Diabetic foot ulcer (DFU) is a leading cause of high-level amputation in DM patients, with a low wound healing rate and a high incidence of infection. Vascular endothelial growth factor (VEGF) plays an important role in diabetes mellitus (DM) related complications. This study aims to explore the VEGF expression and its predictive value for prognosis in DFU, in order to provide basis for the prevention of DFU related adverse events. We analyzed 502 patients, with 328 in healing group and 174 in non-healing/recurrent group. The general clinical data and laboratory indicators of patients were compared through Spearman correlation analysis, ROC analysis and logistic regression analysis. Finally, the independent risk factors for adverse prognosis in DFU patients were confirmed. Spearman analysis reveals a positive correlation between the DFU healing rate and ABI, VEGF in wound tissue, and positive rate of VEGF expression, and a negative correlation with DM duration, FPG, HbA1c, TC, Scr, BUN, and serum VEGF. Further logistic regression analysis finds that the DM duration, FPG, HbA1c, ABI, serum VEGF, VEGF in wound tissue, and positive rate of VEGF expression are the independent risk factors for adverse prognosis in DFU (p < 0.05). DM duration, FPG, HbA1c, ABI, serum VEGF, VEGF in wound tissue, and positive rate of VEGF expression are the independent risk factors for prognosis in DFU patients. Patients with these risk factors should be screened in time, which is of great significance to prevent DFU related adverse events and improve outcomes.

BACKGROUND: We report the case of a woman with drusenoid pigment epithelial detachment (DPED) in age-related macular degeneration who was successfully treated with two monthly intravitreal injections of brolucizumab after failing to respond to previous intravitreal injections of bevacizumab and aflibercept.
METHODS: A 56-year-old woman with mixed DPED and overlying subretinal fluid in her right eye was initially treated with three intravitreal injections of bevacizumab and three intravitreal injections of aflibercept with no visual and anatomical improvement. Switching to intravitreal injection of brolucizumab was performed. After two consecutive monthly intravitreal injections of brolucizumab, optical coherence tomography (OCT) showed first subretinal fluid resolution and then DPED collapse in the following months. After nine months, the best corrected visual acuity had improved from 20/40 to 20/20. There were no signs of retinal atrophy and exudative activity on OCT examination. No serious or minor adverse events were reported during the follow-up period.
CONCLUSIONS: Switching to intravitreal brolucizumab injection might be an effective therapeutic option for treatment of mixed DPED with subretinal fluid refractory to other anti-VEGF drugs.

BACKGROUND: Migration of keratinocyte plays an essential role in wound healing. The proprietary platelet-rich plasma from human blood, named as self-growth colony (SGC), functions in stimulating migration of wounded keratinocytes. In addition, the growth factors, including VEGF, being enriched in SGC could account for this function. Scutellarin, an active phytochemical from root of Scutellaria barbata D. Don, has been proposed to have various pharmacological functions; however, the activity in epidermal skin cells is yet to be explored. Here, the role of scutellarin in potentiating the functionality of SGC to promote the regeneration of wounded keratinocyte was probed.
METHODS: Molecular docking and ultrafiltration-based LC-MS were performed to verify the binding between scutellarin and VEGF, which potentiated the VEGF-mediated functions. Scratch assay, performed on cultured keratinocytes, was to analyze the treatments of SGC and scutellarin in the process of wound healing. Western blot analysis was to confirm the involvement of signaling cascades in observed effects.
RESULTS: We have identified the binding of scutellarin with VEGF. The binding accounted for the potentiation role of scutellarin in skin regeneration, as triggered by SGC. The co-treatment of scutellarin and SGC onto scratched keratinocyte cultures was able to enhance the process of wound healing, that is, scutellarin showed a potentiating effect to SGC. In addition, the potentiation of scutellarin was shown to be mediated by phosphorylation of VEGF receptor-2 (VEGFR2) and mitogen-activated protein kinase (MAPK) signaling.
CONCLUSIONS: These findings support the application of scutellarin as an enhancing agent in potentiating the SGC-mediated wound healing.

