Association between age, gender, and oral traumatic ulcerative lesions: a retrospective study.

BACKGROUND: Oral traumatic ulcerative lesions (OTUL) are commonly encountered in clinical practice, yet there is limited research on their clinical characteristics and traumatic etiological factors. This retrospective study aimed to analyze the age, gender, clinical characteristics, and traumatic etiological factors in a large cohort of patients with OTUL and provide valuable insights for dental clinicians to optimize patient care and prevention strategies. METHODS: A total of 1543 patients with OTUL were enrolled in this study. Age, gender, medical history, clinical characteristics and traumatic etiological factors were collected and analyzed. Logistic regression analysis was performed to determine the significance of age and gender as factors related to OTUL. RESULTS: The study revealed significant variations in clinical characteristics and traumatic etiological factors among different age groups and between genders. Logistic regression analysis demonstrated that both age and gender were significant factors related to OTUL. CONCLUSION: The clinical characteristics of OTUL and traumatic etiological factors appear to be significantly different according to age and gender. More targeted prevention strategies should be implemented for all age and gender groups.

Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial.

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

Baseline neurologic deficit and efficacy of remote ischemic conditioning after acute ischemic stroke: A post hoc analysis of RICAMIS.

RICAMIS (ClinicalTrials.gov Identifier: NCT03740971) trial has demonstrated efficacy of remote ischemic conditioning (RIC) in acute ischemic stroke, but whether baseline NIHSS score can affect outcomes in stroke remains unclear. We conducted a post hoc analysis of RICAMIS to investigate the issue. Patients included in RICAMIS were divided into three groups based on baseline NIHSS score. The primary outcome was excellent functional outcome at 90 days, defined as mRS score of 0-1. Compared with patients receiving usual care, we investigated association of RIC effect with outcomes in each group and interaction between RIC effect and stroke severity. Among 1776 patients, 1255 were assigned into NIHSS score 6-8 group, 402 into NIHSS score 9-12 group, and 119 into NIHSS score 13-16 group. A higher proportion of primary outcome was found associated with RIC in NIHSS score 9-12 group (adjusted risk difference [RD], 14.6 â€‹%; 95 â€‹% CI, 5.0 â€‹%-24.2 â€‹%; P â€‹= â€‹0.003), but no significant association was found in NIHSS score 6-8 group (adjusted RD, 2.3 â€‹%; 95 â€‹% CI, -2.5 â€‹%-7.2 â€‹%; P â€‹= â€‹0.34), or in NIHSS score 13-16 group (adjusted RD, 9.7 â€‹%; 95 â€‹% CI, -7.5 â€‹%-26.9 â€‹%; P â€‹= â€‹0.27). There was a significant interaction between RIC effect and stroke severity when analysis was performed between NIHSS score 6-8 and 9-12 groups (P â€‹= â€‹0.04), but not between NIHSS score 9-12 and 13-16 groups (P â€‹= â€‹0.57). Current study firstly reported patients with NIHSS score 9-12 may get more benefit from RIC after stroke with respect to excellent functional outcome at 90 days.

[Retracted] Functional characterization of the nitrogen permease regulator­like­2 candidate tumor suppressor gene in colorectal cancer cell lines.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the microscopic images shown in Fig. 1C on p. 3489 and the invasion assay images shown in Fig. 5 on p. 3491 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes. Moreover, unexpected similarities were identified comparing between a pair of the flow cytometric assay data panels in Fig. 4 on p. 3490, considering that these data were intended to show the results from differently performed experiments. Owing to the fact that the contentious data in the above article had already been published, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 12: 3487­3493, 2015; DOI: 10.3892/mmr.2015.3881].

MRI-based risk stratification for recurrent ischemic stroke in embolic stroke of undetermined source.

