ObjectiveTo explore the relationship of the level of inflammation and nutritional status with the occurrence and prognosis of refractory diabetic foot.MethodsA total of 70 patients with refractory diabetic foot between August 2015 and August 2017 were randomly selected as the observation group. Another 70 patients with diabetes mellitus (without foot ulcer) who visited the hospital in the same period were set as the control group. The observation group was subgrouped into the non-amputation group and the amputation group according to the follow-up endpoint events, and into the grade Ⅲ, Ⅳ, and Ⅴ groups according to Wagner classification method. The blood levels of inflammatory markers and nutritional markers between groups were compared.ResultsIn the observation group, vascular cell adhesion molecule-1 (VCAM-1), fibroblast growth factor 2 (FGF2), fibrinogen (FIB), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-18, lipoprotein phospholipase A2 (LP-PLA2), C-reactive protein (CRP) levels were significantly higher than those in the control group, and albumin (ALB), prealbumin (PA), and transferrin (TRF) levels were significantly lower than those in the control group, with statistically significant differences (P<0.01). The blood levels of FGF2, FIB, IL-6, IL-18, LP-PLA2, and CRP in the amputation group were significantly higher than those in the non-amputation group, and the levels of TRF, ALB, and PA were significantly lower than those in the non-amputation group (P<0.01). There were statistically significant differences in the levels of FGF2, FIB, IL-6, IL-18, LP-PLA2, CRP, TRF, ALB, and PA in patients with diabetic foot with different Wagner grades (P<0.05). The result of multiple logistic regression analysis showed that IL-6 [odds ratio (OR)=1.487, 95% confidence interval (CI) (1.023, 2.120), P<0.001], IL-18 [OR=1.274, 95%CI (1.052, 1.665), P<0.001], LP-PLA2 [OR=1.478, 95%CI (1.126, 1.789), P<0.001], and CRP [OR=2.085, 95%CI (1.574, 2.782), P<0.001] were independent risk factors for the occurrence of refractory diabetic foot, and TRF [OR=0.645, 95%CI (0.002, 0.898), P<0.001], ALB [OR=0.838, 95%CI (0.429, 0.923), P<0.001], and PA [OR=0.478, 95%CI (0.201, 0.984), P<0.001] were independent protective factors for the occurrence of refractory diabetic foot.ConclusionIn the clinical treatment of diabetic foot, we should pay attention to the monitoring of the level of inflammatory factors and nutritional status, and it is necessary to timely carry out anti-inflammatory treatment and appropriate nutritional support treatment.
There is a close relationship between inflammation and coagulation response. Inflammation and coagulation are activated simultaneously during cardiopulmonary bypass, which induce postperfusion syndrome. Leukocyte depletion filter can inhibit inflammation by reducing neutrophils in circulation. But, its effects on blood conservation are limited. Aprotinin is a serine protease inhibitor, and can prevent postoperative bleeding by anti-fibrinolysis and protection of platelet function. But its effects on anti-inflammation and protection of organs are subjected to be doubted. The combination of leukocyte depletion filter and aprotinin can inhibit inflammation as well as regulate coagulation, and may exert a good protective action during cardiopulmonary bypass.
Age-related macular degeneration (AMD) is one of the leading irreversible causes of blindness in China. The pathogenesis of AMD is not fully understood at present. Under various stress conditions, cellular senescence is activated, characterized by telomere shortening, mitochondrial dysfunction, DNA damage, and the release of various senescence-related secretory phenotype factors. Senescence is implicated in the pathogenesis of AMD through multiple pathways, contributing to chronic inflammation and the onset and progression of AMD. Mechanisms such as oxidative stress, lipofuscin, β amyloid protein and the membrane attack complex have become hotspots of study in the pathogenesis of AMD. The cyclic guanosine phosphate - adenosine synthase - interferon stimulating factor synthase-stimulator of interferon gene pathway has emerged as a critical signaling pathway in the early development of AMD, providing direction for further research on AMD. Currently, senolytics, selective agents targeting the induction of senescent cell apoptosis, show significant potential in the treatment of AMD. The integration of new technologies with cellular senescence may offer a novel approach to AMD treatment, and intervening in the AMD treatment through anti-cellular senescence pathways holds promising prospects.
In recent years, with the development of neuroimaging and the improvement of people’s awareness, the incidence of cerebral venous sinus thrombosis (CVST) has been increasing year by year. CVST with venous infarction or haemorrhage is severe, accounting for about 60% of CVST, and its clinical manifestations are serious. The current therapies including anticoagulation and intravascular treatment have not significantly improved the prognosis of severe CVST patients. The incidence of long-term poor prognosis (modified Rankin scale score≥2) is up to 56.1%. Recent research indicates that inflammation may be an important factor leading to severe CVST and is significantly associated with poor prognosis. Anti-inflammatory treatment with glucocorticoids may provide a novel method for severe CVST, but further clinical studies are needed to verify it. This paper introduces the relationship between inflammation and severe CVST in order to explore the feasibility of glucocorticoid for severe CVST.
