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 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.
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.
Objective To investigate whether human amniotic mesenchymal stem cells (hAMSCs) have the characteristics of mesenchymal stem cells (MSCs) and the differentiation capacity into ligament fibroblastsin vitro. Methods The hAMSCs were separated through trypsin and collagenase digestion from placenta, the phenotypic characteristics of hAMSCs were detected by flow cytometry, the cytokeratin-19 (CK-19) and vimentin expression of hAMSCs were tested through immunofluorescence staining. The hAMSCs at the 3rd passage were cultured with L-DMEM/F12 medium containing transforming growth factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF) as the experimental group and with single L-DMEM/F12 medium as the control group. The morphology of hAMSCs was observed by inverted phase contrast microscope; the cellular activities and ability of proliferation were examined by cell counting kit-8 (CCK-8) method; the ligament fibroblasts related protein expressions including collagen type I, collagen type III, Fibronectin, and Tenascin-C were detected by immunofluorescence staining; specific mRNA expressions of ligament fibroblasts and angiogenesis including collagen type I, collagen type III, Fibronectin, α-smooth muscle actin (α-SMA), and VEGF were measured by real-time fluorescence quantitative PCR. Results The hAMSCs presented monolayer and adherent growth under inverted phase contrast microscope; the flow cytometry results demonstrated that hAMSCs expressed the MSCs phenotypes; the immunofluorescence staining results indicated the hAMSCs had high expression of the vimentin and low expression of CK-19; the hAMSCs possessed the differentiation ability into the osteoblasts, chondroblasts, and lipoblasts. The CCK-8 results displayed that cells reached the peak of growth curve at 7 days in each group, and the proliferation ability in the experimental group was significantly higher than that in the control group at 7 days (P<0.05). The immunofluorescence staining results showed that the expressions of collagen type I, collagen type III, Fibronectin, and Tenascin-C in the experimental group were significantly higher than those in the control group at 5, 10, and15 days after culture (P<0.05). The real-time fluorescence quantitative PCR results revealed that the mRNA relative expressions had an increasing tendency at varying degrees with time in the experimental group (P<0.05). The relative mRNA expressions of collagen type I, collagen type III, Fibronectin, α-SMA, and VEGF in the experimental group were significantly higher than those in the control group at the other time points (P<0.05), but no significant difference was found in the relative mRNA expressions of collagen type I, collagen type III, and VEGF between 2 groups at 5 days (P>0.05). Conclusion The hAMSCs possesses the characteristics of MSCs and good proliferation ability which could be chosen as seed cell source in tissue engineering. The expressions of ligament fibroblasts and angiogenesis related genes could be up-regulated, after inductionin vitro, and the synthesis of ligament fibroblasts related proteins could be strengthened. In addition, the application of TGF-β1 and VEGF could be used as growth factors sources in constructing tissue engineered ligament.
ObjectiveTo observe the clinical features of high myopia domed-shaped macula (DSM) complicated with choroidal neovascularization (CNV) and the efficacy of intravitreal injection of anti-vascular endothelial growth factor (VEGF). MethodsA retrospective clinical study. A total of 23 eyes of 23 patients with high myopia DSM combined with CNV diagnosed by ophthalmology examination in Department of Ophthalmology of The Second People's Hospital of Foshan from January 2019 to December 2023 were included in the study.Best corrected visual acuity (BCVA), intraocular pressure, optical coherence tomography (OCT) were performed in all eyes. BCVA tests are performed using the international standard visual acuity chart, which was statistically converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. DSM height, central macular thickness (CMT) and choroidal thickness (ChT) were measured by OCT. According to OCT image features, DSM was divided into horizontal and vertical elliptic bulges and circular bulges. According to the literature standard, CNV was divided into subfoveal CNV and parafoveal CNV. All patients were treated with 0.05 ml intravitreal injection of ranibizumab or conbercept (IVR or IVC). The treatment regimen was 1+ on-demand treatment. The first IVR and IVC treatment were performed on 17 eyes and 6 eyes, respectively, and were divided into IVR group and IVC group. Follow-up time ≥1 month after treatment. The clinical features of the patients and the changes of BCVA, intraocular pressure, CMT and ChT after treatment were observed. Independent sample t test was used for comparison between groups. ResultsThere were 23 eyes in 23 cases, 7 males had 7 eyes and 16 females had 16 eyes. There were 11 and 12 eyes in the right and left eyes