Objective To investigate the predictive factors of short-term poor outcome in patients with cerebral venous sinus thrombosis (CVST).Methods The clinical data of 42 consecutive inpatients with CVST were analyzed retrospectively.The clinical outcomes were assessed with the modified Rankin scale (mRS) at discharge.The patients were divided into either a good outcome group (mRS 0 to 2) or a poor outcome group (mRS 3 to 6).The related factors,such as demographic,etiology,and clinical features were compared between the two groups,Multivariate logistic regression analysis was used to determine the independent predictive factors for short-term poor outcome in patients with CVST.Results A total of 42 patients with CVST were enrolled,29 of them (69.05％) had good outcome and 13 (30.95％) had poor outcome.The proportions of central nervous system infections (20.69％ vs.61.54％ ; x2 =6.740,P =0.009),cancer (6.90％ vs.38.46％ ;x2 =6.439,P =0.011),pregnancy,postpartum,oral contraceptives or hormone replacement therapy (6.90％ vs.38.46％ ; x2 =6.439,P =0.011),and high homocysteine hyperlipidemia (27.59％ vs.76.92％ ;x2 =8.922,P =0.003),as well as the baseline D-dimer levels (730 ± 240 ng/ml vs.1 060 ± 250 ng/ml; t =4.485,P =0.000) in patients of the good outcome group were significantly lower than those of the poor outcome group.There was significant difference in treatment modalities (x2 =11.274,P =0.004) with the poor outcome group.The proportions of patients in anticoagulants,thrombolysis and anticoagulants + thrombolysis were 13.79％,24.14％,and 62.07％,respectively,in the good outcome group,while those were 61.54％,23.08％,and 15.39％,respectively,in the poor outcome group.Multivariate logistic regression analysis showed that the baseline D-dimer level ＞990 ng/mL was an independent predictive factor for short-term poor outcome in patients with CVST (odds ratio [OR] 1.006,95％ confidence interval [CI] 1.002-1.011; P=0.005).Anticoagulants + thrombolytic therapy was an independent protective factor for short-term poor outcome in patients with CVST (OR 0.027,95％ CI 0.002-0.447; P=0.033).The ROC curve analysis showed that when the cutoff value of the baseline D-dimer was 990 ng/ml,the sensitivity and specificity of predicting short-term poor outcome of CVST were 76.9％ and 86.2％ respectively.Conclusions The level of baseline D-dimer ＞990 ng/ml is an independent predictive factor for short-term poor outcomes in patients with CVST.The effect of anticoagulants in combination with thrombolytic therapy is best in patients with CVST.

Objective To investigate the outcome of endovascular treatment of large or giant intracranial aneu?rysm by long-term angiographic follow-up. Methods Clinical data of 72 patients with large or giant intracranial aneu?rysms receiving endovascular treatment were analyzed retrospectively. Thirty aneurysms were treated with coil emboliza?tion alone, 14 with stent-assisted coiling, 15 with covered stent-deployment and 13 with parent artery occlusion. Results complete occlusion was achieved in 10 cases of pure coil embolization, 7 cases of stent assisted coil embolization,11 cas?es of completely covered stent-deployment and,13 cases of parent artery occlusion. The postoperative immediate com?plete embolism rate was 56.9%. Nearly completely occlusion was achieved in 17 cases of pure coil embolization, in 6 cas?es of stent auxiliary coil embolization, 4 cases of covered stent-deloyment and zero case of parent artery occlusion. The total postoperative immediate nearly completely embolism rate was 37.5%. Incomplete occlusion was achieved in 3 cases of pure coil thrombosis, 1 case of stent assisted coil, zero case of ,covered stent-deloyment and zero case of parent artery occlusion. The total immediate postoperative incomplete embolization rate was 5.6%. Patients were followed up for 6 to 72 months, with an average follow-up of 24.2 months . All patients had no bleeding. The total periprocedural complica?tion rate was 9.7%and there were no death cases. The recurrence of aneurysm in pure spring coil embolization treatment was higher compared with other treatments. The overall recurrence rate was 23.6%. The recurrent 14 aneurysms were suc?cessfully treated endovascularly. Conclusions Endovascular embolization treatment of intracranial large or giant aneu?rysm is safe and effective but its long-term recurrence rate is high. Thus a close follow-up is needed. Endovascular inter?ventional therapy based on the location of aneurysm and shape characteristics can improve treatment effectiveness and re?duce recurrence rate.

