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The relationship between ionized calcium and prognosis of ischemic stroke is controversial. We aim to determine the relationship of admission ionized calcium levels with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT).Consecutive anterior circulation AIS patients treated with recombinant tissue plasminogen activator (rt-PA) were retrospectively enrolled. According to ionized calcium quartiles, the patients were divided into four groups and clinical data were analyzed between groups. Ionized calcium was entered into logistic regression analysis in two models, separately: model 1, calcium as a continuous variable (per 1-mmol/L increase), and model 2, calcium as the four-categorized variable (being collapsed into quartiles: Q1-Q4). Early neurologic improvement (ENI) was defined as improvement of four or more points at 24 h after intravenous rt-PA, while long-term good outcome as the modified Rankin Scale (mRS) 0-1 at 90 days.A total of 546 patients met the study criteria (mean age was 63.51 ± 11.26 years and 365 [66.8%] were men). The median admission National Institute of Health Stroke Scale was 9 (range 4 to 15). When not adjusted, in model 1: ionized calcium was related to good outcome (odds ratio [OR] 69.061, 95%CI: 1.638-2911.111, p=0.027), but not ENI (OR 14.097, 95%CI: 0.133-1492.596, p=0.266); in model 2: compared with Q4, while good outcome was less common in Q1 (OR 0.623, 95%CI: 0.388-0.999, p=0.049). After adjusting for confounding factors, calcium in Q2 (OR 0.502, 95%CI: 0.253-0.997, p=0.049) was independently associated with ENI, but no matter as a continuous variable or categorized variable, ionized calcium displayed no association with a good outcome.The current results found that ionized calcium might be associated with early neurological improvement, but had no association with 3 months' outcome in anterior circulation AIS patients after IVT.

Introduction: The delipid extracorporeal lipoprotein filter from plasma (DELP) has been approved for the treatment of acute ischemic stroke (AIS) by the China Food and Drug Administration, but its effectiveness and mechanism are not yet fully determined. The purpose of this study was to evaluate the effect of DELP treatment on AIS patients after intravenous thrombolysis. Methods: A retrospective study was performed on AIS patients with no improvement within 24 h after intravenous thrombolysis who were subsequently treated with or without DELP. Primary outcome was the proportion with a modified Rankin scale (mRS) of 0–1 at 90 days. Secondary outcomes were changes in National Institute of Health Stroke Scale (NIHSS) score from 24 h to 14 days after thrombolysis, and the rate of improvement in stroke-associated pneumonia (SAP). The main safety outcomes were the rates of symptomatic intracranial hemorrhage and mortality. To investigate its mechanisms, serum biomarkers were measured before and after DELP. Results: A total of 252 patients were recruited, 63 in the DELP group and 189 matched patients in the NO DELP group. Compared with the NO DELP group, the DELP group showed an increase in the proportion of mRS 0–1 at 90 days (p = 0.042). More decrease in NIHSS from 24 h to 14 days (p = 0.024), a higher rate of improvement in SAP (p = 0.022), and lower mortality (p = 0.040) were shown in DELP group. Furthermore, DELP decreased levels of interleukin (IL)-1β, E-selectin, malondialdehyde, matrix metalloprotein 9, total cholesterol, low-density lipoprotein, and fibrinogen, and increased superoxide dismutase (p< 0.05). Conclusions: DELP following intravenous thrombolysis should be safe, and is associated with neurological function improvement, possibly through multiple neuroprotective mechanisms. Prospective trials are needed.

Rationale A large number of basic and clinical studies have proved that remote ischemic conditioning has neuroprotective effect. For example, remote ischemic conditioning showed a neuroprotective role in cerebral ischemia-reperfusion injury model. Recent clinical studies suggested that remote ischemic conditioning may improve neurological function and reduce the risk of recurrence in ischemic stroke patients. However, there is a lack of convincing evidence for the neuroprotective effect of remote ischemic conditioning on ischemic stroke, which deserves further study. Aim To explore the efficacy and safety of remote ischemic conditioning for acute moderate ischemic stroke. Sample size estimates A maximum of 1800 subjects are required to test the superiority hypothesis with 80% power according to a one-sided 0.025 level of significance, stratified by gender, age, time from onset to treatment, National Institutes of Health Stroke Scale (6–10 vs. 11–16), degree of responsible vessel stenosis, location of stenosis, and stroke etiology. Methods and design Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke is a prospective, random, open label, blinded endpoint and multi-center study. The subjects are divided into experimental group and control group randomly. The experimental group was treated with remote ischemic conditioning twice daily with 200 mmHg pressure for 10–14 days besides guideline-based therapy. The control group was treated according to the guidelines. Study outcome The primary efficacy endpoint is favorable functional outcome, defined as modified Rankin Scale 0–1 at 90 days post-randomization.

