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Objective:To explore the impact of pembrolizumab combined with chemotherapy on angiogenesis and circulating endothelial cells in patients with advanced non-small cell lung cancer (NSCLC) .Methods:The retrospective analysis of clinical data from 121 patients diagnosed with advanced NSCLC who were admitted to the Second Affiliated Hospital of Xingtai Medical College from August 2021 to January 2023 was conducted. These patients were divided into a control group ( n=57) and an observation group ( n=64) based on the designated treatment protocol. Specifically, individuals in the control group received standard chemotherapy (cisplatin+paclitaxel), while those in the observation group underwent penpilimab therapy in conjunction with conventional chemotherapy. The comparative assessment encompassed short-term clinical efficacy, quality of life, immune function parameters, angiogenic factors [including endostatin, insulin-like growth factor 1 (IGF-1), and vascular endothelial growth factor (VEGF) ], circulating endothelial cells, and adverse reactions within the two groups. Results:After 6 courses of treatment, the objective response rate [67.19% (43/64) vs. 49.12% (28/57) ] and disease control rate [87.50% (56/64) vs. 70.18% (40/57) ] in observation group were higher than those in control group, with statistically significant differences ( χ2=4.06, P=0.044; χ2=5.52, P=0.019). The quality of life score of observation group [ (56.77±6.81) points] was significantly higher than that of control group [ (47.73±8.23) points], with a statistically significant difference ( t=6.61, P<0.001) ; The T cell subgroup CD3 + levels [ (63.59±9.00) % vs. (53.06±8.80%), t=6.49, P<0.001], CD4 + levels [ (46.54±8.20) % vs. (30.74±7.32) %, t=11.13, P<0.001] and CD4 +/CD8 + ratio (1.90±0.36 vs. 1.21±0.28, t=11.66, P<0.001) in observation group were significantly higher than those in control group, with statistically significant differences; Endostatin in observation group [ (48.99±3.43) μmol/L] was significantly higher than that in control group [ (31.35±3.87) μmol/L], with a statistically significant difference ( t=26.58, P<0.001), IGF-1 [ (102.31±20.35) μg/L vs. (134.98±19.02) μg/L] and VEGF [ (31.70±4.32) pg/ml vs. (58.71±5.99) pg/ml] were significantly lower in observation group than those in control group, with statistically significant differences ( t=18.73, P<0.001; t=28.14, P<0.001). The number of circulating endothelial cells in observation group [ (58.77±10.03) /ml] was significantly lower than that in control group [ (87.01±8.01) /ml], with a statistically significant difference ( t=17.20, P<0.001). During treatment, there were no statistically significant differences in the incidence of gastrointestinal reaction ( χ2=0.01, P=0.908), leukopenia ( χ2=0.64, P=0.424), thrombocytopenia ( χ2=0.28, P=0.597), anemia ( χ2=1.66, P=0.197), nephrotoxicity ( χ2=0.64, P=0.424), skin rash ( χ2=1.33, P=0.249) between the two groups. Conclusion:The combination therapy of pembrolizumab and chemotherapy for the treatment of advanced NSCLC has demonstrated noteworthy effectiveness. This regimen has the potential to enhance patients' immune functionality, ameliorate their overall quality of life, suppress angiogenesis, and exhibits a commendable profile of safety and reliability.
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Objective To investigate the effect of Yiqi Huoxue Tongluo Decoction on microRNA-126a-5p(miR-126a-5p)and vascular endothelial growth factor(VEGF)signaling pathway in cervical spondylotic myelopathy model rats.Methods Thirty healthy male SD rats were divided into the sham operation group,the model group and the traditional Chinese medicine(TCM)group by random number table method.Cervical spondylotic myelopathy models were prepared in the model group and the TCM group.The TCM group was given intragastric administration of Yiqi Huoxue Tongluo Decoction,while the sham operation group and the model group were given intragastric administration of normal saline for 12 weeks.After intervention,the threshold of mechanical stimulation and retraction time of thermal stimulation in each group were measured by behavior tests.Rats were sacrificed to collect intervertebral disc tissue for hematoxylin-eosin(HE)staining and observe the number of vascular buds in intervertebral disc.Rat intervertebral disc annulus fibrosus cells were subjected to terminal dexynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining.The miR-126a-5p and VEGF mRNA of rat intervertebral disc tissue were detected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR).The expression of VEGF protein of rat intervertebral disc tissue was detected by Western blot assay.Results Compared with the sham operation group,the number of vascular buds in intervertebral disc was decreased in the model group and the TCM group.The cell destruction of intervertebral disc annulus was obvious in rats,and apoptosis was high and cell density decreased.Mechanical stimulation threshold decreased,and mechanical stimulation threshold decreased.The level of miR-126a-5p was decreased,and the expression levels of VEGF mRNA and protein were increased.Compared with the model group,the number of vascular buds in intervertebral disc was increased in the TCM group.The destruction of intervertebral disc annulus cells was alleviated in rats.The apoptosis of annulus fibrosus cells in intervertebral disc decreased and cell density increased.The threshold of mechanical stimulation increased,and the retraction time of thermal stimulation was prolonged.The level of miR-126a-5p increased,and the expression levels of VEGF mRNA and protein decreased(P＜0.05).Conclusion The mechanism of Yiqi Huoxue Tongluo Decoction in the treatment of cervical spondylotic myelopathy may be related to the up-regulation of miR-126a-5p expression and the down-regulation of VEGF expression.