Objective:To investigate the effects and underlying mechanisms of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/NF-κB signaling pathway in human kidney-2(HK-2) cells of hyperuricemic nephropathy.Methods:HK-2 cells were cultured in vitro and randomly divided into control group and experimental group. The experimental group was induced by high uric acid (720 μmol/L) immersion for 48 h to establish a cell model of hyperuricemic nephropathy in vitro and subsequently divided into hyperuricemic group, overexpressed protease activated receptor 2 (PAR2) and knockdown PAR2 group. The expressions of PAR2, PI3K, AKT, NF-κB mRNA were measured by real-time PCR. The expressions of PAR2, PI3K, AKT and NF-κB protein were measured by Western blotting. The expressions of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1 (MCP-1), interleukin-6 (IL-6), pro-interleukin-1β (pro-IL-1β), interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) were detected by enzyme linked immunosorbent assay (ELISA). Results:(1) Compared with the control group, the expressions of PAR2, PI3K, AKT and NF-κB mRNA and protein in hyperuricemic group were significantly increased (all P<0.05), the expressions of TNF-α, MCP-1, IL-6, pro-IL-1β, IL-1β and TGF-β1 in the supernatant in hyperuricemic group were significantly increased (all P<0.01). (2) Compared with the hyperuricemic group, the expressions of PAR2, PI3K, AKT and NF-κB mRNA and protein in overexpressed PAR2 group were significantly increased (all P<0.05), the expressions of TNF-α, MCP-1, IL-6, IL-1β and TGF-β1 in the supernatant were significantly increased (all P<0.05). (3) Compared with the hyperuricemic group, the expression of PAR2, PI3K, AKT and NF-κB mRNA and protein in knockdown PAR2 group were significantly decreased (all P<0.05), the expressions of IL-6, pro-IL-1β, IL-1β and TGF-β1 in the supernatant were significantly decreased (all P<0.05). Conclusions:In the process of uric acid-induced HK-2 cell damage, uric acid significantly up-regulates the expression of PI3K/AKT/NF-κB signaling pathway by activating PAR2, leading to a marked increase in inflammatory damage. Knocking down PAR2 inhibits the expression of PI3K/AKT/NF-κB signaling pathway, which can effectively reduce the inflammatory damage of HK-2 cells.

Objective To observe the level of CD4+CD25+ regulatory T cells (CD4+CD25+ Treg cells) with positive fork head transcription factor 3 (Foxp3) and changes of T-box transcription factor TBX1 (TBX1) and myocyte specific enhancer 2D (MEF2D) expression in peripheral blood of rats with acute rejection after renal transplantation,and to investigate its regulatory mechanisms by combined with renal function,plasma interleukin-10 (IL-10),interferon-γ (IFN-γ) and renal histopathological changes.Methods Rat renal transplantation model was established and divided into two groups:acute rejection group (AR group) and non-acute rejection group (non-AR group).Their renal function including serum creatinine (Scr) and blood urea nitrogen (BUN) in plasma was measured.The renal histopathology was observed by HE staining.Levels of IL-10 and IFN-γ in plasma were detected by ELISA.The proportion of CD4+CD25+ Treg cells was measured by flow cytometry.The mRNA expressions of Foxp3,TBX1 and MEF2D in CD4+CD4+Treg cells were detected by real-time PCR,and their protein expressions were tested by Western blotting.Results Compared with these in the non-AR group,the levels of BUN,Scr and IFN-γ significantly increased in AR group (all P ＜ 0.05),while IL-10 decreased (P ＜ 0.05).Renal histopathology in the acute rejection group showed glomerular hypertrophy and mesangial cell proliferation,capillary proliferation and neutrophil infiltration;renal interstitial edema and tubular necrosis,accompanied by lymphocytes,plasma cells and neutrophils infiltration.Compared with that in the non-AR group,the percentage of CD4+CD25+ Treg cells in peripheral blood was notably lowered in AR group (4.50％±0.50％ vs 5.74％±1.96％,P ＜ 0.05).The mRNA and protein expressions of Foxp3 and MEF2D were lower in AR group than those in non-AR group,while the expressions of TBX1 was elevated (all P ＜ 0.05).Conclusions In rats with acute renal allograft rejection,the percentage of CD4+CD25+ Treg cells and expressions of Foxp3,MEF2D and IL-10 decrease,while the expressions of TBX1 and IFN-γ enhance.These participate in the development of acute rejection after renal transplantation,and aggravate the renal damage.

