Objective To investigate the effects and mechanism of Yuyin Qianyang Tongluo Formula on cognitive function in Alzheimer's disease mice.Methods Transgenic negative mice were designated as the normal group,while APP/PS1 double transgenic mice were randomly divided into six groups(ni=6 per group):model group,low-dose Yuyin Qianyang Tongluo Formula group,medium-dose group,high-dose group,and positive drug group.The Yuyin Qianyang Tongluo Formula low-,medium-,high-dose groups correspondingly received intragastric administration of 0.75,1.5,and 3 g·kg-1·d-1,respectively.The positive drug group received 2 mg·kg-1·d-1 donepezil hydrochloride tablets,while the model and normal groups received equal volumes of saline.All groups were treated once daily for 8 weeks.Behavioral tests were conducted using the Morris water maze and Y-maze.Hippocampal β-amyloid(Aβ)1-42 level was measured by enzyme-linked immunosorbent assay(ELISA).Hippocampal CA1 and CA3 neurons were observed hematoxylin-eosin(HE)staining,and Nissl bodies were examined Nissl staining.Protein expression levels of Aβ transporter low-density lipoprotein receptor-related protein 1(LRP-1)and endoplasmic reticulum stress marker glucose-regulated protein 78(GRP78)were detected by Western Blot analysis.Results(1)Compared with the normal group,the model group showed significantly prolonged escape latency(P＜0.000 1),reduced platform crossings,decreased movement distance and time around the platform of Morris water maze test(P＜0.05 or P＜0.01),significantly lower spontaneous alternation percentage in Y-maze test(P＜0.05),and significantly elevated hippocampal Aβ1-42 level(P＜0.000 1).Compared with the model group,all Yuyin Qianyang Tongluo Formula dose groups and the positive drug group exhibited significantly shortened escape latency of Morris water maze test(P＜0.000 1).The high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed significantly increased platform crossings,movement distance and time around the platform of Morris water maze test(P＜0.05),significantly higher spontaneous alternation percentage in Y-maze test(P＜0.05).All Yuyin Qianyang Tongluo Formula dose groups and the positive drug group showed significantly reduced hippocampal Aβ1-42 level(P＜0.000 1).(2)Compared with the normal group,the model group exhibited disordered and deformed hippocampal neurons and Nissl bodies.Compared with the model group,all Yuyin Qianyang Tongluo Formula groups and positive drug group showed improved neuronal and Nissl body organization,with the improvement degree positively correlated with dosage.(3)Compared with the normal group,the model group showed decreased LRP1 level and increased GRP78 level,but there were no statistically significant differences(P＞0.05).Compared with the model group,the high-dose Yuyin Qianyang Tongluo Formula group and positive drug group showed increased LRP1 level,while all Yuyin Qianyang Tongluo Formula dose groups and positive drug group exhibited decreased GRP78 level,but there were no statistically significant differences(P＞0.05).Conclusion Yuyin Qianyang Tongluo Formula significantly improves cognitive and memory function in model mice in a dose-dependent manner,potentially through reducing Aβ aggregation in the brain via endoplasmic reticulum stress pathway.

Objective:To investigate the relevant factors for rupture of basilar tip aneurysms.Methods:This is a retrospective cohort study. Patients who underwent cerebrovascular digital subtraction angiography at Department of Cerebrovascular Disease Surgery,Zhujiang Hospital of Southern Medical University from July 2008 to February 2023 and were confirmed to have basilar tip aneurysms were retrospectively analyzed. There were 45 males and 56 females, aged (57.5±10.2) years (range: 36 to 76 years); the maximum diameter of the basilar tip aneurysm ( M(IQR)) was 6.85 (5.79) mm (range: 1.28 to 27.48 mm). Finally, 101 basilar tip aneurysms were included, and divided into two groups based on whether the basilar tip aneurysm ruptured or not. There were 37 cases (36.6%) in the ruptured group and 64 cases (63.4%) in the unruptured group. Data were analyzed using independent t-test, Mann-Whitney U test, chi-square test, or Fisher′s exact test, as appropriate, and predictive factors for rupture of basilar tip aneurysms were explored by Logistic regression analysis. Variance inflation factors was used for analysis of collinearity. Results:The univariate results showed statistically significant differences between the ruptured and unruptured groups in terms of aneurysm neck width, basilar artery diameter, mean diameter of the parental artery, the ratio of neck width to parent artery diameter, aneurysm width and maximum diameter of the aneurysm (all P<0.05). In multivariate analysis, basilar artery diameter ( OR=0.347, 95% CI:0.176 to 0.687, P=0.002), and NRP ( OR=0.366, 95% CI:0.192 to 0.696, P=0.002) were predictive factors for rupture of aneurysms occurring at the basilar tip. There was no multiple covariance between NRP and basilar artery diameter in the analysis of covariance (VIF=1). Conclusion:Smaller basilar artery diameter and smaller NRP are relevant factors for rupture of basilar tip aneurysms.

