Intravenous Tirofiban Versus Alteplase Before Endovascular Treatment in Acute Ischemic Stroke: A Pooled Analysis of the DEVT and RESCUE BT Trials.

BACKGROUND: The present study aimed to evaluate the efficacy and safety of intravenous tirofiban versus alteplase before endovascular treatment (EVT) in acute ischemic stroke patients with intracranial large vessel occlusion. METHODS: This was a post hoc analysis using data from 2 multicenter, randomized trials: the DEVT trial (Direct Endovascular Treatment for Large Vessel Occlusion Stroke) from May 2018 to May 2020 and the RESCUE BT trial (Intravenous Tirofiban Before Endovascular Thrombectomy for Acute Ischemic Stroke) from October 2018 to October 2021. Patients with acute intracranial large vessel occlusion within 4.5 hours from last known well were dichotomized into 2 groups: tirofiban plus EVT versus alteplase bridging with EVT. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 3-month mortality. Multivariable logistic regression (adjusting for baseline systolic blood pressure, occlusion site, onset-to-puncture time, anesthesia, and first choice of EVT) and propensity score overlap weighting (balance in demographic covariates, stroke characteristics, and initial management between groups) were performed. RESULTS: One-hundred and eighteen alteplase-treated patients in the DEVT trial and 98 tirofiban-treated patients in the RESCUE BT trial were included (median age, 70 years; 115 [53.2%] men). The rate of functional independence was 60.2% in the tirofiban group compared with 46.6% in the alteplase group (adjusted odds ratio, 1.25 [95% CI, 0.60-2.63]). Compared with alteplase, tirofiban was not associated with increased risk of symptomatic intracranial hemorrhage (6.8% versus 9.2%; P=0.51) and mortality (17.8% versus 19.4%; P=0.76). The propensity score overlap weighting analyses showed consistent outcomes. CONCLUSIONS: Among patients with intracranial large vessel occlusion within 4.5 hours of onset, tirofiban plus EVT was comparable to alteplase bridging with EVT regarding the efficacy and safety outcomes. These findings should be interpreted as preliminary and require confirmation in a randomized trial. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Effects of admission hyperglycemia and intravenous thrombolysis allocation in acute basilar artery occlusion after endovascular treatment: Analysis of the ATTENTION registry.

This study was to investigate the admission hyperglycemia and modified effect of intravenous thrombolysis (IVT) on clinical outcomes in acute basilar artery occlusion (BAO) patients receiving endovascular treatment (EVT). We prospectively recruited acute BAO patients from 48 stroke centers across 22 Chinese provinces in the ATTENTION registry from 2017 to 2021. Hyperglycemia on admission was defined as glucose ≥7.8 â€‹mmol/L. We performed multivariable logistic regression analysis to evaluate the correlation of hyperglycemia on admission with the primary outcome defined as a modified Rankin scale (mRS) score of <4 â€‹at 90 days, and the secondary outcomes defined as successful recanalization, mRS 0-1 and 0-2 â€‹at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and mortality within 90 days. There were 1195 patients with acute BAO treated with EVT of whom 519 had hyperglycemia on admission. Hyperglycemia on admission was inversely associated with favorable neurological outcomes (mRS 0-3: adjusted odd ratio [aOR] 0.69, 95 â€‹% confidence intervals [CI] 0.54-0.89, P â€‹= â€‹0.004; mRS 0-1: aOR 0.67, 95 â€‹% CI 0.50-0.90, P â€‹= â€‹0.008; mRS 0-2: aOR 0.73, 95 â€‹% CI 0.56-0.95; P â€‹= â€‹0.02). Hyperglycemia on admission was not correlated to sICH nor successful recanalization. In the subgroup of BAO patients treated with direct EVT, those with hyperglycemia on admission had a higher mortality rate, and overall worse clinical outcomes at 90 days than patients without hyperglycemia. A significant interaction was observed between IVT and hyperglycemia on admission (Pinteraction â€‹= â€‹0.017). In patients with acute BAO treated with EVT, hyperglycemia on admission was associated with worse functional outcomes at 90 days but was not correlated with sICH nor successful recanalization. The effect of admission hyperglycemia appears to be modified by IVT allocation. Unique identifier: ChiCTR2000041117.

