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Abstract: Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived "find-me," "eat-me," and "don't eat-me" molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Background: Serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) have been reported to be associated with outcomes in acute ischemic stroke (AIS). However, whether UA is related to the prognosis of AIS patients undergoing intravenous thrombolysis (IVT) remains inconclusive. We sought to explore the combined effect of UA and NLR on the prognosis of AIS treated with IVT., Methods: A total of 555 AIS patients receiving IVT treatment were enrolled. Patients were categorized into four groups according to the levels of UA and NLR: LNNU (low NLR and normal UA), LNHU (low NLR and high UA), HNNU (high NLR and normal UA), and HNHU (high NLR and high UA). Multivariable logistic regression analysis was used to evaluate the value of serum UA level and NLR in predicting prognosis. The primary outcomes were major disability (modified Rankin scale (mRS) score 3-5) and death within 3 months., Results: After multivariate adjustment, a high NLR (≥ 3.94) increased the risk of 3-month death or major disability (OR, 2.23; 95% CI, 1.42 to 3.55, p < 0.001). However, there was no statistically significant association between a high UA level (≥ 313.00 µmol/L) and clinical outcome. HNHU was associated with a 5.09-fold increase in the risk of death (OR, 5.09; 95% CI, 1.31-19.83; P value = 0.019) and a 1.98-fold increase in the risk of major disability (OR, 1.98; 95% CI 1.07-3.68; P value = 0.030) in comparison to LNNU., Conclusions: High serum UA levels combined with high NLR were independently associated with 3-month death and major disability in AIS patients after IVT., (© 2024. The Author(s).)

Background: The association between atrial fibrillation (AF) and the prognosis of acute ischaemic stroke (AIS) remains controversial; whether the recombinant tissue plasminogen activator dose influences this association remains poorly understood., Methods: Patients who had an AIS were enrolled from eight stroke centres in China. According to the recombinant tissue plasminogen activator dose, patients treated with intravenous recombinant tissue plasminogen activator within 4.5 hours after symptom onset were divided into a low-dose group (recombinant tissue plasminogen activator <0.85 mg/kg) and a standard-dose group (recombinant tissue plasminogen activator ≥0.85 mg/kg). Patients who had an AIS in the low-dose group and the standard dose group were divided into whether or not they had AF. The main outcomes were major disability (modified Rankin scale (mRS) score 3-5), mortality and vascular events occurring within 3 months., Results: The study included 630 patients who received recombinant tissue plasminogen activator after AIS, including 391 males and 239 females, with a mean age of 65.8 years. Of these patients, 305 (48.4%) received low-dose recombinant tissue plasminogen activator and 325 (51.6%) received standard dose recombinant tissue plasminogen activator. The recombinant tissue plasminogen activator dose significantly influenced the association between AF and death or major disability (p-interaction=0.036). After multivariate adjustment, AF was associated with an increased risk of death or major disability (OR 2.90, 95% CI 1.47 to 5.72, p=0.002), major disability (OR 1.93, 95% CI 1.04 to 3.59, p=0.038) and vascular events (HR 5.01, 95% CI 2.25 to 11.14, p<0.001) within 3 months in patients with standard-dose recombinant tissue plasminogen activator. No significant association was found between AF and any clinical outcome in patients with low-dose recombinant tissue plasminogen activator (all p>0.05). With AF, the mRS score distribution showed a significantly worse shift in patients with standard-dose recombinant tissue plasminogen activator (p=0.016) than in those with low-dose recombinant tissue plasminogen activator (p=0.874)., Conclusions: AF may be a strong predictor of poor prognosis in patients who had an AIS receiving standard-dose recombinant tissue plasminogen activator, suggesting that low-dose recombinant tissue plasminogen activator should be administered to patients who had a stroke with AF to improve their prognosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of Postgraduate Medical Journal. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Corin, a physical activator of atrial natriuretic peptide, has been associated with hypertension with unclear mechanisms. Here, we aimed to examine whether CORIN gene methylation was involved in the underlying molecular mechanisms., Methods: DNA methylation levels of CORIN were measured by target bisulfite sequencing using genomic DNA isolated from peripheral blood mononuclear cells in 2498 participants in the Gusu cohort (discovery sample) and 1771 independent participants (replication sample). We constructed a mediation model with DNA methylation as the predictor, serum corin as the mediator, and hypertension as the outcome, adjusting for covariates. Multiple testing was controlled by false discovery rate (FDR) approach., Results: Of the 9 CpGs assayed, hypermethylation at all CpGs were significantly associated with a lower level of blood pressure in the discovery sample and eight associations were also significant in the replication sample (all FDR-adjusted p<0.05). Serum corin mediated approximately 3.07% (p=0.004), 6.25% (p=0.002) and 10.11% (p=0.034) of the associations of hypermethylation at one CpG (Chr4:47840096) with systolic and diastolic blood pressure, and hypertension, respectively. All these mediations passed the causal inference test., Conclusions: These results suggest that hypermethylation in the CORIN gene is associated with a lower odds of prevalent hypertension and may be involved in the role of corin in blood pressure regulation., (© The Author(s) 2022. Published by Oxford University Press on behalf of Postgraduate Medical Journal. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

At present, the main treatment methods of osteosarcoma are chemotherapy and surgery. Its 5-year survival rate has not been significantly improved in the past decades. Osteosarcoma has extremely complex multigenomic heterogeneity and lacks universally applicable signal blocking targets. Osteosarcoma is often found in adolescents or children under the age of 20, so it is very important to explore its genetic pathogenic factors. We used known osteosarcoma-related genes and computer algorithms to find more osteosarcoma pathogenic genes, laying the foundation for the treatment of osteosarcoma immune microenvironment-related treatments, so as to carry out further explorations on these genes. It is a traditional method to identify osteosarcoma related genes by collecting clinical samples, measuring gene expressions by RNA-seq technology and comparing differentially expressed gene. The high cost and time consumption make it difficult to carry out research on a large scale. In this paper, we developed a novel method "RELM" which fuses multiple extreme learning machines (ELM) to identify osteosarcoma pathogenic genes. The AUC and AUPR of RELM are 0.91 and 0.88, respectively, in 10-cross validation, which illustrates the reliability of RELM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhao, Shi, Zhao, Gao, Jiang and Yuan.)

