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Endovascular treatment's (EVT) safety and efficacy have been proven in treating acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, limited data exist in different stroke subtypes. We aimed to investigate the differences in efficacy and safety of EVT for acute LVO according to different stroke subtypes.A total of 1635 AIS patients with LVO undergoing EVT from a prospective cohort of the Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke (ANGEL-ACT) registry were classified into three types according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. We compared the primary outcome: 90-day modified Rankin Scale (mRS) score, the secondary outcomes: 90-day mRS (0-1, 0-2, and 0-3), successful recanalization (mTICI 2b/3), and complete recanalization (mTICI 3), and the safety outcomes: death within 90 days, parenchymal hemorrhage (PH), and symptomatic intracranial hemorrhage (SICH) among the three subtypes of stroke patients. Then, multivariable logistic regression models adjusting for potential baseline-confounding variables to determine the associations between stroke subtypes and safety and efficacy endpoints were performed. Finally, we performed subgroup analyses to explore discrepancies in the relationships.EVT of cardioembolic LVO (CE-LVO) had a higher rate of mTICI 3 (71.7% vs. 65.9% and 63.2%; P = 0.024) and a higher rate of PH (13.8% vs. 5.4% and 6.7%; P 0.001) when compared to other stroke subtypes. Even multivariable analysis demonstrated that CE-LVO was associated with mTICI 3 [adjusted odds ratio (OR), 1.50 (95% CI 1.04-2.17)] and PH [adjusted OR, 1.97 (95% CI 1.09-3.55)]. However, the 90-day mRS distribution and 90-day mRS (0-1, 0-2, and 0-3) did not differ among the stroke subtypes, and nor did the SICH (P 0.05).Functional outcomes were similar among different stroke subtypes. Despite a higher rate of complete recanalization, there is an increased risk of parenchymal hemorrhage in CE-LVO.Clinical trial registration number: NCT03370939.

Medical treatment and endovascular therapy are widely used for intracranial atherosclerotic stenosis, but the best treatment strategy remains uncertain. The goal of this study was to compare the safety and effectiveness of medical treatment, stenting, and primary balloon angioplasty (PBA). We searched PubMed, MEDLINE, and EMBASE for trials comparing these three treatments for intracranial stenosis up to December 24, 2020. We performed a network meta-analysis with random-effects models. The primary outcome was any stroke or death during a long-term follow-up. Secondary outcomes included ischemic stroke, intracranial hemorrhage, and death. This network meta-analysis included 14 trials with 1520 participants. No significant difference was found between the three groups in the primary outcome, while PBA was probably the best treatment according to the ranking plot. Medical treatment had significantly lower rate of any stroke or death (odds ratio (OR), 0.31; 95% CI, 0.17-0.56), ischemic stroke (OR, 0.43; 95% CI, 0.23-0.81), and intracranial hemorrhage (OR, 0.12; 95% CI, 0.02-0.71) within 30 days than stenting but did not differ from PBA. The ranking plot demonstrated that PBA was also most likely to rank the highest for ischemic stroke during the long-term follow-up and beyond 30 days, although no significant difference was identified. Medical treatment had lower risk of any stroke or death within 30 days than stenting but did not differ from PBA. All the treatments had similar effects on the prevention of long-term stroke, while PBA had the highest probability of being the most effective.

BackgroudThe goal of this study was to determine if the choice of imaging paradigm performed in the emergency department influences the procedural or clinical outcomes after mechanical thrombectomy (MT).MethodsThis is a retrospective comparative outcome study which was conducted from the ANGEL-ACT registry. Comparisons were made between baseline characteristics and clinical outcomes of patients with acute ischemic stroke undergoing MT with non-contrast head computed tomography (NCHCT) alone versus patients undergoing NCHCT plus non-invasive vessel imaging (NVI) (including CT angiography (with or without CT perfusion) and magnetic resonance angiography). The primary outcome was the modified Rankin Scale (mRS) score at 90 days. Secondary outcomes included change in mRS score from baseline to 90 days, the proportions of mRS 0–1, 0–2, and 0–3, and dramatic clinical improvement at 24 hours. The safety outcomes were any intracranial hemorrhage (ICH), symptomatic ICH, and mortality within 90 days.ResultsA total of 894 patients met the inclusion criteria; 476 (53%) underwent NCHCT alone and 418 (47%) underwent NCHCT + NVI. In the NCHCT alone group, the door-to-reperfusion time was shorter by 47 min compared with the NCHCT + NVI group (219 vs 266 min, PConclusionsIn patients selected for MT using NCHCT alone versus NCHCT + NVI, there were improved procedural outcomes and smaller increases in baseline mRS scores at 90 days.

BackgroundEarly neurological deterioration (END) may occur in some patients with acute large vessel occlusion (LVO) undergoing endovascular treatment (EVT). Despite several clear causes of END, such as symptomatic intracranial hemorrhage, failure of recanalization, and intraprocedure complications, a particular END, termed unexplained END (ENDunexplained), exists. We aimed to investigate the incidence, independent predictors, and clinical impact of ENDunexplained after EVT in patients with acute LVO.MethodsSubjects were selected from the ANGEL-ACT registry. ENDunexplained was defined as ≥4-point increase in the National Institutes of Health Stroke Scale (NIHSS) score between baseline and 24 hours after EVT, without the causes listed above. Logistic regression analyses were performed to determine the independent predictors of ENDunexplained, as well as the association between ENDunexplained and 90-day outcomes assessed by modified Rankin Scale (mRS) score.ResultsAmong the 1557 enrolled patients, the incidence of ENDunexplained was 4.3% (67/1557). Admission NIHSS ≤8 (OR=6.88, 95% CI 3.86 to 12.26, p5 (OR=2.82, 95% CI 1.61 to 4.94, p3 (OR=2.11, 95% CI 1.14 to 3.89, p=0.018) were associated independently with a high risk of ENDunexplained. Furthermore, patients with ENDunexplained were associated with a shift toward worse 90-day outcomes (mRS 5 vs 3, common OR=5.24, 95% CI 3.22 to 8.52, pConclusionsENDunexplained associated with poor 90day outcomes occurred in 4.3% of patients with acute LVO undergoing EVT. Several independent predictors of ENDunexplained were identified in this study, which should be considered in daily practice to improve acute LVO management.Clinical trial Registrationhttp://wwwclinicaltrialsgovNCT03370939.

Introduction This study aimed to explore the precipitating factors and evaluate the impact of different stenosis types on treatment outcomes in patients with idiopathic intracranial hypertension (IIH) and venous sinus stenosis (VSS). Methods We recruited patients with IIH who presented with VSS, either intrinsic or extrinsic. We observed the clinical and laboratory findings, and we then compared the outcomes of stenting and medical treatment in different stenosis types. Results Among 145 patients with IIH and VSS, 59 were of the intrinsic type and 86 were of the extrinsic type. Patients in the intrinsic group were older (42 vs. 34 years old, P 0.05). Stenting was significantly associated with complete resolution of the headache and impaired vision both in intrinsic (adjusted OR 0.017, 95% CI 0.001–0.35, P = 0.011; adjusted OR 0.056, 95% CI 0.004–0.697, P = 0.025, respectively) and extrinsic types of stenosis (adjusted OR 0.072, 95% CI 0.015–0.343, P = 0.001; adjusted OR 0.241, 95% CI 0.062–0.931, P = 0.039, respectively). Meanwhile, stenting was significantly associated with improvement of the papilledema in extrinsic-type stenosis compared with medical treatment (adjusted OR 0.017, 95% CI 0.002–0.135, P

Background It is becoming more and more important to judge whether patients with coronary heart disease (CHD) have phlegm and blood stasis syndromes in the process of traditional Chinese medicine (TCM) diagnosis and treatment of CHD. The syndrome differentiation strategy of phlegm and blood stasis syndromes of CHD is still not standardized, and it is particularly necessary to make syndrome differentiation simpler and more accurate. Methods Twenty-eight medical cases that met the criteria, comprising 10 ancient medical cases and 18 modern ones, were selected from the TCM literature, which were then analyzed by 57 experts via questionnaire. Statistical analysis of the data was mainly based on frequency analysis. Results (I) The average age of the 57 experts from 20 provinces was 48.9±8.5 years; 89.5% were associate professor or above, and 75.4% of them worked at a tertiary hospital. (II) Consistency of expert consultation over medical cases: for the ancient medical cases, the diagnostic consistency rate of phlegm syndrome was 27/34 (79.4%) and additional diagnosis rate of the blood stasis syndrome was 27/57 (47.4%); for the modern medical cases, the consistency rate compared with the original diagnosis of phlegm syndrome was 54/80 (67.5%) and that of blood stasis syndrome was 73/90 (81.1%). (III) The top five experts' diagnostic basics of phlegm syndrome were oppression in the chest, slippery pulse, greasy fur, coughing of phlegm, and chest pain; the top five diagnostic basics of blood stasis syndrome were chest pain, dark tongue, oppression in chest, red tongue, and ecchymosis on tongue. (IV) In the questionnaire consultation on CHD phlegm-blood stasis syndrome cases, the diagnostic basis of "symptom or (and) tongue manifestation" accounted for 12/27 (44.4%) of the diagnostic basics of phlegm syndrome and 28/38 (73.7%) of that of blood stasis syndrome basis. Conclusions Modern Chinese medicine experts pay much attention to the diagnosis and treatment of CHD based on TCM pathology theories of phlegm and blood stasis. To collect and detect the patients' symptoms and tongue manifestation is an important strategy of the experts for CHD phlegm and blood stasis syndrome differentiation.

