Exploring the Light-Emitting Agents in Renilla Luciferases by an Effective QM/MM Approach.

Bioluminescence is a fascinating natural phenomenon, wherein organisms produce light through specific biochemical reactions. Among these organisms, Renilla luciferase (RLuc) derived from the sea pansy Renilla reniformis is notable for its blue light emission and has potential applications in bioluminescent tagging. Our study focuses on RLuc8, a variant of RLuc with eight amino acid substitutions. Recent studies have shown that the luminescent emitter coelenteramide can adopt multiple protonation states, which may be influenced by nearby residues at the enzyme's active site, demonstrating a complex interplay between protein structure and bioluminescence. Herein, using the quantum mechanical consistent force field method and the semimacroscopic protein dipole-Langevin dipole method with linear response approximation, we show that the phenolate state of coelenteramide in RLuc8 is the primary light-emitting species in agreement with experimental results. Our calculations also suggest that the proton transfer (PT) from neutral coelenteramide to Asp162 plays a crucial role in the bioluminescence process. Additionally, we reproduced the observed emission maximum for the amide anion in RLuc8-D120A and the pyrazine anion in the presence of a Na+ counterion in RLuc8-D162A, suggesting that these are the primary emitters. Furthermore, our calculations on the neutral emitter in the engineered AncFT-D160A enzyme, structurally akin to RLuc8-D162A but with a considerably blue-shifted emission peak, aligned with the observed data, possibly explaining the variance in emission peaks. Overall, this study demonstrates an effective approach to investigate chromophores' bimolecular states while incorporating the PT process in emission spectra calculations, contributing valuable insights for future studies of PT in photoproteins.

Enhancement of therapeutic potential of mesenchymal stem cell by IGF-1 delivery in PLGA microspheres for tissue regeneration.

The use of stem cell-based treatment systems is prevalent in regenerative medicine. To enhance the regenerative capabilities of stem cells, growth factors are typically incorporated into the treatment system. Nonetheless, traditional hydrogel-encapsulated or heparinized scaffolds that bind factors have limitations. In this study, we prepared a biomaterial strategy using uniform poly(lactic-co-glycolic) acid (PLGA) microspheres (uPLGA-Ms) fabricated by microfluidic to sustain delivery of insulin-like growth factor 1 (IGF-1), a critical protein for hMSCs biological functions. The uPLGA-Ms loaded IGF-1 were highly monodispersed through precise manipulation of the flow rate of the two-phase of the flow-focusing microchannle. The results showed that the uPLGA-Ms stabilize IGF-1 and provide a more efficient sustained delivery and cost-effective of growth factor. Gene expression analysis demonstrated the uPLGA delivery of IGF-1 results in a (enhanced) supported hMSCs expansion, survival, stemness, and secretion abilities comparable with the conventional soluble IGF-1 group. In summary, this material-based strategy to stabilize and sustain delivery of growth factor has broad potential to regeneration of various tissues and organs.

Multi-Target Neuroprotection of Thiazolidinediones on Alzheimer's Disease via Neuroinflammation and Ferroptosis.

Alzheimer's disease (AD) is the main cause of dementia in older age. The prevalence of AD is growing worldwide, causing a tremendous burden to societies and families. Due to the complexity of its pathogenesis, the current treatment of AD is not satisfactory, and drugs acting on a single target may not prevent AD progression. This review summarizes the multi-target pharmacological effects of thiazolidinediones (TZDs) on AD. TZDs act as peroxisome proliferator-activated receptor gamma (PPARγ) agonists and long-chain acyl-CoA synthetase family member 4 (ACSL4) inhibitors. TZDs ameliorated neuroinflammation and ferroptosis in preclinical models of AD. Here, we discussed recent findings from clinical trials of pioglitazone in the treatment of AD, ischemic stroke, and atherosclerosis. We also dissected the major limitations in the clinical application of pioglitazone and explained the potential benefit of pioglitazone in AD. We recommend the use of pioglitazone to prevent cognitive decline and lower AD risk in a specific group of patients.

Revisiting the predictive role of truncal-type occlusion sign for acute large vessel stroke treated by endovascular thrombectomy: A scoping review.