Background: Transcatheter closure of aneurysmal perimembranous ventricular septal defect (pmVSD), pmVSD near the aortic valve, and intracristal VSD (icVSD) with symmetrical or asymmetrical ventricular septal defect occluders still presents significant challenges. We report our experience with transcatheter closure of pmVSD and icVSD using Amplatzer duct occluder II (ADO II) in children., Method: We retrospectively analyzed all children, who presented to our hospital consecutively between March 2014 and June 2020 for attempted transcatheter closure of pmVSD or icVSD with the ADO II device. Standard safety and last-follow-up outcomes were assessed and compared., Results: In total, 41 patients underwent transcatheter closure of VSD with the ADO II (28 in pmVSD and 13 in icVSD groups) with a median age of 3.5 years (total range: 0.9 to 12 years) and median weight of 15.0 kg (total range: 10.0 to 43.0 kg). Implantation was successful in 40/41 patients (97.5%, 27/28 in pmVSD group, 13/13 in icVSD group). One patient with mild aortic valve prolapse in pmVSD group developed new-onset moderate aortic regurgitation after a 4/4 mm ADO II was deployed; however, this resolved after the device was retrieved and successfully replaced with a 5 mm zero eccentric VSD occluder. There was no procedure-related mortality. After a median follow-up of six months (total range: 6 to 72 months), complete closure rates were 85.1% and 76.9% among pmVSD and icVSD groups, respectively. In the pmVSD group, one case of new-onset moderate tricuspid regurgitation was observed at six months, and there was one case of severe tricuspid regurgitation that had progressed from mild tricuspid regurgitation at 12 months. No serious complications were noted in the icVSD group., Conclusion: ADO II provides a safe and reproducible alternative for the closure of perimembranous and intracristal ventricular septal defects with a diameter less than 5 mm in young children., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Shenrong Liu et al.)

Introduction: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an increasingly recognized type of steroid-responsive autoimmune disease of the nervous system. Defined in 2016, it is associated with the presence of anti-GFAP immunoglobulinG in the serum or cerebrospinal fluid (CSF) of affected patients., Patient Characteristics: Herein, we report a case of acute neurological symptoms, including headache, fever, confusion, and paralysis of the lower extremities. CSF analysis revealed lymphocytic pleocytosis and elevated protein levels, indicating acute disseminated encephalomyelitis, and the patient was given immunotherapy. Cranial magnetic resonance imaging showed multifocal T2/fluid-attenuated inversion recovery hyperintense signal changes in the periventricular white matter, and electromyography testing showed changes consistent with severe sensorimotor neuropathy, indicating the involvement of the brain and peripheral nerves., Diagnoses: Finally, a diagnosis of autoimmune GFAP astrocytopathy was confirmed due to the presence of GFAP-immunoglobulinG in the patient's CSF., Interventions: The patient was treated with one course of intravenous immunoglobulin therapy, then followed with intravenous methylprednisolone (1.0 g/d for 3 days) and oral prednisolone., Outcomes: At 1 week after intravenous immunoglobulin therapy, his level of consciousness improved. However, flaccid paralysis persisted without substantial improvement., Conclusion: In conclusion, the provision of an accurate early diagnosis and appropriate treatment are crucial for improving the prognosis of patients with autoimmune GFAP astrocytopathy. Further, this case highlights the importance of recognizing the role of peripheral nerve involvement in GFAP autoimmunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: As a key enzyme of natriuretic peptides system playing an integral role in energy homeostasis, furin may be a potential contributor to obesity. However, the association between furin and obesity has been scarcely studied. This study aims to examine the prospective association between serum furin and abdominal obesity., Methods: Waist circumference (WC) was measured twice 4 years apart for a total of 892 Chinese adults free of abdominal obesity at baseline. Abdominal obesity was defined as WC over 85 cm for men and as WC over 80 cm for women. A Cox proportional hazard model was constructed to examine the association of baseline serum furin with incident abdominal obesity., Results: After an average 4 years of follow-up, 184 participants developed new abdominal obesity. Baseline serum furin was significantly associated with dynamic body weight during follow-up (β=-0.593, p=0.003). Participants with a higher level of serum furin at baseline were less likely to develop new abdominal obesity compared with those with a lower level of serum furin (HR=0.81, 95% CI 0.67 to 0.97)., Conclusions: A lower level of serum furin predicts a higher risk of developing future abdominal obesity in Chinese adults. Furin deficiency may be a contributor to abdominal obesity but still needs further investigations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: With the rapid development of transcatheter techniques and instruments, transcatheter occlusion for patients with perimembranous ventricular septal defect (pVSD) and aortic valve prolapse (AVP) was constantly being tried, while the efficacy and safety of pVSD with AVP remain controversial., Objective: The aim of this study was to evaluate long-term efficacy and safety of transcatheter occlusion of pVSD with AVP., Methods: We retrospectively analyzed 164 children with pVSD and AVP who underwent transcatheter occlusion between January 2013 and November 2014. AVP was divided into 3 degrees according to right coronary leaflet morphology at end-diastole during aortic root angiography. Patient demographic and clinical data were collected., Results: There were 97 males and 67 females (median age, 40.0 (30.0-62.7) months; average weight, 16.94 ± 9.02 kg). Mild ( n  = 63), moderate ( n  = 89), and severe ( n  = 12) AVP success rates were 93.7%, 89.9%, and 58.3%, respectively. Immediately after procedure, there was no new-onset aortic regurgitation (AR) above trivial degree, residual shunt above mild degree, or complications requiring medication or operation, except for 1 patient who developed transient complete atrioventricular block. During follow-up, 1 mild AVP patient aggravated from mild to moderate AR and 1 moderate AVP patient aggravated from trivial to moderate AR. The new-onset AR in mild, moderate, and severe AVP was 2%, 1.8%, and 20%, respectively. AR disappeared in 17 patients. Residual shunt occurred in 9 patients after procedure, 4 of which disappeared during the follow-up period. No serious complications occurred in any patient during follow-up. Five-year cardiovascular event-free survival rates for mild, moderate, and severe AVP were 89.6%, 94.5%, and 80.0%, respectively., Conclusion: Transcatheter occlusion of pVSD with mild and moderate AVP has a high success rate and few complications, which is safe and effective in long-term follow-up. Transcatheter occlusion of pVSD with severe AVP has low success rates and high AR incidence. Therefore, transcatheter occlusion of pVSD with AVP is recommended for mild to moderate, but not severe, AVP., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Wenqian Zhang et al.)

