【Abstract】Objective To investigate the protective effect of improving the pancreatic ischemia and calcium channel blockers on preventing the progression of acute pancreatitis. Methods Twenty-four patients with mild acute pancreatitis were randomly divided into two groups： control group and treated group. Within the first 72 hours from the onset of AP, routine conservative managements were performed in control group, improving the pancreatic ischemia and preventing Ca2+ overload were performed in treated group for two weeks. The hemorrheological parameters were measured at 1,4,7,14 days after adimission, simultanously, serum TNFα, IL-1β, C-reactive protein and plasma TXB2, 6-keto-PGF1α levels were determined with ELISA methods. Results The hemorrheological changes were improved in treated group, serum TNFα, IL-1β, C-reactive protein and plasma TXB2, 6-keto-PGF1α levels were significantly decreased each time point in treated group as compared with control group. Conclusion Improving the pancreatic ischemia and calcium channel blockers have protective effect through reducing the generation of cytokines and inflammatory mediators on preventing the progression of acute pancreatitis.
Objective To investigate the effects of recombinant adeno-associated virus type-2 (rAAV2) mediated delivery of pigment epitheliumderived factor (PEDF) on oxygen-induced retinal neovascularization (OIRNV) in mice. Methods A total of 22 C57/BL6 mice at the age of 3 days received intravitreal injections of 1 mu;l rAAV2-PEDF and rAAV2EGFP into the left eyes (experimental group) and the right eyes (control group). All mice were put into the oxygen box right after the injection to induce the OIRNV model.4 mice were sacrificed and PEDF protein in retina was measured by western blot at postnatal days 13 (P13). Twelve mice underwent retinal angiography with high molecular weight fluoresceindextran, and another 6 mice were sacrificed for retinal lectin immunohistochemistry staining at P17. Absolute and relative nonperfusion areas of retinal neovascularization were analyzed by Image-Pro Plus 5.1 software. Results The expression level of PEDF protein was higher in the experimental group than that in the control group.The absolute nonperfusion area was (0.96plusmn;0.22) mm2 in the experimental group and (1.96plusmn;0.34) mm2 in the control group; the difference between the two groups was significant（t=-8.554, P＜0.01）. The relative nonperfusion area was (8.64plusmn;1.52)% in the experimental group and (17.27plusmn;2.98)% in the control group with a significant difference between the two groups (t=-8.97, P＜0.01).The absolute area of retinal neovascularization was (0.37plusmn;0.11) mm2 in the experimental group which was obviously higher than (1.26plusmn;0.38) mm2 in the control group (t=-7.8, P＜0.01); the relative areas in experimental and control groups was (3.96plusmn;0.66)% and (11.45plusmn;2.06)%, respectively, whose difference is apparently(t=-8.51, P＜0.01).The areas of retina neovascularization were (0.11plusmn;0.003) mm2 and (0.41plusmn;0.02) mm2 in the experimental and control groups, respectively, and the difference between the two groups was significant（t=-5.14, P＜0.01）.Conclusions PEDF protein can stably express in the mice retina after rAAV2-PEDF transfetion. rAAV2-PEDF can decrease the retinal non-perfusion areas and inhibit the retinal neovascularization in OIRNV mice.
There are many types of fundus diseases and their causes are complex. They can be caused by metabolic factors or inflammatory factors. Fundus examination and imaging examination tools are the main methods for diagnosing fundus diseases. However, in terms of determining the cause and early diagnosis, if the intraocular fluid detection technology can be reasonably combined, the advantages will be greater. Intraocular fluid is the general term for fluid in the eyeball, including aqueous humor, vitreous humor, etc. The molecular components that can be tested include DNA, RNA, antigens, antibodies, and cytokines. With the advancement of molecular testing technology and equipment, intraocular fluid testing as an evidence-based method has gradually been incorporated into the consensus and guidelines of more fundus disease experts, and is mainly used for infectious fundus diseases and camouflage syndromes. Reasonable use of intraocular fluid testing can help improve the personalized diagnosis and treatment of fundus diseases and reduce unnecessary drug overuse. However, it is worth noting that intraocular fluid detection is only one of many tools and cannot replace other examinations and clinical experience. Excessive intraocular fluid testing not only increases the risk of clinical infections because of invasiveness, but also increases the burden on patients.