Background and purpose The truncal type occlusion (TTO) sign observed during endovascular thrombectomy (EVT) is thought to predict the etiology and prognosis of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, the interpretation of the present results and the clinical utility of this sign needs further investigation. This scoping meta-review aimed to assess the predictive value of the TTO sign, thus identifying methodological limitations in current study designs. Methods Studies published up to January 2023 were identified by systematically searching PubMed, Embase, and Web of Science. A meta-analysis was performed to quantitatively synthesize the evidence on the predictive value of the TTO sign. An 8-point scale was introduced to narratively summarize the current evidence level and methodological quality of included studies. Results We included 10 studies in this review. For the prediction of intracranial atherosclerotic stenosis, the sensitivity, specificity, PLR and NLR of the TTO sign were 0.73, 0.87, 5.5 and 0.31, respectively (all p<0.05). For recanalization failure after primary thrombectomy, the sensitivity, specificity, PLR and NLR were 0.44, 0.91, 4.9 and 0.61, respectively (all p<0.05). The strength of evidence was low due to the methodological limitations and lack of adjustment for potential confounders. Conclusion The predictive values of the TTO sign for the etiology of LVO-AIS was considerable but seemed limited for current interpretation. Several confounders could influence the determination and predictive value of the TTO sign, requiring methodological adjustments in future research. Endovascular practitioners encountering this sign during thrombectomy should draw specific attention to stroke etiology, thus promoting timely adjustment of intra- and postprocedural strategies.

Neuroprotective Effects of Activin A against Cerebral Ischemia/Reperfusion Injury in Mice by Enhancing Nrf2 Expression to Attenuate Neuronal Ferroptosis.

Activin A (Act A) is a member of the transforming growth factor-ß (TGF-ß) superfamily and can protect against ischemic cerebral injury. Ferroptosis, a newly discovered type of programmed cell death, contributes to the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). However, little is known on whether Act A can modulate neuronal ferroptosis to protect against CIRI in a mouse model of middle cerebral artery occlusion (MCAO) and an HT22 cell model of oxygen-glucose deprivation/reoxygenation (OGD/R). The results indicated that Act A treatment relieved CIRI by improving neurological deficits and reducing the infarct volume in mice. MCAO stimulated iron accumulation and malondialdehyde formation and upregulated ACSL4 expression but downregulated GPX4 expression, a hallmark of ferroptosis in the brain of mice. Treatment with Act A significantly mitigated MCAO-triggered ferroptosis in the brain of mice. Furthermore, Act A treatment enhanced the MCAO-upregulated nuclear factor erythroid-2-related factor 2 (Nrf2) expression in the brains of mice. Similar results were observed in HT22 cells following OGD/R and pretreatment with Act A. The neuronal protective effect of Act A in HT22 cells was attenuated by treatment with ML385, an Nrf2 inhibitor. To conclude, Act A attenuated CIRI by enhancing Nrf2 expression and inhibiting neuronal ferroptosis.

Neurovascular compression syndrome:Trigeminal neuralgia, hemifacial spasm, vestibular paroxysmia, glossopharyngeal neuralgia, four case reports and review of literature.

Neurovascular compression syndrome is caused by vessels touching a cranial nerve, resulting in clinical manifestations of abnormal sensory or motor symptoms. The most common manifestations are trigeminal neuralgia and hemifacial spasm. However, neurovascular compression of the vestibular nerve or glossopharyngeal nerve are rare. In this article, we describe four typical cases of neurovascular compression syndrome. In addition, we analyze the main features of the etiology, neuroimaging, and treatment of this disease.

Serum Cystatin, Chemokine, and Gastrin-Releasing Peptide Precursors and Their Clinical Value in Patients with Chronic Renal Failure.