Yating Jian,1 Lili Zhao,1 Baixue Jia,2 Xu Tong,2 Tao Li,1 Yulun Wu,1 Xiaoya Wang,1 Zhen Gao,1 Yu Gong,1 Xuelei Zhang,2 Huqing Wang,1 Ru Zhang,1 Lei Zhang,1 Zhongrong Miao,2 Guilian Zhang1 On behalf of ANGEL-ACT Study Group1Department of Neurology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710004, Shaanxi, People’s Republic of China; 2Department of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Guilian ZhangDepartment of Neurology, the Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 Xiwulu, Xi’an, 710004, Shaanxi, People’s Republic of ChinaTel +86 29 87679346Fax +86 29 87678599Email zhgl_2006@126.comZhongrong MiaoDepartment of Interventional Neuroradiology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South West Road, Fengtai District, Beijing, People’s Republic of ChinaTel +8613601243293Email zhongrongm@163.comPurpose: Elderly people represent a growing stroke population with different pathophysiological states than younger. Whether intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) is beneficial for elderly patients remains unclear. This study compared the efficacy and safety between elderly patients treated with MT alone and those treated with both IVT and MT.Patients and Methods: Patients aged ≥ 65 years who were eligible for IVT within 4.5 h from symptom onset were selected from the ANGEL-ACT (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) registry, a prospective registry program for patients with endovascular treatment from 111 Chinese stroke centers. The primary efficacy outcome was the 90-day modified Rankin Scale score. We compared efficacy and safety outcomes using ordinal or binary logistic regression or a generalized linear model.Results: In total, 482 elderly patients were included: 187 (38.8%) received IVT and MT (bridging MT) and 295 (61.2%) received MT alone (direct MT). There was no significant difference in the 90-day modified Rankin Scale score between the two groups (median: 4 vs 4 points, respectively; adjusted β=− 0.048, P=0.822). The direct MT group had a shorter onset-to-puncture time (225 vs 255 min, respectively; adjusted β=− 55.074, P=0.002) and a lower rate of parenchymal hemorrhage type 2 within 24 h (2.80% vs 6.63%, respectively; adjusted odds ratio [OR]=0.287, 95% confidence interval [CI]=0.096– 0.856, P=0.025). In addition, the direct MT group showed a trend toward a lower incidence of sICH (5.67% vs 10.06%, adjusted OR=0.453, P=0.061), procedure-related complications (7.12% vs 12.30%, adjusted OR=0.499, P=0.052) and distal or new territorial embolization (4.07% vs 6.95%, adjusted OR=0.450, P=0.093).Conclusion: Direct MT had similar efficacy to bridging MT in terms of the 90-day functional outcome in elderly patients, whereas bridging MT had a longer onset-to-puncture time and increased risk of hemorrhagic transformation and procedure-related complications.Keywords: acute ischemic stroke, endovascular treatment, intravenous thrombolysis, elderly patients

Background and Purpose: A recent randomized controlled trial DIRECT-MT (Direct Intra-Arterial Thrombectomy to Revascularize AIS Patients With Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals) compared the safety and efficacy of mechanical thrombectomy (MT) versus combined intravenous thrombolysis (IVT) and MT for acute large vessel occlusion. The current study utilized a prospective, nationwide registry to validate the results of the DIRECT-MT trial in a real-world practice setting. Methods: Subjects were selected from a prospective cohort of acute large vessel occlusion patients undergoing endovascular treatment at 111 hospitals from 26 provinces in China (ANGEL-ACT registry [Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke]) between November 2017 and March 2019. All patients eligible for IVT and receiving MT were reviewed and then grouped according to whether prior IVT or not (MT and combined IVT+MT). After a 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale, successful recanalization, door-to-puncture time, symptomatic intracranial hemorrhage, and intraprocedural embolization were compared. Results: A total of 1026 patients, 600 in the MT group and 426 in the combined group, were included. Among 788 patients identified after matching, there were no significant differences in the 90-day modified Rankin Scale (median, 3 versus 3 points; P =0.82) and successful recanalization (86.6% versus 89.3%; P =0.23) between the two groups; however, patients of the MT group had a shorter door-to-puncture time (median, 112 versus 136 minutes; β=−45.02 [95% CI, −68.31 to −21.74]), lower rates of symptomatic intracranial hemorrhage (5.5% versus 10.1%; odds ratio, 0.52 [95% CI, 0.30–0.91]), and embolization (4.6% versus 8.1%; odds ratio, 0.54 [95% CI, 0.30–0.98]) than those of the combined group. Conclusions: This matched-control study largely confirmed the findings of the DIRECT-MT trial in a real-world practice setting, suggesting that MT may carry similar effectiveness to combined IVT+MT for acute large vessel occlusion patients, despite MT alone seems to be associated with a shorter in-hospital delay until procedure, lower risks of symptomatic intracranial hemorrhage, and embolization. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.

The current study aimed to evaluate whether patients with different pathologic subtypes of basilar artery occlusion (BAO) stroke could affect the clinical outcome after receiving endovascular treatment (EVT). A total of 187 consecutive patients with acute BAO receiving endovascular treatment (EVT) from January 2012 to July 2018 at the Beijing Tiantan Hospital were recruited in this study. The patients were categorized into three groups: embolism without vertebral artery (VA) steno-occlusion (group 1), in situ atherosclerotic thrombosis (group 2), and embolism from tandem VA steno-occlusion (group 3). Among the 187 patients, 4 patients with embolic combined with ICAS and 1 patient with tandem VA steno-occlusion combined with ICAS were excluded. Of the remaining 182 patients (153 men and 29 women; mean age, 60 years), 43 (23.6%) had embolism without vertebral artery (VA) steno-occlusion (group 1), 116 (63.7%) showed in situ atherosclerotic thrombosis (group 2), and 23 (12.6%) had embolism from tandem VA steno-occlusion (group 3). Overall, successful recanalization (modified thrombolysis in cerebral infarction grade 2b or 3) was achieved in 95.3%, 86.2%, and 60.9% in groups 1, 2, and 3, respectively. The favorable outcome (90-day modified Rankin scale score, 0-3) in the three groups was 51.2%, 52.6%, and 30.4%, respectively. Mortality was higher in group 3 (47.8%) as compared with groups 1 (16.3%) (p = 0.009) and 2 (17.2%) (p = 0.004). Embolism from tandem VA steno-occlusion (group 3) seems to be associated with a lower rate of recanalization and significantly higher rate of mortality as compared with another pathological mechanism of BAO.

The perioperative optimal blood pressure targets during mechanical thrombectomy for acute ischemic stroke are uncertain, and randomized controlled trials addressing this issue are lacking. There is still no consensus on the optimal target for perioperative blood pressure in acute ischemic stroke patients with large vessel occlusion. In addition, there are many confounding factors that can influence the outcome including the patient’s clinical history and stroke characteristics. We review the factors that have an impact on perioperative blood pressure change and discuss the influence of perioperative blood pressure on functional outcome after mechanical thrombectomy. In conclusion, we suggest that blood pressure should be carefully and flexibly managed perioperatively in patient-received mechanical thrombectomy. Blood pressure changes during mechanical thrombectomy were independently correlated with poor prognosis, and blood pressure should be maintained in a normal range perioperatively. Postoperative blood pressure control is associated with recanalization status in which successful recanalization requires normal range blood pressure (systolic blood pressure 120–140 mmHg), while non-recanalization requires higher blood pressure (systolic blood pressure 160–180 mmHg). The preoperative blood pressure targets for mechanical thrombectomy should be tailored based on the patient’s clinical history (systolic blood pressure ≤185 mmHg). Blood pressure should be carefully and flexibly managed intraoperatively (systolic blood pressure 140–180 mmHg) in patient-received endovascular therapy.