Objective To observe the clinical effect of single urokinase and urokinase pump combined with low-molecular-weight Heparin in the treatment of autogenous arteriovenous fistula thrombolysis,and the influence on inflammatory factors [interleukin (IL)-1,IL-6,tumor necrosis factor-α (TNF-α)] and CD62p.Methods 20 hemodialysis patients hospitalized in our hospital for the treatment of thrombosis in fistula were selected.They were randomly divided into group A (n =10) and group B (n =10).The group A was treated by urokinase infusion,and the group B was treated with urokinase pump combined with low-molecular heparin respectively.Results Compared with that before thrombolysis,the blood flow rate was increased significantly while the IL-1,TNF-oα and CD62p decreased significantly in the two groups after thrombolytic treatment,with statistically significant difference (P ＜ 0.05).Compared with the group A,the IL-1,IL-6 and CD62p in group B were decreased after thrombolytic therapy,with statistically significant difference (P ＜ 0.05).Conclusions Urokinase combined with low-molecular-weight heparin is better than single urokinase in the treatment of arteriovenous fistula thrombolysis,providing a theoretical basis for clinical fistula thrombolysis treatment.

Objective:To establish a mouse model of intra-jugular arteriovenous fistula (AVF) to screen differentially expressed genes in the process of intimal stenosis of AVF for investigating the abnormal expression signaling pathways and the mechanisms.Methods:Forty-six male C57BL/6 mice were randomly divided into AVF group ( n=23) and sham-operated group ( n=23). The AVF group underwent internal jugular arteriovenous fistuloplasty, and the sham-operated group separated the right external jugular vein and common carotid artery and then sutured the incision. The whole-genome sequences of mice with AVF stenosis were determined by transcriptomic reversible chain terminator and synthetic sequencing. The microarray data set was established, and the Benjamini & Hochberg method of gene microarray data analysis was applied to screen the differentially expressed genes. The differentially expressed genes were screened by R-language enrichment analysis. Then, gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were performed. The subcellular localization of the differentially expressed genes was performed by BUSCA software. The protein network interaction of differentially expressed genes was analyzed by using STRING database and Cytoscape software. Results:In the AVF group, 21 mice were successfully modeled and 2 mice failed. Therefore, there were 21 mice in the AVF group and only 21 mice in the sham-operated group. This mouse internal jugular AVF model was innovated using the continuous-interrupted suture method, which improved the success rate of modeling this model. The differential gene sequencing analysis showed that there were 2 514 differentially expressed genes in the AVF process, including 1 323 up-regulated genes and 1 191 down-regulated genes. GO functional enrichment analysis showed that the differential genes were mainly enriched in metabolic process, activation, redox, mitochondria and so on. KEGG pathway enrichment analysis showed that the differential genes were enriched in metabolism, energy substance synthesis, diabetes, oxidative stress and so on. Statistical analysis of subcellular localization showed that the differences were mainly in mitochondrial proteins (24.24%), cytoplasmic proteins (17.51%), nuclear proteins (13.13%), cell membrane proteins (11.45%), and extracellular proteins (10.77%).Conclusions:Mitochondrial oxidative stress injury may be involved in the pathological damage process of endothelial proliferation stenosis in the AVF.