A Novel Bifunctional µOR Agonist and σ1R Antagonist with Potent Analgesic Responses and Reduced Adverse Effects.

Bifunctional ligands possessing both µOR agonism and σ1R antagonism have shown promise in producing strong analgesic effects with reduced opioid-related side effects. However, the µOR agonism activity of most dual ligands diminishes compared with classical opioids, raising concern about their effectiveness in managing nociceptive pain. In this study, a new class of dual µOR agonist/σ1R antagonist was reported. Through structure-activity relationship analyses, we identified the optimal compound, 4x, which displayed picomolar µOR agonism activity (EC50: 0.6 ± 0.2 nM) and good σ1R inhibitory activity (Ki: 363.7 ± 5.6 nM) with excellent selectivity. Compound 4x exhibited robust analgesic effects in various pain models, with significantly reduced side effects. Importantly, compound 4x also possessed good safety profiles and no abnormalities were observed in biological parameters even under a high dosage. Our findings suggest that 4x may be a promising lead compound for developing safer opioids and warrants further in-depth studies.

Overwintering performance of bamboo leaves, and establishment of mathematical model for the distribution and introduction prediction of bamboos.

Bamboo has great economic values and is used extensively in many industries, and their natural distribution range was divided into 12 zones in China according to the temperature of their geographical distribution in previous works. Different bamboo species had significantly different abilities in low-temperature tolerance, which need to be considered carefully during ex-situ introduction. In this paper, we observed and evaluated the low-temperature damage of 19 bamboo species in winter, and measured the physiological changes of bamboo leaves. A total of 3060 leaf samples were obtained from 102 core collections in 34 bamboo species from the 5 regions of Chinese mainland for anatomical comparison, in order to screen out the key anatomical indicators related to their low-temperature tolerance and to establish a mathematical prediction model for bamboo introduction. The results showed that the low-temperature resistance of clustered bamboos was generally lower than that of the scattered bamboos. The decreased temperature led to the constant decrease of net photosynthetic rate and transpiration rate, but the increase of soluble sugar content in all bamboo species. There was no dormancy for all bamboo species in winter. The temperate bamboos showed lower photosynthesis as compared to tropical bamboos in winter. The leaf shape of bamboos was closely related to their distribution. A total of 13 leaf indicators were screened and more suitable to estimate the low-temperature tolerant abilities of bamboos and to predict their distribution. The MNLR (multiple nonlinear regression) mathematical model showed the highest fitting degree and the optimal prediction ability in the potential northernmost introduction range of bamboos. This study lay a foundation for bamboo introduction, and could also reduce the economic losses caused by the wrong introduction.

Algorithms Research and Precision Comparison of Different Frequency Combinations of BDS-3\GPS\Galileo for Precise Point Positioning in Asia-Pacific Region.

With the continuous construction and development of the BeiDou navigation satellite system (BDS), its positioning performance is constantly being improved. In this study, the positioning performance of different frequency combinations of BDS-3/GPS/Galileo in the Asia-Pacific region was investigated. The precision products of Wuhan University and the observation data of nine MGEX stations were selected to compare and analyze the B1I\B1C\B2a\B3I and L1\E1 pseudo-range Standard Point Positioning (SPP) and B1IB2a\B1IB3I\B1CB2a\B1CB3I\B2aB3I\L1L2\E1E5a precise point positioning (PPP) performance, while B1I\B3I\L1 SPP and B1IB3I PPP were investigated using BDS-2 with QZSS supplemented with BDS-3 and GPS. The experimental results showed that the positioning precision of BDS-3/GPS/Galileo SPP was in the order of B1C > E1 > L1 > B1I > B3I > B2a, and it was not significantly improved after BDS-2 and QZSS were added. Moreover, for the PPP of different frequency combinations, the convergence speed was in the order of L1L2 > B1IB3I > E1E5a > B1CB3I > B1CB2a > B1IB2a > B2aB3I. After adding BDS-2, B1IB3I improved by about 11% in static mode and 27% in kinematic mode, which was similar to the L1L2 frequency combination. The positioning precision of different frequency combinations of BDS-3/GPS/Galileo was B1IB3I > B1CB3I > L1L2 > E1E5a > B1B2a > B1CB2a > B2aB3I. In static mode, after adding BDS-2, B1IB3I did not show significant improvement in the plane direction, and showed ~61% improvement in the elevation direction, and ~67% in the three-dimensional (3D) direction. In kinematic mode, after adding BDS-2, B1IB3I was improved by about 16% in the E direction, the N direction did not show significant change, it improved by ~38% in the U direction and by ~70% in the 3D direction. In general, the positioning performance of BDS-3 was slightly better than those of GPS and Galileo in the Asia-Pacific region, and it is believed that with the continuous development of BDS, its positioning performance will surely be improved further.

