Endovascular therapy in acute ischaemic stroke with large infarction with matched or mismatched clinical-radiological severities: a post-hoc analysis of the ANGEL-ASPECT trial.

Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3-5 or infarct core volume 70-100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18-2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06-2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Prediction of futile recanalisation after endovascular treatment in acute ischaemic stroke: development and validation of a hybrid machine learning model.

BACKGROUND: Identification of futile recanalisation following endovascular therapy (EVT) in patients with acute ischaemic stroke is both crucial and challenging. Here, we present a novel risk stratification system based on hybrid machine learning method for predicting futile recanalisation. METHODS: Hybrid machine learning models were developed to address six clinical scenarios within the EVT and perioperative management workflow. These models were trained on a prospective database using hybrid feature selection technique to predict futile recanalisation following EVT. The optimal model was validated and compared with existing models and scoring systems in a multicentre prospective cohort to develop a hybrid machine learning-based risk stratification system for futile recanalisation prediction. RESULTS: Using a hybrid feature selection approach, we trained and tested multiple classifiers on two independent patient cohorts (n=1122) to develop a hybrid machine learning-based prediction model. The model demonstrated superior discriminative ability compared with other models and scoring systems (area under the curve=0.80, 95% CI 0.73 to 0.87) and was transformed into a web application (RESCUE-FR Index) that provides a risk stratification system for individual prediction (accessible online at fr-index.biomind.cn/RESCUE-FR/). CONCLUSIONS: The proposed hybrid machine learning approach could be used as an individualised risk prediction model to facilitate adherence to clinical practice guidelines and shared decision-making for optimal candidate selection and prognosis assessment in patients undergoing EVT.

Oscillation of type IV pili regulated by the circadian clock in cyanobacterium Synechococcus elongatus PCC7942.

Type IV pili (TFP) are known to be functionally related to cell motilities and natural transformation in many bacteria. However, the molecular and ecological functions of the TFP have rarely been reported for photosynthetic cyanobacteria. Here, by labeling pili in model cyanobacterium Synechococcus elongatus PCC 7942 (Syn7942), we have quantitatively characterized the TFP and its driven twitching motility in situ at the single-cell level. We found an oscillating pattern of TFP in accordance with the light and dark periods during light-dark cycles, which is correlated positively to the oscillating pattern of the natural transformation efficiency. We further showed that the internal circadian clock plays an important role in regulating the oscillating pattern of TFP, which is also supported by evidences at the molecular level by tracking the expression of 16 TFP-related genes. This study adds a detailed picture toward the gap between TFP and its relations to circadian regulations in Syn7942.

Sirt6 regulates the proliferation of neural precursor cells and cortical neurogenesis in mice.

Sirt6, a member of the class III histone deacetylases (HDACs), functions in the regulation of genomic stability, DNA repair, cancer, metabolism and aging. Sirt6 deficiency is lethal, and newborn SIRT6-null cynomolgus monkeys show unfinished brain development. After the generation of a cortex-specific Sirt6 conditional knockout mouse model, we investigated the specific deletion of Sirt6 in NPCs at E10.5. This study found that Sirt6 deficiency causes excessive proliferation of neural precursor cells (NPCs) and retards differentiation. The results suggest that endogenous Sirt6 in NPCs regulates histone acetylation and limits stemness-related genes, including Notch1, in order to participate in NPC fate determination. These findings help elucidate Sirt6's role in brain development and in NPC fate determination while providing data on species generality and differentiation.

Chinese Stroke Association guidelines for clinical management of ischaemic cerebrovascular diseases: executive summary and 2023 update.