OBJECTIVE: To investigate the serum cystatin (CysC), Chemerin, and gastrin-releasing peptide precursor (ProGRP) levels in patients with chronic renal failure (CRF). METHODS: CRF patients admitted to our hospital from February 2019 to July 2019 were selected as the observation group, and 50 healthy patients were selected as the control group. The serum levels of CysC, Chemerin, ProGRP, and Scr of all subjects were detected. Patients with CRF were admitted for peritoneal dialysis (PD) treatment for 1 week, and continued treatment was performed. The survival rate of patients with CRF in nearly 1 year after continuous treatment was observed. Multivariate analysis of factors affecting survival time of CRF patients undergoing peritoneal dialysis was performed. The results were compared with those in the health group. The expression levels of CysC, Chemerin, ProGRP, and Scr in the observation group were all decreased, and the differences were statistically significant (P < 0.05). Pearson correlation analysis showed that Scr expression in CRF patients is positively correlated with CysC, Chemerin, and ProGRP (P < 0.001). The survival rate of 98 patients with CRF was 80.61% (79/98), and the mortality rate was 19.39% (19/98). Serum levels of CysC, Chemerin, ProGRP, and Scr in the death group are all higher than those in the survival group, and the differences are statistically significant (P < 0.05). CysC, Chemerin, ProGRP, and Scr are independent risk factors affecting survival time (P < 0.05). The AUC aspects of serum CysC, Chemerin, ProGRP, and Scr in predicting the survival rate of CRF patients in the treatment phase are 0.840, 0.775, 0.782, and 0.725, respectively. CONCLUSION: The serum levels of CysC, Chemerin, and ProGRP of CRF patients are abnormally elevated and are positively correlated with serum Scr of patients, which can be used as a reliable indicator of pathogenesis and prognosis assessment of CRF patients.

Comparative Efficacy and Acceptability of Cholinesterase Inhibitors and Memantine Based on Dosage in Patients with Vascular Cognitive Impairment: A Network Meta-analysis.

BACKGROUND: Considering the lack of direct comparison between cholinesterase inhibitors and memantine in patients with vascular cognitive impairment (VCI), determining how to choose the best treatment plan remains inconclusive. Hence, we conducted the network meta-analysis to compare the efficacy and acceptability of these drugs. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, Embase and Web of Science were searched for double-blind randomized controlled trials (RCTs) for the treatment of VCI, which involved donepezil, galantamine, rivastigmine, and memantine, from database inception to January 1, 2020. Then, a network meta-analysis based on the frequency method was conducted. RESULTS: Eleven RCTs were included. Compared with the placebo, in terms of efficacy, donepezil 5 mg (standardized mean difference = -1.11, 95% confidence interval = -1.88 to -0.34), donepezil 10 mg (-1.44, -2.31 to -0.56), galantamine 24 mg (-1.99, -3.03 to -0.95), and memantine 20 mg (-1.89, -2.93 to -0.86) were more effective for the cognition of ADAS-cog, and donepezil 5 mg (0.46, 0.12 to 0.81), donepezil 10 mg (0.76, 0.34 to 1.17), and rivastigmine 12mg (0.60, 0.10 to 1.10) exhibited superior benefits for the cognition of MMSE. Donepezil 10 mg (-0.25, -0.44 to -0.06; -1.47, -2.79 to -0.15) exhibited improvements for CDR-SB and EXIT25, respectively. In terms of acceptability, memantine was found to be the best. CONCLUSION: Donepezil 5 mg, donepezil 10 mg, galantamine 24 mg, memantine 20 mg, and rivastigmine 12 mg exerted beneficial effects on cognition, and donepezil 10mg provided beneficial effects for executive function and global status. Based on the network meta-analysis, donepezil 10 mg might be the best choice, considering the benefits on cognition function, executive function and global status, but doserelated adverse reactions need to be noted. In the meantime, memantine is a better comprehensive choice in terms of efficacy and safety.

Better late than never: initial experience of intra-arterial pulsed-urokinase-injection as a salvage therapy for refractory sudden sensorineural hearing loss.