Plasticity in the Morphology of Growing Bamboo: A Bayesian Analysis of Exogenous Treatment Effects on Plant Height, Internode Length, and Internode Numbers.

Sucrose (Suc) and gibberellin (GA) can promote the elongation of certain internodes in bamboo. However, there is a lack of field studies to support these findings and no evidence concerning how Suc and GA promote the plant height of bamboo by regulating the internode elongation and number. We investigated the plant height, the length of each internode, and the total number of internodes of Moso bamboo (Phyllostachys edulis) under exogenous Suc, GA, and control group (CTRL) treatments in the field and analyzed how Suc and GA affected the height of Moso bamboo by promoting the internode length and number. The lengths of the 10th-50th internodes were significantly increased under the exogenous Suc and GA treatments, and the number of internodes was significantly increased by the exogenous Suc treatment. The increased effect of Suc and GA exogenous treatment on the proportion of longer internodes showed a weakening trend near the plant height of 15-16 m compared with the CTRL, suggesting that these exogenous treatments may be more effective in regions where bamboo growth is suboptimal. This study demonstrated that both the exogenous Suc and GA treatments could promote internode elongation of Moso bamboo in the field. The exogenous GA treatment had a stronger effect on internode elongation, and the exogenous Suc treatment had a stronger effect on increasing the internode numbers. The increase in plant height by the exogenous Suc and GA treatments was promoted by the co-elongation of most internodes or the increase in the proportion of longer internodes.

Saliva diagnostics: emerging techniques and biomarkers for salivaomics in cancer detection.

INTRODUCTION: The pursuit of easy-to-use, non-invasive and inexpensive diagnostics is an urgent task for clinicians and scientists. Saliva is an important component of body fluid with regular changes of contents under various pathophysiological conditions, and the biomarkers identified from saliva shows high application potentials and values in disease diagnostics. This review introduces the latest developments in saliva research, with an emphasis on the detection and application of salivary biomarkers in cancer detection. AREAS COVERED: Detection of disease-specific biomarkers in saliva samples by existing salivaomic methods can be used to diagnose various human pathological conditions and was introduced in details. This review also covers the saliva collection methods, the analytical techniques as well as the corresponding commercial products, with an aim to describe an holistic process for saliva-based diagnostics. EXPERT OPINION: Saliva, as a non-invasive and collectable body fluid, can reflect the pathophysiological changes of the human body to a certain extent. Identification of reliable saliva biomarkers can provide a convenient way for cancer detection in clinical applications.

STC1 ameliorates cognitive impairment and neuroinflammation of Alzheimer's disease mice via inhibition of ERK1/2 pathway.