Objectives: We aimed to explore the radiologic characteristics and interventional strategies for perimembranous ventricular septal defect (pmVSD) with aneurysm., Methods: 257 patients who underwent transcatheter closure of pmVSD with aneurysm were included in our study. We retrospectively reviewed the left ventricular opening of the aneurysm (a), diameter of the midsegment of the aneurysm (b), and diameter of the right ventricular opening of the aneurysm (c). If there were multiple defects within the aneurysm, the largest defect was denoted as c 1 and so forth. We developed a novel VSD classification method in which pmVSD with aneurysm was classified into three types (A, B, and C). When a  > b  ≥  c , it was classified as type A, when b  >  a  ≥  c , it was type B, and when c  >  a  ≥  b , it was type C; c / c 1 described the relationship among defects., Results: All of the 257 cases of pmVSD with aneurysm were defined using left ventriculography: type A, 60, type B, 58, and type C, 139. Transcatheter closure was attempted in 244 patients and succeeded in 227 cases (success rate was 93.0%; 227/244). Forty symmetric VSD occluders and 13 asymmetric VSD occluders were used for type A aneurysm occlusion; 31 symmetric VSD occluders, 19 asymmetric VSD occluders, and one Amplatzer duct occluder II (ADOII) were used for type B; 59 VSD symmetric occluders, 59 asymmetric VSD occluders, three eccentric VSD occluders, and two ADOII were used for type C. Within 24 hours after procedure, 2.2% patients had postprocedural residual shunt, and 2.2% experienced malignant arrhythmia (including type II second-degree AVB, cAVB, and CLBBB). Two hundred and twelve patients completed follow-up (93%, 212/227). No new severe complications were reported during follow-up, except in one patient who underwent surgery (removal of the device, VSD repair, and tricuspid valvuloplasty) due to severe postprocedural tricuspid regurgitation., Conclusions: It is safe and effective to apply this method for the classification of pmVSD with aneurysm and its interventional strategy., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Weibing Guo et al.)

Purpose: The natriuretic peptides (NPs) system, and mainly atrial natriuretic peptide (ANP), plays a key role in human metabolism and cardiometabolic disorders. Due to differences in NP levels and in prevalence of metabolic syndrome (MetS) between men and women, we aimed to explore the gender difference of association between N-terminal pro-atrial natriuretic peptide (NT-proANP) and MetS in a general population in China., Methods: Participants' weight, height, waist circumference, blood pressure, plasma NT-proANP, and other traditional biomarkers were measured. Multivariate logistic regression models were used to determine the association between plasma NT-proANP and MetS, and the odds ratio (OR) and 95% confidence interval (CI) were calculated for men and women, respectively., Results: Among 2203 participants, 1361 (61.78%) were women, 687(30.77%) participants had MetS, and the average age was 53 years. Women had a higher level of NT-proANP than men. However, adjusted logistic regression demonstrated that men in the upper quartile group of NT-proANP had 0.60 (95% CI 0.39-0.92) times the risk of having MetS, while women in the upper quartile group had 1.10 (95% CI 0.77-1.56) times the risk of having MetS compared to the lower quartile group. Furthermore, with the increase of the level of NT-proANP, the ORs showed a declining trend in men (P = 0.017), but it was not statistically significant among women (P = 0.700)., Conclusions: There are gender differences in the relationship between NT-proANP and MetS, while an inverse association between plasma NT-proANP and MetS in men suggests that higher levels of NT-proANP may be a protective factor for MetS.