BACKGROUND AND PURPOSE: Cochlear vascular micro-thrombosis has been hypothesized as one of the pathogenic mechanisms for sudden sensorineural hearing loss (SSNHL) refractory to regular management. This study aimed to evaluate the feasibility and safety of intra-arterial pulsed-injection urokinase (IAPU) as a salvage therapy for SSNHL after the failure of conventional therapy. METHODS: We retrospectively reviewed our patient database to identify refractory SSNHL patients between November 2017 and July 2020. Study outcomes before and after the IAPU therapy were compared between IAPU and conventional therapy groups. RESULTS: Sixty-seven moderate-profound SSNHL patients (29 in IAUP group, 38 in control group) were included in this study. Compared to the control group, patients in the IAPU group showed more significant improvement in pure tone average (PTA) (34.2 ± 23.5 vs. 10.7 ± 13.1, p < 0.001) and degree of hearing recovery (total: 20.7% vs. 5.3%, partial: 24.1% vs. 10.5%, mild: 27.6% vs. 13.2% and non: 27.6% vs. 71.1%) 2 weeks after admission. In the IAPU group, a significant improvement of PTA (86.6 ± 11.5 vs. 54.6 ± 20.1 dB, p < 0.005) was observed on the first day after IAPU treatment. CONCLUSION: In carefully selected SSNHL cases with a highly suspected vascular origin, IAPU is a safe and effective therapy when conventional treatments have failed. Despite the encouraging findings of our work, large studies are needed to better investigate the strengths and limitations of this salvage therapy.

Does radiological conjugate eye deviation sign play a role in acute stroke imaging? A meta-analysis.

BACKGROUND AND PURPOSE: The diagnostic value of non-contrast CT (NCCT) in acute stroke imaging remains indispensable, especially under emergency conditions with limited resources. The radiological conjugate eye deviation (RCED) has been demonstrated as a NCCT sign to predict acute ischemic stroke (AIS) or AIS secondary to large vessel occlusion (LVO) in recent studies. We performed a meta-analysis to gain a better understanding into the predictive role of RCED for AISs and LVO-AISs. METHODS: We conducted a systematic literature search using PubMed, Embase, and Cochrane. The search focused on studies published between January 2000 and August 2020 that reported the predictive value of RCED for the diagnosis of AIS or LVO-AIS. Principal measurements of the meta-analysis were the overall sensitivity, specificity, the positive likelihood ratio (PLR), and the negative likelihood ratio (NLR) of RCED in predicting AIS and LVO-AIS. RESULTS: We included 11 studies (n = 2304). For AIS, RCED had a sensitivity of 0.37 (95% CI 0.27-0.47), a specificity of 0.86 (95% CI 0.73-0.93), the area under the receiver operating characteristic curve (AUC) was 0.58 (95% CI 0.53-0.62), PLR was 2.5 (95% CI 1.5-4.4), and NLR was 0.74 (95% CI 0.65-0.84). For LVO-AIS, RCED had a sensitivity of 0.63 (95% CI 0.46-0.77), a specificity of 0.77 (95% CI 0.71-0.82), AUC was 0.63 (95% CI 0.46-0.77), PLR was 2.7 (95% CI 1.7-4.3), and NLR was 0.49 (95% CI 0.3-0.78). CONCLUSION: RCED can be used to predict LVO-AIS. It is expected that this method will be extensively used and validated in acute stroke imaging, especially under emergency conditions with limited resources.

Staged angioplasty: A sensible approach to prevent hyperperfusion syndrome after carotid artery stenting? A meta-analysis.

OBJECTIVE: To investigate whether staged angioplasty (SAP) is a safe and effective treatment to prevent hyperperfusion syndrome after carotid artery stenting (CAS). METHODS: A systematic literature search was performed according to established criteria to identify eligible articles published before October 2020. Pooled dichotomous data were presented as odds ratios (OR) and corresponding 95% confidence intervals (CI) using random-effect models. The efficacy endpoints were hyperperfusion syndrome (HPS), hyperperfusion phenomenon (HPP), and intracerebral hemorrhage (ICH). The safety endpoint was post-procedural thromboembolic events. The feasibility of the procedure was assessed by device-related adverse events (vessel dissection and failed angioplasty) in SAP. RESULTS: Ten studies (1030 participants) were eligible. SAP was superior to regular CAS in preventing HPS (OR = 0.35, 95% CI 0.14-0.86, P = 0.02). There was no significant difference in the rate of thromboembolic events between the SAP group and the regular CAS group. The rates of vessel dissection and failed angioplasty with the use of a 3.0-mm-diameter balloon were 5.4% and 0.4%, respectively. CONCLUSION: SAP may reduce the incidence of post-CAS HPS without increasing procedure-related complications. A 3.0-mm-diameter balloon used in SAP may be appropriate for Asian populations. However, the confounded study design and confused definitions of reporting items hinder the current recommendation of SAP in clinical use.

