Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Background: In acute and chronic renal inflammatory diseases, the activation of inflammatory cells is involved in the defect of erythropoietin (EPO) production. Ras guanine nucleotide-releasing protein-4 (RasGRP4) promotes renal inflammatory injury in type 2 diabetes mellitus (T2DM). Our study aimed to investigate the role and mechanism of RasGRP4 in the production of renal EPO in diabetes. Methods: The degree of tissue injury was observed by pathological staining. Inflammatory cell infiltration was analyzed by immunohistochemical staining. Serum EPO levels were detected by enzyme-linked immunosorbent assay, and EPO production and renal interstitial fibrosis were analyzed by immunofluorescence. Quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of key inflammatory factors and the activation of signaling pathways. In vitro, the interaction between peripheral blood mononuclear cells (PBMCs) and C3H10T1/2 cells was investigated via cell coculture experiments. Results: RasGRP4 decreased the expression of hypoxia-inducible factor 2-alpha (HIF2A) via the ubiquitination–proteasome degradation pathway and promoted myofibroblastic transformation by activating critical inflammatory pathways, consequently reducing the production of EPO in T2DM mice. Conclusion RasGRP4 participates in the production of renal EPO in diabetic mice by affecting the secretion of proinflammatory cytokines in PBMCs, degrading HIF2A, and promoting the myofibroblastic transformation of C3H10T1/2 cells.

Objective:To investigate the risk factors for aneurysm rupture and post-intervention complications in intracranial arterial stenosis patients with intracranial aneurysms.Methods:A retrospective analysis was performed; 238 intracranial arterial stenosis patients with intracranial aneurysms (306 intracranial aneurysms) admitted to Cerebrovascular Disease Department, Neurosurgery Center, Zhujiang Hospital, Southern Medical University from January 2018 to August 2022 were chosen. Ruptured group and unruptured group were divided according to the rupture of intracranial aneurysms. Additionally, 139 patients who underwent interventional therapy and had complete follow-up data were divided into 2 groups according to occurrence of post-intervention complications. Univariate and multivariate Logistic regression analyses were used to identify the risk factors for aneurysm rupture and post-intervention complications.Results:(1) Of 238 patients, 269 unruptured aneurysms and 37 ruptured aneurysms were noted. Univariate regression analysis showed that significant difference was noted between the ruptured group and unruptured group in female ratio, aneurysm distribution, proportion of irregular shaped aneurysms, percentages of patients with increased white blood cell count, neutrophil count, total cholesterol and D-2 polymer, and percentage of patients with decreased blood lymphocyte count ( P<0.05). Multivariate Logistic regression analysis showed that irregular shaped aneurysms ( OR=12.393, 95% CI: 4.114-37.332, P<0.001), elevated neutrophil count ( OR=18.753, 95% CI: 6.555-53.648, P<0.001), and increased D-2 polymer ( OR=4.410, 95% CI: 1.758-11.065, P=0.002) were independent risk factors for aneurysm rupture in intracranial arterial stenosis patients with intracranial aneurysms. (2) Of the 139 patients, 57 had complications and 82 had no complications. Univariate regression analysis showed that the proportion of patients with hypertension history, distribution of arterial stenosis, and proportion of patients with elevated blood D-2 polymer were significantly different between patients with and without complications ( P<0.05); while multivariate Logistic regression analysis did not identify these 3 indexes as independent risk factors for post-intervention complications ( P>0.05). Conclusion:Patients with irregular shaped aneurysms, elevated blood neutrophil count and D-2 polymer trend to have aneurysm rupture; hypertension history, arterial stenosis, and elevated D-2 polymer have impact on postoperative complications in intracranial arterial stenosis patients with intracranial aneurysms.