Poor outcome despite successful recanalization is a relatively common occurrence after endovascular therapy (EVT) in acute intracranial large vessel occlusion. We aimed to develop a simple pre-intervention scale with readily available indicators for predicting the 90-day poor outcome in acute basilar artery occlusion (BAO) patients with successful recanalization after EVT. A prospectively registered consecutive cohort of acute BAO patients treated with EVT in a tertiary stroke center during a 6-year period was reviewed. Poor outcome despite successful recanalization was defined as a 90-day mRS of > 3 despite a post-intervention mTICI of ≥ 2b. A logistic regression analysis was employed to develop the predictive scale. The performance of the scale was estimated by ROC curve and Hosmer-Lemeshow test. Poor outcome was observed in 48 of 109 patients included in this study. The proposed scale consisted of four selected pre-intervention predictors, including the NIHSS score, Pons-Midbrain Index (PMI), bilateral thalamic infarction, and Basilar Artery on Computed Tomography Angiography (BATMAN) collateral score. The 4-item scale revealed good discrimination with an area under curve of 0.83 (95% CI = 0.75–0.90) and acceptable calibration assessed by Hosmer-Lemeshow test (P = 0.48). The optimal cutoff value of the scale (range 0–5 points) was ≥ 3 points with 77% sensitivity, 80% specificity, and 79% accuracy. As a pre-intervention predictive model, the 4-item scale has promising predictive value for poor outcome despite successful recanalization in BAO patients treated with EVT. Nevertheless, external validation with blinded outcome is still needed to confirm its performance before clinical application.

Background and purpose: Endovascular treatment (EVT) is now considered the gold standard for select patient populations with anterior circulation stroke; however, data on the treatment of posterior circulation stroke are less clear. This study aims to determine the characteristics and treatment outcomes of patients with acute basilar artery occlusion (BAO) and to evaluate the effectiveness and safety of EVT for patients with acute BAO in a high-volume stroke center. Methods: This study included 187 consecutive patients with acute BAO who underwent EVT from January 2012 to July 2018 in Beijing Tiantan Hospital. The baseline characteristics, procedure parameters, and functional outcome were assessed. Results: Among the 187 patients, 138 (73.8%) underwent mechanical thrombectomy with a stent retriever, 33 (17.6%) underwent direct intracranial angioplasty (balloon dilation and/or stent implantation) for underlying severe intracranial atherosclerotic disease, and 91 (48.7%) underwent combined mechanical thrombectomy and angioplasty. Successful recanalization [modified Thrombolysis in Cerebral Infarction (mTICI) grade 2b-3] was achieved in 158 patients (84.5%). Overall, the rates of functional independence [modified Rankin Scale (mRS) 0-2] and favorable outcome (mRS 0-3) at 90 days were 36.4% and 49.2%, respectively, and 90- day all-cause mortality was 20.3%. Conclusion􀀌􀀁EVT was effective and safe for treating patients with acute BAO.

Background and Purpose: Drug-eluting stents generally have superior performance to bare metal stents in the treatment of vertebral artery stenosis (VAS). This prospective, multicenter, and single-arm clinical trial was initiated to assess in-stent restenosis (ISR) and midterm outcome after rapamycin-eluting stent placement in patients with symptomatic extracranial VAS.Methods: The subjects underwent angiographic follow-up at 6 months and final clinical follow-up at 12 months. The primary efficacy endpoint was ISR at 6 months. Secondary endpoints included technical success, target lesion-related transient ischemic attack (TIA), stroke, or death, and all-cause TIA, stroke, or death during the 12-month follow-up period.Results: A total of 104 stents were implanted in the 101 patients and 83 patients (82.2%) completed angiographic follow-up at 6 months. The technical success rate was 86.1% (87/101); mean in-stent stenosis rate was 25.1 ± 17.1% and ISR rate was 5.9% (95% CI: 0.8–10.9%). All the patients with ISR were completely asymptomatic and no stent fractures were observed during angiographic follow-up. At the 12-month clinical follow-up, target lesion-related TIA, stroke, or death had occurred in two (2.0%) patients and all-cause TIA, stroke, or death had occurred in six (6.1%) patients.Conclusion: The placement of rapamycin-eluting stents in patients with symptomatic extracranial VAS yields favorable ISR results and showed a trend of favorable safety outcomes including low rates of perioperative complications and late stroke. However, further study is needed to establish the long-term clinical benefits of this stent in the treatment of VA disease.

Background Prior studies have shown an increased risk of ischemic stroke (IS) after myocardial infarction (MI); however, there are limited studies concerning the characteristics, in‐hospital mortality, and complications of patients with IS with a medical history of MI. We hypothesized that patients with IS with a medical history of MI may experience more severe strokes and have a higher risk of in‐hospital mortality and complications than patients with IS without a medical history of MI. Methods and Results Consecutive in‐hospital data were extracted from the China Stroke Center Alliance database from August 2015 to July 2019. Patient characteristics, hospital tests, in‐hospital mortality, and complications were analyzed and compared in patients with IS with or without a history of MI. Of 893 429 patients with IS, we identified 81 646 (9.1%) patients with a history of MI (MI group). Compared with patients with IS without MI, MI group patients were older, had a lower prevalence of current smoking, had a higher prevalence of a relative medical history, and took more medications before admission. Compared with the group with IS without MI, the MI group had a higher National Institute of Health Stroke Scale score after onset (4.0 versus 3.0; Hodges‐Lehmann estimator, 22.5) and a higher proportion of severe strokes (National Institute of Health Stroke Scale score ≥15) (7.1% versus 4.4%; absolute standardized difference=11.6%). In the fully adjusted models, the risk of in‐hospital mortality was higher in the MI group (odds ratio [OR], 1.74; 95% CI, 1.57–1.92; P P P P P P P P Conclusions Patients with IS with a medical history of MI have an increased risk of severe stroke, in‐hospital mortality, and complications. Studies exploring the underlying mechanisms are needed to improve and tailor stroke treatment strategies.

Background and objective The effect of atrial fibrillation (AF) on outcomes of endovascular treatment (EVT) for acute ischemic stroke (AIS) is controversial. This study aimed to investigate the association of AF with outcomes after EVT in AIS patients. Methods Subjects were selected from ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) - a prospective consecutive cohort of AIS patients undergoing EVT at 111 hospitals in China between November 2017 and March 2019, and then grouped according to having a history of AF or not. After 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale (mRS) score, successful recanalization after final attempt, symptomatic intracranial hemorrhage (ICH) within 24 h, and death within 90 days were compared. Results A total of 1755 patients, 550 with AF and 1205 without AF, were included. Among 407 pairs of patients identified after matching, no significant differences were found in the mRS score (median: 3 vs. 3 points; P = 0.29), successful recanalization (87.2 vs. 85.3%; P = 0.42), symptomatic ICH (9. 4 vs. 9.1%; P = 0.86) and death (16.3 vs. 18.4%; P = 0.44) between patients with and without AF. Conclusion The findings of this matched-control study show comparable outcomes of EVT in Chinese AIS patients with and without AF, which do not support withholding EVT in patients with both AIS and AF. Trial registration NCT03370939 First registration date: 28/09/2017 First posted date: 13/12/2017

Background and Purpose: Studies on rescue therapy for acute posterior circulation stroke due to basilar artery occlusion (BAO) are limited in the modern era of mechanical thrombectomy (MT). The aim of this study was to evaluate the safety and efficacy of rescue stenting (RS) following MT failure in patients with BAO.Methods: Data were collected from the Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke (ANGEL-ACT) prospective registry in China. Patients who underwent MT for BAO with failure of recanalization were enrolled in this study. The patients were divided into the RS and non-RS groups. Clinical and laboratory findings, procedural details, and clinical outcomes were compared between the two groups.Results: Overall, 93 patients with acute BAO were analyzed. The RS group included 81 (87.1%) patients, and the non-RS group included 12 patients. A modified treatment in cerebral infarction (mTICI) score of 2b/3 was achieved in 75 (92.6%) patients in the RS group. Compared with the non-RS group, the RS group had a significantly higher rate of successful recanalization and favorable clinical outcomes (modified Rankin Scale score at 90 days post-procedure, 0–3: 16.7 vs. 51.9%, respectively; P = 0.023) without an increase in the rate of symptomatic intracranial hemorrhage and a significantly lower mortality rate (58.3 vs. 18.5%, respectively; P = 0.006). Furthermore, the use of a glycoprotein IIb/IIIa inhibitor improved the rate of recanalization of the target artery without increasing the rate of symptomatic intracranial hemorrhage.Conclusions: Permanent stenting appears to be a feasible rescue modality when MT fails and might provide functional benefits in patients with acute ischemic stroke due to BAO.