Exploration of the mechanism of luteolin against ischemic stroke based on network pharmacology, molecular docking and experimental verification.

Stroke is a leading cause of morbidity and mortality worldwide. As the most common type of stroke cases, treatment effectiveness is still limited despite intensive research. Recently, traditional Chinese medicine has attracted attention because of potential benefits for stroke treatment. Among these, luteolin, a natural plant flavonoid compound, offers neuroprotection following against ischemic stroke, although the specific mechanisms are unknown. Here we used network pharmacology, molecular docking, and experimental verification to explore the mechanisms whereby luteolin can benefit stroke recovery. The pharmacological and molecular properties of luteolin were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The potential targets of luteolin and ischemic stroke were collected from interrogating public databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed by Funrich and Database for Annotation, Visualization and Integrated Discovery respectively, a luteolin-target-pathway network constructed using Cytoscape, Autodock vina was used for molecular docking simulation with Discovery Studio was used to visualize and analyze the docked conformations. Lastly, we employed an in vitro model of stroke injury to evaluate the effects of luteolin on cell survival and expression of the putative targets. From 95 candidate luteolin target genes, our analysis identified six core targets . KEGG analysis of the candidate targets identified that luteolin provides therapeutic effects on stroke through TNF signaling and other pathways. Our experimental analyses confirmed the conclusions analyzed above. In summary, the molecular and pharmacological mechanisms of luteolin against stroke are indicated in our study from a systematic perspective.

Enriched environment remedies cognitive dysfunctions and synaptic plasticity through NMDAR-Ca2+-Activin A circuit in chronic cerebral hypoperfusion rats.

Chronic cerebral ischemia (CCI) is one of the critical factors in the occurrence and development of vascular cognitive impairment (VCI). Apoptosis of nerve cells and changes in synaptic activity after CCI are the key factors to induce VCI. Synaptic stimulation up-regulates intraneuronal Ca2+ level through N-methyl-D-aspartic acid receptor (NMDAR) via induction of the activity-regulated inhibitor of death (AID) expression to produce active-dependent neuroprotection. Moreover, the regulation of synaptic plasticity could improve cognition and learning ability. Activin A (ActA), an exocrine protein of AID, can promote NMDAR phosphorylation and participate in the regulation of synaptic plasticity. We previously found that exogenous ActA can improve the cognitive function of rats with chronic cerebral ischemia and enhance the oxygenated glucose deprivation of intracellular Ca2+ level. In addition to NMDAR, the Wnt pathway is critical in the positive regulation of LTP through activation or inhibition. It plays an essential role in synaptic transmission and activity-dependent synaptic plasticity. The enriched environment can increase ActA expression during CCI injury. We speculated that the NMDAR-Ca2+-ActA signal pathway has a loop-acting mode, and the environmental enrichment could improve chronic cerebral ischemia cognitive impairment via NMDAR-Ca2+-ActA, Wnt/ß-catenin pathway is involved in this process. For the hypothesis verification, this study intends to establish chronic cerebral hypoperfusion (CCH) rat model, explore the improvement effect of enriched environment on VCI, detect the changes in plasticity of synaptic morphology and investigate the regulatory mechanism NMDAR-Ca2+-ActA-Wnt/ß-catenin signaling loop, providing a therapeutic method for the treatment of CCH.

Effects of Microglial Activation and Polarization on Brain Injury After Stroke.

Stroke is one of the most common causes of death worldwide. The subsequent development of neuroinflammation and brain edema dramatically increases the risks associated with stroke, leading to a substantial increase in mortality. Although considerable progress has been made in improving cerebral perfusion in the acute phase of stroke, effective treatment options for the subacute and chronic phases associated with cerebral infarction are limited. Microglia, the innate immune cells of the central nervous system (CNS), can be activated and polarized to take on different phenotypes in response to stimulations associated with stroke, including pro-inflammatory and anti-inflammatory phenotypes, which affect the prognosis of stroke. Therefore, investigation of the activation and polarizing mechanisms of microglia plays a critical role in treating stroke. The aim of this article was to investigate the significance of microglial phenotype regulation in stroke treatment by summarizing the activation, polarizing mechanisms, and general microglia characteristics.

