment regiments, patients were divided into anti-VEGF and DEX combination therapy group (initial combination group), anti-VEGF drug monotherapy group (monotherapy group) with 21 eyes and 33 eyes, respectively. Best corrected visual acuity (BCVA), optical coherence tomography (OCT) examination were performed in all eyes. The thickness of foveal retina (CRT) and the deficiency length of outer membrane (ELM), ellipsoid band (EZ) and chimaera band (IZ) in the 1 mm macular area were measured by OCT. The initiating combination group was treated with anti-VEGF agents or DEX as assessed on demand (PRN) after the combination therapy, and the monotherapy group received 3+PRN regimen. Relevant examinations were performed at 1 (V1), 6 (V6), 12 (V12) months and observation cut-off or the last visit (Vf) after treatment using the same equipment before treatment. The deletion length of ELM, EZ and IZ in V1, V6, V12 and Vf after treatment were compared between the two groups. Repeated measurement ANOVA was used to compare BCVA, CRT and deletion length of ELM, EZ and IZ at different follow-up times. Spearman rank correlation test was used to analyze the correlation between the two groups of continuous variables. ResultsThe follow-up time of patients in the initial combination group and monotherapy group was (18.05±5.66) and (21.90±10.80) months, respectively, with no statistical significance (F=13.430, P=0.229). Compared with baseline, the deletion lengths of ELM, EZ and IZ were significantly improved (F=11.848, 10.880, 29.236), BCVA was increased (F=10.541) and CRT was decreased (F=52.278) in the initial combination group and the monotherapy group at different follow-up times after treatment. The differences were statistically significant (P＜0.001). At V1, EZ and IZ deletion lengths were (344.10±413.03), (593.33±372.96) μm and (354.71±321.75), (604.85±385.77) μm in the initial combination group and monotherapy group, respectively. The improvement of EZ and IZ deletion lengths in the initial combination group was better than that in the single drug group, and the difference was statistically significant (F=5.272, 6.106; P=0.026, 0.017). The CRT of the initial combination group and the monotherapy group were (248.86±59.99) and (314.72±214.91) μm, respectively, and the CRT of the initial combination group was significantly lower than that of the monotherapy group, with statistical significance (F=6.102, P=0.017). At V6, V12 and Vf, the deletion length of ELM, EZ and IZ and BCVA and CRT showed no statistical significance (P＞0.05). Correlation analysis showed that ELM, EZ, IZ were positively correlated with BCVA and CRT in the initial combination group and monotherapy group (P＜0.001). In V6, V12 and Vf, the number of anti-VEGF drug injections in the initial combination group and monotherapy group was (2.67±1.32), (4.43±2.27), (6.05±3.51), (4.58±0.90), (7.33±1.93), (11.33±6.10) times, respectively. The number of injections in the initial combination group was significantly lower than that in the monotherapy group, and the difference was statistically significant (F=5.150, 0.646, 3.433; P＜0.001). ConclusionsThe improvement of BCVA and CRT in the initial combination group is similar to that in the monotherapy group. Compared with the monotherapy group, EZ and IZ deletion are improved more significantly in the initial combination group, and CRT decreased more rapidly and significantly. The initial combination group receives fewer anti-VEGF injections than the monocular group.
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.