Two recently published JNIS commentaries1 2 on eligibility criteria for the clinical trials on patients with large core, acute ischemic stroke (AIS) with large vessel occlusion have caused some debate. Five trials were included.1 Our ongoing trial, ANGEL-ASPECT (NCT 04551664), which represents the only large core trial currently ongoing in the Chinese population, was not included in the discussion. One issue of the debate is the addition of CT perfusion (CTP)/diffusion-weighted image of magnetic resonance imaging (DWI-MRI) to the inclusion criteria, which only the SELECT-2 trial chose to adopt. This raised concern about whether patients already known to benefit from endovascular thrombectomy (EVT) are being randomized to EVT treatment or no treatment. Like the SELECT-2 trial, our ANGEL-ASPECT trial also added CTP/DWI-MRI to our inclusion criteria, but in a manner different from SELECT-2. Here we review the merits of ANGEL-ASPECT’s design and suggest that it be included in the discussion of patient selection criteria in large core trials. The ANGEL-ASPECT trial is an ongoing, multicenter, randomized controlled trial (RCT) currently being conducted in China and sponsored by Beijing Tiantan Hospital. Patients are enrolled according to a prespecified protocol. Each randomized patient is qualified by two core laboratory members who are available at all hours to calculate Alberta Stroke Program Early CT Score (ASPECTS) and infarct core volume using the specialized RAPID software. As for the other five trials discussed in the commentary by Jadhav et al ,1 the primary goal of our trial is to determine whether EVT will benefit or harm patients with AIS and large vessel occlusion and a ‘large core’ infarct. While the ANGEL-ASPECT and SELECT-2 trials both include core volume as defined by CTP in the inclusion criteria in addition to ASPECTS, the other four trials define large core using only ASPECTS. The …

BackgroundAcute ischemic stroke (AIS) leads to a substantial burden of disease among the elderly. There may be a delay in or a poor outcome of endovascular treatment (EVT) among AIS patients with large-vessel occlusion (LVO) during off-hours. By using a prospective, nationwide registry, we compared the workflow intervals and radiological/clinical outcomes between patients with acute LVO treated with EVT presenting during off- and on-hours.MethodsWe analyzed prospectively collected Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke (ANGEL-ACT) data. Patients presenting during off-hours were defined as those presenting to the emergency department from Monday to Friday between the hours of 17:30 and 08:00, on weekends (from 17:30 on Friday to 08:00 on Monday), and on national holidays. We used logistic regression models with adjustment for potential confounders to determine independent associations between the time of presentation and outcomes.ResultsAmong 1788 patients, 1079 (60.3%) presented during off-hours. The median onset-to-door time and onset-to-reperfusion time were significantly longer during off-hours than on-hours (165 vs 125 minutes, P=0.002 and 410 vs 392 minutes, P=0.027). However, there were no significant differences between patients presenting during off- and on-hours in any radiological/clinical outcomes (mRS score: 3 vs 3 points, P=0.204; mortality: 15.9% vs 14.3%, P=0.172; successful reperfusion: 88.5% vs 87.2%, P=0.579; sICH: 7.2% vs 8.4%, P=0.492).ConclusionsOff-hours presentation in the nationwide real-world registry was associated with a delay in the visit and reperfusion time of EVT in patients with AIS. However, this delay did not lead to worse radiological/clinical outcomes.RegistratonURL: https://www.clinicaltrials.gov; Unique identifier: NCT03370939.

Bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation plays an important role in Osteoporosis (OP). LncRNA DGCR5 participates in OP development. However, LncRNA DGCR5's effect on BMSCs in osteoporosis rats and related mechanisms have not been elucidated. SD rats were divided into control group and OP group. Rat BMSCs were cultured and transfected with LncRNA DGCR5 siRNA followed by analysis of LncRNA DGCR5 expression by Real time PCR, cell proliferation by MTT assay, Caspase 3 activity, of ERK/P38 signaling pathway protein expression by Western blot, ALP activity, and the osteogenic genes Runx2 and OC expression by Real time PCR. LncRNA DGCR51 expression was increased in BMSCs of OP rats. Compared with control group, cell proliferation was significantly inhibited, Caspase 3 activity was increased, p-ERK1/2 and p-P38 were downregulated, ALP activity, Runx2 and OC expression was decreased (P < 0.05). DGCR51 siRNA transfection into OP rat BMSCs significantly reduced DGCR51 expression, promoted cell proliferation, decreased Caspase 3 activity, increased p-ERK1/2 and p-P38 expression, increased ALP activity, Runx2 and OC expression compared to OP group (P < 0.05). LncRNA DGCR51 expression is increased in OP rat BMSCs. Down-regulation of LncRNA DGCR51 promoted the activation of ERK/P38 signaling pathway, thereby inhibiting the apoptosis of BMSCs and promoting proliferation and osteogenic differentiation of BMSC in OP rats.

The number of patients with diabetic nephropathy (DN) is still on the rise worldwide, and this requires the development of new therapeutic strategies. Recent reports have highlighted genetic factors in the treatment of DN. Herein, we aimed to study the roles of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and histone 3 lysine 27 trimethylation (H3K27me3) in DN. A model of DN was established by inducing diabetes in mice with streptozotocin. Mouse podocyte clone 5 (MPC5) podocytes and primary podocytes were cultured in normal and high glucose media to observe cell morphology and to quantify PVT1 expression. The roles of PVT1 and enhancer of zeste homolog 2 (EZH2) were validated via loss-of-function and gain-of-function in vitro experiments to identify the interactions among PVT1, EZH2, and forkhead box A1 (FOXA1). The podocyte damage and apoptosis due to PVT1 and FOXA1 were verified with in vivo experiments. PVT1 was highly expressed in MPC5 and primary podocytes in DN patients and in cultures grown in high glucose medium. A large number of CpG (C-phosphate-G) island sites were predicted at the FOXA1 promoter region, where PVT1 recruited EZH2 to promote the recruitment of H3K27me3. The silencing of PVT1 or the overexpression of FOXA1 relieved the damage and inhibited the apoptosis of podocytes in DN, as was evidenced by the upregulated expression of synaptopodin and podocin, higher expression of Bcl-2, and lower expression of Bax and cleaved caspase-3. The key findings of this study collectively indicate that the suppression of lncRNA PVT1 exerts inhibitory effects on podocyte damage and apoptosis via FOXA1 in DN, which is of clinical significance., Diabetic kidney disease: Improving treatment by targeting an RNA molecule Targeting an RNA molecule responsible for disrupting metabolic protein levels in diabetic kidney disease may improve treatment. Diabetic nephropathy (DN) can affect people with type I or type II diabetes, and results in functional deterioration and the need for regular dialysis. DN incidence is rising worldwide, but existing treatments are only partially effective. Zhang-Suo Liu at Zhengzhou University, China, and co-workers examined the role of a long noncoding RNA molecule known as PVT1, which has been recently associated with kidney disease. The team collected serum samples from 32 patients with DN, and also generated a DN mouse model. They found that PVT1 expression was significantly higher in DN, and that this inhibited the expression of a key metabolic protein, FOXA1. Silencing PVT1 restored FOXA1 levels, limiting damage and cell death in kidney cells.

Background: Thoracic radiation therapy plays an important role in the treatment of inoperable lung cancer. However, radiotherapy-induced toxicity poses an important challenge for radiation oncologists. Research has shown that Compound Kushen Injection (CKI) has anti-inflammatory activity and can reduce toxicity when given with chemotherapy. In the present trial, we investigated whether CKI also can decrease chemoradiotherapy-induced thoracic toxicity in lung cancer patients.Methods: A prospective, open, randomized, multi-center study was performed, in which a total of 296 patients were enrolled and randomly divided 1:1 into experimental and control groups. The control group received standard chemoradiotherapy including precise thoracic radiotherapy (60 Gy/30 fractions/6 weeks) plus concurrent platinum-based chemotherapy. The experimental group received standard chemoradiotherapy plus CKI via mainline treatments of 250 ml CKI (20 ml diluted in 0.9% normal saline) daily for 20 continuous days. The incidence of adverse events and severity of thoracic toxicity after treatment were observed according to version 4.0 of the Common Terminology Criteria for Adverse Events. Adverse drug reactions (ADRs) and quality of life (QLQ-C30) also were compared between the two groups.Results: Two hundred ninety-one qualifying patients were included in the statistical analysis. Symptomatic radiation-induced thoracic toxicity was lower in the experimental group than in the control group (14.1% vs 25.6%, p=0.017). According to QLQ-C30 questionnaire findings, CKI provided superior outcomes related to pain relief, relieving fatigue, social functioning and emotional functioning (p0.05) and severe adverse events (5.4% vs 2.8%, p>0.05) did not differ significantly between the experimental and control groups.Conclusion: CKI significantly alleviated symptomatic radiation-induced thoracic toxicity, as well as pain, when given with chemoradiotherapy for lung cancer treatment.