BACKGROUND: China is one of the countries with the highest burden of stroke. Implementing multidimensional management guidelines will help clinicians practise evidence-based care, improve patient outcomes and alleviate societal burdens. This update of the 2019 edition will provide the latest comprehensive recommendations for the diagnosis and treatment of ischaemic cerebrovascular diseases. METHODS: We conducted a comprehensive search on MEDLINE (via PubMed) up to 31 August 2023. The writing team established the recommendations through multiple rounds of online and offline discussions. Each recommendation was graded using the evidence grading algorithm developed by the Chinese Stroke Association (CSA). The draft was reviewed and finalised by the CSA Stroke Guidelines Writing Committee. RESULTS: This update included revisions of 15 existing recommendations and 136 new recommendations in the following areas of stroke care: emergency assessment and diagnosis of ischaemic cerebrovascular disease, acute-phase reperfusion therapy, evaluation of underlying mechanisms, antithrombotic therapy, prevention and treatment of complications, and risk factor management. CONCLUSIONS: This guideline updated the recommendations for the clinical management of ischaemic cerebrovascular disease from 2019.

Early versus delayed antihypertensive treatment in patients with acute ischaemic stroke: multicentre, open label, randomised, controlled trial.

OBJECTIVES: To compared the effect of early antihypertensive treatment started within 24-48 h of stroke onset versus delaying treatment until day eight on reducing dependency or death. DESIGN: Multicentre, randomised, open label trial. SETTING: 106 hospitals in China between 13 June 2018 and 10 July 2022. PARTICIPANTS: 4810 patients (≥40 years) were enrolled with acute ischaemic stroke within 24-48 h of symptom onset and elevated systolic blood pressure between 140 mm Hg and <220 mm Hg. INTERVENTIONS: Patients were randomly assigned to receive antihypertensive treatment immediately after randomisation (aimed at reducing systolic blood pressure by 10%-20% within the first 24 h and a mean blood pressure <140/90 mm Hg within seven days) or to discontinue antihypertensive medications for seven days if they were taking them, and then receive treatment on day 8 (aimed at achieving mean blood pressure <140/90 mm Hg). MAIN OUTCOME MEASURES: The primary outcome was the combination of functional dependency or death (modified Rankin scale score ≥3) at 90 days. Intention to treat analyses were conducted. RESULTS: 2413 patients were assigned to the early treatment group and 2397 were assigned to the delayed treatment group. Mean systolic blood pressure was reduced by 9.7% (from 162.9 mm Hg to 146.4 mm Hg) in the early treatment group and by 4.9% (from 162.8 mm Hg to 154.3 mm Hg) in the delayed treatment group within 24 h after randomisation (P for group difference <0.001). Mean systolic blood pressure was 139.1 mm Hg in the early treatment group and 150.9 mm Hg in the delayed treatment group on day seven (P for group difference <0.001). Additionally, 54.6% of patients in the early treatment group and 22.4% in the delayed treatment group had blood pressure of less than 140/90 mm Hg (P<0.001 for group difference) on day seven. At day 90, 289 trial participants (12.0%) in the early treatment group, compared with 250 (10.5%) in the delayed treatment group, had died or experienced a dependency (odds ratio 1.18 (95% confidence interval 0.98 to 1.41), P=0.08). No significant differences in recurrent stroke or adverse events were reported between the two groups. CONCLUSIONS: Among patients with mild-to-moderate acute ischaemic stroke and systolic blood pressure between 140 mm Hg and <220 mm Hg who did not receive intravenous thrombolytic treatment, early antihypertensive treatment did not reduce the odds of dependency or death at 90 days. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03479554.

Can endophytic microbial compositions in cane roots be shaped by different propagation methods.