OBJECTIVE: To investigate the regulatory role of STC1 (Stanniocalcin-1) mediated ERK1/2 pathway in cognitive impairment and neuroinflammation of Alzheimer's disease (AD). METHODS: WT mice and STC1 Tg mice (transgenic overexpression of STC1) were used to establish AD models to perform behavioral test by Morris water maze. Hippocampal cell apoptosis was quantified by TUNEL staining, the levels of inflammatory cytokines in serum and hippocampal tissues determined by ELISA, as well as oxidative stress-related factors detected by corresponding testing kits, and protein expression of STC1 and ERK1/2 pathway measured by Western blotting. RESULTS: Compared with WT Sham group, WT AD mice had prolonged escape latency, decreased crossing platform times, increased hippocampal cell apoptosis with up-regulated inflammatory cytokines and oxidative stress-related factors, as well as increased STC1 and ERK1/2 pathway-related molecules. By contrast, STC1 Tg AD mice showed shortened escape latency, increased crossing platform times than WT AD mice, and they also exhibited the decreased apoptosis index and inflammatory cytokines, alleviated oxidative stress-injury, down-regulated protein expression of ERK1/2 pathway, and up-regulated the protein expression of STC1 and UCP2. CONCLUSION: STC1 overexpression could alleviate oxidative stress-induced injury, reduce neuroinflammation, improve cognitive function to play a neuro-protective role by inhibiting ERK1/2 signaling pathway.

The atypical binding mechanism of second calcium on phospholipase A2 group IIE.

Secreted phospholipase A2s (sPLA2s) are calcium dependent enzymes involved in various biological events such as lipid metabolism and inflammation. We previously identified the second calcium (Ca2) binding site of human sPLA2 Group IIE (hGIIE) by structural study and suggested that Asn21 act as the switch of Ca2 binding to modulate the enzymatic activity, but the detailed Ca2 binding mechanism is still unclear. Combined with enzymatic assay, model analysis and calcium binding affinity data for mutated hGIIE proteins, we herein further demonstrate that the flexibly bound Ca2 is essential for the catalysis of hGIIE, unlike the stable binding of Ca2 in hGIIA that replenishes the calcium in the typical loop during the reaction. The atypical Ca2 binding feature of hGIIE will provide a better understanding on the catalytic mechanism of hGIIE.

A selective and sensitive near-infrared fluorescent probe for real-time detection of Cu(i).

The disruption of copper homeostasis (Cu+/Cu2+) may cause neurodegenerative disorders. Thus, the need for understanding the role of Cu+ in physiological and pathological processes prompted the development of improved methods of Cu+ analysis. Herein, a new near-infrared (NIR) fluorescent turn-on probe (NPCu) for the detection of Cu+ was developed based on a Cu+-mediated benzylic ether bond cleavage mechanism. The probe showed high selectivity and sensitivity toward Cu+, and was successfully applied for bioimaging of Cu+ in living cells.

Association between carotid intima media thickness and small dense low-density lipoprotein cholesterol in acute ischaemic stroke.

BACKGROUND: Intima-media thickness (IMT) and small dense low-density lipoprotein cholesterol (sdLDL-C) have been reported to be related to atherosclerosis and stroke. This study is trying to explore the association between IMT and sdLDL-C in Chinese acute ischaemic stroke (AIS) subjects. METHODS: This study enrolled total 368 consecutive AIS patients and 165 non-AIS controls from November 2016 to February 2019. Mean IMT and carotid plaques were measured by using carotid ultrasonography method. Blood glucose and lipid parameters were measured by using an automatic biochemical instrument. SdLDL-C was detected by using the Lipoprint LDL system. IMT > 1.0 mm was defined as increased IMT. Plaque stability based on the nature of the echo was determined by ultrasound examination. Risk factors for IMT were identified by using multivariate logistic regression analysis. A logistic regression model was established to predict AIS risk. Python software (Version 3.6) was used for the statistical analysis of all data. RESULTS: The carotid IMT, proportion of plaques, and the sdLDL-C, triglycerides (TG) and glucose levels were obviously higher in AIS patients than those in controls. SdLDL-C level in the IMT thickening group was higher than that in the normal IMT group. SdLDL-C and total cholesterol (TC) were risk factors for IMT, while sdLDL-C was an independent risk factor. The IMT value of the unstable plaque group was markedly higher than that of the stable plaque group. The predictive value of IMT for AIS was better than that of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) but not as good as that of sdLDL-C. A logistic regression model was established to predict AIS risk. Additionally, carotid IMT and sdLDL-C were closely related to AIS severity and outcomes. CONCLUSIONS: SdLDL-C and TC were risk factors for increased IMT, while sdLDL-C was an independent risk factor. A prediction model based on IMT and other variables was established to screen the population with high AIS risk.

