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The drug 3-n-butylphthalide (NBP) was developed and approved in China, where it has been used to treat ischemic cerebrovascular diseases. It is also considered to have a neuroprotective effect. This study aimed to evaluate whether NBP combined with endovascular treatment (EVT) can improve the clinical outcome and safety in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO).Data from three studies of patients treated with EVT for AIS due to LVO were combined in this study. Patients of LVO undergoing EVT were dichotomized into NBP and non-NBP subgroups. The primary efficacy outcome was the shift of the modified Rankin Scale (mRS) score at 90 days. The secondary efficacy outcome included favorable functional outcomes, functional independence, and excellent outcome (defined as an mRS score of 3 or less) at 90 days. Safety outcomes included mortality within 90 days and symptomatic intracranial hemorrhage (sICH) within 48 h.A total of 1820 patients undergoing EVT were included in this study; 628 (37.5%) patients received NBP treatment, whereas 1138 (62.5%) did not. After adjusting for multiple factors, NBP was associated with the improvement of functional outcomes at 90 days (adjusted common odds ratio [OR]: 1.503; 95% confidence interval (CI): 1.254-1.801; p 0.001). NBP was associated with a higher rate of 90-day favorable outcomes (adjusted OR: 1.589; 95% CI: 1.251-2.020; p 0.001) and a lower rate of 90-day mortality (adjusted OR: 0.486 [95% CI: 0.372-0.635]; p 0.001). sICH occurred in 74 of 682 (10.9%) patients in the NBP group and 155 of 1126 (13.8%) patients in the non-NBP group; no statistical difference was detected (adjusted OR: 0.787 [95% CI: 0.567-1.092]; p = 0.152).Among patients with AIS due to LVO, NBP combined with EVT is associated with better functional outcomes and reduced mortality risk without increasing the risk of sICH.

Under ocean conditions, the flow of natural circulation system will fluctuate periodically, and the flow state of single-phase fluid flowing through the heating channel will change in real time, which may be one or more states of laminar flow, transition flow and turbulence. At present, the main CFD calculation programs, in order to be able to solve quickly, the solution of laminar flow process and turbulent process are basically separated. It is difficult to solve the fluid motion process with multiple flow states with the same set of models, which makes it difficult to study the characteristics of flow and heat transfer in this state. Firstly, the pressure drop experimental results in the channel are used to verify and analyze the flow and heat transfer capacity of eight turbulence models in the narrow rectangular channel, and a turbulence model suitable for analyzing the flow and heat transfer characteristics when multiple flow states coexist or change periodically in the narrow rectangular channel is found. At the same time, the model results are verified by multiple groups of experimental results of resistance and heat transfer characteristics, It provides an idea for the prediction and analysis of flow field and heat transfer characteristics under ocean conditions.

PurposeThe construction industry is facing challenges not only for workers' mobility in the pandemic situation but also for Lean Construction (LC) practise in responding to the high-quality development during the post-pandemic. As such, this paper presents a construction workforce management framework based on LC to manage both the emergency goal in migrant worker management and the long-term goal in labour productivity improvement in China.Design/methodology/approachThe framework is created based on the integrated culture and technology strategies of LC. A combination of qualitative and quantitative methods is taken to explore factors influencing the mobility of construction workers and to measure labour productivity improvement. The case study approach is adopted to demonstrate the framework application.FindingsFor method application, a time-and-motion study and Percent Plan Complete indicator are proposed to offer labour productivity measurements of “resources efficiency” and “flow efficiency”. Moreover, the case study provides an industry level solution for construction workforce management and Lean Construction culture shaping, as well as witnesses the LC culture and technology strategies alignment contributing to LC practise innovation.Originality/valueCompared with previous studies which emphasised solely LC techniques rather than socio-technical system thinking, the proposed integration framework as well as implementation of “Worker's Home” and “Lean Work Package” management models in the COVID-19 pandemic contribute to new extensions of both the fundamental of knowledge and practise in LC.