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Objective To observe the value of ultrasound microvascular flow imaging(MV-Flow)combined with maternal serum vascular endothelial growth factor(VEGF)expression level for diagnosis of fetal growth restriction(FGR).Methods Totally 87 pregnant women with FGR(FGR group,including 43 cases of gestational week＜28 weeks[＜28 weeks subgroup]and 44 cases of ≥28 weeks[≥28 weeks subgroup])and 112 normal pregnant women with normal fetuses(normal control group,55 with gestational week＜28 weeks[NC 1 subgroup]and 57 with ≥28 weeks[NC 2 subgroup])were prospectively enrolled.MV-Flow technology was used to measure placental microvascular index(MVI),and the placental microvascular circulation was evaluated.The expression level of maternal serum VEGF was detected simultaneously,also of placental maternal surface immediately after delivery.The receiver operating characteristic curves were drawn to explore the value of placental MVI,maternal serum VEGF and the combination of placental MVI,maternal serum VEGF for diagnosing FGR.Results The levels of placental MVI and maternal serum VEGF in 2 subgroups of FGR group were both lower than those in control group(all P＜0.01).Placental VEGF expression level in FGR group was significantly lower than that in control group(P＜0.01).The area under the curve(AUC)of placental MVI,maternal serum VEGF and their combination for diagnosing FGR＜28 weeks was 0.981,0.870 and 0.997,respectively,while for diagnosing FGR≥28 weeks was 0.991,0.867 and 0.993,respectively.AUC of maternal serum VEGF alone for diagnosing in 2 subgroups of FGR were both lower than that of placental MVI and combination of placental MVI and maternal serum VEGF(all P＜0.05),while no significant difference of AUC was found between placental MVI and combination of maternal serum VEGF and placental MVI(both P＞0.05).Conclusion Both placental MVI and maternal serum VEGF level could be used to screen FGR,and the former was more valuable.
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Objective:To observe any effect of exercise preconditioning on the levels of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in the brain tissue of rats after induced cerebral ischemia and reperfusion, and how it might promote angiogenesis.Methods:Thirty-six male Sprague-Dawley rats were randomly divided into a sham-operation group, a model group and an exercise preconditioning group, each of 12. After adaptive running training for 3 days, the exercise preconditioning group ran daily for 30 minutes at 15m/min for 14 days, while the other two groups did not exercise. Middle cerebral artery occlusion and reperfusion were then induced in the model and exercise preconditioning groups using the modified Zea-Longa suture method. Rats in the sham-operation group were only cut open to expose the right carotid artery. Right after the modeling, and again 24 hours later neurological deficit was evaluated using the Zea-Longa score and modified neurological severity scoring (mNSS). Infarct sizes were measured using 2, 3, 5-triphenyl tetrazolium chloride staining. Any morphological changes were noted using hematoxylin and eosin (HE) staining, and the expression of CD31 protein, hypoxia-inducible factor-1α and vascular endothelial growth factor in the ischemic cerebral cortex were quantified immunohistochemically.Results:Right after the modelling, compared with the sham-operation group, the average Zea-Longa scores of the model and exercise groups had increased significantly, but were not significantly different from each other. Twenty-four hours later the average Zea-Longa score, mNSS score and relative cerebral infarction area of the model group had increased significantly compared with the sham-operation group, while the exercise preconditioning group′s averages had decreased significantly. The HE staining showed that compared with the sham-operation group, pathological changes such as loose tissue, reduced number of nerve cells, nucleolysis, and vacuolization of the cerebral cortex on the ischemic side were found in the model group. Compared with the model group, the pathological changes in the exercise preconditioning group were less serious. The levels of CD31 protein, HIF-1α and VEGF in the ischemic cerebral cortexes of the model group had by then increased significantly. But compared with the model group, those levels had increased more in the exercise preconditioning group.Conclusion:Exercise preconditioning can effectively promote angiogenesis after cerebral ischemia and reduce chronic injury. That may be related to the activation of the HIF-1α and/or VEGF signaling pathways.