Betulinic Acid Ameliorates Cerebral Injury in Middle Cerebral Artery Occlusion Rats through Regulating Autophagy.

Cerebral ischemic stroke (CIS) is an acute cerebrovascular disease that is caused by the sudden rupture of blood vessels inside the brain and the intervention of reperfusion to the brain, resulting in severe cerebral injury. Autophagy has been reported to be involved in the occurrence and progression of CIS. Betulinic acid (BA) is a pentacyclic triterpene acid mainly extracted from birch bark. Studies have shown the neuroprotective effects of BA. Here, the effect and mechanism of BA on ischemia-reperfusion induced cerebral injury was explored using a CIS model in vivo via 1 h middle cerebral artery occlusion (MCAO) and 24 h reperfusion in rats and in vitro via oxygen-glucose deprivation/reperfusion (OGD/R) of PC12 cells, respectively. We found that BA not only reduced cerebral injury by reducing oxidative stress but also activated the SIRT1/FoxO1 pathway to suppress autophagy and improve cerebral injury in MCAO rats. These results provide a basis for the potential clinical application of BA.

CT-negative Subarachnoid Hemorrhage Caused by Telangiectasia: A Case Report.

INTRODUCTION: At present, the mechanism of telangiectasia is unknown, but some evidence suggests that it may be related to genetic abnormalities. Telangiectasia may lead to bleeding of multiple sites. CT-negative subarachnoid hemorrhage is rare, which is mostly related to hemorrhage with a little amount of bleeding. CT-negative subarachnoid hemorrhage due to telangiectasia has not been reported. CASE REPORT: In this case report, the patient experienced severe headache with nausea, vomiting, and blurred vision for 12 days, and had a history of hypertension. Physical examination revealed a clear state of mind, normal speech, normal limb muscle strength, 2 transverse fingers of neck stiffness, and negative bilateral Babinski signs. Brain CT, MRI, MRA, and MRV showed no obvious abnormalities. SWI suggested the possibility of capillary dilation. The cerebrospinal fluid was pale yellow in appearance after lumbar puncture. DIAGNOSIS: The patient was diagnosed with subarachnoid hemorrhage (SAH) and capillary dilatation. INTERVENTIONS: Therapeutic management of blood pressure and brain edema was started. CONCLUSION: Lumbar puncture should be performed when subarachnoid hemorrhage is clinically suspected and CT is negative. While searching for the cause of subarachnoid hemorrhage, the presence of telangiectasia should be ascertained.

Prognostic value of the neutrophil-to-lymphocyte ratio in acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis.

BACKGROUND: The relationship between the neutrophil-to-lymphocyte ratio (NLR) and poor prognostics in acute ischemic stroke (AIS) patients who receive intravenous thrombolysis (IVT) remains controversial. The purpose of this systematic review and meta-analysis was to evaluate the association between the NLR and poor prognosis after IVT. Furthermore, we aimed to determine whether the NLR at admission or post-IVT plays a role in AIS patients who received IVT. METHODS: The PubMed, Embase, Web of Science and China National Knowledge Infrastructure databases were searched for relevant articles until October 7, 2020. Cohort and case-control studies were included if they were related to the NLR in AIS patients treated with IVT. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were pooled to estimate the relationship between NLR and poor prognosis after IVT. A random effects model was used to calculate the pooled data. RESULTS: Twelve studies, including 3641 patients, met the predefined inclusion criteria. Higher NLRs were associated with an increased risk of hemorrhagic transformation (HT) (OR = 1.33, 95 % CI = 1.14-1.56, P < 0.001) and a poor 3-month functional outcome (OR = 1.64, 95 % CI = 1.38-1.94, P < 0.001) in AIS patients who received IVT. Subgroup analysis suggested that the NLR at admission rather than post-IVT was associated with a higher risk of HT (OR = 1.33, 95 % CI = 1.01-1.75, P = 0.039). There was no statistically significant difference between higher NLRs and 3-month mortality (OR = 1.14, 95 % CI = 0.97-1.35, P = 0.120). CONCLUSIONS: A high NLR can predict HT and poor 3-month functional outcomes in AIS patients who receive IVT. The NLR at admission rather than the post-IVT NLR was an independent risk factor for an increased risk of HT after IVT.