This study aimed to investigate the association between dynamic changes in fibrinogen and the prognosis of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). We measured fibrinogen levels at admission and 24 h after IVT in 364 consecutively recruited AIS patients. The primary outcome was the composite measure of death or major disability (modified Rankin Scale score 3-6) at 3 months. During the 3-month follow-up, 127 (34.89%) patients experienced death or major disability. After multivariate adjustment, a ≥ 2.5% increase in fibrinogen was associated with an increased risk of the primary outcome (odds ratio [OR], 2.26; 95% confidence interval [CI] 1.08-4.75; p trend = 0.030) when 2 extreme tertiles were compared. Each 1% increase in fibrinogen after IVT was associated with a 1% increase in the risk of the primary outcome (OR 1.01, 95% CI 1.00-1.03). Multivariable-adjusted spline regression revealed a linear dose-response relationship between fibrinogen changes after IVT and the primary outcome (p for linearity = 0.032). The addition of fibrinogen changes to conventional risk factors improved the re-classification (but not discrimination) of the primary outcome (net reclassification index 27.6%, p = 0.011). These findings indicated that an increase in fibrinogen after IVT was associated with an increased risk of death or major disability in AIS patients, suggesting that monitoring the dynamic profile of fibrinogen levels may help neurologists improve stroke outcomes in clinical settings.

The cardiovascular protective role of furin has been suggested by some animal-based studies but has not been well studied in humans. Therefore, the objective of this study was to examine the prospective association between serum furin and high blood pressure in a longitudinal cohort of Chinese adults. Leveraging a longitudinal prospective cohort with blood pressure examined twice on average 4 years apart, we systemically examined the cross-sectional, longitudinal, and prospective associations of baseline serum furin with blood pressure and incident hypertension. Conventional risk factors, including age, sex, education level, cigarette smoking, alcohol consumption, BMI, fasting glucose, and lipids, were controlled. All participants included were free of cardiovascular and kidney disease at baseline. The cross-sectional analysis of 2312 participants (mean age 53 years) revealed that individuals with the lowest quartile of serum furin had average systolic, diastolic, and mean arterial blood pressures that were 2.58, 1.38, and 1.61 mmHg higher, respectively, than the corresponding pressures in individuals with the highest quartile (all P < 0.001). These negative associations remained significant after controlling for the dynamic risk profiles during follow-up in the longitudinal analysis. The prospective analysis of 1088 participants free of prevalent hypertension at baseline revealed that compared with participants with the highest quartile of serum furin, those with the lowest quartile had a 46% increased risk of incident hypertension (HR = 1.46, P = 0.003). These results indicate that lower serum furin is significantly associated with higher blood pressure and predicts an increased future risk of developing hypertension in Chinese adults. Furin may be a protective factor or marker of hypertension.

Background: Evidence about whether neutrophil counts, neutrophil ratio linked with clinical outcome in patients with minor stroke after thrombolysis is scarce. The purpose of this study is to explore the association of neutrophil counts, neutrophil ratio with the 90-day clinical outcome in patients with minor stroke treated with intravenous thrombolysis., Materials and Methods: A total of 163 patients with minor stroke treated with thrombolysis within window time were recruited from 2013 to 2017. Their total neutrophil and leukocyte counts on admission were measured. Disability or death (defined as a modified Rankin scale score ≥2) at 90-day were captured. Multiple logistic regression models were used to estimate the association between neutrophil counts, and neutrophil ratio to clinical outcome. Receiver operating characteristic curves were used to evaluate the predictive value of neutrophil counts or neutrophil ratio., Results: At the 90-day follow-up, 36 patients (21%) had disability or death after stroke onset. Compared to the first tertile, the higher neutrophil counts increased the risk of 90-day disability or death (adjusted odds ratio [aOR] for third tertile: 2.93 (1.08-7.96); P for trend = .03). Similarly, higher neutrophil ratio also increased the risk of disability or death (aOR for third tertile: 5.81 (1.7-19.88); P for trend = .005). The comparison of area under the curve for neutrophil ratio versus neutrophils was .1 (P = .04). Thus, neutrophil ratio with the cutoff point of .74 had a better discriminative ability to the outcome (6.11, 2.36-15.86)., Conclusions: Baseline higher neutrophil counts and neutrophil ratio were associated with an increased risk of 90-day disability or death in patients with minor stroke who received thrombolytic therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Soluble corin has been associated with cardiovascular disease and its risk factors, but whether it is associated with metabolic syndrome (MetS), a cluster of cardiometabolic disorders, remains unclear. We aimed to examine the association between soluble corin and MetS in Chinese men and women. We examined serum soluble corin using immunoassays in 962 men (mean age, 53 years) and 1536 women (mean age, 54 years) free of cardiovascular disease. Logistic regression was applied to examine the association between soluble corin and MetS in men and women. The results showed that participants in the 3rd and 4th quartiles of serum soluble corin had 1.99 (95% CI: 1.32-3.00) and 3.84 (95% CI: 2.54-5.83) times the risk of having MetS for men and 1.48 (95% CI: 1.06-2.06) and 1.53 (95% CI: 1.10-2.12) times the risk of having MetS for women compared to those in the lowest quartile. The magnitude of the association between serum soluble corin and MetS was significantly stronger for men than for women (P < 0.001). These results indicated that soluble corin was significantly associated with MetS, and this association was stronger for men than for women. Corin may contribute to cardiometabolic risks differently between men and women and thereby accounting, at least partly, for the sex difference in cardiovascular risk.