Background and Aims: Although noninferior to stent retriever (SR) as first-line approach for endovascular treatment (EVT) of acute large vessel occlusion (LVO) stroke, little is known about the current status of direct aspiration (DA) as first-line thrombectomy in China. This analysis of a prospective, nationwide registry (ANGEL-ACT) aimed to investigate the prevalence and comparative effectiveness of DA-first thrombectomy in a real-world practice in China. Methods: All patients receiving thrombectomy were screened from a prospective cohort of LVO patients undergoing EVT at 111 hospitals in China between November 2017 and March 2019, and divided into two groups based upon which type of thrombectomy was attempted first (“DA-first” and “SR-first”). The following outcome measures were compared using logistic regression models with adjustment: successful recanalization after first-device alone and all procedures, use of rescue treatment, intracranial hemorrhage (ICH) within 24 h, and modified Rankin Scale (mRS) score at 90 days. Results: A total of 1225 patients, 102 (8.3%) in DA-first group and 1123 (91.7%) in SR-first group, were included. Patients receiving DA-first had less often successful recanalization after first-device alone [30.4 versus 66.4%; odds ratio (OR) = 0.23, 95% confidence interval (CI) = 0.15–0.37], more frequent rescue treatment (62.8 versus 27.0%; OR = 4.55, 95% CI = 2.92–7.08) and ICH (35.4 versus 22.1%; OR = 1.78, 95% CI = 1.12–2.83) than those receiving SR-first; however, no significant difference was found in successful recanalization after all procedures (84.3 versus 90.3%; p = 0.18) and 90-day mRS (median: 3 versus 3 points; p = 0.90) between both groups. Conclusion: This real-world registry suggested that DA-first thrombectomy for acute stroke patients lagged behind in China during the study period. Far fewer DA-first than SR-first thrombectomies were performed, and DA-first was associated with lower first-device recanalization, more frequently requiring rescue treatment, and increased ICH risk. Clinical Trial Registration: ClinicalTrials.gov , NCT03370939.

Background and Purpose: The benefit of endovascular treatment (EVT) for large vessel occlusion in clinical practice in developing countries like China needs to be confirmed. The aim of the study was to determine whether the benefit of EVT for acute ischemic stroke in randomized trials could be generalized to clinical practice in Chinese population. Methods: We conducted a prospective registry of EVT at 111 centers in China. Patients with acute ischemic stroke caused by imaging-confirmed intracranial large vessel occlusion and receiving EVT were included. The primary outcome was functional independence at 90 days defined as a modified Rankin Scale score of 0 to 2. Outcomes of specific subgroups in the anterior circulation were reported and logistic regression was performed to predict the primary outcome. Results: Among the 1793 enrolled patients, 1396 (77.9%) had anterior circulation large vessel occlusion (median age, 66 [56–73] years) and 397 (22.1%) had posterior circulation large vessel occlusion (median age, 64 [55–72] years). Functional independence at 90 days was reached in 45% and 44% in anterior and posterior circulation groups, respectively. For anterior circulation population, underlying intracranial atherosclerotic disease was identified in 29% of patients, with higher functional independence at 90 days (52% versus 44%; P =0.0122) than patients without intracranial atherosclerotic disease. In the anterior circulation population, after adjusting for baseline characteristics, procedure details, and early outcomes, the independent predictors for functional independence at 90 days were age 6 hours (OR, 1.536 [95% CI, 1.065–2.216]), local anesthesia (OR, 2.194 [95% CI, 1.325–3.633]), final modified Thrombolysis in Cerebral Infarction 2b/3 (OR, 2.052 [95% CI, 1.085–3.878]), puncture-to-reperfusion time ≤1.5 hours (OR, 1.628 [95% CI, 1.098–2.413]), and National Institutes of Health Stroke Scale score 24 hours after the procedure Conclusions: Despite distinct characteristics in the Chinese population, favorable outcome of EVT can be achieved in clinical practice in China. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03370939.

Background and Purpose: Endovascular treatment (EVT) is one of the promising treatment options in patients with intracranial atherosclerotic disease (ICAD)-related basilar artery occlusion (BAO). In this study, we compared the safety and efficacy of direct angioplasty (DA) with stent-retriever thrombectomy (SRT) with or without rescue treatment in ICAD-related BAO.Methods: We retrospectively evaluated 187 patients who underwent EVT for BAO from January 2012 to July 2018. We identified patients who underwent EVT due to ICAD-related BAO. Patients who accepted SRT with or without rescue treatment were classified into the SRT group. Patients treated with DA with or without stent placement were classified into DA group. Clinical and laboratory findings and outcomes were compared between groups.Results: A total of 108 patients were enrolled, among them 77 underwent SRT and 31 underwent DA; 61 (79.2%) SRT group patients underwent angioplasty with or without stent placement. Compared with patients in the SRT group, those in the DA group experienced a significantly shorter procedure time [60 min (60–120 min) vs. 120 min (60–120 min); p = 0.038] and a lower number of device passes [2 passes (1–2 passes) vs. 3 passes (2–4 passes); p < 0.001]. No significant differences in balloon angioplasty (35.5 vs. 22.1%; p = 0.150), emergent stent placement (64.5 vs. 57.1%; p = 0.481), successful recanalization (93.5 vs. 85.7%; p = 0.340), embolization in distal or new territory (3.2 vs. 9.1%, p = 0.314), and reocclusion (22.6 vs. 9.1%; p = 0.109) among DA and SRT groups were found. Additionally, no differences in symptomatic intracranial hemorrhage incidence [adjusted odds ratio (OR), 0.74; 95% CI, 0.06–9.44; p = 0.815], functional independence (adjusted OR, 1.44; 95% CI, 0.50–4.16; p = 0.497), and mortality rate (adjusted OR, 0.36; 95% CI, 0.06–2.04; p = 0.247) were noted among groups.Conclusions: In certain patients with ICAD-related BAO, DA may shorten procedure time and reduce required device passes compared to SRT. In this study, DA was retrospectively found to be of similar safety and efficacy as SRT.

With the acceleration of people’s life rhythm, the incidence of hypopharyngeal cancer has generally increased. This study mainly explores the clinical efficacy and toxicity of lobaplatin compared with cisplatin in the treatment of locally advanced hypopharyngeal carcinoma based on intelligent CT imaging. Group A received lobaplatin combined with docetaxel induction chemotherapy for 2 cycles after cisplatin combined with intensity-modulated radiotherapy. Lobaplatin was added to the patient, then, 200 ml of 5% glucose was added, and the patient was injected intravenously for 1.8 hours. After 2 cycles of induction chemotherapy, simultaneous lobaplatin chemotherapy was performed every week for 5 weeks (10 mg/week), and the efficacy was evaluated after 4 consecutive courses of treatment. Group B received cisplatin combined with docetaxel induction chemotherapy after 2 cycles of cisplatin combined with intensity-modulated radiotherapy. Group C was the control group and was not treated with cisplatin or docetaxel. Stomach protection treatment was given in time throughout the treatment process. All patients underwent normal CT (NCCT) and enhanced CT (CECT) examinations before treatment. We extracted 5 mm plain scan CTQNCCT and enhanced CT (CECT) digital DICOM images from the PACS system for omics feature selection. Toxic and side effects are rated in different degrees according to the evaluation criteria of the National Cancer Institute (NCD) common adverse events. Blood routine and liver and kidney function tests were checked every week, and the medication was stopped immediately if there is a serious reaction. In addition, in vitro cell culture was set up to test the inhibitory effect of cisplatin and lobaplatin on the proliferation of cancer cells. The incidence of digestive tract reaction was 13.0% in the A plan group and 58.3% in the B plan group. The A group was lower than the B group, and the difference was statistically significant ( P = 0.001

Background: We aim to identify the risk factors of early neurological deterioration (END) despite successful recanalization and explore the association of END with 90-day outcomes in acute basilar artery occlusion (BAO) treated by endovascular therapy (EVT). Methods: A prospectively registered consecutive cohort of BAO patients with successful recanalization by EVT in a tertiary stroke center during a 6-year period was reviewed. END was defined as an National Institutes of Health Stroke Scale (NIHSS) score increase ≥4 points, or death, from baseline to 24 h after EVT. Multivariate logistic regression analysis was used to identify the risk factors of END. The 90-day outcomes between END and non-END groups were compared by Pearson's χ2 test. Results: END was observed in 21 of 148 patients included in this study. Multivariate logistic regression analysis showed that patients with progressive or fluctuating symptoms had a higher risk of END than those with symptoms of acute attack (OR 5.52, 95% CI 1.73-17.63), and NIHSS score and puncture-to-recanalization time (PTR), as continuous variables, were also significantly associated with END. Using a generalized additive model with spline smoothing function, we observed a linear relationship between PTR (increased by 1 h) and END (OR 2.57, 95% CI 1.45-4.57), and a non-linear relationship between NIHSS score and END. Only when the NIHSS score was ≥23 points was it related to END (OR 0.7, 95% CI 0.6-0.9). In addition, patients with END had a lower proportion of 90-day favorable outcome (19.0 vs. 59.1%, p < 0.01) and higher mortality (33.3 vs. 13.4%, p = 0.048) than those with non-END. Conclusion: Mode of stroke onset, NIHSS score, and PTR may help to identify BAO patients with a higher risk of END after EVT. Moreover, END may affect the 90-day outcomes of these patients.