In practical production, cane stems with buds are generally used as seed for propagation. However, long-terms cane stems only easily lead to some problems such as disease sensitivity, quality loss, etc. Recently, cane seedings, which are produced by tissue culture were used in sugarcane production, but few studies on cane health related to tissue culture seedings. Therefore, to evaluate the immunity and health of sugarcanes growing from different reproduction modes, the endophytic microbial compositions in cane roots between stem and tissue culture seedlings were analyzed using high-throughput techniques. The results showed that the endophytic microbial compositions in cane roots were significant differences between stem and tissue culture seedlings. At the genus level, Pantoea, Bacillus, Streptomyces, Lechevalieria, Pseudomonas, Nocardioides, unclassified_f__Comamonadaceae enriched as the dominant endophytic bacterial genera, and Rhizoctonia, Sarocladium, Scytalidium, Wongia, Fusarium, unclassified_f__Phaeosphaer, unclassified_c__Sordariom, unclassified_f__Stachybot, Poaceascoma, Microdochium, Arnium, Echria, Mycena and Exophiala enriched as the dominant endophytic fungal genera in cane roots growing from the tissue culture seedlings. In contrast, Mycobacterium, Massilia, Ralstonia, unclassified_f__Pseudonocardiacea, norank_f__Micropepsaceae, Leptothrix and Bryobacter were the dominant endophytic bacterial genera, and unclassified_k__Fungi, unclassified_f__Marasmiaceae, Talaromyces, unclassified_c__Sordariomycetes and Trichocladium were the dominant endophytic fungal genera in cane roots growing from stem seedlings. Additionally, the numbers of bacterial and fungal operational taxonomic units (OTUs) in cane roots growing from tissue culture seedlings were significantly higher than those of stem seedlings. It indicates that not only the endophytic microbial compositions in cane roots can be shaped by different propagation methods, but also the stress resistance of sugarcanes can be improved by the tissue culture propagation method.

Effect of left ventricular ejection fraction Spectrum on 1-Year mortality in patients with acute ischemic stroke or transient ischemic attack.

AIMS: We aimed to investigate the association of the left ventricular ejection fraction (LVEF) spectrum with 1-year clinical outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). METHODS: In a prospective registry for the Third China National Stroke Registry (CNSR-III), AIS or TIA patients with echocardiography records during hospitalization were recruited. All LVEFs were categorized into intervals of 5% in width. The lowest and highest intervals are ≤40% and >70%, respectively. The primary outcome was all-cause death at 1 year. Cox proportional hazards regression analysis was performed to investigate the association between baseline LVEF and clinical outcomes. RESULTS: This analysis included a total of 14,053 patients. In total, 418 patients died during 1-year follow-up. Overall, LVEF ≤60% was associated with a higher risk of all-cause death compared to LVEF >60%, independent of demographic and clinical characteristics (aHR 1.29 [95% CI 1.06-1.58]; p = 0.01). The cumulative incidence of all-cause death was significantly different among the eight LVEF groups that survival declined successively with the decrease of LVEF (log-rank p ≤ 0.0001). CONCLUSIONS: Patients with AIS or TIA with decreased LVEF (≤60%) had a lower 1-year survival rate after onset. LVEF 50%-60% even within the normal range, may still contribute to poor outcomes in AIS or TIA. Comprehensive evaluation of cardiac function after acute ischemic cerebrovascular disease should be strengthened.

Aging microplastic aggravates the pollution of heavy metals in rhizosphere biofilms.

Heavy metals (HMs) and microplastics (MPs) are ubiquitous in agricultural soils. Rhizosphere biofilms are important sites for HM adsorption, and biofilms are easily disturbed by soil MPs. However, the adsorption of HMs on rhizosphere biofilms induced by aged MPs is not clear. In this study, the adsorption behavior of Cd(II) on biofilms and pristine/aged polyethylene (PE/APE) was analyzed and quantified. The results showed that the adsorption amount of Cd(II) on APE was greater than that on PE, in which the oxygen-containing functional groups of APE could provide binding sites to increase the adsorption of HMs. Density functional theory (DFT) calculations revealed that the binding energy of Cd(II) onto APE (-6.00 kcal·mol-1) was much stronger than that of PE (7.11 kcal·mol-1) due to hydrogen bonding interactions and oxygen atom-metal interactions. For HM adsorption on MP biofilms, APE increased the adsorption capacity of Cd(II) by 4.7 % relative to PE. The pseudo-second-order kinetic and Langmuir models suitably described the adsorption kinetics and isothermal adsorption of Cd(II), respectively (R2 > 80 %), indicating that monolayer chemisorption dominated. However, the hysteresis indices of Cd(II) in the Cd(II)-Pb(II) system (< 1) were higher than those in the single system (> 1) due to the competitive adsorption of HMs. Overall, this study clarifies the effect of MPs on the adsorption of HMs in rhizosphere biofilms and will help researchers assess the ecological risks of HMs in soils.