OBJECTIVE: We aimed to observe and investigate the clinical significance of vascular endothelium growth factor (VEGF) levels in exhaled breath condensate (EBC) from patients with acute respiratory distress syndrome (ARDS).
METHODS: An improved EcoScreen condenser was used to collect EBC from 31 ARDS patients on mechanical ventilation and from 22 healthy subjects. Serum and EBC VEGF levels were analyzed with ELISA. VEGF levels in the EBC of patients with different grades of lung injuries were analyzed. The correlation between VEGF levels and clinical indicators was analyzed.
RESULTS: Serum and EBC VEGF levels were linearly and positively correlated with a correlation coefficient of 0.694 (P< 0.01). The VEGF level in the EBC of ARDS patients was significantly lower than that in the control group (P< 0.01). The VEGF level in the EBC of the mild ARDS group was higher than that in the moderate-severe ARDS group (P< 0.01). The VEGF level in the EBC of the survival group was higher than that in the mortality group. The VEGF level in the EBC of ARDS patients was positively correlated with PaO2/FiO2 and PaO2 and was negatively correlated with lung injury score (LIS) and A-aDO2/PaO2.
CONCLUSIONS: The changes in VEGF levels in the EBC of ARDS patients can Respiratory Medicine, reflect the severity of lung injury. Therefore, VEGF level in EBC can be used as an auxiliary index for judging the severity and prognosis of ARDS patients.

UNASSIGNED: Letrozole is widely known for its use as an ovulation inductor. This study aims to investigate the effects of letrozole and clomiphene citrate in females with polycystic ovarian syndrome.
METHODS: This is a randomized non-blinded controlled trial study that included 80 infertile females with polycystic ovarian syndrome receiving a standard dose of either clomiphene citrate or letrozole on day 2 of the cycle. An ultrasound was done to examine growth of the follicle, endometrial thickness on days 12-13, and a Doppler study to measure resistance index (RI), pulsatility index and ratio of systolic/diastolic velocity.
CONCLUSIONS: The mean levels of dominant follicle and oestradiol were significantly higher in the clomiphene citrate group than in the letrozole group. The letrozole group had a significantly greater endometrial thickness than the clomiphene citrate group. The resistance index and pulsatility index were lower in the letrozole group and in pregnant women than in the clomiphene citrate group and the non-pregnant group.
CONCLUSIONS: The use of letrozole for ovulation induction in polycystic ovarian syndrome patients has a better effect on endometrial receptivity markers when compared to clomiphene citrate.

Waterpipe (Wp) use is associated with most devastating diseases and particularly popular among adolescents. Vascular endothelium growth factor (VEGF) is essential for generating new vessels. The effect of smoking tobacco on VEGF is controversial and unknown among adolescents. Therefore, the current study compared serum VEGF in adolescents smoking cigarettes (Cg) only (9.3%), Wp only (19.6%), and dual (Wp and Cg) (36.4%) versus nonsmokers (34.6%) in adolescents. A self-reported questionnaire and enzyme-linked immunosorbent assay (ELISA) were used to obtain smoking status and serum VEGF, respectively, in 475 (age: 14.6 ± 1.0 years) boys (n = 263) and girls (n = 212) from Irbid, Jordan. The analysis showed that smoking status (R² = 0.021; p = 0.001) and gender (R² = 0.035; p = 0.000) can predict VEGF. Furthermore, 2-way-ANCOVA revealed that VEGF was lower in the dual cohort versus the Cg (33.4%; p = 0.04) and nonsmoker (29.6%; p = 0.003) cohorts; VEGF in smokers, was lower (33.6%; p = 0.04) in the Wp versus nonsmokers in the boys but not the girls. These results are unique and suggest that smoking lowers VEGF, which might adversely affect vascular growth and function. This is alarming given that adolescents are still in the development stage and smoking, particularly Wp, is popular among them. Therefore, interventions targeting smoking among schoolchildren are urgently needed to avoid the negative effects of smoking, especially on vascular health.