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Objective:To investigate the efficacy of pulp revascularization in the treatment of pulp necrosis with periapical periodontitis in young permanent teeth and its effect on the levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in gingival crevicular fluid.Methods:From January 2021 to August 2021, 72 young patients with permanent teeth exhibiting pulp necrosis and apical periodontitis who were treated at Haiyang People's Hospital were included in this study. These patients were subsequently divided into a study group ( n = 35) and a control group ( n = 37), depending on their respective treatment methods. The control group underwent conventional apical angioplasty, whereas the study group underwent pulp revascularization. A comparative analysis was conducted to assess the clinical efficacy of both treatments. Additionally, levels of VEGF and bFGF in gingival crevicular fluid were measured before and after surgery, and these values were compared between the two groups. Relevant clinical indicators and the incidence of adverse reactions were also compared between the study and control groups. Results:The overall response rate in the study group was 94.3% (33/35), which was significantly higher than 70.3% (26/37) in the control group ( χ2 = 7.01, P < 0.05). Prior to surgery, there were no notable differences in VEGF level, bFGF level, root length, or root canal thickness between the two groups (all P > 0.05). However, after surgery, VEGF level, bFGF level, root length, and root canal thickness in the study group were (43.25 ± 4.87) ng/L, (40.72 ± 4.83) ng/L, (8.95 ± 0.27) mm, and (3.08 ± 0.24) mm, respectively. These values were (39.90 ± 4.80) ng/L, (36.05 ± 4.66) ng/L, (8.55 ± 0.18) mm, and (2.90 ± 0.20) mm, respectively, in the control group. There were significant differences in VEGF level, bFGF level, root length, and root canal thickness between the two groups ( t = 2.96, 4.18, 5.67, 2.88, all P < 0.05). After surgery, the scores for apical inflammation, root development, and Visual Analogue Scale (VAS) in the study group were significantly higher than those in the control group ( t = 7.61, 4.83, 9.47, all P < 0.001). The incidence of adverse reactions in the study group was 2.9% (1/35), which was significantly lower than 21.6% (8/37) in the control group ( χ2 = 5.79, P < 0.05). Conclusion:Pulp revascularization exhibits superior curative effects compared with conventional apical angioplasty for the treatment of pulp necrosis and apical periodontitis in young permanent teeth. This treatment effectively alleviates pain, markedly improves tooth function, and has a low incidence of adverse reactions, highlighting its clinical value as a therapeutic option.
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Dental pulp stem cells (DPSC) are pluripotent stem cells with high differentiation potential isolated from dental pulp. Using DPSC for vascular regeneration may be a good option. Hypoxia inducible factor-1α (HIF-1α) is an upstream gene of vascular endothelial growth factor (VEGF), and the small ubiquitin like protease 1 (SENP1) can reverse the small ubiquitin like (SUMO) modification of HIF-1α. Through the regulation of SENP1/HIF-1α, good vascular regeneration characteristics have been demonstrated in many in vitro and in vivo experiments. The SENP1/HIF-1α signaling axis has varying degrees of promoting and inhibiting effects on many solid tumors. Although there is relatively little literature on the role of the SENP1/HIF-1α signaling axis in dental pulp stem cells, it can be determined that SENP1/HIF-1α plays an important role in the angiogenesis of dental pulp stem cells. This article will elucidate the SENP1/HIF-1α signaling pathway and its mechanism of promoting vascular differentiation of DPSC.
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Abstract Background Bullous pilomatricoma is a rare variant of pilomatricoma. As it has been published in sporadic case reports, a limited understanding of its clinicopathological characteristics restricts its effective diagnosis and treatment. Objectives This study aimed to analyze the clinicopathological and immunohistochemical characteristics of bullous pilomatricoma to better understand the bullous transformation of pilomatricoma. Methods The authors conducted a retrospective study of 12 patients with bullous pilomatricoma and compared their clinical, histopathological, and immunohistochemical data with those of patients with ordinary pilomatricoma. Results Bullous pilomatricoma showed no sex preference, with a mean onset age of 31.2 years. The common sites were the upper extremities and trunk. Bullous pilomatricoma had a shorter disease duration, a larger diameter, and a greater tendency to increase in size than those of ordinary pilomatricoma. Histopathologically, bullous pilomatricoma had a shorter duration, lesser calcification, more mitotic figures, and distinct dermal features from those of ordinary pilomatricoma. Immunohistochemically, the expression of Matrix Metalloprotease (MMP)-2, MMP-9, vascular endothelial growth factor receptor-3 (VEGFR-3), and VEGF-C was elevated. Study limitations The study was retrospective, and the sample size was small. Conclusion The distinctive features of bullous pilomatricoma potentially result from dermal changes associated with the release of angiogenic factors and proteolytic enzymes. This comprehensive analysis provides novel insights into the clinical features and pathogenesis of bullous pilomatricoma.