SEVs (small extracellular vesicles) contents signatures appear to mirror pathological changes of diseases, and mapping sEVs contents profile is a promising approach for non-invasive diagnosis of the disease. Herein, we propose a universal system for accurately and damage-freely mapping of sEVs content profile using dual-recognition triggered CHA (catalytic hairpin assembly) and DNAzyme based signal amplification strategy. After immunoassay based capture of CD63 positive sEVs by anti-CD63 lgG coated on the surface of polystyrene plates, probes are incubated with fixed sEVs to penetrate sEVs membrane and act to sense sEVs contents. In detection step, integrated CHA and DNAzyme based strategy is initiated by released initiator from capture probe after recognizing targets, forming a dual circle signal recycling process, realizing signal amplification for high sensitivity. Given the attractive analytical features that i) a universal platform for indistinctive sEVs nucleic acids and protein molecules detection; ii) high sensitivity derived from dual circle signal recycling process; iii) enzyme-free characteristic of integrated CHA and DNAzyme minimizes the interference to sEVs biological activity; iv) mapping of sEVs contents profiles indicates a brand-new strategy for non-invasive diagnosis of the disease, the present approach shows great promise for analyzing additional different analytes in clinical and experimental researches.

Importance For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes. Objective To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke. Design, Setting, and Participants Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020). Interventions A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group. Main Outcomes and Measures The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was −10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality. Results The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, −5.1% to ∞)Pfor noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, −0.8%; 95% CI, −7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, −0.5%; 95% CI, −10.3% to 9.2%). Conclusions and Relevance Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold. Trial Registration Chinese Clinical Trial Registry:ChiCTR-IOR-17013568

IMPORTANCE: Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. OBJECTIVE: To evaluate the association between EVT and clinical outcomes of patients with acute BAO. DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized cohort study, the EVT for Acute Basilar Artery Occlusion Study (BASILAR) study, was a nationwide prospective registry of consecutive patients presenting with an acute, symptomatic, radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China between January 2014 and May 2019. Patients with acute BAO within 24 hours of estimated occlusion time were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone. MAIN OUTCOMES AND MEASURES: The primary outcome was the improvement in modified Rankin Scale scores (range, 0 to 6 points, with higher scores indicating greater disability) at 90 days across the 2 groups assessed as a common odds ratio using ordinal logistic regression shift analysis, adjusted for prespecified prognostic factors. The secondary efficacy outcome was the rate of favorable functional outcomes defined as modified Rankin Scale scores of 3 or less (indicating an ability to walk unassisted) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage and 90-day mortality. RESULTS: A total of 1254 patients were assessed, and 829 patients (of whom 612 were men [73.8%]; median [interquartile] age, 65 [57-74] years) were recruited into the study. Of these, 647 were treated with standard medical treatment plus EVT and 182 with standard medical treatment alone. Ninety-day functional outcomes were substantially improved by EVT (adjusted common odds ratio, 3.08 [95% CI, 2.09-4.55]; P

Fukuda and Kobori proposed three types of Leginegg instabilities and five types of density wave instabilities, according to different mechanisms of density wave instabilities. The instability dominated by gravity pressure drop is classified as Type-I flow instability. The instability dominated by friction pressure drop is classified as Type-II flow instability. And the instability dominated by accelerated pressure drop is classified as Type-III flow instability.In present work, the Type-I flow instability between rectangular parallel channels of natural circulation was studied theoretically. Models including two-phase flow instability, natural circulation system components were established in combination based on the homogenous model. A computational program was written. The program was validated with experiments, and the results matched well with the experiment data. The marginal stability boundary (MSB) maps under different parameters were obtained by using nondimensional numbers Nsub and Npch. The influence of different kinds of pressure drop, inlet subcooling temperature of heating channels of type-I flow instability were analyzed separately. And the phenomena were explained from mechanism and the change of void fraction. The results show that the induce of inlet subcooling temperature enhances the stability of system. With the increase in system pressure, the system stability of natural circulation is enhanced.

Summary Background Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion. Methods We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov , NCT02441556 . Findings Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0–3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81–3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0–3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20–7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31–7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group. Interpretation There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study. Funding Jiangsu Provincial Special Program of Medical Science.