Changes in Soil Phosphorus Availability and Microbial Community Structures in Rhizospheres of Oilseed Rapes Induced by Intercropping with White Lupins.

Oilseed rape is sensitive to soil phosphorus deficiencies. In contrast, white lupin is widely used as a model plant because it has efficient phosphorus utilization. Therefore, soil fertility and microbial composition in the rhizospheres of oilseed rapes and root exudate metabolites were compared under monocropping and intercropping systems. The main purpose was to explore whether the phosphorus absorption of rapeseed can be promoted by intercropping with white lupine. In comparison with oilseed rape monoculture (RR), the results showed that the contents of soil-available phosphorus, microbial biomass and phosphorus in the rhizospheres of oilseed rapes in the intercropping system (RL) were all higher than those of RR. Meanwhile, in comparison with RR, not only phosphorus-solubilizing bacteria, such as Streptomyces, Actinomadura and Bacillus, but also phosphorus-solubilizing fungi, such as Chaetomium, Aspergillus, Penicillium, were enriched in the rhizospheres of the oilseed rape under the RL system. Moreover, more abundant soil bacterial functions, organic acids and metabolites were also detected in root exudates of the oilseed rapes under the RL system. All of the above results suggest that soil phosphorus availability in the rhizospheres of oilseed rape could be improved by intercropping with white lupin. Additionally, soil phosphorus-solubilizing microorganisms, that are enriched in the rhizospheres of oilseed rapes under RL systems, have an important function in the improvement of phosphorus absorption of rapeseed by intercropping with white lupin.

Exploring the pharmacological mechanism of Naoxueshu oral liquid in the treatment of intracerebral hemorrhage through weighted gene co-expression network analysis, network pharmacological and experimental validation.

BACKGROUND: Intracerebral hemorrhage (ICH) is a life-threatening stroke subtype with high rates of disability and mortality. Naoxueshu oral liquid is a proprietary Chinese medicine that absorbs hematoma and exhibits neuroprotective effects in patients with ICH. However, the underlying mechanisms remain obscure. PURPOSE: Exploring and elucidating the pharmacological mechanism of Naoxueshu oral liquid in the treatment of ICH. STUDY DESIGN AND METHODS: The Gene Expression Omnibus (GEO) database was used to download the gene expression data on ICH. ICH-related hub modules were obtained by weighted gene co-expression network analysis (WGCNA) of differentially co-expressed genes (DEGs). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the obtained key modules to identify the ICH-related signaling pathways. Network pharmacology technology was applied to forecast the targets of Naoxueshu oral liquid and to establish a protein-protein interaction (PPI) network of overlapping targets between Naoxueshu oral liquid and ICH. Functional annotation and enrichment pathway analyses of the intersectional targets were performed using the omicsbean database. Finally, we verified the therapeutic role and mechanism of Naoxueshu oral liquid in ICH through molecular docking and experiments. RESULTS: Through the WGCNA analysis, combined with network pharmacology, it was found that immune inflammation was closely related to the early pathological mechanism of ICH. Naoxueshu oral liquid suppressed the inflammatory response; hence, it could be a potential drug for ICH treatment. Molecular docking further confirmed that the effective components of Naoxueshu oral liquid docked well with CD163. Finally, the experimental results showed that Naoxueshu oral liquid treatment in the ICH rat model attenuated neurological deficits and neuronal injury, decreased hematoma volume, and promoted hematoma absorption. In addition, Naoxueshu oral liquid treatment also significantly increased the levels of Arg-1, CD163, Nrf2, and HO-1 around hematoma after ICH. CONCLUSION: This study demonstrated that Naoxueshu oral liquid attenuated neurological deficits and accelerated hematoma absorption, possibly by suppressing inflammatory responses, which might be related to the regulation of Nrf2/CD163/HO-1 that interfered with the activation of M2 microglia, thus accelerating the clearance and decomposition of hemoglobin in the hematoma.