Objective:To investigate the safety and efficacy of stent-assisted coil embolization in acute intracranial ruptured wide-necked aneurysms, and explore the safety of different antiplatelet drug regimens during perioperative period and the risk factors for prognoses.Methods:A perspective multicenter study was performed. A total of 417 patients with intracranial ruptured wide-necked aneurysms treated by stent-assisted coil embolization in Neurosurgery Departments of 4 hospitals (First Affiliated Hospital of Wenzhou Medical University [ n=41], Zhujiang Hospital of Southern Medical University [ n=111], Tangdu Hospital of Air Force Military Medical University [ n=100], and Xuanwu Hospital of Capital Medical University [ n=165]) from June 2017 to January 2020 were included. According to the different antiplatelet drugs regimens used in perioperative period, these patients were divided into loaded clopidogrel group ( n=87), loaded clopidogrel combined with aspirin group ( n=212), and tirofiban group ( n=118). Clinical data and perioperative complications of 3 groups were compared. Modified Rankin scale (mRS) was used to evaluate the prognoses of patients at discharge; differences of clinical data between the poor prognosis group and good prognosis group were compared. Independent risk factors for prognoses of patients with intracranial ruptured wide-necked aneurysms were analyzed by multivariate Logistic regression analysis. Receiver operating characteristic (ROC) curve was used to analyze the predictive values of risk factors in poor prognosis. Results:Degrees of aneurysm embolization immediately after surgery: Raymond grading I was noted in 351 patients (84.2%), grading II in 44 patients (10.6%), and grading III in 22 patients (5.2%). Perioperative complications were noted in 44 patients (10.6%), and death was noted in 4 (1%). Intraoperative thrombosis incidence of the loaded clopidogrel group, loaded clopidogrel combined with aspirin group and tirofiban group was 5.7% (5/87), 5.7% (12/212) and 0.8% (1/118); that in tirofiban group was significantly lower than that in the loaded clopidogrel group and loaded clopidogrel combined with aspirin group ( P<0.05). At discharge, 360 patients (86.3%) had good prognosis and 57 patients (13.7%) had poor prognosis. Multivariate Logistic regression analysis showed age≥60 years ( OR=3.407, 95% CI: 1.620-7.166, P=0.001), preoperative Hunt-Hess grading 3 ( OR=11.445, 95% CI: 3.584-36.547, P<0.001), preoperative Hunt-Hess grading 4 ( OR=88.951, 95% CI: 14.519-544.948, P<0.001), preoperative Hunt-Hess grading 5 ( OR=64.949, 95% CI: 12.809-329.325, P<0.001), and multiple stenting ( OR=4.709, 95% CI: 1.215-18.248, P=0.025) were independent risk factors for poor prognosis of these patients. ROC curves showed that area under the curve of combination of age, number of implanted stents, and preoperative Hunt-Hess grading in predicting poor prognosis of these patients was 0.821, with optimal diagnostic threshold of 0.500, sensitivity of 0.667, and specificity of 0.833. Conclusion:Stent-assisted coil embolization is safe and effective in acute intracranial ruptured wide-necked aneurysms; tirofiban is safe as perioperative antiplatelet drug; patients with old age, preoperative Hunt-Hess grading≥3, and multiple stents are prone to have poor prognosis.

Objective:To investigate the relationship between double-triggering and abnormal movement of air in the lungs (pendelluft phenomenon) under pressure support ventilation (PSV).Methods:A prospective observational study was conducted, postoperative patients admitted to department of critical care medicine of Beijing Tiantan Hospital, Capital Medical University from April 1, 2019 to August 31, 2020 and received invasive mechanical ventilation with PSV mode were enrolled. Electrical impedance tomography (EIT) monitoring was performed. Airway pressure-time, flow-time, global and regional impedance-time curves were synchronously collected and analyzed offline. The volume of abnormal movement of air in the lungs at the beginning of inspiration was measured and defined as pendelluft volume. Double-triggered breaths were identified by trained researchers. Pendelluft volume during double-triggering was measured including the first triggered breath, the double-triggered breath, and the breath immediately following the double-triggered breath. Pendelluft volume was also measured for normal breath during the study. According to the frequency of double-triggering, patients were divided into severe (≥1 time/min) and non-severe double-triggering group. Pendelluft volume, parameters of respiratory mechanics, and clinical outcomes between the two groups were compared.Results:In 40 enrolled patients, a total of 9 711 breaths [(243±63) breaths/patient] were collected and analyzed, among which 222 breaths (2.3%) were identified as double-triggering. The Kappa of interobserver reliability to detect double-triggering was 0.964 [95% confidence interval (95% CI) was 0.946-0.982]. In 222 double-triggered breaths, pendelluft volume could not be measured in 7 breaths (3.2%), but the pendelluft phenomenon did exist as shown by opposite regional impedance change at the beginning of double-triggered inspiration. Finally, pendelluft volume was measured in 215 double-triggered breaths. Meanwhile, 400 normal breaths (10 normal breaths randomly selected for each patient) were identified as control. Compared with normal breath, pendelluft volume significantly increased in the first breath, the double-triggered breath, and the following normal breath [mL: 3.0 (1.4, 6.4), 8.3 (3.6, 13.2), 4.3 (1.9, 9.1) vs. 1.4 (0.7, 2.8), all P < 0.05]. Patients in severe double-triggering, pendelluft volume of normal breath and double-triggered breath were significantly higher than those in non-severe double-triggering group [mL: 1.8 (0.9, 3.2) vs. 1.1 (0.5, 2.1), P < 0.001; 8.5 (3.9, 13.4) vs. 2.0 (0.6, 9.1), P = 0.008]. Patients in severe double-triggering group had significantly higher respiratory rate than that in the non-severe double-triggering group (breaths/min: 20.9±3.5 vs. 15.2±3.7, P < 0.001). There were no significant differences in other respiratory mechanics parameters and main clinical outcomes between the two groups. Conclusions:During PSV, the abnormal movement of air in the lungs (pendelluft phenomenon) was more likely to occur in double-triggering especially in double-triggered breath. The more frequent the double-triggering occurred, the more serious the pendelluft phenomenon was. A higher pendelluft volume of normal breath and a higher respiratory rate were related to severity of double-triggering.