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ABSTRACT Objective: This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. Methods: Forty patients, comprising 16 with and 24 without peri-implantitis were selected. Results: Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. Conclusion: This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis.
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Objective:To evaluate the efficacy and safety of intravitreal ranibizumab combined with laser (IVR+ Laser) and the intravitreal ranibizumab (IVR) monotherapy for the treatment of diabetic macular edema (DME).Methods:A meta-analysis was conducted on randomized controlled trial (RCT) literature related to IVR+ Laser therapy and IVR alone for DME.Databases including Cochrane Library, PubMed, EMbase, Web of Science, SinoMed, CNKI, VIP and WanFang Data were searched from their inception to April 2022.Literature screening, data extraction, quality evaluation and cross-checking were conducted independently by two researchers according to inclusion and exclusion criteria.Then a meta-analysis was conducted using RevMan 5.4.1 software.The two therapies were compared in terms of best corrected visual acuity (BCVA), central macular thickness (CMT), mean number of injections and adverse events.Results:Twelve RCTs involving 1 695 eyes were included in the study.Meta-analysis showed that at the end of follow-up, IVR+ Laser demonstrated better improvement in BCVA and CMT than IVR alone, and there were significant differences in the changes in BCVA and CMT between the two groups (weighted mean difference[WMD]=-0.66, 95% confidence interval[ CI]: -1.11--0.21, P<0.01; WMD=-5.05, 95% CI: -9.21--0.89, P=0.02).IVR+ Laser required significantly fewer injections than IVR alone (WMD=-1.16, 95% CI: -2.07--0.25, P=0.01).There were no significant differences in the adverse events incidence between the two therapies (all at P>0.05). Conclusions:The safety of IVR+ Laser is comparable to IVR alone, and it requires fewer injections for the treatment of DME.
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Objective:To investigate the expressions of vascular endothelial growth factor (VEGF), serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) in patients with colorectal cancer liver metastases (CRLM), and diagnostic values of VEGF and IGF-1-to-IGFBP-3 ratio (IGF-1/IGFBP-3).Methods:The clinical data of 41 patients with CRLM (CRLM group), 70 patients with colorectal cancer (CRC group) and 85 patients with colorectal polyp (colorectal polyp group) who were newly diagnosed in Baoji Central Hospital from January 2020 to January 2023 were retrospectively analyzed, while 40 healthy volunteers who had medical checkup in the same period were selected as healthy control group. The level of VEGF was detected by enzyme-linked immunosorbent assay, the levels of serum IGF-1 and IGFBP-3 were detected by chemiluminescence immunoassay, and the results were compared. The efficacy of the above indexes alone and in combination for diagnosing CRLM was assessed using the receiver operating characteristic curve, with pathologic diagnostic results as the gold standard.Results:The levels of VEGF, IGF-1, IGFBP-3 and IGF-1/IGFBP-3 in CRLM group, CRC group, colorectal polyp group and healthy control group decreased in steps, and the differences among different tissues were statistically significant (all P < 0.05). Furthermore, the levels of VEGF, IGF-1, IGFBP-3, IGF-1/IGFBP-3 in CRLM group were higher than those in CRC group, colorectal polyp group and healthy control group, and the differences were statistically significant (all P < 0.05). The levels of VEGF, IGF-1, IGFBP-3 and IGF-1/IGFBP-3 in CRC group were higher than those in colorectal polyp group and healthy control group, and the differences were statistically significant (all P < 0.05). The levels of VEGF, IGF-1, IGFBP-3 and IGF-1/IGFBP-3 in colorectal polyp group were higher than those in healthy control group, and the differences were statistically significant (all P < 0.05). The efficiency analysis of single and combined detection of the serum VEGF, IGF-1/IGFBP-3 for diagnosing CRLM showed that the sensitivity, specificity and accuracy of VEGF, IGF-1/IGFBP-3 and combination of the two were statistically significant ( χ2 values were 6.523, 11.499 and 11.194, all P < 0.05). The optimal cut-off value of VEGF alone for diagnosing CRLM was 326.83 pg/ml, and the optimal cut-off value of IGF-1/IGFBP-3 for diagnosing CRLM was 71.44. The diagnostic sensitivity and area under the curve (AUC) of VEGF alone were lower than those of IGF-1/IGFBP-3 alone, the difference was statistically significant ( P < 0.05), but the specificity and accuracy were higher than those of IGF-1/IGFBP-3, and the difference was statistically significant ( P < 0.05). The sensitivity, specificity, accuracy and AUC of combination of VEGF and IGF-1 and IGF-1/IGFBP-3 for diagnosing CRLM were higher than the single detection of the two, and the differences were statistically significant (all P < 0.05). Conclusions:The serum VEGF, IGF-1 levels and IGF-1/IGFBP-3 are high in CRLM patients, IGFBP-3 level is low in CRLM patients. The detections of these indexes have featured with rapid, accuracy and high sensitivity. Single detection has its own advantages and disadvantages, and the combined detection can complement each other and improve the diagnostic efficiency, which is of high clinical application value for the diagnosis of CRLM.