Diabetic retinopathy (DR) is one of the most common complications of diabetes mellitus (DM), and its pathogenesis remains incompletely understood. Research has identified inflammation as a key factor in the onset and progression of DR. As a group of systemic metabolic disorders, the dysregulation of polyunsaturated fatty acid (PUFA) metabolism induced by DM is closely related to the inflammatory mechanisms in DR. Recent metabolomic studies have revealed that in various stages of DR and in diabetic animal models, most upregulated PUFAs and their derivatives act as pro-inflammatory mediators, while downregulated PUFAs and their derivatives are predominantly anti-inflammatory. In the progression of DR, some PUFAs may exert anti-inflammatory effects by inhibiting microglial activation, reducing the expression of inflammatory proteins, antagonizing the pro-inflammatory effects of arachidonic acid, and suppressing the activation of inflammasomes and the migration of neutrophils. Conversely, other PUFAs may promote inflammation through mechanisms such as the formation of pro-inflammatory mediators resembling prostaglandins, facilitating leukocyte adhesion, and inducing oxidative stress responses. PUFAs play a complex dual role in the inflammatory mechanisms of DR. A deeper understanding of these mechanisms not only aids in elucidating the pathogenesis of DR but also provides potential targets for developing new therapeutic strategies.
ObjectiveTo study the effects of the new small molecular oxygen free radical scavenger Tempol on the survival and vasculogenesis of the long random pattern skin flap (LRPSF) and its mechanism. MethodsEighty-four male Sprague Dawley rats were randomly divided into control and Tempol groups (42 rats in each group). LRPSF of 9 cm×3 cm in size were prepared on the backs of rats in two groups based on the Mcfarlane flap. Rats were administered with Tempol (100 mg/kg) in the Tempol group and with normal saline in the control group by intraperitoneal injection at 15 minutes before operation and at 1-7 day after operation. The rat and the skin flap survival conditions were observed after operation; the survival rate of skin flap was measured, and the vascular structure, vascular volume, and total length of blood vessels were analyzed with Micro-CT three-dimensional imaging after 7 days; HE staining was used to observe the structure of the skin flaps and inflammation, immumohistochemical staining to observe vascular endothelial growth factor (VEGF) expression; water-soluble tetrazolium-1 method was used to measure the content of superoxide dismutase (SOD) and malondialdehyde (MDA), and ELISA to detect the expressions of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) after 1, 3, and 7 days. ResultsAll of rats survived after operation, without hemorrhage, edema, and infection. With the extension of time, necrosis occurred in the distal part of the skin flaps in 2 groups, but the necrosis degree of the Tempol group was lower than that of control group; meanwhile, the blood vessel distribution and continuity were better than those of control group. The skin flaps survival rate, vascular volume, and total length of blood vessels of Tempol group were significantly higher than those of control group after 7 days (P<0.05). The clearer skin flaps structure, lighter inflammation reaction and inflammation cell infiltration, and higher VEGF staining intensity were observed in the Tempol group than the control group after 7 days. There was no significant difference in SOD, MDA, and TNF-α, and IL-6 contents between the 2 groups at immediate after operation. SOD significantly increased, but MDA, TNF-α, and IL-6 contents significantly decreased in the Tempol group when compared with control group after 1, 3, and 7 days (P<0.05). ConclusionTempol can significantly promote the LRPSF survival rates, its mechanism is closely related to the promotion of vasculogenesis and reduction of oxidative stress and inflammation.