Flow diverter (FD) devices have gradually become the mainstream approach for interventional treatment of intracranial aneurysms. In-stent stenosis (ISS) is a common complication after FD implantation, which can lead to ischemic events and affect the prognosis of patients. Current studies have shown that ISS occurrence is closely related to hemodynamic changes. From the perspective of hemodynamics, this article reviews the research progress of mechanisms, evaluation methods and treatments of ISS after FD implantation, in order to provide reference for clinical practice.

Objective:To investigate the safety and efficacy of Pipeline embolization device (PED) Shield in intracranial unruptured saccular aneurysms.Methods:This is a retrospective cohort study; 124 patients with intracranial unruptured saccular aneurysms treated with PED Shield at Department of Cerebrovascular Surgery, Neurosurgery Center, Zhujiang Hospital, Southern Medical University from July 2023 to October 2024 were enrolled. Intraoperative device-related complications and occurrence of hemorrhagic and ischemic complications within 30 days of the procedure were recorded. The clinical results and imaging results (degrees of stent patency and aneurysm occlusion rate) 6 months after follow-up were statistically analyzed. Modified Rankin scale (mRS) score>2 was defined as poor prognosis in clinical follow-up, and grade D according to O'Kelly Marotta (OKM) classification was considered as complete aneurysm occlusion in imaging follow-up.Results:Eighty-seven females and 37 males, aged (56.44±12.17) years (ranging from 27 to 80 years) were enrolled, with a maximum aneurysm diameter of 5.12 (3.73, 7.24) mm. Among the 124 patients, incidence of intraoperative instrument-related complications was 6.5% (8/124); and within 30 days of the procedure, incidence of ischemic complications was 4.8% (6/124) and that of hemorrhagic complications was 1.6% (2/124). Eighty-four patients had a 6-month clinical follow-up, with 1 patient (1.2%) having poor prognosis. Eighty-four patients (67.7%) completed a 6-month imaging follow-up: complete occlusion rate of aneurysms was 82.1% (69/84), incidence of in-stent stenosis (stenosis degree ≥25%) was 4.8% (4/84), and no symptomatic in-stent stenosis was found.Conclusion:Result of this study shows that PED Shield may be an effective and safe clinical option for intracranial unruptured saccular aneurysms.

Objective:To investigate the efficacy and safety of off-label use of flow diverters (FDs) in aneurysms beyond the circle of Willis.Methods:Seventy-one patients with aneurysms beyond the circle of Willis treated with FDs from January 2016 to September 2023 at Department of Cerebrovascular Surgery, Neurosurgery Center (Zhujiang Hospital of Southern Medical University), Department of Neurosurgery (Guangdong Provincial People's Hospital), Department of Neurosurgery (First Affiliated Hospital of Chongqing Medical University), and Department of Neurosurgery (Beijing Tiantan Hospital, Capital Medical University) were selected. The clinical and imaging data of these patients were analyzed retrospectively, and the clinical characteristics, aneurysm characteristics, endovascular treatments, perioperative complications, and clinical and imaging follow-up results were summarized and analyzed.Results:Among the 71 patients, 22 (31.0%) had ischemic stroke history and 43 (60.6%) had hypertension history. A total of 76 aneurysms were found, including 5 aneurysms (6.6%) at the anterior communicating artery, 10 (13.2%) at the anterior cerebral artery, 53 (69.7%) at the middle cerebral artery, and 8 (10.5%) at the posterior cerebral artery. The median aneurysm size (Inter Quartile Range) was 5.65 (3.63, 10.12) mm, and mean diameter of the parent artery was (2.70±0.57) mm. A total of 80 FDs were used, including 38 (47.5%) Pipeline embolization devices and 42 (52.5%) Tubridge embolization devices; the implantation success rate was 98.8% (79/80). Seven patients (9.9%) had perioperative complications, of which 2 (2.8%) were permanent (1 patient with visual field defect and 1 patient with intracranial hemorrhage). Seventy-one patients had clinical follow-up for (19.73±11.90) months, of which 68 patients (95.8%) had good outcome (modified Rankin scale score of 0-2), 10 patients (14.1%) had ischemic complications, and one patient (1.4%) had hemorrhage complications. Sixty-seven aneurysms (88.2%) underwent angiographic follow-up for 7 (6-12) months, of which 44 aneurysms (65.7%) were completely occluded and 10 (14.9%) had in-stent stenosis.Conclusion:The results of this study preliminarily confirm that off-label use of FDs is relatively safe and effective in aneurysms beyond the circle of Willis.