Increased serum uric acid level is associated with better outcome after endovascular treatment for acute ischemic stroke-a prospective cohort study.

Background: The role of serum uric acid (SUA) in affecting outcomes after endovascular treatment (EVT) in patients with ischemic stroke remains unclear. This study investigated the association of SUA with outcomes of patients with acute large vessel occlusion (LVO) who had received EVT. Methods: Patients with acute LVO stroke who underwent EVT within 24 hours were enrolled from a prospective, nationwide registry study. Baseline characteristics and SUA level within 24 hours of EVT were collected. The primary outcome was an excellent 90-day functional outcome [modified Rankin Scale (mRS) score 0-1]. Secondary outcomes included a favorable 90-day outcome (mRS score 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality. The SUA level was analyzed in quartiles and as a continuous variable. We investigated the independent association of SUA with the primary outcome using multivariable logistic regression. Results: Among 780 patients (mean age 64 years; 66.28% males), 230 (29.49%) had an excellent 90-day outcome. A higher SUA level was significantly associated with an excellent outcome in univariate logistic regression (P=0.045) and after adjusting for confounders in multivariate analysis [adjusted odds ratio (aOR), 0.998; 95% confidence interval (CI), 0.996-1.000; P=0.018]. Multivariate logistic regression analysis showed patients with SUA level in the fourth quartile had an excellent 90-day outcome (aOR, 0.367; 95% CI, 0.154-0.876; P=0.024). There was no significant association for SUA level with favorable 90-day outcome, sICH, or 90-day mortality (P>0.05). Conclusions: Among patients with acute LVO type of stroke who received EVT, baseline high SUA level may predict a better 90-day functional outcome.

Effectiveness of herbal medicine on patients with amyotrophic lateral sclerosis: Analysis of the PRO-ACT data using propensity score matching.

BACKGROUND: Patients with amyotrophic lateral sclerosis (ALS) have restricted pharmacotherapy options and thus resort to herbal medicines (HMs), despite limited and conflicting evidence. Therefore, use of HMs needs to be assessed in patients with ALS. PURPOSE: This study aimed to evaluate the benefits of HMs in ALS and to describe the characteristics of HM users. STUDY DESIGN: The correlation between HMs and prognosis was determined based on data obtained from the largest ALS database with high-quality clinical trials. Propensity score (PS) matching was used to address confounding and selection bias. METHODS: In total, 321 and 231 HM users with at least a 4-week HM prescription were identified and PS-matched with non-HM users at a 1:1 ratio based on predefined confounders. Time-to-event models with censoring at 12 or 18 months were established for survival analyses. For evaluating activity limitation and respiratory function, 320 and 376 HM users were included, respectively, and analyzed using multivariate analysis of variance (MANOVA). RESULTS: The profiles of 321 HM users indicated a better condition compared with that of non-HM users before PS-matching, including higher weight (median [IQR], 77.90 [21.8] kg vs. 74.00 [21.2] kg, p < 0.01), higher body mass index (26.00 [5.4] vs. 25.20 [5.8], p < 0.01), more percentage of limb onset (261 [81.3%] vs. 2366 [67.2%], p < 0.01), and slower progression (0.47 [0.5] vs. 0.51 [0.5], p = 0.03). HM did not significantly affect survival at 12 months (adjusted hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.49-1.03; log-rank p = 0.069), but it significantly prolonged survival at 18 months (adjusted HR 0.74, 95% CI 0.56-0.98; log-rank p = 0.038). After imputation of missing data, MANOVA revealed significant effectiveness of HMs in improving activity limitation (Pillai trace, 0.0195; p = 0.03). CONCLUSION: PS-based methods eliminated baseline differences between HM and non-HM users. Overall, the use of HM to treat patients with ALS is favored based on their association with prolonged overall survival within 18 months and improved activity limitation.

Interactions of microplastics and soil pollutants in soil-plant systems.