respectively. Age were (49±16) years old; logMAR BCVA was 0.94±0.39. Shapes of DSM were in 13 (56.52%, 13/23), 6 (26.09%, 6/23), and 4 (17.39%, 4/23) eyes, respectively. The dome height was (97.83±46.14) μm. CMT and ChT were (276.39±98.35) and (49.48±31.66) μm, respectively. There were 17 eyes in the IVR group, including 4 males and 13 females. There were 6 cases in the IVC group, 3 cases were male and 3 cases were female. At the last follow-up, logMAR BCVA and CMT were 0.60±0.39 and (209.96±71.38) μm, respectively. BCVA was significantly increased and CMT was significantly decreased compared with before treatment, with statistical significance (t=2.98, 2.62; P=0.005, 0.010). One month after treatment and at the last follow-up, there were no significant differences in the degree of BCVA improvement (t=1.47, 1.35), intraocular pressure change (t=?0.20, ?0.56) and ChT reduction thickness (t=0.80, ?0.62) between IVR group and IVC group (P＞0.05). At 1 month after treatment and last follow-up, the CMT of patients in IVR group and IVC group was decreased by (57.94±67.61), (83.17±78.37) μm and (13.33±9.73), (18.17±17.88) μm compared with that before treatment, respectively, and the differences were statistically significant (t=2.64, 3.21; P＜0.05). ConclusionsIVR or IVC in the treatment of high myopia DSM combined with CNV can effectively improve BCVA. The reduction of CMT with ranibizumab is better than conbercept.
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.
Vascular endothelial growth factor (VEGF) is a multifunctional factor that promotes blood vessel formation and increases vascular permeability. Its abnormal elevation plays a key role in common retinal diseases such as wet age-related macular degeneration and diabetic macular edema. Anti-VEGF therapy can inhibit angiogenesis, reduce vascular leakage and edema, thereby delaying disease progression and stabilizing or improving vision. Currently, the clinical application of anti-VEGF drugs has achieved satisfactory therapeutic effects, but there are also issues such as high injection frequency, heavy economy burden, potential systemic side effects, and non-responsiveness. To address these issues, current research and development mainly aim on biosimilars, multi-target drugs, drug delivery systems, oral anti-VEGF drugs, and gene therapy. Some drugs have shown great potential and are expected to turn over a new leaf for anti-VEGF treatment in ophthalmology.
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.
Diabetic retinopathy (DR) is the leading cause of visual impairment worldwide. Severe non-proliferative diabetic retinopathy, diabetic macular edema, and proliferative DR (PDR) are defined as vision-threatening DR (VTDR). In the context of managing systemic disease, the primary treatments for VTDR include panretinal photocoagulation (PRP), intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs or dexamethasone sustained release agents, and microincision vitreous surgery. Although these therapies are already widely used in clinical practice, there is still much debate about the optimal timing and method of their application, especially in the pursuit of optimal efficacy, cost-effectiveness, patient compliance, and the reduction of frequent ongoing treatments. There is no consensus on the best treatment for PDR. Determining the specific criteria for each therapy indication is one of the key considerations. In addition, consideration should be given to the priority between PRP and intravitreal injection, as well as to compare the relative effectiveness of anti-VEGF agents with PRP. Early surgical intervention is not always a necessary option for PDR patients with vitreous hemorrhage and fibrovascular membranes. Combining different therapies to optimize treatment strategies is also an important topic. These issues address several points of contention in best practice guidelines that need to be addressed through more in-depth research to provide better guidance for clinical practice and ultimately improve patient outcomes.
ObjectiveTo analyze the status of applying programmed death-1 (PD-1) / programmed death-ligand 1 (PD-L1) inhibitors combined with vascular endothelial growth factor (VEGF) / vascular endothelial growth factor receptor (VEGFR) inhibitors in advanced refractory colorectal cancer. MethodThe relevant literature on domestic and foreign research in recent years was summarized. ResultsThe discovery of immune checkpoint PD-1/PD-L1 and the clinical application of related drugs had changed the treatment pattern of advanced solid tumors, but PD-1/PD-L1 inhibitors had a poor efficacy in the mismatch repair prodicient tumors, and most advanced colorectal cancer belonged to this type. The combination of PD-1/PD-L1 inhibitors and VEGF/VEGFR inhibitors could enhance the therapeutic effect in the advanced refractory colorectal cancer, and their interaction mechanisms and clinical efficacy were continuously being proven. ConclusionsThe combination of PD-1/PD-L1 inhibitors and VEGF/VEGFR inhibitors is a promising treatment strategy for advanced refractory colorectal cancer. More studies need to be further clarified its efficacy.