Rationale The evidence of intravenous thrombolysis in patients with not clearly disabling minor stroke (low National Institutes of Health Stroke Scale of 0–5) is still insufficient. Recent early terminated PRISMS trial could not provide definitive conclusion, although suggesting the similar functional outcome between alteplase and aspirin groups. Recent two clinical trials provide a definitive evidence for the superiority of dual antiplatelet to mono-antiplatelet in minor stroke. However, the efficacy and safety of dual antiplatelet vs. alteplase in the treatment of acute minor stroke are not known. Aim To explore the efficacy and safety of dual antiplatelet with aspirin and clopidogrel vs. alteplase in the treatment of acute minor stroke. Sample size estimates A maximum of 760 subjects are required to test the non-inferiority hypothesis with 80% power according to a one-sided 0.025 level of significance, stratified by age, diabetes, time from onset to treatment, stroke etiology, degree of vascular stenosis, location of index vessel. Methods and design ARAMIS is a prospective, randomized, open label, blinded assessment of endpoints (PROBE) and multicenter clinical trial in China. The subjects are randomized to the control arm (intravenous alteplase with standard dose of 0.9 mg/kg, followed by guideline-based treatment 24 h after thrombolysis) or the experiment arm (clopidogrel: loading dose of 300 mg on the first day, followed by 75 mg daily for 10–14 days; aspirin: 100 mg on the first day, followed by 100 mg daily for 10–14 days; after the combination, antiplatelet will be given based on guideline till 90 days). Study outcome The primary efficacy endpoint is favorable functional outcome, defined as a mRS 0–1 assessed at 90-day post-randomization.

There is a lack of studies on anticoagulant plus antiplatelet therapy for acute ischemic stroke. The present study made a pilot effort to investigate the efficacy and safety of argatroban plus dual antiplatelet therapy (DAPT) in patients with acute posterior circulation ischemic stroke (PCIS). We retrospectively collected patients diagnosed with acute PCIS according to inclusion/exclusion criteria. According to treatment drugs, patients were divided into an argatroban plus DAPT group and a DAPT group. The primary efficacy end point was the proportion of early neurological deterioration (END). The primary safety outcome was symptomatic intracranial hemorrhage. All outcomes were compared between the 2 groups before and after propensity score matching (PSM). A total of 502 patients were enrolled in the study, including 35 patients with argatroban plus DAPT and 467 patients with DAPT. There was a higher National Institutes of Health Stroke Scale (NIHSS) score in the argatroban plus DAPT group than the DAPT group before PSM (3 vs 2, P = .017). Compared with the DAPT group, the argatroban plus DAPT group had no END (before PSM: 0% vs 6.2%, P = .250; after PSM: 0% vs 5.9%, P = .298). Argatroban plus DAPT yielded a significant decrease in the NIHSS score from baseline to 7 days after hospitalization, compared with that of the DAPT group before PSM ( P = .032), but not after PSM ( P = .369). No symptomatic intracranial hemorrhage was found in any patient. A short-term combination of argatroban with DAPT appears safe in acute minor PCIS.