In recent years, increasing studies have been reported on characterization and detection of microplastics (MPs), and their interactions with organic pollutants (OPs) and heavy metals (HMs) in soils. However, a comprehensive review on the characteristics and factors that influence MPs distribution in soils, the sorption characteristics and mechanisms of soil contaminants by MPs, especially the interactions of MPs and their complexes with pollutants in the soil-plant systems remains rarely available at present. This review focuses on the sorption features and mechanisms of pollutants by MPs in soil and discussed the effects of MPs and their complexing with pollutants on soil properties, microbe and plants. The polarity of MPs significantly influenced the sorption of OPs, and different sorption mechanisms are involved for the hydrophobic and hydrophilic OPs. The sorption of OPs on MPs in soils is different from that in water. Aging of MPs can promote the sorption and migration of contaminants. The enhanced effects of biofilm in microplastisphere on the sorption of pollutants by MPs are critical, and interactions of soil environment-MPs-microbe-HMs-antibiotics increase the potential pathogens and larger release of resistance genes. The coexistence of HMs and MPs affected the growth of plants and the uptake of HMs and MPs by the plants. Moreover, the type, dose, shape and particle size of MPs have important influences on their interactions with pollutants and subsequent effects on soil properties, microbial activities and plant growth. This review also pointed out some knowledge gaps and constructive countermeasures to promote future research in this field.

Spatio-temporal distribution of vector borne diseases in Australia and Papua New Guinea vis-à-vis climatic factors.

BACKGROUND & OBJECTIVES: Weather and climate are directly linked to human health including the distribution and occurrence of vector-borne diseases which are of significant concern for public health. METHODS: In this review, studies on spatiotemporal distribution of dengue, Barmah Forest Virus (BFV) and Ross River Virus (RRV) in Australia and malaria in Papua New Guinea (PNG) under the influence of climate change and/ or human society conducted in the past two decades were analysed and summarised. Environmental factors such as temperature, rainfall, relative humidity and tides were the main contributors from climate. RESULTS: The Socio-Economic Indexes for Areas (SEIFA) index (a product from the Australian Bureau of Statistics that ranks areas in Australia according to relative socio-economic advantage and disadvantage) was important in evaluating contribution from human society. INTERPRETATION & CONCLUSION: For future studies, more emphasis on evaluation of impact of the El Niño-Southern Oscillation (ENSO) and human society on spatio-temporal distribution of vector borne diseases is recommended to highlight importance of the environmental factors in spreading mosquito-borne diseases in Australia and PNG.

Platelet-activating factor receptor antagonists of natural origin for acute ischemic stroke: a systematic review of current evidence.

Background: Acute ischemic stroke (AIS) is a common cause of death and long-term disability worldwide. Recent trials of platelet-activating factor receptor antagonists (PAFRA) appeared to indicate that they could play a neuroprotective role in the treatment of AIS; therefore, we conducted a systematic literature review to evaluate the clinical efficacy and safety of PAFRA in patients with AIS. Methods: A systematic literature search was performed in seven electronic databases from inception to 11 March 2022. All randomized controlled trials (RCTs) in which patients were treated with PAFRA strategies within 7 days of stroke onset were included. Modified Rankin Scale (mRS) was selected as the primary outcome of this systematic review. The methodological quality of included studies was assessed based on the Cochrane Collaborations tool. The review protocol was previously registered (PROSPERO CRD42020182075). Results: Fifteen RCTs comprising a total of 3,907 participants were included in this study. The PAFRA-related compounds included natural preparations of terpenoids, flavonoids, and saponins, namely, ginkgo endoterpene diester meglumine (GEDM, seven RCTs), ginkgo biloba dropping pill (GBDP, one RCT), ginkgolide injection (GDI, four RCTs), hesperidin (HES, one RCT), ginsenoside Rd injection (GSRI, one RCT), and hydroxysafflor yellow A (HSYA, one RCT). All studies were conducted in China between 2017 and 2021, employing a two-arm parallel design with sample sizes ranging from 40 to 1,113. Eight studies (53.3%) provided no information on their method of randomization, and only two studies (13.3%) utilized the double-blind design. Treatment was associated with improved clinical outcomes for (1) GEDM, GDI, and GBDP in patients treated with conventional treatment (CM) [GEDM + CM for AIS on mRS: MDmRS = -0.42, 95% CI (-0.47, -0.37), five trials, p < 0.00001; GEDM + CM for AIS on NIHSS: MDNIHSS = -1.02, 95% CI (-1.51, -0.52), four trials, p < 0.0001]; (2) GEDM and GDI in patients treated with neuroprotective agent (NPA) [GEDM + NPA + CM for AIS on mRS: MDmRS = -0.40, 95% CI (-0.54, -0.26), p < 0.00001; GEDM + NPA + CM for AIS on NIHSS: MDNIHSS = -3.93, 95%CI (-7.72, -0.14), p = 0.04]; (3) GBDP in patients treated with CM; (4) GDI and GSRI in patients treated with IV rt-PA therapy (IVT); and (5) HSYA in patients compared with Dengzhan Xixin injection (DZXXI). No access to improved clinical outcome was associated with HES in patients treated with IVT. Seven RCTs reported adverse events (AEs) but found that taking PAFRA-related preparations was not associated with an increased incidence of AEs. Conclusions: This systematic review not only makes an important contribution to the existing body of current evidence but also lays a well-conducted basis for providing opinions and recommendation on the evaluation of PAFRA-based medicine, which could also highlight the need for well-designed clinical trials of PAFRA for AIS to increase the quality of available evidence. Further research is required, using standardized functional outcome measures for AIS, adequate blinding and suitable comparator groups reflecting current best practice.