Background: Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. This study aimed to evaluate the safety and efficacy of EVT for patients with acute BAO. Methods: The EVT for acute basilar artery occlusion study (BASILAR) was a nationwide prospective registry of consecutive patients presenting with an acute symptomatic and radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China. Patients with acute BAO within 24 hours of estimated occlusion time were divided into standard medical treatment (SMT) plus EVT or SMT alone groups. The primary outcome was the improvement in the modified Rankin Scale (mRS, scores range from 0 to 6, with higher scores indicating greater disability) score at 90 days across the two groups assessed as a common odds ratio (cOR) using ordinal logistic regression shift analysis, adjusted for prespecified prognostic factors. The secondary efficacy outcome was the rate of favorable functional outcomes defined as mRS ≤ 3 (indicating ability to walk unassisted) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage (sICH) and 90-day mortality. Findings: Between January, 2014, and May, 2019, 829 patients were recruited into the study, 647 treated with SMT plus EVT and 182 with SMT alone. 90-day functional outcomes were substantially improved by EVT (adjusted cOR, 3·07 [95% confidence interval, 2·07 to 4·54], P < 0·001). Moreover, EVT was associated with a significantly higher rate of 90-day mRS ≤ 3 (adjusted OR, 4·70 [95% CI, 2·53 to 8·75], P < 0·001) and a lower rate of 90-day mortality (adjusted OR, 2·93 [95% CI, 1·95 to 4·40], P < 0·001) despite an increase in sICH (7·1% vs. 0·5%, P < 0·001). Interpretation: Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality. Trial Registration: BASILAR is registered on www.chictr.org.cn (ChiCTR180001475). Funding Statement: This work was supported by National Science Fund for Distinguished Young Scholars (No. 81525008), Chongqing Major Disease Prevention and Control Technology Research Project (No. 2019ZX001)， Army Medical University Clinical Medical Research Talent Training Program (No. 2018XLC2013 and No. 2018XLC3039), and Major clinical innovation technology project of the Second Affiliated Hospital of the Army Medical University (No. 2018JSLC0017). Declaration of Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Ethics Approval Statement: The study protocol was approved by the ethics committee of the Xinqiao hospital, Army Medical University, Chongqing, China and each subcenter. All patients or their legally authorized representatives provided signed, informed consent.

Adenosine A2A receptors (A2ARs) in distinct cellular types may exert different and even opposite effects on many neurologic disorders; A2ARs in bone marrow-derived cells (BMDCs) have been shown to play important roles in various brain injuries. We previously showed that global A2AR inactivation aggravates chronic cerebral hypoperfusion-induced white matter lesions (WMLs); however, the specific cell populations responsible for A2AR-mediated signaling remain unknown. In the present study, we developed chimeric mice in which A2ARs were either selectively inactivated or reconstituted in BMDCs by transplanting bone marrow from global A2AR gene knockout or wild-type mice into wild-type or gene knockout mice, respectively. Chimeric mice were subsequently subjected to chronic cerebral hypoperfusion by bilateral common carotid artery stenosis, and the effects of BMDC A2ARs on WMLs were evaluated. The selective inactivation of A2AR in BMDCs aggravated chronic cerebral hypoperfusion-induced WMLs, promoted microglial activation, and increased proinflammatory cytokine expression, whereas the selective reconstitution or activation of A2AR in BMDCs using the agonist CGS21680 produced the opposite effects. These results demonstrate that A2ARs in BMDCs are important modulators of WMLs induced by chronic cerebral hypoperfusion; this modulation might be associated with the regulation of inflammatory cytokine production.

OBJECTIVE Our aim was to investigate a novel approach to perform preoperative evaluation patients who underwent middle cerebral artery (MCA) percutaneous transluminal angioplasty and stenting (PTAS). METHOD Sixty-five patients with symptomatic MCA stenosis of at least >70% who underwent MCA PTAS were enrolled. The multimodal stroke assessment using CT (MOSAIC) score was used to evaluate the preoperative condition. The Alberta Stroke Program Early Computed Tomography Scoring (ASPECTS) was used to assess the time-to-peak (TTP) parameter of Computer tomography perfusion (CTP). The factors potentially improving TTP following stenting were investigated. The prognostic value of the MOSAIC scores to predict TTP improvement was analyzed and compared. RESULTS The MOSAIC score was a reliable prognostic tool for the degree of improvement of TTP (odds ratio 1.89 [1.08-2.07], P < .01) in patients with PTAS. The MOSAIC score had a higher prognostic accuracy than the degree of CBF deficit, the degree of stenosis, and the amount of tissue infarction. During 1-year follow-up, the stroke and death rate of was 8.1%, the in-stent restenosis rate was 6.5%, and good final outcome (modified Rankin Scale ≤ 2) was observed in 76.9%. CONCLUSIONS The MOSAIC score can be reliably used in selecting patients with MCA stenosis for PTAS.