to study serum levels of vascular endothelium growth factor family peptides (VEGF-A, VEGF-C and VEGF-D) and functional gene polymorphisms of VEGFA gene (rs699947 and rs3025039) in patients with type 2 diabetes (T2D) depending on the presence of ischemic heart disease (IHD).
The study involved 196 Caucasian patients with T2D (age 43-70 years, 76 with IHD). The concentrations of VEGF-A, VEGF-C and VEGF-D in blood serum were determined by Multiplex assay. Twenty-four persons without diabetes and IHD served as controls. The genotyping of VEGFA polymorphism -2578A/C (rs699947) and +936C/ (rs3025039) was performed by TaqMan.
Concentrations of VEGF-A and VEGF-C in patients with T2D were significantly lower than those in controls (p=0.03 and p=0.006, respectively). The level of VEGF-D showed a tendency to decrease (p=0.14). Patients with IHD, as compared to other patients, had higher levels of VEGF-A (p=0.04) and a tendency to VEGF-D increase (p=0.06). The concentration of VEGF-C was not different between groups. No relationships were found between VEGF-A, VEGF-C and VEGF-D levels, HbA1c or glucose variability parameters. C-allele and CC-genotype at +936 position of VEGFA were more frequent among patients with IHD (odds ratio 2.14 and 2.41, respectively, p=0.02). The rs699947 polymorphism was not related to IHD and VEGF-A levels.
Patients with T2D have decreased serum levels of angiogenic factors VEGF-A and VEGF-C. VEGFA rs3025039 polymorphism is associated with presence of IHD and levels of circulating VEGF-A in these patients.

BACKGROUND: Sunitinib is an orally delivered tyrosine kinase inhibitor that exhibits antiangiogenic effects. FDA has approved sunitinib for the treatment of metastatic renal cell carcinoma. However, its efficacy for the treatment of advanced breast cancer (ABC) remains controversial. Therefore, we performed this systematic review and meta-analysis to synthesize evidence from published randomized controlled trials (RCTs) about the efficacy of sunitinib alone and in combination with chemotherapy for the treatment of ABC.
METHODS: We followed PRISMA statement guidelines during the preparation of this systematic review and meta-analysis. A computer literature search of PubMed, SCOPUS, web of knowledge, and Cochrane Central Register of Controlled Trials (CENTRAL) has been conducted using relevant keywords. Studies were screened for eligibility and data were extracted to an online data extraction form. Progression free survival (PFS) and overall survival (OS) were pooled as Hazard ratio (HR) in a meta-analysis model using generic inverse variance method. Objective response rate (ORR) and complications were pooled as relative risk (RR) in a random effect model meta-analysis using Mantel-Haenzel method.
RESULTS: Six RCTs, with a total sample size of 2273 patients, met our eligibility criteria and were included in this meta-analysis. Sunitinib monotherapy was not superior to chemotherapy in terms of PFS (HR = 1.00, 95% CI [0.86 to 1.16], P = 0.99), OS (HR = 1.07; 95% CI [0.87 to 1.32], P = 0.5), or ORR (RR = 0.70, 95% CI [0.74 to 1.03], P = 0.07). Sunitinib in combination with chemotherapy did not show superiority to chemotherapy in terms of PFS (HR = 0.99, 95% CI [0.86 to 1.14], P = 0.89) and OS (HR = 1.04, 95% CI [0.85 to 1.28], P = 0.69). However, the ORR favored sunitinib in combination with chemotherapy group (RR = 1.15, 95% CI [1.01 to 1.31]) with a statistically significant P value (P = 0.03).
CONCLUSIONS: Current evidence shows that sunitinib, either alone or in combination with chemotherapy, has no clinical benefit for patients with advanced breast cancer. However, previous studies did not considered patient stratification and outcome assessment based on molecular markers. In terms of safety, toxicity was common with sunitinib treatment.