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Objective:To investigate the expression levels of serum miR-126 and miR-9 in patients with wet age-related macular degeneration (wAMD) and their relationship with vascular endothelial growth factor (VEGF) and central macular thickness (CMT).Methods:A total of 73 wAMD patients(observation group) admitted to the ophthalmology department of Taizhou Municipal Hospital from May 2020 to May 2021 and 60 healthy subjects (control group) who underwent physical examination during the same period were selected. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-126 and miR-9 in serum of the two groups. Serum angiogenesis regulatory factors [VEGF, tissue inhibitor of melalloproteinuses-1 (TIMP-1), endostatin (ES), platelet-derived growth factor (PDGF)] were detected by enzyme-linked immunosorbent assay (ELISA), and CMT and intraocular pressure (IOP) were measured. Pearson correlation analysis was performed to determine the correlation between miR-126 and miR-9 and serum angiogenesis regulatory factor levels, CMT and IOP. The diagnostic value of miR-126 and miR-9 in wAMD was analyzed by receiver operating characteristic (ROC) curve.Results:The relative expression level of serum miR-126 in observation group was significantly lower than that in control group ( P<0.05) , while the relative expression level of serum miR-9 was significantly higher than that in control group ( P<0.05). The levels of serum VEGF and PDGF in observation group were significantly higher than those in control group (all P<0.05), while the levels of serum TIMP-1 and ES were significantly lower than those in control group (all P<0.05). CMT and IOP in observation group were significantly higher than those in control group (all P<0.05). The expression level of serum miR-126 in observation group was negatively correlated with serum VEGF, PDGF, CMT and IOP ( r=-0.275, -0.523, -0.302, -0.542, all P<0.05), and was positively correlated with TIMP-1 and ES ( r=0.460, 0.263, all P<0.05). Serum miR-9 expression level was positively correlated with serum VEGF, PDGF, CMT and IOP ( r=0.434, 0.438, 0.396, 0.307, all P<0.05), and was negatively correlated with TIMP-1 and ES ( r=-0.256, -0.310, all P<0.05). The area under curve (AUC) values of serum miR-126 and miR-9 in diagnosing wAMD were 0.713 and 0.847 respectively. Conclusions:The expression level of serum miR-126 is significantly decreased while the expression level of miR-9 is significantly increased in patients with wAMD. miR-126 is negatively correlated with VEGF and CMT, and miR-9 is positively correlated with VEGF and CMT, which may aggravate the disease by promoting the inflammatory response. The detection of expression levels of serum miR-126 and miR-9 is helpful to provide the reference basis for early diagnosis of wAMD and early prevention and treatment.
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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.