OBJECTIVE: Leukoaraiosis and other brain MRI-assessed parameters were shown to be associated with recurrent stroke in this population. We aimed to develop an MRI-based predictive tool for risk stratification of ESUS patients. METHODS: We retrospectively assessed consecutive patients who were diagnosed with ESUS and underwent brain MRI and performed a multivariable analysis with the outcome of recurrent stroke/TIA. Based on the coefficient of each covariate, we generated an integer-based point scoring system. The discrimination and calibration of the score were assessed using the area under the receiver operator characteristic curve, net reclassification improvement, integrated discrimination improvement, calibration curve, and decision curve analysis. Also, we compared the new score with a previously published score (ALM score). RESULTS: Among 176 patients followed for an overall period of 902.3 patient-years (median of 74 months), there were 39 recurrent ischemic stroke/TIAs (4.32 per 100 patient-years). Fazekas score (HR: 1.26, 95% CI: 1.03-1.54), enlarged perivascular space (EPVS) (HR: 2.76, 95% CI: 1.12-6.17), NIHSS at admission (HR: 1.11, 95% CI: 1.02-1.18), and infarct subtypes (HR: 2.88, 95% CI: 1.34-6.17) were associated with recurrent stroke/TIA. Accordingly, a score (FENS score) was developed with AUC-ROC values of 0.863, 0.788, and 0.858 for 1, 3, and 5 years, respectively. These were significantly better than the AUC-ROC of ALM score (0.635, 0.695, and 0.705, respectively). The FENS score exhibited better calibration and discrimination ability than the ALM score (Hosmer-Lemeshow test χ2 : 4.402, p = 0.819). CONCLUSION: The MRI-based FENS score can provide excellent predictive performance for recurrent stroke/TIA and may assist in risk stratification of ESUS patients.

Intracranial plaque with large lipid core is associated with embolic stroke of undetermined source.

OBJECTIVE: To investigate an association between percentage lipid-rich necrotic core (LRNC) and an index ischemic stroke in an embolic stroke of undetermined source (ESUS) cohort. METHODS: A total of 167 ESUS patients with 259 non-stenotic intracranial plaques including 155 ipsilateral and 104 contralateral to stroke were finally enrolled in the current analysis. The multi-dimensional parameters involving remodeling index (RI), plaque burden (PB), LRNC, discontinuity of plaque surface (DPS), intraplaque hemorrhage (IPH), and vulnerable plaque defined as presence of complicated plaque were evaluated by high-resolution magnetic resonance imaging. RESULTS: We found that %LRNC was an independent predictor for ESUS in model 1 (OR: 2.574, 95% CI: 1.854-3.573, P < 0.001), and model 2 (OR: 2.550, 95% CI: 1.835-3.545, P < 0.001), but the association was not seen in PB. In receiver operating characteristic curve analysis, the discrimination of LRNC for ESUS was significantly superior to that of PB (absolute difference: 0.121, 95% CI: 0.056-0.205, P < 0.001). Importantly, a significantly positive synergy between the remodeling pattern and LRNC in response to plaque vulnerability was found by Sankey diagram (P for interaction = 0.001). CONCLUSION: This is the first report that LRNC, beyond PB, may be correlated with an index ESUS, and a synergistic effect between positive remodeling and larger LRNC could promote plaque vulnerability. The findings suggest that a potential target subgroup may benefit from stroke prevention with intensive statin, although this must be confirmed in future.

The association of admission ionized calcium with outcomes of thrombolysed patients with anterior circulation ischemic stroke.

BACKGROUND AND PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Early antiplatelet for minor stroke following thrombolysis (EAST): Rationale and design.

BACKGROUND: Early neurological deterioration (END) occurs in about 10% of patients after intravenous thrombolysis (IVT) and is related to poor outcome. In theory, early antiplatelet following IVT could reduce END by preventing re-occlusion and stroke progression, but current guidelines recommend starting antiplatelet treatment at 24 h after IVT due to concerns about hemorrhagic transformation. Given higher risk of hemorrhagic transformation in severe stroke, we hypothesized that minor stroke patients following IVT can safely benefit from early antiplatelet treatment. AIMS: To explore the efficacy and safety of early antiplatelet in minor stroke patients after IVT. SAMPLE SIZE ESTIMATES: A maximum of 1022 patients are required to test the superiority hypothesis with 80% power according to a two-side 0.05 level of significance, stratified by age, gender, history of stroke or transient ischemic attack, history of hypertension, history of diabetes mellitus, systolic blood pressure at admission, time from IVT to treatment, thrombolysis drug, stroke territory, and stroke etiology. DESIGN: Early antiplatelet for minor stroke following thrombolysis is a prospective, double-blinded, multicenter, randomized and placebo-controlled trial. Minor stroke patients within 6 h following IVT are randomly assigned into experimental group and control group with the ratio of 1:1. The experimental group is orally administered with 300 mg clopidogrel and 100 mg aspirin, and control group with placebo. Subsequently, both groups received guideline-based antithrombotic treatment from 24 h after IVT to 90 days. OUTCOME: The primary efficacy endpoint is excellent functional outcome, defined as the modified Rankin Scale 0-1 at 90 days after randomization, while primary safety endpoint is symptomatic intracerebral hemorrhage, defined as National Institutes of Health Stroke Scale score increase ⩾ 4 caused by intracranial hemorrhage within 36 h after randomization. CONCLUSIONS: The results of EAST will provide us powerful early antiplatelet evidence for minor stroke population following intravenous thrombolysis in clinical practice.