The stenosis and embolization of internal fistula vessels directly affect the clinical treatment effect of maintenance hemodialysis patients, and the study of the mechanism of internal fistula stenosis has become a research hotspot in recent years. Previous studies mainly focused on the hemodynamics and pathophysiology of blood vessel wall, and there were few studies on molecular biology and its related signaling pathways. This paper reviews the hemodynamics of the vascular pathway of internal arteriovenous fistula (AVF), the pathophysiological mechanism, molecular biology, and changes in various signaling pathways of AVF dysfunction at home and abroad, in order to provide references for the study of AVF dysfunction.

This study aims to establish a rat model of renal ischemia reperfusion injury (RIRI) to observe the alterations in the expression of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway following various exosome treatments. Additionally, differential miRNA expression analysis will be conducted to elucidate the molecular mechanisms underlying the effects of exosomes derived from ischemic preconditioned (IPC) renal tubular cells in mitigating RIRI in rats. Initially, ten SD rats were subjected to bilateral nephrectomy under general anesthesia to prepare primary renal tubular cells. The second-generation renal tubular cells were then subjected to the following treatments for 12 hours: normoxia (38% O 2, 5% CO 2), hypoxia (1% O 2, 5% CO 2), and hypoxia plus inactivation (heated at 65 ℃ for 30 minutes). Following these treatments, exosomes were extracted, yielding normoxic exosomes, IPC exosomes, and inactivated exosomes, respectively. A subsequent cohort of 50 SD rats was randomly divided into five groups: Sham group, RIRI group, RIRI + normoxic exosome group (NC group), RIRI + IPC exosome group (IPC group), and RIRI + inactivated exosome group (INA group). RIRI model was established in the latter four groups. Twenty-four hours after RIRI modeling, the NC, IPC, and INA groups received intravenous injections of 200 μg of normoxic exosomes, IPC exosomes, and inactivated exosomes via the tail vein, respectively. Six days later, venous blood samples were collected, and both kidneys were excised to observe renal function, histopathological changes in kidney tissue, and alterations in the PI3K/AKT/mTOR signaling pathway among the five groups. Furthermore, differential miRNA expression analysis [ P<0.05, |log 2(Fold Change)|≥1] was conducted between the NC and IPC groups to investigate the changes in the miRNA expression profile. Subsequently, GO analysis and KEGG pathway enrichment analysis were performed. The results revealed that: (1) Compared with the Sham group, the RIRI and INA groups exhibited elevated levels of serum creatinine and urea nitrogen (all P<0.01). Histopathological examination of kidney tissues showed substantial inflammatory cell infiltration in the interstitium accompanied by varying degrees of edema, degenerative swelling of tubular structures, necrosis, and detachment of tubular epithelial cells. Notably, the number of TUNEL-positive cells was significantly increased, while the number of Ki67-stained positive cells was markedly decreased. Additionally, the mRNA and protein expression of PI3K/AKT/mTOR signaling pathway in RIRI group and INA group were down-regulated. (2) Compared to the NC group, the IPC group demonstrated lower levels of serum creatinine and urea nitrogen (both P<0.01). Notably, there was a significant decrease in the accumulation of inflammatory cells in the renal interstitium, and tissue edema was markedly improved. Moreover, the number of TUNEL-positive cells was reduced, while the number of Ki67-stained positive cells was significantly increased. Additionally, the mRNA and protein expressions of PI3K, PDK1, AKT, and mTOR were all up-regulated (all P<0.05). (3) Compared to the NC group, 56 miRNAs were up-regulated and 42 miRNAs were down-regulated in the IPC group. The target genes of GO enrichment analysis were PIK3C2A, PIK3CA, PIK3CB, PIK3CD, PIK3C2G, AKT1, mTOR, Rheb, and KEGG enrichment analysis revealed significant enrichment in PI3K/AKT signal pathway and mTOR signal pathway. In conclusion, this study reveals that during the course of RIRI, exosomes derived from IPC renal tubular cells induce differential miRNA expression in kidney tissues, resulting in enhanced expression of the PI3K/AKT/mTOR signaling pathway, which plays a pivotal role in mitigating RIRI in rats.