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Objective:To investigate the predictive value of vascular endothelial growth factor (VEGF) expression and microvascular density (MVD) for the depth of infiltration in early gastric cancer.Methods:The pathological tissues of 24 patients with early gastric cancer (early gastric cancer group), 23 patients with advanced gastric cancer (advanced gastric cancer group) and 10 patients with gastritis (gastritis group) who admitted to Fenyang Hospital Affiliated of Shanxi Medical University from January 2020 to January 2022 were retrospectively collected. Immunohistochemistry was used to detect VEGF expression and MVD in the lesion tissues of each group, and the correlation of VEGF expression and MVD in gastric cancer tissues with the clinicopathological characteristics of patients was analyzed. Postoperative pathological diagnosis was treated as the gold standard. The efficacy of VEGF and MVD in predicting the depth of infiltration in gastric cancer and early gastric cancer was assessed by using the receiver operating characteristic (ROC) curve.Results:The VEGF positive expression rate was 10.00% (1/10), 29.17% (7/24) and 78.26% (18/23) in gastritis group, early gastric cancer group and advanced gastric cancer group, respectively, and the MVD was (21±5) strips/field, (23±9) strips/field and (43±15) strips/field, respectively. The positive expression rate of VEGF and MVD were related with the tumor diameter [>2 cm vs. ≤2 cm:69.70% (23/33) vs. 14.29% (2/14), (39±15) strips/field vs. (20±8) strips/field] and infiltration depth of gastric cancer [intramucosal carcinoma vs. submucosal carcinoma vs. advanced gastric cancer: 26.31% (5/19) vs. 40.00% (2/5) vs. 78.26% (18/23), (20±7) strips/field vs. (36±3) strips/field vs. (43±15) strips/field] (all P > 0.01), while not related with gender, age, tumor location, differentiation degree (all P > 0.05). The ROC curve analysis showed that the area under the curve (AUC) of VEGF and MVD in predicting the depth of infiltration in gastric cancer was 0.716 (95% CI 0.581-0.828) and 0.711 (95% CI 0.573-0.823), respectively; the optimal cut-off value of VEGF and MVD was positive and 24.8 strips/field, with the sensitivity of 53.19%, 61.70%, and the specificity of 90.00% both. The AUC of VEGF and MVD in predicting the depth of infiltration in early gastric cancer was 0.596 (95% CI 0.414-0.760) and 0.506 (95% CI 0.330-0.681) , respectively; the optimal cut-off value of VEGF and MVD was positive and 32.5 strips/field, with the sensitivity of 29.17% , 70.83%, and the specificity of 90.00%, 0, respectively. Conclusions:VEGF expression and MVD are elevated with the increase of depth of gastric cancer infiltration, while the value of the combination of both in predicting the depth of infiltration in early gastric cancer is not high.
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Objective:To investigate the effects of alum ice nanoemulsion on VEGF and TGF-β1 in hypertrophic scar based on Notch signaling pathway.Methods:Totally 144 SD rats were divided into blank control group, model group, triamcinolone acetonide group and alum ice nanoemulsion low-, medium- and high-dose groups according to random number table method, with 24 rats in each group. Except for the blank control group, the rats in other groups were prepared with deep Ⅱ ° burn models. 24 hours after the successful modeling, the model group was given the same amount of normal saline, the rats in alum ice nanoemulsion low-, medium- and high-dose groups were given 8.15, 6.30 and 32.60 mg/ml alum ice nanoemulsion respectively, and the triamcinolone acetonide group was given triamcinolone acetonide twice a day, 0.2 ml each time, for 35 consecutive days. At 14, 21, 28 and 35 d, the collagen fiber surface density was calculated by VG staining. The protein expressions of vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), Notch1 and Jagged1 were detected by Western Blot. The expressions of Notch1 mRNA and Jagged1 mRNA were detected by RT-PCR.Results:Compared with model group, triamcinolone acetonide and different doses of alum ice nanoemulsion groups could decrease collagen fiber surface density, protein expressions of VEGF, TGF-β1, Notch1, Jagged1 and mRNA expressions of Notch1, Jagged1 in different degrees ( P<0.05). Compared with the triamcinolone acetonide group, the collagen fiber surface density, protein expressions of VEGF, TGF-β1, Notch1 and Jagged1 and mRNA expressions of Notch1, Jagged1 in the alum ice nanoemulsion medium-dosage group decreased ( P<0.05). Conclusion:Alum ice nanoemulsion can inhibit hypertrophic scar formation, and its mechanism is related to down-regulating Notch signal pathway related molecules Notch1, Jagged1 protein and mRNA levels, and then down-regulating VEGF and TGF-β1 protein expressions.