Little is known about the prognostic value of the estimated glomerular filtration rate (eGFR) and the effect of dynamic changes in the eGFR on mortality in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). We aim to investigate the association between the eGFR and dynamic changes in the eGFR after IVT with all-cause mortality in AIS patients. A total of 391 AIS patients treated with IVT between May 2010 and May 2017 were included in the final analysis. Serum creatinine was measured at admission and within 24 h after IVT. The main outcomes included 3-month all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE). During the 3-month follow-up, 37 (9.5%) patients died from all causes. Mortality was associated with a reduced eGFR at admission (adjusted hazard ratio (HR), 4.17; 95% confidence interval (CI), 1.50-11.58; P trend = 0.016) and within 24 h after IVT (adjusted HR, 5.88; 95% CI, 1.41-24.52; P trend = 0.009). Mortality was negatively correlated with increased eGFR after IVT (adjusted HR, 0.70; 95% CI, 0.51-0.96; P trend = 0.027). Additionally, a reduced eGFR after IVT was also associated with increased risk of MACCE (adjusted HR, 3.64; 95% CI, 1.41-9.39; P trend = 0.009). Using a multivariable Cox regression model with restricted cubic splines, we observed an L-shaped association between the eGFR and 3-month all-cause mortality and MACCE and observed a linear association between dynamic changes in the eGFR and 3-month all-cause mortality. A reduced eGFR and dynamic decreases in the eGFR after IVT independently predict 3-month all-cause mortality in AIS patients.

Background and Purpose- CLEC-2 (C-type lectin-like receptor 2) is a C-type lectin receptor highly expressed on platelets with the prominent involvement in platelet activation, which was increased in coronary heart disease. Given the role of platelet activation in ischemic stroke and the connections between coronary heart disease and ischemic stroke, CLEC-2 might be a candidate marker of ischemic stroke. Here, we aimed to examine the prognostic significance of CLEC-2 in patients with acute ischemic stroke (AIS). Methods- Three hundred fifty-two patients with AIS within 7 days and 112 healthy controls were prospectively studied. Plasma CLEC-2 (pCLEC-2) and some conventional risk factors of stroke were examined. Stroke progression was defined as any new neurological symptoms/signs or any neurological worsening within 7 days after stroke onset, and poor prognosis was defined as modified Rankin Scale scores >2 at 90 days. The association between pCLEC-2 and stroke progression/prognosis was evaluated using regression models. Results- Patients with AIS had a significantly higher level of pCLEC-2 than that of healthy controls ( P <0.05). Patients with AIS with progressive stroke or poor prognosis had a much higher level of pCLEC-2 compared with those with stable stroke or good prognosis (all P <0.05). Increasing pCLEC-2 was significantly associated with an increased risk of stroke progression (odds ratio, 1.97; 95% CI, 1.11-3.50; P =0.021) and poor prognosis (odds ratio, 1.70; 95% CI, 1.17-2.48; P =0.006). Patients with the highest pCLEC-2 level were 7- to 8-fold more likely to have stroke progression compared with the lowest quartile (odds ratio, 7.69; 95% CI, 1.43-41.41). Patients with the highest pCLEC-2 level were also more likely to have poor prognosis at 90 days (odds ratio, 5.58; 95% CI, 1.76-17.68). The optimal cutoff points of pCLEC-2 for predicting stroke progression and poor prognosis were 235.48 and 207.08 pg/mL, respectively. Conclusions- Increased pCLEC-2 was associated with stroke progression and poor prognosis at 90 days significantly, which indicates the prognostic role of pCLEC-2 in AIS. However, it needs to be confirmed in large-scale studies.