Objective To investigate the expression levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B l igand (RANKL) mRNAs in BMSCs in patients suffering glucocorticoid-induced necrosis of the femoral head (GNFH), and to discuss the relationshi p between OPG/RANKL system and GNFH. Methods The bone tissue and BMSCs of femoral head were collected from 35 patients suffering GNFH (experimental group) and from 21 patients suffering fracture of femoral neck (control group). The ratio of men to women was 4 ∶ 3 in two groups, aged 41 to 70 years (mean 55.34years in the experimental group and mean 55.33 years in the control group). The patients of experimental group received over 3 weeks’ glucocorticoid treatment or more than 1 week’s high-dose glucocorticoid therapy in recent 2 years, but patients of the control group did not receive more than 1 week’s hormone therapy. In 2 groups, the microstructure of bone tissue of femoral head was detected by HE staining. The BMSCs were isolated and cultured by adherent-wall method; the expression levels of OPG and RANKL mRNAs were examined by real-time quantitative polymerase chain reaction and the ratio of OPG mRNA to RANKL mRNA was caculated. Results Bone trabeculae and bone units were replaced by interrupted bone fragments, which were surrounded by inflammation and granulation tissue and few osteocytes were seen in bone lacunae in the experimental group. In control group, bone trabeculae and bone units were made by complete lamellar bone which surrounded blood vessels and osteocytes were seen in lacunae. The expression levels of OPG mRNA in the experimental group (0.37 ± 0.12) was significantly lower than that in the control group (0.47 ± 0.13), and the levels of RANKL mRNA in the experimental group (1.12 ± 0.39) was significantly higher than that in the control group (0.84 ± 0.24), showing statistically significant difference (P lt; 0.05). The ratio of OPG mRNA to RANKL mRNA in the experimental group (0.37 ± 0.17) was significantly lower than that in the control group (0.61 ± 0.26, P lt; 0.05). Conclusion The GNFH may be related to the expression levels of OPG mRNA and RANKL mRNA in BMSCs.
ObjectiveTo study the changes the changes of cytokine expression the aqueous humor of patients with macular edema secondary to branch retinal vein occlusion (BRVO-ME) before and after intravitreal ranibizumab (IVR). MethodsA prospective clinical study. From June 2018 to June 2021, 31 eyes of 31 patients with non-ischemic BRVO-ME diagnosed by ophthalmic examination in Department of Ophthalmology, Beijing Hepingli Hospital were included in the study. Among them, 15 males had 15 eyes, and 16 females had 16 eyes. Age was 70 (65, 72) years; the course of disease was 10 (9, 15) days. All of them were first-time patients. All eyes were treated with IVR once a month for 3 consecutive months. At the end of each IVR treatment, 0.1 ml aqueous humor was extracted immediately. The concentrations of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in aqueous humor were detected by flow cytometry. The concentrations of cytokines in aqueous humor before and after treatment were compared by Kruskal-Wallis or Wilcoxon signed-rank test. Spearman correlation analysis was performed on the correlation between VEGF and MCP-1 expression level in aqueous humor before treatment. ResultsThe concentrations of VEGF and ICAM-1 in aqueous humor were significantly lower at 1 month after treatment compared with that before treatment, and at 2 months after treatment compared with that at 1 month after treatment (Z=4.03, 3.25, 2.50, 3.48; P＜0.05); the concentrations of IL-6 and VCAM-1 increased and the concentration of MCP-1 decreased, but there was no significant difference (Z=－0.21, 1.42, 0.86, －0.53, 0.92, －1.57; P＞0.05). Spearman correlation analysis showed that there was a strong positive correlation between VEGF and MCP-1 in aqueous humor before treatment (r=0.78, P＜0.001). ConclusionThe concentrations of VEGF and ICAM-1 in aqueous humor significantly decrease after IVR treatment in BRVO-ME; the concentrations of IL-6, MCP-1 and VCAM-1 do not obviously change.
ObjectiveTo observe the expression levels of related cytokines in the vitreous humor of eyes with rhegmatogenous retinal detachment (RRD) associated with lattice degeneration (LD). MethodsA clinical observational study. From May 2022 to February 2023, 43 patients of 43 eyes diagnosed with RRD, with or without accompanying LD, who underwent their first pars plana vitrectomy (PPV) at Zhongda Hospital Southeast University and The Affiliated Eye Hospital of Nanjing Medical University were included in the study. The patients were divided into two groups: RRD with LD (LD group), consisting of 27 patients with 27 eyes, and RRD without LD (Non-LD group), consisting of 16 patients with 16 eyes. Additionally, 6 patients (6 eyes) with idiopathic macular holes and 4 patients (4 eyes) with idiopathic epiretinal membranes during the same period were selected as the control group. Before initiating PPV and without intraocular perfusion, a 0.5 ml sample of undiluted vitreous fluid from the central portion was excised and aspirated. The concentrations of monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP)-1α, MIP-1β, interferon-γ- inducible protein 10 (IP-10), interleukin-6 (IL-6), IL-8, macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha-α, interferon-γ, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule 1 (PECAM-1), placental growth factor (PLGF) and vascular endothelial growth factor (VEGF) in the vitreous fluid were quantitatively measured using the Luminex high-throughput multiplex assay technology. The comparison of cytokine expression levels between groups was performed using the Kruskal-Wallis rank sum test, with significance levels for post-hoc pairwise comparisons adjusted by DSCF methods. ResultsThe eyes of the patients in the LD group, Non-LD group, and control group showed statistically significant differences (P＜0.05) in the concentrations of IL-6 (H=14.400), IL-8 (H=13.610), MCP-1 (H=12.050), VEGF (H=9.920), MIP-1α (H=6.620), IP-10 (H=7.780), MIF (H=12.920), PECAM-1 (H=9.990), ICAM-1 (H=8.070), and PLGF (H=16.850). Upon pairwise comparison between groups, the vitreous fluid concentrations of IL-6, IL-8, and PLGF in the LD group were found to be significantly higher than those in the Non-LD group (P＜0.05). ConclusionThe expression levels of IL-6, IL-8, and PLGF are elevated in the vitreous fluid of eyes with RRD accompanied by LD.