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Objective:To analyze the occurrence of early hypotony after the intravitreal injection of anti-vascular endothelial growth factor (VEGF) and its risk factors.Methods:A case-control study was performed.One hundred and twenty-seven eyes of 127 patients with fundus vascular disease who received intravitreal injections of anti-VEGF drugs were enrolled in Henan Provincial People's Hospital from January 2020 to January 2022.Of the 127 patients, there were 71 males and 56 females, with an average age of (61.85±11.53) years and a mean intraocular pressure of (15.28±3.71)mmHg (1 mmHg=0.133 kPa). All subjects were intravitreally injected with 0.05 ml of anti-VEGF drugs, including 56 cases receiving ranibizumab, 38 cases receiving conbercept and 33 cases receiving aflibercept.The intraocular pressure was measured with a non-contact tonometer at 30 minutes, 1 hour and 2 hours after the injection.The cases were grouped as hypotony group or non-hypotony group according to the intraocular pressure of subjects was less than 10 mmHg or not.The differences in sex, age, distribution of left eye and right eye, disease type, intraocular pressure before injection, injection frequency, lens status, drug type, injection timing, injection site, with or without high myopia, with or without a history of glaucoma or ocular hypertension, and with or without a history of vitreoretinal surgery were analyzed to investigate the factors with a P-value <0.05, which were used as the independent variable and the occurrence of hypotony as the dependent variable in logistic regression analysis to explore the risk factors for hypotony.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEEC-2022-42). Results:Hopotony occurred in 8 eyes within 2 hours after the injection.There were significant differences in intraocular pressure at different time points before and after injection between the hypotony and non-hypotony groups ( Fgroup=62.177, P<0.001; Ftime=25.128, P<0.001). The intraocular pressure of the hypotony group at 30 minutes, 1 hour and 2 hours after injection were lower than before injection, and the intraocular pressure of the non-hypotony group was higher at 30 minutes after injection than before injection (all at P<0.05). The average reduction of intraocular pressure of the hypotony group was 7.88, 7.63 and 7.23 mmHg at 30 minutes, 1 hour and 2 hours after the injection, and the intraocular pressure returned to baseline level at 1 day after injection.There was no significant difference in sex, distribution of left and right eyes, disease type, pre-injection intraocular pressure, injection frequency, lens status, drug type, injection timing, injection site, with or without a history of high myopia and with or without a history of glaucoma or ocular hypertension between the two groups.There were significant differences in age and with or without a history of vitreoretinal surgery between the two groups ( t=8.265, P<0.001; χ2=6.907, P=0.035). Multivariate logistic regression analysis showed younger patients and having a history of vitreoretinal surgery were the risk factors for early hypotony after anti-VEGF intravitreal injection (odds ratio=88.563, P<0.001; odds ratio=20.991, P=0.009). Conclusions:Patients with younger age and having a history of vitreoretinal surgery are susceptible to early hypotony after anti-VEGF intravitreal injection.
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Despite the continuous improvement and development of modern cataract surgery technology, posterior capsule opacification (PCO) is still the common long-term complication causing secondary visual acuity decline after cataract surgery.Previous studies have shown that the occurrence of PCO is closely related to the proliferation, migration, epithelial-mesenchymal transition (EMT) and myofibroblast fibrosis of lens epithelial cells in the anterior capsule and lens equator.In terms of pathogenesis, recent research focuses on the role of cytokines, especially various growth factors.Vascular endothelial growth factor (VEGF) is a kind of growth factor that can promote vascular endothelial cell proliferation and migration, extracellular matrix degeneration and angiogenesis.In addition, there is increasing evidence showing that VEGF plays an important role in fibrosis, inflammation, neuroprotection and other aspects.In recent years, VEGF has been found to promote PCO formation directly or cooperatively with transforming growth factor-β2.Based on the function of VEGF and the relationship between VEGF and EMT, this paper mainly reviewed the advances in the role of VEGF in the eye and the pathogenesis of posterior capsule opacification.
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Neovascularization is the hallmark of many fundus diseases, including diabetic retinopathy, retinal vein occlusion and neovascular age-related macular degeneration.More and more evidence suggests that vascular endothelial growth factor (VEGF) plays a critical role in neovascularization.Anti-VEGF drugs are the first-line treatment for neovascular fundus diseases and have achieved significant results.However, there are drawbacks such as short drug half-lives and the need for long-term administration to maintain effective concentrations, which increases the economic burden and medical risk for patients and reduces compliance.Therefore, finding a new method for intraocular drug delivery is of great clinical importance.Based on the principle that diabetes patients use insulin pumps to gradually release drugs, the ocular anti-VEGF drug delivery system can continuously release anti-VEGF drugs over a period of time, significantly reducing the injection frequency and improving patient compliance.At present, the research on ocular anti-VEGF drug delivery systems is still immature, and various systems are in different stages of clinical trials.According to different design principles, they can be divided into three categories with their characteristics, micropump (extraocular storage delivery systems), biodegradable implants, and non-biodegradable implants.This article summarized and analyzed the controlled ocular anti-VEGF drug release delivery systems currently in clinical trials.