[Lipid-lowering effect of drug pair Scutellariae Radix-Coptidis Rhizoma based on lipomics].

This study investigated the mechanism of action of Scutellariae Radix-Coptidis Rhizoma(SR-CR) in intervening in non-alcoholic fatty liver disease(NAFLD) in rats based on lipidomics. Thirty-six SD rats were divided into a control group, a model group, SR-CR groups of different doses, and a simvastatin group, with six rats in each group. Rats in the control group were fed on a normal diet, while those in the remaining groups were fed on a high-lipid diet. After four weeks of feeding, drug treatment was carried out and rats were sacrificed after 12 weeks. Serum liver function and lipid indexes were detected using kits, and the pathomorphology of liver tissues was evaluated by hematoxylin-eosin(HE) staining and oil red O staining. Changes in lipid levels in rats were detected using the LC-MS technique. Differential lipid metabolites were screened by multivariate statistical analysis, and lipid metabolic pathways were plotted. The changes in lipid-related protein levels were further verified by Western blot. The results showed that compared with the control group, the model group showed increased levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c)(P<0.01), and decreased levels of γ-glutamyl transferase(γ-GT) and high-density lipoprotein cholesterol(HDL-c)(P<0.01), which were significantly recovered by the intervention of SR-CR. HE staining and oil red O staining showed that different doses of SR-CR could reverse the steatosis in the rat liver in a dose-dependent manner. After lipidomics analysis, there were significant differences in lipid metabolism between the model group and the control group, with 54 lipids significantly altered, mainly including glycerolipids, phosphatidylcholine, and sphingolipids. After administration, 44 differential lipids tended to normal levels, which indicated that SR-CR groups of different doses significantly improved the lipid metabolism level in NAFLD rats. Western blot showed that SR-CR significantly decreased TG-synthesis enzyme 1(DGAT1), recombinant lipin 1(LPIN1), fatty acid synthase(FASN), acetyl-CoA carboxylase 1(ACC1), and increased the phosphorylation level of ACC1. These changes significantly decreased the synthesis of TG and increased the rate of its decomposition, which enhanced the level of lipid metabolism in the body and finally achieved the lipid-lowering effect. SR-CR can improve NAFLD by inhibiting the synthesis of fatty acids and TG.

[Activity of Codonopsis canescens against rheumatoid arthritis based on TLRs/MAPKs/NF-κB signaling pathways and its mechanism].