ObjectiveTo observe the effects of RasGRP4 gene deletion on the structure and function of the retina in diabetic mice, and to explore the mechanism of RasGRP4 in diabetic retinopathy (DR) by transcriptome sequencing in conjunction with bioinformatics analysis. MethodsA total of 12 male C57BL/6J mice were divided into normal group, diabetic group (DM group), with 6 mice in each group. Six male RasGRP4 knockout mice were uesd as RasGRP4 knockout diabetic group (DM-KO group). Mice in the DM group and DM-KO group were fed with high-fat diet combined with intraperitoneal injection of streptozotocin to establish diabetic model and body weight and blood glucose were monitored regularly. Three months after modeling, optical coherence tomography was used to detect the retinal thickness and ganglion cell layer thickness. Electroretinography was used to detect the function of the retina in mice under dark-adapted conditions. Total RNA was extracted from the retinas of mice in DM group and DM-KO group, and transcriptomic sequencing was performed to screen differentially expressed genes (DEG). Core genes were screened using MCODE and Cytohubba plug-ins of Cytoscape v3.8.2 software. At the same time, the functional enrichment analysis of gene samples (GO) of the selected DEG was performed. The mRNA relative expression levels of interleukin-8, transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), NOd-like receptor thermal protein domain protein 3 (NLRP3), Caspase-1 and IL-1β in each group were detected by real-time quantitative polymerase chain reaction. t test was used to compare the two groups. One-way analysis of variance was used to compare the three groups.ResultsCompared with the DM group, there was no significant difference in blood glucose and body weight in the DM-KO group with the extension of high-fat diet (t=0.12, 2.02, 0.22, 0.10, 0.59, 0.41, 1.35, 0.31, 1.12, 1.58, 1.47, 1.20, 1.24, 0.39, 0.66, 0.14; P＞0.05). The retinal thickness and ganglion cell layer thickness of mice in the three groups were significantly reduced in the DM group compared with the normal group, while DM-KO was significantly increased compared with the DM group, and the differences were statistically significant (F=30.43, 7.81; P＜0.000 1, 0.01). Comparison of a-wave and b-wave amplitudes among the three groups showed that the DM group was significantly lower than the normal group, while the DM-KO was significantly higher than the DM group, and the differences were statistically significant (F=16.46, 35.58; P＜0.001, 0.000 1). Compared with the DM group, 184 differential genes (DEG) were screened in the DM-KO group, among which 39 up-regulated and 145 down-regulated genes were detected, respectively. The results of the MCODE plug-in analysis showed that Col1a2, Fbln1, Fbn1, Col6a3, Fmod, Ogn, Tgfb, Mfap4, Vcan, Nid2, and Col18a1 were core genes in the DEG. Cytohubba plug-in analysis showed that Col1a2, Mrc1, Cd47, Fbn1, Cybb, Cd163, Fbln1, Fmod, Adgre1, and Col6a3 were the core genes in DEG. The results of the GO functional enrichment analysis showed that DEG was mainly involved in hemoglobin complexes, MHC class Ⅱ protein complex, apical plasma membrane, inflammasome complex, immunological synapse, response to bacterium, inflammatory response, immune system processe, response to hypoxia, and cell adhesion were significantly enriched. Comparison of mRNA relative expression levels of IL-8, TGF-β, IFN-γ, NLRP3, Caspase-1 and IL-1β in the three groups showed that the DM group was significantly higher than the normal group, while the DM-KO was significantly lower than the DM group, with statistical significance (F=12.43, 15.41, 70.09, 29.04, 11.79, 41.28; P＜0.01). Conclusion RasGRP4 deficiency plays a therapeutic role in the development of DR through inhibition of inflammatory factor secretion and NLRP 3 inflammasome pathway activation.
Atrial fibrillation(AF)is one of the most common cardiac dysrhythmia encountered in clinical practice. Although major advances in management and prophylaxis in recent years, AF continues to be associated with increased morbidity, repeated hospitalization, reduced quality of life, and even death, causing great social and economic burden. So far, the mechanism underlying AF is not completely elucidated. There is an enormous and complicated pathogenesis involved in the occurrence and maintenance of AF. At present, a lot of studies show that inflammation is closely associated with AF. Inflammation may take part in the occurrence and maintenance of AF through the influence of cardiac electrical remodeling and structural remodeling. This review focuses on research progress of correlation evidence of inflammation and atrial fibrillation and anti-inflammatory drug therapies of AF.
ObjectiveTo review the research progress of microenvironment for the treatment of peripheral nervous injuries. MethodsThe recent literature concerning the treatment mechanism of peripheral nervous injuries was extensively consulted, and the microenvironment response involved in the treatment of peripheral nervous injuries was reviewed. ResultsThe complex microenvironment for treatment of peripheral nervous injuries is dependent on nerve regeneration chamber, the formation of neurotrophic factors, inflammation response, regulation of hormones, signaling pathways, and related enzymes in regulation. In-depth study will help us have a clearer understanding on the distal and proximal neurons axons at the cellular and molecular levels after peripheral nervous injuries. ConclusionIn recent years, the researches of microenvironment for the treatment of peripheral nervous injuries have achieved obvious progress. With the current nanotechnology, materials science, genetic engineering, and stem cell transplantation technology, it will provide new ideas and corresponding basis for clinical treatment.
The application of gene therapy in ocular diseases is gradually expanding from mono-gene inherited diseases to multigene, multifactorial, common and chronic diseases. This emerging therapeutic approach is still in the early exploratory stage of treating diseases, and the expected benefits and risks remain highly uncertain. In the delivery process of gene therapy drugs, viral vector is currently one of the most mature and widely used vectors. The occurrence of vector-associated immunity will affect the short-term and long-term effects of gene therapy, and even cause permanent and serious damage to visual function. Therefore, gene therapy vector-associated immunity is the focus and challenge for the safety and long-term efficacy of gene therapy. During the perioperative and follow-up of gene therapy, attention should be paid to the monitoring of vector-associated immune inflammation, and appropriate measures should be taken to deal with the corresponding immune response, so as to achieve the best visual benefits for patients.