Background and objective The research on the effect of anesthesia on endovascular therapy (EVT) of acute ischemic stroke is mainly focused on the anterior circulation, and little is known about the data of basilar artery occlusion (BAO). This study aims to investigate the association of anesthesia strategy with 90-day clinical outcomes of patients with acute BAO treated with EVT. Methods We reviewed our prospectively collected data from the endovascular treatment database at the Beijing Tiantan Hospital. This included patients with acute BAO who had a documented 90-day modified Rankin Scale (mRS) score from January 2012 to July 2018. Options for EVT included general anesthesia (GA) and conscious sedation (CS) performed by an anesthesia care team in the institution. The recommendation of anesthesia for patients was a joint decision between anesthesiologist and neurointerventionalist according to a pre-designed scheme. Patients who required tracheal intubation for airway protection prior to EVT were excluded. The clinical outcomes we observed were functional independence (mRS ≤2), favorable outcome (mRS ≤3), and mortality at 90 days after the procedure. Univariate and multivariable logistic regression analyses were used to explore the relationship between anesthesia methods and 90-day outcomes. Results A total of 187 patients with BAO were treated by EVT in this study. Nine cases requiring emergent intubation prior to EVT were excluded. 139 patients (78.1%) underwent GA and 39 patients (21.9%) underwent CS. In univariate analysis, GA was associated with less functional independence [odds ratio (OR), 0.28; 95% confidence interval (CI), 0.13–0.59] and less favorable outcome (OR, 0.23; 95% CI, 0.10–0.52) than was CS. After adjusting for potential confounders, multivariable analysis showed that there were still significant differences between GA and CS in functional independence (OR, 0.31; 95%CI, 0.10–0.97) and favorable outcome (OR, 0.24; 95%CI, 0.07–0.75). Conclusion Our retrospective analysis suggested that the anesthesia strategy may affect outcome, in which general anesthesia may result in less favorable outcomes. Nevertheless, future multicenter randomized controlled trials are needed to confirm our findings.

Background and purpose We performed a retrospective analysis of the “Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS‐China)” registry to explore the benefit and risk of intravenous thrombolysis (IVT) followed by intravenous heparin (IVH) in acute ischemic stroke (AIS) patients. Methods In the TIMS‐China database, the patients who received IVH immediately after IVT (Early IVH group) and those who initiated antithrombotic therapy (ATT) until 24 hr after IVT (Standard ATT group) were screened for this comparison. Propensity score (PS) matching was performed between both groups. The logistic regression analysis was performed in the matched population to compare all the efficacy and safety outcomes. Results Of 1,437 patients in this study, 119 received early IVH and 1,318 cases initiated standard ATT. After PS matching (1:2), 117 pairs were identified. The early IVH group had higher proportions of neurological improvement at 24 hr (OR = 2.24, 95% CI = 1.42–3.53) and 7 days (OR = 1.92, 95% CI = 1.22–3.03), better chance of excellent recovery (OR = 1.69, 95% CI = 1.07–2.67) and functional independence (OR = 1.77, 95% CI = 1.13–2.78) at 90 days, and a lower 90‐day mortality (OR = 0.44, 95% CI = 0.21–0.92) than standard ATT group. Additionally, early IVH did not increase the risk of symptomatic intracranial hemorrhage (OR = 0.92, 95% CI = 0.34–2.48). Conclusions IVH immediately after thrombolysis seems to be safe and potentially more effective as compared with standard ATT delay of 24 hr for a subset of AIS patients., We aimed to explore the risk and benefit of bridging intravenous heparin (IVH) after intravenous thrombolysis (IVT) in patients with acute ischemic stroke (AIS). Therefore, we conducted this propensity score matched‐control study by using the data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS‐China). Our results suggested that in this cohort of AIS patients, such combination therapy with IVT followed by IVH might improve their functional outcomes and not increase their risk of hemorrhagic transformation.

The predictive value of and the influencing factors associated with early neurological improvement (ENI) among patients with acute basilar artery occlusion (BAO) have not been well studied. The present study aimed to evaluate whether ENI predicted a better functional outcome and to identify the influencing factors of ENI. We performed a prospective observational analysis among 187 patients with acute BAO who underwent endovascular treatment (EVT) in Beijing Tiantan Hospital from January 2012 to July 2018. ENI was defined as having a drop on the National Institutes of Health Stroke Scale (NIHSS) by 8 or more scores or having a NIHSS of 0–1 within 24 h after EVT. A multivariate logistic regression model with backward selection was used to identify the influencing factors associated with ENI. ENI had a sensitivity of 0.69 and a specificity of 0.68 to predict a favorable outcome at 90 days after EVT. In addition, patients with ENIs had lower modified Rankin Scale score (mRS) (median: 2.0 vs. 5.0, p

Multidrug resistance (MDR) transporters of the major facilitator superfamily (MFS) were previously believed to drive the extrusion of multiple antimicrobial drugs through the coupling to proton translocation. Here, we present the identification of the first Na+-coupled MFS-MDR transporter, MdrP, which also can achieve H+-coupled drug efflux independently of Na+. Importantly, we propose that MdrP can extrude norfloxacin in a mode of drug/Na+ antiport, which has not yet been reported in any MFS member. On this basis, we further provide the insights into a novel Na+ and H+ coupling mechanism of MFS-MDR transporters, even for all secondary transporters. The most important finding lies in that D223 should mainly act as a key determinant in the Na+ translocation coupled to norfloxacin efflux. Furthermore, our results partially modify the knowledge of the conformational stability-related residues in the motif A of MFS transporters and imply the importance of a new positively charged residue, R361, for the stabilization of outward-facing conformation of MFS transporters. These novel findings positively contribute to the knowledge of MFS-MDR transporters, especially about Na+ and H+ coupling mechanism. This study is based mainly on measurements in intact cells or everted membranes, and a biochemical assay with a reconstituted MdrP protein should be necessary to come to conclusion to be assured.

Background To design a simplified NIH Stroke Scale (sNIHSS) that requires minimal training but can reflect acute basilar artery occlusion (BAO) severity and is predictive for the 90-day outcome after endovascular therapy (EVT). Methods We analyzed the prospectively gathered data of acute BAO treated with EVT in a tertiary stroke center during a 6-year period. The sNIHSS (range: 0 to 20 points) consisted of 4 NIHSS items: level of consciousness - (1) questions and (2) commands; motor function - (3) arms and (4) legs. The 90-day outcomes included functional independence (mRS ≤ 2), favorable outcome (mRS ≤ 3) and death. Results Of 173 patients, 62, 83 and 36 achieved functional independence, favorable outcome and death, respectively. Interobserver reliability of sNIHSS was high (ICC = 0.95), and compared with NIHSS, sNIHSS had a significant reduction of assessment time (median: 1.5 min vs. 5 min, P < 0.01). A multivariable logistic model demonstrated that sNIHSS was independently associated with functional independence (OR = 0.82, 95% CI = 0.77-0.87), favorable outcome (OR = 0.86, 95% CI = 0.81-0.92) and death (OR = 1.24, 95% CI = 1.12-1.37). Additionally, the sNIHSS predicted 90-day outcomes almost as same discrimination as NIHSS by using DeLong test. The optimal cutoff value of sNIHSS was determined to be 12 points for predicting any outcome. Conclusions The sNIHSS reflects acute BAO severity well and predicts 90-day outcomes with reasonable accuracy. Nevertheless, the sNIHSS needs further validation before it can be applied as a predictive tool for acute BAO outcome.

Podocyte apoptosis is considered as the important element that promotes the development and progress of membranous nephropathy (MN). Unfortunately, the underlying mechanism of podocytes apoptosis in MN remains elusive. We compared the renal expressions of miR-130a-5p and M-type phospholipase A2 receptor (PLA2R) between MN patients (n = 30) and 30 controls by qRT-PCR and western blot, respectively. The podocyte damage model in vitro was established by angiotensin II (Ang II, 100 nmol/L) exposure for 24 h. Interaction between miR-130a-5p and PLA2R was determined using dual-luciferase reporter gene assay. MN mice were induced by intravenous injection of cBSA. In this study, miR-130a-5p expression was significantly decreased both in the renal biopsy specimens from MN patients and podocyte cell line AB8/13 following stimulation of Ang II. Overexpressed miR-130a-5p in AB8/13 cells significantly attenuated the Ang II induced-apoptosis in vitro. In contrast, down-regulated miR-130a-5p induced podocyte apoptosis. PLA2R was identified as the target of miR-130a-5p in AB8/13 cells. And up-regulated or down-regulated PLA2R could obviously attenuate the effect of miR-130a-5p overexpression or knockdown on the apoptosis of AB8/13 cells. Furthermore, it was also observed that overexpressed miR-130a-5p by miR-130a-5p agomir could obviously alleviate renal injury in MN mice. In conclusion, decreased miR-130a-5p was contributed to the pathological mechanism of MN through increasing PLA2R expression, which induced podocyte apoptosis.