This paper aims to explore the activity of Codonopsis canescens extract against rheumatoid arthritis(RA) based on the Toll-like receptors(TLRs)/mitogen-activated protein kinases(MAPKs)/nuclear factor kappa B(NF-κB) signaling pathways and its mechanism. The ultra-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF-MS) was used to identify the components of C. canescens extract. Forty-eight male SD rats were randomly divided into six groups, namely the normal group, the model group, the methotrexate(MTX) tablet group, and the low, medium, and high-dose C. canescens extract(ZDS-L, ZDS-M, and ZDS-H) groups, with 8 rats in each group. The model of collagen-induced arthritis in rats was induced by injection of bovine type Ⅱ collagen emulsion. MTX(2.5 mg·kg~(-1)), ZDS-L, ZDS-M, and ZDS-H(0.3 g·kg~(-1), 0.6 g·kg~(-1), and 1.2 g·kg~(-1)) were administrated by gavage. Rats in the normal group and the model group received distilled water. MTX was given once every three days for 28 days, and the rest medicines were given once daily for 28 days. Body weight, degree of foot swelling, arthritis index, immune organ index, synovial histopathological changes, and serum levels of tumor necrosis factor-α(TNF-α), interleukin-1ß(IL-1ß), and interleukin-6(IL-6) were observed. Protein expressions of TLR2, TLR4, NF-κB p65, p38 MAPK, and p-p38 MAPK in rats were determined by Western blot. Thirty-four main components were identified by UPLC-Q-TOF-MS, including 15 flavonoids, 7 phenylpropanoids, 4 terpenoids, 4 organic acids, 2 esters, and 2 polyalkynes. As compared with the normal group, the body weight of the model group was significantly decreased(P<0.01), and foot swelling(P<0.05, P<0.01), arthritis index(P<0.01), and the immune organ index(P<0.01) were significantly increased. The synovial histopathological injury was obviously observed in the model group. The serum levels of inflammatory factors TNF-α, IL-1ß, and IL-6 were significantly increased(P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK in the synovial tissue were significantly increased(P<0.01) in the model group. As compared with the model group, the body weights of the ZDS dose groups were increased(P<0.01), and the degree of foot swelling(P<0.01) and the arthritis index were decreased(P<0.05, P<0.01). The immune organ index was decreased(P<0.01) in the ZDS dose groups, and the synovial tissue hyperplasia and inflammatory cell infiltration were alleviated. The serum levels of TNF-α, IL-1ß, and IL-6 were significantly decreased(P<0.05, P<0.01), and the protein expression levels of TLR2, TLR4, NF-κB p65, p-p38 MAPK/p38 MAPK were decreased(P<0.05, P<0.01) in the ZDS dose groups. C. canescens extract containing apigenin, tricin, chlorogenic acid, aesculin, ferulic acid, caffeic acid, and oleanolic acid has a good anti-RA effect, and the mechanism may be related to the inhibition of TLRs/MAPKs/NF-κB signaling pathways.

[Environmental Process, Effects and Risks of Emerging Contaminants in the Estuary-Coastal Environment].

Human activities and global climate change have contributed substantially to the input of land-sourced pollutants into the aquatic environment, especially for emerging or newly identified contaminants, such as microplastics, emerging persistent organic pollutants, pharmaceuticals, and personal care products. The prevalence and toxicity of these emerging pollutants has raised continued concern for the health and safety of the public worldwide. A review of sources, distribution, interfacial transport processes of microplastics, per-and polyfluorinated compounds, antibiotics, and endocrine-disrupting chemicals and factors that influence their environmental behavior in the estuary-coastal environment have been included. The adverse ecological effects and health risks of these emerging contaminants to humans were also reviewed. Lastly, the direction of future research was provided regarding the environmental behavior of multiple emerging pollutants in the coastal environment and the health risks resulting from their interactions, supporting the prevention and control of marine pollution and the healthy development of the marine economy.

[Pollution Characteristics of Microplastics in Sediments of Xiamen Bay Beach].

Microplastics widely exist in various environmental media and have become a global environmental problem. To investigate the pollution characteristics, deposition patterns, and influencing factors of microplastics in the sediments of bay beach, five typical beaches were selected in Xiamen Bay. According to the tidal variation, 0-10 cm, 10-20 cm, and 20-30 cm sediment column samples were collected in layers at the high tide line, middle tide line, and low tide line at the same time, and the characteristics of the horizontal and vertical distribution of microplastics in the beach sediments were studied. The results showed that the abundance of microplastics in 45 sediment samples in Xiamen Bay beach ranged from 39 to 260 n·kg-1, with an average abundance of (114±26) n·kg-1. The shapes of microplastics were mainly fibers, fragments, granules, and foams, with fibers making up the largest proportion. The main components were polyethylene terephthalate (PET), cellophane, and polyethylene (PE). The colors of microplastics included transparent, yellow, blue, black, white, etc. The average abundance of microplastics showed a certain pattern depending on the beach location, intertidal zone, and sampling depth. Moreover, the abundance and distribution of microplastics on the beach were affected by various natural and human factors such as waves, tides, shoreline shape, the number of tourists, and the cleaning of marine floating debris. These results aid the understanding of the distribution characteristics and sources of microplastics in beach sediments, provide a basis for the transport of microplastics from land to sea, and provide data support for the collection of sea floating garbage and shoreline garbage.