Background: Less is known about the prognostic value of serum cystatin C in acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). The aim of the present study was to examine the association between serum cystatin C levels and prognosis of AIS patients after IVT., Methods: Serum cystatin C was measured within 24 hours after recombinant tissue plasminogen activator (rt-PA) treatment in 280 consecutively recruited patients with AIS. The main outcomes included combination of death and major disability, death, major disability (modified Rankin Scale score 3-5) and vascular events at 3-month follow-up., Results: During the 3-month follow-up, 94 patients (33.6%) experienced death or major disability (28 deaths and 66 major disability) and 49 patients (17.5%) experienced vascular events. After multivariate adjustment, serum cystatin C was significantly associated with an increased risk of the combined outcome of death and major disability (OR=4.51, P = 0.006). Adding serum cystatin C quartiles to a model containing conventional risk factors improved the predictive power for the combined outcome of death and major disability (continuous net reclassification index 43.88%, P < 0.001; categorical net reclassification index 9.15%, P = 0.013; integrated discrimination improvement 2.31%, P = 0.025). Similar phenomena were also observed in major disability and vascular events., Conclusion: Higher levels of serum cystatin C in AIS patients after IVT were independently associated with increased risks of poor functional outcomes and vascular events, especially combining conventional risk factors, suggesting that serum cystatin C might improve risk prediction for poor prognosis in AIS patients receiving rt-PA treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The impact of Total Bile Acids (TBA) level on clinical outcomes after acute Intracerebral Hemorrhage (ICH) is still not understood., Objective: We investigated whether admission TBA level is associated with hematoma volume, stroke clinical severity, and 3-month outcomes in acute ICH patients., Methods: A total of 335 ICH patients were prospectively enrolled. Patients were divided into four groups, according to the quartiles of serum TBA level at the time of admission. Three-month outcomes were evaluated by interviews with patients or their family members., Results: The median hematoma volumes for the quartiles of TBA level (Q1 to Q4) were 12.0, 12.3, 10.0, and 6.7 mL (P<0.001) and the median National Institutes of Health Stroke Scale (NIHSS) scores were 8, 8, 6, and 5 (P=0.002), respectively. In the adjusted models, patients in the highest quartile (Q4) had smaller hematoma volumes (P=0.039) and lower NIHSS scores (P=0.037) than patients in Q1. At three months follow-up, there were 136 patients with poor outcomes (defined as having modified Rankin Scale scores≥3) and 46 cases of all-cause deaths. TBA level was not significantly associated with poor outcome nor all-cause death after adjusting for age, sex, hematoma volume, and baseline NIHSS(all P-trend≥0.380)., Conclusions: Higher admission TBA was associated with smaller hematoma volume and decreased clinical severity, but not three month outcomes in patients with acute ICH., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: The prognostic value of White Blood Cell (WBC) counts and C-reactive Protein (CRP) in clinical outcomes of Acute Ischemic Stroke (AIS) patients after Intravenous Thrombolysis (IVT) remains unknown. We investigated the association of WBC counts and CRP with 3-month functional outcomes and all-cause mortality in AIS patients., Methods: 447 AIS patients treated with IVT between May 2010 and May 2017 were enrolled. WBC counts and CRP were measured within 24 hours after IVT. The main outcomes included poor functional outcomes (modified Rankin score ≥3) at 3 months and 3-month all-cause mortality., Results: High WBC counts were associated with poor functional outcomes (adjusted OR (odds ratio) 4.48; 95% CI (confidence interval) 2.00-10.03; P-trend<0.001) and with all-cause mortality (adjusted HR (hazard ratio) 2.19; 95% CI 1.07-4.49; P-trend=0.018). In addition, high CRP levels were associated with poor functional outcomes (adjusted OR 4.95; 95% CI 1.39-17.65; Ptrend= 0.002). However, no significant association between high CRP levels and all-cause mortality was observed (adjusted HR 2.61; 95% CI 0.80-8.47; P-trend=0.138)., Conclusion: Our analysis indicated that elevated WBC counts and CRP levels after IVT can independently predict poor outcome among AIS patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Neutrophil to lymphocyte ratio (NLR) serves as a powerful inflammatory marker for predicting cardiovascular events. Here, we investigate whether admission NLR is associated with hematoma volume, stroke severity, and 3-month outcomes in patients with acute intracerebral hemorrhage (ICH)., Methods: 352 patients with acute ICH were prospectively identified in this study. Demographic characteristics, lifestyle risk factors, NIHSS score, hematoma volumes, and other clinical features were recorded for all participants. Patients was divided into quartiles based on the admission NLR levels (Q1: <2.78; Q2: 2.78-4.08; Q3: 4.08-7.85; Q4: ≥7.85). Multivariable linear regression models and logistic regression models were used to evaluate the association between NLR and hematoma volume, admission severity, or the outcomes after ICH., Results: Median NIHSS scores for each quartile (Q1 to Q4) were 6.0, 6.0, 6.0, and 11.0 (P=.001), and median hematoma volumes were 9.5, 9.3, 9.1, and 15.0ml (P=.005), respectively. After adjusting the age, sex, and other potential risk factors, the patients in Q4 had higher NIHSS scores (P=.042) and larger hematoma volume (P=.014). After 3-month follow-up, 148 poor outcomes (mRS, 3-6) and 47 all-cause deaths were documented. There were more patients with poor outcomes in Q4 than Q1. However, compared with the patients in Q1, those in Q4 were not associated with poor outcomes (P-trend=0.379), and all-cause mortality (P-trend=0.843) after adjust for other risk factors., Conclusions: Higher admission NLR are associated with larger hematoma volume and more serious stroke, but not 3-month outcomes in patients with acute ICH., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Monocyte and monocyte to high-density lipoprotein ratio (MHR) recently emerged as markers of inflammation and have been reported to be novel prognostic indicators of cardiovascular diseases. We investigated the association of monocyte and MHR with hospital discharge and 3-month outcome after acute intracerebral hemorrhage (ICH)., Methods: A total of 316 patients with acute ICH were enrolled from November 2011 to March 2014. Demographic characteristics, lifestyle risk factors, medical history, admission laboratory parameters, and monocyte level were recorded. Clinical outcome was disability or death (defined as having a modified Rankin Scale score≥2) upon discharge or at 3months., Results: 202 patients (63.9%) experienced disability or death at hospital discharge, and 176 patients (55.7%) at 3months post-ICH. Admission monocyte level was associated with clinical outcome at 3months (adjusted OR, 4.17; 95% CI, 1.45-12.00; P-trend=0.028) when highest and lowest quartiles were compared. However, no significant association was found between monocyte and discharge outcome (P-trend=0.102). Compared to the lowest category of MHR, the highest category was associated with a 3.87-fold increase in the odds of disability or death at discharge (95% CI, 1.17-12.76; P-trend=0.045) and 3.08-fold increased odds of disability or death at 3-month (95% CI, 1.05-9.08; P-trend=0.024)., Conclusions: In patients with acute ICH, higher MHR was associated with increased risk of disability or death at discharge and at 3months post-ICH, however higher monocyte was only associated with increased risk of 3-month disability or death., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Previous clinical studies suggest that intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator benefits stroke patients, but the efficacy of IVT in young stroke patients is not well-studied in China., Objective: We compared the safety and efficacy of IVT with recombinant tissue plasminogen activator between Chinese young stroke patients (18-50 years old) and older patients (51-80 years old)., Method: We analyzed data from the Soochow Stroke Registry for 373 stroke patients (18-50 years, n=74 vs. 51-80 years, n=299) who received IVT between May 2009 and January 2016. Main outcomes included symptomatic intracerebral hemorrhage (sICH) within 7 days, and mortality and favorable outcome (modified Rankin scale 0-2) at 3 months. Associations between baseline characteristics and outcomes for the two groups were analyzed by logistic regression., Results: Favorable outcome at 3 months was significantly higher in young adults (adjusted odds ratio 2.09; 95% confidence interval 1.09-3.99, p=0.026). The incidence of sICH and mortality was low for young adults compared with older patients, but there were no statistically significant differences between the two groups. Multivariable analysis showed that baseline National Institutes of Health Stroke Score was associated with favorable outcome (p=0.026) in young adults., Conclusion: Our analysis indicated that young stroke patients treated with IVT had a more favorable outcome without an increased risk of sICH and mortality compared with older patients. We conclude that IVT is safe and at least as beneficial for Chinese young adults with acute ischemic stroke compared with older patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: The low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio has been recognized as a strong risk predictor of cardiovascular diseases. However, the association between the LDL-C/HDL-C ratio and the prognosis of acute intracranial hemorrhage (ICH) is unclear. Thus, we prospectively investigated whether a low LDL-C/HDL-C ratio could predict all-cause mortality and whether LDL-C/HDL-C ratio is superior to traditional lipid profiles in predicting mortality among Chinese patients with acute ICH., Methods: A prospective cohort study of 356 patients with acute ICH was conducted, and the mean follow-up time point was 80.4 days. Participants were divided into four categories based on LDL-C/HDL-C ratio quartiles. Three-month outcomes were evaluated by in-person or telephone interviews with patients or their family members. The end point was three-month mortality from all causes., Results: Forty-seven deaths from all causes were documented. The multivariate analysis found that LDL-C/HDL-C ratio [hazard ratio (HR) = 0.49, p = 0.008] and LDL-C (HR = 0.27, p = 0.044) were significantly associated with all-cause mortality. The Kaplan-Meier curves show that patients in the lowest quartiles had the highest cumulative incidence rates (log-rank p = 0.027). After adjusting for covariates, a low LDL-C/HDL-C ratio was associated with a 3.55-fold increase in the risk of all-cause mortality (HR, 3.55 [95% confidence interval, 1.04-12.14]; P-trend = 0.011) when the highest and lowest quartiles were compared. The C-statistic of the LDL-C/HDL-C ratio was significantly larger than other traditional lipid profiles (all p < 0.05)., Conclusions: A low LDL-C/HDL-C ratio was independently associated with an increased risk of all-cause mortality at three months in patients with ICH. Moreover, the LDL-C/HDL-C ratio appeared to be a best lipid predictor of all-cause mortality than traditional lipid profiles.