Chronic restraint stress exacerbates pain and inflammation. The present study was designed to evaluate the effect of chronic restraint stress on inflammatory pain induced by subcutaneous injection of bee venom (BV).First, we investigated: (1) the effect of two-week restraint stress with daily 2 or 8 h on the baseline paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL) and paw circumference (PC); (2) the effect of chronic stress on the spontaneous paw-flinching reflex (SPFR), decrease in PWM, PWTL and increase in PC of the injected paw induced by BV.The results showed that (1) chronic restraint decreased significantly the PWMT and inhibited significantly the increase in PC, but had no effect on PWTL, compared with control group; (2) chronic restraint enhanced significantly BV-induced SPFR and inflammatory swelling of the injected paw. In a second series of experiments, the role of P2X7 receptor (P2X7R) in the enhancement of BV-induced inflammatory pain produced by chronic restraint stress was determined. Systemic pretreatment with P2X7R antagonist completely reversed the decrease in PWMT produced by chronic restraint, inhibited significantly the enhancement of BV-induced inflammatory pain produced by chronic restraint stress.Taken together, our data indicate that chronic restraint stress-enhanced nociception and inflammation in the BV pain model, possibly involving the P2X7R.

A recent study showed that brain-derived neurotrophic factor (BDNF) may play a role in the development of the neuropathic pain resulting from injury to motor efferent fibres, such as that in the ventral root transection (VRT) model. Capsaicin stimulation of afferent fibres was also shown to result in the release of BDNF into the spinal cord. Here, the effects of ablation of capsaicin-sensitive primary afferents (CSPAs) by local application of capsaicin on the sciatic nerve on VRT-induced mechanical hyperalgesia were observed.The paw withdrawal mechanical threshold (PWMT) was measured before and then 1 and 3 days and 1, 2, 3, 4 and 6 weeks after VRT.The results showed that local application of capsaicin significantly inhibited the decrease in the PWMT induced by VRT, suggesting the inhibitory effect of locally delivered capsaicin. Furthermore, intrathecal administration of exogenous BDNF not only produced mechanical hyperalgesia but also significantly blocked the inhibitory effect of capsaicin.Taken together, the results of this study suggest that CSPA fibres may contribute to mechanical hyperalgesia in the VRT model.

Objective To investigate the effects of adenosine 5'-monophosphate-activated protein kinase (AMPK) and phosphated AMPK (pAMPK) signals in ischemic preconditioning (IPC), and the effect of pharmacological intervention of AMPK on infarct size of the brain. Methods A brief (3min) middle cerebral artery occlusion (MCAO) was employed to induce IPC in male rat, and another 90-min MCAO was performed 4 or 72h later. The levels of AMPK and pAMPK were assessed after IPC. A pharmacological activator metformin, or inhibitor compound C of AMPK, was used to analyze the correlation of IPC to AMPK signaling in MCAO rats. Results The infarct size of total cerebral hemisphere and cortex was significantly decreased in MCAO animals by IPC for 72h (P0.05, n=6). The AMPK activator metformin can significantly reverse the protective effect of IPC (P

Introduction We aimed to explore potential cytokines involved in the malignant middle cerebral artery infarction (MMI) and elucidate their underlying regulatory mechanisms. Methods We first developed a cytokine profile by Quantibody® Human Cytokine Antibody Array7000 using serum samples from eight patients with MMI and eight patients with non-acute cerebral infarction (NACI). The differentially expressed cytokines were then identified in patients with MMI using two-tailed Student's t-test and Fisher's Exact Test compared with patients with NACI. Gene Ontology and pathway enrichment analyses were performed using DAVID. Protein–protein interaction (PPI) network was constructed based on STRING database. Results A total of 10 differentially expressed cytokines were identified from 320 unique inflammatory cytokines in serums. Among them, four cytokines, like NCAM1 (neural cell adhesion molecule 1), IGFBP-6 (insulin-like growth factor binding protein 6), LYVE1 (lymphatic vessel endothelial hyaluronan receptor 1), and LCN2 (Lipocalin2), were up-regulated, while another six cytokines, such as TGFB1 (transforming growth factor, beta 1, also known as LAP), EGF (epidermal growth factor), PDGFA (platelet-derived growth factor alpha polypeptide), MMP-10 (matrix metallopeptidase 10), IL-27 (interleukin 27), and CCL2 (chemokine (C-C motif) receptor 2), were down-regulated. Moreover, cytokine–cytokine receptor interaction pathway was significantly enriched. Conclusions Our findings indicate that 10 differentially expressed cytokines, such as NCAM1, LCN2, IGFBP-6, LYVE1, MMP-10, IL-27, PDGFA, EGF, CCL2, and TGFB1 may participate in the development of MMI. Moreover, cytokine–cytokine receptor interaction pathway may be an important mechanism involved in this disease. These differentially expressed cytokines may serve as diagnostic biomarkers or drug targets for MMI.