Association of Small Dense Low-Density Lipoprotein Cholesterol with Stroke Risk, Severity and Prognosis.

AIM: To investigate the association of small dense low-density lipoprotein cholesterol (sdLDL-C) and acute ischemic stroke (AIS) in terms of risk, severity, and outcomes. Prediction models were established to screen high-risk patients and predict prognosis of AIS patients. METHODS: We enrolled in this study 355 AIS patients and 171 non-AIS controls. AIS was subtyped according to TOAST criteria, and the severity and outcomes of AIS were measured. Blood glucose and lipid profiles including total cholesterol, triglyceride, and lipoproteins were measured in all patients using automatic measure. Lipoprotein subfractions were detected by the Lipoprint LDL system. RESULTS: As compared with the non-AIS control group, the AIS group had higher sdLDL-C levels. Pearson correlation analysis revealed that the sdLDL-C level and risk of AIS, especially non-cardioembolic stroke, were positively correlated. The area under the curve of sdLDL-C for AIS risk was 0.665, better than that of other lipids. Additionally, the sdLDL-C level was significantly correlated with AIS severity and bad outcomes. A logistic regression model for assessing the probability of AIS occurrence and a prognostic prediction model were established based on sdLDL-C and other variables. CONCLUSIONS: Elevated levels of sdLDL-C were associated with a higher prevalence of AIS, especially in non-cardioembolic stroke subtypes. After adjustment for other risk factors, sdLDL-C was found to be an independent risk factor for AIS. Also, sdLDL-C level was strongly associated with AIS severity and poor functional outcomes. Logistic regression models for AIS risk and prognosis prediction were established to help clinicians provide better prevention for high-risk subjects and monitor their prognosis.

The Effect of Intensive Statin Therapy on Symptomatic Intracranial Arterial Stenosis.

BACKGROUND: The aim of this study was to observe the effect of intensive statin therapy on symptomatic intracranial arterial stenosis. METHODS: overall, 120 patients with symptomatic intracranial arterial stenosis were admitted to the Xiangyang No.1 People's Hospital, Hubei University of Medicine, Xiangyang, China from January 2010 to May 2013. They were randomly divided into three groups and were given different doses of atorvastatin orally for 1 year or more, and followed up for 12 months. The three groups were assessed for clinical end-point event rates and changes in cerebral blood flow value before and after treatment to assess the effectiveness of intensive statin therapy. RESULTS: The incidence rates of end-point cerebrovascular events in the low-dose group (10 mg/d), the general-dose group (20 mg/d) and the intensive treatment group (40 mg/d) were 26.3%, 13.5% and 5.4% respectively during the 12-month follow-up after treatment. There was a significant difference between the low dose group and the intensive treatment group (P<0.05). The relative cerebral blood flow and relative cerebral blood volume of the three groups were significantly higher than those before treatment (P<0.05), and the relative time to peak for the intensive treatment group was shorter than that before treatment (P<0.001). CONCLUSION: Atorvastatin at 40 mg/d has a significant advantage compared with atorvastatin at 20 mg/d and 10 mg/d in reducing cerebrovascular events and improving cerebral blood flow.

The association of hormone signalling genes, transcription and changes in shoot anatomy during moso bamboo growth.