Objective: Serum soluble corin has been associated with stroke. However, whether it is associated with stroke prognosis has not yet been studied. Therefore, we aimed to study the association of serum soluble corin with risk of poor outcomes within 3 months after stroke., Methods: We followed 522 stroke patients for 3 months to identify major disability, death and vascular events. Serum soluble corin was measured at baseline for all participants. Logistic regression was used to examine the associations of baseline serum soluble corin with outcomes of stroke, adjusting for age, sex, baseline NIHSS score, hours from onset to hospitalization, smoking, drinking, hypertension, diabetes, coronary heart disease, atrial fibrillation, family history of stroke, and stroke subtype., Results: Patients with high corin had a significantly lower crude risk for the composite outcome of major disability or death (OR = 0.64, 95%CI: 0.43-0.96) than patients with low corin (the lowest tertile). After adjustment for age and baseline NIHSS score, patients with high corin still had a significantly lower risk for the composite outcome of major disability or death (OR = 0.60, 95%CI: 0.36-0.99). This association became bottom line significant after additionally adjusting for other conventional factors (OR = 0.61, P = 0.058). No association was found between serum soluble corin and other composite outcomes., Conclusion: Serum soluble corin deficiency predicted risk for major disability within 3 months after stroke, independent of baseline neurological deficient. Our results may indicate a probable role of corin in stroke prognosis., Competing Interests: The authors have declared that no competing interests exist.

Bow hunter's syndrome (BHS), also known as rotational vertebral artery (VA) occlusion syndrome, is a rare yet treatable type of symptomatic vertebrobasilar insufficiency resulting from mechanical occlusion or stenosis of the VA during head and neck rotation or extension. The symptoms of BHS range from transient vertigo to posterior circulation stroke. The underlying pathology is dynamic stenosis or compression of the VA by abnormal bony structures with neck rotation or extension in many cases, such as osteophyte, disc herniation, cervical spondylosis, tendinous bands or tumors. Imaging approaches, such as Doppler sonography, computed tomography and angiography, as well as magnetic resonance imaging and angiography, are widely used in the diagnosis and evaluation of this syndrome. Digital subtraction angiography with head rotation remains the gold standard diagnostic method. Conservative management, surgery and endovascular procedures are the three major treatment methods for BHS, whereas some symptomatic patients may need operative treatment including surgery and endovascular procedures when conservative management is not adequate.