Parkinson’s disease (PD) and Parkinsonism are common neurodegenerative disorders with continuously increasing prevalence, causing high global burdens. However, data concerning the comorbidity burden of patients with PD or Parkinsonism in China are lacking. To investigate the health condition and comorbidity burden, a total of 3367 PD and 823 Parkinsonism patients were included from seven tertiary hospitals in seven cities across China from 2003 to 2012. Their comorbidity burden was collected and quantified by the Elixhauser Comorbidity Index (ECI) and Charlson Comorbidity Index (CCI). The comorbidity spectra differed between PD and Parkinsonism patients. Compared with PD patients, Parkinsonism patients were older (69.8 ± 11.5 vs. 67.9 ± 11.4, P P P P P

Background and Purpose Dehydration was found to be involved in the poor prognosis of patients with acute ischemic stroke. It is unclear whether dehydration status before onset is related with prognosis of thrombolysed patients with acute ischemic stroke. If it is the case, quickly hydrating may improve the prognosis. The present study was designed to explore the issue. Methods Eligible 294 patients with acute ischemic stroke after thrombolysis were enrolled in the present study according to inclusion/exclusion criteria. According to the modified Rankin scale (mRS) 90 days post stroke, the patients were divided into two groups: mRS 0–2 (n = 191) and mRS 3–6 (n = 103). In the present study, BUN/Cr ≥ 15 combined with USG > 1.010 or either of them were chosen as dehydration marker. Clinical data were analyzed between two groups. Univariate and multivariate statistical analyses were carried out. Results Age, fibrinogen, blood glucose, BUN/Cr, NIHSS score at admission, the systolic blood pressure (SBP) before thrombolysis, dehydration status (BUN/Cr ≥ 15 plus USG > 1.010), hyperlipidemia, USG and D‐dimer on admission day, and TOAST classification showed significant difference between two groups (p 150 were markedly associated with poor outcome (mRS 3–6, p 1.010 as a marker of dehydration status was an independent risk factor for long‐term poor prognosis of thrombolysed patients with acute ischemic stroke.

This paper gets a further study to cladding of Ni-based Titanium Carbide in the surface of die steel of 718, This paper introduces the effect of laser process parameters on the titanium carbide and nickel solid solution and cemented carbide in cladding layer; on that basis, this paper studied the effect of the different of powder paving thickness, laser power and scanning velocity and other parameters on microstructure and properties of cladding layer. By controlling the powder-bed depth, using suitable laser cladding power and scanning speed, we can get the cladding layer of compact structure, no holes or no cracks. Experiments were carried out to get suitable process parameters, and analyzed its mechanism. It has certain significance guiding to improve the laser cladding of 718 die steel quality

It is generally believed that the development of neuropathic pain primarily results from injuries to sensory afferent fibers. Recent studies found that injuries to the motor efferent fibers (e.g. ventral root transection) also contribute to the development of neuropathic pain. Furthermore, an increase in brain-derived neurotrophic factor (BDNF) synthesis has been found in the ventral root transection model, suggesting a possible role of BDNF in this model. To determine the role of BDNF, we observed the effects of intrathecal antibody against BDNF treatment on ventral root transection-induced mechanical hyperalgesia. Paw withdrawal thresholds to mechanical stimuli were measured before and after surgery. The results showed that ventral root transection in rats produced a significant, lasting decrease of mechanical withdrawal thresholds, presenting the development of mechanical hyperalgesia. Intrathecal antibody against BDNF treatment markedly inhibited ventral root transection-induced mechanical hyperalgesia in a dose-related manner. The findings suggest that BDNF-mediated signaling pathway within spinal cord may be involved in the development of neuropathic pain involving injuries to motor efferent fibers.