Background We performed a meta-analysis to compare the efficacy and safety between low- and standard-dose intravenous (IV) tissue-type plasminogen activator (tPA) for acute ischemic stroke (AIS) patients within 4.5 hours of symptom onset. Methods We searched PubMed and EMBASE for relevant studies from inception to June1, 2017. Cohort or randomized controlled studies for AIS within 4.5 hours of symptom onset with comparison between low-dose and standard-dose tPA were included. The primary efficacy end point was favorable functional outcome (modified Rankin scale scores [mRS] of 0-1) at 90 days. The primary safety end point was the incidence rate of symptomatic intracerebral hemorrhage (sICH). The secondary end points were independent functional outcome (mRS scores of 0-2) and mortality. Results A total of 11 studies were pooled in this meta-analysis. The low-dose strategy appeared to be as effective as standard-dose tPA (43.4% versus 45.4%; odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.78-1.10; P = .38) in primary efficacy outcome. The secondary efficacy outcome produced similar results (57.3% versus 57.0%; OR = 0.95, 95% CI: 0.86-1.05; P = .33). There was no evidence of statistical difference for sICH (4.2% versus 4.9%; OR = 1.02 [0.66-1.55]; P = .94) and mortality (9.0% versus 10.6%; OR = 0.99 [0.74-1.31]; P = .92) at 90 days between low- and standard-dose therapy. In a subgroup analysis by ethnicity, there was no significant difference between patients of Asian and non-Asian descent for any of the end points. Conclusions This study showed that AIS patients receiving low-dose IV-tPA had comparably efficacy and safety to those receiving standard-dose IV-tPA. However, the effect is especially pronounced within the Asian population, which limits the generalizability of these results.

To create a novel animal model of ocular hypertension via the intracameral injection of Healaflow. Unilateral chronic ocular hypertension model of rats was created by the intracameral injection of 3 μL Healaflow. The IOP of subjects was monitored. Dynamic morphological changes were evaluated by fundus imaging, OCT and histological examination. Visual function changes were measured by electroretinography and flash visual-evoked potentials. 24 and 72 hours after injection, the retinal tissue was collected for transcriptome analysis. The expression levels of related genes and proteins were further evaluated by qRT-PCR and Western blotting. The IOP peaked within 1 day after a single intracameral injection of Healaflow and then decreased gradually within 4 weeks. Furthermore, the persistently degenerating retinal ganglion cells occurred within 4 weeks. The visual function of these rats was also impaired. The results of transcriptome analyses, qRT-PCR and Western blotting showed that the expression levels of B2m, Ikzf1 and Stat3 were up-regulated, while the expression levels of Six3 and Prss56 were down-regulated in the retinal tissues. Intracameral injection of Healaflow is an effective approach to induce glaucomatous neurodegeneration in rats. Six3 and Prss56 may be involved in the pathogenesis of progressive glaucomatous damage.

Background and purpose: Tirofiban and oral antiplatelet drugs can be used to inhibit reocclusion and restore microvascular reperfusion during endovascular treatment (EVT). This study compared recanalization rates, symptomatic intracranial hemorrhage (SICH), 90 day mortality, and functional outcomes between periprocedural tirofiban and antiplatelet therapy in patients with acute intracranial atherosclerosis-related vertebrobasilar artery occlusion. Methods: A total of 105 consecutive patients with acute intracranial atherosclerosis-related vertebrobasilar artery occlusion who underwent EVT + tirofiban + oral antiplatelet or EVT + oral antiplatelet therapy at the Beijing Tiantan Hospital between January 2012 and July 2018 were included. Baseline characteristics, procedural parameters, and functional outcomes were assessed. Results: Among the 105 patients, 74 underwent EVT + tirofiban + oral antiplatelet therapy, while 31 underwent EVT + oral antiplatelet drug therapy. EVT + tirofiban + oral antiplatelet therapy resulted in higher recanalization rates compared to EVT + oral antiplatelet drug therapy (93.24% vs. 77.42%; p = 0.038), whereas the risk for SICH, 90 day mortality, and functional independence outcomes did not differ between the groups. Logistic regression analysis revealed that EVT + tirofiban + oral antiplatelet therapy had an increased probability of higher recanalization rates (OR 0.18 [95% confidence interval (CI) 1.24-24.39]; p = 0.025). There were no differences in SICH (OR 0.00 [95% CI 0.00-Inf]; p = 0.998), 90 day mortality (OR 1.19 [95% CI 0.17-4.05]; p = 0.826), or functional independence (modified Rankin score 0 to ≤ 2) (OR 1.43 [95% CI 0.23-2.17]; p = 0.538) between the groups. Conclusions: Ninety day functional outcomes of EVT + tirofiban + oral antiplatelet therapy were not superior to those of EVT + oral antiplatelet drug therapy; however, the recanalization rate was higher and the risks for SICH and 90 day mortality were lower.

Optimal blood pressure (BP) management in vertebrobasilar circulation stroke patients undergoing thrombectomy remains undetermined. We aimed to evaluate the impact of perioperative BP on clinical outcome after MT in acute basilar artery occlusion (BAO) patients.We retrospectively analyzed all consecutive patients hospitalized with acute basilar artery occlusion administered endovascular treatment within 24 h from January 2012 to July 2018 in Beijing Tiantan Hospital. BP was measured at regular intervals during the first 24 h after stroke onset, during and after thrombectomy. The clinical outcomes assessed at 3-month follow up were functional independence (mRS score of 0-2) and mortality (mRS score of 6).Of the 187 treated patients, 157 were male; patient ages were 60±10 years. The median NIHSS on admission was 22. Totally in 179 patients had complete BP level assessment. In these individuals, univariate analysis revealed significant associations of postoperative Max SBP and Max MAP with mortality (all P0.05). Multivariate regression analysis also demonstrated that postoperative Max SBP (OR=0.964, 95% CI 0.941 to 0.987, P0.003) and Max MAP (OR=0.942, 95% CI 0.907 to 0.979, P0.002) were independent predictors of mortality.In acute BAO patients administered thrombectomy, Max SBP between 120 and 160 mmHg may be associated with better outcome, with a trend of reduced risk of mortality.

Based on our recently reported selective hMAO-A inhibitors, on which, the intramolecular cyclization led to a very interesting change of isoform selectivity. A series of selective hMAO-B inhibitors (3a-3u) with novel scaffold of tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one were designed and synthesized. Compound 3u (IC50=221 nM) exhibited the best inhibitory activity and isoform selectivity against hMAO-B, superior to selegiline (IC50=321 nM), which is a commercial selective hMAO-B inhibitor used to Parkinson's disease. Modeling study indicated that the selectivity of our compounds to hMAO-B is determined by at least two residues, i.e., Ile 199 and Cys 172 (or corresponded Phe 208 and Asn 181 of hMAO-A). These data support further studies to assess rational design of more efficiently selective hMAO-B inhibitors.

Background and Purpose— We aimed to explore the risk factors of subacute thrombosis (SAT) after intracranial stenting for patients with symptomatic intracranial arterial stenosis. Methods— From January to December 2013, all symptomatic intracranial arterial stenosis patients who underwent intracranial stenting in Beijing Tiantan Hospital were prospectively registered into this study. Baseline clinical features and operative data were compared in patients who developed SAT with those who did not. Binary logistic regression model was used to determine the risk factors associated with SAT. Results— Of the 221 patients enrolled, 9 (4.1%) cases had SAT 2 to 8 days after stenting. Binary logistic analysis showed that SAT was related with tandem stenting (odds ratio [OR], 11.278; 95% confidence interval [CI], 2.422–52.519) and antiplatelet resistance (aspirin resistance: OR, 6.267; 95% CI, 1.574–24.952; clopidogrel resistance: OR, 15.526; 95% CI, 3.105–77.626; aspirin and clopidogrel resistance: OR, 12.246; 95% CI, 2.932–51.147; and aspirin or clopidogrel resistance: OR, 11.340; 95% CI, 2.282–56.344). Conclusions— Tandem stenting and antiplatelet resistance might contribute to the development of SAT after intracranial stenting in patients with symptomatic intracranial arterial stenosis.