[Distribution, Migration, and Transformation Mechanism of Labile Phosphorus in Sediments of Xixi River Estuary, Xiamen].

To explore the effect of manganese, iron, and sulfur geochemistry on the distribution of labile phosphorus in different estuarine areas, the diffusion gradient in thin-film (DGT) sampling technique was used for in-situ high-resolution monitoring of available phosphorus (DGT-P), manganese, iron, and sulfur in sediments from Xixi River estuary in Xiamen. The results showed that the distribution of DGT-P in the vertical profile was closely related to the redox transformation of iron and sulfur and the background value of active phosphorus in sediments. The passivation/activation of phosphorus was mainly controlled by the oxidative adsorption/reductive dissolution of phosphorus by iron oxides and the activation of phosphorus induced by sulfate reduction and sulfide accumulation. Along the sampling sites, the average concentration of DGT-P varied greatly (0.075-0.80 mg·L-1), which was not related to salinity but closely related to redox conditions, that is, the deeper the oxidation zone, the lower the average concentration of DGT-P. The simulation results showed that the phosphorus resupply capacity from surface sediments to porewater was correlated with DGT-P concentration and redox conditions, that is, the oxidative environment was unconducive to the desorption and resupply of sediment phosphorus, whereas the coupling with iron and sulfur geochemistry in the reducing environment was conducive to the maintenance of high labile phosphorus concentration and the continuous release of phosphorus.

Association of serum biomarkers with early neurologic improvement after intravenous thrombolysis in ischemic stroke.

BACKGROUND: Early neurologic improvement (ENI) after intravenous thrombolysis is associated with favorable outcome, but associated serum biomarkers were not fully determined. We aimed to investigate the issue based on a prospective cohort. METHODS: In INTRECIS study, five centers were designed to consecutively collect blood sample from enrolled patients. The patients with ENI and without ENI were matched by propensity score matching with a ratio of 1:1. Preset 49 biomarkers were measured through microarray analysis. Enrichment of gene ontology and pathway, and protein-protein interaction network were analyzed in the identified biomarkers. RESULTS: Of 358 patients, 19 patients with ENI were assigned to ENI group, while 19 matched patients without ENI were assigned to Non ENI group. A total of nine biomarkers were found different between two groups, in which serum levels of chemokine (C-C motif) ligand (CCL)-23, chemokine (C-X-C motif) ligand (CXCL)-12, insulin-like growth factor binding protein (IGFBP)-6, interleukin (IL)-5, lymphatic vessel endothelial hyaluronan receptor (LYVE)-1, plasminogen activator inhibitor (PAI)-1, platelet-derived growth factor (PDGF)-AA, suppression of tumorigenicity (ST)-2, and tumor necrosis factor (TNF)-α were higher in the ENI group, compared with those in the Non ENI group. CONCLUSIONS: We found that serum levels of CCL-23, CXCL-12, IGFBP-6, IL-5, LYVE-1, PAI-1, PDGF-AA, ST-2, and TNF-α at admission were associated with post-thrombolytic ENI in stroke. The role of biomarkers warrants further investigation. TRIAL REGISTRATION: Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT02854592.

Development of spirocyclic phosphoramidite-based hybrid diphosphorus ligands for enantioselective iridium-catalyzed hydrogenation of imines.

Unsymmetrical hybrid chiral diphosphorus ligands bearing a spirocyclic phosphoramidite scaffold have been developed and successfully applied in the iridium-catalyzed asymmetric hydrogenation of imines. With this newly developed chiral iridium catalytic system, a wide range of imines including sterically hindered ones could be hydrogenated to give the corresponding optically active amines in high yields (up to >99%) and with excellent enantioselectivities (up to >99% ee). The utility of this hydrogenation has been demonstrated by the preparation of the chiral fungicide (S)-benalaxyl.

Effect of Remote Ischemic Conditioning vs Usual Care on Neurologic Function in Patients With Acute Moderate Ischemic Stroke: The RICAMIS Randomized Clinical Trial.