The fundus lesions caused by high myopia (HM) often lead to irreversible visual impairment or even blindness. However, the pathogenesis of HM and its fundus lesions is still unclear, the intraocular fluid detection technology of micro samples has brought new prospects for the early diagnosis, monitoring and intervention of the fundus lesions. The molecules associated with HM are various and functionally diverse, intermolecular interactions are staggered and the specific mechanism is complex. With the development of intraocular fluid detection technology, while gradually revealing the role of each molecule in the pathogenesis of HM, it is expected to successfully assist clinical work in the future, providing outpost markers for the progress of myopia and targets for early intervention, or providing a new therapy choice for HM fundus lesions at the molecular level targeting pathogenesis, which is expected to provide more accurate and effective treatment for HM patients in the future.
Objective The effects of endotoxin, cytokines, nitric oxide were reviewed in the development of hyperdynamic circulatory syndrome in portal hypertension. Methods Liceratures of overseas main studies in hyperdynamic circulatory syndrome of portal hypertension in recent 10 years were reviewed. Results The hyperdynamic circulatory syndrome was found in 30%-50% of patients with cirrhosis and in all animal models of portal hypertension. The research results of the effects of endotoxin, cytokines, nitric oxide in the development of hyperdynamic circulatory syndrome were different. Conclusion Hyperdynamic circulatory syndrome contribute to the maintenance and aggregation of portal hypertension. Endotoxin, cytokines, nitric oxide may play a role in the development of hyperdynamic circulatory syndrome. Nitric oxide is a more important factor. The effect of other factors is probably mediated by nitric oxide.
ObjectiveTo study the changes and correlation of cytokines in aqueous humor before and after intravitreal injection of conbercept (IVC) treatment in patients with proliferative diabetic retinopathy (PDR).MethodsA prospective clinical study. From March to December 2019, 36 patients (42 eyes) of PDR patients treated with IVC combined with pars plana vitrectomy (PPV) (the observation group) and 27 patients (31 eyes) underwent cataract surgery in the same period (control group) in Department of Ophthalmology of the First Affiliated Hospital of Guangzhou University of Chinese Medicine were included in this study. Before PPV 5-7 days, IVC treatment was performed, and the aqueous humor were extracted during IVC and second-stage PPV in the observation group. The aqueous humor was extracted during cataract surgery in the control group. Luminex assay was used to detect VEGF-A, placental growth factor (PLGF), platelet-derived growth factor-AA (PDGF-AA), platelet-derived growth factor-BB (PDGF-BB), angiopoietin-like protein 4 (ANGPTL4), IL-6, IL-8, IL-1β, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α) cytokine expression. For normally distributed data, the independent sample t test was used for comparison between two independent samples; for non-normally distributed data, the Wilcoxon rank sum test was used for comparison between two independent samples. The correlation analysis used Spearman rank correlation test.ResultsBefore IVC treatment, the concentrations of VEGF-A, PLGF, PDGF-AA, ANGPTL4, IL-6, IL-8, MCP-1 and ICAM-1 in the aqueous humor of PDR patients were significantly higher than those in the control group (P＜0.05). After IVC treatment, the concentration of VEGF-A in the aqueous humor was significantly lower than that before treatment, and the concentrations of ANGPTL4 and IL-8 were significantly higher than those before treatment (P＜0.05). There were no significant differences in the concentrations of PLGF, PDGF-AA, PDGF-BB, IL-6, IL-1β, MCP-1, ICAM-1 and TNF-α before and after IVC treatment (P＞0.05). Before IVC treatment, the concentration of VEGF-A was positively correlated with PLGF, PDGF-AA, PDGF-BB, ANGPTL4, IL-6, IL-8, MCP-1 and TNF-α (P＜0.05).ConclusionsIVC treatment can reduce the concentration of VEGF-A and increase the concentrations of ANGPTL4 and IL-8 in aqueous humor in PDR patients before PPV.
The aim of this study was to investigate the role of tumor necrosis factor (TNF), interleukin-6(IL-6), C-reactive protein (CRP) in pancreatitis and its systemic complications. Thirty six patients with acute pancreatitis were studied, 12 with mild disease, and 24 severe disease, of whom 9 developed systemic complications. TNF, IL-6, CRP in these patients with pancreatitis was assessed during the first, 4th, 8th days of admission. The serum concentration of TNF, IL-6, CRP were significantly increased, and significantly higher in complicated group than in mild group and severe group. These findings suggest that proinflammatory cytokines play a central role in the pathophysiology of the disease, the host systemic response to pancreatic inflammation and the level of the response did relate to the development of organ dysfunction.