Emotion can be regarded as a special brain status and it can be captured by Electroencephalography (EEG) via deploying number of channels all over the scalp. To find out the characteristics of emotional responses, the scalp level connectivity is one of the interests that considered. Nevertheless, to distinguish the significant EEG channels, which can imply the special regions at scalp level, has not yet been studied well. Therefore, in this work, we aim to identify the representative channels towards different emotional status by considering the connectivity derived from the values of coherence and correlation. In this purpose, DEAP, an online database has been investigated. Certainly, the emotional status can be evaluated on the valence-arousal (V-A) space and here, four groups contain HVHA, HVLA, LVHA, and LVLA have been studied. The results from 16 subjects show that the EEG channels AF3, F7, P7 and O1 have higher percentages in term of the connectivity and they could be considered as the representative channels in this case. Such findings could be useful to understand the scalp responses in emotional status.

Objective To propose and test a new approach based on community detection in the field of social computing for uncovering consensuses and treatment principles in traditional Chinese medicine (TCM). Methods Three Chinese databases (CNKI, VIP, and Wan Fang Data) were searched for published articles on TCM treatment of diabetic nephropathy (DN) from their inception until September 31, 2014. Zheng classification and herb data were extracted from included articles and used to construct a Zheng classification and treatment of diabetic nephropathy (DNZCT) network with nodes denoting Zhengs and herbs and edges denoting corresponding treating relationships among them. Community detection was applied to the DNZCT and detected community structures were analyzed. Results A network of 201 nodes and 743 edges were constructed and six communities were detected. Nodes clustered in the same community captured the same semantic topic; different communities had unique characteristics, and indicated different treatment principles. Large communities usually represented similar points of view or consensuses on common Zheng diagnoses and herb prescriptions; small communities might help to indicate unusual Zhengs and herbs. Conclusion The results suggest that the community detection-based approach is useful and feasible for uncovering consensuses and treatment principles of DN treatment in TCM, and could be used to address other similar problems in TCM.

Epilepsy is a typical neurological disorder. To find the characteristics of epilepsy, scalp level connectivity is one of the interests that widely studied before. However, another aspect about the scalp representative channels, which presents the synchronous regions, has not yet been investigated. In this work, we focus on study the scalp responses of epilepsy by connectivity and representative channels. Electroencephalography (EEG), the technique to record the electrical activities of brain, has been utilized. An online EEG database of epilepsy reported from Karunya University in India was selected to be the testbed. By using two methods, coherence and correlation, the scalp level connectivity which shows the networks of scalp responses, can be mapped. Moreover, the representative channels can also be obtained based on the mentioned two methods. According to the statistical results of 94 subjects, the scalp channels F4, C4, P4, and T4 occupied higher percentages than others. These findings are beneficial for us to enrich the understanding of scalp responses in epilepsy.

Early recanalization of acute posterior circulation stroke caused by large intracranial vessel occlusion by mechanical thrombectomy with stent retrievers may improve the outcome of patients. However, evidence of patient selection is still lacking. This study investigated the prognostic factors of acute posterior circulation stroke caused by large intracranial arterial occlusion when treated with stent-retriever thrombectomy.A total of 69 patients from March 2012 to November 2016 were included in the study. These patients presented with acute posterior circulation stroke caused by large intracranial vessel occlusion and underwent mechanical thrombectomy with Solitaire AB or combined with additional balloon and/or stenting angioplasty. Baseline characteristics, clinical course, and imaging data of the patients were analyzed. Good clinical outcome (defined as a modified Rankin Scale score of 0-2 at 90 days) and safety outcome (defined as death within 90 days after thrombectomy) were considered as end points. The association between factors with good clinical outcome and safety outcome was evaluated with both logistic regression and receiver operating characteristic curve analyses.Of the 69 patients, mean age was 59 years (standard deviation, 8 years) and men comprised 82.6% (57/69). The median onset-to-treatment time was 360 minutes (interquartile range, 250-537 minutes). The median National Institutes of Health Stroke Scale (NIHSS) score was 25 (interquartile range, 17-30) on admission. Successful recanalization was achieved in 62 of the 69 cases (89.9%) and 36.2% (25/69) were independent at 90 days. Regression analysis showed that stroke subtype (intracranial atherosclerotic disease vs. embolism; odds ratio [OR], 0.101; 95% confidence interval [CI], 0.020-0.501; P = 0.005), baseline NIHSS score (≥22 vs.22; OR, 0.157; 95% CI, 0.040-0.614; P = 0.008) and posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) on diffusion-weighted imaging [DWI] (weighted magnetic resonance imaging) before thrombectomy (≥6 vs.6; OR, 7.335; 95% CI, 1.495-36.191; P = 0.014) were independent predictive factors of good clinical outcome, respectively at 90 days, whereas high NIHSS score (≥30 vs.30; OR, 5.569; 95% CI, 1.573-19.716; P = 0.008) and collateral status (≥2 vs.2; OR, 0.210; 95% CI, 0.059-0.752; P = 0.016) before treatment were associated with mortality at 90 days. Based on receiver operating characteristic curves, baseline NIHSS score (area under the curve [AUC] = 0.779; cutoff, ≥22; P0.001; sensitivity, 72%; specificity, 77.3%), pc-ASPECTS on DWI (AUC = 0.820; cutoff, ≥6; P0.001; sensitivity, 72%; specificity, 77.3%) before treatment were independent indicators predicting good clinical outcome at 90 days. Increased risk of death by 90 days was associated with baseline NIHSS score (AUC = 0.719; cutoff, ≥30; P = 0.007; sensitivity, 64.7%; specificity, 78.9%) and worse collateral status (AUC = 0.820; cutoff, ≥2; P0.001; sensitivity, 58.8%; specificity, 80.8%) before treatment.Stroke subtype, initial stroke severity, and pc-ASPECTS on DWI as well as collateral status before thrombectomy are independent factors affecting the clinical outcome in patients treated with Solitaire AB thrombectomy for acute posterior circulation stroke caused by large intracranial vessel occlusion.

The aim of our study was to investigate the relationship between the waist-to-height ratio (WHR) and all-cause mortality and functional outcomes after acute ischemic stroke in a prospective cohort study. A total of 2076 patients (36.66% females) with ischemic stroke were analyzed from ACROSS-China, which is a nationwide, prospective, hospital-based stroke registry aimed to detect the glucose abnormality in China. One-year follow-up evaluation was done by telephone interview. Outcome measures were all-cause mortality and functional outcome defined as modified Rankin score being 6 and from 0 to 6, respectively. We identified predictors for functional outcomes using logistic regression analysis, and mortality outcome using Cox proportional hazards model which incorporated covariates with P value of

Background and Purpose: We performed a meta-analysis to compare the outcomes between lower dose and standard dose intravenous tissue-type plasminogen activator (tPA) for acute ischemic stroke in randomized and non- randomized controlled trials. Methods: We searched PubMed for relevant studies and calculated pooled odds ratios (ORs) using random effects models.The primary endpoint was good functional outcome[modified Rankin Scale (mRS) of 0-1] at 3 month after stroke onset. Other major end points were all-cause mortality and symptomatic intracerebral haemorrhage (sICH). Results: From 2010 to 2016, 7 Cohort studies and 1 randomized controlled trial (ENCHANTED trial) were pooled in meta-analysis. The lower tPA strategy was likely to be less effective than the standard dose treatment (OR=0.87; 95% confidence interval [CI], 0.73-1.04, P=0.136; I 2 =47.9%, P=0.044 in random effects models and OR=0.88; 95% CI 0.88-0.98,P=0.016 ;I 2 =0.0%, P=0.693 in non- random effects models after 2 cohort studies were excluded due to heterogeneity). No difference was found for mortality at 90 days (OR=0.87; 95% CI 0.74-1.03, P=0.102 ;I 2 =0.0%, P=0.635 in non-random effects models)and sICH (OR=1.12; 95% CI 0.68-1.83,P=0.659; I 2 =57.6%, P=0.016 in random effects models and OR=1.23; 95% CI 0.92-1.65, P=0.168; I 2 =0.0%, P=0.547 in non-random effects models after 2 cohort studies were excluded due to heterogeneity ) between lower tPA group and standard dose . Conclusions: The low-dose alteplase strategy was less effective comparable to the standard-dose treatment .The safety was similar between the two strategies.

A miniature quad-channel optically pumped atomic magnetometer (OPM) has been developed based on the spin-exchange relaxation-free (SERF) mechanism. With a vapor cell of size 8 mm×8 mm×8 mm, we have incorporated four SERF magnetometer channels, which provides sufficient spatial resolution for magnetoencephalography (MEG). The four channels share the same laser beam for the best cancellation of common mode noise due to laser fluctuations. With gradient measurement, the sensitivities of the four sensors are better than 6 fT/Hz1/2, which is also good enough for MEG measurement. The vapor cell is heated to 160 °C by a novel nonmagnetic current-heating structure. Our sensor with high spatial resolution and compact size is particularly suitable for MEG systems.