Importance: Preclinical and clinical studies have suggested a neuroprotective effect of remote ischemic conditioning (RIC), which involves repeated occlusion/release cycles on bilateral upper limb arteries; however, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy of RIC for acute moderate ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded-end point, randomized clinical trial including 1893 patients with acute moderate ischemic stroke was conducted at 55 hospitals in China from December 26, 2018, through January 19, 2021, and the date of final follow-up was April 19, 2021. Interventions: Eligible patients were randomly assigned within 48 hours after symptom onset to receive treatment with RIC (using a pneumatic electronic device and consisting of 5 cycles of cuff inflation for 5 minutes and deflation for 5 minutes to the bilateral upper limbs to 200 mm Hg) for 10 to 14 days as an adjunct to guideline-based treatment (n = 922) or guideline-based treatment alone (n = 971). Main Outcomes and Measures: The primary end point was excellent functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 1. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 1893 eligible patients with acute moderate ischemic stroke who were randomized (mean [SD] age, 65 [10.3] years; 606 women [34.1%]), 1776 (93.8%) completed the trial. The number with excellent functional outcome at 90 days was 582 (67.4%) in the RIC group and 566 (62.0%) in the control group (risk difference, 5.4% [95% CI, 1.0%-9.9%]; odds ratio, 1.27 [95% CI, 1.05-1.54]; P = .02). The proportion of patients with any adverse events was 6.8% (59/863) in the RIC group and 5.6% (51/913) in the control group. Conclusions and Relevance: Among adults with acute moderate ischemic stroke, treatment with remote ischemic conditioning compared with usual care significantly increased the likelihood of excellent neurologic function at 90 days. However, these findings require replication in another trial before concluding efficacy for this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT03740971.

Safety and preliminary efficacy of argatroban plus dual antiplatelet therapy for acute mild to moderate ischemic stroke with large artery atherosclerosis.

OBJECTIVE: Previous studies suggest the benefit of dual antiplatelet therapy (DAPT) for acute ischemic stroke with large artery atherosclerosis (LAA) etiology, but there is no study about the effect of DAPT plus anticoagulant in this population. METHODS: A prospective single arm trial was performed to determine the effect of DAPT combined with argatroban on acute mild to moderate ischemic stroke patients with LAA, which was compared with historical populations. The main outcome was the proportion of early neurological deterioration (END). The secondary outcomes included scores of 0 to 1 and 0 to 2 on the modified Rankin Scale (mRS) at 90 days, and changes in National Institutes of Health Stroke Scale (NIHSS) from baseline to day 7 after admission. The safety outcomes included intracranial hemorrhage at 7 days, organ hemorrhage, and all-cause mortality at 90 days. RESULTS: A total of 120 patients with argatroban plus DAPT were prospectively enrolled and 529 patients with only DAPT were retrospectively collected. There was no significant difference in baseline characteristics between groups. Compared with control group, combined treatment group had lower proportion of END (4.2% vs. 10.0%, adjusted p = .046), more reduction in NIHSS score from the baseline to day 7 after admission (1.06 ± 2.03 vs. 0.39 ± 1.97, adjusted p = .003), and higher proportion of mRS (0-2) at 90 days (87.5% vs. 79.2%, adjusted p = .048). No intracranial hemorrhage was found between groups. CONCLUSIONS: This is the first report that short-term argatroban combined with DAPT seems to be safe and may effectively prevent END and improve neurological prognosis for acute mild to moderate ischemic stroke patients with LAA; however, interpretation of the conclusion required caution due to nonrandomized controlled trial with medium sample size.

Change of Serum Biomarkers to Post-Thrombolytic Symptomatic Intracranial Hemorrhage in Stroke.

Background: Symptomatic intracranial hemorrhage (sICH) is a terrible complication after intravenous alteplase in stroke, and numerous biomarkers have been investigated. However, the change of biomarkers to sICH has not been well determined. Aim: To investigate the association between the change of biomarkers and sICH. Methods: This is a prospective cohort study, and patients with sICH within 24 h after thrombolysis were enrolled, while patients without sICH were matched by propensity score matching with a ratio of 1:1. The blood samples were collected before and 24 h after intravenous thrombolysis (IVT), and preset 49 serum biomarkers were measured by microarray analysis. Protein function enrichment analyses were performed to detect the association between the change of biomarkers and sICH. Results: Of consecutive 358 patients, 7 patients with sICH in 24 h were assigned to the sICH group, while 7 matched patients without any ICH were assigned to the non-sICH group. A total of 9 biomarkers were found to significantly change before vs. after thrombolysis between groups, including increased biomarkers, such as brain-derived neurotrophic factor, C-C motif chemokine ligand (CCL)-24, interleukin (IL)-6, IL-10, IL-18, and vascular endothelial growth factor, and decreased biomarkers, such as CCL-11, intercellular adhesion molecule-1, and IL-7. Conclusions: This is the first study to identify changes in serum biomarkers in patients with sICH after IVT, and found that 6 neuroinflammatory and 3 neuroprotective biomarkers may be associated with brain injury following post-thrombolytic sICH. Clinical Trial Registration: https://www.clinicaltrials.gov, identifier: NCT02854592.