We aimed to profile cytokines in patients with malignant middle cerebral artery infarction (MMI) and non-acute cerebral infarction (NACI), and identify potential cytokines for early prediction of MMI.A total of 16 subjects were recruited, including 8 patients with MMI and 8 patients with NACI. Cytokine profiles and levels in serums were analyzed by QuantibodyThe concentrations of 320 unique inflammatory cytokines in serums were measured. Ten cytokines were discovered to be differentially expressed between patients with MMI and patients with NACI, including transforming growth factor beta-1 (TGFB1), matrix metallopeptidase 10 (MMP10), neural cell adhesion molecule 1 (NCAM1), interleukin-27 (IL27), epidermal growth factor (EGF), insulin-like growth factor-binding protein 6 (IGFBP6), platelet-derived growth factor subunit A (PDGFA), C-C motif chemokine 2 (C-C CCL2), neutrophil gelatinase-associated lipocalin (Lipocalin 2) and lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1). Among these cytokines, the concentrations of NCAM1, IGFBP6, Lipocalin2 and LYVE1 were significantly higher while the concentrations of the other six cytokines were significantly lower in patients with MMI compared with those in patients with NACI. Multivariate logistic regression analysis verified the association of these 10 cytokines with MMI except for IL-27 (p = 0.5422).Nine cytokines, including NCAM1, IGFBP6, Lipocalin2, LYVE1, TGFB1, MMP10, EGF, PDGFA and CCL2, might act as potential markers for early prediction of MMI and involve in the progression from NACI to MMI. Further studies with a better control group are still needed.

The present study investigated the role of thrombin in the expression of protease-activated receptor-1 (PAR-1), and the effect of argatroban (Arg) a direct thrombin inhibitor, on PAR-1 expression in perihematomal tissue with intracerebral hemorrhage (ICH). For these experiments 90 rats were divided into 5 groups: sham, ICH, argatroban-treated ICH (ICH+Arg), thrombin (TM) and argatroban-treated thrombin (TM+Arg). The ICH model or thrombin injection models were established by injecting autologous blood or thrombin, respectively. Rats in TM+Arg and ICH+Arg groups were administered argatroban (0.9mg/kg) after models were established for 3h and 12h, intraperitoneally. All rats were killed to harvest brains after models were established for 24h. The levels of PAR-1 protein and PAR-1 mRNA expression were detected by Western blot and RT-PCR, respectively. Brain water content was also measured. Our results showed that the levels of PAR-1 protein or PAR-1 mRNA in ICH and TM groups were up-regulated compared to that observed for the sham group; while the levels observed in ICH+Arg group and TM+Arg group were significantly lower than that observed for the ICH group and TM group (P

The exploitation of Lamadian oil field P layer has been in the ultra-high water stage, there is a serious inefficient circulation of injected water. Low cost asphalt particle profile control technology has been researched and carried out in this reservoir. While, there is still no guidance for size-selection of asphalt particles in application. In this paper, based on simulation profile control experiment in laboratory, using three layer heterogeneous cores with rectangle conducting section, the asphalt particle size had been selected under two kinds of injection rate to match different permeability formation. At the same time, the scour resistance of asphalt particle was evaluated. This paper illusrates that different permeability cores can be injected different particle size limit: 0.06mm asphalt particle can be injected into 500×10 -3 μm 2 permeability core; 0.1mm asphalt particle can be injected into 1500×10 -3 μm 2 permeability core; 0.3mm asphalt particle can be injected into 3000×10 -3 μm 2 permeability core. The bigger the size of asphalt particle, the greater the resistance to scour.

Recently, P2X7 receptor (P2X7R) has been found to contribute to the development of inflammatory pain, however, the role of spinal P2X7R is not clear. The present study was designed to determine the roles of spinal P2X7R in the bee venom (BV) model, characterized by multiple pain-related behaviors and obvious inflammatory edema. We determined the effects of P2X7R antagonist A438790 on BV-induced PSN, mechanical allodynia and inflammatory swelling. Pre-treatment with intrathecal administration of A438079 significantly inhibited BV-induced PSN and mechanical allodynia in a dose-dependent manner, but had no effect on BV-induced inflammatory swelling. These data suggest that the activation of spinal P2X7Rs may play a key role in BV-induced nociception, but not inflammation.