Congenital long QT syndrome (LQTS) is a life-threatening ion channelopathy caused by mutations in genes encoding specific ion channels, which can result in malignant arrhythmia of the torsades de pointes type. LQTS type 4 represents less than 1% of inherited LQTS cases, in contrast to the 90% attributable to types 1-3, it is specifically caused by loss-of-function mutations in the membrane-binding domain of ANK2. Here, a novel ANK2 variant ( ANK2c 2245 A>C, resulting in p.Lys749Gln) associated with LQTS type 4 and Wolff-Parkinson-White syndrome was identified in a previously healthy 61-year-old male patient who suffered paroxysmal palpitations and pre-syncope due to recurrent torsades de pointes.

Congenital long QT syndrome (LQTS) is a life-threatening ion channelopathy caused by mutations in genes encoding specific ion channels, which can result in malignant arrhythmia of the torsades de pointes type. LQTS type 4 represents less than 1% of inherited LQTS cases, in contrast to the 90% attributable to types 1-3, it is specifically caused by loss-of-function mutations in the membrane-binding domain of ANK2. Here, a novel ANK2 variant ( ANK2c 2245 A>C, resulting in p.Lys749Gln) associated with LQTS type 4 and Wolff-Parkinson-White syndrome was identified in a previously healthy 61-year-old male patient who suffered paroxysmal palpitations and pre-syncope due to recurrent torsades de pointes.

Objective To summarize the results of different perioperative anticoagulation protocols for elderly patients with atrial fibrillation(AF)undergoing catheter radiofrequency ablation in our center.Methods A total of 197 elderly AF patients undergoing catheter radiofrequency ablation by a single operator in the First and Sixth Medical Centers of Chinese PLA General Hospital from January 2021 to December 2023 were retrospectively recruited,and the results of relevant exami-nations were collected.Based on the use of different direct oral anticoagulants,they were divided into dabigatran(n=125)and rivaroxaban(n=72)groups.During the procedure,the appropriate dose of unfractionated heparin was administered according to the initial activated clotting time(ACT)with a self-made formula.The time and rate of ACT were recorded,and perioperative ad-verse reactions such as bleeding and thrombosis were observed.Results There were no statistical differences between the two groups in baseline data,including age,gender,BMI,medical history,CHA2DS2-VASc score,HAS-BLED score,and left atrial anteroposterior diameter(P＞0.05).The baseline ACT value was obviously shorter(149.73+23.52 s vs 157.91±24.58 s,P=0.032),the initial heparin dose was significantly higher(0.71±0.12 mg/kg vs 0.65±0.13 mg/kg,P=0.031),and the rate of ACT reaching the target within 15 min was notably lower(60％vs 74％,P＜0.05)in the dabigatran group than the rivaroxaban group.But no significant difference was observed in the rate of ACT reaching the target in 45 min after additional heparin administration according to the formula(86％vs 88％,P＞0.05).The dabigatran group used higher dose of heparin during the procedure than the rivaroxaban group(0.99±0.30 mg/kg vs 0.85±0.31 mg/kg,P=0.009).Peri-cardial effusion was observed in one patient of the rivaroxaban group,and hematoma at the site of femoral vein puncture was seen in one patients of the dabigatran group in 1 d after procedure,which was treated surgically.No other severe complications occurred.Conclusion For elderly pa-tients with AF undergoing catheter ablation therapy,continuous perioperative anticoagulation and individualized application of unfractionated heparin based on initial ACT value can rapidly achieve ACT targets and improve anticoagulation efficacy.