The diagnostic and prognostic performance of Lp-PLA2 in acute ischemic stroke

Objective: We aimed to investigate the correlation between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and acute ischemic stroke (AIS) severity and recurrence, which could indicate the diagnostic and prognostic values of Lp-PLA2.MethodsTwo hundred and fifty-one AIS patients who were diagnosed in the department of neurology, China-Japan Union Hospital, from April 2018 to June 2019 and 100 non-cerebrovascular disease patients were included in this study. Demographic data and clinical materials including age, sex, BMI, medical history, bad habits, imaging data, blood tests, etc., were collected. Stroke severity and risk were evaluated, respectively. AIS patients were followed up for 6 months for stroke recurrence monitoring.ResultsThe AIS group had significantly higher Lp-PLA2 level than the control group. High Lp-PLA2 level was the independent risk factor of AIS (OR 1.010; 95% CI 1.007–1.013, P<0.001). Admission NIHSS was compared between Lp-PLA2 categories dichotomized by median. Serum Lp-PLA2 level was positively correlated with NIHSS (r=0.268, P<0.001). Mild stroke group and severe stroke group were defined based on NIHSS. Compared with the mild stroke group, the severe stroke group had higher smoking ratio, posterior circulation stenosis incidence, LDL level, Lp-PLA2 level and admission Essen score. (AU)

Objetivo: Nuestro objetivo fue investigar la correlación entre el nivel sérico de fosfolipasa A2 asociada a lipoproteína (Lp-PLA2) y la gravedad y recurrencia de los accidentes cerebrovasculares agudos (ACV), lo cual podría ser indicativo de los valores diagnóstico y pronóstico de Lp-PLA2.MétodosSe incluyó en el estudio a 251 pacientes de ACV diagnosticados en el Departamento de Neurología del Hospital China-Japan Union, desde abril de 2018 a junio de 2019, y a 100 pacientes sin enfermedad cerebrovascular. Se recopilaron los datos demográficos y materiales clínicos incluyendo edad, sexo IMC, historia médica, malos hábitos, estudios por imagen, análisis de sangre, etc. Se evaluaron la gravedad del accidente cerebrovascular y el riesgo, respectivamente, realizándose un seguimiento de supervisión de la recurrencia del accidente, de 6 meses de duración, a los pacientes de ACV.ResultadosEl grupo ACV tuvo un nivel de Lp-PLA2 significativamente superior al del grupo control. El nivel alto de Lp-PLA2 fue el factor de riesgo independiente de ACV (OR: 1,010; IC 95%: 1,007-1,013; p<0,001). Se comparó el valor de la escala NIHSS durante el ingreso entre las categorías Lp-PLA2, dicotomizadas por mediana. El nivel sérico de Lp-PLA2 se correlacionó positivamente con NIHSS (r=0,268; p<0,001). Se definieron el grupo de accidente leve y el grupo de accidente grave sobre la base de NIHSS. En comparación con el grupo de accidente leve, el grupo de accidente grave tenía un ratio más alto de fumadores, incidencia de estenosis circulatoria posterior, nivel de LDL, nivel de Lp-PLA2 y puntuación Essen durante el ingreso. La regresión logística reflejó que los niveles Lp-PLA2 por 50ng/ml (OR: 1,381; IC 95%: 1,212-1,573; p<0,001) y la categoría Lp-PLA2 (OR: 2,420; IC 95%: 1,363-4,297; p=0,003) estaban independientemente asociados a los accidentes graves. Durante el seguimiento de 6 meses realizado a los 251 pacientes de ACV, se observaron 31 casos de recurrencia de accidentes. (AU)

The diagnostic and prognostic performance of Lp-PLA2 in acute ischemic stroke.