Background: The effects of the estimated glomerular filtration rate (eGFR) and cystatin C on clinical outcomes on intracerebral hemorrhage (ICH) remain unclear. We investigated the associations of eGFR and cystatin C with 3-month functional outcome and all-cause mortality in acute ICH patients., Methods: A total of 365 patients with acute ICH were enrolled. Serum creatinine and cystatin C levels were measured within 24 h of admission. Outcomes at 3-month were evaluated by interviews with patients or their family members. Poor functional outcome was defined as a modified Rankin Scale score ≥3., Results: During the 3-month follow-up, 154 patients experienced poor functional outcome, and 48 patients died from all causes. Low eGFR level was associated with poor outcome (adjusted OR 8.95; 95% CI 2.13-37.66; p-trend = 0.045) and all-cause mortality (adjusted hazards ratio (HR) 5.10; 95% CI 2.00-13.03; p-trend = 0.001). Additionally, a high cystatin C level was also found to be associated with all-cause mortality (adjusted HR 4.01; 95% CI 1.09-14.72; p-trend = 0.015). However, no significant association between cystatin C and poor functional outcome was observed (p-trend = 0.615)., Conclusions: Low eGFR at baseline predicts poor functional outcome and all-cause mortality at 3-month in acute ICH patients. Also, high cystatin C was associated with increased risk of mortality but not with poor functional outcome., (© 2016 S. Karger AG, Basel.)

Objective: To evaluate the relation of serum uric acid levels on admission with short-term clinical outcome and hemorrhagic transformation (HT) in patients with acute ischemic stroke treated with thrombolysis., Methods: A total of 230 acute ischemic stroke patients treated with thrombolysis in our stroke unit from 2010 to 2013 were included. Demographics, disease severity, the uric acid levels on admission and hemorrhagic transformation were prospectively collected. At 90 days, the scores of the modified Rankin Scale>2 (mRS>2) was defined as poor prognosis and the scores of mRS≤2 was defined as excellent outcome. Stepwise Logistic regression models were used to analyze potential factors affecting the prognosis., Results: The levels of serum uric acid in the patients with excellent outcome were significantly higher than in patients with poor outcome [(375±42) µmol/L vs (250±36) µmol/L, P=0.0026]. Logistic regression analysis revealed that high level of serum uric acid was related to excellent outcome (OR=1.25, 95% CI, 1.04-1.47, P=0.013). The serum uric acid level of non HT patients was significantly higher than the HT patients [(350±51) µmol/L vs (282±38) µmol/L, P=0.015]. After adjustment for the influence factors including age and hypertension, the level of uric acid was still negatively correlated with HT., Conclusion: Increased serum uric acid levels are associated with low incidence of HT and better prognosis in patients with stroke treated with reperfusion therapy.

Background and Purpose: Soluble corin was decreased in coronary heart disease. Given the connections between cardiac dysfunction and stroke, circulating corin might be a candidate marker of stroke risk. However, the association between circulating corin and stroke has not yet been studied in humans. Here, we aimed to examine the association in patients wtith stroke and community-based healthy controls., Methods: Four hundred eighty-one patients with ischemic stroke, 116 patients with hemorrhagic stroke, and 2498 healthy controls were studied. Serum soluble corin and some conventional risk factors of stroke were examined. Because circulating corin was reported to be varied between men and women, the association between serum soluble corin and stroke was evaluated in men and women, respectively., Results: Patients with ischemic and hemorrhagic stroke had a significantly lower level of serum soluble corin than healthy controls in men and women (all P values, <0.05). In multivariate analysis, men in the lowest quartile of serum soluble corin were more likely to have ischemic (odds ratio [OR], 4.90; 95% confidence interval, 2.99-8.03) and hemorrhagic (OR, 17.57; 95% confidence interval, 4.85-63.71) stroke than men in the highest quartile. Women in the lowest quartile of serum soluble corin were also more likely to have ischemic (OR, 3.10; 95% confidence interval, 1.76-5.44) and hemorrhagic (OR, 8.54; 95% confidence interval, 2.35-31.02) stroke than women in the highest quartile. ORs of ischemic and hemorrhagic stroke were significantly increased with the decreasing levels of serum soluble corin in men and women (all P values for trend, <0.001)., Conclusions: Serum soluble corin was decreased in patients with stroke compared with healthy controls. Our findings raise the possibility that serum soluble corin may have a pathogenic role in stroke., (© 2015 American Heart Association, Inc.)

Background: Autophagy has been found to be involved in animal and cell models of atherosclerosis, but to date, it lacks general observation in human atherosclerotic plaques. Here, we investigated autophagy in smooth muscle cells (SMCs), endothelial cells (ECs), and macrophages in human atherosclerotic plaques via transmission electron microscopy (TEM), western blotting, and immunohistochemistry analysis., Methods: The histopathologic morphology of these plaques was observed via hematoxylin and eosin staining. The ultrastructural morphology of the SMCs, ECs, and macrophages in these plaques was observed via TEM. The localization of microtubule-associated protein 1 light chain 3 (MAP1-LC3), a relatively special maker of autophagy, in plaques was observed by double fluorescent immunochemistry and western blotting., Results: All of these human atherosclerotic plaques were considered advanced and unstable in histologically observation. By double fluorescent immunochemistry, the expression of LC3-II increased in the SMCs of the fibrous cap, the macrophages, and the microvascular ECs of the plaque shoulders. The protein level of LC3-II by western blotting significantly increased in plaques compared with normal controls. In addition, TEM observation of plaques revealed certain features of autophagy in SMCs, ECs, and macrophages including the formation of myelin figures, vacuolization, and the accumulation of inclusions in the cytosol. These results indicate that autophagy is activated in SMCs, ECs, and macrophages in human advanced atherosclerotic plaques., Conclusions: Our study is to demonstrate the existence of autophagy in human atherosclerotic plaques by different methods, which may contribute to the development of pharmacological approaches to stabilize vulnerable and rupture-prone lesions.

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