Objective To summarize the results of different perioperative anticoagulation protocols for elderly patients with atrial fibrillation(AF)undergoing catheter radiofrequency ablation in our center.Methods A total of 197 elderly AF patients undergoing catheter radiofrequency ablation by a single operator in the First and Sixth Medical Centers of Chinese PLA General Hospital from January 2021 to December 2023 were retrospectively recruited,and the results of relevant exami-nations were collected.Based on the use of different direct oral anticoagulants,they were divided into dabigatran(n=125)and rivaroxaban(n=72)groups.During the procedure,the appropriate dose of unfractionated heparin was administered according to the initial activated clotting time(ACT)with a self-made formula.The time and rate of ACT were recorded,and perioperative ad-verse reactions such as bleeding and thrombosis were observed.Results There were no statistical differences between the two groups in baseline data,including age,gender,BMI,medical history,CHA2DS2-VASc score,HAS-BLED score,and left atrial anteroposterior diameter(P＞0.05).The baseline ACT value was obviously shorter(149.73+23.52 s vs 157.91±24.58 s,P=0.032),the initial heparin dose was significantly higher(0.71±0.12 mg/kg vs 0.65±0.13 mg/kg,P=0.031),and the rate of ACT reaching the target within 15 min was notably lower(60％vs 74％,P＜0.05)in the dabigatran group than the rivaroxaban group.But no significant difference was observed in the rate of ACT reaching the target in 45 min after additional heparin administration according to the formula(86％vs 88％,P＞0.05).The dabigatran group used higher dose of heparin during the procedure than the rivaroxaban group(0.99±0.30 mg/kg vs 0.85±0.31 mg/kg,P=0.009).Peri-cardial effusion was observed in one patient of the rivaroxaban group,and hematoma at the site of femoral vein puncture was seen in one patients of the dabigatran group in 1 d after procedure,which was treated surgically.No other severe complications occurred.Conclusion For elderly pa-tients with AF undergoing catheter ablation therapy,continuous perioperative anticoagulation and individualized application of unfractionated heparin based on initial ACT value can rapidly achieve ACT targets and improve anticoagulation efficacy.

Objective:To investigate the efficacy and safety of off-label use of flow diverters (FDs) in aneurysms beyond the circle of Willis.Methods:Seventy-one patients with aneurysms beyond the circle of Willis treated with FDs from January 2016 to September 2023 at Department of Cerebrovascular Surgery, Neurosurgery Center (Zhujiang Hospital of Southern Medical University), Department of Neurosurgery (Guangdong Provincial People's Hospital), Department of Neurosurgery (First Affiliated Hospital of Chongqing Medical University), and Department of Neurosurgery (Beijing Tiantan Hospital, Capital Medical University) were selected. The clinical and imaging data of these patients were analyzed retrospectively, and the clinical characteristics, aneurysm characteristics, endovascular treatments, perioperative complications, and clinical and imaging follow-up results were summarized and analyzed.Results:Among the 71 patients, 22 (31.0%) had ischemic stroke history and 43 (60.6%) had hypertension history. A total of 76 aneurysms were found, including 5 aneurysms (6.6%) at the anterior communicating artery, 10 (13.2%) at the anterior cerebral artery, 53 (69.7%) at the middle cerebral artery, and 8 (10.5%) at the posterior cerebral artery. The median aneurysm size (Inter Quartile Range) was 5.65 (3.63, 10.12) mm, and mean diameter of the parent artery was (2.70±0.57) mm. A total of 80 FDs were used, including 38 (47.5%) Pipeline embolization devices and 42 (52.5%) Tubridge embolization devices; the implantation success rate was 98.8% (79/80). Seven patients (9.9%) had perioperative complications, of which 2 (2.8%) were permanent (1 patient with visual field defect and 1 patient with intracranial hemorrhage). Seventy-one patients had clinical follow-up for (19.73±11.90) months, of which 68 patients (95.8%) had good outcome (modified Rankin scale score of 0-2), 10 patients (14.1%) had ischemic complications, and one patient (1.4%) had hemorrhage complications. Sixty-seven aneurysms (88.2%) underwent angiographic follow-up for 7 (6-12) months, of which 44 aneurysms (65.7%) were completely occluded and 10 (14.9%) had in-stent stenosis.Conclusion:The results of this study preliminarily confirm that off-label use of FDs is relatively safe and effective in aneurysms beyond the circle of Willis.