Different rhizosphere soil microbes are recruited by tomatoes with different fruit color phenotypes.

BACKGROUND: To explore and utilize abundant soil microbes and their beneficial functions, the bacterial and fungal compositions in rhizospheres between red- and yellow-fruited tomato varieties were analyzed using high-throughput sequencing technique. RESULT: Our results indicated that different soil microbes in rhizospheres of tomatoes were exactly recruited by different color fruit tomatoes. For the reasons as not only soil bacterial community, but also soil fungal compositions were all different between red and yellow fruit tomatoes. For example, Nocardioides, norank_f_norank_o_Vicinamibacterales, norank_f_norank_o_norank_c_KD4-96, norank_f_Birii41, norank_f_norank_o_S085 and Bradyrhizobium were the specific dominant soil bacterial genera, and Lecythophora, Derxomyces and unclassified_f_Pyronemataceae were the dominant soil fungal genera in the rhizospheres of red tomato varieties. By contrast, unclassified_f__Micromonsporaceae, Acidipila, Roseisolibacter, Gaiella and norank_f_Xanthobacteraceae were the unique dominant soil bacterial genera in the rhizospheres of yellow tomato varieties. And unclassified_o__Onygenales, Trichocladium, unclassified_c__Sordariomycetes, Pseudogymnoascus, Acremonium, Oidiodendron, Phialemonium, Penicillium, Phialosimplex were the unique dominant soil fungal genera in rhizospheres of yellow tomato varieties. Moreover, a higher abundance of specific soil bacterial and fungal genera in the rhizosphere was found in rhizospheres of the yellow than those of the red tomato varieties. CONCLUSION: Soil bacterial and fungal compositions in rhizospheres between red- and yellow-fruited tomato varieties were found significantly different which growing in the same environment under the identical managements. It suggested that different soil microbes in rhizospheres exactly were recruited by different phenotypes tomato varieties related to fruit color formation.

Impact of Early Rehabilitation on Outcomes in Patients With Acute Ischemic Stroke After Endovascular Treatment.