OBJECTIVE: This study was to investigate the impact of ranibizumab on the level of intercellular adhesion molecule type 1 (ICAM-1) in the vitreous of eyes with PDR.
METHODS: This is an interventional case-control study. A total of 82 eyes from 82 patients who had undergone vitreous surgery for the treatment of retinal disorders were included. Twenty-two eyes with PDR received an intravitreal ranibizumab injection (IVR) 3-7 days before vitrectomy and were grouped as \'PDR with recent IVR\' or Group 1. Sixteen eyes with PDR received IVR more than 7 days before vitrectomy and were grouped as \'PDR with remote IVR\' or Group 2. Twenty-two matched PDR eyes did not receive IVR before vitrectomy and were grouped as \'PDR without IVR\' or Group 3. Finally, 22 eyes from 22 patients with idiopathic macular pucker (IMP) served as the \'non-diabetic control\' group, or Group 4. Vitreous samples were obtained at the time of vitrectomy from all eyes, and the levels of vascular endothelium growth factor (VEGF) and ICAM-1 were analysed using ELISA.
RESULTS: PDR without IVR (Group 3) had the highest vitreous VEGF concentration; the difference was significant compared with those in the PDR with recent IVR (Group 1), PDR with remote IVR (Group 2) and the non-diabetic control group (Group 4) (p < 0.001). Group 2 had a lower vitreous VEGF level than Group 1 (p = 0.041). Group 1 had the highest vitreous ICAM-1 levels (p < 0.001 versus. Groups 2, 3 and 4); Group 2 had a lower vitreous ICAM-1 level than Group 3 (p = 0.028).
CONCLUSIONS: The vitreous fluid level of ICAM-1 was significantly increased within 1 week of IVR administration, but markedly decreased after a week of administration in eyes with PDR. This suggests that leucostasis, vascular leakage and endothelial dysfunction may be amplified in the early days after IVR, but that a therapeutic effect of IVR in these processes may appear after 1 week of ranibizumab administration in eyes with PDR.

Ascorbic acid bound to KMUP-1 and sildenafil were examined for their antioxidant effects on vascular endothelium growth factor (VEGF) and endothelium nitric oxide synthase (eNOS) in hypoxic pulmonary artery (PA). Inhaled KMUP-1 and oral sildenafil released NO from eNOS. The effect of buffered l-ascorbic acid, alone and bound to KMUP-1 or sildenafil, for treating pulmonary arterial hypertension (PAH) is unclear. In this study, the antioxidant capacity of ascorbic acid increased the beneficial effects of KMUP-1 on PAH. KMUP-1A and sildenafil-A (5 mg/kg/d) were administered to hypoxic PAH rats. Pulmonary artery blood pressure, and VEGF, Rho kinase II (ROCK II), eNOS, soluble guanylate cyclase (sGC-α), and protein kinase G expression in lung tissues were measured to link PAH and right ventricular hypertrophy. Hypoxic rats had higher pulmonary artery blood pressure, greater PA medial wall thickness and cardiac weight, and a higher right ventricle/left ventricle + septum [RV/(LV+S)] ratio than normoxic rats. Oral KMUP-1A or sildenafil-A for 21 days in hypoxia prevented the rarefaction of eNOS in immunohistochemistry (IHC), reduced the IHC of VEGF in PAs, restored eNOS/protein kinase G/phosphodiesterase 5A; unaffected sGC-α and inactivated ROCK II expression were also found in lung tissues. In normoxic PA, KMUP-1A/Y27632 (10μM) increased eNOS and reduced ROCK II. ROCK II/reactive oxidative species was increased and eNOS was reduced after long-term hypoxia for 21 days. KMUP-1A or Y27632 blunted ROCK II in short-term hypoxic PA at 24 hours. l-Ascorbic acid + l-sodium ascorbate (40, 80μM) buffer alone directly inhibited the IHC of VEGF in hypoxic PA. Finally, KMUP-1A or sildenafil-A reduced PAH and associated right ventricular hypertrophy.