OBJECTIVE: We aimed to investigate the correlation between serum lipoprotein-associated phospholipase A2 (Lp-PLA2) level and acute ischemic stroke (AIS) severity and recurrence, which could indicate the diagnostic and prognostic values of Lp-PLA2. METHODS: Two hundred and fifty-one AIS patients who were diagnosed in the department of neurology, China-Japan Union Hospital, from April 2018 to June 2019 and 100 non-cerebrovascular disease patients were included in this study. Demographic data and clinical materials including age, sex, BMI, medical history, bad habits, imaging data, blood tests, etc., were collected. Stroke severity and risk were evaluated, respectively. AIS patients were followed up for 6 months for stroke recurrence monitoring. RESULTS: The AIS group had significantly higher Lp-PLA2 level than the control group. High Lp-PLA2 level was the independent risk factor of AIS (OR 1.010; 95% CI 1.007-1.013, P<0.001). Admission NIHSS was compared between Lp-PLA2 categories dichotomized by median. Serum Lp-PLA2 level was positively correlated with NIHSS (r=0.268, P<0.001). Mild stroke group and severe stroke group were defined based on NIHSS. Compared with the mild stroke group, the severe stroke group had higher smoking ratio, posterior circulation stenosis incidence, LDL level, Lp-PLA2 level and admission Essen score. Logistic regression showed Lp-PLA2 levels per 50ng/mL (OR 1.381, 95% CI 1.212-1.573, P<0.001) and Lp-PLA2 category (OR 2.420, 95% CI 1.363-4.297, P=0.003) were both independently associated with severe stroke. During the 6-month follow-up of all 251 AIS patients, 31 stroke recurrence cases were observed. Both Lp-PLA2 levels per 50ng/mL (OR 1.420, 95% CI 1.212-1.664, P<0.001) and Lp-PLA2 category (OR 2.726, 95% CI 1.201-6.178, P=0.016) were significantly associated with the stroke recurrence. Under the receiver Operating Characteristic curve, Lp-PLA2 showed significant predicting ability for stroke recurrence (AUC 0.723; 95% CI 0.620-0.826, P<0.001). CONCLUSION: High serum Lp-PLA2 level is correlated with AIS incidence, disease severity and recurrence, which could be utilized to guide clinical practice.

Gender-related difference in altered fractional amplitude of low-frequency fluctuations after electroacupuncture on primary insomnia patients: A resting-state fMRI study.

BACKGROUND: Primary insomnia (PI) is defined as a sleep disorder with no definite cause or inducement. Electroacupuncture, a treatment of inserting needles into specific points on the body surface and applying electrical stimulation, has been proved effective in treating PI with minimal adverse effects. However, the influence of gender difference on the clinical treatment efficacy of electroacupuncture for PI patients remains unclear. Therefore, we designed a clinical trial to compare the clinical treatment efficacy of electroacupuncture for PI patients with different genders. The research on the mechanism of electroacupuncture suggested it could modulate the sleep and wakefulness by activating or deactivating brain regions via a needling/tactile somatosensory specific stimulus. Therefore, we also designed a resting-state functional magnetic resonance imaging (rs-fMRI) study to detect the spontaneous brain activity of PI patients before and after the electroacupuncture treatment. METHOD: Thirty PI patients were recruited to accept 5-week electroacupuncture treatment on HT-7. Athens Insomnia Scale (AIS) and Pittsburgh sleep quality index (PSQI) questionnaires were used to evaluate the clinical treatment efficacy. Rs-fMRI was employed to observe the spontaneous brain activity in the resting state at the baseline and after 5 weeks of electroacupuncture treatment, which was measured by the fractional amplitude of low-frequency fluctuations (fALFF). RESULT: The AIS and PSQI scores were significantly decreased both in the female PI group and the male PI group after treatment. The decreased PSQI of female patients was significantly more than that of male patients (p < .05). The gender-related difference in the cerebral response to electroacupuncture was mainly in posterior cingulate and supramarginal gyrus. CONCLUSION: There is a gender-related difference in the clinical treatment efficacy of electroacupuncture for PI patients, and female patients may benefit more from electroacupuncture. Gender-related differences in the cerebral response to electroacupuncture may be one of the factors affecting clinical treatment efficacy.