Background: This study aims to examine the effects of early rehabilitation on functional outcomes in patients with acute ischemic stroke treated with endovascular treatment (EVT). Methods: Eligible patients with large vessel occlusion stroke treated with EVT, who received early rehabilitation or standard care treatment during hospitalization, were enrolled in a multicenter registration, prospective observational study, a registration study for Critical Care of Acute Ischemic Stroke After Recanalization. Early rehabilitation was defined as rehabilitation interventions initiated within 1 week after acute stroke. The primary outcome was the favorable functional outcome (defined as modified Rankin Scale scores of 0 to 2) at 90 days. Independent association between early rehabilitation and the primary outcome was investigated using multivariable logistic regression in the entire sample and in subgroups. Results: A total of 1,126 patients (enrolled from July 2018 to May 2019) were included in the analyses, 273 (24.2%) in the early rehabilitation group and 853 (75.8%) in the standard care group. There was no significant difference in favorable functional outcomes at 90 days between the two groups (45.4 vs. 42.6%, p = 0.41). Patients in the early rehabilitation group had a lower death rate within 90 days compared with the standard care group (6.2 vs. 20.5%, p < 0.01). The multivariable logistic regression analyses showed that the early rehabilitation was not significantly associated with the favorable functional outcome at 90 days (adjusted odds ratio, 1.01 [95% CI, 0.70-1.47]; p = 0.95). There was no significant difference between subgroups in the favorable functional outcome at 90 days. No significant interaction was found between subgroups. Conclusions: Patients with stroke receiving early rehabilitation had a lower death rate. However, these clinically meaningful effects of early rehabilitation did not show on functional outcome at 90 days in patients with large vessel occlusion stroke treated with EVT. Registration: URL: http://www.chictr.org.cn; Unique identifier: ChiCTR1900022154.

Targeting the multifaceted roles of mitochondria in intracerebral hemorrhage and therapeutic prospects.

Intracerebral hemorrhage (ICH) is a severe, life-threatening subtype of stoke that constitutes a crucial health and socioeconomic problem worldwide. However, the current clinical treatment can only reduce the mortality of patients to a certain extent, but cannot ameliorate neurological dysfunction and has a high recurrence rate. Increasing evidence has demonstrated that mitochondrial dysfunction occurs in the early stages of brain injury and participates in all stages of secondary brain injury (SBI) after ICH. As the energy source of cells, various pathobiological processes that lead to SBI closely interact with the mitochondria, such as oxidative stress, calcium overload, and neuronal injury. In this review, we discussed the structure and function of mitochondria and the abnormal morphological changes after ICH. In addition, we discussed recent research on the involvement of mitochondrial dynamics in the pathological process of SBI after ICH and introduced the pathological variations and related molecular mechanisms of mitochondrial dysfunction in the occurrence of brain injury. Finally, we summarized the latest progress in mitochondrion-targeted agents for ICH, which provides a direction for the development of emerging therapeutic strategies targeting the mitochondria after ICH.

Endovascular treatment with or without intravenous alteplase for acute ischaemic stroke due to basilar artery occlusion.

BACKGROUND AND PURPOSE: It remains controversial if endovascular treatment (EVT) can improve the outcome of patients with acute basilar artery occlusion (BAO). This study aims to compare the functional outcomes between EVT with and without intravenous thrombolysis (IVT) first in patients who had acute ischaemic stroke (AIS) due to BAO. METHODS: Patients who had AIS with BAO who underwent EVT within 24 hours of onset were enrolled in this multicentre cohort study, and the efficacy and safety were compared between IVT+EVT and direct EVT. The primary outcome was 90-day functional independence. All outcomes were assessed with adjusted OR (aOR) from the multivariable logistic regression. In addition, a meta-analysis was performed on all recently published pivotal studies on functional independence after EVT in patients with BAO. RESULTS: Of 310 enrolled patients with BAO, 241 (78%) were treated with direct EVT and 69 (22%) with IVT+EVT. Direct EVT was associated with a worse functional outcome (aOR, 0.46 (95% CI 0.24 to 0.85), p=0.01). IVT+EVT was associated with a lower percentage of patients who needed ≥3 passes of stent retriever (10.14% vs 20.75%). The meta-analysis regression revealed a potential positive correlation between bridging with IVT first and functional independence (r=0.14 (95% CI 0.05 to 0.24), p<0.01). CONCLUSIONS: This study showed that compared with direct EVT, EVT with IVT first was associated with better functional outcomes in patients with BAO treated within 24 hours of onset. The meta-analysis demonstrated similar favourable efficacy of IVT first followed by EVT in patients with BAO.