Moso bamboo is a large, woody bamboo with the highest ecological, economic and cultural value of all the bamboo types and accounts for up to 70% of the total area of bamboo grown. However, the spatiotemporal variation role of moso bamboo shoot during growth period is still unclear. We found that the bamboo shoot growth can be divided into three distinct periods, including winter growth, early growth and late growth based on gene expression and anatomy. In the early growth period, lateral buds germinated from the top of the bamboo joint in the shoot tip. Intercalary meristems grew vigorously during the winter growth period and early growth period, but in the late growth period, mitosis in the intercalary meristems decreased. The expression of cell cycle-associated genes and the quantity of differentially expressed genes were higher in early growth than those in late growth, appearing to be influenced by hormonal concentrations. Gene expression analysis indicates that hormone signalling genes play key roles in shoot growth, while auxin signalling genes play a central role. In situ hybridization analyses illustrate how auxin signalling genes regulate apical dominance, meristem maintenance and lateral bud development. Our study provides a vivid picture of the dynamic changes in anatomy and gene expression during shoot growth in moso bamboo, and how hormone signalling-associated genes participate in moso bamboo shoot growth.

Efficacy and safety of intensive statin therapy in Chinese patients with atherosclerotic intracranial arterial stenosis: a single-center, randomized, single-blind, parallel-group study with one-year follow-up.

OBJECTIVES: The purpose of this study is to validate the efficacy of intensive statin therapy for patients with atherosclerotic intracranial arterial stenosis (AICAS). METHODS: In this study, we performed a single-center, randomized, single-blind, parallel-group clinical trial. A total of 120 Chinese patients with AICAS were enrolled and randomly divided into three groups [low-dose atorvastatin therapy (LAT, 10mg/day), standard-dose atorvastatin therapy (SAT, 20mg/day), and intensive-dose atorvastatin therapy (IAT, 40mg/day) groups] in a 1:1:1 ratio. Evaluation variables, including changes in serum lipid profiles, degree of stenosis, and perfusion-related parameters derived from computed tomography perfusion (CTP) imaging from baseline to weeks 26 and 52, as well as the occurrence of cerebrovascular events during the study period, were used to compare the benefits of these three statin therapies. RESULTS: After 52 weeks of treatment, improvement of serum lipid profiles, degree of stenosis, and perfusion-related parameters were all significantly better in the IAT group. In addition, the cumulative probability of cerebrovascular events at 52 weeks was significantly lower in the IAT group than in the LAT group, although there was no statistical difference between the IAT group and the SAT group. The proportion of patients experiencing any adverse event was similar among the three treatment groups. Adverse events caused by IAT were generally mild; no serious adverse events occurred throughout the entire period of study. CONCLUSION: In conclusion, long-term use of IAT appears to be a safe and effective treatment at least for Chinese patients with AICAS.

[Effect of adenovirus-mediated mutant exogenous P27kip1 gene expression on the chemosensitivities of cholangiocarcinoma cell line].

OBJECTIVE: To investigate the effects of mutant exogenous P27(kip1) gene on chemosensitivity of human cholangiocarcinoma cell line. METHODS: The recombinant vector was constructed and the mutant P27(kip1) gene was transfected into human cholangiocarcinoma cell line (QBC(939)). RT-PCR and Western blot were used to determine the expression of target genes. The effects of 5-fluorouracil (5-FU), mitomycin C (MMC) and cyclophosphamide (CTX) on the transfected cells were detected by assaying the apoptotic rate and growth inhibition by methabenzthiazuron (MTT) assay and flow cytometry (FCM). RESULTS: The mutant exogenous P27(kip1) gene was expressed effectively in the cells, and the expression enhanced the apoptosis and growth inhibition of QBC(939) inducted by 5-FU, MMC and CTX. The ratio of growth inhibiting increased significantly from 41.89% (5-FU), 45.59% (MMC), 38.91% (CTX) to 56.15% (5-FU), 55.65% (MMC), 51.69% (CTX), and apoptosis index from 13.76% +/- 3.03% (5-FU), 11.76% +/- 3.99% (MMC), 10.46% +/- 2.10% (CTX) to 41.39% +/- 4.32% (5-FU), 35.94% +/- 2.71% (MMC), 34.46% +/- 2.32% (CTX) (P < 0.05). CONCLUSIONS: The exogenous P27(kip1) gene transfer can remarkably increase the drug sensibility of the cholangiocarcinoma cells. The strategy targeted to control the cell cycle may be more effective in cancer treatment by combination of P27(kip1) gene therapy.