Sulforaphane Ameliorates the Intestinal Injury in Necrotizing Enterocolitis by Regulating the PI3K/Akt/GSK-3ß Signaling Pathway.

Objective: Necrotizing enterocolitis (NEC) is a serious neonatal disease; this study aims to investigate the role of sulforaphane (SFN) in NEC-induced intestinal injury. Methods: An animal model of NEC was established in newborn mice and intragastrically administrated with SFN; then, the general status and survival of the mice were observed. H&E staining was used to observe the pathological changes of intestinal tissues. ELISA, immunohistochemical staining, and flow cytometry assays were used to detect the levels of inflammatory factors, including TNF-α, IL-6, and IL-17, the expression of Bax, Bcl-2, TLR4, and NF-κB, and the percentages of the Th17 and Treg cells, respectively. GSK-3ß expression levels were measured by immunofluorescence. IEC-6 and FHC cells were induced with LPS to mimic NEC in vitro and coincubated with SFN; then, the inflammatory factor levels and cell apoptosis rate were detected. Finally, Western blot was used to assess the expression of PI3K/Akt/GSK-3ß pathway-related proteins in vitro and in vivo. Results: SFN improved the survival rate of NEC mice during modeling, alleviated the severity of the intestinal injury, and reduced the proportion of Th17/Treg cells. SFN could inhibit TLR4 and NF-κB levels, decrease the release of inflammatory factors TNF-α and IL-6, suppress Bax expression, increase Bcl-2 expression, and inhibit apoptosis both in in vitro and in vivo models of NEC. Meanwhile, SFN regulated the expression of PI3K/Akt/GSK-3ß pathway-related proteins in vitro and in vivo. Conclusion: SFN relieved the inflammatory response and apoptosis by regulating the PI3K/Akt/GSK-3ß signaling pathway, thereby alleviating NEC in model mice and cells.

Atrial cardiopathy and non-stenotic intracranial complicated atherosclerotic plaque in patients with embolic stroke of undetermined source.

OBJECTIVE: To assess (1) the association between atrial cardiopathy (AC) and non-stenotic intracranial complicated atherosclerotic plaque (NICAP) in patients with embolic stroke of undetermined source (ESUS) or small-vessel disease (SVD), and (2) the performance of previously proposed biomarkers to identify AC as the underlying aetiology in ESUS. METHODS: Based on our high-resolution MRI (HR-MRI) cohort, 403 subjects (243 ESUS and 160 SVD) were enrolled in the final analysis. All patients underwent intracranial HR-MRI to assess the presence of ipsilateral NICAP. Biomarkers of AC (ie, P-wave terminal force in lead V1 (PTFV1) on ECG, N-terminal probrain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T and left atrial diameter) were collected within 24 hours after admission. RESULTS: Among patients without ipsilateral NICAP, we found an association between the presence of AC (adjusted OR (aOR): 4.76, 95% CI 2.48 to 9.14), increased PTFV1 (aOR: 5.70, 95% CI: 2.43 to 13.39) and NT-proBNP (aOR: 1.65, 95% CI: 1.16 to 2.35) with ESUS. This association was not evident among patients with ipsilateral NICAP. The discrimination between ESUS versus SVD by AC/AC-related biomarkers was significantly improved after excluding ipsilateral NICAP. Similarly, the discrimination between ESUS and SVD by ipsilateral NICAP was notably augmented after excluding AC, PTFV1 and NT-proBNP. INTERPRETATION: AC is more prevalent in patients who had ESUS without ipsilateral NICAP compared with patients with, implying that AC and ipsilateral NICAP are two distinct, competing aetiologies of ESUS. Among the AC biomarkers studied in this analysis, PTFV1 seems to be the most informative.