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Polypoidal choroidal vasculopathy (PCV) occurs in the middle-aged and elderly population and is characterized by abnormal intrachoroidal vascular patterns such as branching choroidal vascular networks and polypoidal dilatation of vessel terminals, subretinal orange nodular lesions and hemorrhagic or plasma retinal pigment epithelial detachment (PED), which can cause retinal hemorrhage or vitreous hematopoiesis and is one of the major blinding fundus lesions.Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is currently the main method of PCV treatment, and has certain advantages in eliminating abnormal vascular networks and removing polypoidal lesions, reducing vascular exudation and promoting exudate absorption, and improving visual prognosis.However, frequent intravitreal drug injections increase the risk of infection and the treatment burden for patients.In addition, the high recurrence rate after treatment poses a significant challenge to clinical practice, so the search for new therapeutic agents that are durable and less costly is a focus of clinical research in PCV.The literature from abroad suggests that brolucizumab is a novel small-molecule anti-VEGF humanized monoclonal antibody with the advantages of high tissue penetration, high local drug concentration and bioavailability, small injectable dose, long-lasting efficacy and long injection interval, which brings new hope for the clinical treatment of PCV and improving the prognosis of affected eyes.Although the efficacy and safety of brolucizumab in the treatment of PCV have been well documented, the literature is mainly from Japan, India and Korea, and clinical practice data from China are still lacking.With the approval of the drug in several countries, it is believed that more PCV patients could benefit from this treatment in the near future.Ophthalmologists and researchers in China should closely follow the progress of brolucizumab in the treatment of PCV.
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SUMMARY OBJECTIVE: Coronavirus disease 2019 emerges as a disease caused by severe acute respiratory syndrome coronavirus 2. It is a systemic disease associated with vascular inflammation and endothelial damage. In this study, we aimed to investigate whether vascular endothelial growth factor gene insertion/deletion polymorphism is associated with coronavirus disease 2019 in the Turkish population. METHODS: The study included 179 participants (79 patients with coronavirus disease 2019 and 100 controls). DNA isolation was made from peripheral blood, and then the polymerase chain reaction analysis was performed. RESULTS: When we analyze vascular endothelial growth factor gene insertion/deletion polymorphism in the study group, we found that the DD genotype and D allele were found to be statistically significantly different when compared to coronavirus disease 2019 patients with high vitamin D value (p=0.005 for DD genotype and p=0.006 for D allele) in the control group. In this high-level control group, when we analyze II+ID genotype versus DD, a statistically significant difference was also detected (p=0.007). CONCLUSION: As a result of the study, we found that DD genotype and D allele were associated with vitamin D level in Turkish patients with coronavirus disease 2019.
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SUMMARY OBJECTIVE: In this study, we aimed to determine the impact of the antiangiogenic medications, namely, aflibercept and cabergoline in the prevention and treatment of ovarian hyperstimulation syndrome in a rat model. METHODS: A total of 36 female Wistar rats were randomly allocated to one of the five groups, including disease-free and ovarian hyperstimulation syndrome controls: Group no OHSS (control, n=6) received saline only intraperitoneally (i.p.); group just OHSS (ovarian hyperstimulation syndrome only, n=6) received 10 IU pregnant mare serum gonadotropin and 30 IU human chorionic gonadotropin subcutaneously to produce ovarian hyperstimulation syndrome; group cabergoline+OHSS (cabergoline+ovarian hyperstimulation syndrome, n=8) received 100 μg/kg oral cabergoline; group aflibercept (12.5 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 12.5 mg/kg i.p. aflibercept; and group aflibercept (25 mg/kg)+OHSS (aflibercept+ovarian hyperstimulation syndrome, n=8) received 25 mg/kg i.p. aflibercept. The groups were compared for ovarian weight, immunohistochemical vascular endothelial growth factor expression, spectrophotometric vascular permeability evaluated with methylene blue solution in peritoneal lavage, and body weight growth. RESULTS: Vascular endothelial growth factor immunoexpression was substantially greater in the just OHSS group (22.00±10.20%) than in the aflibercept (12.5 mg/kg)+OHSS (7.87±6.13%) and aflibercept (25 mg/kg)+OHSS (5.63±4.53%) groups (p=0.008 and p=0.005, respectively). Post-hoc tests indicated that cabergoline, 12.5 mg/kg aflibercept, and 25 mg/kg aflibercept decreased vascular permeability compared to the untreated ovarian hyperstimulation syndrome group (p=0.003, p=0.003, and p=0.001, respectively). JOH group had the heaviest ovaries, whereas aflibercept (25 mg/kg)+OHSS group had the lightest. In terms of body weight gain, cabergoline+OHSS group was substantially greater than the aflibercept (12.5 mg/kg)+OHSS and aflibercept (25 mg/kg)+OHSS groups (p=0.006 and p=0.007, respectively). CONCLUSION: Aflibercept, an antiangiogenic medication, decreased ovarian hyperstimulation syndrome by lowering the vascular permeability and vascular endothelial growth factor expression.