Atrial fibrillation, also known as atrial fibrillation, is a common cardiac arrhythmia, and its incidence increases with age. Catheter ablation is considered to be an effective means to treat atrial fibrillation and maintain sinus rhythm. The common ablation technologies are radiofrequency ablation and cryoablation. However, the existing catheter ablation technology has a "zero-sum effect", and it is difficult to control the optimal dose clinically. In this study, a new method of pulsed electric field ablation for atrial fibrillation was proposed, which effectively solved the "zero-sum effect" problem of temperature ablation. The clinical application results show that the proposed technology effectively overcomes the shortcomings of existing temperature ablation, and can form durable pulmonary vein isolation.

Objective:To evaluate the safety and effectiveness of stent-assisted coil embolization in treatment of acute intracranial rupture wide-necked aneurysms.Methods:A total of 249 patients with acute intracranial wide-necked aneurysms (301 aneurysms) treated with stent-assisted coil embolization in our hospital from January 2014 to December 2018 were chosen in our study; these patients were divided into ruptured group ( n=114) and non-ruptured group ( n=135). The differences in the prognoses (modified Rankin scale [mRS] scores) and perioperative complications, mortality, and aneurysm recurrence rate were retrospectively analyzed. Univariate analysis and multivariate Logistic regression analysis were used to screen the risk factors for perioperative complications and recurrence of aneurysms in patients from the ruptured group. Results:The incidence of perioperative complications in the ruptured group (10.5%) was slightly higher than that in the un-ruptured group (6.6%), and the recurrence rate of aneurysms in the un-ruptured group (12.8%) was slightly higher than that in the ruptured group (9.6%), but the differences were not statistically significant ( P>0.05); except for 2 patients in the ruptured group who died of postoperative recurrent hemorrhage, the prognosis of the rest patients in the 2 groups was good (mRS scores≤3). Univariate analysis showed that there was significant difference in the age distribution between the complication group and the non-complication group in the ruptured patients ( P<0.05), and the sizes and degrees of embolization between the ruptured group and un-ruptured group showed significant differences ( P<0.05). Multivariate Logistic regression analysis showed that ages at 40-60 years was independent risk factor for perioperative complication ( OR=17.819, 95%CI: 2.356-137.719, P=0.005), and aneurysm diameter>10 mm and aneurysm Raymond grading 3 embolization were independent risk factors for aneurysm recurrence ( OR=36.823, 95%CI: 0.862-768.308, P=0.000; OR=52.813, 95%CI: 2.967-938.152, P=0.007). Conclusion:Stent-assisted coil embolization in the treatment of acute intracranial rupture wide-necked aneurysms is safe and effective, but patients aged 40-60 years should be wary of high incidence of perioperative complications, and patients with large aneurysms and incomplete embolization should be wary of their high risk of aneurysm recurrence.

Objective To explore the risk factors of perioperative complications of cerebral aneurysms after stent-assisted coiling. Methods A retrospective analysis of clinical data of 395 patients with cerebral aneurysms after stent-assisted coiling, admitted to our hospital from January 1, 2011 to December 31, 2017, was performed. Univariate and multivariate Logistic regression analyses were used to determine the risk factors of perioperative complications of cerebral aneurysms after stent-assisted coiling (intraoperative stent thrombosis and bleeding events, postoperative ischemic and hemorrhage events, and other unclassified complications). The preoperative aneurysm status was analyzed by Hunt-Hess grading and Trend test was conducted to analyze its statistical significance. Results Intraprocedural thrombosis and hemorrhage occurred in 2.28％ patients (9/395) and 1.01％patients (4/395), respectively. Postprocedural ischemic stroke and hemorrhage occurred in 3.54％ patients (14/395) and 1.27％ patients (5/395), respectively. One patient suffered intraprocedural thrombosis and postprocedural ischemic stroke. Univariate Logistic regression analysis showed that pretreatment ruptured aneurysm was the risk factor of perioperative complications (OR=2.466, 95％CI: 1.267-4.797, P=0.008).In multivariate Logistic regression analysis, diabetes and pretreatment ruptured aneurysm were independent risk factors of perioperative complications (OR=4.275, 95％CI: 1.260-14.508, P=0.020;OR=2.442, 95％CI: 1.182-5.043, P=0.016). As compared with patients with low Hunt-Hess grading, patients with high Hunt-Hess grading had higher risk of perioperative complications in tests for linear trend (OR=1.509, 95％CI: 1.142-1.993, P=0.004). Conclusions The incidence of perioperative complications is high in patients with diabetes or pretreatment ruptured aneurysm. Hunt-Hess grading can accurately determine the risk of perioperative complications.