The fractalkine (FKN)-CX3CR1 (FKN receptor) axis reportedly plays an important role in the progression of many neural pathologies. However, its role in the recruitment of bone marrow-derived progenitor cells for neurogenesis remains elusive. The chemokine-based mechanism underlying the migration of bone marrow-derived mesenchymal stem cells (BMSCs) was investigated in a double-chamber transmigration model with recombinant FKN and endogenous FKN extract, and the results confirmed the involvement of FKN in migration. This chemotactic response was CX3CR1-dependent and FKN-sensitive. Western blotting, immunoprecipitation and transmigration assays revealed that the Janus kinase (Jak)2-signal transducer and activator of transcription (Stat)5α-extracellular signal-related kinase (ERK)1/2 pathway was activated by FKN. Confocal laser scanning microscopy was used to demonstrate cytoskeletal reorganization caused by remodeling of the surface receptor integrin α5β1, intracellular phosphorylation of Fak and Pax, and upregulation of intercellular adhesion molecule-1 during BMSC migration. Moreover, significant inhibition of signaling and migration was detected after treatment of cells with Jak2-interfering RNA or the antagonist AG490. In addition, the results of a fluorescence immunohistochemical analysis of an in vivo chemotactic model, developed via transplantation of BMSCs into transient middle cerebral artery-occluded rats, were consistent with the in vitro results. These findings suggest that FKN activates Jak2-Stat5α-ERK1/2 signaling through CX3CR1, thereby triggering integrin-dependent machinery reorganization to allow chemotactic migration of BMSCs towards an ischemic cerebral lesion.

In this study, bone marrow stromal cells (MSCs) were transplanted into the brain of adult rats after forebrain ischemia induced by 4VO. SD rats (n = 60) were randomly divided into three groups: (I) rats (n = 20) were subjected to 4VO and transplanted with MSCs into the ischemic region using ultrasound-microbubble method, (2) rats (n = 20) were subjected to 4VO and transplanted with MSCs into the ischemic region (n = 20), and (3) 4VO alone (n = 20). Rats were sacrificed 28 days after treatment. Neurological functions of rats were evaluated by Morris Water Maze. The current findings suggest that the ultrasound microbubble transplanted MSCs survived in the ischemic brain and significantly improved functional recovery of adult rats compared to regular transplantation.

Tracheostomy is frequently performed in severe cervical spinal cord injury (SCI) patients with the pulmonary dysfunction. A series of respiratory nursing interventions are required to plan tracheostomy removal. Tracheostomy was performed in 29 patients after acute traumatic cervical SCI. A series of respiratory nursing interventions were introduced in these patients after closed tracheostomy and decannulation, including closed tracheostomy tube training, manually assisted cough. Chacheostomy was successfully removed in 21 patients after the respiratory nursing interventions. In contrast, eight patients died from associated injuries. The average time from tracheostomy to decannulation was 40 days (14–104 days), the average time from closed tracheostomy to decannulation was 18.80 ± 13.50 days. Second tracheostomy was performed in one patient after 29 days’ removal due to pulmonary infection. One patient presented with delayed incision healing for 29 days. Closed tracheostomy tube training and manually assisted cough are key factors for tracheostomy removal, although intensive nursing are also needed. The time from tracheostomy to decannulation and from closed tracheostomy to decannulation is increased in case of "late" (>24 h) tracheostomy and longer mechanical ventilation.

Our aim was to investigate a novel approach to perform preoperative evaluation patients who underwent middle cerebral artery (MCA) percutaneous transluminal angioplasty and stenting (PTAS).Sixty-five patients with symptomatic MCA stenosis of at least70% who underwent MCA PTAS were enrolled. The multimodal stroke assessment using CT (MOSAIC) score was used to evaluate the preoperative condition. The Alberta Stroke Program Early Computed Tomography Scoring (ASPECTS) was used to assess the time-to-peak (TTP) parameter of Computer tomography perfusion (CTP). The factors potentially improving TTP following stenting were investigated. The prognostic value of the MOSAIC scores to predict TTP improvement was analyzed and compared.The MOSAIC score was a reliable prognostic tool for the degree of improvement of TTP (odds ratio 1.89 [1.08-2.07], P.01) in patients with PTAS. The MOSAIC score had a higher prognostic accuracy than the degree of CBF deficit, the degree of stenosis, and the amount of tissue infarction. During 1-year follow-up, the stroke and death rate of was 8.1%, the in-stent restenosis rate was 6.5%, and good final outcome (modified Rankin Scale ≤ 2) was observed in 76.9%.The MOSAIC score can be reliably used in selecting patients with MCA stenosis for PTAS.